Non-conjugate models - Statistical modeling and Monte
non conjugate prior example
non conjugate prior example - win
Millsian photons and neutrinos as a superposition of anapoles
THE CIRCULAR MAGNETIC FIELDS OF MILLSIAN PHOTONS Millsian Photon: https://miguelvaca.github.io/gutcp/GUTCP_Photon.html Millsian Photon Absorption: https://www.youtube.com/watch?v=a8P0tep8x4k Millsian Neutrino https://twitter.com/anti_quark/status/699935569254592512/photo/1 As we know, photons in free-space don't themselves emit photons. They don't themselves possess charge distributions - or can they? Certainly Millsian trapped photons may induce charge distributions. Should such alterations to the charge distribution be attributed to the electron orbitsphere or the trapped photon itself? Since the Millsian photon in the photon frame contains circular magnetic fields trapped to a "2D" shell, then a charge-current distribution which could produce it must also be trapped within a "2D" shell. It is peculiar that in the Millsian model of the orbitsphere, there are no net polar currents, only net azimuthal currents, with radial currents possible during transitions. Yet if we want to generate magnetic fields that are azimuthal to a surface, you'd need radial or polar currents. However, it is clear that purely polar currents that also happen to be axially-symmetrically distributed would lead to divergences at the poles. Since these divergences cannot be constant, as that would lead to an unbounded charge density, they would have to be a function of time. As we can see in the photon absorption animation, the trapped left-handed circularly polarized photon induces an axially-symmetric charge density that rotates in an plane. Hypothetically, this could be produced by the superposition of two orthogonal anapoles with a 90-degree phase difference. ANAPOLES https://andreysquare.com/anapole-from-dark-matter-to-nanophotonics/
Anapole – from dark matter to nanophotonics The possibility of the existence of non-radiating sources has attracted the attention of physicists for many years in different branches of science. One the of the intriguing examples is the so-called anapole moment proposed by Zel’dovich in connection with the radiation-less properties of a toroid solenoid. Furthermore, such electromagnetic configurations were recently suggested to classically describe the nature of dark matter. [....] It is a common understanding that accelerating charged particles radiate electromagnetic waves. However, from the early days of electromagnetic theory one of the most intriguing questions was the possibility of existence of non-radiating sources. It has puzzled physicists in connection with models of dynamically stable atoms and electron configurations. Ehrenfest was probably the first to explicitly recognise that radiation-less motions of extended charge distributions are possible [1]. Later, in 1933, Schott [2] demonstrated the radiation-less properties of a rigid charged spherical shell moving along a periodic orbit. In 1948 Bohm and Weinstein [3] extended Schott’s treatment to other spherically-symmetric charge distributions, and Goedecke [4] in 1964 demonstrated that there exists at least one asymmetric, spinning, extended charge distribution that does not radiate. Such models were suggested, for example, for a classical description of stable elementary particles, including, neutrons, muons and atomic nuclei. [....] Furthermore, such non-radiating electromagnetic configurations were recently proposed to classically describe the origin of dark matter [7]. According to this theory most of the matter in the Universe may be made of a basic particle (called the Majorana fermion) that possess an unusual, donut-shaped electromagnetic field similar to that of an anapole configuration. Due to its unique electromagnetic field profile, the elusive Majorana fermion would not act like a common atom. The lack of electromagnetic radiation of an anapole explains why they are so difficult to detect.
Two-photon interactions with Majorana fermions David C. Latimer Because Majorana fermions are their own antiparticles, their electric and magnetic dipole moments must vanish, leaving the anapole moment as their only static electromagnetic property. But the existence of induced dipole moments is not necessarily prohibited. Through a study real Compton scattering, we explore the constraints that the Majorana fermion's self-conjugate nature has on induced moments. In terms of the Compton amplitude, we find no constraints if the interactions are separately invariant under charge conjugation, parity, and time reversal. However, if the interactions are odd under parity and even under time reversal, then these contributions to the Compton amplitude must vanish. We employ a simple model to confirm these general findings via explicit calculation of the Majorana fermion's polarizabilities. We then use these polarizabilities to estimate the cross-section for s-wave annihilation of two Majorana fermions into photons. The cross-section is larger than a naïve estimate might suggest.
So as we can see here, others have been suggesting a "classical" explanation for dark matter, the Majorana (MY-ER-ON-UH) fermion. They serve as their own antiparticle, so they are not intrinsically matter or antimatter. If two Majorana fermions can "annihilate" and produce a photon, then surely the orthogonal superposition of two them could produce a rotating (circulating) trapped photon. THE RADIAL FORCE OF THE TRAPPED PHOTON At last, I believe that there exists a plausible explanation for the spherically-symmetric force of the Millsian trapped photon. Simply put, each magnetic great circle loop of a Millsian trapped photon is actually a torus containing a toroidal magnetic field. The magnetic field inside the torus is axially-symmetric while being a function of the radial distance from the axis of the torus. The torus has poloidal currents which cross the azimuthal magnetic field, resulting in a Lorentz force toward the interior of the torus. The superposition of all such "great toroidal loops" over a "2D" spherical shell would, to close approximation, actually be two closely-spaced "2D" shells possessing opposite polar currents. The superposition of the photon's azimuthal magnetic fields with the polar currents should be capable of producing, on a time-average basis, a central magnetic force, though not on an instanteous-basis. Nevertheless, in the case of a trapped hydrino atom, this state should not radiate, in which case, there must exist an oscillating electric dipole charge distribution that cancels out the radiation of the rotating toroidal magnetic moment. This would be the superposition of two orthogonal non-radiating anapole states. That right there is, I think, the underlying central force mechanism behind the hydrino's trapped photon. Presumably, exicited states of atoms are somehow incapable of producing the right amount of rotating toroidal magnetic moment to cancel out the radiation field of the rotating electric dipole moment. EXCITED STATES VS. HYDRINO STATES It should be said that a rotating electric dipole moment produces radiation in proportion to the 4th power of the frequency, whereas a rotating toroidal magnetic moment would produce radiation that increases with the 6th power of the frequency (See "Far-field radiation of electric and toroidal dipoles in loss-lessnon-magnetic dielectric medium with refractive index n" by V. Savinov https://arxiv.org/pdf/1811.02424.pdf). So it may be that the radiation of the rotating toroidal magnetic moment can only cancel out the radiation of the induced electric dipoles at the higher frequencies corresponding to hydrino states characterized by their smaller radius, higher surface velocity, and therefore higher angular frequency, when compared to excited states. ENERGY IMPLICATIONS In the mean time, I am studying the implications of what it would mean if the great circles on a ground state orbitsphere already possessed toroidal magnetic fields throughout its interior volume (and perhaps on the outside as well). If the mass-energy of an electron were stored in the toroidal magnetic field, and when in an spin-unpaired condition also distributed over a volume on the order of an atomic radius, then this would result in a significant toroidal magnetic moment. If the toroidal magnetic moment of the spin-unpaired electron were at some fixed angle (or absence thereof) to its magnetic moment, then it is conceivable that precessing the spin, such as by coupling the unpaired electron spin to the nuclear magnetic field under NMR, would allow us to produce modest, yet useful, toroidal electric fields (on the order of one or more hundred millivolts per meter) having long-range order when an RF field of several millitesla is applied at several megahertz, allowing us to tap directly into the mass-energy of unpaired electrons. Presumably, this would result in a frequency shift that would cause the unpaired electrons to possess a lower "temperature" (or rather, a higher "thermodynamic beta") than its surroundings. Regarding thermodynamic beta: https://en.wikipedia.org/wiki/Thermodynamic_beta
Though completely equivalent in conceptual content to temperature, β is generally considered a more fundamental quantity than temperature owing to the phenomenon of negative temperature, in which β is continuous as it crosses zero whereas T has a singularity.[6]
It should be noted that "negative temperature" may emerge from systems that have "negative heat capacity", particularly those systems where "negative" potential energy plays a significant role in the energy state of a particle. https://en.wikipedia.org/wiki/Heat_capacity#Negative_heat_capacity
Most physical systems exhibit a positive heat capacity. However, even though it can seem paradoxical at first,[4][5] there are some systems for which the heat capacity is negative. These are inhomogeneous systems that do not meet the strict definition of thermodynamic equilibrium. They include gravitating objects such as stars and galaxies, and also sometimes some nano-scale clusters of a few tens of atoms, close to a phase transition.[6] A negative heat capacity can result in a negative temperature.
I suspect that there may be a way to harness this energy directly into an electrical circuit when the relativistically-generated electric dipoles, in the form of toroidal electric fields of the precessing toroidal magnetic moments of unpaired electrons, can drive significant amounts of static electricity into and out of dielectric-conductor interfaces. Charge density fluctuations would be required because the electricity in our circuit cannot flow through the axes of atom-sized toroidal magnetic moments (and the displacement currents that can are simply too small), thus the electric field applied to the circuit wire by these precessing toroidal magnetic moments would closely obey Poisson's equation, and therefore the mechanism of energy transfer would, in the lab frame, constitute electrostatic induction (or electric evanescent wave coupling), as opposed to electromagnetic induction. Perhaps a device relying on such principles could be called a "flux capacitor" or an "arc reactor", or maybe we should leave out sci-fi inspired names and simply call it an NMR Electrostatic Generator. Or we could be semi-serious and called it an Atomic Spin Magnetoelectric Resonance (or ASMR) Generator. A BASIC MODEL OF THE PROPERTIES OF THE TUMBLING TOROIDAL MAGNETIC MOMENT A toroidal magnetic moment lacks its own magnetic dipole moment. However, we can rotate a toroidal magnetic moment by Larmor precessing whatever magnetic dipole moment that it may be coupled to due to the conservation of magnetic helicity in the absence of resistivity. Suppose that the azimuthal magnetic field inside the torus is curl-free. This requires that the azimuthal magnetic field strength to be inversely proportional to the distance from the z-axis, per Ampere's law. Thus, the product of the azimuthal magnetic field with the distance from the z-axis is independent of position within the toroidal volume. The toroidal magnetic moment density is uniform throughout that volume, as is the associated electric dipole moment which it produces as a result of precession. The z-component of toroidal magnetic moment density of the azimuthal magnetic field inside the torus is:
toroidal magnetic moment density = (1/2) azimuthal magnetic field[H] * distance from the z-axis
The precession of the toroidal magnetic moment about an axis perpendicular to it produces an electric polarization perpendicular to both the toroidal magnetic moment and that precession axis:
electric dipole moment density = (1/c^2) toroidal magnetic moment density * 2 pi * rotation frequency = (1/c^2) (1/2) azimuthal magnetic field[H] * distance from the z-axis * 2 pi * rotation frequency
The poloidal current I produces a magnetic field inside the torus equal to:
azimuthal magnetic field[H] = I / (2 * pi * distance from the z-axis)
Therefore, the above simplifies to:
toroidal magnetic moment density = I / (4 pi) electric dipole moment density = (1/c^2) (1/2) I * rotation frequency
The energy stored in the torus equals:
energy = (1/2) L I^2
The number of turns N = 1. Therefore, the magnetic flux stored in the torus equals the magnetic flux linkage:
magnetic flux = L * I
Consider a case where the energy stored is equal to the mass-energy of the electron and the magnetic flux through the torus is equal to the magnetic flux quantum:
energy = m_e * c^2 magnetic flux = h / (2 e)
The inductance implied by the energy and magnetic flux values of the "one-turned" torus is:
Assuming that there is one turn of current I so that N=1, the magnetomotive force F = I. Therefore, the ratio of the cross-section to the magnetic path length must equal:
A / l = inductance / mu_0 = (1/2) (h/(2 e))^2 epsilon_0 / m_e = 0.2078 angstroms
The volume of the torus is equal to:
volume = 2 pi^2 r^2 R = (pi r^2) (2 pi R) = A * l Where r is the minor radius, and R is the major radius.
Therefore in our example:
A / l = (pi r^2)/(2 pi R) = r^2/(2 R)
In the special case that R=r (a horn torus):
A / l = 2 r = 2 A / l r = (h/(2 e))^2 epsilon_0 / m_e r = pi/4 * Bohr radius
So it is conceivable that the entire mass-energy of an electron could be contained within the azimuthal magnetic field in a volume smaller than an atom such as iron, which has a radius more than twice the Bohr radius. To get the average electric field produced by the rotating toroidal magnetic moments, let's refer to the prior result above:
electric dipole moment density = (1/c^2) (1/2) I * rotation frequency
In our example, the polodial current is:
I = m_e * c^2 / ((1/2) h / (2 e))
Substituting for current I, the electric dipole moment density inside the torus could be expressed as:
electric dipole moment density = (1/c^2) (1/2) (m_e * c^2 / ((1/2) h / (2 e))) * rotation frequency = (1/2) (m_e / ((1/2) h / (2 e))) * rotation frequency = m_e / (h / (2 e)) * rotation frequency = 2 e * m_e / h * rotation frequency
The average electric field generated perpendicular to the rotating toroidal dipole moment would be:
electric field = (2 e * m_e / h)/epsilon_0 * rotation frequency * fill fraction = (49.7536128 (volts per meter) per megahertz) * rotation frequency * fill fraction
In our example, R = r = pi/4 the Bohr radius = 0.416 angstroms, so the torus volume V simplifies to:
V = 2 pi^2 r^3 = 1.417 cubic angstroms
A unit BCC cell of iron contains two atoms, and the lattice constant is 2.866 angstroms. So our fill fraction could be:
Therefore, the induced electric polarization could be:
electric polarization = (5.99 (volts per meter) per megahertz) * rotation frequency
This would depend on the transverse magnetization during nuclear magnetic resonance which could reduce this figure by perhaps 1 to 3 orders of magnitude due between 0.1 % to 10% of the unpaired magnetic moments contributing to the transverse magnetization. On the other hand, the energy (= electron mass * c^2) and magnetic flux (= magnetic flux) values may perhaps differ little for one toroidal magnetic moment to the next, but their ratio determines the density of the toroidal magnetic moment, not its total value. So as the volume occupied by a toroidal magnetic moment increases, the resultant electric polarization should also grow. To what exent, I am not sure, but perhaps as far as the neighboring atoms, increasing the fill fraction by up to several fold. Furthermore all the above assumes that the magnetic flux quantum wraps around the z-axis once, though perhaps it is possible for it to wrap around the z-axis multiple times, perhaps as a way to include the mass-energy of all the other electrons that are part of the atom. EVANESCENT WAVES NUCLEAR MAGNETIC RESONANCE If the NMR material possessing an electric polarization were placed adjacent to a conductor, the charges in that conductor could rearrange. In the process, energy could be stored in the magnetic and electric fields of the circuit. The technique is near-field or evanescent wave coupling. Nodes of one evanescent wave oscillate at the same phase, as it is a standing wave. However, if you take another evanescent wave (standing wave) with its own different phase throughout it and superimpose it with the first, you get travelling waves, and as a result power transfers from one to the other. If you suspect that someone would have already thought of this as a way to generate useful power if it were possible, consider what some experts had to say: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0144483
Evanescent Waves Nuclear Magnetic Resonance El Mohamed Halidi, Eric Nativel, Mohamad Akel, Samir Kenouche, Christophe Coillot, Eric Alibert, Bilal Jabakhanji, Remy Schimpf, Michel Zanca, Paul Stein, Christophe Goze-Bac Published: January 11, 2016 https://doi.org/10.1371/journal.pone.0144483 Nuclear Magnetic Resonance spectroscopy and imaging can be classified as inductive techniques working in the near- to far-field regimes. We investigate an alternative capacitive detection with the use of micrometer sized probes positioned at sub wavelength distances of the sample in order to characterize and model evanescent electromagnetic fields originating from NMR phenomenon. We report that in this experimental configuration the available NMR signal is one order of magnitude larger and follows an exponential decay inversely proportional to the size of the emitters. Those investigations open a new road to a better understanding of the evanescent waves component in NMR with the opportunity to perform localized spectroscopy and imaging. [....] To our knowledge, evanescent electric fields emitted from nuclear spins have never been explored, even if they potentially contain the same local information conventionally picked-up by coils. Our work presents an alternative method to detect electromagnetic fields which has not been fully exploited in NMR spectroscopy and imaging.
If in 2016 scientists were just then considering to even measure the NMR evanescent waves, how long will it be before they decide to create a bifilar probe consisting of rolled thin foil conductors and measure the signal produced by NMR material consisting of thin foil magnetic material rolled between the thin bifilar conductor layers so as to absolutely maximize any potential energy transfer between the NMR excited material and the bifilar "probe" via evanescent wave coupling, rather than to maximize imaging quality as is often done? Am I wrong to believe that something like this hasn't been done yet?
Rhuyeve tamile Amaharukwe, Rhux̌akwe tanajha chiwirachive, Tanapm Rhalamereve. ”Amaharu said it to me, I have come to say it to you, And I will go say it to the world (OR: And you will go say it to the world)"
Phonotactics: CV syllables only. /ə/ is pronounced [ɨ] in a stressed syllable unless preceded by a pharyngeal/pharyngealized consonant, otherwise it is pronounced [ə]. Syllabic consonants /l̩/, /r̩/, /n̩/ and /m̩/ appear word finally, but these are best understood as underlying /ənə/, /əmə/, /ələ/ and /ərə/ respectively. With voiced consonants, pharyngealization is realised as:
A pharyngeal/epiglottal voiced trill-release of the consonant.
The following vowel is pronounced with a murmured voice.
With voiceless consonants (including ejectives), pharyngealization is realised as:
A pharyngeal/epiglottal voiceless trill-release of the consonant.
The following vowel is pronounced with a noisy, aspirated release.
Furthermore, vowels /i/ and are diphthongized following pharyngeals: /i/ -> [əi], -> [əu] Thus: /dˁu/ -> [d͡ʢə̤ṳ] /tˁi/ -> [t͡ʜʰəi] (This is based on Chechen btw) Sound changes since Kesan: The aspirated series shift to fricatives: /pʰ/ -> /f/ /tʰ/ -> /s/ /kʲʰ/ -> /xʲ/ /kʷʰ/ -> /xʷ/ /qʰ/ -> /χ/ /qʷʰ/ -> /χʷ/ Palatalized velars shift to Alveopalatals, leaving the language with only a labialized velar series. /kʲ/ -> /t͡ʃ/ /xʲ/ -> /ʃ/ /kʲ'/ -> /t͡ʃ'/ /gʲ/ -> /d͡ʒ/ Following this, alveolars also shift to alveopalatals when followed by /i/ /ti/ -> /t͡ʃi/ /si/ -> /ʃi/ /t’i/ -> /t͡ʃ’i/ /zi/ -> /ʒi/ /t͡si/ -> /t͡ʃi/ /d͡zi/ -> /d͡ʒi/ Glottals become pharyngeals when followed by a pharyngealized vowel: /hVˁ/ -> [ħVˁ] /ʔVˁ/ -> [ʕVˁ] Pharyngealization shifts from vowels to adjacent alveolalabial consonants, If no eligible consonants are adjacent to the vowel pharyngealization is lost, if both adjacent consonants are eligible, the consonant following the vowel is pharyngealized. P=eligible consonant. K=non-eligible consonant. /PVˁK/ -> /PˁVK/ /KVˁP/ -> /KVPˁ/ /KVˁK/ -> /KVK/ /PVˁP/ -> /PVPˁ/ Some time following this, /vˁ/ and /fˁ/ shift to /ʕ/ and /ħ/, respectively. /ə/ inserted errywhere: /CC/ -> /CəC/ /CVC__/ -> /CVCə/ (is this how you denote word-final consonants? pls halp my linguistics formulafu is weak) Vowel reduction? I haven't figured out the exact details yet, open to suggestions. Word final voiceless fricatives and word-final syllables composed of a voiceless fricative and an /ə/ are dropped. This has an interesting effect on certain words, which now develop two distinct forms depending on whether or not they take any suffixes. For instance, the 1st person singular pronoun nominative /ʕuχə/ loses the final syllable, becoming /ʕu/, but in the plural, the final syllable is "protected" by the plural suffix, and so the original form remains: /ʕuχa-t͡ʃə/ Lastly: /ɮ/ -> /ʒ/ /ɬ/ -> /l/ /t͡s’/ -> /səʔ/ /t͡s/ -> /s/ /d͡z/ -> /z/ /ji/ -> /jə/ /wu/ -> /wə/ /Cʷu/ -> /Cʷə/ /VhV/ -> /VnV/ (unless at least one of V=, in which case /VhV/->/VmV/) Overall grammatical changes from the proto-language:
Pronouns developed tripartite allignment (rest of the language stays ergative-absolutive)
Developed a three-way gender system (masculine animate, feminine animate, inanimate)
BECAME NON-CONFIGURATIONAL. Word order is more or less random, discontinuity all over the place, pro-dropping, this language doesn't give a shit.
Lost most of the inflected verbs, so might only have 3 verbs depending on how you look at it. See below.
Omni-predicative? Sort of? Technically not? It's hard to explain, see below, in practice everything can be verbified, but it's less that nouns serve as verbs and more that semantically deficient verbs can have nouns bolted on to them to give them an actual meaning... it's weird.
Pronouns, which are now tripartite:
Singular
Dual
Plural
1.
Nominative
ʕu
ʕuʕu
ʕuχat͡ʃə
Ergative
ʕuχakʷə
ʕuʕuχakʷə
ʕuχat͡ʃəkʷə
Accusative
ʕuju
ʕuʕuju
ʕuχat͡ʃəju
Genitive
ʕujə-
ʕuʕujə-
ʕuχat͡ʃi-
2.
Nominative
t͡ʃiwira
t͡ʃit͡ʃiwira
t͡ʃiwirat͡ʃə
Ergative
t͡ʃiwirakʷə
t͡ʃit͡ʃiwirakʷə
t͡ʃiwirat͡ʃəkʷə
Accusative
t͡ʃiwiju
t͡ʃit͡ʃiwiju
t͡ʃiwirat͡ʃəju
Genitive
t͡ʃiwi-
t͡ʃit͡ʃiwi-
t͡ʃiwirat͡ʃi-
3.
Nominative
kʷ’ə
kʷ’əkʷ’ə
kʷ’əʃat͡ʃə
Ergative
-
-
-
Accusative
kʷ’əʃu
kʷ’əkʷ’əʃu
kʷ’əʃat͡ʃu
Genitive
kʷ’i-
kʷ’əkʷ’i-
kʷ’əʃat͡ʃi-
As you can see above, Chesar has a tripartite pronoun system, with distinct forms for intransitive subject (nominative), transitive subject (ergative) and transitive object (accusative). Note that the lack of ergative pronouns in the third person is not an accident, as Kesar completely lacks them. Demonstratives are instead used. Other 3rd person pronouns exist, but demonstratives are again commonly in their place. True 3rd person pronouns are only used for emphasis. Genitive pronouns may appear on their own without an overt head and may thus both be translated as "my" and "mine". ("That's my book. It's mine"). They agree with their head in gender and case. The tripartite system developed, in parts, as a result of the increased use of demonstratives in lieu of third person pronouns. The fact that these demonstratives, unlike pronouns, but like other nouns, followed an ergative allignment, brought further confusion to to an already complex system. The pattern of these demonstratives, which were marked with an Ergative case suffix when transitive subjects, was regularized to apply to other pronouns, and formed by attaching an ergative /-(a)kʷə/ suffix to the nominative form. However, pronouns had distinct Nominative and Accusative forms, and these stuck around even after the addition of the ergative. Thus you get a tripartite system, with no distinct ergative form for 3rd person pronouns. Examples: ”I went” Rhu rhuzigwe.
GRAMMATICAL GENDER SYSTEM: Each grammatical gender has a "common" ending that many words in the group end on, and this ending is used to derive further words into the group. Gender is also mostyl semantically determined, so it is somewhat predictable. But still, for a lot of words you just have to memorize it. The grammatical gender of a noun triggers agreement in adjectives (whose only distinction from nouns is having no inherent gender) and usually demonstratives and genitive pronouns. Gender suffixes: Masculine: /-Ø ~ -na/ (/-na/ is used for deriving new words into the class and also functions as a generic nomen agentis, in agreement context it only appears on adjectives. Genitive pronouns and demonstratives show null-agreement) Feminine (smaller): /-waʃi ~ -ʃi/ (/-waʃi/ is the prefered form for derivation, while /-ʃi/ is the prefered form for agreement) Inanimate: /-Ø ~ -sə-/ (The /-sə-/ form appears only when followed by another suffix, otherwise /-Ø/ is used) ”That big man” Br zejhina rhala
The gender-system developed as a result of a combination of several things... stuff... stuff happened. The basic idea is that continued dislocation resulted in certain derivational suffixes becoming used A LOT, think of the following: "I killed that fat woman", a sentence we have all said at some point in our life. Over time it became more and more common for Chesar speakers to dislocate parts of the sentence: "I killed fat woman, that (one)", or "I killed that woman, (the) fat (one)". With sentences like these becoming more and more common, speakers needed to disambiguate who the dislocated bit refered to. In the above example, the referent is a woman, and the language already had a derivational suffix /-wasi/ used for deriving words, typically refering to females. This suffix was expanded and applied to the dislocated part when it refered back to a female, so the above would be rendered: "I killed fat woman, that-FEM (one)", or "I killed that woman, (the) fat-FEM (one)". This was then regularized to be used even when these elements were not dislocated, and over time dislocation would become simple discontinuity, so the above would end out as: "I killed fat-FEM woman that-FEM" "I killed that-FEM woman fat-FEM." "I killed that-FEM fat-FEM woman." See? Easy peasy. So the development of gender and non-configurationality was closely related. Anyway, the origin of gender: (WIP) The feminine animate came about due to the following:
Increased productivity of the "feminine/odd" derivational suffix /-wasi/ (/-waʃi/ following sound changes).
Generalization/reinterpretation of many words ending on /-si/ (mostly small birds) as part of a grammatical group, along with words that refered to "odd" members of a particular group (such as flightless birds or legless lizards).
The masculine animate (largest group, default for refering to animates):
Old nomen agentis suffix /-na/ reanalyzed as a masculine/non-feminine animate gender marker.
The inanimate:
The old nominalizing/gerundive suffix /-tʰ/ (/-sə/ following sound changes) reanalyzed as an inanimate/abstract gender marker. It is then lost word-finally as a result of regular sound changes, and only surfaces when followed by other suffixes (such as case markers).
Since all gender markers originated as derivational suffixes, they appear before any other nominal inflectional suffixes. VERBS Form: SIGNIFIER-AGREEMENT-LIGHT.VERB "We went to drink it" Chitekweyenazi. /t͡ʃitəkʷə-jəna-zi/ drink-1.PLU.ERG:3.SG.ABS-go.PERF Verbs in Chesar are unspecified for transitivity, the only thing determining their transitivity is the upper number of arguments they can meaningfully take. The verb meaning "go" can also mean "bring", the verb meaning "dive" can mean "throw into water". "He died" Brhule
bˁu-Ø-lə die-3.SG.ABS-do.PERF
"He killed him" (lit. "he died him") Brhumile
bˁu-mi-lə die-3.SG.ERG:3.SG.ABS-do.PERF
Changes from Kesan: The verbs overall structure is mostly unchanged from Kesan (see the previous post), but six major developments have taken place in the interim:
The Uninflected verbs have integrated fully with whatever inflected verb postcedes them, becoming morphologically part of the same word. They are now refered to as "signifiers" (not sure what else to call them). So /ɮaˁ mid͡zigʷɨd͡zɨ/ -> /ɮaˁmid͡zigʷɨd͡zɨ/. Furthermore, there is no longer a clear distinction between them and nouns; signifiers can serve as nouns if marked for gender, and nouns can serve as signifiers (in most cases losing their gender)
The vast majority of the Inflected Verbs have been lost, reducing the class to a mere handful. This class is now refered to as the "Light Verbs".
Nouns may now be verbed freely, this came about as a result of A: some nouns also serving as uninflected verbs/signifiers set a precedence. B: reduced subordinate clauses became a mainstay: /magʷəχʷə ʔə-lə/ "a bear he-was" became /magʷəχʷə-lə/ "(he) was a bear"
The light verb base has fused with aspect/mode/tense suffixes.
The agreement affixes have undergone some degree of fusion.
The subordinating relativizer affix /-fə/ has been lost as part of regular sound changes.
Signifier: The Signifier is the element of the verb that carries most of the core meaning of the verb, /t͡ʃitəkʷə/, for instance, means "to drink". Signifiers may serve as predicates on their own, with no agreement or light verb, in certain subordinate clauses (see below), but oddly enough, in spite of what I just wrote, they aren't really the core of the verb - the light verb is. A regular noun may also serve as a signifier. The exact meaning of the resulting verb varries, but generally it means "to be NOUN" or "to do (as one would do if one were a) NOUN to X". Signifiers aren't truly distinct from regular nouns, and may in fact just be interpreted as inanimate nouns incorporated into the verb (it's weird). Agreement: See the link below for a comparison between verbal agreement in Kesan (Proto-Dwarf) and Chesar. https://imgur.com/a/mLoU80Z Reflexives and reciprocals are formed by specialized affixes followed by an intransitive agreement affix. Light Verb: There is, in one way of looking at it, only 3 verbs in Chesar. "to do/be", "to go" and "to come". These are the light verbs. They are the final part of the full verb and serve as a way of indicating associated motion, as well as tense, aspect and modality. Light verbs may appear (with agreement) without any signifier when refering to simple motion. "I go to you" could be expressed simply as: Nawegweze.
nawə-gʷəzə 1SG.ERG:2SG.ABS-go.IMPF
No signifier necessary. The same is true when the action refered to refers back to one previously mentioned, or when it is obvious from context: "I killed him, I did it". or "I did that" (pointing to a corpse) Some inflections have two forms: a short and a long form. The short form is used if the light verb is preceded by four or more syllables (including signifier and agreement), the long form is used otherwise. The light verbs are as follows: To go: Four conjugations: Perfect, Imperfect, Future and Imperative (used for positive imperatives which include motion, "go and X") PERFECT: /-zi ~ -zigʷə/ IMPERFECT: /-gʷə ~ -gʷəzə/ FUTURE: /-pəmə/ MOVEMENT-IMPERATIVE: /-ma ~ -d͡ʒima/ To come: Three conjugations: Perfect, Imperfect and Future. PERFECT: /-χa ~ -χad͡ʒa)/ IMPERFECT: /-d͡ʒa/ FUTURE: /-xʷi/ To be/to do: Rather than indicating a lack of motion, this light verb is simply unspecified for motion - it may refer to motion to-or-from an endpoint, it may not. Unlike the other two light verbs, this one has a bunch of forms, including various irrealis forms. It may be treated as many forms of one light verb or many light verbs with a single form, hard to say. PERFECT: /-lə/ IMPERFECT: /-dˁa ~ -nidˁa/ FUTURE: /-dələ/ HABITUAL: /-t’əka/ PERFECT HABITUAL: /-t’ət’ə/ IMPERATIVE: /-da/ NEGATIVE IMPERATIV: /-dənə ~ -nadənə/ SUBJUNCTIVE: /-bˁa/ JUSSIVE: /-χʷəlu/ Subordinate clauses: Due to the loss of the subordinating relative suffix /-fə/ , there is no longer any formal distinction between verbs in subordinate clauses and verbs in main clauses. Instead you just know them from context, and from the fact that most subordinate clauses are headed by some kind of subordinating particle (haven't done any work on them yet). The aspect/tense used in subordinate clauses is always relative to that of the main clause. When the referent and tense is identical to that of the main clause, the agreement and light verb may be omitted entirely, leaving nothing but a naked signifier as the predicate of the subordinate clause. "I fell and cut my leg" Qwagwerhule, qaye t'ume.
qʷagʷə-ʕu-lə qajə t'umə fall-1SG.ABS-do.PERF leg cut
Note how the signifier /t'umə/ lacks both agreement and light verb. This developed from nominalized signifiers which then lost the nominalizing /-sə/ suffix due to sound changes. The alternate system of forming subordinate clauses by attaching case suffixes to the nominalized verb was completely lost in Chesar. But it would have a massive impact on another branch of the family, but more about that next week. Fun, isn't it? Still a bunch of stuff I haven't figured out, including how exactly the case system turned out (Reduced? Mostly unchanged? Expanded?). But it works.
The Next Pandemic: Confronting Emerging Disease and Antibiotic Resistance
Two problems not commonly discussed prior to the novel Coronavirus outbreak are the emergence of infectious disease and the related increasing prevalence of antimicrobial resistance. Here, I will explain the science behind these problems and some solutions that can be driven by legislation. My background is more squarely rooted in the science, so I apologize if I lean too heavily in this area as opposed to the economics and policy focus of this subreddit. I frequent this sub and enjoy the discourse here, and in my area this is one topic that overlaps with public health policy that I am passionate about. To understand emerging disease and antimicrobial resistance, it’s important to understand evolution The novel coronavirus, SARS-CoV2, is an example of an emerging infectious disease. SARS-CoV2 is a disease that, prior to 2019, had not to the best of our knowledge infected a human being. The genetic makeup of the virus indicates that the virus is natural, originating likely as a bat or pangolin Coronavirus that acquired the ability to infect humans, and that it is not man-made (1). Why do new diseases come into existence? Why haven’t humans encountered all the diseases capable of infecting us? Furthermore, why do diseases that we had previously thought conquered have the newfound ability to harm us again, in spite of our advancements in antibiotic development? The answer to these questions is partially answered by evolution. Several novel viruses, like SARS-CoV1, MERS, and SARS-CoV2, began as zoonosis: infection by a pathogen with an animal source. Viruses, though generally considered non-living, contain nucleic acid genomes (either RNA or DNA) similar to every other organism in the tree of life. This genome is subject to selective pressures, just as with every other nucleic-acid containing being, and mutates non-specifically (that is, an organism develops a mutation, then selective pressures have a positive, negative, or neutral effect on retaining or discarding the mutation). An animal coronavirus that recognizes surface molecules on animal cells that have some similarity to human cell surface molecules may only be a few small genome changes away from being capable of infecting humans. It is likely that SARS-CoV2 emerged in one of two ways: as either an animal virus that mutated within an animal that gained the ability to infect humans, or as an animal virus that jumped to humans, and within the human host was selected for the ability to infect humans (1). The advent of novel viruses is also facilitated by the horizontal transfer of genetic material between distinct viral lineages. In Influenza viruses, this can take the form of segments of genome being transferred wholesale between viruses. Influenza viruses contain a genome composed entirely of RNA in multiple segments of sequence. Segments “re-assort” when flu viruses of distinct lineage infect the same cell, and viral genomes are mixed during the process of producing new viruses. Alternatively, as would be the case in coronaviruses, recombination occurs through a mechanism not fully understood, where whole portions of genome are exchanged between viruses (2). The problem of antimicrobial resistance is also best understood through evolution. To explain this phenomenon, I will describe mainly how resistance manifests in bacteria, but similar processes drive resistance to anti-virals, anti-fungals, and anti-parasitics. Antibiotics are largely derived from natural sources: as microbes compete for resources, there is a drive to reduce competitors numbers by killing them or inhibiting their growth. Antibiotics are typically small molecules that target essential processes for bacterial growth; commonly cell wall biosynthesis (preventing growth and division of the cell, an example being penicillin), protein synthesis (blocks the process of translation, an example being erythromycin), production of RNA (blocks the process of transcription, an example being rifampin) or production of DNA (blocks the process of replication, an example being fluoroquinolone). These antibiotics arose through selective pressures, and in response bacteria have developed systems to circumvent the deleterious effects of antibiotics. These include: rapidly excreting the antibiotic before it is capable of inhibiting growth (efflux pumps, a notable offender being Pseudomonas aeruginosa, a common pathogen in patients with cystic fibrosis), degrading the antibiotic (beta-lactamases are a class of enzyme that degrade beta-lactam family antibiotics, such as penicillin), modifying the antibiotic (the most common mechanism for aminoglycoside resistance is to chemically modify the antibiotic so it doesn’t work), or simply modifying the target (Streptococcus pneumoniae is a microbe that causes multiple diseases that is naturally resistant to beta-lactams by modification of the drug target, the aptly-named Penicilin-binding protein) (3). As humans, it has been beneficial to identify these natural compounds and use them medically to treat infection. Bacteria have incredible genome plasticity, engaging in a process known as horizontal gene transfer (HGT; sometimes referred to as lateral gene transfer) that increases the prevalence of resistant microbes. Not all bacteria are capable of this set of processes, but importantly several medically important pathogens, such as E. coli, Salmonella, Yersinia pestis, Acinetobacter baumannii engage in processes that facilitate the transfer of genetic material between bacteria. There are several molecular mechanisms for HGT: bacteria-infecting viruses can transmit pieces of genetic material between similar bacteria (transduction), bacteria can form a bridge that transfers plasmids (conjugation; plasmids are typically circular pieces of DNA, and are typically maintained independently of the bacterial chromosome and commonly encode antibiotic resistance genes), or bacteria can simply pick up naked DNA in the environment and integrate that DNA into their chromosomes (natural transformation) (3). The effect of these processes is that, when a gene that imparts resistance to a particular antibiotic is introduced into a population, it may spread between members of the population, not just within the progeny of the cells that encode the resistance gene. This is especially true when a gene that imparts resistance is on a plasmid or is otherwise mobilizable (transposons, or jumping genes, are also common perpetrators of transmission in that they move somewhat readily and often encode drug resistance). The key point to understand here is that while genes are present in bacteria, either on a chromosome or on a mobilizable element, these genes are capable of moving to many other members of the same population. To understand this in more practical terms, many people have undergone a course of antibiotics and experienced gastrointestinal distress or stomach pains. This can be attributed to disturbing your normal intestinal microbiome, as you kill off non-resistant bacteria. Now assume you have an infection of some sort, it could be anywhere in your body accessible to an orally administered antibiotic, and your doctor prescribes you an antibiotic. It is possible, and possibly probable, that within your gut are bacteria that harbor resistance genes. In the absence of the antibiotic, these are likely to have a neutral or possibly deleterious effect; think of this like a welder that is unable to remove his welding mask: it certainly helps when he is welding, but is cumbersome at other times of the day. Taking the antibiotic results in high selection for resistant microbes to grow and prosper. This allows the resistant bugs to soon outnumber the non-resistant bugs. Ultimately, this increases the concentration of the resistance genes in the population of microbes in your gut. Subsequent to this, you may encounter an infection of a gastrointestinal pathogen that, in infecting your gut, acquires the resistance genes that you selected for. In disseminating this pathogen, you are also disseminating this resistance gene. Additionally, and perhaps more importantly, in taking antibiotics you select for drug resistance in the opportunistic pathogens of your body, notably Clostridium dificile and Staphylococcus epidermidis. These microbes are capable of causing disease, but reside in you or on you and cause infection when conditions are optimal for their growth. The problem of antimicrobial resistance is convergent with emerging pathogens, as many pathogens “re-emerge” as they develop resistance to antimicrobials. While TB cannot be said to be an emerging pathogen as the world has been experiencing a TB pandemic since at least the early 1800’s, TB is re-emerging in the since that increased drug resistance has led to strains of TB that are not treatable via the traditional course of antibiotics (4). Similarly, common pathogens such as E. coli, Klebsiella, and Clostridium dificile are bugs that have become increasingly resistant to the antibitoics used to treat them (5). Acinetobacter baumanii, a soil microbe with resistance to a spectrum of antibiotics, became a common Gulf and Iraq War wound infection. Many of these pathogens find a home in hospitals, where the use of antibiotics is prevalent and potential hosts are abundant. Furthermore, the recently emerged pathogen HIV, the causal agent of AIDS, is intersectional with that of antibiotic resistance, as infection with HIV increases susceptibility to bacterial infections due to reduced immune cell numbers; increased infection rates of Both issues, antibiotic resistance and emerging pathogens, pose a threat to human health the world over, and I will attempt to address both of these issues in this post. The problem of emerging disease and antibiotic resistance is exacerbated by humans To what extent do emerging diseases and antibiotic resistance affect humans? SARS-CoV2 has had an extensive impact on human health and living, and the response to shut down to stop the spread of the virus has had a large economic impact. It is impossible to accurately predict the threat posed by non-discovered viruses, so the next threat could be relatively benign, or truly horrific. This is not to fearmonger, there is no reason to suspect that such a virus is bound to steamroll us soon, but to say that the next plague may be brewing inside a pig in a Chinese farm or outside our homes in the bodies of ticks, and we would not know it. The US Center for Disease Control and Prevention (CDC) has published two Antibiotic Resistance Threat reports on the subject, in 2013 and 2019. In the 2013 edition, it was reported that 2 million people in the United States will acquire an antibiotic resistant infection, and that 23,000 will die as a direct result of that infection (5). While by 2019 this was realized to be an underestimation of the drug-resistant cases, new approaches had determined that the true value had lowered from 2013 to 2019, with an updated estimate of 2.8 million cases and 35,000 fatalities in 2019 (6). An excellent illustration of the problem can be found on page 28 of the 2013 report, which reports the introduction date (left) and the date at which resistance was observed on the right for crucial antibiotic groups. Commonly, within a decade of the introduction of an antibiotic, resistance emerges. This problem cannot be expected to go away on its own, and more than likely pathogens commonly thought vanquished will re-emerge with drug-resistant characteristics. There are human processes that contribute to the emergence of disease and spread of antibiotic resistance. In China, Wet Markets bring together livestock from all over the country, creating an environment that is diverse in the microbial life that live commensally and parasitically in and on these animals. The proximity of these animals allows for the exchange of these microbes; these microbes are then capable of exchanging genetic material. As I described for Flu and Coronaviruses, viruses that come into contact within cells are capable of genetic recombination, a process that can result in viruses that are capable of infecting humans. This is not to say this is a common phenomenon, just that 1) the process is accelerated by live animal markets and 2) this practice and resulting genetic recombination of zoonotic viruses is thought to have contributed to both the original and novel SARS-CoV outbreaks. In the United States, a textbook example of an emerging disease is Lyme Disease (7). Named for the town of Lyme, Connecticut, Lyme Disease is caused by the peculiar bacterium known as Borellia burgdorferi. Borellia is a corkscrew-shaped bacteria that is interesting for its ability to grow without iron (a key component of the immune response is the sequestration of iron away from pathogens). Lyme Disease is spread through ticks, and the number of infectious cases is exacerbated by reforestation and settlement close to wooded areas in suburban environments. As building projects move closer to forested areas, exposure to arthropod-borne illnesses will be expected to rise. Beyond settlement and the wet market practice, the emergence of new infectious disease is complicated by global warming and healthcare practices. Global warming is hypothesized to drive heat resistance in fungi, potentially improving their capacity to grow within the human body (8). The pathogenic potential of fungi is hypothesized to be limited by the heat of the human body, and there is some speculation that global warming is a contributing factor to the emergence of the notorious fungal pathogen Candida auris (8). These claims should be taken with a grain of salt and evaluated critically, but it is possible that human-caused climate change will disturb the ecology of our planet with as of yet unforeseen consequences, among them the generation novel and resurgent diseases. In healthcare, over-prescription of and a lack of regulation on antibiotics has caused the problem to worsen (5,6). When a patient receives an antibiotic, the drug has an effect on all microbes where the drug is bioavailable. This includes the intestines, which contain a resident population of microbes, and the skin, which contains Staphylococci resident species that prevent colonization by pathogenic strains of similar bacteria. These residents are then selected for their ability to resist the drug, causing an increase in resistance among the healthy microbiota. These resistance genes, as I have described, can then move between dissimilar bacteria in the same environment. If a harmful strain of E. coli is introduced into such an environment, for example, it has a higher likelihood of encountering and assimilating the genetic potential to resist antibiotics than in an environment that is naïve to the antibiotic. Patients are commonly prescribed antibiotics for infections that are more likely to be caused by a virus, or in instances where an infection is likely to run course without medical intervention. The increased exposure to antibiotics causes the microbiota to increase the concentration of resistance genes. Additionally, in places like India, the regulations on antibiotics are much more laxed than even the United States, where one is able to purchase over-the-counter antibiotics. This allows anyone to give themselves an incomplete course of antibiotics for any condition, even if the symptoms are not caused by an infection of any kind. Additionally, prescription antibiotics that have deteriorated with time, or are manufactured with subpar quality control resulting in lower concentrations, that remain in circulation exacerbate the problem by establishing sub-inhibitory concentrations of the antibiotic in the body and resulting in selection for resistance. Furthermore, environmental pollution of antibiotics into natural water sources and sewage results in increased environmental concentrations of resistance genes. These genes can spill into humans by exposure to microbes in these environments (9). Agriculture provides another increase in the concentration of resistance genes (10). Livestock are fed antibiotics, which increase the weight of animals in an as-of-yet not understood mechanism. A deleterious consequence of this increase in yield with antibiotic usage is the increase in resistance in response to this widespread antibiotic usage. These resistance genes then find their way into humans, whether through ingestion of food contaminated with resistant microbes. Science and technology can solve the problem, but face institutional and biological challenges There are both institutional and scientific challenges to combating emerging disease and antibiotic resistance. Some of these problems are easily apparent as I have described above: countries with laxed restrictions on who can obtain antibiotics, countries where the drugs are used often over-prescribed, suburbanization, and global warming all contribute to the problem. Scientifically, there are challenges in that novel diseases are difficult to combat. The novel Coronavirus had the precedent of other coronaviruses (i.e. SARS and MERS) that had been studied and their virology dissected, but that won’t necessarily be the case everytime a novel pathogen infects a human. A technological benefit to this problem is the use of meta-genomics, which allows for DNA/RNA sequencing without prior knowledge of the nucleic acid sequence of the genome. Within weeks of the first identification of the virus, its sequence was available to researchers. This was not the case during the outbreak of SARS-CoV1, when meta-genomics approaches such as Illumina Sequencing, NanoPore Sequencing, and Pacific Biosciences Sequencing were not available. In the event of a novel disease emergence, this information would be vital to combating the pathogen. Despite not knowing necessarily what the next threat will be, expanding the human knowledge base on microbes is an essential component of any plan to fight emerging diseases. Any emerging disease is likely to be similar to other microbes that we have encountered, and knowledge of the physiology of these organisms helps to understand weaknesses, transmission, and potential therapeutic targets. The study of all microorganisms therefore benefits the effort to combat the next pandemic, as any one piece of information could be critical. Surveillance is perhaps the most important tool to fight emerging infectious disease; knowing the problem exists is a crucial step to curbing spread. A recent example of successful surveillance can be seen in a recent PNAS publication regarding the presence of potential pandemic influenza in hogs, and the presence of antibodies against this particular class of flu viruses in swine workers (11). While at present it does not appear that the virus has acquired the ability to cause a pandemic, this knowledge allows for immunologists to potentially include viral antigens specific to this particular viral class in seasonal vaccines. Surveillance is critical in controlling both emerging diseases and antibiotic resistance: knowledge of what potential pathogens emerge where, and what microbes are exhibiting resistance to what drugs, can drive containment and treatment efforts. To combat antibiotic resistance, new drugs must be developed, but there are hurdles in identification, validation, and production of new antibiotics. First, potential new antibiotics have to be either identified or designed. This often involves looking through filtered environmental samples to determine the presence of small molecules that inhibit bacterial growth, or chemically altering known drugs to circumvent drug resistance. This is not necessarily difficult, as there are microbes in the soil and water that produce potential therapeutics, but this does require both time and money, as well as the consideration that it is likely that resistance to that novel therapeutic exists in the environment from which it was pulled. New drugs must be safe, but due to the abundance of antibiotics presently in use and their historic efficacy, the standard for antibiotics to pass safety regulations is extremely high. As drug resistance becomes more common, it will become apparent that more and more side effects may have to be tolerated to prevent death due to bacterial infection. Finally, and the most important challenge to developing antibiotics is that the profit margin on antibiotics is low for drug companies in the present market, disincentivizing research and production of novel drugs. In addition to stand-alone antibiotics, new inhibitors of resistance must be developed as well. Clavulanic acid is one such inhibitor, and is administered with the beta-lactam drug amoxicillin to improve its ability to kill bacteria. Bacteria that are resistant beta-lactams often encode enzymes called beta-lactamases. Beta-lactamases break open the active portion of the beta-lactam molecule, rendering it ineffective in attacking its target. Clavulanic acid is a beta-lactam itself, and is a target for the beta-lactamase enzyme; however, when the enzyme begins to degrade clavulanic acid, the enzyme becomes stuck at an intermediate step in the reaction, rendering the beta-lactamase enzyme useless. These drugs must also be explored and screened for in environmental samples, as well as developed. It is possible to take a rational approach to drug design, with increasing knowledge of how resistance mechanisms work. This means that scientists specifically look at, say, a beta-lactamase enzyme at the molecular level, and design a small molecule that will fit into the enzyme and block its function. Chemists then design the molecule to test its efficacy. Ultimately, scientists either know how to solve the problem, or know how to get the tools they need to solve the problem. It is the institutional challenges that make the problem more difficult to solve. How legislation can improve the ability of scientists to combat emerging disease and drug resistance In discussing emerging diseases and antibiotic resistance, I try to draw parallels to the problem of global warming: a global problem with global solutions. I don’t have a novel solution to climate change to discuss here, other than to parrot this subreddit’s typical ideas, so I will omit that discussion here. That is to say, global warming is a driver for emerging infectious disease, and fighting global warming is important to combat the potential rise of fungal pathogens. I will, however, discuss some ideas for combating emerging disease and drug resistance. These ideas are mostly derived from scientists familiar with the problem, Funding for research, basic and applied, is crucial. No bit of knowledge hurts in the fight against human disease. Learning how Alphaviruses replicate, determining the structure of E. coli outer membrane proteins, and examining the life cycle of the non-pathogen Caulobacter crescentus all contribute to the fight against the next disease. The more we know, the more powerful our vision is in understanding the inner machinations of disease. Every immune response, every molecular mechanism, and every aspect of microbial physiology is potentially a drug or vaccine target, a clue into pathogenesis, or an indication of how a bug is likely to spread. The Trump administration has not been kind to science funding (12). Science that does not appear to have benefit at first glance often does in the long run, and for this reason I will stress the importance of funding research of this sort, as well as funding applied research. Knowing is half the battle. In combating emerging diseases, it is important to know they exist. As I have mentioned the example of recent viral surveillance with regard to the novel reassortment influenza viruses, I would like to stress the importance of funding surveillance programs in fighting emerging disease and drug resistance. There are currently US governmental surveillance programs that provide valuable information about the spread of drug resistance, such as NARMS in the United States (13). In the United States, there is a need for greater accountability in using antibiotics. Resistance is unlikely to completely go away, even when the use of an antibiotic is discontinued, but the levels of resistant bacteria dwindle when the selective pressure is reduced. For this reason, several medical practitioners have proposed a rotating schedule of prescription antibiotics, that includes the retention of some new antibiotics from use. The reasoning for this is that, in the years following the halted use of a particular antibiotic, it is expected that the concentration of resistant bacteria will decrease. As I discussed with the example of always wearing a welding helmet, carrying resistance genes often imparts some form of growth defect on the resistant bacteria (for example, altering an essential gene targeted by an antibiotic may render the bacteria resistant, but there is a reason such a gene is essential, in that it’s required for growth; changing the gene in a substantive way may negatively impact its performance and by extension make these resistant bacteria less fit). A rotating cycle of what antibiotics are allowed to be prescribed, informed by surveillance data, would buy time for the development of new antibiotics as well. Additionally, higher standards should be required for the prescription of antibiotics, to increase accountability of physicians; these standards could involve clinically verifying the presence of susceptible bacteria prior to administering a drug in situations where the disease in not life-threatening. There is a need to reduce the environmental pollution of drugs into sewage and natural bodies of water as well. This will require research into cost-effective methods for reducing the population of resistant bugs and drugs in these environments. In the case of natural bodies of water, a source of contamination is often factories where drugs are produced. Often, waters near these factories have high levels of antibiotics that select for resistance to develop and spread. This may require legislation to improve environmental outcomes, as well as surveillance of drug resistance gene levels and the levels of antibiotics in these waters to ensure compliance. There is also a need to halt the use of antibiotics in treating livestock (14). Halting the use of antibiotics typically results in reductions of antibiotic resistant bug populations within a year or two (10). I don’t know of studies that estimate the economic cost of halting use of antibiotics in American meat, but in the case of Denmark, livestock production does not appear to have been significantly impacted. I think that the most challenging problem will be for drug companies to develop new antibiotics when there is not presently a financial incentive to do so. Because antibiotics are still largely effective, and the financial benefit to adding an antibiotic to the market does not outweigh the cost to put a drug to market, there is not currently a large incentive to produce new drugs (15). To address this negative externality, it is necessary to generate financial incentives of some form for the production of new antibiotics. This may take the form of subsidizing antibiotic discovery efforts and drug safety trials; additionally, applied research with the goal of specifically finding new antibiotics should see increased funding. To combat the problem overseas, it is obvious that obtaining an antibiotic course must occur through a doctor. This eliminates false self-diagnoses of bacterial infections. The problem of wet markets may be partially resolved by preventing animals that do not regularly contact each other from being traded and stored in the same vicinity as animals that are not typically encountered. This may involve limiting a particular wet market to the trade of animals that come from a particular geographic area, preventing geographically diverse microbes from encountering each other. It's on all of us to stop the next pandemic: If you made it this far, thank you reading this post and I hope that I have convinced you of the importance of this issue! There are simple steps that we can all take as consumers to reduce antimicrobial resistance: don’t take antibiotics unless prescribed by a doctor and buy meat that was produced without antibiotics. I welcome any and all criticism, and would love to hear people's ideas! Please let me know of any errors as well, or any missed concepts that I glossed over. I've been excited to give my two cents to this sub, and I don't want to mislead in any way. Sources: 1: Andersen, KG, et al. 2020. The Proximal Origin of Sars-CoV-2. Nature Medicine 26: 450-452. 2: Su, Shou, et al. 2016. Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses. Cell Trends in Microbiology 24(6): 490-502. https://doi.org/10.1016/j.tim.2016.03.003 3: Munita, JM; Arias, CA. 2016. Mechanisms of Antibiotic Resistance. Microbiology Spectrum VMBF-0016-2015. doi:10.1128 /microbiolspec.VMBF-0016-2015. 4: Shah, NS; et al. 2007. Worldwide Emergence of Extensively Drug-resistant Tuberculosis. Emerging Infectious Diseases 13(3): 380-387. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725916/ 5: CDC Antibiotic Threats Report, 2013. https://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf 6: CDC Antibiotic Threats Report, 2019. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf 7: Barbour, AG; Fish, D. 1993. The Biological and Social Phenomenon of Lyme Disease. Science 260(5114):1610-1616. https://pubmed.ncbi.nlm.nih.gov/8503006/ 8: Casadevall, A; Kontoyiannis, DP; Robert, V. 2019. On the Emergence of Candida auris: Climate Change, Azoles, Swamps, and Birds. mBio 10.1128/mBio.01397-19. https://mbio.asm.org/content/10/4/e01397-19 9: Kraemer, SA; Ramachandran, A; Perron, GG. 2019. Antibiotic Pollution in the Environment: From Microbial Ecology to Public Policy. Microorgansims 7(6): 180. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616856/ 10: Levy, S. 2014. Reduced Antibiotic Use in Livestock: How Denmark Tackled Resistance. Environmental Health Perspectives 122(6): A160-A165. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050507/ 11: Sun, H, et al. 2020. Prevalent Eurasian avian-like H1N1 swine influenza virus with 2009 pandemic viral genes facilitating human infection. Proceedings of the National Academy of Sciencehttps://doi.org/10.1073/pnas.1921186117. 12: Kaiser, J. 2020. National Institutes of Health would see 7% cut in 2021 under White House plan. Science Magazine. https://www.sciencemag.org/news/2020/02/national-institutes-health-would-see-7-cut-2021-under-white-house-plan 13: About NARMS: National Antimicrobial Resistance Monitoring System for Enteric Bacteria. https://www.cdc.gov/narms/about/index.html 14: Khachatourians, GG. 1998. Agricultural use of antibiotics and the evolution and transfer of antibiotic-resistant bacteria. CMAJ 159(9):1129-1136 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1229782/ 15: Jacobs, Andrew. 2019. Crisis Looms in Antibiotics as Drug Makers Go Bankrupt. The New York Times. https://nyti.ms/366f7it
Inquiries about usted get posted here so frequently that I felt compelled to make a little write-up summarizing a few important points. NOTE: The following likely applies to much of the Spanish speaking world, where I live, but the disclaimer is that I don’t have much experience elsewhere, although my longtime girlfriend’s family is Chilean and what you’re about to read is likely applicable there, too. DO I NEED TO USE IT? IF SO, WHEN? This seems to be at the forefront of every usted-related doubt. Forget about manners for a moment, about how you may come off should you whimsically choose to use it or not use it. Non-native speakers seems to have gotten it into their minds that there are some situations in which failing to deploy the usted form appropriately may result in some catastrophic social breakdown, and that being able to aptly identify said situations before they happen is therefore an imperative. Strictly speaking, in modern-day Spain, there is only one situation that I believe truly qualifies for the above-mentioned “USTED ALERT!” designation, which I must emphasize is otherwise a misconception. When you think about it, the very idea that something which by nature is so fluid and improvised as a social interaction can have hard and fast rules is hardly a scientific one (or at least we can say that it’s more of, well, a social science). In any case, the situation I’m referring to involves the elderly. If you’ll be so kind, a mundane personal anecdote: I was surprised when, years ago, I attended a holiday gathering with a former girlfriend, who we’ll call Marta, who was seated to my left and whose great-grandmother was seated to hers, at the head of the table. Marta turned to her ancestor and began to make conversation in the usted form. I thought it curious. Is this not a family member that has known you since birth, I thought? So I asked her about it, in English, right then and there. “Ah, bueno. Sí, es que es mayor,” was the reply I got. Not much more to it, then? As the luncheon went on, I saw that the elder guest of honor was frail, hard of hearing, and perhaps not entirely aware of her surroundings. Drifting in and out of clarity, let’s say, as people that age often are. With her grandparents, Marta would have never used usted, because there was still that social intimacy, still a high level of emotional interpersonal engagement that would have rendered its use comical. Marta’s great-grandmother, on the other hand, having unfortunately retreated into senility, was being addressed in a way meant to prioritize her dignity above all else. If interacting with an elder family member can feel less intimate because they are old, should elders who are complete or even partial strangers to you be addressed in the usted form, at least initially? Logically, yes. It is prudent to do so. But here’s the kicker: here in Spain, a youthful, mentally sound elder will invariably drop a “Trátame de tú, eh?” after a few minutes of conversation. Moreover, you should NOT be afraid to ask permission retroactively if you find that you have committed a pronominal or conjugational blunder! A simple “¿No te importa que te tutee, verdad?” will always be met with an enthusiastic “No hombre, claro que no.” This doesn’t mean that every Spaniard who is on the older side dreads being addressed politely. It means that they won’t sour if you forget to, or choose not to. A point of clarification: if the person is elderly and you find yourselves engaging with them in a professional context, the invitation to switch to the second person may never come. Which brings me to my next point. THE PERSON IS NOT OLD BUT I DON’T KNOW THEM. TO USTED OR NOT TO USTED? Now that we’ve established that the only situation in which you should invariably use usted is when speaking to elders who are unmistakably old enough (and, though it may seem crass to say so, mentally distant enough) to warrant it, what of the slightly younger population? Of course by “younger” I’m referring to people who are still older than you, but perhaps not, in the immortal words of the bouncer in “Knocked Up”, old “for the Earth.” The answer, in my view, is that in informal social situations, you should not use it with young people at all. The world will not come to a screeching halt due to your awkwardness if you do. Rather, you should be aware that the other person will not. It is in formal, often professional contexts where the waters become a bit murkier, and where we find ourselves having to make an individual determination not only about how old the person is but how formal the situation is. A couple of nondescript examples are in order. Let’s take a phone call with the water utility company. First of all, you should know that the call center rep will ALWAYS address YOU as usted, no matter what, even though as a “cliente fichado” they can see your date of birth on their computer screens. Because of this, it is perfectly fine for you to address them with the usted form as well. However, the traditional view is that people rendering a service owe their customers more respect and patience than they should expect to receive. There is therefore no issue if you decide to use the tú form on the phone with someone whom you do not know but whose job it is to serve you. Now let’s say you walk into a Spanish bank to apply for a loan. The woman assisting you looks to be 55-60 years old. She is dressed in formal attire as is customary for bank personnel. Like the telephone rep, the bank rep will almost invariably address you as usted, but this time it definitely depends on HOW young you look. (I am 32 and my hair is thinning, so ¯_(ツ)_/¯ these days you can basically toss a die.) Want a hard and fast rule? OK, yes, you can use usted with this bank rep the whole time without fear of offending her or sounding awkward. It is a professional environment. This takes precedence over the fact that she may indeed feel that she is still relatively young, and moreover 99% of her customers both young and old address her as usted on a daily basis because she’s at work. But for those of you who are looking for an excuse to never use usted at all, in this situation I must say it is optional. Is the bank rep, on the other hand, young? Like, really young? As young as the average Redditor reading this? Are you both basically fresh out of uni and, looking deep into Jordi’s eyes, you realize that not 12 hours prior, he was likely regarding himself in the mirror as he unbuttoned the penultimate button on his freshly pressed Ralph Lauren shirt a la Tony Montana, mentally prepping himself for a memorable, gintonic-fueled, flirtation-laden summer night? Is that Marlboro Reds on his breath? Jordi will address you in the second person and you should return the favor. TL;DR: If you’re in Spain and someone is really old, use usted. If they’re kind of old but possibly still employed and clearly in pristine mental condition AND YOU DO NOT KNOW THEM WELL OR AT ALL, use it unless/until you are asked not to. If you’re on the phone with a company, maybe use it because who knows how old they are? but as a customer you’re not really obligated to and should not feel pressured to. If you’re in a store or office as a customer, use it unless both of you are really visibly young.
Introduction This is my first conlang, so I'm definitely open for any constructive criticism you may have. This language is very heavily based on Latvian, a Baltic language, to the point where I'm not sure if it's a true conlang or a cypher—there are a few differences, but they're fairly minor. My major goal with this language was to create a functioning language for the major setting of my high fantasy story and to give proper etymologies and meanings for the names I've been coming up with. Because I'm new to this business, I leant very heavily on the language it's based off for knowing what to do. Ārevsarāšu kūrunali is the language of Ārevsarāšu Veli, the Land of the Strivers, the northernmost country in the continent of Tāresķaraūrā Veli, which is populated solely by elves and dwarves. The language is very rigid, with an almost anal-retentive emphasis on correct pronunciation, especially of vowels, and spelling. This reflects the culture of its native speakers, who are infamously perfectionistic to the point where it's the defining feature of their way of life. I believe it's a synthetic language, but I'm not entirely familiar with the concept and can't be sure. It is also somewhat tonal, with vowels being assigned tones that can change the meaning of a word, but again, as this is a concept I'm not familiar with, I may end up dropping it. Alphabet Ārevsarāšu kūrunali has its own alphabet, but for the purposes of Romanisation, I use the Latvian alphabet, like so (a few letters, notably F, H, O, and Ž, are missing): A Ā B C Č D E Ē G Ģ I Ī J K Ķ L Ļ M N Ņ P R S Š T U Ū V Z a ā b c č d e ē g ģ i ī j k ķ l ļ m n ņ p r s š t u ū v z The most common combinations in the alphabet, such as the nominative endings for the six declensions, get their own letters. Special diacritics include an equivalent to the macron, cedilla, and caron, as well as an inversion of the diaeresis—that is, a character that is used to mark a diphthong, rather than a vowel pronounced separately. This is because hiatus is the norm in Ārevsarāšu kūrunali, to the point where diphthongs are non-existent except in certain border dialects. Phonology Consonants
Labial
Dental/Alveolar
Palatal/Post-alveolar
Velar
Nasal
m
n
ɲ
ŋ
Stop
p b
t d
c ɟ
k g
Affricate
t͡s d͡z
t͡ʃ
Fricative
v
s z
ʃ
Central approximant
j
Lateral approximant
l
ʎ
Trill
r
Certain notes are as follows (all ripped straight from Latvian, most particularly its Wikipedia page, though some of the fourth point is from my imagination):
[ŋ] only appears as an allophone of nasal consonants prior to /k/ and /g/.
Plosives are not aspirated.
/n t d t͡s d͡z s z/ are denti-alveolar, while /l are alveolar.
Vocal assimilation is uncommon among the educated and the nobility due to the rigid, highly particular standard of pronunciation common across Ārevsarāšu Veli. It is more present in 'common' speech and border dialects, however; in this case, voiced and voiceless consonants assimilate to the next consonant, e.g. /p/ → /b/ next to /g/. Single voiced consonants are not devoiced word-finally in educated speech but can be in common speech.
Doubled consonants and plosives and fricatives between short vowels are pronounced longer, with the exception of /l/, which is substituted for /ʎ/. zs is pronounced as /sː/, and šs as /ʃː/. When /t/ and /s/ are put together, they are replaced with /c/ (which is pronounced like 'ds' in 'lids').
The proto-language contained a palatalised dental trill, /rʲ/, but this has long since fallen out of usage and is no longer part of the alphabet.
Vowels
Front
Central
Back
Short
Long
Short
Long
Short
Long
Close
i
iː
u
uː
Mid
e
eː
Open
æ
æː
a
aː
As mentioned, the language utterly lacks diphthongs, except in the more rapid common speech and border dialects influenced by neighbouring languages, and even these are uncommon and not held to be an official part of the language. Diaeresis is the norm. However, the same vowel does not occur twice in a row except in diminutives (e.g. 'Iriis' from Irialis).
Vowel length is phonemic—a slight change in length can change the whole meaning of a word.
Pitch accent, syllables, and stress
The language has fixed initial and fixed penultimate stress, though stress tends to be more variable in border dialects, especially on the border with Erūndsarāšu Veli, a neighbouring rival nation. One of the major dialects has fixed stress on the second syllable, which is so at odds with the standard version of the language that it easily identifies people from the dialect's region.
Regardless of their position in a word, long vowels take a tone in the standard language. The three tones are level (high throughout the syllable), falling (brief rise followed by a long fall), and broken (rising tone followed by falling, with a brief interruption). In other dialects, the tones have merged in various ways. Again, this isn't a concept I totally understand, so I might end up dropping it from the language.
Syllables can follow a pattern of (C)(C)(V)(C), with a max of two consonants before a vowel. It is, however, common to see words with a regular alternation of vowels and consonants, e.g. the names Aleris and Vanalani. Some words, such as gesm ('to live', infinitive), have two consonants to a syllable, but these are rare. Two vowels can regularly be found next to each other. (Note: I don't know if that's how you write syllable patterns, but I hope I've made it clear.)
Other Phonology
I haven't worked it all out yet, as I'm not familiar with this area. As mentioned above /t/ and /s/ become /c/ when a word starting in /s/ is attached to a word ending in /t/. The / is also dropped next to /aː/ when it's in the same syllable (this was mostly a stylistic thing to keep my words from being one letter away from 'arse'). /l/ becomes /ʎ/ in situations where it would be doubled.
The language does have some palatalisation and iotation, but it's not as prominent as in Latvian—again, I'm not familiar with the topic. Rigid standards of language ensure that there isn't as much change in the 'standard' speech as there is in other languages, and careful enunciation is the mark of a noble, scholar, or priest (the common tongue and border dialects more flexible).
Grammar Word order Word order is relatively free, but is most commonly SVO. Due to the complexity of adjectives and their use in determining definiteness and indefiniteness, they always come before the noun. Nouns, Cases, and Declensions Ārevsarāšu kūrunali has two genders, masculine and feminine, six declensions, and seven noun cases: nominative, genitive, dative, accusative, locative, instrumental, vocative. (The instrumental case is no longer really a 'thing' in Latvian, but I chose to make it a thing here due to the Ārevsarāšu's culture. Most notably, the actions of slaves are always described in the instrumental case, e.g. "I got my slave to do this," not, "My slave did this.") The first three declensions are masculine, the next three are feminine. Their endings are, respectively: -is, -ūs, -es, -i, -ā, and -e. https://preview.redd.it/skohr2o37su41.png?width=1557&format=png&auto=webp&s=0860bdf6e80863f973d26d3bb57e025150a1938b Pronouns Pronouns are a fairly different business due to being derived from archaic words no longer present in the language. Nominative pronouns have an informal and formal variant; the former is used with family and close friends, the latter with social superiors, strangers, and acquaintances. Formal pronouns are also used in songs and stories. 1st, 2nd, and reflexive pronouns have no gender distinction and irregular declensions. https://preview.redd.it/85oofqb67su41.png?width=1516&format=png&auto=webp&s=d5e6217cbb32ee1ee492e20eb179561343a29d26 Possessive pronouns take the same endings as the first and fourth declensions, depending on gender. Other pronouns, such as cins/cini (such), take regular indefinite adjectival declensions. (This, that, who, and the intensifier have their own forms as well, but I'm trying to save space here.) Adjectives Adjectives are important, as the language lacks articles by which to express definiteness or indefiniteness. This is instead marked on the adjectives. Adjectives agree with the nouns in case, number, and gender. Indefinite adjectives are declined like the 1st and 4th declensions and are not used in the vocative case, while definite adjectives are constructed from the same archaic pronouns that form the modern 1st and 2nd person pronouns, modified to take the endings of the 3rd and 5th declensions. (The latter can be seen in the table below.) The stem of an adjective is quite simple, often no more than two or three syllables, e.g. teres/tere, meaning 'high', and kērans/kērane, meaning 'free'. When the comparative is to be used, the suffix ķara, similar to English '-er', is added. This is followed by the indefinite or definite declension. If the superlative is to be used, then the prefix em is attached. A full adjective can be quite lengthy, for example: emtereķaraūrāni, meaning 'the highest'.
Masc.
Fem.
Singular
Plural
Singular
Plural
Nom.
-ūres
-ūlren
-ūrā
-ūrāni
Gen.
-sel
-rer
-sāša
-rāšu
Dat.
-cem
-came
-cāmai
-cāmei
Accus.
-keč
-keča
-kāču
-kāčun
Loc.
-nev
-elvu
-nāva
-nāvus
Instr.
-let
-dzec
-lāte
-dzācel
Voc.
-tued
-ķused/-kused
-tuādi
-ķādre/kādre
Verbs Ārevsarāšu kūrunali has three tenses: past, present, and future; three compound perfect constructions: present perfect, past perfect, and future perfect; six moods: indicative, imperative, conditional, debitive, conjunctive, and quotative; and two voices: active and passive. The passive voice is formed from a combination of the auxiliary verb gēbe with the past passive participle. There are three conjugation classes. In the first, the thematic vowel is absent in the present, past, and infinitive forms of the verb. In the second, the thematic vowel is retained throughout. This is divided into two subgroups: one for words with ē and e as thematic vowel, one for all other vowels. In the third, the thematic vowel is retained in the present and past. An example conjugation table is presented below, albeit for the verb gesm, 'to be', which is irregularly conjugated. This was heavily based off a conjugation table on Wikipedia—I wasn't kidding when I said I wasn't sure if this is truly a conlang or just a cypher, so any advice would be appreciated! https://preview.redd.it/pj7grt330su41.png?width=1459&format=png&auto=webp&s=af0f696749f16b08293f228820322248d443483d Suffixes
-atūs: forms nouns meaning 'the practice or craft of', e.g. dičalatūs, 'slavery'.
-ces: forms abstract nouns, e.g. erielces, 'hope'.
-ēdes/-ēde: equivalent to '-y', added to nouns or adjectives to form adjectives meaning 'having' or 'characterised by' the original noun, e.g. emlirenēdesķaraūres, 'the stormiest', from lirenēdes.
-sāris/-sārā: forms agent nouns, e.g. ārevsāris, 'striver', and occupations. (The macron is shifted to the penultimate syllable in this case, so is not always on this particular 'a'.)
-silā: forms nouns corresponding to activity of original word, e.g. gēsilā, 'living'. Equivalent to '-ing' or '-tion'.
Other
Negation is expressed via mā, which is appended as a prefix (e.g. mādais, 'nothing', mātenūres, 'the profane', literally 'the impure') and also is the word for no. Conversely, the word for yes is zi.
Particles are under construction, but include aē (equivalent to 'oh', e.g. 'Aē ransārin!' means, 'Oh, gods!' and ece, meaning 'also, as well as, too'.
Names are fairly rigid; masculine names all end in -is and feminine names all end in -i; surnames are the same and change depending on the bearer's gender. Foreign names are assimilated to this system and rewritten to conform to the alphabet, so the dwarven names Esren and Kasara become Esrenis and Kasarai. Men receive patronymics, women matronymics. Slaves do not take surnames, but instead the name of their master. For example, Aleris Kālreil junis Kāvranil dičalūs would be in English Aleris, son of Kālreis, slave of Kāvranis.
Place names are determined based on geographic features for cities (e.g. Lirenešu Cēane, the City of Storms, is named for its near-constant storms) or defining qualities of the culture for nations (the Ārevsarāšu call their land Ārevsarāšu Veli, the Land of the Strivers, to themselves, Emtereķararāšu Ķelišu Veli, the Land of the Highest Ones, to everyone else; the rival nation Erūndsarāšu Veli is the Land of the Competitors—or Zelvenrešu Veli, the Land of the Corrupt).
Due to the tonal nature of the vowels, correct pronunciation is extremely important, and pronouncing a vowel too short or long is a fine way to be identified as an outsider and a good source of much humour.
Ārevsarāšu poetry is based around rhythm, assonance, and alliteration rather than rhyme.
Sample Sentence I haven't made many verbs in my language yet, so I can't offer a very complicated sentence. I hope this will suffice. I've also never tried to gloss anything before, so please let me know how I did! "Ķūrač ķūve Īlarānil Jārisanēsāris, neam ķūrač ķūve kēranis." "I am the Restrainer of Magic, and I am free." I-NOM.SG 1SG-am-PRES Magic-GEN Restrain-AG.NOM, and I-NOM.SG 1SG-am-PRES free-ADJ. Conclusion My God, that got long. As I said, I'd be more than happy to hear people's constructive criticism and to answer any questions you may have! I really want to make this a solid conlang, and I'm quite enjoying making it, so hit me with all your advice, please. And if you can suggest ways for me to take it a bit further from its roots in Latvian, I'd love to hear it. Thanks a lot!
I've seen a lot of questions about this on here and a lot of okay-to-wrong information (although there's been a fair amount of right stuff, which is good). Annulments are a topic that is poorly understood by the vast majority of Catholics, because this is quite frankly the only interaction with Canon Law most of them have. So I figured I'd put something together as a sort of reference for the sub. A very, very important note: If you have been baptized Catholic, made a profession of the Catholic faith, or otherwise received into the Catholic Church, you are a Catholic bound by Canon Law, regardless of your practice. If you belong to one of the other sui iuris churches (Eastern rites), you have your own Code of Canons to follow, but you're still bound by those. 1: What is a marriage? According to the Code of Canon Law, Marriage is a union of the whole of life, ordered to the good of the spouses and the procreation and education of offspring (Canon 1055). Every single case starts with this definition. Marriage also "possesses the favor of the law" (Canon 1060), which means that we always assume a (first) marriage is valid, until it is proven otherwise. It's like innocent until proven guilty, but for marriage. So that's the definition of marriage and its relation to the law. But there's one other piece that's critical:
The consent of the parties, legitimately manifested between persons qualified by law makes marriage; no human power is able to supply this consent. Matrimonial consent is an act of the will by which a man and a woman mutually give and accept each other through an irrevocable covenant in order to establish marriage. (Canon 1057)
Marriage happens at consent. Also, Canon 1062 specifically states that a promise to marry does not supply sufficient consent for the marriage. (Just because I know that will be a question) There's an urban legend out there that a marriage that is not consummated is not valid. This is false. It is a valid marriage, but the marriage can be dissolved (Canon 1142). But consummation is to be assumed if the parties live together after the wedding, so this is a very, very rare thing. Point is: At the exchange of consent, we have a marriage. Any investigation into the validity of this exchange of consent is trying to find out what happened at this point in time, not at the time of divorce. 2: How is marriage done? This part is pretty simple. Where Canon 1057 says "legitimately manifested", we have an explanation later on. Catholics are bound by "Canonical form" (Canon 1108), which just means in front of an authorized minister of the Church (clergy) and two witnesses, and with the correct words. Ordinarily, if a Catholic attempts marriage without following canonical form, it is invalid. It is possible to be dispensed from canonical form, which means that you are no longer bound to follow it and may instead follow a different form. If you did not receive a dispensation, this is incredibly easy to do. This is called a "documentary process annulment" and, provided you have records, takes about 15 minutes. In some dioceses, this is allowed at the parish level. 3: Impediments Okay. So we have what marriage is, and we have how it is supposed to be done. There are a couple of different types of impediments. First, we have: Impediments (generally) and diriment impediments. Impediments generally just mean that there is something unlawful or illicit about the marriage. It does not necessarily weigh into the validity, it just means you did it not quite right. A diriment impediment means that the attempt to marry is invalid. (Canon 1073) These are the only ones that we care about when we're talking about annulments. In diriment impediments, we again have two types: Those in natural law and those in ecclesiastical law. Natural law binds all attempts to marry, regardless of baptismal status. Ecclesiastical law only binds Catholics and those attempting to marry Catholics, and these can be dispensed of. Canonical form is an example of an impediment found in ecclesiastical, not natural, law. Any investigation of grounds for nullity is based upon an investigation into whether an impediment existed at the time of marriage. We'll dig a little bit more into those later. 4: Dispensations Dispensations are relaxations of the law to permit valid and licit marriages when there is cause to do so. Some examples include a marriage between a baptized and an unbaptized person, getting married outside a sacred space, or getting married outside canonical form. The Pope alone is allowed to give dispensations for those who have taken vows associated with Holy Orders or religious institutes or for those who have brought about the death of a previous spouse. But nobody is allowed to give a dispensation for people too closely related. (Canon 1078) 5: Specific Impediments This is just going to be a list of specific impediments, with a note about whether it's generally considered ecclesiastical or natural law. Remember, ecclesiastical law can be dispensed with, if/when the bishop feels it is appropriate.
Lack of Age (Canon 1083) - A man must be 16 and a woman must be 14. Conferences of bishops are free to establish higher ages. (Both, the numbers are ecclesiastical though)
Impotence (Canon 1084) - This means an inability to have intercourse, not infertility. If there is a doubt about the impotence, it's not to be enforced as an impediment. (Natural)
Prior Bonds (Canon 1085) - If you are already married, you cannot remarry. Even if it's invalid, you are still bound until the nullity of the prior bond is legitimately and certainly established. (Natural)
Disparity of Worship/Cult (Canon 1086) - One baptized, one unbaptized. If we thought both were baptized at the time of marriage, you now have to prove that you were not baptized. (Ecclesiastical)
Sacred Orders (Canon 1087) - Yep, celibacy. This includes remarriage for those who were married at their ordination. (Ecclesiastical)
Perpetual vows of Chastity (Canon 1088) - Same idea as above. You took a vow of perfect chastity. This does only apply to religious institutes, though. (Ecclesiastical)
Abduction (Canon 1089) - Fun fact about this impediment, it's worded specifically if the man abducts the woman. No kidnapping for marriage, unless the victim goes home and still wants to get married. Note: This does not mean eloping. (Ecclesiastical)
Crime (Canon 1090) - If you've brought about the death of your or your intended's spouse for the purpose of marrying someone else, you cannot validly marry. (Ecclesiastical, reserved to Pope)
Consanguinity (Canon 1091) - Can't marry anyone in your immediate family line (parents, grandparents, children, grandchildren) and no marriage to cousins, either. Second cousins are allowed. If there is doubt, marriage is never permitted. (Both, but dispensations are not to be granted within particular bounds).
Affinity (Canon 1092) - This is related by valid marriage. Same bounds apply. (Ecclesiastical)
Adoption (Canon 1094) - Same thing as above, except about adoption this time. (Ecclesiastical)
Public Propriety (Canon 1093) - After public life is established (cohabitating, usually), the impediments of affinity apply. (Ecclesiastical)
6: Grounds for Nullity Now we're getting to the meat of the thing. There's 3 general "categories" of grounds we investigate. Before we start diving into those, I want to note that these are deliberately somewhat vague. It is up to the judge in each and every case to determine of the case meets the requirements of these grounds of nullity. Also note that just because something isn't contained in one ground, that doesn't mean it won't be included somewhere else. 6.1: Psychological Grounds These are all contained in Canon 1095. There are 3 degrees involved. Any case involving any of these grounds typically requires the Tribunal to use a psychological expert.
Lack of Sufficient Use of Reason (Canon 1095.1) - For the most part, this gets subsumed into the next one. It's rare for someone to not have enough mere use of reason. This is where being blackout drunk at the wedding would typically fall.
Grave Lack of Discretion of Judgment (Canon 1095.2) - This canon refers to both the intellect making a mature decision and the will making a free choice. This is also referring to making the decision about this particular marriage, not just marriage in general. This is frequently manifested in personality disorders, excessive youth, or a teenage pregnancy.
Incapacity to Assume the Essential Obligations of Marriage (Canon 1095.3) - This canon only applies to incapacity of a psychic nature. There are two essential obligations of marriage - procreation (incapacity is found in impotence) and the good of the spouse. Here, we're talking about a psychic incapacity to reveal oneself, to understand the spouse as a person, and to love the spouse. This is where you see things like personality disorders, anxiety, alcoholism, and some forms of Schizophrenia come into play.
These psychological grounds tend to be the ones most used by Tribunals because, quite frankly, they're the easiest ones to prove. Note that when you're given an affirmative decision on these grounds, we're not saying you're a terrible person or can't live a good life. We're saying at the time you got married, there was something in play here that somehow inhibited your ability to make a full judgment and exchange the full consent necessary for marriage. 6.2: Defects So, it turns out that in order to give proper consent to enter marriage, you need to actually know what's going on. But, for the most part, these aren't that common. Important note: Canon 126 clarifies that when we're talking about ignorance or error, it has to be concerning the substance of the act. If it's incidental (I thought he lived in this house, turns out he lives next door), it doesn't affect validity.
Ignorance (Canon 1096) - You have to know that marriage is a permanent partnership between man and woman ordered to procreation through some sexual cooperation. After puberty, we assume you've learned this.
Error of Persons (Canon 1097) - 99% of the time, we're talking about marrying the literal wrong person. Think of the story of Jacob, when he thought he was marrying Rachel but really married Leah. That would be invalid under this canon. There's a lot of debate about an error concerning the quality of a person, but 99% of the time, if you think he's rich and he's not, that doesn't make it invalid. But if you think he's a prince and that's the only reason you're marrying him, that could be a ground for nullity. Canonists debate what this would actually look like in practice. It doesn't come up much.
Imposed Error (Canon 1098) - This goes hand in hand with the above canon. You see it called Fraud a lot, but because the one marrying invalidly is the one who's being defrauded, not the liar, Imposed Error more accurately captures what the problem is. There are four parts to actually using this canon. The liar has to know that the other party would not marry them if they knew the lie was not true. This does not need to be malicious. It has to be important enough that it impacts conjugal life in a grave way. The lie has to be in place at the wedding, it can't be a lie about something happening in the future (like eventually going to law school). And finally, the other person can't know the truth at the wedding.
Error of Law (Canon 1099) - Error of the indissolubility, unity, or sacramentality does not invalidate consent, unless it determines the will. This means that as long as you intend to do whatever it is people do when they marry, you don't have to have the Church's understanding of marriage, unless your understanding of marriage includes being able to get out later. This is another one that has lots of discussion around it, especially in the West with the current status of divorce in society.
Opinion of Nullity (Canon 1100) - If a person thinks there's an impediment, that's not enough for the marriage to be invalid.
Error is a pretty rare ground for us to deal with. 6.3: Simulation If you've ever watched House, Simulation is the Lupus of nullity grounds. It's never simulation. We always assume that you are meaning what you say and do, until someone has proven otherwise. It's incredibly difficult to prove and very easy to fake. All simulation is based upon excluding some particular element of marriage at the exchange of consent, meaning you're not agreeing to a marriage. Simulation and all exclusion flow out of Canon 1101.
Total Simulation - Faking consent during the wedding while internally excluding marriage. On this one we're talking specifically about excluding marriage itself, not one of the effects of marriage. If you want to get technical, there are some who argue any of the below things is a part of total simulation. That's an open debate.
Exclusion of Children - This is actually slightly misleading. It's actually exclusion of the right to the conjugal act (Which is part of what is exchanged in marriage). Postponing children does not mean excluding children, it's a private agreement outside the exchange of vows that could be re-evaluated later. We're talking about something firm, inflexible, and non-negotiable. The conjugal right of the spouse is denied entirely in this ground.
Exclusion of Fidelity - This does not mean someone has an affair 15 years into the marriage. We're talking about someone at the wedding having a specific plan that is intense and important to a party that it affects the will. People love to bring this one to us and we almost universally drop the ground because of how hard it is to prove.
Exclusion of Perpetuity - This does not mean that just because you got divorced, you excluded perpetuity. But this is the most black and white of the simulation grounds. Either you intended to enter a perpetual union or you did not. This most commonly winds up being some sort of hypothetical, "I'll stay married until we're not happy" or something to that effect. But again, you have to prove this at the time of consent. And you're usually signing a piece of paper from the diocese saying you intend to enter a lifelong union, so you've got to go against that.
Exclusion of the Good of the Spouses - Once again, just because you got in your first fight and it got physical after 25 years of happy marriage does not mean this happened. Usually this has to do with the Canon 1095 stuff (psychological grounds). The simulation version usually comes along in cases where someone gets married for the purpose of abusing their spouse (which, terrifyingly, does happen).
Exclusion of Sacramentality - This is incredibly rare, because most cases of it wind up being Total Simulation cases. There's actually debate about whether this should even be its own ground.
Future Conditions (Canon 1102) - Any marriage with a condition concerning the future is invalid. However, because of the way the law works, this does not apply to marriages of non-Catholics, or those married before 11/27/1983. I also want to clarify: We're talking specifically about conditions that are more important than the marriage itself, such that the presence or absence of this thing would determine whether they got married.
Force and Fear (Canon 1103) - This is external, grave fear, so that the person chooses marriage in order to be free of it. This is the "shotgun wedding" canon. The source of fear must come from outside the person. Marrying because you're worried you can't support your children does not come from outside you. Marriage also has to be the only option available to you. We're looking at cases where the only escape is marriage. If you have other options and chose marriage, there may be psychological causes to investigate (lack of discretion, probably), but fear merely accelerated the marriage, it did not cause it. Finally, the fear must be grave. So being afraid that you won't be able to use this particular venue is not good enough. Reverential fear of parents is a thing, but it's not a common thing.
And that's simulation. It's never simulation. 7: Conclusion So that's it for now. At some point in the future, maybe next week, I'll work on a write-up of the process itself. But that's what we're talking about when we're talking about marriage, the grounds of nullity, and impediments.
Some dope project phoenix approved content for y'all: First 40,000 characters of the LSD wikipedia. Enjoy!
No one likes pictures anyway. Now you can only post about what a badass you are taking 50 tabs at once or other great text based content like the LSD wikipedia page(made sure to remove the music and art section): From Wikipedia, the free encyclopedia (Redirected from Lsd)Jump to navigationJump to search"LSD" redirects here. For other uses, see LSD (disambiguation).Lysergic acid diethylamide (LSD) INN: Lysergide📷2D structural formula and 3D models of LSDClinical dataPronunciation/daɪ eθəl ˈæmaɪd/, /æmɪd/, or /eɪmaɪd/[3][4][5]Other namesLSD, LSD-25, Acid, Delysid, othersAHFS/Drugs.comReferencePregnancy category - US: C (Risk not ruled out) Dependence liabilityLow[2]Addiction liabilityLow-rare[1]Routes of administrationBy mouth, under the tongue, intravenousDrug classHallucinogen (serotonergic psychedelic)ATC code - None Legal statusLegal status - AU: S9 (Prohibited) - CA: Schedule III - DE: Anlage I (Authorized scientific use only) - NZ: Class A - UK: Class A - US: Schedule I - UN: Psychotropic Schedule I Pharmacokinetic dataBioavailability71%[6]Protein bindingUnknown[7]MetabolismLiver (CYP450)[6]Metabolites2-Oxo-3-hydroxy-LSD[6]Onset of action30–40 minutes[8]Elimination half-life3.6 hours[6][9]Duration of action8–12 hours[10]ExcretionKidneys[6][9]IdentifiersIUPAC name[show]CAS Number - 50-37-3 📷 PubChem CID - 5761 IUPHABPS - 17 DrugBank - DB04829 📷 ChemSpider - 5558 📷 UNII - 8NA5SWF92O ChEBI - CHEBI:6605 📷 ChEMBL - ChEMBL263881 📷 PDB ligand - 7LD (PDBe, RCSB PDB) CompTox Dashboard (EPA) - DTXSID1023231 📷 ECHA InfoCard100.000.031 📷Chemical and physical dataFormulaC20H25N3OMolar mass323.440 g·mol−13D model (JSmol) - Interactive image Melting point80 to 85 °C (176 to 185 °F)SMILES[show]InChI[show] (verify) Lysergic acid diethylamide (LSD),[a] also known as acid, is a hallucinogenic drug.[11] Effects typically include altered thoughts, feelings, and awareness of one's surroundings.[11] Many users see or hear things that do not exist.[12] Dilated pupils, increased blood pressure, and increased body temperature are typical.[13] Effects typically begin within half an hour and can last for up to 12 hours.[13] It is used mainly as a recreational drug and for spiritual reasons.[13][14] LSD does not appear to be addictive, although tolerance may occur with use of increasing doses.[11][15] Adverse psychiatric reactions are possible, such as anxiety, paranoia, and delusions.[7] Distressing flashbacks might occur in spite of no further use, a condition called hallucinogen persisting perception disorder.[16][17] Death is very rare as a result of LSD, though it occasionally occurs in accidents.[13] The effects of LSD are believed to occur as a result of alterations in the serotonin system.[13] As little as 20 micrograms can produce an effect.[13] In pure form, LSD is clear or white in color, has no smell, and is crystalline.[11] It breaks down with exposure to ultraviolet light.[13] About 10 percent of people in the United States have used LSD at some point in their lives as of 2017, while 0.7 percent have used it in the last year.[12] It was most popular in the 1960s to 1980s.[13] LSD is typically either swallowed or held under the tongue.[11] It is most often sold on blotter paper and less commonly as tablets or in gelatin squares.[13] There is no known treatment for addiction, if it occurs.[16] LSD was first made by Albert Hofmann in 1938 from lysergic acid, a chemical from the fungus ergot.[13][16] Hofmann discovered its hallucinogenic properties in 1943.[18] In the 1950s, the Central Intelligence Agency (CIA) believed that the drug might be useful for mind control, so they tested it on people, some without their knowledge, in a program called MKUltra.[19] LSD was sold as a medication for research purposes under the trade-name Delysid in the 1950s and 1960s.[13][20] It was listed as a schedule 1 controlled substance by the United Nations in 1971.[13] It currently has no approved medical use.[13] In Europe, as of 2011, the typical cost of a dose was between €4.50 and €25.[13] Contents - 1Uses - 1.1Recreational - 1.2Spiritual - 1.3Medical - 2Effects - 2.1Physical - 2.2Psychological - 2.3Sensory - 3Adverse effects - 3.1Mental disorders - 3.2Suggestibility - 3.3Flashbacks - 3.4Cancer and pregnancy - 3.5Tolerance - 3.6Addiction - 4Overdose - 5Pharmacology - 5.1Pharmacodynamics - 5.2Pharmacokinetics - 6Chemistry - 6.1Synthesis - 6.2Dosage - 6.3Reactivity and degradation - 6.4Detection - 7History - 8Society and culture - 8.1Counterculture - 8.2Music and art - 8.3Legal status - 8.4Economics - 9Research - 9.1Psychedelic therapy - 9.2Other uses - 10Notable individuals - 11See also - 12Notes - 13References - 14Further reading - 15External links - 15.1Documentaries Uses Recreational LSD is commonly used as a recreational drug.[21] Spiritual LSD is considered an entheogen because it can catalyze intense spiritual experiences, during which users may feel they have come into contact with a greater spiritual or cosmic order. Users sometimes report out of body experiences. In 1966, Timothy Leary established the League for Spiritual Discovery with LSD as its sacrament.[22][23] Stanislav Grof has written that religious and mystical experiences observed during LSD sessions appear to be phenomenologically indistinguishable from similar descriptions in the sacred scriptures of the great religions of the world and the texts of ancient civilizations.[24] Medical See also: Lysergic acid diethylamide § Research LSD currently has no approved uses in medicine.[25][26] A meta analysis concluded that a single dose was effective at reducing alcohol consumption in alcoholism.[27] LSD has also been studied in depression, anxiety, and drug dependence, with positive preliminary results.[28] Effects 📷Some symptoms reported for LSD[29][30] Physical LSD can cause pupil dilation, reduced appetite, and wakefulness. Other physical reactions to LSD are highly variable and nonspecific, some of which may be secondary to the psychological effects of LSD. Among the reported symptoms are numbness, weakness, nausea, hypothermia or hyperthermia, elevated blood sugar, goose bumps, heart rate increase, jaw clenching, perspiration, saliva production, mucus production, hyperreflexia, and tremors. Psychological The most common immediate psychological effects of LSD are visual hallucinations and illusions (colloquially known as "trips"), which can vary depending on how much is used and how the brain responds. Trips usually start within 20–30 minutes of taking LSD by mouth (less if snorted or taken intravenously), peak three to four hours after ingestion, and last up to 12 hours. Negative experiences, referred to as "bad trips," produce intense negative emotions, such as irrational fears and anxiety, panic attacks, paranoia, rapid mood swings, hopelessness, intrusive thoughts of harming others, and suicidal ideation. It is impossible to predict when a bad trip will occur.[31][32] Good trips are stimulating and pleasurable, and typically involve feeling as if one is floating, feeling disconnected from reality, feelings of joy or euphoria (sometimes called a "rush"), decreased inhibitions, and the belief that one has extreme mental clarity or superpowers.[31] "Reliable reports of bizarre crimes of violence, homicides, suicides and self-mutilations directly associated with the use of hallucinogens are uncommon, although unsubstantiated rumors are abundant."[33] Sensory Some sensory effects may include an experience of radiant colors, objects and surfaces appearing to ripple or "breathe," colored patterns behind the closed eyelids (eidetic imagery), an altered sense of time (time seems to be stretching, repeating itself, changing speed or stopping), crawling geometric patterns overlaying walls and other objects, and morphing objects.[34] Some users, including Albert Hofmann, report a strong metallic taste for the duration of the effects.[35] LSD causes an animated sensory experience of senses, emotions, memories, time, and awareness for 6 to 14 hours, depending on dosage and tolerance. Generally beginning within 30 to 90 minutes after ingestion, the user may experience anything from subtle changes in perception to overwhelming cognitive shifts. Changes in auditory and visual perception are typical.[34][36] Visual effects include the illusion of movement of static surfaces ("walls breathing"), after image-like trails of moving objects ("tracers"), the appearance of moving colored geometric patterns (especially with closed eyes), an intensification of colors and brightness ("sparkling"), new textures on objects, blurred vision, and shape suggestibility. Some users report that the inanimate world appears to animate in an inexplicable way; for instance, objects that are static in three dimensions can seem to be moving relative to one or more additional spatial dimensions.[37] Many of the basic visual effects resemble the phosphenes seen after applying pressure to the eye and have also been studied under the name "form constants." The auditory effects of LSD may include echo-like distortions of sounds, changes in ability to discern concurrent auditory stimuli, and a general intensification of the experience of music. Higher doses often cause intense and fundamental distortions of sensory perception such as synaesthesia, the experience of additional spatial or temporal dimensions, and temporary dissociation. Adverse effects 📷Addiction experts in psychiatry, chemistry, pharmacology, forensic science, epidemiology, and the police and legal services engaged in delphic analysis regarding 20 popular recreational drugs. LSD was ranked 14th in dependence, 15th in physical harm, and 13th in social harm.[38] Of the 20 drugs ranked according to individual and societal harm by David Nutt, LSD was third to last, approximately 1/10th as harmful as alcohol. The most significant adverse effect was impairment of mental functioning while intoxicated.[39] Mental disorders LSD may trigger panic attacks or feelings of extreme anxiety, known familiarly as a "bad trip." Review studies suggest that LSD likely plays a role in precipitating the onset of acute psychosis in previously healthy individuals with an increased likelihood in individuals who have a family history of schizophrenia.[7][40] There is evidence that people with severe mental illnesses like schizophrenia have a higher likelihood of experiencing adverse effects from taking LSD.[40] Suggestibility While publicly available documents indicate that the CIA and Department of Defense have discontinued research into the use of LSD as a means of mind control,[41] research from the 1960s suggests that both mentally ill and healthy people are more suggestible while under its influence.[42][43][non-primary source needed] Flashbacks "Flashbacks" are a reported psychological phenomenon in which an individual experiences an episode of some of LSD's subjective effects after the drug has worn off, "persisting for months or years after hallucinogen use."[44] A diagnosable condition called hallucinogen persisting perception disorder has been defined to describe intermittent or chronic flashbacks that cause distress or impairment in life and work, and are caused only by prior hallucinogen use and not some other condition.[17] Cancer and pregnancy The mutagenic potential of LSD is unclear. Overall, the evidence seems to point to limited or no effect at commonly used doses.[45] Studies showed no evidence of teratogenic or mutagenic effects.[7] Tolerance Tolerance to LSD builds up with consistent use[46] and cross-tolerance has been demonstrated between LSD, mescaline[47] and psilocybin.[48] Researchers believe that tolerance returns to baseline after two weeks of being drug free.[49] Addiction The NIH comments that LSD is addictive,[16] while other sources state it is not.[15][50] A 2009 textbook states that it "rarely produce[s] compulsive use."[1] A 2006 review states it is readily abused but does not result in addiction.[15] Overdose As of 2008 there were no documented fatalities attributed directly to an LSD overdose.[7] Despite this several behavioral fatalities and suicides have occurred due to LSD.[51][52] Eight individuals who accidentally consumed very high amounts by mistaking LSD for cocaine developed comatose states, hyperthermia, vomiting, gastric bleeding, and respiratory problems—however, all survived with supportive care.[7] Reassurance in a calm, safe environment is beneficial. Agitation can be safely addressed with benzodiazepines such as lorazepam or diazepam. Neuroleptics such as haloperidol are recommended against because they may have adverse effects. LSD is rapidly absorbed, so activated charcoal and emptying of the stomach is of little benefit, unless done within 30–60 minutes of ingesting an overdose of LSD. Sedation or physical restraint is rarely required, and excessive restraint may cause complications such as hyperthermia (over-heating) or rhabdomyolysis.[53] Research suggests that massive doses are not lethal, but do typically require supportive care, which may include endotracheal intubation or respiratory support.[53] It is recommended that high blood pressure, tachycardia (rapid heart-beat), and hyperthermia, if present, are treated symptomatically, and that low blood pressure is treated initially with fluids and then with pressors if necessary. Intravenous administration of anticoagulants, vasodilators, and sympatholytics may be useful with massive doses.[53] Pharmacology Pharmacodynamics 📷Binding affinities of LSD for various receptors. The lower the dissociation constant (Ki), the more strongly LSD binds to that receptor (i.e. with higher affinity). The horizontal line represents an approximate value for human plasma concentrations of LSD, and hence, receptor affinities that are above the line are unlikely to be involved in LSD's effect. Data averaged from data from the Ki Database Most serotonergic psychedelics are not significantly dopaminergic, and LSD is therefore atypical in this regard. The agonism of the D2 receptor by LSD may contribute to its psychoactive effects in humans.[54][55] LSD binds to most serotonin receptor subtypes except for the 5-HT3 and 5-HT4 receptors. However, most of these receptors are affected at too low affinity to be sufficiently activated by the brain concentration of approximately 10–20 nM.[50] In humans, recreational doses of LSD can affect 5-HT1A (Ki=1.1nM), 5-HT2A (Ki=2.9nM), 5-HT2B (Ki=4.9nM), 5-HT2C (Ki=23nM), 5-HT5A (Ki=9nM [in cloned rat tissues]), and 5-HT6 receptors (Ki=2.3nM).[56][57] 5-HT5B receptors, which are not present in humans, also have a high affinity for LSD.[58] The psychedelic effects of LSD are attributed to cross-activation of 5-HT2A receptor heteromers.[59] Many but not all 5-HT2A agonists are psychedelics and 5-HT2A antagonists block the psychedelic activity of LSD. LSD exhibits functional selectivity at the 5-HT2A and 5HT2C receptors in that it activates the signal transduction enzyme phospholipase A2 instead of activating the enzyme phospholipase C as the endogenous ligand serotonin does.[60] Exactly how LSD produces its effects is unknown, but it is thought that it works by increasing glutamate release in the cerebral cortex[50] and therefore excitation in this area, specifically in layers IV and V.[61] LSD, like many other drugs of recreational use, has been shown to activate DARPP-32-related pathways.[62] The drug enhances dopamine D2 receptor protomer recognition and signaling of D2–5-HT2A receptor complexes,[63] which may contribute to its psychotic effects.[63] LSD has been shown to have low affinity for H1 receptors, displaying antihistamine effects.[64][65][66] The crystal structure of LSD bound in its active state to a serotonin receptor, specifically the 5-HT2B receptor, has been elucidated for the first time in 2017.[67][68][69] The LSD-bound 5-HT2B receptor is regarded as an excellent model system for the 5-HT2A receptor and the structure of the LSD-bound 5-HT2B receptor was used in the study as a template to determine the structural features necessary for the activity of LSD at the 5-HT2A receptor.[67][68][69] The diethylamide moiety of LSD was found to be a key component for its activity, which is in accordance with the fact that the related lysergamide lysergic acid amide (LSA) is far less hallucinogenic in comparison.[69] LSD was found to stay bound to both the 5-HT2A and 5-HT2B receptors for an exceptionally long amount of time, which may be responsible for its long duration of action in spite of its relatively short terminal half-life.[67][68][69] The extracellular loop 2 leucine 209 residue of the 5-HT2B receptor forms a 'lid' over LSD that appears to trap it in the receptor, and this was implicated in the potency and functional selectivity of LSD and its very slow dissociation rate from the 5-HT2 receptors.[67][68][69] Pharmacokinetics The effects of LSD normally last between 6 and 12 hours depending on dosage, tolerance, body weight, and age.[70] The Sandoz prospectus for "Delysid" warned: "intermittent disturbances of affect may occasionally persist for several days."[71] Aghajanian and Bing (1964) found LSD had an elimination half-life of only 175 minutes (about 3 hours).[56] However, using more accurate techniques, Papac and Foltz (1990) reported that 1 µg/kg oral LSD given to a single male volunteer had an apparent plasma half-life of 5.1 hours, with a peak plasma concentration of 5 ng/mL at 3 hours post-dose.[72] The pharmacokinetics of LSD were not properly determined until 2015, which is not surprising for a drug with the kind of low-μg potency that LSD possesses.[9][6] In a sample of 16 healthy subjects, a single mid-range 200 μg oral dose of LSD was found to produce mean maximal concentrations of 4.5 ng/mL at a median of 1.5 hours (range 0.5–4 hours) post-administration.[9][6] After attainment of peak levels, concentrations of LSD decreased following first-order kinetics with a terminal half-life of 3.6 hours for up to 12 hours and then with slower elimination with a terminal half-life of 8.9 hours thereafter.[9][6] The effects of the dose of LSD given lasted for up to 12 hours and were closely correlated with the concentrations of LSD present in circulation over time, with no acute tolerance observed.[9][6] Only 1% of the drug was eliminated in urine unchanged whereas 13% was eliminated as the major metabolite 2-oxo-3-hydroxy-LSD (O-H-LSD) within 24 hours.[9][6] O-H-LSD is formed by cytochrome P450 enzymes, although the specific enzymes involved are unknown, and it does not appear to be known whether O-H-LSD is pharmacologically active or not.[9][6] The oral bioavailability of LSD was crudely estimated as approximately 71% using previous data on intravenous administration of LSD.[9][6] The sample was equally divided between male and female subjects and there were no significant sex differences observed in the pharmacokinetics of LSD.[9][6] Chemistry 📷The four possible stereoisomers of LSD. Only (+)-LSD is psychoactive. LSD is a chiral compound with two stereocenters at the carbon atoms C-5 and C-8, so that theoretically four different optical isomers of LSD could exist. LSD, also called (+)-D-LSD,[citation needed] has the absolute configuration (5R,8R). The C-5 isomers of lysergamides do not exist in nature and are not formed during the synthesis from d-lysergic acid. Retrosynthetically, the C-5 stereocenter could be analysed as having the same configuration of the alpha carbon of the naturally occurring amino acid L-tryptophan, the precursor to all biosynthetic ergoline compounds. However, LSD and iso-LSD, the two C-8 isomers, rapidly interconvert in the presence of bases, as the alpha proton is acidic and can be deprotonated and reprotonated. Non-psychoactive iso-LSD which has formed during the synthesis can be separated by chromatography and can be isomerized to LSD. Pure salts of LSD are triboluminescent, emitting small flashes of white light when shaken in the dark.[70] LSD is strongly fluorescent and will glow bluish-white under UV light. Synthesis LSD is an ergoline derivative. It is commonly synthesized by reacting diethylamine with an activated form of lysergic acid. Activating reagents include phosphoryl chloride[73] and peptide coupling reagents.[74] Lysergic acid is made by alkaline hydrolysis of lysergamides like ergotamine, a substance usually derived from the ergot fungus on agar plate; or, theoretically possible, but impractical and uncommon, from ergine (lysergic acid amide, LSA) extracted from morning glory seeds.[75] Lysergic acid can also be produced synthetically, eliminating the need for ergotamines.[76][77] Dosage 📷White on White blotters (WoW) for sublingual administration A single dose of LSD may be between 40 and 500 micrograms—an amount roughly equal to one-tenth the mass of a grain of sand. Threshold effects can be felt with as little as 25 micrograms of LSD.[78][79] Dosages of LSD are measured in micrograms (µg), or millionths of a gram. By comparison, dosages of most drugs, both recreational and medicinal, are measured in milligrams (mg), or thousandths of a gram. For example, an active dose of mescaline, roughly 0.2 to 0.5 g, has effects comparable to 100 µg or less of LSD.[71] In the mid-1960s, the most important black market LSD manufacturer (Owsley Stanley) distributed acid at a standard concentration of 270 µg,[80] while street samples of the 1970s contained 30 to 300 µg. By the 1980s, the amount had reduced to between 100 and 125 µg, dropping more in the 1990s to the 20–80 µg range,[81] and even more in the 2000s (decade).[80][82] Reactivity and degradation "LSD," writes the chemist Alexander Shulgin, "is an unusually fragile molecule ... As a salt, in water, cold, and free from air and light exposure, it is stable indefinitely."[70] LSD has two labile protons at the tertiary stereogenic C5 and C8 positions, rendering these centres prone to epimerisation. The C8 proton is more labile due to the electron-withdrawing carboxamide attachment, but removal of the chiral proton at the C5 position (which was once also an alpha proton of the parent molecule tryptophan) is assisted by the inductively withdrawing nitrogen and pi electron delocalisation with the indole ring.[citation needed] LSD also has enamine-type reactivity because of the electron-donating effects of the indole ring. Because of this, chlorine destroys LSD molecules on contact; even though chlorinated tap water contains only a slight amount of chlorine, the small quantity of compound typical to an LSD solution will likely be eliminated when dissolved in tap water.[70] The double bond between the 8-position and the aromatic ring, being conjugated with the indole ring, is susceptible to nucleophilic attacks by water or alcohol, especially in the presence of light. LSD often converts to "lumi-LSD," which is inactive in human beings.[70] A controlled study was undertaken to determine the stability of LSD in pooled urine samples.[83] The concentrations of LSD in urine samples were followed over time at various temperatures, in different types of storage containers, at various exposures to different wavelengths of light, and at varying pH values. These studies demonstrated no significant loss in LSD concentration at 25 °C for up to four weeks. After four weeks of incubation, a 30% loss in LSD concentration at 37 °C and up to a 40% at 45 °C were observed. Urine fortified with LSD and stored in amber glass or nontransparent polyethylene containers showed no change in concentration under any light conditions. Stability of LSD in transparent containers under light was dependent on the distance between the light source and the samples, the wavelength of light, exposure time, and the intensity of light. After prolonged exposure to heat in alkaline pH conditions, 10 to 15% of the parent LSD epimerized to iso-LSD. Under acidic conditions, less than 5% of the LSD was converted to iso-LSD. It was also demonstrated that trace amounts of metal ions in buffer or urine could catalyze the decomposition of LSD and that this process can be avoided by the addition of EDTA. Detection LSD may be quantified in urine as part of a drug abuse testing program, in plasma or serum to confirm a diagnosis of poisoning in hospitalized victims or in whole blood to assist in a forensic investigation of a traffic or other criminal violation or a case of sudden death. Both the parent drug and its major metabolite are unstable in biofluids when exposed to light, heat or alkaline conditions and therefore specimens are protected from light, stored at the lowest possible temperature and analyzed quickly to minimize losses.[84] The apparent plasma half life of LSD is considered to be around 5.1 hours with peak plasma concentrations occurring 3 hours after administration.[85] LSD can be detected using an Ehrlich's reagent and a Hofmann's reagent. History ... affected by a remarkable restlessness, combined with a slight dizziness. At home I lay down and sank into a not unpleasant intoxicated-like condition, characterized by an extremely stimulated imagination. In a dreamlike state, with eyes closed (I found the daylight to be unpleasantly glaring), I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors. After some two hours this condition faded away. —Albert Hofmann, on his first experience with LSD[86] Main article: History of lysergic acid diethylamide LSD was first synthesized on November 16, 1938[87] by Swiss chemist Albert Hofmann at the Sandoz Laboratories in Basel, Switzerland as part of a large research program searching for medically useful ergot alkaloid derivatives. LSD's psychedelic properties were discovered 5 years later when Hofmann himself accidentally ingested an unknown quantity of the chemical.[88] The first intentional ingestion of LSD occurred on April 19, 1943,[89] when Hofmann ingested 250 µg of LSD. He said this would be a threshold dose based on the dosages of other ergot alkaloids. Hofmann found the effects to be much stronger than he anticipated.[90] Sandoz Laboratories introduced LSD as a psychiatric drug in 1947 and marketed LSD as a psychiatric panacea, hailing it "as a cure for everything from schizophrenia to criminal behavior, 'sexual perversions,' and alcoholism."[91] The abbreviation "LSD" is from the German "Lysergsäurediethylamid".[92] 📷Albert Hofmann in 2006 Beginning in the 1950s, the US Central Intelligence Agency (CIA) began a research program code named Project MKUltra. The CIA introduced LSD to the United States, purchasing the entire world's supply for $240,000 and propagating the LSD, through CIA front organizations to American hospitals, clinics, prisons and research centers.[93] Experiments included administering LSD to CIA employees, military personnel, doctors, other government agents, prostitutes, mentally ill patients, and members of the general public in order to study their reactions, usually without the subjects' knowledge. The project was revealed in the US congressional Rockefeller Commission report in 1975. In 1963, the Sandoz patents expired on LSD.[81] Several figures, including Aldous Huxley, Timothy Leary, and Al Hubbard, began to advocate the consumption of LSD. LSD became central to the counterculture of the 1960s.[94] In the early 1960s the use of LSD and other hallucinogens was advocated by new proponents of consciousness expansion such as Leary, Huxley, Alan Watts and Arthur Koestler,[95][96] and according to L. R. Veysey they profoundly influenced the thinking of the new generation of youth.[97] On October 24, 1968, possession of LSD was made illegal in the United States.[98] The last FDA approved study of LSD in patients ended in 1980, while a study in healthy volunteers was made in the late 1980s. Legally approved and regulated psychiatric use of LSD continued in Switzerland until 1993.[99] Society and culture Counterculture 📷This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. Find sources: "Lysergic acid diethylamide" – news · newspapers · books · scholar · JSTOR (March 2016) (Learn how and when to remove this template message)📷Psychedelic art attempts to capture the visions experienced on a psychedelic trip By the mid-1960s, the youth countercultures in California, particularly in San Francisco, had adopted the use of hallucinogenic drugs, with the first major underground LSD factory established by Owsley Stanley.[100] From 1964, the Merry Pranksters, a loose group that developed around novelist Ken Kesey, sponsored the Acid Tests, a series of events primarily staged in or near San Francisco, involving the taking of LSD (supplied by Stanley), accompanied by light shows, film projection and discordant, improvised music known as the psychedelic symphony.[101][102] The Pranksters helped popularize LSD use, through their road trips across America in a psychedelically-decorated converted school bus, which involved distributing the drug and meeting with major figures of the beat movement, and through publications about their activities such as Tom Wolfe's The Electric Kool-Aid Acid Test (1968).[103] In San Francisco's Haight-Ashbury neighborhood, brothers Ron and Jay Thelin opened the Psychedelic Shop in January 1966. The Thelins' store is regarded as the first ever head shop. The Thelins opened the store to promote safe use of LSD, which was then still legal in California. The Psychedelic Shop helped to further popularize LSD in the Haight and to make the neighborhood the unofficial capital of the hippie counterculture in the United States. Ron Thelin was also involved in organizing the Love Pageant rally, a protest held in Golden Gate park to protest California's newly adopted ban on LSD in October 1966. At the rally, hundreds of attendees took acid in unison. Although the Psychedelic Shop closed after barely a year-and-a-half in business, its role in popularizing LSD was considerable.[104] 📷"Lysergic Acid Diethylamide"📷MENU0:00by Lambert P. Lambert and the Gorgettes, from the album Abbra Cadaver, 1967Problems playing this file? See media help. A similar and connected nexus of LSD use in the creative arts developed around the same time in London. A key figure in this phenomenon in the UK was British academic Michael Hollingshead, who first tried LSD in America in 1961 while he was the Executive Secretary for the Institute of British-American Cultural Exchange. After being given a large quantity of pure Sandoz LSD (which was still legal at the time) and experiencing his first "trip," Hollingshead contacted Aldous Huxley, who suggested that he get in touch with Harvard academic Timothy Leary, and over the next few years, in concert with Leary and Richard Alpert, Hollingshead played a major role in their famous LSD research at Millbrook before moving to New York City, where he conducted his own LSD experiments. In 1965 Hollingshead returned to the UK and founded the World Psychedelic Center in Chelsea, London.
Here's a different example (a simplified version of something I've seen come up): Consider a Bayesian posterior for the variance, $\sigma^2$ of a normal distribution with known mean $\mu$. The conjugate prior is inverse gamma, but what if we wanted a lognormal prior? Then we'd effectively have an integral whose integrand is of the form And that is why Bayesian inference languished for so many decades until computational power enabled numerical solutions. But now we have such tools. And of them is called JAGS or Just Another Gibbs Sampler. If we apply JAGS to the RU-486 data with this non-conjugate prior, we can find the posterior distribution. Chapter 2 Conjugate distributions. Conjugate distribution or conjugate pair means a pair of a sampling distribution and a prior distribution for which the resulting posterior distribution belongs into the same parametric family of distributions than the prior distribution. We also say that the prior distribution is a conjugate prior for this sampling distribution. Non-conjugate models. We'll first look at an example of a one parameter model that is not conjugate. Suppose we have values that represent the percentage change in total personnel from last year to this year for, we'll say, We know that the conjugate prior for mu in this location would be a normal distribution. Statistics 3858b : Bayesian Nonconjugate Prior Example Bernoulli with Non-Conjugate Prior For Binomial we usually use a conjugate prior : having a Beta distribution Below we consider what happens if we instead use a non-conjugate prior. We will see that while all Are there any prior, likelihood pairs such that the posterior's distribution is known but not from the same family as the prior? Meaning, non conjugate priors where the posterior is still easy to find. If so, how is this called? 2.3.1 Non-Conjugate Priors. In many applications, a Bayesian may not be able to use a conjugate prior. Sometimes she may want to use a reference prior, which injects the minimum amount of personal belief into the analysis. Non-conjugate prior distribution assessment for multivariate normal sampling Paul H. Garthwaite The Open University, Milton Keynes, UK An example comparing methods is given in Section 7 and concluding comments are given in Section 8. 2. Eliciting a multivariate t-distribution Conjugate prior in essence. For some likelihood functions, if you choose a certain prior, the posterior ends up being in the same distribution as the prior.Such a prior then is called a Conjugate Prior. It is a lways best understood through examples. Below is the code to calculate the posterior of the binomial likelihood. θ is the probability of success and our goal is to pick the θ that 4.1.3 Example : non-conjugate prior for Poisson model; 4.2 Monte Carlo integration. 4.2.1 Strong law of large numbers (SLL) 4.2.2 Example of SLL : coinflips; 4.2.3 Example of Monte carlo integration; 4.3 Monte Carlo markov chain (MCMC) methods. 4.3.1 Markov chain; 4.3.2 MCMC sampling; 4.3.3 Example of MCMC: Gibbs sampler; 4.4 Probabilistic
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