Warfarin, the most commonly prescribed anticoagulant, is principally metabolized by cytochrome P450 2C9 which functions by inhibiting the Vitamin K epoxide reductase. Genes CYP2C9 and VKORC1 code for these two proteins, respectively. CYP2C9 and VKORC1 exhibit genetic polymorphisms that have been shown to affect warfarin response and favorably facilitate warfarin dosing and improve clinical outcomes. However, none of these studies have involved populations from sub-Saharan Africa where the potential benefit of optimal dosing and reduced complications is greatest. Therefore, the thesis describes a study designed to investigate the role of genetic variations in CYP2C9 and VKORC1 on the time taken to reach a stable therapeutic international normalized ratio (INR) and warfarin dose required to maintain a therapeutic INR. This was a cross-sectional study of patients on warfarin to determine the relationship between genetic polymorphism in CYP2C9 and VKORC1 amongst black and mixed ancestry South Africans and clinical surrogates of warfarin metabolism. Medical records were accessed to determine time to INR and warfarin doses. DNA was extracted from blood samples, and genotyping for polymorphism in CYP2C9 (*2,*3,*8,*11) and VKORC1 (1173C>T, 1639G>A, 3730G>A) was accomplished by PCR-RFLP, Sanger sequencing and iPlex Mass Sequencing. Our results show that the genetic profile of CYP2C9 and VKORC1 differs between Black Africans (BA) and their Mixed Ancestry (MA) counterparts. VKORC1-1639AA genotype was observed at frequencies of 0.11 and 0.01 in the MA and BA, respectively. Time to stable INR was not influenced by CYP2C9 and VKORC1. Furthermore, compared to known genetic polymorphisms in these genes from population out of Africa, both qualitative and quantitative differences were observed. Finally, we found that VKORC1 genetic variation significantly affected the doses of warfarin in MA but had no effect in BA. These results suggest that further research in this area is warranted, and that it will be important to include populations from sub-Saharan Africa in future if the potential to develop personalized algorithms which integrate pharmacogenomics to assist with effective warfarin dosing and prevention of warfarin related complications is to be realized.

The present study analyzes cranial nonmetric traits used in forensic ancestry estimation on contemporary skeletal remains of modern European Americans in order to determine if there are statistically significant differences between males and females in trait expression. Research on cranial nonmetric traits for ancestry estimation has largely ignored the effects of sexual dimorphism on trait expression; however, there is growing evidence that some traits may be impacted by sex, among other variables. The 17 macromorphoscopic traits described in Hefner and Linde (2018) and the six mandibular morphoscopic traits described in Berg (2008) were scored on 97 females and 113 males from the Texas State University Donated Skeletal Collection in San Marcos, Texas. Chi-square tests were used to analyze if there are statistically significant cranial nonmetric trait expressions between males and females. From these tests, the results indicate that 14 out of the 23 cranial and mandibular nonmetric traits are statistically significantly different between the sexes, with a p-value less than 0.05. Gonial angle flare is the most significant feature, while the zygomaticomaxillary suture is the least significant feature. Additionally, correspondence analyses (CA) show the relationship between each cranial nonmetric trait score, that demonstrated significance, and both sexes. Ultimately, this research demonstrates that several nonmetric traits used in ancestry estimation are affected by sex; thus, it may be beneficial to develop sex-specific ancestry models for nonmetric traits.

One of the basic goals of the physical anthropologist is to create a biological profile, consisting of sex, ancestry, age, and stature, from the skeletal material that they are presented with. This thesis seeks to explore size and shape differences related to sex and ancestry from the hyoid bones of the Robert J. Terry Anatomical Collection in order to gauge its usefulness in the process of developing a biological profile. A series of measurements were taken from 398 hyoids and analysis was conducted using a number of statistical methods. Independent samples t-tests were used to examine size differences between sexes and ancestries, while linear regression analysis and principle component analysis were used to examine shape differences. Discriminant function analysis was employed to test the ability of the hyoids to be classified by sex or ancestry. The ultimate goal of the thesis is to provide physical anthropologists with a series of discriminant function equations that can be used to estimate the sex and ancestry of a hyoid. Five equations ranging in accuracy from 83-88% were developed to determine sex of a hyoid, while four equations ranging in accuracy from 70-89% can be used to determine ancestry. In addition, the t-tests, regression analyses, and principle component analysis have identified several variations in size and shape between sexes and ancestries. These analyses have provided further knowledge as to the morphological form of the hyoid, as well as a method that can be easily used by physical anthropologists to assess sex and ancestry.

Please note: creative writing theses are permanently embargoed in OpenBU. No public access is forecasted for these. To request private access, please click on the lock icon and filled out the appropriate web form. / The names of three sections—Tributaries, Levees, and Deltas—are borrowed from riverine terminology. Tributaries are the sources of water near the headwaters of a river that come together to create and support the continued existence of the singularly named river (e.g., the Ohio River, Missouri, and Arkansas are all tributaries of the Mississippi. Their existence does not negate the identity of the Mississippi as a singularity but informs it.). Levees, manmade or natural, are barriers typically created from sediment and riverine detritus due to the natural flow of the river, preventing the river from going a particular direction—a levee is a place where something tries to go but is stopped; this does not change the river only its course. Finally, Deltas are the “end” of a river. Also called Mouths, Deltas are places where the river bed flattens out, and the freshwater spills out in multiple directions, typically into an ocean or sea. This way, Deltas are where the river “lets go” and gives itself back. The narrator of these poems believes that humans are not so different from rivers. The typical state of man is a self-perception of moments, narrative fragments strung together by man’s overly developed cortex, wherein the self believes itself to be flitting from moment to moment in the eternal state of the present. However, if we could see the whole of existence from the outside, we would see that the individual does not exist at any singular point but as a flowing system eddying and bubbling through the Universe. Einstein wrote after his close friend Michael Besso’s death, “Now he has departed from this strange world a little ahead of me. That signifies nothing. For those of us who believe in physics, the distinction between past, present, and future is only a stubbornly persistent illusion.” If we could see past the illusion, literal enlightenment, we would know the truth of our individual existence. The self is only real in the way that a river is—the river exists, but the waters are constantly changing. Humans have our physical tributaries existing in ancestral genomes and subjective formation through the stories they are told of who we are. So, likewise, the things we let go or are forced to part with build our levees, ushering each of us into new directions of existence, and, in the end, we are given back to the whole, spreading, emptying, flowing out into the unknowable consumption of the future. Yet, the course of the river/human, which is the story of comings and goings, remains carved upon the landscape. What may follow in these channels, what may chart new courses, or what may finish the work that began by another is yet to be seen, but, as Einstein said, what was, is never lost, only moved out of sight. The goal throughout this collection is to celebrate existence, but a true celebration is necessarily accompanied by mourning. The cost of the narrator’s awareness of the self in the quantum sense is its own form of isolation. Yet, following Rilke’s advice to another young poet, the narrator sees the act of Love and the mercy and modesty of human needs as profoundly sufficient. There is, for the narrator, some level of charity from the divine which gives commensurately with our needs; partiality is, therefore, sufficient. The center does not hold, it’s true, but the narrator is content with its falling apart. The dissonance between the experiential self and the true cosmic self is mended in the assertion, “We remember things, not as they are, but as we need them to be.” Which is to say, we are left only with what is needful, and that is enough. / 2999-01-01T00:00:00Z

Thesis (Ph. D.)--Case Western Reserve University, 2008. / Frances Payne Bolton [School of Nursing]. Includes bibliographical references.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2009. / Title from first page of PDF file (viewed on June 9, 2009). Includes bibliographical references.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2012-07-16T21:36:49Z No. of bitstreams: 1 Enio Paulo Estimativa de mistura étnica avaliada por Marcadores Informativos de.pdf: 352598 bytes, checksum: 7d448dc54afe1ec271f59fc912275f41 (MD5) / Made available in DSpace on 2012-07-16T21:36:49Z (GMT). No. of bitstreams: 1 Enio Paulo Estimativa de mistura étnica avaliada por Marcadores Informativos de.pdf: 352598 bytes, checksum: 7d448dc54afe1ec271f59fc912275f41 (MD5) Previous issue date: 2010 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil / A miscigenação entre os três principais grupos étnicos (ameríndios, europeus e africanos) originou a alta diversidade genética da população brasileira. Na Bahia a proporção de afrodescendentes é de 77,5%, sendo que em Salvador 79,8% se auto-denominam negros ou pardos. Poucos estudos descrevem a diversidade genética da população baiana e a contribuição de cada grupo étnico na sua formação. Diversos marcadores de DNA são atualmente utilizados para estimar mistura étnica em populações miscigenadas. Estes marcadores são denominados alelos específicos de população (PSAs) ou marcadores informativos de ancestralidade (AIMs) e apresentam alelos com grandes diferenciais de freqüência, superiores a 30%, entre populações geográfica ou etnicamente definidas. Os microssatélites (STRs) são variantes genéticos úteis no mapeamento genético de espécies, na identificação de pessoas, mapeamento genético e análise de populações. Alguns STRs apresentam alelos com freqüências marcantes em determinados grupos populacionais. Com objetivo de comparar a ancestralidade genomica avaliada com dois tipos de marcadores, foram estudados 8 microssatélites STRs autossômicos (TH01, vWA31, D18S51, FGA, TPOX, D7S820, D3S1358, D8S1179) e 9 AIMs (FY-Null, LPL, AT3-I/D, Sb19.3, APO, PV92, CYP3A4, CKMM, GC-1F e GC-1S), em 203 indivíduos miscigenados da Bahia. A genotipagem foi realizada por PCR (Polimerase Chain Reaction), para deleções, inserções e para os microssatélites e PCR quantitativo em tempo real para mutações pontuais. As contribuições africana, européia e ameríndia observadas foram respectivamente 33,5%, 58,6% e 7,9% para os STRs e 45,08%, 45,16% e 9,75% para os AIMs, comprovando a miscigenação da população. O Índice Kappa, mostrou que a concordância entre as estimativas de ancestralidade utilizando os dois tipos de marcadores (AIMs e STRs), foi muito baixa (kappa = 0,12). Foi observada associação entre sobrenome de conotação religiosa e ancestralidade africana / The mixing between the three main ethnic groups (Amerindians, Europeans and Africans) produced a high genetic diversity of the braziliam population. In Bahia, the proportion of African descent that call themselves black or brown is 77.5% and 79.8% in Salvador. Few studies describe the genetic diversity of the population of Bahia and the contribution of each ethnic group in its formation. Several DNA markers are currently used to estimate ethnic mix in admixed populations. These markers are called alleles specific population (PSAs) or ancestry informative markers (AIMs) and carry alleles with large differences in frequency above 30% between populations geographically or ethnically defined. Microsatellites (STRs) are useful genetic variants in the genetic mapping of species, identification of persons, genetic mapping and analysis of populations. Some STRs have alleles with frequencies marked in certain population groups. To compare the ancestry genomica evaluated with two types of markers were studied 8 microsatellite autosomal STRs (TH01, vWA31, D18S51, FGA, TPOX, D7S820, D3S1358, D8S1179) and 9 AIMs (FY-Null, LPL, AT3-I /D, Sb19.3, APO, PV92, CYP3A4, CK-MM, GC and GC-1F-1S) in 203 subjects with mixed Bahia. Genotyping was performed by PCR (Polymerase Chain Reaction), for deletions, insertions and for microsatellite and quantitative PCR in real time for mutations. The contributions of African, European and Amerindian observed were respectively 33.5%, 58.6% and 7.9% for the STRs and 45.08%, 45.16% and 9.75% for the AIMs, proving the mixing of population. The Kappa index showed that the correlation between the estimates of ancestry using both types of markers (AIMs and STRs), was very low (kappa = 0.12). Association was found between devotional surnames and African ancestry.

No description available.

Chronic environmental exposure to inorganic arsenic is widely associated with human disease. Low human arsenic secondary methylation efficiency (SME), represented by high urinary monomethylarsonic acid (%uMMA) and low urinary dimethylarsinic acid to monomethylarsonic acid ratio (uDMA/uMMA), has been consistently associated with increased risk of arsenic-related diseases. Therefore the determination of factors modulating arsenic SME acquires particular importance. The aims of the present study are to identify novel factors of variability in arsenic secondary methylation, and to test for potential factors influencing arsenic SME for which there is equivocal literature support. A population of 808 subjects was recruited from northwest Mexico environmentally exposed to arsenic. The mean total urinary arsenic in the population was 171 μg/L. Great interindividual variability in %uMMA excretion was observed (0.85% - 40.5%). Three intronic polymorphisms in arsenic (3+ oxidation state) methyltransferase (AS3MT), the key gene in the metabolism of arsenic, were confirmed to be associated with increased arsenic SME in this study. Further analysis of this genomic region showed a large block of linkage disequilibrium (LD) comprising these three genetic variants and other 43 intronic polymorphisms within AS3MT and four additional genes. Genetic association analysis showed that all linked polymorphisms in this region except one were significantly associated with higher arsenic SME. The existence of this long region of LD associated with arsenic SME underscores the complexity of association studies involving any of these linked polymorphisms since there is no certainty of which polymorphism or gene is the causative of the association. In addition, a strong positive association between body mass index (BMI) and arsenic SME was observed in females but not in males. This association was replicated in two independently recruited populations of adult women. Moreover a unique finding of this study is the association between higher genetically estimated indigenous American (AME) ancestry and increased arsenic SME in this ancestrally admixed Mexican population. These results establish the importance of genetic and phenotypic factors in the efficiency of arsenic secondary methylation. Furthermore this study has identified several arsenic-associated risk factors that should be carefully considered in future studies seeking to better understand disease susceptibility in arsenic-exposed populations.

The debate on personal identity in philosophy is about what makes a person at one point intime the same person as a person at another point in time. Animalism is a point of view whichhas it that being the same human animal is what makes a person at one point in time the sameperson as a person at another point in time. Animalism makes the claim that a person isnumerically identical to a human animal. The two most prominent arguments in favor ofanimalism is the thinking animal argument and the animal ancestry argument. Thinkinganimal argument says that there is a thinking human animal where you are, but you are theonly thinking being where you are. therefore you are a human animal. Animal ancestryargument says that you are a product of evolution and that only living organisms are productsof evolution. Therefore you are a living organism, a human animal. In this thesis these twoarguments, as well as multiple objections against them, were evaluated. It was argued thatarguments about persons being numerically identical to thinking parts and to organs mightpose a threat to the thinking animal argument and the animal ancestry argument, but that thearguments supporting animalism should not be discarded.Abstrakt / Debatten om personlig identitet inom filosofin handlar om vad som gör att en person vid entidpunkt är densamma som en person vid en annan tidpunkt. Animalism är en ståndpunkt somsäger att vad som gör att en person vid en tidpunkt är densamma som en person vid en annantidpunkt, är att de är samma mänskliga djur. Animalism säger alltså att en person är numerisktidentisk med ett mänskligt djur. De två mest framstående argumenten för animalism ärthinking animal argument och animal ancestry argument. Thinking animal argument säger attdet finns ett tänkande mänskligt djur där du är men att du är den enda tänkande varelsen därdu är, alltså är du ett mänskligt djur. Animal ancestry argument säger att du är en produkt avevolutionen och att endast levande organismer är produkter av evolutionen. Alltså är du enlevande organism, ett mänskligt djur. I denna uppsats granskades dessa argument samt ettantal argument mot dessa två argument. Utredningen visade att argument om att personer kanvara numeriskt identiska med tänkande delar och med organ kan vara ett problem för thinkinganimal argument och animal ancestry argument men den slutgiltiga bedömningen är attargumenten för animalism inte bör förkastas.