Hereditary pancreatitis in a family of Aboriginal descent

Hereditary pancreatitis is an autosomal dominant condition characterized by recurrent episodes of acute pancreatitis, usually starting in childhood. We present a family who was ascertained when an 11-year-old girl presented with an episode of acute pancreatitis. Her father and other family members had also had recurrent bouts of acute pancreatitis. Genetic testing revealed a pathogenic mutation in the cationic trypsinogen gene in the proband, her father and her paternal grandmother. As far as we are aware, this is the first Aboriginal kindred with mutation-proven hereditary pancreatitis. Hereditary pancreatitis is an important differential diagnosis to consider in a patient with recurrent episodes of acute pancreatitis with no obvious precipitating cause. This family is of Aboriginal descent and the implications of the family's background are also discussed when considering the aetiology of the condition. We emphasize the need to ascertain a full family history from patients with a history of repeated episodes of acute pancreatitis and also emphasize the need to avoid ethnic stereotypes when assessing patients.

Assumption-free estimation of heritability from genome-wide identity-by-descent sharing between full siblings

The study of continuously varying, quantitative traits is important in evolutionary biology, agriculture, and medicine. Variation in such traits is attributable to many, possibly interacting, genes whose expression may be sensitive to the environment, which makes their dissection into underlying causative factors difficult. An important population parameter for quantitative traits is heritability, the proportion of total variance that is due to genetic factors. Response to artificial and natural selection and the degree of resemblance between relatives are all a function of this parameter. Following the classic paper by R. A. Fisher in 1918, the estimation of additive and dominance genetic variance and heritability in populations is based upon the expected proportion of genes shared between different types of relatives, and explicit, often controversial and untestable models of genetic and non-genetic causes of family resemblance. With genome-wide coverage of genetic markers it is now possible to estimate such parameters solely within families using the actual degree of identity-by-descent sharing between relatives. Using genome scans on 4,401 quasi-independent sib pairs of which 3,375 pairs had phenotypes, we estimated the heritability of height from empirical genome-wide identity-by-descent sharing, which varied from 0.374 to 0.617 (mean 0.498, standard deviation 0.036). The variance in identity-by-descent sharing per chromosome and per genome was consistent with theory. The maximum likelihood estimate of the heritability for height was 0.80 with no evidence for non-genetic causes of sib resemblance, consistent with results from independent twin and family studies but using an entirely separate source of information. Our application shows that it is feasible to estimate genetic variance solely from within- family segregation and provides an independent validation of previously untestable assumptions. Given sufficient data, our new paradigm will allow the estimation of genetic variation for disease susceptibility and quantitative traits that is free from confounding with non-genetic factors and will allow partitioning of genetic variation into additive and non-additive components.

A gradient descent algorithm for minimizing amino acid coupling reactions when synthesizing cyclic-peptide libraries

Combinatorial chemistry has become an invaluable tool in medicinal chemistry for the identification of new drug leads. For example, libraries of predetermined sequences and head-to-tail cyclized peptides are routinely synthesized in our laboratory using the IRORI approach. Such libraries are used as molecular toolkits that enable the development of pharmacophores that define activity and specificity at receptor targets. These libraries can be quite large and difficult to handle, due to physical and chemical constraints imposed by their size. Therefore, smaller sub-libraries are often targeted for synthesis. The number of coupling reactions required can be greatly reduced if the peptides having common amino acids are grouped into the same sub-library (batching). This paper describes a schedule optimizer to minimize the number of coupling reactions by rotating and aligning sequences while simultaneously batching. The gradient descent method thereby reduces the number of coupling reactions required for synthesizing cyclic peptide libraries. We show that the algorithm results in a 75% reduction in the number of coupling reactions for a typical cyclic peptide library.

Dynamics of on-line gradient descent learning for multilayer neural networks

We consider the problem of on-line gradient descent learning for general two-layer neural networks. An analytic solution is presented and used to investigate the role of the learning rate in controlling the evolution and convergence of the learning process.

Computationally efficient natural gradient descent

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

Women of African descent: Persistence in completing doctorates

This study examines the educational persistence of women of African descent (WOAD) in pursuit of a doctorate degree at universities in the southeastern United States. WOAD are women of African ancestry born outside the African continent. These women are heirs to an inner dogged determination and spirit to survive despite all odds (Pulliam, 2003, p. 337).This study used Ellis’s (1997) Three Stages for Graduate Student Development as the conceptual framework to examine the persistent strategies used by these women to persist to the completion of their studies. Semi-structured interviews were conducted, transcribed, and analyzed for the 10 study participants. The study examined their beliefs, roles, and support systems utilized during their studies to help propel them to succeed. Interview data were analyzed using cross-case analysis to discover emerging themes and patterns. A comparative analysis was used to analyze the participants’ experiences and discover themes and patterns to review against the historical data. The findings showed that WOAD experienced feelings of isolation, neglect and racial prejudice as doctoral students. Their ability to formulate supportive relationships among each other and in their communities outside the university was key to their persistence to graduation. There still remains a need to create a more engaging and inclusive environment for nontraditional students, particularly those who are WOAD. The study concludes with six strategies of success used by these WOAD to persist to completion. Those six strategies include 1. Keeping the goal of earning a doctorate and graduating foremost on your mind. 2. Set a class and study schedule that allows you to balance family, work and study. 3. Take care of yourself, physically, mentally and emotionally. 4. Keep a goal chart to track your strides toward completion/graduation. 5. Establish a strong support system among your family, friends, colleagues and community; and 6. Do not let the “isms” (racism, sexism, and ageism) deter you.

Students of Haitian Descent in American Schools: Challenges and Issues

This paper examines the ways the reception of students of Haitian descent in this country has shaped their educational careers. Additionally, this paper explores the racial, cultural, and individual differences that need to be understood in order to help educators, parents, and students make their schooling a positive experience.

Substructuring in four populations of African descent

When a suspect's DNA profile is admitted into court as a match to evidence the probability of the perpetrator being another individual must be calculated from database allele frequencies. The two methods used for this calculation are phenotypic frequency and likelihood ratio. Neither of these calculations takes into account substructuring within populations. In these substructured populations the frequency of homozygotes increases and that of heterozygotes usually decreases. The departure from Hardy- Weinberg expectation in a sample population can be estimated using Sewall Wright's Fst statistic. Fst values were calculated in four populations of African descent by comparing allele frequencies at three short tandem repeat loci. This was done by amplifying the three loci in each sample using the Polymerase Chain Reaction and separating these fragments using polyacrylamide gel electrophoresis. The gels were then silver stained and autoradiograms taken, from which allele frequencies were estimated. Fst values averaged 0.007+- 0.005 within populations of African descent and 0.02+- 0.01 between white and black populations.

TAFRO Syndrome in a Patient of South-American Descent

A 31-year-old Caucasian woman of South-American descent was diagnosed with a variant of multicentric Castleman disease (MCD) that has been reported in Japan as Castleman-Kojima disease. This is a systemic inflammatory disorder known as TAFRO Syndrome which includes thrombocytopenia, polyserositis (ascites/pleural effusion), microcytic anemia, myelofibrosis, fever, renal dysfunction and organomegaly, with immunologic disorder, polyclonal hypergammaglobulinemia, and elevated levels of interleukin-6 (IL-6) and the vascular endothelial growth factor present in serum and/or effusions. Optimal therapies are not well established. The patient was treated with methylprednisolone and rituximab. Following the start of treatment, the patient has been asymptomatic for over 8 months.

The Descent of Pluto: Interactive dynamics, specialisation and reciprocity of roles in a Wikipedia debate

International audience

Lines of Descent d'Anthony K. Appiah : un regard oblique sur le panafricanisme

Sur les traces de l’auteur afro-américain W.E.B. Du Bois, le philosophe Anthony Kwame Appiah se préoccupe dans son Lines of Descent (2014) de l’articulation entre identité personnelle, nationalisme culturel et universel cosmopolitique, à la lumière du signifiant social de la race. Appiah se penche spécifiquement sur l’influence qu’a exercée la pensée allemande de la fin du 19e siècle sur le développement de la pensée de Du Bois. Dans la foulée de travaux antérieurs 1, il s’y intéresse à la question de l’identité raciale et à la place qu’elle occupe dans sa théorisation du panafricanisme. Après un survol biographique des auteurs abordés, cette note de lecture s’intéressera à ces trois thèses fortes en les soumettant à quelques réflexions critiques.

"Lines of Descent" d'Anthony K. Appiah : un regard oblique sur le panafricanisme.

Sur les traces de l’auteur afro-américain W.E.B. Du Bois, le philosophe Anthony Kwame Appiah se préoccupe dans son Lines of Descent (2014) de l’articulation entre identité personnelle, nationalisme culturel et universel cosmopolitique, à la lumière du signifiant social de la race. Appiah se penche spécifiquement sur l’influence qu’a exercée la pensée allemande de la fin du 19e siècle sur le développement de la pensée de Du Bois. Dans la foulée de travaux antérieurs 1, il s’y intéresse à la question de l’identité raciale et à la place qu’elle occupe dans sa théorisation du panafricanisme. Après un survol biographique des auteurs abordés, cette note de lecture s’intéressera à ces trois thèses fortes en les soumettant à quelques réflexions critiques.

Teste de banco com carga continua para analise do volume de oxigenio (VO2) predito e analisado por tempo de esforço em pessoas treinadas (TRD), ativas (ATV) e destreinadas (DTR) a partir dos 13 anos : proposta de validação

Universidade Estadual de Campinas . Faculdade de Educação Física

CYP2C19 and ABCB1 gene polymorphisms are differently distributed according to ethnicity in the Brazilian general population

Background: Recent studies have reported the clinical importance of CYP2C19 and ABCB1 polymorphisms in an individualized approach to clopidogrel treatment. The aims of this study were to evaluate the frequencies of CYP2C19 and ABCB1 polymorphisms and to identify the clopidogrel-predicted metabolic phenotypes according to ethnic groups in a sample of individuals representative of a highly admixtured population. Methods: One hundred and eighty-three Amerindians and 1,029 subjects of the general population of 4 regions of the country were included. Genotypes for the ABCB1c.C3435T (rs1045642), CYP2C19*2 (rs4244285), CYP2C19*3 (rs4986893), CYP2C19*4 (rs28399504), CYP2C19*5 (rs56337013), and CYP2C19*17 (rs12248560) polymorphisms were detected by polymerase chain reaction followed by high resolution melting analysis. The CYP2C19*3, CYP2C19*4 and CYP2C19*5 variants were genotyped in a subsample of subjects (300 samples randomly selected). Results: The CYP2C19*3 and CYP2C19*5 variant alleles were not detected and the CYP2C19*4 variant allele presented a frequency of 0.3%. The allelic frequencies for the ABCB1c.C3435T, CYP2C19*2 and CYP2C19*17 polymorphisms were differently distributed according to ethnicity: Amerindian (51.4%, 10.4%, 15.8%); Caucasian descent (43.2%, 16.9%, 18.0%); Mulatto (35.9%, 16.5%, 21.3%); and African descent (32.8%, 20.2%, 26.3%) individuals, respectively. As a result, self-referred ethnicity was able to predict significantly different clopidogrel-predicted metabolic phenotypes prevalence even for a highly admixtured population. Conclusion: Our findings indicate the existence of inter-ethnic differences in the ABCB1 and CYP2C19 variant allele frequencies in the Brazilian general population plus Amerindians. This information could help in stratifying individuals from this population regarding clopidogrel-predicted metabolic phenotypes and design more cost-effective programs towards individualization of clopidogrel therapy.