Boy Gothic and Other Stories

[i]Boy Gothic and Other Stories[/i], by James Benjamin Storey, is a collection of short stories related by theme. Most of the stories follow the life of Sam, our main character, as he confronts and explores the modern condition--poverty, race, politics, gender, sexual orientation, etc. Perhaps the most important conflict is Sam's Ptolemaic struggle to overcome his father, a large man whose influence restricts Sam to the role of "perpetual boy." The thesis is organized in a morning, noon, night cycle corresponding to Sam's age. The collection is patterned after Hemingway's [i]In Our Time[/i] in the inclusion of short-shorts between longer stories. Other major influences include Faulkner, Joyce, Ellison, and Anderson. As an example of its writer's current development, the thesis includes works created throughout its author's graduate studies. The result is a collection that reflects the major literary movements of the 20th century

Of Bookworms & Busybodies

The virtues of liberal education -- and why it is worth pursuing

An Overview of Stress Response and Hypometabolic Strategies in Caenorhabditis elegans: Conserved and Contrasting Signals with the Mammalian System

Studies of the molecular mechanisms that are involved in stress responses (environmental or physiological) have long been used to make links to disease states in humans. The nematode model organism, Caenorhabditis elegans, undergoes a state of hypometabolism called the 'dauer' stage. This period of developmental arrest is characterized by a significant reduction in metabolic rate, triggered by ambient temperature increase and restricted oxygen/ nutrients. C. elegans employs a number of signal transduction cascades in order to adapt to these unfavourable conditions and survive for long times with severely reduced energy production. The suppression of cellular metabolism, providing energetic homeostasis, is critical to the survival of nematodes through the dauer period. This transition displays molecular mechanisms that are fundamental to control of hypometabolism across the animal kingdom. In general, mammalian systems are highly inelastic to environmental stresses (such as extreme temperatures and low oxygen), however, there is a great deal of conservation between the signal transduction pathways of nematodes and mammals. Along with conserving many of the protein targets in the stress response, many of the critical regulatory mechanisms are maintained, and often differ only in their level of expression. Hence, the C. elegans model outlines a framework of critical molecular mechanisms that may be employed in the future as therapeutic targets for addressing disease states

Glucose-6-Phosphate Dehydrogenase Regulation in Anoxia Tolerance of the Freshwater Crayfish Orconectes virilis

Glucose-6-phosphate dehydrogenase (G6PDH), the enzyme which catalyzes the rate determining step of the pentose phosphate pathway (PPP), controls the production of nucleotide precursor molecules (R5P) and powerful reducing molecules (NADPH) that support multiple biosynthetic functions, including antioxidant defense. G6PDH from hepatopancreas of the freshwater crayfish (Orconectes virilis) showed distinct kinetic changes in response to 20 h anoxic exposure. Km values for both substrates decreased significantly in anoxic crayfish; Km NADP+ dropped from 0.015 ± 0.008 mM to 0.012 ± 0.008 mM, and Km G6P decreased from 0.13 ± 0.02 mM to 0.08 ± 0.007 mM. Two lines of evidence indicate that the mechanism involved is reversible phosphorylation. In vitro incubations that stimulated protein kinase or protein phosphatase action mimicked the effects on anoxia on Km values, whereas DEAE-Sephadex chromatography showed the presence of two enzyme forms (low- and high-phosphate) whose proportions changed during anoxia. Incubation studies implicated protein kinase A and G in mediating the anoxia-responsive changes in G6PDH kinetic properties. In addition, the amount of G6PDH protein (measured by immunoblotting) increased by ∼60% in anoxic hepatopancreas. Anoxia-induced phosphorylation of G6PDH could contribute to modifying carbon flow through the PPP under anoxic conditions, potentially maintaining NADPH supply for antioxidant defense during prolonged anoxia-induced hypometabolism

Can routinely collected hospital admission data be used to study temporal morbidity and mortality trends in maintenance renal replacement patients? Analyses from the Oxford Record Linkage Study and all England Hospital Episode Statistics, 1965 2011

Maintenance dialysis programmes for end-stage renal disease (ESRD) began in the United Kingdom in the 1960s. Until the 1980s, renal replacement therapy (RRT, i.e., dialysis or kidney transplantation) was restricted to ESRD patients who were considered the most economically active and those with diabetes or other comorbidities were often not referred or treated. This contrasts with the situation 50 years later when the median age of patients starting maintenance RRT is 65 years and diabetes is the leading cause of ESRD. Examining long-term temporal mortality trends helps describe past and current serious health risks. Their interpretation is difficult in RRT populations as comparisons between treated ESRD and other populations need to take account of the substantial secular changes in the prevalence of comorbid illnesses which influence both mortality and the likelihood of receiving RRT. To date, no large study has standardized mortality rates in treated ESRD and general population cohorts to the same comorbidity as well as age/sex structure. Therefore, although data from ESRD registries in the United States 1977-2007, Europe 1998-2007, Australasia 1992-2005,and UK 2002-2011 have all shown modest improvements in mortality for people with treated ESRD, it is unclear whether the magnitude of this change is comparable to those observed in the general population during the same period. The Oxford Record Linkage Study (ORLS) was established in 1963 and recorded information about all hospital inpatient admissions in Oxfordshire and the surrounding counties. Hospital Episode Statistics (HES) succeeded ORLS and established nationwide coverage from 1998. Mortality trends among new maintenance RRT patients and a set of general population controls, extracted from these two datasets were performed. Novel approaches ensured that both cohorts could be corrected for changes in prior comorbidity over time and the effects of transplantation, and stratified analyses in patients with and without diabetes could be performed.   Key aims of thesis 1) Derive and validate a cohort of end-stage renal disease (ESRD) patients exclusively from anonymised, individually-linked prospectively collected hospital inpatients datasets 2) Analyse the temporal trends of age, sex and comorbidity adjusted mortality rates in the ESRD cohort 3) Concurrently derive a comparative general population to provide an opportunity to compare trends between the ESRD and general populations 4) Demonstrate other uses of routinely collected hospital inpatients datasets in renal epidemiolog

Non-adherence to eye care in people with diabetes

Objective Evaluate individual factors that impact adherence to eye care follow-up in patients with diabetes. Design and methods A 4-year retrospective chart review was conducted for 1968 patients with diabetes over age 40 from an urban academic center. Data collected included demographics, insurance, visual acuity, smoking status, medications, dates of dilated fundus examinations (DFE), and reported hemoglobin A1C and blood glucose levels. The primary outcome was timely DFE follow-up adherence following the initial eye exam visit. Results Overall, 41.6% of patients adhered to initial follow-up eye care recommendations. Multivariable analysis demonstrated that patients with severe diabetic retinopathy (DR) were more adherent than patients with mild DR (OR 1.86). Other variables associated with increased adherence were visual impairment and reported A1C or blood glucose. Smoking was associated with decreased adherence. Ethnicity and insurance were also significantly associated with adherence. Longitudinal follow-up rates were influenced by additional factors, including ethnicity and neighborhood deprivation index. Conclusions Patients with moderate to severe DR and/ or visual impairment were more likely to adhere to timely DFE follow-up. This could relate to the presence of visual symptoms and/or other systemic manifestations of diabetes. Smokers were less likely to adhere to timely DFE follow-up. One hypothesis is patients who smoke have other symptomatic health problems which patients prioritize over asymptomatic ocular disorders. In order to reduce vision loss from DR, practitioners should be aware that patients with mild and moderate DR, patients with normal vision, and smokers are at greater risk for poor follow-up eye care adherence. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved

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Glucose-6-phosphate dehydrogenase (G6PDH), the enzyme which catalyzes the rate determining step of the pentose phosphate pathway (PPP), controls the production of nucleotide precursor molecules (R5P) and powerful reducing molecules (NADPH) that support multiple biosynthetic functions, including antioxidant defense. G6PDH from hepatopancreas of the freshwater crayfish (Orconectes virilis) showed distinct kinetic changes in response to 20 h anoxic exposure. K m values for both substrates decreased significantly in anoxic crayfish; K m NADP + dropped from 0.015 ± 0.008 mM to 0.012 ± 0.008 mM, and K m G6P decreased from 0.13 ± 0.02 mM to 0.08 ± 0.007 mM. Two lines of evidence indicate that the mechanism involved is reversible phosphorylation. In vitro incubations that stimulated protein kinase or protein phosphatase action mimicked the effects on anoxia on K m values, whereas DEAE-Sephadex chromatography showed the presence of two enzyme forms (low-and high-phosphate) whose proportions changed during anoxia. Incubation studies implicated protein kinase A and G in mediating the anoxiaresponsive changes in G6PDH kinetic properties. In addition, the amount of G6PDH protein (measured by immunoblotting) increased by ∼60% in anoxic hepatopancreas. Anoxia-induced phosphorylation of G6PDH could contribute to modifying carbon flow through the PPP under anoxic conditions, potentially maintaining NADPH supply for antioxidant defense during prolonged anoxia-induced hypometabolism

Analysis of two SMC HII Regions Considering Thermal Inhomogeneities: Implications for the Determinations of Extragalactic Chemical Abundances

We present long slit spectrophotometry considering the presence of thermal inhomogeneities (t^2) of two HII regions in the Small Magellanic Cloud (SMC): NGC 456 and NGC 460. Physical conditions and chemical abundances were determined for three positions in NGC 456 and one position in NGC 460, first under the assumption of uniform temperature and then allowing for the possibility of thermal inhomogeneities. We determined t^2 values based on three different methods: i) by comparing the temperature derived using oxygen forbidden lines with the temperature derived using helium recombination lines, ii) by comparing the abundances derived from oxygen forbidden lines with those derived from oxygen recombination lines, and iii) by comparing the abundances derived from ultraviolet carbon forbidden lines with those derived from optical carbon recombination lines. The first two methods averaged t^2=0.067+-0.013 for NGC 456 and t^2=0.036+-0.027 for NGC 460. These values of t^2 imply that when gaseous abundances are determined with collisionally excited lines they are underestimated by a factor of nearly 2. From these objects and others in the literature, we find that in order to account for thermal inhomogeneities and dust depletion, the O/H ratio in low metallicity HII regions should be corrected by 0.25-0.45 dex depending on the thermal structure of the nebula, or by 0.35 dex if such information is not available.Comment: Accepted for publication in The Astrophysical Journal. 41 pages in pre-print format. 3 figure

A Bayesian method for evaluating and discovering disease loci associations

Background: A genome-wide association study (GWAS) typically involves examining representative SNPs in individuals from some population. A GWAS data set can concern a million SNPs and may soon concern billions. Researchers investigate the association of each SNP individually with a disease, and it is becoming increasingly commonplace to also analyze multi-SNP associations. Techniques for handling so many hypotheses include the Bonferroni correction and recently developed Bayesian methods. These methods can encounter problems. Most importantly, they are not applicable to a complex multi-locus hypothesis which has several competing hypotheses rather than only a null hypothesis. A method that computes the posterior probability of complex hypotheses is a pressing need. Methodology/Findings: We introduce the Bayesian network posterior probability (BNPP) method which addresses the difficulties. The method represents the relationship between a disease and SNPs using a directed acyclic graph (DAG) model, and computes the likelihood of such models using a Bayesian network scoring criterion. The posterior probability of a hypothesis is computed based on the likelihoods of all competing hypotheses. The BNPP can not only be used to evaluate a hypothesis that has previously been discovered or suspected, but also to discover new disease loci associations. The results of experiments using simulated and real data sets are presented. Our results concerning simulated data sets indicate that the BNPP exhibits both better evaluation and discovery performance than does a p-value based method. For the real data sets, previous findings in the literature are confirmed and additional findings are found. Conclusions/Significance: We conclude that the BNPP resolves a pressing problem by providing a way to compute the posterior probability of complex multi-locus hypotheses. A researcher can use the BNPP to determine the expected utility of investigating a hypothesis further. Furthermore, we conclude that the BNPP is a promising method for discovering disease loci associations. © 2011 Jiang et al