Testing the Paleolithic-human-warfare hypothesis of blood-injectiion phobia in the Balitmore ECA Follow-up Study-Towards a more etiologically-based conceptualization for DSM-V

Objective: The research agenda for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) has emphasized the need for a more etiologically-based classification system, especially for stress-induced and fear-circuitry disorders. Testable hypotheses based on threats to survival during particular segments of the human era of evolutionary adaptedness (EEA) may be useful in developing a brain-evolution-based classification for the wide spectrum of disorders ranging from disorders which are mostly overconsolidationally such as PTSD, to fear-circuitry disorders which are mostly innate such as specific phobias. The recently presented Paleolithic-human-warfare hypothesis posits that blood–injection phobia can be traced to a “survival (fitness) enhancing” trait, which evolved in some females of reproductive-age during the millennia of intergroup warfare in the Paleolithic EEA. The study presented here tests the key a priori prediction of this hypothesis—that current blood–injection phobia will have higher prevalence in reproductive-age women than in post-menopausal women. Method: The Diagnostic Interview Schedule (version III-R) , which included a section on blood and injection phobia, was administered to 1920 subjects in the Baltimore ECA Follow-up Study. Results: Data on BII phobia was available on 1724 subjects (1078 women and 646 males) . The prevalence of current blood– injection phobia was 3.3% in women aged 27–49 and 1.1% in women over age 50 (OR 3.05, 95% CI 1.20–7.73) . [The corresponding figures for males were 0.8% and 0.7% (OR 1.19, 95% CI 0.20–7.14)] . Conclusions: This epidemiological study provides one source of support for the Paleolithic-human-warfare (Paleolithic-threat) hypothesis regarding the evolutionary (distal) etiology of bloodletting-related phobia, and may contribute to a more brain- evolution-based re-conceptualization and classification of this fear circuitry-related trait for the DSM-V. In addition, the finding reported here may also stimulate new research directions on more proximal mechanisms which can lead to the development of evidence-based psychopharmacological preventive interventions for this common and sometimes disabling fear-circuitry disorder

Prevalence and Comorbidity of Alcohol Dependence, Depression, and Anxiety Disorders in their Association with the Serotonin Transporter Gene

Introduction: Depression and anxiety disorders have been found to be highly comorbid in epidemiologic studies. Furthermore, the presence of the short allele of the serotonin transporter gene (5HTT) has been found to be associated with an increased prevalence of major depressive disorder (MDD), bipolar disorder, anxiety disorders, as well as personality disorders. Aims: To examine the association of the 5HTT and the risk of prevalence and comorbidity for, Major Depressive Disorder, Bipolar Disorder, as well as several anxiety disorders in a sample of the Baltimore Epidemiologic Catchment Area Survey Follow-up Study. Methods: We estimated lifetime prevalence and the risk of comorbidity for Major Depressive Disorder, Bipolar Disorder, Panic Disorder, Agoraphobia, Social Phobia, Obsessive Compulsive Disorder, Generalized Anxiety Disorder, Simple Phobia, Dysthymic Disorder. All subjects were evaluated by a psychiatrist using the Schedules for Clinical Assessment in Neuropsychiatry. In addition, we assessed the impact of the carrier status into the prevalence and comorbidity estimates of the aforementioned disorders. Results: A significant association was found between an increased risk for the lifetime prevalence of Panic Disorder and the 5-HTT “s” polymorphism (OR (95% CI): 3.10 (1.33; 7.27). A higher risk for lifetime prevalence of Panic Disorder and the 5-HTT “s” polymorphism was found in women carriers as compared to men(OR (95% CI): 3.54 (1.41; 8.91)). Panic Disorder had significant comorbidities with Alcohol Dependence, Alcohol Abuse, MDD, Bipolar Disorder, Agoraphobia, Social Phobia, OCD, Simple Phobia and Adjustment Disorder. These associations were higher in women as compared to men carriers. Comorbidities for Simple Phobia were highly significant in males for most anxiety disorders and MDD. Conclusions: There was a high prevalence of comorbidity amongst most of the anxiety disorders in this population. The effect of the 5HTT carrier status was only associated with an increment in the risk of having a Panic Disorder

'To live and die [for] Dixie': Irish civilians and the Confederate States of America

Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism

Development of an Acute and Highly Pathogenic Nonhuman Primate Model of Nipah Virus Infection

Nipah virus (NiV) is an enigmatic emerging pathogen that causes severe and often fatal neurologic and/or respiratory disease in both animals and humans. Amongst people, case fatality rates range between 40 and 75 percent and there are no vaccines or treatments approved for human use. Guinea pigs, hamsters, cats, ferrets, pigs and most recently squirrel monkeys (New World monkey) have been evaluated as animal models of human NiV infection, and with the exception of the ferret, no model recapitulates all aspects of NiV-mediated disease seen in humans. To identify a more viable nonhuman primate (NHP) model, we examined the pathogenesis of NiV in African green monkeys (AGM). Exposure of eight monkeys to NiV produced a severe systemic infection in all eight animals with seven of the animals succumbing to infection. Viral RNA was detected in the plasma of challenged animals and occurred in two of three subjects as a peak between days 7 and 21, providing the first clear demonstration of plasma-associated viremia in NiV experimentally infected animals and suggested a progressive infection that seeded multiple organs simultaneously from the initial site of virus replication. Unlike the cat, hamster and squirrel monkey models of NiV infection, severe respiratory pathology, neurological disease and generalized vasculitis all manifested in NiV-infected AGMs, providing an accurate reflection of what is observed in NiV-infected humans. Our findings demonstrate the first consistent and highly pathogenic NHP model of NiV infection, providing a new and critical platform in the evaluation and licensure of either passive and active immunization or therapeutic strategies for human use

Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans

The electrocardiographic QRS duration, a measure of ventricular depolarization and conduction, is associated with cardiovascular mortality. While single nucleotide polymorphisms (SNPs) associated with QRS duration have been identified at 22 loci in populations of European descent, the genetic architecture of QRS duration in non-European populations is largely unknown. We therefore performed a genome-wide association study (GWAS) meta-analysis of QRS duration in 13,031 African Americans from ten cohorts and a transethnic GWAS meta-analysis with additional results from populations of European descent. In the African American GWAS, a single genome-wide significant SNP association was identified (rs3922844, P = 4 × 10−14) in intron 16 of SCN5A, a voltage-gated cardiac sodium channel gene. The QRS-prolonging rs3922844 C allele was also associated with decreased SCN5A RNA expression in human atrial tissue (P = 1.1 × 10−4). High density genotyping revealed that the SCN5A association region in African Americans was confined to intron 16. Transethnic GWAS meta-analysis identified novel SNP associations on chromosome 18 in MYL12A (rs1662342, P = 4.9 × 10−8) and chromosome 1 near CD1E and SPTA1 (rs7547997, P = 7.9 × 10−9). The 22 QRS loci previously identified in populations of European descent were enriched for significant SNP associations with QRS duration in African Americans (P = 9.9 × 10−7), and index SNP associations in or near SCN5A, SCN10A, CDKN1A, NFIA, HAND1, TBX5 and SETBP1 replicated in African Americans. In summary, rs3922844 was associated with QRS duration and SCN5A expression, two novel QRS loci were identified using transethnic meta-analysis, and a significant proportion of QRS–SNP associations discovered in populations of European descent were transferable to African Americans when adequate power was achieved

Why is Pollution from U.S. Manufacturing Declining? The Roles of Trade, Regulation, Productivity, and Preferences

Between 1990 and 2008, emissions of the most common air pollutants from U.S. manufacturing fell by 60 percent, even as real U.S. manufacturing output grew substantially. This paper develops a quantitative model to explain how changes in trade, environmental regulation, productivity, and consumer preferences have contributed to these reductions in pollution emissions. We estimate the model’s key parameters using administrative data on plant-level production and pollution decisions. We then combine these estimates with detailed historical data to provide a model-driven decomposition of the causes of the observed pollution changes. Finally, we compare the model-driven decomposition to a statistical decomposition. The model and data suggest three findings. First, the fall in pollution emissions is due to decreasing pollution per unit output within narrowly defined products, rather than to changes in the types of products produced or changes to the total quantity of manufacturing output. Second, the implicit pollution tax that rationalizes firm production and abatement behavior more than doubled between 1990 and 2008. Third, environmental regulation explains 75 percent or more of the observed reduction in pollution emissions from manufacturing

HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials.

BACKGROUND: Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target. METHODS: We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis. FINDINGS: Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05-0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18-0·43), waist circumference (0·32 cm, 0·16-0·47), plasma insulin concentration (1·62%, 0·53-2·72), and plasma glucose concentration (0·23%, 0·02-0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00-1·05); the rs12916-T allele association was consistent (1·06, 1·03-1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18-1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10-0·38 in all trials; 0·33 kg, 95% CI 0·24-0·42 in placebo or standard care controlled trials and -0·15 kg, 95% CI -0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9-6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06-1·18 in all trials; 1·11, 95% CI 1·03-1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04-1·22 in intensive-dose vs moderate dose trials). INTERPRETATION: The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition. FUNDING: The funding sources are cited at the end of the paper

Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the Clavicipitaceae reveals dynamics of alkaloid Loci

The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (Epichloë and Neotyphodium species), which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some—including the infamous ergot alkaloids—have potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne), and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses

Bostonia: The Boston University Alumni Magazine. Volume 6

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs