AlleleCoder: a PERL script for coding co-dominant polymorphism data for PCA

A useful biological interpretation of diploid heterozygotes is in terms of the dose of the common allele (0, 1 or 2 copies). We have developed a PERL script that converts FASTA files into coded spreadsheets suitable for principal component analysis. In combination with R and R Commander, two- and three-dimensional plots can be generated for visualizing genetic relationships. Such plots are useful for characterizing plant genetic resources. This method nicely illustrated the spectrum of genetic diversity in tomato landraces and the varieties categorized according to human-mediated dispersa

Generalized AdS/CFT Dualities and Space-Time Symmetries of M/Superstring Theory

I review the relationship between AdS/CFT (anti-de Sitter / conformal field theory) dualities and the general theory of unitary lowest weight (ULWR) (positive energy) representations of non-compact space-time groups and supergroups. The ULWR's have the remarkable property that they can be constructed by tensoring some fundamental ULWR's (singletons or doubletons). Furthermore, one can go from the manifestly unitary compact basis of the ULWR's of the conformal group (Wigner picture) to the manifestly covariant coherent state basis (Dirac picture) labelled by the space-time coordinates. Hence every irreducible ULWR corresponds to a covariant field with a definite conformal dimension. These results extend to higher dimensional generalized spacetimes (superspaces) defined by Jordan (super) algebras and Jordan (super) triple systems. In particular, they extend to the ULWR's of the M-theory symmetry superalgebra OSp(1/32,R).Comment: Latex file, 11 pages; invited talk to appear in the Proceedings of the IXth Marcel Grossmann Meeting (Rome, July 2000

Vasoplegic Shock treated with Methylene Blue complicated by Severe Serotonin Syndrome.

Introduction: Management of severe vasoplegic shock in overdose can be very challenging. We describe a case of severe refractory vasodilatory shock in poisoning where methylene blue (MB) was used with success. Case Report. A 70kg 15-year-old male presented 1.5 hours post ingestion of a large polypharmacy overdose of quetiapine slow release 1.5g, quetiapine immediate release 12g, desvenlafaxine slow release 5.6g, venlafaxine 1050mg, amlodipine 290mg, ramipril 100mg, fluoxetine 560mg, promethazine 500mg and an unknown amount of lithium. He developed severe vasoplegic shock that was resistant to maximal doses of noradrenaline and vasopressin. MB was administered 6.5 hour post ingestion. Within 1 hour there was an improvement in his haemodynamic status and reduction of catecholamine requirements. Twelve hours post ingestion, he developed severe serotonin syndrome that lasted 5 days as a result of interaction between MB, a reversible monoamine oxidase inhibitor, and the antidepressants taken in overdose. MB had a calculated half-life of 38 hours. Conclusion MB is a useful second or third line strategy for severe drug induced vasodilatory shock, and may be potentially life-saving. Conversely, physicians should be aware that it can interact with other drugs and cause life-threatening serotonin syndrome. Lower doses or shorter durations may be wise in patients at risk of this interaction

Evaluating the impact of Mexico’s drug policy reforms on people who inject drugs in Tijuana, B.C., Mexico, and San Diego, CA, United States: a binational mixed methods research agenda

Background: Policymakers and researchers seek answers to how liberalized drug policies affect people who inject drugs (PWID). In response to concerns about the failing “war on drugs,” Mexico recently implemented drug policy reforms that partially decriminalized possession of small amounts of drugs for personal use while promoting drug treatment. Recognizing important epidemiologic, policy, and socioeconomic differences between the United States—where possession of any psychoactive drugs without a prescription remains illegal—and Mexico—where possession of small quantities for personal use was partially decriminalized, we sought to assess changes over time in knowledge, attitudes, behaviors, and infectious disease profiles among PWID in the adjacent border cities of San Diego, CA, USA, and Tijuana, Baja California, Mexico. Methods: Based on extensive binational experience and collaboration, from 2012–2014 we initiated two parallel, prospective, mixed methods studies: Proyecto El Cuete IV in Tijuana (n = 785) and the STAHR II Study in San Diego (n = 575). Methods for sampling, recruitment, and data collection were designed to be compatible in both studies. All participants completed quantitative behavioral and geographic assessments and serological testing (HIV in both studies; hepatitis C virus and tuberculosis in STAHR II) at baseline and four semi-annual follow-up visits. Between follow-up assessment visits, subsets of participants completed qualitative interviews to explore contextual factors relating to study aims and other emergent phenomena. Planned analyses include descriptive and inferential statistics for quantitative data, content analysis and other mixed-methods approaches for qualitative data, and phylogenetic analysis of HIV-positive samples to understand cross-border transmission dynamics. Results: Investigators and research staff shared preliminary findings across studies to provide feedback on instruments and insights regarding local phenomena. As a result, recruitment and data collection procedures have been implemented successfully, demonstrating the importance of binational collaboration in evaluating the impact of structural-level drug policy reforms on the behaviors, health, and wellbeing of PWID across an international border. Conclusions: Our prospective, mixed methods approach allows each study to be responsive to emerging phenomena within local contexts while regular collaboration promotes sharing insights across studies. The strengths and limitations of this approach may serve as a guide for other evaluations of harm reduction policies internationally

Genetic testing of children for adult-onset conditions: opinions of the British adult population and implications for clinical practice

This study set out to explore the attitudes of a representative sample of the British public towards genetic testing in children to predict disease in the future. We sought opinions about genetic testing for adult-onset conditions for which no prevention/treatment is available during childhood, and about genetic 'carrier' status to assess future reproductive risks. The study also examined participants' level of agreement with the reasons professional organisations give in favour of deferring such testing. Participants (n=2998) completed a specially designed questionnaire, distributed by email. Nearly half of the sample (47%) agreed that parents should be able to test their child for adult-onset conditions, even if there is no treatment or prevention at time of testing. This runs contrary to professional guidance about genetic testing in children. Testing for carrier status was supported by a larger proportion (60%). A child's future ability to decide for her/himself if and when to be tested was the least supported argument in favour of deferring testing.European Journal of Human Genetics advance online publication, 5 November 2014; doi:10.1038/ejhg.2014.221

Pandemic (H1N1) 2009 Surveillance in Marginalized Populations, Tijuana, Mexico

To detect early cases of pandemic (H1N1) 2009 infection, in 2009 we surveyed 303 persons from marginalized populations of drug users, sex workers, and homeless persons in Tijuana, Mexico. Six confirmed cases of pandemic (H1N1) 2009 were detected, and the use of rapid, mobile influenza testing was demonstrated

Elevated serum IL-10 is associated with severity of neonatal encephalopathy and adverse early childhood outcomes

BACKGROUND: Neonatal encephalopathy (NE) contributes substantially to child mortality and disability globally. We compared cytokine profiles in term Ugandan neonates with and without NE, with and without perinatal infection or inflammation and identified biomarkers predicting neonatal and early childhood outcomes. METHODS: In this exploratory biomarker study, serum IL-1α, IL-6, IL-8, IL-10, TNFα, and VEGF (<12 h) were compared between NE and non-NE infants with and without perinatal infection/inflammation. Neonatal (severity of NE, mortality) and early childhood (death or neurodevelopmental impairment to 2.5 years) outcomes were assessed. Predictors of outcomes were explored with multivariable linear and logistic regression and receiver-operating characteristic analyses. RESULTS: Cytokine assays on 159 NE and 157 non-NE infants were performed; data on early childhood outcomes were available for 150 and 129, respectively. NE infants had higher IL-10 (p < 0.001), higher IL-6 (p < 0.017), and lower VEGF (p < 0.001) levels. Moderate and severe NE was associated with higher IL-10 levels compared to non-NE infants (p < 0.001). Elevated IL-1α was associated with perinatal infection/inflammation (p = 0.013). Among NE infants, IL-10 predicted neonatal mortality (p = 0.01) and adverse early childhood outcome (adjusted OR 2.28, 95% CI 1.35-3.86, p = 0.002). CONCLUSIONS: Our findings support a potential role for IL-10 as a biomarker for adverse outcomes after neonatal encephalopathy. IMPACT: Neonatal encephalopathy is a common cause of child death and disability globally. Inflammatory cytokines are potential biomarkers of encephalopathy severity and outcome. In this Ugandan health facility-based cohort, neonatal encephalopathy was associated with elevated serum IL-10 and IL-6, and reduced VEGF at birth. Elevated serum IL-10 within 12 h after birth predicted severity of neonatal encephalopathy, neonatal mortality, and adverse early childhood developmental outcomes, independent of perinatal infection or inflammation, and provides evidence to the contribution of the inflammatory processes. Our findings support a role for IL-10 as a biomarker for adverse outcomes after neonatal encephalopathy in a sub-Saharan African cohort

Reducing harm from HIV/AIDS misconceptions among female sex workers in Tijuana and Ciudad Juarez, Mexico: A cross sectional analysis

Abstract Background HIV prevalence is increasing among female sex workers (FSWs) in Mexico’s Northern border region, who experience multiple occupational risks. Improving vulnerable populations’ education, empowerment, and access to preventive services are important components of harm reduction strategies. Given the increasing interest in adapting harm reduction principles from drug use to sex work and other public health responses to the HIV epidemic, we used a sex work harm reduction framework to guide our investigation of FSWs’ HIV knowledge. Methods From 2004–2006, FSWs aged ≥18 years in Tijuana and Ciudad Juarez participated in a behavioral intervention study and completed structured interviews. Measures included HIV knowledge assessment and factors within each domain of our theoretical framework for sex work harms: (1) socio-demographic factors that may lead to sex work, (2) sex work characteristics and behaviors that may lead to harm, and (3) mutually reinforcing harms that lead to sex work and result from it (e.g., drug abuse). Negative binomial regression identified factors independently associated with suboptimal HIV knowledge (i.e., incorrect responses during the HIV knowledge assessment). Results Among 924 FSWs, the median proportion of incorrect responses was nearly one third (28% incorrect). Examination of item responses revealed misconceptions regarding specific transmission and prevention mechanisms, including prevention of mother to child transmission. Suboptimal HIV knowledge was independently associated with older age, lower education, living in Tijuana (vs. Ciudad Juarez), inconsistent condom use for vaginal sex with male clients, and lacking prior HIV testing. Conclusions Our application of a sex work harm reduction framework to the study of FSWs’ HIV knowledge is an important first step in enhancing HIV prevention efforts in Northern Mexican border cities. Our findings imply that interventions should identify and discredit local HIV misconceptions to improve knowledge of specific HIV transmission routes and self-protective strategies (e.g., condom negotiation). Interventions will require materials appropriate for women from diverse socio-economic backgrounds and may benefit from innovative harm reduction approaches such as peer education and outreach