The deuteron: structure and form factors

A brief review of the history of the discovery of the deuteron in provided. The current status of both experiment and theory for the elastic electron scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic

Disruption of TLR3 Signaling Due to Cleavage of TRIF by the Hepatitis A Virus Protease-Polymerase Processing Intermediate, 3CD

Toll-like receptor 3 (TLR3) and cytosolic RIG-I-like helicases (RIG-I and MDA5) sense viral RNAs and activate innate immune signaling pathways that induce expression of interferon (IFN) through specific adaptor proteins, TIR domain-containing adaptor inducing interferon-β (TRIF), and mitochondrial antiviral signaling protein (MAVS), respectively. Previously, we demonstrated that hepatitis A virus (HAV), a unique hepatotropic human picornavirus, disrupts RIG-I/MDA5 signaling by targeting MAVS for cleavage by 3ABC, a precursor of the sole HAV protease, 3Cpro, that is derived by auto-processing of the P3 (3ABCD) segment of the viral polyprotein. Here, we show that HAV also disrupts TLR3 signaling, inhibiting poly(I:C)-stimulated dimerization of IFN regulatory factor 3 (IRF-3), IRF-3 translocation to the nucleus, and IFN-β promoter activation, by targeting TRIF for degradation by a distinct 3ABCD processing intermediate, the 3CD protease-polymerase precursor. TRIF is proteolytically cleaved by 3CD, but not by the mature 3Cpro protease or the 3ABC precursor that degrades MAVS. 3CD-mediated degradation of TRIF depends on both the cysteine protease activity of 3Cpro and downstream 3Dpol sequence, but not 3Dpol polymerase activity. Cleavage occurs at two non-canonical 3Cpro recognition sequences in TRIF, and involves a hierarchical process in which primary cleavage at Gln-554 is a prerequisite for scission at Gln-190. The results of mutational studies indicate that 3Dpol sequence modulates the substrate specificity of the upstream 3Cpro protease when fused to it in cis in 3CD, allowing 3CD to target cleavage sites not normally recognized by 3Cpro. HAV thus disrupts both RIG-I/MDA5 and TLR3 signaling pathways through cleavage of essential adaptor proteins by two distinct protease precursors derived from the common 3ABCD polyprotein processing intermediate

An average/deprivation/inequality (ADI) analysis of chronic disease outcomes and risk factors in Argentina

<p>Abstract</p> <p>Background</p> <p>Recognition of the global economic and epidemiological burden of chronic non-communicable diseases has increased in recent years. However, much of the research on this issue remains focused on individual-level risk factors and neglects the underlying social patterning of risk factors and disease outcomes.</p> <p>Methods</p> <p>Secondary analysis of Argentina's 2005 <it>Encuesta Nacional de Factores de Riesgo </it>(National Risk Factor Survey, <it>N </it>= 41,392) using a novel analytical strategy first proposed by the United Nations Development Programme (UNDP), which we here refer to as the Average/Deprivation/Inequality (ADI) framework. The analysis focuses on two risk factors (unhealthy diet and obesity) and one related disease outcome (diabetes), a notable health concern in Latin America. Logistic regression is used to examine the interplay between socioeconomic and demographic factors. The ADI analysis then uses the results from the logistic regression to identify the most deprived, the best-off, and the difference between the two ideal types.</p> <p>Results</p> <p>Overall, 19.9% of the sample reported being in poor/fair health, 35.3% reported not eating any fruits or vegetables in five days of the week preceding the interview, 14.7% had a BMI of 30 or greater, and 8.5% indicated that a health professional had told them that they have diabetes or high blood pressure. However, significant variation is hidden by these summary measures. Educational attainment displayed the strongest explanatory power throughout the models, followed by household income, with both factors highlighting the social patterning of risk factors and disease outcomes. As educational attainment and household income increase, the probability of poor health, unhealthy diet, obesity, and diabetes decrease. The analyses also point toward important provincial effects and reinforce the notion that both compositional factors (i.e., characteristics of individuals) and contextual factors (i.e., characteristics of places) are important in understanding the social patterning of chronic diseases.</p> <p>Conclusion</p> <p>The application of the ADI framework enables identification of the regions or groups worst-off for each outcome measure under study. This can be used to highlight the variation embedded within national averages; as such, it encourages a social perspective on population health indicators that is particularly attuned to issues of inequity. The ADI framework is an important tool in the evaluation of policies aiming to prevent or control chronic non-communicable diseases.</p

Depression and HIV in Botswana: A Population-Based Study on Gender-Specific Socioeconomic and Behavioral Correlates

Depression is a leading contributor to the burden of disease worldwide, a critical barrier to HIV prevention and a common serious HIV co-morbidity. However, depression screening and treatment are limited in sub-Saharan Africa, and there are few population-level studies examining the prevalence and gender-specific factors associated with depression.We conducted a cross-sectional population-based study of 18–49 year-old adults from five districts in Botswana with the highest prevalence of HIV-infection. We examined the prevalence of depressive symptoms, using a Hopkins Symptom Checklist for Depression (HSCL-D) score of ≥1.75 to define depression, and correlates of depression using multivariate logistic regression stratified by sex.Of 1,268 participants surveyed, 25.3% of women and 31.4% of men had depression. Among women, lower education (adjusted odds ratio [AOR] 2.07, 95% confidence interval [1.30–3.32]), higher income (1.77 [1.09–2.86]), and lack of control in sexual decision-making (2.35 [1.46–3.81]) were positively associated with depression. Among men, being single (1.95 [1.02–3.74]), living in a rural area (1.63 [1.02–2.65]), having frequent visits to a health provider (3.29 [1.88–5.74]), anticipated HIV stigma (fearing discrimination if HIV status was revealed) (2.04 [1.27–3.29]), and intergenerational sex (2.28 [1.17–4.41]) were independently associated with depression.Depression is highly prevalent in Botswana, and its correlates are gender-specific. Our findings suggest multiple targets for screening and prevention of depression and highlight the need to integrate mental health counseling and treatment into primary health care to decrease morbidity and improve HIV management efforts

Immunological Change in a Parasite-Impoverished Environment: Divergent Signals from Four Island Taxa

Dramatic declines of native Hawaiian avifauna due to the human-mediated emergence of avian malaria and pox prompted an examination of whether island taxa share a common altered immunological signature, potentially driven by reduced genetic diversity and reduced exposure to parasites. We tested this hypothesis by characterizing parasite prevalence, genetic diversity and three measures of immune response in two recently-introduced species (Neochmia temporalis and Zosterops lateralis) and two island endemics (Acrocephalus aequinoctialis and A. rimitarae) and then comparing the results to those observed in closely-related mainland counterparts. The prevalence of blood parasites was significantly lower in 3 of 4 island taxa, due in part to the absence of certain parasite lineages represented in mainland populations. Indices of genetic diversity were unchanged in the island population of N. temporalis; however, allelic richness was significantly lower in the island population of Z. lateralis while both allelic richness and heterozygosity were significantly reduced in the two island-endemic species examined. Although parasite prevalence and genetic diversity generally conformed to expectations for an island system, we did not find evidence for a pattern of uniformly altered immune responses in island taxa, even amongst endemic taxa with the longest residence times. The island population of Z. lateralis exhibited a significantly reduced inflammatory cell-mediated response while levels of natural antibodies remained unchanged for this and the other recently introduced island taxon. In contrast, the island endemic A. rimitarae exhibited a significantly increased inflammatory response as well as higher levels of natural antibodies and complement. These measures were unchanged or lower in A. aequinoctialis. We suggest that small differences in the pathogenic landscape and the stochastic history of mutation and genetic drift are likely to be important in shaping the unique immunological profiles of small isolated populations. Consequently, predicting the impact of introduced disease on the many other endemic faunas of the remote Pacific will remain a challenge

Global Analysis of Extracytoplasmic Stress Signaling in Escherichia coli

The Bae, Cpx, Psp, Rcs, and σE pathways constitute the Escherichia coli signaling systems that detect and respond to alterations of the bacterial envelope. Contributions of these systems to stress response have previously been examined individually; however, the possible interconnections between these pathways are unknown. Here we investigate the dynamics between the five stress response pathways by determining the specificities of each system with respect to signal-inducing conditions, and monitoring global transcriptional changes in response to transient overexpression of each of the effectors. Our studies show that different extracytoplasmic stress conditions elicit a combined response of these pathways. Involvement of the five pathways in the various tested stress conditions is explained by our unexpected finding that transcriptional responses induced by the individual systems show little overlap. The extracytoplasmic stress signaling pathways in E. coli thus regulate mainly complementary functions whose discrete contributions are integrated to mount the full adaptive response

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700