The Causes of HIV-Associated Cardiomyopathy: A Tale of Two Worlds

Antiretroviral therapy (ART) has transformed the clinical profile of human immunodeficiency virus (HIV) from an acute infection with a high mortality into a treatable, chronic disease. As a result, the clinical sequelae of HIV infection are changing as patients live longer. HIV-associated cardiomyopathy (HIVAC) is a stage IV, HIV-defining illness and remains a significant cause of morbidity and mortality among HIV-infected individuals despite ART. Causes and clinical manifestations of HIVAC depend on the degree of host immunosuppression. Myocarditis from direct HIV toxicity, opportunistic infections, and nutritional deficiencies are implicated in causing HIVAC when HIV viral replication is unchecked, whereas cardiac autoimmunity, chronic inflammation, and ART cardiotoxicity contribute to HIVAC in individuals with suppressed viral loads. The initiation of ART has dramatically changed the clinical manifestation of HIVAC in high income countries from one of severe, left ventricular systolic dysfunction to a pattern of subclinical cardiac dysfunction characterized by abnormal diastolic function and strain. In low and middle income countries, however, HIVAC is the most common HIV-associated cardiovascular disease. Clear diagnostic and treatment guidelines for HIVAC are currently lacking but should be prioritized given the global burden of HIVAC

Hard Two-Photon Contribution to Elastic Lepton-Proton Scattering: Determined by the OLYMPUS Experiment

The OLYMPUS collaboration reports on a precision measurement of the positron-proton to electron-proton elastic cross section ratio, $R_{2\gamma}$, a direct measure of the contribution of hard two-photon exchange to the elastic cross section. In the OLYMPUS measurement, 2.01~GeV electron and positron beams were directed through a hydrogen gas target internal to the DORIS storage ring at DESY. A toroidal magnetic spectrometer instrumented with drift chambers and time-of-flight scintillators detected elastically scattered leptons in coincidence with recoiling protons over a scattering angle range of $\approx 20\degree$ to $80\degree$. The relative luminosity between the two beam species was monitored using tracking telescopes of interleaved GEM and MWPC detectors at $12\degree$, as well as symmetric M{\o}ller/Bhabha calorimeters at $1.29\degree$. A total integrated luminosity of 4.5~fb$^{-1}$ was collected. In the extraction of $R_{2\gamma}$, radiative effects were taken into account using a Monte Carlo generator to simulate the convolutions of internal bremsstrahlung with experiment-specific conditions such as detector acceptance and reconstruction efficiency. The resulting values of $R_{2\gamma}$, presented here for a wide range of virtual photon polarization $0.456<\epsilon<0.978$, are smaller than some hadronic two-photon exchange calculations predict, but are in reasonable agreement with a subtracted dispersion model and a phenomenological fit to the form factor data.Comment: 5 pages, 3 figures, 2 table

The Causes of HIV-Associated Cardiomyopathy: A Tale of Two Worlds

Antiretroviral therapy (ART) has transformed the clinical profile of human immunodeficiency virus (HIV) from an acute infection with a high mortality into a treatable, chronic disease. As a result, the clinical sequelae of HIV infection are changing as patients live longer. HIV-associated cardiomyopathy (HIVAC) is a stage IV, HIV-defining illness and remains a significant cause of morbidity and mortality among HIV-infected individuals despite ART. Causes and clinical manifestations of HIVAC depend on the degree of host immunosuppression. Myocarditis from direct HIV toxicity, opportunistic infections, and nutritional deficiencies are implicated in causing HIVAC when HIV viral replication is unchecked, whereas cardiac autoimmunity, chronic inflammation, and ART cardiotoxicity contribute to HIVAC in individuals with suppressed viral loads. The initiation of ART has dramatically changed the clinical manifestation of HIVAC in high income countries from one of severe, left ventricular systolic dysfunction to a pattern of subclinical cardiac dysfunction characterized by abnormal diastolic function and strain. In low and middle income countries, however, HIVAC is the most common HIV-associated cardiovascular disease. Clear diagnostic and treatment guidelines for HIVAC are currently lacking but should be prioritized given the global burden of HIVAC

Racial Differences in Nontraditional Risk Factors Associated with Cardiovascular Conditions in Pregnancy Among U.S. Women Veterans

Background: Pregnancy-related cardiovascular (CV) conditions are important predictors of future cardiovascular disease (CVD). Nontraditional factors, such as depression and chronic stress, have been associated with CVD, but their role in pregnancy-related CVD conditions (pCVD) remains unknown. To determine the association between nontraditional factors and CV conditions in pregnancy, and to explore if this risk varies by race. Methods: Using data from a prospective study of pregnant women within the veterans affairs health system (COMFORT study), we described the prevalence of nontraditional factors (e.g., depression, post-traumatic stress disorder [PTSD], chronic stress) and used logistic regression to determine the association between nontraditional factors and pregnancy-related CV conditions (pre-eclampsia/eclampsia, gestational hypertension, gestation diabetes, or preterm delivery). Analyses were then stratified by race. Results: Among 706 enrollees, 26% had pregnancy-related CV conditions. These women had significantly higher rates of depression (62% vs. 45%, p \u3c 0.01), anxiety (50% vs. 37%, p = 0.01), PTSD (44% vs. 29%, p \u3c 0.01), and high stress levels before pregnancy (22% vs. 16%, p = 0.05) compared with women with normal pregnancies. Overall, these factors were not associated with increased adjusted odds of pCVD. Overall, Black women had disproportionately higher rates of prepregnancy hypertension compared with White women (22% vs. 6%, p \u3c 0.01). Conclusion: Women Veterans with pCVD are a high-risk group for future CVD, with disproportionately high rates of depression, anxiety, PTSD, and chronic stress. Racial disparities exist in pregnancy-related CV risk factors, which may further compound existing racial disparities in CVD among women Veterans

Pathological lymph node regression following neoadjuvant chemotherapy predicts recurrence and survival in esophageal adenocarcinoma: a multicentre study in the United Kingdom

Background: there is limited evidence regarding the prognostic effects of pathological lymph node (LN) regression after neoadjuvant chemotherapy for esophageal adenocarcinoma, and a definition of LN response is lacking. This study aimed to evaluate how LN regression influences survival after surgery for esophageal adenocarcinoma.Methods: multicentre cohort study of patients with esophageal adenocarcinoma treated with neoadjuvant chemotherapy followed by surgical resection at five high-volume centres in the United Kingdom. LNs retrieved at esophagectomy were examined for chemotherapy response and given a LN regression score (LNRS) – LNRS 1, complete response; 2, &lt;10% residual tumor; 3, 10-50% residual tumor; 4, &gt;50% residual tumor; 5, no response. Survival analysis was performed using Cox regression adjusting for confounders including primary tumor regression. The discriminatory ability of different LN response classifications to predict survival was evaluated using Akaike’s information criterion and Harrell’s C-index.Results: 17,930 LNs from 763 patients were examined. LN response classified as: complete LN-response (LNRS 1 ≥1 LN, no residual tumor in any LN; n=62, 8.1%), partial LN-response (LNRS 1-3 ≥1 LN, residual tumor ≥1 LN; n=155, 20.3%), poor/no LN-response (LNRS 4-5; n=303, 39.7%), or LN negative (no tumor/regression; n=243, 31.8%) demonstrated superior discriminatory ability. Mortality was reduced in patients with complete LN-response (HR 0.35, 95%CI 0.22-0.56), partial LN-response (HR 0.72, 95%CI 0.57-0.93) or negative LNs (HR 0.32 95%CI 0.25-0.42) compared to those with poor/no LN-response. Primary tumor regression and LN regression were discordant in 165 patients (21.9%).Conclusion: pathological LN regression following neoadjuvant chemotherapy was a strong prognostic factor and provides important information beyond pathological TNM staging and primary tumor regression grading. LN regression should be included as standard in the pathological reporting of esophagectomy specimens.<br/

Evolutionary accounts of human behavioural diversity

Human beings persist in an extraordinary range of ecological settings, in the process exhibiting enormous behavioural diversity, both within and between populations. People vary in their social, mating and parental behaviour and have diverse and elaborate beliefs, traditions, norms and institutions. The aim of this theme issue is to ask whether, and how, evolutionary theory can help us to understand this diversity. In this introductory article, we provide a background to the debate surrounding how best to understand behavioural diversity using evolutionary models of human behaviour. In particular, we examine how diversity has been viewed by the main subdisciplines within the human evolutionary behavioural sciences, focusing in particular on the human behavioural ecology, evolutionary psychology and cultural evolution approaches. In addition to differences in focus and methodology, these subdisciplines have traditionally varied in the emphasis placed on human universals, ecological factors and socially learned behaviour, and on how they have addressed the issue of genetic variation. We reaffirm that evolutionary theory provides an essential framework for understanding behavioural diversity within and between human populations, but argue that greater integration between the subfields is critical to developing a satisfactory understanding of diversity