Obesity as a risk factor for severe influenza-like illness

Background: Obesity was recognized as in independent risk factor for influenza during the 2009 H1N1 influenza pandemic. Objectives: We evaluated the association between body mass index (BMI) and influenza-like illness (ILI) during two non-pandemic influenza seasons (2003–2004 and 2004–2005) and during the spring and fall waves of the 2009 H1N1 pandemic. Methods: Adults with severe (inpatient) and mild (outpatient) ILI were compared to those without ILI using a case-cohort design. The study was nested among those insured by a single health insurance company, receiving care from a large multispecialty practice. Data were collected from insurance claims and the electronic health record. The primary exposure was obesity (BMI ≥ 30·0 kg/m2). Results: Across three seasons, the crude and adjusted ORs for obesity and severe ILI were 1·65 (95% CI 1·31, 2·08) and 1·23 (95% CI 0·97, 1·57), respectively. An association was observed for those aged 20–59 years (adjusted OR 1·92, 95% CI 1·26, 2·90), but not for those 60 and older (adjusted OR 1·08, 95% CI 0·80, 1·46). The adjusted ORs for obesity and severe ILI in 2003–2004, 2004–2005, and during H1N1 were 1·14 (95% CI 0·80, 1·64), 1·24 (95% CI 0·86, 1·79), and 1·76 (95% CI 0·91, 3·42), respectively. Among those with a Charlson Comorbidity Index score of zero, the adjusted ORs for 2003–2004, 2004–2005, and H1N1 were 1·60 (95% CI 0·93, 2·76), 1·43 (95% CI 0·80, 2·56), and 1·90 (95% CI 0·68, 5·27), respectively. Conclusions: Our results suggest a small to moderate association between obesity and hospitalized ILI among adults

Unification via intermediate symmetry breaking scales with the quartification gauge group

The idea of quark-lepton universality at high energies has been introduced as a natural extension to the standard model. This is achieved by endowing leptons with new degrees of freedom -- leptonic colour, an analogue of the familiar quark colour. Grand and partially unified models which utilise this new gauge symmetry SU(3)_\ell have been proposed in the context of the quartification gauge group SU(3)^4. Phenomenologically successful gauge coupling constant unification without supersymmetry has been demonstrated for cases where the symmetry breaking leaves a residual SU(2)_\ell unbroken. Though attractive, these schemes either incorporate ad hoc discrete symmetries and non-renormalisable mass terms, or achieve only partial unification. We show that grand unified models can be constructed where the quartification group can be broken fully [i.e. no residual SU(2)_\ell] to the standard model gauge group without requiring additional discrete symmetries or higher dimension operators. These models also automatically have suppressed nonzero neutrino masses. We perform a systematic analysis of the renormalisation-group equations for all possible symmetry breaking routes from SU(3)^4 --> SU(3)_q x SU(2)_L x U(1)_Y. This analysis indicates that gauge coupling unification can be achieved for several different symmetry breaking patterns and we outline the requirements that each gives on the unification scale. We also show that the unification scenarios of those models which leave a residual SU(2)_\ell symmetry are not unique. In both symmetry breaking cases, some of the scenarios require new physics at the TeV scale, while others do not allow for new TeV phenomenology in the fermionic sector.Comment: 25 page

Pharmacological eEF2K activation promotes cell death and inhibits cancer progression.

Activation of the elongation factor 2 kinase (eEF2K) leads to the phosphorylation and inhibition of the elongation factor eEF2, reducing mRNA translation rates. Emerging evidence indicates that the regulation of factors involved in protein synthesis may be critical for controlling diverse biological processes including cancer progression. Here we show that inhibitors of the HIV aspartyl protease (HIV-PIs), nelfinavir in particular, trigger a robust activation of eEF2K leading to the phosphorylation of eEF2. Beyond its anti-viral effects, nelfinavir has antitumoral activity and promotes cell death. We show that nelfinavir-resistant cells specifically evade eEF2 inhibition. Decreased cell viability induced by nelfinavir is impaired in cells lacking eEF2K. Moreover, nelfinavir-mediated anti-tumoral activity is severely compromised in eEF2K-deficient engrafted tumors in vivo Our findings imply that exacerbated activation of eEF2K is detrimental for tumor survival and describe a mechanism explaining the anti-tumoral properties of HIV-PIs

Building Psychosocial Assets And Wellbeing Among Adolescent Girls: A Randomized Controlled Trial

We conducted a randomized controlled trial of a 5-month resilience-based program (Girls First Resilience Curriculum or RC) among 2308 rural adolescent girls at 57 government schools in Bihar, India. Local women with at least a 10th grade education served as group facilitators. Girls receiving RC improved more (vs. controls) on emotional resilience, self-efficacy, social-emotional assets, psychological wellbeing, and social wellbeing. Effects were not detected on depression. There was a small, statistically significant negative effect on anxiety (though not likely clinically significant). Results suggest psychosocial assets and wellbeing can be improved for girls in high-poverty, rural schools through a brief school-day program. To our knowledge, this is one of the largest developing country trials of a resilience-based school-day curriculum for adolescents. (C) 2015 The Authors. Published by Elsevier Ltd on behalf of The Foundation for Professionals in Services for Adolescents. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Comparison of two- and three-dimensional echocardiography with cineventriculography for measurement of left ventricular volume in patients

AbstractObjectives. We compared two- and three-dimensional echocardiopaphy with cineventriculography for measurement of left ventricular volume in patients.Background. Three-dimensional echocardiography has been shown to be highly accurate and superior to two-dimensional echocardiography in measuring left ventricular volume in vitro. However, there has been little comparison of the two methods in patients.Methods. Two- and three-dimensional echocardiography were performed in 35 patients (mean age 48 years) 1 to 3 h before left ventricular cineventriculography. Three-dimensional echocardiography used an acoustic spatial locator to register image position. Volume was computed using a polyhedral surface reconstruction algorithm based on multiple nonparallel, unevenly spaced short-axis cross sections. Two-dimensional echocardiography used the apical biplane summation of disks method. Single-plane cineventriculographic volumes were calculated using the summation of disks algorithm. The methods were compared by linear regression and a limits of agreement analysis. For the latter, systematic error was assessed by the mean of the deferences (cineventriculography minus echocardiography), and the limits of agreement were defined as ±2 SD from the mean difference.Results. Three-dimensional echocardiographic volumes demonstrated excellent correlation (end-diastole r = 0.97; end-systole r = 0.98) with cineventriculography. Standard errors of the estimate were approximately half those of two-dimensional echocardiography (end-diastole ±11.0 ml vs. ±21.5 ml; end-systole ±10.2 ml vs. ±17.0 ml). By limits of agreement analysis the end-diastolic mean diferences for two- and three-dimensional echocardiography were 21.1 and 12.9 ml, respectively. The limits of agreement (±2 SD) were ±54.0 and ±24.8 ml, respectively. For end-systole, comparable improvement was obtained by three-dimensional echocardiography. Results for ejection fraction by the two methods were similar.Conclusions. Three-dimensional echocardiography correlates highly with cineventriculography for estimation of ventricular volumes in patients and has approximately half the variability of two-dimensional echocardiography for these measurements. On the basis of this study, three-dimensional echocardiography is the preferred echocardiographic technique for measurement of ventricular volume. Three-dimensional echocardiography is equivalent to two-dimensional echocardiography for measuring ejection fraction

Assessment of left atrial volume before and after pulmonary thromboendarterectomy in chronic thromboembolic pulmonary hypertension.

BackgroundImpaired left ventricular diastolic filling is common in chronic thromboembolic pulmonary hypertension (CTEPH), and recent studies support left ventricular underfilling as a cause. To investigate this further, we assessed left atrial volume index (LAVI) in patients with CTEPH before and after pulmonary thromboendarterectomy (PTE).MethodsForty-eight consecutive CTEPH patients had pre- & post-PTE echocardiograms and right heart catheterizations. Parameters included mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index, LAVI, & mitral E/A ratio. Echocardiograms were performed 6 ± 3 days pre-PTE and 10 ± 4 days post-PTE. Regression analyses compared pre- and post-PTE LAVI with other parameters.ResultsPre-op LAVI (mean 19.0 ± 7 mL/m2) correlated significantly with pre-op PVR (R = -0.45, p = 0.001), mPAP (R = -0.28, p = 0.05) and cardiac index (R = 0.38, p = 0.006). Post-PTE, LAVI increased by 18% to 22.4 ± 7 mL/m2 (p = 0.003). This change correlated with change in PVR (765 to 311 dyne-s/cm5, p = 0.01), cardiac index (2.6 to 3.2 L/min/m2, p = 0.02), and E/A (.95 to 1.44, p = 0.002).ConclusionIn CTEPH, smaller LAVI is associated with lower cardiac output, higher mPAP, and higher PVR. LAVI increases by ~20% after PTE, and this change correlates with changes in PVR and mitral E/A. The rapid increase in LAVI supports the concept that left ventricular diastolic impairment and low E/A pre-PTE are due to left heart underfilling rather than inherent left ventricular diastolic dysfunction

Five-dimensional Trinification Improved

We present improved models of trinification in five dimensions. Unified symmetry is broken by a combination of orbifold projections and a boundary Higgs sector. The latter can be decoupled from the theory, realizing a Higgsless limit in which the scale of exotic massive gauge fields is set by the compactification radius. Electroweak Higgs doublets are identified with the fifth components of gauge fields and Yukawa interactions arise via Wilson loops. The result is a simple low-energy effective theory that is consistent with the constraints from proton decay and gauge unification.Comment: 13 pages LaTeX. v2: reference adde

Impairment of both IRE1 expression and XBP1 activation is a hallmark of GCB DLBCL and contributes to tumor growth.

The endoplasmic reticulum kinase inositol-requiring enzyme 1 (IRE1) and its downstream target X-box-binding protein 1 (XBP1) drive B-cell differentiation toward plasma cells and have been shown to contribute to multiple myeloma development; yet, little is known of the role of this pathway in diffuse large B-cell lymphoma (DLBCL). Here, we show that in the germinal center B-cell-like (GCB) DLBCL subtype, IRE1 expression is reduced to a level that prevents XBP1 activation. Gene expression profiles indicated that, in GCB DLBCL cancer samples, expression of IRE1 messenger RNA was inversely correlated with the levels and activity of the epigenetic repressor, histone methyltransferase enhancer of zeste homolog 2 (EZH2). Correspondingly, in GCB-derived cell lines, the IRE1 promoter carried increased levels of the repressive epigenetic mark histone 3 lysine 27 trimethylation. Pharmacological inhibition of EZH2 erased those marks and restored IRE1 expression and function in vitro and in vivo. Moreover, reconstitution of the IRE1-signaling pathway, by expression of the XBP1-active form, compromised GCB DLBCL tumor growth in a mouse xenograft cancer model. These findings indicate that IRE1-XBP1 downregulation distinguishes GCB DLBCL from other DLBCL subtypes and contributes to tumor growth

Fostering Emotional, Social, Physical And Educational Wellbeing In Rural India: The Methods Of A Multi-Arm Randomized Controlled Trial Of Girls First

Background: There are 600 million girls in low and middle income countries (LMICs), many of whom are at great risk for poor health and education. There is thus great need for programs that can effectively improve wellbeing for these girls. Although many interventions have been developed to address these issues, most focus on health and education without integrating attention to social and emotional factors. This omission is unfortunate, as nascent evidence indicates that these factors are closely related to health and education. This paper describes the methods of a 4-arm randomized controlled trial among 3,560 adolescent girls in rural Bihar, India that tested whether adding an intervention targeting social-emotional issues (based on a “resilience framework”) to an adolescent health intervention would improve emotional, social, physical, and educational wellbeing to a greater extent than its components and a control group. Study arms were: (1) Girls First, a combination of the Girls First Resilience Curriculum (RC) and the Girls First Health Curriculum (HC); (2) Girls First Resilience Curriculum (RC) alone; (3) Girls First Health Curriculum (HC) alone; and (4) a school-as-usual control group (SC). Methods: Seventy-six schools were randomized (19 per condition) and 74 local women with a tenth grade education were trained and monitored to facilitate the program. Quantitative data were collected from 3,560 girls over 4 assessment points with very low rates of participant attrition. Qualitative assessments were conducted with a subset of 99 girls and 27 facilitators. Results and conclusions: In this article, we discuss guiding principles that facilitated trial implementation, including integrating diverse local and non-local sources of knowledge, focusing on flexibility of planning and implementation, prioritizing systematic measurement selection, and striking a balance between scientific rigor and real-world feasibility