Boosting of HIV Envelope Cd4 Binding Site Antibodies with Long Variable Heavy Third Complementarity Determining Region in the Randomized Double Blind Rv305 Hiv-1 Vaccine Trial

The canary pox vector and gp120 vaccine (ALVAC-HIV and AIDSVAX B/E gp120) in the RV144 HIV-1 vaccine trial conferred an estimated 31% vaccine efficacy. Although the vaccine Env AE.A244 gp120 is antigenic for the unmutated common ancestor of V1V2 broadly neutralizing antibody (bnAbs), no plasma bnAb activity was induced. The RV305 (NCT01435135) HIV-1 clinical trial was a placebo-controlled randomized double-blinded study that assessed the safety and efficacy of vaccine boosting on B cell repertoires. HIV-1- uninfected RV144 vaccine recipients were reimmunized 6–8 years later with AIDSVAX B/E gp120 alone, ALVAC-HIV alone, or a combination of ALVAC-HIV and AIDSVAX B/E gp120 in the RV305 trial. Env-specific post-RV144 and RV305 boost memory B cell VH mutation frequencies increased from 2.9% post-RV144 to 6.7% post-RV305. The vaccine was well tolerated with no adverse events reports

Corruption in migration management: a network perspective

This paper explores the relation between networks as an emerging mode of public governance and corruption. Adopting the theoretical lens of actor-network theory (ANT), the paper investigates an Italian episode of corruption related to the awarding of government contracts for the management of the Mineo’s CARA, the Europe's largest reception centre for migrants. The analysis shows that a governance network may turn corruption itself into a network where abuse of power can proliferate thanks to the opacity resulting from the multiplicity of actors, interactions, and fragmentation characterizing the governance system

A Mediterranean Low-Glycemic-Load Diet alone or in Combination with a Medical Food Improves Insulin Sensitivity and Reduces Inflammation in Women with Metabolic Syndrome

Aim: To determine the effects of a Mediterranean-style low-glycemic load diet alone or in combination with a medical food (MF) on insulin resistance and inflammation in women with metabolic syndrome (MetS). Study design: Two groups, Parallel study with control. Place and Duration of Study: Department of Nutritional Sciences, University of Connecticut, Storrs, CT; Department of Emergency Medicine, University of Florida, Jacksonville, FL; Department of Medicine, University of California, Irvine, CA. The study was carried out from September of 2009 to May 2010. Methodology: Eighty three women (20-75 y) with MetS. Participants were randomly allocated to consume diet alone (control group) or the diet plus the MF (MF group) for 12 wk. Body composition was measured at baseline, week 8 and week 12 by use of bioelectrical impedance in all participants while Dual-emission X-ray absorptiometry was used for 37 of the subjects. Insulin resistance, plasma insulin, leptin, adiponectin and the inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), adhesion molecules, sICAM-1 and sVCAM-1, were measured at the same time points. Results: Independent of group allocation, women had decreases in body mass index (p \u3c 0.0001) and body and trunk fat (p \u3c 0.0001). Plasma insulin, insulin resistance, and leptin were also significantly decreased over time (p \u3c 0.0001), while plasma adiponectin levels did not change. Regarding inflammatory markers, significant reductions were found in TNF-α (p \u3c 0.0001) and sICAM-1 levels (p \u3c 0.001), but not in IL-6 or sVCAM-1. At 12 wk, sICAM was reduced only in the MF group (

Análise crítica da dietoterapia anti-obesidade: caminho a uma posição SAN

Un aspecto controvertido del abordaje terapéutico de la obesidad es la selección del plan dietoterápico más efectivo. Existe consenso acerca de la necesidad de que éste sea hipocalórico, como aspecto fundamental del tratamiento. Sin embargo, la comunidad científica experimenta un intenso debate respecto de qué tipo de dieta resulta más eficaz, ya sea en términos de proporción de macronutrientes como de valor calórico total, para alcanzar y mantener un descenso de peso significativo. Aunque el estilo de vida es universalmente aceptado como eje del abordaje del sobrepeso, aún no existen estrategias efectivas para mejorar la escasa adherencia a las dietas en el mediano y largo plazo. Esto genera la proliferación de dietas heterodoxas que prometen resultados mágicos y no están sustentadas en la evidencia científica. El plan alimentario ideal debería ser balanceado, placentero, sostenible en el tiempo y generar consecuencias positivas, más allá del peso corporal. El Grupo de Trabajo de Obesidad de la Sociedad Argentina de Nutrición se propuso llevar adelante una revisión crítica de la bibliografía disponible respecto de los beneficios, riesgos y evidencias de las dietas más difundidas en la actualidad. Esta revisión tiene como meta servir como marco teórico para la generación de una toma de posición al respecto por parte de la Sociedad Argentina de Nutrición.One controversial aspect of the therapeutic approach to obesity is the selection of the most effective dietotherapic plan. There is consensus that it should be hypocaloric as a basic feature. However, there is strong debate in the scientific community about which type of diet is more effective (in terms of macronutrients proportion or total caloric value) to reach and maintain a significant weight loss. Although lifestyle is universally accepted as the main pillar of obesity treatment, there is still no optimal strategy that helps improving mid- and long-term adherence to diets. This leads to a proliferation of heterodox diets that promote magic results and are not based on scientific evidence. The ideal dietary plan should be balanced, pleasant, sustainable and also able to produce positive consequences beyond body weight. The Obesity Workgroup of the Sociedad Argentina de Nutrición (Argentinian Society for Nutrition, SAN) decided to carry out a critical revision of the available bibliography on the benefits, risks and evidences of today's most widespread diets. The aim of this revision was to serve as a theoretical framework for the conception of SAN's official position on this matter.Um aspecto controvertido da abordagem terapêutica da obesidade é a escolha do plano dietoterápico mais efetivo. Existe um consenso sobre a necessidade de que o mesmo seja hipocalórico, como aspecto fundamental do tratamento. No entanto, a comunidade científica experimenta um intenso debate em relação ao tipo de dieta que resulta mais eficaz, seja em termos de proporção de macronutrientes ou de valor calórico total, para alcançar e manter uma perda de peso significativa. Ainda que o estilo de vida seja universalmente aceito como eixe da abordagem do sobrepeso, ainda não existem estratégias efetivas para melhorar a escassa adesão às dietas a médio e longo prazo. Isto gera a proliferação de dietas heterodoxas que prometem resultados mágicos e não estão sustentadas na evidência científica. O plano alimentício ideal deveria ser balanceado, prazeroso, sustentável no tempo e gerar consequências positivas, independente do peso corporal. O Grupo de Trabalho de Obesidade da Sociedade Argentina de Nutrição se propôs levar adiante uma revisão científica da bibliografia disponível em relação aos benefícios, riscos e evidências das dietas mais difundidas atualmente. Esta revisão tem como objetivo servir como marco teórico para a geração de uma toma de posição a respeito por parte da Sociedade Argentina de Nutrição.Fil: Katz, Mónica. Sociedad Argentina de Nutrición. Grupo de Trabajo de Obesidad; ArgentinaFil: Cappelletti, Ana María. Sociedad Argentina de Nutrición. Grupo de Trabajo de Obesidad; ArgentinaFil: Viñuales, Martín. Sociedad Argentina de Nutrición. Grupo de Trabajo de Obesidad; ArgentinaFil: de la Plaza, Marcela. Sociedad Argentina de Nutrición. Grupo de Trabajo de Obesidad; ArgentinaFil: Langellotti, Alicia. Sociedad Argentina de Nutrición. Grupo de Trabajo de Obesidad; ArgentinaFil: Lerotich, Vesna. Sociedad Argentina de Nutrición. Grupo de Trabajo de Obesidad; ArgentinaFil: Aguirre Ackerman, Marianela. Sociedad Argentina de Nutrición. Grupo de Trabajo de Obesidad; ArgentinaFil: Anger, Vanesa. Sociedad Argentina de Nutrición. Grupo de Trabajo de Obesidad; ArgentinaFil: Armeno, Marisa. Sociedad Argentina de Nutrición. Grupo de Trabajo de Obesidad; ArgentinaFil: Bertoloti, Daniela. Sociedad Argentina de Nutrición. Grupo de Trabajo de Obesidad; ArgentinaFil: Cortegoso, Inés. Sociedad Argentina de Nutrición. Grupo de Trabajo de Obesidad; ArgentinaFil: Giannini, Martín. Sociedad Argentina de Nutrición. Grupo de Trabajo de Obesidad; ArgentinaFil: Harwicz, Paola. Sociedad Argentina de Nutrición. Grupo de Trabajo de Obesidad; ArgentinaFil: Kawior, Inés. Sociedad Argentina de Nutrición. Grupo de Trabajo de Obesidad; ArgentinaFil: Mayer, Marcos Alejandro. Sociedad Argentina de Nutrición. Grupo de Trabajo de Obesidad; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pentreath, Carolina. Sociedad Argentina de Nutrición. Grupo de Trabajo de Obesidad; Argentin

Knowledge to Serve the City: Insights from an Emerging Knowledge-Action Network to Address Vulnerability and Sustainability in San Juan, Puerto Rico

This paper presents initial efforts to establish the San Juan Urban Long-Term Research Area Exploratory (ULTRA-Ex), a long-term program aimed at developing transdisciplinary social-ecological system (SES) research to address vulnerability and sustainability for the municipality of San Juan. Transdisciplinary approaches involve the collaborations between researchers, stakeholders, and citizens to produce socially-relevant knowledge and support decision-making. We characterize the transdisciplinary arrangement emerging in San Juan ULTRA-Ex as a knowledge-action network composed of multiple formal and informal actors (e.g., scientists, policymakers, civic organizations and other stakeholders) where knowledge, ideas, and strategies for sustainability are being produced, evaluated, and validated. We describe in this paper the on-the-ground social practices and dynamics that emerged from developing a knowledge-action network in our local context. Specifically, we present six social practices that were crucial to the development of our knowledge-action network: 1) understanding local framings; 2) analyzing existing knowledge-action systems in the city; 3) framing the social-ecological research agenda; 4) collaborative knowledge production and integration; 5) boundary objects and practices; and 6) synthesis, application, and adaptation. We discuss key challenges and ways to move forward in building knowledge-action networks for sustainability. Our hope is that the insights learned from this process will stimulate broader discussions on how to develop knowledge for urban sustainability, especially in tropical cities where these issues are under-explored

Low HDL cholesterol is associated with increased atherogenic lipoproteins and insulin resistance in women classified with metabolic syndrome

Both metabolic syndrome (MetS) and elevated LDL cholesterol (LDL-C) increase the risk for cardiovascular disease (CVD). We hypothesized that low HDL cholesterol (HDL-C) would further increase CVD risk in women having both conditions. To assess this, we recruited 89 women with MetS (25-72 y) and LDL-C ≥ 2.6 mmol/L. To determine whether plasma HDL-C concentrations were associated with dietary components, circulating atherogenic particles, and other risk factors for CVD, we divided the subjects into two groups: high HDL-C (H-HDL) (≥ 1.3 mmol/L, n = 32) and low HDL-C (L-HDL) (< 1.3 mmol/L, n = 57). Plasma lipids, insulin, adiponectin, apolipoproteins, oxidized LDL, Lipoprotein(a), and lipoprotein size and subfractions were measured, and 3-d dietary records were used to assess macronutrient intake. Women with L-HDL had higher sugar intake and glycemic load (P < 0.05), higher plasma insulin (P < 0.01), lower adiponectin (P < 0.05), and higher numbers of atherogenic lipoproteins such as large VLDL (P < 0.01) and small LDL (P < 0.001) than the H-HDL group. Women with L-HDL also had larger VLDL and both smaller LDL and HDL particle diameters (P < 0.001). HDL-C was positively correlated with LDL size (r = 0.691, P < 0.0001) and HDL size (r = 0.606, P < 0.001), and inversely correlated with VLDL size (r = -0.327, P < 0.01). We concluded that L-HDL could be used as a marker for increased numbers of circulating atherogenic lipoproteins as well as increased insulin resistance in women who are already at risk for CVD

The modulating effect of education on semantic interference during healthy aging

Aging has traditionally been related to impairments in name retrieval. These impairments have usually been explained by a phonological transmission deficit hypothesis or by an inhibitory deficit hypothesis. This decline can, however, be modulated by the educational level of the sample. This study analyzed the possible role of these approaches in explaining both object and face naming impairments during aging. Older adults with low and high educational level and young adults with high educational level were asked to repeatedly name objects or famous people using the semantic-blocking paradigm. We compared naming when exemplars were presented in a semantically homogeneous or in a semantically heterogeneous context. Results revealed significantly slower rates of both face and object naming in the homogeneous context (i.e., semantic interference), with a stronger effect for face naming. Interestingly, the group of older adults with a lower educational level showed an increased semantic interference effect during face naming. These findings suggest the joint work of the two mechanisms proposed to explain age-related naming difficulties, i.e., the inhibitory deficit and the transmission deficit hypothesis. Therefore, the stronger vulnerability to semantic interference in the lower educated older adult sample would possibly point to a failure in the inhibitory mechanisms in charge of interference resolution, as proposed by the inhibitory deficit hypothesis. In addition, the fact that this interference effect was mainly restricted to face naming and not to object naming would be consistent with the increased age-related difficulties during proper name retrieval, as suggested by the transmission deficit hypothesis.This research was supported by grants PSI2013-46033-P to A.M., PSI2015-65502-C2-1-P to M.T.B., PCIN-2015-165-C02-01 to D.P., PSI2017-89324-C2-1-P to DP from the Spanish Ministry of Economy and Competitiveness (http://www.mineco.gob.es/)

Utilization of mechanical power and associations with clinical outcomes in brain injured patients: a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

Background: There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes. Methods: In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale ≤ 12 before intubation) who required mechanical ventilation (MV) ≥ 24&nbsp;h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS). Results: We included 1217 patients (mean age 51.2&nbsp;years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9&nbsp;J/min [IQR 9.2-15.1], 13&nbsp;J/min [IQR 10-17], and 14&nbsp;J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9&nbsp;J/min, aRR at 17&nbsp;J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22). Conclusions: Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation

COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms.

Funder: Bundesministerium für Bildung und ForschungFunder: Bundesministerium für Bildung und Forschung (BMBF)We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective

Utilization of mechanical power and associations with clinical outcomes in brain injured patients. a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

BackgroundThere is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes.MethodsIn this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale &lt;= 12 before intubation) who required mechanical ventilation (MV) &gt;= 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS).ResultsWe included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2-15.1], 13 J/min [IQR 10-17], and 14 J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22).ConclusionsExposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation