Increased systemic inflammation is associated with cardiac and vascular dysfunction over the first 12 weeks of antiretroviral therapy among undernourished, HIV-infected adults in Southern Africa.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.INTRODUCTION: Persistent systemic inflammation is associated with mortality among undernourished, HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa, but the etiology of these deaths is not well understood. We hypothesized that greater systemic inflammation is accompanied by cardiovascular dysfunction over the first 12 weeks of ART. METHODS: In a prospective cohort of 33 undernourished (body mass index <18.5 kg/m2) Zambian adults starting ART, we measured C-reactive protein (CRP), tumor necrosis factor-α receptor 1 (TNF-α R1), and soluble CD163 and CD14 at baseline and 12 weeks. An EndoPAT device measured the reactive hyperemia index (LnRHI; a measure of endothelial responsiveness), peripheral augmentation index (AI; a measure of arterial stiffness), and heart rate variability (HRV; a general marker of autonomic tone and cardiovascular health) at the same time points. We assessed paired changes in inflammation and cardiovascular parameters, and relationships independent of time point (adjusted for age, sex, and CD4+ T-cell count) using linear mixed models. RESULTS: Serum CRP decreased (median change -3.5 mg/l, p=0.02), as did TNF-α R1 (-0.31 ng/ml, p<0.01), over the first 12 weeks of ART. A reduction in TNF-α R1 over 12 weeks was associated with an increase in LnRHI (p=0.03), and a similar inverse relationship was observed for CRP and LnRHI (p=0.07). AI increased in the cohort as a whole over 12 weeks, and a reduction in sCD163 was associated with a rise in the AI score (p=0.04). In the pooled analysis of baseline and 12 week data, high CRP was associated with lower HRV parameters (RMSSD, p=0.01; triangular index, p<0.01), and higher TNF- α R1 accompanied lower HRV (RMSSD, p=0.07; triangular index, p=0.06). CONCLUSIONS: Persistent inflammation was associated with impaired cardiovascular health over the first 12 weeks of HIV treatment among undernourished adults in Africa, suggesting cardiac events may contribute to high mortality in this population.This work was supported by the Vanderbilt Meharry Center for AIDS Research (NIH grant number P30 AI54999); the NIH Fogarty International Center, Office of the Director, National Institutes of Health, National Heart, Blood, and Lung Institute, and National Institute of Mental Health, through the Vanderbilt-Emory-Cornell-Duke Consortium for Global Health Fellows (grant number R25 TW009337); the National Center for Advancing Translational Sciences (CTSA award number UL1TR000445) and the European and Developing Countries Clinical Trials Partnership (grant IP.2009.33011.004)

Assessing connectivity between an overlying aquifer and a coal seam gas resource using methane isotopes, dissolved organic carbon and tritium

Coal seam gas (CSG) production can have an impact on groundwater quality and quantity in adjacent or overlying aquifers. To assess this impact we need to determine the background groundwater chemistry and to map geological pathways of hydraulic connectivity between aquifers. In south-east Queensland (Qld), Australia, a globally important CSG exploration and production province, we mapped hydraulic connectivity between the Walloon Coal Measures (WCM, the target formation for gas production) and the overlying Condamine River Alluvial Aquifer (CRAA), using groundwater methane (CH4) concentration and isotopic composition (δ13C-CH4), groundwater tritium (3H) and dissolved organic carbon (DOC) concentration. A continuous mobile CH4 survey adjacent to CSG developments was used to determine the source signature of CH4 derived from the WCM. Trends in groundwater δ13C-CH4 versus CH4 concentration, in association with DOC concentration and 3H analysis, identify locations where CH4 in the groundwater of the CRAA most likely originates from the WCM. The methodology is widely applicable in unconventional gas development regions worldwide for providing an early indicator of geological pathways of hydraulic connectivity

Systematic review and meta-analysis of reduction in all-cause mortality from walking and cycling and shape of dose response relationship

BACKGROUND AND OBJECTIVE: Walking and cycling have shown beneficial effects on population risk of all-cause mortality (ACM). This paper aims to review the evidence and quantify these effects, adjusted for other physical activity (PA). DATA SOURCES: We conducted a systematic review to identify relevant studies. Searches were conducted in November 2013 using the following health databases of publications: Embase (OvidSP); Medline (OvidSP); Web of Knowledge; CINAHL; SCOPUS; SPORTDiscus. We also searched reference lists of relevant texts and reviews. STUDY ELIGIBILITY CRITERIA AND PARTICIPANTS: Eligible studies were prospective cohort design and reporting walking or cycling exposure and mortality as an outcome. Only cohorts of individuals healthy at baseline were considered eligible. STUDY APPRAISAL AND SYNTHESIS METHODS: Extracted data included study population and location, sample size, population characteristics (age and sex), follow-up in years, walking or cycling exposure, mortality outcome, and adjustment for other co-variables. We used random-effects meta-analyses to investigate the beneficial effects of regular walking and cycling. RESULTS: Walking (18 results from 14 studies) and cycling (8 results from 7 studies) were shown to reduce the risk of all-cause mortality, adjusted for other PA. For a standardised dose of 11.25 MET.hours per week (or 675 MET.minutes per week), the reduction in risk for ACM was 11% (95% CI = 4 to 17%) for walking and 10% (95% CI = 6 to 13%) for cycling. The estimates for walking are based on 280,000 participants and 2.6 million person-years and for cycling they are based on 187,000 individuals and 2.1 million person-years. The shape of the dose-response relationship was modelled through meta-analysis of pooled relative risks within three exposure intervals. The dose-response analysis showed that walking or cycling had the greatest effect on risk for ACM in the first (lowest) exposure interval. CONCLUSIONS AND IMPLICATIONS: The analysis shows that walking and cycling have population-level health benefits even after adjustment for other PA. Public health approaches would have the biggest impact if they are able to increase walking and cycling levels in the groups that have the lowest levels of these activities. REVIEW REGISTRATION: The review protocol was registered with PROSPERO (International database of prospectively registered systematic reviews in health and social care) PROSPERO 2013: CRD42013004266

Pattern-Sensitive Epilepsy. I: A Demonstration of a Spatial Frequency Selective Epileptic Response to Gratings

Rare individuals suffer epileptic seizures when they view certain images, particularly stripes. Contrast-threshold functions (the ability to see faint stripes of various widths) were determined for two pattern-sensitive brothers, and the epileptogenicity of various patterns was assessed for one of them. Sine wave grating contrast-detection thresholds for the two subjects were essentially normal, with lowest thresholds at approximately 2 cycles/ degree (c/deg). Epileptiform discharges occurred maximally at 5 c/deg with a 1-octave 50% bandwidth. Pattern epileptogenicity was increased by the addition of a third harmonic sine wave grating to its fundamental, but was unaffected by the phase relation of the two gratings. The frequency selectivity of epileptic responsiveness was quantitatively similar to a “spatial frequency channel.” Inhibitory interactions were not present. The findings suggest relations between the phenomena of pattern-sensitive epilepsy and hypothesized spatial frequency channels which merit further exploration. RESUMEN De manera excepcional, hay personas que pueden tener ataques epilÉpticos cuando ven ciertas imÁgenes, particularmente rayas. Se determinaron los umbrales para contrastes (la capacidad de ver rayas de diversas anchuras y muy tenues) en dos hermanos sensibles a patrones y se estableciÓ la epileptogeneidad de di versos patrones en uno de ellos. Los umbrales para contrastes fueron esencialmente normales en los dos sujetos cuando se utilizeÓ una rejilla hecha con ondas sinusoidales, siendo el umbral inferior unos 2 ciclos/ grado (c/deg). Descargas epileptiformes tuvieron lugar de modo mÁximo a 5 c/deg con una amplitud de banda del 50% de una octava. la capacidad epileptogÉnica del partÓn aumentÓ cuando se aÑadiÓ una tercera sinusoide armÓnica a la rejilla base pero esa capacidad no se viÓ alterada por la relaciÓn de fase entre las dos rejillas. La selectividad de la frecuencia de la respuesta epileptogÉnica fue cuantitativamente similar al “canal de frecuencia espacial”. No se observaron interacciones inhibitorias. Los hallazgos sugieren que hay relaciones entre la epilepsyÍa secundaria a patrones visuales y los hipotÉticos canales de frecuencia espacial, lo cual merece mÁs investigaciÓn.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65270/1/j.1528-1157.1980.tb04075.x.pd

Attaching metabolic expenditures to standard occupational classification systems: perspectives from time-use research

Abstract Background Traditionally, time-use data have been used to inform a broad range of economic and sociological research topics. One of the new areas in time-use research is the study of physical activity (PA) and physical activity energy expenditure (PAEE). Time-use data can be used to study PAEE by assigning MET values to daily activities using the Ainsworth Compendium of Physical Activities. Although most diarists record their daily activities accurately and in detail, they are only required to record their paid working hours, not the job-specific tasks they undertake. This makes it difficult to assign MET values to paid work episodes. Methods In this methodological paper, we explain how we addressed this problem by using the detailed information about respondents’ occupational status included in time-use survey household and individual questionnaires. We used the 2008 ISCO manual, a lexicon of the International Labour Organization of occupational titles and their related job-specific tasks. We first assigned a MET value to job-specific tasks using the Ainsworth compendium (2011) then calculated MET values for each of the 436 occupations in the ISCO-08 manual by averaging all job-specific MET values for each occupation. Results The ISCO-08 Major Groups of ‘elementary occupations’ and ‘craft and related trades workers’ are associated with high PAEE variation in terms of their job-specific MET values and together represented 21.6% of the Belgian working population in 2013. We recommend that these occupational categories should be prioritised for further in-depth research into occupational activity (OA). Conclusions We developed a clear and replicable procedure to calculate occupational activity for all ISCO-08 occupations. All of our calculations are attached to this manuscript which other researchers may use, replicate and refine

Simultaneous determination of wave speed and arrival time of reflected waves using the pressure-velocity loop

This is the post print version of the article. The official published version can be found at the link below.In a previous paper we demonstrated that the linear portion of the pressure–velocity loop (PU-loop) corresponding to early systole could be used to calculate the local wave speed. In this paper we extend this work to show that determination of the time at which the PU-loop first deviates from linearity provides a convenient way to determine the arrival time of reflected waves (Tr). We also present a new technique using the PU-loop that allows for the determination of wave speed and Tr simultaneously. We measured pressure and flow in elastic tubes of different diameters, where a strong reflection site existed at known distances away form the measurement site. We also measured pressure and flow in the ascending aorta of 11 anaesthetised dogs where a strong reflection site was produced through total arterial occlusion at four different sites. Wave speed was determined from the initial slope of the PU-loop and Tr was determined using a new algorithm that detects the sampling point at which the initial linear part of the PU-loop deviates from linearity. The results of the new technique for detecting Tr were comparable to those determined using the foot-to-foot and wave intensity analysis methods. In elastic tubes Tr detected using the new algorithm was almost identical to that detected using wave intensity analysis and foot-to-foot methods with a maximum difference of 2%. Tr detected using the PU-loop in vivo highly correlated with that detected using wave intensity analysis (r 2 = 0.83, P < 0.001). We conclude that the new technique described in this paper offers a convenient and objective method for detecting Tr, and allows for the dynamic determination of wave speed and Tr, simultaneously

Outcome Predictors of Pediatric Extracorporeal Cardiopulmonary Resuscitation

Extracorporeal cardiopulmonary resuscitation (ECPR) allows clinicians to potentially rescue pediatric patients unresponsive to traditional cardiopulmonary resuscitation (CPR). Clinical and laboratory variables predictive of survival to hospital discharge are beginning to emerge. In this retrospective, historical cohort case series, clinical, and laboratory data from 31 pediatric patients (<21 years of age) receiving ECPR from March 2000 to April 2006 at our university-affiliated, tertiary-care children’s hospital were statistically analyzed in an attempt to identify variables predictive of survival to hospital discharge. Seven patients survived to hospital discharge (23%), and 24 patients died. Survival was independent of gender, age, and CPR duration. ECPR survival was, however, associated with a lower pre-ECPR phosphorus concentration (P = 0.002) and a lower pre-ECPR creatinine concentration (P = 0.05). A classification tree analysis, using, in part, a pre-ECPR phosphorus concentration threshold and a CPR ABG base excess concentration threshold, yielded a 96% nominal accuracy of predicting survival to hospital discharge or death. A large, multicenter, prospective cohort study aimed at validating these predictive variables is needed to guide appropriate ECPR patient selection. This study reveals the potential survival benefit of ECPR for pediatric patients, regardless of CPR duration prior to ECPR cannulation

New mutations at the imprinted Gnas cluster show gene dosage effects of Gsα in postnatal growth and implicate XLαs in bone and fat metabolism, but not in suckling

The imprinted Gnas cluster is involved in obesity, energy metabolism, feeding behavior, and viability. Relative contribution of paternally expressed proteins XLαs, XLN1, and ALEX or a double dose of maternally expressed Gsα to phenotype has not been established. In this study, we have generated two new mutants (Ex1A-T-CON and Ex1A-T) at the Gnas cluster. Paternal inheritance of Ex1A-T-CON leads to loss of imprinting of Gsα, resulting in preweaning growth retardation followed by catch-up growth. Paternal inheritance of Ex1A-T leads to loss of imprinting of Gsα and loss of expression of XLαs and XLN1. These mice have severe preweaning growth retardation and incomplete catch-up growth. They are fully viable probably because suckling is unimpaired, unlike mutants in which the expression of all the known paternally expressed Gnasxl proteins (XLαs, XLN1 and ALEX) is compromised. We suggest that loss of ALEX is most likely responsible for the suckling defects previously observed. In adults, paternal inheritance of Ex1A-T results in an increased metabolic rate and reductions in fat mass, leptin, and bone mineral density attributable to loss of XLαs. This is, to our knowledge, the first report describing a role for XLαs in bone metabolism. We propose that XLαs is involved in the regulation of bone and adipocyte metabolism