Phylogeographic and genome-wide investigations of Vietnam ethnic groups reveal signatures of complex historical demographic movements

The territory of present-day Vietnam was the cradle of one of the world’s earliest civilizations, and one of the first world regions to develop agriculture. We analyzed the mitochondrial DNA (mtDNA) complete control region of six ethnic groups and the mitogenomes from Vietnamese in The 1000 Genomes Project (1000G). Genome-wide data from 1000G (~55k SNPs) were also investigated to explore different demographic scenarios. All Vietnamese carry South East Asian (SEA) haplotypes, which show a moderate geographic and ethnic stratification, with the Mong constituting the most distinctive group. Two new mtDNA clades (M7b1a1f1 and F1f1) point to historical gene flow between the Vietnamese and other neighboring countries. Bayesian-based inferences indicate a time-deep and continuous population growth of Vietnamese, although with some exceptions. The dramatic population decrease experienced by the Cham 700 years ago (ya) fits well with the Nam tiến (“southern expansion”) southwards from their original heartland in the Red River Delta. Autosomal SNPs consistently point to important historical gene flow within mainland SEA, and add support to a main admixture event occurring between Chinese and a southern Asian ancestral composite (mainly represented by the Malay). This admixture event occurred ~800 ya, again coinciding with the Nam tiến.This study received support from the Instituto de Salud Carlos III (Proyecto de Investigación en Salud, Acción Estratégica en Salud: project GePEM ISCIII/PI16/01478/Cofinanciado FEDER) (AS) and project ReSVinext ISCIII/PI16/01569/Cofinanciado FEDER (FMT); Consellería de Sanidade, Xunta de Galicia (RHI07/2-intensificación actividad investigadora, PS09749 and 10PXIB918184PR), Instituto de Salud Carlos III (Intensificación de la actividad investigadora 2007–2012, PI16/01569), Fondo de Investigación Sanitaria (FIS; PI070069/PI1000540) del plan nacional de I+D+I and “fondos FEDER” (FMT), and 2016-PG071 Consolidación e Estructuración REDES 2016GI-1344 G3VIP (Grupo Gallego de Genética Vacunas Infecciones y Pediatría, ED341D R2016/021) (AS and FMT)S

Dedifferentiation of Immortalized Human Podocytes in Response to Transforming Growth Factor-β: A Model for Diabetic Podocytopathy

OBJECTIVE: Diabetic nephropathy is associated with dedifferentiation of podocytes, losing the specialized features required for efficient glomerular function and acquiring a number of profibrotic, proinflammatory, and proliferative features. These result from tight junction and cytoskeletal rearrangement, augmented proliferation, and apoptosis. RESEARCH DESIGN AND METHODS: Experiments were performed in conditionally immortalized human podocytes developed by transfection with the temperature-sensitive SV40-T gene. Cells were then cultured in the presence of transforming growth factor (TGF)-β1 or angiotensin II in the presence or absence of a selective inhibitor of the TGF-β type I receptor kinase, SB-431542. Gene and protein expression were then examined by real-time RT-PCR and immunofluorescence, and correlated with changes observed in vivo in experimental diabetes. RESULTS: Treatment of cells with TGF-β1 resulted in dynamic changes in their morphology, starting with retraction and shortening of foot processes and finishing with the formation of broad and complex tight junctions between adjacent podocytes. This dedifferentiation was also associated with dose- and time-dependent reduction in the expression of glomerular epithelial markers (nephrin, p-cadherin, zonnula occludens-1) and increased expression of mesenchymal markers (α-smooth muscle actin, vimentin, nestin), matrix components (fibronectin, collagen I, and collagen IV α3), cellular proliferation, and apoptosis. The induction of diabetes in mice was also associated with similar changes in morphology, protein expression, and proliferation in glomerular podocytes. CONCLUSIONS: In response to TGF-β and other TGF-dependent stimuli, mature podocytes undergo dedifferentiation that leads to effacement of foot processes, morphologic flattening, and increased formation of intercellular tight junctions. This simplification of their phenotype to a more embryonic form is also associated with reentry of mature podocytes into the cell cycle, which results in enhanced proliferation and apoptosis. These "pathoadaptive" changes are seen early in the diabetic glomerulus and ultimately contribute to albuminuria, glomerulosclerosis, and podocytopenia

Cost-efficiency assessment of Advanced Life Support (ALS) courses based on the comparison of advanced simulators with conventional manikins

<p>Abstract</p> <p>Background</p> <p>Simulation is an essential tool in modern medical education. The object of this study was to assess, in cost-effective measures, the introduction of new generation simulators in an adult life support (ALS) education program.</p> <p>Methods</p> <p>Two hundred fifty primary care physicians and nurses were admitted to ten ALS courses (25 students per course). Students were distributed at random in two groups (125 each). Group A candidates were trained and tested with standard ALS manikins and Group B ones with new generation emergency and life support integrated simulator systems.</p> <p>Results</p> <p>In group A, 98 (78%) candidates passed the course, compared with 110 (88%) in group B (p < 0.01). The total cost of conventional courses was €7689 per course and the cost of the advanced simulator courses was €29034 per course (p < 0.001). Cost per passed student was €392 in group A and €1320 in group B (p < 0.001).</p> <p>Conclusion</p> <p>Although ALS advanced simulator systems may slightly increase the rate of students who pass the course, the cost-effectiveness of ALS courses with standard manikins is clearly superior.</p

Geriatric patients' expectations of their physicians: findings from a tertiary care hospital in Pakistan

<p>Abstract</p> <p>Background</p> <p>Geriatric health is a neglected and under-explored area internationally and in Pakistan. We aimed to ascertain the expectations of the geriatric patients from their physicians and the factors associated with patient satisfaction in this particular age bracket.</p> <p>Methods</p> <p>A cross-sectional survey was carried out at a tertiary care teaching hospital in Karachi, Pakistan. Data collection was carried out via face-to-face interviews based on structured, pre-tested questionnaires. All consenting individuals aged 65 years or above were recruited into the study. Convenience sampling was used to draw the sample. The data was analyzed using SPSS version 16. Geriatric patient's expectations from physicians were elicited using a set of 11 questions that were graded on a scale of 1-3 where 1 = not important, 2 = important, 3 = very important.</p> <p>Results</p> <p>Three hundred and eighty geriatric patients were interviewed. The response rate of this study was 89.8%. The mean age of the respondents was 73.4 ± 6.8 years. Two hundred and forty eight respondents (65.3%) were female. Diabetes mellitus (53.7%), hypertension (59.5%), arthritis (40.5%) and renal disease (32.1%) were common ailments among geriatric patients. More than 50% of the patients were visiting their physicians once every two to three months. Discussing treatment options and letting patients make the final decision (79.2%), prescribing minimum possible medications (84.5%), physician's holistic knowledge about the spectrum of care issues for geriatric patients (79.2%), being given a realistic but optimistic picture of future health by physicians (85.5%) were ranked as very important expectations by patients from their physicians. Cumulative household income (p = 0.005), most important health complaint (p = 0.01) and frequency of experiencing health complaint (p < 0.001) emerged as independent predictors of the satisfaction of geriatric patients from care provided by physicians.</p> <p>Conclusion</p> <p>We have documented the expectations of the geriatric patients from their physicians in a developing country. Physicians belonging to all disciplines should keep these expectations in mind during clinical encounters with geriatric patients.</p

Belle II Technical Design Report

The Belle detector at the KEKB electron-positron collider has collected almost 1 billion Y(4S) events in its decade of operation. Super-KEKB, an upgrade of KEKB is under construction, to increase the luminosity by two orders of magnitude during a three-year shutdown, with an ultimate goal of 8E35 /cm^2 /s luminosity. To exploit the increased luminosity, an upgrade of the Belle detector has been proposed. A new international collaboration Belle-II, is being formed. The Technical Design Report presents physics motivation, basic methods of the accelerator upgrade, as well as key improvements of the detector.Comment: Edited by: Z. Dole\v{z}al and S. Un

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO