Radiative corrections to the semileptonic and hadronic Higgs-boson decays H -> W W/Z Z -> 4 fermions

The radiative corrections of the strong and electroweak interactions are calculated for the Higgs-boson decays H -> WW/ZZ -> 4f with semileptonic or hadronic four-fermion final states in next-to-leading order. This calculation is improved by higher-order corrections originating from heavy-Higgs-boson effects and photonic final-state radiation off charged leptons. The W- and Z-boson resonances are treated within the complex-mass scheme, i.e. without any resonance expansion or on-shell approximation. The calculation essentially follows our previous study of purely leptonic final states. The electroweak corrections are similar for all four-fermion final states; for integrated quantities they amount to some per cent and increase with growing Higgs-boson mass M_H, reaching 7-8% at M_H \sim 500 GeV. For distributions, the corrections are somewhat larger and, in general, distort the shapes. Among the QCD corrections, which include corrections to interference contributions of the Born diagrams, only the corrections to the squared Born diagrams turn out to be relevant. These contributions can be attributed to the gauge-boson decays, i.e. they approximately amount to \alpha_s/\pi for semileptonic final states and 2\alpha_s/\pi for hadronic final states. The discussed corrections have been implemented in the Monte Carlo event generator PROPHECY4F.Comment: 29 pages, LaTeX, 30 postscript figure

Understanding the chronology and occupation dynamics of oversized pit houses in the southern Brazilian highlands

A long held view about the occupation of southern proto-Je pit house villages of the southern Brazilian highlands is that these sites represent cycles of long-term abandonment and reoccupation. However, this assumption is based on an insufficient number of radiocarbon dates for individual pit houses. To address this problem, we conducted a programme of comprehensive AMS radiocarbon dating and Bayesian modelling at the deeply stratified oversized pit Houe 1, Baggio 1 site (Cal. A.D. 1395-1650), Campo Belo do Sul, Santa Catarina, Brazil. The straigraphy of House 1 revealed an unparalleled sequence of twelve well preserved floors evidencing a major change in occupation dynamics including five completely burnt collapsed roofs. The results of the radiocarbon dating allowed us to understand for the first time the occupation dynamics of an oversized pit house in the southern Brazilian highlands. The Bayesian model demonstrates that House 1 was occupied for over two centuries with no evidence of major periods of abandonment, calling into question previous models of long-term abandonment. In addition, the House 1 sequence allowed us to tie transformations in ceramic style and lithic technology to an absolute chronology. Finally, we can provide new evidence that the emergence of oversized domestic structures is a relatively recent phenomenon among the southern proto-Je. As monumental pit houses start to be bulit, small pit houses continue to be inhabited, evidencing emerging disparities in domestic architecture after AD 1000. Our research shows the importance of programmes of intensive dating of individual structures to understand occupation dynamcis and site permanence, and challenges long held assumptions that the southern Brazilian highlands were home to marginal cultures in the context of lowland South America

The Role of the st313-td Gene in Virulence of Salmonella Typhimurium ST313

Multidrug-resistant Salmonella enterica serovar Typhimurium ST313 has emerged in sub-Saharan Africa causing severe infections in humans. Therefore, it has been speculated that this specific sequence type, ST313, carries factors associated with increased pathogenicity. We assessed the role in virulence of a gene with a yet unknown function, st313-td, detected in ST313 through comparative genomics. Additionally, the structure of the genomic island ST313-GI, harbouring the gene was determined. The gene st313-td was cloned into wild type S. Typhimurium 4/74 (4/74-C) as well as knocked out in S. Typhimurium ST313 02-03/002 (Δst313-td) followed by complementation (02-03/002-C). Δst313-td was less virulent in mice following i.p. challenge than the wild type and this phenotype could be partly complemented in trans, indicating that st313-td plays a role during systemic infection. The gene st313-td was shown not to affect invasion of cultured epithelial cells, while the absence of the gene significantly affects uptake and intracellular survival within macrophages. The gene st313-td was proven to be strongly associated to invasiveness, harboured by 92.5% of S. Typhimurium blood isolates (n = 82) and 100% of S. Dublin strains (n = 50) analysed. On the contrary, S. Typhimurium isolates of animal and food origin (n = 82) did not carry st313-td. Six human, non-blood isolates of S. Typhimurium from Belarus, China and Nepal harboured the gene and belonged to sequence types ST398 and ST19. Our data showed a global presence of the st313-td gene and in other sequence types than ST313. The gene st313-td was shown to be expressed during logarithmic phase of growth in 14 selected Salmonella strains carrying the gene. This study reveals that st313-td plays a role in S. Typhimurium ST313 pathogenesis and adds another chapter to understanding of the virulence of S. Typhimurium and in particular of the emerging sequence type ST313

Nothing Lasts Forever: Environmental Discourses on the Collapse of Past Societies

The study of the collapse of past societies raises many questions for the theory and practice of archaeology. Interest in collapse extends as well into the natural sciences and environmental and sustainability policy. Despite a range of approaches to collapse, the predominant paradigm is environmental collapse, which I argue obscures recognition of the dynamic role of social processes that lie at the heart of human communities. These environmental discourses, together with confusion over terminology and the concepts of collapse, have created widespread aporia about collapse and resulted in the creation of mixed messages about complex historical and social processes

Accelerated and Improved Quantification of Lymphocytic Choriomeningitis Virus (LCMV) Titers by Flow Cytometry

Lymphocytic choriomeningitis virus (LCMV), a natural murine pathogen, is a member of the Arenavirus family, may cause atypical meningitis in humans, and has been utilized extensively as a model pathogen for the study of virus-induced disease and immune responses. Historically, viral titers have been quantified by a standard plaque assay, but for non-cytopathic viruses including LCMV this requires lengthy incubation, so results cannot be obtained rapidly. Additionally, due to specific technical constraints of the plaque assay including the visual detection format, it has an element of subjectivity along with limited sensitivity. In this study, we describe the development of a FACS-based assay that utilizes detection of LCMV nucleoprotein (NP) expression in infected cells to determine viral titers, and that exhibits several advantages over the standard plaque assay. We show that the LCMV-NP FACS assay is an objective and reproducible detection method that requires smaller sample volumes, exhibits a ∼20-fold increase in sensitivity to and produces results three times faster than the plaque assay. Importantly, when applied to models of acute and chronic LCMV infection, the LCMV-NP FACS assay revealed the presence of infectious virus in samples that were determined to be negative by plaque assay. Therefore, this technique represents an accelerated, enhanced and objective alternative method for detection of infectious LCMV that is amenable to adaptation for other viral infections as well as high throughput diagnostic platforms

A randomized, placebo-controlled, double-blind, prospective trial to evaluate the effect of vildagliptin in new-onset diabetes mellitus after kidney transplantation

<p>Abstract</p> <p>Background</p> <p>New-onset diabetes mellitus after transplantation (NODAT), a frequent and serious complication after transplantation, is associated with decreased graft and patient survival. Currently, it is diagnosed and treated primarily according to existing guidelines for type II diabetes. To date, only a few trials have studied antidiabetic drugs in patients with NODAT. Vildagliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor that improves pancreatic islet function by enhancing both α- and β-cell responsiveness to increased blood glucose. Experimental data show potential protective effects of DPP-4 inhibitors on islet function after exogenous stress stimuli including immunosuppressants. Therefore, the therapy of NODAT with this class of compounds seems attractive. At present, vildagliptin is used to treat type II diabetes as monotherapy or in combination with other antidiabetic drugs, since that it efficiently decreases glycated hemoglobin (HbA1c) values. Additionally, vildagliptin has been shown to be safe in patients with moderately impaired kidney function. This study will evaluate the safety and efficacy of vildagliptin monotherapy in renal transplant recipients with recently diagnosed NODAT.</p> <p>Methods/Design</p> <p>This study is a randomized, placebo-controlled, double-blind, prospective phase II trial. Using the results of routinely performed oral glucose tolerance tests (OGTT) in stable renal transplant patients at our center, we will recruit patients without a history of diabetes and a 2 h glucose value surpassing 200 mg/dl (11.1 mmol/l). They are randomized to receive either 50 mg vildagliptin or placebo once daily. A total of 32 patients with newly diagnosed NODAT will be included. The primary endpoint is the difference in the 2 h glucose value between baseline and the repeated OGTT performed 3 months after treatment start, compared between the vildagliptin- and the placebo-group. Secondary endpoints include changes in HbA1c and fasting plasma glucose (FPG). The safety of vildagliptin in renal transplant patients will be assessed by the number of symptomatic hypoglycemic episodes (glucose <72 mg/dl or 4 mmol/l), the number of adverse events, and possible medication-associated side-effects.</p> <p>Discussion</p> <p>NODAT is a severe complication after kidney transplantation. Few trials have assessed the safety and efficacy of antidiabetic drugs for these patients. The purpose of this study is to assess the safety and efficacy of vildagliptin in renal transplant patients with NODAT.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00980356</p

Surgical clipping is still a good choice for the treatment of paraclinoid aneurysms

ABSTRACT Paraclinoid aneurysms are lesions located adjacent to the clinoid and ophthalmic segments of the internal carotid artery. In recent years, flow diverter stents have been introduced as a better endovascular technique for treatment of these aneurysms. Method From 2009 to 2014, a total of 43 paraclinoid aneurysms in 43 patients were surgically clipped. We retrospectively reviewed the records of these patients to analyze clinical outcomes. Results Twenty-six aneurysms (60.5%) were ophthalmic artery aneurysms, while 17 were superior hypophyseal artery aneurysms (39.5%). The extradural approach to the clinoid process was used to clip these aneurysms. One hundred percent of aneurysms were clipped (complete exclusion in 100% on follow-up angiography). The length of follow-up ranged from 1 to 60 months (mean, 29.82 months). Conclusion Surgical clipping continues to be a good option for the treatment of paraclinoid aneurysms

Brain regions essential for improved lexical access in an aged aphasic patient: a case report

BACKGROUND: The relationship between functional recovery after brain injury and concomitant neuroplastic changes is emphasized in recent research. In the present study we aimed to delineate brain regions essential for language performance in aphasia using functional magnetic resonance imaging and acquisition in a temporal sparse sampling procedure, which allows monitoring of overt verbal responses during scanning. CASE PRESENTATION: An 80-year old patient with chronic aphasia (2 years post-onset) was investigated before and after intensive language training using an overt picture naming task. Differential brain activation in the right inferior frontal gyrus for correct word retrieval and errors was found. Improved language performance following therapy was mirrored by increased fronto-thalamic activation while stability in more general measures of attention/concentration and working memory was assured. Three healthy age-matched control subjects did not show behavioral changes or increased activation when tested repeatedly within the same 2-week time interval. CONCLUSION: The results bear significance in that the changes in brain activation reported can unequivocally be attributed to the short-term training program and a language domain-specific plasticity process. Moreover, it further challenges the claim of a limited recovery potential in chronic aphasia, even at very old age. Delineation of brain regions essential for performance on a single case basis might have major implications for treatment using transcranial magnetic stimulation

Unusual Dengue Virus 3 Epidemic in Nicaragua, 2009

The four dengue virus serotypes (DENV1–4) cause the most prevalent mosquito-borne viral disease affecting humans worldwide. In 2009, Nicaragua experienced the largest dengue epidemic in over a decade, marked by unusual clinical presentation, as observed in two prospective studies of pediatric dengue in Managua. From August 2009–January 2010, 212 dengue cases were confirmed among 396 study participants at the National Pediatric Reference Hospital. In our parallel community-based cohort study, 170 dengue cases were recorded in 2009–10, compared to 13–65 cases in 2004–9. In both studies, significantly more patients experienced “compensated shock” (poor capillary refill plus cold extremities, tachycardia, tachypnea, and/or weak pulse) in 2009–10 than in previous years (42.5% [90/212] vs. 24.7% [82/332] in the hospital study (p<0.001) and 17% [29/170] vs. 2.2% [4/181] in the cohort study (p<0.001). Signs of poor peripheral perfusion presented significantly earlier (1–2 days) in 2009–10 than in previous years according to Kaplan-Meier survival analysis. In the hospital study, 19.8% of subjects were transferred to intensive care, compared to 7.1% in previous years – similar to the cohort study. DENV-3 predominated in 2008–9, 2009–10, and 2010–11, and full-length sequencing revealed no major genetic changes from 2008–9 to 2010–11. In 2008–9 and 2010–11, typical dengue was observed; only in 2009–10 was unusual presentation noted. Multivariate analysis revealed only “2009–10” as a significant risk factor for Dengue Fever with Compensated Shock. Interestingly, circulation of pandemic influenza A-H1N1 2009 in Managua was shifted such that it overlapped with the dengue epidemic. We hypothesize that prior influenza A H1N1 2009 infection may have modulated subsequent DENV infection, and initial results of an ongoing study suggest increased risk of shock among children with anti-H1N1-2009 antibodies. This study demonstrates that parameters other than serotype, viral genomic sequence, immune status, and sequence of serotypes can play a role in modulating dengue disease outcome

Therapy-induced tumour secretomes promote resistance and tumour progression.

Drug resistance invariably limits the clinical efficacy of targeted therapy with kinase inhibitors against cancer. Here we show that targeted therapy with BRAF, ALK or EGFR kinase inhibitors induces a complex network of secreted signals in drug-stressed human and mouse melanoma and human lung adenocarcinoma cells. This therapy-induced secretome stimulates the outgrowth, dissemination and metastasis of drug-resistant cancer cell clones and supports the survival of drug-sensitive cancer cells, contributing to incomplete tumour regression. The tumour-promoting secretome of melanoma cells treated with the kinase inhibitor vemurafenib is driven by downregulation of the transcription factor FRA1. In situ transcriptome analysis of drug-resistant melanoma cells responding to the regressing tumour microenvironment revealed hyperactivation of several signalling pathways, most prominently the AKT pathway. Dual inhibition of RAF and the PI(3)K/AKT/mTOR intracellular signalling pathways blunted the outgrowth of the drug-resistant cell population in BRAF mutant human melanoma, suggesting this combination therapy as a strategy against tumour relapse. Thus, therapeutic inhibition of oncogenic drivers induces vast secretome changes in drug-sensitive cancer cells, paradoxically establishing a tumour microenvironment that supports the expansion of drug-resistant clones, but is susceptible to combination therapy