Phylogenetic analysis of hepatitis C virus isolates from hemodialysis patients

Phylogenetic analysis of hepatitis C virus isolates from hemodialysis patients. A high prevalence of hepatitis C virus (HCV) infection has been reported in hemodialysis patients. Main risk factors for transmission are previous blood transfusions and possibly nosocomial infections within the dialytic environment. In the present study 224 hemodialysis patients from the same department were tested for the presence of anti-HCV antibodies and HCV-RNA. The presence of anti-HCV in hemodialysis patients was correlated with a history of more than 10 blood transfusions (P = 0.001) and with a duration of hemodialysis treatment for more than 10 years (P = 0.001). The issue of possible patient-to-patient infection was addressed by sequence analysis of all HCV-RNA positive hemodialysis patients (N = 14) together with a control panel of HCV isolates from 56 unrelated non-hemodialysis patients with hepatitis C from the same geographical area. Subsequent phylogenetic analysis of nucleotide sequences obtained from the 5′-noncoding region and the nonstructural NS-5 region of the HCV genome revealed that only two hemodialysis patients were infected by a highly related HCV isolate. The remaining HCV-RNA positive hemodialysis patients including those without previous blood transfusions were all infected by phylogenetically-distant HCV isolates, providing evidence against a nosocomial transmission route. The data of the present study show that molecular epidemiological techniques are important to investigate the issue of nosocomial infection. In our hemodialysis unit patient-to-patient infection appears uncommon and draws attention towards other possible (such as, blood products such as human serum albumin, immunoglobulins) or even yet unrecognized transmission routes

A Community in Life and Death: The Late Neolithic Megalithic Tomb at Alto de Reinoso (Burgos, Spain)

The analysis of the human remains from the megalithic tomb at Alto de Reinoso represents the widest integrative study of a Neolithic collective burial in Spain. Combining archaeology, osteology, molecular genetics and stable isotope analysis (87Sr/86Sr, δ15N, δ13C) it provides a wealth of information on the minimum number of individuals, age, sex, body height, pathologies, mitochondrial DNA profiles, kinship relations, mobility, and diet. The grave was in use for approximately one hundred years around 3700 cal BC, thus dating from the Late Neolithic of the Iberian chronology. At the bottom of the collective tomb, six complete and six partial skeletons lay in anatomically correct positions. Above them, further bodies represented a subsequent and different use of the tomb, with almost all of the skeletons exhibiting signs of manipulation such as missing skeletal parts, especially skulls. The megalithic monument comprised at least 47 individuals, including males, females, and subadults, although children aged 0–6 years were underrepresented. The skeletal remains exhibited a moderate number of pathologies, such as degenerative joint diseases, healed fractures, cranial trauma, and a low intensity of caries. The mitochondrial DNA profiles revealed a pattern pointing to a closely related local community with matrilineal kinship patterns. In some cases adjacent individuals in the bottom layer showed familial relationships. According to their strontium isotope ratios, only a few individuals were likely to have spent their early childhood in a different geological environment, whilst the majority of individuals grew up locally. Carbon and nitrogen isotope analysis, which was undertaken to reconstruct the dietary habits, indicated that this was a homogeneous group with egalitarian access to food. Cereals and small ruminants were the principal sources of nutrition. These data fit in well with a lifestyle typical of sedentary farming populations in the Spanish Meseta during this period of the Neolithi

Psychosocial primary care – what patients expect from their General Practitioners A cross-sectional trial

BACKGROUND: Psychosocial Primary Care (PPC) is a model of service delivery for patients with mental disorders and psychosocial problems which was established in Germany in 1987. This study was performed as part of the evaluation of a PPC training program. We investigated patients' expectations of the psychosocial treatment offered by GPs trained in PPC. METHODS: Ten general practitioners trained in PPC were randomly selected. Two hundred and twenty patients were surveyed in the waiting room regarding their expectations concerning psychological treatment. RESULTS: Eighty-five per cent of patients could envisage making use of psychosocial treatments. Counselling by the GP was considered most important (65%). Fifty-four per cent of patients indicated that there was sufficient counselling, but further distinctions revealed dissatisfaction with both the extent and content of the counselling. Lack of time was the most frequent reason (53%) cited for insufficient counselling. A willingness to discuss the psychological aspects of illness was exhibited by between 55% (current illness) and 79% of patients. Two-thirds of patients believed that discussing psychological aspects and counselling by the doctor could exert a healing effect or contribute to symptomatic improvement in physical illnesses. Younger patients and patients with experience in psychotherapy expected referral to mental health services. CONCLUSIONS: Primary care patients desire and accept psychological treatment from their GP. Training in psychosocial competence in primary care should be offered more frequently

Massive migration from the steppe is a source for Indo-European languages in Europe

We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost four hundred thousand polymorphisms. Enrichment of these positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies and to obtain new insights about the past. We show that the populations of western and far eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, ~8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary, and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a ~24,000 year old Siberian6 . By ~6,000-5,000 years ago, a resurgence of hunter-gatherer ancestry had occurred throughout much of Europe, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but from a population of Near Eastern ancestry. Western and Eastern Europe came into contact ~4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced ~3/4 of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least ~3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for the theory of a steppe origin of at least some of the Indo-European languages of Europe

A Novel Diagnostic Target in the Hepatitis C Virus Genome

Christian Drosten and colleagues develop, validate, and make openly available a prototype hepatitis C virus assay based on the conserved 3' X-tail element, with potential for clinical use in developing countries

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Anatomy of the sign-problem in heavy-dense QCD

QCD at finite densities of heavy quarks is investigated using the density-of-states method. The phase factor expectation value of the quark determinant is calculated to unprecedented precision as a function of the chemical potential. Results are validated using those from a reweighting approach where the latter can produce a significant signalto-noise ratio. We confirm the particle–hole symmetry at low temperatures, find a strong sign problem at intermediate values of the chemical potential, and an inverse Silver Blaze feature for chemical potentials close to the onset value: here, the phase-quenched theory underestimates the density of the full theory

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure