The role of external broadcasting in a closed political system

This article investigates the role and impact of external broadcasting (radio and television) on a closed political system, through the example of the two post-war German states: the West German Federal Republic of Germany (FRG) and the East German German Democratic Republic (GDR). The aim is to debunk myths about the influence of external broadcasting on the events that led to German reunification in 1990. The study follows a historical approach and discusses what role external media played during the years of a divided Germany. The findings are based on several historical sources, research reports from the 1950s and 1960s and over 100 biographical interviews with former residents of the German Democratic Republic (GDR). The article analyses the impact of external broadcasting on citizens and the political elite in times of crisis as well as during everyday life

The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis.

The recently completed European trial of interferon beta-1b (IFN beta -1b) in patients with secondary progressive multiple sclerosis (SP multiple sclerosis) has given an opportunity to assess the impact of treatment on cerebral atrophy using serial MRI. Unenhanced T-1-weighted brain imaging was acquired in a subgroup of 95 patients from five of the European centres; imaging was performed at 6-month intervals from month 0 to month 36. A blinded observer measured cerebral volume on four contiguous 5 mm cerebral hemisphere slices at each time point, using an algorithm with a high level of reproducibility and automation. There was a significant and progressive reduction in cerebral volume in both placebo and treated groups, with a mean reduction of 3.9 and 2.9%, respectively, by month 36 (P = 0.34 between groups). Exploratory subgroup analyses indicated that patients without gadolinium (Gd) enhancement at the baseline had a greater reduction of cerebral volume in the placebo group (mean reduction at month 36: placebo 5.1%, IFN beta -1b 1.8%, P < 0.05) whereas those with Gd-enhancing lesions showed a trend to greater reduction of cerebral volume if the patient was on IFN<beta>-1b (placebo 2.6%, IFN beta -1b, 3.7%; P > 0.05). These results are consistent with ongoing tissue loss in both arms of this study of secondary progressive multiple sclerosis. This finding is concordant with previous observations that disease progression, although delayed, is not halted by IFN beta. The different pattern seen in patients with and without baseline gadolinium enhancement suggests that part of the cerebral volume reduction observed in IFN beta -treated patients may be due to the anti-inflammatory/antioedematous effect of the drug. Longer periods of observation and larger groups of patients may be needed to detect the effects of treatment on cerebral atrophy in this population of patients with advanced disease

Methodological bias in cluster randomised trials

Background: Cluster randomised trials can be susceptible to a range of methodological problems. These problems are not commonly recognised by many researchers. In this paper we discuss the issues that can lead to bias in cluster trials. Methods: We used a sample of cluster randomised trials from a recent review and from a systematic review of hip protectors. We compared the mean age of participants between intervention groups in a sample of 'good' cluster trials with a sample of potentially biased trials. We also compared the effect sizes, in a funnel plot, between hip protector trials that used individual randomisation compared with those that used cluster randomisation. Results: There is a tendency for cluster trials, with evidence methodological biases, to also show an age imbalance between treatment groups. In a funnel plot we show that all cluster trials show a large positive effect of hip protectors whilst individually randomised trials show a range of positive and negative effects, suggesting that cluster trials may be producing a biased estimate of effect. Conclusion: Methodological biases in the design and execution of cluster randomised trials is frequent. Some of these biases associated with the use of cluster designs can be avoided through careful attention to the design of cluster trials. Firstly, if possible, individual allocation should be used. Secondly, if cluster allocation is required, then ideally participants should be identified before random allocation of the clusters. Third, if prior identification is not possible, then an independent recruiter should be used to recruit participants

Measurement of 222Rn dissolved in water at the Sudbury Neutrino Observatory

The technique used at the Sudbury Neutrino Observatory (SNO) to measure the concentration of 222Rn in water is described. Water from the SNO detector is passed through a vacuum degasser (in the light water system) or a membrane contact degasser (in the heavy water system) where dissolved gases, including radon, are liberated. The degasser is connected to a vacuum system which collects the radon on a cold trap and removes most other gases, such as water vapor and nitrogen. After roughly 0.5 tonnes of H2O or 6 tonnes of D2O have been sampled, the accumulated radon is transferred to a Lucas cell. The cell is mounted on a photomultiplier tube which detects the alpha particles from the decay of 222Rn and its daughters. The overall degassing and concentration efficiency is about 38% and the single-alpha counting efficiency is approximately 75%. The sensitivity of the radon assay system for D2O is equivalent to ~3 E(-15) g U/g water. The radon concentration in both the H2O and D2O is sufficiently low that the rate of background events from U-chain elements is a small fraction of the interaction rate of solar neutrinos by the neutral current reaction.Comment: 14 pages, 6 figures; v2 has very minor change

Quantifying single nucleotide variant detection sensitivity in exome sequencing

BACKGROUND: The targeted capture and sequencing of genomic regions has rapidly demonstrated its utility in genetic studies. Inherent in this technology is considerable heterogeneity of target coverage and this is expected to systematically impact our sensitivity to detect genuine polymorphisms. To fully interpret the polymorphisms identified in a genetic study it is often essential to both detect polymorphisms and to understand where and with what probability real polymorphisms may have been missed. RESULTS: Using down-sampling of 30 deeply sequenced exomes and a set of gold-standard single nucleotide variant (SNV) genotype calls for each sample, we developed an empirical model relating the read depth at a polymorphic site to the probability of calling the correct genotype at that site. We find that measured sensitivity in SNV detection is substantially worse than that predicted from the naive expectation of sampling from a binomial. This calibrated model allows us to produce single nucleotide resolution SNV sensitivity estimates which can be merged to give summary sensitivity measures for any arbitrary partition of the target sequences (nucleotide, exon, gene, pathway, exome). These metrics are directly comparable between platforms and can be combined between samples to give “power estimates” for an entire study. We estimate a local read depth of 13X is required to detect the alleles and genotype of a heterozygous SNV 95% of the time, but only 3X for a homozygous SNV. At a mean on-target read depth of 20X, commonly used for rare disease exome sequencing studies, we predict 5–15% of heterozygous and 1–4% of homozygous SNVs in the targeted regions will be missed. CONCLUSIONS: Non-reference alleles in the heterozygote state have a high chance of being missed when commonly applied read coverage thresholds are used despite the widely held assumption that there is good polymorphism detection at these coverage levels. Such alleles are likely to be of functional importance in population based studies of rare diseases, somatic mutations in cancer and explaining the “missing heritability” of quantitative traits

Living biointerfaces based on non-pathogenic bacteria to direct cell differentiation

Genetically modified Lactococcus lactis, non-pathogenic bacteria expressing the FNIII7-10 fibronectin fragment as a protein membrane have been used to create a living biointerface between synthetic materials and mammalian cells. This FNIII7-10 fragment comprises the RGD and PHSRN sequences of fibronectin to bind α5β1 integrins and triggers signalling for cell adhesion, spreading and differentiation. We used L. lactis strain to colonize material surfaces and produce stable biofilms presenting the FNIII7-10 fragment readily available to cells. Biofilm density is easily tunable and remains stable for several days. Murine C2C12 myoblasts seeded over mature biofilms undergo bipolar alignment and form differentiated myotubes, a process triggered by the FNIII7-10 fragment. This biointerface based on living bacteria can be further modified to express any desired biochemical signal, establishing a new paradigm in biomaterial surface functionalisation for biomedical applications

The difficult doctor? Characteristics of physicians who report frustration with patients: an analysis of survey data

BACKGROUND: Literature on difficult doctor-patient relationships has focused on the "difficult patient." Our objective was to determine physician and practice characteristics associated with greater physician-reported frustration with patients. METHODS: We conducted a secondary analysis of the Physicians Worklife Survey, which surveyed a random national sample of physicians. Participants were 1391 family medicine, general internal medicine, and medicine subspecialty physicians. The survey assessed physician and practice characteristics, including stress, depression and anxiety symptoms, practice setting, work hours, case-mix, and control over administrative and clinical practice. Physicians estimated the percentage of their patients who were "generally frustrating to deal with." We categorized physicians by quartile of reported frustrating patients and compared characteristics of physicians in the top quartile to those in the other three quartiles. We used logistic regression to model physician characteristics associated with greater frustration. RESULTS: In unadjusted analyses, physicians who reported high frustration with patients were younger (p < 0.001); worked more hours per week (p = 0.041); and had more symptoms of depression, stress, and anxiety (p < 0.004 for all). In the final model, factors independently associated with high frustration included age < 40 years, work hours > 55 per week, higher stress, practice in a medicine subspeciality, and greater number of patients with psychosocial problems or substance abuse. CONCLUSION: Personal and practice characteristics of physicians who report high frustration with patients differ from those of other physicians. Understanding factors contributing to physician frustration with patients may allow us to improve the quality of patient-physician relationships

Spatially-resolved electronic and vibronic properties of single diamondoid molecules

Diamondoids are a unique form of carbon nanostructure best described as hydrogen-terminated diamond molecules. Their diamond-cage structures and tetrahedral sp3 hybrid bonding create new possibilities for tuning electronic band gaps, optical properties, thermal transport, and mechanical strength at the nanoscale. The recently-discovered higher diamondoids (each containing more than three diamond cells) have thus generated much excitement in regards to their potential versatility as nanoscale devices. Despite this excitement, however, very little is known about the properties of isolated diamondoids on metal surfaces, a very relevant system for molecular electronics. Here we report the first molecular scale study of individual tetramantane diamondoids on Au(111) using scanning tunneling microscopy and spectroscopy. We find that both the diamondoid electronic structure and electron-vibrational coupling exhibit unique spatial distributions characterized by pronounced line nodes across the molecular surfaces. Ab-initio pseudopotential density functional calculations reveal that the observed dominant electronic and vibronic properties of diamondoids are determined by surface hydrogen terminations, a feature having important implications for designing diamondoid-based molecular devices.Comment: 16 pages, 4 figures. to appear in Nature Material

Application and investigation of a bound for outcome reporting bias

BACKGROUND: Direct empirical evidence for the existence of outcome reporting bias is accumulating and this source of bias is recognised as a potential threat to the validity of meta-analysis of randomised clinical trials. METHODS: A method for calculating the maximum bias in a meta-analysis due to publication bias is adapted for the setting where within-study selective non-reporting of outcomes is suspected, and compared to the alternative approach of missing data imputation. The properties of both methods are investigated in realistic small sample situations. RESULTS: The results suggest that the adapted Copas and Jackson approach is the preferred method for reviewers to apply as an initial assessment of robustness to within-study selective non-reporting. CONCLUSION: The Copas and Jackson approach is a useful method for systematic reviewers to apply to assess robustness to outcome reporting bias

CHIIMP: An automated high-throughput microsatellite genotyping approach reveals greater allelic diversity in wild chimpanzees

Short tandem repeats (STRs), also known as microsatellites, are commonly used to non invasively genotype wild-living endangered species, including African apes. Until recently, capillary electrophoresis has been the method of choice to determine the length of polymorphic STR loci. However, this technique is labor intensive, difficult to compare across platforms, and notoriously imprecise. Here we developed a MiSeq-based approach and tested its performance using previously genotyped fecal samples from long-term studied chimpanzees in Gombe National Park, Tanzania. Using data from eight microsatellite loci as a reference, we designed a bioinformatics platform that converts raw MiSeq reads into locus-specific files and automatically calls alleles after filtering stutter sequences and other PCR artifacts. Applying this method to the entire Gombe population, we confirmed previously reported genotypes, but also identified 31 new alleles that had been missed due to sequence differences and size homoplasy. The new genotypes, which increased the allelic diversity and heterozygosity in Gombe by 61% and 8%, respectively, were validated by replicate amplification and pedigree analyses. This demonstrated inheritance and resolved one case of an ambiguous paternity. Using both singleplex and multiplex locus amplification, we also genotyped fecal samples from chimpanzees in the Greater Mahale Ecosystem in Tanzania, demonstrating the utility of the MiSeq-based approach for genotyping non-habituated populations and performing comparative analyses across field sites. The new automated high-throughput analysis platform (available at https://github.com/ShawHahnLab/chiimp) will allow biologists to more accurately and effectively determine wildlife population size and structure, and thus obtain information critical for conservation efforts