Limit on the Radiative Neutrinoless Double Electron Capture of 36^{36}Ar from GERDA Phase I

Neutrinoless double electron capture is a process that, if detected, would give evidence of lepton number violation and the Majorana nature of neutrinos. A search for neutrinoless double electron capture of $^{36}$Ar has been performed with germanium detectors installed in liquid argon using data from Phase I of the GERmanium Detector Array (GERDA) experiment at the Gran Sasso Laboratory of INFN, Italy. No signal was observed and an experimental lower limit on the half-life of the radiative neutrinoless double electron capture of $^{36}$Ar was established: $T_{1/2} >$ 3.6 $\times$ 10$^{21}$ yr at 90 % C.I.Comment: 7 pages, 3 figure

Systems Biology in ELIXIR: modelling in the spotlight

In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR\u27s future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives

Personalized therapies in psychiatry: promises, pitfalls and perspectives

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PATENT PLUS: A blinded, randomised and extension study of riociguat plus sildenafil in pulmonary arterial hypertension

Abstract PATENT PLUS evaluated the safety and efficacy of riociguat in combination with sildenafil in pulmonary arterial hypertension patients. Patients receiving sildenafil (20\u2005mg three times daily) were randomised to placebo or riociguat (up to 2.5\u2005mg three times daily) for 12\u2005weeks. The primary outcome was maximum change in supine systolic blood pressure (SBP) from baseline within 4\u2005h of dosing. Secondary objectives comprised additional blood pressure, heart rate and exploratory efficacy variables, and safety. Patients could enter a long-term extension (LTE), where all patients received riociguat plus sildenafil. There was no difference in maximum change in supine SBP from baseline within 4\u2005h between the riociguat (n=12) (mean\ub1sd baseline: -20.2\ub115.3\u2005mmHg; week 12: -20.7\ub118.0\u2005mmHg) and placebo groups (n=6) (-7.6\ub13.9 and -20.2\ub112.9\u2005mmHg, respectively). Changes in standing SBP and supine or standing diastolic blood pressure were also not different. Combination therapy showed no favourable effects on exploratory clinical parameters, including haemodynamics and exercise capacity. In the LTE, there were high rates of discontinuation due to hypotension and three (18%) deaths (not considered study drug-related by the investigator). There were potentially unfavourable safety signals with sildenafil plus riociguat and no evidence of a positive benefit/risk ratio. Concomitant use of riociguat with phosphodiesterase-5 inhibitors is therefore contraindicated

Afterword: Walking the Edges

Articles in this section embrace different historical periods and contexts, which comprise Latin Christian Middle Ages, Christians and Jews of the early modern period from Northern Europe to the Ottoman Empire, and the modern period that connects continental Europe, Great Britain, India and the United States. It implies that we are dealing with very different notions of \u201creligion\u201d and equally different concepts of the individual self or non individual self. Despite the huge differences in historical and cultural contexts, the papers share common features: they all deal with case studies that move on the sideways of the mainstream. They deal with religious minorities, excluded or expelled people, but also with single exceptions and splinter groups. In different ways they all do walk the edges, either of one or between several religions, cultures or geographical regions

Genome-wide association study in musician's dystonia: A risk variant at the arylsulfatase G locus?

Musician's dystonia (MD) affects 1% to 2% of professional musicians and frequently terminates performance careers. It is characterized by loss of voluntary motor control when playing the instrument. Little is known about genetic risk factors, although MD or writer's dystonia (WD) occurs in relatives of 20% of MD patients. We conducted a 2-stage genome-wide association study in whites. Genotypes at 557,620 single-nucleotide polymorphisms (SNPs) passed stringent quality control for 127 patients and 984 controls. Ten SNPs revealed P\u2009<\u200910(-5) and entered the replication phase including 116 MD patients and 125 healthy musicians. A genome-wide significant SNP (P\u2009<\u20095 7 10(-8) ) was also genotyped in 208 German or Dutch WD patients, 1,969 Caucasian, Spanish, and Japanese patients with other forms of focal or segmental dystonia as well as in 2,233 ethnically matched controls. Genome-wide significance with MD was observed for an intronic variant in the arylsulfatase G (ARSG) gene (rs11655081; P\u2009=\u20093.95 7 10(-9) ; odds ratio [OR], 4.33; 95% confidence interval [CI], 2.66-7.05). rs11655081 was also associated with WD (P\u2009=\u20092.78 7 10(-2) ) but not with any other focal or segmental dystonia. The allele frequency of rs11655081 varies substantially between different populations. The population stratification in our sample was modest (\u3bb\u2009=\u20091.07), but the effect size may be overestimated. Using a small but homogenous patient sample, we provide data for a possible association of ARSG with MD. The variant may also contribute to the risk of WD, a form of dystonia that is often found in relatives of MD patients. \ua9 2013 International Parkinson and Movement Disorder Society

Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences

Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated (|r^g| ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance