Assigning the right credit to the wrong action: compulsivity in the general population is associated with augmented outcome-irrelevant value-based learning.

Funder: NIHR Senior InvestigatorCompulsive behavior is enacted under a belief that a specific act controls the likelihood of an undesired future event. Compulsive behaviors are widespread in the general population despite having no causal relationship with events they aspire to influence. In the current study, we tested whether there is an increased tendency to assign value to aspects of a task that do not predict an outcome (i.e., outcome-irrelevant learning) among individuals with compulsive tendencies. We studied 514 healthy individuals who completed self-report compulsivity, anxiety, depression, and schizotypal measurements, and a well-established reinforcement-learning task (i.e., the two-step task). As expected, we found a positive relationship between compulsivity and outcome-irrelevant learning. Specifically, individuals who reported having stronger compulsive tendencies (e.g., washing, checking, grooming) also tended to assign value to response keys and stimuli locations that did not predict an outcome. Controlling for overall goal-directed abilities and the co-occurrence of anxious, depressive, or schizotypal tendencies did not impact these associations. These findings indicate that outcome-irrelevant learning processes may contribute to the expression of compulsivity in a general population setting. We highlight the need for future research on the formation of non-veridical action-outcome associations as a factor related to the occurrence and maintenance of compulsive behavior

Long-term Observations Reveal Environmental Conditions and Food Supply Mechanisms at an Arctic Deep-Sea Sponge Ground

Deep-sea sponge grounds are hotspots of benthic biomass and diversity. To date, very limited data exist on the range of environmental conditions in areas containing deep-sea sponge grounds and which factors are driving their distribution and sustenance. We investigated oceanographic conditions at a deep-sea sponge ground located on an Arctic Mid-Ocean Ridge seamount. Hydrodynamic measurements were performed along Conductivity-Temperature-Depth transects, and a lander was deployed within the sponge ground that recorded near-bottom physical properties as well as vertical fluxes of organic matter over an annual cycle. The data demonstrate that the sponge ground is found at water temperatures of −0.5°C to 1°C and is situated at the interface between two water masses at only 0.7° equatorward of the turning point latitude of semi-diurnal lunar internal tides. Internal waves supported by vertical density stratification interact with the seamount topography and produce turbulent mixing as well as resuspension of organic matter with temporarily very high current speeds up to 0.72 m s−1. The vertical movement of the water column delivers food and nutrients from water layers above and below toward the sponge ground. Highest organic carbon flux was observed during the summer phytoplankton bloom period, providing fresh organic matter from the surface. The flux of fresh organic matter is unlikely to sustain the carbon demand of this ecosystem. Therefore, the availability of bacteria, nutrients, and dissolved and particulate matter, delivered by tidally forced internal wave turbulence and transport by horizontal mean flows, likely plays an important role in meeting ecosystem-level food requirements

Active Galactic Nuclei under the scrutiny of CTA

Active Galactic Nuclei (hereafter AGN) produce powerful outflows which offer excellent conditions for efficient particle acceleration in internal and external shocks, turbulence, and magnetic reconnection events. The jets as well as particle accelerating regions close to the supermassive black holes (hereafter SMBH) at the intersection of plasma inflows and outflows, can produce readily detectable very high energy gamma-ray emission. As of now, more than 45 AGN including 41 blazars and 4 radiogalaxies have been detected by the present ground-based gamma-ray telescopes, which represents more than one third of the cosmic sources detected so far in the VHE gamma-ray regime. The future Cherenkov Telescope Array (CTA) should boost the sample of AGN detected in the VHE range by about one order of magnitude, shedding new light on AGN population studies, and AGN classification and unification schemes. CTA will be a unique tool to scrutinize the extreme high-energy tail of accelerated particles in SMBH environments, to revisit the central engines and their associated relativistic jets, and to study the particle acceleration and emission mechanisms, particularly exploring the missing link between accretion physics, SMBH magnetospheres and jet formation. Monitoring of distant AGN will be an extremely rewarding observing program which will inform us about the inner workings and evolution of AGN. Furthermore these AGN are bright beacons of gamma-rays which will allow us to constrain the extragalactic infrared and optical backgrounds as well as the intergalactic magnetic field, and will enable tests of quantum gravity and other "exotic" phenomena.Comment: 28 pages, 23 figure

A novel camera type for very high energy gamma-ray astronomy based on Geiger-mode avalanche photodiodes

Geiger-mode avalanche photodiodes (G-APD) are promising new sensors for light detection in atmospheric Cherenkov telescopes. In this paper, the design and commissioning of a 36-pixel G-APD prototype camera is presented. The data acquisition is based on the Domino Ring Sampling (DRS2) chip. A sub-nanosecond time resolution has been achieved. Cosmic-ray induced air showers have been recorded using an imaging mirror setup, in a self-triggered mode. This is the first time that such measurements have been carried out with a complete G-APD camera.Comment: 9 pages with 11 figure

Genetic Variants Associated With Glycine Metabolism and Their Role in Insulin Sensitivity and Type 2 Diabetes

Circulating metabolites associated with insulin sensitivity may represent useful biomarkers, but their causal role in insulin sensitivity and diabetes is less certain. We previously identified novel metabolites correlated with insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp. The top-ranking metabolites were in the glutathione and glycine biosynthesis pathways. We aimed to identify common genetic variants associated with metabolites in these pathways and test their role in insulin sensitivity and type 2 diabetes. With 1,004 nondiabetic individuals from the RISC study, we performed a genome-wide association study (GWAS) of 14 insulin sensitivity-related metabolites and one metabolite ratio. We replicated our results in the Botnia study (n = 342). We assessed the association of these variants with diabetes-related traits in GWAS meta-analyses (GENESIS [including RISC, EUGENE2, and Stanford], MAGIC, and DIAGRAM). We identified four associations with three metabolites-glycine (rs715 at CPS1), serine (rs478093 at PHGDH), and betaine (rs499368 at SLC6A12; rs17823642 at BHMT)-and one association signal with glycine-to-serine ratio (rs1107366 at ALDH1L1). There was no robust evidence for association between these variants and insulin resistance or diabetes. Genetic variants associated with genes in the glycine biosynthesis pathways do not provide consistent evidence for a role of glycine in diabetes-related traits

The genome and transcriptome of Trichormus sp NMC-1: insights into adaptation to extreme environments on the Qinghai-Tibet Plateau

The Qinghai-Tibet Plateau (QTP) has the highest biodiversity for an extreme environment worldwide, and provides an ideal natural laboratory to study adaptive evolution. In this study, we generated a draft genome sequence of cyanobacteria Trichormus sp. NMC-1 in the QTP and performed whole transcriptome sequencing under low temperature to investigate the genetic mechanism by which T. sp. NMC-1 adapted to the specific environment. Its genome sequence was 5.9 Mb with a G+C content of 39.2% and encompassed a total of 5362 CDS. A phylogenomic tree indicated that this strain belongs to the Trichormus and Anabaena cluster. Genome comparison between T. sp. NMC-1 and six relatives showed that functionally unknown genes occupied a much higher proportion (28.12%) of the T. sp. NMC-1 genome. In addition, functions of specific, significant positively selected, expanded orthogroups, and differentially expressed genes involved in signal transduction, cell wall/membrane biogenesis, secondary metabolite biosynthesis, and energy production and conversion were analyzed to elucidate specific adaptation traits. Further analyses showed that the CheY-like genes, extracellular polysaccharide and mycosporine-like amino acids might play major roles in adaptation to harsh environments. Our findings indicate that sophisticated genetic mechanisms are involved in cyanobacterial adaptation to the extreme environment of the QTP

Protocol for the development and validation procedure of the managing the link and strengthening transition from child to adult mental health care (MILESTONE) suite of measures

Background: Mental health disorders in the child and adolescent population are a pressing public health concern. Despite the high prevalence of psychopathology in this vulnerable population, the transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) has many obstacles such as deficiencies in planning, organisational readiness and policy gaps. All these factors contribute to an inadequate and suboptimal transition process. A suite of measures is required that would allow young people to be assessed in a structured and standardised way to determine the on-going need for care and to improve communication across clinicians at CAMHS and AMHS. This will have the potential to reduce the overall health economic burden and could also improve the quality of life for patients travelling across the transition boundary. The MILESTONE (Managing the Link and Strengthening Transition from Child to Adult Mental Health Care) project aims to address the significant socioeconomic and societal challenge related to the transition process. This protocol paper describes the development of two MILESTONE transition-related measures: The Transition Readiness and Appropriateness Measure (TRAM), designed to be a decision-making aide for clinicians, and the Transition Related Outcome Measure (TROM), for examining the outcome of transition. Methods: The TRAM and TROM have been developed and were validated following the US FDA Guidance for Patient-reported Outcome Measures which follows an incremental stepwise framework. The study gathers information from service users, parents, families and mental health care professionals who have experience working with young people undergoing the transition process from eight European countries. Discussion: There is an urgent need for comprehensive measures that can assess transition across the CAMHS/AMHS boundary. This study protocol describes the process of development of two new transition measures: the TRAM and TROM. The TRAM has the potential to nurture better transitions as the findings can be summarised and provided to clinicians as a clinician-decision making support tool for identifying cases who need to transition and the TROM can be used to examine the outcomes of the transition process. Trial registration: MILESTONE study registration: ISRCTN83240263 Registered 23-July-2015 - ClinicalTrials.gov NCT03013595 Registered 6 January 2017

Meropenem vs standard of care for treatment of neonatal late onset sepsis (NeoMero1): A randomised controlled trial.

BACKGROUND: The early use of broad-spectrum antibiotics remains the cornerstone for the treatment of neonatal late onset sepsis (LOS). However, which antibiotics should be used is still debatable, as relevant studies were conducted more than 20 years ago, recruited in single centres or countries, evaluated antibiotics not in clinical use anymore and had variable inclusion/exclusion criteria and outcome measures. Moreover, antibiotic-resistant bacteria have become a major problem in many countries worldwide. We hypothesized that efficacy of meropenem as a broad-spectrum antibiotic is superior to standard of care regimens (SOC) in empiric treatment of LOS and aimed to compare meropenem to SOC in infants aged 44 weeks meeting the Goldstein criteria of sepsis, were randomized in a 1:1 ratio to receive meropenem or one of the two SOC regimens (ampicillin+gentamicin or cefotaxime+gentamicin) chosen by each site prior to the start of the study for 8-14 days. The primary outcome was treatment success (survival, no modification of allocated therapy, resolution/improvement of clinical and laboratory markers, no need of additional antibiotics and presumed/confirmed eradication of pathogens) at test-of-cure visit (TOC) in full analysis set. Stool samples were tested at baseline and Day 28 for meropenem-resistant Gram-negative organisms (CRGNO). The primary analysis was performed in all randomised patients and in patients with culture confirmed LOS. Proportions of participants with successful outcome were compared by using a logistic regression model adjusted for the stratification factors. From September 3, 2012 to November 30th 2014, total of 136 patients (instead of planned 275) in each arm were randomized; 140 (52%) were culture positive. Successful outcome at TOC was achieved in 44/136 (32%) in the meropenem arm vs. 31/135 (23%) in the SOC arm (p = 0.087). The respective numbers in patients with positive cultures were 17/63 (27%) vs. 10/77 (13%) (p = 0.022). The main reason of failure was modification of allocated therapy. Treatment emergent adverse events occurred in 72% and serious adverse events in 17% of patients, the Day 28 mortality was 6%. Cumulative acquisition of CRGNO by Day 28 occurred in 4% of patients in the meropenem and 12% in the SOC arm (p = 0.052). CONCLUSIONS: Within this study population, we found no evidence that meropenem was superior to SOC in terms of success at TOC, short term hearing disturbances, safety or mortality were similar in both treatment arms but the study was underpowered to detect the planned effect. Meropenem treatment did not select for colonization with CRGNOs. We suggest that meropenem as broad-spectrum antibiotic should be reserved for neonates who are more likely to have Gram-negative LOS, especially in NICUs where microorganisms producing extended spectrum- and AmpC type beta-lactamases are circulating

Progress in Monte Carlo design and optimization of the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) will be an instrument covering a wide energy range in very-high-energy (VHE) gamma rays. CTA will include several types of telescopes, in order to optimize the performance over the whole energy range. Both large-scale Monte Carlo (MC) simulations of CTA super-sets (including many different possible CTA layouts as sub-sets) and smaller-scale simulations dedicated to individual aspects were carried out and are on-going. We summarize results of the prior round of large-scale simulations, show where the design has now evolved beyond the conservative assumptions of the prior round and present first results from the on-going new round of MC simulations.Comment: 4 pages, 5 figures. In Proceedings of the 33rd International Cosmic Ray Conference (ICRC2013), Rio de Janeiro (Brazil). All CTA contributions at arXiv:1307.223