Bayesian Inversion of Stokes Profiles

[abridged] Inversion techniques are the most powerful methods to obtain information about the thermodynamical and magnetic properties of solar and stellar atmospheres. In the last years, we have witnessed the development of highly sophisticated inversion codes that are now widely applied to spectro-polarimetric observations. The majority of these inversion codes are based on the optimization of a complicated non-linear merit function. However, no reliable and statistically well-defined confidence intervals can be obtained for the parameters inferred from the inversions. A correct estimation of the confidence intervals for all the parameters that describe the model is mandatory. Additionally, it is fundamental to apply efficient techniques to assess the ability of models to reproduce the observations and to what extent the models have to be refined or can be simplified. Bayesian techniques are applied to analyze the performance of the model to fit a given observed Stokes vector. The posterior distribution, is efficiently sampled using a Markov Chain Monte Carlo method. For simplicity, we focus on the Milne-Eddington approximate solution of the radiative transfer equation and we only take into account the generation of polarization through the Zeeman effect. However, the method is extremely general and other more complex forward models can be applied. We illustrate the ability of the method with the aid of academic and realistic examples. We show that the information provided by the posterior distribution turns out to be fundamental to understand and determine the amount of information available in the Stokes profiles in these particular cases.Comment: 15 pages, 12 figures, accepted for publication in A&

Driving task-related factors

Driving task-related factors by definition are ‘directly and causally contributing to the accident occurrence, very specific and detailed, are short-term lasting or dynamic in nature, and refer to the actual conditions of the components’. The aim was to analyse specific driving task-related factors to investigate how these type of factors affect the driver undertaking their tasks within driving. A selection of driving task-related factors were chosen and analysed using two types of analysis; by a statistical method and by an in-depth methodology developed in TRACE. Typical characteristics of these accidents were identified, and for a number of factors, typical failure generating scenarios were also identified. From this, a list of possible countermeasures were defined with the aim of preventing such accidents occurring. These included driver education, in-vehicle technologies and design issues. Finally, benefits and limitations of the analysis undertaken are given, with recommendation for future work on driving task-related factors

GDNF-RET signaling in ER-positive breast cancers is a key determinant of response and resistance to aromatase inhibitors.

Most breast cancers at diagnosis are estrogen receptor-positive (ER(+)) and depend on estrogen for growth and survival. Blocking estrogen biosynthesis by aromatase inhibitors has therefore become a first-line endocrine therapy for postmenopausal women with ER(+) breast cancers. Despite providing substantial improvements in patient outcome, aromatase inhibitor resistance remains a major clinical challenge. The receptor tyrosine kinase, RET, and its coreceptor, GFRα1, are upregulated in a subset of ER(+) breast cancers, and the RET ligand, glial-derived neurotrophic factor (GDNF) is upregulated by inflammatory cytokines. Here, we report the findings of a multidisciplinary strategy to address the impact of GDNF-RET signaling in the response to aromatase inhibitor treatment. In breast cancer cells in two-dimensional and three-dimensional culture, GDNF-mediated RET signaling is enhanced in a model of aromatase inhibitor resistance. Furthermore, GDNF-RET signaling promoted the survival of aromatase inhibitor-resistant cells and elicited resistance in aromatase inhibitor-sensitive cells. Both these effects were selectively reverted by the RET kinase inhibitor, NVP-BBT594. Gene expression profiling in ER(+) cancers defined a proliferation-independent GDNF response signature that prognosed poor patient outcome and, more importantly, predicted poor response to aromatase inhibitor treatment with the development of resistance. We validated these findings by showing increased RET protein expression levels in an independent cohort of aromatase inhibitor-resistant patient specimens. Together, our results establish GDNF-RET signaling as a rational therapeutic target to combat or delay the onset of aromatase inhibitor resistance in breast cancer

Arsenic exposure, diabetes-related genes and diabetes prevalence in a general population from Spain

Inorganic arsenic exposure may be associated with diabetes, but the evidence at low-moderate levels is not sufficient. Polymorphisms in diabetes-related genes have been involved in diabetes risk. We evaluated the association of inorganic arsenic exposure on diabetes in the Hortega Study, a representative sample of a general population from Valladolid, Spain. Total urine arsenic was measured in 1451 adults. Urine arsenic speciation was available in 295 randomly selected participants. To account for the confounding introduced by non-toxic seafood arsenicals, we designed a multiple imputation model to predict the missing arsenobetaine levels. The prevalence of diabetes was 8.3%. The geometric mean of total arsenic was 66.0 µg/g. The adjusted odds ratios (95% confidence interval) for diabetes comparing the highest with the lowest tertile of total arsenic were 1.76 (1.01, 3.09) and 2.14 (1.47, 3.11) before and after arsenobetaine adjustment, respectively. Polymorphisms in several genes including IL8RA, TXN, NR3C2, COX5A and GCLC showed suggestive differential associations of urine total arsenic with diabetes. The findings support the role of arsenic on diabetes and the importance of controlling for seafood arsenicals in populations with high seafood intake. Suggestive arsenic-gene interactions require confirmation in larger studies

A systematic review of the effectiveness and cost-effectiveness of peer education and peer support in prisons.

BACKGROUND: Prisoners experience significantly worse health than the general population. This review examines the effectiveness and cost-effectiveness of peer interventions in prison settings. METHODS: A mixed methods systematic review of effectiveness and cost-effectiveness studies, including qualitative and quantitative synthesis was conducted. In addition to grey literature identified and searches of websites, nineteen electronic databases were searched from 1985 to 2012. Study selection criteria were: Population: Prisoners resident in adult prisons and children resident in Young Offender Institutions (YOIs). INTERVENTION: Peer-based interventions Comparators: Review questions 3 and 4 compared peer and professionally led approaches. OUTCOMES: Prisoner health or determinants of health; organisational/ process outcomes; views of prison populations. STUDY DESIGNS: Quantitative, qualitative and mixed method evaluations. RESULTS: Fifty-seven studies were included in the effectiveness review and one study in the cost-effectiveness review; most were of poor methodological quality. Evidence suggested that peer education interventions are effective at reducing risky behaviours, and that peer support services are acceptable within the prison environment and have a positive effect on recipients, practically or emotionally. Consistent evidence from many, predominantly qualitative, studies, suggested that being a peer deliverer was associated with positive effects. There was little evidence on cost-effectiveness of peer-based interventions. CONCLUSIONS: There is consistent evidence from a large number of studies that being a peer worker is associated with positive health; peer support services are also an acceptable source of help within the prison environment and can have a positive effect on recipients. Research into cost-effectiveness is sparse. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ref: CRD42012002349

The Quest for Orthologs benchmark service and consensus calls in 2020.

The identification of orthologs-genes in different species which descended from the same gene in their last common ancestor-is a prerequisite for many analyses in comparative genomics and molecular evolution. Numerous algorithms and resources have been conceived to address this problem, but benchmarking and interpreting them is fraught with difficulties (need to compare them on a common input dataset, absence of ground truth, computational cost of calling orthologs). To address this, the Quest for Orthologs consortium maintains a reference set of proteomes and provides a web server for continuous orthology benchmarking (http://orthology.benchmarkservice.org). Furthermore, consensus ortholog calls derived from public benchmark submissions are provided on the Alliance of Genome Resources website, the joint portal of NIH-funded model organism databases

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Paleo-methane emissions recorded in foraminifera near the landward limit of the gas hydrate stability zone offshore western Svalbard

We present stable isotope and geochemical data from four sediment cores from west of Prins Karls Forland (ca. 340 m water depth), offshore western Svalbard, recovered from close to sites of active methane seepage, as well as from shallower water depths where methane seepage is not presently observed. Our analyses provide insight into the record of methane seepage in an area where ongoing ocean warming may be fueling the destabilization of shallow methane hydrate. The ?13C values of benthic and planktonic foraminifera at the methane seep sites show distinct intervals with negative values (as low as ?27.8‰) that do not coincide with the present-day depth of the sulfate methane transition zone (SMTZ). These intervals are interpreted to record long-term fluctuations in methane release at the present-day landward limit of the gas hydrate stability zone (GHSZ). Shifts in the radiocarbon ages obtained from planktonic foraminifera toward older values are related to methane-derived authigenic carbonate overgrowths of the foraminiferal tests, and prevent us from establishing the chronology of seepage events. At shallower water depths, where seepage is not presently observed, no record of past methane seepage is recorded in foraminifera from sediments spanning the last 14 ka cal BP (14C-AMS dating). ?13C values of foraminiferal carbonate tests appear to be much more sensitive to methane seepage than other sediment parameters. By providing nucleation sites for authigenic carbonate precipitation, foraminifera thus record the position of even a transiently stable SMTZ, which is likely to be a characteristic of temporally variable methane fluxes

Pentanol isomer synthesis in engineered microorganisms

Pentanol isomers such as 2-methyl-1-butanol and 3-methyl-1-butanol are a useful class of chemicals with a potential application as biofuels. They are found as natural by-products of microbial fermentations from amino acid substrates. However, the production titer and yield of the natural processes are too low to be considered for practical applications. Through metabolic engineering, microbial strains for the production of these isomers have been developed, as well as that for 1-pentanol and pentenol. Although the current production levels are still too low for immediate industrial applications, the approach holds significant promise for major breakthroughs in production efficiency