Effect of Soil Chemistry on Microbial Biodiversity and Functionality in Grassland and Tilled Soils

Microorganisms are excellent indicators of soil health, because of their rapid response to environmental change. Traditional microbiology is ineffective for the study of soil, as \u3c 1% of microorganisms are currently culturable (Torsvik et al., 1996). Nucleic acid based methods, however, allow rapid detection of organisms, or particular genes, directly from soil samples. This work investigated, using polymerase chain reaction (PCR)-based approaches, the relationship between key chemical properties and bacterial biodiversity in grassland and tilled soils, with particular emphasis on the abundance and diversity of ammonium oxidisers

NCI-MATCH Arms N & P: Phase II study of PI3K beta inhibitor GSK2636771 in patients (pts) with cancers (ca) with PTEN mutation/deletion (mut/del) or PTEN protein loss

Background: The NCI-MATCH trial is the largest national study (1173 sites) for ptswith relapsed/ refractory solid tumors, lymphomas and myeloma, which assigns tar-geted therapies based on individual tumor molecular alterations detected using theadapted Oncomine AmpliSeq panel (143 genes) and immunohistochemistry (IHC).We hypothesized that patients with PTEN-deficient cancers enrolled to Arms N and Pmay benefit from treatment with the PI3K beta-selective inhibitor GSK2636771. Methods: Eligibility: relapsed/refractory ca, good end-organ function, and ECOG PS ≤ 1. Pts were screened for molecular alterations by centralized testing on fresh tumor biopsy and had deleterious PTEN mut/del without loss of expression (Arm N) or complete loss of cytoplasmic and nuclear PTEN staining on IHC (Arm P), and no other aberrations activating the PI3K/MTOR and MAPK pathways (mut in PIK3CA, PIK3R1, BRAF, KRAS, AKT1, TSC1/2, mTOR, RHEB, NF2, NRAS, HRAS). Pts received GSK2636771 400mg/day (28-days cycles). RECIST 1.1 overall response rate (ORR) was the primary endpoint. Results: Of 59 enrolled pts, 56 were eligible and received treatment. Of 22 pts with PTEN mut/del (Arm N: 6 uterine, 2 breast, 2 prostate, 2 head/neck ca, 10 other), all are off treatment as of analysis (14 disease progression, 4 for adverse events [AEs], 4 other). One pt (4.5%) with prostate ca (PTEN deletion, MPRSS2-ERG fusion) attained a partial response (-42%). Of 7 (32%) pts with stable disease (SD), 2 had SD \u3e 6 months (uterine leiomyosarcoma; endometrial carcinoma). Of 34 pts with loss of PTEN protein by IHC (Arm P: 7 prostate, 6 breast, 3 squamous anal ca, 2 cholangiocarcinoma, 16 other), all are off treatment as of analysis (26 disease progression, 4 for AE, 4 other). Of 9 (37.5%) pts with SD, 3 had SD \u3e 6 months (prostate cancer; squamous bladder cancer, squamous anal cancer). Median progression-free survival was 1.8 months for both arms. Gr ≥ 3 treatment-related (tr) reversible toxicities were experienced by 30% (7) and 20% (7) of pts in arms N and P, respectively. No tr Gr 5 toxicities were observed in either arm. Conclusions: Single agent GSK2636771 has very modest activity in ca with PTEN gene mutation/deletion and/or PTEN protein loss

Stereotyping starlings are more 'pessimistic'.

Negative affect in humans and animals is known to cause individuals to interpret ambiguous stimuli pessimistically, a phenomenon termed 'cognitive bias'. Here, we used captive European starlings (Sturnus vulgaris) to test the hypothesis that a reduction in environmental conditions, from enriched to non-enriched cages, would engender negative affect, and hence 'pessimistic' biases. We also explored whether individual differences in stereotypic behaviour (repetitive somersaulting) predicted 'pessimism'. Eight birds were trained on a novel conditional discrimination task with differential rewards, in which background shade (light or dark) determined which of two covered dishes contained a food reward. The reward was small when the background was light, but large when the background was dark. We then presented background shades intermediate between those trained to assess the birds' bias to choose the dish associated with the smaller food reward (a 'pessimistic' judgement) when the discriminative stimulus was ambiguous. Contrary to predictions, changes in the level of cage enrichment had no effect on 'pessimism'. However, changes in the latency to choose and probability of expressing a choice suggested that birds learnt rapidly that trials with ambiguous stimuli were unreinforced. Individual differences in performance of stereotypies did predict 'pessimism'. Specifically, birds that somersaulted were more likely to choose the dish associated with the smaller food reward in the presence of the most ambiguous discriminative stimulus. We propose that somersaulting is part of a wider suite of behavioural traits indicative of a stress response to captive conditions that is symptomatic of a negative affective state

Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials

Rationale Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology—a non-profit international organisation dedicated to consensus methodology in identification of outcome measures—conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). Results A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Conclusion Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field

Molecular profiling of melanoma brain metastases compared to primary cutaneous melanoma and to extracranial metastases.

BACKGROUND: Brain metastases are a significant cause of mortality and morbidity for patients with melanoma. We hypothesize that the development of brain metastases may be explained by molecular heterogeneity between primary cutaneous melanoma (PCM) or extracranial (ECM) and brain (MBM) melanoma metastases. MATERIALS AND METHODS: We compared next-generation sequencing, tumor mutational burden (TMB), and immunohistochemical staining for PD-L1 expression, among 132 MBM, 745 PCM, and 1190 ECM. RESULTS: The most common genetic alterations among MBM included: BRAF (52.4%), NRAS (26.6%), CDKN2A (23.3%), NF1 (18.9%), TP53 (18%), ARID2 (13.8%), SETD2 (11.9%), and PBRM1 (7.5%). Four genes were found with higher frequency among MBM compared to PCM or ECM: BRAF (52.4% v 40.4% v 40.9%), SETD2 (11.9% v 1.9% v 3.9%), PBRM1 (7.5% v 1.6% v 2.6%), and DICER1 (4.4% v 0.6% v 0.4%). MBM showed higher TMB ( CONCLUSIONS: Our findings suggest a unique molecular profile for MBM, including higher rates of BRAF mutations, higher TMB and higher PD-L1 expression, and also implicate chromatin remodeling in the pathogenesis of MBM

Age, Sex, and Racial Differences in Neuroimaging Use in Acute Stroke: A Population-Based Study

BACKGROUND AND PURPOSE: Limited information is available regarding differences in neuroimaging use for acute stroke work-up. Our objective was to assess whether race, sex, or age differences exist in neuroimaging use and whether these differences depend on the care center type in a population-based study. MATERIALS AND METHODS: Patients with stroke (ischemic and hemorrhagic) and transient ischemic attack were identified in a metropolitan, biracial population using the Greater Cincinnati/Northern Kentucky Stroke Study in 2005 and 2010. Multivariable regression was used to determine the odds of advanced imaging use (CT angiography/MR imaging/MR angiography) for race, sex, and age. RESULTS: In 2005 and 2010, there were 3471 and 3431 stroke/TIA events, respectively. If one adjusted for covariates, the odds of advanced imaging were higher for younger (55 years or younger) compared with older patients, blacks compared with whites, and patients presenting to an academic center and those seen by a stroke team or neurologist. The observed association between race and advanced imaging depended on age; in the older age group, blacks had higher odds of advanced imaging compared with whites (odds ratio, 1.34; 95% CI, 1.12–1.61; P < .01), and in the younger group, the association between race and advanced imaging was not statistically significant. Age by race interaction persisted in the academic center subgroup (P < .01), but not in the nonacademic center subgroup (P = .58). No significant association was found between sex and advanced imaging. CONCLUSIONS: Within a large, biracial stroke/TIA population, there is variation in the use of advanced neuroimaging by age and race, depending on the care center type

Acute Heart Failure Syndromes in Patients With Coronary Artery Disease

n/

Circumstellar discs: What will be next?

This prospective chapter gives our view on the evolution of the study of circumstellar discs within the next 20 years from both observational and theoretical sides. We first present the expected improvements in our knowledge of protoplanetary discs as for their masses, sizes, chemistry, the presence of planets as well as the evolutionary processes shaping these discs. We then explore the older debris disc stage and explain what will be learnt concerning their birth, the intrinsic links between these discs and planets, the hot dust and the gas detected around main sequence stars as well as discs around white dwarfs.Comment: invited review; comments welcome (32 pages

Tracing light propagation to the intrinsic accuracy of space-time geometry

Advancement in astronomical observations and technical instrumentation requires coding light propagation at high level of precision; this could open a new detection window of many subtle relativistic effects suffered by light while it is propagating and entangled in the physical measurements. Light propagation and its subsequent detection should indeed be conceived in a fully relativistic context, in order to interpret the results of the observations in accordance with the geometrical environment affecting light propagation itself, as an unicum surrounding universe. One of the most intriguing aspects is the boost towards the development of highly accurate models able to recon- struct the light path consistently with General Relativity and the precepts of measurements. This paper deals with the complexity of such a topic by showing how the geometrical framework of models like RAMOD, initially developed for astrometric observations, constitutes an appropriate physical environment for back tracing a light ray conforming to the intrinsic accuracy of space-time. This article discusses the reasons why RAMOD stands out among the existent approaches applied to the light propagation problem and provides a proof of its capability in recasting recent literature cases.Comment: 15 pages, 5 figures. Revised version, references and appendixes added. PRD re-submitte