Vector boson production in association with a jet at forward rapidities.

Final states with a vector boson and a hadronic jet allow one to infer the Born-level kinematics of the underlying hard scattering process, thereby probing the partonic structure of the colliding protons. At forward rapidities, the parton collisions are highly asymmetric and resolve the parton distributions at very large or very small momentum fractions, where they are less well constrained by other processes. Using theory predictions accurate to next-to-next-to-leading order (NNLO) in QCD for both W ± and Z production in association with a jet at large rapidities at the LHC, we perform a detailed phenomenological analysis of recent LHC measurements. The increased theory precision allows us to clearly identify specific kinematical regions where the description of the data is insufficient. By constructing ratios and asymmetries of these cross sections, we aim to identify possible origins of the deviations, and highlight the potential impact of the data on improved determinations of parton distributions.

Next-to-Next-to-Leading-Order QCD Corrections to the Transverse Momentum Distribution of Weak Gauge Bosons.

The transverse momentum spectra of weak gauge bosons and their ratios probe the underlying dynamics and are crucial in testing our understanding of the standard model. They are an essential ingredient in precision measurements, such as the W boson mass extraction. To fully exploit the potential of the LHC data, we compute the second-order [next-to-next-to-leading-order (NNLO)] QCD corrections to the inclusive-p_{T}^{W} spectrum as well as to the ratios of spectra for W^{-}/W^{+} and Z/W. We find that the inclusion of NNLO QCD corrections considerably improves the theoretical description of the experimental CMS data and results in a substantial reduction of the residual scale uncertainties.

Editor's Choice - Frailty and the management of patients with acute cardiovascular disease: A position paper from the Acute Cardiovascular Care Association.

Frailty is increasingly seen among patients with acute cardiovascular disease. A combination of an ageing population, improved disease survival, treatable long-term conditions as well as a greater recognition of the syndrome has accelerated the prevalence of frailty in the modern world. Yet, this has not been matched by an expansion of research. National and international bodies have identified acute cardiovascular disease in the frail as a priority area for care and an entity that requires careful clinical decisions, but there remains a paucity of guidance on treatment efficacy and safety, and how to manage this complex group. This position paper from the Acute Cardiovascular Care Association presents the latest evidence about frailty and the management of frail patients with acute cardiovascular disease, and suggests avenues for future research.

Dynamics of social behaviour at parturition in a gregarious ungulate.

Group living is the behavioural response that results when individuals assess the costs vs benefits of sociality, and these trade-offs vary across an animal's life. Here we quantitatively assess how periparturient condition (mother/non-mother) and births affect the dynamics of social interactions of a gregarious ungulate, and how such can help to explain evolutionary hypotheses of the mother-offspring bond. To achieve this we used data of the individual movement of a group of Scottish blackface sheep (Ovis aries) marked with GPS collars and properties of mathematical graphs (networks). Euclidean pair-wise distance between sheep were threshold at different percentiles to determine network links, and these thresholds have a profound effect on the connectivity of the resulting network. Births increased the average pair-wise distance between mothers, and between mothers and non-mothers, with less effect on the distance between non-mothers. Mothers occupied peripheral positions within the flock, more evident following births. Associations between individuals (i.e. network community change) were highly dynamic, though mothers were less likely to change community than non-mothers, especially after births. Births hampered individual communication within the flock (assessed via network closeness centrality), especially in mothers. Overall leadership (lead positioning relative to flock movement) was not associated to reproductive condition, and individual leadership rank was not affected by births. A ten minute GPS acquisition time was adequate to capture complex social dynamics in sheep movement. The results on mother's isolation behaviour support the hypotheses of selection for maternal imprint facilitation, reducing risks to nursing alien offspring, and group/multilevel selection on group formation.

The dendritic spine morphogenic effects of repeated cocaine use occur through the regulation of serum response factor signaling.

The nucleus accumbens (NAc) is a primary brain reward region composed predominantly of medium spiny neurons (MSNs). In response to early withdrawal from repeated cocaine administration, de novo dendritic spine formation occurs in NAc MSNs. Much evidence indicates that this new spine formation facilitates the rewarding properties of cocaine. Early withdrawal from repeated cocaine also produces dramatic alterations in the transcriptome of NAc MSNs, but how such alterations influence cocaine's effects on dendritic spine formation remain unclear. Studies in non-neuronal cells indicate that actin cytoskeletal regulatory pathways in nuclei have a direct role in the regulation of gene transcription in part by controlling the access of co-activators to their transcription factor partners. In particular, actin state dictates the interaction between the serum response factor (SRF) transcription factor and one of its principal co-activators, MAL. Here we show that cocaine induces alterations in nuclear F-actin signaling pathways in the NAc with associated changes in the nuclear subcellular localization of SRF and MAL. Using in vivo optogenetics, the brain region-specific inputs to the NAc that mediate these nuclear changes are investigated. Finally, we demonstrate that regulated SRF expression, in turn, is critical for the effects of cocaine on dendritic spine formation and for cocaine-mediated behavioral sensitization. Collectively, these findings reveal a mechanism by which nuclear-based changes influence the structure of NAc MSNs in response to cocaine.

Individual placement and support (IPS) for patients with offending histories: the IPSOH feasibility cluster randomised trial protocol.

INTRODUCTION: People with involvement in forensic psychiatric services face many obstacles to employment, arising from their offending, as well as their mental health problems. This study aims to assess the feasibility of conducting a randomised controlled trial (RCT) to evaluate the effectiveness of individual placement and support (IPS), in improving employment rates and associated psychosocial outcomes in forensic psychiatric populations. IPS has been found consistently to achieve employment rates above 50% in psychiatric patients without a history of involvement in criminal justice services. METHODS/DESIGN: This is a single-centre feasibility cluster RCT. Clusters will be defined according to clinical services in the community forensic services of Nottinghamshire Healthcare NHS Foundation Trust (NHCT). IPS will be implemented into 2 of the randomly assigned intervention clusters in the community forensic services of NHCT. A feasibility cluster RCT will estimate the parameters required to design a full RCT. The primary outcome is the proportion of people in open employment at 12-month follow-up. Secondary outcome measures will include employment, educational activities, psychosocial and economic outcomes, as well as reoffending rates. Outcome measures will be recorded at baseline, 6 months and 12 months. In accordance with the UK Medical Research Council guidelines on the evaluation of complex interventions, a process evaluation will be carried out; qualitative interviews with patients and staff will explore general views of IPS as well as barriers and facilitators to implementation. Fidelity reviews will assess the extent to which the services follow the principles of IPS prior, during and at the end of the trial. ETHICS AND DISSEMINATION: Ethical approval was obtained from the East Midlands Research Ethics Committee-Nottingham 1 (REC reference number 15/EM/0253). Final and interim reports will be prepared for project funders, the study sponsor and clinical research network. Findings will be disseminated through peer-reviewed journals, conferences and event presentations. TRIAL REGISTRATION NUMBER: NCT02442193; Pre-results.

Fungal Planet description sheets: 128-153.

Novel species of microfungi described in the present study include the following from Australia: Catenulostroma corymbiae from Corymbia, Devriesia stirlingiae from Stirlingia, Penidiella carpentariae from Carpentaria, Phaeococcomyces eucalypti from Eucalyptus, Phialophora livistonae from Livistona, Phyllosticta aristolochiicola from Aristolochia, Clitopilus austroprunulus on sclerophyll forest litter of Eucalyptus regnans and Toxicocladosporium posoqueriae from Posoqueria. Several species are also described from South Africa, namely: Ceramothyrium podocarpi from Podocarpus, Cercospora chrysanthemoides from Chrysanthemoides, Devriesia shakazului from Aloe, Penidiella drakensbergensis from Protea, Strelitziana cliviae from Clivia and Zasmidium syzygii from Syzygium. Other species include Bipolaris microstegii from Microstegium and Synchaetomella acerina from Acer (USA), Brunneiapiospora austropalmicola from Rhopalostylis (New Zealand), Calonectria pentaseptata from Eucalyptus and Macadamia (Vietnam), Ceramothyrium melastoma from Melastoma (Indonesia), Collembolispora aristata from stream foam (Czech Republic), Devriesia imbrexigena from glazed decorative tiles (Portugal), Microcyclospora rhoicola from Rhus (Canada), Seiridium phylicae from Phylica (Tristan de Cunha, Inaccessible Island), Passalora lobeliae-fistulosis from Lobelia (Brazil) and Zymoseptoria verkleyi from Poa (The Netherlands). Valsalnicola represents a new ascomycete genus from Alnus (Austria) and Parapenidiella a new hyphomycete genus from Eucalyptus (Australia). Morphological and culture characteristics along with ITS DNA barcodes are also provided.

Newly diagnosed heart failure: change in quality of life, mood, and illness beliefs in the first 6 months after diagnosis.

OBJECTIVES: This study sought to examine how patients' mood and quality of life (QoL) change during the early high-risk period after a diagnosis of heart failure (HF) and to identify factors that may influence change. DESIGN: A within-subjects, repeated-measures design was used. Assessments took place within 4 weeks of diagnosis and 6 months later. METHODS: One hundred and sixty six patients with HF completed assessments of their mood, QoL, and beliefs about HF and its treatment. Correlation analysis was conducted between the variables and analysis of variance and t-tests were used to assess differences in categorical variables. To examine which variables predicted mood and QoL, hierarchical multiple regressions were conducted. RESULTS: At follow-up, patients' beliefs indicated a realization of the chronicity of their HF, however their beliefs about the consequences of having HF did not change and their satisfaction with their treatment remained high. QoL and anxiety improved significantly over time but there was no significant change in depressed mood. As would be expected, improvement in symptoms was a key factor in improved mood and QoL. Other significant explanatory variables included age, comorbid chronic obstructive pulmonary disease, depressed mood, patients' beliefs about the consequences of their HF and their concerns about treatment. CONCLUSIONS: This study suggests that addressing patients' mood and beliefs about their illness and its treatment may be additional ways of improving patient QoL in the early period after the diagnosis of HF.

Level and pattern of neuropsychological functioning in early-onset psychoses.

The present study aimed to compare the level and pattern of cognitive deficits in patients with early-onset psychoses with an age, gender and IQ matched control group. In order to ensure a representative sample of patients with psychoses, participants with an IQ of less than 70 were included. Forty-eight patients with an onset of psychoses before the age of 16, and 47 age, gender and IQ matched controls without psychoses were recruited. Psychotic symptomatology was assessed using the Schedules for Clinical Assessment to obtain DSM-IV and ICD-10 diagnoses. Positive and negative symptoms were assessed using the Positive and Negative Symptoms Scale. Levels of cognitive function were measured using a comprehensive neuropsychological battery. A pattern of specific impairments was not found, with few significant differences between the two cohorts. However both cohort groups performed lower than age derived norms. Therefore it appears that there are global cognitive deficits rather than specific deficits in early-onset psychoses when compared to normative data, in-line with conclusions of early-onset schizophrenia research, but patients did not have greater deficit than controls when matched on IQ, gender and age, even after excluding participants with IQ less than 70.

d3-GHR genotype does not explain heterogeneity in GH responsiveness in hypopituitary adults.

OBJECTIVE: Heterogeneity in growth hormone (GH) responsiveness in adult hypopituitary patients receiving recombinant human GH (rhGH) is poorly understood; doses vary up to fourfold between individuals. Deletion of exon 3 in the GH receptor (d3-GHR) has been linked to enhanced rhGH responsiveness in children. We investigated the role of the d3-GHR polymorphism in determining adult rhGH responsiveness. METHODS: One hundred and ninety-four patients treated with an identical rhGH dosing protocol in a single centre were genotyped for the d3-GHR, and the results correlated with changes in serum IGF-I and clinical parameters of GH responsiveness after 6 and 12 months of GH replacement therapy. RESULTS: Allele frequencies for homozygous full length (fl/fl), heterozygous d3 (fl/d3) and homozygous d3 (d3/d3) were 52%, 38.7% and 9.3%, respectively, and were in Hardy-Weinberg equilibrium. Baseline IGF-I and DeltaIGF-I at 6 months were comparable between groups. DeltaIGF-I at 12 months was significantly greater in the d3/d3 group (P = 0.028). No difference was detected between fl/d3 and fl/fl groups. Regression analyses of DeltaIGF-I at 12 months and DeltaIGF-I/rhGH dose confirmed a significant relationship of d3/d3 genotype on rhGH response. There was no difference between groups in maintenance rhGH dose between genotypes. CONCLUSION: Homozygosity for d3-GHR confers a marginal increase in GH responsiveness at 12 months but without a detectable change in maintenance rhGH dose required. Both d3 alleles are required to achieve this response; given that only 10% of the population are d3 homozygotes, the d3GHR does not explain the marked heterogeneity of GH responsiveness in hypopituitary adults.

Improving survival in the 6 months after diagnosis of heart failure in the past decade: population-based data from the UK.

OBJECTIVE: To investigate the secular trend in survival after a new diagnosis of heart failure in the UK population. DESIGN AND SETTING: Comparison of all-cause mortality in the 6 months after diagnosis of heart failure in population-based studies in the south east of England in 2004-5 (Hillingdon-Hastings Study) and 1995-7 (Hillingdon-Bromley Studies). PARTICIPANTS: 396 patients in the 2004-5 cohort and 552 patients in the 1995-7 cohort with incident (new) heart failure. MAIN OUTCOME MEASURES: All-cause mortality. RESULTS: All-cause mortality rates were 6% (95% CI 3% to 8%) at 1 month, 11% (8% to 14%) at 3 months and 14% (11% to 18%) at 6 months in the 2004-5 cohort compared with 16% (13% to 20%), 22% (19% to 25%) and 26% (22% to 29%), respectively, in the 1995-7 cohort (difference between the two cohorts, p<0.001). The difference in survival was not explained by any difference in the demographics or severity of heart failure at presentation. There was a difference at baseline and thereafter in the use of neurohormonal antagonists (beta-blockers and angiotensin-converting enzyme inhibitors). CONCLUSIONS: Although early mortality remains high among patients with newly diagnosed heart failure in the UK general population, there is strong evidence of a marked improvement in survival from 1995-7 to 2004-5, perhaps partly explained by an increased usage of neurohormonal antagonists.

Radiometric pooled faecal culture for the detection of Mycobacterium avium subsp paratuberculosis in low-shedder cattle.

OBJECTIVE: To identify the optimum pooling rate for pooled faecal culture (PFC) as a diagnostic tool in bovine Johne's disease control, for detection of cattle shedding low concentrations of Mycobacterium avium subsp paratuberculosis (Map). METHOD: Thirteen target animals were selected by delayed growth of Map from initial individual radiometric faecal cultures (first growth index at 5 weeks or later). A procedure based on radiometric culture and IS900 polymerase chain reaction and restriction endonuclease analysis confirmation was then used for PFC. RESULTS: Eight samples (stored for up to 17 months at -80 degrees C) yielded Map on subsequent culture, either from undiluted faeces or those mixed with normal cattle faeces at dilution rates from 1 in 5 to 1 in 50. From a regression equation, culture-positive animals were considered to be shedding relatively low levels of Map (< 6 x 10(4)/g of faeces). Pooling dilutions of more than 1 in 5 reduced PFC sensitivity. A minimum incubation period of 10 weeks at a dilution of 1 in 5 is recommended to detect such infected cattle. This pooling rate in radiometric culture is probably capable of detecting cattle shedding < or = 5 x 10(3) Map organisms/g of faeces, representing an estimated inoculum per culture vial of fewer than 20 viable organisms. CONCLUSION: Map was detected in more than 50% of the stored faecal samples from cattle shedding low concentrations of the organism. A pooling rate of 5 samples per pool is required to reliably detect infected low-shedder cattle using PFC based on radiometric culture.

Neurocognitive outcome following fetal growth restriction.

This review evaluates neurological and cognitive outcomes as they relate to fetal growth restriction. The aim is to clarify the relationship between poor fetal growth and abnormal brain development in order to understand the research directions required to untangle this complex issue.

Pooled faecal culture for the detection of Mycobacterium avium subsp paratuberculosis in goats.

OBJECTIVE: To evaluate pooled faecal culture for herd diagnosis of caprine Johne's disease and relate these findings to faecal shedding rates of Mycobacterium avium subsp paratuberculosis (Map). DESIGN: Radiometric broth culture was applied to several pooling dilutions, and shedding rates were estimated from a regression equation based on bacterial growth rates and known processing losses during radiometric culture. PROCEDURE: Sixteen faecal samples from goats naturally infected with sheep (n = 3) or cattle (n = 13) strains of Map, were diluted in normal goat faeces from 1 in 5 to 1 in 50. Cultures were confirmed by IS900 polymerase chain reaction and restriction endonuclease analysis, and mycobactin dependency. The numbers of viable Map in the culture inocula were determined by endpoint titration (most probable number) of nine samples and related to a cumulative growth index. RESULTS: A pooling dilution of 1 in 25 with an incubation period of 10 weeks detected 13 of 16 culture positive goats, all shedding > or = 2 x 10(4) Map per gram of faeces. Two samples containing very low numbers of Map (< 2 x 10(3)/g) were only culture positive from undiluted faeces. Thirteen of 16 goats were considered to be shedding low to moderate concentrations of Map (< 2 x 10(5)/g faeces). CONCLUSIONS: These data support a pooling dilution of 1 in 25 for application of pooled faecal culture as a diagnostic tool in caprine Johne's disease control. A test based on this dilution would reduce laboratory costs of whole herd testing in goats by approximately 40% relative to serology and 75 to 90% relative to individual faecal culture.

Primary orbital Ewing sarcoma in a middle-aged man.

A 54-year-old man presented with a painful left proptosis and a soft tissue mass at the inferolateral aspect of the left orbit with bone involvement. There was no clinical or investigational evidence of systemic disease. Both light microscopy and immunohistochemistry were required for the diagnosis of Ewing sarcoma. After failure of chemotherapy alone, management included extensive surgical excision and postoperative adjuvant radiotherapy and chemotherapy. Despite intervention, the patient died of widespread metastatic disease 17 months after initial presentation. Although rare, Ewing sarcoma should be included in the differential diagnosis of uniform round cell orbital tumors in adults.