The impact of the ATLAS zero-lepton, jets and missing momentum search on a CMSSM fit

Recent ATLAS data significantly extend the exclusion limits for supersymmetric particles. We examine the impact of such data on global fits of the constrained minimal supersymmetric standard model (CMSSM) to indirect and cosmological data. We calculate the likelihood map of the ATLAS search, taking into account systematic errors on the signal and on the background. We validate our calculation against the ATLAS determinaton of 95% confidence level exclusion contours. A previous CMSSM global fit is then re-weighted by the likelihood map, which takes a bite at the high probability density region of the global fit, pushing scalar and gaugino masses up.Comment: 16 pages, 7 figures. v2 has bigger figures and fixed typos. v3 has clarified explanation of our handling of signal systematic

'Being there' for women with metastatic breast cancer: a pan-European patient survey

BACKGROUND: Understanding their experiences of diagnosis is integral to improving the quality of care for women living with advanced/metastatic breast cancer. METHODS: A survey, initiated in March 2011, was conducted in two stages. First, the views of 47 breast cancer-related patient groups in eight European countries were sought on standards of breast cancer care and unmet needs of patients. Findings were used to develop a patient-centric survey to capture personal experiences of advanced breast cancer to determine insights into the ‘trade-off' between extending overall survival and side effects associated with its treatment. The second online survey was open to women with locally advanced or metastatic breast cancer, or their carers, and responders were recruited through local patient groups. Data were collected via anonymous local language questionnaires. RESULTS: The online stage II survey received a total of 230 responses from 17 European countries: 94% of respondents had locally advanced or metastatic breast cancer and 6% were adult carers. Although the overall experience of care was generally good/excellent (77%), gaps were still perceived in terms of treatment choice and information provision. Treatment choice for patients was felt to be lacking by 32% of responders. In addition, 68% of those who responded would have liked more information about future medical treatments and research, with 57% wishing to receive this information from their oncologist. Two-thirds (66%) of women with advanced breast cancer, or their carers, believed life-extending treatment to be important so that they can spend more time with family and friends, and 67% said that the treatment was worthwhile, despite potential associated side effects. CONCLUSION: These findings show a continuing need to provide women with advanced breast cancer with better information and emphasise the importance that these patients often place on prolonging survival

Incidence of Influenza in Healthy Adults and Healthcare Workers: A Systematic Review and Meta-Analysis

BACKGROUND: Working in healthcare is often considered a risk factor for influenza; however, this risk has not been quantified. We aimed to systematically review evidence describing the annual incidence of influenza among healthy adults and healthcare workers (HCWs). METHODS AND FINDINGS: We searched OVID MEDLINE (1950 to 2010), EMBASE (1947 to 2010) and reference lists of identified articles. Observational studies or randomized trials reporting full season or annual influenza infection rates for healthy, working age adult subjects and HCWs were included. Influenza infection was defined as a four-fold rise in antibody titer, or positive viral culture or polymerase chain reaction. From 24,707 citations, 29 studies covering 97 influenza seasons with 58,245 study participants were included. Pooled influenza incidence rates (IR) (95% confidence intervals (CI)) per 100 HCWs per season and corresponding incidence rate ratios (IRR) (95% CI) as compared to healthy adults were as follows. All infections: IR 18.7 (95% CI, 15.8 to 22.1), IRR 3.4 (95% CI, 1.2 to 5.7) in unvaccinated HCWs; IR 6.5 (95% CI, 4.6 to 9.1), IRR 5.4 (95% CI, 2.8 to 8.0) in vaccinated HCWs. Symptomatic infections: IR 7.5 (95% CI, 4.9 to 11.7), IRR 1.5 (95% CI, 0.4 to 2.5) in unvaccinated HCWs, IR 4.8 (95% CI, 3.2 to 7.2), IRR 1.6 (95% CI, 0.5 to 2.7) in vaccinated HCWs. CONCLUSIONS: Compared to adults working in non-healthcare settings, HCWs are at significantly higher risk of influenza

Microarray identifies ADAM family members as key responders to TGF-β1 in alveolar epithelial cells

The molecular mechanisms of Idiopathic Pulmonary Fibrosis (IPF) remain elusive. Transforming Growth Factor beta 1(TGF-β1) is a key effector cytokine in the development of lung fibrosis. We used microarray and computational biology strategies to identify genes whose expression is significantly altered in alveolar epithelial cells (A549) in response to TGF-β1, IL-4 and IL-13 and Epstein Barr virus. A549 cells were exposed to 10 ng/ml TGF-β1, IL-4 and IL-13 at serial time points. Total RNA was used for hybridisation to Affymetrix Human Genome U133A microarrays. Each in vitro time-point was studied in duplicate and an average RMA value computed. Expression data for each time point was compared to control and a signal log ratio of 0.6 or greater taken to identify significant differential regulation. Using normalised RMA values and unsupervised Average Linkage Hierarchical Cluster Analysis, a list of 312 extracellular matrix (ECM) proteins or modulators of matrix turnover was curated via Onto-Compare and Gene-Ontology (GO) databases for baited cluster analysis of ECM associated genes. Interrogation of the dataset using ontological classification focused cluster analysis revealed coordinate differential expression of a large cohort of extracellular matrix associated genes. Of this grouping members of the ADAM (A disintegrin and Metalloproteinase domain containing) family of genes were differentially expressed. ADAM gene expression was also identified in EBV infected A549 cells as well as IL-13 and IL-4 stimulated cells. We probed pathologenomic activities (activation and functional activity) of ADAM19 and ADAMTS9 using siRNA and collagen assays. Knockdown of these genes resulted in diminished production of collagen in A549 cells exposed to TGF-β1, suggesting a potential role for these molecules in ECM accumulation in IPF

ADAM33 gene silencing by promoter hypermethylation as a molecular marker in breast invasive lobular carcinoma

<p>Abstract</p> <p>Background</p> <p>ADAM33 protein is a member of the family of transmembrane glycoproteins composed of multidomains. ADAM family members have different activities, such as proteolysis and adhesion, making them good candidates to mediate the extracellular matrix remodelling and changes in cellular adhesion that characterise certain pathologies and cancer development. It was reported that one family member, <it>ADAM23</it>, is down-regulated by promoter hypermethylation. This seems to correlate with tumour progression and metastasis in breast cancer. In this study, we explored the involvement of ADAM33, another ADAM family member, in breast cancer.</p> <p>Methods</p> <p>First, we analysed <it>ADAM33 </it>expression in breast tumour cell lines by RT-PCR and western blotting. We also used 5-aza-2'-deoxycytidine (5azadCR) treatment and DNA bisulphite sequencing to study the promoter methylation of ADAM33 in breast tumour cell lines. We evaluated ADAM33 methylation in primary tumour samples by methylation specific PCR (MSP). Finally, <it>ADAM33 </it>promoter hypermethylation was correlated with clinicopathological data using the chi-square test and Fisher's exact test.</p> <p>Results</p> <p>The expression analysis of <it>ADAM33 </it>in breast tumour cell lines by RT-PCR revealed gene silencing in 65% of tumour cell lines. The corresponding lack of ADAM33 protein was confirmed by western blotting. We also used 5-aza-2'-deoxycytidine (5-aza-dCR) demethylation and bisulphite sequencing methodologies to confirm that gene silencing is due to <it>ADAM33 </it>promoter hypermethylation. Using MSP, we detected <it>ADAM33 </it>promoter hypermethylation in 40% of primary breast tumour samples. The correlation between methylation pattern and patient's clinicopathological data was not significantly associated with histological grade; tumour stage (TNM); tumour size; ER, PR or ERBB2 status; lymph node status; metastasis or recurrence. Methylation frequency in invasive lobular carcinoma (ILC) was 76.2% compared with 25.5% in invasive ductal carcinoma (IDC), and this difference was statistically significant (p = 0.0002).</p> <p>Conclusion</p> <p><it>ADAM33 </it>gene silencing may be related to the discohesive histological appearance of ILCs. We suggest that <it>ADAM33 </it>promoter methylation may be a useful molecular marker for differentiating ILC and IDC.</p

Dystrophin Is Required for the Normal Function of the Cardio-Protective KATP Channel in Cardiomyocytes

Duchenne and Becker muscular dystrophy patients often develop a cardiomyopathy for which the pathogenesis is still unknown. We have employed the murine animal model of Duchenne muscular dystrophy (mdx), which develops a cardiomyopathy that includes some characteristics of the human disease, to study the molecular basis of this pathology. Here we show that the mdx mouse heart has defects consistent with alteration in compounds that regulate energy homeostasis including a marked decrease in creatine-phosphate (PC). In addition, the mdx heart is more susceptible to anoxia than controls. Since the cardio-protective ATP sensitive potassium channel (KATP) complex and PC have been shown to interact we investigated whether deficits in PC levels correlate with other molecular events including KATP ion channel complex presence, its functionality and interaction with dystrophin. We found that this channel complex is present in the dystrophic cardiac cell membrane but its ability to sense a drop in the intracellular ATP concentration and consequently open is compromised by the absence of dystrophin. We further demonstrate that the creatine kinase muscle isoform (CKm) is displaced from the plasma membrane of the mdx cardiac cells. Considering that CKm is a determinant of KATP channel complex function we hypothesize that dystrophin acts as a scaffolding protein organizing the KATP channel complex and the enzymes necessary for its correct functioning. Therefore, the lack of proper functioning of the cardio-protective KATP system in the mdx cardiomyocytes may be part of the mechanism contributing to development of cardiac disease in dystrophic patients

Evolutionary conservation of lampbrush-like loops in drosophilids

<p>Abstract</p> <p>Background</p> <p>Loopin-1 is an abundant, male germ line specific protein of <it>Drosophila melanogaster</it>. The polyclonal antibody T53-F1 specifically recognizes Loopin-1 and enables its visualization on the Y-chromosome lampbrush-like loop named kl-3 during primary spermatocyte development, as well as on sperm tails. In order to test lampbrush-like loop evolutionary conservation, extensive phase-contrast microscopy and immunostaining with T53-F1 antibody was performed in other drosophilids scattered along their genealogical tree.</p> <p>Results</p> <p>In the male germ line of all species tested there are cells showing giant nuclei and intranuclear structures similar to those of <it>Drosophila melanogaster </it>primary spermatocytes. Moreover, the antibody T53-F1 recognizes intranuclear structures in primary spermatocytes of all drosophilids analyzed. Interestingly, the extent and conformation of the staining pattern is species-specific. In addition, the intense staining of sperm tails in all species suggests that the terminal localization of Loopin-1 and its orthologues is conserved. A comparison of these cytological data and the data coming from the literature about sperm length, amount of sperm tail entering the egg during fertilization, shape and extent of both loops and primary spermatocyte nuclei, seems to exclude direct relationships among these parameters.</p> <p>Conclusion</p> <p>Taken together, the data reported strongly suggest that lampbrush-like loops are a conserved feature of primary spermatocyte nuclei in many, if not all, drosophilids. Moreover, the conserved pattern of the T53-F1 immunostaining indicates that a Loopin-1-like protein is present in all the species analyzed, whose localization on lampbrush-like loops and sperm tails during spermatogenesis is evolutionary conserved.</p

A framework for integrated environmental health impact assessment of systemic risks

Traditional methods of risk assessment have provided good service in support of policy, mainly in relation to standard setting and regulation of hazardous chemicals or practices. In recent years, however, it has become apparent that many of the risks facing society are systemic in nature – complex risks, set within wider social, economic and environmental contexts. Reflecting this, policy-making too has become more wide-ranging in scope, more collaborative and more precautionary in approach. In order to inform such policies, more integrated methods of assessment are needed. Based on work undertaken in two large EU-funded projects (INTARESE and HEIMTSA), this paper reviews the range of approaches to assessment now in used, proposes a framework for integrated environmental health impact assessment (both as a basis for bringing together and choosing between different methods of assessment, and extending these to more complex problems), and discusses some of the challenges involved in conducting integrated assessments to support policy