A Profile Likelihood Analysis of the Constrained MSSM with Genetic Algorithms

The Constrained Minimal Supersymmetric Standard Model (CMSSM) is one of the simplest and most widely-studied supersymmetric extensions to the standard model of particle physics. Nevertheless, current data do not sufficiently constrain the model parameters in a way completely independent of priors, statistical measures and scanning techniques. We present a new technique for scanning supersymmetric parameter spaces, optimised for frequentist profile likelihood analyses and based on Genetic Algorithms. We apply this technique to the CMSSM, taking into account existing collider and cosmological data in our global fit. We compare our method to the MultiNest algorithm, an efficient Bayesian technique, paying particular attention to the best-fit points and implications for particle masses at the LHC and dark matter searches. Our global best-fit point lies in the focus point region. We find many high-likelihood points in both the stau co-annihilation and focus point regions, including a previously neglected section of the co-annihilation region at large m_0. We show that there are many high-likelihood points in the CMSSM parameter space commonly missed by existing scanning techniques, especially at high masses. This has a significant influence on the derived confidence regions for parameters and observables, and can dramatically change the entire statistical inference of such scans.Comment: 47 pages, 8 figures; Fig. 8, Table 7 and more discussions added to Sec. 3.4.2 in response to referee's comments; accepted for publication in JHE

Perceptions of, and reactions to, environmental heat: a brief note on issues of concern in relation to occupational health

Average temperatures around the world are already increasing, and climate change projections suggest that global mean temperatures will continue to rise. As the effects, and projected effects, of climate change are becoming clearer, it is more apparent that the health effects of heat exposure will need further investigation. The risks associated with heat exposure are especially relevant to understandings of occupational health for people involved in labouring or agricultural work in low-income countries. This review is a partial look at the ways in which issues surrounding heat exposure and occupational health have been treated in some of the available literature. This literature focuses on military-related medical understandings of heat exposure as well as heat exposure in working environments. The ways that these issues have been treated throughout the literature reflect the ways in which technologies of observation are intertwined with social attitudes. The effects of heat on the health of working people, as well as identification of risk groups, will require further research in order to promote prophylactic measures as well as to add to understandings of the actual and potential consequences of climatic change

A Model of Mindful Parenting: Implications for Parent–Child Relationships and Prevention Research

This paper introduces a model of “mindful parenting” as a framework whereby parents intentionally bring moment-to-moment awareness to the parent–child relationship. This is done by developing the qualities of listening with full attention when interacting with their children, cultivating emotional awareness and self-regulation in parenting, and bringing compassion and nonjudgmental acceptance to their parenting interactions. First, we briefly outline the theoretical and empirical literature on mindfulness and mindfulness-based interventions. Next, we present an operational definition of mindful parenting as an extension of mindfulness to the social context of parent–child relationships. We discuss the implications of mindful parenting for the quality of parent–child relationships, particularly across the transition to adolescence, and we review the literature on the application of mindfulness in parenting interventions. We close with a synopsis of our own efforts to integrate mindfulness-based intervention techniques and mindful parenting into a well-established, evidence-based family prevention program and our recommendations for future research on mindful parenting interventions

Trans Fatty Acids Induce Vascular Inflammation and Reduce Vascular Nitric Oxide Production in Endothelial Cells

Intake of trans fatty acids (TFA), which are consumed by eating foods made from partially hydrogenated vegetable oils, is associated with a higher risk of cardiovascular disease. This relation can be explained by many factors including TFA's negative effect on endothelial function and reduced nitric oxide (NO) bioavailability. In this study we investigated the effects of three different TFA (2 common isomers of C18 found in partially hydrogenated vegetable oil and a C18 isomer found from ruminant-derived—dairy products and meat) on endothelial NF-κB activation and nitric oxide (NO) production. Human endothelial cells were treated with increasing concentrations of Elaidic (trans-C18:1 (9 trans)), Linoelaidic (trans-C18:2 (9 trans, 12 trans)), and Transvaccenic (trans-C18:1 (11 trans)) for 3 h. Both Elaidic and Linoelaidic acids were associated with increasing NF-κB activation as measured by IL-6 levels and phosphorylation of IκBα, and impairment of endothelial insulin signaling and NO production, whereas Transvaccenic acid was not associated with these responses. We also measured superoxide production, which has been hypothesized to be necessary in fatty acid-dependent activation of NF-κB. Both Elaidic acid and Linoelaidic acid are associated with increased superoxide production, whereas Transvaccenic acid (which did not induce inflammatory responses) did not increase superoxide production. We observed differential activation of endothelial superoxide production, NF-κB activation, and reduction in NO production by different C18 isomers suggesting that the location and number of trans double bonds effect endothelial NF-κB activation

The role of chemotherapeutic drugs in the evaluation of breast tumour response to chemotherapy using serial FDG-PET

INTRODUCTION: The aims of this study were to investigate whether drug sequence (docetaxel followed by anthracyclines or the drugs in reverse order) affects changes in the maximal standard uptake volume (SUVmax) on [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) during neoadjuvant chemotherapy in women with locally advanced breast cancer. METHODS: Women were randomly assigned to receive either drug sequence, and FDG-PET scans were taken at baseline, after four cycles and after eight cycles of chemotherapy. Tumour response to chemotherapy was evaluated based on histology from a surgical specimen collected upon completion of chemotherapy. RESULTS: Sixty women were enrolled into the study. Thirty-one received docetaxel followed by anthracyclines (Arm A) and 29 received drugs in the reverse order (Arm B). Most women (83%) had ductal carcinoma and 10 women (17%) had lobular or lobular/ductal carcinoma. All but one tumour were downstaged during therapy. Overall, there was no significant difference in response between the two drug regimens. However, women in Arm B who achieved complete pathological response had mean FDG-PET SUVmax reduction of 87.7% after four cycles, in contrast to those who had no or minor pathological response. These women recorded mean SUVmax reductions of only 27% (P < 0.01). Women in Arm A showed no significant difference in SUVmax response according to pathological response. Sensitivity, specificity, accuracy and positive and negative predictive values were highest in women in Arm B. CONCLUSIONS: Our results show that SUVmax uptake by breast tumours during chemotherapy can be dependent on the drugs used. Care must be taken when interpreting FDG-PET in settings where patients receive varied drug protocols

Residual sleep disturbance and risk of relapse during the continuation/maintenance phase treatment of major depressive disorder with the selective serotonin reuptake inhibitor fluoxetine

<p>Abstract</p> <p>Background</p> <p>Relapse of major depressive disorder (MDD) is a common clinical problem. This study was designed to determine whether residual sleep disturbance (insomnia and hypersomnia) predict risk of relapse during the continuation and maintenance treatment of MDD.</p> <p>Methods</p> <p>A total of 570 patients with MDD were treated with open-label, flexible dose fluoxetine (range 20 to 60 mg; mean dose = 45.8 mg/day; SD = 15.1) for 12 weeks. Under double blind conditions, 262 patients who achieved clinical response were randomly assigned to continue fluoxetine or to switch to placebo for 52 weeks or until relapse. Residual sleep disturbance during the baseline visit of the double-blind phase was assessed using items 4, 5, 6 (insomnia) and 22, 23, 24 (hypersomnia) of the Hamilton Depression Rating Scale (HDRS). Survival analysis was utilized to determine the effect of residual sleep disturbance on risk of relapse.</p> <p>Results</p> <p>The severities of early (<it>P </it>> 0.05), middle (<it>P </it>> 0.05), late (<it>P </it>> 0.05), or total (<it>P </it>> 0.05) residual insomnia were not found to significantly predict risk of relapse during continuation and maintenance-phase treatment. Similarly, the severities of early bedtime (<it>P </it>> 0.05), oversleeping (<it>P </it>> 0.05), napping (<it>P </it>> 0.05), or total (<it>P </it>> 0.05) residual hypersomnia were not found to significantly predict risk of relapse during continuation and maintenance-phase treatment.</p> <p>Conclusion</p> <p>The present study did not identify the severity of residual sleep disturbance among fluoxetine responders to predict risk of MDD relapse. The size of our sample may have precluded us from identifying more modest effects of residual sleep disturbance on the risk of relapse in MDD patients. Future studies are needed to further explore the relationship between residual sleep disturbance and relapse in MDD.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: NCT00427128</p

A Rapid and Simple Procedure for the Establishment of Human Normal and Cancer Renal Primary Cell Cultures from Surgical Specimens

The kidney is a target organ for the toxicity of several xenobiotics and is also highly susceptible to the development of malignant tumors. In both cases, in vitro studies provide insight to cellular damage, and represent adequate models to study either the mechanisms underlying the toxic effects of several nephrotoxicants or therapeutic approaches in renal cancer. The development of efficient methods for the establishment of human normal and tumor renal cell models is hence crucial. In this study, a technically simple and rapid protocol for the isolation and culture of human proximal tubular epithelial cells and human renal tumor cells from surgical specimens is presented. Tumor and normal tissues were processed by using the same methodology, based on mechanical disaggregation of tissue followed by enzymatic digestion and cell purification by sequential sieving. The overall procedure takes roughly one hour. The resulting cell preparations have excellent viabilities and yield. Establishment of primary cultures from all specimens was achieved successfully. The origin of primary cultured cells was established through morphological evaluation. Normal cells purity was confirmed by immunofluorescent staining and reverse transcription-polymerase chain reaction analysis for expression of specific markers

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Temporal Dynamics of European Bat Lyssavirus Type 1 and Survival of Myotis myotis Bats in Natural Colonies

Many emerging RNA viruses of public health concern have recently been detected in bats. However, the dynamics of these viruses in natural bat colonies is presently unknown. Consequently, prediction of the spread of these viruses and the establishment of appropriate control measures are hindered by a lack of information. To this aim, we collected epidemiological, virological and ecological data during a twelve-year longitudinal study in two colonies of insectivorous bats (Myotis myotis) located in Spain and infected by the most common bat lyssavirus found in Europe, the European bat lyssavirus subtype 1 (EBLV-1). This active survey demonstrates that cyclic lyssavirus infections occurred with periodic oscillations in the number of susceptible, immune and infected bats. Persistence of immunity for more than one year was detected in some individuals. These data were further used to feed models to analyze the temporal dynamics of EBLV-1 and the survival rate of bats. According to these models, the infection is characterized by a predicted low basic reproductive rate (R0 = 1.706) and a short infectious period (D = 5.1 days). In contrast to observations in most non-flying animals infected with rabies, the survival model shows no variation in mortality after EBLV-1 infection of M. myotis. These findings have considerable public health implications in terms of management of colonies where lyssavirus-positive bats have been recorded and confirm the potential risk of rabies transmission to humans. A greater understanding of the dynamics of lyssavirus in bat colonies also provides a model to study how bats contribute to the maintenance and transmission of other viruses of public health concern