Heavy Squarks at the LHC

The LHC, with its seven-fold increase in energy over the Tevatron, is capable of probing regions of SUSY parameter space exhibiting qualitatively new collider phenomenology. Here we investigate one such region in which first generation squarks are very heavy compared to the other superpartners. We find that the production of these squarks, which is dominantly associative, only becomes rate-limited at mSquark > 4(5) TeV for L~10(100) fb-1. However, discovery of this scenario is complicated because heavy squarks decay primarily into a jet and boosted gluino, yielding a dijet-like topology with missing energy (MET) pointing along the direction of the second hardest jet. The result is that many signal events are removed by standard jet/MET anti-alignment cuts designed to guard against jet mismeasurement errors. We suggest replacing these anti-alignment cuts with a measurement of jet substructure that can significantly extend the reach of this channel while still removing much of the background. We study a selection of benchmark points in detail, demonstrating that mSquark= 4(5) TeV first generation squarks can be discovered at the LHC with L~10(100)fb-1

Cytokine/chemokine profiles in squamous cell carcinoma correlate with precancerous and cancerous disease stage.

Actinic Keratosis (AK), Intraepidermal Carcinoma (IEC), and Squamous Cell Carcinoma (SCC) are generally considered to be advancing stages of the same disease spectrum. However, while AK often regress spontaneously, and IEC often regress in response to immune-activating treatments, SCC typically do not regress. Therefore, it is vital to define whether fundamental immunological changes occur during progression to SCC. Here we show that proinflammatory cytokine expression, chemokine expression, and immune cell infiltration density change during progression to SCC. Our findings suggest a switch from predominantly proinflammatory cytokine production to chemokine production is a key feature of progression from precancer to cancer. Together, these observations propose a model that can underpin current research and open new avenues of exploration into the clinical significance of these profiles with respect to immunotherapeutic or other treatment outcomes

Protocol for the development of a CONSORT-equity guideline to improve reporting of health equity in randomized trials.

BACKGROUND: Health equity concerns the absence of avoidable and unfair differences in health. Randomized controlled trials (RCTs) can provide evidence about the impact of an intervention on health equity for specific disadvantaged populations or in general populations; this is important for equity-focused decision-making. Previous work has identified a lack of adequate reporting guidelines for assessing health equity in RCTs. The objective of this study is to develop guidelines to improve the reporting of health equity considerations in RCTs, as an extension of the Consolidated Standards of Reporting Trials (CONSORT). METHODS/DESIGN: A six-phase study using integrated knowledge translation governed by a study executive and advisory board will assemble empirical evidence to inform the CONSORT-equity extension. To create the guideline, the following steps are proposed: (1) develop a conceptual framework for identifying "equity-relevant trials," (2) assess empirical evidence regarding reporting of equity-relevant trials, (3) consult with global methods and content experts on how to improve reporting of health equity in RCTs, (4) collect broad feedback and prioritize items needed to improve reporting of health equity in RCTs, (5) establish consensus on the CONSORT-equity extension: the guideline for equity-relevant trials, and (6) broadly disseminate and implement the CONSORT-equity extension. DISCUSSION: This work will be relevant to a broad range of RCTs addressing questions of effectiveness for strategies to improve practice and policy in the areas of social determinants of health, clinical care, health systems, public health, and international development, where health and/or access to health care is a primary outcome. The outcomes include a reporting guideline (CONSORT-equity extension) for equity-relevant RCTs and a knowledge translation strategy to broadly encourage its uptake and use by journal editors, authors, and funding agencies

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

Association of nail biting and psychiatric disorders in children and their parents in a psychiatrically referred sample of children

<p>Abstract</p> <p>Background</p> <p>Nail biting (NB) is a very common unwanted behavior. The majority of children are motivated to stop NB and have already tried to stop it, but are generally unsuccessful in doing so. It is a difficult behavior to modify or treat. The objective of this study was to investigate the prevalence of co-morbid psychiatric disorders in a clinical sample of children with NB who present at a child and adolescent mental healthcare outpatient clinic and the prevalence of psychiatric disorders in their parents.</p> <p>Method</p> <p>A consecutive sample of 450 referred children was examined for NB and 63 (14%) were found to have NB. The children and adolescents with nail biting and their parents were interviewed according to DSM-IV diagnostic criteria. They were also asked about lip biting, head banging, skin biting, and hair pulling behaviors.</p> <p>Results</p> <p>Nail biting is common amongst children and adolescents referred to a child and adolescent mental health clinic. The most common co-morbid psychiatric disorders in these children were attention deficit hyperactivity disorder (74.6%), oppositional defiant disorder (36%), separation anxiety disorder (20.6%), enuresis (15.6%), tic disorder (12.7%) and obsessive compulsive disorder (11.1%). The rates of major depressive disorder, mental retardation, and pervasive developmental disorder were 6.7%, 9.5%, 3.2%, respectively. There was no association between the age of onset of nail biting and the co-morbid psychiatric disorder. Severity and frequency of NB were not associated with any co-morbid psychiatric disorder. About 56.8% of the mothers and 45.9% of the fathers were suffering from at least one psychiatric disorder. The most common psychiatric disorder found in these parents was major depression.</p> <p>Conclusion</p> <p>Nail biting presents in a significant proportion of referrals to a mental healthcare clinic setting. Nail biting should be routinely looked for and asked for in the child and adolescent mental healthcare setting because it is common in a clinical population, easily visible in consultation and relatively unintrusive to ask about. If present, its detection can then be followed by looking for other more subtle stereotypic or self-mutilating behaviors.</p

Effects of FVB/NJ and C57Bl/6J strain backgrounds on mammary tumor phenotype in inducible nitric oxide synthase deficient mice

The ability to genetically manipulate mice has led to rapid progress in our understanding of the roles of different gene products in human disease. Transgenic mice have often been created in the FVB/NJ (FVB) strain due to its high fecundity, while gene-targeted mice have been developed in the 129/SvJ-C57Bl/6J strains due to the capacity of 129/SvJ embryonic stem cells to facilitate germline transmission. Gene-targeted mice are commonly backcrossed into the C57Bl/6J (B6) background for comparison with existing data. Genetic modifiers have been shown to modulate mammary tumor latency in mouse models of breast cancer and it is commonly known that the FVB strain is susceptible to mammary tumors while the B6 strain is more resistant. Since gene-targeted mice in the B6 background are frequently bred into the polyomavirus middle T (PyMT) mouse model of breast cancer in the FVB strain, we have sought to understand the impact of the different genetic backgrounds on the resulting phenotype. We bred mice deficient in the inducible nitric oxide synthase (iNOS) until they were congenic in the PyMT model in the FVB and B6 strains. Our results reveal that the large difference in mean tumor latencies in the two backgrounds of 53 and 92 days respectively affect the ability to discern smaller differences in latency due to the Nos2 genetic mutation. Furthermore, the longer latency in the B6 strain enables a more detailed analysis of tumor formation indicating that individual tumor development is not stoichastic, but is initiated in the #1 glands and proceeds in early and late phases. NO production affects tumors that develop early suggesting an association of iNOS-induced NO with a more aggressive tumor phenotype, consistent with human clinical data positively correlating iNOS expression with breast cancer progression. An examination of lung metastases, which are significantly reduced in PyMT/iNOS(−/−) mice compared with PyMT/iNOS(+/+) mice only in the B6 background, is concordant with these findings. Our data suggest that PyMT in the B6 background provides a useful model for the study of inflammation-induced breast cancer

Intraspecies Transmission of BASE Induces Clinical Dullness and Amyotrophic Changes

The disease phenotype of bovine spongiform encephalopathy (BSE) and the molecular/ biological properties of its prion strain, including the host range and the characteristics of BSE-related disorders, have been extensively studied since its discovery in 1986. In recent years, systematic testing of the brains of cattle coming to slaughter resulted in the identification of at least two atypical forms of BSE. These emerging disorders are characterized by novel conformers of the bovine pathological prion protein (PrPTSE), named high-type (BSE-H) and low-type (BSE-L). We recently reported two Italian atypical cases with a PrPTSE type identical to BSE-L, pathologically characterized by PrP amyloid plaques and known as bovine amyloidotic spongiform encephalopathy (BASE). Several lines of evidence suggest that BASE is highly virulent and easily transmissible to a wide host range. Experimental transmission to transgenic mice overexpressing bovine PrP (Tgbov XV) suggested that BASE is caused by a prion strain distinct from the BSE isolate. In the present study, we experimentally infected Friesian and Alpine brown cattle with Italian BSE and BASE isolates via the intracerebral route. BASE-infected cattle developed amyotrophic changes accompanied by mental dullness. The molecular and neuropathological profiles, including PrP deposition pattern, closely matched those observed in the original cases. This study provides clear evidence of BASE as a distinct prion isolate and discloses a novel disease phenotype in cattle

The potential of Virtual Reality as anxiety management tool: a randomized controlled study in a sample of patients affected by Generalized Anxiety Disorder

Background: Generalized anxiety disorder (GAD) is a psychiatric disorder characterized by a constant and unspecific anxiety that interferes with daily-life activities. Its high prevalence in general population and the severe limitations it causes, point out the necessity to find new efficient strategies to treat it. Together with the cognitive-behavioural treatments, relaxation represents a useful approach for the treatment of GAD, but it has the limitation that it is hard to be learned. To overcome this limitation we propose the use of virtual reality (VR) to facilitate the relaxation process by visually presenting key relaxing images to the subjects. The visual presentation of a virtual calm scenario can facilitate patients' practice and mastery of relaxation, making the experience more vivid and real than the one that most subjects can create using their own imagination and memory, and triggering a broad empowerment process within the experience induced by a high sense of presence. According to these premises, the aim of the present study is to investigate the advantages of using a VR-based relaxation protocol in reducing anxiety in patients affected by GAD. Methods/Design: The trialis based on a randomized controlled study, including three groups of 25 patients each (for a total of 75 patients): (1) the VR group, (2) the non-VR group and (3) the waiting list (WL) group. Patients in the VR group will be taught to relax using a VR relaxing environment and audio-visual mobile narratives; patients in the non-VR group will be taught to relax using the same relaxing narratives proposed to the VR group, but without the VR support, and patients in the WL group will not receive any kind of relaxation training. Psychometric and psychophysiological outcomes will serve as quantitative dependent variables, while subjective reports of participants will be used as qualitative dependent variables. Conclusion: We argue that the use of VR for relaxation represents a promising approach in the treatment of GAD since it enhances the quality of the relaxing experience through the elicitation of the sense of presence. This controlled trial will be able to evaluate the effects of the use of VR in relaxation while preserving the benefits of randomization to reduce bias

A mechanistic model of infection: why duration and intensity of contacts should be included in models of disease spread

<p>Abstract</p> <p>Background</p> <p>Mathematical models and simulations of disease spread often assume a constant per-contact transmission probability. This assumption ignores the heterogeneity in transmission probabilities, e.g. due to the varying intensity and duration of potentially contagious contacts. Ignoring such heterogeneities might lead to erroneous conclusions from simulation results. In this paper, we show how a mechanistic model of disease transmission differs from this commonly used assumption of a constant per-contact transmission probability.</p> <p>Methods</p> <p>We present an exposure-based, mechanistic model of disease transmission that reflects heterogeneities in contact duration and intensity. Based on empirical contact data, we calculate the expected number of secondary cases induced by an infector (i) for the mechanistic model and (ii) under the classical assumption of a constant per-contact transmission probability. The results of both approaches are compared for different basic reproduction numbers <it>R</it>₀.</p> <p>Results</p> <p>The outcomes of the mechanistic model differ significantly from those of the assumption of a constant per-contact transmission probability. In particular, cases with many different contacts have much lower expected numbers of secondary cases when using the mechanistic model instead of the common assumption. This is due to the fact that the proportion of long, intensive contacts decreases in the contact dataset with an increasing total number of contacts.</p> <p>Conclusion</p> <p>The importance of highly connected individuals, so-called super-spreaders, for disease spread seems to be overestimated when a constant per-contact transmission probability is assumed. This holds particularly for diseases with low basic reproduction numbers. Simulations of disease spread should weight contacts by duration and intensity.</p