Photon polarisation in b->s gamma using B->K*e+e- at LHCb

The b->s gamma transition proceeds through flavour changing neutral currents, and thus is particularly sensitive to the effects of new physics. An overview of the method to measure the photon polarisation at the LHCb experiment via an angular analysis of B->K*e+e- at low q^2 is presented. The status of the B->K*mu+mu- analysis with 309 pb-1 of pp collisions at sqrt(s)=7 TeV at LHCb is also given.Comment: Presented at the 2011 Hadron Collider Physics symposium (HCP-2011), Paris, France, November 14-18 2011, 2 pages, 4 figure

Tele-AAC Resolution.

Approximately 1.3% of all people, or about 4 million Americans, cannot rely on their natural speech to meet their daily communication needs. Telepractice offers a potentially cost-effective service delivery mechanism to provide clinical AAC services at a distance to the benefit of underserved populations in the United States and worldwide. Tele-AAC is a unique cross-disciplinary clinical service delivery model that requires expertise in both telepractice and augmentative and alternative communication (AAC) systems. The Tele-AAC Working Group of the 2012 ISAAC Research Symposium therefore drafted a resolution underscoring the importance of identifying and characterizing the unique opportunities and constraints of Tele-AAC in all aspects of service delivery. These include, but are not limited to: needs assessments; implementation planning; device/system procurement, set-up and training; quality assurance, client progress monitoring, and follow-up service delivery. Tele-AAC, like other telepractice applications, requires adherence to the ASHA Code of Ethics and other policy documents, and state, federal, and international laws, as well as a competent technological infrastructure. The Working Group recommends that institutions of higher education and professional organizations provide training in Tele-AAC service provision. In addition, research and development are needed to create validity measures across Tele-AAC practices (i.e., assessment, implementation, and consultation); determine the communication competence levels achieved by Tele-AAC users; discern stakeholders' perceptions of Tele-AAC services (e.g., acceptability and viability); maximize Tele-AAC's capacity to engage multiple team members in AAC assessment and ongoing service; identify the limitations and barriers of Tele-AAC provision; and develop potential solutions

Complementary role of cardiac CT in the assessment of aortic valve replacement dysfunction

Aortic valve replacement is the second most common cardiothoracic procedure in the UK. With an ageing population, there are an increasing number of patients with prosthetic valves that require follow-up. Imaging of prosthetic valves is challenging with conventional echocardiographic techniques making early detection of valve dysfunction or complications difficult. CT has recently emerged as a complementary approach offering excellent spatial resolution and the ability to identify a range of aortic valve replacement complications including structural valve dysfunction, thrombus development, pannus formation and prosthetic valve infective endocarditis. This review discusses each and how CT might be incorporated into a multimodal cardiovascular imaging pathway for the assessment of aortic valve replacements and in guiding clinical management

Validity of the new lifestyles NL-1000 accelerometer for measuring time spent in moderate-to-vigorous physical activity in school settings

Current interest in promoting physical activity in the school environment necessitates an inexpensive, accurate method of measuring physical activity in such settings. Additionally, it is recognized that physical activity must be of at least moderate intensity in order to yield substantial health benefits. The purpose of the study, therefore, was to determine the validity of the New Lifestyles NL-1000 (New Lifestyles, Inc., Lee's Summit, Missouri, USA) accelerometer for measuring moderate-to-vigorous physical activity in school settings, using the Actigraph GT1M (ActiGraph, Pensacola, Florida, USA) as the criterion. Data were collected during a cross-country run (n = 12), physical education (n = 18), and classroom-based physical activities (n = 42). Significant and meaningful intraclass correlations between methods were found, and NL-1000 estimates of moderate-to-vigorous physical activity were not meaningfully different from GT1M-estimated moderate- to-vigorous physical activity. The NL-1000 therefore shows promising validity evidence as an inexpensive, convenient method of measuring moderate-to-vigorous physical activity in school settings

Intracapsular neck of femur fractures secondary to civilian gunshot injuries: an inter- and intra-observer agreement study on classification and treatment using the AO/OTA classification.

Numerous classification systems have been developed for neck of femur fractures, but none have been tested for reliability in gunshot injuries. Our primary objective was to assess the inter-observer and intra-observer reliability of the AO/OTA classification system when applied to intracapsular neck of femur fractures secondary to low-velocity civilian gunshots wounds (GSWs). Our secondary objective was to test the reliability of the AO/OTA classification system in guiding surgeon treatment choices for these fractures. Eighteen reviewers (six orthopaedic traumatologists, six general orthopaedic surgeons and six junior orthopaedic fellows) were given a set of 25 plain radiographs and CT scans of femur neck fractures secondary to GSW. For each clinical case, all reviewers selected a classification as well as treatment option from a list of given options. Inter-observer reliability was measured at the initial classification. The exercise was repeated 10-12 weeks later by the same 18 reviewers to test intra-observer reliability. The Fleiss kappa values indicate only slight agreement amongst raters, across all experience levels, for both injury classification and treatment. Intra-observer agreement was fair across all experience levels for both injury classification and treatment. The AO/OTA classification showed only slight reliability in classification of gunshot fractures of the femur neck. With only fair reliability, it also failed to guide surgical treatment thus rendering its routine use in daily clinical practice of questionable value

Recommendations for accurate CT diagnosis of suspected acute aortic syndrome (AAS)-on behalf of the British Society of Cardiovascular Imaging (BSCI)/British Society of Cardiovascular CT (BSCCT)

Accurate and timely assessment of suspected acute aortic syndrome is crucial in this life-threatening condition. Imaging with CT plays a central role in the diagnosis to allow expedited management. Diagnosis can be made using locally available expertise with optimized scanning parameters, making full use of recent advances in CT technology. Each imaging centre must optimize their protocols to allow accurate diagnosis, to optimize radiation dose and in particular to reduce the risk of false-positive diagnosis that may simulate disease. This document outlines the principles for the acquisition of motion-free imaging of the aorta in this context.published_or_final_versio

Enhanced antitumor immunity through sequential targeting of PI3Kδ and LAG3

Background Despite striking successes, immunotherapies aimed at increasing cancer-specific T cell responses are unsuccessful in most patients with cancer. Inactivating regulatory T cells (Treg) by inhibiting the PI3Kδ signaling enzyme has shown promise in preclinical models of tumor immunity and is currently being tested in early phase clinical trials in solid tumors. Methods Mice bearing 4T1 mammary tumors were orally administered a PI3Kδ inhibitor (PI-3065) daily and tumor growth, survival and T cell infiltrate were analyzed in the tumor microenvironment. A second treatment schedule comprised PI3Kδ inhibitor with anti-LAG3 antibodies administered sequentially 10 days later. Results As observed in human immunotherapy trials with other agents, immunomodulation by PI3Kδ-blockade led to 4T1 tumor regressor and non-regressor mice. Tumor infiltrating T cells in regressors were metabolically fitter than those in non-regressors, with significant enrichments of antigen-specific CD8+ T cells, T cell factor 1 (TCF1)+ T cells and CD69− T cells, compatible with induction of a sustained tumor-specific T cell response. Treg numbers were significantly reduced in both regressor and non-regressor tumors compared with untreated tumors. The remaining Treg in non-regressor tumors were however significantly enriched with cells expressing the coinhibitory receptor LAG3, compared with Treg in regressor and untreated tumors. This striking difference prompted us to sequentially block PI3Kδ and LAG3. This combination enabled successful therapy of all mice, demonstrating the functional importance of LAG3 in non-regression of tumors on PI3Kδ inhibition therapy. Follow-up studies, performed using additional cancer cell lines, namely MC38 and CT26, indicated that a partial initial response to PI3Kδ inhibition is an essential prerequisite to a sequential therapeutic benefit of anti-LAG3 antibodies. Conclusions These data indicate that LAG3 is a key bottleneck to successful PI3Kδ-targeted immunotherapy and provide a rationale for combining PI3Kδ/LAG3 blockade in future clinical studies

Expression of Six Drug Transporters in Vaginal, Cervical, and Colorectal Tissues: Implications for Drug Disposition in HIV Prevention

Effective antiretroviral (ARV)-based HIV prevention strategies require optimizing drug exposure in mucosal tissues; yet factors influencing mucosal tissue disposition remain unknown. We hypothesized drug transporter expression in vaginal, cervical, and colorectal tissues is a contributing factor and selected 3 efflux (ABCB1/MDR1, ABCC2/MRP2, ABCC4/MRP4) and 3 uptake (SLC22A6/OAT1, SLC22A8/OAT3, SLCO1B1/OATP1B1) transporters to further investigate based on their affinity for 2 ARVs central to prevention (tenofovir, maraviroc). Tissue was collected from 98 donors. mRNA and protein expression were quantified using qPCR and immunohistochemistry (IHC). Hundred percent of tissues expressed efflux transporter mRNA. IHC localized them to the epithelium and/or submucosa. Multivariable analysis adjusted for age, smoking, and co-medications revealed significant (P  colorectal; vaginal ABCC2 2.9-fold > colorectal; colorectal ABCC4 2.0-fold > cervical). In contrast, uptake transporter mRNA was expressed in <25% of tissues. OAT1 protein was detected in 0% of female genital tissues and in 100% of colorectal tissues, but only in rare epithelial cells. These data support clinical findings of higher maraviroc and tenofovir concentrations in rectal tissue compared to vaginal or cervical tissue after oral dosing. Quantifying mucosal transporter expression and localization can facilitate ARV selection to target these tissues

Deep-Learning for Epicardial Adipose Tissue Assessment with Computed Tomography: Implications for Cardiovascular Risk Prediction

Background: Epicardial adipose tissue (EAT) volume is a marker of visceral obesity that can be measured in coronary computed tomography angiograms (CCTA). The clinical value of integrating this measurement in routine CCTA interpretation has not been documented./ Objectives: This study sought to develop a deep-learning network for automated quantification of EAT volume from CCTA, test it in patients who are technically challenging, and validate its prognostic value in routine clinical care./ Methods: The deep-learning network was trained and validated to autosegment EAT volume in 3,720 CCTA scans from the ORFAN (Oxford Risk Factors and Noninvasive Imaging Study) cohort. The model was tested in patients with challenging anatomy and scan artifacts and applied to a longitudinal cohort of 253 patients post-cardiac surgery and 1,558 patients from the SCOT-HEART (Scottish Computed Tomography of the Heart) Trial, to investigate its prognostic value./ Results: External validation of the deep-learning network yielded a concordance correlation coefficient of 0.970 for machine vs human. EAT volume was associated with coronary artery disease (odds ratio [OR] per SD increase in EAT volume: 1.13 [95% CI: 1.04-1.30]; P = 0.01), and atrial fibrillation (OR: 1.25 [95% CI:1.08-1.40]; P = 0.03), after correction for risk factors (including body mass index). EAT volume predicted all-cause mortality (HR per SD: 1.28 [95% CI: 1.10-1.37]; P = 0.02), myocardial infarction (HR: 1.26 [95% CI:1.09-1.38]; P = 0.001), and stroke (HR: 1.20 [95% CI: 1.09-1.38]; P = 0.02) independently of risk factors in SCOT-HEART (5-year follow-up). It also predicted in-hospital (HR: 2.67 [95% CI: 1.26-3.73]; P ≤ 0.01) and long-term post–cardiac surgery atrial fibrillation (7-year follow-up; HR: 2.14 [95% CI: 1.19-2.97]; P ≤ 0.01). Conclusions: Automated assessment of EAT volume is possible in CCTA, including in patients who are technically challenging; it forms a powerful marker of metabolically unhealthy visceral obesity, which could be used for cardiovascular risk stratification