To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

Exercise for depression

Background Depression is a common and important cause of morbidity and mortality worldwide. Depression is commonly treated with antidepressants and/or psychotherapy, but some people may prefer alternative approaches such as exercise. There are a number of theoretical reasons why exercise may improve depression. Objectives To determine the effectiveness of exercise in the treatment of depression. Search strategy We searched Medline, Embase, Sports Discus, PsycINFO, the Cochrane Controlled Trials Register, and the Cochrane Database of Systematic Reviews for eligible studies in March 2007. In addition, we hand-searched several relevant journals, contacted experts in the field, searched bibliographies of retrieved articles, and performed citation searches of identified studies. We also searched www.controlled-trials.com in May 2008. Selection criteria Randomised controlled trials in which exercise was compared to standard treatment, no treatment or a placebo treatment in adults (aged 18 and over) with depression, as defined by trial authors. We excluded trials of post-natal depression. Data collection and analysis We calculated effect sizes for each trial using Cohen's method and a standardised mean difference (SMD) for the overall pooled effect, using a random effects model. Where trials used a number of different tools to assess depression, we included the main outcome measure only in the meta-analysis. Main results Twenty-eight trials fulfilled our inclusion criteria, of which 25 provided data for meta-analyses. Randomisation was adequately concealed in a minority of studies, most did not use intention to treat analyses and most used self-reported symptoms as outcome measures. For the 23 trials (907 participants) comparing exercise with no treatment or a control intervention, the pooled SMD was -0.82 (95% CI -1.12, -0.51), indicating a large clinical effect. However, when we included only the three trials with adequate allocation concealment and intention to treat analysis and blinded outcome assessment, the pooled SMD was -0.42 (95% CI -0.88, 0.03) i.e. moderate, nonsignificant effect. The effect of exercise was not significantly different from that of cognitive therapy. There was insufficient data to determine risks and costs. Authors' conclusions Exercise seems to improve depressive symptoms in people with a diagnosis of depression, but when only methodologically robust trials are included, the effect sizes are only moderate and not statistically significant. Further, more methodologically robust trials should be performed to obtain more accurate estimates of effect sizes, and to determine risks and costs. Further systematic reviews could be performed to investigate the effect of exercise in people with dysthymia who do not fulfil diagnostic criteria for depression. This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 2010, Issue 1. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.</p

Patient and public involvement in health literacy interventions: a mapping review

Background: Health literacy is a critical mediating factor that impacts on the health of older adults. Patient and public involvement in health and social care research, policy and design of care delivery is one mechanism that can promote production of better health literacy. This mapping review looks for and describes practices, concepts and methods that have been reported involving patients, public and (non-researcher) professionals in the development and design of health literacy interventions for older people. Methods: Studies that aimed to improve health literacy were identified within a previously created compatible inventory of health behaviour studies for older people. Articles were screened for whether they addressed health literacy and featured involvement of stakeholders other than investigators and patients. Two reviewers independently read each study to identify any patient, public and professional involvement in the research process. We also noted some aspects of outcomes. Results: Twenty-two studies included patient, public and/or professional involvement in at least one research domain: design, management or evaluation. Involvement included volunteers, older people, professionals, patients, and community representatives. All studies were driven by an organisational or biomedical agenda. Conclusions: Patient, public and professional involvement wasrarely reported in studies on health literacy interventions for older people. This could help explain why some interventions fail to improve health literacy in older people. Key words – health literacy intervention research, older people, patient and public involvement, mapping revie

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

An approach for particle sinking velocity measurements in the 3–400 μm size range and considerations on the effect of temperature on sinking rates

The flux of organic particles below the mixed layer is one major pathway of carbon from the surface into the deep ocean. The magnitude of this export flux depends on two major processes—remineralization rates and sinking velocities. Here, we present an efficient method to measure sinking velocities of particles in the size range from approximately 3–400 μm by means of video microscopy (FlowCAM®). The method allows rapid measurement and automated analysis of mixed samples and was tested with polystyrene beads, different phytoplankton species, and sediment trap material. Sinking velocities of polystyrene beads were close to theoretical values calculated from Stokes’ Law. Sinking velocities of the investigated phytoplankton species were in reasonable agreement with published literature values and sinking velocities of material collected in sediment trap increased with particle size. Temperature had a strong effect on sinking velocities due to its influence on seawater viscosity and density. An increase in 9 °C led to a measured increase in sinking velocities of ~40 %. According to this temperature effect, an average temperature increase in 2 °C as projected for the sea surface by the end of this century could increase sinking velocities by about 6 % which might have feedbacks on carbon export into the deep ocean

Benign follicular tumors

Benign follicular tumors comprise a large and heterogeneous group of neoplasms that share a common histogenesis and display morphological features resembling one or several portions of the normal hair follicle, or recapitulate part of its embryological development. Most cases present it as clinically nondescript single lesions and essentially of dermatological relevance. Occasionally, however, these lesions be multiple and represent a cutaneous marker of complex syndromes associated with an increased risk of visceral neoplasms. In this article, the authors present the microscopic structure of the normal hair follicle as a basis to understand the type and level of differentiation of the various follicular tumors. The main clinicopathological features and differential diagnosis of benign follicular tumors are then discussed, including dilated pore of Winer, pilar sheath acanthoma, trichoadenoma, trichilemmoma, infundibuloma, proliferating trichilemmal cyst/tumor, trichoblastoma and its variants, pilomatricoma, trichodiscoma/fibrofolliculoma, neurofollicular hamartoma and trichofolliculoma. In addition, the main syndromes presenting with multiple follicular tumors are also discussed, namely Cowden, Birt-Hogg-Dubé, Rombo and Bazex-Dupré-Christol syndromes, as well as multiple tumors of follicular infundibulum (infundibulomatosis) and multiple trichoepitheliomas. Although the diagnosis of follicular tumors relies on histological examination, we highlight the importance of their knowledge for the clinician, especially when in presence of patients with multiple lesions that may be the cutaneous marker of a cancer-prone syndrome. The dermatologist is therefore in a privileged position to recognize these lesions, which is extremely important to provide further propedeutic, appropriate referral and genetic counseling for these patients.info:eu-repo/semantics/publishedVersio

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

WalkMore: a randomized controlled trial of pedometer-based interventions differing on intensity messages

Pedometer-based programs have elicited increased walking behaviors associated with improvements in blood pressure in sedentary/low active postmenopausal women, a population at increased risk of cardiovascular disease. Such programs typically encourage increasing the volume of physical activity with little regard for its intensity. Recent advances in commercially available pedometer technology now permit tracking of both steps/day and time in moderate (or greater) intensity physical activity on a daily basis. It is not known whether the dual message to increase steps/day while also increasing time spent at higher intensity walking will elicit additional improvements in blood pressure relative to a message to only focus on increasing steps/day. The purpose of this paper is to present the rationale, study design, and protocols employed in WalkMore, a 3-arm 3-month blinded and randomized controlled trial (RCT) designed to compare the effects of two community pedometer-based walking interventions (reflecting these separate and combined messages) relative to a control group on blood pressure in sedentary/low active post-menopausal women, a population at increased risk of cardiovascular disease. 120 sedentary/low active post-menopausal women (45-74 years of age) will be randomly assigned (computer-generated) to 1 of 3 groups: A) 10,000 steps/day (with no guidance on walking intensity/speed/cadence; BASIC intervention, n = 50); B) 10,000 steps/day and at least 30 minutes in moderate intensity (i.e., a cadence of at least 100 steps/min; ENHANCED intervention, n = 50); or a Control group (n = 20). An important strength of the study is the strict control and quantification of the pedometer-based physical activity interventions. The primary outcome is systolic blood pressure. Secondary outcomes include diastolic blood pressure, anthropometric measurements, fasting blood glucose and insulin, flow mediated dilation, gait speed, and accelerometer-determined physical activity and sedentary behavior. This study can make important contributions to our understanding of the relative benefits that walking volume and/or intensity may have on blood pressure in a population at risk of cardiovascular disease. ClinicalTrials.gov Record NCT01519583, January 18, 2012