Novel concepts in virally induced asthma

Viruses are the predominant infectious cause of asthma exacerbations in the developed world. In addition, recent evidence strongly suggests that viral infections may also have a causal role in the development of childhood asthma. In this article, we will briefly describe the general perception of how the link between infections and asthma has changed over the last century, and then focus on very recent developments that have provided new insights into the contribution of viruses to asthma pathogenesis. Highlighted areas include the contribution of severe early life viral infections to asthma inception, genetic determinants of severe viral infections in infancy, the differences in innate and adaptive immune system cytokine responses to viral infection between asthmatic and nonasthmatic subjects, and a potential vaccine strategy to prevent severe early life virally-induced illness

Microbes Bind Complement Inhibitor Factor H via a Common Site

To cause infections microbes need to evade host defense systems, one of these being the evolutionarily old and important arm of innate immunity, the alternative pathway of complement. It can attack all kinds of targets and is tightly controlled in plasma and on host cells by plasma complement regulator factor H (FH). FH binds simultaneously to host cell surface structures such as heparin or glycosaminoglycans via domain 20 and to the main complement opsonin C3b via domain 19. Many pathogenic microbes protect themselves from complement by recruiting host FH. We analyzed how and why different microbes bind FH via domains 19–20 (FH19-20). We used a selection of FH19-20 point mutants to reveal the binding sites of several microbial proteins and whole microbes (Haemophilus influenzae, Bordetella pertussis, Pseudomonas aeruginosa, Streptococcus pneumonia, Candida albicans, Borrelia burgdorferi, and Borrelia hermsii). We show that all studied microbes use the same binding region located on one side of domain 20. Binding of FH to the microbial proteins was inhibited with heparin showing that the common microbial binding site overlaps with the heparin site needed for efficient binding of FH to host cells. Surprisingly, the microbial proteins enhanced binding of FH19-20 to C3b and down-regulation of complement activation. We show that this is caused by formation of a tripartite complex between the microbial protein, FH, and C3b. In this study we reveal that seven microbes representing different phyla utilize a common binding site on the domain 20 of FH for complement evasion. Binding via this site not only mimics the glycosaminoglycans of the host cells, but also enhances function of FH on the microbial surfaces via the novel mechanism of tripartite complex formation. This is a unique example of convergent evolution resulting in enhanced immune evasion of important pathogens viautilization of a “superevasion site.

Effectiveness of service models and organisational structures supporting tuberculosis identification and management in hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review

OBJECTIVE: To determine which service models and organisational structures are effective and cost-effective for delivering tuberculosis (TB) services to hard-to-reach populations. DESIGN: Embase and MEDLINE (1990–2017) were searched in order to update and extend the 2011 systematic review commissioned by National Institute for Health and Care Excellence (NICE), discussing interventions targeting service models and organisational structures for the identification and management of TB in hard-to-reach populations. The NICE and Cochrane Collaboration standards were followed. SETTING: European Union, European Economic Area, European Union candidate countries and Organisation for Economic Co-operation and Development countries. PARTICIPANTS: Hard-to-reach populations, including migrants, homeless people, drug users, prisoners, sex workers, people living with HIV and children within vulnerable and hard-to-reach populations. PRIMARY AND SECONDARY OUTCOME MEASURES: Effectiveness and cost-effectiveness of the interventions. RESULTS: From the 19 720 citations found, five new studies were identified, in addition to the six discussed in the NICE review. Community health workers from the same migrant community, street teams and peers improved TB screening uptake by providing health education, promoting TB screening and organising contact tracing. Mobile TB clinics, specialised TB clinics and improved cooperation between healthcare services can be effective at identifying and treating active TB cases and are likely to be cost-effective. No difference in treatment outcome was detected when directly observed therapy was delivered at a health clinic or at a convenient location in the community. CONLCUSIONS: Although evidence is limited due to the lack of high-quality studies, interventions using peers and community health workers, mobile TB services, specialised TB clinics and improved cooperation between health services can be effective to control TB in hard-to-reach populations. Future studies should evaluate the (cost-)effectiveness of interventions on TB identification and management in hard-to-reach populations and countries should be urged to publish the outcomes of their TB control systems

Decitabine immunosensitizes human gliomas to NY-ESO-1 specific T lymphocyte targeting through the Fas/Fas Ligand pathway

<p>Abstract</p> <p>Background</p> <p>The lack of effective treatments for gliomas makes them a significant health problem and highlights the need for the development of novel and innovative treatment approaches. Immunotherapy is an appealing strategy because of the potential ability for immune cells to traffic to and destroy infiltrating tumor cells. However, the absence of well-characterized, highly immunogenic tumor-rejection antigens (TRA) in gliomas has limited the implementation of targeted immune-based therapies.</p> <p>Methods</p> <p>We hypothesized that treatment with the demethylating agent, decitabine, would upregulate the expression of TRA on tumor cells, thereby facilitating enhanced surveillance by TRA-specific T cells.</p> <p>Results and Discussion</p> <p>Treatment of human glioma cells with decitabine increased the expression of NY-ESO-1 and other well characterized cancer testes antigens. The upregulation of NY-ESO-1 made these tumors susceptible to NY-ESO-1-specific T-cell recognition and lysis. Interestingly, decitabine treatment of T98 glioma cells also sensitized them to Fas-dependent apoptosis with an agonistic antibody, while a Fas blocking antibody could largely prevent the enhanced functional recognition by NY-ESO-1 specific T cells. Thus, decitabine treatment transformed a non-immunogenic glioma cell into an immunogenic target that was efficiently recognized by NY-ESO-1--specific T cells.</p> <p>Conclusions</p> <p>Such data supports the hypothesis that agents which alter epigenetic cellular processes may "immunosensitize" tumor cells to tumor-specific T cell-mediated lysis.</p

Eating patterns and overweight in 9- to 10-year-old children in Telemark County, Norway: a cross-sectional study

Background/Objectives: Increasing prevalence of overweight in children is a growing health problem. The aim of this study was to describe the eating patterns of 9-to 10-year-old schoolchildren, and to investigate the relationship between overweight and eating patterns. Subjects/Methods: We recruited 1045 children for a cross-sectional study in Telemark County, Norway. The children&apos;s food, snacking and meal frequencies were reported by their parents using a retrospective food frequency questionnaire. Height and weight were measured by health professionals, and body mass index categories were calculated using international standard cutoff points (International Obesity Task Force values). Complete data were obtained for 924 children. Four distinct eating patterns were identified using principal component analysis. We used multiple logistic regression and calculated odds ratios (ORs) with 95% confidence intervals (CIs) for being overweight, and adjusted for parental characteristics and physical activity levels of the children (aORs). Results: Parental characteristics and physical activity were associated with both obesity and eating patterns. Children adhering to a &apos;junk/convenient&apos; eating pattern had a significantly lower likelihood of being overweight (aOR: 0.6; 95% CI: 0.4, 0.9), whereas children adhering to a &apos;varied Norwegian&apos; or a &apos;dieting&apos; eating pattern had a significantly higher likelihood of being overweight (respective values: aOR: 2.1; 95% CI: 1.3, 3.2; aOR: 2.2; 95% CI: 1.4, 3.4). No association with overweight was seen for a &apos;snacking pattern&apos;. Conclusions: The main finding was that, although family characteristics influenced both the prevalence of overweight and overall dietary behaviour, independent associations were evident between eating patterns and overweight, indicating parental modification of the diets of overweight children

Responsiveness of the EQ-5D in breast cancer patients in their first year after treatment

<p>Abstract</p> <p>Background/aim</p> <p>The EQ-5D is a generic health-related quality of life (HRQoL) measure that is used for the purpose of economic evaluations of health interventions. Therefore, it has to be responsive to meaningful changes in health in the patient population under investigation. The aim of this study was to investigate the responsiveness of the EQ-5D in breast cancer patients in their first year after treatment.</p> <p>Methods</p> <p>The subscale global health of the disease-specific HRQoL measure EORTC QLQ-C30 was used as a reference instrument to determine meaningful changes in health and identify subgroups of patients: patients reporting a moderate-large deterioration, small deterioration, a small improvement, moderate-large improvement, or no change in health status. Responsiveness was evaluated by calculating standardized response means (SRMs) in the five subgroups of patients and performing analysis of variance procedures. The two HRQoL measures were filled out two weeks and one year after finalizing curative treatment for breast cancer (n = 192).</p> <p>Results</p> <p>The EQ-5D was able to capture both improvements and deteriorations in HRQoL. SRMs of the EQ VAS and EQ-5D Index were close to zero in the subgroup reporting no change and increased and decreased adequately in the subgroups reporting small and moderate changes. Additional analysis of variance procedures showed that the EQ-5D was able to differentiate between subgroups of patients with no change and moderate-large deterioration or improvement in health.</p> <p>Conclusion</p> <p>The EQ-5D seems an appropriate measure for the purpose of economic evaluations of health intervention in breast cancer patients after treatment.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN74071417.</p

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

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

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV