The experience of taking methotrexate for juvenile idiopathic arthritis: results of a cross-sectional survey with children and young people

Background: Children and young people (CYP) with juvenile idiopathic arthritis (JIA) are known to have impaired health-related quality of life (HRQoL), which is improved significantly for many by treatment with methotrexate (MTX). However, a significant proportion of CYP experience difficulties in taking MTX, which may reduce its potential benefits for HRQoL. The aim of this research was to examine how CYP with JIA perceive MTX treatment and how this relates to HRQoL. Methods: CYP aged 8-16 years taking MTX for JIA completed an adapted Parent Adherence Report Questionnaire, which contains 100mm visual analogue scales, to assess difficulty taking MTX, adherence, frequency of negative reactions and helpfulness of MTX. They also completed the Pediatric Quality of Life Inventory (PedsQL) Generic and Rheumatology scales. We collected data on age, gender, JIA course, disease duration, MTX duration of use, route and dose. Number of inflamed and limited joints were indicators of disease severity. Results: 116 CYP participated. Most considered MTX helpful (median 87; interquartile range (IQR) 50.75–98) and reported adherence was high (median 98; IQR 90–100). There was greater variability on scores for difficulty (median 22; IQR 2–69) and frequency of negative reactions (median 14.5; IQR 1.25–80). Mean (S.D.) scores on the PedsQL Physical and Psychosocial subscales were 71.63 (24.02) and 71.78 (19.59) respectively, indicating poorer HRQoL than that reported by healthy children. After controlling for demographic and disease variables, poorer physical HRQoL was significantly accounted for by greater difficulty in taking MTX. Poorer psychosocial HRQoL was significantly accounted for by subcutaneous MTX administration, a lower rating of MTX helpfulness and a greater reported difficulty in taking MTX. Conclusions: Taking MTX for JIA was viewed as helpful by most CYP but HRQoL was poorer in those who reported greater difficulty in taking MTX

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

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO