Rasch analysis of a new Patient Reported Outcome Measure for Psoriasis Treatment (PROMPT)

OBJECTIVES A draft patient-reported outcome measure for psoriasis treatment (PROMPT) was developed through patient interviews and comprised 91 items across seven core domains. This study aimed to evaluate the scaling properties and construct validity of the draft measure using the Rasch measurement model. METHODS Patients with chronic plaque psoriasis were identified and recruited according to pre-defined inclusion and exclusion criteria through psoriasis-specific secondary care clinics in the United Kingdom and two national patient organizations. Patients completed the draft measure at two time points, 14 days apart. Respondents with ≥40% of missing data were removed from the final analyses. Data from each sub-scale were analyzed separately using RUMM2030 software to explore Rasch model fit, item difficulty, local dependence, item category thresholds, and differential item functioning (DIF) by age and gender. Where necessary, items were removed individually and the scale iteratively reassessed for fit and unidimensionality. RESULTS A sample of n=209 patients with chronic plaque psoriasis completed the draft measure. Initial fit to the model was poor; disordered category thresholds were identified for items in all scales. Post-hocre-scoring from a 5-point Likert scale to a 3-point Likert scale improved model fit. Items which showed local dependence were removed in context of qualitative findings. Following removal of 11 items, all 7 scales demonstrated acceptable fit with the Rasch model (Chi Sq = 0.09 to 0.2) There was no evidence of DIF by age and gender. CONCLUSIONS The new measure, PROMPT, comprised 80 items in 6 independent, unidimensional scales, free from age or gender bias, with acceptable fit to the Rasch model. As such, the measure is considered to show initial promise for use with patients with chronic plaque psoriasis in a clinical setting. The psychometric properties and scoring of the measure should be explored further and confirmed in future studies

Psoriasis and mental health workshop report : Exploring the links between psychosocial factors, psoriasis, neuroinflammation and cardiovascular disease risk

Psoriasis is a systemic, relapsing, inflammatory disease associated with serious comorbidities including mood problems and/or unhealthy lifestyle behaviours. Cutaneous and systemic abnormalities in innate and acquired immunity play a role in its pathogenesis. The exact pathogenetic mechanism remains elusive. Evidence is accumulating that TNF-alpha, IL-17 and IL-23 signalling are highly relevant as targeting these pathways reduces disease activity. Evidence suggests a strong link between psoriasis and depression in adults. The International Psoriasis Council (IPC) held a roundtable event, "Psoriasis and Mental Health", in Barcelona, Spain which focused on the presence of depression and suicidality, plus the role of neuroinflammation in psoriasis, sleep disruption and the impact of depression on cardiovascular disease outcomes. We summarize here the expert presentations to provide additional insight into the understanding of psychiatric comorbidities of psoriasis and of the impact of chronic, systemic inflammation on neuro-and cardiovascular outcomes. the associations between psoriasis and other psychiatric comorbidities are still controversial and warrant further attention

Solar Hydrogen Burning and Neutrinos

We summarize the current status of laboratory measurements of nuclear cross sections of the pp chain and CN cycle. We discuss the connections between such measurements, predictions of solar neutrino fluxes, and the conclusion that solar neutrinos oscillate before reaching earth.Comment: 34 pages, 6 figure

A diagnostic PCR assay for the detection of an Australian epidemic strain of Pseudomonas aeruginosa

Background Chronic lung infection with the bacterium Pseudomonas aeruginosa is one of the hallmarks of cystic fibrosis (CF) and is associated with worsening lung function, increased hospitalisation and reduced life expectancy. A virulent clonal strain of P. aeruginosa (Australian epidemic strain I; AES-I) has been found to be widespread in CF patients in eastern Australia. Methods Suppression subtractive hybridization (SSH) was employed to identify genetic sequences that are present in the AES-I strain but absent from the sequenced reference strain PAO1. We used PCR to evaluate the distribution of several of the AES-I loci amongst a collection of 188 P. aeruginosa isolates which was comprised of 35 AES-I isolates (as determined by PFGE), 78 non-AES-I CF isolates including other epidemic CF strains as well as 69 P. aeruginosa isolates from other clinical and environmental sources. Results We have identified a unique AES-I genetic locus that is present in all 35 AES-I isolates tested and not present in any of the other 153 P. aeruginosa strains examined. We have used this unique AES-I locus to develop a diagnostic PCR and a real-time PCR assay to detect the presence of P. aeruginosa and AES-I in patient sputum samples

Casimir scaling of SU(3) static potentials

Potentials between static colour sources in eight different representations are computed in four dimensional SU(3) gauge theory. The simulations have been performed with the Wilson action on anisotropic lattices where the renormalised anisotropies have been determined non-perturbatively. After an extrapolation to the continuum limit we are able to exclude any violations of the Casimir scaling hypothesis that exceed 5% for source separations of up to 1 fm.Comment: 12 pages, 10 figures, RevTeX, v2: 1 reference added, more explanation about advantages of anisotrop

The phase transition of the quantum Ising model is sharp

An analysis is presented of the phase transition of the quantum Ising model with transverse field on the d-dimensional hypercubic lattice. It is shown that there is a unique sharp transition. The value of the critical point is calculated rigorously in one dimension. The first step is to express the quantum Ising model in terms of a (continuous) classical Ising model in d+1 dimensions. A so-called `random-parity' representation is developed for the latter model, similar to the random-current representation for the classical Ising model on a discrete lattice. Certain differential inequalities are proved. Integration of these inequalities yields the sharpness of the phase transition, and also a number of other facts concerning the critical and near-critical behaviour of the model under study.Comment: Small changes. To appear in the Journal of Statistical Physic

Radiotherapy exposure directly damages the uterus and causes pregnancy loss

Female cancer survivors are significantly more likely to experience infertility than the general population. It is well established that chemotherapy and radiotherapy can damage the ovary and compromise fertility, yet the ability of cancer treatments to induce uterine damage, and the underlying mechanisms, have been understudied. Here, we show that in mice total-body γ-irradiation (TBI) induced extensive DNA damage and apoptosis in uterine cells. We then transferred healthy donor embryos into ovariectomized adolescent female mice that were previously exposed to TBI to study the impacts of radiotherapy on the uterus independent from effects to ovarian endocrine function. Following TBI, embryo attachment and implantation were unaffected, but fetal resorption was evident at midgestation in 100% of dams, suggesting failed placental development. Consistent with this hypothesis, TBI impaired the decidual response in mice and primary human endometrial stromal cells. TBI also caused uterine artery endothelial dysfunction, likely preventing adequate blood vessel remodeling in early pregnancy. Notably, when pro-apoptotic protein Puma-deficient (Puma–/–) mice were exposed to TBI, apoptosis within the uterus was prevented, and decidualization, vascular function, and pregnancy were restored, identifying PUMA-mediated apoptosis as a key mechanism. Collectively, these data show that TBI damages the uterus and compromises pregnancy success, suggesting that optimal fertility preservation during radiotherapy may require protection of both the ovaries and uterus. In this regard, inhibition of PUMA may represent a potential fertility preservation strategy.Meaghan J. Griffiths, Sarah A. Marshall, Fiona L. Cousins, Lauren R. Alesi, Jordan Higgins, Saranya Giridharan, Urooza C. Sarma, Ellen Menkhorst, Wei Zhou, Alison S. Care, Jacqueline F. Donoghue, Sarah J. Holdsworth-Carson, Peter A.W. Rogers, Evdokia Dimitriadis, Caroline E. Gargett, Sarah A. Robertson, Amy L. Winship, and Karla J. Hut

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe