An exploration of parents’ preferences for foot care in juvenile idiopathic arthritis: a possible role for the discrete choice experiment

Background: An increased awareness of patients’ and parents’ care preferences regarding foot care is desirable from a clinical perspective as such information may be utilised to optimise care delivery. The aim of this study was to examine parents’ preferences for, and valuations of foot care and foot-related outcomes in juvenile idiopathic arthritis (JIA).<p></p> Methods: A discrete choice experiment (DCE) incorporating willingness-to-pay (WTP) questions was conducted by surveying 42 parents of children with JIA who were enrolled in a randomised-controlled trial of multidisciplinary foot care at a single UK paediatric rheumatology outpatients department. Attributes explored were: levels of pain; mobility; ability to perform activities of daily living (ADL); waiting time; referral route; and footwear. The DCE was administered at trial baseline. DCE data were analysed using a multinomial-logit-regression model to estimate preferences and relative importance of attributes of foot care. A stated-preference WTP question was presented to estimate parents’ monetary valuation of health and service improvements.<p></p> Results: Every attribute in the DCE was statistically significant (p < 0.01) except that of cost (p = 0.118), suggesting that all attributes, except cost, have an impact on parents’ preferences for foot care for their child. The magnitudes of the coefficients indicate that the strength of preference for each attribute was (in descending order): improved ability to perform ADL, reductions in foot pain, improved mobility, improved ability to wear desired footwear, multidisciplinary foot care route, and reduced waiting time. Parents’ estimated mean annual WTP for a multidisciplinary foot care service was £1,119.05.<p></p> Conclusions: In terms of foot care service provision for children with JIA, parents appear to prefer improvements in health outcomes over non-health outcomes and service process attributes. Cost was relatively less important than other attributes suggesting that it does not appear to impact on parents’ preferences.<p></p&gt

Prevalence and determinants of the use of self-tests by members of the public: a mixed methods study

Background Self-tests can be used by members of the public to diagnose conditions without involving a doctor, nurse or other health professional. As technologies to design and manufacture diagnostic tests have developed, a range of self-tests have become available to the public to buy over-the-counter and via the Internet. This study aims to describe how many people have used self-tests and identify factors associated with their use. Methods A postal questionnaire will elicit basic information, including sociodemographic characteristics, and whether the person has used or would use specified self-tests. Consent will be sought to recontact people who want to participate further in the study, and interviews and focus groups will be used to develop hypotheses about factors associated with self-test use. These hypotheses will be tested in a case-control study. An in-depth questionnaire will be developed incorporating the identified factors. This will be sent to: people who have used a self-test (cases); people who have not used a self-test but would use one in the future (controls); and people who have not used and would not use a self-test (controls). Logistic regression analysis will be used to establish which factors are associated with self-test use. Discussion Self-tests do have potential benefits, for example privacy and convenience, but also potential harms, for example delay seeking treatment after a true negative result when the symptoms are actually due to another condition. It is anticipated that the outcomes from this study will include recommendations about how to improve the appropriate use of self-tests and existing health services, as well as information to prepare health professionals for patients who have used self-tests

Characterisation of the genomic landscape of CRLF2-rearranged acute lymphoblastic leukemia

Deregulated expression of the type I cytokine receptor, CRLF2, is observed in 5–15% of precursor B-cell acute lymphoblastic leukaemia (B-ALL). We aimed to determine the clinical and genetic landscape of those with IGH-CRLF2 or P2RY8-CRLF2 (CRLF2-r) using multiple genomic approaches. Clinical and demographic features of CRLF2-r patients were characteristic of B-ALL. Patients with IGH-CRLF2 were older (14 y vs. 4 y, P < .001), while the incidence of CRLF2-r among Down syndrome patients was high (50/161, 31%). CRLF2-r co-occurred with primary chromosomal rearrangements but the majority (111/161, 69%) had B-other ALL. Copy number alteration (CNA) profiles were similar to B-other ALL, although CRLF2-r patients harbored higher frequencies of IKZF1 (60/138, 43% vs. 77/1351, 24%) and BTG1 deletions (20/138, 15% vs. 3/1351, 1%). There were significant differences in CNA profiles between IGH-CRLF2 and P2RY8-CRLF2 patients: IKZF1 (25/35, 71% vs. 36/108, 33%, P < .001), BTG1 (11/35, 31% vs. 10/108, 9%, P =.004), and ADD3 deletions (9/19, 47% vs. 5/38, 13%, P =.008). A novel gene fusion, USP9X-DDX3X, was discovered in 10/54 (19%) of patients. Pathway analysis of the mutational profile revealed novel involvement for focal adhesion. Although the functional relevance of many of these abnormalities are unknown, they likely activate additional pathways, which may represent novel therapeutic targets

Gestational diabetes mellitus and retinal microvasculature.

BACKGROUND: Small-vessel dysfunction may be an important consequence of chronic hyperglycemia. We examined the association between gestational diabetes mellitus (GDM), a state of transient hyperglycemia during pregnancy, and retinal microvascular changes in pregnant women at 26-28 weeks of pregnancy. METHODS: A total of 1136 pregnant women with singleton pregnancies were recruited during their first trimester at two major Singapore maternity hospitals in an on-going birth cohort study. Participants underwent an oral glucose tolerance test and retinal imaging at 26-28 weeks gestation (n = 542). We used the 1999 World Health Organization (WHO) criteria to define GDM: ≥7.0 mmol/L for fasting glucose and/or ≥7.8 mmol/L for 2-h post-glucose. Retinal microvasculature was measured using computer software (Singapore I Vessel Analyzer, SIVA version 3.0, Singapore Eye Research Institute, Singapore) from the retinal photographs. RESULTS: In a multiple linear regression model adjusting for age, ethnicity and maternal education, mothers with GDM had narrower arteriolar caliber (-1.6 μm; 95% Confidence Interval [CI]: -3.1 μm, -0.2 μm), reduced arteriolar fractal dimension (-0.01 Df; 95% CI: -0.02 Df, -0.001 Df;), and larger arteriolar branching angle (1.8°; 95% CI: 0.3°, 3.3°) than mothers without GDM. After further adjusting for traditional risks of GDM, arteriolar branching angle remained significantly larger in mothers with GDM than those without GDM (2.0°; 95% CI: 0.5°, 3.6°). CONCLUSIONS: GDM was associated with a series of retinal arteriolar abnormalities, including narrower caliber, reduced fractal dimension and larger branching angle, suggesting that transient hyperglycemia during pregnancy may cause small-vessel dysfunction

Does Uptake of Pharmaceuticals Vary Across Earthworm Species?

This study compared the uptake and depuration of four commonly used pharmaceuticals (carbamazepine, diclofenac, fluoxetine and orlistat) in two earthworm species (Lumbricus terrestris and Eisenia fetida). L. terrestris are a larger species and often found in deep burrows whereas E. fetida prefer to reside near the soil surface. Species burrowing habits and sizes may alter uptake by earthworms. All four pharmaceuticals were taken up into both L. terrestris and E. fetida tissue after 21 days exposure to spiked soil. Bioconcentration factors (BCFs) ranged between 1.72 and 29.83 for L. terrestris and 1.14 and 63.03 for E. fetida. For carbamazepine and diclofenac, BCFs were similar whereas for fluoxetine and orlistat, BCFs in E. fetida were more than double those seen in L. terrestris. Results indicate that uptake into earthworms cannot be generalised between species and that the influence of species traits can vary depending on the nature of the study chemical

Internal construct validity of the Warwick-Edinburgh Mental Well-being Scale (WEMWBS): a Rasch analysis using data from the Scottish Health Education Population Survey

Background: The Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) was developed to meet demand for instruments to measure mental well-being. It comprises 14 positively phrased Likert-style items and fulfils classic criteria for scale development. We report here the internal construct validity of WEMWBS from the perspective of the Rasch measurement model. Methods: The model was applied to data collected from 779 respondents in Wave 12 (Autumn 2006) of the Scottish Health Education Population Survey. Respondents were aged 16–74 (average 41.9) yrs. Results: Initial fit to model expectations was poor. The items 'I've been feeling good about myself', 'I've been interested in new things' and 'I've been feeling cheerful' all showed significant misfit to model expectations, and were deleted. This led to a marginal improvement in fit to the model. After further analysis, more items were deleted and a strict unidimensional seven item scale (the Short Warwick Edinburgh Mental Well-Being Scale (SWEMWBS)) was resolved. Many items deleted because of misfit with model expectations showed considerable bias for gender. Two retained items also demonstrated bias for gender but, at the scale level, cancelled out. One further retained item 'I've been feeling optimistic about the future' showed bias for age. The correlation between the 14 item and 7 item versions was 0.954. Given fit to the Rasch model, and strict unidimensionality, SWEMWBS provides an interval scale estimate of mental well-being. Conclusion: A short 7 item version of WEMWBS was found to satisfy the strict unidimensionality expectations of the Rasch model, and be largely free of bias. This scale, SWEMWBS, provides a raw score-interval scale transformation for use in parametric procedures. In terms of face validity, SWEMWBS presents a more restricted view of mental well-being than the 14 item WEMWBS, with most items representing aspects of psychological and eudemonic well-being, and few covering hedonic well-being or affect. However, robust measurement properties combined with brevity make SWEMWBS preferable to WEMWBS at present for monitoring mental well-being in populations. Where face validity is an issue there remain arguments for continuing to collect data on the full 14 item WEMWBS

A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus

Generally, the second messenger bis-(3’-5’)-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiates a developmental program that culminates in formation of spore-filled fruiting bodies. We show that c-di-GMP accumulates at elevated levels during development and that this increase is essential for completion of development whereas excess c-di-GMP does not interfere with development. MXAN3735 (renamed DmxB) is identified as a diguanylate cyclase that only functions during development and is responsible for this increased c-di-GMP accumulation. DmxB synthesis is induced in response to starvation, thereby restricting DmxB activity to development. DmxB is essential for development and functions downstream of the Dif chemosensory system to stimulate exopolysaccharide accumulation by inducing transcription of a subset of the genes encoding proteins involved in exopolysaccharide synthesis. The developmental defects in the dmxB mutant are non-cell autonomous and rescued by co-development with a strain proficient in exopolysaccharide synthesis, suggesting reduced exopolysaccharide accumulation as the causative defect in this mutant. The NtrC-like transcriptional regulator EpsI/Nla24, which is required for exopolysaccharide accumulation, is identified as a c-diGMP receptor, and thus a putative target for DmxB generated c-di-GMP. Because DmxB can be—at least partially—functionally replaced by a heterologous diguanylate cyclase, these results altogether suggest a model in which a minimum threshold level of c-di-GMP is essential for the successful completion of multicellular development in M. xanthus

Burden of Illness in UK Subjects with Reported Respiratory Infections Vaccinated or Unvaccinated against Influenza: A Retrospective Observational Study

<div><p>Objective</p><p>Detailed data are lacking on influenza burden in the United Kingdom (UK). The objective of this study was to estimate the disease burden associated with influenza-like illness (ILI) in the United Kingdom stratified by age, risk and influenza vaccination status.</p><p>Methods</p><p>This retrospective, cross-sectional, exploratory, observational study used linked data from the General Practice Research Database and the Hospital Episode Statistics databases to estimate resource use and cost associated with ILI in the UK.</p><p>Results</p><p>Data were included from 156,193 patients with ≥1 general practitioner visit with ILI. There were 21,518 high-risk patients, of whom 12,514 (58.2%) were vaccinated and 9,004 (41.8%) were not vaccinated, and 134,675 low-risk patients, of whom 17,482 (13.0%) were vaccinated and 117,193 (87.0%) were not vaccinated. High-risk vaccinated patients were older (p<0.001) and had more risk conditions (p<0.001). High-risk (odds ratio [OR] 2.16) or vaccinated (OR 1.19) patients had a higher probability of >1 general practitioner visit compared with low-risk and unvaccinated patients. Patients who were high-risk and vaccinated had a reduced risk of >1 general practitioner visit (OR 0.82; p<0.001). High-risk individuals who were also vaccinated had a lower probability of ILI-related hospitalisation than individuals who were high-risk or vaccinated alone (OR 0.59). In people aged ≥65 years, the mortality rate was lower in vaccinated than unvaccinated individuals (OR 0.75). The cost of ILI-related GP visits and hospital admissions in the UK over the study period in low-risk vaccinated patients was £27,391,142 and £141,932,471, respectively. In low-risk unvaccinated patients the corresponding values were £168,318,709 and £112,534,130, respectively.</p><p>Conclusions</p><p>Although vaccination rates in target groups have increased, many people are still not receiving influenza vaccination, and the burden of ILI in the United Kingdom remains substantial. Improving influenza vaccination uptake may have the potential to reduce this burden.</p></div

Reviewing evidence of marine ecosystem change off South Africa

Recent changes have been observed in South African marine ecosystems. The main pressures on these ecosystems are fishing, climate change, pollution, ocean acidification and mining. The best long-term datasets are for trends in fishing pressures but there are many gaps, especially for non-commercial species. Fishing pressures have varied over time, depending on the species being caught. Little information exists for trends in other anthropogenic pressures. Field observations of environmental variables are limited in time and space. Remotely sensed satellite data have improved spatial and temporal coverage but the time-series are still too short to distinguish long-term trends from interannual and decadal variability. There are indications of recent cooling on the West and South coasts and warming on the East Coast over a period of 20 - 30 years. Oxygen concentrations on the West Coast have decreased over this period. Observed changes in offshore marine communities include southward and eastward changes in species distributions, changes in abundance of species, and probable alterations in foodweb dynamics. Causes of observed changes are difficult to attribute. Full understanding of marine ecosystem change requires ongoing and effective data collection, management and archiving, and coordination in carrying out ecosystem research.DHE

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