Clinical effectiveness of a rehabilitation program integrating exercise, self-management, and active coping strategies for chronic knee pain: a cluster randomized trial.

OBJECTIVE: Chronic knee pain is a major cause of disability and health care expenditure, but there are concerns about efficacy, cost, and side effects associated with usual primary care. Conservative rehabilitation may offer a safe, effective, affordable alternative. We compared the effectiveness of a rehabilitation program integrating exercise, self-management, and active coping strategies (Enabling Self-management and Coping with Arthritic Knee Pain through Exercise [ESCAPE-knee pain]) with usual primary care in improving functioning in persons with chronic knee pain. METHODS: We conducted a single-blind, pragmatic, cluster randomized controlled trial. Participants age >/=50 years, reporting knee pain for >6 months, were recruited from 54 inner-city primary care practices. Primary care practices were randomized to continued usual primary care (i.e., whatever intervention a participant's primary care physician deemed appropriate), usual primary care plus the rehabilitation program delivered to individual participants, or usual primary care plus the rehabilitation program delivered to groups of 8 participants. The primary outcome was self-reported functioning (Western Ontario and McMaster Universities Osteoarthritis Index physical functioning [WOMAC-func]) 6 months after completing rehabilitation. RESULTS: A total of 418 participants were recruited; 76 (18%) withdrew, only 5 (1%) due to adverse events. Rehabilitated participants had better functioning than participants continuing usual primary care (-3.33 difference in WOMAC-func score; 95% confidence interval [95% CI] -5.88, -0.78; P = 0.01). Improvements were similar whether participants received individual rehabilitation (-3.53; 95% CI -6.52, -0.55) or group rehabilitation (-3.16; 95% CI -6.55, -0.12). CONCLUSION: ESCAPE-knee pain provides a safe, relatively brief intervention for chronic knee pain that is equally effective whether delivered to individuals or groups of participants

Willingness to participate in future HIV prevention studies among gay and bisexual men in Scotland, UK: a challenge for intervention trials

This article examines willingness to participate in future HIV prevention research among gay and bisexual men in Scotland, UK. Anonymous, self-complete questionnaires and Orasure Gäó oral fluid samples were collected in commercial gay venues. 1,320 men were eligible for inclusion. 78.2% reported willingness to participate in future HIV prevention research; 64.6% for an HIV vaccine, 57.4% for a behaviour change study, and 53.0% for a rectal microbicide. In multivariate analysis, for HIV vaccine research, greater age, minority ethnicity, and not providing an oral fluid sample were associated with lower willingness; heterosexual orientation and not providing an oral fluid sample were for microbicides; higher education and greater HIV treatment optimism were for behaviour change. STI testing remained associated with being more willing to participate in microbicide research and frequent gay scene use remained associated with being more willing to participate in behaviour change research. Having an STI in the past 12 months remained significantly associated with being willing to participate in all three study types. There were no associations between sexual risk behaviour and willingness. Although most men expressed willingness to participate in future research, recruitment of high-risk men, who have the potential to benefit most, is likely to be more challenging

In situ observation of compressive deformation of an interconnected network of zinc oxide tetrapods

Zinc oxide tetrapods have remarkable functional and mechanical properties with potential applications in different fields including nanoelectronic and optoelectronic sensing, functional composites and coatings, as well as energy harvesting and storage. Based on the 3D shape of these microparticles, they can be assembled into highly porous (up to 98%) macroscopic ceramic framework structures that can be utilized as a versatile template for the fabrication of other multi-scaled foam-like materials. Here we investigated the three-dimensional structure of low density interconnected zinc oxide tetrapod networks by high resolution X-ray computed tomography. In situ observations during mechanical loading show inhomogeneous development of anelastic strain (damage) during compression, and homogeneous elastic recovery on unloading. Individual tetrapods are observed to deform by arm rotation to accommodate strain

The DNA methylome of human sperm is distinct from blood with little evidence for tissue-consistent obesity associations

Epidemiological research suggests that paternal obesity may increase the risk of fathering small for gestational age offspring. Studies in non-human mammals indicate that such associations could be mediated by DNA methylation changes in spermatozoa that influence offspring development in utero. Human obesity is associated with differential DNA methylation in peripheral blood. It is unclear, however, whether this differential DNA methylation is reflected in spermatozoa. We profiled genome-wide DNA methylation using the Illumina MethylationEPIC array in a cross-sectional study of matched human blood and sperm from lean (discovery n = 47; replication n = 21) and obese (n = 22) males to analyse tissue covariation of DNA methylation, and identify obesity-associated methylomic signatures. We found that DNA methylation signatures of human blood and spermatozoa are highly discordant, and methylation levels are correlated at only a minority of CpG sites (~1%). At the majority of these sites, DNA methylation appears to be influenced by genetic variation. Obesity-associated DNA methylation in blood was not generally reflected in spermatozoa, and obesity was not associated with altered covariation patterns or accelerated epigenetic ageing in the two tissues. However, one cross-tissue obesity-specific hypermethylated site (cg19357369; chr4:2429884; P = 8.95 × 10^{-8}; 2% DNA methylation difference) was identified, warranting replication and further investigation. When compared to a wide range of human somatic tissue samples (n = 5,917), spermatozoa displayed differential DNA methylation across pathways enriched in transcriptional regulation. Overall, human sperm displays a unique DNA methylation profile that is highly discordant to, and practically uncorrelated with, that of matched peripheral blood. We observed that obesity was only nominally associated with differential DNA methylation in sperm, and therefore suggest that spermatozoal DNA methylation is an unlikely mediator of intergenerational effects of metabolic traits

Modeling the impact of prevention policies on future diabetes prevalence in the United States: 2010-2030

Background Although diabetes is one of the most costly and rapidly increasing serious chronic diseases worldwide, the optimal mix of strategies to reduce diabetes prevalence has not been determined. Methods Using a dynamic model that incorporates national data on diabetes prevalence and incidence, migration, mortality rates, and intervention effectiveness, we project the effect of five hypothetical prevention policies on future US diabetes rates through 2030: 1) no diabetes prevention strategy; 2) a “high-risk” strategy, wherein adults with both impaired fasting glucose (IFG) (fasting plasma glucose of 100–124 mg/dl) and impaired glucose tolerance (IGT) (2-hour post-load glucose of 141–199 mg/dl) receive structured lifestyle intervention; 3) a “moderate-risk” strategy, wherein only adults with IFG are offered structured lifestyle intervention; 4) a “population-wide” strategy, in which the entire population is exposed to broad risk reduction policies; and 5) a “combined” strategy, involving both the moderate-risk and population-wide strategies. We assumed that the moderate- and high-risk strategies reduce the annual diabetes incidence rate in the targeted subpopulations by 12.5% through 2030 and that the population-wide approach would reduce the projected annual diabetes incidence rate by 2% in the entire US population. Results We project that by the year 2030, the combined strategy would prevent 4.6 million incident cases and 3.6 million prevalent cases, attenuating the increase in diabetes prevalence by 14%. The moderate-risk approach is projected to prevent 4.0 million incident cases, 3.1 million prevalent cases, attenuating the increase in prevalence by 12%. The high-risk and population approaches attenuate the projected prevalence increases by 5% and 3%, respectively. Even if the most effective strategy is implemented (the combined strategy), our projections indicate that the diabetes prevalence rate would increase by about 65% over the 23 years (i.e., from 12.9% in 2010 to 21.3% in 2030). Conclusions While implementation of appropriate diabetes prevention strategies may slow the rate of increase of the prevalence of diabetes among US adults through 2030, the US diabetes prevalence rate is likely to increase dramatically over the next 20 years. Demand for health care services for people with diabetes complications and diabetes-related disability will continue to grow, and these services will need to be strengthened along with primary diabetes prevention efforts

New mutations at the imprinted Gnas cluster show gene dosage effects of Gsα in postnatal growth and implicate XLαs in bone and fat metabolism, but not in suckling

The imprinted Gnas cluster is involved in obesity, energy metabolism, feeding behavior, and viability. Relative contribution of paternally expressed proteins XLαs, XLN1, and ALEX or a double dose of maternally expressed Gsα to phenotype has not been established. In this study, we have generated two new mutants (Ex1A-T-CON and Ex1A-T) at the Gnas cluster. Paternal inheritance of Ex1A-T-CON leads to loss of imprinting of Gsα, resulting in preweaning growth retardation followed by catch-up growth. Paternal inheritance of Ex1A-T leads to loss of imprinting of Gsα and loss of expression of XLαs and XLN1. These mice have severe preweaning growth retardation and incomplete catch-up growth. They are fully viable probably because suckling is unimpaired, unlike mutants in which the expression of all the known paternally expressed Gnasxl proteins (XLαs, XLN1 and ALEX) is compromised. We suggest that loss of ALEX is most likely responsible for the suckling defects previously observed. In adults, paternal inheritance of Ex1A-T results in an increased metabolic rate and reductions in fat mass, leptin, and bone mineral density attributable to loss of XLαs. This is, to our knowledge, the first report describing a role for XLαs in bone metabolism. We propose that XLαs is involved in the regulation of bone and adipocyte metabolism

Effects of adding Tiotropium or Aclidinium as triple therapy using impulse oscillometry in COPD

INTRODUCTION: Long-acting muscarinic antagonists confer improvements in spirometry when used in addition to inhaled corticosteroids and long-acting beta-agonists (ICS/LABA) in COPD. The dual objectives of this proof of concept study were to evaluate trough effects of tiotropium (TIO) or aclidinium (ACL) when used as triple therapy and to assess if impulse oscillometry (IOS) might be more sensitive than spirometry in detecting subtle differences in bronchodilator response. METHODS: Patients with moderate to severe COPD already taking ICS/LABA were randomized to receive add-on therapy in cross-over fashion with either TIO 18 µg od or ACL 322 µg bid for 2–3 weeks each. Measurements of IOS, spirometry, 6-min walk test, St George’s Respiratory Questionnaire (SGRQ) and Baseline/Transition Dyspnoea Index (TDI) were made at baseline and after chronic dosing at trough (12 h for ACL and 24 h for TIO), in addition to domiciliary diurnal spirometry. RESULTS: 13 patients were completed: mean age 69 years, FEV(1) 52 % predicted, FEV(1)/FVC 0.48, and R5 202 % predicted. There were no differences in any visit-based trough IOS or spirometry outcomes comparing TIO versus ACL. Resonant frequency but not total airway resistance at 5 Hz (R5) significantly improved from baseline with both treatments while peripheral airway resistance (R5–R20) significantly improved with ACL. Visit-based FEV(1), and forced and relaxed vital capacity were also significantly improved from baseline with both treatments. There were no significant differences in diurnal FEV(1) and FEV(6) profiles between treatments. 6-min walk distance and post-walk fatigue significantly improved from baseline with ACL, while post-walk dyspnea improved with TIO. SGRQ symptom score significantly improved to a similar degree with both treatments. TDI significantly improved with ACL versus TIO by 1.54 units. CONCLUSION: We observed comparable bronchodilator efficacy at trough with TIO and ACL when used as triple therapy in COPD, while IOS was no more sensitive than spirometry

Self-Compensation in Transparent Conducting F-Doped SnO2

The factors limiting the conductivity of fluorine-doped tin dioxide (FTO) produced via atmospheric pressure chemical vapor deposition are investigated. Modeling of the transport properties indicates that the measured Hall effect mobilities are far below the theoretical ionized impurity scattering limit. Significant compensation of donors by acceptors is present with a compensation ratio of 0.5, indicating that for every two donors there is approximately one acceptor. Hybrid density functional theory calculations of defect and impurity formation energies indicate the most probable acceptor-type defects. The fluorine interstitial defect has the lowest formation energy in the degenerate regime of FTO. Fluorine interstitials act as singly charged acceptors at the high Fermi levels corresponding to degenerately n-type films. X-ray photoemission spectroscopy of the fluorine impurities is consistent with the presence of substitutional F O donors and interstitial F i in a roughly 2:1 ratio in agreement with the compensation ratio indicated by the transport modeling. Quantitative analysis through Hall effect, X-ray photoemission spectroscopy, and calibrated secondary ion mass spectrometry further supports the presence of compensating fluorine-related defects

Factors associated with pleurisy in pigs: a case-control analysis of slaughter pig data for England and Wales

UNLABELLED: A case-control investigation was undertaken to determine management and health related factors associated with pleurisy in slaughter pigs in England and Wales. METHODS: The British Pig Executive Pig Health Scheme database of abattoir pathology was used to identify 121 case (>10% prevalence of pleurisy on 3 or more assessment dates in the preceding 24 months) and 121 control units (≤5% prevalence of pleurisy on 3 or more assessment dates in the preceding 24 months). Farm data were collected by postal questionnaire. Data from respondents (70 cases and 51 controls) were analysed using simple logistic regression models with Bonferroni corrections. Limited multivariate analyses were also performed to check the robustness of the overall conclusions. RESULTS AND CONCLUSIONS: Management factors associated with increased odds of pleurisy included no all-in all-out pig flow (OR 9.3, 95% confidence interval [CI]: 3.3-29), rearing of pigs with an age difference of >1 month in the same airspace (OR 6.5 [2.8-17]) and repeated mixing (OR 2.2 [1.4-3.8]) or moving (OR 2.2 [1.5-3.4]) of pigs during the rearing phase. Those associated with decreased odds of pleurisy included filling wean-to-finish or grower-to-finish systems with piglets from ≤3 sources (OR 0.18 [0.07-0.41]) compared to farrow-to-finish systems, cleaning and disinfecting of grower (ORs 0.28 [0.13-0.61] and 0.29 [0.13-0.61]) and finisher (ORs 0.24 [0.11-0.51] and 0.2 [0.09-0.44]) accommodation between groups, and extended down time of grower and finisher accommodation (OR 0.84 [0.75-0.93] and 0.86 [0.77-0.94] respectively for each additional day of downtime). This study demonstrated the value of national-level abattoir pathology data collection systems for case control analyses and generated guidance for on-farm interventions to help reduce the prevalence of pleurisy in slaughter pigs.The authors thank the British Pig Executive (BPEX - a part of the UK's Agricultural and Horticultural Development Board) for funding this project and providing the BPHS data base. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Recommendations for a core outcome set for measuring standing balance in adult populations: a consensus-based approach

Standing balance is imperative for mobility and avoiding falls. Use of an excessive number of standing balance measures has limited the synthesis of balance intervention data and hampered consistent clinical practice.To develop recommendations for a core outcome set (COS) of standing balance measures for research and practice among adults.A combination of scoping reviews, literature appraisal, anonymous voting and face-to-face meetings with fourteen invited experts from a range of disciplines with international recognition in balance measurement and falls prevention. Consensus was sought over three rounds using pre-established criteria.The scoping review identified 56 existing standing balance measures validated in adult populations with evidence of use in the past five years, and these were considered for inclusion in the COS.Fifteen measures were excluded after the first round of scoring and a further 36 after round two. Five measures were considered in round three. Two measures reached consensus for recommendation, and the expert panel recommended that at a minimum, either the Berg Balance Scale or Mini Balance Evaluation Systems Test be used when measuring standing balance in adult populations.Inclusion of two measures in the COS may increase the feasibility of potential uptake, but poses challenges for data synthesis. Adoption of the standing balance COS does not constitute a comprehensive balance assessment for any population, and users should include additional validated measures as appropriate.The absence of a gold standard for measuring standing balance has contributed to the proliferation of outcome measures. These recommendations represent an important first step towards greater standardization in the assessment and measurement of this critical skill and will inform clinical research and practice internationally