Clinically feasible diffusion MRI in muscle: Time dependence and initial findings in Duchenne muscular dystrophy

Purpose: To characterize the diffusion time-dependence in muscle in healthy adult volunteers, boys with Duchenne’s muscular dystrophy (DMD), and age-matched controls in a clinically feasible acquisition time for pediatric applications. / Methods: Diffusion data were acquired using a pulsed gradient stimulated echo diffusion preparation at 5 different diffusion times (70, 130, 190, 250, and 330 ms), at 4 different b-values (0, 200, 400, 600, and 800 s/mm2) and 6 directions (orthogonal x, y, and z and diagonal xy, xz, and yz) and processed to obtain standard diffusion indices (mean diffusivity [MD] and fractional anisotropy [FA]) at each diffusion time. / Results Time-dependent diffusion was seen in muscle in healthy adult volunteers, boys with DMD, and age-matched controls. Boys with DMD showed reduced MD and increased FA values in comparison to age matched controls across a range of diffusion times. A diffusion time of Δ = 190 ms had the largest effect size. / Conclusions: These results could be used to optimize diffusion imaging in this disease further and imply that these diffusion indices may become an important biomarker in monitoring progression in DMD in the future

Quality of Life in Oncological Patients with Oropharyngeal Dysphagia: Validity and Reliability of the Dutch Version of the MD Anderson Dysphagia Inventory and the Deglutition Handicap Index

Quality of life is an important outcome measurement in objectifying the current health status or therapy effects in patients with oropharyngeal dysphagia. In this study, the validity and reliability of the Dutch version of the Deglutition Handicap Index (DHI) and the MD Anderson Dysphagia Inventory (MDADI) have been determined for oncological patients with oropharyngeal dysphagia. At Maastricht University Medical Center, 76 consecutive patients were selected and asked to fill in three questionnaires on quality of life related to oropharyngeal dysphagia (the SWAL-QOL, the MDADI, and the DHI) as well as a simple one-item visual analog Dysphagia Severity Scale. None of the quality-of-life questionnaires showed any floor or ceiling effect. The test-retest reliability of the MDADI and the Dysphagia Severity Scale proved to be good. The test-retest reliability of the DHI could not be determined because of insufficient data, but the intraclass correlation coefficients were rather high. The internal consistency proved to be good. However, confirmatory factor analysis could not distinguish the underlying constructs as defined by the subscales per questionnaire. When assessing criterion validity, both the MDADI and the DHI showed satisfactory associations with the SWAL-QOL (reference or gold standard) after having removed the less relevant subscales of the SWAL-QOL. In conclusion, when assessing the validity and reliability of the Dutch version of the DHI or the MDADI, not all psychometric properties have been adequately met. In general, because of difficulties in the interpretation of study results when using questionnaires lacking sufficient psychometric quality, it is recommended that researchers strive to use questionnaires with the most optimal psychometric properties

Borrelia recurrentis employs a novel multifunctional surface protein with anti-complement, anti-opsonic and invasive potential to escape innate immunity

Borrelia recurrentis, the etiologic agent of louse-borne relapsing fever in humans, has evolved strategies, including antigenic variation, to evade immune defence, thereby causing severe diseases with high mortality rates. Here we identify for the first time a multifunctional surface lipoprotein of B. recurrentis, termed HcpA, and demonstrate that it binds human complement regulators, Factor H, CFHR-1, and simultaneously, the host protease plasminogen. Cell surface bound factor H was found to retain its activity and to confer resistance to complement attack. Moreover, ectopic expression of HcpA in a B. burgdorferi B313 strain, deficient in Factor H binding proteins, protected the transformed spirochetes from complement-mediated killing. Furthermore, HcpA-bound plasminogen/plasmin endows B. recurrentis with the potential to resist opsonization and to degrade extracellular matrix components. Together, the present study underscores the high virulence potential of B. recurrentis. The elucidation of the molecular basis underlying the versatile strategies of B. recurrentis to escape innate immunity and to persist in human tissues, including the brain, may help to understand the pathological processes underlying louse-borne relapsing fever

Development and validation of a questionnaire to measure moral distress in community pharmacists

The Author(s) 2016. . This article is published with open access at Springerlink.com This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Jayne L. Astbury, and Cathal T. Gallagher, 'Development and validation of a questionnaire to measure moral distress in community pharmacists', International Journal of Clinical Pharmacy (2017) Vol 39(1): 156-164, first published online on 22 December 2016, the version of record is available on line via doi: 10.1007/s11096-016-0413-3 Funding for this work was provided by Pharmacy Research UK (PRUK).Background Pharmacists work within a highly-regulated occupational sphere, and are bound by strict legal frameworks and codes of professional conduct. This regulatory environment creates the potential for moral distress to occur due to the limitations it places on acting in congruence with moral judgements. Very little research regarding this phenomenon has been undertaken in pharmacy: thus, prominent research gaps have arisen for the development of a robust tool to measure and quantify moral distress experienced in the profession. Objective The aim of this study was to develop an instrument to measure moral distress in community pharmacists. Setting Community pharmacies in the United Kingdom. Method This study adopted a three-phase exploratory sequential mixed-method design. Three semi-structured focus groups were then conducted to allow pharmacists to identify and explore scenarios that cause moral distress. Each of the identified scenarios were developed into a statement, which was paired with twin seven-point Likert scales to measure the frequency and intensity of the distress, respectively. Content validity, reliability, and construct validity were all tested, and the questionnaire was refined. Main outcome measure The successful development of the valid instrument for use in the United Kingdom. Results This research has led to the development of a valid and reliable instrument to measure moral distress in community pharmacists in the UK. The questionnaire has already been distributed to a large sample of community pharmacists. Conclusion Results from this distribution will be used to inform the formulation of coping strategies for dealing with moral distress.Peer reviewedFinal Published versio

The increasing importance of atmospheric demand for ecosystem water and carbon fluxes

Soil moisture supply and atmospheric demand for water independently limit—and profoundly affect—vegetation productivity and water use during periods of hydrologic stress1, 2, 3, 4. Disentangling the impact of these two drivers on ecosystem carbon and water cycling is difficult because they are often correlated, and experimental tools for manipulating atmospheric demand in the field are lacking. Consequently, the role of atmospheric demand is often not adequately factored into experiments or represented in models5, 6, 7. Here we show that atmospheric demand limits surface conductance and evapotranspiration to a greater extent than soil moisture in many biomes, including mesic forests that are of particular importance to the terrestrial carbon sink8, 9. Further, using projections from ten general circulation models, we show that climate change will increase the importance of atmospheric constraints to carbon and water fluxes in all ecosystems. Consequently, atmospheric demand will become increasingly important for vegetation function, accounting for >70% of growing season limitation to surface conductance in mesic temperate forests. Our results suggest that failure to consider the limiting role of atmospheric demand in experimental designs, simulation models and land management strategies will lead to incorrect projections of ecosystem responses to future climate conditions

Hip disability and osteoarthritis outcome score (HOOS) – validity and responsiveness in total hip replacement

BACKGROUND: The aim of the study was to evaluate if physical functions usually associated with a younger population were of importance for an older population, and to construct an outcome measure for hip osteoarthritis with improved responsiveness compared to the Western Ontario McMaster osteoarthritis score (WOMAC LK 3.0). METHODS: A 40 item questionnaire (hip disability and osteoarthritis outcome score, HOOS) was constructed to assess patient-relevant outcomes in five separate subscales (pain, symptoms, activity of daily living, sport and recreation function and hip related quality of life). The HOOS contains all WOMAC LK 3.0 questions in unchanged form. The HOOS was distributed to 90 patients with primary hip osteoarthritis (mean age 71.5, range 49–85, 41 females) assigned for total hip replacement for osteoarthritis preoperatively and at six months follow-up. RESULTS: The HOOS met set criteria of validity and responsiveness. It was more responsive than WOMAC regarding the subscales pain (SRM 2.11 vs. 1.83) and other symptoms (SRM 1.83 vs. 1.28). The responsiveness (SRM) for the two added subscales sport and recreation and quality of life were 1.29 and 1.65, respectively. Patients ≤ 66 years of age (range 49–66) reported higher responsiveness in all five subscales than patients >66 years of age (range 67–85) (Pain SRM 2.60 vs. 1.97, other symptoms SRM 3.0 vs. 1.60, activity of daily living SRM 2.51 vs. 1.52, sport and recreation function SRM 1.53 vs. 1.21 and hip related quality of life SRM 1.95 vs. 1.57). CONCLUSION: The HOOS 2.0 appears to be useful for the evaluation of patient-relevant outcome after THR and is more responsive than the WOMAC LK 3.0. The added subscales sport and recreation function and hip related quality of life were highly responsive for this group of patients, with the responsiveness being highest for those younger than 66

Efficacy of intra-articular hyaluronan (Synvisc®) for the treatment of osteoarthritis affecting the first metatarsophalangeal joint of the foot (hallux limitus): study protocol for a randomised placebo controlled trial

<p>Abstract</p> <p>Background</p> <p>Osteoarthritis of the first metatarsophalangeal joint (MPJ) of the foot, termed <it>hallux limitus</it>, is common and painful. Numerous non-surgical interventions have been proposed for this disorder, however there is limited evidence for their efficacy. Intra-articular injections of hyaluronan have shown beneficial effects in case-series and clinical trials for the treatment of osteoarthritis of the first metatarsophalangeal joint. However, no study has evaluated the efficacy of this form of treatment using a randomised placebo controlled trial. This article describes the design of a randomised placebo controlled trial to evaluate the efficacy of intra-articular hyaluronan (Synvisc^®) to reduce pain and improve function in people with hallux limitus.</p> <p>Methods</p> <p>One hundred and fifty community-dwelling men and women aged 18 years and over with hallux limitus (who satisfy inclusion and exclusion criteria) will be recruited.</p> <p>Participants will be randomised, using a computer-generated random number sequence, to receive a single intra-articular injection of up to 1 ml hyaluronan (Synvisc^®) or sterile saline (placebo) into the first MPJ. The injections will be performed by an interventional radiologist using fluoroscopy to ensure accurate deposition of the hyaluronan in the joint. Participants will be given the option of a second and final intra-articular injection (of Synvisc^®or sterile saline according to the treatment group they are in) either 1 or 3 months post-treatment if there is no improvement in pain and the participant has not experienced severe adverse effects after the first injection. The primary outcome measures will be the pain and function subscales of the Foot Health Status Questionnaire. The secondary outcome measures will be pain at the first MPJ (during walking and at rest), stiffness at the first MPJ, passive non-weightbearing dorsiflexion of the first MPJ, plantar flexion strength of the toe-flexors of the hallux, global satisfaction with the treatment, health-related quality of life (assessed using the Short-Form-36 version two questionnaire), magnitude of symptom change, use of pain-relieving medication and changes in dynamic plantar pressure distribution (maximum force and peak pressure) during walking. Data will be collected at baseline, then 1, 3 and 6 months post-treatment. Data will be analysed using the intention to treat principle.</p> <p>Discussion</p> <p>This study is the first randomised placebo controlled trial to evaluate the efficacy of intra-articular hyaluronan (Synvisc^®) for the treatment of osteoarthritis of the first MPJ (hallux limitus). The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if this form of treatment is found to be an effective treatment strategy.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry: ACTRN12607000654459</p

Synergy of extreme drought and shrub invasion reduce ecosystem functioning and resilience in water-limited climates

Extreme drought events and plant invasions are major drivers of global change that can critically affect ecosystem functioning and alter ecosystem-atmosphere exchange. Invaders are expanding worldwide and extreme drought events are projected to increase in frequency and intensity. However, very little is known on how these drivers may interact to affect the functioning and resilience of ecosystems to extreme events. Using a manipulative shrub removal experiment and the co-occurrence of an extreme drought event (2011/2012) in a Mediterranean woodland, we show that native shrub invasion and extreme drought synergistically reduced ecosystem transpiration and the resilience of key-stone oak tree species. Ecosystem transpiration was dominated by the water use of the invasive shrub Cistus ladanifer, which further increased after the extreme drought event. Meanwhile, the transpiration of key-stone tree species decreased, indicating a competitive advantage in favour of the invader. Our results suggest that in Mediterranean-type climates the invasion of water spending species and projected recurrent extreme drought events may synergistically cause critical drought tolerance thresholds of key-stone tree species to be surpassed, corroborating observed higher tree mortality in the invaded ecosystems. Ultimately, this may shift seasonally water limited ecosystems into less desirable alternative states dominated by water spending invasive shrubs

Biogeographic distributions of neotropical trees reflect their directly measured drought tolerances

High levels of species diversity hamper current understanding of how tropical forests may respond to environmental change. In the tropics, water availability is a leading driver of the diversity and distribution of tree species, suggesting that many tropical taxa may be physiologically incapable of tolerating dry conditions, and that their distributions along moisture gradients can be used to predict their drought tolerance. While this hypothesis has been explored at local and regional scales, large continental-scale tests are lacking. We investigate whether the relationship between drought-induced mortality and distributions holds continentally by relating experimental and observational data of drought-induced mortality across the Neotropics to the large-scale bioclimatic distributions of 115 tree genera. Across the different experiments, genera affiliated to wetter climatic regimes show higher drought-induced mortality than dry-affiliated ones, even after controlling for phylogenetic relationships. This pattern is stronger for adult trees than for saplings or seedlings, suggesting that the environmental filters exerted by drought impact adult tree survival most strongly. Overall, our analysis of experimental, observational, and bioclimatic data across neotropical forests suggests that increasing moisture-stress is indeed likely to drive significant changes in floristic composition