Gaining insights from Candida biofilm heterogeneity: one size does not fit all

Despite their clinical significance and substantial human health burden, fungal infections remain relatively under-appreciated. The widespread overuse of antibiotics and the increasing requirement for indwelling medical devices provides an opportunistic potential for the overgrowth and colonization of pathogenic Candida species on both biological and inert substrates. Indeed, it is now widely recognized that biofilms are a highly important part of their virulence repertoire. Candida albicans is regarded as the primary fungal biofilm forming species, yet there is also increasing interest and growing body of evidence for non-Candida albicans species (NCAS) biofilms, and interkingdom biofilm interactions. C. albicans biofilms are heterogeneous structures by definition, existing as three-dimensional populations of yeast, pseudo-hyphae, and hyphae, embedded within a self-produced extracellular matrix. Classical molecular approaches, driven by extensive studies of laboratory strains and mutants, have enhanced our knowledge and understanding of how these complex communities develop, thrive, and cause host-mediated damage. Yet our clinical observations tell a different story, with differential patient responses potentially due to inherent biological heterogeneity from specific clinical isolates associated with their infections. This review explores some of the recent advances made in an attempt to explore the importance of working with clinical isolates, and what this has taught us

Injection therapies for Achilles tendinopathy

Background: Achilles tendinopathy is a common condition, often with significant functional consequences. As a wide range of injection treatments are available, a review of randomised trials evaluating injection therapies to help inform treatment decisions is warranted. Objectives: To assess the effects (benefits and harms) of injection therapies for people with Achilles tendinopathy. Search methods: We searched the following databases up to 20 April 2015: the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AMED, CINAHL and SPORTDiscus. We also searched trial registers (29 May 2014) and reference lists of articles to identify additional studies. Selection criteria: We included randomised and quasi-randomised controlled trials evaluating injection therapies in adults with an investigator-reported diagnosis of Achilles tendinopathy. We accepted comparison arms of placebo (sham) or no injection control, or other active treatment (such as physiotherapy, pharmaceuticals or surgery). Our primary outcomes were function, using measures such as the VISA-A (Victorian Institute of Sport Assessment-Achilles questionnaire), and adverse events. Data collection and analysis: Two review authors independently extracted data from the included studies. We assessed treatment effects using mean differences (MDs) and 95% confidence intervals (CIs) for continuous variables and risk ratios (RRs) and 95% CIs for dichotomous variables. For follow-up data, we defined short-term as up to six weeks, medium-term as up to three months and longer-term as data beyond three months. We performed meta-analysis where appropriate. Main results: We included 18 studies (732 participants). Seven trials exclusively studied athletic populations. The mean ages of the participants in the individual trials ranged from 20 years to 50 years. Fifteen trials compared an injection therapy with a placebo injection or no injection control, four trials compared an injection therapy with active treatment, and one compared two different concentrations of the same injection. Thus no trials compared different injection therapies. Two studies had three trial arms and we included them twice in two different categories. Within these categories, we further subdivided injection therapies by mode of action (injury-causing versus direct repair agents). The risk of bias was unclear (due to poor reporting) or high in six trials published between 1987 and 1994. Improved methodology and reporting for the subsequent trials published between 2004 and 2013 meant that these were at less risk of bias. Given the very low quality evidence available from each of four small trials comparing different combinations of injection therapy versus active treatment and the single trial comparing two doses of one injection therapy, only the results of the first comparison (injection therapy versus control) are presented. There is low quality evidence of a lack of significant or clinically important differences in VISA-A scores (0 to 100: best function) between injection therapy and control groups at six weeks (MD 0.79, 95% CI -4.56 to 6.14; 200 participants, five trials), three months (MD -0.94, 95% CI -6.34 to 4.46; 189 participants, five trials) or between six and 12 months (MD 0.14, 95% CI -6.54 to 6.82; 132 participants, three trials). Very low quality evidence from 13 trials showed little difference between the two groups in adverse events (14/243 versus 12/206; RR 0.97, 95% CI 0.50 to 1.89), most of which were minor and short-lasting. The only major adverse event in the injection therapy group was an Achilles tendon rupture, which happened in a trial testing corticosteroid injections. There was very low quality evidence in favour of the injection therapy group in short-term (under three months) pain (219 participants, seven trials) and in the return to sports (335 participants, seven trials). There was very low quality evidence indicating little difference between groups in patient satisfaction with treatment (152 participants, four trials). There was insufficient evidence to conclude on subgroup differences based on mode of action given that only two trials tested injury-causing agents and the clear heterogeneity of the other 13 trials, which tested seven different therapies that act directly on the repair pathway. Authors' conclusions: There is insufficient evidence from randomised controlled trials to draw conclusions on the use, or to support the routine use, of injection therapies for treating Achilles tendinopathy. This review has highlighted a need for definitive research in the area of injection therapies for Achilles tendinopathy, including in older non-athletic populations. This review has shown that there is a consensus in the literature that placebo-controlled trials are considered the most appropriate trial design

Perspectives on pre-exposure prophylaxis for people who inject drugs in the context of an HIV outbreak: a qualitative study

Background: There is an ongoing HIV outbreak amongst people who inject drugs (PWID) in Glasgow, Scotland, and one response which has not yet been widely implemented is the provision of Pre-exposure prophylaxis (PrEP). PrEP is the use of HIV anti-retrovirals prior to HIV infection to provide a barrier to infection. This has been shown to be effective amongst various at-risk populations in preventing HIV spread. The present study aimed to explore views of PWID who might benefit from PrEP provision and Service Providers working with PWID to understand will to use PrEP and literacy of PrEP, contributing to the development of a PrEP service. Methods: A qualitative approach was taken, with semi structured interviews conducted in Glasgow at two third sector service sites. 11 Service Providers and 21 PWID participated in the study. Data was analysed thematically. Results: Participants, both PWID and Service Providers, were keen to engage with PrEP and perceived substantial potential benefits of PrEP for this population. Potential barriers to engagement were identified as a lack of health literacy, motivation, and self-ascribed risk, as well as the overwhelming unpredictability of substance use. Participants wanted PrEP to be provided within already existing structures, particularly community pharmacies, and for promotion and provision to involve peers. Conclusion: This sample reported willingness to engage with PrEP, and suggested there is a specific need amongst PWID for PrEP. However, PWID have specific lived experienced contexts and needs, and are burdened by social and economic marginalisation and inequality at every level. This contrasts them from other populations currently being provided with PrEP, and must be considered in the development of provision

Test-Retest Reliability of a Commercial Linear Position Transducer (GymAware PowerTool) to Measure Velocity and Power in the Back Squat and Bench Press

This study examined the test-retest reliability of the GymAware PowerTool (GYM) to measure velocity and power in the free-weight back squat and bench press. Twenty-nine academy rugby league players (age: 17.6 ± 1.0 years; body mass: 87.3 ± 20.8 kg) completed 2 test-retest sessions for the back squat followed by 2 test-retest sessions for the bench press. GYM measured mean velocity (MV), peak velocity (PV), mean power (MP), and peak power at 20, 40, 60, 80, and 90% of 1 repetition maximum (1RM). GYM showed good reliability (intraclass correlation coefficient [ICC] and standard error of measurement percentage, respectively) for the measurement of MV at loads of 40 (0.77, 3.9%), 60 (0.83, 4.8%), 80 (0.83, 5.8%), and 90% (0.79, 7.9%) of 1RM in the back squat. In the bench press, good reliability was evident for PV at 40 (0.82, 3.9%), 60 (0.81, 5.1%), and 80% (0.77, 8.4%) of 1RM, and for MV at 80 (0.78, 7.9%) and 90% (0.87, 9.9%) of 1RM. The measurement of MP showed good to excellent levels of reliability across all relative loads (ICC ≥0.75). In conclusion, GYM provides practitioners with reliable kinematic information in the back squat and bench press, at least with loads of 40–90% of 1RM. This suggests that strength and conditioning coaches can use the velocity data to regulate training load according to daily readiness and target specific components of the force-velocity curve. However, caution should be taken when measuring movement velocity at loads <40% of 1RM

Test-Retest reliability of a commercial linear position transducer (GymAware PowerTool) to measure velocity and power in the Back Squat and Bench Press

This study examined the test-retest reliability of the GymAware PowerTool (GYM) to measure velocity and power in the free-weight back squat and bench press. Twenty-nine academy rugby league players (age: 17.6 ± 1.0 years; body mass: 87.3 ± 20.8 kg) completed 2 test-retest sessions for the back squat followed by 2 test-retest sessions for the bench press. GYM measured mean velocity (MV), peak velocity (PV), mean power (MP), and peak power at 20, 40, 60, 80, and 90% of 1 repetition maximum (1RM). GYM showed good reliability (intraclass correlation coefficient [ICC] and standard error of measurement percentage, respectively) for the measurement of MV at loads of 40 (0.77, 3.9%), 60 (0.83, 4.8%), 80 (0.83, 5.8%), and 90% (0.79, 7.9%) of 1RM in the back squat. In the bench press, good reliability was evident for PV at 40 (0.82, 3.9%), 60 (0.81, 5.1%), and 80% (0.77, 8.4%) of 1RM, and for MV at 80 (0.78, 7.9%) and 90% (0.87, 9.9%) of 1RM. The measurement of MP showed good to excellent levels of reliability across all relative loads (ICC ≥0.75). In conclusion, GYM provides practitioners with reliable kinematic information in the back squat and bench press, at least with loads of 40–90% of 1RM. This suggests that strength and conditioning coaches can use the velocity data to regulate training load according to daily readiness and target specific components of the force-velocity curve. However, caution should be taken when measuring movement velocity at load

The First Detections of the Extragalactic Background Light at 3000, 5500, and 8000A (III): Cosmological Implications

(Abridged) We have used HST WFPC2 and ground-based spectroscopy to measure the integrated extragalactic background light (EBL) at optical wavelengths. We have also computed the integrated light from individual galaxy counts in the images used to measure the EBL and in the Hubble Deep Field. We find that the flux in galaxies as measured by standard galaxy photometry methods has generally been underestimated by about 50%. Further, we find that the total flux in individually detected galaxies is a factor of 2 to 3 less than the EBL at 3000--8000A. We show that a significant fraction of the EBL may come from normal galaxies at z<4, which are simply undetectable as a result of K-corrections and cosmological surface brightness dimming. This is consistent with recent redshift surveys at z<4. In the context of some simple models, we discuss the constraints placed by the EBL on the evolution of the luminosity density at z>1. Based on our optical EBL and published UV and IR EBL measurements, we estimate that the total EBL from 0.1--1000 microns is 100+/-20 nW/m^2/sr. If the total EBL were produced entirely by stellar nucleosynthesis, then we estimate that the total baryonic mass processed through stars is Omega_* = 0.0062 (+/- 0.0022) h^{-2}, which corresponds to 0.33+/-0.12 Omega_B for currently favored values of the baryon density. This estimate is smaller by roughly 7% if 7 h_{0.7} nW/m^2/sr of the total EBL comes from accretion onto central black holes. This estimate of Omega_* suggests that the universe has been enriched to a total metal mass of 0.21(+/-0.13) Z_sun Omega_B. Our estimate is consistent with other measurements of the cumulative metal mass fraction of stars, stellar remnants, and the intracluster medium of galaxy clusters in the local universe.Comment: Accepted for publication in ApJ, 20 pages using emulateapj.sty, version with higher resolution figures available at http://www.astro.lsa.umich.edu/~rab/publications.html or at http://nedwww.ipac.caltech.edu/level5/Sept01/Bernstein3/frames.htm

Validity and reliability of a wearable inertial sensor to measure velocity and power in the back squat and bench press

Orange, ST, Metcalfe, JW, Liefeith, A, Marshall, P, Madden, LA, Fewster, CR, and Vince, RV. Validity and reliability of a wearable inertial sensor to measure velocity and power in the back squat and bench press. J Strength Cond Res 33(9): 2398-2408, 2019-This study examined the validity and reliability of a wearable inertial sensor to measure velocity and power in the free-weight back squat and bench press. Twenty-nine youth rugby league players (18 ± 1 years) completed 2 test-retest sessions for the back squat followed by 2 test-retest sessions for the bench press. Repetitions were performed at 20, 40, 60, 80, and 90% of 1 repetition maximum (1RM) with mean velocity, peak velocity, mean power (MP), and peak power (PP) simultaneously measured using an inertial sensor (PUSH) and a linear position transducer (GymAware PowerTool). The PUSH demonstrated good validity (Pearson's product-moment correlation coefficient [r]) and reliability (intraclass correlation coefficient [ICC]) only for measurements of MP (r = 0.91; ICC = 0.83) and PP (r = 0.90; ICC = 0.80) at 20% of 1RM in the back squat. However, it may be more appropriate for athletes to jump off the ground with this load to optimize power output. Further research should therefore evaluate the usability of inertial sensors in the jump squat exercise. In the bench press, good validity and reliability were evident only for the measurement of MP at 40% of 1RM (r = 0.89; ICC = 0.83). The PUSH was unable to provide a valid and reliable estimate of any other criterion variable in either exercise. Practitioners must be cognizant of the measurement error when using inertial sensor technology to quantify velocity and power during resistance training, particularly with loads other than 20% of 1RM in the back squat and 40% of 1RM in the bench press

The 'One in a Million' study:creating a database of UK primary care consultations

BackgroundAround 1 million primary care consultations happen in England every day. Despite this, much of what happens in these visits remains a ‘black box’.AimTo create an archive of videotaped consultations and linked data based on a large sample of routine face-to-face doctor–patient consultations with consent for use in future research and training.Design and settingCross-sectional study in 12 general practices in the west of England, UK.MethodUp to two GPs from each practice took part in the study. Over 1 to 2 days, consecutive patients were approached until up to 20 eligible patients for each GP consented to be videotaped. Eligible patients were aged ≥18 years, consulting on their own behalf, fluent in English, and with capacity to consent. GP questionnaires were self-administered. Patient questionnaires were self-administered immediately pre-consultation and post-consultation, and GPs filled in a checklist after each recording. A follow-up questionnaire was sent to patients after 10 days, and data about subsequent related consultations were collected from medical records 3 months later.ResultsOf the 485 patients approached, 421 (86.8%) were eligible. Of the eligible patients, 334 (79.3%) consented to participate and 327 consultations with 23 GPs were successfully taped (307 video, 20 audio-only). Most patients (n = 300, 89.8%) consented to use by other researchers, subject to specific ethical approval.ConclusionMost patients were willing to allow their consultations to be videotaped, and, with very few exceptions, to allow recordings and linked data to be stored in a data repository for future use for research and training.</jats:sec