The TLR2/6 ligand PAM2CSK4 is a Th2 polarizing adjuvant in Leishmania major and Brugia malayi murine vaccine models.

Toll-like receptors (TLRs) play an important role in the innate and adaptive immune responses to pathogens, and are the target of new vaccine adjuvants. TLR2 plays a role in parasite recognition and activation of immune responses during cutaneous leishmaniasis infection, suggesting that TLR2 could be targeted by adjuvants for use in Leishmania vaccines. We therefore explored using Pam2CSK4 (Pam2) and Pam3CSK4 (Pam3) lipopeptide adjuvants, which activate TLR2/6 and TLR2/1 heterodimers respectively, in vaccine models for parasitic infections.The use of lipopeptide adjuvants was explored using two vaccine models. For cutaneous leishmaniasis, the lipopeptide adjuvants Pam2 and Pam3 were compared to that of the Th1-driving double-stranded DNA TLR9 agonist CpG for their ability to improve the efficacy of the autoclaved Leishmania major (ALM) vaccine to protect against L. major infection. The ability of Pam2 to enhance the efficacy of a soluble Brugia malayi microfilariae extract (BmMfE) vaccine to protect against filarial infection was also assessed in a peritoneal infection model of B. malayi filariasis. Parasite antigen-specific cellular and humoral immune responses were assessed post-challenge.The use of lipopeptides in ALM-containing vaccines did not provide any protection upon infection with L. major, and Pam2 exacerbated the disease severity in vaccinated mice post-challenge. Pam2, and to a lesser extent Pam3, were able to elevate antigen-specific immune responses post-challenge in this model, but these responses displayed a skewed Th2 phenotype as characterised by elevated levels of IgG1. In the B. malayi vaccine model, the use of Pam2 as an adjuvant with BmMfE induced significant protective immunity to the same level as inclusion of an Alum adjuvant. Here, both Pam2 and Alum were found to enhance antigen-specific antibody production post-challenge, and Pam2 significantly elevated levels of antigen-specific IL-4, IL-5 and IL-13 produced by splenocytes.These data indicate that TLR2/6-targeting ligands could be considered as adjuvants for vaccines that require robust Th2 and/or antibody-dependent immunity

Activity-promoting gaming systems in exercise and rehabilitation

Commercial activity-promoting gaming systems provide a potentially attractive means to facilitate exercise and rehabilitation. The Nintendo Wii, Sony EyeToy, Dance Dance Revolution, and Xbox Kinect are examples of gaming systems that use the movement of the player to control gameplay. Activity-promoting gaming systems can be used as a tool to increase activity levels in otherwise sedentary gamers and also be an effective tool to aid rehabilitation in clinical settings. Therefore, the aim of this current work is to review the growing area of activity-promoting gaming in the context of exercise, injury, and rehabilitation

Microphytobenthic extracellular polymeric substances (EPS) in intertidal sediments fuel both generalist and specialist EPS-degrading bacteria

Microphytobenthic biofilms contain high concentrations of carbohydrate-rich extracellular polymeric substances (EPS) that are important in sediment carbon cycling. Field measurements at two locations in the Colne Estuary, U.K., showed that a significant curvilinear relationship explained 50% of the variability in chlorophyll a and EPS content. Estimates of EPS production, based on field data and published rates of production by diatoms, revealed that EPS turnover of 52% to 369% over the tidal cycle was required to account for field standing stocks. We investigated EPS degradation in sediment slurries using purified 13C-EPS produced by the diatom Nitzschia tubicola. Although EPS constituted only 5% of the sediment dissolved organic carbon (DOC) pool, 100% of the added EPS was utilized within 30 h, before decreases in other sediment-carbohydrate fractions and DOC concentrations. A general 13C enrichment of phospholipid fatty acids (PLFAs), representative of Gram-positive and Gram-negative bacteria, occurred within 6 h, with the PLFAs a15:0, i15:0, and 18:1?7c being highly enriched. The diatom PLFA 20:5?3 had relatively low but significant 13C enrichment. Stable isotope probing of 16S ribosomal ribonucleic acid (RNA-SIP) at 30 h revealed 13C-enriched sequences from the diatom genus Navicula; further evidence that diatoms assimilated the EPS, or EPS-breakdown products, from other diatom taxa. RNA-SIP also demonstrated a diverse range of highly 13C-enriched bacterial taxa, including a distinct subset (Alphaproteobacteria and Gammaproteobacteria) found only in the heavily labeled microbial assemblages. Thus, cycling of diatom EPS is rapid, and involves a wide range of microbial taxa, including some apparent specialists

The impact of warm-up on youth golfer clubhead speed and self-reported shot quality

Background/Purpose: Physical preparation in golf is now considered a key component of the game. With players becoming more athletic, warm-up has become an important area in a player's preparation for practice and competition. Much of the research to date has focused on the adult golfer, showing potential for improvements in clubhead speed, driving distance and shot quality, as well as reductions in injury risk. However, there is currently no work specifically investigating the impacts of warm-up in youth golf. The aim of this study was to examine the impact of a club only warm-up and a dynamic exercise routine followed by a club warm-up on club head speed and self-reported shot quality. Methods: Using a counterbalanced repeated measures design, eight male and 13 female youth golfers completed a control (no warm-up), club only warm-up and an exercise based dynamic warm-up followed by club warm-up on three non-consecutive days. In each session, players were required to hit 10 maximal effort shots with a driver and clubhead speed (CHS) was recorded using a launch monitor alongside self-reported shot quality scores. Results: Statistically significant improvements in clubhead speed and self-reported shot quality were seen in the dynamic warm-up combined with club warm-up. No significant differences were seen in the club-warm up only or control groups for either clubhead speed or self-reported shot quality. Conclusion: A combined dynamic physical warm-up and club warm-up improves clubhead speed and self-reported shot quality in youth golfers. However, a club warm-up alone does not seem to be sufficient in eliciting these same improvements. Level of Evidence: 3

Data processing of remotely sensed airborne hyperspectral data using the Airborne Processing Library (APL): Geocorrection algorithm descriptions and spatial accuracy assessment

This is the author's preprint. The final version is available from the publisher via the DOI in this record.The authors would like to thank Dr. Peter Land for useful discussions on reflectance spectra of ground targets. Fig. 9 contains Ordnance Survey OpenData © Crown copyright and database right 2013. The hyperspectral data used in this report were collected by the Natural Environment Research Council Airborne Research and Survey Facility.Remote sensing airborne hyperspectral data are routinely used for applications including algorithm development for satellite sensors, environmental monitoring and atmospheric studies. Single flight lines of airborne hyperspectral data are often in the region of tens of gigabytes in size. This means that a single aircraft can collect terabytes of remotely sensed hyperspectral data during a single year. Before these data can be used for scientific analyses, they need to be radiometrically calibrated, synchronised with the aircraft's position and attitude and then geocorrected. To enable efficient processing of these large datasets the UK Airborne Research and Survey Facility has recently developed a software suite, the Airborne Processing Library (APL), for processing airborne hyperspectral data acquired from the Specim AISA Eagle and Hawk instruments. The APL toolbox allows users to radiometrically calibrate, geocorrect, reproject and resample airborne data. Each stage of the toolbox outputs data in the common Band Interleaved Lines (BILs) format, which allows its integration with other standard remote sensing software packages. APL was developed to be user-friendly and suitable for use on a workstation PC as well as for the automated processing of the facility; to this end APL can be used under both Windows and Linux environments on a single desktop machine or through a Grid engine. A graphical user interface also exists. In this paper we describe the Airborne Processing Library software, its algorithms and approach. We present example results from using APL with an AISA Eagle sensor and we assess its spatial accuracy using data from multiple flight lines collected during a campaign in 2008 together with in situ surveyed ground control points. © 2013 Elsevier Ltd

Active bacterioplankton community response to dissolved ‘free’ deoxyribonucleic acid (dDNA) in surface coastal marine waters

Seawater contains dissolved ‘free’ DNA (dDNA) that is part of a larger <0.2 μm pool of DNA (D-DNA) including viruses and uncharacterised bound DNA. Previous studies have shown that bacterioplankton readily degrade dDNA and culture-based approaches have identified several potential dDNA-utilising taxa. This study characterised the seasonal variation in D-DNA concentrations at Station L4, a coastal marine observatory in the Western English Channel, and linked changes in concentration to cognate physicochemical and biological factors. The impact of dDNA addition on active bacterioplankton communities at Station L4 was then determined using 16S rRNA high-throughput sequencing and RNA Stable Isotope Probing (RNA SIP) with 13C-labelled diatom-derived dDNA. Compared to other major bacterioplankton orders, the Rhodobacterales actively responded to dDNA additions in amended microcosms and RNA SIP identified two Rhodobacterales populations most closely associated with the genera Halocynthiibacter and Sulfitobacter that assimilated the 13C-labelled dDNA. Here we demonstrate that dDNA is a source of dissolved organic carbon for some members of the major bacterioplankton group the Marine Roseobacter Clade. This study enhances our understanding of roles of specific bacterioplankton taxa in dissolved organic matter cycling in coastal waters with potential implications for nitrogen and phosphorus regeneration processes

Biomechanics in Paralympics: Implications for Performance

Purpose: To provide an overview of biomechanical studies in Paralympic research and their relevance for performance in Paralympic sports. Methods: The search terms paralympic biomechanics, paralympic sport performance, paralympic athlete performance, and paralympic athlete were entered into the electronic database PubMed. Results: Thirty-four studies were found. Biomechanical studies in Paralympics mainly contributed to performance enhancement by technical optimization (n = 32) and/or injury prevention (n = 6). In addition, biomechanics was found to be important in understanding activity limitation caused by various impairments, which is relevant for evidence-based classification in Paralympic sports (n = 6). Distinctions were made between biomechanical studies in sitting (41%), standing (38%), and swimming athletes (21%). In sitting athletes, mostly kinematics and kinetics in wheelchair propulsion were studied, mainly in athletes with spinal-cord injuries. In addition, kinetics and/or kinematics in wheelchair basketball, seated discus throwing, stationary shot-putting, hand-cycling, sit-skiing, and ice sledge hockey received attention. In standing sports, primarily kinematics of athletes with amputations performing jump sports and running and the optimization of prosthetic devices were investigated. No studies were reported on other standing sports. In swimming, mainly kick rate and resistance training were studied. Conclusions: Biomechanical research is important for performance by gaining insight into technical optimization, injury prevention, and evidence-based classification in Paralympic sports. In future studies it is advised to also include physiological and biomechanical measures, allowing the assessment of the capability of the human body, as well as the resulting movement

Community responses to seawater warming are conserved across diverse biological groupings and taxonomic resolutions

Temperature variability is a major driver of ecological pattern, with recent changes in average and extreme temperatures having significant impacts on populations, communities and ecosystems. In the marine realm, very few experiments have manipulated temperature in situ, and current understanding of temperature effects on community dynamics is limited. We developed new technology for precise seawater temperature control to examine warming effects on communities of bacteria, microbial eukaryotes (protists) and metazoans. Despite highly contrasting phylogenies, size spectra and diversity levels, the three community types responded similarly to seawater warming treatments of +3°C and +5°C, highlighting the critical and overarching importance of temperature in structuring communities. Temperature effects were detectable at coarse taxonomic resolutions and many taxa responded positively to warming, leading to increased abundances at the community-level. Novel field-based experimental approaches are essential to improve mechanistic understanding of how ocean warming will alter the structure and functioning of diverse marine communities

Primary Care Atrial Fibrillation Service: outcomes from consultant-led anticoagulation assessment clinics in the primary care setting in the UK

OBJECTIVE: Stroke-risk in atrial fibrillation (AF) can be significantly reduced by appropriate thromboembolic prophylaxis. However, National Institute for Health and Care Excellence estimates suggest that up to half of eligible patients with AF are not anticoagulated, with severe consequences for stroke prevention. We aimed to determine the outcome of an innovative Primary Care AF (PCAF) service on anticoagulation uptake in a cohort of high-risk patients with AF in the UK. METHODS: The PCAF service is a novel cooperative pathway providing specialist resources within general practitioner (GP) practices. It utilises a four-phase protocol to identify high-risk patients with AF (CHA(2)DS(2)-VASc ≥1) who are suboptimally anticoagulated, and delivers Consultant-led anticoagulation assessment within the local GP practice. We assessed rates of anticoagulation in high-risk patients before and after PCAF service intervention, and determined compliance with newly-initiated anticoagulation at follow-up. RESULTS: The PCAF service was delivered in 56 GP practices (population 386 624; AF prevalence 2.1%) between June 2012 and June 2014. 1579 high-risk patients with AF with suboptimal anticoagulation (either not taking any anticoagulation or taking warfarin but with a low time-in-therapeutic-range) were invited for review, with 86% attending. Of 1063 eligible patients on no anticoagulation, 1020 (96%) agreed to start warfarin (459 (43%)) or a non-vitamin K antagonist oral anticoagulant (NOAC, 561 (53%)). The overall proportion of eligible patients receiving anticoagulation improved from 77% to 95% (p<0.0001). Additionally, 111/121 (92%) patients suboptimally treated with warfarin agreed to switch to a NOAC. Audit of eight practices after 195 (185–606) days showed that 90% of patients started on a new anticoagulant therapy had continued treatment. Based on data extrapolated from previous studies, around 30–35 strokes per year may have been prevented in these previously under-treated high-risk patients. CONCLUSIONS: Systematic identification of patients with AF with high stroke-risk and consultation in PCAF consultant-led clinics effectively delivers oral anticoagulation to high-risk patients with AF in the community

Estimation of Dietary Iron Bioavailability from Food Iron Intake and Iron Status

Currently there are no satisfactory methods for estimating dietary iron absorption (bioavailability) at a population level, but this is essential for deriving dietary reference values using the factorial approach. The aim of this work was to develop a novel approach for estimating dietary iron absorption using a population sample from a sub-section of the UK National Diet and Nutrition Survey (NDNS). Data were analyzed in 873 subjects from the 2000–2001 adult cohort of the NDNS, for whom both dietary intake data and hematological measures (hemoglobin and serum ferritin (SF) concentrations) were available. There were 495 men aged 19–64 y (mean age 42.7±12.1 y) and 378 pre-menopausal women (mean age 35.7±8.2 y). Individual dietary iron requirements were estimated using the Institute of Medicine calculations. A full probability approach was then applied to estimate the prevalence of dietary intakes that were insufficient to meet the needs of the men and women separately, based on their estimated daily iron intake and a series of absorption values ranging from 1–40%. The prevalence of SF concentrations below selected cut-off values (indicating that absorption was not high enough to maintain iron stores) was derived from individual SF concentrations. An estimate of dietary iron absorption required to maintain specified SF values was then calculated by matching the observed prevalence of insufficiency with the prevalence predicted for the series of absorption estimates. Mean daily dietary iron intakes were 13.5 mg for men and 9.8 mg for women. Mean calculated dietary absorption was 8% in men (50th percentile for SF 85 µg/L) and 17% in women (50th percentile for SF 38 µg/L). At a ferritin level of 45 µg/L estimated absorption was similar in men (14%) and women (13%). This new method can be used to calculate dietary iron absorption at a population level using data describing total iron intake and SF concentration