Tri-axial loading response to anti-gravity running highlights movement strategy compensations during knee injury rehabilitation of a professional soccer player.

Anti-gravity treadmills have been used in rehabilitation to manipulate exposure to loading and to prescribe return to outside running. Analysis is typically restricted to the vertical plane, but tri-axial accelerometry facilitates multi-planar analysis with relevance to injury mechanism. In this case a professional male soccer player, 4 weeks post-operative surgery to repair a medial meniscectomy, 8 months after Anterior Cruciate Ligament reconstruction to the same knee, completed anti-gravity treadmill running at 70-95% bodyweight (BW) at 5% increments. Tri-axial accelerometers were placed proximal to the Achilles tendon of the injured and healthy leg, and at C7. The planar acceleration at touchdown highlighted an increase at 85% BW, identifying 70% and 85% BW as discrete loading progressions. C7 (3.21 ± 0.68 m·s-2) elicited lower (P < 0.001) vertical acceleration than the lower limb (9.31 ± 1.82 m·s-2), with no difference between limbs suggesting bilateral symmetry. However, in the medio-lateral plane the affected limb (-0.15 ± 1.82 m·s-2) was exposed to lower (P = 0.001) medio-lateral acceleration than the non-affected limb (2.92 ± 1.35 m·s-2) at touchdown, indicative of bilateral asymmetry. PlayerLoad during foot contact was sensitive to accelerometer location, with the affected limb exposed to greater loading in all planes (P ≤ 0.082), exacerbated at 90-95% BW. Tri-axial accelerometry provides a means of assessing multi-planar loading during rehabilitation, enhancing objective progression.

Peak instantaneous PlayerLoad metrics highlight movement strategy deficits in professional male soccer players.

To investigate the influence of task, limb dominance and previous injury on single leg hop task performance and loading response, 25 professional male soccer players completed anterior, medial and lateral hop tests with an accelerometer at mid-calf. Performance outcome was defined as hop distance with loading response defined as the magnitude of, and time to peak instantaneous planar PlayerLoad. The performance was sensitive to task and previous injury (P < 0.001) but not limb dominance, with no evidence of bilateral asymmetry (P = 0.668). Despite impaired performance, previously injured players did not exhibit lower peak instantaneous PlayerLoad after impact in any plane (P ≥ 0.110). There was however a significantly (P = 0.001) longer time to peak medio-lateral loading after impact in previously injured players' affected limb. This observation was exacerbated when the injury was to the non-dominant limb (P = 0.041). Lower-limb accelerometry enhances understanding of movement strategy beyond task outcome, with practical implications in player screening and objective rehabilitation.

Factors influencing optimum countermovement jump performance and movement strategy in Championship professional football players: implications for player profiling.

Single leg countermovement jump (CMJ) is a common profiling test influenced by sport, age, sex and playing level. Controlling for these confounding variables, outfield players from an English Championship squad (n = 36) were retrospectively categorized as best (n = 10) or worst (n = 10), based on mean single leg CMJ height and flight time:contraction time ratio. Movement strategy was quantified as force-time history metrics differentiating eccentric and concentric phases. Jump height revealed that best performers elicited greater rate of force development in both phases (P ≤ 0.033), with concentric impulse the strongest predictor of performance. Time ratio also differentiated best performers as utilizing a shallower (P = 0.002) countermovement, with concentric rate of force development the strongest predictor of good performance. Successful jump height performance can mask ineffectual eccentric and stretch shortening cycle neuromuscular characteristics. Time ratio is therefore advocated as the key performance indicator, with movement strategy prioritized over gross outcome measures.

Tuberculosis in badgers where the bovine tuberculosis epidemic is expanding in cattle in England.

Bovine tuberculosis (bTB) is an important animal health and economic problem for the cattle industry and a potential zoonotic threat. Wild badgers (Meles meles) play a role on its epidemiology in some areas of high prevalence in cattle, particularly in the UK and Republic of Ireland and increasingly in parts of mainland Europe. However, little is known about the involvement of badgers in areas on the spatial edge of the cattle epidemic, where increasing prevalence in cattle is seen. Here we report the findings of a study of found-dead (mainly road-killed) badgers in six counties on the edge of the English epidemic of bTB in cattle. The overall prevalence of Mycobacterium tuberculosis complex (MTC) infection detected in the study area was 51/610 (8.3%, 95% CI 6.4-11%) with the county-level prevalence ranging from 15 to 4-5%. The MTC spoligotypes of recovered from badgers and cattle varied: in the northern part of the study area spoligotype SB0129 predominated in both cattle and badgers, but elsewhere there was a much wider range of spoligotypes found in badgers than in cattle, in which infection was mostly with the regional cattle spoligotype. The low prevalence of MTC in badgers in much of the study area, and, relative to in cattle, the lower density of sampling, make firm conclusions difficult to draw. However, with the exception of Cheshire (north-west of the study area), little evidence was found to link the expansion of the bTB epidemic in cattle in England to widespread badger infection.

The Influence of Injury History on Countermovement Jump Performance and Movement Strategy in Professional Soccer Players: Implications for Profiling and Rehabilitation Foci.

CONTEXT: Professional soccer players who have sustained a lower limb injury are up to 3× more likely to suffer a reinjury, often of increased severity. Previous injury has been shown to induce compensatory strategies during neuromuscular screening tests, which might mask deficits and lead to misinterpretation of readiness to play based on task outcome measures. OBJECTIVE: To investigate the influence of previous injury in professional soccer players on countermovement jump (CMJ) performance and movement strategy. DESIGN: Cross-sectional. SETTING: Professional soccer club competing in the English Championship (tier 2). Patients (or Other Participants): Outfield players with a minimum of 6 years as a professional. INTERVENTION(S): Players were categorized as previously injured (n = 10) or not injured (n = 10). All players completed double- and single-leg CMJ trials. MAIN OUTCOME MEASURES: CMJ performance was quantified as jump height and flight time:contraction time ratio. CMJ movement strategy was quantified as force-time history, differentiating eccentric and concentric phases and CMJ depth. RESULTS: Double-leg CMJ was not sensitive to previous injury in performance or movement strategy. In contrast, single-leg CMJ performance was impaired in players with previous injury, who generated significantly lower eccentric and concentric peak force and rate of force development, and a deeper countermovement. Impaired single-leg CMJ performance was also evident in the nonaffected limb of previously injured players, suggesting cross-contamination. Hierarchical ordering revealed that the eccentric phase of the CMJ contributed little to performance in previously injured players. In noninjured players, the eccentric rate of force development and concentric peak force were able to account for up to 89% of the variation in CMJ performance. CONCLUSIONS: Single-leg CMJ is advocated for player profiling, being more sensitive to previous injury, and negating the opportunity for interlimb compensation strategies. Movement strategy deficits in previously injured players suggest rehabilitation foci specific to eccentric force development.

The Crucible simulation: Behavioral simulation improves clinical leadership skills and understanding of complex health policy change.

BACKGROUND: The Health and Social Care Act 2012 represents the most complex National Health Service reforms in history. High-quality clinical leadership is important for successful implementation of health service reform. However, little is known about the effectiveness of current leadership training. PURPOSE: This study describes the use of a behavioral simulation to improve the knowledge and leadership of a cohort of medical doctors expected to take leadership roles in the National Health Service. METHODOLOGY: A day-long behavioral simulation (The Crucible) was developed and run based on a fictitious but realistic health economy. Participants completed pre- and postsimulation questionnaires generating qualitative and quantitative data. Leadership skills, knowledge, and behavior change processes described by the "theory of planned behavior" were self-assessed pre- and postsimulation. RESULTS: Sixty-nine medical doctors attended. Participants deemed the simulation immersive and relevant. Significant improvements were shown in perceived knowledge, capability, attitudes, subjective norms, intentions, and leadership competency following the program. Nearly one third of participants reported that they had implemented knowledge and skills from the simulation into practice within 4 weeks. CONCLUSIONS: This study systematically demonstrates the effectiveness of behavioral simulation for clinical management training and understanding of health policy reform. Potential future uses and strategies for analysis are discussed. PRACTICE IMPLICATIONS: High-quality care requires understanding of health systems and strong leadership. Policymakers should consider the use of behavioral simulation to improve understanding of health service reform and development of leadership skills in clinicians, who readily adopt skills from simulation into everyday practice.

Development of a Novel Continuous Filtration Unit for Pharmaceutical Process Development and Manufacturing.

The lack of a commercial laboratory, pilot and small manufacturing scale dead end continuous filtration and drying unit it is a significant gap in the development of continuous pharmaceutical manufacturing processes for new active pharmaceutical ingredients (APIs). To move small-scale pharmaceutical isolation forward from traditional batch Nutsche filtration to continuous processing a continuous filter dryer prototype unit (CFD20) was developed in collaboration with Alconbury Weston Ltd. The performance of the prototype was evaluated by comparison with manual best practice exemplified using a modified Biotage VacMaster unit to gather data and process understanding for API filtration and washing. The ultimate objective was to link the chemical and physical attributes of an API slurry with equipment and processing parameters to improve API isolation processes. Filtration performance was characterized by assessing filtrate flow rate by application of Darcy's law, the impact on product crystal size distribution and product purity were investigated using classical analytical methods. The overall performance of the 2 units was similar, showing that the prototype CFD20 can match best manual lab practice for filtration and washing while allowing continuous processing and real-time data logging. This result is encouraging and the data gathered provides further insight to inform the development of CFD20.

Spatial Targeting for Bovine Tuberculosis Control: Can the Locations of Infected Cattle Be Used to Find Infected Badgers?

Bovine tuberculosis is a disease of historical importance to human health in the UK that remains a major animal health and economic issue. Control of the disease in cattle is complicated by the presence of a reservoir species, the Eurasian badger. In spite of uncertainty in the degree to which cattle disease results from transmission from badgers, and opposition from environmental groups, culling of badgers has been licenced in two large areas in England. Methods to limit culls to smaller areas that target badgers infected with TB whilst minimising the number of uninfected badgers culled is therefore of considerable interest. Here, we use historical data from a large-scale field trial of badger culling to assess two alternative hypothetical methods of targeting TB-infected badgers based on the distribution of cattle TB incidents: (i) a simple circular 'ring cull'; and (ii) geographic profiling, a novel technique for spatial targeting of infectious disease control that predicts the locations of sources of infection based on the distribution of linked cases. Our results showed that both methods required coverage of very large areas to ensure a substantial proportion of infected badgers were removed, and would result in many uninfected badgers being culled. Geographic profiling, which accounts for clustering of infections in badger and cattle populations, produced a small but non-significant increase in the proportion of setts with TB-infected compared to uninfected badgers included in a cull. It also provided no overall improvement at targeting setts with infected badgers compared to the ring cull. Cattle TB incidents in this study were therefore insufficiently clustered around TB-infected badger setts to design an efficient spatially targeted cull; and this analysis provided no evidence to support a move towards spatially targeted badger culling policies for bovine TB control.

Age-dependent patterns of bovine tuberculosis in cattle.

Bovine tuberculosis (BTB) is an important livestock disease, seriously impacting cattle industries in both industrialised and pre-industrialised countries. Like TB in other mammals, infection is life long and, if undiagnosed, may progress to disease years after exposure. The risk of disease in humans is highly age-dependent, however in cattle, age-dependent risks have yet to be quantified, largely due to insufficient data and limited diagnostics. Here, we estimate age-specific reactor rates in Great Britain by combining herd-level testing data with spatial movement data from the Cattle Tracing System (CTS). Using a catalytic model, we find strong age dependencies in infection risk and that the probability of detecting infection increases with age. Between 2004 and 2009, infection incidence in cattle fluctuated around 1%. Age-specific incidence increased monotonically until 24-36 months, with cattle aged between 12 and 36 months experiencing the highest rates of infection. Beef and dairy cattle under 24 months experienced similar infection risks, however major differences occurred in older ages. The average reproductive number in cattle was greater than 1 for the years 2004-2009. These methods reveal a consistent pattern of BTB rates with age, across different population structures and testing patterns. The results provide practical insights into BTB epidemiology and control, suggesting that targeting a mass control programme at cattle between 12 and 36 months could be beneficial.

Evidence for genetic variance in resistance to tuberculosis in Great Britain and Irish Holstein-Friesian populations.

BACKGROUND: Here, we jointly summarise scientific evidence for genetic variation in resistance to infection with Mycobacterium bovis, the primary agent of bovine tuberculosis (TB), provided by two recent and separate studies of Holstein-Friesian dairy cow populations in Great Britain (GB) and Ireland. METHODS: The studies quantified genetic variation within archived data from field and abattoir surveillance control programmes within each country. These data included results from the single intradermal comparative tuberculin test (SICTT), abattoir inspection for TB lesions and laboratory confirmation of disease status. Threshold animal models were used to estimate variance components for responsiveness to the SICTT and abattoir confirmed M. bovis infection. The link functions between the observed 0/1 scale and the liability scale were the complementary log-log in the GB, and logit link function in the Irish population. RESULTS AND DISCUSSION: The estimated heritability of susceptibility to TB, as judged by responsiveness to the SICTT, was 0.16 (0.012) and 0.14 (0.025) in the GB and Irish populations, respectively. For abattoir or laboratory confirmation of infection, estimates were 0.18 (0.044) and 0.18 (0.041) from the GB and the Irish populations, respectively. CONCLUSIONS: Estimates were all significantly different from zero and indicate that exploitable variation exists among GB and Irish Holstein Friesian dairy cows for resistance to TB. Epidemiological analysis suggests that factors such as variation in exposure or imperfect sensitivity and specificity would have resulted in underestimation of the true values.

Compilation of a panel of informative single nucleotide polymorphisms for bovine identification in the Northern Irish cattle population.

BACKGROUND: Animal identification is pivotal in governmental agricultural policy, enabling the management of subsidy payments, movement of livestock, test scheduling and control of disease. Advances in bovine genomics have made it possible to utilise inherent genetic variability to uniquely identify individual animals by DNA profiling, much as has been achieved with humans over the past 20 years. A DNA profiling test based on bi-allelic single nucleotide polymorphism (SNP) markers would offer considerable advantages over current short tandem repeat (STR) based industry standard tests, in that it would be easier to analyse and interpret. In this study, a panel of 51 genome-wide SNPs were genotyped across panels of semen DNA from 6 common breeds for the purposes of ascertaining allelic frequency. For SNPs on the same chromosome, the extent of linkage disequilbrium was determined from genotype data by Expectation Maximization (EM) algorithm. Minimum probabilities of unique identification were determined for each breed panel. The usefulness of this SNP panel was ascertained by comparison to the current bovine STR Stockmarks II assay. A statistically representative random sampling of bovine animals from across Northern Ireland was assembled for the purposes of determining the population allele frequency for these STR loci and subsequently, the minimal probability of unique identification they conferred in sampled bovine animals from Northern Ireland. RESULTS: 6 SNPs exhibiting a minor allele frequency of less than 0.2 in more than 3 of the breed panels were excluded. 2 Further SNPs were found to reside in coding areas of the cattle genome and were excluded from the final panel. The remaining 43 SNPs exhibited genotype frequencies which were in Hardy Weinberg Equilibrium. SNPs on the same chromosome were observed to have no significant linkage disequilibrium/allelic association. Minimal probabilities of uniquely identifying individual animals from each of the breeds were obtained and were observed to be superior to those conferred by the industry standard STR assay. CONCLUSIONS: The 43 SNPs characterised herein may constitute a starting point for the development of a SNP based DNA identification test for European cattle.

The involvement of calcium in the protective and toxic (nonlinear) responses of rodent and human astroglial cells.

The involvement of [Ca(2+)](i) in the reactive changes of astrocytes which accompany exposure to different chemicals were studied in cultures of C6 and 1321N1 cells. Cells were exposed to up to three serial pulses of the differentiating agent dBcAMP, which induces activation-type changes in the cells. Other cells, with or without the dBcAMP treatments, were treated with a range of concentrations of the antidepressants amitriptyline and fluoxetine and the glial toxicants acrylamide and chloroquine. In some experiments the L-type voltage calcium channel blocker Nifedipine was employed. [Ca(2+)](i) was measured in populations of the cells using Fura-2AM and a charge coupled device (CCD) camera attached to a fluorescence microscope. dBcAMP induced both dose- and time-dependent changes in [ Ca(2+)](i) with increases in both the [Ca(2+)](i) oscillations and mean [Ca(2+)](i) (e.g. in C6 cells at 18 min mean [Ca(2+)](i) was 318 +/- 20nM following the single differentiating dBcAMP pulses, 489 +/- 17nM (p < 0.001) following two serial pulses, and 275 +/- 30nM (not significant) following three pulses). Therapeutic doses of fluoxetine and amitriptyline caused increases in the calcium oscillations and the mean calcium concentrations ( maximum recorded mean increase was in the C6 cells at 10min by 0.02 muM fluoxetine when [Ca(2+)](i) was 411 +/- 35nM c.f. control 254 +/- 25nM, p = 0.01). Higher (non-therapeutic) doses of both antidepressants caused significant reductions. Chloroquine and acrylamide also caused dose-dependent bi-phasic types of alterations in [Ca(2+)](i), with significant reductions at lower, sub-cytotoxic doses followed by significant increases at higher concentrations, approaching those which cause cell damage. Nifedipine treatment caused some reductions in the dBcAMP, antidepressant or toxicant-induced calcium changes, but this substance also initiated cytotoxic alterations. The findings show that both the activation-type changes (which are frequently associated with increased protective capacities) and toxic responses of C6 and 1321N1 cells to different chemical agents are associated with dose-dependent alterations in [Ca(2+)](i).