The relationship between baseline and physical performance screening tests, and game performance outcomes in elite youth basketball.

Introduction: To date, limited research has examined the relationships between baseline (Range of Movement tests active, passive and loaded) and physical performance screening tests and game performance outcomes in elite youth basketball. Therefore, the experimental hypothesis for this thesis was that useful screening tests would correlate with selected game performance metrics. In addition to this, categorical data and injury correlations were considered. Tests were grouped according to their type (baseline, neuromuscular, upper limb, strength and endurance, speed and agility and jumps). The grouping allowed a clearer observation of the link between tests and game performance outcomes. The hypothesis for each group is that some tests would correlate to some game's performance outcomes. One example of this is that jump tests would correlate with both defensive and offensive rebounds. This exploratory study was primarily conducted to inform practice within elite academy basketball settings from a physiotherapy practice perspective. Method: 19 elite youth male basketball players (Mean age = 17 years; range 16-19 years) performed a series of baseline range of movement and physical performance tests divided across three sessions. Baseline testing included passive and active range of movement at the ankle, hip and shoulder. Physical tests included upper limb stability and strength, vertical jumps, reactive and non-reactive agility, lower limb balance and neuromuscular control, speed tests and strength endurance tests of hamstring and core. Results: A series of moderate and strong correlations were found between baseline range of movement (ROM), physical performance tests and some game statistic outcomes. Strongest correlations were found between offensive rebounds and shoulder passive internal rotation (Left r = .57, p < 0.01, Right r = .66, p < 0.01). Right hip passive internal rotation and free throw percentage (r = -.61 p < 0.01). Straight leg raise and free throws made (Right r = .74, p < 0.01, Left r = .62, p < 0.01). Straight leg raise and free throws season percentage (Right r = .65, p < 0.01). = r = -.56, p < 0.05, Left r = .52, p < 0.05). Right hamstring 90/90 correlated with free throws made (r = -.66, p < 0.01. Left hamstring 90/90 correlated with assists season average 9 r = -.66, p < 0.01). Left dorsiflexion with assists season average (r = -.61, p < 0.01). Right dorsiflexion passive correlated with 2 pt field goal percentage (r = -.62, p < 0.01) and defensive rebounds (r = -.64, p < 0.01). Qualitative assessment single leg squat correlated with Free throws made (Left r = .62, p < 0.01, Right .51, p < 0.05) and offensive rebounds (Left r = .61, p < 0.01, Right r = .47, p < 0.05). Side plank left correlated with defensive rebounds (r = -.70, p < 0.01). Closed kinetic chain upper extremity stability test (CKCUEST) correlated with with assists season average (r = -.72, p < 0.01). Agility T-Test correlated with number of games played season (r = -.62, p < 0.01), defensive rebound (r = -.64, p < 0.01) and total points season average (r = -.66, p < 0.01). No significant correlation was found between baseline testing and injuries Discussion: The findings of the present study suggest that some baseline range of movement (ROM) and physical performance tests correlate with game performance outcomes in elite youth basketball. Understanding and interpreting the data and progressing testing protocols to fully integrate elements of sport specific movement and analysis is key to developing protocols that ultimately have a bearing on their relationship to game performance. The findings will have direct implication on applied practice as these results are used to adapt interventions and develop further testing. Conclusion: Multiple correlations were found between baseline range of movement (ROM) and physical performance tests with season long game statistics. The findings from the present study can be used to elicit changes in practice so as to ensure tests provide information for performance as oppose to just baseline data for comparison

Perfectionism predicts injury in junior athletes: Preliminary evidence from a prospective study

According to the stress-injury model (Williams & Andersen, 1998), personality factors predisposing athletes to elevated levels of stress may increase the risk of injury. As perfectionism has been associated with chronic stress, it may be one such personality factor. So far, however, no study has investigated the relationships between perfectionism and injury utilising a prospective design. Therefore, the present study examined perfectionistic strivings, perfectionistic concerns, and injury in 80 junior athletes from team and individual sports (mean age 17.1 years, range 16-19 years) over 10 months of active training. The results of logistic regression analyses showed that perfectionism positively predicted injury, but only perfectionistic concerns emerged as a significant positive predictor. The likelihood of sustaining an injury was increased by over 2 times for each 1 SD increase in perfectionistic concerns. The findings suggest that perfectionistic concerns may be a possible factor predisposing athletes to an increased risk of injury

Myeloid cell-targeted miR-146a mimic alleviates NF-κB-driven cytokine storm without interfering with CD19-specific CAR T cell activity against B cell lymphoma

Background: NF-κB is a key regulator of inflammation, myeloproliferation and cancer progression, with an important role in leukemogenesis. Despite therapeutic potential, targeting NF-κB proved challenging. However, in non-malignant myeloid cells NF-κB activity is tightly regulated through many molecular mechanisms, including miRNA. Methods: Here, we describe an original approach to NF-κB inhibition using miR146a, which targets upstream regulators of NF-κB signaling. We generated a myeloid cell-targeted NF-κB inhibitor by tethering a chemically-modified miR146a mimic oligonucleotide to a scavenger receptor (SR)/Toll-like receptor 9 (TLR9) ligand (C-miR146a). Results: Unlike an unconjugated miR-146a molecule, C-miR146a was rapidly internalized and delivered to cytoplasm of target myeloid cells such as macrophages or myeloid leukemia cells. C-miR146a reduced protein levels of classic miR-146a targets, IRAK1 and TRAF6, thereby efficiently blocking NF-κB activation in target cells. Intravenous injections of C-miR146a mimic to miR-146-deficient mice prevented excessive NF-κB activation in myeloid cells, thereby alleviating myeloproliferation and exaggerated inflammatory responses to bacterial challenge. The NF-κB-driven release of IL-1 and IL-6 from monocytes is known to be responsible for cytokine release syndrome (CRS), which can occur in response to bacterial infections, antibody-based therapies and relatively frequently as a serious adverse effect of chimeric antigen receptor (CAR) T-cell therapies. While low expression of miR146a has not yet been implicated in CRS, C-miR146a treatments did reduce pro-inflammatory activity of human monocytes, at the level of IL-1 and IL-6 production, induced by the CD19-specific but not by the naive CAR T cells in vitro. Repeated systemic administration of C-miR146a oligonucleotide alleviated human monocyte-dependent CRS in xenotransplanted B-cell lymphoma model without impeding the on-target therapeutic effects of CAR T-cells against lymphoma cells. Conclusions: Our results demonstrate potential of using myeloid cell-targeted miR146a mimics for treatment of inflammatory diseases and prevention of potential side effects of immunotherapies. The SR/TLR9-targeted miR-146a mimic design provides an outline for the development of miRNA therapeutics for a variety of myeloid cell-related diseases

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

A Delphi study of rescue and clinical subject matter experts on the extrication of patients following a motor vehicle collision

Background Approximately 1.3 million people die each year globally as a direct result of motor vehicle collisions (MVCs). Following an MVC some patients will remain trapped in their vehicle; these patients have worse outcomes and may require extrication. Following new evidence, updated multidisciplinary guidance for extrication is needed. Methods This Delphi study has been developed, conducted and reported to CREDES standards. A literature review identified areas of expertise and appropriate individuals were recruited to a Steering Group. The Steering Group formulated initial statements for consideration. Stakeholder organisations were invited to identify subject matter experts (SMEs) from a rescue and clinical background (total 60). SMEs participated over three rounds via an online platform. Consensus for agreement / disagreement was set at 70%. At each stage SMEs could offer feedback on, or modification to the statements considered which was reviewed and incorporated into new statements or new supporting information for the following rounds. Stakeholders agreed a set of principles based on the consensus statements on which future guidance should be based. Results Sixty SMEs completed Round 1, 53 Round 2 (88%) and 49 Round 3 (82%). Consensus was reached on 91 statements (89 agree, 2 disagree) covering a broad range of domains related to: extrication terminology, extrication goals and approach, self-extrication, disentanglement, clinical care, immobilisation, patient-focused extrication, emergency services call and triage, and audit and research standards. Thirty-three statements did not reach consensus. Conclusion This study has demonstrated consensus across a large panel of multidisciplinary SMEs on many key areas of extrication and related practice that will provide a key foundation in the development of evidence-based guidance for this subject area

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Prospects for the Third Sector

This paper explores the prospects for the Third Sector following the next General Election in the United Kingdom. The paper provides a context for understanding the third sector and some of the key agendas which will impact upon it, including its role in the delivery of public services, the implications of public expenditure cuts, the shift in funding models for the sector including both social investment and personalisation, localism and the demonstration of impact and value for money. Although the paper finds cause to expect much continuity in terms of third sector policy (whichever party wins the election), it also identifies three notable fault lines. These are around the relationship between state and society, resources and scale, and equity and disadvantage. Given the wider context for third sector policy, it is anticipated that 2010 will mark a significant disjuncture in the development of the third sector