Part 2 of the 11+ as an effective home-based exercise programme in elite academy football (soccer) players:A one-club matched-paired randomised controlled trial

Background:Although the 11+ is known to reduce injuries and improve performance in adolescent footballers, its duration presents a notable barrier to implementation. Hence, this study investigated injury and performance outcomes when 65 elite male academy footballers either performed Part 2 3x/week at training (TG) or at home (HG). Methods:Time to stabilisation (TTS), eccentric hamstring strength (EH-S) and countermovement jump height (CMJ-H) were collected 4 times during the 2019 football season. Linear mixed models were used to evaluate main and interaction effects of group and time. Bonferroni post-hoc tests were used to account for multiple comparisons. Differences in time loss and medical attention injuries were determined using a two-tailed Z test for a comparison of rates. Results:Relative to baseline, EH-S (HG 4.3 kg, 95% CI 3 to 5.7, p \u3c 0.001; TG 5.5 kg, 95% CI 4.3 to 6.6, p \u3c 0.001) and CMJ-H (HG 3.5 cm, 95% CI 2.2 to 4.7, p \u3c 0.001; TG 3.2 cm, 95% CI 2.2 to 4.3, p \u3c 0.001) increased, with no difference between groups observed at the end of the season. All injury outcomes were similar. Conclusion: Rescheduling Part 2 did not affect performance or increased injury risks in academy footballers

An Anti-Urban Education? Work camps and ideals of the land in Interwar Britain

The article examines the role of work camp movements in developing rural critiques of urban living in interwar Britain. A variety of work camp movements flourished in Europe during the interwar years, often partly as a reaction against urbanisation, and this paper explores the ways in which three such movements developed the work camp as a means of countering the socialising influences of city life. Yet while all of the interwar British work camps were located in the countryside, they varied in the extent to which they tried to promote rural values and orientations among their trainees.We can see the work camp as a liminal pedagogic space, designed to lead trainees to particular educational outcomes, using techniques and methods that focused on bodily change as well as cognitive development

Expression of chemokines and their receptors by human brain endothelium: Implications for multiple sclerosis

Leukocyte migration into the CNS is mediated by chemokines, expressed on the surface of brain endothelium. This study investigated the production of chemokines and expression of chemokine receptors by human brain endothelial cells (HBEC), in vitro and in situ in multiple sclerosis tissue. Four chemokines (CCL2, CCL5, CXCL8 and CXCL10), were demonstrated in endothelial cells in situ, which was reflected in the chemokine production by primary HBEC and a brain endothelial cell line, hCEMC/D3. CXCL8 and CCL2 were constitutively released and increased in response to TNF and/or IFN . CXCL10 and CCL5 were undetectable in resting cells but were secreted in response to these cytokines. TNF strongly increased the production of CCL2, CCL5 and CXCL8, while IFN up-regulated CXCL10 exclusively. CCL3 was not secreted by HBECs and appeared to be confined to astrocytes in situ. The chemokine receptors CXCR1 and CXCR3 were expressed by HBEC both in vitro and in situ, and CXCR3 was up-regulated in response to cytokine stimulation in vitro. By contrast, CXCR3 expression was reduced in silent MS lesions. Brain endothelium expresses particularly high levels of CXCL10 and CXCL8, which may account for the predominant TH1-type inflammatory reaction seen in chronic conditions such as multiple sclerosis

Ca2+-Dependent Phosphorylation of RyR2 Can Uncouple Channel Gating from Direct Cytosolic Ca2+ Regulation

Phosphorylation of the cardiac ryanodine receptor (RyR2) is thought to be important not only for normal cardiac excitation-contraction coupling but also in exacerbating abnormalities in Ca2+ homeostasis in heart failure. Linking phosphorylation to specific changes in the single-channel function of RyR2 has proved very difficult, yielding much controversy within the field. We therefore investigated the mechanistic changes that take place at the single-channel level after phosphorylating RyR2 and, in particular, the idea that PKA-dependent phosphorylation increases RyR2 sensitivity to cytosolic Ca2+. We show that hyperphosphorylation by exogenous PKA increases open probability (Po) but, crucially, RyR2 becomes uncoupled from the influence of cytosolic Ca2+; lowering [Ca2+] to subactivating levels no longer closes the channels. Phosphatase (PP1) treatment reverses these gating changes, returning the channels to a Ca2+-sensitive mode of gating. We additionally found that cytosolic incubation with Mg2+/ATP in the absence of exogenously added kinase could phosphorylate RyR2 in approximately 50% of channels, thereby indicating that an endogenous kinase incorporates into the bilayer together with RyR2. Channels activated by the endogenous kinase exhibited identical changes in gating behavior to those activated by exogenous PKA, including uncoupling from the influence of cytosolic Ca2+. We show that the endogenous kinase is both Ca2+-dependent and sensitive to inhibitors of PKC. Moreover, the Ca2+-dependent, endogenous kinase–induced changes in RyR2 gating do not appear to be related to phosphorylation of serine-2809. Further work is required to investigate the identity and physiological role of this Ca2+-dependent endogenous kinase that can uncouple RyR2 gating from direct cytosolic Ca2+ regulation

Three-Dimensional and Chemical Mapping of Intracellular Signaling Nanodomains in Health and Disease with Enhanced Expansion Microscopy

Nanodomains are intracellular foci which transduce signals between major cellular compartments. One of the most ubiquitous signal transducers, the ryanodine receptor (RyR) calcium channel, is tightly clustered within these nanodomains. Super-resolution microscopy has previously been used to visualize RyR clusters near the cell surface. A majority of nanodomains located deeper within cells have remained unresolved due to limited imaging depths and axial resolution of these modalities. A series of enhancements made to expansion microscopy allowed individual RyRs to be resolved within planar nanodomains at the cell periphery and the curved nanodomains located deeper within the interiors of cardiomyocytes. With a resolution of ∼ 15 nm, we localized both the position of RyRs and their individual phosphorylation for the residue Ser2808. With a three-dimensional imaging protocol, we observed disturbances to the RyR arrays in the nanometer scale which accompanied right-heart failure caused by pulmonary hypertension. The disease coincided with a distinct gradient of RyR hyperphosphorylation from the edge of the nanodomain toward the center, not seen in healthy cells. This spatial profile appeared to contrast distinctly from that sustained by the cells during acute, physiological hyperphosphorylation when they were stimulated with a β-adrenergic agonist. Simulations of RyR arrays based on the experimentally determined channel positions and phosphorylation signatures showed how the nanoscale dispersal of the RyRs during pathology diminishes its intrinsic likelihood to ignite a calcium signal. It also revealed that the natural topography of RyR phosphorylation could offset potential heterogeneity in nanodomain excitability which may arise from such RyR reorganization

The contribution of theory to the design, delivery, and evaluation of interprofessional curricula: BEME Guide No. 49

BACKGROUND: Interprofessional curricula have often lacked explicit reference to theory despite calls for a more theoretically informed field that illuminates curricular assumptions and justifies curricular practices. AIM: To review the contributions of theory to the design, delivery, and evaluation of interprofessional curricula. METHODS: Four databases were searched (1988-2015). Studies demonstrating explicit and a high-quality contribution of theory to the design, delivery or evaluation of interprofessional curricula were included. Data were extracted against a comprehensive framework of curricular activities and a narrative synthesis undertaken. RESULTS: Ninety-one studies met the inclusion criteria. The majority of studies (86%) originated from the UK, USA, and Canada. Theories most commonly underpinned "learning activities" (47%) and "evaluation" (54%). Theories of reflective learning, identity formation, and contact hypothesis dominated the field though there are many examples of innovative theoretical contributions. CONCLUSIONS: Theories contribute considerably to the interprofessional field, though many curricular elements remain under-theorized. The literature offers no "gold standard" theory for interprofessional curricula; rather theoretical selection is contingent upon the curricular component to which theory is to be applied. Theories contributed to interprofessional curricula by explaining, predicting, organizing or illuminating social processes embedded in interprofessional curricular assumptions. This review provides guidance how theory might be robustly and appropriately deployed in the design, delivery, and evaluation of interprofessional curricula

An investigation of structure-function relationships of (Ca2-Mg2+)- ATPase with monoclonal antibodies

Thirty seven monoclonal antibodies (mAbs) were generated against (Ca2+-Mg2+)-ATPase from rabbit skeletal muscle sarcoplasmic reticulum for the purpose of studying structure-function relationships. No conformation specific (E1, E2) antibodies were found, indicating the limited extent of structural alteration of the antibody binding sites (epitopes) during calcium transport, which may reflect the magnitude of change accompanying E1-E2 transitions. Five distinct binding regions were identified on the ATPase by competitive binding of labelled and unlabelled mAbs. Limited proteolysis of the ATPase enabled description of the epitope location of 14 mAbs in the primary sequence. Following digestion of ATPase, anti-peptide antibodies specific for the N- and C-termini of the ATPase were used to identify the origin of fragments recognised by individual mABs. Antibody epitopes were defined to an apparent resolution of 11-16 residues, although these limits were extended to 75-94 residues in the absence of the precise molecular weight of proteolytic fragments. Ten mAbs (6 of which bind in the same spatial region, as defined in competitive displacement assays) produce inhibition of ATPase activity (30-70% inhibition). Inhibition was generally more marked at low ATPase concentrations (1-10&mu;M) but a return to control levels of activity was not exhibited at high ATP (1-10mM). Release of enzyme-bound calcium at steady state was used as a measure of the ratio of E1_total/E2_total. This ratio was reduced by one inhibitory mAb, consistent with a reduction in the rate of dephosphorylation. Three other inhibitory mAbs increased this ratio, without stabilising E1. One of these (the only one tested) also decreased the rate of phosphoenzyme formation by ATP, and the concentration of phosphoenzyme at steady state. Potential mechanisms of inhibition of ATPase activity compatible with the data in the presence of mAb are discussed.</p

Electronic collisions with molecules of biological relevance.

Experimental studies of radiation damage in living tissue indicate that it is not just the primary ionizing particle responsible for the bulk of the radiation damage, but also secondary species generated by the ionizing particle. There is much interest in how these secondary particles, commonly electrons, interact with bio-molecules and in particular DNA. In this thesis, I report relative triple differential cross section measurements for the electron impact ionization of formic acid, tetrahydrofuran and thymine. Formic acid can be considered one of the simplest building blocks for biological systems, particularly in the formation of glycine and amino acids. Tetrahydrofuran is a simple ring structure that can be used as a good approximation to the sugar component of the deoxyribose backbone. Thymine, together with cytosine, guanine and adenine, are the DNA bases and their interactions with electrons are considered to be of great importance. Single differential cross sections for elastic electron interactions with cytosine and thymine are also reported.Thesis (Ph.D.) -- University of Adelaide, School of Chemistry and Physics, 201

Developing bird-strike risk assessment models for open-water restorations

Mineral extraction sites that are restored to open water can increase bird-strike risk if they are planned near airports. This can generate conflict between the minerals industry and safeguarding authorities. To help resolve this potential conflict, it would be useful to predict how new restorations affect local water-bird populations so that mineral deposits can be exploited and restored in safeguarded zones without compromising flight safety. Bird abundances and movements at new restorations can be estimated with statistical models that use the environmental characteristics of restoration schemes as predictor variables. These models can improve guidance in safeguarding, provided that they comprise parameters that can be quantified or conceived at the planning stage. In this paper, we present suitable models based on bird counts conducted during 2004–2006 at 256 open-water restoration sites. We used the morphology of the restorations, their geo-spatial relationships, ecological characteristics and usage as explanatory variables in regression models that describe waterbird abundances, the likely presence of geese and gulls, and the frequency of bird movements in the nonbreeding and breeding seasons. The models that can best be used as predictive tools were selected using multi-modal inference techniques. We demonstrated how their application can provide objective data on the likely impact a restoration design will have on bird-strike risk