Platelet-rich plasma injection for adults with acute Achilles tendon rupture: the PATH-2 RCT

BACKGROUND:Achilles tendon rupture (ATR) has a long healing period, which is challenging for patients and clinicians. Platelet-rich plasma (PRP) is an autologous concentration of platelets thought to improve tendon function recovery. Although preliminary research has indicated positive effects, there is, as yet, no evidence of clinical efficacy from adequately powered robust clinical trials. OBJECTIVES:The objectives were to determine the clinical efficacy of PRP in patients with acute ATR using an objective mechanical muscle–tendon function measure and patient-reported outcome measures (PROMs), and to determine which PRP components contribute to its mechanism. DESIGN:This was a multicentre, parallel-group, participant- and outcome assessor-blinded randomised controlled trial (RCT) comparing PRP with placebo. Two embedded substudies investigated the PRP’s quality and composition and its effects on healing tendon tissues. SETTING:This trial was set in trauma and orthopaedic surgery departments in 19 NHS hospitals in England and Wales. PARTICIPANTS:Adults with acute ATR presenting within 12 days of injury to be treated non-surgically were eligible. Patients with platelet dysfunction or leg functional deficiency were excluded. INTERVENTIONS:Participants were randomised 1 : 1 to the PRP injection group or the placebo group (dry needle in the rupture gap) by central computer-based randomisation using minimisation, stratified by centre and age. MAIN OUTCOME MEASURES:The primary outcome measure was the Limb Symmetry Index (LSI) of work during the heel-rise endurance test at 24 weeks. Secondary outcomes measures, collected at 4, 7, 13 and 24 weeks, were repetitions, maximum heel-rise height, Achilles tendon Total Rupture Score (ATRS), quality of life (as measured using the Short Form questionnaire-12 items version 2), pain and participant goal attainment. Needle biopsies of the affected tendon zone were taken under ultrasound guidance at 6 weeks from 16 participants from one centre. Whole blood was analysed for cell count. PRP was analysed for cell count, platelet activation and growth factor concentration. The primary analysis was intention to treat. RESULTS:A total of 230 participants were randomised: 114 to the PRP group (103 treated) and 116 to the placebo group (all treated). One participant withdrew after randomisation but before the intervention. At 24 weeks, 201 out of 230 participants (87.4%) completed the primary outcome and 216 out of 230 participants (93.9%) completed the PROMs. The treatment groups had similar participant characteristics. At 24 weeks, there was no difference in work LSI (mean difference –3.872; 95% confidence interval –10.454 to 2.710; p = 0.231), ATRS, pain or goal attainment between PRP- and placebo-injected participants. There were no differences between the groups in any PROM at any time point or in complication rates, including re-rupture and deep-vein thrombosis. There was no correlation between work LSI and platelet activation in PRP, or erythrocyte, leucocyte or platelet counts in whole blood or PRP. Biopsies showed similar cellularity and vascularity between groups. CONCLUSIONS:This trial design and standardised PRP preparation gives the first robust RCT evidence about PRP’s role in managing ATR, which suggests that PRP offers no patient benefit. Equally robust evidence to investigate PRP application in tendon and soft tissue injuries is required. The 24-month follow-up will be completed in April 2020. TRIAL REGISTRATION:Current Controlled Trials ISRCTN54992179. FUNDING:This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. The trial was supported by the NIHR Biomedical Research Centre, Oxford, and the NIHR Fellowship programme

A typology of alcohol consumption among young people – A narrative synthesis

Background: Currently, alcohol consumption levels are significantly higher among younger age groups. However, previous research has noted the diversity of motivations and patterns. These patterns of drinking have yet to be synthesised into a typology. The aim of the current study was to synthesise information from studies that produced types of alcohol consumption among young people. Method: Quantitative and qualitative literature investigating the different types of drinkers among young people [aged 12–24 years], published in peer reviewed journals, were eligible for inclusion in this systematic review. MEDLINE, PsychInfo and CINAHL were systematically searched for relevant articles published between January 1st 2000 and December 31st 2014. Included papers were critically appraised. A narrative synthesis approach was employed based on guidance from the UK Economic and Social Research Council. Results: In total, 13 studies were eligible for inclusion: 11 quantitative, one qualitative and one mixed methods. Six classes of drinkers were formed within this typology. Abstainers reported no alcohol consumption. Light drinkers reported drinking small amounts of alcohol infrequently. In comparison, social and hedonistic drinkers drank most in social situations and to have fun. Heavy and harmful consumers reported increased volume and frequency of consumption including harmful consequences. Conclusion: Currently, policy makers are attempting to combat the high levels of harmful alcohol consumption among young people. The current typology provides guidance for targeted interventions in addition to a practical analytic tool in future research

Academic Performance and Behavioral Patterns

Identifying the factors that influence academic performance is an essential part of educational research. Previous studies have documented the importance of personality traits, class attendance, and social network structure. Because most of these analyses were based on a single behavioral aspect and/or small sample sizes, there is currently no quantification of the interplay of these factors. Here, we study the academic performance among a cohort of 538 undergraduate students forming a single, densely connected social network. Our work is based on data collected using smartphones, which the students used as their primary phones for two years. The availability of multi-channel data from a single population allows us to directly compare the explanatory power of individual and social characteristics. We find that the most informative indicators of performance are based on social ties and that network indicators result in better model performance than individual characteristics (including both personality and class attendance). We confirm earlier findings that class attendance is the most important predictor among individual characteristics. Finally, our results suggest the presence of strong homophily and/or peer effects among university students

Future-oriented constructs and their role in suicidal ideation and enactment

Despite the heavy focus upon risk factors for suicide, the presence or absence of protective factors are also instrumental in individuals’ vulnerability for developing suicidal ideation and behaviours. Future oriented constructs, including future thinking, future orientation, hope and optimism have been associated with suicidal ideation and behaviour; individuals who are less able to generate positive thoughts about the future, and those are less hopeful and optimistic are more likely to think about or engage in suicidal behaviours. The content and expectations of future thoughts as achievable also play a key role in their protective capacity. Within this chapter we discuss the relationships between future orientated constructs and suicidal ideation and behaviour, as well as potential mediators of these relationships, within the context of the new generation of ideation-to-action frameworks of suicidal behaviour. We also highlight challenges and opportunities for future research and intervention development for suicidal thoughts and behaviours using future oriented constructs

Age is no barrier: predictors of academic success in older learners

Although predictors of academic success have been identified in young adults, such predictors are unlikely to translate directly to an older student population, where such information is scarce. The current study aimed to examine cognitive, psychosocial, lifetime, and genetic predictors of university-level academic performance in older adults (50–79 years old). Participants were mostly female (71%) and had a greater than high school education level (M = 14.06 years, SD = 2.76), on average. Two multiple linear regression analyses were conducted. The first examined all potential predictors of grade point average (GPA) in the subset of participants who had volunteered samples for genetic analysis (N = 181). Significant predictors of GPA were then re-examined in a second multiple linear regression using the full sample (N = 329). Our data show that the cognitive domains of episodic memory and language processing, in conjunction with midlife engagement in cognitively stimulating activities, have a role in predicting academic performance as measured by GPA in the first year of study. In contrast, it was determined that age, IQ, gender, working memory, psychosocial factors, and common brain gene polymorphisms linked to brain function, plasticity and degeneration (APOE, BDNF, COMT, KIBRA, SERT) did not influence academic performance. These findings demonstrate that ageing does not impede academic achievement, and that discrete cognitive skills as well as lifetime engagement in cognitively stimulating activities can promote academic success in older adults

The Explosion Mechanism of Core-Collapse Supernovae and Its Observational Signatures

The death of massive stars is shrouded in many mysteries. One of them is the mechanism that overturns the collapse of the degenerate iron core into an explosion, a process that determines the supernova explosion energy, properties of the surviving compact remnant, and the nucleosynthetic yields. The number of core-collapse supernova observations has been growing with an accelerating pace thanks to modern time-domain astronomical surveys and new tests of the explosion mechanism are becoming possible. We review predictions of parameterized supernova explosion models and compare them with explosion properties inferred from observed light curves, spectra, and neutron star masses.Comment: Reviews in Frontiers of Modern Astrophysics; From Space Debris to Cosmology, edited by Kab\'ath, Petr; Jones, David; Skarka, Marek. ISBN: 978-3-030-38509-5. Cham: Springer International Publishing, 2020, pp. 189-21

Supernovae from massive stars

Massive stars, by which we mean those stars exploding as core collapse supernovae, play a pivotal role in the evolution of the Universe. Therefore, the understanding of their evolution and explosion is fundamental in many branches of physics and astrophysics, among which, galaxy evolution, nucleosynthesis, supernovae, neutron stars and pulsars, black holes, neutrinos and gravitational waves. In this chapter, the author presents an overview of the presupernova evolution of stars in the range between 13 and 120 $\rm M_\odot$, with initial metallicities between [Fe/H]=-3 and [Fe/H]=0 and initial rotation velocities $\rm v=0,~150,~300~km/s$. Emphasis is placed upon those evolutionary properties that determine the final fate of the star with special attention to the interplay among mass loss, mixing and rotation. A general picture of the evolution and outcome of a generation of massive stars, as a function of the initial mass, metallicity and rotation velocity, is finally outlined.Comment: Author version of a chapter for 'Handbook of Supernovae,' edited by A. Alsabti and P. Murdin, Springer. 59 pages, 27 figure

Community led active schools programme (CLASP) exploring the implementation of health interventions in primary schools: headteachers’ perspectives

Background: Schools are repeatedly utilised as a key setting for health interventions. However, the translation of effective research findings to the school setting can be problematic. In order to improve effective translation of future interventions, it is imperative key challenges and facilitators of implementing health interventions be understood from a school's perspective. Methods: Nineteen semi-structured interviews were conducted in primary schools (headteachers n = 16, deputy headteacher n = 1, healthy school co-ordinator n = 2). Interviews were transcribed verbatim and analysed using thematic analysis. Results: The main challenges for schools in implementing health interventions were; government-led academic priorities, initiative overload, low autonomy for schools, lack of staff support, lack of facilities and resources, litigation risk and parental engagement. Recommendations to increase the application of interventions into the school setting included; better planning and organisation, greater collaboration with schools and external partners and elements addressing sustainability. Child-centred and cross-curricular approaches, inclusive whole school approaches and assurances to be supportive of the school ethos were also favoured for consideration. Conclusions: This work explores schools' perspectives regarding the implementation of health interventions and utilises these thoughts to create guidelines for developing future school-based interventions. Recommendations include the need to account for variability between school environments, staff and pupils. Interventions with an element of adaptability were preferred over the delivery of blanket fixed interventions. Involving schools in the developmental stage would add useful insights to ensure the interventions can be tailored to best suit each individual schools' needs and improve implementation.11 page(s

Dlgap1 knockout mice exhibit alterations of the postsynaptic density and selective reductions in sociability

Abstract The scaffold protein DLGAP1 is localized at the post-synaptic density (PSD) of glutamatergic neurons and is a component of supramolecular protein complexes organized by PSD95. Gain-of-function variants of DLGAP1 have been associated with obsessive-compulsive disorder (OCD), while haploinsufficient variants have been linked to autism spectrum disorder (ASD) and schizophrenia in human genetic studies. We tested male and female Dlgap1 wild type (WT), heterozygous (HT), and knockout (KO) mice in a battery of behavioral tests: open field, dig, splash, prepulse inhibition, forced swim, nest building, social approach, and sucrose preference. We also used biochemical approaches to examine the role of DLGAP1 in the organization of PSD protein complexes. Dlgap1 KO mice were most notable for disruption of protein interactions in the PSD, and deficits in sociability. Other behavioral measures were largely unaffected. Our data suggest that Dlgap1 knockout leads to PSD disruption and reduced sociability, consistent with reports of DLGAP1 haploinsufficient variants in schizophrenia and ASD