Advancing Our Understanding of Psychological Stress and Coping Among Parents in Organized Youth Sport.

The current study investigated psychological stress among parents of competitive British tennis players. Adopting a multipart concurrent mixed method design, 135 British tennis parents completed a cross sectional online questionnaire to examine their primary appraisals, emotions, and coping strategies associated with self-disclosed stressors. Hierarchical content analysis was conducted on open ended questionnaire responses to identify key stressors and coping strategies, and descriptive and inferential statistics were utilized to explore the differences between various components of the process. The findings revealed a range of organizational, competitive, and developmental stressors. These stressors were predominantly appraised as harm or challenge, and anxiety and anger were the most prominent emotions that the parents experienced. Statistically, parents experienced greater anger in relation to competition (compared to organizational and developmental) stressors, whilst harm appraisal increased negative emotions, and challenge appraisal increased positive emotions. Findings also highlighted how parents used a number of mastery, internal regulation, and goal withdrawal coping strategies, which varied statistically in degrees of reported effectiveness. The contribution of these findings to the stress literature and their applied implications are discussed

Management of trypanosomiasis and leishmaniasis

<p>Background: The current treatments for human African trypanosomiasis (HAT), Chagas disease and leishmaniasis (collectively referred to as the kinetoplastid diseases) are far from ideal but, for some, there has been significant recent progress. For HAT the only advances in treatment over the past two decades have been the introduction of an eflornithine/nifurtimox co-administration and a shorter regime of the old standard melarsoprol.</p> <p>Sources of data: PubMed.</p> <p>Areas of Agreement: There is a need for new safe, oral drugs for cost-effective treatment of patients and use in control programmes for all the trypanosomatid diseases.</p> <p>Areas of controversy: Cutaneous leishmaniasis is not on the agenda and treatments are lagging behind.</p> <p>Growing points: There are three compounds in development for the treatment of the CNS stage of HAT: fexinidazole, currently due to entry into phase II clinical studies, a benzoxaborole (SCYX-7158) in phase I trials and a diamidine derivative (CPD-0802), in advanced pre-clinical development. For Chagas disease, two anti-fungal triazoles are now in clinical trial. In addition, clinical studies with benznidazole, a drug previously recommended only for acute stage treatment, are close to completion to determine the effectiveness in the treatment of early chronic and indeterminate Chagas disease. For visceral leishmaniasis new formulations, therapeutic switching, in particular AmBisome, and the potential for combinations of established drugs have significantly improved the opportunities for the treatment in the Indian subcontinent, but not in East Africa.</p> <p>Areas timely for developing research: Improved diagnostic tools are needed to support treatment, for test of cure in clinical trials and for monitoring/surveillance of populations in control programmes.</p&gt

Assay strategies for the discovery and validation of therapeutics targeting <i>Brugia pahangi</i> Hsp90

The chemotherapy of lymphatic filariasis relies upon drugs such as diethylcarbamazine and ivermectin that largely target the microfilarial stages of the parasite, necessitating continued treatment over the long reproductive life span of the adult worm. The identification of compounds that target adult worms has been a long-term goal of WHO. Here we describe a fluorescence polarization assay for the identification of compounds that target Hsp90 in adult filarial worms. The assay was originally developed to identify inhibitors of Hsp90 in tumor cells, and relies upon the ability of small molecules to inhibit the binding of fluorescently labelled geldanamycin to Hsp90. We demonstrate that the assay works well with soluble extracts of Brugia, while extracts of the free-living nematode C. elegans fail to bind the probe, in agreement with data from other experiments. The assay was validated using known inhibitors of Hsp90 that compete with geldanamycin for binding to Hsp90, including members of the synthetic purine-scaffold series of compounds. The efficacy of some of these compounds against adult worms was confirmed in vitro. Moreover, the assay is sufficiently sensitive to differentiate between binding of purine-scaffold compounds to human and Brugia Hsp90. The assay is suitable for high-throughput screening and provides the first example of a format with the potential to identify novel inhibitors of Hsp90 in filarial worms and in other parasitic species where Hsp90 may be a target

Multidecadal Basal Melt Rates and Structure of the Ross Ice Shelf, Antarctica, Using Airborne Ice Penetrating Radar

Basal melting of ice shelves is a major source of mass loss from the Antarctic Ice Sheet. In situ measurements of ice shelf basal melt rates are sparse, while the more extensive estimates from satellite altimetry require precise information about firn density and characteristics of near‐surface layers. We describe a novel method for estimating multidecadal basal melt rates using airborne ice penetrating radar data acquired during a 3‐year survey of the Ross Ice Shelf. These data revealed an ice column with distinct upper and lower units whose thicknesses change as ice flows from the grounding line toward the ice front. We interpret the lower unit as continental meteoric ice that has flowed across the grounding line and the upper unit as ice formed from snowfall onto the relatively flat ice shelf. We used the ice thickness difference and strain‐induced thickness change of the lower unit between the survey lines, combined with ice velocities, to derive basal melt rates averaged over one to six decades. Our results are similar to satellite laser altimetry estimates for the period 2003–2009, suggesting that the Ross Ice Shelf melt rates have been fairly stable for several decades. We identify five sites of elevated basal melt rates, in the range 0.5–2 m a⁻¹, near the ice shelf front. These hot spots indicate pathways into the sub‐ice‐shelf ocean cavity for warm seawater, likely a combination of summer‐warmed Antarctic Surface Water and modified Circumpolar Deep Water, and are potential areas of ice shelf weakening if the ocean warms

Lead optimization of a pyrazole sulfonamide series of trypanosoma brucei N -myristoyltransferase inhibitors:Identification and evaluation of CNS penetrant compounds as potential treatments for stage 2 human african trypanosomiasis

[Image: see text] Trypanosoma bruceiN-myristoyltransferase (TbNMT) is an attractive therapeutic target for the treatment of human African trypanosomiasis (HAT). From previous studies, we identified pyrazole sulfonamide, DDD85646 (1), a potent inhibitor of TbNMT. Although this compound represents an excellent lead, poor central nervous system (CNS) exposure restricts its use to the hemolymphatic form (stage 1) of the disease. With a clear clinical need for new drug treatments for HAT that address both the hemolymphatic and CNS stages of the disease, a chemistry campaign was initiated to address the shortfalls of this series. This paper describes modifications to the pyrazole sulfonamides which markedly improved blood–brain barrier permeability, achieved by reducing polar surface area and capping the sulfonamide. Moreover, replacing the core aromatic with a flexible linker significantly improved selectivity. This led to the discovery of DDD100097 (40) which demonstrated partial efficacy in a stage 2 (CNS) mouse model of HAT

An individual-based model of the evolution of pesticide resistance in heterogeneous environments : Control of meligethes aeneus population in oilseed rape crops

Copyright: © 2014 Stratonovitch et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Preventing a pest population from damaging an agricultural crop and, at the same time, preventing the development of pesticide resistance is a major challenge in crop protection. Understanding how farming practices and environmental factors interact with pest characteristics to influence the spread of resistance is a difficult and complex task. It is extremely challenging to investigate such interactions experimentally at realistic spatial and temporal scales. Mathematical modelling and computer simulation have, therefore, been used to analyse resistance evolution and to evaluate potential resistance management tactics. Of the many modelling approaches available, individual-based modelling of a pest population offers most flexibility to include and analyse numerous factors and their interactions. Here, a pollen beetle (Meligethes aeneus) population was modelled as an aggregate of individual insects inhabiting a spatially heterogeneous landscape. The development of the pest and host crop (oilseed rape) was driven by climatic variables. The agricultural land of the landscape was managed by farmers applying a specific rotation and crop protection strategy. The evolution of a single resistance allele to the pyrethroid lambda cyhalothrin was analysed for different combinations of crop management practices and for a recessive, intermediate and dominant resistance allele. While the spread of a recessive resistance allele was severely constrained, intermediate or dominant resistance alleles showed a similar response to the management regime imposed. Calendar treatments applied irrespective of pest density accelerated the development of resistance compared to ones applied in response to prescribed pest density thresholds. A greater proportion of springs own oilseed rape was also found to increase the speed of resistance as it increased the period of insecticide exposure. Our study demonstrates the flexibility and power of an individual-based model to simulate how farming practices affect pest population dynamics, and the consequent impact of different control strategies on the risk and speed of resistance development.Peer reviewe

The Good Behaviour Game intervention to improve behavioural and other outcomes for children aged 7–8 years: a cluster RCT

Background Universal, school-based behaviour management interventions can produce meaningful improvements in children’s behaviour and other outcomes. However, the UK evidence base for these remains limited.Objective The objective of this trial was to investigate the impact, value for money and longer-term outcomes of the Good Behaviour Game. Study hypotheses centred on immediate impact (hypothesis 1); subgroup effects (at-risk boys, hypothesis 2); implementation effects (dosage, hypothesis 3); maintenance/sleeper effects (12- and 24-month post-intervention follow-ups, hypothesis 4); the temporal association between mental health and academic attainment (hypothesis 5); and the health economic impact of the Good Behaviour Game (hypothesis 6). Design This was a two-group, parallel, cluster-randomised controlled trial. Primary schools (n = 77) were randomly assigned to implement the Good Behaviour Game for 2 years or continue their usual practice, after which there was a 2-year follow-up period. Setting The trial was set in primary schools across 23 local authorities in England. Participants Participants were children (n= 3084) aged 7–8 years attending participating schools. Intervention The Good Behaviour Game is a universal behaviour management intervention. Its core components are classroom rules, team membership, monitoring behaviour and positive reinforcement. It is played alongside a normal classroom activity for a set time, during which children work in teams to win the game to access the agreed rewards. The Good Behaviour Game is a manualised intervention delivered by teachers who receive initial training and ongoing coaching. Main outcome measures The measures were conduct problems (primary outcome; teacher-rated Strengths and Difficulties Questionnaire scores); emotional symptoms (teacher-rated Strengths and Difficulties Questionnaire scores); psychological well-being, peer and social support, bullying (i.e. social acceptance) and school environment (self-report Kidscreen survey results); and school absence and exclusion from school (measured using National Pupil Database records). Measures of academic attainment (reading, standardised tests), disruptive behaviour, concentration problems and prosocial behaviour (Teacher Observation of Child Adaptation Checklist scores) were also collected during the 2-year follow-up period. Results There was no evidence that the Good Behaviour Game improved any outcomes (hypothesis 1). The only significant subgroup moderator effect identified was contrary to expectations: at-risk boys in Good Behaviour Game schools reported higher rates of bullying (hypothesis 2). The moderating effect of the amount of time spent playing the Good Behaviour Game was unclear; in the context of both moderate (≥ 1030 minutes over 2 years) and high (≥ 1348 minutes over 2 years) intervention compliance, there were significant reductions in children’s psychological well-being, but also significant reductions in their school absence (hypothesis 3). The only medium-term intervention effect was for peer and social support at 24 months, but this was in a negative direction (hypothesis 4). After disaggregating within- and between-individual effects, we found no temporal within-individual associations between children’s mental health and their academic attainment (hypothesis 5). Last, our cost–consequences analysis indicated that the Good Behaviour Game does not provide value for money (hypothesis 6).Limitations Limitations included the post-test-only design for several secondary outcomes; suboptimal implementation dosage (mitigated by complier-average causal effect estimation); and moderate child-level attrition (18.5% for the primary outcome analysis), particularly in the post-trial follow-up period (mitigated by the use of full information maximum likelihood procedures). Future work Questions remain regarding programme differentiation (e.g. how distinct is the Good Behaviour Game from existing behaviour management practices, and does this makes a difference in terms of its impact?) and if the Good Behaviour Game is impactful when combined with a complementary preventative intervention (as has been the case in several earlier trials).Conclusion The Good Behaviour Game cannot be recommended based on the findings reported here. Trial registration This trial is registered as ISRCTN64152096. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 10, No. 7. See the NIHR Journals Library website for further project information

Phytosulfokine stimulates cell divisions in sugar beet (Beta vulgaris L.) mesophyll protoplast cultures

The aim of this work was to improve plating efficiency of sugar beet mesophyll protoplast cultures. Preliminary experiments showed that cultures of good quality, viable protoplasts were obtained in rich media based on the Kao and Michayluk formulation and with the calcium alginate as an embedding matrix. Nevertheless, in these cultures cell divisions were either not observed or very seldom confirming earlier reported recalcitrance of sugar beet protoplasts. The recalcitrant status of these cultures was reversed upon application of exogenous phytosulfokine (PSK)—a peptidyl plant growth factor. The highest effectiveness of PSK was observed at 100 nM concentration. Plating efficiencies obtained in the presence of PSK reached approximately 20% of the total cultured cells. The stimulatory effect of phytosulfokine was observed for all tested breeding stocks of sugar beet. Our data indicate that PSK is a powerful agent able to overcome recalcitrance of plant protoplast cultures

Plasmodial sugar transporters as anti-malarial drug targets and comparisons with other protozoa

Glucose is the primary source of energy and a key substrate for most cells. Inhibition of cellular glucose uptake (the first step in its utilization) has, therefore, received attention as a potential therapeutic strategy to treat various unrelated diseases including malaria and cancers. For malaria, blood forms of parasites rely almost entirely on glycolysis for energy production and, without energy stores, they are dependent on the constant uptake of glucose. Plasmodium falciparum is the most dangerous human malarial parasite and its hexose transporter has been identified as being the major glucose transporter. In this review, recent progress regarding the validation and development of the P. falciparum hexose transporter as a drug target is described, highlighting the importance of robust target validation through both chemical and genetic methods. Therapeutic targeting potential of hexose transporters of other protozoan pathogens is also reviewed and discussed