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The use of sodium bicarbonate (NaHCO3) supplementation to improve repeated high-intensity performance is recommended; however, most swimming performance studies examine time trial efforts rather than repeated swims with interspersed recovery that are more indicative of training sessions. The aim of this study, therefore, was to investigate the effects of 0.3 g.kg−1 BM NaHCO3 supplementation on sprint interval swimming (8 × 50 m) in regionally trained swimmers. Fourteen regionally competitive male swimmers (body mass (BM): 73 ± 8 kg) volunteered for this double-blind, randomised, crossover designed study. Each participant was asked to swim 8 × 50 m (front crawl) at a maximum intensity from a diving block, interspersed with 50 m active recovery swimming. After one familiarisation trial, this was repeated on two separate occasions whereby participants ingested either 0.3 g.kg−1 BM NaHCO3 or 0.05 g.kg−1 BM sodium chloride (placebo) in solution 60 min prior to exercise. Whilst there were no differences in time to complete between sprints 1–4 (p > 0.05), improvements were observed in sprint 5 (p = 0.011; ES = 0.26), 6 (p = 0.014; ES = 0.39), 7 (p = 0.005; ES = 0.60), and 8 (p = 0.004; ES = 0.79). Following NaHCO3 supplementation, pH was greater at 60 min (p 3− was greater at 60 min (p p = 0.016; ES = 0.53) compared to placebo. These findings suggest NaHCO3 supplementation can improve the latter stages of sprint interval swimming performance, which is likely due to the augmentation of pH and HCO3− prior to exercise and the subsequent increase in buffering capacity during exercise.

Background and aims This systematic review sought to identify, explain and interpret the prominent or recurring themes relating to the barriers and facilitators of reporting and recording of self-harm in young people across different settings, such as the healthcare setting, schools and the criminal justice setting. Methods A search strategy was developed to ensure all relevant literature around the reporting and recording of self-harm in young people was obtained. Literature searches were conducted in six databases and a grey literature search of policy documents and relevant material was also conducted. Due to the range of available literature, both quantitative and qualitative methodologies were considered for inclusion. Results Following the completion of the literature searches and sifting, nineteen papers were eligible for inclusion. Facilitators to reporting self-harm across the different settings were found to be recognising self-harm behaviours, using passive screening, training and experience, positive communication, and safe, private information sharing. Barriers to reporting self-harm included confidentiality concerns, negative perceptions of young people, communication difficulties, stigma, staff lacking knowledge around self-harm, and a lack of time, money and resources. Facilitators to recording self-harm across the different settings included being open to discussing what is recorded, services working together and co-ordinated help. Barriers to recording self-harm were mainly around stigma, the information being recorded and the ability of staff being able to do so, and their length of professional experience. Conclusion Following the review of the current evidence, it was apparent that there was still progress to be made to improve the reporting and recording of self-harm in young people, across the different settings. Future work should concentrate on better understanding the facilitators, whilst aiming to ameliorate the barriers.

Most mental disorders appear by age 14, but in most cases, they remain undiagnosed and untreated well into adulthood. A scoping review showed an absence of systematic reviews that address prevalence rates of mental disorders among children and adolescents in Europe that are based on community studies conducted between 2015 and 2020. To estimate the updated pooled prevalence of Anxiety Disorder, Depressive Disorder, Attention Deficit Hyperactivity Disorder (ADHD), Conduct Disorder (CD), Oppositional Defiant Disorder (ODD), Autism Spectrum Disorder, Eating Disorders, Substance Use Disorders (SUD), among children and adolescents living in Europe, a search strategy was conducted using MEDLINE, Embase and Psych Info and studies were also identified from reference lists and gray literature. Eligible studies were evaluated for reliability, validity, and bias. Trends of prevalence rates for each mental disorder were calculated. Almost one in five young people in Europe were found to suffer from a mental disorder, with a pooled prevalence rate of 15.5%. Anxiety disorders had the highest pooled prevalence rate (7.9% (95% CI 5.1–11.8%, I2: 98.0%)), followed by ADHD (2.9% (95% CI 1.2–6.9%, I2 = 94.3%)), ODD (1.9% (95% CI 1.0–3.7%, I2 = 98.4%)), depressive disorder (1.7% (95% CI 1.0–2.9%, I2 = 97.7%)), CD (1.5% (95% CI 0.6–3.8%, I2 = 98.8%)) and ASD (1.4% (95% CI 0.4–5.4%, I2 = 99.7%). No studies on SUD were identified. The mental health of children and adolescents may be improved by introducing routine screening, refining diagnostic sensitivity, raising awareness of mental disorders, minimizing stigma and socioeconomic inequality, as well as developing early intervention services. These facilitators of good mental health need to be prioritized, especially at a time of unprecedented risk factors for poor mental health.

Diffuse intrinsic pontine glioma (DIPG) is an aggressive incurable brainstem tumor that targets young children. Complete resection is not possible, and chemotherapy and radiotherapy are currently only palliative. This study aimed to identify potential therapeutic agents using a computational pipeline to perform an in silico screen for novel drugs. We then tested the identified drugs against a panel of patient-derived DIPG cell lines. Using a systematic computational approach with publicly available databases of gene signature in DIPG patients and cancer cell lines treated with a library of clinically available drugs, we identified drug hits with the ability to reverse a DIPG gene signature to one that matches normal tissue background. The biological and molecular effects of drug treatment was analyzed by cell viability assay and RNA sequence. In vivo DIPG mouse model survival studies were also conducted. As a result, two of three identified drugs showed potency against the DIPG cell lines Triptolide and mycophenolate mofetil (MMF) demonstrated significant inhibition of cell viability in DIPG cell lines. Guanosine rescued reduced cell viability induced by MMF. In vivo, MMF treatment significantly inhibited tumor growth in subcutaneous xenograft mice models. In conclusion, we identified clinically available drugs with the ability to reverse DIPG gene signatures and anti-DIPG activity in vitro and in vivo. This novel approach can repurpose drugs and significantly decrease the cost and time normally required in drug discovery.

The water sector in India has undergone several institutional and structural reforms through different policies and legislation changes over the past decades to address the water scarcity challenges. This study presents and analyses various water utility policies chronologically emphasising persuasive conservation and use efficiency approach towards their implementation. A review of existing policies indicated that most of them have been only partially effective in implementing efficient water management due to the lack of a need-specific institutional framework, further deepening the water crisis. Moreover, the Indian water sector has been identified to concentrate majorly on water resource management, while overlooking sustainable aspects like water use efficiency through water metering. This study performed an 'indicator-based analysis', applying the framework of bounded rationality coupled with a 'cause-effect' model to recognise the effect of 12 significant water supply policies executed since independence. While initial policies focused on coverage and supply of adequate, safe, and improved drinking water majorly to rural sectors, the water sector gained holistic importance during the post-1990s considering aspects of the water source, supply frequency, water tariffing, etc. However, the gap coherence analysis illustrated that the concept of ‘water metering’ has not been distinctly considered in these policies. The findings from this study indicate a need for a discrete water metering policy, an equitable, universal, and cost-reflective tariff structuring, and the formulation of an institutional metering framework involving codes, testing laboratories, water metering standard associations. The above offers an alternate approach to the existing policy and a feasible solution to the water crisis in India. Internalising the advantages of metering in policy agenda may unlock the possibilities of success of the forthcoming policies.

Differential thermal analysis (DTA) and microstructural and microprobe measurements of DTA and as-cast Ni-Re alloys with compositions between 0.20 and 0.44 mass fraction Re provide information to resolve differences in previously published Ni-Re phase diagrams. This investigation determines that the peritectic invariant between liquid, Re-rich hexagonal close packed and Ni-rich face center cubic phases, L + HCP → FCC, occurs at 1561.1 °C ± 3.4 °C (1σ) with compositions of liquid, FCC and HCP phases of 0.283 ± 0.036, 0.436 ± 0.026, and 0.828 ± 0.037 mass fraction Re, respectively. Analysis of the microsegregation in FCC alloys yields a partition coefficient for solidification, k = 1.54 ± 0.09 (mass frac./mass frac.). A small deviation from Scheil behavior due to dendrite tip kinetics is documented in as-cast samples. No evidence of an intermetallic phase is observed.

Trio based whole exome sequencing via the Deciphering Developmental Disorders (DDD) study has identified three individuals with de novo frameshift variants in the Suppressor of Variegation, Enhancer of Zeste, and Trithorax (SET) gene. Variants in the SET gene have not previously been recognised to be associated with human developmental disorders. Here we report detailed phenotypic information and propose that SET is a new Intellectual Disability/Developmental Delay (ID/DD) gene.

This paper outlines a service evaluation of an exercise referral scheme for adults suffering from a variety of physical or mental health conditions or who were deemed are at risk of developing such conditions. The evaluation aimed to assess the impact of the scheme at increasing physical activity and at reducing BMI and waist circumference. This was a retrospective evaluation looking at levels of physical activity and changes to anthropometric measures over a period of 6 months. Each participant self-reported their levels of physical activity for the previous 7 days at three time points: baseline (T1), at 12-week exit from the scheme (T2), and at 6-month follow-up (T3). Waist circumference and BMI were also recorded by either a health professional or self-reported at these time points. Six hundred seventy participants were referred during the evaluation period, of whom 494 were eligible. Of those 494, 211 completed the 12-week scheme and 135 completed a 6-month follow-up. Significant increases in levels of physical activity were recorded between T1 and T2 and between T1 and T3. Furthermore, significant reductions in waist circumference were noted between T1 and T2 and between T1 and T3, and BMI significantly decreased between T1 and T2 but significantly increased between T2 and T3. The service has proven effective at increasing levels of physical activity among participants and has had a positive impact on waist circumference and BMI for clients who remain engaged with the programme.

Background: Fleas (Siphonaptera) are the most clinically important ectoparasites of dogs and cats worldwide. Rising levels of pet ownership, climate change and globalisation are increasing the importance of a detailed understanding of the endemicity and prevalence of flea-borne pathogens. This requires continued surveillance to detect change. This study reports a large-scale survey of pathogens in fleas collected from client-owned cats and dogs in the UK.Methods: Recruited veterinary practices were asked to follow a standardised flea inspection protocol on a randomised selection of cats and dogs brought into the practice in April and June 2018. A total of 326 practices participated and 812 cats and 662 dogs were examined. Fleas were collected, identified to species and pooled flea samples from each host were analysed for the presence of pathogens using PCR and sequence analysis.Results: Overall, 28.1% of cats and 14.4% of dogs were flea infested. More than 90% of the fleas on both cats and dogs were cat fleas, Ctenocephalides felis felis. Fleas of the same species from each infested host were pooled. DNA was amplified from 470 of the pooled flea samples using conventional PCR, 66 of which (14% ± 95% CI 3.14%) were positive for at least one pathogen. Fifty-three (11.3% ± 95% CI 2.85%) of the pooled flea DNA samples were positive for Bartonella spp., 35 were from cats and 4 from dogs, the remainder had no host record. Seventeen of the Bartonella spp. samples were found to be Bartonella henselae, 27 were Bartonella clarridgeiae (of two different strains), 4 samples were Bartonella alsatica and one was Bartonella grahamii; 4 samples could not be identified. Fourteen (3% ± 95% CI 1.53%) of the flea DNA samples were found to be positive for Dipylidium caninum, 10 of the D. caninum-infected samples were collected from cats and one from a dog, the other 3 positive flea samples had no host species record. Only 3 flea samples were positive for Mycoplasma haemofelis or Mycoplasma haemocanis; 2 were collected from cats and one had no host species record. Three fleas were positive for both D. caninum and Bartonella spp. One flea was positive for both Bartonella spp. and M. haemofelis or M. haemocanis.Conclusions: This study highlights the need for ongoing flea control, particularly given the relatively high prevalence of Bartonella spp., which is of concern for both animal welfare and human health. The study demonstrates the ongoing need to educate pet owners about the effects of both flea infestation and also the pathogen risks these fleas present.

Exposure to extreme heat is a familiar seasonal experience for many rural communities across Australia, which is projected to increase in frequency and intensity with climate change. This has wide-ranging implications for community health and well-being, livelihoods, recreation, and the natural and built environments. In this study, we have examined how rural and remote communities in South Australia experience and respond to extreme heat, and how this is influenced by physical, social and psychological aspects of place. Interviews with participants across different climatic regions of South Australia were analysed using a broad thematic framework that included physical aspects of place, human activities, social and community aspects, and relationships with place; providing a descriptive account of heat impacts and responses. We further suggest that some narratives expressed the construction of a rural or remote identity, with climate being a part of this relationship; suggesting that place identity may be a subjective aspect underpinning appraisals of extreme heat. We discuss the implications for adaptation choices in a warming climate.

Mindfulness has been used as an intervention for specific sexual dysfunctions in women; evidence has also accumulated for the role of mindfulness in treating the kinds of psychological difficulties which are associated with sexual dysfunction. This paper describes, within a clinical context, a qualitative approach to protocol and theory development for a mindfulness-based sex and intimate relationship (MSIR) programme as a generic adjunct to sex therapy. The aim was to adapt the mindfulness-based cognitive therapy (MBCT) group protocol to address diverse sexual and intimacy difficulties. The protocol was developed on an iterative basis and piloted with 30 patients referred from a sexual dysfunction clinic. Twelve participants came forward to be interviewed and their transcripts were analysed in two phases using a grounded theory approach, to produce a model generating testable hypotheses. The reduction of experiential and behavioural avoidance was central to the model that emerged from the analysis, along with the relinquishing of sexual goals in favour of focus on sensory experience. The analysis led also to a tentative staging of mindfulness, associated with enhanced experience. The adapted MBCT protocol for diverse sexual difficulties was found to be feasible and appeared positive for participants. Thus, MSIR shows promise as a generic adjunct to sex therapy.

By analyzing the whole-exome sequences of 4,264 schizophrenia cases, 9,343 controls and 1,077 trios, we identified a genome-wide significant association between rare loss-of-function (LoF) variants in SETD1A and risk for schizophrenia (P = 3.3 × 10(-9)). We found only two heterozygous LoF variants in 45,376 exomes from individuals without a neuropsychiatric diagnosis, indicating that SETD1A is substantially depleted of LoF variants in the general population. Seven of the ten individuals with schizophrenia carrying SETD1A LoF variants also had learning difficulties. We further identified four SETD1A LoF carriers among 4,281 children with severe developmental disorders and two more carriers in an independent sample of 5,720 Finnish exomes, both with notable neuropsychiatric phenotypes. Together, our observations indicate that LoF variants in SETD1A cause a range of neurodevelopmental disorders, including schizophrenia. Combining these data with previous common variant evidence, we suggest that epigenetic dysregulation, specifically in the histone H3K4 methylation pathway, is an important mechanism in the pathogenesis of schizophrenia.

Objectives: We conducted and measured outcomes from the Jerry Lee Program of 12 randomized trials over two decades in Australia and the United Kingdom (UK), testing an identical method of restorative justice taught by the same trainers to hundreds of police officers and others who delivered it to 2231 offenders and 1179 victims in 1995–2004. The article provides a review of the scientific progress and policy effects of the program, as described in 75 publications and papers arising from it, including previously unpublished results of our ongoing analyses. Methods: After random assignment in four Australian tests diverting criminal or juvenile cases from prosecution to restorative justice conferences (RJCs), and eight UK tests of supplementing criminal or juvenile proceedings with RJCs, we followed intention-to-treat group differences between offenders for up to 18 years, and for victims up to 10 years. Results: We distil and modify prior research reports into 18 updated evidence-based conclusions about the effects of RJCs on both victims and offenders. Initial reductions in repeat offending among offenders assigned to RJCs (compared to controls) were found in 10 of our 12 tests. Nine of the ten successes were for crimes with personal victims who participated in the RJCs, with clear benefits in both short- and long-term measures, including less prevalence of post-traumatic stress symptoms. Moderator effects across and within experiments showed that RJCs work best for the most frequent and serious offenders for repeat offending outcomes, with other clear moderator effects for poly-drug use and offense seriousness. Conclusions: RJ conferences organized and led (most often) by specially-trained police produced substantial short-term, and some long-term, benefits for both crime victims and their offenders, across a range of offense types and stages of the criminal justice processes on two continents, but with important moderator effects. These conclusions are made possible by testing a new kind of justice on a programmatic basis that would allow prospective meta-analysis, rather than doing one experiment at a time. This finding provides evidence that funding agencies could get far more evidence for the same cost from programs of identical, but multiple, RCTs of the identical innovative methods, rather than funding one RCT at a time.