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Rodents are the predominant species used for scientific research and must be humanely killed upon completion of the work. In the UK this is regulated by Schedule 1 of the Animals Scientific Procedures Act 1986, which lists permitted methodologies considered capable of humane killing, including overdose of an anaesthetic, exposure to carbon dioxide (CO2) gas, dislocation of the neck and concussion of the brain by striking the cranium. Although all are permitted, operator motivations behind method selection and individual operator preference remain unknown. The views of 219 laboratory animal personnel on institutional availability and use of Schedule 1 killing methods for laboratory rodents were obtained. Only 10% of participants reported that all four methods were available at their institution with 57.5% of respondents preferring cervical dislocation. For CO2, only 18.6% of participants reported using the recommended flow rate, while 45.5% did not know the flow rate employed. We highlight the urgent requirement for the development of quality-controlled training programmes, to improve knowledge and confidence in the selection and application of killing methods. We advocate for continuous review of killing practices to ensure best practice is reflected in legislation and achieve optimal protection of the welfare of laboratory rodents during killing. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease is a complex neurodegenerative condition with significant impact on quality of life (QoL), wellbeing and function. The objective of this review is to evaluate the clinical effectiveness of self-management interventions for people with Parkinson's disease, taking a broad view of self-management and considering effects on QoL, wellbeing and function.Methods: Systematic searches of four databases (MEDLINE, Embase, PsycINFO, Web of Science) were conducted for studies evaluating self-management interventions for people with Parkinson's disease published up to 16th November 2020. Original quantitative studies of adults with idiopathic Parkinson's disease were included, whilst studies of atypical Parkinsonism were excluded. Full-text articles were independently assessed by two reviewers, with data extracted by one reviewer and reliability checked by a second reviewer, then synthesised through a narrative approach and, for sufficiently similar studies, a meta-analysis of effect size was conducted (using a random-effects meta-analysis with restricted maximum likelihood method pooled estimate). Interventions were subdivided into self-management components according to PRISMS Taxonomy. Risk of bias was examined with the Cochrane Risk of Bias 2 (RoB2) tool or ROBIN-I tool as appropriate.Results: Thirty-six studies were included, evaluating a diverse array of interventions and encompassing a range of study designs (RCT n = 19; non-randomised CT n = five; within subject pre- and post-intervention comparisons n = 12). A total of 2884 participants were assessed in studies across ten countries, with greatest output from North America (14 studies) and UK (six studies). Risk of bias was moderate to high for the majority of studies, mostly due to lack of participant blinding, which is not often practical for interventions of this nature. Only four studies reported statistically significant improvements in QoL, wellbeing or functional outcomes for the intervention compared to controls. These interventions were group-based self-management education and training programmes, either alone, combined with multi-disciplinary rehabilitation, or combined with Cognitive Behaviour Therapy; and a self-guided community-based exercise programme. Four of the RCTs evaluated sufficiently similar interventions and outcomes for meta-analysis: these were studies of self-management education and training programmes evaluating QoL (n = 478). Meta-analysis demonstrated no significant difference between the self-management and the control groups with a standardised mean difference (Hedges g) of - 0.17 (- 0.56, 0.21) p = 0.38. By the GRADE approach, the quality of this evidence was deemed "very low" and the effect of the intervention is therefore uncertain. Components more frequently observed in effective interventions, as per PRISMS taxonomy analysis, were: information about resources; training or rehearsing psychological strategies; social support; and lifestyle advice and support. The applicability of these findings is weakened by the ambiguous and at times overlapping nature of self-management components.Conclusion: Approaches and outcomes to self-management interventions in Parkinson's disease are heterogenous. There are insufficient high quality RCTs in this field to show effectiveness of self-management interventions in Parkinson's disease. Whilst it is not possible to draw conclusions on specific intervention components that convey effectiveness, there are promising findings from some studies, which could be targeted in future evaluations. [ABSTRACT FROM AUTHOR]

Background: Public health initiatives seek to modify lifestyle behaviours associated with risk (e.g., diet, exercise, and smoking), but underpinning psychological and affective processes must also be considered to maximize success. Objective: This study aimed to qualitatively assess how participants engaged with and utilized the best possible self (BPS)‐intervention specifically as a type 2 diabetes (T2D) prevention tool. Design and Methods: Fourteen participants engaged with a tailored BPS intervention. Reflexive thematic analysis analysed accounts of participant's experiences and feasibility of use. Results: All participants submitted evidence of engagement with the intervention. The analysis considered two main themes: Holistic Health and Control. The analysis highlighted several nuanced ways in which individuals conceptualized their health, set goals, and received affective benefits, offering insights into how people personalized a simple intervention to meet their health needs. Conclusions: To our knowledge, this is the first study to tailor the BPS intervention as a public health application for the prevention of T2D. The intervention enabled users to identify their best possible selves in a way that encouraged T2D preventive behaviours. We propose that our tailored BPS intervention could be a flexible and brief tool to assist public health efforts in encouraging change to aid T2D prevention. Public Contribution: The format, language and application of the BPS intervention were adapted in response to a public consultation group that developed a version specifically for application in this study. [ABSTRACT FROM AUTHOR]

In the face of the COVID-19 pandemic, the swift response of mental health research funders and institutions, service providers, and academics enabled progress toward understanding the mental health consequences. Nevertheless, there remains an urgent need to understand the true extent of the short- and long-term effects of the COVID-19 pandemic on mental health, necessitating ongoing research. Although the speed with which mental health researchers have mobilized to respond to the pandemic so far is to be commended, there are valid concerns as to whether speed may have compromised the quality of our work. As the pandemic continues to evolve, we must take time to reflect on our initial research response and collectively consider how we can use this to strengthen ensuing COVID-19 mental health research and our response to future crises. Here, we offer our reflections as members of the UK mental health research community to discuss the continuing progress and persisting challenges of our COVID-19 response, which we hope can encourage reflection and discussion among the wider research community. We conclude that (1) Fragmentation in our infrastructure has challenged the efficient, effective and equitable deployment of resources, (2) In responding quickly, we may have overlooked the role of experts by experience, (3) Robust and open methods may have been compromised by speedy responses, and (4) This pandemic may exacerbate existing issues of inequality in our workforce. [ABSTRACT FROM AUTHOR]

Objective: Investigate the psychometric properties of the Severity of Dependence Scale (SDS) for codeine and its association with aberrant codeine related behaviors. Design: A voluntary and uncompensated cross-sectional online survey. Setting: Online population (≥18 years). Respondents: Two hundred and eighty-six respondents (66% women) who had used codeine containing medicines in the last 3 months and were living in the UK. Results: Of the respondents (mean age = 35.4 years, SD = 12.5), more than half were employed. Only 3.5% respondents reported no income. The majority of respondents (45.1%) primarily obtained prescription-only codeine from a consultation with a health professional, whilst 40.9% mainly purchased "over-the-counter" codeine containing medicines in a pharmacy without a medical prescription. Principal component analysis indicated a single factor solution accounting for 75% of the variance. Factor loadings ranged from 0.83 to 0.89. Cronbach's Alpha was high (α = 0.92). Several behaviors relating to codeine use were found to significantly predict probable codeine dependence. These included: daily codeine use in the last 3 months (OR = 66.89, 95% CI = 15.8–283.18); tolerance to codeine (OR = 32.14, 95% CI = 13.82–74.75); problems with role responsibility due to intoxication (OR = 9.89, 95% CI = 4.95–19.78); having sought advice on the internet to manage codeine use (OR = 9.56, 95% CI = 4.5–20.31); history of alcohol or drug treatment (OR = 3.73, 95% CI = 1.88–7.43). Conclusions: The SDS was acceptable and feasible to use to assess probable psychological codeine dependence in an online sample of people using codeine containing medicines. SDS scores were associated with behaviors known to be indicators of codeine dependence. Studies are needed in well-defined populations of people who use codeine to test the different aspects of psychometry of the scale compared against "gold standard" criterion [a diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)]. [ABSTRACT FROM AUTHOR]

This review covers the last 20 years of UK drug control policy leading up to the recent Psychoactive Substances Act. It explores policy decision made in relation to MDMA and mephedrone that not only were associated with increased drug harms overall but also had a significant detrimental effect on the UK research base. The new UK legislation on synthetic cannabinoids and other novel psychoactive substances threatens to do the same, showing that there is still much to learn from the decisions of the past. In future input from academic societies such as the BPS could help improve policy evaluation and policy development and so help avoid such problems in the future. [ABSTRACT FROM AUTHOR]

Novel psychoactive substances (NPS) are new drugs of abuse. Over the last 10 years 50–100 new NPS have been detected for the first time each year. This has led to numerous deaths and challenges to healthcare providers and law‐makers worldwide. We review preclinical studies of NPS and discuss how these studies have influenced legislative decisions. We focus on the UK legal system but include experiences from Europe. We reviewed manuscripts from 2008–2019 and have summarised the in vitro and in vivo data on NPS, highlighting how these studies define pharmacological mechanisms and how they might predict harm in humans. We found that only a small percentage of NPS have been examined in preclinical studies. Most preclinical studies of NPS focus on basic pharmacological mechanisms (46% of studies reviewed) and/or addictive liability (32%) rather than toxicity and harm (24%). Very few preclinical studies into NPS include data from chronic dosing schedules (9%) or female rodents (4%). We conclude that preclinical studies can predict harm to humans, but most of the predictions are based on basic pharmacology rather than demonstrated toxicity. Some of these studies have been used to make changes to the law in the UK and Europe and perhaps, because of the paucity of toxicology data, most NPS have been placed in the highly dangerous schedule 1 or Class A category in the UK. We suggest that in silico studies and high throughput toxicology screens might be the most economical way forward to rapidly screen the health harms of NPS. [ABSTRACT FROM AUTHOR]

Novel psychoactive substances (NPS), especially those newly created, are largely an unknown quantity, particularly in terms of their potential serious adverse effects. This means that policy‐makers and clinicians are under‐informed about appropriate responses. Collation of detailed information on deaths related to NPS use can help in providing knowledge and understanding these aspects of the NPS phenomenon. The purpose of this review is to outline the role(s) which such evidence‐based data can play in this respect. UK NPS‐related cases demonstrate differences in definitions used by the General Mortality Registers, and differences between countries, not only in terms of the type of NPS implicated in deaths, but the number and extent of such deaths over time. NPS deaths are continuing to increase numerically and as a proportion of all drug‐poisoning deaths. In order to better understand how specific molecules contribute to and/or cause death, detailed information collected by Special Mortality Registers can provide examples of substances' modes of action, adverse effects, symptomatology, treatment interventions, mechanisms of death, etc. This information can provide clinicians and policy‐makers with objective information on the serious harms from such emerging molecules. Such evidence‐based advice informs public health interventions, service provision and policy decisions on regulation and control of NPS. However, without reliable, accurate and complete information that is correctly collated, scientifically analysed and disseminated in a timely manner, an understanding of the phenomenon of what deaths can be ascribed to NPS, their characteristics and nature will remain unachieved, and thus limit what can be done to reduce them. [ABSTRACT FROM AUTHOR]

This review paper is based on a talk given at the British Pharmaceutical Society Winter Meeting in 2018 derived from the Home Office Report on the workings of the UK Psychoactive Substances Act (PSA) published in November 2018. The review deals with the context in which the PSA 2016 arose and how this piece of legislation differs from other UK drug regulations. It attempts to put the PSA in context with other control schemes being instituted around the world and to assess the success of the Act in its first 2 years of implementation. For more details the reader is referred to Review of the Psychoactive Substances Act 2016, Home Office, November 2018. [ABSTRACT FROM AUTHOR]

Aims: The risk of potential harms prompted the UK government to introduce the Psychoactive Substances Act in 2016. The aim of the present study was to evaluate the impact and effectiveness of this new legislation on patterns of novel psychoactive substance (NPS) awareness, use, experiences and risk awareness in a self‐selected sample of UK consumers to inform education and policy. Methods: The Bristol Online Survey was advertised on the Bluelight drug forum and social media Facebook pages and University email between 7 January and 7 February 2015 (168 responses) and 9 March to 18 September 2017 (726 responses). UK country of residence responses were extracted for analysis (SPSS). Results: In a predominantly university‐educated, young (< 25 years) self‐selecting sample, 1 year after introduction of the legislation, NPS use (in males, under 18s, those educated to school/college level, P <.001) has increased, whilst health risk awareness has not changed and remains poor. Users are switching to sourcing NPSs via street dealers (49%) and the darknet (31%) and showing an increase in preference for the herbal NPS Salvia divinorum (P <.05). The main reasons for NPS use remain the influence of friends (69%) in a social setting and to get high (76%) usually in combination with alcohol, cannabis or ecstasy. Conclusion: Regulation alone, so far, has not impacted on health risk awareness, NPS drug demand and culture in our UK survey sample. Alongside regulation, NPS health promotion education (particularly in schools, colleges) is needed that addresses resilience and both the risks and beneficial effects of NPS. [ABSTRACT FROM AUTHOR]

Ninety per cent of the human population has been right-handed since the Paleolithic, yet the brain signature and genetic basis of handedness remain poorly characterized. Here, we correlated brain imaging phenotypes from ∼9000 UK Biobank participants with handedness, and with loci found significantly associated with handedness after we performed genome-wide association studies (GWAS) in ∼400 000 of these participants. Our imaging-handedness analysis revealed an increase in functional connectivity between left and right language networks in left-handers. GWAS of handedness uncovered four significant loci (rs199512, rs45608532, rs13017199, and rs3094128), three of which are in-or expression quantitative trait loci of-genes encoding proteins involved in brain development and patterning. These included microtubule-related MAP2 and MAPT, as well as WNT3 and MICB, all implicated in the pathogenesis of diseases such as Parkinson's, Alzheimer's and schizophrenia. In particular, with rs199512, we identified a common genetic influence on handedness, psychiatric phenotypes, Parkinson's disease, and the integrity of white matter tracts connecting the same language-related regions identified in the handedness-imaging analysis. This study has identified in the general population genome-wide significant loci for human handedness in, and expression quantitative trait loci of, genes associated with brain development, microtubules and patterning. We suggest that these genetic variants contribute to neurodevelopmental lateralization of brain organization, which in turn influences both the handedness phenotype and the predisposition to develop certain neurological and psychiatric diseases. [ABSTRACT FROM AUTHOR]

Background This paper describes the development of a complex intervention to promote mental wellbeing using the revised framework for developing and evaluating complex interventions produced by the UK Medical Research Council (UKMRC). Methods Application of the first two phases of the framework is described—development and feasibility and piloting. The theoretical case and evidence base were examined analytically to explicate the theoretical and empirical foundations of the intervention. These findings informed the design of a 12-week mental wellbeing promotion programme providing early intervention for people showing signs of mental health difficulties. The programme is based on the theoretical constructs of self-efficacy, self-esteem, purpose in life, resilience and social support and comprises 10 steps. A mixed methods approach was used to conduct a feasibility study with community and voluntary sector service users and in primary care. Results A significant increase in mental wellbeing was observed following participation in the intervention. Qualitative data corroborated this finding and suggested that the intervention was feasible to deliver and acceptable to participants, facilitators and health professionals. Conclusions The revised UKMRC framework can be successfully applied to the development of public health interventions. [ABSTRACT FROM PUBLISHER]

Following a large outbreak of foodborne gastrointestinal (GI) disease, a multiplex PCR approach was used retrospectively to investigate faecal specimens from 88 of the 413 reported cases. Gene targets from a range of bacterial GI pathogens were detected, including Salmonella species, Shigella species and Shiga toxin-producing Escherichia coli, with the majority (75%) of faecal specimens being PCR positive for aggR associated with the Enteroaggregative E. coli (EAEC) group. The 20 isolates of EAEC recovered from the outbreak specimens exhibited a range of serotypes, the most frequent being O104:H4 and O131:H27. None of the EAEC isolates had the Shiga toxin (stx) genes. Multilocus sequence typing and single nucleotide polymorphism analysis of the core genome confirmed the diverse phylogeny of the strains. The analysis also revealed a close phylogenetic relationship between the EAEC O104:H4 strains in this outbreak and the strain of E. coli O104:H4 associated with a large outbreak of haemolytic ureamic syndrome in Germany in 2011. Further analysis of the EAEC plasmids, encoding the key enteroaggregative virulence genes, showed diversity with respect to FIB/FII type, gene content and genomic architecture. Known EAEC virulence genes, such as aggR, aat and aap, were present in all but one of the strains. A variety of fimbrial genes were observed, including genes encoding all five known fimbrial types, AAF/1 to AAF/V. The AAI operon was present in its entirety in 15 of the EAEC strains, absent in three and present, but incomplete, in two isolates. EAEC is known to be a diverse pathotype and this study demonstrates that a high level of diversity in strains recovered from cases associated with a single outbreak. Although the EAEC in this study did not carry the stx genes, this outbreak provides further evidence of the pathogenic potential of the EAEC O104:H4 serotype. [ABSTRACT FROM AUTHOR]

The substituted β-keto amphetamine mephedrone (4-methylmethcathinone) was banned in the UK in April 2010 but continues to be used recreationally in the UK and elsewhere. Users have compared its psychoactive effects to those of 3,4-methylenedioxymethamphetamine ( MDMA, 'ecstasy'). This review critically examines the preclinical data on mephedrone that have appeared over the last 2-3 years and, where relevant, compares the pharmacological effects of mephedrone in experimental animals with those obtained following MDMA administration. Both mephedrone and MDMA enhance locomotor activity and change rectal temperature in rodents. However, both of these responses are of short duration following mephedrone compared with MDMA probably because mephedrone has a short plasma half-life and rapid metabolism. Mephedrone appears to have no pharmacologically active metabolites, unlike MDMA. There is also little evidence that mephedrone induces a neurotoxic decrease in monoamine concentration in rat or mouse brain, again in contrast to MDMA. Mephedrone and MDMA both induce release of dopamine and 5- HT in the brain as shown by in vivo and in vitro studies. The effect on 5- HT release in vivo is more marked with mephedrone even though both drugs have similar affinity for the dopamine and 5-HT transporters in vitro. The profile of action of mephedrone on monoamine receptors and transporters suggests it could have a high abuse liability and several studies have found that mephedrone supports self-administration at a higher rate than MDMA. Overall, current data suggest that mephedrone not only differs from MDMA in its pharmacological profile, behavioural and neurotoxic effects, but also differs from other cathinones. [ABSTRACT FROM AUTHOR]

Reserve and National Guard forces have been mobilized to an unprecedented degree in recent overseas conflicts. There is concern that rates of psychological problems may continue to rise for many years after deployment. The authors conducted a cohort study of 552 United Kingdom Reservists who deployed to Iraq in 2003 and 391 nondeployed Reservists. Measures of mental health and social functioning were collected a mean of 16 months and 4.8 years after return from possible deployment. At the first follow-up, deployment was associated with increased common mental disorder, post-traumatic stress disorder (PTSD), and poor general health. By the second follow-up, those who had deployed were no longer at increased risk for common mental disorder or poor general health and had good levels of social functioning. However, those who deployed continued to have over twice the odds of PTSD (odds ratio = 2.42, 95% confidence interval: 1.04, 5.62) and were more likely to report actual or serious consideration of separation from their partner. In conclusion, the authors found that the majority of mental health and social problems following deployment are transient. However, Reservists who deployed in the Iraq War remain at increased risk of PTSD and relationship problems 5 years after their tour of duty. [ABSTRACT FROM AUTHOR]

Background Whether the quality of life (QOL) impacts longevity is an interesting research question that has been investigated only in the context of disease and health-related QOL. This paper aims to examine prospectively whether Control, Autonomy, Selfrealisation, and Pleasure (CASP) scores, a measure of generic QOL, can predict mortality in the British Household Panel Survey sample during 2001-2006. Methods The authors used data from the British Household Panel Survey wave 11 (2001-2002) when CASP was first presented to the participants in the survey. The authors selected all those who were interviewed directly and face to face and who were 40 years or older (N=10 291). The authors followed them for the next five waves (waves 12-16) and in this study primary outcome was all-cause mortality. Other covariates used were age, sex, socioeconomic position, household income, self-rated health, limiting longstanding illness and medical conditions. Results Compared with a mortality of 12/1000 personyears in those having average QOL (CASP score 29.4-45.8), those with below-average QOL had more than twice (27/1000 person-years) and those above average had a third less (8/1000 person-years) mortality. This gradient was retained for the most part when age and sex strata were examined separately. Regression models adjusted for covariates confirmed the protective effect of QOL on mortality. Domain-specific analysis showed that only control and self-realisation had this effect. Conclusion CASP predicted 5-year all-cause mortality significantly. Improvement in the QOL reduced the probability of death. [ABSTRACT FROM AUTHOR]

The article focuses on the militarism, socialism, communism and conscription that emerged in France and Britain. It presents the struggle of House of Commons legislator William Gallacher to defend the actions and pronouncements of communists internationally. The British communist party and its French counterpart were committed to strict principles of international discipline. It notes that militarism was described as the shared civic duty of self-defence, adding that the identification of citizenship with military service does not necessarily mean the barracks life. Moreover, universal military service in France has been legitimized as an exercise in citizenship, while Great Britain identified it as free British citizen having exempted from compulsory service.

In this article, the author discusses the paper of Dr. Simon Moore which opposes the alcohol control policy proposal that increases alcohol prices in Great Britain. The author states that Moore has overvalued the possibility that a decline in alcohol consumption would increase dangerous material utilization. He says that the policy could be successful due to its impact to the remaining population of drinkers. He suggests to expand policy evaluation and assess policy impact with various views.