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The apparent absorption of copper (Cu) in ruminants is low, with between 0.01 and 0.07 g/g absorbed from sources such as copper oxide (CuO) under typical feeding conditions, resulting in high levels of excretion. Improving the bioavailability of Cu could reduce the supplemental amount required to maintain Cu status and reduce excretion, particularly in the presence of dietary antagonists such as sulfur (S) and molybdenum (Mo). The objective of our study was to determine the Cu status of cows when fed nanoparticle CuO coated with Lys compared with conventional CuO when fed without or in combination with antagonists to Cu absorption (S and Mo) in the diet of dairy cows. Fifty-six multiparous Holstein-Friesian cows that were 48 d ± 17.4 (mean ± SD) post calving and yielding 40.6 ± 6.9 kg milk/d were used in a 2 × 2 factorial design. The 4 treatment groups were; CuO (O-), CuO with added antagonists (O+), nano CuO with a lysine coating (N-), and nano CuO with a Lys coating with added antagonists (N+), fed for 16 wks. We formulated the diets to contain approximately 17 mg Cu/kg dry matter (DM) and diets with antagonists contained an additional 1 g S/kg DM and 6 mg Mo/kg DM, with Lys added to O- and O+ to provide the same daily supply as N- and N+. Blood samples were collected at wk 0, 2, 4, 6, 10 and 16, and liver biopsy samples at wk 0 and 16. We found no effect of dietary treatment on DM intake, milk yield, live weight or body condition score, with mean values of 23.3 kg/d, 40.1 kg/d, 646 kg and 2.68, but milk SCC was higher in cows fed conventional compared with non CuO, or with added antagonist. We also found no effect of treatment on blood activity of gamma glutamyl transferase, superoxide dismutase or ceruloplasmin, hematology profile, or plasma Cu and iron concentration. We found that plasma Mo concentration was increased from 0.36 µmol/L in cows fed O- or N- to 0.80 µmol/L in those receiving O+ or N+. Additional dietary antagonists also decreased the concentration of Cu in the liver of cows fed conventional CuO (C+) over the study period by 1.3 mg/kg DM/d, but in cows fed dietary antagonists and nano CuO coated with Lys (N+), liver Cu concentration was increased by 1.1 mg/kg DM/d. Our study is the first to demonstrate that reducing the particle size of CuO into the nano scale with a lysine coating improves the bioavailability of CuO in the presence of dietary antagonists in dairy cattle, and we did not observe any negative effects on performance or health.

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This multicentre, retrospective medical record audit evaluated opioid analgesia prescribing within a Victorian metropolitan public hospital network. The study included all surgical patients discharged between January 2012 and December 2020 with one or more discharge prescriptions from three metropolitan hospitals (n = 117,989). The main outcome measures were mean oral morphine equivalent daily dose (OMEDD), mean number of opioid types and proportion of patients prescribed one or more slow-release opioids on discharge.Total opioid prescribing (mean OMEDD) peaked in 2013. Between 2017 and 2020 there was a trend towards prescribing fewer opioids on discharge. Over the study period, there was decreasing prescription of codeine and increasing prescription of oxycodone and tapentadol. The proportion of patients prescribed slow-release opioids increased in the earlier years of the study, reaching a peak of 20.6% in 2017. Since 2017 there has been a rapid reduction in the prescription of slow-release opioids.Subanalysis was undertaken to evaluate key changes in the opioid prescribing landscape in the health network. The removal of default opioid pack sizes in the electronic medication management system (December 2014) and the release of the Faculty of Pain Medicine-Australian and New Zealand College of Anaesthetists' statement regarding the use of opioid analgesics in patients with chronic non-cancer pain (March 2018) were associated with significant reductions in mean OMEDD prescribed on discharge (136 mg vs 122 mg and 120 mg vs 85.4 mg, respectively, P < 0.001).In conclusion, the quantity of opioids prescribed on discharge in this patient group peaked in 2013 and has been decreasing since.

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PURPOSE: Historically, the healthcare needs of 'Looked After Children' (LAC) within the UK have been relatively neglected and there is no universally adopted designated dental care pathway (DDCP) in place to ensure their care. This paper aims to discover the contribution of the community dental service (CDS) to the dental health of LAC throughout England and Wales. MATERIALS AND METHODS: An electronic questionnaire was sent to CDS Clinical Directors in England and local health boards in Wales between November 2011 and January 2012. Ten questions were included with 5-point Likert scale responses and the option for free text comments. RESULTS: In Wales, 41 questionnaires were returned (35% response rate) of which 37 services provided care for LAC. In England, 67 questionnaires were returned (44% response rate), of which 59 services provided care for LAC. CONCLUSION: The study found that the majority of CDSs in the UK provide care for LAC, However, we cannot ascertain if the CDS is the most appropriate service to provide dental care for this group of patients. The use of DDCPs, non-attendance and other care policies varied markedly amongst respondents, which may suggest that provision of dental care for LAC within the CDS in England and Wales is inconsistent. The authors believe that the utilisation of an LAC-specific and universally accepted DDCP that has been developed could help to reduce these inconsistencies. Further surveys are planned in order to monitor the care of this vulnerable group of patients and assess the impact of these recommendations.

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Family support services, an integral part of many welfare systems across the developed world, have witnessed a growing demand for the use of relationship and strengths-based whole-family approaches in the belief that this increases service engagement and effect. Despite this, knowledge that delivering services using such approaches can be challenging and calls for the identification and exploration of methods likely to promote and sustain their use. Restorative approach is an ethos and method centred on building and sustaining positive relationships, which is increasingly being adopted in family and children's services in the United Kingdom. Despite this, the scarcity of research conducted in this area as yet, means little is known of its use and effect in this context. This article draws on empirical data collected in a wider study exploring the efficacy of different family service delivery models to describe the use of restorative approach in family service provision and determine whether its adoption promotes sustained use of strengths and relationship-based whole-family approaches when working with families. Furthermore, it explores whether the process incorporates wider evidence-based methods of change.

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BACKGROUND: Alcohol-related violence is associated with licensed premise environments and their management. There is a lack of evidence for effective interventions to address these, and there are significant barriers to implementation. This study aims to understand how development and implementation processes can facilitate intervention reach, fidelity and receipt and therefore provides key process data necessary to interpret the results of the randomised controlled trial conducted in parallel. METHODS: A process evaluation, embedded within a randomised controlled trial. Intervention development and implementation were assessed via focus groups (n = 2) and semi-structured interviews (n = 22) with Environmental Health Practitioners (EHPs). Reach and fidelity were assessed via routinely collected intervention data, which was was collected from 276 licenced premises across Wales, UK. Case study semi-structured interviews with licensed premises proprietors (n = 30) explored intervention receipt. RESULTS: Intervention co-production with senior EHPs facilitated organisational adoption and implementation. Training events for EHPs played an important role in addressing wider organisational concerns regarding partnership working and the contextual integration of the intervention. EHPs delivered the intervention to 98 % of intervention premises; 35 % of premises should have received a follow up enforcement visit, however EHP confidence in dealing with alcohol risk factors meant only 7 % of premises received one. Premises therefore received a similar intervention dose regardless of baseline risk. Intervention receipt appeared to be greatest in premises with an existing commitment to prevention and those in urban environments. CONCLUSIONS: The study suggests that a collaborative approach to the development and diffusion of interventions is associated with high levels of organisational adoption, implementation and reach. However, the lack of enforcement visits represents implementation failure for a key mechanism of action that is likely to influence intervention effectiveness. To be effective, any future intervention may require a longer implementation period to develop EHP confidence in using enforcement approaches in this area and multiagency enforcement support, which includes the police, to deliver an adequate intervention dose.

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Organismal performance directly depends on an individual's ability to cope with a wide array of physiological challenges. For social animals, social isolation is a stressor that has been shown to increase oxidative stress. Another physiological challenge, routine locomotor activity, has been found to decrease oxidative stress levels. Because we currently do not have a good understanding of how diverse physiological systems like stress and locomotion interact to affect oxidative balance, we studied this interaction in the prairie vole (Microtus ochrogaster). Voles were either pair housed or isolated and within the isolation group, voles either had access to a moving wheel or a stationary wheel. We found that chronic periodic isolation caused increased levels of oxidative stress. However, within the vole group that was able to run voluntarily, longer durations of locomotor activity were associated with less oxidative stress. Our work suggests that individuals who demonstrate increased locomotor activity may be better able to cope with the social stressor of isolation.

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Insulin monotherapy can neither maintain normoglycemia in type 1 diabetes (T1D) nor prevent the long-term damage indicated by elevated glycation products in blood, such as glycated hemoglobin (HbA1c). Here we find that hyperglycemia, when unaccompanied by an acute increase in insulin, enhances itself by paradoxically stimulating hyperglucagonemia. Raising glucose from 5 to 25 mM without insulin enhanced glucagon secretion ∼two- to fivefold in InR1-G9 α cells and ∼18-fold in perfused pancreata from insulin-deficient rats with T1D. Mice with T1D receiving insulin treatment paradoxically exhibited threefold higher plasma glucagon during hyperglycemic surges than during normoglycemic intervals. Blockade of glucagon action with mAb Ac, a glucagon receptor (GCGR) antagonizing antibody, maintained glucose below 100 mg/dL and HbA1c levels below 4% in insulin-deficient mice with T1D. In rodents with T1D, hyperglycemia stimulates glucagon secretion, up-regulating phosphoenolpyruvate carboxykinase and enhancing hyperglycemia. GCGR antagonism in mice with T1D normalizes glucose and HbA1c, even without insulin.

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AIMS: This exploratory trial examines the feasibility of implementing a social norms marketing campaign to reduce student drinking in universities in Wales, and evaluating it using cluster randomised trial methodology. METHODS: Fifty residence halls in 4 universities in Wales were randomly assigned to intervention or control arms. Web and paper surveys were distributed to students within these halls (n = 3800), assessing exposure/contamination, recall of and evaluative responses to intervention messages, perceived drinking norms and personal drinking behaviour. Measures included the Drinking Norms Rating Form, the Daily Drinking Questionnaire and AUDIT-C. RESULTS: A response rate of 15% (n = 554) was achieved, varying substantially between sites. Intervention posters were seen by 80% and 43% of students in intervention and control halls respectively, with most remaining materials seen by a minority in both groups. Intervention messages were rated as credible and relevant by little more than half of students, though fewer felt they would influence their behaviour, with lighter drinkers more likely to perceive messages as credible. No differences in perceived norms were observed between intervention and control groups. Students reporting having seen intervention materials reported lower descriptive and injunctive norms than those who did not. CONCLUSIONS: Attention is needed to enhancing exposure, credibility and perceived relevance of intervention messages, particularly among heavier drinkers, before definitive evaluation can be recommended. A definitive evaluation would need to consider how it would achieve sufficient response rates, whilst hall-level cluster randomisation appears subject to a significant degree of contamination. TRIAL REGISTRATION: ISRCTN: ISRCTN48556384.

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BACKGROUND: Excessive alcohol consumption amongst university students has received increasing attention. A social norms approach to reducing drinking behaviours has met with some success in the USA. Such an approach is based on the assumption that student's perceptions of the norms of their peers are highly influential, but that these perceptions are often incorrect. Social norms interventions therefore aim to correct these inaccurate perceptions, and in turn, to change behaviours. However, UK studies are scarce and it is increasingly recognised that social norm interventions need to be supported by socio ecological approaches that address the wider determinants of behaviour. OBJECTIVES: To describe the research design for an exploratory trial examining the acceptability, hypothesised process of change and implementation of a social norm marketing campaign designed to correct misperceptions of normative alcohol use and reduce levels of misuse, implemented alongside a university wide alcohol harm reduction toolkit. It also assesses the feasibility of a potential large scale effectiveness trial by providing key trial design parameters including randomisation, recruitment and retention, contamination, data collection methods, outcome measures and intracluster correlations. METHODS/DESIGN: The study adopts an exploratory cluster randomised controlled trial design with halls of residence as the unit of allocation, and a nested mixed methods process evaluation. Four Welsh (UK) universities participated in the study, with residence hall managers consenting to implementation of the trial in 50 university owned campus based halls of residence. Consenting halls were randomised to either a phased multi channel social norm marketing campaign addressing normative discrepancies (n = 25 intervention) or normal practice (n = 25 control). The primary outcome is alcohol consumption (units per week) measured using the Daily Drinking Questionnaire. Secondary outcomes assess frequency of alcohol consumption, higher risk drinking, alcohol related problems and change in perceptions of alcohol-related descriptive and injunctive norms. Data will be collected for all 50 halls at 4 months follow up through a cross-sectional on line and postal survey of approximately 4000 first year students. The process evaluation will explore the acceptability and implementation of the social norms intervention and toolkit and hypothesised process of change including awareness, receptivity and normative changes. DISCUSSION: Exploratory trials such as this are essential to inform future definitive trials by providing crucial methodological parameters and guidance on designing and implementing optimum interventions. TRIAL REGISTRATION NUMBER: ISRCTN: ISRCTN48556384.

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