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Summary: Background: Intermittent preventive treatment (IPT) is a well established malaria control intervention. Evidence that delivering IPT to schoolchildren could provide community-level benefits is limited. We did a cluster-randomised controlled trial to assess the effect of IPT of primary schoolchildren with dihydroartemisinin-piperaquine (DP) on indicators of malaria transmission in the community, in Jinja, Uganda. Methods: We included 84 clusters, each comprising one primary school and the 100 closest available households. The clusters were randomly assigned 1:1 to receive IPT with DP or standard care (control) by restricted randomisation to ensure balance by geography and school type. Children in intervention schools received IPT monthly for up to six rounds (June to December, 2014). We did cross-sectional community surveys in randomly selected households at baseline and in January to April, 2015, during which we measured participants' temperatures and obtained finger-prick blood smears for measurement of parasite prevalence by microscopy. We also did entomological surveys 1 night per month in households from 20 randomly selected IPT and 20 control clusters. The primary trial outcome was parasite prevalence in the final community survey. The primary entomological survey outcome was the annual entomological inoculation rate (aEIR) from July, 2014, to April, 2015. This trial is registered at ClinicalTrials.gov, number NCT02009215. Findings: Among 23 280 students registered in the 42 intervention schools, 10 079 (43%) aged 5–20 years were enrolled and received at least one dose of DP. 9286 (92%) of 10 079 received at least one full course of DP (three doses). Community-level parasite prevalence was lower in the intervention clusters than in the control clusters (19% vs 23%, adjusted risk ratio 0·85, 95% CI 0·73–1·00, p=0·05). The aEIR was lower in the intervention group than in the control group, but not significantly so (10·1 vs 15·2 infective bites per person, adjusted incidence rate ratio 0·80, 95% CI 0·36–1·80, p=0·59). Interpretation: IPT of schoolchildren with DP might have a positive effect on community-level malaria indicators and be operationally feasible. Studies with greater IPT coverage are needed. Funding: UK Medical Research Council, UK Department for International Development, and Wellcome Trust.

Background: In Uganda, health system challenges limit access to good quality healthcare and contribute to slow progress on malaria control. We developed a complex intervention (PRIME), which was designed to improve quality of care for malaria at public health centres. Objective: Responding to calls for increased transparency, we describe the PRIME intervention's design process, rationale, and final content and reflect on the choices and challenges encountered during the design of this complex intervention. Design: To develop the intervention, we followed a multistep approach, including the following: 1) formative research to identify intervention target areas and objectives; 2) prioritization of intervention components; 3) review of relevant evidence; 4) development of intervention components; 5) piloting and refinement of workshop modules; and 6) consolidation of the PRIME intervention theories of change to articulate why and how the intervention was hypothesized to produce desired outcomes. We aimed to develop an intervention that was evidence-based, grounded in theory, and appropriate for the study context; could be evaluated within a randomized controlled trial; and had the potential to be scaled up sustainably. Results: The process of developing the PRIME intervention package was lengthy and dynamic. The final intervention package consisted of four components: 1) training in fever case management and use of rapid diagnostic tests for malaria (mRDTs); 2) workshops in health centre management; 3) workshops in patient-centred services; and 4) provision of mRDTs and antimalarials when stocks ran low. Conclusions: The slow and iterative process of intervention design contrasted with the continually shifting study context. We highlight the considerations and choices made at each design stage, discussing elements we included and why, as well as those that were ultimately excluded. Reflection on and reporting of ‘behind the scenes’ accounts of intervention design may improve the design, assessment, and generalizability of complex interventions and their evaluations.

Background: In other populations, the psychological impact of abuse has been conceptualized as Post Traumatic Stress Disorder (PTSD, DSM-IV, American Psychiatric Association (APA), 1994), but little is known about whether this is appropriate for adults with severe intellectual disabilities and very limited communication skills. Methods: An informant interview, based on the framework provided by PTSD, but supplemented with additional questions, was developed and was used to elicit the emotional, behavioural and physiological symptoms of alleged abuse in 18 people with intellectual disabilities at three time points: in the 3 months immediately prior to the alleged abuse (Time 1), in the 3 months immediately after the abuse (Time 2) and in the last 3 months prior to interview (Time 3). Results: The reports of the family and carer informants indicated that, following their alleged abuse, the victims experienced marked increases in the frequency and severity of emotional, physiological and behavioural symptoms of psychological distress. Over time, there was some alleviation of these difficulties, but psychological functioning remained severely compromised. Conclusions: While the established PTSD framework is appropriate for examining the psychological impact of abuse, some amendments are required to enable clinicians to examine fully the distress of alleged victims with severe intellectual disabilities. (Contains 5 tables.)

Background: Cortisol is a marker of physiological arousal, exhibiting a characteristic pattern of diurnal activity. The daily cortisol profile has been examined extensively and is atypical in a number of clinical disorders. However, there are very few studies focussing on the cortisol profile in adults with intellectual disabilities (ID). This paper reports a preliminary investigation into the nature of the cortisol profile in adults with mild or moderate ID and provides reflections on the challenges of psychophysiological research in this population. Methods: On two consecutive days, 39 adults with mild or moderate ID each donated saliva samples for cortisol analysis, at multiple times between waking and evening. A comparison between these data and the published literature permitted a descriptive assessment of the cortisol awakening response (CAR) and diurnal profile. A variety of psychometric measures and an assessment of behavioural history were also collected in order to describe aspects of the participants' emotional and behavioural states. Results: Individuals with ID exhibit a diurnal cortisol secretion profile, qualitatively similar to that of the typical, healthy, adult population. However, the findings also suggested a blunted CAR, warranting further investigation. There was also some evidence that cortisol secretion was affected by anxiety and a recent history of aggression. Conclusion: While further work is required to characterise the CAR fully, there was no indication that the diurnal cortisol profile among people with ID differs from that of the typical population. This study also demonstrates that, although challenging, it is feasible, and acceptable to participants, to collect repeated physiological measures from men and women with mild and moderate ID. (Contains 2 figures and 2 tables.)

Epigenetic mechanisms allow cells to fine-tune gene expression in response to environmental stimuli. For decades, it has been known that mitochondria have genetic material. Still, only recently have studies shown that epigenetic factors regulate mitochondrial DNA (mtDNA) gene expression. Mitochondria regulate cellular proliferation, apoptosis, and energy metabolism, all critical areas of dysfunction in gliomas. Methylation of mtDNA, alterations in mtDNA packaging via mitochondrial transcription factor A (TFAM), and regulation of mtDNA transcription via the micro-RNAs (mir 23-b) and long noncoding RNAs [RNA mitochondrial RNA processing (RMRP)] have all been identified as contributing to glioma pathogenicity. Developing new interventions interfering with these pathways may improve glioma therapy. [ABSTRACT FROM AUTHOR]

This section offers information on European artworks acquired by the Detroit Institute of Arts (DIA) museum in Michigan from 2016 to 2022. Topics discussed include a 1480 limewood sculpture of archangel Michael attributed to the Harburg Master workshop, the 1500 oil painting "Descent from the Cross," by the Master of the Embroidered Foliage, and the 17th century painting "Infant St John the Baptist in the wilderness," by Bartolomé Esteban Murillo.

BACKGROUND:Rapid diagnostic tests for malaria (mRDTs) have been scaled-up widely across Africa. The PRIME study evaluated an intervention aiming to improve fever case management using mRDTs at public health centers in Uganda. METHODS:A cluster-randomized trial was conducted from 2010-13 in Tororo, a high malaria transmission setting. Twenty public health centers were randomized in a 1:1 ratio to intervention or control. The intervention included training in health center management, fever case management with mRDTs, and patient-centered services; plus provision of mRDTs and artemether-lumefantrine (AL) when stocks ran low. Three rounds of Interviews were conducted with caregivers of children under five years of age as they exited health centers (N = 1400); reference mRDTs were done in children with fever (N = 1336). Health worker perspectives on mRDTs were elicited through semi-structured questionnaires (N = 49) and in-depth interviews (N = 10). The primary outcome was inappropriate treatment of malaria, defined as the proportion of febrile children who were not treated according to guidelines based on the reference mRDT. FINDINGS:There was no difference in inappropriate treatment of malaria between the intervention and control arms (24.0% versus 29.7%, adjusted risk ratio 0.81 [95% CI: 0.56, 1.17] p = 0.24). Most children (76.0%) tested positive by reference mRDT, but many were not prescribed AL (22.5% intervention versus 25.9% control, p = 0.53). Inappropriate treatment of children testing negative by reference mRDT with AL was also common (31.3% invention vs 42.4% control, p = 0.29). Health workers appreciated mRDTs but felt that integrating testing into practice was challenging given constraints on time and infrastructure. CONCLUSIONS:The PRIME intervention did not have the desired impact on inappropriate treatment of malaria for children under five. In this high transmission setting, use of mRDTs did not lead to the reductions in antimalarial prescribing seen elsewhere. Broader investment in health systems, including infrastructure and staffing, will be required to improve fever case management.

BACKGROUND:Many patients with malaria-like symptoms seek treatment in private medicine retail outlets (PMR) that distribute malaria medicines but do not traditionally provide diagnostic services, potentially leading to overtreatment with antimalarial drugs. To achieve universal access to prompt parasite-based diagnosis, many malaria-endemic countries are considering scaling up malaria rapid diagnostic tests (RDTs) in these outlets, an intervention that may require legislative changes and major investments in supporting programs and infrastructures. This review identifies studies that introduced malaria RDTs in PMRs and examines study outcomes and success factors to inform scale up decisions. METHODS:Published and unpublished studies that introduced malaria RDTs in PMRs were systematically identified and reviewed. Literature published before November 2016 was searched in six electronic databases, and unpublished studies were identified through personal contacts and stakeholder meetings. Outcomes were extracted from publications or provided by principal investigators. RESULTS:Six published and six unpublished studies were found. Most studies took place in sub-Saharan Africa and were small-scale pilots of RDT introduction in drug shops or pharmacies. None of the studies assessed large-scale implementation in PMRs. RDT uptake varied widely from 8%-100%. Provision of artemisinin-based combination therapy (ACT) for patients testing positive ranged from 30%-99%, and was more than 85% in five studies. Of those testing negative, provision of antimalarials varied from 2%-83% and was less than 20% in eight studies. Longer provider training, lower RDT retail prices and frequent supervision appeared to have a positive effect on RDT uptake and provider adherence to test results. Performance of RDTs by PMR vendors was generally good, but disposal of medical waste and referral of patients to public facilities were common challenges. CONCLUSIONS:Expanding services of PMRs to include malaria diagnostic services may hold great promise to improve malaria case management and curb overtreatment with antimalarials. However, doing so will require careful planning, investment and additional research to develop and sustain effective training, supervision, waste-management, referral and surveillance programs beyond the public sector.

Background: For many adults with an intellectual disability (ID), mealtimes carry significant health risks. While research and allied clinical guidance has focused mainly on dysphagia, adults with a range of physical and behavioural difficulties require mealtime support to ensure safety and adequate nutrition. The extent of need for and nature of such support within the wider ID population has yet to be reported. Methods: In this study, we have estimated the prevalence of need for mealtime support among people with ID in the UK, using a population of 2230 adults known to specialist ID services (in Cambridgeshire, UK, total population 586 900). In a sample (n = 69, aged 19 to 79 years, with mild to profound ID), we characterised the support provided, using a structured proforma to consult support workers and carers providing mealtime support, and health and social care records. Results: Mealtime support was found to be required by a significant minority of people with ID for complex and varied reasons. Prevalence of need for such support was estimated at 15% of adults known to specialist ID services or 56 per 100 000 total population. Within a sample, support required was found to vary widely in nature (from texture modification or environmental adaptation to enteral feeding) and in overall level (from minimal to full support, dependent on functional skills). Needs had increased over time in almost half (n = 34, 49.3%). Reasons for support included difficulties getting food into the body (n = 56, 82.2%), risky eating and drinking behaviours (n = 31, 44.9%) and slow eating or food refusal (n = 30, 43.5%). These proportions translate into crude estimates of the prevalence of these difficulties within the known ID population of 11.9%, 6.6% and 6.4% respectively. Within the sample of those requiring mealtime support, need for support was reported to be contributed to by the presence of additional disability or illness (e.g. visual impairment, poor dentition and dementia; n = 45, 65.2%) and by psychological or behavioural issues (e.g. challenging behaviour, emotional disturbance; n = 36, 52.2%). Conclusions: These findings not only highlight the need for a multidisciplinary approach to mealtime interventions (paying particular attention to psychological and environmental as well as physical issues), but also signal the daily difficulties faced by carers and paid support workers providing such support and illustrate their potentially crucial role in managing the serious health risks associated with eating and drinking difficulties in this population.

Environmental DNA (eDNA) is an increasingly used non-invasive molecular tool for detecting species presence and monitoring populations. In this article, we review the current state of non-avian reptile eDNA work in aquatic systems, and present a field experiment on detecting the presence of painted turtle (Chrysemys picta) eDNA. Thus far, turtle and snake eDNA studies have shown mixed results in detecting the presence of these animals under field conditions. However, some instances of low detection rates and non-detection occur for these non-avian reptiles, especially for squamates. We explored non-avian reptile eDNA quantification by sampling four lentic ponds with different densities (0 kg/ha, 6 kg/ha, 9 kg/ha, and 13 kg/ha) of painted turtles over three months to detect differences in eDNA using a qPCR assay amplifying the COI gene of the mtDNA genome. Only one sample of the highest-density pond amplified eDNA for a positive detection. Yet, estimates of eDNA concentration from pond eDNA were rank-order correlated with turtle density. We present the “shedding hypothesis„—the possibility that animals with hard, keratinized integument do not shed as much DNA as mucus-covered organisms—as a potential challenge for eDNA studies. Despite challenges with eDNA inhibition and availability in water samples, we remain hopeful that eDNA can be used to detect freshwater turtles in the field. We provide key recommendations for biologists wishing to use eDNA methods for detecting non-avian reptiles.

Background: In England and Wales, the "Mental Capacity Act 2005" (MCA) provides a new legal framework to regulate substitute decision-making relating to the welfare of adults who lack the capacity to make one or more autonomous decisions about their care and support. Any substitute decision made on behalf of an adult lacking capacity must be in his/her "best interests". However, the value of adopting established principles and procedures for substitute decision-making in practice is uncertain, and little is known about the legal or ethical dynamics of social care support, including the day-to-day residential support provided to adults with intellectual disabilities (ID). Methods: This paper reports a qualitative, grounded theory analysis of 21 interviews with support workers working in residential care homes for adults with ID, and observations of care practices. Results: In contrast to the narrow legal responsibilities placed upon them, it is argued that support workers interpret substitute decision-making within a broad moral account of their care role, orientating their support towards helping residents to live "a life like ours". In so doing, support workers describe how they draw on their own values and life experiences to shape the substitute decisions that they make on behalf of residents. Conclusions: Support workers' accounts reveal clear discrepancies between the legal regulation of substitute decision-making and the ways that these support workers make sense of their work. Such discrepancies have implications both for the implementation of the MCA, and for the role of support workers' values in the conceptualisation and delivery of "good" care.

Background: International and UK legislation confirms and supports the right of adults with intellectual disabilities (ID) to vote. It is widely accepted, although not previously empirically confirmed, that citizens with ID are under-represented at the polls. Method: To document the extent of their under-representation at the polls, the names and addresses of adults using services for people with ID in one county in the UK, were compared with the marked electoral register following the 2005 general election. Adults using services for people with ID were identified either as un-registered, as registered to vote but not having voted, or as having voted. Results: Adults with ID living in the county at the time of 2005 general election were substantially under-represented at the polls. Compared with the general population, proportionally fewer of them were registered to vote, and proportionally fewer of them voted. Compared with adults living in private homes, those in supported accommodation were more likely to be registered to vote, but less likely to use their vote. The most significant predictor of participation was living in a household with at least one other active voter. Conclusions: The importance of the close proximity of an active voter is likely to be different for adults in supported accommodation compared with those living in private households. Further research is required to understand what features of these two very different types of residences are affecting voting opportunities. (Contains 1 figure and 3 tables.)

Background: People with intellectual disabilities (ID) are particularly vulnerable to abuse, and most incidents come to light through victim disclosure. Those people with severe or profound ID are not able to describe what has happened to them. This project aimed to describe the consequences of abuse and changes in behaviour following alleged abuse in 18 adults with severe ID. Method: Family members or other carers were interviewed to collect information about the alleged abuse. They were also asked about the person's adaptive and challenging behaviours at three time points: in the 3 months immediately prior to the abuse (time 1), in the 3 months immediately after the abuse (time 2) and in the 3 months prior to interview (time 3). Results: A typical pattern emerged for both adaptive and challenging behaviours: there were few problems or difficulties at time 1, major difficulties at time 2 and some recovery by time 3. Conclusions: Evidence is mounting that clinicians considering the sequelae of abuse for people with severe or profound ID need to consider changes in adaptive and challenging behaviours, as well as the typical symptoms of post-traumatic stress disorder.

Among adults with intellectual disabilities (IDs), there is a need not only to assess financial decision-making capacity, but also to understand how it can be maximized. Although increased financial independence is a goal for many people, it is essential that individuals decision-making abilities are sufficient, and many factors may affect the development of such abilities. As part of a wider project on financial decision-making, we analysed previous data from a group of 30 adults with mild IDs, identifying correlations among four variables: (i) financial decision-making abilities; (ii) intellectual ability; (iii) understanding of some basic concepts relevant to finance; and (iv) decision-making opportunities in everyday life. Results The analysis indicated a direct relationship between ID and basic financial understanding. Strong relationships of a potentially reciprocal nature were identified between basic financial understanding and everyday decision-making opportunities, and between such opportunities and financial decision-making abilities. The findings suggest that the role of intellectual ability in determining financial decision-making abilities is only indirect, and that access to both basic skills education and everyday decision-making opportunities is crucial for maximizing capacity. The implications of this are discussed.

Although there has been growing recognition of the importance of enabling people with intellectual disabilities (ID) to be more directly involved in managing their own financial affairs, so far, little is known about this aspect of their decision- making. Using vignettes and semi-structured interviews, the financial decision-making abilities of men and women with mild ID (n=30; mean FSIQ=61.80; SD=10.59) were compared with those of their counterparts in the general population (n=16; mean FSIQ=101.56; SD=7.62) and very able individuals (n=14; mean FSIQ=123.93; SD=7.60). Whilst the financial decision-making abilities of participants with ID were generally weaker than those of other participants, the differences were not discrete, and many individuals were judged to be able to make at least some personal financial decisions. For all three groups, understanding information relevant to the decision, and reasoning with it, were the hardest parts of the process. The findings support a functional approach to the assessment of financial decision-making for both legal and clinical purposes, but raise concerns about mental incapacity legislation and assessment.

Background Raising awareness of antimicrobial resistance is a cornerstone of action plans to tackle this global One Health challenge. Tools that can reliably assess levels of awareness of antibiotic resistance (ABR) among human or animal healthcare professionals (HCPs) are required to guide and evaluate interventions. Methods We designed and tested an ABR awareness scale, a self-administered questionnaire completed by human and animal HCPs trained to prescribe and dispense antibiotics in six countries—Ghana, Nigeria, Tanzania, Vietnam, Thailand and Peru. Questionnaires also elicited demographic, practice, and contextual information. Psychometric analysis for the scale followed Rasch Measurement Theory. Bivariate analysis was carried out to identify factors associated with awareness scores. Results Overall, 941 HCPs (625 human and 316 animal) from Ghana, Nigeria, Tanzania, Vietnam, Thailand and Peru were included in the study. The 23-item ABR awareness scale had high-reliability coefficients (0.88 for human and 0.90 for animal HCPs) but performed better within countries than across countries. Median ABR awareness scores were 54.6–63.5 for human HCPs and 55.2–63.8 for animal HCPs (scale of 0–100). Physicians and veterinarians scored higher than other HCPs in every country tested. HCPs in this study reported working in contexts with limited laboratory infrastructures. More than 95% of HCPs were interested in receiving information or training on ABR and antimicrobial stewardship. Conclusion HCPs' awareness of ABR can be reliably assessed with this validated 23-item scale within the countries tested. Using the scale alongside context questions and objective measurement of practices is recommended to inform interventions to improve antibiotic use. [ABSTRACT FROM AUTHOR]