Re‐analysis of late Quaternary dust mass accumulation rates in Serbia using new luminescence chronology for loess–palaeosol sequence at Surduk

Despite numerous palaeoenvironmental investigations of loess–palaeosol sequences across the Carpathian Basin, well‐dated high‐resolution records are scarce. This paper presents a new high‐resolution chronology for the loess‐palaeosol sequence at Surduk (Serbia), based on optically stimulated luminescence (quartz) and post‐infrared infrared stimulated luminescence (polymineral) dating. The presented record spans 53–19 ka, with primary loess deposition occurring after 52±2 ka, and differs from previously published chronologies that relied on less precise and now superseded dating protocols. Based on the new chronology, mass accumulation rates (MAR s) for Surduk were constructed and compared with sites in the Carpathian Basin. The results demonstrate that accumulation periods across this area are not consistent in timing or rates. The high‐resolution dating strategy identifies a disturbance in sediment deposition that occurred after 45±2 ka and implies that site contains a hiatus. Finally, we show samples that failed routine dose recovery and preheat plateau tests, and had low fast ratios. Supported by bulk sample geochemical analysis it is proposed that a potential abrupt source shift, during the Last Glacial Maximum, may be the cause of the anomalous luminescence behaviour

Challenges and opportunities for ex-offender support through community nursing

This study was a qualitative case study underpinned by “The Silences Framework” aimed at mapping the ex-offender health pathway towards identifying “touch points” in the community for the delivery of a nurse-led intervention. Participants meeting the study inclusion criteria were quantitatively ranked based on poor health. Participants scoring the lowest and endorsing their ranking through a confirmation of a health condition were selected as cases and interviewed over 6 months. Individuals in the professional networks of offenders contextualized emergent themes. The study indicated that pre-release, offenders were not prepared in prison for the continuity in access to healthcare in the community. On release, reintegration preparation did not routinely enquire whether offenders were still registered with a general practitioner or had the agency to register self in the community. Participants identified the site of post-release supervision as the “touch point” where a nurse-led intervention could be delivere

Identifying parkinsonism in mild cognitive impairment.

Introduction Clinical parkinsonism is a core diagnostic feature for mild cognitive impairment with Lewy bodies (MCI-LB) but can be challenging to identify. A five-item scale derived from the Unified Parkinson’s Disease Rating Scale (UPDRS) has been recommended for the assessment of parkinsonism in dementia. This study aimed to determine whether the five-item scale is effective to identify parkinsonism in MCI. Methods Participants with MCI from two cohorts (n=146) had a physical examination including the UPDRS and [123I]-FP-CIT SPECT striatal dopaminergic imaging. Participants were classified as having clinical parkinsonism (P+) or no parkinsonism (P-), and with abnormal striatal dopaminergic imaging (D+) or normal imaging (D-). The five-item scale was the sum of UPDRS tremor at rest, bradykinesia, action tremor, facial expression, and rigidity scores. The ability of the scale to differentiate P+D+ and P-D- participants was examined. Results The five-item scale had an AUROC of 0.92 in Cohort 1, but the 7/8 cut-off defined for dementia had low sensitivity to identify P+D+ participants (sensitivity 25%, specificity 100%). Optimal sensitivity and specificity was obtained at a 3/4 cut-off (sensitivity 83%, specificity 88%). In Cohort 2, the five-item scale had an AUROC of 0.97, and the 3/4 cut-off derived from Cohort 1 showed sensitivity of 100% and a specificity of 82% to differentiate P+D+ from P-D- participants. The five-item scale was not effective in differentiating D+ from D- participants. Conclusions The five-item scale is effective to identify parkinsonism in MCI, but a lower threshold must be used in MCI compared with dementia

Idiopathic intracranial hypertension: the association between weight loss and the requirement for systemic treatment

<p>Abstract</p> <p>Background</p> <p>To determine whether weight loss is significantly associated with a discontinuation of treatment for idiopathic intracranial hypertension</p> <p>Methods</p> <p>The notes of 36 patients with idiopathic intracranial hypertension under regular review for at least 12 months by a single neuro-ophthalmologist were retrospectively reviewed. Weight was recorded at each assessment and weight loss recommended. Treatment was adjusted according to symptoms, visual function including visual fields and optic disc appearance only. Patients were divided according to duration of continuous follow-up, and then sub-divided as to whether they were on or not on treatment at most recent review and whether weight loss had been achieved compared to presentation. Survival analysis was performed to assess the probability of remaining on treatment having lost weight.</p> <p>Results</p> <p>Considering the patients as 3 groups, those with at least 12 months follow-up (n = 36), those with at least 18 months follow-up (n = 24) and those with 24 months or more follow-up (n = 19), only the group with 24 months or more follow-up demonstrated a significant association between weight loss and stopping systemic treatment (Fisher's exact test, p = 0.04). Survival analysis demonstrated that the probability of being on treatment at 5 years having gained weight was 0.63 and having lost weight was 0.38 (log rank test, p = 0.04). The results suggest that final absolute body mass index is more important than the change in body mass index for patients who stop treatment (Mann Whitney U, p = 0.05).</p> <p>Conclusion</p> <p>This is the first study to demonstrate that weight loss is associated with discontinuation of treatment. Unlike previous studies, our results suggest that final absolute body mass index is more important for stopping treatment than a proportional reduction in weight.</p

Using multiple case studies of health and justice services to inform the development of a new complex intervention for prison-leavers with common mental health problems (Engager)

Abstract Background People in the criminal justice system have complex needs but often do not make use of services outside of prison, in many cases due to poorly joined up working between health and criminal justice services. The ‘Engager’ programme aimed to develop a complex collaborative care intervention for people leaving prison with common mental health problems that could support their transition into the community and facilitate joined up working between health, justice and social services. To augment our core intervention theory, we wanted to learn from innovative and forward-thinking services providing interagency support and/or treatment for people experiencing common mental health problems within the criminal justice system. We wanted to identify key elements of interagency practice to understand what was and was not effective in engaging people, maintaining their contact and improving mental health and other aspects of their lives. Method We used a multiple case study design with a focused ethnographic approach in four study sites. Data came from three sources (documents, field notes and semi-structured interviews) underwent a framework analysis. Results We identified seven main themes, namely: collaboration, client engagement, client motivation, supervision, therapeutic approach, peers and preparations for ending. Engaging and motivating clients was dependent on the relationship built with the professional. This relationship was developed through building trust and rapport, which required time and respectful, open and honest communication. Professionals were often unable to build this relationship effectively if they did not work in effective interagency collaborations, particularly those which included shared practices and were supported by effective supervision. Conclusions The multiple case study design contributed insights as to how health and justice services work together. The main themes identified are well known factors in health and justice co-working. However, the novel insights were gleaned examining interdependence and interactions in complex, multifactorial phenomena and practice, in particular the importance of shared practice and supervision models. The approach of selecting a small number of cases representing identified knowledge gaps contributed a valuable addition to the program theory and delivery for an innovative complex intervention. </jats:sec

The pharmacological regulation of cellular mitophagy

Small molecules are pharmacological tools of considerable value for dissecting complex biological processes and identifying potential therapeutic interventions. Recently, the cellular quality-control process of mitophagy has attracted considerable research interest; however, the limited availability of suitable chemical probes has restricted our understanding of the molecular mechanisms involved. Current approaches to initiate mitophagy include acute dissipation of the mitochondrial membrane potential (ΔΨm) by mitochondrial uncouplers (for example, FCCP/CCCP) and the use of antimycin A and oligomycin to impair respiration. Both approaches impair mitochondrial homeostasis and therefore limit the scope for dissection of subtle, bioenergy-related regulatory phenomena. Recently, novel mitophagy activators acting independently of the respiration collapse have been reported, offering new opportunities to understand the process and potential for therapeutic exploitation. We have summarized the current status of mitophagy modulators and analyzed the available chemical tools, commenting on their advantages, limitations and current applications

Evaluation of a complex intervention (Engager) for prisoners with common mental health problems, near to and after release: study protocol for a randomised controlled trial.

INTRODUCTION: The 'Engager' programme is a 'through-the-gate' intervention designed to support prisoners with common mental health problems as they transition from prison back into the community. The trial will evaluate the clinical and cost-effectiveness of the Engager intervention. METHODS AND ANALYSIS: The study is a parallel two-group randomised controlled trial with 1:1 individual allocation to either: (a) the Engager intervention plus standard care (intervention group) or (b) standard care alone (control group) across two investigation centres (South West and North West of England). Two hundred and eighty prisoners meeting eligibility criteria will take part. Engager is a person-centred complex intervention delivered by practitioners and aimed at addressing offenders' mental health and social care needs. It comprises one-to-one support for participants prior to release from prison and for up to 20 weeks postrelease. The primary outcome is change in psychological distress measured by the Clinical Outcomes in Routine Evaluation-Outcome Measure at 6 months postrelease. Secondary outcomes include: assessment of subjective met/unmet need, drug and alcohol use, health-related quality of life and well-being-related quality of life measured at 3, 6 and 12 months postrelease; change in objective social domains, drug and alcohol dependence, service utilisation and perceived helpfulness of services and change in psychological constructs related to desistence at 6 and 12 months postrelease; and recidivism at 12 months postrelease. A process evaluation will assess fidelity of intervention delivery, test hypothesised mechanisms of action and look for unintended consequences. An economic evaluation will estimate the cost-effectiveness. ETHICS AND DISSEMINATION: This study has been approved by the Wales Research Ethics Committee 3 (ref: 15/WA/0314) and the National Offender Management Service (ref: 2015-283). Findings will be disseminated to commissioners, clinicians and service users via papers and presentations. TRIAL REGISTRATION NUMBER: ISRCTN11707331; Pre-results

Interrogating intervention delivery and participants' emotional states to improve engagement and implementation: A realist informed multiple case study evaluation of Engager.

BACKGROUND: 'Engager' is an innovative 'through-the-gate' complex care intervention for male prison-leavers with common mental health problems. In parallel to the randomised-controlled trial of Engager (Trial registration number: ISRCTN11707331), a set of process evaluation analyses were undertaken. This paper reports on the depth multiple case study analysis part of the process evaluation, exploring how a sub-sample of prison-leavers engaged and responded to the intervention offer of one-to-one support during their re-integration into the community. METHODS: To understand intervention delivery and what response it elicited in individuals, we used a realist-informed qualitative multiple 'case' studies approach. We scrutinised how intervention component delivery lead to outcomes by examining underlying causal pathways or 'mechanisms' that promoted or hindered progress towards personal outcomes. 'Cases' (n = 24) were prison-leavers from the intervention arm of the trial. We collected practitioner activity logs and conducted semi-structured interviews with prison-leavers and Engager/other service practitioners. We mapped data for each case against the intervention logic model and then used Bhaskar's (2016) 'DREIC' analytic process to categorise cases according to extent of intervention delivery, outcomes evidenced, and contributing factors behind engagement or disengagement and progress achieved. RESULTS: There were variations in the dose and session focus of the intervention delivery, and how different participants responded. Participants sustaining long-term engagement and sustained change reached a state of 'crises but coping'. We found evidence that several components of the intervention were key to achieving this: trusting relationships, therapeutic work delivered well and over time; and an in-depth shared understanding of needs, concerns, and goals between the practitioner and participants. Those who disengaged were in one of the following states: 'Crises and chaos', 'Resigned acceptance', 'Honeymoon' or 'Wilful withdrawal'. CONCLUSIONS: We demonstrate that the 'implementability' of an intervention can be explained by examining the delivery of core intervention components in relation to the responses elicited in the participants. Core delivery mechanisms often had to be 'triggered' numerous times to produce sustained change. The improvements achieved, sustained, and valued by participants were not always reflected in the quantitative measures recorded in the RCT. The compatibility between the practitioner, participant and setting were continually at risk of being undermined by implementation failure as well as changing external circumstances and participants' own weaknesses. TRIAL REGISTRATION NUMBER: ISRCTN11707331, Wales Research Ethics Committee, Registered 02-04-2016-Retrospectively registered https://doi.org/10.1186/ISRCTN11707331

Neuropsychological Impairments and their cognitive architecture in Mild Cognitive Impairment (MCI) with Lewy Bodies and MCI-Alzheimer’s Disease

This is the final version. Available on open access from Cambridge University Press via the DOI in this recordObjective: The present study aimed to clarify the neuropsychological profile of the emergent diagnostic category of Mild Cognitive Impairment with Lewy bodies (MCI-LB) and determine whether domain-specific impairments such as in memory were related to deficits in domain-general cognitive processes (executive function or processing speed). Method: Patients (n=83) and healthy age- and sex-matched controls (n=34) underwent clinical and imaging assessments. Probable MCI-LB (n=44) and MCI-AD (n=39) were diagnosed following National Institute on Aging-Alzheimer’s Association (NIA-AA) and DLB consortium criteria. Neuropsychological measures included cognitive and psychomotor speed, executive function, working memory, and verbal and visuospatial recall. Results: MCI-LB scored significantly lower than MCI-AD on processing speed (Trail Making Test B: p=0.03, g=0.45; Digit Symbol Substitution Test [DSST]: p=0.04, g=0.47; DSST Error Check: p.05) Conclusions: MCI-LB was characterised by executive dysfunction and slowed processing speed but did not show the visuospatial dysfunction expected, whilst MCI-AD displayed an amnestic profile. However, there was considerable neuropsychological profile overlap and processing speed mediated performance in both MCI subtypes.Alzheimer’s Research UKMedical Research Council (MRC)GE HealthcareAlzheimer’s SocietyNational Institute for Health Research (NIHR

Olfactory impairment in mild cognitive impairment with Lewy bodies and Alzheimer’s disease

This is the author accepted manuscript. The final version is available from Cambridge University Press via the DOI in this recordObjectives: Impaired olfaction may be a biomarker for early Lewy body disease but its value in Mild Cognitive Impairment with Lewy bodies (MCI-LB) is unknown. We compared olfaction in MCI-LB with MCI due to Alzheimer’s disease (MCI-AD) and healthy older adults. We hypothesised that olfactory function would be worse in probable MCI-LB than in both MCI- AD and healthy comparison subjects (HC). Design: Cross-sectional study assessing olfaction using Sniffin’ Sticks 16 (SS-16) in MCI-LB, MCI- AD and HC with longitudinal follow-up. Differences were adjusted for age and receiver operating characteristic curves were used for discriminating MCI-LB from MCI-AD andHC. Setting: Participants were recruited from Memory Services in the North East of England Participants: 38 probable MCI-LB, 33 MCI-AD, 19 possible MCI-LB and 32HC. Measurements: Olfaction was assessed using SS-16 and a questionnaire. Results: Participants with probable MCI-LB had worse olfaction than both MCI-AD (Age-adjusted mean difference (B)=2.05,95% CI:0.62-3.49, p=.005) and HC (B=3.96, 95% CI:2.51–5.40, p<.001). The previously-identified cut-off score for the SS-16 of ≤ 10 had 84% sensitivity for probable MCI-LB (95% CI: 69-94%) but 30% specificity vs MCI-AD. ROC analysis found a lower cut-off of ≤ 7 was better (63% sensitivity for MCI-LB, with 73% specificity vs MCI-AD and 97% vsHC). Asking about olfactory impairments was not useful in identifying them. Conclusions: MCI-LB had worse olfaction than MCI-AD and normal ageing. A lower cut-off score of ≤ 7 is required when using SS-16 in such patients. Olfactory testing may have value in identifying early LB disease in memory services.Alzheimer’s Research UKNational Institute for Health Research (NIHR