An assessment protocol for determining decision making capacity

There is a bourgeoning elderly population, an increase in District Court estate disputes, and an identified need to refer at risk clients for formal assessment. However, there is limited research into effective and efficient assessment protocols vis-à-vis testamentary capacity and capacity to appoint an enduring power of attorney. Statistical limitations of neuropsychological tests are often overlooked. The current study reviews the interaction of legal principles and the scientic method in common law jurisdictions. Preliminary findings from expert opinions are presented. Participants are 13 general practitioners, seven lawyers and seven psychologists. Data was collected through a nominal group technique (focus group). Investigation of qualitative results indicated similarities and differences in approach adopted by the differing disciplines. The next phase of this research is to test-run an assessment protocol informed from the current findings

Alice in recidivism land: The Queens logic and child protection workers\u27 assessment of sexual dangerousness

This article is based on a case that highlights the dearth of cogent and pertinent risk assessment information in the reports and testimonies of many involved in assessing risks to children in real life problematic circumstances. In the case, the decision to exclude an intrafamilial sexual offender from the family home was made in large measure on the basis that the offender\u27s wife accepted the offender\u27s "denial of guilt" to accusations previously made against him. Keeping families apart should not be entertained without reliable and valid evidence pointing to that decision. However, as will be seen, the evidence often relied upon by child protection workers, albeit in good faith, is neither. The assessment processes described in the case point directly to what appears to be a wider lack of knowledge specific to assessment of recidivism, to misrepresentation of risk assessment information, and to overarching epistemological issues that appear to be widely ignored and/or misunderstood within the overall field of risk assessment and threat management. The purpose of this article is to describe how the information used to decide upon exclusion in the case cannot be considered probative and to iterate the methodological processes that must be considered in such cases if miscarriages of justice are to be avoided

Predicting beneficial effects of atomoxetine and citalopram on response inhibition in Parkinson's disease with clinical and neuroimaging measures.

Recent studies indicate that selective noradrenergic (atomoxetine) and serotonergic (citalopram) reuptake inhibitors may improve response inhibition in selected patients with Parkinson's disease, restoring behavioral performance and brain activity. We reassessed the behavioral efficacy of these drugs in a larger cohort and developed predictive models to identify patient responders. We used a double-blind randomized three-way crossover design to investigate stopping efficiency in 34 patients with idiopathic Parkinson's disease after 40 mg atomoxetine, 30 mg citalopram, or placebo. Diffusion-weighted and functional imaging measured microstructural properties and regional brain activations, respectively. We confirmed that Parkinson's disease impairs response inhibition. Overall, drug effects on response inhibition varied substantially across patients at both behavioral and brain activity levels. We therefore built binary classifiers with leave-one-out cross-validation (LOOCV) to predict patients' responses in terms of improved stopping efficiency. We identified two optimal models: (1) a "clinical" model that predicted the response of an individual patient with 77-79% accuracy for atomoxetine and citalopram, using clinically available information including age, cognitive status, and levodopa equivalent dose, and a simple diffusion-weighted imaging scan; and (2) a "mechanistic" model that explained the behavioral response with 85% accuracy for each drug, using drug-induced changes of brain activations in the striatum and presupplementary motor area from functional imaging. These data support growing evidence for the role of noradrenaline and serotonin in inhibitory control. Although noradrenergic and serotonergic drugs have highly variable effects in patients with Parkinson's disease, the individual patient's response to each drug can be predicted using a pattern of clinical and neuroimaging features.The BCNI is supported by the Wellcome Trust and Medical Research Council. We are grateful to Dr Gordon Logan for advice on stop-signal reaction time estimation and to Dr Marta Correia for advice on diffusion-weighted imaging data analysis. Conflict of interest: Prof. Sahakian has received grants from Janssen/J&J, personal fees from Cambridge Cognition, personal fees from Lundbeck, and personal fees from Servier, outside the submitted work. Prof. Robbins has received personal fees and royalties from Cambridge Cognition, personal fees and grants from Eli Lilly Inc, personal fees and grants from Lundbeck, grants from GSK, personal fees from Teva Pharmaceuticals, personal fees from Shire Pharmaceuticals, grants from Medical Research Council, editorial honorarium from Springer Verlag Germany, and personal fees from Chempartners, outside the submitted work. Prof. Rowe has received grant funding from AZ-Medimmune unrelated to the current work. Dr Housden is an employee of Cambridge Cognition. Other authors reported no biomedical financial interests or potential conflict of interest.This is the final version of the article. It was first available from Wiley via http://dx.doi.org/10.1002/hbm.2308

Network connectivity and structural correlates of survival in progressive supranuclear palsy and corticobasal syndrome

There is a pressing need to understand the factors that predict prognosis in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), with high heterogeneity over the poor average survival. We test the hypothesis that the magnitude and distribution of connectivity changes in PSP and CBS predict the rate of progression and survival time, using datasets from the Cambridge Centre for Parkinson-plus and the UK National PSP Research Network (PROSPECT-MR). Resting-state functional MRI images were available from 146 participants with PSP, 82 participants with CBS, and 90 healthy controls. Large-scale networks were identified through independent component analyses, with correlations taken between component time series. Independent component analysis was also used to select between-network connectivity components to compare with baseline clinical severity, longitudinal rate of change in severity, and survival. Transdiagnostic survival predictors were identified using partial least squares regression for Cox models, with connectivity compared to patients' demographics, structural imaging, and clinical scores using five-fold cross-validation. In PSP and CBS, between-network connectivity components were identified that differed from controls, were associated with disease severity, and were related to survival and rate of change in clinical severity. A transdiagnostic component predicted survival beyond demographic and motion metrics but with lower accuracy than an optimal model that included the clinical and structural imaging measures. Cortical atrophy enhanced the connectivity changes that were most predictive of survival. Between-network connectivity is associated with variability in prognosis in PSP and CBS but does not improve predictive accuracy beyond clinical and structural imaging metrics

Economics methods in Cochrane systematic reviews of health promotion and public health related interventions.

Peer reviewedPublisher PD

Meteorological measurements at Auchencorth Moss from 1995 to 2016

The Auchencorth Moss atmospheric observatory has being measuring meteorological parameters since 1995. The site was originally set‐up to measure the deposition of sulphur dioxide at a site that represented the vegetation and climate typical of NW Europe, in relatively clean background air. It is one of the longest running flux monitoring sites in the region, over semi‐natural vegetation, providing infrastructure and support for many measurement campaigns and continuous monitoring of air pollutants and greenhouse gases. The meteorological sensors that are used, data processing and quality reviewing procedures are described for a set of core measurements up to 2016. These core measurements are essential for the interpretation of the other atmospheric variables

Do specialty registrars change their attitudes, intentions and behaviour towards reporting incidents following a patient safety course?

<p>Abstract</p> <p>Background</p> <p>Reporting incidents can contribute to safer health care, as an awareness of the weaknesses of a system could be considered as a starting point for improvements. It is believed that patient safety education for specialty registrars could improve their attitudes, intentions and behaviour towards incident reporting. The objective of this study was to examine the effect of a two-day patient safety course on the attitudes, intentions and behaviour concerning the voluntary reporting of incidents by specialty registrars.</p> <p>Methods</p> <p>A patient safety course was designed to increase specialty registrars' knowledge, attitudes and skills in order to recognize and cope with unintended events and unsafe situations at an early stage. Data were collected through an 11-item questionnaire before, immediately after and six months after the course was given.</p> <p>Results</p> <p>The response rate at all three points in time assessed was 100% (n = 33). There were significant changes in incident reporting attitudes and intentions immediately after the course, as well as during follow-up. However, no significant changes were found in incident reporting behaviour.</p> <p>Conclusions</p> <p>It is shown that patient safety education can have long-term positive effects on attitudes towards reporting incidents and the intentions of registrars. However, further efforts need to be undertaken to induce a real change in behaviour.</p

Limbic-Predominant Age-Related TDP-43 Encephalopathy (LATE): Consensus Working Group Report

We describe a recently recognized disease entity, limbic-predominant age-related TDP-43 encephalopathy (LATE). LATE neuropathological change (LATE-NC) is defined by a stereotypical TDP-43 proteinopathy in older adults, with or without coexisting hippocampal sclerosis pathology. LATE-NC is a common TDP-43 proteinopathy, associated with an amnestic dementia syndrome that mimicked Alzheimer’s-type dementia in retrospective autopsy studies. LATE is distinguished from frontotemporal lobar degeneration with TDP-43 pathology based on its epidemiology (LATE generally affects older subjects), and relatively restricted neuroanatomical distribution of TDP-43 proteinopathy. In community-based autopsy cohorts, ∼25% of brains had sufficient burden of LATE-NC to be associated with discernible cognitive impairment. Many subjects with LATE-NC have comorbid brain pathologies, often including amyloid-β plaques and tauopathy. Given that the ‘oldest-old’ are at greatest risk for LATE-NC, and subjects of advanced age constitute a rapidly growing demographic group in many countries, LATE has an expanding but under-recognized impact on public health. For these reasons, a working group was convened to develop diagnostic criteria for LATE, aiming both to stimulate research and to promote awareness of this pathway to dementia. We report consensus-based recommendations including guidelines for diagnosis and staging of LATE-NC. For routine autopsy workup of LATE-NC, an anatomically-based preliminary staging scheme is proposed with TDP-43 immunohistochemistry on tissue from three brain areas, reflecting a hierarchical pattern of brain involvement: amygdala, hippocampus, and middle frontal gyrus. LATE-NC appears to affect the medial temporal lobe structures preferentially, but other areas also are impacted. Neuroimaging studies demonstrated that subjects with LATE-NC also had atrophy in the medial temporal lobes, frontal cortex, and other brain regions. Genetic studies have thus far indicated five genes with risk alleles for LATE-NC: GRN, TMEM106B, ABCC9, KCNMB2, and APOE. The discovery of these genetic risk variants indicate that LATE shares pathogenetic mechanisms with both frontotemporal lobar degeneration and Alzheimer’s disease, but also suggests disease-specific underlying mechanisms. Large gaps remain in our understanding of LATE. For advances in prevention, diagnosis, and treatment, there is an urgent need for research focused on LATE, including in vitro and animal models. An obstacle to clinical progress is lack of diagnostic tools, such as biofluid or neuroimaging biomarkers, for ante-mortem detection of LATE. Development of a disease biomarker would augment observational studies seeking to further define the risk factors, natural history, and clinical features of LATE, as well as eventual subject recruitment for targeted therapies in clinical trials

Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report.

We describe a recently recognized disease entity, limbic-predominant age-related TDP-43 encephalopathy (LATE). LATE neuropathological change (LATE-NC) is defined by a stereotypical TDP-43 proteinopathy in older adults, with or without coexisting hippocampal sclerosis pathology. LATE-NC is a common TDP-43 proteinopathy, associated with an amnestic dementia syndrome that mimicked Alzheimer's-type dementia in retrospective autopsy studies. LATE is distinguished from frontotemporal lobar degeneration with TDP-43 pathology based on its epidemiology (LATE generally affects older subjects), and relatively restricted neuroanatomical distribution of TDP-43 proteinopathy. In community-based autopsy cohorts, ∼25% of brains had sufficient burden of LATE-NC to be associated with discernible cognitive impairment. Many subjects with LATE-NC have comorbid brain pathologies, often including amyloid-β plaques and tauopathy. Given that the 'oldest-old' are at greatest risk for LATE-NC, and subjects of advanced age constitute a rapidly growing demographic group in many countries, LATE has an expanding but under-recognized impact on public health. For these reasons, a working group was convened to develop diagnostic criteria for LATE, aiming both to stimulate research and to promote awareness of this pathway to dementia. We report consensus-based recommendations including guidelines for diagnosis and staging of LATE-NC. For routine autopsy workup of LATE-NC, an anatomically-based preliminary staging scheme is proposed with TDP-43 immunohistochemistry on tissue from three brain areas, reflecting a hierarchical pattern of brain involvement: amygdala, hippocampus, and middle frontal gyrus. LATE-NC appears to affect the medial temporal lobe structures preferentially, but other areas also are impacted. Neuroimaging studies demonstrated that subjects with LATE-NC also had atrophy in the medial temporal lobes, frontal cortex, and other brain regions. Genetic studies have thus far indicated five genes with risk alleles for LATE-NC: GRN, TMEM106B, ABCC9, KCNMB2, and APOE. The discovery of these genetic risk variants indicate that LATE shares pathogenetic mechanisms with both frontotemporal lobar degeneration and Alzheimer's disease, but also suggests disease-specific underlying mechanisms. Large gaps remain in our understanding of LATE. For advances in prevention, diagnosis, and treatment, there is an urgent need for research focused on LATE, including in vitro and animal models. An obstacle to clinical progress is lack of diagnostic tools, such as biofluid or neuroimaging biomarkers, for ante-mortem detection of LATE. Development of a disease biomarker would augment observational studies seeking to further define the risk factors, natural history, and clinical features of LATE, as well as eventual subject recruitment for targeted therapies in clinical trials.Sally Hunter and Carol Brayne are supported by funding from the National Institute for Health Research, Senior Investigator Award, awarded to Carol Brayne. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Sally Hunter is supported by the Addenbrooke’s Charitable Trust, the Paul G. Allen Family Foundation and Alzheimer’s Research, UK. Suvi Hokkanen was supported by Alzheimer’s Research, UK

Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the Genetic Frontotemporal dementia Initiative (GENFI) study: A cross-sectional analysis

Background: Frontotemporal dementia is a highly heritable neurodegenerative disorder. In about a third of patients, the disease is caused by autosomal dominant genetic mutations usually in one of three genes: progranulin (. GRN), microtubule-associated protein tau (. MAPT), or chromosome 9 open reading frame 72 (. C9orf72). Findings from studies of other genetic dementias have shown neuroimaging and cognitive changes before symptoms onset, and we aimed to identify whether such changes could be shown in frontotemporal dementia. Methods: We recruited participants to this multicentre study who either were known carriers of a pathogenic mutation in GRN, MAPT, or C9orf72, or were at risk of carrying a mutation because a first-degree relative was a known symptomatic carrier. We calculated time to expected onset as the difference between age at assessment and mean age at onset within the family. Participants underwent a standardised clinical assessment and neuropsychological battery. We did MRI and generated cortical and subcortical volumes using a parcellation of the volumetric T1-weighted scan. We used linear mixed-effects models to examine whether the association of neuropsychology and imaging measures with time to expected onset of symptoms differed between mutation carriers and non-carriers. Findings: Between Jan 30, 2012, and Sept 15, 2013, we recruited participants from 11 research sites in the UK, Italy, the Netherlands, Sweden, and Canada. We analysed data from 220 participants: 118 mutation carriers (40 symptomatic and 78 asymptomatic) and 102 non-carriers. For neuropsychology measures, we noted the earliest significant differences between mutation carriers and non-carriers 5 years before expected onset, when differences were significant for all measures except for tests of immediate recall and verbal fluency. We noted the largest Z score differences between carriers and non-carriers 5 years before expected onset in tests of naming (Boston Naming Test -0·7; SE 0·3) and executive function (Trail Making Test Part B, Digit Span backwards, and Digit Symbol Task, all -0·5, SE 0·2). For imaging measures, we noted differences earliest for the insula (at 10 years before expected symptom onset, mean volume as a percentage of total intracranial volume was 0·80% in mutation carriers and 0·84% in non-carriers; difference -0·04, SE 0·02) followed by the temporal lobe (at 10 years before expected symptom onset, mean volume as a percentage of total intracranial volume 8·1% in mutation carriers and 8·3% in non-carriers; difference -0·2, SE 0·1). Interpretation: Structural imaging and cognitive changes can be identified 5-10 years before expected onset of symptoms in asymptomatic adults at risk of genetic frontotemporal dementia. These findings could help to define biomarkers that can stage presymptomatic disease and track disease progression, which will be important for future therapeutic trials. Funding: Centres of Excellence in Neurodegenerati