Ambulance location for maximum survival

This article proposes new location models for emergency medical service stations. The models are generated by incorporating a survival function into existing covering models. A survival function is a monotonically decreasing function of the response time of an emergency medical service (EMS) vehicle to a patient that returns the probability of survival for the patient. The survival function allows for the calculation of tangible outcome measures—the expected number of survivors in case of cardiac arrests. The survival-maximizing location models are better suited for EMS location than the covering models which do not adequately differentiate between consequences of different response times. We demonstrate empirically the superiority of the survival-maximizing models using data from the Edmonton EMS system.NSERCpre-prin

Frontotemporal dementia and its subtypes: a genome-wide association study

SummaryBackground Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes—MAPT, GRN, and C9orf72—have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with {FTD} and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with {FTD} and 4308 controls), we did separate association analyses for each {FTD} subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and {FTD} overlapping with motor neuron disease FTD-MND), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10−8) single-nucleotide polymorphisms. Findings We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10−8). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, \{HLA\} locus (immune system), for rs9268877 (p=1·05 × 10−8; odds ratio=1·204 95% \{CI\} 1·11–1·30), rs9268856 (p=5·51 × 10−9; 0·809 0·76–0·86) and rs1980493 (p value=1·57 × 10−8, 0·775 0·69–0·86) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural \{FTD\} subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10−7; 0·814 0·71–0·92). Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation in cis. Interpretation Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and to shed light on the pathomechanisms contributing to FTD. Funding The National Institute of Neurological Disorders and Stroke and National Institute on Aging, the Wellcome/MRC Centre on Parkinson's disease, Alzheimer's Research UK, and Texas Tech University Health Sciences Center

Support at Home: Interventions to Enhance Life in Dementia (SHIELD) – evidence, development and evaluation of complex interventions

Background Dementia is a national priority and this research addresses the Prime Minister’s commitment to dementia research as demonstrated by his 2020 challenge and the new UK Dementia Research Institute. In the UK > 800,000 older people have dementia. It has a major impact on the lives of people with dementia themselves, on the lives of their family carers and on services, and costs the nation £26B per year. Pharmacological cures for dementias such as Alzheimer’s disease are not expected before 2025. If no cure can be found, the ageing demographic will result in 2 million people living with dementia by 2050. People with dementia lose much more than just their memory and their daily living skills; they can also lose their independence, their dignity and status, their confidence and morale, and their roles both within the family and beyond. They can be seen as a burden by society, by their families and even by themselves, and may feel unable to contribute to society. This programme of research aims to find useful interventions to improve the quality of life of people with dementia and their carers, and to better understand how people with dementia can be supported at home and avoid being admitted to hospital. Objectives (1) To develop and evaluate the maintenance cognitive stimulation therapy (MCST) for people with dementia; (2) to develop the Carer Supporter Programme (CSP), and to evaluate the CSP and Remembering Yesterday, Caring Today (RYCT) for people with dementia both separately and together in comparison with usual care; and (3) to develop a home treatment package (HTP) for dementia, to field test the HTP in practice and to conduct an exploratory trial. Methods (1) The MCST programme was developed for people with dementia based on evidence and qualitative work. A randomised controlled trial (RCT) [with a pilot study of MCST plus acetylcholinesterase inhibitors (AChEIs)] compared MCST with cognitive stimulation therapy (CST) only. The MCST implementation study conducted a trial of outreach compared with usual care, and assessed implementation in practice. (2) The CSP was developed based on existing evidence and the engagement of carers of people with dementia. The RCT (with internal pilot) compared the CSP and reminiscence (RYCT), both separately and in combination, with usual care. (3) A HTP for dementia, including the most promising interventions and components, was developed by systematically reviewing the literature and qualitative studies including consensus approaches. The HTP for dementia was evaluated in practice by conducting in-depth field testing. Results (1) Continuing MCST improved quality of life and improved cognition for those taking AChEIs. It was also cost-effective. The CST implementation studies indicated that many staff will run CST groups following a 1-day training course, but that outreach support helps staff go on to run maintenance groups and may also improve staff sense of competence in dementia care. The study of CST in practice found no change in cognition or quality of life at 8-month follow-up. (2) The CSP/RYCT study found no benefits for family carers but improved quality of life for people with dementia. RYCT appeared beneficial for the quality of life of people with dementia but at an excessively high cost. (3) Case management for people with dementia reduces admissions to long-term care and reduces behavioural problems. In terms of managing crises, staff suggested more costly interventions, carers liked education and support, and people with dementia wanted family support, home adaptations and technology. The easy-to-use home treatment manual was feasible in practice to help staff working in crisis teams to prevent hospital admissions for people with dementia. Limitations Given constraints on time and funding, we were unable to compete the exploratory trial of the HTP package or to conduct an economic evaluation. Future research To improve the care of people with dementia experiencing crises, a large-scale clinical trial of the home treatment manual is needed. Conclusion There is an urgent need for effective psychosocial interventions for dementia. MCST improved quality of life and was cost-effective, with benefits to cognition for those on AChEIs. MCST was feasible in practice. Both CSP and RYCT improved the quality of life of people with dementia, but the overall costs may be too high. The HTP was useful in practice but requires evaluation in a full trial. Dementia care research may improve the lives of millions of people across the world. Trial registrations Current Controlled Trials ISRCTN26286067 (MCST), ISRCTN28793457 (MCST implementation) and ISRCTN37956201 (CSP/RYCT). Funding This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 5, No. 5. See the NIHR Journals Library website for further project information

Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis

Funder: QingLan Research Project of Jiangsu for Outstanding Young TeachersFunder: Project funded by Postdoctoral Science Foundation of Xuzhou Medical UniversityFunder: Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) for Xuzhou Medical UniversityAbstract: We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population

Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity

The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once

Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity

The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once

Implicit and explicit attention to pictures and words : An fMRI-study of concurrent emotional stimulus processing

The present study utilized functional magnetic resonance imaging (fMRI) to examine the neural processing of concurrently presented emotional stimuli under varying explicit and implicit attention demands. Specifically, in separate trials, participants indicated the category of either pictures or words. The words were placed over the center of the pictures and the picture-word compound-stimuli were presented for 1500 ms in a rapid event-related design. The results reveal pronounced main effects of task and emotion: the picture categorization task prompted strong activations in visual, parietal, temporal, frontal, and subcortical regions; the word categorization task evoked increased activation only in left extrastriate cortex. Furthermore, beyond replicating key findings regarding emotional picture and word processing, the results point to a dissociation of semantic-affective and sensory-perceptual processes for words: while emotional words engaged semantic-affective networks of the left hemisphere regardless of task, the increased activity in left extrastriate cortex associated with explicitly attending to words was diminished when the word was overlaid over an erotic image. Finally, we observed a significant interaction between Picture Category and Task within dorsal visual-associative regions, inferior parietal, and dorsolateral and medial prefrontal cortices: during the word categorization task, activation was increased in these regions when the words were overlaid over erotic as compared to romantic pictures. During the picture categorization task, activity in these areas was relatively decreased when categorizing erotic as compared to romantic pictures. Thus, the emotional intensity of the pictures strongly affected brain regions devoted to the control of task-related word or picture processing. These findings are discussed with respect to the interplay of obligatory stimulus processing with task-related attentional control mechanisms.publishe