The pathway to secondary prevention of Alzheimer\u27s disease

Alzheimer\u27s disease (AD) is a continuum consisting of a preclinical stage that occurs decades before symptoms appear. As researchers make advances in investigating the continuum, the importance of developing drugs for secondary prevention is garnering increased discussion. For efficacious drug development for secondary prevention it is important to define what are the earliest biological stages of AD. The Alzheimer\u27s Association Research Roundtable convened November 27 to 28, 2018 to focus on pre-clinical AD. This review will address the biological approach to defining pre-clinical AD, detection, identification of at-risk individuals, and lessons learned from trials such as A4 and TOMMORROW

Graphical Reasoning in Compact Closed Categories for Quantum Computation

Compact closed categories provide a foundational formalism for a variety of important domains, including quantum computation. These categories have a natural visualisation as a form of graphs. We present a formalism for equational reasoning about such graphs and develop this into a generic proof system with a fixed logical kernel for equational reasoning about compact closed categories. Automating this reasoning process is motivated by the slow and error prone nature of manual graph manipulation. A salient feature of our system is that it provides a formal and declarative account of derived results that can include `ellipses'-style notation. We illustrate the framework by instantiating it for a graphical language of quantum computation and show how this can be used to perform symbolic computation.Comment: 21 pages, 9 figures. This is the journal version of the paper published at AIS

Clinical services for adults with an intellectual disability and epilepsy: A comparison of management alternatives

Background Intellectual disability (ID) is relatively common in people with epilepsy, with prevalence estimated to be around 25%. Surprisingly, given this relatively high frequency, along with higher rates of refractory epilepsy than in those without ID, little is known about outcomes of different management approaches/clinical services treating epilepsy in adults with ID—we investigate this area. Materials & methods We undertook a naturalistic observational cohort study measuring outcomes in n = 91 adults with ID over a 7-month period (recruited within the period March 2008 to April 2010). Participants were receiving treatment for refractory epilepsy (primarily) in one of two clinical service settings: community ID teams (CIDTs) or hospital Neurology services. Results The pattern of comorbidities appeared important in predicting clinical service, with Neurologists managing the epilepsy of relatively more of those with neurological comorbidities whilst CIDTs managed the epilepsy of relatively more of those with psychiatric comorbidities. Epilepsy-related outcomes, as measured by the Glasgow Epilepsy Outcome Scale 35 (GEOS-35) and the Epilepsy and Learning Disabilities Quality of Life Scale (ELDQoL) did not differ significantly between Neurology services and CIDTs. Discussion In the context of this study, the absence of evidence for differences in epilepsy-related outcomes amongst adults with ID and refractory epilepsy between mainstream neurology and specialist ID clinical services is considered. Determining the selection of the service managing the epilepsy of adults with an ID on the basis of the skill sets also required to treat associated comorbidities may hence be a reasonable heuristic.This paper presents independent research funded by the National Institute for Health Research (NIHR - www.nihr.ac.uk) under its Research for Patient Benefit (RfPB - https://www.nihr.ac.uk/funding-and-support/funding-for-research-studies/funding-programmes/research-for-patient-benefit/) Programme (Grant PB-PG-0706-10051; PI Dr H Ring). During the time that this research was carried out, AP Wagner, TJ Croudace, M Redley and H Ring also received support from the NIHR CLAHRC for Cambridgeshire and Peterborough (http://clahrc-cp.nihr.ac.uk/). In preparing this manuscript AP Wagner and H Ring received support from the NIHR Collaboration for Leadership in Applied Health Research and Care East of England at the Cambridgeshire and Peterborough NHS Foundation Trust (http://www.clahrc-eoe.nihr.ac.uk/). SR White was supported by the Medical Research Council (Unit Programme no. U105292687 - http://www.mrc.ac.uk/)

\u3ci\u3eSnowedOut Atlanta\u3c/i\u3e: Examining digital emergence on facebook during a crisis

Individuals in emergencies form spontaneous, emergent groups to respond and recover. With the rise of social media use in crises, academics and professionals must be aware of how groups digitally coordinate emergent response efforts. This paper examines digital emergence through the case of SnowedOut Atlanta, a Facebook group formed during the 2014 ice storms in Atlanta. The posts and actions of the group members are in line with those of traditional emergent groups. For example, group members shared informational, material, and emotional support. The findings also provide implications for practitioners and insight into the communication of such groups. In particular, emergency managers have an opportunity to seek out and partner with these types of groups in future similar events

The Surgical Infection Society revised guidelines on the management of intra-abdominal infection

Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations. Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council. Results: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included. Summary: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline

A retrospective analysis of noise-induced hearing loss in the Dutch construction industry

Purpose Noise exposure is an important and highly prevalent occupational hazard in the construction industry. This study examines hearing threshold levels of a large population of Dutch construction workers and compares their hearing thresholds to those predicted by ISO-1999. Methods In this retrospective study, medical records of periodic occupational health examinations of 29,644 construction workers are analysed. Pure-tone audiometric thresholds of noise-exposed workers are compared to a non-exposed control group and to ISO-1999 predictions. Regression analyses are conducted to explore the relationship between hearing loss and noise intensity, noise exposure time and the use of hearing protection. Results Noise-exposed workers had greater hearing losses compared to their non-noise-exposed colleagues and to the reference population reported in ISO-1999. Noise exposure explained only a small proportion of hearing loss. When the daily noise exposure level rose from 80 dB(A) towards 96 dB(A), only a minor increase in hearing loss is shown. The relation of exposure time and hearing loss found was similar to ISO-1999 predictions when looking at durations of 10 years or more. For the first decade, the population medians show poorer hearing than predicted by ISO-1999. Discussion Duration of noise exposure was a better predictor than noise exposure levels, probably because of the limitations in noise exposure estimations. In this population, noise-induced hearing loss was already present at the beginning of employment and increased at the same rate as is predicted for longer exposure duration

Improving mental and neurological health research in Latin America: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Research evidence is essential to inform policies, interventions and programs, and yet research activities in mental and neurological (MN) health have been largely neglected, particularly in low- and middle-income countries. Many challenges have been identified in the production and utilization of research evidence in Latin American countries, and more work is needed to overcome this disadvantageous situation. This study aims to address the situation by identifying initiatives that could improve MN health research activities and implementation of their results in the Latin American region.</p> <p>Methods</p> <p>Thirty-four MN health actors from 13 Latin American countries were interviewed as part of an initiative by the Global Forum for Health Research and the World Health Organization to explore the status of MN health research in low- and middle-income countries in Africa, Asia and Latin-America.</p> <p>Results</p> <p>A variety of recommendations to increase MN health research activities and implementation of their results emerged in the interviews. These included increasing skilled human resources in MN health interventions and research, fostering greater participation of stakeholders in the generation of research topics and projects, and engendering the interest of national and international institutions in important MN health issues and research methodologies. In the view of most participants, government agencies should strive to have research results inform the decision-making process in which they are involved. Thus these agencies would play a key role in facilitating and funding research. Participants also pointed to the importance of academic recognition and financial rewards in attracting professionals to primary and translational research in MN health. In addition, they suggested that institutions should create intramural resources to provide researchers with technical support in designing, carrying out and disseminating research, including resources to improve scientific writing skills.</p> <p>Conclusion</p> <p>Fulfillment of these recommendations would increase research production in MN health in Latin American countries. This, in turn, will raise the profile of these health problems, and consequently will underscore the need of continued high-quality and relevant research, thus fostering a virtuous cycle in the decision-making process to improve MN health care.</p

The protocols for the 10/66 dementia research group population-based research programme

BACKGROUND: Latin America, China and India are experiencing unprecedentedly rapid demographic ageing with an increasing number of people with dementia. The 10/66 Dementia Research Group's title refers to the 66% of people with dementia that live in developing countries and the less than one tenth of population-based research carried out in those settings. This paper describes the protocols for the 10/66 population-based and intervention studies that aim to redress this imbalance. METHODS/DESIGN: Cross-sectional comprehensive one phase surveys have been conducted of all residents aged 65 and over of geographically defined catchment areas in ten low and middle income countries (India, China, Nigeria, Cuba, Dominican Republic, Brazil, Venezuela, Mexico, Peru and Argentina), with a sample size of between 1000 and 3000 (generally 2000). Each of the studies uses the same core minimum data set with cross-culturally validated assessments (dementia diagnosis and subtypes, mental disorders, physical health, anthropometry, demographics, extensive non communicable disease risk factor questionnaires, disability/functioning, health service utilisation, care arrangements and caregiver strain). Nested within the population based studies is a randomised controlled trial of a caregiver intervention for people with dementia and their families (ISRCTN41039907; ISRCTN41062011; ISRCTN95135433; ISRCTN66355402; ISRCTN93378627; ISRCTN94921815). A follow up of 2.5 to 3.5 years will be conducted in 7 countries (China, Cuba, Dominican Republic, Venezuela, Mexico, Peru and Argentina) to assess risk factors for incident dementia, stroke and all cause and cause-specific mortality; verbal autopsy will be used to identify causes of death. DISCUSSION: The 10/66 DRG baseline population-based studies are nearly complete. The incidence phase will be completed in 2009. All investigators are committed to establish an anonymised file sharing archive with monitored public access. Our aim is to create an evidence base to empower advocacy, raise awareness about dementia, and ensure that the health and social care needs of older people are anticipated and met

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Nuclear anomalies in the buccal cells of calcite factory workers

The micronucleus (MN) assay on exfoliated buccal cells is a useful and minimally invasive method for monitoring genetic damage in humans. To determine the genotoxic effects of calcite dust that forms during processing, MN assay was carried out in exfoliated buccal cells of 50 (25 smokers and 25 non-smokers) calcite factory workers and 50 (25 smokers and 25 non-smokers) age- and sex-matched control subjects. Frequencies of nuclear abnormalities (NA) other than micronuclei, such as binucleates, karyorrhexis, karyolysis and ‘broken eggs', were also evaluated. Micronuclei and the other aforementioned anomalies were analysed by two way analysis of covariance. The linear correlations between the types of micronucleus and nuclear abnormalities were determined by Spearman's Rho. There was a positive correlation between micronuclei and other types of nuclear abnormalities in accordance with the Spearman's Rho test. Results showed statistically significant difference between calcite fabric workers and control groups. MN and NA frequencies in calcite fabric workers were significantly higher than those in control groups (p < 0.05). The results of this study indicate that calcite fabric workers are under risk of significant cytogenetic damage