Random forest prediction of Alzheimer's disease using pairwise selection from time series data

Time-dependent data collected in studies of Alzheimer's disease usually has missing and irregularly sampled data points. For this reason time series methods which assume regular sampling cannot be applied directly to the data without a pre-processing step. In this paper we use a machine learning method to learn the relationship between pairs of data points at different time separations. The input vector comprises a summary of the time series history and includes both demographic and non-time varying variables such as genetic data. The dataset used is from the 2017 TADPOLE grand challenge which aims to predict the onset of Alzheimer's disease using including demographic, physical and cognitive data. The challenge is a three-fold diagnosis classification into AD, MCI and control groups, the prediction of ADAS-13 score and the normalised ventricle volume. While the competition proceeds, forecasting methods may be compared using a leaderboard dataset selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and with standard metrics for measuring accuracy. For diagnosis, we find an mAUC of 0.82, and a classification accuracy of 0.73. The results show that the method is effective and comparable with other methods.Comment: 6 pages, 1 figure, 6 table

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD

Support and Assessment for Fall Emergency Referrals (SAFER 1) trial protocol. Computerised on-scene decision support for emergency ambulance staff to assess and plan care for older people who have fallen: evaluation of costs and benefits using a pragmatic cluster randomised trial

Background: Many emergency ambulance calls are for older people who have fallen. As half of them are left at home, a community-based response may often be more appropriate than hospital attendance. The SAFER 1 trial will assess the costs and benefits of a new healthcare technology - hand-held computers with computerised clinical decision support (CCDS) software - to help paramedics decide who needs hospital attendance, and who can be safely left at home with referral to community falls services. Methods/Design: Pragmatic cluster randomised trial with a qualitative component. We shall allocate 72 paramedics ('clusters') at random between receiving the intervention and a control group delivering care as usual, of whom we expect 60 to complete the trial. Patients are eligible if they are aged 65 or older, live in the study area but not in residential care, and are attended by a study paramedic following an emergency call for a fall. Seven to 10 days after the index fall we shall offer patients the opportunity to opt out of further follow up. Continuing participants will receive questionnaires after one and 6 months, and we shall monitor their routine clinical data for 6 months. We shall interview 20 of these patients in depth. We shall conduct focus groups or semi-structured interviews with paramedics and other stakeholders. The primary outcome is the interval to the first subsequent reported fall (or death). We shall analyse this and other measures of outcome, process and cost by 'intention to treat'. We shall analyse qualitative data thematically. Discussion: Since the SAFER 1 trial received funding in August 2006, implementation has come to terms with ambulance service reorganisation and a new national electronic patient record in England. In response to these hurdles the research team has adapted the research design, including aspects of the intervention, to meet the needs of the ambulance services. In conclusion this complex emergency care trial will provide rigorous evidence on the clinical and cost effectiveness of CCDS for paramedics in the care of older people who have fallen

Do Children Who Move Home and School Frequently Have Poorer Educational Outcomes in Their Early Years at School? An Anonymised Cohort Study

Frequent mobility has been linked to poorer educational attainment. We investigated the association between moving home and moving school frequently and the early childhood formal educational achievement. We carried out a cohort analysis of 121,422 children with anonymised linked records. Our exposure measures were: 1) the number of residential moves registered with a health care provider, and 2) number of school moves. Our outcome was the formal educational assessment at age 6–7. Binary regression modeling was used to examine residential moves within the three time periods: 0 – ,1 year; 1 – ,4 years and 4 – ,6 years. School moves were examined from age 4 to age 6. We adjusted for demographics, residential moves at different times, school moves and birth related variables. Children who moved home frequently were more likely not to achieve in formal assessments compared with children not moving. Adjusted odds ratios were significant for 3 or more moves within the time period 1 –,4 years and for any number of residential moves within the time period 4– ,6 years. There was a dose response relationship, with increased odds ratios with increased frequency of residential moves (2 or more moves at 4–,6 years, adjusted odds ratio 1.16 (1.03, 1.29). The most marked effect was seen with frequent school moves where 2 or more moves resulted in an adjusted odds ratio of 2.33 (1.82, 2.98). This is the first study to examine the relationship between residential and school moves in early childhood and the effect on educational attainment. Children experiencing frequent mobility may be disadvantaged and should be closely monitored. Additional educational support services should be afforded to children, particularly those who frequently change school, in order to help them achieve the expected educational standards

Elimination of Schistosomiasis Transmission in Zanzibar: Baseline Findings before the Onset of a Randomized Intervention Trial.

Gaining and sustaining control of schistosomiasis and, whenever feasible, achieving local elimination are the year 2020 targets set by the World Health Organization. In Zanzibar, various institutions and stakeholders have joined forces to eliminate urogenital schistosomiasis within 5 years. We report baseline findings before the onset of a randomized intervention trial designed to assess the differential impact of community-based praziquantel administration, snail control, and behavior change interventions. In early 2012, a baseline parasitological survey was conducted in ∼20,000 people from 90 communities in Unguja and Pemba. Risk factors for schistosomiasis were assessed by administering a questionnaire to adults. In selected communities, local knowledge about schistosomiasis transmission and prevention was determined in focus group discussions and in-depths interviews. Intermediate host snails were collected and examined for shedding of cercariae. The baseline Schistosoma haematobium prevalence in school children and adults was 4.3% (range: 0-19.7%) and 2.7% (range: 0-26.5%) in Unguja, and 8.9% (range: 0-31.8%) and 5.5% (range: 0-23.4%) in Pemba, respectively. Heavy infections were detected in 15.1% and 35.6% of the positive school children in Unguja and Pemba, respectively. Males were at higher risk than females (odds ratio (OR): 1.45; 95% confidence interval (CI): 1.03-2.03). Decreasing adult age (OR: 1.04; CI: 1.02-1.06), being born in Pemba (OR: 1.48; CI: 1.02-2.13) or Tanzania (OR: 2.36; CI: 1.16-4.78), and use of freshwater (OR: 2.15; CI: 1.53-3.03) showed higher odds of infection. Community knowledge about schistosomiasis was low. Only few infected Bulinus snails were found. The relatively low S. haematobium prevalence in Zanzibar is a promising starting point for elimination. However, there is a need to improve community knowledge about disease transmission and prevention. Control measures tailored to the local context, placing particular attention to hot-spot areas, high-risk groups, and individuals, will be necessary if elimination is to be achieved

Intensity modulated radiotherapy (IMRT) in patients with carcinomas of the paranasal sinuses: clinical benefit for complex shaped target volumes

INTRODUCTION: The aim of the study was to evaluate the clinical outcome of intensity modulated radiotherapy (IMRT) in 46 patients with paranasal sinus tumors with special respect to treatment-related toxicity. PATIENTS AND METHODS: We treated 46 patients with histologically proven tumors of the paranasal sinuses with IMRT. Histological classification included squamous cell carcinoma in 6, adenocarcinoma in 8, adenoidcystic carcinoma in 20 and melanoma in 8 patients, respectively. Six patients had been treated with RT during initial therapy after primary diagnosis, and IMRT was performed for the treatment of tumor progression as re-irradiation. RESULTS: Overall survival rates were 96% at 1 year, 90% at 3 years. Calculated from the initiation of IMRT as primary radiotherapy, survival rates at 1 and 3 years were 95% and 80%. In six patients IMRT was performed as re-irradiation, and survival rate calculated from re-irradiation was 63% at 1 year. Local control rates were 85% at 1, 81% at 2 and 49% at 3 years after primary RT and 50% at 1 year after re-irradiation. Distant metastases-free survival in patients treated with IMRT as primary RT was 83% after 1 and 64% after 3 years. For patients treated as primary irradiation with IMRT, the distant control rate was 83% at 1 year and 0% at 2 years. No severe radiation-induced side-effects could be observed. CONCLUSION: IMRT for tumors of the paranasal sinuses is associated with very good tumor control rates. Treatment-related acute and long-term toxicity can be minimized as compared to historical results with conventional RT

There are no whole truths in meta-analyses: all their truths are half truths

In a recent letter, Thomsen & Wernberg (2015) rean-alyzed data compiled for our recent paper (Lyonset al., 2014). In that paper, we examined the effectsof macroalgal blooms and macroalgal mats on sevenimportant measures of community structure and eco-system functioning and explored several ecologicaland methodological factors that might explain someof the variation in the observed effects. Thomsen &Wernberg (2015) re-analyzed two small subsets of the data, focusing on experimental studies examining effects of blooms/mats on invertebrate abundance.Their analyses revealed two interesting patterns.First, they showed that macroalgal blooms reducedthe abundance of communities that Thomsen andWernberg categorized as ‘mainly infauna’, whileincreasing the abundance of communities categorized as ‘mainly epifauna’. Second, they showed that theimpacts of macroalgal blooms on ‘mainly infauna’communities increased with algal density in experiments that included multiple levels of algal density.These findings, as well as the conclusions that Thomsen & Wernberg (2015) draw from them, are largely consistent with our own expectations and interpretations. However, we also feel that some caution is required when interpreting the results of their analyses

Bayesian analysis of Jolly-Seber type models; Incorporating heterogeneity in arrival and departure

We propose the use of finite mixtures of continuous distributions in modelling the process by which new individuals, that arrive in groups, become part of a wildlife population. We demonstrate this approach using a data set of migrating semipalmated sandpipers (Calidris pussila) for which we extend existing stopover models to allow for individuals to have different behaviour in terms of their stopover duration at the site. We demonstrate the use of reversible jump MCMC methods to derive posterior distributions for the model parameters and the models, simultaneously. The algorithm moves between models with different numbers of arrival groups as well as between models with different numbers of behavioural groups. The approach is shown to provide new ecological insights about the stopover behaviour of semipalmated sandpipers but is generally applicable to any population in which animals arrive in groups and potentially exhibit heterogeneity in terms of one or more other processes

A cohort study: temporal trends in prevalence of antecedents, comorbidities and mortality in Aboriginal and non-Aboriginal Australians with first heart failure hospitalization, 2000-2009

Abstract Background/objectives: Little is known about trends in risk factors and mortality for Aboriginal Australians with heart failure (HF). This population-based study evaluated trends in prevalence of risk factors, 30-day and 1-year all-cause mortality following first HF hospitalization among Aboriginal and non-Aboriginal Western Australians in the decade 2000-2009. Methods: Linked-health data were used to identify patients (20-84 years), with a first-ever HF hospitalization. Trends in demographics, comorbidities, interventions and risk factors were evaluated. Logistic and Cox regression models were fitted to test and compare trends over time in 30-day and 1-year mortality. Results: Of 17,379 HF patients, 1,013 (5.8 %) were Aboriginal. Compared with 2000-2002, the prevalence (as history) of myocardial infarction and hypertension increased more markedly in 2006-2009 in Aboriginal (versus non-Aboriginal) patients, while diabetes and chronic kidney disease remained disproportionately higher in Aboriginal patients. Risk factor trends, including the Charlson comorbidity index, increased over time in younger Aboriginal patients. Risk-adjusted 30-day mortality did not change over the decade in either group. Risk-adjusted 1-year mortality (in 30-day survivors) was non-significantly higher in Aboriginal patients in 2006-2008 compared with 2000-2002 (hazard ratio (HR) 1.44; 95 % CI 0.85-2.41; p-trend = 0.47) whereas it decreased in non-Aboriginal patients (HR 0.87; 95 % CI 0.78-0.97; p-trend = 0.01). Conclusions: Between 2000 and 2009, the prevalence of HF antecedents increased and remained disproportionately higher in Aboriginal (versus non-Aboriginal) HF patients. Risk-adjusted 1-year mortality did not improve in Aboriginal patients over the period in contrast with non-Aboriginal patients. These findings highlight the need for better prevention and post-HF care in Aboriginal Australians

Antibody Labelling of Resilin in Energy Stores for Jumping in Plant Sucking Insects

The rubbery protein resilin appears to form an integral part of the energy storage structures that enable many insects to jump by using a catapult mechanism. In plant sucking bugs that jump (Hemiptera, Auchenorrhyncha), the energy generated by the slow contractions of huge thoracic jumping muscles is stored by bending composite bow-shaped parts of the internal thoracic skeleton. Sudden recoil of these bows powers the rapid and simultaneous movements of both hind legs that in turn propel a jump. Until now, identification of resilin at these storage sites has depended exclusively upon characteristics that may not be specific: its fluorescence when illuminated with specific wavelengths of ultraviolet (UV) light and extinction of that fluorescence at low pH. To consolidate identification we have labelled the cuticular structures involved with an antibody raised against a product of the Drosophila CG15920 gene. This encodes pro-resilin, the first exon of which was expressed in E. coli and used to raise the antibody. We show that in frozen sections from two species, the antibody labels precisely those parts of the metathoracic energy stores that fluoresce under UV illumination. The presence of resilin in these insects is thus now further supported by a molecular criterion that is immunohistochemically specific