Applying Deep Learning to Predicting Dementia and Mild Cognitive Impairment

Dementia has a large negative impact on the global healthcare and society. Diagnosis is rather challenging as there is no standardised test. The purpose of this paper is to conduct an analysis on ADNI data and determine its effectiveness for building classification models to differentiate the categories Cognitively Normal (CN), Mild Cognitive Impairment (MCI), and Dementia (DEM), based on tuning three Deep Learning models: two Multi-Layer Perceptron (MLP1 and MLP2) models and a Convolutional Bidirectional Long Short-Term Memory (ConvBLSTM) model. The results show that the MLP1 and MLP2 models accurately distinguish the DEM, MCI and CN classes, with accuracies as high as 0.86 (SD 0.01). The ConvBLSTM model was slightly less accurate but was explored in view of comparisons with the MLP models, and for future extensions of this work that will take advantage of time-related information. Although the performance of ConvBLSTM model was negatively impacted by a lack of visit code data, opportunities were identified for improvement, particularly in terms of pre-processing

A randomised controlled trial and cost-effectiveness evaluation of "booster" interventions to sustain increases in physical activity in middle-aged adults in deprived urban neighbourhoods

Background: Systematic reviews have identified a range of brief interventions which increase physical activity in previously sedentary people. There is an absence of evidence about whether follow up beyond three months can maintain long term physical activity. This study assesses whether it is worth providing motivational interviews, three months after giving initial advice, to those who have become more active. Methods/Design: Study candidates (n = 1500) will initially be given an interactive DVD and receive two telephone follow ups at monthly intervals checking on receipt and use of the DVD. Only those that have increased their physical activity after three months (n = 600) will be randomised into the study. These participants will receive either a "mini booster" (n = 200), "full booster" (n = 200) or no booster (n = 200). The "mini booster" consists of two telephone calls one month apart to discuss physical activity and maintenance strategies. The "full booster" consists of a face-to-face meeting with the facilitator at the same intervals. The purpose of these booster sessions is to help the individual maintain their increase in physical activity. Differences in physical activity, quality of life and costs associated with the booster interventions, will be measured three and nine months from randomisation. The research will be conducted in 20 of the most deprived neighbourhoods in Sheffield, which have large, ethnically diverse populations, high levels of economic deprivation, low levels of physical activity, poorer health and shorter life expectancy. Participants will be recruited through general practices and community groups, as well as by postal invitation, to ensure the participation of minority ethnic groups and those with lower levels of literacy. Sheffield City Council and Primary Care Trust fund a range of facilities and activities to promote physical activity and variations in access to these between neighbourhoods will make it possible to examine whether the effectiveness of the intervention is modified by access to community facilities. A one-year integrated feasibility study will confirm that recruitment targets are achievable based on a 10% sample.Discussion: The choice of study population, study interventions, brief intervention preceding the study, and outcome measure are discussed

Partial sequencing of the bottle gourd genome reveals markers useful for phylogenetic analysis and breeding

<p>Abstract</p> <p>Background</p> <p>Bottle gourd [<it>Lagenaria siceraria </it>(Mol.) Standl.] is an important cucurbit crop worldwide. Archaeological research indicates that bottle gourd was domesticated more than 10,000 years ago, making it one of the earliest plants cultivated by man. In spite of its widespread importance and long history of cultivation almost nothing has been known about the genome of this species thus far.</p> <p>Results</p> <p>We report here the partial sequencing of bottle gourd genome using the 454 GS-FLX Titanium sequencing platform. A total of 150,253 sequence reads, which were assembled into 3,994 contigs and 82,522 singletons were generated. The total length of the non-redundant singletons/assemblies is 32 Mb, theoretically covering ~ 10% of the bottle gourd genome. Functional annotation of the sequences revealed a broad range of functional types, covering all the three top-level ontologies. Comparison of the gene sequences between bottle gourd and the model cucurbit cucumber (<it>Cucumis sativus</it>) revealed a 90% sequence similarity on average. Using the sequence information, 4395 microsatellite-containing sequences were identified and 400 SSR markers were developed, of which 94% amplified bands of anticipated sizes. Transferability of these markers to four other cucurbit species showed obvious decline with increasing phylogenetic distance. From analyzing polymorphisms of a subset of 14 SSR markers assayed on 44 representative China bottle gourd varieties/landraces, a principal coordinates (PCo) analysis output and a UPGMA-based dendrogram were constructed. Bottle gourd accessions tended to group by fruit shape rather than geographic origin, although in certain subclades the lines from the same or close origin did tend to cluster.</p> <p>Conclusions</p> <p>This work provides an initial basis for genome characterization, gene isolation and comparative genomics analysis in bottle gourd. The SSR markers developed would facilitate marker assisted breeding schemes for efficient introduction of desired traits.</p

A single, one-off measure of depression and anxiety predicts future symptoms, higher healthcare costs, and lower quality of life in coronary heart disease patients: Analysis from a multi-wave, primary care cohort study

To determine whether a one-off, baseline measure of depression and anxiety in a primary care, coronary heart disease (CHD) population predicts ongoing symptoms, costs, and quality of life across a 3-year follow-up.Longitudinal cohort study.16 General Practice surgeries across South-East London.803 adults (70% male, mean age 71 years) contributing up to 7 follow-up points.Ongoing reporting of symptoms, health care costs, and quality of life.At baseline, 27% of the sample screened positive for symptoms of depression and anxiety, as measured by the Hospital Anxiety and Depression Scale (HADS). The probability of scoring above the cut-off throughout the follow-up was 71.5% (p<0.001) for those screening positive at baseline, and for those screening negative, the probability of scoring below the cut-off throughout the follow-up was 97.6% (p<0.001). Total health care costs were 39% higher during follow-up for those screening positive (p<0.05). Quality of life as measured by the SF-12 was lower on the mental component during follow-up for those screening positive (-0.75, CI -1.53 to 0.03, p = 0.059), and significantly lower on the physical component (-4.99, CI -6.23 to -.376, p<0.001).A one-off measure for depression and anxiety symptoms in CHD predicts future symptoms, costs, and quality of life over the subsequent three-years. These findings suggest symptoms of depression and anxiety in CHD persist throughout long periods and are detrimental to a patient's quality of life, whilst incurring higher health care costs for primary and secondary care services. Screening for these symptoms at the primary care level is important to identify and manage patients at risk of the negative effects of this comorbidity. Implementation of screening, and possible collaborative care strategies and interventions that help mitigate this risk should be the ongoing focus of researchers and policy-makers

HCV Induces Oxidative and ER Stress, and Sensitizes Infected Cells to Apoptosis in SCID/Alb-uPA Mice

Hepatitis C virus (HCV) is a blood-borne pathogen and a major cause of liver disease worldwide. Gene expression profiling was used to characterize the transcriptional response to HCV H77c infection. Evidence is presented for activation of innate antiviral signaling pathways as well as induction of lipid metabolism genes, which may contribute to oxidative stress. We also found that infection of chimeric SCID/Alb-uPA mice by HCV led to signs of hepatocyte damage and apoptosis, which in patients plays a role in activation of stellate cells, recruitment of macrophages, and the subsequent development of fibrosis. Infection of chimeric mice with HCV H77c also led an inflammatory response characterized by infiltration of monocytes and macrophages. There was increased apoptosis in HCV-infected human hepatocytes in H77c-infected mice but not in mice inoculated with a replication incompetent H77c mutant. Moreover, TUNEL reactivity was restricted to HCV-infected hepatocytes, but an increase in FAS expression was not. To gain insight into the factors contributing specific apoptosis of HCV infected cells, immunohistological and confocal microscopy using antibodies for key apoptotic mediators was done. We found that the ER chaperone BiP/GRP78 was increased in HCV-infected cells as was activated BAX, but the activator of ER stress–mediated apoptosis CHOP was not. We found that overall levels of NF-κB and BCL-xL were increased by infection; however, within an infected liver, comparison of infected cells to uninfected cells indicated both NF-κB and BCL-xL were decreased in HCV-infected cells. We conclude that HCV contributes to hepatocyte damage and apoptosis by inducing stress and pro-apoptotic BAX while preventing the induction of anti-apoptotic NF-κB and BCL-xL, thus sensitizing hepatocytes to apoptosis

Functional and neurometabolic asymmetry in SHR and WKY rats following vasoactive treatments

A lateralized distribution of neuropeptidase activities in the frontal cortex of normotensive and hypertensive rats has been described depending on the use of some vasoactive drugs and linked to certain mood disorders. Asymmetrical neuroperipheral connections involving neuropeptidases from the left or right hemisphere and aminopeptidases from the heart or plasma have been suggested to play a role in this asymmetry. We hypothesize that such asymmetries could be extended to the connection between the brain and physiologic parameters and metabolic factors from plasma and urine. To assess this hypothesis, we analyzed the possible correlation between neuropeptidases from the left and right frontal cortex with peripheral parameters in normotensive (Wistar Kyoto [WKY]) rats and hypertensive rats (spontaneously hypertensive rats [SHR]) untreated or treated with vasoactive drugs such as captopril, propranolol and L-nitro-arginine methyl ester. Neuropeptidase activities from the frontal cortex were analyzed fluorometrically using arylamide derivatives as substrates. Physiological parameters and metabolic factors from plasma and urine were determined using routine laboratory techniques. Vasoactive drug treatments differentially modified the asymmetrical neuroperipheral pattern by changing the predominance of the correlations between peripheral parameters and central neuropeptidase activities of the left and right frontal cortex. The response pattern also differed between SHR and WKY rats. These results support an asymmetric integrative function of the organism and suggest the possibility of a different neurometabolic response coupled to particular mood disorders, depending on the selected vasoactive drug.This work was supported by the Ministry of Science and Innovation through project no. SAF 2008 04685 C02 01

Should I Stay or Should I Go? A Habitat-Dependent Dispersal Kernel Improves Prediction of Movement

The analysis of animal movement within different landscapes may increase our understanding of how landscape features affect the perceptual range of animals. Perceptual range is linked to movement probability of an animal via a dispersal kernel, the latter being generally considered as spatially invariant but could be spatially affected. We hypothesize that spatial plasticity of an animal's dispersal kernel could greatly modify its distribution in time and space. After radio tracking the movements of walking insects (Cosmopolites sordidus) in banana plantations, we considered the movements of individuals as states of a Markov chain whose transition probabilities depended on the habitat characteristics of current and target locations. Combining a likelihood procedure and pattern-oriented modelling, we tested the hypothesis that dispersal kernel depended on habitat features. Our results were consistent with the concept that animal dispersal kernel depends on habitat features. Recognizing the plasticity of animal movement probabilities will provide insight into landscape-level ecological processes

Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology

OBJECTIVE: Research and clinical translation in schizophrenia is limited by inconsistent definitions of treatment resistance and response. To address this issue, the authors evaluated current approaches and then developed consensus criteria and guidelines. METHODS: A systematic review of randomized antipsychotic clinical trials in treatment-resistant schizophrenia was performed, and definitions of treatment resistance were extracted. Subsequently, consensus operationalized criteria were developed through 1) a multiphase, mixed methods approach, 2) identification of key criteria via an online survey, and 3) meetings to achieve consensus. RESULTS: Of 2,808 studies identified, 42 met inclusion criteria. Of these, 21 studies (50%) did not provide operationalized criteria. In the remaining studies, criteria varied considerably, particularly regarding symptom severity, prior treatment duration, and antipsychotic dosage thresholds; only two studies (5%) utilized the same criteria. The consensus group identified minimum and optimal criteria, employing the following principles: 1) current symptoms of a minimum duration and severity determined by a standardized rating scale; 2) moderate or worse functional impairment; 3) prior treatment consisting of at least two different antipsychotic trials, each for a minimum duration and dosage; 4) systematic monitoring of adherence and meeting of minimum adherence criteria; 5) ideally at least one prospective treatment trial; and 6) criteria that clearly separate responsive from treatment-resistant patients. CONCLUSIONS: There is considerable variation in current approaches to defining treatment resistance in schizophrenia. The authors present consensus guidelines that operationalize criteria for determining and reporting treatment resistance, adequate treatment, and treatment response, providing a benchmark for research and clinical translation

Reef fishes at all trophic levels respond positively to effective marine protected areas

Marine Protected Areas (MPAs) offer a unique opportunity to test the assumption that fishing pressure affects some trophic groups more than others. Removal of larger predators through fishing is often suggested to have positive flow-on effects for some lower trophic groups, in which case protection from fishing should result in suppression of lower trophic groups as predator populations recover. We tested this by assessing differences in the trophic structure of reef fish communities associated with 79 MPAs and open-access sites worldwide, using a standardised quantitative dataset on reef fish community structure. The biomass of all major trophic groups (higher carnivores, benthic carnivores, planktivores and herbivores) was significantly greater (by 40% - 200%) in effective no-take MPAs relative to fished open-access areas. This effect was most pronounced for individuals in large size classes, but with no size class of any trophic group showing signs of depressed biomass in MPAs, as predicted from higher predator abundance. Thus, greater biomass in effective MPAs implies that exploitation on shallow rocky and coral reefs negatively affects biomass of all fish trophic groups and size classes. These direct effects of fishing on trophic structure appear stronger than any top down effects on lower trophic levels that would be imposed by intact predator populations. We propose that exploitation affects fish assemblages at all trophic levels, and that local ecosystem function is generally modified by fishing