Identifying and mitigating Sudden Unexpected Death in Epilepsy (SUDEP) risk factors

INTRODUCTION: Sudden Unexpected Death in Epilepsy (SUDEP) is a significant cause of death for people with chronic epilepsy. Good practice guidance in the UK and the USA expect SUDEP to be discussed with the individual. The event rarity, methodological variance and lack of robust research into the pathological mechanisms, associated risk factors, and management strategies have created a challenge on how and what to discuss. There are some significant associations which allows for risk assessment and mitigation. Areas covered: The current understanding of static and modifiable risk factors for SUDEP and how to manage these more effectively are reviewed. Longitudinal risk may be assessed using standardised risk assessment tools which help in communicating risk. Technological advancement allows measurement of physiological parameters associated with seizures and risk of SUDEP using small wearable devices. Further evidence is needed to demonstrate such technologies are efficacious and safe. Expert commentary: Risk reduction should be an important part of epilepsy management and we suggest a Gold Standard of Care which healthcare professionals and services should aim for when approaching SUDEP risk management. A Minimum Standard of Care is also proposed that is practical to implement, that all people with epilepsy should expect to receive

Developing Prognosis Tools to Identify Learning Difficulties in Children Using Machine Learning Technologies

The Mental Attributes Profiling System was developed in 2002 (Laouris and Makris, Proceedings of multilingual & cross-cultural perspectives on Dyslexia, Omni Shoreham Hotel, Washington, D.C, 2002), to provide a multimodal evaluation of the learning potential and abilities of young children’s brains. The method is based on the assessment of non-verbal abilities using video-like interfaces and was compared to more established methodologies in (Papadopoulos, Laouris, Makris, Proceedings of IDA 54th annual conference, San Diego, 2003), such as the Wechsler Intelligence Scale for Children (Watkins et al., Psychol Sch 34(4):309–319, 1997). To do so, various tests have been applied to a population of 134 children aged 7–12 years old. This paper addresses the issue of identifying a minimal set of variables that are able to accurately predict the learning abilities of a given child. The use of Machine Learning technologies to do this provides the advantage of making no prior assumptions about the nature of the data and eliminating natural bias associated with data processing carried out by humans. Kohonen’s Self Organising Maps (Kohonen, Biol Cybern 43:59–69, 1982) algorithm is able to split a population into groups based on large and complex sets of observations. Once the population is split, the individual groups can then be probed for their defining characteristics providing insight into the rationale of the split. The characteristics identified form the basis of classification systems that are able to accurately predict which group an individual will belong to, using only a small subset of the tests available. The specifics of this methodology are detailed herein, and the resulting classification systems provide an effective tool to prognose the learning abilities of new subjects

Illusory temporal binding in meditators

We investigate conditions in which more accurate metacognition may lead to greater susceptibility to illusion; and thus conditions under which mindfulness meditation may lead to less accurate perceptions. Specifically, greater awareness of intentions may lead to an illusory compression of time between a voluntary action and its outcome (“intentional binding”). Here we report that experienced Buddhist mindfulness meditators rather than non-meditators display a greater illusory shift of the timing of an outcome towards an intentional action. Mindfulness meditation involves awareness of causal connections between different mental states, including intentions. We argue that this supports improvements in metacognition targeted at motor intentions. Changes in metacognitive ability may result in an earlier and less veridical experience of the timing of action outcomes either through increased access to sensorimotor pre-representations of an action outcome or by affording greater precision to action timing judgements. Furthermore, as intentional binding is an implicit measure of the sense of agency, these results also provide evidence that mindfulness meditators experience a stronger sense of agency

Prolonged residence of an albumin–IL-4 fusion protein in secondary lymphoid organs ameliorates experimental autoimmune encephalomyelitis

Interleukin-4 (IL-4) suppresses the development of multiple sclerosis in a murine model of experimental autoimmune encephalomyelitis (EAE). Here, we show that, in mice with EAE, the accumulation and persistence in the lymph nodes and spleen of a systemically administered serum albumin (SA)–IL-4 fusion protein leads to higher efficacy in preventing disease development than the administration of wild-type IL-4 or of the clinically approved drug fingolimod. We also show that the SA–IL-4 fusion protein prevents immune-cell infiltration in the spinal cord, decreases integrin expression in antigen-specific CD4+ T cells, increases the number of granulocyte-like myeloid-derived suppressor cells (and their expression of programmed-death-ligand-1) in spinal cord-draining lymph nodes and decreases the number of T helper 17 cells, a pathogenic cell population in EAE. In mice with chronic EAE, SA–IL-4 inhibits immune-cell infiltration into the spinal cord and completely abrogates immune responses to myelin antigen in the spleen. The SA–IL-4 fusion protein may be prophylactically and therapeutically advantageous in the treatment of multiple sclerosis

Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution

It has recently been shown that nucleosome distribution, histone modifications and RNA polymerase II (Pol II) occupancy show preferential association with exons (“exon-intron marking”), linking chromatin structure and function to co-transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing studies suggested that these marking patterns reflect the nucleosomal landscape. By analyzing ChIP-chip datasets across the human genome in three cell types, we have found that this marking system is far more complex than previously observed. We show here that a range of histone modifications and Pol II are preferentially associated with exons. However, there is noticeable cell-type specificity in the degree of exon marking by histone modifications and, surprisingly, this is also reflected in some histone modifications patterns showing biases towards introns. Exon-intron marking is laid down in the absence of transcription on silent genes, with some marking biases changing or becoming reversed for genes expressed at different levels. Furthermore, the relationship of this marking system with splicing is not simple, with only some histone modifications reflecting exon usage/inclusion, while others mirror patterns of exon exclusion. By examining nucleosomal distributions in all three cell types, we demonstrate that these histone modification patterns cannot solely be accounted for by differences in nucleosome levels between exons and introns. In addition, because of inherent differences between ChIP-chip array and ChIP-sequencing approaches, these platforms report different nucleosome distribution patterns across the human genome. Our findings confound existing views and point to active cellular mechanisms which dynamically regulate histone modification levels and account for exon-intron marking. We believe that these histone modification patterns provide links between chromatin accessibility, Pol II movement and co-transcriptional splicing

Head Position in Stroke Trial (HeadPoST)- sitting-up vs lying-flat positioning of patients with acute stroke: study protocol for a cluster randomised controlled trial

Background Positioning a patient lying-flat in the acute phase of ischaemic stroke may improve recovery and reduce disability, but such a possibility has not been formally tested in a randomised trial. We therefore initiated the Head Position in Stroke Trial (HeadPoST) to determine the effects of lying-flat (0°) compared with sitting-up (≥30°) head positioning in the first 24 hours of hospital admission for patients with acute stroke. Methods/Design We plan to conduct an international, cluster randomised, crossover, open, blinded outcome-assessed clinical trial involving 140 study hospitals (clusters) with established acute stroke care programs. Each hospital will be randomly assigned to sequential policies of lying-flat (0°) or sitting-up (≥30°) head position as a ‘business as usual’ stroke care policy during the first 24 hours of admittance. Each hospital is required to recruit 60 consecutive patients with acute ischaemic stroke (AIS), and all patients with acute intracerebral haemorrhage (ICH) (an estimated average of 10), in the first randomised head position policy before crossing over to the second head position policy with a similar recruitment target. After collection of in-hospital clinical and management data and 7-day outcomes, central trained blinded assessors will conduct a telephone disability assessment with the modified Rankin Scale at 90 days. The primary outcome for analysis is a shift (defined as improvement) in death or disability on this scale. For a cluster size of 60 patients with AIS per intervention and with various assumptions including an intracluster correlation coefficient of 0.03, a sample size of 16,800 patients at 140 centres will provide 90 % power (α 0.05) to detect at least a 16 % relative improvement (shift) in an ordinal logistic regression analysis of the primary outcome. The treatment effect will also be assessed in all patients with ICH who are recruited during each treatment study period. Discussion HeadPoST is a large international clinical trial in which we will rigorously evaluate the effects of different head positioning in patients with acute stroke. Trial registration ClinicalTrials.gov identifier: NCT02162017 (date of registration: 27 April 2014); ANZCTR identifier: ACTRN12614000483651 (date of registration: 9 May 2014). Protocol version and date: version 2.2, 19 June 2014

Approaches to the evaluation of outbreak detection methods

BACKGROUND: An increasing number of methods are being developed for the early detection of infectious disease outbreaks which could be naturally occurring or as a result of bioterrorism; however, no standardised framework for examining the usefulness of various outbreak detection methods exists. To promote comparability between studies, it is essential that standardised methods are developed for the evaluation of outbreak detection methods. METHODS: This analysis aims to review approaches used to evaluate outbreak detection methods and provide a conceptual framework upon which recommendations for standardised evaluation methods can be based. We reviewed the recently published literature for reports which evaluated methods for the detection of infectious disease outbreaks in public health surveillance data. Evaluation methods identified in the recent literature were categorised according to the presence of common features to provide a conceptual basis within which to understand current approaches to evaluation. RESULTS: There was considerable variation in the approaches used for the evaluation of methods for the detection of outbreaks in public health surveillance data, and appeared to be no single approach of choice. Four main approaches were used to evaluate performance, and these were labelled the Descriptive, Derived, Epidemiological and Simulation approaches. Based on the approaches identified, we propose a basic framework for evaluation and recommend the use of multiple approaches to evaluation to enable a comprehensive and contextualised description of outbreak detection performance. CONCLUSION: The varied nature of performance evaluation demonstrated in this review supports the need for further development of evaluation methods to improve comparability between studies. Our findings indicate that no single approach can fulfil all evaluation requirements. We propose that the cornerstone approaches to evaluation identified provide key contributions to support internal and external validity and comparability of study findings, and suggest these be incorporated into future recommendations for performance assessment

ERGONOMIA E SEGURANÇA EM ATIVIDADES EXTRATIVISTAS NO ESTADO DO ACRE

A ergonomia é a ciência que estuda a adaptação do trabalho ao homem, tendo como objetivo a melhoria das condições de saúde, segurança e bem estar do trabalhador. Apesar de existirem diversos estudos de ergonomia em vários setores, ao que tange atividades extrativistas, ainda são poucas as informações obtidas. Esta pesquisa teve como objetivo analisar e compreender as condições de trabalho, saúde e segurança das atividades na coleta e transporte de castanha e açaí na Reserva Extrativista Cazumbá - Iracema no Estado do Acre, a fim de propor sugestões à referida categoria a partir da análise dos fatores ergonômicos. As variáveis analisadas foram os fatores humanos, ambientais (clima e iluminação), carga física, posturas adotadas e o manuseio de cargas. Foram avaliados ao total 40 trabalhadores. De acordo com os resultados, os trabalhadores tinham idade média de 35 anos, peso médio de 69 kg, baixo índice de analfabetismo (2,3%), de origem predominantemente rural (94,1%), tendo um consumo alto de bebidas alcoólicas (49%) e tabaco (15%). A maioria dos trabalhadores já tiveram acidentes em suas atividades. A exposição ao calor e a iluminância foram considerados elevados e inadequados entre os horários de 12 e 13:30 horas. A carga física foi considerada moderadamente pesada na maioria das operações, destacando-se o transporte de castanha e a coleta do açai, sendo considerados pesados. As posturas mais prejudiciais foram observadas na coleta do açaí e no transporte de castanha. O manuseio de cargas apresentou alto risco de lesão nas atividades de transporte de castanha. Para melhoria das condições de trabalho, saúde, bem estar e segurança, deve haver uma conscientização a fim de diminuir os vícios e fiscalização para que haja o uso devido dos equipamentos de proteção individual. Ainda assim, os trabalhadores devem ser treinados e conscientizados para utilizar medidas adequadas de controle onde os níveis de exposição a iluminância são elevados. Também necessita-se de adoção de tempo de repouso por hora efetiva de trabalho nas atividades de coleta do açaí e transporte de castanha. A fim de evitar danos a coluna do trabalhador, é necessário a adoção de pausas durante as atividades de coleta e transporte de ambas as cadeias analisadas. E com relação ao manuseio de cargas é necessária uma reorganização ergonômica a fim de reduzir o peso manuseado para execução da atividade de transporte de castanha. Palavra - chave: Processo Produtivo, Unidades de Conservação, Condições de Trabalho