Neurophysiology Based Performance Analysis of a Novel Automated Seizure Detection Algorithm for Neonatal EEG

To aid seizure detection in sick neonates, our group has developed an automated seizure detection algorithm (ANSeR) and published initial performance results. In this thesis a validation study of the performance of ANSeR on a large unedited, unseen dataset of 70 EEGs from 2 institutions is presented. Results indicate that ANSeR sensitivity thresholds between 0.5-0.3 provide performance considered acceptable for clinical use with seizure detection rates of 52.6-75% and false detection rates of 0.04 -0.36 FD/h respectively. To determine the features of seizures affecting automated detection, a subset of 20 EEGs from the validation study were selected and seizures were manually analysed using a novel set of 10 criteria. Using multivariate analysis, 4 seizure features were found to affect automated detection including; seizure amplitude, duration, rhythmicity and propagation. The main causes of false detection were also characterised and quantified leading to an adaptation of the algorithm with improved performance. Observations suggest that phenobarbitone, a first line anticonvulsant, may affect seizure morphology and potentially the performance of ANSeR. Using similar seizure analysis criteria to compare pre and post phenobarbitone seizures, it was shown that post phenobarbitone seizures were both lower amplitude and showed reduced propagation but the performance of ANSeR was unaffected. As well as an ongoing quantification of seizure burden, it is important that automated algorithms detect seizures soon after onset to facilitate prompt treatment. Results of retrospective analysis of seizure detection by ANSeR here suggests that the use of ANSeR may reduce the latency of first treatment after seizure onset by 30-40 minutes at clinically relevant ANSeR thresholds, compared to current practice. As rhythmic artefacts and other sources may result in ANSeR false detections, clinicians reviewing the EEG as a result of ANSeR detections must decide if the detection is a true seizure or a false detection. A training resource developed by the author improved the ability of clinical staff to discriminate true seizures from false detections in a randomised study

Neonatal Seizure Management – Is the Timing of Treatment Critical?

OBJECTIVE: To assess the impact of the time to treatment of the first electrographic seizure on subsequent seizure burden; secondary aim was to describe overall seizure management in a large neonatal cohort. STUDY DESIGN: Newborns (36-44 weeks' gestation) requiring electroencephalographic (EEG) monitoring recruited to two multicentre European studies were included. Infants who received anti-seizure medication exclusively after electrographic seizure onset, were grouped based on time to treatment of the first seizure: ASM within 1-hour, ASM between 1-2 hours and ASM after 2-hours. Outcomes measured were seizure burden, maximum seizure burden, status epilepticus, number of seizures and ASM dose over 24-hours following seizure onset. RESULTS: Out of 472 newborns recruited, 154(32.6%) infants had confirmed electrographic seizures. Sixty-nine infants were exclusively treated after onset of electrographic seizures: 21 infants received ASM within 1 hour, 15 infants between 1-2 hours and 33 infants after 2 hours of seizure onset. Significantly lower seizure burden and less seizures were noted in infants treated with ASM within 1 hour from seizure onset (p value=0.029 and 0.035, respectively). Overall, 258/472(54.7%) infants received ASM throughout the study period, of which 40 infants without electrographic seizures had treatment during EEG monitoring and 11 infants with electrographic seizures had no treatment. CONCLUSION: Treatment of neonatal seizures may be time-critical, but more research is required to confirm this. We also need to improve neonatal seizure diagnosis and treatment

Characterisation of neonatal seizures and their treatment using continuous EEG monitoring: a multicentre experience.

OBJECTIVE: The aim of this multicentre study was to describe detailed characteristics of electrographic seizures in a cohort of neonates monitored with multichannel continuous electroencephalography (cEEG) in 6 European centres. METHODS: Neonates of at least 36 weeks of gestation who required cEEG monitoring for clinical concerns were eligible, and were enrolled prospectively over 2 years from June 2013. Additional retrospective data were available from two centres for January 2011 to February 2014. Clinical data and EEGs were reviewed by expert neurophysiologists through a central server. RESULTS: Of 214 neonates who had recordings suitable for analysis, EEG seizures were confirmed in 75 (35%). The most common cause was hypoxic-ischaemic encephalopathy (44/75, 59%), followed by metabolic/genetic disorders (16/75, 21%) and stroke (10/75, 13%). The median number of seizures was 24 (IQR 9-51), and the median maximum hourly seizure burden in minutes per hour (MSB) was 21 min (IQR 11-32), with 21 (28%) having status epilepticus defined as MSB>30 min/hour. MSB developed later in neonates with a metabolic/genetic disorder. Over half (112/214, 52%) of the neonates were given at least one antiepileptic drug (AED) and both overtreatment and undertreatment was evident. When EEG monitoring was ongoing, 27 neonates (19%) with no electrographic seizures received AEDs. Fourteen neonates (19%) who did have electrographic seizures during cEEG monitoring did not receive an AED. CONCLUSIONS: Our results show that even with access to cEEG monitoring, neonatal seizures are frequent, difficult to recognise and difficult to treat. OBERSERVATION STUDY NUMBER: NCT02160171

Filtro natural aplicado ao tratamento da água na comunidade indígena de Killuyacu Alto - Equador

Trabalho de Conclusão de Curso apresentado à Banca Examinadora do Curso de Engenharia Civil de Infraestrutura da UNILA, como parte dos requisitos para obtenção do Grau de Bacharel em Engenharia Civil. Orientador: Profo. Dro. Jiam Pires Frigo Co-orientadora: Profo. Samara Silva de SouzaO filtro natural aplicado ao tratamento da água pluvial na comunidade indígena de Killuyacu Alto na província de Napo no Equador tem como finalidade melhorar a qualidade da água para consumo humano através da proposta de um sistema de filtragem natural lento de baixo custo e instalação simples. A água usada atualmente para consumo da comunidade Killuyacu Alto é captada num manancial localizada numa caverna á montante, armazenada e transportada por gravidade até a comunidade sem passar por nenhum tratamento. O estudo visa promover soluções para o consumo de água potável na região amazônica do Equador, melhorar a saúde nas povoações mais vulneráveis do território amazônico, através de um tratamento de água simplificado, e além disso, reduzir as doenças provocadas pelo consumo de água de baixa qualidade. Para isso, foi realizado um estúdio socioeconômico e levantamento de dados na comunidade, extração e coletas de amostras de água no sistema de abastecimento, análise e avaliação dos padrões de potabilidade antes e depois da implantação do filtro natural para a comparação da qualidade da água. O projeto forneceu uma melhoria na qualidade da água pela implantação do sistema de filtragem natural lenta, embora não foi possível atingir a qualidade necessária para o consumo humano.The natural filter applied to the treatment of rainwater in the indigenous community of Killuyacu Alto in the province of Napo in Ecuador aims to improve the quality of water for human consumption through the proposal of a slow natural filtration system of low cost and simple installation. The water currently used for consumption by the Killuyacu Alto community is taken from a source located in an upstream cave, stored and transported by gravity to the community without undergoing any water treatment. The study promoted solutions for the consumption of drinking water in the Amazonian region of Ecuador and improve health in the most vulnerable settlements in the Amazonian territory through a simplified water treatment and also reduce diseases caused by the consumption of low quality water. For this, a socioeconomic study and community data collection, extraction and collection of water samples were carried out in the supply system, the potability standards were analyzed and evaluated before and after the implantation of the natural filter, if we compare the quality of the water. The project provided an improvement in water quality through the implementation of the slow natural filtration system, although it was not possible to reach the required quality for human consumption

Scans for signatures of selection in Russian cattle breed genomes reveal new candidate genes for environmental adaptation and acclimation

Domestication and selective breeding has resulted in over 1000 extant cattle breeds. Many of these breeds do not excel in important traits but are adapted to local environments. These adaptations are a valuable source of genetic material for efforts to improve commercial breeds. As a step toward this goal we identified candidate regions to be under selection in genomes of nine Russian native cattle breeds adapted to survive in harsh climates. After comparing our data to other breeds of European and Asian origins we found known and novel candidate genes that could potentially be related to domestication, economically important traits and environmental adaptations in cattle. The Russian cattle breed genomes contained regions under putative selection with genes that may be related to adaptations to harsh environments (e.g., AQP5, RAD50, and RETREG1). We found genomic signatures of selective sweeps near key genes related to economically important traits, such as the milk production (e.g., DGAT1, ABCG2), growth (e.g., XKR4), and reproduction (e.g., CSF2). Our data point to candidate genes which should be included in future studies attempting to identify genes to improve the extant breeds and facilitate generation of commercial breeds that fit better into the environments of Russia and other countries with similar climates

Is no news good news? Inconclusive genetic test results in BRCA1 and BRCA2 from patients and professionals' perspectives

<p>Abstract</p> <p>Background</p> <p>Women from families with a high risk of breast or ovarian cancer in which genetic testing for mutations in the <it>BRCA1/2 </it>genes is inconclusive are a vulnerable and understudied group. Furthermore, there are no studies of the professional specialists who treat them - geneticists, genetic counsellors/nurses, oncologists, gynaecologists and breast surgeons.</p> <p>Methods</p> <p>We conducted a small qualitative study that investigated women who had developed breast cancer under the age of 45 and who had an inconclusive <it>BRCA1/2 </it>genetic diagnostic test (where no mutations or unclassified variants were identified). We arranged three focus groups for affected women and their close female relatives - 13 women took part. We also interviewed 12 health professionals who were involved in the care of these women.</p> <p>Results</p> <p>The majority of the women had a good grasp of the meaning of their own or a family member's inconclusive result, but a few indicated some misunderstanding. Most of the women in this study underwent the test for the benefit of others in the family and none mentioned that they were having the test purely for themselves. A difficult issue for sisters of affected women was whether or not to undertake prophylactic breast surgery. The professionals were sensitive to the difficulties in explaining an inconclusive result. Some felt frustrated that technology had not as yet provided them with a better tool for prediction of risk.</p> <p>Conclusions</p> <p>Some of the women were left with the dilemma of what decision to make regarding medical management of their cancer risk. For the most part, the professionals believed that the women should be supported in whatever management decisions they considered best, provided these decisions were based on a complete and accurate understanding of the genetic test that had taken place in the family.</p

Phenotypic Expression of ADAMTS13 in Glomerular Endothelial Cells

Background: ADAMTS13 is the physiological von Willebrand factor (VWF)-cleaving protease. The aim of this study was to examine ADAMTS13 expression in kidneys from ADAMTS13 wild-type (Adamts13+/+) and deficient (Adamts13-/-) mice and to investigate the expression pattern and bioactivity in human glomerular endothelial cells. Methodology/Principal Findings: Immunohistochemistry was performed on kidney sections from ADAMTS13 wild-type and ADAMTS13-deficient mice. Phenotypic differences were examined by ultramorphology. ADAMTS13 expression in human glomerular endothelial cells and dermal microvascular endothelial cells was investigated by real-time PCR, flow cytometry, immunofluorescence and immunoblotting. VWF cleavage was demonstrated by multimer structure analysis and immunoblotting. ADAMTS13 was demonstrated in glomerular endothelial cells in Adamts13+/+ mice but no staining was visible in tissue from Adamts13-/- mice. Thickening of glomerular capillaries with platelet deposition on the vessel wall was detected in Adamts13-/- mice. ADAMTS13 mRNA and protein were detected in both human endothelial cells and the protease was secreted. ADAMTS13 activity was demonstrated in glomerular endothelial cells as cleavage of VWF. Conclusions/Significance: Glomerular endothelial cells express and secrete ADAMTS13. The proteolytic activity could have a protective effect preventing deposition of platelets along capillary lumina under the conditions of high shear stress present in glomerular capillaries. © 2011 Tati et al.published_or_final_versio

Fly Photoreceptors Encode Phase Congruency

More than five decades ago it was postulated that sensory neurons detect and selectively enhance behaviourally relevant features of natural signals. Although we now know that sensory neurons are tuned to efficiently encode natural stimuli, until now it was not clear what statistical features of the stimuli they encode and how. Here we reverse-engineer the neural code of Drosophila photoreceptors and show for the first time that photoreceptors exploit nonlinear dynamics to selectively enhance and encode phase-related features of temporal stimuli, such as local phase congruency, which are invariant to changes in illumination and contrast. We demonstrate that to mitigate for the inherent sensitivity to noise of the local phase congruency measure, the nonlinear coding mechanisms of the fly photoreceptors are tuned to suppress random phase signals, which explains why photoreceptor responses to naturalistic stimuli are significantly different from their responses to white noise stimuli

Circulating CD14brightCD16+ 'intermediate' monocytes exhibit enhanced parasite pattern recognition in human helminth infection.

Circulating monocyte sub-sets have recently emerged as mediators of divergent immune functions during infectious disease but their role in helminth infection has not been investigated. In this study we evaluated whether 'classical' (CD14brightCD16-), 'intermediate' (CD14brightCD16+), and 'non-classical' (CD14dimCD16+) monocyte sub-sets from peripheral blood mononuclear cells varied in both abundance and ability to bind antigenic material amongst individuals living in a region of Northern Senegal which is co-endemic for Schistosoma mansoni and S. haematobium. Monocyte recognition of excretory/secretory (E/S) products released by skin-invasive cercariae, or eggs, of S. mansoni was assessed by flow cytometry and compared between S. mansoni mono-infected, S. mansoni and S. haematobium co-infected, and uninfected participants. Each of the three monocyte sub-sets in the different infection groups bound schistosome E/S material. However, 'intermediate' CD14brightCD16+ monocytes had a significantly enhanced ability to bind cercarial and egg E/S. Moreover, this elevation of ligand binding was particularly evident in co-infected participants. This is the first demonstration of modulated parasite pattern recognition in CD14brightCD16+ intermediate monocytes during helminth infection, which may have functional consequences for the ability of infected individuals to respond immunologically to infection