Pipelined Asynchronous Circuits

This thesis presents a design style for implementing communicating sequential processes (CSP) as quasi delay insensitive asynchronous circuits, based on the compilation method of [1]. Although hand compilation can always yield optimal circuits to a good designer, a restricted approach is suggested which can easily implement circuits with some slack between inputs and outputs. These circuits are fast and versatile building blocks for highly pipelined designs. The first chapter presents the implementation approach for individual cells. The second chapter investigates the time behavior of complex pipelined circuits, with the goal of adding slack where necessary and adjusting transistor sizes to optimize the overall throughput

Atomic-scale compensation phenomena at polar interfaces

The interfacial screening charge that arises to compensate electric fields of dielectric or ferroelectric thin films is now recognized as the most important factor in determining the capacitance or polarization of ultrathin ferroelectrics. Here we investigate using aberration-corrected electron microscopy and density functional theory how interfaces cope with the need to terminate ferroelectric polarization. In one case, we show evidence for ionic screening, which has been predicted by theory but never observed. For a ferroelectric film on an insulating substrate, we found that compensation can be mediated by interfacial charge generated, for example, by oxygen vacancies.Comment: 3 figure

A tale of two toolkits, report the third: on the usage and performance of HIVE-COTE v1.0

The Hierarchical Vote Collective of Transformation-based Ensembles (HIVE-COTE) is a heterogeneous meta ensemble for time series classification. Since it was first proposed in 2016, the algorithm has undergone some minor changes and there is now a configurable, scalable and easy to use version available in two open source repositories. We present an overview of the latest stable HIVE-COTE, version 1.0, and describe how it differs to the original. We provide a walkthrough guide of how to use the classifier, and conduct extensive experimental evaluation of its predictive performance and resource usage. We compare the performance of HIVE-COTE to three recently proposed algorithms

Development of criteria for epilepsy genetic testing in Ontario, Canada

Multiple genes/variants have been implicated in various epileptic conditions. However, there is little general guidance available on the circumstances in which genetic testing is indicated and test selection in order to guide optimal test appropriateness and benefit. This is an account of the development of guidelines for genetic testing in epilepsy, which have been developed in Ontario, Canada. The Genetic Testing Advisory Committee was established in Ontario to review the clinical utility and validity of genetic tests and the provision of genetic testing in Ontario. As part of their mandate, the committee also developed recommendations and guidelines for genetic testing in epilepsy. The recommendations include mandatory prerequisites for an epileptology/geneticist/clinical biochemical geneticist consultation, prerequisite diagnostic procedures, circumstances in which genetic testing is indicated and not indicated and guidance for selection of genetic tests, including their general limitations and considerations. These guidelines represent a step toward the development of evidence-based gene panels for epilepsy in Ontario, the repatriation of genetic testing for epilepsy into Ontario molecular genetic laboratories and public funding of genetic tests for epilepsy in Ontario

Patient experiences of cancer care: scoping review, future directions, and introduction of a new data resource: Surveillance Epidemiology and End Results-Consumer Assessment of Healthcare Providers and Systems (SEER-CAHPS)

The shift towards providing high value cancer care has placed increasing importance on patient experiences. This scoping review summarizes patient experience literature, highlights research gaps, and provides future research directions. We then introduce a new resource that links the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) program with the Centers for Medicare and Medicaid Services Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey and longitudinal medical claims data. We conducted a scoping review to identify relevant research within the Medicare CAHPS domain that examine factors associated with patient-reported experiences with their cancer care. Gaps indicate a need for population-based research to explore relationships between cancer patient experiences, healthcare utilization, and subsequent patient outcomes. SEER-CAHPS, a publicly accessible data resource, may assist in addressing these gaps by linking cancer registry (SEER), survey data reported by Medicare beneficiaries (CAHPS), and Medicare claims, providing unique insight into quality of care. Linked data include 231,089 surveys from patients with a cancer diagnosis, and 4,236,529 surveys from patients without a cancer diagnosis. Results indicate substantial gaps in our knowledge of patient experiences and the need for additional resources. SEER-CAHPS links direct patient feedback with cancer registry and Medicare claims, making it an important source of information on experiences and healthcare utilization. Increasing recognition of the importance of patient-centeredness points to the need for population-based studies. Findings from SEER-CAHPS will inform initiatives to improve care delivery

<i>PHKA2</i> variants expand the phenotype of phosphorylase B kinase deficiency to include patients with ketotic hypoglycemia only

Idiopathic ketotic hypoglycemia (IKH) is a diagnosis of exclusion with glycogen storage diseases (GSDs) as a differential diagnosis. GSD IXa presents with ketotic hypoglycemia (KH), hepatomegaly, and growth retardation due to PHKA2 variants. In our multicenter study, 12 children from eight families were diagnosed or suspected of IKH. Whole‐exome sequencing or targeted next‐generation sequencing panels were performed. We identified two known and three novel (likely) pathogenic PHKA2 variants, such as p.(Pro869Arg), p.(Pro498Leu), p.(Arg2Gly), p.(Arg860Trp), and p.(Val135Leu), respectively. Erythrocyte phosphorylase kinase activity in three patients with the novel variants p.(Arg2Gly) and p.(Arg860Trp) were 15%–20% of mean normal. One patient had short stature and intermittent mildly elevated aspartate aminotransferase, but no hepatomegaly. Family testing identified two asymptomatic children and 18 adult family members with one of the PHKA2 variants, of which 10 had KH symptoms in childhood and 8 had mild symptoms in adulthood. Our study expands the classical GSD IXa phenotype of PHKA2 missense variants to a continuum from seemingly asymptomatic carriers, over KH‐only with phosphorylase B kinase deficiency, to more or less complete classical GSD IXa. In contrast to typical IKH, which is confined to young children, KH may persist into adulthood in the KH‐only phenotype of PHKA2

HIVE-COTE 2.0: a new meta ensemble for time series classification

The Hierarchical Vote Collective of Transformation-based Ensembles (HIVE-COTE) is a heterogeneous meta ensemble for time series classification. HIVE-COTE forms its ensemble from classifiers of multiple domains, including phase-independent shapelets, bag-of-words based dictionaries and phase-dependent intervals. Since it was first proposed in 2016, the algorithm has remained state of the art for accuracy on the UCR time series classification archive. Over time it has been incrementally updated, culminating in its current state, HIVE-COTE 1.0. During this time a number of algorithms have been proposed which match the accuracy of HIVE-COTE. We propose comprehensive changes to the HIVE-COTE algorithm which significantly improve its accuracy and usability, presenting this upgrade as HIVE-COTE 2.0. We introduce two novel classifiers, the Temporal Dictionary Ensemble and Diverse Representation Canonical Interval Forest, which replace existing ensemble members. Additionally, we introduce the Arsenal, an ensemble of ROCKET classifiers as a new HIVE-COTE 2.0 constituent. We demonstrate that HIVE-COTE 2.0 is significantly more accurate on average than the current state of the art on 112 univariate UCR archive datasets and 26 multivariate UEA archive datasets

Tools for delivering entomopathogenic fungi to malaria mosquitoes: effects of delivery surfaces on fungal efficacy and persistence.

BACKGROUND\ud \ud Entomopathogenic fungi infection on malaria vectors increases daily mortality rates and thus represents a control measure that could be used in integrated programmes alongside insecticide-treated bed nets (ITNs) and indoor residual spraying (IRS). Before entomopathogenic fungi can be integrated into control programmes, an effective delivery system must be developed.\ud \ud METHODS\ud \ud The efficacy of Metarhizium anisopliae ICIPE-30 and Beauveria bassiana I93-825 (IMI 391510) (2 × 10(10) conidia m(-2)) applied on mud panels (simulating walls of traditional Tanzanian houses), black cotton cloth and polyester netting was evaluated against adult Anopheles gambiae sensu stricto. Mosquitoes were exposed to the treated surfaces 2, 14 and 28 d after conidia were applied. Survival of mosquitoes was monitored daily.\ud \ud RESULTS\ud \ud All fungal treatments caused a significantly increased mortality in the exposed mosquitoes, descending with time since fungal application. Mosquitoes exposed to M. anisopliae conidia on mud panels had a greater daily risk of dying compared to those exposed to conidia on either netting or cotton cloth (p < 0.001). Mosquitoes exposed to B. bassiana conidia on mud panels or cotton cloth had similar daily risk of death (p = 0.14), and a higher risk than those exposed to treated polyester netting (p < 0.001). Residual activity of fungi declined over time; however, conidia remained pathogenic at 28 d post application, and were able to infect and kill 73 - 82% of mosquitoes within 14 d.\ud \ud CONCLUSION\ud \ud Both fungal isolates reduced mosquito survival on immediate exposure and up to 28 d after application. Conidia were more effective when applied on mud panels and cotton cloth compared with polyester netting. Cotton cloth and mud, therefore, represent potential substrates for delivering fungi to mosquitoes in the field

Increasing outdoor host-seeking in Anopheles gambiae over 6 years of vector control on Bioko Island.

BACKGROUND: Vector control through indoor residual spraying (IRS) has been employed on Bioko Island, Equatorial Guinea, under the Bioko Island Malaria Control Project (BIMCP) since 2004. This study analyses the change in mosquito abundance, species composition and outdoor host-seeking proportions from 2009 to 2014, after 11 years of vector control on Bioko Island. METHODS: All-night indoor and outdoor human landing catches were performed monthly in the Bioko Island villages of Mongola, Arena Blanca, Biabia and Balboa from 2009 to 2014. Collected mosquitoes were morphologically identified and a subset of Anopheles gambiae sensu lato (s.l.) were later identified molecularly to their sibling species. Mosquito collection rates, species composition and indoor/outdoor host-seeking sites were analysed using generalized linear mixed models to assess changes in mosquito abundance and behaviour. RESULTS: The overall mosquito collection rate declined in each of the four Bioko Island villages. Anopheles coluzzii and Anopheles melas comprised the An. gambiae s.l. mosquito vector population, with a range of species proportions across the four villages. The proportion of outdoor host-seeking An. gambiae s.l. mosquitoes increased significantly in all four villages with an average increase of 58.8 % [57.9, 59.64 %] in 2009 to 70.0 % [67.8, 72.0 %] in 2014. Outdoor host-seeking rates did not increase in the month after an IRS spray round compared to the month before, suggesting that insecticide repellency has little impact on host-seeking behaviour. CONCLUSION: While vector control on Bioko Island has succeeded in substantial reduction in overall vector biting rates, populations of An. coluzzii and An. melas persist. Host-seeking behaviour has changed in these An. gambiae s.l. populations, with a shift towards outdoor host-seeking. During this study period, the proportion of host-seeking An. gambiae s.l. caught outdoors observed on Bioko Island increased to high levels, exceeding 80 % in some locations. It is possible that there may be a genetic basis underlying this large shift in host-seeking behaviour, in which case outdoor feeding could pose a serious threat to current vector control programmes. Currently, the BIMCP is preparing for this potential challenge by testing source reduction as a complementary control effort that also targets outdoor transmission