PULSE - Spring 2016, Issue One

PULSE is the bi-quarterly student-run lifestyle magazine of Central Washington University.https://digitalcommons.cwu.edu/pulse/1003/thumbnail.jp

NeuroProv: Provenance data visualisation for neuroimaging analyses

© 2019 Elsevier Ltd Visualisation underpins the understanding of scientific data both through exploration and explanation of analysed data. Provenance strengthens the understanding of data by showing the process of how a result has been achieved. With the significant increase in data volumes and algorithm complexity, clinical researchers are struggling with information tracking, analysis reproducibility and the verification of scientific output. In addition, data coming from various heterogeneous sources with varying levels of trust in a collaborative environment adds to the uncertainty of the scientific outputs. This provides the motivation for provenance data capture and visualisation support for analyses. In this paper a system, NeuroProv is presented, to visualise provenance data in order to aid in the process of verification of scientific outputs, comparison of analyses, progression and evolution of results for neuroimaging analyses. The experimental results show the effectiveness of visualising provenance data for neuroimaging analyses

An Irish perspective on Cryptosporidium. Part 1

Cryptosporidiosis, a protozoal disease which causes significant morbidity in humans, is one of the chief causes of diarrhoea in neonatal ruminants. Although the parasite poses a significant threat to public health and animal health in Ireland, its epidemiology on the island is only poorly understood. Environmental studies have shown the waterborne parasite to be widespread in some untreated waterbodies around Ireland. The island's hydrogeological situation, combined with high stocking rates of livestock and the absence of filtration from regular water treatment, render it vulnerable to large-scale outbreaks. This review discusses the parasite in the Irish context and underlines the need for a reference facility to provide active surveillance on the island

SNi from SN2: a front-face mechanism ‘synthase’ engineered from a retaining hydrolase

SNi or SNi-like mechanisms, in which leaving group departure and nucleophile approach occur on the same ‘front’ face, have been observed previously experimentally and computationally in both the chemical and enzymatic (glycosyltransferase) substitution reactions of α-glycosyl electrophiles. Given the availability of often energetically comparable competing pathways for substitution (SNi vs SN1 vs SN2) the precise modulation of this archetypal reaction type should be feasible. Here, we show that the drastic engineering of a protein that catalyzes substitution, a retaining β-glycosidase (from Sulfolobus solfataricus SSβG), apparently changes the mode of reaction from “SN2” to “SNi”. Destruction of the nucleophilic Glu387 of SSβG-WT through Glu387Tyr mutation (E387Y) created a catalyst (SSβG-E387Y) with lowered but clear transglycosylation substitution activity with activated substrates, altered substrate and reaction preferences and hence useful synthetic (‘synthase’) utility by virtue of its low hydrolytic activity with unactivated substrates. Strikingly, the catalyst still displayed retaining β stereoselectivity, despite lacking a suitable nucleophile; pH-activity profile, mechanism-based inactivators and mutational analyses suggest that SSβG-E387Y operates without either the use of nucleophile or general acid/base residues, consistent with a SNi or SNi-like mechanism. An x-ray structure of SSβG-E387Y and subsequent metadynamics simulation suggest recruitment of substrates aided by a π-sugar interaction with the introduced Tyr387 and reveal a QM/MM free energy landscape for the substitution reaction catalyzed by this unnatural enzyme similar to those of known natural, SNi-like glycosyltransferase (GT) enzymes. Proton flight from the putative hydroxyl nucleophile to the developing p-nitrophenoxide leaving group of the substituted molecule in the reactant complex creates a hydrogen bond that appears to crucially facilitate the mechanism, mimicking the natural mechanism of SNi-GTs. An oxocarbenium ion-pair minimum along the reaction pathway suggests a step-wise SNi-like DN*ANss rather than a concerted SNi DNAN mechanism. This first observation of a front face mechanism in a β-retaining glycosyl transfer enzyme highlights, not only that unusual SNi reaction pathways may be accessed through direct engineering of catalysts with suitable environments, but also suggests that ‘β-SNi’ reactions are also feasible for glycosyl transfer enzymes and the more widespread existence of SNi or SNi-like mechanism in nature

Information retrieval and text mining technologies for chemistry

Efficient access to chemical information contained in scientific literature, patents, technical reports, or the web is a pressing need shared by researchers and patent attorneys from different chemical disciplines. Retrieval of important chemical information in most cases starts with finding relevant documents for a particular chemical compound or family. Targeted retrieval of chemical documents is closely connected to the automatic recognition of chemical entities in the text, which commonly involves the extraction of the entire list of chemicals mentioned in a document, including any associated information. In this Review, we provide a comprehensive and in-depth description of fundamental concepts, technical implementations, and current technologies for meeting these information demands. A strong focus is placed on community challenges addressing systems performance, more particularly CHEMDNER and CHEMDNER patents tasks of BioCreative IV and V, respectively. Considering the growing interest in the construction of automatically annotated chemical knowledge bases that integrate chemical information and biological data, cheminformatics approaches for mapping the extracted chemical names into chemical structures and their subsequent annotation together with text mining applications for linking chemistry with biological information are also presented. Finally, future trends and current challenges are highlighted as a roadmap proposal for research in this emerging field.A.V. and M.K. acknowledge funding from the European Community’s Horizon 2020 Program (project reference: 654021 - OpenMinted). M.K. additionally acknowledges the Encomienda MINETAD-CNIO as part of the Plan for the Advancement of Language Technology. O.R. and J.O. thank the Foundation for Applied Medical Research (FIMA), University of Navarra (Pamplona, Spain). This work was partially funded by Consellería de Cultura, Educación e Ordenación Universitaria (Xunta de Galicia), and FEDER (European Union), and the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684). We thank Iñigo Garciá -Yoldi for useful feedback and discussions during the preparation of the manuscript.info:eu-repo/semantics/publishedVersio

2018 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1005/thumbnail.jp

Challenge Demcare: management of challenging behaviour in dementia at home and in care homes:Development, evaluation and implementation of an online individualised intervention for care homes; and a cohort study of specialist community mental health care for families

Background: Dementia with challenging behaviour (CB) causes significant distress for caregivers and the person with dementia. It is associated with breakdown of care at home and disruption in care homes. Challenge Demcare aimed to assist care home staff and mental health practitioners who support families at home to respond effectively to CB. Objectives: To study the management of CB in care homes (ResCare) and in family care (FamCare). Following a conceptual overview, two systematic reviews and scrutiny of clinical guidelines, we (1) developed and tested a computerised intervention; (2) conducted a cluster randomised trial (CRT) of the intervention for dementia with CB in care homes; (3) conducted a process evaluation of implementation of the intervention; and (4) conducted a longitudinal observational cohort study of the management of people with dementia with CB living at home, and their carers. Review methods: Cochrane review of randomised controlled trials; systematic meta-ethnographic review of quantitative and qualitative studies. Design: ResCare – survey, CRT, process evaluation and stakeholder consultations. FamCare – survey, longitudinal cohort study, participatory development design process and stakeholder consultations. Comparative examination of baseline levels of CB in the ResCare trial and the FamCare study participants. Settings: ResCare – 63 care homes in Yorkshire. FamCare – 33 community mental health teams for older people (CMHTsOP) in seven NHS organisations across England. Participants: ResCare – 2386 residents and 861 staff screened for eligibility; 555 residents with dementia and CB; 277 ‘other’ residents; 632 care staff; and 92 staff champions. FamCare – every new referral (n = 5360) reviewed for eligibility; 157 patients with dementia and CB, with their carer; and 26 mental health practitioners. Stakeholder consultations – initial workshops with 83 practitioners and managers from participating organisations; and 70 additional stakeholders using eight group discussions and nine individual interviews. Intervention: An online application for case-specific action plans to reduce CB in dementia, consisting of e-learning and bespoke decision support care home and family care e-tools. Main outcome measures: ResCare – survey with the Challenging Behaviour Scale; measurement of CB with the Neuropsychiatric Inventory (NPI) and medications taken from prescriptions; implementation with thematic views from participants and stakeholders. FamCare – case identification from all referrals to CMHTsOP; measurement of CB with the Revised Memory and Behaviour Problems Checklist and NPI; medications taken from prescriptions; and thematic views from stakeholders. Costs of care calculated for both settings. Comparison of the ResCare trial and FamCare study participants used the NPI, Clinical Dementia Rating and prescribed medications. Results: ResCare – training with group discussion and decision support for individualised interventions did not change practice enough to have an impact on CB in dementia. Worksite e-learning opportunities were not readily taken up by care home staff. Smaller homes with a less hierarchical management appear more ready than others to engage in innovation. FamCare – home-dwelling people with dementia and CB are referred to specialist NHS services, but treatment over 6 months, averaging nine contacts per family, had no overall impact on CB. Over 60% of people with CB had mild dementia. Families bear the majority of the care costs of dementia with CB. A care gap in the delivery of post-diagnostic help for families supporting relatives with dementia and significant CB at home has emerged. Higher levels of CB were recorded in family settings; and prescribing practices were suboptimal in both care home and family settings. Limitations: Functionality of the software was unreliable, resulting in delays. This compromised the feasibility studies and undermined delivery of the intervention in care homes. A planned FamCare CRT could not proceed because of insufficient referrals. Conclusions: A Cochrane review of individualised functional analysis-based interventions suggests that these show promise, although delivery requires a trained dementia care workforce. Like many staff training interventions, our interactive e-learning course was well received by staff when delivered in groups with facilitated discussion. Our e-learning and decision support e-tool intervention in care homes, in its current form, without ongoing review of implementation of recommended action plans, is not effective at reducing CB when compared with usual care. This may also be true for staff training in general. A shift in priorities from early diagnosis to early recognition of dementia with clinically significant CB could bridge the emerging gap and inequities of care to families. Formalised service improvements in the NHS, to co-ordinate such interventions, may stimulate better opportunities for practice models and pathways. Separate services for care homes and family care may enhance the efficiency of delivery and the quality of research on implementation into routine care. Future work: There is scope for extending functional analysis-based interventions with communication and interaction training for carers. Our clinical workbooks, video material of real-life episodes of CB and process evaluation tool resources require further testing. There is an urgent need for evaluation of interventions for home-dwelling people with dementia with clinically significant CB, delivered by trained dementia practitioners. Realist evaluation designs may illuminate how the intervention might work, and for whom, within varying service contexts

Interventions for hyperhidrosis in secondary care : a systematic review and value-of-information analysis

Background: Hyperhidrosis is uncontrollable excessive sweating that occurs at rest, regardless of temperature. The symptoms of hyperhidrosis can significantly affect quality of life. The management of hyperhidrosis is uncertain and variable. Objective: To establish the expected value of undertaking additional research to determine the most effective interventions for the management of refractory primary hyperhidrosis in secondary care. Methods: A systematic review and economic model, including a value-of-information (VOI) analysis. Treatments to be prescribed by dermatologists and minor surgical treatments for hyperhidrosis of the hands, feet and axillae were reviewed; as endoscopic thoracic sympathectomy (ETS) is incontestably an end-of-line treatment, it was not reviewed further. Fifteen databases (e.g. CENTRAL, PubMed and PsycINFO), conference proceedings and trial registers were searched from inception to July 2016. Systematic review methods were followed. Pairwise meta-analyses were conducted for comparisons between botulinum toxin (BTX) injections and placebo for axillary hyperhidrosis, but otherwise, owing to evidence limitations, data were synthesised narratively. A decision-analytic model assessed the cost-effectiveness and VOI of five treatments (iontophoresis, medication, BTX, curettage, ETS) in 64 different sequences for axillary hyperhidrosis only. Results and conclusions: Fifty studies were included in the effectiveness review: 32 randomised controlled trials (RCTs), 17 non-RCTs and one large prospective case series. Most studies were small, rated as having a high risk of bias and poorly reported. The interventions assessed in the review were iontophoresis, BTX, anticholinergic medications, curettage and newer energy-based technologies that damage the sweat gland (e.g. laser, microwave). There is moderate-quality evidence of a large statistically significant effect of BTX on axillary hyperhidrosis symptoms, compared with placebo. There was weak but consistent evidence for iontophoresis for palmar hyperhidrosis. Evidence for other interventions was of low or very low quality. For axillary hyperhidrosis cost-effectiveness results indicated that iontophoresis, BTX, medication, curettage and ETS was the most cost-effective sequence (probability 0.8), with an incremental cost-effectiveness ratio of £9304 per quality-adjusted life-year. Uncertainty associated with study bias was not reflected in the economic results. Patients and clinicians attending an end-of-project workshop were satisfied with the sequence of treatments for axillary hyperhidrosis identified as being cost-effective. All patient advisors considered that the Hyperhidrosis Quality of Life Index was superior to other tools commonly used in hyperhidrosis research for assessing quality of life. Limitations: The evidence for the clinical effectiveness and safety of second-line treatments for primary hyperhidrosis is limited. This meant that there was insufficient evidence to draw conclusions for most interventions assessed and the cost-effectiveness analysis was restricted to hyperhidrosis of the axilla. Future work: Based on anecdotal evidence and inference from evidence for the axillae, participants agreed that a trial of BTX (with anaesthesia) compared with iontophoresis for palmar hyperhidrosis would be most useful. The VOI analysis indicates that further research into the effectiveness of existing medications might be worthwhile, but it is unclear that such trials are of clinical importance. Research that established a robust estimate of the annual incidence of axillary hyperhidrosis in the UK population would reduce the uncertainty in future VOI analyses