A comparative study of machine learning methods for verbal autopsy text classification

A Verbal Autopsy is the record of an interview about the circumstances of an uncertified death. In developing countries, if a death occurs away from health facilities, a field-worker interviews a relative of the deceased about the circumstances of the death; this Verbal Autopsy can be reviewed offsite. We report on a comparative study of the processes involved in Text Classification applied to classifying Cause of Death: feature value representation; machine learning classification algorithms; and feature reduction strategies in order to identify the suitable approaches applicable to the classification of Verbal Autopsy text. We demonstrate that normalised term frequency and the standard TFiDF achieve comparable performance across a number of classifiers. The results also show Support Vector Machine is superior to other classification algorithms employed in this research. Finally, we demonstrate the effectiveness of employing a ’locally-semisupervised’ feature reduction strategy in order to increase performance accuracy

Peptide redesign for inhibition of the complement system: Targeting age-related macular degeneration.

PurposeTo redesign a complement-inhibiting peptide with the potential to become a therapeutic for dry and wet age-related macular degeneration (AMD).MethodsWe present a new potent peptide (Peptide 2) of the compstatin family. The peptide is developed by rational design, based on a mechanistic binding hypothesis, and structural and physicochemical properties derived from molecular dynamics (MD) simulation. The inhibitory activity, efficacy, and solubility of Peptide 2 are evaluated using a hemolytic assay, a human RPE cell-based assay, and ultraviolet (UV) absorption properties, respectively, and compared to the respective properties of its parent peptide (Peptide 1).ResultsThe sequence of Peptide 2 contains an arginine-serine N-terminal extension (a characteristic of parent Peptide 1) and a novel 8-polyethylene glycol (PEG) block C-terminal extension. Peptide 2 has significantly improved aqueous solubility compared to Peptide 1 and comparable complement inhibitory activity. In addition, Peptide 2 is more efficacious in inhibiting complement activation in a cell-based model that mimics the pathobiology of dry AMD.ConclusionsWe have designed a new peptide analog of compstatin that combines N-terminal polar amino acid extensions and C-terminal PEGylation extensions. This peptide demonstrates significantly improved aqueous solubility and complement inhibitory efficacy, compared to the parent peptide. The new peptide overcomes the aggregation limitation for clinical translation of previous compstatin analogs and is a candidate to become a therapeutic for the treatment of AMD

Addressing SRGBV in Ethiopia: A scoping study of policy and practice to reduce gender-based violence in and around schools

School-related gender-based violence (SRGBV) describes physical, sexual and psychological acts of violence in and around schools, underpinned by unequal access to resources and power, and inequitable norms and stereotypes. While there is increasing recognition of SRGBV as a major issue globally, rigorous reviews of literature have concluded that evidence about effective ways to address it is lacking. The End Gender Violence in Schools (EGVS) initiative, led by UNICEF with support from the Global Partnership for Education (GPE) and UNGEI, aims to build evidence to better understand, inform and strengthen the process of policy enactment on SRGBV in Ethiopia, Zambia, Togo and Cote d’Ivoire. Findings from the initiative in these four countries will contribute to global debates on how to address SRGBV. This summary presents draft findings from a scoping study of policy, practice and evidence on SRGBV in Ethiopia, which was carried out in 2016. The main objective of the study was to analyse responses to gender-based violence in and around schools in Ethiopia, in order to inform future planning of policy and practice initiatives. The study was a collaboration between the Government of Ethiopia, UNICEF, and the UCL Institute of Education. Several methods for data collection were employed: 1) Two interactive workshops led by the Ministry of Education and facilitated by UNICEF and the UCL Institute of Education (March 2016; December 2016); 2) Literature review and documentary analysis of legislative and policy texts, research reports and datasets, and documents describing programmes or interventions addressing SRGBV in Ethiopia; 3) 23 in-depth interviews with governmental and non-governmental experts. The research questions addressed 1) what we know about SRGBV in Ethiopia, 2) what policies, laws and programmes exist and how well they are enacted, and 3) the availability and quality of evidence on SRGBV

Associations between maternal characteristics and pharmaceutical treatment of gestational diabetes: an analysis of the UK Born in Bradford (BiB) cohort study

Objectives: To identify the maternal characteristics associated with pharmaceutical treatment of gestational diabetes mellitus (GDM). Design: Prospective birth cohort study. Setting: Bradford, UK. Participants: 762 women from the Born in Bradford (BiB) cohort who were treated for GDM in a singleton pregnancy. BiB cohort participants were recruited from 2007 to 2010. All women booked for delivery were screened for GDM between 26 and 28 weeks of gestation using a 75 g 2-hour oral glucose tolerance test (OGTT). Outcome measure: GDM treatment type: lifestyle changes advice (lifestyle changes), lifestyle changes advice with supplementary insulin (insulin) and lifestyle changes advice with supplementary metformin (metformin). Results: 244 (32%) women were prescribed lifestyle changes advice alone while 518 (68%) were offered supplemental pharmaceutical treatment. The odds of receiving pharmaceutical treatment relative to lifestyle changes advice alone were increased for mothers who were obese (OR 4.6, 95% CI 2.8 to 7.5), those who smoked (OR 2.6, 95% CI 1.2 to 5.5) and had higher fasting glucose levels at OGTT (OR 2.1, 95% CI 1.6 to 2.7). The odds of being prescribed pharmaceutical treatment rather than lifestyle changes advice were lower for Pakistani women (OR 0.7, 95% CI 0.4 to 1.0)) than White British women. Relative to insulin treatment, metformin was more likely to be offered to obese women than normal weight women (relative risk ratio, RRR 3.2, 95% CI 1.3 to 7.8) and less likely to be prescribed to women with higher fasting glucose concentrations at OGTT (RRR 0.3, 95% CI 0.2 to 0.6). Conclusions: In the BiB cohort, GDM pharmaceutical treatment tended to be prescribed to women who were obese, White British, who smoked and had more severe hyperglycaemia. The characteristics of metformin-treated mothers differed from those of insulin-treated mothers as they were more likely to be obese but had lower glucose concentrations at diagnosis

Addressing School Related Gender Based Violence in Zambia: A Scoping Study

This report presents findings from a scoping study of policy, practice and evidence on school-related gender-based violence (SRGBV) in Zambia, which was carried out in 2016. The main objective of the study was to analyse responses to gender-based violence in and around schools in Zambia, in order to inform future planning of policy and practice initiatives. The study was a collaboration between the government of Zambia, UNICEF, and researchers at the UCL Institute of Education working alongside consultant, Romana Maumbu. Its core elements consist of: analysis of legislation and policy; analysis of programming on SRGBV; mapping of stakeholders working on SRGBV; and the identification and evaluation of research and data sets. The findings presented here will be used to guide decision making for phase two of the initiative which will take place during 2017, as well as longer term planning and action on SRGBV in Zambia. The findings will provide the basis for reflection and the development of the action plan for the next phase of the EGVS initiative

Cdk1 and SUMO Regulate Swe1 Stability

The Swe1/Wee1 kinase phosphorylates and inhibits Cdk1-Clb2 and is a major mitotic switch. Swe1 levels are controlled by ubiquitin mediated degradation, which is regulated by interactions with various mitotic kinases. We have recently reported that Swe1 levels are capable of sensing the progress of the cell cycle by measuring the levels of Cdk1-Clb2, Cdc5 and Hsl1. We report here a novel mechanism that regulates the levels of Swe1. We show that S.cerevisiae Swe1 is modified by Smt3/SUMO on residue K594 in a Cdk1 dependant manner. A degradation of the swe1K594R mutant that cannot be modified by Smt3 is considerably delayed in comparison to wild type Swe1. Swe1K594R cells express elevated levels of Swe1 protein and demonstrate higher levels of Swe1 activity as manifested by Cdk1-Y19 phosphorylation. Interestingly this mutant is not targeted, like wild type Swe1, to the bud neck where Swe1 degradation takes place. We show that Swe1 is SUMOylated by the Siz1 SUMO ligase, and consequently siz1Δ cells express elevated levels of Swe1 protein and activity. Finally we show that swe1K594R cells are sensitive to osmotic stress, which is in line with their compromised regulation of Swe1 degradation

Development of FRET Assay into Quantitative and High-throughput Screening Technology Platforms for Protein–Protein Interactions

Förster resonance energy transfer (FRET) technology has been widely used in biological and biomedical research and is a very powerful tool in elucidating protein interactions in many cellular processes. Ubiquitination and SUMOylation are multi-step cascade reactions, involving multiple enzymes and protein–protein interactions. Here we report the development of dissociation constant (Kd) determination for protein–protein interaction and cell-based high-throughput screening (HTS) assay in SUMOylation cascade using FRET technology. These developments are based on steady state and high efficiency of fluorescent energy transfer between CyPet and YPet fused with SUMO1 and Ubc9, respectively. The developments in theoretical and experimental procedures for protein interaction Kd determination and cell-based HTS provide novel tools in affinity measurement and protein interaction inhibitor screening. The Kd determined by FRET between SUMO1 and Ubc9 is compatible with those determined with other traditional approaches, such as isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR). The FRET-based HTS is pioneer in cell-based HTS. Both Kd determination and cell-based HTS, carried out in 384-well plate format, provide powerful tools for large-scale and high-throughput applications

The Origin of Black Hole Entropy in String Theory

I review some recent work in which the quantum states of string theory which are associated with certain black holes have been identified and counted. For large black holes, the number of states turns out to be precisely the exponential of the Bekenstein-Hawking entropy. This provides a statistical origin for black hole thermodynamics in the context of a potential quantum theory of gravity.Comment: 18 pages (To appear in the proceedings of the Pacific Conference on Gravitation and Cosmology, Seoul, Korea, February 1-6, 1996.

Direct and indirect links between children’s socio-economic status and education: pathways via mental health, attitude, and cognition

AbstractA child’s socio-economic environment can profoundly affect their development. While existing literature focusses on simplified metrics and pair-wise relations between few variables, we aimed to capture complex interrelationships between several relevant domains using a broad assessment of 519 children aged 7–9 years. Our analyses comprised three multivariate techniques that complimented each other, and worked at different levels of granularity. First, an exploratory factor analysis (principal component analysis followed by varimax rotation) revealed that our sample varied along continuous dimensions of cognition, attitude and mental health (from parallel analysis); with potentially emerging dimensions speed and socio-economic status (passed Kaiser’s criterion). Second, k-means cluster analysis showed that children did not group into discrete phenotypes. Third, a network analysis on the basis of bootstrapped partial correlations (confirmed by both cross-validated LASSO and multiple comparisons correction of binarised connection probabilities) uncovered how our developmental measures interconnected: educational outcomes (reading and maths fluency) were directly related to cognition (short-term memory, number sense, processing speed, inhibition). By contrast, mental health (anxiety and depression symptoms) and attitudes (conscientiousness, grit, growth mindset) showed indirect relationships with educational outcomes via cognition. Finally, socio-economic factors (neighbourhood deprivation, family affluence) related directly to educational outcomes, cognition, mental health, and even grit. In sum, cognition is a central cog through which mental health and attitude relate to educational outcomes. However, through direct relations with all components of developmental outcomes, socio-economic status acts as a great ‘unequaliser’.</jats:p

Alcohol-induced retrograde facilitation renders witnesses of crime less suggestible to misinformation

RATIONALE: Research has shown that alcohol can have both detrimental and facilitating effects on memory: intoxication can lead to poor memory for information encoded after alcohol consumption (anterograde amnesia) and may improve memory for information encoded before consumption (retrograde facilitation). This study examined whether alcohol consumed after witnessing a crime can render individuals less vulnerable to misleading post-event information (misinformation). METHOD: Participants watched a simulated crime video. Thereafter, one third of participants expected and received alcohol (alcohol group), one third did not expect but received alcohol (reverse placebo), and one third did not expect nor receive alcohol (control). After alcohol consumption, participants were exposed to misinformation embedded in a written narrative about the crime. The following day, participants completed a cued-recall questionnaire about the event. RESULTS: Control participants were more likely to report misinformation compared to the alcohol and reverse placebo group. CONCLUSION: The findings suggest that we may oversimplify the effect alcohol has on suggestibility and that sometimes alcohol can have beneficial effects on eyewitness memory by protecting against misleading post-event information