A guide to machine learning for biologists

The expanding scale and inherent complexity of biological data have encouraged a growing use of machine learning in biology to build informative and predictive models of the underlying biological processes. All machine learning techniques fit models to data; however, the specific methods are quite varied and can at first glance seem bewildering. In this Review, we aim to provide readers with a gentle introduction to a few key machine learning techniques, including the most recently developed and widely used techniques involving deep neural networks. We describe how different techniques may be suited to specific types of biological data, and also discuss some best practices and points to consider when one is embarking on experiments involving machine learning. Some emerging directions in machine learning methodology are also discussed

Cost of a diagonal sexual and reproductive health package to enhance reproductive health among female sex workers in Durban, South Africa

Background and objectives: In response to HIV epidemic in Sub- Saharan Africa, there has been widespread concern about the structure and delivery of Sexual Reproductive Health (SRH) and HIV services to improve outcomes among high-risk groups, including sex workers. The ‘Diagonal Interventions to Fast-Forward Enhanced Reproductive health’ (DIFFER) project was conceptualised based on the hypothesis that integrating vertical SRH interventions targeted to FSW, with horizontal health systems strengthening, is likely to be more effective and cost-effective than current practice. The aim of the study was to measure the cost of designing and delivering a SRH package for female sex workers in Durban, South Africa, as part of the DIFFER project. / Methods: We measured the total and incremental costs of the DIFFER intervention package in Durban from a provider perspective, using a combination of ingredients and activity based costing approaches. An excel-based data capture tool was developed to collect the intervention package cost data. The intervention costs were collected prospectively from the project accounts of the implementing agencies and costs to the public health providers were collected via key informant interviews using a cost data capture form and subsequently entered into the spreadsheet. The total and average annual costs, as well as total and average annual costs per sex worker covered were estimated. All costs were adjusted for inflation, discounted and converted to 2016 International dollar. / Results: Total and average annual program costs of implementing the DIFFER intervention in Durban were INT$411,239 (INT$ 428,461, including services provided to the general population) and INT$256,594 (INT$ 273,816, including services provided to the general population) respectively. The total cost and average annual cost per sex worker covered were INT$117 and INT$ 73 respectively. Staff costs accounted for the largest proportion of the intervention cost, comprising more than 80% of the total cost, following by material and supplies, accounting for 10% of costs. / Conclusion: The DIFFER intervention package in Durban is a low cost intervention and likely to be cost-effective and sustainable. The intervention can be considered for replication and scale-up in South Africa and similar settings elsewhere

Decentralisation and performance: Autonomy and incentives in Local Health Economies

This project will examine the inter-relationship between governance mechanisms, autonomy and incentives in local health economies (LHEs). This interaction shapes decentralisation policies in the NHS and is thought to shape LHE performance. Recently, English health policy has been implementing new forms of decentralisation (eg. earned autonomy, Foundation Trusts) by altering the mix of governance mechanisms (command, collaboration and competition) and making explicit use of autonomy and incentives, thereby aiming to improve NHS performance. Local contextual factors might also shape performance outcomes. The project involves a synergy between the multi-disciplinary teams involved in 2 previous NCC-SDO funded studies. The aim is to investigate the inter-relationship between decentralisation and performance in LHEs. The project has 5 objectives: a. To examine the impact of decentralisation upon performance through analysis of selected 'tracers (as examples of current priorities) in 3 case-studies; b. To describe the local interaction of governance mechanisms; c. To evaluate the degree of autonomy available to local health-care organisations; d. To assess the (financial and non-financial) incentives associated with different policy initiatives; e. To provide lessons for policy-makers and managers at all levels in implementing decentralisation, managing the implications of autonomy and incentives, and addressing performance management through incentives. The study will use mixed methods. First, analysis of policy and performance data will generate the broad pattern of decentralisation and performance across England. Analysis of these data will aid selection of case-studies and 'tracers (examples within case-studies). Second, three case-studies will be selected which represent a maximum variety of pre-defined criteria. Longitudinal, comparative case-study methods include (a) 'mapping LHE performance and organisational characteristics (using local performance and activity data, and published reports); (b) a survey of senior staff in 3 LHEs (n=c.180) to provide their perceptions of current LHE issues and constraints (especially relating to tracer examples); (c) interviews with a sample of stakeholders (n=c.120) will identify the strengths and effects of organisational relationships across the LHE (such as the impact of service developments in the tracer examples); (d) observation of local planning meetings. Parts (a) and (b) will be conducted in year 1, parts (c) and (d) in years 2 and 3. Quantitative analysis will provide descriptive statistics of broad patterns and association. Qualitative analysis will provide thematic comparisons by LHE, organisational type and tracer example. Analysis will identify the pathways by which governance, autonomy and incentives can facilitate improved performance and also the conditions under which the optimal balance of these may be achieved in different contexts. The study will also consider conceptual frameworks (including 'decision space , resource dependency and principal-agent) to improve understanding of the inter-relationships within LHE and the intersection of national/vertical and local/horizontal pressures affecting performance. The study will engage decision-makers at all stages (via data collection, formative and summative feedback and as members of an Advisory Group). Formative feedback to LHEs (and NCC-SDO) will help validate emergent findings and sharpen subsequent fieldwork. Final dissemination will include such (oral and written) feedback, NCC-SDO report, presentations and publications to practitioner and research communities

Pharmacology of HIV integrase inhibitors

The purpose of this paper is to review recent and relevant pharmacology data for three HIV integrase inhibitors: raltegravir (marketed), dolutegravir and elvitegravir (both in Phase III drug development)

Programmable Deuteration of Indoles via Reverse Deuterium Exchange

Methods for selective deuterium incorporation into drug-like molecules have become extremely valuable due to the commercial, mechanistic, and biological importance of deuterated compounds. Herein, we report a programmable labeling platform that allows access to C2, C3, or C2- and C3-deuterated indoles under mild, user-friendly conditions. The C2-deuterated indoles are accessed using a reverse hydrogen isotope exchange strategy which represents the first non-directed C2-deuteration of indoles

South Africans with Recent Pregnancy Rarely Know Partner’s HIV Serostatus: Implications for Serodiscordant Couples Interventions

Background: Implementation of safer conception strategies requires knowledge of partner HIV-serostatus. We recruited women and men in a high HIV-prevalence setting for a study to assess periconception risk behavior among individuals reporting HIV-serodiscordant partnerships. We report screening data from that study with the objective of estimating the proportion of individuals who are aware that they are in an HIV-serodiscordant relationship at the time of conception. Methods: We screened women and men attending antenatal and antiretroviral clinics in Durban, South Africa for enrollment in a study of periconception risk behavior among individuals with serodiscordant partners. Screening questionnaires assessed for study eligibility including age 18–45 years (for women) or at least 18 years of age (for men), pregnancy in past year (women) or partner pregnancy in the past 3 years (men), HIV status of partner for recent pregnancy, participant’s HIV status, and infected partner’s HIV status having been known before the referent pregnancy. Results: Among 2620 women screened, 2344 (90%) met age and pregnancy criteria and knew who fathered the referent pregnancy. Among those women, 963 (41%) did not know the pregnancy partner’s HIV serostatus at time of screening. Only 92 (4%) reported knowing of a serodiscordant partnership prior to pregnancy. Among 1166 men screened, 225 (19%) met age and pregnancy criteria. Among those men, 71 (32%) did not know the pregnancy partner’s HIV status and only 30 (13%) reported knowing of a serodiscordant partnership prior to pregnancy. Conclusions: In an HIV-endemic setting, awareness of partner HIV serostatus is rare. Innovative strategies to increase HIV testing and disclosure are required to facilitate HIV prevention interventions for serodiscordant couples

SDSS-IV MaNGA: spatially resolved dust attenuation in spiral galaxies

Dust attenuation in star-forming spiral galaxies affects stars and gas in different ways due to local variations in dust geometry. We present spatially resolved measurements of dust attenuation for a sample of 232 such star-forming spiral galaxies, derived from spectra acquired by the SDSS-IV MaNGA survey. The dust attenuation affecting the stellar populations of these galaxies (obtained using full spectrum stellar population fitting methods) is compared with the dust attenuation in the gas (derived from the Balmer decrement). Both of these attenuation measures increase for local regions of galaxies with higher star formation rates; the dust attenuation affecting the stellar populations increases more so than the dust attenuation in the gas, causing the ratio of the dust attenuation affecting the stellar populations to the dust attenuation in the gas to decrease for local regions of galaxies with higher star formation rate densities. No systematic difference is discernible in any of these dust attenuation quantities between the spiral arm and inter-arm regions of the galaxies. While both the dust attenuation in the gas and the dust attenuation affecting the stellar populations decrease with galactocentric radius, the ratio of the two quantities does not vary with radius. This ratio does, however, decrease systematically as the stellar mass of the galaxy increases. Analysis of the radial profiles of the two dust attenuation measures suggests that there is a disproportionately high concentration of birth clouds (incorporating gas, young stars and clumpy dust) nearer to the centres of star-forming spiral galaxies.Comment: 17 pages, 8 figures, accepted for publication in Monthly Notices of the Royal Astronomical Societ

Changes in household food and drink purchases following restrictions on the advertisement of high fat, salt, and sugar products across the Transport for London network: A controlled interrupted time series analysis.

Funder: Cancer Research UKBACKGROUND: Restricting the advertisement of products with high fat, salt, and sugar (HFSS) content has been recommended as a policy tool to improve diet and tackle obesity, but the impact on HFSS purchasing is unknown. This study aimed to evaluate the impact of HFSS advertising restrictions, implemented across the London (UK) transport network in February 2019, on HFSS purchases. METHODS AND FINDINGS: Over 5 million take-home food and drink purchases were recorded by 1,970 households (London [intervention], n = 977; North of England [control], n = 993) randomly selected from the Kantar Fast Moving Consumer Goods panel. The intervention and control samples were similar in household characteristics but had small differences in main food shopper sex, socioeconomic position, and body mass index. Using a controlled interrupted time series design, we estimated average weekly household purchases of energy and nutrients from HFSS products in the post-intervention period (44 weeks) compared to a counterfactual constructed from the control and pre-intervention (36 weeks) series. Energy purchased from HFSS products was 6.7% (1,001.0 kcal, 95% CI 456.0 to 1,546.0) lower among intervention households compared to the counterfactual. Relative reductions in purchases of fat (57.9 g, 95% CI 22.1 to 93.7), saturated fat (26.4 g, 95% CI 12.4 to 40.4), and sugar (80.7 g, 95% CI 41.4 to 120.1) from HFSS products were also observed. Energy from chocolate and confectionery purchases was 19.4% (317.9 kcal, 95% CI 200.0 to 435.8) lower among intervention households than for the counterfactual, with corresponding relative reductions in fat (13.1 g, 95% CI 7.5 to 18.8), saturated fat (8.7 g, 95% CI 5.7 to 11.7), sugar (41.4 g, 95% CI 27.4 to 55.4), and salt (0.2 g, 95% CI 0.1 to 0.2) purchased from chocolate and confectionery. Relative reductions are in the context of secular increases in HFSS purchases in both the intervention and control areas, so the policy was associated with attenuated growth of HFSS purchases rather than absolute reduction in HFSS purchases. Study limitations include the lack of out-of-home purchases in our analyses and not being able to assess the sustainability of observed changes beyond 44 weeks. CONCLUSIONS: This study finds an association between the implementation of restrictions on outdoor HFSS advertising and relative reductions in energy, sugar, and fat purchased from HFSS products. These findings provide support for policies that restrict HFSS advertising as a tool to reduce purchases of HFSS products