High-spatial resolution epidemic surveillance of bacterial meningitis in the African meningitis belt in Burkina Faso.

Despite improved surveillance capacities and WHO recommendations for subdistrict analysis, routine epidemic surveillance of acute bacterial meningitis in the African meningitis belt remains largely limited to the district level. We evaluated the appropriateness and performance of analyses at higher spatial resolution. We used suspected meningitis surveillance data at health centre (HC) resolution from Burkina Faso from 14 health districts spanning years 2004-2014 and analysed them using spatio-temporal statistics and generative models.

Live-cell micromanipulation of a genomic locus reveals interphase chromatin mechanics.

Our understanding of the physical principles organizing the genome in the nucleus is limited by the lack of tools to directly exert and measure forces on interphase chromosomes in vivo and probe their material nature. Here, we introduce an approach to actively manipulate a genomic locus using controlled magnetic forces inside the nucleus of a living human cell. We observed viscoelastic displacements over micrometers within minutes in response to near-piconewton forces, which are consistent with a Rouse polymer model.

Investigation of Cardiovascular Health and Risk Factors Among the Diverse and Contemporary Population in London (the TOGETHER Study): Protocol for Linking Longitudinal Medical Records.

Background: Global trends in cardiovascular disease (CVD) exhibit considerable interregional and interethnic differences, which in turn affect long-term CVD risk across diverse populations. An in-depth understanding of the interplay between ethnicity, socioeconomic status, and CVD risk factors and mortality in a contemporaneous population is crucial to informing health policy and resource allocation aimed at mitigating long-term CVD risk. Generating bespoke large-scale and reliable data with sufficient numbers of events is expensive and time-consuming but can be circumvented through utilization and linkage of data routinely collected in electronic health records (EHR).

Single-molecule diffusometry reveals no catalysis-induced diffusion enhancement of alkaline phosphatase as proposed by FCS experiments.

Theoretical and experimental observations that catalysis enhances the diffusion of enzymes have generated exciting implications about nanoscale energy flow, molecular chemotaxis, and self-powered nanomachines. However, contradictory claims on the origin, magnitude, and consequence of this phenomenon continue to arise. To date, experimental observations of catalysis-enhanced enzyme diffusion have relied almost exclusively on fluorescence correlation spectroscopy (FCS), a technique that provides only indirect, ensemble-averaged measurements of diffusion behavior.

How the Genome Folds: The Biophysics of Four-Dimensional Chromatin Organization.

The genetic information that instructs transcription and other cellular functions is carried by the chromosomes, polymers of DNA in complex with histones and other proteins. These polymers are folded inside nuclei five orders of magnitude smaller than their linear length, and many facets of this folding correlate with or are causally related to transcription and other cellular functions. Recent advances in sequencing and imaging-based techniques have enabled new views into several layers of chromatin organization.

What do care home managers believe constitutes an 'assessment for frailty' of care home residents in North-West London? A survey.

Background: Frail individuals are at risk of significant clinical deterioration if their frailty is not identified and managed appropriately. Research suggests that any interaction between an older person and a health or social care professional should include an assessment for frailty. Many older care home residents are frail when admitted, but we have little knowledge of whether or how this is assessed.

American Heart Association's Cholesterol CarePlan as a Smartphone-Delivered Web App for Patients Prescribed Cholesterol-Lowering Medication: Protocol for an Observational Feasibility Study.

Background: Adoption of healthy lifestyle and compliance with cholesterol-lowering medication reduces the risk of cardiovascular disease (CVD). The use of digital tools and mobile technology may be important for sustaining positive behavioral change.

Objective: The primary objective of this study is to evaluate the feasibility and acceptability of administering the Cholesterol CarePlan Web app developed by the American Heart Association aimed at improving lifestyle and medication adherence among patients prescribed cholesterol-lowering medication.

Compartmental models for seasonal hyperendemic bacterial meningitis in the African meningitis belt.

The pathophysiological mechanisms underlying the seasonal dynamic and epidemic occurrence of bacterial meningitis in the African meningitis belt remain unknown. Regular seasonality (seasonal hyperendemicity) is observed for both meningococcal and pneumococcal meningitis and understanding this is critical for better prevention and modelling. The two principal hypotheses for hyperendemicity during the dry season imply (1) an increased risk of invasive disease given asymptomatic carriage of meningococci and pneumococci; or (2) an increased transmission of these bacteria from carriers and ill individuals.

Atmospheric Dust, Early Cases, and Localized Meningitis Epidemics in the African Meningitis Belt: An Analysis Using High Spatial Resolution Data.

Background: Bacterial meningitis causes a high burden of disease in the African meningitis belt, with regular seasonal hyperendemicity and sporadic short, but intense, localized epidemics during the late dry season occurring at a small spatial scale [i.e., below the district level, in individual health centers (HCs)].

Protein motion in the nucleus: from anomalous diffusion to weak interactions.

Understanding how transcription factors (TFs) regulate mammalian gene expression in space and time is a central topic in biology. To activate a gene, a TF has first to diffuse in the available space of the nucleus until it reaches a target DNA sequence or protein (target site). This eventually results in the recruitment of the whole transcriptional machinery.

Robust model-based analysis of single-particle tracking experiments with Spot-On.

Single-particle tracking (SPT) has become an important method to bridge biochemistry and cell biology since it allows direct observation of protein binding and diffusion dynamics in live cells. However, accurately inferring information from SPT studies is challenging due to biases in both data analysis and experimental design. To address analysis bias, we introduce 'Spot-On', an intuitive web-interface.

Development of a questionnaire to evaluate patients' awareness of cardiovascular disease risk in England's National Health Service Health Check preventive cardiovascular programme.

Background: The National Health Service (NHS) Health Check is a cardiovascular disease (CVD) risk assessment and management programme in England aiming to increase CVD risk awareness among people at increased risk of CVD. There is no tool to assess the effectiveness of the programme in communicating CVD risk to patients.

Aims: The aim of this paper was to develop a questionnaire examining patients' CVD risk awareness for use in health service research evaluations of the NHS Health Check programme.

The association between respiratory tract infection incidence and localised meningitis epidemics: an analysis of high-resolution surveillance data from Burkina Faso.

Meningococcal meningitis epidemics in the African meningitis belt consist of localised meningitis epidemics (LME) that reach attack proportions of 1% within a few weeks. A meningococcal serogroup A conjugate vaccine was introduced in meningitis belt countries from 2010 on, but LME due to other serogroups continue to occur. The mechanisms underlying LME are poorly understood, but an association with respiratory pathogens has been hypothesised.

Does use of point-of-care testing improve cost-effectiveness of the NHS Health Check programme in the primary care setting? A cost-minimisation analysis.

Objective: To determine if use of point of care testing (POCT) is less costly than laboratory testing to the National Health Service (NHS) in delivering the NHS Health Check (NHSHC) programme in the primary care setting.

Design: Observational study and theoretical mathematical model with microcosting approach.

Setting: We collected data on NHSHC delivered at nine general practices (seven using POCT; two not using POCT).

Faster and less phototoxic 3D fluorescence microscopy using a versatile compressed sensing scheme.

Three-dimensional fluorescence microscopy based on Nyquist sampling of focal planes faces harsh trade-offs between acquisition time, light exposure, and signal-to-noise. We propose a 3D compressed sensing approach that uses temporal modulation of the excitation intensity during axial stage sweeping and can be adapted to fluorescence microscopes without hardware modification. We describe implementations on a lattice light sheet microscope and an epifluorescence microscope, and show that images of beads and biological samples can be reconstructed with a 5-10 fold reduction of light exposure and acquisition time.

Evaluation of community provision of a preventive cardiovascular programme - the National Health Service Health Check in reaching the under-served groups by primary care in England: cross sectional observational study.

Background: Cardiovascular disease (CVD) is the leading cause of premature mortality and a major contributor of health inequalities in England. Compared to more affluent and white counterparts, deprived people and ethnic minorities tend to die younger due to preventable CVD associated with lifestyle. In addition, deprived, ethnic minorities and younger people are less likely to be served by CVD prevention services.

Coverage of a national cardiovascular risk assessment and management programme (NHS Health Check): Retrospective database study.

Objective: To determine coverage of NHS Health Check, a national cardiovascular risk assessment programme in England, in the first four years after implementation, and to examine prevalence of high cardiovascular disease (CVD) risk and uptake of statins in high risk patients.

Method: Study sample was 95,571 patients in England aged 40-74years continuously registered with 509 practices in the Clinical Practice Research Datalink between April 2009 and March 2013. Multilevel logistic regression models were used to assess predictors of Health Check attendance; elevated CVD risk factors and statin prescribing among attendees.

Geometry of the nucleus: a perspective on gene expression regulation.

Gene expression control results from the combined interactions of the nearly hundred proteins forming the pre-initiation complex, thousands of transcription regulators, and genomic DNA. In the recent years, new technologies have revealed several key aspects of nuclear spatial organization that showed a fine interplay between the function of nuclear proteins, their 3D organization, and their dynamics. Here we review several concepts that link biochemical reactivity in the nucleus to its 3D spatial organization.