Assessing smectic liquid-crystal continuum models for elastic bilayer deformations

For four decades, since W. Helfrich’s pioneering study of smectic A liquid crystals in 1973, continuum elastic models (CEMs) have been employed as tools to understand the energetics of protein-induced lipid bilayer deformations. Among the assumptions underlying this use is that all relevant protein–lipid interactions can be included in the continuum representation of the protein–bilayer interactions through the physical parameters determined for protein-free bilayers and the choice of boundary conditions at the protein/bilayer interface. To better understand this assumption, we review the general structure of CEMs, examine how different choices of boundary conditions and physical moduli profiles alter the predicted bilayer thickness profiles around gramicidin A (gA) and mitochondrial voltage-dependent anion channels (VDAC), respectively, and compare these profiles with those obtained from all-atom molecular dynamics simulations. We find that the profiles differ qualitatively in the first lipid shell around the channels, indicating that the CEMs do not capture accurately the consequences of the protein-induced local changes in lipid bilayer dynamics. Therefore, one needs to be careful when interpreting the results of CEM-based analyses of lipid bilayer-membrane protein interactions

Measuring Accuracy of Automated Parsing and Categorization Tools and Processes in Digital Investigations

This work presents a method for the measurement of the accuracy of evidential artifact extraction and categorization tasks in digital forensic investigations. Instead of focusing on the measurement of accuracy and errors in the functions of digital forensic tools, this work proposes the application of information retrieval measurement techniques that allow the incorporation of errors introduced by tools and analysis processes. This method uses a `gold standard' that is the collection of evidential objects determined by a digital investigator from suspect data with an unknown ground truth. This work proposes that the accuracy of tools and investigation processes can be evaluated compared to the derived gold standard using common precision and recall values. Two example case studies are presented showing the measurement of the accuracy of automated analysis tools as compared to an in-depth analysis by an expert. It is shown that such measurement can allow investigators to determine changes in accuracy of their processes over time, and determine if such a change is caused by their tools or knowledge.Comment: 17 pages, 2 appendices, 1 figure, 5th International Conference on Digital Forensics and Cyber Crime; Digital Forensics and Cyber Crime, pp. 147-169, 201

Trends in diabetic retinopathy screening attendance and associations with vision impairment attributable to diabetes in a large nationwide cohort

AIMS: To investigate diabetic retinopathy screening attendance and trends in certified vision impairment caused by diabetic eye disease. METHODS: This was a retrospective study of attendance in three urban UK diabetic eye screening programmes in England. A survival analysis was performed to investigate time from diagnosis to first screen by age and sex. Logistic regression analysis of factors influencing screening attendance during a 15-month reporting period was conducted, as well as analysis of new vision impairment certifications (Certificate of Vision Impairment) in England and Wales from 2009 to 2019. RESULTS: Of those newly registered in the Routine Digital Screening pathway (n = 97 048), 80% attended screening within the first 12 months and 88% by 36 months. Time from registration to first eye screening was longer for people aged 18-34 years, and 20% were unscreened after 3 years. Delay in first screen was associated with increased risk of referable retinopathy. Although 95% of participants (n = 291 296) attended during the 15-month reporting period, uptake varied considerably. Younger age, social deprivation, ethnicity and duration of diabetes were independent predictors of non-attendance and referable retinopathy. Although the last 10 years has seen an overall reduction in vision impairment certification attributable to diabetic eye disease, the incidence of vision impairment in those aged <35 years was unchanged. CONCLUSIONS: Whilst the majority of participants are screened in a timely manner, there is considerable variation in uptake. Young adults, have sub-optimal attendance, and levels of vision impairment in this population have not changed over the last 10 years. There is an urgent need to explore barriers to/enablers of attendance in this group to inform policy initiatives and tailored interventions to address this issue

Mapping the Spread of Malaria Drug Resistance

Tim Anderson discusses a new study of molecular variation in alleles at the dihydropteroate synthase locus, which underlies resistance to sulfadoxine, in over 5,000 parasites from 50 locations

Traffic pollution and the incidence of cardiorespiratory outcomes in an adult cohort in London.

OBJECTIVES: The epidemiological evidence for adverse health effects of long-term exposure to air and noise pollution from traffic is not coherent. Further, the relative roles of background versus near traffic pollution concentrations in this process are unclear. We investigated relationships between modelled concentrations of air and noise pollution from traffic and incident cardiorespiratory disease in London. METHODS: Among 211 016 adults aged 40-79 years registered in 75 Greater London practices between 2005 and 2011, the first diagnosis for a range of cardiovascular and respiratory outcomes were identified from primary care and hospital records. Annual baseline concentrations for nitrogen oxide (NOx), particulate matter with a median aerodynamic diameter <2.5 μm (PM2.5) attributable to exhaust and non-exhaust sources, traffic intensity and noise were estimated at 20 m(2) resolution from dispersion models, linked to clinical data via residential postcode. HRs were adjusted for confounders including smoking and area deprivation. RESULTS: The largest observed associations were between traffic-related air pollution and heart failure (HR=1.10 for 20 μg/m(3) change in NOx, 95% CI 1.01 to 1.21). However, no other outcomes were consistently associated with any of the pollution indicators, including noise. The greater variations in modelled air pollution from traffic between practices, versus within, hampered meaningful fine spatial scale analyses. CONCLUSIONS: The associations observed with heart failure may suggest exacerbatory effects rather than underlying chronic disease. However, the overall failure to observe wider associations with traffic pollution may reflect that exposure estimates based on residence inadequately represent the relevant pattern of personal exposure, and future studies must address this issue

Historical geography II: traces remain

The second report in this series turns to focus on the trace in relation to life-writing and biography in historical geography and beyond. Through attention to tracing journeys, located moments and listening to the presence of ghosts (Ogborn, 2005), this report seeks to highlight the range of different ways in which historical geographers have explored lives, deaths, and their transient traces through varied biographical terrains. Continuing to draw attention in historical geography to the darkest of histories, this piece will pivot on moments of discovering the dead to showcase the nuanced ways in which historical geography is opening doors into uncharted lives and unspoken histories