ISPIDER Central: an integrated database web-server for proteomics

Despite the growing volumes of proteomic data, integration of the underlying results remains problematic owing to differences in formats, data captured, protein accessions and services available from the individual repositories. To address this, we present the ISPIDER Central Proteomic Database search (http://www.ispider.manchester.ac.uk/cgi-bin/ProteomicSearch.pl), an integration service offering novel search capabilities over leading, mature, proteomic repositories including PRoteomics IDEntifications database (PRIDE), PepSeeker, PeptideAtlas and the Global Proteome Machine. It enables users to search for proteins and peptides that have been characterised in mass spectrometry-based proteomics experiments from different groups, stored in different databases, and view the collated results with specialist viewers/clients. In order to overcome limitations imposed by the great variability in protein accessions used by individual laboratories, the European Bioinformatics Institute's Protein Identifier Cross-Reference (PICR) service is used to resolve accessions from different sequence repositories. Custom-built clients allow users to view peptide/protein identifications in different contexts from multiple experiments and repositories, as well as integration with the Dasty2 client supporting any annotations available from Distributed Annotation System servers. Further information on the protein hits may also be added via external web services able to take a protein as input. This web server offers the first truly integrated access to proteomics repositories and provides a unique service to biologists interested in mass spectrometry-based proteomics

Strain‐Promoted Cycloadditions in Lipid Bilayers Triggered by Liposome Fusion

Due to the variety of roles served by the cell membrane, its composition and structure are complex, making it difficult to study. Bioorthogonal reactions, such as the strain promoted azide-alkyne cycloaddition (SPAAC), are powerful tools for exploring the function of biomolecules in their native environment but have been largely unexplored within the context of lipid bilayers. Here, we developed a new approach to study the SPAAC reaction in liposomal membranes using azide- and strained alkyne-functionalized Förster resonance energy transfer (FRET) dye pairs. This study represents the first characterization of the SPAAC reaction between diffusing molecules inside liposomal membranes. Potential applications of this work include in situ bioorthogonal labeling of membrane proteins, improved understanding of membrane dynamics and fluidity, and the generation of new probes for biosensing assays

Can we avoid high coupling?

It is considered good software design practice to organize source code into modules and to favour within-module connections (cohesion) over between-module connections (coupling), leading to the oft-repeated maxim "low coupling/high cohesion". Prior research into network theory and its application to software systems has found evidence that many important properties in real software systems exhibit approximately scale-free structure, including coupling; researchers have claimed that such scale-free structures are ubiquitous. This implies that high coupling must be unavoidable, statistically speaking, apparently contradicting standard ideas about software structure. We present a model that leads to the simple predictions that approximately scale-free structures ought to arise both for between-module connectivity and overall connectivity, and not as the result of poor design or optimization shortcuts. These predictions are borne out by our large-scale empirical study. Hence we conclude that high coupling is not avoidable--and that this is in fact quite reasonable

National trends in emergency conditions through the Omicron COVID-19 wave in commercial and Medicare Advantage enrollees

Objective: To evaluate trends in emergency care sensitive conditions (ECSCs) from pre-COVID (March 2018–February 2020) through Omicron (December 2021–February 2022). Methods: This cross-sectional analysis evaluated trends in ECSCs using claims (OptumLabs Data Warehouse) from commercial and Medicare Advantage enrollees. Emergency department (ED) visits for ECSCs (acute appendicitis, aortic aneurysm/dissection, cardiac arrest/severe arrhythmia, cerebral infarction, myocardial infarction, pulmonary embolism, opioid overdose, pre-eclampsia) were reported per 100,000 person months from March 2018 to February 2022 by pandemic wave. We calculated the percent change for each pandemic wave compared to the pre-pandemic period. Results: There were 10,268,554 ED visits (March 2018−February 2022). The greatest increases in ECSCs were seen for pulmonary embolism, cardiac arrest/severe arrhythmia, myocardial infarction, and pre-eclampsia. For commercial enrollees, pulmonary embolism visit rates increased 22.7% (95% confidence interval [CI], 18.6%–26.9%) during Waves 2−3, 37.2% (95% CI, 29.1%–45.8%] during Delta, and 27.9% (95% CI, 20.3%–36.1%) during Omicron, relative to pre-pandemic rates. Cardiac arrest/severe arrhythmia visit rates increased 4.0% (95% CI, 0.2%–8.0%) during Waves 2−3; myocardial infarction rates increased 4.9% (95% CI, 2.1%–7.8%) during Waves 2−3. Similar patterns were seen in Medicare Advantage enrollees. Pre-eclampsia visit rates among reproductive-age female enrollees increased 31.1% (95% CI, 20.9%–42.2%), 23.7% (95% CI, 7.5%,–42.3%), and 34.7% (95% CI, 16.8%–55.2%) during Waves 2−3, Delta, and Omicron, respectively. ED visits for other ECSCs declined or exhibited smaller increases. Conclusions: ED visit rates for acute cardiovascular conditions, pulmonary embolism and pre-eclampsia increased despite declines or stable rates for all-cause ED visits and ED visits for other conditions. Given the changing landscape of ECSCs, studies should identify drivers for these changes and interventions to mitigate them

Costs of falls in an ageing population: A nationwide study from the Netherlands (2007-2009)

Background: Falls are a common mechanism of injury in the older population, putting an increasing demand on scarce healthcare resources. The objective of this study was to determine healthcare costs due to falls in the older population. Methods: An incidence-based cost model was used to estimate the annual healthcare costs and costs per case spent on fall-related injuries in patients ≥65 years, The Netherlands (2007-2009). Costs were subdivided by age, gender, nature of injury, and type of resource use. Results: In the period 2007-2009, each year 3% of all persons aged ≥65 years visited the Emergency Department due to a fall incident. Related medical costs were estimated at €675.4 million annually. Fractures led to 80% (€540 million) of the fall-related healthcare costs. The mean costs per fall were €9370, and were higher for women (€9990) than men (€7510) and increased with age (from €3900 at ages 65-69 years to €14,600 at ages ≥85 year). Persons ≥80 years accounted for 47% of all fall-related Emergency Department visits, and 66% of total costs. The costs of long-term care at home and in nursing homes showed the largest age-related increases and accounted together for 54% of the fall-related costs in older people. Discussion: Fall-related injuries are leading to a high healthcare consumption and related healthcare costs, which increases with age. Programmes to prevent falls and fractures should be further implemented in order to reduce costs due to falls in the older population and to avoid that healthcare systems become overburdened

Cut-points for waist circumference in Europids and South Asians

There is little strong evidence that currently recommended higher waist circumference cut-points for Europids compared with South Asians are associated with similar risk for type 2 diabetes. This study was designed to provide such evidence. Longitudinal studies over 5 years were conducted among 5,515 Europid and 2,214 ethnically South Asian participants. Age-standardized diabetes incidence at different levels of waist circumference and incidence difference relative to a reference value were calculated. The Youden Index was used to determine waist circumference cut-points. At currently recommended cut-points, estimated annual diabetes incidence for a 50-year-old Europid was &lt;0.6% for both sexes, and for a 50-year-old South Asian, 5.8% for men and 2.1% for women. Annual diabetes incidence of 1% was observed for a 50 year old at a waist circumference 35&ndash;40 cm greater in Europid compared to South Asian men and women. Incidence difference between recommended cut-points and a reference value (80 cm in men, 70 cm in women) was 0.3 and 4.4% per year for Europid and South Asian men, and 0.2 and 0.8% per year for Europid and South Asian women, respectively. Waist circumference cut-points chosen using the Youden Index were shown to be dependent on obesity levels in the population. The much higher observed risk of diabetes in South Asians compared to Europids at the respective recommended waist circumference cut-points suggests that differences between them should be greater. Approaches that use the Youden Index to select waist circumference cut-points are inappropriate and should not be used for this purpose.<br /

Flux-Bubble Models and Mesonic Molecules

It has been shown that the string-flip potential model reproduces most of the bulk properties of nuclear matter, with the exception of nuclear binding. Furthermore, it was postulated that this model, with the inclusion of the colour-hyperfine interaction, should produce binding. In some recent work a modified version of the string-flip potential model was developed, called the flux-bubble model, which would allow for the addition of perturbative QCD interactions. In attempts to construct a simple $q\bar q$ nucleon system using the flux-bubble model (which only included colour-Coulomb interactions) difficulties arose with trying to construct a many-body variational wave function that would take into account the locality of the flux-bubble interactions. In this talk we consider a toy system, a mesonic molecule in order to understand these difficulties. En route, a new variational wave function is proposed that may have a significant enough impact on the old string-flip potential model results that the inclusion of perturbative effects may not be needed.Comment: 8 pages, Latex, avec 9 eps files, http://www.physics.carleton.ca/~boyce/papers/mrst97.p