Modelling-based evaluation of the costs, benefits and cost-effectiveness of multipathogen point-of-care tests for sexually transmitted infections in symptomatic genitourinary medicine clinic attendees

Objectives To quantify the costs, benefits and cost-effectiveness of three multipathogen point-of-care (POC) testing strategies for detecting common sexually transmitted infections (STIs) compared with standard laboratory testing. Design Modelling study. Setting Genitourinary medicine (GUM) services in England. Population A hypothetical cohort of 965 988 people, representing the annual number attending GUM services symptomatic of lower genitourinary tract infection. Interventions The decision tree model considered costs and reimbursement to GUM services associated with diagnosing and managing STIs. Three strategies using hypothetical point-of-care tests (POCTs) were compared with standard care (SC) using laboratory-based testing. The strategies were: A) dual POCT for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG); B) triplex POCT for CT-NG and Mycoplasma genitalium (MG); C) quadruplex POCT for CT-NG-MG and Trichomonas vaginalis (TV). Data came from published literature and unpublished estimates. Primary and secondary outcome measures Primary outcomes were total costs and benefits (quality-adjusted life years (QALYs)) for each strategy (2016 GB, £) and associated incremental cost-effectiveness ratios (ICERs) between each of the POC strategies and SC. Secondary outcomes were inappropriate treatment of STIs, onward STI transmission, pelvic inflammatory disease in women, time to cure and total attendances. Results In the base-case analysis, POC strategy C, a quadruplex POCT, was the most cost-effective relative to the other strategies, with an ICER of £36 585 per QALY gained compared with SC when using microcosting, and cost-savings of £26 451 382 when using tariff costing. POC strategy C also generated the most benefits, with 240 467 fewer clinic attendances, 808 fewer onward STI transmissions and 235 135 averted inappropriate treatments compared with SC. Conclusions Many benefits can be achieved by using multipathogen POCTs to improve STI diagnosis and management. Further evidence is needed on the underlying prevalence of STIs and SC delivery in the UK to reduce uncertainty in economic analyses

The Structure and Entrainment Characteristics of Partially Confined Gravity Currents

Seafloor channels are the main conduit for turbidity currents transporting sediment to the deep ocean, and they can extend for thousands of kilometers along the ocean floor. Although it is common for channel‐traversing turbidity currents to spill onto levees and other out‐of‐channel areas, the associated flow development and channel‐current interaction remain poorly understood; much of our knowledge of turbidity current dynamics comes from studies of fully confined scenarios. Here we investigate the role that partial lateral confinement may play in affecting turbidity current dynamics. We report on laboratory experiments of partially confined, dilute saline flows of variable flux rate traversing fixed, straight channels with cross‐sectional profiles representative of morphologies found in the field. Complementary numerical experiments, validated against high‐resolution laboratory velocity data, extend the scope of the analysis. The experiments show that partial confinement exerts a first‐order control on flow structure. Overbank and downstream discharges rapidly adjust over short length scales, providing a mechanism via which currents of varying sizes can be tuned by a channel and conform to a given channel geometry. Across a wide range of flow magnitudes and states of flow equilibration to the channel, a high‐velocity core remains confined within the channel with a constant ratio of velocity maximum height to channel depth. Ongoing overbank flow prevents any flow thickening due to ambient entrainment, allowing stable downstream flow evolution. Despite dynamical differences, the entrainment rates of partially confined and fully confined flows remain comparable for a given Richardson number

A novel mixing mechanism in sinuous seafloor channels: Implications for submarine channel evolution

Previous experimental studies of density currents in sinuous seafloor channels have almost exclusively studied hydrodynamics either by considering time independent, instantaneous, flow measurements or by compiling time-averaged flow measurements. Here we present a novel study of the time dependent dynamics of a density driven flow in a sinuous channel fed by a source of constant discharge. The experiments show that whilst source conditions may be temporally steady, flow conditions are temporally unsteady with timescales of flow variation driven by flow interaction with channel topography. Temporal variations reveal that both downstream and cross-stream flows vary significantly from time average observations and predictions, across scales larger than those predicted for turbulence in equivalent straight channels. Large-scale variations are shown to increase the average production of turbulence across the height of the flow, providing a new mechanism for enhanced mixing of sediment within gravity currents. Further such large-scale variations in flow conditions are recorded in the change in orientation of near-bed secondary flow, providing a plausible mechanism to reduce the cross-stream transport of bedload material and explain the ultimate stabilisation of sinuous seafloor channel systems

Improving Hurricane Power Outage Prediction Models Through the Inclusion of Local Environmental Factors

Tropical cyclones can significantly damage the electrical power system, so an accurate spatiotemporal forecast of outages prior to landfall can help utilities to optimize the power restoration process. The purpose of this article is to enhance the predictive accuracy of the Spatially Generalized Hurricane Outage Prediction Model (SGHOPM) developed by Guikema et al. (2014). In this version of the SGHOPM, we introduce a new two‐step prediction procedure and increase the number of predictor variables. The first model step predicts whether or not outages will occur in each location and the second step predicts the number of outages. The SGHOPM environmental variables of Guikema et al. (2014) were limited to the wind characteristics (speed and duration of strong winds) of the tropical cyclones. This version of the model adds elevation, land cover, soil, precipitation, and vegetation characteristics in each location. Our results demonstrate that the use of a new two‐step outage prediction model and the inclusion of these additional environmental variables increase the overall accuracy of the SGHOPM by approximately 17%.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147200/1/risa12728_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147200/2/risa12728.pd

Examining the extent to which repeat and near repeat patterns can prevent crime

PURPOSE: The purpose of this paper is to examine the extent and variation in the estimates to which crime can be prevented using patterns of repeats and near repeats, and whether hotspot analysis complements these patterns. DESIGN/METHODOLOGY/APPROACH: Crime data for four study areas in New Zealand are used to examine differences in the extent of burglary repeat and near repeat victimisation. Hotspots of burglary are also created to determine the extent to which burglary repeats and near repeats spatially intersect hotspots. FINDINGS: The extent of repeats and near repeats varies, meaning there is variation in the estimated prevention benefits that repeat and near repeat patterns offer. In addition, at least half of the burglaries repeats and near repeats were not located within hotspots. RESEARCH LIMITATIONS/IMPLICATIONS: The use of other techniques for examining crime concentration could be used to improve the research observations. PRACTICAL IMPLICATIONS: By showing that levels of repeats and near repeats vary, the extent to which these observations coincide in hotspots offers practitioners a better means of determining whether repeat and near repeat patterns are reliable for informing crime prediction and crime prevention activities. ORIGINALITY/VALUE: The paper is the first known research study that explicitly measures the variation in the extent of repeats and near repeats and the spatial intersection of these patterns within crime hotspots. The results suggest that rather than considering the use of repeat and near repeat patterns as a superior method for predicting and preventing crime, value remains in using hotspot analysis for determining where crime is likely to occur, particularly when hotspot analysis emphasises other locations for resource targeting

The Warburg effect as a therapeutic target for bladder cancers and intratumoral heterogeneity in associated molecular targets

Bladder cancer is the 10th most common cancer worldwide. For muscle-invasive bladder cancer (MIBC), treatment includes radical cystectomy, radiotherapy, and chemotherapy; however, the outcome is generally poor. For non–muscle-invasive bladder cancer (NMIBC), tumor recurrence is common. There is an urgent need for more effective and less harmful therapeutic approaches. Here, bladder cancer cell metabolic reprogramming to rely on aerobic glycolysis (the Warburg effect) and expression of associated molecular therapeutic targets by bladder cancer cells of different stages and grades, and in freshly resected clinical tissue, is investigated. Importantly, analyses indicate that the Warburg effect is a feature of both NMIBCs and MIBCs. In two in vitro inducible epithelial-mesenchymal transition (EMT) bladder cancer models, EMT stimulation correlated with increased lactate production, the end product of aerobic glycolysis. Protein levels of lactate dehydrogenase A (LDH-A), which promotes pyruvate enzymatic reduction to lactate, were higher in most bladder cancer cell lines (compared with LDH-B, which catalyzes the reverse reaction), but the levels did not closely correlate with aerobic glycolysis rates. Although LDH-A is expressed in normal urothelial cells, LDH-A knockdown by RNAi selectively induced urothelial cancer cell apoptotic death, whereas normal cells were unaffected—identifying LDH-A as a cancer-selective therapeutic target for bladder cancers. LDH-A and other potential therapeutic targets (MCT4 and GLUT1) were expressed in patient clinical specimens; however, positive staining varied in different areas of sections and with distance from a blood vessel. This intratumoral heterogeneity has important therapeutic implications and indicates the possibility of tumor cell metabolic coupling

Entrepreneurial capital, social values and Islamic traditions: exploring the growth of women-owned enterprises in Pakistan

Main ArticleThis study seeks to explore the variables contributing to the growth of women-owned enterprises in the Islamic Republic of Pakistan. Based on a previously established multivariate model, it uses two econometric approaches: first classifying variables into predetermined blocks; and second, using the general to specific approach. Statistical analyses and in-depth interviews confirm that women entrepreneurs’ personal resources and social capital have a significant role in their business growth. Further, it reveals that the moral support of immediate family, independent mobility and being allowed to meet with men play a decisive role in the sales and employment growth of women-owned enterprises in an Islamic country such as Pakistan

Scaling Analysis of Multipulsed Turbidity Current Evolution With Application to Turbidite Interpretation

Deposits of submarine turbidity currents, turbidites, commonly exhibit upward‐fining grain size profiles reflecting deposition under waning flow conditions. However, more complex grading patterns such as multiple cycles of inverse‐to‐normal grading are also seen and interpreted as recording deposition under cycles of waxing and waning flow. Such flows are termed multipulsed turbidity currents, and their deposits pulsed or multipulsed turbidites. Pulsing may arise at flow initiation, or following downstream flow combination. Prior work has shown that individual pulses within multipulsed flows are advected forward and merge, such that complex longitudinal velocity profiles eventually become monotonically varying, although transition length scales in natural settings could not be predicted. Here we detail the first high frequency spatial (vertical, streamwise) and temporal measurements of flow velocity and density distribution in multipulsed gravity current experiments. The data support both a process explanation of pulse merging and a phase‐space analysis of transition length scales; in prototype systems, the point of merging corresponds to the transition in any deposit from multipulsed to normally graded turbidites. The scaling analysis is limited to quasi‐horizontal natural settings in which multipulsed flows are generated by sequences of relatively short sediment failures (10 km) sequences of breaches or where pulsing arises from combination at confluences of single‐pulsed flows, such flows may be responsible for the pulsing signatures seen in some distal turbidites, >100 km from source

Rings in the Solar System: a short review

Rings are ubiquitous around giant planets in our Solar System. They evolve jointly with the nearby satellite system. They could form either during the giant planet formation process or much later, as a result of large scale dynamical instabilities either in the local satellite system, or at the planetary scale. We review here the main characteristics of rings in our solar system, and discuss their main evolution processes and possible origin. We also discuss the recent discovery of rings around small bodies.Comment: Accepted for the Handbook of Exoplanet

Optimisation of flow resistance and turbulent mixing over bed forms

Previous work on the interplay between turbulent mixing and flow resistance for flows over periodic rib roughness elements is extended to consider the flow over idealized shapes representative of naturally occurring sedimentary bed forms. The primary motivation is to understand how bed form roughness affects the carrying capacity of sediment-bearing flows in environmental fluid dynamics applications, and in engineering applications involving the transport of particulate matter in pipelines. For all bed form shapes considered, it is found that flow resistance and turbulent mixing are strongly correlated, with maximum resistance coinciding with maximum mixing, as was previously found for the special case of rectangular roughness elements. Furthermore, it is found that the relation between flow resistance to eddy viscosity collapses to a single monotonically increasing linear function for all bed form shapes considered, indicating that the mixing characteristics of the flows are independent of the detailed morphology of individual roughness elements