Three-dimensional separated flows past ground vehicles

The separated flow past a thick body is calculated using a theoretical model based on a discrete wake-vortex representation. Rehbach's unsteady inviscid scheme (1977) was used in the three-dimensional analysis. The obstacle is represented by singularities, and the wake is modeled by vortex particles emitted at the separation line. Calculated results for an axisymmetric body are compared with flow visualization results

A Qualitative Exploration of Community Ownership of a Maternity Waiting Home Model in Rural Zambia

Context Ownership is an important construct of sustainability for community-based health programming, though it is often not clearly defined or measured. We implemented and evaluated a community-driven maternity waiting home (MWH) model in rural Zambia. We engaged stakeholders at all levels and provided intensive mentorship to an MWH governance committee comprised of community-selected members. We then examined how different stakeholders perceive community ownership of the MWH. Methods We conducted 42 focus group discussions with community stakeholders (pregnant women, fathers, elders, and community health volunteers) and 161 in-depth interviews with MWH stakeholders (health facility staff, district health officials, and MWH governance committee and management unit members) at multiple time-points over 24 months. We conducted a content analysis and triangulated findings to understand community ownership of the MWH and observe changes in perceptions of ownership over time. Results Community members’ perceptions of ownership were related to their ability to use the MWH and a responsibility toward its success. Community and MWH stakeholders described increasingly more specific responsibilities over time. Governance committee and management unit members perceived their ability to represent the community as a crucial component of their role. Multiple respondent types saw collaboration between the governance committee and the health facility staff as key to allowing the MWH to meet its goal of serving the community. Conclusion The perceptions of community ownership evolved as the intervention became more established. Use of the MWH, and clear understanding of roles and responsibilities in management of the MWH, seemed to foster feelings of community ownership. To improve the sustainability of community-based maternal and child health programs, interventions should be accessible to target communities and clear roles should be established among stakeholders

Limited effect of highly active antiretroviral therapy among HIV-positive injecting drug users on the population level

There is evidence that HIV-positive injecting drug users benefit less than other risk groups from highly active antiretroviral therapy that has been available since 1996. In this multicentre European study the impact of the availability of highly active antiretroviral therapy on the progression rates to AIDS and death among injecting drug users with a documented date of HIV seroconversion is studied. After highly active antiretroviral therapy became available the risk of AIDS and death for injecting drug users decreased by 28% and 36%, which is less than has been reported for other risk group

Transmission of HIV-1 infection in sub-Saharan Africa and effect of elimination of unsafe injections

During the past year, a group has argued that unsafe injections are a major if not the main mode of HIV-1 transmission\ud in sub-Saharan Africa. We review the main arguments used to question the epidemiological interpretations on the lead\ud role of unsafe sex in HIV-1 transmission, and conclude there is no compelling evidence that unsafe injections are a\ud predominant mode of HIV-1 transmission in sub-Saharan Africa. Conversely, though there is a clear need to eliminate\ud all unsafe injections, epidemiological evidence indicates that sexual transmission continues to be by far the major\ud mode of spread of HIV-1 in the region. Increased efforts are needed to reduce sexual transmission of HIV-1

Rationale and design of the Novel Uses of adaptive Designs to Guide provider Engagement in Electronic Health Records (NUDGE-EHR) pragmatic adaptive randomized trial: a trial protocol

Background: The prescribing of high-risk medications to older adults remains extremely common and results in potentially avoidable health consequences. Efforts to reduce prescribing have had limited success, in part because they have been sub-optimally timed, poorly designed, or not provided actionable information. Electronic health record (EHR)-based tools are commonly used but have had limited application in facilitating deprescribing in older adults. The objective is to determine whether designing EHR tools using behavioral science principles reduces inappropriate prescribing and clinical outcomes in older adults. Methods: The Novel Uses of Designs to Guide provider Engagement in Electronic Health Records (NUDGE-EHR) project uses a two-stage, 16-arm adaptive randomized pragmatic trial with a “pick-the-winner” design to identify the most effective of many potential EHR tools among primary care providers and their patients ≥ 65 years chronically using benzodiazepines, sedative hypnotic (“Z-drugs”), or anticholinergics in a large integrated delivery system. In stage 1, we randomized providers and their patients to usual care (n = 81 providers) or one of 15 EHR tools (n = 8 providers per arm) designed using behavioral principles including salience, choice architecture, or defaulting. After 6 months of follow-up, we will rank order the arms based upon their impact on the trial’s primary outcome (for both stages): reduction in inappropriate prescribing (via discontinuation or tapering). In stage 2, we will randomize (a) stage 1 usual care providers in a 1:1 ratio to one of the up to 5 most promising stage 1 interventions or continue usual care and (b) stage 1 providers in the unselected arms in a 1:1 ratio to one of the 5 most promising interventions or usual care. Secondary and tertiary outcomes include quantities of medication prescribed and utilized and clinically significant adverse outcomes. Discussion: Stage 1 launched in October 2020. We plan to complete stage 2 follow-up in December 2021. These results will advance understanding about how behavioral science can optimize EHR decision support to improve prescribing and health outcomes. Adaptive trials have rarely been used in implementation science, so these findings also provide insight into how trials in this field could be more efficiently conducted. Trial registration: Clinicaltrials.gov (NCT04284553, registered: February 26, 2020

Plasmodium vivax Recurrence Following Falciparum and Mixed Species Malaria: Risk Factors and Effect of Antimalarial Kinetics

On the Thai-Myanmar border, Plasmodium vivax is the most common cause of parasitological failure following treatment for acute falciparum malaria. Slowly eliminated antimalarials significantly reduce the risk of early recurrence

Serum Alpha-Fetoprotein Predicts Treatment Outcome in Chronic Hepatitis C Patients Regardless of HCV Genotype

We examined the association between serum alpha-fetoprotein (AFP) level and sustained virological response (SVR) in 93 chronic hepatitis C patients. The SVR rate was much higher among patients with serum AFP levels below rather than above the median value (5.7 ng/ml) (58.7% and 19.2%, respectively; P<0.0001). Serum AFP should be added to the list of factors predictive of treatment response in chronic hepatitis C

Risk Factors for Buruli Ulcer: A Case Control Study in Cameroon

Buruli ulcer (BU) is a neglected tropical infectious disease caused by Mycobacterium ulcerans. While BU is associated with areas where the water is slow-flowing or stagnant, the exact mechanism of transmission of the bacillus is unknown, impairing efficient control programs. Two hypotheses are proposed in the literature: previous trauma at the lesion site, and transmission through aquatic insect bites. Using results from a face-to-face questionnaire, our study compared characteristics from Cameroonian patients with Buruli ulcer to people without Buruli ulcer. This latter group of people was chosen within the community or within the family of case patients. The statistical analysis confirmed some well-known factors associated with the presence of BU, such as wearing short lower-body clothing while farming, but it showed that the use of bed nets and the treatment of wounds with leaves is less frequent in case patients. These newly identified factors may provide new insight into the mode of transmission of M. ulcerans. The implication of domestic or peridomestic insects, suggested by the influence of the use of bed nets, should be confirmed in specific studies

Large Interferometer For Exoplanets (LIFE): II. Signal simulation, signal extraction, and fundamental exoplanet parameters from single-epoch observations

peer reviewedContext. The Large Interferometer For Exoplanets (LIFE) initiative is developing the science and a technology road map for an ambitious space mission featuring a space-based mid-infrared (MIR) nulling interferometer in order to detect the thermal emission of hundreds of exoplanets and characterize their atmospheres. Aims. In order to quantify the science potential of such a mission, in particular in the context of technical trade-offs, an instrument simulator is required. In addition, signal extraction algorithms are needed to verify that exoplanet properties (e.g., angular separation and spectral flux) contained in simulated exoplanet data sets can be accurately retrieved. Methods. We present LIFEsim, a software tool developed for simulating observations of exoplanetary systems with an MIR space-based nulling interferometer. It includes astrophysical noise sources (i.e., stellar leakage and thermal emission from local zodiacal and exozodiacal dust) and offers the flexibility to include instrumental noise terms in the future. Here, we provide some first quantitative limits on instrumental effects that would allow the measurements to remain in the fundamental noise limited regime. We demonstrate updated signal extraction approaches to validating signal-to-noise ratio (S/N) estimates from the simulator. Monte Carlo simulations are used to generate a mock survey of nearby terrestrial exoplanets and determine to which accuracy fundamental planet properties can be retrieved. Results. LIFEsim provides an accessible way to predict the expected S/N of future observations as a function of various key instrument and target parameters. The S/Ns of the extracted spectra are photon noise dominated, as expected from our current simulations. Signals from multi-planet systems can be reliably extracted. From single-epoch observations in our mock survey of small (R < 1.5 REarth) planets orbiting within the habitable zones of their stars, we find that typical uncertainties in the estimated effective temperature of the exoplanets are ≲10%, for the exoplanet radius ≲20%, and for the separation from the host star ≲2%. Signal-to-noise-ratio values obtained in the signal extraction process deviate by less than 10% from purely photon-counting statistics-based S/Ns. Conclusions. LIFEsim has been sufficiently well validated so that it can be shared with a broader community interested in quantifying various exoplanet science cases that a future space-based MIR nulling interferometer could address. Reliable signal extraction algorithms exist, and our results underline the power of the MIR wavelength range for deriving fundamental exoplanet properties from single-epoch observations.Large Interferometer For Exoplanets (LIFE

ISG15 Is Critical in the Control of Chikungunya Virus Infection Independent of UbE1L Mediated Conjugation

Chikungunya virus (CHIKV) is a re-emerging alphavirus that has caused significant disease in the Indian Ocean region since 2005. During this outbreak, in addition to fever, rash and arthritis, severe cases of CHIKV infection have been observed in infants. Challenging the notion that the innate immune response in infants is immature or defective, we demonstrate that both human infants and neonatal mice generate a robust type I interferon (IFN) response during CHIKV infection that contributes to, but is insufficient for, the complete control of infection. To characterize the mechanism by which type I IFNs control CHIKV infection, we evaluated the role of ISG15 and defined it as a central player in the host response, as neonatal mice lacking ISG15 were profoundly susceptible to CHIKV infection. Surprisingly, UbE1L−/− mice, which lack the ISG15 E1 enzyme and therefore are unable to form ISG15 conjugates, displayed no increase in lethality following CHIKV infection, thus pointing to a non-classical role for ISG15. No differences in viral loads were observed between wild-type (WT) and ISG15−/− mice, however, a dramatic increase in proinflammatory cytokines and chemokines was observed in ISG15−/− mice, suggesting that the innate immune response to CHIKV contributes to their lethality. This study provides new insight into the control of CHIKV infection, and establishes a new model for how ISG15 functions as an immunomodulatory molecule in the blunting of potentially pathologic levels of innate effector molecules during the host response to viral infection