Abstract
While adult clinical trials of coronavirus disease 2019 (COVID-19) vaccines have moved quickly into phase 3 clinical trials, clinical trials have not started in children in the United ...States. The direct COVID-19 impact upon children is greater than that observed for a number of other pathogens for which we now have effective pediatric vaccines. Additionally, the role of children in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has clearly been underappreciated. Carefully conducted phase 2 clinical trials can adequately address potential COVID-19 vaccine safety concerns. Delaying phase 2 vaccine clinical trials in children will delay our recovery from COVID-19 and unnecessarily prolong its impact upon children’s education, health, and emotional well-being, and equitable access to opportunities for development and social success. Given the potential direct and indirect benefits of pediatric vaccination, implementation of phase 2 clinical trials for COVID-19 vaccines should begin now.
While COVID-19 vaccines have moved quickly into adult Phase 3 clinical trials, clinical trials have not started in children in the US. Given potential direct and indirect benefits, implementation of pediatric COVID-19 Phase II vaccine clinical trials should begin now.
Landscape approaches attempt to achieve balance amongst multiple goals over long time periods and to adapt to changing conditions. We review project reports and the literature on integrated landscape ...approaches, and found a lack of documented studies of their long-term effectiveness. The combination of multiple and potentially changing goals presents problems for the conventional measures of impact. We propose more critical use of theories of change and measures of process and progress to complement the conventional impact assessments. Theories of change make the links between project deliverables, outputs, outcomes, and impacts explicit, and allow a full exploration of the landscape context. Landscape approaches are long-term engagements, but short-term process metrics are needed to confirm that progress is being made in negotiation of goals, meaningful stakeholder engagement, existence of connections to policy processes, and effectiveness of governance. Long-term impact metrics are needed to assess progress on achieving landscapes that deliver multiple societal benefits, including conservation, production, and livelihood benefits. Generic criteria for process are proposed, but impact metrics will be highly situation specific and must be derived from an effective process and a credible theory of change.
In this study of 4758 HIV-1–serodiscordant heterosexual couples in Kenya and Uganda, daily antiretroviral prophylaxis (with tenofovir or emtricitabine–tenofovir) in the HIV-1–negative partner ...significantly decreased the risk of HIV infection.
The use of antiretroviral medications for the prevention of HIV type 1 (HIV-1) transmission is a promising strategy for reducing the spread of HIV-1.
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Antiretroviral treatment for persons infected with HIV-1 provides important clinical benefits and substantially reduces infectiousness.
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Antiretroviral prophylaxis is a potential HIV-1–prevention strategy for those not yet infected with HIV-1, administered either as postexposure prophylaxis after high-risk occupational or nonoccupational exposure or as preexposure prophylaxis in those with ongoing HIV-1 exposure.
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The rationale for antiretroviral prophylaxis in persons with ongoing exposure is based on its efficacy in infants exposed to HIV-1 during birth and . . .
The objective of this study was to compare acute effects of prolonged sitting, prolonged standing and sitting interrupted with regular activity breaks on vascular function and postprandial glucose ...metabolism. In a randomized cross-over trial, 18 adults completed: 1. Prolonged Sitting; 2. Prolonged Standing and 3. Sitting with 2-min walking (5 km/h, 10% incline) every 30 min (Regular Activity Breaks). Flow mediated dilation (FMD) was measured in the popliteal artery at baseline and 6 h. Popliteal artery hemodynamics, and postprandial plasma glucose and insulin were measured over 6 h. Neither raw nor allometrically-scaled FMD showed an intervention effect (p = 0.285 and 0.159 respectively). Compared to Prolonged Sitting, Regular Activity Breaks increased blood flow (overall effect of intervention p<0.001; difference = 80%; 95% CI 34 to 125%; p = 0.001) and net shear rate (overall effect of intervention p<0.001; difference = 72%; 95% CI 30 to 114%; p = 0.001) at 60 min. These differences were then maintained for the entire 6 h. Prolonged Standing increased blood flow at 60 min only (overall effect of intervention p<0.001; difference = 62%; 95% CI 28 to 97%; p = 0.001). Regular Activity Breaks decreased insulin incremental area under the curve (iAUC) when compared to both Prolonged Sitting (overall effect of intervention P = 0.001; difference = 28%; 95% CI 14 to 38%; p<0.01) and Prolonged Standing (difference = 19%; 95% CI 4 to 32%, p = 0.015). There was no intervention effect on glucose iAUC or total AUC (p = 0.254 and 0.450, respectively). In normal-weight participants, Regular Activity Breaks induce increases in blood flow, shear stress and improvements in postprandial metabolism that are associated with beneficial adaptations. Physical activity and sedentary behaviour messages should perhaps focus more on the importance of frequent movement rather than simply replacing sitting with standing.
Modeling the Effects of Topography on Delay-Doppler Maps Campbell, James D.; Melebari, Amer; Moghaddam, Mahta
IEEE journal of selected topics in applied earth observations and remote sensing,
2020, Letnik:
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Journal Article
Recenzirano
Odprti dostop
A method for simulating delay-Doppler maps (DDMs) of global navigation satellite system signals reflected from land surfaces with heterogeneous terrain is developed from first principles. The method ...follows previous work for ocean DDMs in the geometric optics limit of the Kirchhoff approximation. Unlike the ocean method, however, where surface heights are assumed to be random with homogeneous statistics, this method decomposes the surface heights into a deterministic part obtained from a digital elevation map (DEM) and a random part representing the residual between the surface and the DEM. The method accounts for the displacement of reflected power into bins of lower delay due to raised surface terrain. The method also provides for the modulation of the normalized bistatic radar cross section by DEM-derived surface slopes over the glistening zone of the DDM. A technique to register Cyclone Global Navigation Satellite System (CYGNSS) DDM bins in delay-Doppler space for land applications is also proposed. The DEM-based method is applied to a CYGNSS track over the Soil Moisture Sensing Controller And oPtimal Estimator (SoilSCAPE) site at Tonzi Ranch, CA, USA. The DEM-based method has potential application for spaceborne monitoring of a variety of environmental parameters.
Summary Background The 2014 west African Zaire Ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine ...expressing Zaire Ebola virus glycoprotein (ChAd3-EBO-Z). We aimed to investigate the safety, tolerability, and immunogenicity of ChAd3-EBO-Z in Malian and US adults, and assess the effect of boosting of Malians with modified vaccinia Ankara expressing Zaire Ebola virus glycoprotein and other filovirus antigens (MVA-BN-Filo). Methods In the phase 1, single-blind, randomised trial of ChAd3-EBO-Z in the USA, we recruited adults aged 18–65 years from the University of Maryland medical community and the Baltimore community. In the phase 1b, open-label and double-blind, dose-escalation trial of ChAd3-EBO-Z in Mali, we recruited adults 18–50 years of age from six hospitals and health centres in Bamako (Mali), some of whom were also eligible for a nested, randomised, double-blind, placebo-controlled trial of MVA-BN-Filo. For randomised segments of the Malian trial and for the US trial, we randomly allocated participants (1:1; block size of six Malian or four US; ARB produced computer-generated randomisation lists; clinical staff did randomisation) to different single doses of intramuscular immunisation with ChAd3-EBO-Z: Malians received 1 × 1010 viral particle units (pu), 2·5 × 1010 pu, 5 × 1010 pu, or 1 × 1011 pu; US participants received 1 × 1010 pu or 1 × 1011 pu. We randomly allocated Malians in the nested trial (1:1) to receive a single dose of 2 × 108 plaque-forming units of MVA-BN-Filo or saline placebo. In the double-blind segments of the Malian trial, investigators, clinical staff, participants, and immunology laboratory staff were masked, but the study pharmacist (MK), vaccine administrator, and study statistician (ARB) were unmasked. In the US trial, investigators were not masked, but participants were. Analyses were per protocol. The primary outcome was safety, measured with occurrence of adverse events for 7 days after vaccination. Both trials are registered with ClinicalTrials.gov , numbers NCT02231866 (US) and NCT02267109 (Malian). Findings Between Oct 8, 2014, and Feb 16, 2015, we randomly allocated 91 participants in Mali (ten 11% to 1 × 1010 pu, 35 38% to 2·5 × 1010 pu, 35 38% to 5 × 1010 pu, and 11 12% to 1 × 1011 pu) and 20 in the USA (ten 50% to 1 × 1010 pu and ten 50% to 1 × 1011 pu), and boosted 52 Malians with MVA-BN-Filo (27 52%) or saline (25 48%). We identified no safety concerns with either vaccine: seven (8%) of 91 participants in Mali (five 5% received 5 × 1010 and two 2% received 1 × 1011 pu) and four (20%) of 20 in the USA (all received 1 × 1011 pu) given ChAd3-EBO-Z had fever lasting for less than 24 h, and 15 (56%) of 27 Malians boosted with MVA-BN-Filo had injection-site pain or tenderness. Interpretation 1 × 1011 pu single-dose ChAd3-EBO-Z could suffice for phase 3 efficacy trials of ring-vaccination containment needing short-term, high-level protection to interrupt transmission. MVA-BN-Filo boosting, although a complex regimen, could confer long-lived protection if needed (eg, for health-care workers). Funding Wellcome Trust, Medical Research Council UK, Department for International Development UK, National Cancer Institute, Frederick National Laboratory for Cancer Research, Federal Funds from National Institute of Allergy and Infectious Diseases.
Efforts to draw inferences about species occurrence frequently account for false negatives, the common situation when individuals of a species are not detected even when a site is occupied. However, ...recent studies suggest the need to also deal with false positives, which occur when species are misidentified so that a species is recorded as detected when a site is unoccupied. Bias in estimators of occupancy, colonization, and extinction can be severe when false positives occur. Accordingly, we propose models that simultaneously account for both types of error. Our approach can be used to improve estimates of occupancy for study designs where a subset of detections is of a type or method for which false positives can be assumed to not occur. We illustrate properties of the estimators with simulations and data for three species of frogs. We show that models that account for possible misidentification have greater support (lower AIC for two species) and can yield substantially different occupancy estimates than those that do not. When the potential for misidentification exists, researchers should consider analytical techniques that can account for this source of error, such as those presented here.
The watch-and-wait (WW) strategy aims to spare patients with rectal cancer unnecessary resection.
To analyze the outcomes of WW among patients with rectal cancer who had a clinical complete response ...to neoadjuvant therapy.
This retrospective case series analysis conducted at a comprehensive cancer center in New York included patients who received a diagnosis of rectal adenocarcinoma between January 1, 2006, and January 31, 2015. The median follow-up was 43 months. Data analyses were conducted from June 1, 2016, to October 1, 2018.
Patients had a clinical complete response after completing neoadjuvant therapy and agreed to a WW strategy of active surveillance and possible salvage surgery (n = 113), or patients underwent total mesorectal excision and were found to have a pathologic complete response (pCR) at resection (n = 136).
Kaplan-Meier estimates were used for analyses of local regrowth and 5-year rates of overall survival, disease-free survival, and disease-specific survival.
Compared with the 136 patients in the pCR group, the 113 patients in the WW group were older (median range, 67.2 32.1-90.9 vs 57.3 25.0-87.9 years, P < .001) with cancers closer to the anal verge (median range height from anal verge, 5.5 0.0-15.0 vs 7.0 0.0-13.0 cm). All 22 local regrowths in the WW group were detected on routine surveillance and treated by salvage surgery (20 total mesorectal excisions plus 2 transanal excisions). Pelvic control after salvage surgery was maintained in 20 of 22 patients (91%). No pelvic recurrences occurred in the pCR group. Rectal preservation was achieved in 93 of 113 patients (82%) in the WW group (91 patients with no local regrowths plus 2 patients with local regrowths salvaged with transanal excision). At 5 years, overall survival was 73% (95% CI, 60%-89%) in the WW group and 94% (95% CI, 90%-99%) in the pCR group; disease-free survival was 75% (95% CI, 62%-90%) in the WW group and 92% (95% CI, 87%-98%) in the pCR group; and disease-specific survival was 90% (95% CI, 81%-99%) in the WW group and 98% (95% CI, 95%-100%) in the pCR group. A higher rate of distant metastasis was observed among patients in the WW group who had local regrowth vs those who did not have local regrowth (36% vs 1%, P < .001).
A WW strategy for select rectal cancer patients who had a clinical complete response after neoadjuvant therapy resulted in excellent rectal preservation and pelvic tumor control; however, in the WW group, worse survival was noted along with a higher incidence of distant progression in patients with local regrowth vs those without local regrowth.
This trial involving 451 healthy adults assessed responses to two intramuscular doses of a subvirion H5N1 influenza vaccine. At the highest dose (90 μg of hemagglutinin), 54 percent of the subjects ...had neutralization antibody titers of 1:40 or greater. The subvirion vaccine did not cause severe side effects, and in most subjects, it generated neutralizing-antibody responses typically associated with protection against influenza. A conventional subvirion H5 influenza vaccine may be effective in preventing influenza A (H5N1) disease (avian influenza) in humans.
This trial involving 451 healthy adults assessed responses to two intramuscular doses of a subvirion H5N1 influenza vaccine. This vaccine may be effective in preventing influenza A (H5N1) disease in humans.
Avian influenza A viruses of the H5N1 subtype are currently causing widespread infections in bird populations throughout Southeast Asia, with spread into Central Asia, Africa, and Europe.
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There have been numerous instances of transmission of these viruses to humans, resulting in severe disease or death.
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These viruses possess a new H5 subtype of hemagglutinin, against which at present there is little immunity in human populations. The viruses have the potential to cause extremely severe respiratory illness in humans, and of the 169 cases reported to the World Health Organization as of February 13, 2006, 91 (54 percent) have been fatal. . . .
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