46 research outputs found
DC Cancellation As a Method of Generating a t^2 Response and of Solving the Radial Nonobservability Problem in a Concentric Free-Falling Two-Sphere Equivalence-Principle Experiment in a Drag-Free Satellite
This paper solves two major problems which have blocked a free-fall
Equivalence-Principle (EP) in a satellite for 25 years: a semimajor-axis error
between the two proof masses cannot be distinguished from an EP violation and
the response to an EP violation only grows as t not t^2. Using the cancellation
method described in this paper, the nonobservability problem can be suppressed
and a t^2 response can be generated which lasts between 10^4 and 10^6 seconds
depending on the cancellation accuracy. t^2 response times between 10^5 and
10^6 seconds are equivalent to a very tall (0.1 to 10 AU) drop tower with a
constant gravitational field of 3/7 ge.Comment: 40 pages, 7 figures, Revision 3.0: Reviewer's suggested corrections
for journal submissio
Azithromycin for community treatment of suspected COVID-19 in people at increased risk of an adverse clinical course in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial
This is the final version. Available on open access from Elsevier via the DOI in this recordData sharing:
Data can be shared with qualifying researchers who submit a proposal with a valuable research question as assessed by a committee formed from the Trial Management Group, including senior statistical and clinical representation. A contract should be signed. Requests should be directed to [email protected]
Azithromycin, an antibiotic with potential antiviral and anti-inflammatory properties, has been used to treat COVID-19, but evidence from community randomised trials is lacking. We aimed to assess the effectiveness of azithromycin to treat suspected COVID-19 among people in the community who had an increased risk of complications.
Methods
In this UK-based, primary care, open-label, multi-arm, adaptive platform randomised trial of interventions against COVID-19 in people at increased risk of an adverse clinical course (PRINCIPLE), we randomly assigned people aged 65 years and older, or 50 years and older with at least one comorbidity, who had been unwell for 14 days or less with suspected COVID-19, to usual care plus azithromycin 500 mg daily for three days, usual care plus other interventions, or usual care alone. The trial had two coprimary endpoints measured within 28 days from randomisation: time to first self-reported recovery, analysed using a Bayesian piecewise exponential, and hospital admission or death related to COVID-19, analysed using a Bayesian logistic regression model. Eligible participants with outcome data were included in the primary analysis, and those who received the allocated treatment were included in the safety analysis. The trial is registered with ISRCTN, ISRCTN86534580.
Findings
The first participant was recruited to PRINCIPLE on April 2, 2020. The azithromycin group enrolled participants between May 22 and Nov 30, 2020, by which time 2265 participants had been randomly assigned, 540 to azithromycin plus usual care, 875 to usual care alone, and 850 to other interventions. 2120 (94%) of 2265 participants provided follow-up data and were included in the Bayesian primary analysis, 500 participants in the azithromycin plus usual care group, 823 in the usual care alone group, and 797 in other intervention groups. 402 (80%) of 500 participants in the azithromycin plus usual care group and 631 (77%) of 823 participants in the usual care alone group reported feeling recovered within 28 days. We found little evidence of a meaningful benefit in the azithromycin plus usual care group in time to first reported recovery versus usual care alone (hazard ratio 1·08, 95% Bayesian credibility interval [BCI] 0·95 to 1·23), equating to an estimated benefit in median time to first recovery of 0·94 days (95% BCI −0·56 to 2·43). The probability that there was a clinically meaningful benefit of at least 1·5 days in time to recovery was 0·23. 16 (3%) of 500 participants in the azithromycin plus usual care group and 28 (3%) of 823 participants in the usual care alone group were hospitalised (absolute benefit in percentage 0·3%, 95% BCI −1·7 to 2·2). There were no deaths in either study group. Safety outcomes were similar in both groups. Two (1%) of 455 participants in the azothromycin plus usual care group and four (1%) of 668 participants in the usual care alone group reported admission to hospital during the trial, not related to COVID-19.
Interpretation
Our findings do not justify the routine use of azithromycin for reducing time to recovery or risk of hospitalisation for people with suspected COVID-19 in the community. These findings have important antibiotic stewardship implications during this pandemic, as inappropriate use of antibiotics leads to increased antimicrobial resistance, and there is evidence that azithromycin use increased during the pandemic in the UK.UK Research and InnovationUK Department of Health and Social Car
Ivermectin for COVID-19 in adults in the community (PRINCIPLE): an open, randomised, controlled, adaptive platform trial of short- and longer-term outcomes
This is the final version. Available on open access from Elsevier via the DOI in this recordBACKGROUND: The evidence for whether ivermectin impacts recovery, hospital admissions, and longer-term outcomes in COVID-19 is contested. The WHO recommends its use only in the context of clinical trials. METHODS: In this multicentre, open-label, multi-arm, adaptive platform randomised controlled trial, we included participants aged ≥18 years in the community, with a positive SARS-CoV-2 test, and symptoms lasting ≤14 days. Participants were randomised to usual care, usual care plus ivermectin tablets (target 300-400 μg/kg per dose, once daily for 3 days), or usual care plus other interventions. Co-primary endpoints were time to first self-reported recovery, and COVID-19 related hospitalisation/death within 28 days, analysed using Bayesian models. Recovery at 6 months was the primary, longer term outcome. TRIAL REGISTRATION: ISRCTN86534580. FINDINGS: The primary analysis included 8811 SARS-CoV-2 positive participants (median symptom duration 5 days), randomised to ivermectin (n=2157), usual care (n=3256), and other treatments (n=3398) from June 23, 2021 to July 1, 2022. Time to self-reported recovery was shorter in the ivermectin group compared with usual care (hazard ratio 1·15 [95% Bayesian credible interval, 1·07 to 1·23], median decrease 2.06 days [1·00 to 3·06]), probability of meaningful effect (pre-specified hazard ratio ≥1.2) 0·192). COVID-19-related hospitalisations/deaths (odds ratio 1·02 [0·63 to 1·62]; estimated percentage difference 0% [-1% to 0·6%]), serious adverse events (three and five respectively), and the proportion feeling fully recovered were similar in both groups at 6 months (74·3% and 71·2% respectively (RR = 1·05, [1·02 to 1·08]) and also at 3 and 12 months.,. INTERPRETATION: Ivermectin for COVID-19 is unlikely to provide clinically meaningful improvement in recovery, hospital admissions, or longer-term outcomes. Further trials of ivermectin for SARS-Cov-2 infection in vaccinated community populations appear unwarranted. FUNDING: UKRI / National Institute of Health Research (MC_PC_19079).National Institute for Health and Care Research (NIHR
Multi-Collision Resistance: A Paradigm for Keyless Hash Functions
We introduce a new notion of multi-collision resistance for keyless hash functions. This is a natural relaxation of collision resistance where it is hard to find multiple inputs with the same hash in the following sense. The number of colliding inputs that a polynomial-time non-uniform adversary can find is not much larger than its advice. We discuss potential candidates for this notion and study its applications.
Assuming the existence of such hash functions, we resolve the long-standing question of the round complexity of zero knowledge protocols --- we construct a 3-message zero knowledge argument against arbitrary polynomial-size non-uniform adversaries. We also improve the round complexity in several other central applications, including a 3-message succinct argument of knowledge for NP, a 4-message zero-knowledge proof, and a 5-message public-coin zero-knowledge argument. Our techniques can also be applied in the keyed setting, where we match the round complexity of known protocols while relaxing the underlying assumption from collision-resistance to keyed multi-collision resistance.
The core technical contribution behind our results is a domain extension transformation from multi-collision-resistant hash functions for a fixed input length to ones with an arbitrary input length and a local opening property. The transformation is based on a combination of classical domain extension techniques, together with new information-theoretic tools. In particular, we define and construct a new variant of list-recoverable codes, which may be of independent interest
Pinning adaptive synchronization of neutral-type coupled neural networks with stochastic perturbation
Multi-dimensional Geologic Mapping of the Villa Grove Quadrangle, Douglas County, Illinois
Computer generated map"Mapping team: Curtis C. Abert ... [et al.]."The base is an aerial photoIncludes 2 3-D views, text, col. ill., location map, and 2 stratigraphic columnsSurficial geology -- Bedrock geology -- Drift aquifers -- Bedrock Aquifers -- General aquifer sensitivity -- Aquifer sensitivity to nitrate leaching -- Coal and aggregate resources -- Bedrock topography -- Drift thickness
Multi-dimensional Geologic Mapping of the Villa Grove Quadrangle, Douglas County, Illinois
Computer generated map"Mapping team: Curtis C. Abert ... [et al.]."The base is an aerial photoIncludes 2 3-D views, text, col. ill., location map, and 2 stratigraphic columnsSurficial geology -- Bedrock geology -- Drift aquifers -- Bedrock Aquifers -- General aquifer sensitivity -- Aquifer sensitivity to nitrate leaching -- Coal and aggregate resources -- Bedrock topography -- Drift thickness