Several health organizations, mainly in Western countries, have recently authorized the use of a booster dose of the COVID-19 vaccine for patients previously vaccinated with mRNA vaccines, with ...criteria that do not always coincide. The COVID Scientific Committee of the Illustrious College of Physicians of Madrid (ICOMEM) has received and asked several questions about this situation, to which the group has tried to give answers, after deliberation and consensus. The efficacy of the vaccines administered so far is beyond doubt and they have managed to reduce, fundamentally, the severe forms of the disease. The duration of this protection is not well known, is different in different individuals and for different variants of the virus and is not easily predictable with laboratory tests. Data on the real impact of a supplementary or "booster" dose in the scientific literature are scarce for the moment and its application in large populations such as those in the state of Israel may be associated with a decrease in the risk of new and severe episodes in the short observation period available. We also lack sufficient data on the safety and potential adverse effects of these supplementary doses and we do not know the ideal time to administer them in different situations. In this state of affairs, it seems prudent to administer supplemental doses to those exposed to a higher risk, such as immunocompromised individuals and the elderly. On the other hand, we consider that this is not the time to accelerate, on the spur of the moment, a massive administration of a third dose to other population groups that are less exposed and at lower risk, without waiting for adequate scientific information, which will undoubtedly arrive gradually. We do not believe that this position is incompatible with the practical and ethical warnings made by the World Health Organization in this respect.
For the first time, a small dual-phase (liquid/gas) xenon time projection chamber was equipped with a top array of silicon photomultipliers for light and charge readout. Here we describe the ...instrument in detail, as well as the data processing and the event position reconstruction algorithms. We obtain a spatial resolution of Formula omitted in the horizontal plane. To characterise the detector performance, we show calibration data with internal Formula omitted and Formula omitted sources, and we detail the production of the latter as well as its introduction into the system. We finally compare the observed light and charge yields down to electronic recoil energies of Formula omitted to predictions based on NEST v2.0.
The DARWIN observatory is a proposed next-generation experiment to search for particle dark matter and for the neutrinoless double beta decay of
136
Xe. Out of its 50 t total natural xenon inventory, ...40 t will be the active target of a time projection chamber which thus contains about 3.6 t of
136
Xe. Here, we show that its projected half-life sensitivity is
2.4
×
10
27
year
, using a fiducial volume of 5 t of natural xenon and 10 year of operation with a background rate of less than 0.2 events/(t
·
year) in the energy region of interest. This sensitivity is based on a detailed Monte Carlo simulation study of the background and event topologies in the large, homogeneous target. DARWIN will be comparable in its science reach to dedicated double beta decay experiments using xenon enriched in
136
Xe.
Injectable cabotegravir was superior to daily oral tenofovir disoproxil fumarate plus emtricitabine for HIV prevention in two clinical trials. Both trials had the primary aim of establishing the HIV ...prevention efficacy of long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) compared with tenofovir disoproxil fumarate plus emtricitabine daily oral PrEP. Long-acting PrEP was associated with diagnostic delays and integrase strand-transfer inhibitor (INSTI) resistance. This report presents findings from the first unblinded year of the HIV Prevention Trials Network (HPTN) 083 study.
The HPTN 083 randomised controlled trial enrolled HIV-uninfected cisgender men and transgender women at elevated HIV risk who have sex with men, from 43 clinical research sites in Africa, Asia, Latin America, and the USA. Inclusion criteria included: a negative HIV serological test at the screening and study entry, undetectable HIV RNA levels within 14 days of study entry, age 18 years or older, overall good health as determined by clinical and laboratory evaluations, and a creatinine clearance of 60 mL/min or higher. Participants were randomly allocated to receive long-acting injectable cabotegravir or daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP. After study unblinding, participants remained on their original regimen awaiting an extension study. HIV infections were characterised retrospectively at a central laboratory. Here we report the secondary analysis of efficacy and safety for the first unblinded year. The primary outcome was incident HIV infection. Efficacy analyses were done on the modified intention-to-treat population using a Cox regression model. Adverse events were compared across treatment groups and time periods (blinded vs unblinded). This trial is registered with ClinicalTrials.gov, NCT02720094.
Of the 4488 participants who contributed person-time to the blinded analysis, 3290 contributed person-time to the first unblinded year analysis between May 15, 2020, and May 14, 2021. Updated HIV incidence in the blinded phase was 0·41 per 100 person-years for long-acting injectable cabotegravir PrEP and 1·29 per 100 person-years for daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP (hazard ratio HR 0·31 95% CI 0·17-0·58, p=0·0003). HIV incidence in the first unblinded year was 0·82 per 100 person-years for long-acting PrEP and 2·27 per 100 person-years for daily oral PrEP (HR 0·35 0·18-0·69, p=0·002). Adherence to both study products decreased after study unblinding. Additional infections in the long-acting PrEP group included two with on-time injections; three with one or more delayed injections; two detected with long-acting PrEP reinitiation; and 11 more than 6 months after their last injection. Infection within 6 months of cabotegravir exposure was associated with diagnostic delays and INSTI resistance. Adverse events were generally consistent with previous reports; incident hypertension in the long-acting PrEP group requires further investigation.
Long-acting injectable cabotegravir PrEP retained high efficacy for HIV prevention in men and transgender women who have sex with men during the first year of open-label follow-up, with a near-identical HR for HIV risk reduction between long-acting injectable cabotegravir and daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP during the first year after unblinding compared with the blinded period. Extended follow-up further defined the risk period for diagnostic delays and emergence of INSTI resistance.
Division of AIDS at the National Institute of Allergy and Infectious Diseases, ViiV Healthcare, and Gilead Sciences.
Abstract
For the first time, a small dual-phase (liquid/gas) xenon time projection chamber was equipped with a top array of silicon photomultipliers for light and charge readout. Here we describe the ...instrument in detail, as well as the data processing and the event position reconstruction algorithms. We obtain a spatial resolution of
$$\sim 1.5\,\text {mm}$$
∼
1.5
mm
in the horizontal plane. To characterise the detector performance, we show calibration data with internal
$$^{83\text {m}}\hbox {Kr}$$
83
m
Kr
and
$$^{37}\hbox {Ar}$$
37
Ar
sources, and we detail the production of the latter as well as its introduction into the system. We finally compare the observed light and charge yields down to electronic recoil energies of
$$2.82\,\text {keV}$$
2.82
keV
to predictions based on NEST v2.0.
For the first time, a small dual-phase (liquid/gas) xenon time projection chamber was equipped with a top array of silicon photomultipliers for light and charge readout. Here we describe the ...instrument in detail, as well as the data processing and the event position reconstruction algorithms. We obtain a spatial resolution of
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\begin{document}$$\sim 1.5\,\text {mm}$$\end{document}
∼
1.5
mm
in the horizontal plane. To characterise the detector performance, we show calibration data with internal
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\begin{document}$$^{83\text {m}}\hbox {Kr}$$\end{document}
83
m
Kr
and
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\begin{document}$$^{37}\hbox {Ar}$$\end{document}
37
Ar
sources, and we detail the production of the latter as well as its introduction into the system. We finally compare the observed light and charge yields down to electronic recoil energies of
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\begin{document}$$2.82\,\text {keV}$$\end{document}
2.82
keV
to predictions based on NEST v2.0.
Deep neural networks are a powerful technique that have found ample applications in several branches of physics. In this work, we apply deep neural networks to a specific problem of cosmic ray ...physics: the estimation of the muon content of extensive air showers when measured at the ground. As a working case, we explore the performance of a deep neural network applied to large sets of simulated signals recorded for the water-Cherenkov detectors of the Surface Detector of the Pierre Auger Observatory. The inner structure of the neural network is optimized through the use of genetic algorithms. To obtain a prediction of the recorded muon signal in each individual detector, we train neural networks with a mixed sample of simulated events that contain light, intermediate and heavy nuclei. When true and predicted signals are compared at detector level, the primary values of the Pearson correlation coefficients are above 95%. The relative errors of the predicted muon signals are below 10% and do not depend on the event energy, zenith angle, total signal size, distance range or the hadronic model used to generate the events.