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The genus is an efficiently computable arithmetic invariant for lattices up to isomorphism. Given the recent proposals of basing cryptography on the lattice isomorphism problem, it is of cryptographic interest to classify relevant families of lattices according to their genus. We propose such a classification for q-ary lattices, and also study their distribution. In particular, for an odd prime q, we show that random q-ary lattices are mostly concentrated on two genera. Because the genus is local, this also provides information on the distribution for general odd q. The case of q a power of 2 is also studied, although we only achieve a partial classification.

The lattice isomorphism problem (LIP) asks one to find an isometry between two lattices. It has recently been proposed as a foundation for cryptography in two independent works [Ducas & van Woerden, EUROCRYPT 2022, Bennett et al. preprint 2021]. This problem is the lattice variant of the code equivalence problem, on which the notion of the hull of a code can lead to devastating attacks. In this work we study the cryptanalytic role of an adaptation of the hull to the lattice setting, namely, the s-hull. We first show that the s-hull is not helpful for creating an arithmetic distinguisher. More specifically, the genus of the s-hull can be efficiently predicted from s and the original genus and therefore carries no extra information. However, we also show that the hull can be helpful for geometric attacks: for certain lattices the minimal distance of the hull is relatively smaller than that of the original lattice, and this can be exploited. The attack cost remains exponential, but the constant in the exponent is halved. This second result gives a counterexample to the general hardness conjecture of LIP proposed by Ducas & van Woerden. Our results suggest that one should be very considerate about the geometry of hulls when instantiating LIP for cryptography. They also point to unimodular lattices as attractive options, as they are equal to their dual and their hulls, leaving only the original lattice to an attacker. Remarkably, this is already the case in proposed instantiations, namely the trivial lattice Zn and the Barnes-Wall lattices.

Background: The European AIDS Clinical Society (EACS) Guidelines cover key aspects of HIV management with major updates every two years. Guideline highlights: The 2019 Guidelines were extended with a new section focusing on drug–drug interactions and other prescribing issues in people living with HIV (PLWH). The recommendations for treatment-naïve PLWH were updated with four preferred regimens favouring unboosted integrase inhibitors. A two-drug regimen with dolutegravir and lamivudine, and a three-drug regimen including doravirine were also added to the recommended initial regimens. Lower thresholds for hypertension were expanded to all PLWH and for cardiovascular disease prevention, the 10-year predicted risk threshold for consideration of antiretroviral therapy (ART) modification was lowered from 20% to 10%. Frailty and obesity were added as new topics. It was specified to use urine albumin to creatinine ratio to screen for glomerular disease and urine protein to creatinine ratio for tubular diseases, and thresholds were streamlined with the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations. Hepatitis C virus (HCV) treatment recommendations were split into preferred and alternative treatment options. The algorithm for management of recently acquired HCV infection was updated and includes recommendations for early chronic infection management. Treatment of resistant tuberculosis (TB) was streamlined with the World Health Organization (WHO) recommendations, and new tables on immune reconstitution inflammatory syndrome, on when to start ART in the presence of opportunistic infections and on TB drug dosing were included. Conclusions: The EACS Guidelines underwent major revisions of all sections in 2019. They are available in four different formats including a new interactive web-based version and are translated into Chinese, French, German, Japanese, Portuguese, Russian and Spanish.

Item does not contain fulltext, The coronavirus disease 2019 (COVID-19) antiviral nirmatrelvir/ritonavir (Paxlovid) has been granted authorization or approval in several countries for the treatment of patients with mild to moderate COVID-19 at high risk of progression to severe disease and with no requirement for supplemental oxygen. Nirmatrelvir/ritonavir will be primarily administered outside the hospital setting as a 5-day course oral treatment. The ritonavir component boosts plasma concentrations of nirmatrelvir through the potent and rapid inhibition of the key drug-metabolizing enzyme cytochrome P450 (CYP) 3A4. Thus nirmatrelvir/ritonavir, even given as a short treatment course, has a high potential to cause harm from drug-drug interactions (DDIs) with other drugs metabolized through this pathway. Options for mitigating risk from DDIs with nirmatrelvir/ritonavir are limited due to the clinical illness, the short window for intervention, and the related difficulty of implementing clinical monitoring or dosage adjustment of the comedication. Pragmatic options are largely confined to preemptive or symptom-driven pausing of the comedication or managing any additional risk through counseling. This review summarizes the effects of ritonavir on drug disposition (i.e., metabolizing enzymes and transporters) and discusses factors determining the likelihood of having a clinically significant DDI. Furthermore, it provides a comprehensive list of comedications likely to be used in COVID-19 patients which are categorized according to their potential DDI risk with nirmatrelvir/ritonavir. It also discusses recommendations for the management of DDIs which balance the risk of harm from DDIs with a short course of ritonavir, against unnecessary denial of nirmatrelvir/ritonavir treatment.

Item does not contain fulltext, Nirmatrelvir–ritonavir (NMV/r) is now being used to treat high-risk patients with mild to moderate COVID-19. This article provides advice to clinicians regarding recognition of medications likely to interact with NMV/r and suggests approaches to managing such drug–drug interactions. An algorithm is provided to assist in decision making.

The genus is an efficiently computable arithmetic invariant for lattices up to isomorphism. Given the recent proposals of basing cryptography on the lattice isomorphism problem, it is of cryptographic interest to classify relevant families of lattices according to their genus. We propose such a classification for q-ary lattices, and also study their distribution. In particular, for an odd prime q, we show that random q-ary lattices are mostly concentrated on two genera. Because the genus is local, this also provides information on the distribution for general odd q. The case of q a power of 2 is also studied, although we only achieve a partial classification.

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Contains fulltext : 232502.pdf (Publisher’s version ) (Open Access), INTRODUCTION: In December 2019, an outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began, resulting in a number of antivirals and immune modulators being repurposed to treat the associated coronavirus disease 2019 (COVID-19). Many patients requiring treatment for COVID-19 may have either pre-existing renal or hepatic disease or experience acute renal/hepatic injury as a result of the acute infection. Altered renal or hepatic function can significantly affect drug concentrations of medications due to impaired drug metabolism and excretion, resulting in toxicity or reduced efficacy. The aim of this paper is to review the pharmacokinetics and available study data for the experimental COVID-19 therapies in patients with any degree of renal or hepatic impairment to make recommendations for dosing. METHODS: COVID-19 agents included in these recommendations were listed as primaries on the University of Liverpool COVID-19 drug interaction website ( www.covid19-druginteractions.org ), initially identified from Clinicialtrials.gov and ChicCTR.org.cn. A literature search was performed using PubMed and EMBASE as well as product licences and pharmacokinetic databases. FINDINGS: Remdesivir, dexamethasone, azithromycin, favipiravir, lopinavir/ritonavir, atazanavir, hydroxychloroquine, interferon beta, ribavirin, tocilizumab, anakinra and sarilumab were identified as experimental drugs being used in COVID-19 trials as of November 2020. Limited study data was found for these drugs in patients with renal or hepatic impairment for COVID-19 or other indications. Recommendations were made based on available data, consideration of pharmacokinetic properties (including variability), the dosing and anticipated treatment duration of each regimen in COVID-19 and known toxicities. CONCLUSION: Dosing of drugs used to treat COVID-19 in patients with renal or hepatic impairment is complex. These recommendations were produced to provide guidance to clinicians worl

Contains fulltext : 229144.pdf (Publisher’s version ) (Closed access), As global health services respond to the coronavirus pandemic, many prescribers are turning to experimental drugs. This review aims to assess the risk of drug-drug interactions in the severely ill COVID-19 patient. Experimental therapies were identified by searching ClinicalTrials.gov for 'COVID-19', '2019-nCoV', '2019 novel coronavirus' and 'SARS-CoV-2'. The last search was performed on 30 June 2020. Herbal medicines, blood-derived products and in vitro studies were excluded. We identified comorbidities by searching PubMed for the MeSH terms 'COVID-19', 'Comorbidity' and 'Epidemiological Factors'. Potential drug-drug interactions were evaluated according to known pharmacokinetics, overlapping toxicities and QT risk. Drug-drug interactions were graded GREEN and YELLOW: no clinically significant interaction; AMBER: caution; RED: serious risk. A total of 2378 records were retrieved from ClinicalTrials.gov, which yielded 249 drugs that met inclusion criteria. Thirteen primary compounds were screened against 512 comedications. A full database of these interactions is available at www.covid19-druginteractions.org. Experimental therapies for COVID-19 present a risk of drug-drug interactions, with lopinavir/ritonavir (10% RED, 41% AMBER; mainly a perpetrator of pharmacokinetic interactions but also risk of QT prolongation particularly when given with concomitant drugs that can prolong QT), chloroquine and hydroxychloroquine (both 7% RED and 27% AMBER, victims of some interactions due to metabolic profile but also perpetrators of QT prolongation) posing the greatest risk. With management, these risks can be mitigated. We have published a drug-drug interaction resource to facilitate medication review for the critically ill patient.

Summary ‘Precision seismology’ encompasses a set of methods which use differential measurements of time-delays to estimate the relative locations of earthquakes and explosions. Delay-times estimated from signal correlations often allow far more accurate estimates of one event location relative to another than is possible using classical hypocentre determination techniques. Many different algorithms and software implementations have been developed and different assumptions and procedures can often result in significant variability between different relative event location estimates. We present a Ground Truth (GT) dataset of 55 military surface explosions in northern Finland in 2007 that all took place within 300 m of each other. The explosions were recorded with a high signal-to-noise ratio to distances of about 2°, and the exceptional waveform similarity between the signals from the different explosions allows for accurate correlation-based time-delay measurements. With exact coordinates for the explosions, we are able to assess the fidelity of relative location estimates made using any location algorithm or implementation. Applying double-difference calculations using two different 1-D velocity models for the region results in hypocentre-to-hypocentre distances which are too short and it is clear that the wavefield leaving the source region is more complicated than predicted by the models. Using the GT event coordinates, we are able to measure the slowness vectors associated with each outgoing ray from the source region. We demonstrate that, had such corrections been available, a significant improvement in the relative location estimates would have resulted. In practice we would of course need to solve for event hypocentres and slowness corrections simultaneously, and significant work will be needed to upgrade relative location algorithms to accommodate uncertainty in the form of the outgoing wavefield. We present this data set, together with GT coordinates, raw wa