52 research outputs found

    CT-Wasm: Type-Driven Secure Cryptography for the Web Ecosystem

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    A significant amount of both client and server-side cryptography is implemented in JavaScript. Despite widespread concerns about its security, no other language has been able to match the convenience that comes from its ubiquitous support on the "web ecosystem" - the wide variety of technologies that collectively underpins the modern World Wide Web. With the introduction of the new WebAssembly bytecode language (Wasm) into the web ecosystem, we have a unique opportunity to advance a principled alternative to existing JavaScript cryptography use cases which does not compromise this convenience. We present Constant-Time WebAssembly (CT-Wasm), a type-driven, strict extension to WebAssembly which facilitates the verifiably secure implementation of cryptographic algorithms. CT-Wasm's type system ensures that code written in CT-Wasm is both information flow secure and resistant to timing side channel attacks; like base Wasm, these guarantees are verifiable in linear time. Building on an existing Wasm mechanization, we mechanize the full CT-Wasm specification, prove soundness of the extended type system, implement a verified type checker, and give several proofs of the language's security properties. We provide two implementations of CT-Wasm: an OCaml reference interpreter and a native implementation for Node.js and Chromium that extends Google's V8 engine. We also implement a CT-Wasm to Wasm rewrite tool that allows developers to reap the benefits of CT-Wasm's type system today, while developing cryptographic algorithms for base Wasm environments. We evaluate the language, our implementations, and supporting tools by porting several cryptographic primitives - Salsa20, SHA-256, and TEA - and the full TweetNaCl library. We find that CT-Wasm is fast, expressive, and generates code that we experimentally measure to be constant-time

    Facial Mask Use and COVID-19 Protection Measures in Jefferson County, Kentucky: Results from an Observational Survey, November 5−11, 2020

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    Introduction: The transmission of respiratory infectious diseases such as COVID-19 can significantly decrease by mask-wearing. However, accurate information about the extent and proper use of the facial mask is scarce. This study’s main objective was to observe and analyze mask-wearing behavior and the level of COVID-19 protection measures in indoor public areas (PAs) of Jefferson County, Kentucky. Methods: For conducting the observational survey study, targets were indoor PAs, and zip codes were defined as surveying clusters. The number of selected PAs in each zip code was proportional to the population and the total number of PAs in that zip code. The PA pool in a zip code was divided into four groups, followed by random selection without replacement from each group. Results: A total of 191 PAs were surveyed: 50 of them were grocery stores, 56 were convenience stores or pharmacies, 39 were wine and liquor stores, and 46 were other stores. At least one unmasked and one incorrectly masked staff were observed in 26% and 40% of the sampled PAs, respectively. Also, in 29% and 35% of the PAs, at least one unmasked and one incorrectly masked visitor were observed, respectively. The rates varied by PA size and county district. Eighty percent of unmasked staff and 75% of the unmasked visitors were male. The rate of unmasked males varied from 50% to 100% across districts. About 66% of unmasked staff among all Jefferson County districts were young adults. More than one-fourth of all the PAs provided hand sanitizer for visitors’ use, and only 2% of the PAs provided masks to their visitors. Conclusion: Messaging about mask use and correct usage may need to particularly target the 19-44-year-old male population, as these individuals were the most prevalent among those unmasked and masked incorrectly. Additionally, businesses’ protective measures may depend on their resources to operate in such a manner. Hand sanitizer is easier to offer visitors, while staffing to regularly sanitize carts or funds to provide a sufficient number of wipes, gloves, or masks may present further opportunities for government assistance

    Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

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    Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

    Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

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    Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

    Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

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    Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

    Repression of BLADE-ON-PETIOLE genes by KNOX homeodomain protein BREVIPEDICELLUS is essential for differentiation of secondary xylem in Arabidopsis root

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    Main conclusion: Repression of boundary genes by KNOTTED1-like homeodomain transcription factor BREVIPEDICELLUS promotes the differentiation of phase II secondary xylem in Arabidopsis roots.Plant growth and development relies on the activity of meristems. Boundaries are domains of restricted growth that separate forming organs and the meristem. Class I KNOX homeodomain transcription factors are important regulators of meristem maintenance. Members of this class including BREVIDICELLUS also called KNOTTED-LIKE FROM ARABIDOPSIS THALIANA1 (BP/KNAT1) fulfill this function in part by spatially regulating boundary genes. The vascular cambium is a lateral meristem that allows for radial expansion of organs during secondary growth. We show here that BP/KNAT1 repression of boundary genes plays a crucial role in root secondary growth. In particular, exclusion of BLADE-ON-PETIOLE1/2 (BOP1/2) and other members of this module from xylem is required for the differentiation of lignified fibers and vessels during the xylem expansion phase of root thickening. These data reveal a previously undiscovered role for boundary genes in the root and shed light on mechanisms controlling wood development in trees
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