Real-world Effectiveness and Tolerability of Interferon-free Direct-acting Antiviral for 15,849 Patients with Chronic Hepatitis C: A Multinational Cohort Study

BACKGROUND AND AIMS: As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6. METHODS: We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014-07/01/2021. RESULTS: The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12. CONCLUSIONS: In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (\u3e91%)

The United States COVID-19 Forecast Hub dataset

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Healing of scratches atop polymeric materials

This report covers the experimental investigation of the shape memory effect of low melt-flow index thermoplastic polyurethane (TPU) 262A. Several tests were conducted to observe how TPU 262A recovers from different forms of plastic deformation made at room temperature. Results concluded that significant shape recovery is achievable when the material is heated past its melting point, but within a certain range.Bachelor of Engineering (Mechanical Engineering

Design and analysis of a K-band wideband voltage-controlled oscillator with robust start-up and frequency boost

This study presents a K-band differential voltage-controlled oscillator (VCO) with robust start-up. A hybrid technique that combines open-loop digitally controlled tail current with switchable auxiliary cross-coupled pairs (ACCPs) is proposed to ensure robust start-up for wideband operation. Compared with prior closed-loop current controlling method, the proposed technique does not suffer from phase-noise degradation. Furthermore, by evenly distributing the ACCPs, transistors with smaller size are allowed to achieve the same start-up condition, which leads to frequency boost and phase-noise improvement. Implemented in 0.18 μm complementary metal-oxide-semiconductor technology, the VCO achieves a wide-frequency tuning range of 21.4-26.29 GHz (20.5%) and a low phase noise of -108.8 dBc/Hz at 1 MHz offset from 25.8 GHz carrier frequency. At 1.1 V power supply, the power consumption of the core circuit is 7.9-11.4 mW across the entire output frequency range.MOE (Min. of Education, S’pore)Accepted versio

Vitrimer-Like Shape Memory Polymers: Characterization and Applications in Reshaping and Manufacturing

The shape memory effect (SME) refers to the ability of a material to recover its original shape, but only in the presence of a right stimulus. Most polymers, either thermo-plastic or thermoset, can have the SME, although the actual shape memory performance varies according to the exact material and how the material is processed. Vitrimer, which is between thermoset and thermo-plastic, is featured by the reversible cross-linking. Vitrimer-like shape memory polymers (SMPs) combine the vitrimer-like behavior (associated with dissociative covalent adaptable networks) and SME, and can be utilized to achieve many novel functions that are difficult to be realized by conventional polymers. In the first part of this paper, a commercial polymer is used to demonstrate how to characterize the vitrimer-like behavior based on the heating-responsive SME. In the second part, a series of cases are presented to reveal the potential applications of vitrimer-like SMPs and their composites. It is concluded that the vitrimer-like feature not only enables many new ways in reshaping polymers, but also can bring forward new approaches in manufacturing, such as, rapid 3D printing in solid state on space/air/sea missions

Vitrimer-like shape memory polymers : characterization and applications in reshaping and manufacturing

The shape memory effect (SME) refers to the ability of a material to recover its original shape, but only in the presence of a right stimulus. Most polymers, either thermo-plastic or thermoset, can have the SME, although the actual shape memory performance varies according to the exact material and how the material is processed. Vitrimer, which is between thermoset and thermo-plastic, is featured by the reversible cross-linking. Vitrimer-like shape memory polymers (SMPs) combine the vitrimer-like behavior (associated with dissociative covalent adaptable networks) and SME, and can be utilized to achieve many novel functions that are difficult to be realized by conventional polymers. In the first part of this paper, a commercial polymer is used to demonstrate how to characterize the vitrimer-like behavior based on the heating-responsive SME. In the second part, a series of cases are presented to reveal the potential applications of vitrimer-like SMPs and their composites. It is concluded that the vitrimer-like feature not only enables many new ways in reshaping polymers, but also can bring forward new approaches in manufacturing, such as, rapid 3D printing in solid state on space/air/sea missions.Published versio