Cost-effectively 3d-printed rigid and versatile interpenetrating polymer networks

Versatile acrylate–epoxy hybrid formulations are becoming widespread in photo/thermal dual-processing scenarios, especially in 3D printing applications. Usually, parts are printed in a stereolithography or digital light processing (DLP) 3D printer, after which a thermal treatment would bestow the final material with superior mechanical properties. We report the successful formulation of such a hybrid system, consisting of a commercial 3D printing acrylate resin modified by an epoxy– anhydride mixture. In the final polymeric network, we observed segregation of an epoxy-rich phase as nano-domains, similar to what was observed in a previous work. However, in the current work, we show the effectiveness of a coupling agent added to the formulation to mitigate this segregation for when such phase separation is undesired. The hybrid materials showed significant improvement of Young’s modulus over the neat acrylate. Once the flexible, partially-cured material was printed with a minimal number of layers, it could be molded into a complex form and thermally cured. Temporary shapes were readily programmable on this final material, with easy shape recovery under mild temperatures. Inspired by repairable 3D printed materials described recently, we manufactured a large object by printing its two halves, and then joined them covalently at the thermal cure stage with an apparently seamless unionPeer ReviewedPostprint (author's final draft

Analiza czynników wpływających na dyspersję QTc u pacjentów z ostrym zespołem wieńcowym leczonych za pomocą pierwotnej angioplastyki wieńcowej

Wstęp: Dyspersja QTc jako wskaźnik niejednorodnej repolaryzacji komór jest uznanym czynnikiem wystąpienia zagrażających życiu komorowych zaburzeń rytmu. W ostrym zespole wieńcowym zmiany dynamiki dyspersji QTc spowodowane są niedokrwieniem. Celem pracy było określenie czynników wiążących się z dynamiką dyspersji QTc u pacjentów z ostrym zespołem wieńcowym leczonych za pomocą pierwotnej angioplastyki wieńcowej (PTCA). Materiał i metody: Badaniem objęto 52 pacjentów z ostrym zespołem wieńcowym, których poddano interwencyjnemu leczeniu reperfuzyjnemu za pomocą PTCA. Badanie EKG wykonywano przy przyjęciu (badanie wyjściowe) i po 12 godzinach po przeprowadzeniu zabiegu PTCA. Pomiarów dokonywały ręcznie dwie niezależne osoby; w przypadku niezgodności wyliczano średnią i taki wynik uznawano za ostateczny. W obu badaniach EKG obliczano QTc według wzoru Bezetta oraz dyspersję QTc jako różnicę miedzy maksymalną i minimalną wartością QTc w tej samej ewolucji serca. Ze względu na dynamikę dyspersji QTc pacjentów podzielono na dwie grupy: grupę A - ze skróceniem dyspersji QTc po interwencji i grupę B - z wydłużeniem dyspersji QTc po interwencji. Wyniki: Grupa A liczyła 27 pacjentów (19 mężczyzn i 8 kobiet), zaś grupa B - 25 osób (17 mężczyzn i 8 kobiet). W grupie A średnia wartość dyspersji QTc przed zabiegiem wyniosła 123,92 &plusmn; 33,78 ms, po zabiegu 85,73 &plusmn; 56,06 ms, w grupie B odpowiednio: 78,24 &plusmn; 60 ms oraz 119,53 &plusmn; 44,33. Ryzyko zwiększenia dyspersji QTc po angioplastyce wzrastało 5-krotnie, jeżeli doszło do niepełnej rewaskularyzacji (OR = 4,89; p < 0,03). Wnioski: Brak spadku dyspersji QTc po angioplastyce wieńcowej jest charakterystyczny dla pacjentów z chorobą wielonaczyniową. Skuteczne przywrócenie przepływu wieńcowego skraca dyspersję QTc w ostrej fazie zawału serca. (Folia Cardiol. 2004; 11: 513&#8211;519

Analiza czynników wpływających na dyspersję QTc u pacjentów z ostrym zespołem wieńcowym leczonych za pomocą pierwotnej angioplastyki wieńcowej

Wstęp: Dyspersja QTc jako wskaźnik niejednorodnej repolaryzacji komór jest uznanym czynnikiem wystąpienia zagrażających życiu komorowych zaburzeń rytmu. W ostrym zespole wieńcowym zmiany dynamiki dyspersji QTc spowodowane są niedokrwieniem. Celem pracy było określenie czynników wiążących się z dynamiką dyspersji QTc u pacjentów z ostrym zespołem wieńcowym leczonych za pomocą pierwotnej angioplastyki wieńcowej (PTCA). Materiał i metody: Badaniem objęto 52 pacjentów z ostrym zespołem wieńcowym, których poddano interwencyjnemu leczeniu reperfuzyjnemu za pomocą PTCA. Badanie EKG wykonywano przy przyjęciu (badanie wyjściowe) i po 12 godzinach po przeprowadzeniu zabiegu PTCA. Pomiarów dokonywały ręcznie dwie niezależne osoby; w przypadku niezgodności wyliczano średnią i taki wynik uznawano za ostateczny. W obu badaniach EKG obliczano QTc według wzoru Bezetta oraz dyspersję QTc jako różnicę miedzy maksymalną i minimalną wartością QTc w tej samej ewolucji serca. Ze względu na dynamikę dyspersji QTc pacjentów podzielono na dwie grupy: grupę A - ze skróceniem dyspersji QTc po interwencji i grupę B - z wydłużeniem dyspersji QTc po interwencji. Wyniki: Grupa A liczyła 27 pacjentów (19 mężczyzn i 8 kobiet), zaś grupa B - 25 osób (17 mężczyzn i 8 kobiet). W grupie A średnia wartość dyspersji QTc przed zabiegiem wyniosła 123,92 &plusmn; 33,78 ms, po zabiegu 85,73 &plusmn; 56,06 ms, w grupie B odpowiednio: 78,24 &plusmn; 60 ms oraz 119,53 &plusmn; 44,33. Ryzyko zwiększenia dyspersji QTc po angioplastyce wzrastało 5-krotnie, jeżeli doszło do niepełnej rewaskularyzacji (OR = 4,89; p < 0,03). Wnioski: Brak spadku dyspersji QTc po angioplastyce wieńcowej jest charakterystyczny dla pacjentów z chorobą wielonaczyniową. Skuteczne przywrócenie przepływu wieńcowego skraca dyspersję QTc w ostrej fazie zawału serca. (Folia Cardiol. 2004; 11: 513&#8211;519

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

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

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation