| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Micah, Angela E., et al.
(författare)
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Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
- 2021
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
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Forskningsöversikt (refereegranskat)abstract
- Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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| 4. |
- Bass, Gary Alan, 1979-, et al.
(författare)
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Techniques for mesoappendix transection and appendix resection: insights from the ESTES SnapAppy study
- 2023
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Ingår i: European Journal of Trauma and Emergency Surgery. - : Springer Science and Business Media LLC. - 1863-9933 .- 1615-3146 .- 1863-9941. ; 49, s. 17-32
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Surgically managed appendicitis exhibits great heterogeneity in techniques for mesoappendix transection and appendix amputation from its base. It is unclear whether a particular surgical technique provides outcome benefit or reduces complications. Material and methods: We undertook a pre-specified subgroup analysis of all patients who underwent laparoscopic appendectomy at index admission during SnapAppy (ClinicalTrials.gov Registration: NCT04365491). We collected routine, anonymized observational data regarding surgical technique, patient demographics and indices of disease severity, without change to clinical care pathway or usual surgeon preference. Outcome measures of interest were the incidence of complications, unplanned reoperation, readmission, admission to the ICU, death, hospital length of stay, and procedure duration. We used Poisson regression models with robust standard errors to calculate incident rate ratios (IRRs) and 95% confidence intervals (CIs). Results: Three-thousand seven hundred sixty-eight consecutive adult patients, included from 71 centers in 14 countries, were followed up from date of admission for 90days. The mesoappendix was divided hemostatically using electrocautery in 1564(69.4%) and an energy device in 688(30.5%). The appendix was amputated by division of its base between looped ligatures in 1379(37.0%), with a stapler in 1421(38.1%) and between clips in 929(24.9%). The technique for securely dividing the appendix at its base in acutely inflamed (AAST Grade 1) appendicitis was equally divided between division between looped ligatures, clips and stapled transection. However, the technique used differed in complicated appendicitis (AAST Grade 2 +) compared with uncomplicated (Grade 1), with a shift toward transection of the appendix base by stapler (58% vs. 38%; p < 0.001). While no statistical difference in outcomes could be detected between different techniques for division of appendix base, decreased risk of any [adjusted IRR (95% CI): 0.58 (0.41–0.82), p = 0.002] and severe [adjusted IRR (95% CI): 0.33 (0.11–0.96), p = 0.045] complications could be detected when using energy devices. Conclusions: Safe mesoappendix transection and appendix resection are accomplished using heterogeneous techniques. Technique selection for both mesoappendix transection and appendix resection correlates with AAST grade. Higher grade led to more ultrasonic tissue transection and stapled appendix resection. Higher AAST appendicitis grade also correlated with infection-related complication occurrence. Despite the overall well-tolerated heterogeneity of approaches to acute appendicitis, increasing disease acuity or complexity appears to encourage homogeneity of intraoperative surgical technique toward advanced adjuncts.
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| 5. |
- Forssten, Maximilian Peter, 1996-, et al.
(författare)
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Surgical management of acute appendicitis during the European COVID-19 second wave: safe and effective
- 2023
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Ingår i: European Journal of Trauma and Emergency Surgery. - : Springer Science and Business Media LLC. - 1863-9933 .- 1615-3146 .- 1863-9941. ; 49, s. 57-67
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The COVID-19 (SARS-CoV-2) pandemic drove acute care surgeons to pivot from long established practice patterns. Early safety concerns regarding increased postoperative complication risk in those with active COVID infection promoted antibiotic-driven non-operative therapy for select conditions ahead of an evidence-base. Our study assesses whether active or recent SARS-CoV-2 positivity increases hospital length of stay (LOS) or postoperative complications following appendectomy. Methods: Data were derived from the prospective multi-institutional observational SnapAppy cohort study. This preplanned data analysis assessed consecutive patients aged ≥ 15years who underwent appendectomy for appendicitis (November 2020–May 2021). Patients were categorized based on SARS-CoV-2 seropositivity: no infection, active infection, and prior infection. Appendectomy method, LOS, and complications were abstracted. The association between SARS-CoV-2 seropositivity and complications was determined using Poisson regression, while the association with LOS was calculated using a quantile regression model. Results: Appendectomy for acute appendicitis was performed in 4047 patients during the second and third European COVID waves. The majority were SARS-CoV-2 uninfected (3861, 95.4%), while 70 (1.7%) were acutely SARS-CoV-2 positive, and 116 (2.8%) reported prior SARS-CoV-2 infection. After confounder adjustment, there was no statistically significant association between SARS-CoV-2 seropositivity and LOS, any complication, or severe complications. Conclusion: During sequential SARS-CoV-2 infection waves, neither active nor prior SARS-CoV-2 infection was associated with prolonged hospital LOS or postoperative complication. Despite early concerns regarding postoperative safety and outcome during active SARS-CoV-2 infection, no such association was noted for those with appendicitis who underwent operative management.
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| 6. |
- Hosseini, Vahid, et al.
(författare)
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Engineered Contractile Skeletal Muscle Tissue on a Microgrooved Methacrylated Gelatin Substrate
- 2012
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Ingår i: Tissue Engineering - Part A. - : Mary Ann Liebert Inc. - 1937-3341 .- 1937-335X. ; 18:23-24, s. 2453-2465
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Tidskriftsartikel (refereegranskat)abstract
- To engineer tissue-like structures, cells must organize themselves into three-dimensional (3D) networks that mimic the native tissue microarchitecture. Microfabricated hydrogel substrates provide a potentially useful platform for directing cells into biomimetic tissue architecture in vitro. Here, we present microgrooved methacrylated gelatin hydrogels as a suitable platform to build muscle-like fibrous structures in a facile and highly reproducible fashion. Microgrooved hydrogel substrates with two different ridge sizes (50 and 100 [mu m) were fabricated to assess the effect of the distance between engineered myofibers on the orientation of the bridging C2C12 myoblasts and the formation of the resulting multinucleated myotubes. It was shown that although the ridge size did not significantly affect the C2C12 myoblast alignment, the wider-ridged micropatterned hydrogels generated more myotubes that were not aligned to the groove direction as compared to those on the smaller-ridge micropatterns. We also demonstrated that electrical stimulation improved the myoblast alignment and increased the diameter of the resulting myotubes. By using the microstructured methacrylated gelatin substrates, we built free-standing 3D muscle sheets, which contracted when electrically stimulated. Given their robust contractility and biomimetic microarchitecture, engineered tissues may find use in tissue engineering, biological studies, high-throughput drug screening, and biorobotics.
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| 7. |
- Chi, Kim N, et al.
(författare)
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Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer
- 2019
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 381:1, s. 13-24
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Apalutamide is an inhibitor of the ligand-binding domain of the androgen receptor. Whether the addition of apalutamide to androgen-deprivation therapy (ADT) would prolong radiographic progression-free survival and overall survival as compared with placebo plus ADT among patients with metastatic, castration-sensitive prostate cancer has not been determined.METHODS: In this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castration-sensitive prostate cancer to receive apalutamide (240 mg per day) or placebo, added to ADT. Previous treatment for localized disease and previous docetaxel therapy were allowed. The primary end points were radiographic progression-free survival and overall survival.RESULTS: A total of 525 patients were assigned to receive apalutamide plus ADT and 527 to receive placebo plus ADT. The median age was 68 years. A total of 16.4% of the patients had undergone prostatectomy or received radiotherapy for localized disease, and 10.7% had received previous docetaxel therapy; 62.7% had high-volume disease, and 37.3% had low-volume disease. At the first interim analysis, with a median of 22.7 months of follow-up, the percentage of patients with radiographic progression-free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (hazard ratio for radiographic progression or death, 0.48; 95% confidence interval [CI], 0.39 to 0.60; P<0.001). Overall survival at 24 months was also greater with apalutamide than with placebo (82.4% in the apalutamide group vs. 73.5% in the placebo group; hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P = 0.005). The frequency of grade 3 or 4 adverse events was 42.2% in the apalutamide group and 40.8% in the placebo group; rash was more common in the apalutamide group.CONCLUSIONS: In this trial involving patients with metastatic, castration-sensitive prostate cancer, overall survival and radiographic progression-free survival were significantly longer with the addition of apalutamide to ADT than with placebo plus ADT, and the side-effect profile did not differ substantially between the two groups. (Funded by Janssen Research and Development; TITAN ClinicalTrials.gov number, NCT02489318.).
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| 8. |
- Feigin, Valery L., et al.
(författare)
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Global, regional, and national burden of stroke and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019
- 2021
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 20:10, s. 795-820
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Tidskriftsartikel (refereegranskat)abstract
- Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12.2 million (95% UI 11.0-13.6) incident cases of stroke, 101 million (93.2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6.55 million (6.00-7.02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11.6% [10.8-12.2] of total deaths) and the third-leading cause of death and disability combined (5.7% [5.1-6.2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70.0% (67.0-73.0), prevalent strokes increased by 85.0% (83.0-88.0), deaths from stroke increased by 43.0% (31.0-55.0), and DALYs due to stroke increased by 32.0% (22.0-42.0). During the same period, age-standardised rates of stroke incidence decreased by 17.0% (15.0-18.0), mortality decreased by 36.0% (31.0-42.0), prevalence decreased by 6.0% (5.0-7.0), and DALYs decreased by 36.0% (31.0-42.0). However, among people younger than 70 years, prevalence rates increased by 22.0% (21.0-24.0) and incidence rates increased by 15.0% (12.0-18.0). In 2019, the age-standardised stroke-related mortality rate was 3.6 (3.5-3.8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3.7 (3.5-3.9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62.4% of all incident strokes in 2019 (7.63 million [6.57-8.96]), while intracerebral haemorrhage constituted 27.9% (3.41 million [2.97-3.91]) and subarachnoid haemorrhage constituted 9.7% (1.18 million [1.01-1.39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79.6 million [67.7-90.8] DALYs or 55.5% [48.2-62.0] of total stroke DALYs), high body-mass index (34.9 million [22.3-48.6] DALYs or 24.3% [15.7-33.2]), high fasting plasma glucose (28.9 million [19.8-41.5] DALYs or 20.2% [13.8-29.1]), ambient particulate matter pollution (28.7 million [23.4-33.4] DALYs or 20.1% [16.6-23.0]), and smoking (25.3 million [22.6-28.2] DALYs or 17.6% [16.4-19.0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.
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| 9. |
- Ramon-Azcon, J., et al.
(författare)
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Gelatin methacrylate as a promising hydrogel for 3D microscale organization and proliferation of dielectrophoretically patterned cells
- 2012
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Ingår i: Lab on a Chip - Miniaturisation for Chemistry and Biology. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 12:16, s. 2959-2969
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Tidskriftsartikel (refereegranskat)abstract
- Establishing the 3D microscale organization of cells has numerous practical applications, such as in determining cell fate (e. g., proliferation, migration, differentiation, and apoptosis) and in making functional tissue constructs. One approach to spatially pattern cells is by dielectrophoresis (DEP). DEP has characteristics that are important for cell manipulation, such as high accuracy, speed, scalability, and the ability to handle both adherent and non-adherent cells. However, widespread application of this method is largely restricted because there is a limited number of suitable hydrogels for cell encapsulation. To date, polyethylene glycol-diacrylate (PEG-DA) and agarose have been used extensively for dielectric patterning of cells. In this study, we propose gelatin methacrylate (GelMA) as a promising hydrogel for use in cell dielectropatterning because of its biocompatibility and low viscosity. Compared to PEG hydrogels, GelMA hydrogels showed superior performance when making cell patterns for myoblast (C2C12) and endothelial (HUVEC) cells as well as in maintaining cell viability and growth. We also developed a simple and robust protocol for co-culture of these cells. Combined application of the GelMA hydrogels and the DEP technique is suitable for creating highly complex microscale tissues with important applications in fundamental cell biology and regenerative medicine in a rapid, accurate, and scalable manner.
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| 10. |
- Ryan, Charles J, et al.
(författare)
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Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302) : final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study
- 2015
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Ingår i: The Lancet Oncology. - 1474-5488. ; 16:2, s. 60-152
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Abiraterone acetate plus prednisone significantly improved radiographic progression-free survival compared with placebo plus prednisone in men with chemotherapy-naive castration-resistant prostate cancer at the interim analyses of the COU-AA-302 trial. Here, we present the prespecified final analysis of the trial, assessing the effect of abiraterone acetate plus prednisone on overall survival, time to opiate use, and use of other subsequent therapies.METHODS: In this placebo-controlled, double-blind, randomised phase 3 study, 1088 asymptomatic or mildly symptomatic patients with chemotherapy-naive prostate cancer stratified by Eastern Cooperative Oncology performance status (0 vs 1) were randomly assigned with a permuted block allocation scheme via a web response system in a 1:1 ratio to receive either abiraterone acetate (1000 mg once daily) plus prednisone (5 mg twice daily; abiraterone acetate group) or placebo plus prednisone (placebo group). Coprimary endpoints were radiographic progression-free survival and overall survival analysed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT00887198.FINDINGS: At a median follow-up of 49.2 months (IQR 47.0-51.8), 741 (96%) of the prespecified 773 death events for the final analysis had been observed: 354 (65%) of 546 patients in the abiraterone acetate group and 387 (71%) of 542 in the placebo group. 238 (44%) patients initially receiving prednisone alone subsequently received abiraterone acetate plus prednisone as crossover per protocol (93 patients) or as subsequent therapy (145 patients). Overall, 365 (67%) patients in the abiraterone acetate group and 435 (80%) in the placebo group received subsequent treatment with one or more approved agents. Median overall survival was significantly longer in the abiraterone acetate group than in the placebo group (34.7 months [95% CI 32.7-36.8] vs 30.3 months [28.7-33.3]; hazard ratio 0.81 [95% CI 0.70-0.93]; p=0.0033). The most common grade 3-4 adverse events of special interest were cardiac disorders (41 [8%] of 542 patients in the abiraterone acetate group vs 20 [4%] of 540 patients in the placebo group), increased alanine aminotransferase (32 [6%] vs four [<1%]), and hypertension (25 [5%] vs 17 [3%]).INTERPRETATION: In this randomised phase 3 trial with a median follow-up of more than 4 years, treatment with abiraterone acetate prolonged overall survival compared with prednisone alone by a margin that was both clinically and statistically significant. These results further support the favourable safety profile of abiraterone acetate in patients with chemotherapy-naive metastatic castration-resistant prostate cancer.FUNDING: Janssen Research & Development.
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| 11. |
- Sepanlou, Sadaf G., et al.
(författare)
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The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017 : a systematic analysis for the Global Burden of Disease Study 2017
- 2020
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Ingår i: The Lancet Gastroenterology & Hepatology. - 2468-1253. ; 5:3, s. 245-266
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Tidskriftsartikel (refereegranskat)abstract
- Background Cirrhosis and other chronic liver diseases (collectively referred to as cirrhosis in this paper) are a major cause of morbidity and mortality globally, although the burden and underlying causes differ across locations and demographic groups. We report on results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 on the burden of cirrhosis and its trends since 1990, by cause, sex, and age, for 195 countries and territories. Methods We used data from vital registrations, vital registration samples, and verbal autopsies to estimate mortality. We modelled prevalence of total, compensated, and decompensated cirrhosis on the basis of hospital and claims data. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost due to premature death and years lived with disability. Estimates are presented as numbers and age-standardised or age-specific rates per 100 000 population, with 95% uncertainty intervals (UIs). All estimates are presented for five causes of cirrhosis: hepatitis B, hepatitis C, alcohol-related liver disease, non-alcoholic steatohepatitis (NASH), and other causes. We compared mortality, prevalence, and DALY estimates with those expected according to the Socio-demographic Index (SDI) as a proxy for the development status of regions and countries. Findings In 2017, cirrhosis caused more than 1.32 million (95% UI 1.27-1.45) deaths (440000 [416 000-518 000; 33.3%] in females and 883 000 [838 000-967 000; 66.7%] in males) globally, compared with less than 899 000 (829 000-948 000) deaths in 1990. Deaths due to cirrhosis constituted 2.4% (2.3-2.6) of total deaths globally in 2017 compared with 1.9% (1.8-2.0) in 1990. Despite an increase in the number of deaths, the age-standardised death rate decreased from 21.0 (19.2-22.3) per 100 000 population in 1990 to 16.5 (15.8-18-1) per 100 000 population in 2017. Sub-Saharan Africa had the highest age-standardised death rate among GBD super-regions for all years of the study period (32.2 [25.8-38.6] deaths per 100 000 population in 2017), and the high-income super-region had the lowest (10.1 [9.8-10-5] deaths per 100 000 population in 2017). The age-standardised death rate decreased or remained constant from 1990 to 2017 in all GBD regions except eastern Europe and central Asia, where the age-standardised death rate increased, primarily due to increases in alcohol-related liver disease prevalence. At the national level, the age-standardised death rate of cirrhosis was lowest in Singapore in 2017 (3.7 [3.3-4.0] per 100 000 in 2017) and highest in Egypt in all years since 1990 (103.3 [64.4-133.4] per 100 000 in 2017). There were 10.6 million (10.3-10.9) prevalent cases of decompensated cirrhosis and 112 million (107-119) prevalent cases of compensated cirrhosis globally in 2017. There was a significant increase in age-standardised prevalence rate of decompensated cirrhosis between 1990 and 2017. Cirrhosis caused by NASH had a steady age-standardised death rate throughout the study period, whereas the other four causes showed declines in age-standardised death rate. The age-standardised prevalence of compensated and decompensated cirrhosis due to NASH increased more than for any other cause of cirrhosis (by 33.2% for compensated cirrhosis and 54.8% for decompensated cirrhosis) over the study period. From 1990 to 2017, the number of prevalent cases snore than doubled for compensated cirrhosis due to NASH and more than tripled for decompensated cirrhosis due to NASH. In 2017, age-standardised death and DALY rates were lower among countries and territories with higher SDI. Interpretation Cirrhosis imposes a substantial health burden on many countries and this burden has increased at the global level since 1990, partly due to population growth and ageing. Although the age-standardised death and DALY rates of cirrhosis decreased from 1990 to 2017, numbers of deaths and DALYs and the proportion of all global deaths due to cirrhosis increased. Despite the availability of effective interventions for the prevention and treatment of hepatitis B and C, they were still the main causes of cirrhosis burden worldwide, particularly in low-income countries. The impact of hepatitis B and C is expected to be attenuated and overtaken by that of NASH in the near future. Cost-effective interventions are required to continue the prevention and treatment of viral hepatitis, and to achieve early diagnosis and prevention of cirrhosis due to alcohol-related liver disease and NASH.
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| 12. |
- Abrishami, Vahid, et al.
(författare)
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Localized reconstruction in Scipion expedites the analysis of symmetry mismatches in cryo-EM data
- 2021
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Ingår i: Progress in Biophysics and Molecular Biology. - : Elsevier BV. - 0079-6107 .- 1873-1732. ; 160, s. 43-52
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Forskningsöversikt (refereegranskat)abstract
- Technological advances in transmission electron microscopes and detectors have turned cryogenic electron microscopy (cryo-EM) into an essential tool for structural biology. A commonly used cryo-EM data analysis method, single particle analysis, averages hundreds of thousands of low-dose images of individual macromolecular complexes to determine a density map of the complex. The presence of symmetry in the complex is beneficial since each projection image can be assigned to multiple views of the complex. However, data processing that applies symmetry can average out asymmetric features and consequently data analysis methods are required to resolve asymmetric structural features. Scipion is a cryo-EM image processing framework that integrates functions from different image processing packages as plugins. To extend its functionality for handling symmetry mismatches, we present here a Scipion plugin termed LocalRec implementing the localized reconstruction method. When tested on an adenovirus data set, the plugin enables resolving the symmetry-mismatched trimeric fibre bound to the five-fold vertices of the capsid. Furthermore, it improves the structure determination of the icosahedral capsid by dealing with the defocus gradient across the particle. LocalRec is expected to be widely applicable in a range of cryo-EM investigations of flexible and symmetry mismatched complexes.
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| 13. |
- Agarwal, Neeraj, et al.
(författare)
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Health-related quality of life after apalutamide treatment in patients with metastatic castration-sensitive prostate cancer (TITAN) : a randomised, placebo-controlled, phase 3 study
- 2019
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Ingår i: The Lancet Oncology. - 1470-2045. ; 20:11, s. 1518-1530
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the phase 3 TITAN study, the addition of apalutamide to androgen deprivation therapy (ADT) significantly improved the primary endpoints of overall survival and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer. We aimed to assess health-related quality of life (HRQOL) in TITAN, including pain and fatigue. Methods: In this randomised, placebo-controlled, double-blind, phase 3 study, patients with metastatic castration-sensitive prostate cancer (defined as not receiving ADT at the time of metastatic disease progression) aged 18 years and older, receiving continuous ADT (selected at the investigator's discretion), and with an Eastern Cooperative Oncology Group performance status score of 0 or 1 were randomly assigned (1:1), using an interactive web response system, to receive oral apalutamide (four 60 mg tablets, once daily) or matching placebo. Previous localised disease treatment or previous docetaxel for metastatic castration-sensitive prostate cancer were allowed. Randomisation was stratified by Gleason score at diagnosis, region, and previous docetaxel treatment. Randomisation was done using randomly permuted blocks (block size of four). Investigators, research staff, sponsor study team, and patients were masked to the identities of test and control treatments. Patient-reported outcomes were prespecified exploratory endpoints and were the Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and EuroQoL 5D questionnaire 5 level (EQ-5D-5L). BPI and BFI were completed for 7 consecutive days (days −6 to 1 inclusive of each cycle visit), then at months 4, 8, and 12 in follow-up. FACT-P and EQ-5D-5L were completed during cycles 1–7, then every other cycle until the end of treatment, and at months 4, 8, and 12 in follow-up. Analyses were based on the intention-to-treat population. Missing patient-reported outcome assessments were calculated as the expected number of assessments for a visit minus the actual number of assessments received for that visit. For time-to-event endpoints, when median values could not be calculated because less than 50% of patients had degradation, 25th percentiles were compared. This study is registered with ClinicalTrials.gov, number NCT02489318, and is ongoing. Findings: Between Dec 9, 2015, and July 25, 2017, 1052 eligible patients were enrolled randomly assigned to apalutamide (n=525) or placebo (n=527). Data cutoff for this analysis of patient-reported outcomes was Nov 23, 2018. Median follow-up for time to pain-related endpoints ranged from 19·4 to 22·1 months. Patients were mostly asymptomatic at baseline: on the BPI-SF pain severity scale of 0–10, median pain scores (indicating worst pain in the past 24 h) were 1·14 (IQR 0–3·17) in the apalutamide group and 1·00 (0–2·86) in the placebo group, and median worst fatigue scores on the BFI were 1·29 (IQR 0–3·29) in the apalutamide group and 1·43 (0·14–3·14) in the placebo group. Patient experience of pain and fatigue (intensity and interference) did not differ between the groups for the duration of treatment. Median time to worst pain intensity progression was 19·09 months (95% CI 11·04–not reached) in the apalutamide group versus 11·99 months (8·28–18·46) in the placebo group (HR 0·89 [95% CI 0·75–1·06]; p=0·20). Median time to pain interference progression was not reached in either group (95% CI 28·58–not reached in the apalutamide group; not reached–not reached in the placebo group). 25th percentiles for time to pain interference progression were 9·17 months (5·55–11·96) in the apalutamide group and 6·24 months (4·63–7·43) in the placebo group (HR 0·90 [95% CI 0·73–1·10]; p=0·29). FACT-P total scores and EQ-5D-5L data showed preservation of HRQOL in both groups. The median time to deterioration as determined by FACT-P total score was 8·87 months (95% CI 4·70–11·10) in the apalutamide group and 9·23 months (7·39–12·91) in the placebo group (HR 1·02 [95% CI 0·85–1·22]; p=0·85). Interpretation: Apalutamide with ADT is a well-tolerated and effective option for men with metastatic castration-sensitive prostate cancer. The combination significantly improves survival outcomes compared with ADT alone while maintaining HRQOL despite additive androgen blockade. Funding: Janssen Research & Development.
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| 14. |
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| 15. |
- Ghoreishi, Farzaneh S., et al.
(författare)
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Enhanced performance of CH3NH3PbI3 perovskite solar cells via interface modification using phenyl ammonium iodide derivatives
- 2020
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Ingår i: Journal of Power Sources. - : ELSEVIER. - 0378-7753 .- 1873-2755. ; 473
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Tidskriftsartikel (refereegranskat)abstract
- Interface modification in perovskite solar cells is a key factor for achieving high power conversion efficiency by suppressing electron-hole recombination and accelerating charge carrier extraction. Here, we use a series of phenyl ammonium derivatives, phenyl ammonium iodide (PAI), benzyl ammonium iodide (BAI), and phenyl ethyl ammonium iodide (PEAI), to modify the interface between methylammonium lead triiodide (MAPbI(3)) perovskite and Spiro-OMeTAD as a hole transport layer in solar cell devices. The structural and optical properties of the perovskite films are studied and the results reveal the formation of two-dimensional perovskite interfacial layers on the surface of the MAPbI(3) film modified with PEAI and BAI whereas the MAPbI(3) layer modified with PAI gives an interface layer with slightly different properties compared to the two-dimensional perovskite. Impedance spectroscopy shows that the charge transport resistance of the interface engineered solar cells decreases when compared to pristine MAPbI(3). In addition, slower open-circuit voltage decay and longer carrier lifetime are also observed for the modified cells which in total lead to the improvement of the photovoltaic performance. The investigation therefore gives insight in the effect of interface modifications, and especially how different sizes of the molecular interface modifier results in different interface formation and characteristics.
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| 16. |
- Ghoreishi, Farzaneh S., et al.
(författare)
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Enhancing the efficiency and stability of perovskite solar cells based on moisture-resistant dopant free hole transport materials by using a 2D-BA2PbI4 interfacial layer
- 2022
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 24:3, s. 1675-1684
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Tidskriftsartikel (refereegranskat)abstract
- In this work, the photovoltaic performance and stability of perovskite solar cells (PSCs) based on a dopant-free hole transport layer (HTL) are efficiently improved by inserting a two-dimensional (2D) interfacial layer. The benzyl ammonium lead iodide (BA2PbI4) 2D perovskite is used as an interfacial layer between the 3D CH3NH3PbI3 perovskite and two moisture-resistant dopant-free HTLs including poly[[2,3-bis(3-octyloxyphenyl)-5,8-quinoxalinediyl]-2,5-thiophenediyl] (TQ1) and poly(3-hexylthiophene) (P3HT). TQ1 with a facile synthesis procedure has a higher moisture resistivity compared to P3HT which can improve the stability of PSCs. The 2D BA2PbI4 perovskite with a less-volatile bulkier organic cation efficiently passivates the defects at the perovskite/HTL interface, leading to 11.95% and 15.04% efficiency for the modified TQ1 and P3HT based cells, respectively. For a better understanding, the structural, optical, and electrical properties of PSCs comprising P3HT and TQ1 HTLs with and without interface modification are studied. The interface modified PSCs show slower open-circuit voltage decay and longer carrier lifetimes compared to unmodified cells. In addition, impedance spectroscopy reveals lower charge transport resistance and higher recombination resistance for the modified devices, which could be associated with the modification of the interface between the 3D CH3NH3PbI3 perovskite and HTL caused by the 2D interfacial layer. Also after aging under ambient conditions for about 800 hours, the modified PCSs retain more than 80% of their initial PCEs. These results give us the hope of achieving simpler, cheaper, and more stable PSCs with dopant-free HTLs through 2D interfacial layers, which have great potential for commercialization.
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| 17. |
- Hertzberg, Joachim, et al.
(författare)
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The RACE Project : Robustness by Autonomous Competence Enhancement
- 2014
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Ingår i: Künstliche Intelligenz. - : Springer Berlin/Heidelberg. - 0933-1875 .- 1610-1987. ; 28:4, s. 297-304
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports on the aims, the approach, and the results of the European project RACE. The project aim was to enhance the behavior of an autonomous robot by having the robot learn from conceptualized experiences of previous performance, based on initial models of the domain and its own actions in it. This paper introduces the general system architecture; it then sketches some results in detail regarding hybrid reasoning and planning used in RACE, and instances of learning from the experiences of real robot task execution. Enhancement of robot competence is operationalized in terms of performance quality and description length of the robot instructions, and such enhancement is shown to result from the RACE system.
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| 18. |
- Hosseini, Vahid, et al.
(författare)
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Study on the eutectic and post-eutectic reactions in LM13 aluminum alloy using cooling curve thermal analysis technique
- 2016
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Ingår i: Journal of thermal analysis and calorimetry (Print). - : Springer Science and Business Media LLC. - 1388-6150 .- 1588-2926. ; 124:2, s. 611-617
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Tidskriftsartikel (refereegranskat)abstract
- Effect of non-equilibrium solidification conditions on the eutectic and post-eutectic reactions temperature and percentage of the phases were investigated using computer-aided cooling curve thermal analysis. In addition, hardness, secondary dendrite arm spacing, and maximum pore size were studied at different cooling conditions. Cooling curves were determined by setting thermocouples in the center of the molds. Solid fractions were calculated by Newtonian baseline technique. Results showed that increasing the cooling rate shifted the temperature of post-eutectic reaction upward, except final reaction. Higher cooling rate increased eutectic percentage about 4 %, but reduced total percentage of post-eutectic phases. Additionally, increasing the cooling rate shortened the maximum porosity diameter and secondary dendrite arm spacing and increased the hardness of the alloy. © 2015 Akadémiai Kiadó, Budapest, Hungary
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| 19. |
- Kahnt, Maik, et al.
(författare)
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Measurement of the coherent beam properties at the CoSAXS beamline
- 2021
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Ingår i: Journal of Synchrotron Radiation. - 0909-0495. ; 28, s. 1948-1953
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Tidskriftsartikel (refereegranskat)abstract
- The CoSAXS beamline at the MAX IV Laboratory is a modern multi-purpose (coherent) small-Angle X-ray scattering (CoSAXS) instrument, designed to provide intense and optionally coherent illumination at the sample position, enabling coherent imaging and speckle contrast techniques. X-ray tracing simulations used to design the beamline optics have predicted a total photon flux of 1012-1013 photons s-1 and a degree of coherence of up to 10% at 7.1 keV. The normalized degree of coherence and the coherent flux of this instrument were experimentally determined using the separability of a ptychographic reconstruction into multiple mutually incoherent modes and thus the Coherence in the name CoSAXS was verified. How the beamline can be used both for coherent imaging and XPCS measurements, which both heavily rely on the degree of coherence of the beam, was demonstrated. These results are the first experimental quantification of coherence properties in a SAXS instrument at a fourth-generation synchrotron light source.
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| 20. |
- Kapitza, R., et al.
(författare)
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CheapBFT : Resource-efficient Byzantine fault tolerance
- 2012
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Ingår i: EuroSys'12 - Proceedings of the EuroSys 2012 Conference. - New York : Association for Computing Machinery (ACM). - 9781450312233 ; , s. 295-308
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Konferensbidrag (refereegranskat)abstract
- One of the main reasons why Byzantine fault-tolerant (BFT) systems are not widely used lies in their high resource consumption: 3f + 1 replicas are necessary to tolerate only f faults. Recent works have been able to reduce the minimum number of replicas to 2f + 1 by relying on a trusted subsystem that prevents a replica from making conflicting statements to other replicas without being detected. Nevertheless, having been designed with the focus on fault handling, these systems still employ a majority of replicas during normal-case operation for seemingly redundant work. Furthermore, the trusted subsystems available trade off performance for security; that is, they either achieve high throughput or they come with a small trusted computing base. This paper presents CheapBFT, a BFT system that, for the first time, tolerates that all but one of the replicas active in normal-case operation become faulty. CheapBFT runs a composite agreement protocol and exploits passive replication to save resources; in the absence of faults, it requires that only f + 1 replicas actively agree on client requests and execute them. In case of suspected faulty behavior, CheapBFT triggers a transition protocol that activates f extra passive replicas and brings all non-faulty replicas into a consistent state again. This approach, for example, allows the system to safely switch to another, more resilient agreement protocol. CheapBFT relies on an FPGA-based trusted subsystem for the authentication of protocol messages that provides high performance and comprises a small trusted computing base.
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| 21. |
- Le, Quang Tuan, 1976-, et al.
(författare)
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Ultra-high frequency tunability in low-current and low-field spin-torque oscillators based on perpendicular magnetic tunnel junctions
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Annan publikation (populärvet., debatt m.m.)abstract
- We demonstrate ultra-high frequency tunability of up to 4.4 GHz/mA, and low threshold currents of about -21 $\mu$A, in spin-torque oscillators based on CoFeB/MgO/CoFeB magnetic tunnel junctions, in which both free and fixed layers have perpendicular magnetic anisotropy (PMA). By using different thicknesses of the two CoFeB layers, their individual PMA strengths can be tailored to achieve significant relative misalignment of their respective magnetizations in moderate in-plane fields. We observe a broad maximum in both the device resistance and the generated microwave power around maximum misalignment. Maximum frequency tunability is observed at low-to-moderate fields and decrease rapidly after maximum misalignment.
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| 22. |
- Mauree, D., et al.
(författare)
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A new framework to evaluate urban design using urban microclimatic modeling in future climatic conditions
- 2018
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Ingår i: Sustainability. - : MDPI AG. - 2071-1050. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Building more energy-efficient and sustainable urban areas that will both mitigate the effects of climate change and anticipate living conditions in future climate scenarios requires the development of new tools and methods that can help urban planners, architects and communities achieve this goal. In the current study, we designed a workflow that links different methodologies developed separately, to derive the energy consumption of a university school campus for the future. Three different scenarios for typical future years (2039, 2069, 2099) were run, as well as a renovation scenario (Minergie-P). We analyzed the impact of climate change on the heating and cooling demand of buildings and determined the relevance of taking into account the local climate in this particular context. The results from the simulations confirmed that in the future, there will be a constant decrease in the heating demand, while the cooling demand will substantially increase. Significantly, it was further demonstrated that when the local urban climate was taken into account, there was an even higher rise in the cooling demand, but also that a set of proposed Minergie-P renovations were not sufficient to achieve resilient buildings. We discuss the implication of this work for the simulation of building energy consumption at the neighborhood scale and the impact of future local climate on energy system design. We finally give a few perspectives regarding improved urban design and possible pathways for future urban areas.
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| 23. |
- Mauree, D., et al.
(författare)
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A review of assessment methods for the urban environment and its energy sustainability to guarantee climate adaptation of future cities
- 2019
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Ingår i: Renewable and Sustainable Energy Reviews. - : Elsevier BV. - 1879-0690 .- 1364-0321. ; 112, s. 733-746
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Tidskriftsartikel (refereegranskat)abstract
- The current climate change is calling for a drastic reduction of energy demand as well as of greenhouse gases. Besides this, cities also need to adapt to face the challenges related to climate change. Cities, with their complex urban texture and fabric, can be represented as a diverse ecosystem that does not have a clear and defined boundary. Multiple software tools that have been developed, in recent years, for assessment of urban climate, building energy demand, the outdoor thermal comfort and the energy systems. In this review, we, however, noted that these tools often address only one or two of these urban planning aspects. There is nonetheless an intricate link between them. For instance, the outdoor comfort assessment has shown that there is a strong link between biometeorology and architecture and urban climate. Additionally, to address the challenges of the energy transition, there will be a convergence of the energy needs in the future with an energy nexus regrouping the energy demand of urban areas. It is also highlighted that the uncertainty related to future climatic data makes urban adaptation and mitigation strategies complex to implement and to design given the lack of a comprehensive framework. We thus conclude by suggesting the need for a holistic interface to take into account this multi-dimensional problem. With the help of such a platform, a positive loop in urban design can be initiated leading to the development of low carbon cities and/or with the use of blue and green infrastructure to have a positive impact on the mitigation and adaptation strategies.
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| 24. |
- Nik, Vahid, 1979, et al.
(författare)
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Investigating the importance of future climate typology on estimating the energy performance of buildings in the EPFL campus
- 2017
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Ingår i: Energy Procedia. - : Elsevier BV. - 1876-6102. ; 122, s. 1088-1093
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Konferensbidrag (refereegranskat)abstract
- Climate changes induce warmer climate with stronger and more frequent extreme events. Due to the uncertain nature of climate, accurate simulation of future conditions is impossible and a major challenge is the selection of climate data in the impact assessment. This work compares application of three climate data sets in an energy simulation of the EPFL campus: i) Regional Climate Models (RCM data), ii) statically representative RCM data, and iii) morphed data. The energy behavior of the campus is analyzed, including its future thermal behavior, as well as its dynamic hourly variation due to the climatic data. The objective of this paper is to understand and quantify the energy transition, from 2010 to 2100, by focusing on the thermal behavior of buildings, as well as their energy demand for heating and cooling. Results explain the difference between three cases, underling the important impact related to a sound selection of the weather data.
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| 25. |
- Perera, Amarasinghage Tharindu Dasun, et al.
(författare)
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Linking Neighborhoods into Sustainable Energy Systems
- 2019
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Ingår i: Energy, Environment, and Sustainability. - Singapore : Springer Singapore. - 2522-8366. ; , s. 93-110
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Improving the energy efficiency and sustainability in the urban sector plays a vital role in the energy transition. Hence, it is important to consider promising ways to design sustainable urban energy hubs linking neighborhoods into energy systems. Improving the efficiency and sustainability of urban energy infrastructure is a process with multiple steps. This chapter presents the workflow that is required to be followed in this process. A brief overview about the methods that can be used to consider urban climate, urban simulation, and energy system design are presented in this chapter highlighting the crosslinks among these topics. Finally, the chapter presents the research gaps and promising areas to conduct future research.
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