| 1. |
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| 2. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
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| 6. |
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| 7. |
- James, SL, et al.
(författare)
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Global injury morbidity and mortality from 1990 to 2017: results from the Global Burden of Disease Study 2017
- 2020
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Ingår i: Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention. - : BMJ. - 1475-5785. ; 26:SUPP_1Supp 1, s. 96-114
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Tidskriftsartikel (refereegranskat)abstract
- Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries.MethodsWe reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs).FindingsIn 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505).InterpretationInjuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.
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| 8. |
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| 9. |
- 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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| 10. |
- Liu, DJ, et al.
(författare)
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Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations
- 2023
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 369-
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This recent study—and most other large-scale human genetics studies—was mainly composed of individuals of European (EUR) ancestry, and the generalizability of the findings in non-EUR populations remains unclear. To address this gap, we designed a custom sequencing panel of 161 genes selected based on the current knowledge of SCZ genetics and sequenced a new cohort of 11,580 SCZ cases and 10,555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48; P = 5.4 × 10−6). In meta-analyses with existing datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five ancestral populations. Two genes (SRRM2 and AKAP11) were newly implicated as SCZ risk genes, and one gene (PCLO) was identified as shared by individuals with SCZ and those with autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of SCZ being conserved across diverse human populations.
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| 11. |
- Fabian, ID, et al.
(författare)
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Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries
- 2021
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Ingår i: The British journal of ophthalmology. - : BMJ. - 1468-2079 .- 0007-1161. ; 105:10, s. 1435-1443
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Tidskriftsartikel (refereegranskat)abstract
- The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe.MethodsA cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries.ResultsCapture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI −12.4 to −5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease.ConclusionsFewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral.
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| 12. |
- Karaye, Kamilu M., et al.
(författare)
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Incidence, clinical characteristics, and risk factors of peripartum cardiomyopathy in Nigeria : results from the PEACE Registry
- 2020
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Ingår i: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 7:1, s. 236-244
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of this study was to describe the incidence, clinical characteristics and risk factors of peripartum cardiomyopathy (PPCM) in Nigeria.Methods and Results: The study was conducted in 22 hospitals in Nigeria, and PPCM patients were consecutively recruited between June 2017 and March 2018. To determine factors associated with PPCM, the patients were compared with apparently healthy women who recently delivered, as controls. Four hundred six patients were compared with 99 controls. The incidence and disease burden (based on the rate of consecutive recruitment of subjects) varied widely between the six geographical zones of Nigeria. From the North-West zone, 72.3% of the patients was recruited, where an incidence as high as 1 per 96 live births was obtained in a centre, while the disease was uncommon (7.6% of all recruited patients) in the South. Majority of the patients (76.6%) and controls (74.8%) (p = 0.694) were of Hausa-Fulani ethnic group. Atrial fibrillation, intracardiac thrombus, stroke, and right ventricular systolic dysfunction were found in 1.7%, 6.4%, 2.2%, and 54.9% of the patients, respectively. Lack of formal education (odds ratio [OR] 3.08, 95% confidence interval [1.71, 5.53]; P < 0.001), unemployment (OR: 3.28 [2.05, 5.24]; P < 0.001), underweight (OR: 13.43 [4.17, 43.21]; P < 0.001) and history of pre-eclampsia (OR: 9.01 [2.18, 37.75]; P = 0.002) emerged as independent PPCM risk factors using regression models. Customary hot baths (OR: 1.24 [0.80, 1.93]; P = 0.344), pap enriched with dried lake salt (OR: 1.20 [0.74, 1.94]; P = 0.451), and Hausa-Fulani ethnicity (OR: 1.11 [0.67, 1.84]; P = 0.698) did not achieve significance as PPCM risk factors.Conclusions: In Nigeria, the burden of PPCM was greatest in the North-West zone, which has the highest known incidence. PPCM was predicted by sociodemographic factors and pre-eclampsia, which should be considered in its control at population level. Postpartum customary birth practices and Hausa-Fulani ethnicity were not associated with PPCM in Nigeria.
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| 13. |
- Razavi-Shearer, Devin M., et al.
(författare)
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Adjusted estimate of the prevalence of hepatitis delta virus in 25 countries and territories
- 2024
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Ingår i: JOURNAL OF HEPATOLOGY. - 0168-8278 .- 1600-0641. ; 80:2, s. 232-242
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Hepatitis delta virus (HDV) is a satellite RNA virus that requires the hepatitis B virus (HBV) for assembly and propagation. Individuals infected with HDV progress to advanced liver disease faster than HBV-monoinfected individuals. Recent studies have estimated the global prevalence of anti-HDV antibodies among the HBV-infected population to be 5-15%. This study aimed to better understand HDV prevalence at the population level in 25 countries/territories. Methods: We conducted a literature review to determine the prevalence of anti-HDV and HDV RNA in hepatitis B surface antigen (HBsAg)-positive individuals in 25 countries/territories. Virtual meetings were held with experts from each setting to discuss the findings and collect unpublished data. Data were weighted for patient segments and regional heterogeneity to estimate the prevalence in the HBV-infected population. The findings were then combined with The Polaris Observatory HBV data to estimate the anti-HDV and HDV RNA prevalence in each country/territory at the population level. Results: After adjusting for geographical distribution, disease stage and special populations, the anti-HDV prevalence among the HBsAg+ population changed from the literature estimate in 19 countries. The highest anti-HDV prevalence was 60.1% in Mongolia. Once adjusted for the size of the HBsAg+ population and HDV RNA positivity rate, China had the highest absolute number of HDV RNA+ cases. Conclusions: We found substantially lower HDV prevalence than previously reported, as prior meta-analyses primarily focused on studies conducted in groups/regions that have a higher probability of HBV infection: tertiary care centers, specific risk groups or geographical regions. There is large uncertainty in HDV prevalence estimates. The implementation of reflex testing would improve estimates, while also allowing earlier linkage to care for HDV RNA+ individuals. The logistical and economic burden of reflex testing on the health system would be limited, as only HBsAg+ cases would be screened.
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| 14. |
- 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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| 15. |
- 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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| 16. |
- Kayambankadzanja, RK, et al.
(författare)
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Emergency and critical care services in Malawi: Findings from a nationwide survey of health facilities
- 2020
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Ingår i: Malawi medical journal : the journal of Medical Association of Malawi. - : African Journals Online (AJOL). - 1995-7270. ; 32:1, s. 19-23
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGlobally, critical illness causes up to 45 million deaths every year. The burden is highest in low-income countries such as Malawi. Critically ill patients require good quality, essential care in emergency departments and in hospital wards to avoid negative outcomes such as death. Little is known about the quality of care or the availability of necessary resources for emergency and critical care in Malawi. The aim of this study was to assess the availability of resources for emergency and critical care in Malawi using data from the Service Provision Assessment (SPA).MethodsWe conducted a secondary data analysis of the SPA – a nationwide survey of all health facilities. We assessed the availability of resources for emergency and critical care using previously developed standards for hospitals in low-income countries. Each health facility received an availability score, calculated as the proportion of resources that were present. Resource availability was sub-divided into the seven a-priori defined categories of drugs, equipment, support services, emergency guidelines, infrastructure, training and routines.ResultsOf the 254 indicators in the standards necessary for assessing the quality of emergency and critical care, SPA collected data for 102 (40.6%). Hospitals had a median resource availability score of 51.6% IQR (42.2-67.2) and smaller health facilities had a median of 37.5% (IQR 28.1-45.3). For the category of drugs, the hospitals’ median score was 62.0% IQR (52.4-81.0), for equipment 51.9% IQR (40.7-66.7), support services 33.3% IQR (22.2-77.8) and emergency guidelines 33.3% IQR (0-66.7). SPA did not collect any data for resources in the categories of infrastructure, training or routines. ConclusionHospitals in Malawi lack resources for providing emergency and critical care. Increasing data about the availability of resources for emergency and critical care and improving the hospital systems for the care of critically ill patients in Malawi should be prioritized.
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| 17. |
- Mahmood, Zafar, et al.
(författare)
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MHD mixed convective stagnation point flow of nanofluid past a permeable stretching sheet with nanoparticles aggregation and thermal stratification
- 2022
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Using a thermally stratified water-based nanofluid and a permeable stretching sheet as a simulation environment, this research examines the impact of nanoparticle aggregation on MHD mixed convective stagnation point flow. Nanoparticle aggregation is studied using two modified models: the Krieger–Dougherty and the Maxwell–Bruggeman. The present problem's governing equations were transformed into a solvable mathematical model utilizing legitimate similarity transformations, and numerical solutions were then achieved using shooting with Runge–Kutta Fehlberg (RKF) technique in Mathematica. Equilibrium point flow toward permeable stretching surface is important for the extrusion process because it produces required heat and mass transfer patterns and identifies and clarifies fragmented flow phenomena using diagrams. Nanoparticle volume fraction was shown to have an impact on the solutions' existence range, as well. Alumina and copper nanofluids have better heat transfer properties than regular fluids. The skin friction coefficients and Nusselt number, velocity, temperature profiles for many values of the different parameters were obtained. In addition, the solutions were shown in graphs and tables, and they were explained in detail. A comparison of the current study's results with previous results for a specific instance is undertaken to verify the findings, and excellent agreement between them is observed.
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| 18. |
- Niazi, Muhammad Umar B., et al.
(författare)
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Feedback Design for Devising Optimal Epidemic Control Policies
- 2023
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Ingår i: <em>IFAC-PapersOnLine</em>. - : Elsevier BV. ; , s. 4031-4036
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Konferensbidrag (refereegranskat)abstract
- This paper proposes a feedback design that effectively copes with uncertainties for reliable epidemic monitoring and control. There are several optimization-based methods to estimate the parameters of an epidemic model by utilizing past reported data. However, due to the possibility of noise in the data, the estimated parameters may not be accurate, thereby exacerbating the model uncertainty. To address this issue, we provide an observer design that enables robust state estimation of epidemic processes, even in the presence of uncertain models and noisy measurements. Using the estimated model and state, we then devise optimal control policies by minimizing a predicted cost functional. To demonstrate the effectiveness of our approach, we implement it on a modified SIR epidemic model. The results show that our proposed method is efficient in mitigating the uncertainties that may arise.
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| 19. |
- Olszewski, Adam J., et al.
(författare)
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Burkitt Lymphoma International Prognostic Index
- 2021
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 0732-183X. ; 39:10, s. 1129-1138
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Burkitt lymphoma (BL) has unique biology and clinical course but lacks a standardized prognostic model. We developed and validated a novel prognostic index specific for BL to aid risk stratification, interpretation of clinical trials, and targeted development of novel treatment approaches. METHODS: We derived the BL International Prognostic Index (BL-IPI) from a real-world data set of adult patients with BL treated with immunochemotherapy in the United States between 2009 and 2018, identifying candidate variables that showed the strongest prognostic association with progression-free survival (PFS). The index was validated in an external data set of patients treated in Europe, Canada, and Australia between 2004 and 2019. RESULTS: In the derivation cohort of 633 patients with BL, age ≥ 40 years, performance status ≥ 2, serum lactate dehydrogenase > 3× upper limit of normal, and CNS involvement were selected as equally weighted factors with an independent prognostic value. The resulting BL-IPI identified groups with low (zero risk factors, 18% of patients), intermediate (one factor, 36% of patients), and high risk (≥ 2 factors, 46% of patients) with 3-year PFS estimates of 92%, 72%, and 53%, respectively, and 3-year overall survival estimates of 96%, 76%, and 59%, respectively. The index discriminated outcomes regardless of HIV status, stage, or first-line chemotherapy regimen. Patient characteristics, relative size of the BL-IPI groupings, and outcome discrimination were consistent in the validation cohort of 457 patients, with 3-year PFS estimates of 96%, 82%, and 63% for low-, intermediate-, and high-risk BL-IPI, respectively. CONCLUSION: The BL-IPI provides robust discrimination of survival in adult BL, suitable for use as prognostication and stratification in trials. The high-risk group has suboptimal outcomes with standard therapy and should be considered for innovative treatment approaches.
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| 20. |
- Read, Emily, et al.
(författare)
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Bi-directional signaling between the intestinal epithelium and type-3 innate lymphoid cells regulates secretory dynamics and interleukin-22
- 2024
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Ingår i: Mucosal Immunology. - 1933-0219 .- 1935-3456. ; 17:1, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Type-3 innate lymphoid cells (ILC3) respond to localized environmental cues to regulate homeostasis and orchestrate immunity in the intestine. The intestinal epithelium is an important upstream regulator and downstream target of ILC3 signaling, however, the complexity of mucosal tissues can hinder efforts to define specific interactions between these two compartments. Here, we employ a reductionist co-culture system of murine epithelial small intestinal organoids (SIO) with ILC3 to uncover bi-directional signaling mechanisms that underlie intestinal homeostasis. We report that ILC3 induce global transcriptional changes in intestinal epithelial cells, driving the enrichment of secretory goblet cell signatures. We find that SIO enriched for goblet cells promote NKp46+ ILC3 and interleukin (IL)-22 expression, which can feedback to induce IL-22-mediated epithelial transcriptional signatures. However, we show that epithelial regulation of ILC3 in this system is contact-dependent and demonstrate a role for epithelial Delta-Like-Canonical-Notch-Ligand (Dll) in driving IL-22 production by ILC3, via subset-specific Notch1-mediated activation of T-bet+ ILC3. Finally, by interfering with Notch ligand-receptor dynamics, ILC3 appear to upregulate epithelial Atoh1 to skew secretory lineage determination in SIO-ILC3 co-cultures. This research outlines two complimentary bi-directional signaling modules between the intestinal epithelium and ILC3, which may be relevant in intestinal homeostasis and disease.
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| 21. |
- Sa'idu, H., et al.
(författare)
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Influence of systolic blood pressure on outcomes in Nigerians with peripartum cardiomyopathy
- 2022
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Ingår i: Nigerian Journal of Clinical Practice. - : Wolters Kluwer. - 1119-3077 .- 2229-7731. ; 25:12, s. 1963-1968
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Tidskriftsartikel (refereegranskat)abstract
- Background: The relationship between blood pressure (BP) trajectories and outcomes in patients with peripartum cardiomyopathy (PPCM) is not clear.Aim: The study aimed to assess the clinical features and outcomes (all-cause mortality and unrecovered left ventricular [LV] systolic function) of PPCM patients grouped according to their baseline systolic BP (SBP).Patients and Methods: PPCM patients presenting to 14 tertiary hospitals in Nigeria were consecutively recruited between June 2017 and March 2018 and then followed up till March 2019. SBP at first presentation was used to categorize the patients into seven groups: <90, 90-99, 100-109, 110-119, 120-129, 130-139, and ≥140 mmHg. Unrecovered LV systolic function was defined as echocardiographic LV ejection fraction (LVEF) below 55% at the last profiling.Results: Two hundred and twenty-seven patients were recruited and followed up for a median of 18 months. Of these, 4.0% had <90 mmHg, 16.3% had 90-99 mmHg, 24.7% had 100-109 mmHg, 24.7% had 110-119 mmHg, 18.5% had 120-129 mmHg, 7.5% had 130-139 mmHg, and 4.4% had ≥140 mmHg of SBP at presentation. The highest frequency of all-cause mortality was recorded among patients with SBP ≤90 mmHg (30.8%) followed by those with 90-99 mmHg (20.5%) (P = 0.076), while unrecovered LV systolic function did not differ significantly between the groups (P = 0.659). In a Cox proportional regression model for all-cause mortality, SBP <90 mmHg had a hazard ratio (HR) of 4.00 (95% confidence interval [CI] 1.49-10.78, P = 0.006), LVEF had an HR of 0.94 (95% CI 0.91-0.98, P = 0.003, B = 0.06%), and use of angiotensin-converting enzyme or angiotensin receptor and/or β-receptor blockers had an HR of 1.71 (95% CI 0.93-3.16, P = 0.085). However, SBP was not associated with LV function recovery.Conclusion: In our cohort of PPCM patients, one-fifth was hypotensive at presentation. SBP <90 mmHg at presentation was associated with a four-fold higher risk of all-cause mortality during a median follow-up of 18 months.
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| 22. |
- Studnicka, Michael, et al.
(författare)
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COPD : Should Diagnosis Match Physiology?
- 2020
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Ingår i: Chest. - : Elsevier BV. - 0012-3692 .- 1931-3543. ; 157:2, s. 473-475
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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