| 1. |
- Ademuyiwa, Adesoji O., et al.
(author)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Journal article (peer-reviewed)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 2. |
- Abbafati, Cristiana, et al.
(author)
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- 2020
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Journal article (peer-reviewed)
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| 3. |
- Feigin, Valery L., et al.
(author)
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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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In: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 20:10, s. 795-820
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Journal article (peer-reviewed)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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| 4. |
- Lozano, Rafael, et al.
(author)
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Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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In: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Journal article (peer-reviewed)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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| 5. |
- Murray, Christopher J. L., et al.
(author)
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Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
-
In: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
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Journal article (peer-reviewed)abstract
- Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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| 6. |
- Sabri, Muhammad Haziq Mohammad, et al.
(author)
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Very High Frequency and Microwave Radiation Associated with Initial Breakdown Process in CG Lightning Flashes from Tropical Storms
- 2021
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In: 2021 35TH INTERNATIONAL CONFERENCE ON LIGHTNING PROTECTION (ICLP) AND XVI INTERNATIONAL SYMPOSIUM ON LIGHTNING PROTECTION (SIPDA). - : Institute of Electrical and Electronics Engineers (IEEE). - 9781665423465
-
Conference paper (peer-reviewed)abstract
- We present the observation of VHF and microwave radiation pulses associated with initial breakdown process of five negative cloud-to-ground (-CG) flashes from two tropical storms. The -CG flashes were detected within and beyond reversal distances with the locations of the first return stroke were less than 10 km. Out of five flashes, only one detected with initial electric field change (IEC) process. Both VHF and microwave pulses were detected before the first classic IB pulse and the first microwave pulses were found to lead the first VHF pulses ranging between 0.03 and 23.9 mu s.
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| 7. |
- Stanaway, Jeffrey D., et al.
(author)
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Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
- 2018
-
In: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
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Journal article (peer-reviewed)abstract
- Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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| 8. |
- Ahmed, Mona, et al.
(author)
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Cellular Uptake of Plain and SPION-Modified Microbubbles for Potential Use in Molecular Imaging
- 2017
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In: Cellular and Molecular Bioengineering. - : SPRINGER. - 1865-5025 .- 1865-5033. ; 10:6, s. 537-548
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Journal article (peer-reviewed)abstract
- Both diagnostic ultrasound (US) and magnetic resonance imaging (MRI) accuracy can be improved by using contrast enhancement. For US gas-filled microbubbles (MBs) or silica nanoparticles (SiNPs), and for MRI superparamagnetic or paramagnetic agents, contribute to this. However, interactions of MBs with the vascular wall and cells are not fully known for all contrast media. We studied the in vitro interactions between three types of non-targeted air-filled MBs with a polyvinyl-alcohol shell and murine macrophages or endothelial cells. The three MB types were plain MBs and two types that were labelled (internally and externally) with superparamagnetic iron oxide nanoparticles (SPIONs) for US/MRI bimodality. Cells were incubated with MBs and imaged by microscopy to evaluate uptake and adhesion. Interactions were quantified and the MB internalization was confirmed by fluorescence quenching of non-internalized MBs. Macrophages internalized each MB type within different time frames: plain MBs 6 h, externally labelled MBs 25 min and internally labelled MBs 2 h. An average of 0.14 externally labelled MBs per cell were internalized after 30 min and 1.34 after 2 h; which was 113% more MBs than the number of internalized internally labelled MBs. The macrophages engulfed these three differently modified new MBs at various rate, whereas endothelial cells did not engulf MBs. Polyvinyl-alcohol MBs are not taken up by endothelial cells. The MB uptake by macrophages is promoted by SPION labelling, in particular external such, which may be important for macrophage targeting.
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| 9. |
- Ahmed, Mona
(author)
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Development of probes for molecular imaging : evaluation in models of inflammation and atherosclerosis
- 2019
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Doctoral thesis (other academic/artistic)abstract
- The imaging field is rapidly evolving and in the last two decades there have been tremendous developments in the field of multimodal imaging. Multimodal molecular imaging approaches that utilize ultrasound/magnetic resonance imaging (US/MRI), single-photon emission computed tomography/computed tomography (SPECT/CT), or positron emission tomography/MRI (PET/MRI) may provide additional detailed information at the cellular and molecular level to help identify patients with vulnerable plaques that are at risk of rupture. The search for specific biomarkers in combination with specific and optimized molecular probes may help to prevent adverse events such as myocardial infarctions or strokes. Current clinical contrast agents do not provide information on the inflammatory components of atherosclerotic plaques; thus, more specific molecular probes are needed. This thesis focuses on probe development for different molecular imaging techniques using multimodal and targeting approaches. Several types of molecular probe were evaluated: bimodal and multimodal microbubbles, as well as chemically modified human serum albumin (HSA)-based probes (aconitylated (Aco) and maleylated (Mal)) for targeting markers of inflammation; adhesion molecules on endothelial cells or macrophages, and scavenger receptor A1 (SR-A1) on macrophages. Evaluation of these molecular probes was facilitated by their physical properties enabling assessment with fluorescence microscopy, flow cytometry, and nuclear imaging properties for in vivo molecular imaging with SPECT/CT and PET/MRI. We found that functionalizing molecular probes with targeting moieties greatly improved the targeting specificity and avidity to the target compared to non-targeted molecular probes. Furthermore, these molecular probes were successfully radiolabeled with a detectable in vivo signal by 99mTc-anti-ICAM-1-MBs imaging of inflammation with SPETC/CT, and atherosclerosis by 89Zr-Mal-HSA with PET/MRI. Ex vivo evaluation of HSA-based probes showed significant accumulation in atherosclerotic lesions of Apoe-/- mice, as quantified by gamma counter and phosphor imaging autoradiography, compared to wild type (WT) mice. In conclusion, adhesion molecule targeting and scavenger receptor targeting with functionally modified probes in this thesis showed potential for the imaging of inflammation and atherosclerosis. Of the evaluated probes, modified HSA-based probes seem to have the greatest potential for clinical application in molecular imaging of atherosclerosis.
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| 10. |
- Ashry, Noha M., et al.
(author)
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Evaluation of graphene oxide, chitosan and their complex as antibacterial agents and anticancer apoptotic effect on HeLa cell line
- 2022
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In: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 13
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Journal article (peer-reviewed)abstract
- Cancer and bacterial infection are the most serious problems threatening people's lives worldwide. However, the overuse of antibiotics as antibacterial and anticancer treatments can cause side effects and lead to drug-resistant bacteria. Therefore, developing natural materials with excellent antibacterial and anticancer activity is of great importance. In this study, different concentrations of chitosan (CS), graphene oxide (GO), and graphene oxide-chitosan composite (GO-CS) were tested to inhibit the bacterial growth of gram-positive (Bacillus cereus MG257494.1) and gram-negative (Pseudomonas aeruginosa PAO1). Moreover, we used the most efficient natural antibacterial material as an anticancer treatment. The zeta potential is a vital factor for antibacterial and anticancer mechanism, at pH 3–7, the zeta potential of chitosan was positive while at pH 7–12 were negative, however, the zeta potential for GO was negative at all pH values, which (p < 0.05) increased in the GO-CS composite. Chitosan concentrations (0.2 and 1.5%) exhibited antibacterial activity against BC with inhibition zone diameters of 4 and 12 mm, respectively, and against PAO1 with 2 and 10 mm, respectively. Treating BC and PAO1 with GO:CS (1:2) and GO:CS (1:1) gave a larger (p < 0.05) inhibition zone diameter. The viability and proliferation of HeLa cells treated with chitosan were significantly decreased (p < 0.05) from 95.3% at 0% to 12.93%, 10.33%, and 5.93% at 0.2%, 0.4%, and 0.60% concentrations of chitosan, respectively. Furthermore, CS treatment increased the activity of the P53 protein, which serves as a tumor suppressor. This study suggests that chitosan is effective as an antibacterial and may be useful for cancer treatment.
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| 11. |
- Ghareeb, Waleed M., et al.
(author)
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Deep Neural Network for the Prediction of KRAS Genotype in Rectal Cancer
- 2022
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In: Journal of the American College of Surgeons. - 1879-1190. ; 235:3, s. 482-493
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Journal article (peer-reviewed)abstract
- BACKGROUND: KRAS mutation can alter the treatment plan after resection of colorectal cancer. Despite its importance, the KRAS status of several patients remains unchecked because of the high cost and limited resources. This study developed a deep neural network (DNN) to predict the KRAS genotype using hematoxylin and eosin (H&E)-stained histopathological images. STUDY DESIGN: Three DNNs were created (KRAS_Mob, KRAS_Shuff, and KRAS_Ince) using the structural backbone of the MobileNet, ShuffleNet, and Inception networks, respectively. The Cancer Genome Atlas was screened to extract 49,684 image tiles that were used for deep learning and internal validation. An independent cohort of 43,032 image tiles was used for external validation. The performance was compared with humans, and a virtual cost-saving analysis was done. RESULTS: The KRAS_Mob network (area under the receiver operating curve [AUC] 0.8, 95% CI 0.71 to 0.89) was the best-performing model for predicting the KRAS genotype, followed by the KRAS_Shuff (AUC 0.73, 95% CI 0.62 to 0.84) and KRAS_Ince (AUC 0.71, 95% CI 0.6 to 0.82) networks. Combing the KRAS_Mob and KRAS_Shuff networks as a double prediction approach showed improved performance. KRAS_Mob network accuracy surpassed that of two independent pathologists (AUC 0.79 [95% CI 0.64 to 0.93], 0.51 [95% CI 0.34 to 0.69], and 0.51 (95% CI 0.34 to 0.69]; p < 0.001 for all comparisons). CONCLUSION: The DNN has the potential to predict the KRAS genotype directly from H&E-stained histopathological slide images. As an algorithmic screening method to prioritize patients for laboratory confirmation, such a model might possibly reduce the number of patients screened, resulting in significant test-related time and economic savings.
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| 12. |
- Griswold, Max G., et al.
(author)
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Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016
- 2018
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In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 392:10152, s. 1015-1035
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Journal article (peer-reviewed)abstract
- Background: Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older.Methods: Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health.Findings: Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week.Interpretation: Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.
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| 13. |
- Gstrein, Chiara, et al.
(author)
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Solvatochromism of dye-labeled dendronized polymers of generation numbers 1–4: comparison to dendrimers
- 2016
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In: Chemical Science. - 2041-6539. ; :7, s. 4644-4652
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Journal article (peer-reviewed)abstract
- Two series of dendronized polymers (DPs) of generations g = 1–4 with different levels of dendritic substitution (low and high) and a solvatochromic probe at g = 1 level are used to study their swelling behavior in a collection of solvents largely differing in polarity as indicated by the Kamlet–Taft parameters. This is done by measuring the UV-Vis spectra of all samples in all solvents and determining the longest wavelength absorptions (λmax). The λmax values fall into a range defined by the extreme situations, when the solvatochromic probe is either fully surrounded by solvent or completely shielded against it. The former situation is achieved in a model compound and the latter situation is believed to be reached when in a poor solvent the dendritic shell around the backbone is fully collapsed. We observe that solvent penetration into the interior of the DPs decreases with increasing g and does so faster for the more highly dendritically substituted series than for the less highly substituted one. Interestingly, the swelling of the more highly substituted DP series already at the g = 4 level has decreased to approximately 20% of that at the g = 1 level which supports an earlier proposal that high g DPs can be viewed as nano-sized molecular objects. Furthermore, when comparing these two DP series with a g = 1–6 series of dendrimers investigated by Fréchet et al. it becomes evident that even the less substituted series of DPs is much less responsive to solvent changes as assessed by the solvatochromic probe than the dendrimers, suggesting the branches around the (polymeric) core in DPs to be more densely packed compared to those in dendrimers, thus, establishing a key difference between these two dendritic macromolecules.
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| 14. |
- Henein, Michael Y., et al.
(author)
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Biomarkers predict in-hospital major adverse cardiac events in covid-19 patients : A multicenter international study
- 2021
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In: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 10:24
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Journal article (peer-reviewed)abstract
- Background: The COVID-19 pandemic carries a high burden of morbidity and mortality worldwide. We aimed to identify possible predictors of in-hospital major cardiovascular (CV) events in COVID-19.Methods: We retrospectively included patients hospitalized for COVID-19 from 10 centers. Clinical, biochemical, electrocardiographic, and imaging data at admission and medications were collected. Primary endpoint was a composite of in-hospital CV death, acute heart failure (AHF), acute myocarditis, arrhythmias, acute coronary syndromes (ACS), cardiocirculatory arrest, and pulmonary embolism (PE).Results: Of the 748 patients included, 141(19%) reached the set endpoint: 49 (7%) CV death, 15 (2%) acute myocarditis, 32 (4%) sustained-supraventricular or ventricular arrhythmias, 14 (2%) cardiocirculatory arrest, 8 (1%) ACS, 41 (5%) AHF, and 39 (5%) PE. Patients with CV events had higher age, body temperature, creatinine, high-sensitivity troponin, white blood cells, and platelet counts at admission and were more likely to have systemic hypertension, renal failure (creatinine ≥ 1.25 mg/dL), chronic obstructive pulmonary disease, atrial fibrillation, and cardiomyopathy. On univariate and multivariate analysis, troponin and renal failure were associated with the composite endpoint. Kaplan–Meier analysis showed a clear divergence of in-hospital composite event-free survival stratified according to median troponin value and the presence of renal failure (Log rank p < 0.001).Conclusions: Our findings, derived from a multicenter data collection study, suggest the routine use of biomarkers, such as cardiac troponin and serum creatinine, for in-hospital prediction of CV events in patients with COVID-19.
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| 15. |
- Mansour, Mona Farouk, et al.
(author)
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Therapeutic potential of human umbilical cord derived mesenchymal stem cells on rat model of liver fibrosis
- 2019
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In: American Journal of Stem Cells. - : E-CENTURY PUBLISHING CORP. - 2160-4150. ; 8:1
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Journal article (peer-reviewed)abstract
- End-stage liver disease is a worldwide cause of morbidity and mortality, which is associated with a considerable economic burden. As the disease progresses, fibrosis will replace the hepatic architecture and compromise liver functions. The regenerative approach for the injured liver can provide a hope for these patients; however, it is still facing many challenges. In the current study, we aimed at (1) assessing hepatic regenerative capacity of mesenchymal stem cells, isolated from human umbilical cord blood (HMSCs), in a rat model of carbon-tetrachloride (CCL4) induced liver fibrosis, (2) comparing the therapeutic effects with other cell populations derived from umbilical cord blood and (3) evaluating the host response to the human-derived cells. Fifteen rats received either the whole mononuclear cell fraction (HMNCs), CD34-ve subpopulation or HMSCs. A fourth group did not receive any treatment and another group was left without induction of fibrosis as positive and negative controls. All groups that received cellular treatment showed homing of the human cells and improvement of the liver architecture and functional capacity. The groups received CD34-ve cells and HMSCs had the most efficient improvement in liver functions, microscopic regenerative markers and histological appearance while the least immune reaction was noted with HMSCs. HUCB-MSCs showed significant immunemodulatory effect on rat immune cells. This study can provide a clue about a simple and effective method for the management of fibrotic liver diseases.
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| 16. |
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| 17. |
- Prokopishyn, Nicole L., et al.
(author)
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The Concentration of Total Nucleated Cells in Harvested Bone Marrow for Transplantation Has Decreased over Time
- 2019
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In: Biology of blood and marrow transplantation. - : ELSEVIER SCIENCE INC. - 1083-8791 .- 1523-6536. ; 25:7, s. 1325-1330
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Journal article (peer-reviewed)abstract
- Bone marrow (BM) is an essential source of hematopoietic stem cell grafts for many allogeneic hematopoietic cell transplant (HCT) recipients, including adult patients (for specific diseases and transplantation strategies) and the majority of pediatric recipient. However, since the advent of granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (PBSC) grafts, there has been a significant decrease in the use of BM in HCT, thought to be due mainly to the increased logistical challenges in harvesting BM compared with PBSCs, as well as generally no significant survival advantage of BM over PBSCs. The decreased frequency of collection has the potential to impact the quality of BM harvests. In this study, we examined >15,000 BM donations collected at National Marrow Donor Program centers between 1994 and 2016 and found a significant decline in the quality of BM products, as defined by the concentration of total nucleated cells (TNCs). The mean TNC concentration in BM donations dropped from 21.8 x 10(6) cells/mL in the earliest era (1994 to 1996) to 18.7 x 10(6) cells/mL in the most recent era (2012 to 2016) (means ratio,.83; P < .001). This decline in BM quality was seen despite the selection of more donors perceived to be optimal (eg, younger and male). Multivariate regression analysis showed that higher volume centers (performing >30 collections per era) had better-quality harvests with higher concentrations of TNCs collected. In conclusion, we have identified a significant decrease in the quality of BM collections over time, and lower-volume collection centers had poorer-quality harvests. In this analysis, we could not elucidate the direct cause for this finding, suggesting the need for further studies to investigate the key factors responsible and to explore the impact on transplant recipients. (C) 2019 American Society for Blood and Marrow Transplantation.
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| 18. |
- Sabri, Muhammad Haziq Mohamad, et al.
(author)
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Environmental Analysis of Quasi-Static Electric Field Changes of Tropical Lightning Flashes
- 2019
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In: Ekoloji. - 1300-1361. ; 28:107, s. 373-378
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Journal article (peer-reviewed)abstract
- The environmental conditions leading to the bouncing-wave discharge and the subsequent electron beam remain to be investigated in more detailed future studies. The analysis of quasi-static initial electric field changes (IECs) were found at the beginning of all 24 lightning flashes detected within reversal distance (22 Negative Cloud-to-Ground (–CG) and 2 normal Intra-Cloud (IC) flashes) in a tropical storm on June 15th, 2017 close to our station in Malacca, Malaysia (2.314077° N, 102.318282° E). The IECs durations averaged 4.28 ms for –CG flashes (range 1.48 to 9.45 ms) and averaged 11.30 ms for normal ICs flashes (range 7.24 to 15.35 ms). In comparison to Florida storms, the duration of IECs for –CG and IC flashes were 0.18 ms (range 0.08 to 0.33 ms) and 1.53 ms (range 0.18 to 5.70 ms), respectively. Moreover, the magnitudes of E-change for tropical thunderstorm were 0.13 V/m (range 0.03 to 0.44 V/m) for –CG flashes and -0.20 V/m (range -0.13 to -0.27 V/m) for IC flashes. The E-change magnitudes of tropical flashes are significantly larger than Florida flashes.
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| 19. |
- Sánchez Van Kammen, Mayte, et al.
(author)
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Characteristics and Outcomes of Patients with Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia
- 2021
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In: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 78:11, s. 1314-1323
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Journal article (peer-reviewed)abstract
- Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson).Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS.Design, Setting, and Participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination.Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria.Main Outcomes and Measures: Clinical characteristics and mortality rate.Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later.Conclusions and Relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination..
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| 20. |
- Scutelnic, Adrian, et al.
(author)
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Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination.
- 2022
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In: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 92:4, s. 562-573
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Journal article (peer-reviewed)abstract
- Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality.We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis.Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p<0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR]=0.43, 95% confidence interval [CI]=0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR=0.19, 95% CI=0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR=0.70, 95% CI=0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR=2.19, 95% CI=0.74-6.54).In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573.
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| 21. |
- Van De Munckhof, Anita, et al.
(author)
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Outcomes of cerebral venous thrombosis due to vaccine-induced immune thrombotic thrombocytopenia after the acute phase
- 2022
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In: Stroke. - : American Heart Association. - 0039-2499 .- 1524-4628. ; 53:10, s. 3206-3210
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Journal article (peer-reviewed)abstract
- Background: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization.Methods: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization).Results: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed).Conclusions: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.
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| 22. |
- Weller, Johannes, et al.
(author)
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Endovascular treatment of cerebral sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia
- 2024
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In: EUROPEAN STROKE JOURNAL. - 2396-9873 .- 2396-9881. ; 9:1, s. 105-113
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Journal article (peer-reviewed)abstract
- Introduction: There is little data on the role of endovascular treatment (EVT) of cerebral venous sinus thrombosis (CVST) due to vaccine-induced immune thrombotic thrombocytopenia (VITT). Here, we describe clinical characteristics and outcomes of CVST-VITT patients who were treated with EVT. Patients and methods: We report data from an international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 6 March 2023. VITT was defined according to the Pavord criteria. Results: EVT was performed in 18/136 (13%) patients with CVST-VITT (92% aspiration and/or stent retrieval, 8% local thrombolysis). Most common indications were extensive thrombosis and clinical or radiological deterioration. Compared to non-EVT patients, those receiving EVT had a higher median thrombus load (4.5 vs 3). Following EVT, local blood flow was improved in 83% (10/12, 95% confidence interval [CI] 54-96). One (6%) asymptomatic sinus perforation occurred. Eight (44%) patients treated with EVT also underwent decompressive surgery. Mortality was 50% (9/18, 95% CI 29-71) and 88% (8/9, 95% CI 25-66) of surviving EVT patients achieved functional independence with a modified Rankin Scale score of 0-2 at follow-up. In multivariable analysis, EVT was not associated with increased mortality (adjusted odds ratio, 0.66, 95% CI 0.16-2.58). Discussion and conclusion: We describe the largest cohort of CVST-VITT patients receiving EVT. Half of the patients receiving EVT died during hospital admission, but most survivors achieved functional independence.
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