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| 2. |
- Ahmad, Shafqat, et al.
(author)
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A novel interaction between the FLJ33534 locus and smoking in obesity: a genome-wide study of 14 131 Pakistani adults.
- 2016
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In: International Journal of Obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 40:1, s. 186-190
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Journal article (peer-reviewed)abstract
- BackgroundObesity is a complex disease caused by the interplay of genetic and lifestyle factors, but identification of gene-lifestyle interactions in obesity has remained challenging. Few large-scale studies have reported use of genome-wide approaches to investigate gene-lifestyle interactions in obesity.MethodsIn the PROMIS study, a cross-sectional study based in Pakistan, we calculated BMI variance estimates (square of the residual of inverse-normal transformed BMI z-score) in 14 131 participants and conducted genome-wide heterogeneity of variance analyses (GWHVA) for this outcome. All analyses were adjusted for age, age(2), sex and genetic ancestry.ResultsThe GWHVA analyses yielded a genome-wide significance (P-value=3.1 × 10(-8)) association of the rs140133294 variant at FLJ33534 with BMI variance. In explicit tests of gene × lifestyle interaction, smoking was found to significantly modify the effect of rs140133294 on BMI (Pinteraction=0.0005), whereby the minor allele (T) was associated with lower BMI in current smokers, while positively associated with BMI in never-smokers. No interactions with physical activity were observed. Analyses of ENCODE data at the FLJ33534 locus revealed features indicative of open chromatin and high confidence DNA-binding motifs for several transcription factors, providing suggestive biological support for a mechanism of interaction.ConclusionIn summary, we have identified a novel interaction between smoking and variation at the FLJ33534 locus in relation to BMI in people from Pakistan.International Journal of Obesity accepted article preview online, 17 August 2015. doi:10.1038/ijo.2015.152.
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| 3. |
- Rosengren, Annika, 1951, et al.
(author)
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Education and risk for acute myocardial infarction in 52 high, middle and low-income countries: INTERHEART case-control study
- 2009
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In: Heart. - 1468-201X. ; 95:24, s. 2014-22
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To determine the effect of education and other measures of socioeconomic status (SES) on risk of acute myocardial infarction (AMI) in patients and controls from countries with diverse economic circumstances (high, middle, and low income countries). DESIGN: Case-control study. SETTING: 52 countries from all inhabited regions of the world. PARTICIPANTS: 12242 cases and 14622 controls. MAIN OUTCOME MEASURES: First non-fatal AMI. RESULTS: SES was measured using education, family income, possessions in the household and occupation. Low levels of education (< or =8 years) were more common in cases compared to controls (45.0% and 38.1%; p<0.0001). The odds ratio (OR) for low education adjusted for age, sex and region was 1.56 (95% confidence interval 1.47 to 1.66). After further adjustment for psychosocial, lifestyle, other factors and mutually for other socioeconomic factors, the OR associated with education < or =8 years was 1.31 (1.20 to 1.44) (p<0.0001). Modifiable lifestyle factors (smoking, exercise, consumption of vegetables and fruits, alcohol and abdominal obesity) explained about half of the socioeconomic gradient. Family income, numbers of possessions and non-professional occupation were only weakly or not at all independently related to AMI. In high-income countries (World Bank Classification), the risk factor adjusted OR associated with low education was 1.61 (1.33 to 1.94), whereas it was substantially lower in low-income and middle-income countries: 1.25 (1.14 to 1.37) (p for interaction 0.045). CONCLUSION: Of the SES measures we studied, low education was the marker most consistently associated with increased risk for AMI globally, most markedly in high-income countries.
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| 4. |
- Ellaf, A., et al.
(author)
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Energy, exergy, economic, environment, exergo-environment based assessment of amine-based hybrid solvents for natural gas sweetening
- 2023
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In: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 313
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Journal article (peer-reviewed)abstract
- Natural gas is the cleanest form of fossil fuel that needs to be purified from CO2 and H2S to diminish harmful emissions and provide feasible processing. The conventional chemical and physical solvents used for this purpose have many drawbacks, including corrosion, solvent loss, high energy requirement, and the formation of toxic compounds, which ultimately disrupt the process and affect the environment. Hybrid solvents have lately been researched to cater to these liabilities and enhance process economics. This study screened eight solvents based on CO2 selectivity viscosity, absorption enthalpy, corrosivity, working capacity, specific heat, and vapor pressure. From the screened solvents, ten cases of hybrid solvents are simulated and optimized on Aspen HYSYS®. Furthermore, 5Es (Energy, Exergy, Economic, Environmental, and Exergy-environmental) analyses were performed on optimized cases, and results were compared with the base case, MEA (30 wt%). The hybrid blend of Sulfolane and MDEA with weight percentages of 6% and 24%, respectively, showed the highest energy savings of 20% concerning the base case. In addition, it offered 93% savings in exergy destruction and 17.26% in the total operating cost of the process. It is also promising to the environment due to reduced entropy sent to the ecosystem and controlled CO2 emissions. Therefore, the blend of Sulfolane and MDEA is proposed to Supersede the conventional solvent MEA for the natural gas sweetening process.
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| 5. |
- Khatib, R., et al.
(author)
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Availability and affordability of cardiovascular disease medicines and their effect on use in high-income, middle-income, and low-income countries: an analysis of the PURE study data
- 2016
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In: Lancet. - 0140-6736 .- 1474-547X. ; 387:10013, s. 61-69
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Journal article (peer-reviewed)abstract
- BACKGROUND: WHO has targeted that medicines to prevent recurrent cardiovascular disease be available in 80% of communities and used by 50% of eligible individuals by 2025. We have previously reported that use of these medicines is very low, but now aim to assess how such low use relates to their lack of availability or poor affordability. METHODS: We analysed information about availability and costs of cardiovascular disease medicines (aspirin, beta blockers, angiotensin-converting enzyme inhibitors, and statins) in pharmacies gathered from 596 communities in 18 countries participating in the Prospective Urban Rural Epidemiology (PURE) study. Medicines were considered available if present at the pharmacy when surveyed, and affordable if their combined cost was less than 20% of household capacity-to-pay. We compared results from high-income, upper middle-income, lower middle-income, and low-income countries. Data from India were presented separately given its large, generic pharmaceutical industry. FINDINGS: Communities were recruited between Jan 1, 2003, and Dec 31, 2013. All four cardiovascular disease medicines were available in 61 (95%) of 64 urban and 27 (90%) of 30 rural communities in high-income countries, 53 (80%) of 66 urban and 43 (73%) of 59 rural communities in upper middle-income countries, 69 (62%) of 111 urban and 42 (37%) of 114 rural communities in lower middle-income countries, eight (25%) of 32 urban and one (3%) of 30 rural communities in low-income countries (excluding India), and 34 (89%) of 38 urban and 42 (81%) of 52 rural communities in India. The four cardiovascular disease medicines were potentially unaffordable for 0.14% of households in high-income countries (14 of 9934 households), 25% of upper middle-income countries (6299 of 24 776), 33% of lower middle-income countries (13 253 of 40 023), 60% of low-income countries (excluding India; 1976 of 3312), and 59% households in India (9939 of 16 874). In low-income and middle-income countries, patients with previous cardiovascular disease were less likely to use all four medicines if fewer than four were available (odds ratio [OR] 0.16, 95% CI 0.04-0.57). In communities in which all four medicines were available, patients were less likely to use medicines if the household potentially could not afford them (0.16, 0.04-0.55). INTERPRETATION: Secondary prevention medicines are unavailable and unaffordable for a large proportion of communities and households in upper middle-income, lower middle-income, and low-income countries, which have very low use of these medicines. Improvements to the availability and affordability of key medicines is likely to enhance their use and help towards achieving WHO's targets of 50% use of key medicines by 2025. FUNDING: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier, GlaxoSmithKline, Novartis, King Pharma, and national or local organisations in participating countries.
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| 9. |
- Frohlich, H, et al.
(author)
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Epidemiology and long-term outcome in outpatients with chronic heart failure in Northwestern Europe
- 2019
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In: Heart (British Cardiac Society). - : BMJ. - 1468-201X .- 1355-6037. ; 105:16, s. 1252-1259
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Journal article (peer-reviewed)abstract
- To describe the epidemiology, long-term outcomes and temporal trends in mortality in ambulatory patients with chronic heart failure (HF) with reduced (HFrEF), mid-range (HFmrEF) or preserved ejection fraction (HFpEF) from three European countries.MethodsWe identified 10 312 patients from the Norwegian HF Registry and the HF registries of the universities of Heidelberg, Germany, and Hull, UK. Patients were classified according to baseline left ventricular ejection fraction (LVEF) and time of enrolment (period 1: 1995–2005 vs period 2: 2006–2015). Predictors of mortality were analysed by use of univariable and multivariable Cox regression analyses.ResultsAmong 10 312 patients with stable HF, 7080 (68.7%), 2086 (20.2%) and 1146 (11.1%) were classified as having HFrEF, HFmrEF or HFpEF, respectively. A total of 4617 (44.8%) patients were included in period 1, and 5695 (55.2%) patients were included in period 2. Baseline characteristics significantly differed with respect to type of HF and time of enrolment. During a median follow-up of 66 (33–105) months, 5297 patients (51.4%) died. In multivariable analyses, survival was independent of LVEF category (p>0.05), while mortality was lower in period 2 as compared with period 1 (HR 0.81, 95% CI 0.72 to 0.91, p<0.001). Significant predictors of all-cause mortality regardless of HF category were increasing age, New York Heart Association functional class, N-terminal pro-brain natriuretic peptide and use of loop diuretics.ConclusionAmbulatory patients with HF stratified by LVEF represent different phenotypes. However, after adjusting for a wide range of covariates, long-term survival is independent of LVEF category. Outcome significantly improved during the last two decades irrespective from type of HF.
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| 12. |
- Merid, Simon Kebede, et al.
(author)
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Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
- 2020
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In: Genome Medicine. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 1756-994X.
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Journal article (peer-reviewed)abstract
- Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
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| 16. |
- Greco, R, et al.
(author)
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Hematopoietic stem cell transplantation for autoimmune diseases in the time of COVID-19: EBMT guidelines and recommendations
- 2021
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In: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 56:7, s. 1493-1508
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Journal article (peer-reviewed)abstract
- Coronavirus disease-19 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), represents one of the biggest challenges of 21st century, threatening public health around the globe. Increasing age and presence of co-morbidities are reported risk factors for severe disease and mortality, along with autoimmune diseases (ADs) and immunosuppressive treatments such as haematopoietic stem cell transplantation (HSCT), which are also associated with adverse outcomes. We review the impact of the pandemic on specific groups of patients with neurological, rheumatological, and gastroenterological indications, along with the challenges delivering HSCT in adult and pediatric populations. Moving forward, we developed consensus-based guidelines and recommendations for best practice and quality of patient care in order to support clinicians, scientists, and their multidisciplinary teams, as well as patients and their carers. These guidelines aim to support national and international organizations related to autoimmune diseases and local clinical teams delivering HSCT. Areas of unmet need and future research questions are also highlighted. The waves of the COVID-19 pandemic are predicted to be followed by an “endemic” phase and therefore an ongoing risk within a “new normality”. These recommendations reflect currently available evidence, coupled with expert opinion, and will be revised according to necessary modifications in practice.
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| 17. |
- Joseph, Philip G, et al.
(author)
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Global variations in the prevalence, treatment, and impact of atrial fibrillation in a multi-national cohort of 153,152 middle-aged individuals.
- 2021
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In: Cardiovascular research. - : Oxford University Press (OUP). - 1755-3245 .- 0008-6363. ; 117:6, s. 1523-1531
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Journal article (peer-reviewed)abstract
- To compare the prevalence of electrocardiogram (ECG)-documented atrial fibrillation (or flutter) (AF) across eight regions of the world, and to examine anti-thrombotic use and clinical outcomes.Baseline ECGs were collected in 153,152 middle-aged participants (ages 35 to 70 years) to document AF in two community-based studies, spanning 20 countries. Medication use and clinical outcome data (mean follow up of 7.4 years) were available in one cohort. Cross sectional analyses were performed to document the prevalence of AF and medication use, and associations between AF and clinical events were examined prospectively. Mean age of participants was 52.1 years, and 57.7% were female. Age and sex-standardized prevalence of AF varied 12-fold between regions; with the highest in North America, Europe, China and Southeast Asia (270-360 cases per 100,000 persons); and lowest in the Middle East, Africa, and South Asia (30-60 cases per 100,000 persons)(p<0.001). Compared with low-income countries (LICs), AF prevalence was 7-fold higher in middle-income countries (MICs) and 11-fold higher in high-income countries (HICs)(p<0.001). Differences in AF prevalence remained significant after adjusting for traditional AF risk factors. In LICs/MICs, 24% of participants with AF and a CHADS2 score ≥1 received anti-thrombotic therapy, compared with 85% in HICs. AF was associated with an increased risk of stroke (hazard ratio [HR: 2.29; 95% confidence interval [CI] 1.49-3.52) and death (HR: 2.97; 95% CI 2.25-3.93); with similar rates in different country income levels.Large variations in AF prevalence occur in different regions and country income settings, but this is only partially explained by traditional AF risk factors. Anti-thrombotic therapy is infrequently used in poorer countries despite the high risk of stroke associated with AF.We examined atrial fibrillation (AF) prevalence in 153,152 middle-aged participants spanning 20 countries. Age and sex-standardized prevalence of AF varied by as much as 12-fold between regions; highest in North America, Europe, China and Southeast Asia (270-360 cases per 100,000 persons); and lowest in the Middle East, Africa, and South Asia (30-60 cases per 100,000 persons)(p<0.001); and by as much as 11-fold between groups of countries at different income levels (p<0.001). Global variations were poorly explained by traditional AF risk factors. Future studies are needed to understand the predominant determinants driving the variation in AF burden across different regions of the world.
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| 18. |
- Nguyen Dang, Tri, et al.
(author)
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A Contract-Theory-Based Incentive Mechanism for UAV-Enabled VR-Based Services in 5G and Beyond
- 2023
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In: IEEE Internet of Things Journal. - : Institute of Electrical and Electronics Engineers (IEEE). - 2327-4662. ; 10:18, s. 16465-16479
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Journal article (peer-reviewed)abstract
- The proliferation of novel infotainment services, such as virtual reality (VR)-based services, has fundamentally changed the existing mobile networks. These bandwidth-hungry services expanded at a tremendously rapid pace, thus, generating a burden of data traffic in the mobile networks. To cope with this issue, one can use multiaccess edge computing (MEC) to bring the resource to the edge. By doing so, we can release the burden of the core network by taking the communication, computation, and caching resources nearby the end users (UEs). Nevertheless, due to the vast adoption of VR-enabled devices, MEC resources might be insufficient in peak times or dense settings. To overcome these challenges, we propose a system model where the service provider (SP) might rent unmanned area vehicles (UAVs) from UAV SPs (USPs) to serve as micro-base stations (UBSs) that expand the service area and improve the spectrum efficiency. In which, UAV can precached certain sets of VR-based contents and serve UEs via air-to-ground (A2G) communication. Furthermore, future intelligent devices are capable of 5G and B5G communication interfaces, and thus, they can communicate with UAVs via A2G links. By doing so, we can significantly reduce a considerable amount of data traffic in mobile networks. In order to successfully enable such kinds of services, an attractive incentive mechanism is required. Therefore, we propose a contract theory-based incentive mechanism for UAV-assisted MEC in VR-based infotainment services, in which the MEC offers an amount reward to a UAV for serving as a UBS in a specific location for certain time slots. We then derive an optimal contract-based scheme with individual rationality and incentive compatibility conditions. The numerical findings show that our proposed approach outperforms the linear pricing (LP) technique and is close to the optimal solution in terms of social welfare. Additionally, our proposed scheme significantly enhanced the fairness of utility for UAVs in asymmetric information problems.
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| 19. |
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| 20. |
- Pipe, Steven W., et al.
(author)
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Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B
- 2023
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In: New England Journal of Medicine. - 0028-4793. ; 388:8, s. 706-718
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Journal article (peer-reviewed)abstract
- Background: Moderate-to-severe hemophilia B is treated with lifelong, continuous coagulation factor IX replacement to prevent bleeding. Gene therapy for hemophilia B aims to establish sustained factor IX activity, thereby protecting against bleeding without burdensome factor IX replacement. Methods: In this open-label, phase 3 study, after a lead-in period (≥6 months) of factor IX prophylaxis, we administered one infusion of adeno-associated virus 5 (AAV5) vector expressing the Padua factor IX variant (etranacogene dezaparvovec; 2×1013 genome copies per kilogram of body weight) to 54 men with hemophilia B (factor IX activity ≤2% of the normal value) regardless of preexisting AAV5 neutralizing antibodies. The primary end point was the annualized bleeding rate, evaluated in a noninferiority analysis comparing the rate during months 7 through 18 after etranacogene dezaparvovec treatment with the rate during the lead-in period. Noninferiority of etranacogene dezaparvovec was defined as an upper limit of the two-sided 95% Wald confidence interval of the annualized bleeding rate ratio that was less than the noninferiority margin of 1.8. Superiority, additional efficacy measures, and safety were also assessed. Results: The annualized bleeding rate decreased from 4.19 (95% confidence interval [CI], 3.22 to 5.45) during the lead-in period to 1.51 (95% CI, 0.81 to 2.82) during months 7 through 18 after treatment, for a rate ratio of 0.36 (95% Wald CI, 0.20 to 0.64; P<0.001), demonstrating noninferiority and superiority of etranacogene dezaparvovec as compared with factor IX prophylaxis. Factor IX activity had increased from baseline by a least-squares mean of 36.2 percentage points (95% CI, 31.4 to 41.0) at 6 months and 34.3 percentage points (95% CI, 29.5 to 39.1) at 18 months after treatment, and usage of factor IX concentrate decreased by a mean of 248,825 IU per year per participant in the post-treatment period (P<0.001 for all three comparisons). Benefits and safety were observed in participants with predose AAV5 neutralizing antibody titers of less than 700. No treatment-related serious adverse events occurred. Conclusions: Etranacogene dezaparvovec gene therapy was superior to prophylactic factor IX with respect to the annualized bleeding rate, and it had a favorable safety profile.
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| 23. |
- Viafora, N., et al.
(author)
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Day-ahead dispatch optimization with dynamic thermal rating of transformers and overhead lines
- 2019
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In: Electric power systems research. - : Elsevier. - 0378-7796 .- 1873-2046. ; 171, s. 194-208
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Journal article (peer-reviewed)abstract
- Several studies have demonstrated how Dynamic Line Rating (DLR) could be an effective solution for increasing transmission capacity of existing overhead lines. As opposed to Static Line Ratings (SLR), DLR allows for higher power flows depending on real time thermal state of conductors, which highly depend on actual weather conditions. Similarly, recent advances in transformer thermal modelling revealed the feasibility of Dynamic Transformer Rating (DTR) based on the temporal evolution of top oil and winding hot spot temperatures. However, the joint dynamic thermal rating of both overhead lines and transformers in transmission networks has not been thoroughly addressed yet in the literature. This paper proposes a day-ahead dispatch optimization problem based on DC-Optimal Power Flow, where transformer top oil and hot spot dynamics are directly accounted for together with dynamic line ratings of selected transmission lines. Simulated weather data from an actual power system are mapped to the IEEE RTS 24 bus system thus allowing for the estimation of DLR on several lines and the influence of ambient temperature on transformer rating. Results indicate the potential benefits that using DLR in conjunction with DTR could provide for the optimal power system dispatch. The proposed approach does not only indicate advantages compared to standard rating scenarios, but also shows a positive impact that dynamic line rating has on unlocking transformer constraints and vice versa.
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