| 1. |
- Barrett, Jennifer H., et al.
(författare)
-
Fine mapping of genetic susceptibility loci for melanoma reveals a mixture of single variant and multiple variant regions
- 2015
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:6, s. 1351-1360
-
Tidskriftsartikel (refereegranskat)abstract
- At least 17 genomic regions are established as harboring melanoma susceptibility variants, in most instances with genome-wide levels of significance and replication in independent samples. Based on genome-wide single nucleotide polymorphism (SNP) data augmented by imputation to the 1,000 Genomes reference panel, we have fine mapped these regions in over 5,000 individuals with melanoma (mainly from the GenoMEL consortium) and over 7,000 ethnically matched controls. A penalized regression approach was used to discover those SNP markers that most parsimoniously explain the observed association in each genomic region. For the majority of the regions, the signal is best explained by a single SNP, which sometimes, as in the tyrosinase region, is a known functional variant. However in five regions the explanation is more complex. At the CDKN2A locus, for example, there is strong evidence that not only multiple SNPs but also multiple genes are involved. Our results illustrate the variability in the biology underlying genome-wide susceptibility loci and make steps toward accounting for some of the missing heritability. What's new? In genome-wide association studies, researchers identify genetic variants that frequently associate with a particular disease, though the variants identified may not contribute to the molecular cause of the disease. This study took a closer look at 17 regions associated with melanoma, fine mapping the regions both in people with melanoma and in healthy controls. Though single SNPs account for the association in some regions, they found that in a few regions, several SNPs - and possibly multiple genes - contributed to the association signal. These findings illustrate the importance of not overlooking the interaction between multiple genetic markers when conducting such studies.
|
|
| 2. |
- Barrett, Jennifer H., et al.
(författare)
-
Genome-wide association study identifies three new melanoma susceptibility loci
- 2011
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1108-1113
-
Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 x 10(-9)), an SNP in MX2 (rs45430, P = 2.9 x 10-9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 x 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 x 10(-7) under a fixed-effects model and P = 1.2 x 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.
|
|
| 3. |
- Kehoe, Laura, et al.
(författare)
-
Make EU trade with Brazil sustainable
- 2019
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 4. |
- Olsen, Rikke K J, et al.
(författare)
-
ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency.
- 2007
-
Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 130:Pt 8, s. 2045-54
-
Tidskriftsartikel (refereegranskat)abstract
- Multiple acyl-CoA dehydrogenation deficiency (MADD) is a disorder of fatty acid, amino acid and choline metabolism that can result from defects in two flavoproteins, electron transfer flavoprotein (ETF) or ETF: ubiquinone oxidoreductase (ETF:QO). Some patients respond to pharmacological doses of riboflavin. It is unknown whether these patients have defects in the flavoproteins themselves or defects in the formation of the cofactor, FAD, from riboflavin. We report 15 patients from 11 pedigrees. All the index cases presented with encephalopathy or muscle weakness or a combination of these symptoms; several had previously suffered cyclical vomiting. Urine organic acid and plasma acyl-carnitine profiles indicated MADD. Clinical and biochemical parameters were either totally or partly corrected after riboflavin treatment. All patients had mutations in the gene for ETF:QO. In one patient, we show that the ETF:QO mutations are associated with a riboflavin-sensitive impairment of ETF:QO activity. This patient also had partial deficiencies of flavin-dependent acyl-CoA dehydrogenases and respiratory chain complexes, most of which were restored to control levels after riboflavin treatment. Low activities of mitochondrial flavoproteins or respiratory chain complexes have been reported previously in two of our patients with ETF:QO mutations. We postulate that riboflavin-responsive MADD may result from defects of ETF:QO combined with general mitochondrial dysfunction. This is the largest collection of riboflavin-responsive MADD patients ever reported, and the first demonstration of the molecular genetic basis for the disorder.
|
|
| 5. |
- Daelman, Bo, et al.
(författare)
-
Frailty and cognitive function in middle-aged and older adults with congenital heart disease
- 2024
-
Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 83:12, s. 1149-1159
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Life expectancy of patients with congenital heart disease (CHD) has increased rapidly, resulting in a growing and aging population. Recent studies have shown that older people with CHD have higher morbidity, health care use, and mortality. To maintain longevity and quality of life, understanding their evolving medical and psychosocial challenges is essential.Objectives: The authors describe the frailty and cognitive profile of middle-aged and older adults with CHD to identify predictor variables and to explore the relationship with hospital admissions and outpatient visits.Methods: Using a cross-sectional, multicentric design, we included 814 patients aged ≥40 years from 11 countries. Frailty phenotype was determined using the Fried method. Cognitive function was assessed by the Montreal Cognitive Assessment.Results: In this sample, 52.3% of patients were assessed as robust, 41.9% as prefrail, and 5.8% as frail; 38.8% had cognitive dysfunction. Multinomial regression showed that frailty was associated with older age, female sex, higher physiologic class, and comorbidities. Counterintuitively, patients with mild heart defects were more likely than those with complex lesions to be prefrail. Patients from middle-income countries displayed more prefrailty than those from higher-income countries. Logistic regression demonstrated that cognitive dysfunction was related to older age, comorbidities, and lower country-level income.Conclusions: Approximately one-half of included patients were (pre-)frail, and more than one-third experienced cognitive impairment. Frailty and cognitive dysfunction were identified in patients with mild CHD, indicating that these concerns extend beyond severe CHD. Assessing frailty and cognition routinely could offer valuable insights into this aging population.
|
|
| 6. |
- Farooq, Muhammad, et al.
(författare)
-
Thermodynamic Performance Analysis of Hydrofluoroolefins (HFO) Refrigerants in Commercial Air-Conditioning Systems for Sustainable Environment
- 2020
-
Ingår i: Processes. - : MDPI. - 2227-9717. ; 8:2
-
Tidskriftsartikel (refereegranskat)abstract
- Global warming is one of most severe environmental concerns that our planet is facing today. One of its causes is the previous generation of refrigerants that, upon release, remain in the atmosphere for longer periods and contribute towards global warming. This issue could potentially be solved by replacing the previous generation's high global warming potential (GWP) refrigerants with environmentally friendly refrigerants. This scenario requires an analysis of new refrigerants for a comparison of the thermodynamic properties of the previously used refrigerants. In the present research, a numerical study was conducted to analyze the thermodynamic performance of specifically low GWP hydrofluoroolefens (HFO) refrigerants for an actual vapor compression refrigeration cycle (VCRC) with a constant degree of 3 K superheat. The output parameters included the refrigeration effect, compressor work input, the coefficient of performance (COP), and the volumetric refrigeration capacity (VRC), all of which were calculated by varying the condenser pressure from 6 to 12 bars and vapor pressure from 0.7 to 1.9 bars. Results showed that R1234ze(Z) clearly possessed the desired thermodynamic performance. The drop in refrigeration effect for R1234ze(Z) was merely 14.6% less than that of R134a at a 12 bar condenser pressure; this was minimum drop among candidate refrigerants. The drop in the COP was the minimum for R1234ze(Z)-5.1% less than that of R134a at a 9 bar condenser pressure and 4.7% less than that of R134a at a 1.9 bar evaporator pressure, whereas the COP values of the other refrigerants dropped more drastically at higher condenser pressures. R1234ze(Z) possessed favorable thermodynamic characteristics, with a GWP of 7, and it can serve as an alternative refrigerant for refrigeration systems for a sustainable environment.
|
|
| 7. |
- Olausson, Michael, 1956, et al.
(författare)
-
Long-term Transplant Function After Thrombolytic Treatment Ex Vivo of Donated Kidneys Retrieved 4 to 5 H After Circulatory Death
- 2022
-
Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337. ; 106:12, s. 2348-2359
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Using a novel thrombolytic technique, we present long-term transplant function, measured by creatinine and iohexol clearance, after utilizing kidneys from porcine donors with uncontrolled donation after circulatory deaths, with 4.5-5 h of warm ischemia. Methods. Pigs in the study group were subjected to simulated circulatory death. After 2 h, ice slush was inserted into the abdomen and 4.5 h after death, the kidneys were retrieved. Lys-plasminogen, antithrombin-III, and alteplase were injected through the renal arteries on the back table. Subsequent ex vivo perfusion was continued for 3 h at 15 degrees C, followed by 3 h with red blood cells at 32 degrees C, and then transplanted into pigs as an autologous graft as only renal support. Living-donor recipient pigs that did not receive ex vivo perfusion, and unilateral nephrectomized pigs served as the controls. Results. Pigs in the study group (n = 13), surviving 10 d or more were included, of which 7 survived for 3 mo. Four animals in the living-donor group (n = 6) and all 5 nephrectomized animals survived for 3 mo. Creatinine levels in the plasma and urine, neutrophil gelatinaseassociated lipocalin levels, Kidney Injury Marker-1 expression, and iohexol clearance at 3 mo did not differ significantly between the study and living-donor groups. Histology and transmission electron microscopy after 3 mo showed negligible fibrosis and no other damage. Conclusions. The present method salvages kidneys from extended unontrolled donation after circulatory death using thrombolytic treatment while preserving histology and enabling transplantation after ex vivo reconditioning, with clinically acceptable late function after 3 mo, as measured by creatinine and iohexol clearance.
|
|
| 8. |
- Olausson, Michael, et al.
(författare)
-
Long-term Transplant Function After Thrombolytic Treatment Ex Vivo of Donated Kidneys Retrieved 4 to 5 Hours After Circulatory Death
- 2022
-
Ingår i: Transplantation. - 0041-1337. ; 106:12, s. 2348-2359
-
Tidskriftsartikel (refereegranskat)abstract
- Background. Using a novel thrombolytic technique, we present long-term transplant function, measured by creatinine and iohexol clearance, after utilizing kidneys from porcine donors with uncontrolled donation after circulatory deaths, with 4.5–5 h of warm ischemia. Methods. Pigs in the study group were subjected to simulated circulatory death. After 2 h, ice slush was inserted into the abdomen and 4.5 h after death, the kidneys were retrieved. Lys-plasminogen, antithrombin-III, and alteplase were injected through the renal arteries on the back table. Subsequent ex vivo perfusion was continued for 3 h at 15°C, followed by 3 h with red blood cells at 32°C, and then transplanted into pigs as an autologous graft as only renal support. Living-donor recipient pigs that did not receive ex vivo perfusion, and unilateral nephrectomized pigs served as the controls. Results. Pigs in the study group (n = 13), surviving 10 d or more were included, of which 7 survived for 3 mo. Four animals in the living-donor group (n = 6) and all 5 nephrectomized animals survived for 3 mo. Creatinine levels in the plasma and urine, neutrophil gelatinase-associated lipocalin levels, Kidney Injury Marker-1 expression, and iohexol clearance at 3 mo did not differ significantly between the study and living-donor groups. Histology and transmission electron microscopy after 3 mo showed negligible fibrosis and no other damage. Conclusions. The present method salvages kidneys from extended unontrolled donation after circulatory death using thrombolytic treatment while preserving histology and enabling transplantation after ex vivo reconditioning, with clinically acceptable late function after 3 mo, as measured by creatinine and iohexol clearance.
|
|
| 9. |
- Qureshi, Tayyab, et al.
(författare)
-
Structural and thermal investigation of lignocellulosic biomass conversion for enhancing sustainable imperative in progressive organic refinery paradigm for waste-to-energy applications
- 2024
-
Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 246
-
Tidskriftsartikel (refereegranskat)abstract
- The depletion of finite fossil fuel reserves and the severe environmental degradation resulting from human activities have compelled the expeditious development and application of sustainable waste to energy technologies. To encapsulate energy and environment in sustainability paradigm, bio waste based energy production is need to be forged in organic bio refinery setup. According to world bioenergy association, biomass can cover 50 % of the primary energy demand of the world. Therefore, the present study focuses on reforming the energy mix for a clean energy generation, where, sample composition of cotton stalk was acidified in dilute (5% wt.) hydrochloric acid (HCL) for analyzing material burnout patterns in biomass conversion systems utilized in organic bio refinery sector. Advanced thermochemical burning technique, which includes pyrolysis and combustion was applied at four different leaching times from 0 to 180 min under nitrogen environment from 0 degrees C to 500 degrees C and air from 500 degrees C to 900 degrees C, respectively. Different analyses including proximate, ultimate, gross calorific value (GCV), thermos-gravimetric, kinetic, XRD, FTIR, SEM-EDS were used for analyzing the degradation of demineralized cotton stalk at different treatment rates. Proximate study demonstrated that cotton stalk leaching for 180 min has efficiently infused HCL, leading in a significant increase in fixed carbon and higher heating value of 20.23 % and 12.48%, respectively, as well as a reduction in carbon footprint of around 54.80%. The findings of proximate was validated by GCV analysis and CHNS analysis as value of carbon and hydrogen has shown increasing behavior with the time delay in demineralization Thermo-gravimetric and derivative thermo-gravimetric data analyses shows an increasing trend of conversion efficiency, with the maximum increase of 98 % reported for sample 3H. TT.DEM. XRD characterization has reported 23 degrees to 25 degrees angle for all the observed peaks. Sample 3H.TT.DEM has shown maximum angle inclination along with matured crystalline peak. The latter observations has been validated by FTIR spectroscopy as sample 3H.TT.DEM has reported maximum O-H group formation. Sample 3H.TT. DEM has reported lowest activation energy of 139.51 kJ*mole-1 and lowest reactivity of 0.000293649%*min 0C, due to moderate and stable reactiveness. In SEM examination, increment in pore size and number of pores within the structural matrix of cotton stalk was observed with the enhancement in acidulation process. Furthermore, in EDS analysis, 3H.TT.DEM has shown most balanced distribution of the elements. In this research, sustainable transformation of biomass is envisioned to improve the waste bio refinery system, significantly contributing to the achievement of Sustainable Development Goals 7, 12 and 13.
|
|
| 10. |
- Van Bulck, Liesbet, et al.
(författare)
-
Rationale, design and methodology of APPROACH-IS II: International study of patient-reported outcomes and frailty phenotyping in adults with congenital heart disease.
- 2022
-
Ingår i: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 363, s. 30-39
-
Tidskriftsartikel (refereegranskat)abstract
- In recent years, patient-reported outcomes (PROs) have received increasing prominence in cardiovascular research and clinical care. An understanding of the variability and global experience of PROs in adults with congenital heart disease (CHD), however, is still lacking. Moreover, information on epidemiological characteristics and the frailty phenotype of older adults with CHD is minimal. The APPROACH-IS II study was established to address these knowledge gaps. This paper presents the design and methodology of APPROACH-IS II.APPROACH-IS II is a cross-sectional global multicentric study that includes Part 1 (assessing PROs) and Part 2 (investigating the frailty phenotype of older adults). With 53 participating centers, located in 32 countries across six continents, the aim is to enroll 8000 patients with CHD. In Part 1, self-report surveys are used to collect data on PROs (e.g., quality of life, perceived health, depressive symptoms, autonomy support), and explanatory variables (e.g., social support, stigma, illness identity, empowerment). In Part 2, the cognitive functioning and frailty phenotype of older adults are measured using validated assessments.APPROACH-IS II will generate a rich dataset representing the international experience of individuals in adult CHD care. The results of this project will provide a global view of PROs and the frailty phenotype of adults with CHD and will thereby address important knowledge gaps. Undoubtedly, the project will contribute to the overarching aim of improving optimal living and care provision for adults with CHD.
|
|
