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| 2. |
- Chami, Nathalie, et al.
(författare)
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Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits
- 2016
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 99:1, s. 8-21
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Tidskriftsartikel (refereegranskat)abstract
- Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 x 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 x 10(-8) for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribution width (rs3211938, MAF = 8.7%, p = 7 x 10(-11)) and showed that it is associated with lower CD36 expression and strong allelic imbalance in ex vivo differentiated human erythroblasts. We also identified a rare missense variant in ALAS2 (rs201062903, MAF = 0.2%) associated with lower mean corpuscular volume and mean corpuscular hemoglobin (p < 8 x 10(-9)). Mendelian mutations in ALAS2 are a cause of sideroblastic anemia and erythropoietic protoporphyria. Gene-based testing highlighted three rare missense variants in PKLR, a gene mutated in Mendelian non-spherocytic hemolytic anemia, associated with HGB and HCT (SKAT p < 8 x 10(-7)). These rare, low-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white blood cell, and lipid traits. Our association results and functional annotation suggest the involvement of new genes in human erythropoiesis. We also confirm that rare and low-frequency variants play a role in the architecture of complex human traits, although their phenotypic effect is generally smaller than originally anticipated.
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| 3. |
- Elfgren, Lennart, et al.
(författare)
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Krister Cederwall, 1932-2006 : Minnesord
- 2007
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Annan publikation (populärvet., debatt m.m.)abstract
- Krister Cederwall föddes I Borås den 1 oktober 1932. Efter civilingenjörsexamen I väg- och vattenbyggnad på KTH arbetade han som konstruktör. Han flyttade efter några år till Göteborg och knöts till Chalmers tekniska högskola som forskningsassistent vid Hjalmar Granholms institution för byggnadsteknik där han blev tekn lic 1961. Under åren 1960-65 var han brokonstruktör vid Granholms konstruktionsbyrå och var bland annat med om att utforma broarna i Essingeleden I Stockholm. År 1965 utnämndes han till universitetslektor I betongbyggnad vid Chalmers och disputerade 1971 på en avhandling om stabilitet och långstidsdeformationer I tryckta betongkonstruktioner. När den nya tekniska högskolan I Luleå byggdes upp blev Krister Cederwall dess förste innehavare av professuren I Konstruktionsteknik. Han byggde med stor energi upp nya forskningsinriktningar som byggteknik i kallt klimat och studier av isbärighet och ishållfasthet. Han initierade även studier av massiva betongkonstruktioner och deras sprickbenägenhet. Han arbetade nära samman med byggföretag och knöt adjungerade professorer till högskolan. Han var tidigt ute med att använda sannolikhetsteori för att studera bärighet och att använda brottmekanik för att förstå hur konstruktioner går sönder och hur man undviker spröda brott. När professuren i betongbyggnad blev ledig på Chalmers 1983 efter Anders Losberg flyttade han tillbaka till Göteborg. Hans hjärta fortsatte dock att klappa för Luleå, och han var många gånger på besök för att gästföreläsa och delta i disputationer och licentiatseminarier i ämnen som han en gång initierat. Han blev professor emeritus I januari 1995 och avled den 1 november 2006 vid 74 års ålder.
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| 4. |
- Engström, Kent, et al.
(författare)
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Benchmarking an intelligent network prototype implemented in parallel Erlang
- 1996
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Ingår i: High-Performance Computing and Networking. - Berlin, Heidelberg : Springer Berlin/Heidelberg. - 9783540611424 - 9783540499558 ; , s. 905-906
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Konferensbidrag (refereegranskat)abstract
- We have adapted the Erlang language for MIMD computers using PVM for communication. We have then used an Erlang application, the Intelligent Network Prototype, to demonstrate the usefulness and performance of the Erlang version.
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| 5. |
- Fagman, Johan Bourghardt, 1980, et al.
(författare)
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EGFR, but not COX-2, protein in resected pancreatic ductal adenocarcinoma is associated with poor survival.
- 2019
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Ingår i: Oncology letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 17:6, s. 5361-5368
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Tidskriftsartikel (refereegranskat)abstract
- The effects of EGFR and COX-2 protein overexpression on clinical outcomes in pancreatic ductal adenocarcinoma (PDAC) patients remains unclear. Therefore, the aim of the present study was to evaluate the protein expression of epithelial growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in tumor cells in surgically resected PDAC, in comparison with clinicopathological characteristics and clinical outcomes. Immunohistochemical staining of formalin-fixed paraffin-embedded tissue derived from surgically resected tumors was performed. Tissue slides were evaluated for membrane wild-type EGFR and cytoplasmic COX-2 staining using a histoscore system. Statistical associations between EGFR and COX-2 staining and clinicopathological characteristics were examined to predict survival. In a cohort of 32 resected PDAC patients, high EGFR protein expression in tumor cells was significantly associated with shorter median overall survival (7.9 vs. 39.2 months, P=0.0038). The corresponding hazard ratio (HR) for patients with high EGFR protein expression in tumor cells was 3.12 [95% confidence interval (CI): 1.39-7.00, P=0.006]. COX-2 protein expression was not associated with survival (22.6 vs. 24.5 months P=0.60; HR 1.22 95% CI: 0.59-2.51, P=0.60). Following multivariate Cox regression analysis, high EGFR protein expression in tumor cells (P=0.043) remained as significant independent prognostic factor for survival. In conclusion, high wild-type EGFR protein expression, but not COX-2 protein expression, in tumor cells is a prognostic factor for reduced overall survival following pancreatic tumor resection, supporting a role for EGFR in identifying resected patients that may benefit from EGFR-targeted therapy.
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| 6. |
- Hellstrand, Mats, et al.
(författare)
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A health dialogue intervention reduces cardiovascular risk factor levels : a population based randomised controlled trial in Swedish primary care setting with 1-year follow-up
- 2017
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Ingår i: BMC Public Health. - : BIOMED CENTRAL LTD. - 1471-2458. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Background: The total number of cardiovascular (CVD) deaths accounted for almost a third of all deaths globally in 2013. Population based randomised controlled trials, managed within primary care, on CVD risk factor interventions are scarce. The aim of the study was to evaluate the effects of a health dialogue intervention in a primary care setting offered to a population at the age of 55 years, focusing on CVD risk factors. Methods: The study was performed in five primary health care centres in the county of Vastmanland, Sweden between April 2011 and December 2012. Men and women were randomly assigned to intervention (n = 440) and control groups (n = 440). At baseline, both groups filled in a health questionnaire and serum cholesterol, fasting plasma glucose, glycated haemoglobin (HbA1c), weight, height, waist (WC) and hip circumference, waist hip ratio (WHR) and systolic/diastolic blood pressure were measured. Intervention group attended a health dialogue, supported by a visualised health profile, with a possibility for further activities. Participation rates at baseline were 53% and 52% respectively. A 1-year follow-up was carried out. Results: The intervention group (n = 165) showed reductions compared to the control group (n = 177) concerning body mass index (BMI) (0.3 kg/m(2), p = .031), WC (2.1 cm, p <= .001) and WHR (. 002, p <= .001) at the 1-year follow-up. No differences between the intervention and control groups were found in other variables. Intervention group, compared to baseline, had reduced weight, BMI, WC, WHR, HbA1c, and diet, while the men in the control group had reduced their alcohol consumption. Conclusions: A health dialogue intervention at the age of 55 years, conducted in ordinary primary care, showed a moderate effect on CVD risk factor levels, in terms of BMI, WC and WHR.
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| 7. |
- Hubrich, Martin, et al.
(författare)
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Feasibility and Functions of Central Venous Catheters versus Peripherally Inserted Central Venous Catheter
- 2019
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Ingår i: Open Journal of Surgery. - 2689-0593. ; 3:2, s. 028-033
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Tidskriftsartikel (refereegranskat)abstract
- Safety, risk of complications and the functional feasibility among diff erent kinds of central venous access are still a matter of debate. Not many clinical trials have reported a comparison of complications and patency of CVCs versus Peripherally Inserted Catheters (PICC) as central venous access for indoor patients with advanced gastrointestinal disorder. The aim of the present study was to compare CVCs and PICCs regarding function, complications and convenience in a controlled clinical study on patients aimed for oncology surgery aimed for cure. Distributions of patients were comparable. Malignant diagnoses were signifi cantly higher among CVC-patients. CVCs and PICCs were used for treatment during equal number of days, without any signifi cant complication rates and with comparable number of days on antibiotics and other potent drugs. The overall cumulative hazard (risk) for treatment interruptions, due to either full-fi lled clinical indications or due to any complication among the subgroups of patients did not diff er. Central Venous Catheter and Peripheral Inserted Central Venous Catheter, for central venous access, did not diff er among consecutive unselected patients with serious gastro-intestinal disorders.
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| 8. |
- Iresjö, Britt-Marie, 1963, et al.
(författare)
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Acute appendicitis: A block-randomized study on active observation with or without antibiotic treatment.
- 2024
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Ingår i: Surgery. - 0039-6060. ; 175:4, s. 929-935
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Tidskriftsartikel (refereegranskat)abstract
- Antibiotic treatment of unselected patients with acute appendicitis is safe and effective. However, it is unknown to what extent early provision of antibiotic treatment may represent overtreatment due to spontaneous healing of appendix inflammation. The aim of the present study was to evaluate the role of antibiotic treatment versus active in-hospital observation on spontaneous regression of acute appendicitis.Patients who sought acute medical care at Sahlgrenska University Hospital were block-randomized according to age (18-60 years) and systemic inflammation (C-reactive protein <60 mg/L, white blood cell <13,000/μL), in combination with clinical and abdominal characteristics of acute appendicitis. Study patients received antibiotic treatment and active observation, while control patients were allocated to classic active "wait and see observation" for either disease regression or the need for surgical exploration. According to our standard surgical care, certified surgeons in charge decided whether and when appendectomy was necessary. In total, 1,019 patients were screened for eligibility; 203 patients met inclusion criteria, 126 were accepted to participate, 29 declined, and 48 were missed for inclusion.The antibiotic group (n= 69) and the control group (n= 57) were comparable at inclusion. Appendectomy at first hospital stay was 28% and 53% for study and control patients (χ2, P < .004). Life table analysis indicated a time-dependent difference in the need for appendectomy during follow-up (P < .03). Antibiotics prevented surgical exploration and appendectomy by 72% to 50% compared to 47% to 37% in the control group across the time course follow-ups between 5 and 1,200 days.Early antibiotic treatment is superior to traditional "wait and see observation" to avoid surgical exploration and appendectomy.
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| 9. |
- Iresjö, Britt-Marie, 1963, et al.
(författare)
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Overnight Steady-State Infusions of Parenteral Nutrition on Myosin Heavy Chain Transcripts in Rectus Abdominis Muscle Related to Amino Acid Transporters, Insulin-like Growth Factor 1, and Blood Amino Acids in Patients Aimed at Major Surgery.
- 2019
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Ingår i: JPEN - Journal of Parenteral and Enteral Nutrition. - : Wiley. - 0148-6071 .- 1941-2444. ; 43:4, s. 497-507
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Tidskriftsartikel (refereegranskat)abstract
- Evaluation of improvements by nutrition support to severely ill patients requires sensitive methods to demonstrate activation of protein synthesis in various tissues from groups with a limited number of patients to be statistically efficient. This study examines effects of standard parenteral nutrition (PN) on abdominal muscle transcripts of amino acid (AA) transporters, myosin heavy chains (MHCs), and the insulin-like growth factor 1 and its receptor (IGF-1/IGF-1R) in patients aimed at major surgery.Twenty-two randomized patients received steady-state PN (0.16 gN/kg/d, 30 kcal/kg/d) or saline infusions for 12 hours before operation. Blood samples and muscle biopsies were obtained at operation start. Muscle messenger RNA (mRNA) levels of AA transporters (solute carrier family members SNAT2, LAT1, LAT3, LAT4, TAUT, PAT1, CD98), IGF-1, IGF-1R, MHC isoforms (MHC1, MHC2A, MHC2X), and LAT3 protein were quantified and related to concentrations of AA, IGF-1, insulin, and metabolic substrates in blood.Muscle mRNA LAT3, LAT4, IGF-1R, and MHC2A increased by PN infusion, with correlations to specific AA transporters and MHC isoforms (P < .01-.05). TAUT and LAT3 correlated to slow (MHC1) and fast (MHC2A, MHC2X) isoforms (P < .001-.02). Muscle IGF-1 mRNA correlated to plasma essential AAs, whereas IGF-1R mRNA was related to LAT3, MHC2A, and serum IGF-1 (P < .001-.03).The results confirm that short-term preoperative PN activates transcription of AA transporters and myosin isoforms. Thus, combinations of methods on gene transcription and translation of muscle proteins can be applied to define efficient combinations of nutrition and hormones to catabolic patients in preoperative and postoperative settings.
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| 10. |
- Iresjö, Britt-Marie, 1963, et al.
(författare)
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Preoperative overnight parenteral nutrition (TPN) improves skeletal muscle protein metabolism indicated by microarray algorithm analyses in a randomized trial
- 2016
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 4:11
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Tidskriftsartikel (refereegranskat)abstract
- Loss of muscle mass is associated with increased risk of morbidity and mortality in hospitalized patients. Uncertainties of treatment efficiency by short-term artificial nutrition remain, specifically improvement of protein balance in skeletal muscles. In this study, algorithmic microarray analysis was applied to map cellular changes related to muscle protein metabolism in human skeletal muscle tissue during provision of overnight preoperative total parenteral nutrition (TPN). Twenty-two patients (11/group) scheduled for upper GI surgery due to malignant or benign disease received a continuous peripheral all-in-one TPN infusion (30 kcal/kg/day, 0.16 gN/kg/day) or saline infusion for 12 h prior operation. Biopsies from the rectus abdominis muscle were taken at the start of operation for isolation of muscle RNA. RNA expression microarray analyses were performed with Agilent Sureprint G3, 8 9 60K arrays using one-color labeling. 447 mRNAs were differently expressed between study and control patients (P < 0.1). mRNAs related to ribosomal biogenesis, mRNA processing, and translation were upregulated during overnight nutrition; particularly anabolic signaling S6K1 (P < 0.01-0.1). Transcripts of genes associated with lysosomal degradation showed consistently lower expression during TPN while mRNAs for ubiquitin-mediated degradation of proteins as well as transcripts related to intracellular signaling pathways, PI3 kinase/MAPkinase, were either increased or decreased. In conclusion, muscle mRNA alterations during overnight standard TPN infusions at constant rate altered mRNAs associated with mTOR signaling; increased initiation of protein translation; and suppressed autophagy/lysosomal degradation of proteins. This indicates that overnight preoperative parenteral nutrition is effective to promote muscle protein metabolism.
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