An experimental analysis has been performed to validate the measurement error of cooling curves measured in thin walled ductile cast iron. Specially designed thermocouples (TCs) with Ø0·2 mm TC wire in Ø1·6 mm ceramic tube were used for the experiments. Temperatures were measured in plates with thicknesses between 2 and 4·3 mm. The TCs were accurately placed at the same distance from the surface of the casting for different plate thicknesses. It is shown that when measuring the temperature in plates with thickness between 2 and 4·3 mm the measured temperature will be parallel shifted to a level ∼20°C lower than the actual temperature in the casting. Factors affecting the measurement error (oxide layer on the TC wire, penetration into the ceramic tube and variation in placement of TC) are discussed. Finally, it is shown how useful cooling curve may be obtained in thin walled castings.
The authors describe the principal clinical and pathological aspects of the solitary hyperfunctioning adenoma or the multifocal hyperfunction of a multinodular goitre. Successively they report the incidence of these conditions in countries with different iodine intake as well as the age distribution of the examined patients. In the area with low iodine intake the incidence of hyperthyroidism caused by multinodular goitre is 10 times higher than in the high iodine intake area. Finally, the role of the laboratory in the diagnosis of hyperthyroidism and in identifying the type of hyperthyroidism is discussed; an up-todate flow-sheme is also reported.
Elevated apoB-containing lipoproteins (=remnants+LDLs [low-density lipoproteins]) are a major risk factor for atherosclerotic cardiovascular disease, including peripheral artery disease (PAD) and myocardial infarction. We tested the hypothesis that remnants and LDL both explain part of the increased risk of PAD conferred by elevated apoB-containing lipoproteins. For comparison, we also studied the risk of chronic limb-threatening ischemia and myocardial infarction.
Whether inflammation is independently associated with development of JAK2V617F mutation and myeloproliferative neoplasm is not clear. We tested the hypothesis that a loss-of-function polymorphism in IL6R (marked by rs4537545) reduces risk of JAK2V617F mutation and myeloproliferative neoplasm in a Mendelian randomization study.We genotyped 107,969 Danes from the Copenhagen General Population Study for the IL6R rs4537545 genotype, where the T-allele is associated with impaired interleukin-6 receptor signaling and reduced inflammation. JAK2V617F was examined in a subset of 49,143 individuals. We investigated the association between IL6R rs4537545 and risk of JAK2V617F using logistic regression and myeloproliferative neoplasm using Cox regression.36,871 were non-carriers, 52,500 heterozygotes, and 18,598 homozygotes for the T-allele of the IL6R rs4537545 genotype. Among 107,969 individuals, 352 were diagnosed with myeloproliferative neoplasm, and among 49,143 individuals, 62 were JAK2V617F-positive (of these 62 individuals, 46 had myeloproliferative neoplasm diagnosed). Compared to non-carriers, age- and sex-adjusted odds ratios for risk of JAK2V617F were 0·55(95%CI:0·32-0·94) in heterozygotes, 0·51(0·24-1·12) in homozygotes, 0·54(0·33-0·89) in carriers, and 0·66(0·45-0·96) per T-allele. Compared to non-carriers, age- and sex-adjusted hazard ratios for risk of myeloproliferative neoplasm were 0·82(95% CI: 0·65-1·02) in heterozygotes, 0·65(0·47-0·91) in homozygotes, 0·77(0·63-0·96) in carriers, and 0·81(0·70-0·94) per T-allele. Associations were primarily observed for polycythaemia vera and myelofibrosis, and for JAK2V617F-positive myeloproliferative neoplasm.A loss-of-function polymorphism in IL6R reduces risk of JAK2V617F mutation and myeloproliferative neoplasm. This finding supports inflammation as an independent risk factor for JAK2V617F mutation and myeloproliferative neoplasm and indicates that therapeutics designed to block interleukin-6 receptor signaling might prevent or retard progression of myeloproliferative neoplasm.Karen Elise Jensen Foundation.
ABSTRACT Aims Elevated remnant cholesterol (= the cholesterol carried in triglyceride‐rich lipoproteins) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and is common in individuals with diabetes. We tested the hypothesis that ASCVD in individuals with diabetes can be partly attributed to elevated remnant cholesterol. Materials and Methods We included 3806 individuals with diabetes identified among 107,243 individuals from the Copenhagen General Population Study and used multivariable adjusted Poisson regression to estimate the fraction of ASCVD attributable to elevated remnant cholesterol. Elevated remnant cholesterol was defined as levels higher than those observed in individuals with non‐high‐density lipoprotein (non‐HDL) cholesterol < 2.6 mmol/L (100 mg/dL), the European guideline goal. Results were replicated in the UK Biobank. Results During 15 years of follow‐up, 498 patients were diagnosed with ASCVD, 172 with peripheral artery disease, 185 with myocardial infarction and 195 with ischaemic stroke. In individuals with non‐HDL cholesterol < 2.6 mmol/L (100 mg/dL) and in all individuals with diabetes, median remnant cholesterol levels were 0.5 mmol/L (20 mg/dL) and 0.8 mmol/L (31 mg/dL). The fraction of events attributable to elevated remnant cholesterol was 19% (95% confidence interval: 10%–28%) for ASCVD, 21% (5%–37%) for peripheral artery disease, 24% (10%–37%) for myocardial infarction and 17% (1%–31%) for ischaemic stroke; in the UK Biobank, corresponding values were 16% (9%–22%), 25% (12%–36%), 17% (8%–25%) and 7% (0%–19%), respectively. Conclusions One in five ASCVD events in individuals with diabetes can be attributed to elevated remnant cholesterol. It remains to be determined in clinical trials if remnant cholesterol‐lowering therapy may prevent ASCVD.
Metabolic syndrome (MetS) is a growing concern in survivors of pediatric hematopoietic stem cell transplantation (HSCT), but little is known about the underlying mechanisms. This study aimed to determine the prevalence and clinical presentation of MetS in male long-term survivors of pediatric HSCT and to investigate predisposing factors, including low-grade inflammation, altered fat distribution, and low testosterone levels. We included 98 survivors age 19 to 47 years at a median follow-up of 18 years (range, 8 to 35 years) after pediatric HSCT. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. The prevalence and clinical manifestations of MetS were compared between our cohort and a control group of males from the background population (n = 4767). Fat distribution was assessed by android/gynoid ratio from a whole-body dual-energy X-ray absorptiometry scan. Systemic inflammation was evaluated by IL-6 and high-sensitivity C-reactive protein (hsCRP). Serum testosterone levels were measured in morning samples. The prevalence of MetS was 30%, corresponding to the prevalence in the 50- to 80-year-old males from the background population. In individuals with MetS, hyperglycemia was more frequent in the HSCT survivors compared with age-matched controls with MetS (76% versus 20%; P < .001), whereas hypertension was more dominant in the control group with MetS (69% versus 93%; P = .01). In addition, normal or low body mass index was more commonly observed among HSCT survivors with MetS compared with age-matched controls with MetS (41% versus 11%; P = .002). MetS was more often associated with total body irradiation (TBI) compared with chemotherapy regimens (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.2 to 24.4; P = .02), lower testosterone levels (OR, 5.4; 95% CI, 1.3 to 23.6; P = .02), higher IL-6 levels (OR, 1.8; 95% CI, 1.2 to 2.8; P = .004), and higher hsCRP levels (OR, 1.8; 95% CI, 1.3 to 2.6; P < .001) (estimates per 2-fold increase). In addition, an increased android/gynoid (AG) fat ratio was strongly associated with MetS (OR, 2.1; 95% CI, 1.5 to 2.9; P < .001), even though only 7% of patients met the criteria for increased abdominal circumference. Our results indicate an increased risk of MetS in early adulthood after pediatric HSCT. The clinical manifestations differed from those seen in age-matched controls with MetS, indicating different pathophysiology driven by hyperglycemia, altered fat distribution (despite no clinical abdominal obesity), and low-grade inflammation. Risk factors included TBI-based conditioning and low testosterone levels. These results underline the importance of continuous clinical assessment of the cardiometabolic risk profile and stress the presence of important dissimilarities in the pathophysiology of MetS in HSCT survivors compared with the background population.
Abstract Background Elevated remnant cholesterol is observationally and causally associated with increased risk of atherosclerotic cardiovascular disease (ASCVD) in the general population; the association in individuals with diabetes is not known. Purpose We tested the hypothesis that elevated remnant cholesterol is associated with increased risk of peripheral artery disease, myocardial infarction, ischemic stroke, and any ASCVD in individuals with diabetes. Methods We studied 4,569 individuals with diabetes and 102,674 individuals without diabetes from the Copenhagen General Population Study (2003-2015). In those with diabetes, during up to 15 years of follow-up, 236 were diagnosed with peripheral artery disease, 234 with myocardial infarction, 226 with ischemic stroke, and 498 with any ASCVD in national Danish health registries. Remnant cholesterol was calculated from a standard lipid-profile as total cholesterol minus HDL cholesterol minus LDL cholesterol. Results Individuals with diabetes had higher levels of remnant cholesterol, but lower levels of LDL cholesterol, compared to individuals without diabetes (Figure 1). Statin use could explain the lower levels of LDL cholesterol but did not associate with levels of remnant cholesterol. Multivariable adjusted hazard ratios (95% confidence interval) per doubling of remnant cholesterol and LDL cholesterol were 1.8 (1.2-2.5) and 0.9 (0.6-1.2) for peripheral artery disease, 1.8 (1.3-2.6) and 1.0 (0.7-1.4) for myocardial infarction, 1.6 (1.1-2.3) and 1.1 (0.8-1.6) for ischemic stroke, and 1.7 (1.4-2.2) and 0.9 (0.7-1.1) for any ASCVD, respectively. Excess risk conferred by diabetes was 2.5-fold for peripheral artery disease, 1.6-fold for myocardial infarction, 1.4-fold for ischemic stroke, and 1.6-fold for any ASCVD. Elevated remnant cholesterol explained 14% (95% confidence interval: 6-23%) of excess risk of PAD; corresponding numbers were 26% (10-41%) for myocardial infarction, 34% (5-64%) for ischemic stroke, and 24% (12-36%) for any ASCVD (Figure 2). LDL cholesterol was lower in individuals with diabetes than in individuals without diabetes and could therefore not explain excess risk. Conclusions Elevated remnant cholesterol was associated with increased risk of ASCVD in individuals with diabetes and explained 24% of their excess risk of ASCVD. Clinical trials should determine if remnant cholesterol lowering can prevent ASCVD in individuals with diabetes.
Casting experiments have been performed with eutectic and hypereutectic castings with plate thicknesses from 2 to 8 mm involving both temperature measurements during solidification and microstructural examination afterwards. The nodule count was the same for the eutectic and hypereutectic castings in the thin plates (≤4·3 mm) while in the 8 mm plate the nodule count was higher in the hypereutectic than in the eutectic castings. The minimum temperature before the eutectic recalescence (T min) was 15 to 20°C lower for the eutectic than for the hypereutectic castings. This is due to nucleation of graphite nodules which begins at a lower temperature in the eutectic than in the hypereutectic castings. The recalescence ΔT rec was however also larger for the eutectic casting and in the thin plates the maximum temperature after recalescence (T max) was the same in the eutectic and hypereutectic plates. This is because higher undercooling gives a larger driving force for the solidification process and the equal nodule counts therefore give the same T max. However, the higher undercooling before recalescence increases the risk for formation of carbides during the solidification. In the 8 mm plates, the lower nodule count in the eutectic plates also gave a lower T max than in the hypereutectic castings.
