Individualized study systems in theory and practice

After a short characterization of individualized study systems (ISS) and a survey of the number and subject fields of individualized courses in the USA and Europe, the construction and evaluation of an ISSystem in freshman mathematics at the Twente University of Technology is discussed. On the basis of their own experience and data received from others, the authors present a scheme in which the main characteristics of successful ISSystems are outlined

Microfabrics and deformation processes in magmatic veins of the Thuringian Forest, Germany

The research area is located in the Ruhla-Brotterode crystalline complex in the western part of the Thuringian Forest (Germany), about 20km southsouthwest of Eisenach. The investigated outcrops occur at the eastern and western flanks of the valleys north of the villages Trusetal and Hohleborn. Deformed magmatic veins only occur in the Hohleborn area. Both areas have relative fresh outcropping rocks, due to the steep relief, former quarries and fresh road cuts. According to Obst & Katzung (2000) several periods with the formation of magmatic veins with different chemical composition occur in the Ruhla-Brotterode crystalline complex. Presumably older lamprophyric veins and younger doleritic, syenitporphyric and granitporphyric veins have been identified (Obst & Katzung 2000). Benek & Schust (1988) already pointed out that some of these magmatic veins have experienced ductile deformation. The subject of this work is the occurrence of deformed magmatic veins in the Hohleborn area. The contact to their host rocks, their petrography and their microfabrics have been investigated and related to deformation processes, which led to a better understanding of their deformation conditions within the late-to post-variscan development of the area.conferenc

The nationwide case-cohort study in pharmacoepidemiology: a study of iatrogenic anaphylaxis and agranulocytosis

Drug safety is an important palt of postmarketing surveillance. In ancient times, people were already aware of the fact that drugs could have side effects. The oldest drugs were mainly of plant and animal origin, but also mercury, arsenic and antimony were used, the toxic effects of which were well known. In 1224 Frederick II, Emperor of Hohenstaufen ordered inspection of drugs and mixtures prepared by apothecaries and in 1518 the Royal college of Physicians was founded, whose Fellows were also concemed with quality control of drugs. The first drug to be banned because of its toxicity was antimony in the 17th century. It was used again, however, after it cured Louis XIV from typhoid fever. One of the first descriptions of an intoxication to a drug which is still in use today, was made by William Withering in 1785. He described digitalis intoxication as follows: "The Foxglove, when given in very large and quickly repeated doses, occasions sickness, vomiting, purging, giddiness, confused vision, objects appearing green or yellow, increased secretion of urine with frequent motions to patt with it, and sometimes inability to retain it; slow pulse, even as low as 35 in a minute, cold sweats, convulsions, syncope and death"

A non-invasive risk score including skin autofluorescence predicts diabetes risk in the general population

Abstract Increased skin autofluorescence (SAF) predicts the development of diabetes-related complications and cardiovascular disease. We assessed the performance of a simple model which includes SAF to identify individuals at high risk for undiagnosed and incident type 2 diabetes, in 58,377 participants in the Lifelines Cohort Study without known diabetes. Newly-diagnosed diabetes was defined as fasting blood glucose ≥ 7.0 mmol/l and/or HbA1c ≥ 6.5% (≥ 48 mmol/mol) or self-reported diabetes at follow-up. We constructed predictive models based on age, body mass index (BMI), SAF, and parental history of diabetes, and compared to results with the concise FINDRISC model. At 2nd visit to Lifelines, 1113 (1.9%) participants were identified with undiagnosed diabetes and 1033 (1.8%) participants developed diabetes during follow-up. A model comprising age, BMI and SAF yielded an AUC of 0.783 and was non-inferior to the concise FINDRISC model, which had an AUC of 0.797 to predict new diabetes. At a score of 5.8, sensitivity was 78% and specificity of 66%. Model 2 which also incorporated parental diabetes history, had an AUC of 0.792, and a sensitivity of 74% and specificity of 70% at a score of 6.5. Net reclassification index (NRI) did not improve significantly (NRI 1.43% (− 0.50–3.37 p = 0.15). The combination of an easy to perform SAF measurement with age and BMI is a good alternative screening tool suitable for medical and non-medical settings. Parental history of diabetes did not significantly improve model performance in this homogeneous cohort

Genome-wide association study identifies novel loci associated with skin autofluorescence in individuals without diabetes

BACKGROUND: Skin autofluorescence (SAF) is a non-invasive measure reflecting accumulation of advanced glycation endproducts (AGEs) in the skin. Higher SAF levels are associated with an increased risk of developing type 2 diabetes and cardiovascular disease. An earlier genome-wide association study (GWAS) revealed a strong association between NAT2 variants and SAF. The aim of this study was to calculate SAF heritability and to identify additional genetic variants associated with SAF through genome-wide association studies (GWAS). RESULTS: In 27,534 participants without diabetes the heritability estimate of lnSAF was 33% ± 2.0% (SE) in a model adjusted for covariates. In meta-GWAS for lnSAF five SNPs, on chromosomes 8, 11, 15 and 16 were associated with lnSAF (P  T), which results in a Met30Val missense variant in MMP27 exon 1 (NM_022122.3); 2. rs2470893 (Chr15:75,019,449,C > T), in intergenic region between CYP1A1 and CYP1A2; with attenuation of the SNP-effect when coffee consumption was included as a covariate; 3. rs12931267 (Chr16:89,818,732,C > G) in intron 30 of FANCA and near MC1R; and following conditional analysis 4. rs3764257 (Chr16:89,800,887,C > G) an intronic variant in ZNF276, 17.8 kb upstream from rs12931267; finally, 30 kb downstream from NAT2 5. rs576201050 (Chr8:18,288,053,G > A). CONCLUSIONS: This large meta-GWAS revealed five SNPs at four loci associated with SAF in the non-diabetes population. Further unravelling of the genetic architecture of SAF will help in improving its utility as a tool for screening and early detection of diseases and disease complications. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-022-09062-x

Offline and online scheduling of electric vehicle charging with a minimum charging threshold

The increasing penetration of electric vehicles (EVs) requires the development of smart charging strategies that accommodate the increasing load of these EVs on the distribution grid. Many existing charging strategies assume that an EV is allowed to charge at any rate up to a given maximum rate. However, in practice, charging at low rates is inefficient and often even impossible. Therefore, this paper presents an efficient algorithm for scheduling an EV within a decentralized energy management system that allows only charging above a given threshold. We show that the resulting optimal EV schedule is characterized by an activation level and a fill-level. Moreover, based on this result, we derive an online approach that does not require predictions of uncontrollable loads as input, but merely a prediction of these two characterizing values. Simulation results show that the online algorithm is robust against prediction errors in these values and can produce near-optimal online solutions

Differences in lipid and blood pressure measurements between individuals with type 1 diabetes and the general population:a cross-sectional study

OBJECTIVES: Cardiovascular disease (CVD) is a precarious complication of type 1 diabetes (T1D). Alongside glycaemic control, lipid and blood pressure (BP) management are essential for the prevention of CVD. However, age-specific differences in lipid and BP between individuals with T1D and the general population are relatively unknown.DESIGN: Cross-sectional study.SETTING: Six diabetes outpatient clinics and individuals from the Lifelines cohort, a multigenerational cohort from the Northern Netherlands.PARTICIPANTS: 2178 adults with T1D and 146 22 individuals without diabetes from the general population.PRIMARY AND SECONDARY OUTCOME MEASURES: Total cholesterol, low-density lipoprotein cholesterol (LDL-cholesterol), systolic BP (SBP) and diastolic BP (DBP), stratified by age group, glycated haemoglobin category, medication use and sex.RESULTS: In total, 2178 individuals with T1D and 146 822 without diabetes were included in this study. Total cholesterol and LDL-cholesterol were lower and SBP and DBP were higher in individuals with T1D in comparison to the background population. When stratified by age and medication use, total cholesterol and LDL-cholesterol were lower and SBP and DBP were higher in the T1D population. Men with T1D achieved lower LDL-cholesterol levels both with and without medication in older age groups in comparison to women. Women with T1D had up to 8 mm Hg higher SBP compared with the background population, this difference was not present in men.CONCLUSIONS: Lipid and BP measurements are not comparable between individuals with T1D and the general population and are particularly unfavourable for BP in the T1D group. There are potential sex differences in the management of LDL-cholesterol and BP.</p

The Many Faces of Cobalamin (Vitamin B12) Deficiency

Although cobalamin (vitamin B12) deficiency was described over a century ago, it is still difficult to establish the correct diagnosis and prescribe the right treatment. Symptoms related to vitamin B12 deficiency may be diverse and vary from neurologic to psychiatric. A number of individuals with vitamin B12 deficiency may present with the classic megaloblastic anemia. In clinical practice, many cases of vitamin B12 deficiency are overlooked or sometimes even misdiagnosed. In this review, we describe the heterogeneous disease spectrum of patients with vitamin B12 deficiency in whom the diagnosis was either based on low serum B12 levels, elevated biomarkers like methylmalonic acid and/or homocysteine, or the improvement of clinical symptoms after the institution of parenteral vitamin B12 therapy. We discuss the possible clinical signs and symptoms of patients with B12 deficiency and the various pitfalls of diagnosis and treatment.</p