On Multi-Disciplinary Standardisation – The Case of Spatial Data on the Web

With the emergence of smart applications multi-disciplinarity is becoming an issue in standards setting, as is the need to involve a broader range of stakeholders in the process. One approach to accommodate these needs is the creation of dedicated multi-disciplinary Working Groups (WGs). Following some theoretical deliberations about today’s standardisation environment in general and the need for multi-disciplinarity in standardisation we present a case study of one such joint multi-disciplinary WG. It turns out that this joint WG is seen as both necessary and helpful by those involved. It also turns out the broader organisational setting needs to be adapted to better address the needs of such joint WGs

Bewust en bekwaam toetsen:Wat zouden lerarenopleiders moeten weten over toetsing?

Kwaliteit van toetsen staat prominent op de politieke en maatschappelijke agenda van het hoger onderwijs. In dit artikel wordt betoogd dat kwaliteit van toetsen in hoge mate wordt bepaald door de toetsbekwaamheid van opleiders en hun bewustzijn van het belang van goed toetsen. Tot op heden is onvoldoende helder welke kennis lerarenopleiders in huis moeten hebben om die kwaliteit te kunnen borgen. Het ontbreken van een nationale kennisbasis ’Toetsing voor lerarenopleiders’ vormt het uitgangspunt van ons onderzoek Bewust en bekwaam toetsen. In dit mede door SURF gefinancierd onderzoek hebben vier lerarenopleidingen hun krachten gebundeld om de kwaliteit van toetsbekwaamheid te versterken: het ILS van de HAN, FLOT van Fontys Hogescholen, de ULO van de VU en De Nieuwste PABO van de Hogeschool Zuyd. Een eerste belangrijke vraag in dit project is: Welke toetskennis is van belang voor lerarenopleiders? Om deze vraag te beantwoorden is een literatuurstudie uitgevoerd en zijn schriftelijke interviews afgenomen bij (inter)nationale toetsexperts. Resultaten laten zien dat er geen eenduidig beeld is over wat lerarenopleiders zouden moeten beheersen en dat reeds bestaande standaarden vaak abstract geformuleerd zijn. De kwaliteitspiramide voor eigentijds toetsen en beoordelen (Joosten-ten Brinke, 2011) is gebruikt voor een eerste aanscherping van leerdoelen over toetsing. In totaal zijn 57 leerdoelen benoemd en verdeeld over de vier niveaus van de piramide:8 leerdoelen op het niveau van toetsitems, 28 leerdoelen op het niveau van toetsen, 9 leerdoelen op het niveau van toetsprogramma's en 12 leerdoelen op het niveau van toetsbeleid. Verdere validering van de leerdoelen is nodig voordat instrumenten kunnen worden ontwikkeld waarmee lerarenopleiders zich kunnen professionaliseren. Het artikel sluit af met enkele aanbevelingen en een inkijk in het vervolg van het project

Antidiabetic Effects of Flavan-3-ols and Their Microbial Metabolites

Diet is one of the pillars in the prevention and management of diabetes mellitus. Particularly, eating patterns characterized by a high consumption of foods such as fruits or vegetables and beverages such as coffee and tea could influence the development and progression of type 2 diabetes. Flavonoids, whose intake has been inversely associated with numerous negative health outcomes in the last few years, are a common constituent of these food items. Therefore, they could contribute to the observed positive effects of certain dietary habits in individuals with type 2 diabetes. Of all the different flavonoid subclasses, flavan-3-ols are consumed the most in the European region. However, a large proportion of the ingested flavan-3-ols is not absorbed. Therefore, the flavan-3-ols enter the large intestine where they become available to the colonic bacteria and are metabolized by the microbiota. For this reason, in addition to the parent compounds, the colonic metabolites of flavan-3-ols could take part in the prevention and management of diabetes. The aim of this review is to present the available literature on the effect of both the parent flavan-3-ol compounds found in different food sources as well as the specific microbial metabolites of diabetes in order to better understand their potential role in the prevention and treatment of the disease

Serum testosterone levels measured by isotope dilution-liquid chromatography–tandem mass spectrometry in postmenopausal women versus those in women who underwent bilateral oophorectomy

Background: Differentiation between subtle changes in low serum testosterone concentrations, common in women and children, is not possible with current commercially available assays. The objectives of the study were to develop a method based on stable isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) with adequate sensitivity and specificity and to investigate the applicability of this assay in serum samples from pre- and postmenopausal women. Methods: For 16 women, testosterone levels were measured in blood samples drawn two years before and after physiological menopause, and for eight women in samples drawn before and after bilateral oophorectomy. Testosterone was extracted from serum, derivatized and analysed on an LC-MS/MS. Results: The developed ID-LC-MS/MS method allowed for specific and reproducible measurement of testosterone. Comparison with stable isotope dilution-gas chromatography coupled to mass spectrometry detection by During regression analysis gave a slope of 1.025 and an intercept of 0.055 nmol/L (r = 0.9998). A significant decrease was found in testosterone concentrations before and after bilateral oophorectomy (P = 0.02), whereas no significant difference was found before and after natural menopause (P = 0.4). Conclusions: The ID-LC-MS/MS assay measures serum testosterone with acceptable accuracy and is useful in female samples, supporting the conclusion that the postmenopausal ovary contributes to circulating testosterone. To our knowledge, our analytical method compares favourably to similar published methods in terms of sensitivity. The sensitivity and specificity of this method comply with the reference method for measurement of testosterone in serum samples of women, children and men suffering from hypogonadism and can also be used for men with testosterone in the reference range

Fortifying a meal with oyster mushroom powder beneficially affects postprandial glucagon-like peptide-1, non-esterified free fatty acids and hunger sensation in adults with impaired glucose tolerance:a double-blind randomized controlled crossover trial

PURPOSE: Impaired glucose tolerance (IGT) is a pathophysiological condition characterized by insulin resistance with known metabolic consequences such as postprandial hyperglycemia and hypertriglyceridemia. We hypothesized that fortifying a meal with mushrooms rich in β-glucans may diminish glucose and triglyceride responses by improving postprandial gastrointestinal hormone release. METHODS: In a randomized controlled crossover study, 22 subjects with IGT ingested a meal either enriched with 20 g powder (8.1 g β-glucans) of oven-dried Pleurotus ostreatus (enriched meal, EN) or without enrichment (control meal, CON). Blood was collected before and repeatedly within 4 h after the meal to determine AUC of glucose (primary outcome), insulin, triglycerides, non-esterified free fatty acids (NEFAs), glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP) and ghrelin. Appetite sensations (hunger, satiety, fullness, and desire to eat) were assessed before and after meal consumption by visual analog scales. RESULTS: Postprandial glucose, insulin, triglycerides, GIP and ghrelin concentrations as well as the corresponding AUCs did not differ between EN and CON. NEFAs-AUC was 14% lower (P = 0.026) and GLP-1-AUC 17% higher (P = 0.001) after EN compared to CON. Appetite ratings did not differ between treatments, except for hunger (AUC 22% lower after EN vs. CON; P = 0.031). CONCLUSION: The observed immediate postprandial metabolic changes indicate that an easily manageable fortification of a single meal with powder from dried oyster mushrooms as β-glucan source may improve postprandial metabolism. If the effect is preserved long term, this measure can diminish the risk for further development of overweight/obesity and type 2 diabetes in subjects with IGT. CLINICAL TRIAL REGISTRATION: German Clinical Trial Register on 09/08/2018; trial-ID: DRKS00015244. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00394-021-02674-1

Effectiveness of a girls’ empowerment programme on early childbearing, marriage and school dropout among adolescent girls in rural Zambia: study protocol for a cluster randomized trial

Background: Adolescent pregnancies pose a risk to the young mothers and their babies. In Zambia, 35% of young girls in rural areas have given birth by the age of 18 years. Pregnancy rates are particularly high among out-of-school girls. Poverty, low enrolment in secondary school, myths and community norms all contribute to early childbearing. This protocol describes a trial aiming to measure the effect on early childbearing rates in a rural Zambian context of (1) economic support to girls and their families, and (2) combining economic support with a community intervention to enhance knowledge about sexual and reproductive health and supportive community norms. Methods/design: This cluster randomized controlled trial (CRCT) will have three arms. The clusters are rural schools with surrounding communities. Approximately 4900 girls in grade 7 in 2016 will be recruited from 157 schools in 12 districts. In one intervention arm, participating girls and their guardians will be offered cash transfers and payment of school fees. In the second intervention arm, there will be both economic support and a community intervention. The interventions will be implemented for approximately 2 years. The final survey will be 4.5 years after recruitment. The primary outcomes will be “incidence of births within 8 months of the end of the intervention period”, “incidence of births before girls’ 18th birthday” and “proportion of girls who sit for the grade 9 exam”. Final survey interviewers will be unaware of the intervention status of respondents. Analysis will be by intention-to-treat and adjusted for cluster design and confounders. Qualitative process evaluation will be conducted. Discussion: This is the first CRCT to measure the effect of combining economic support with a community intervention to prevent adolescent childbearing in a low- or middle-income country. We have designed a programme that will be sustainable and feasible to scale up. The findings will be relevant for programmes for adolescent reproductive health in Zambia and similar contexts

Metagenomic DNA sequencing for semi-quantitative pathogen detection from urine: a prospective, laboratory-based, proof-of-concept study

Background: Semi-quantitative bacterial culture is the reference standard to diagnose urinary tract infection, but culture is time-consuming and can be unreliable if patients are receiving antibiotics. Metagenomics could increase diagnostic accuracy and speed by sequencing the microbiota and resistome directly from urine. We aimed to compare metagenomics to culture for semi-quantitative pathogen and resistome detection from urine. Methods: In this proof-of-concept study, we prospectively included consecutive urine samples from a clinical diagnostic laboratory in Amsterdam. Urine samples were screened by DNA concentration, followed by PCR-free metagenomic sequencing of randomly selected samples with a high concentration of DNA (culture positive and negative). A diagnostic index was calculated as the product of DNA concentration and fraction of pathogen reads. We compared results with semi-quantitative culture using area under the receiver operating characteristic curve (AUROC) analyses. We used ResFinder and PointFinder for resistance gene detection and compared results to phenotypic antimicrobial susceptibility testing for six antibiotics commonly used for urinary tract infection treatment: nitrofurantoin, ciprofloxacin, fosfomycin, cotrimoxazole, ceftazidime, and ceftriaxone. Findings: We screened 529 urine samples of which 86 were sequenced (43 culture positive and 43 culture negative). The AUROC of the DNA concentration-based screening was 0·85 (95% CI 0·81–0·89). At a cutoff value of 6·0 ng/mL, culture positivity was ruled out with a negative predictive value of 91% (95% CI 87–93; 26 of 297 samples), reducing the number of samples requiring sequencing by 56% (297 of 529 samples). The AUROC of the diagnostic index was 0·87 (95% CI 0·79–0·95). A diagnostic index cutoff value of 17·2 yielded a positive predictive value of 93% (95% CI 85–97) and a negative predictive value of 69% (55–80), correcting for a culture-positive prevalence of 66%. Gram-positive pathogens explained eight (89%) of the nine false-negative metagenomic test results. Agreement of phenotypic and genotypic antimicrobial susceptibility testing varied between 71% (22 of 31 samples) and 100% (six of six samples), depending on the antibiotic tested. Interpretation: This study provides proof-of-concept of metagenomic semi-quantitative pathogen and resistome detection for the diagnosis of urinary tract infection. The findings warrant prospective clinical validation of the value of this approach in informing patient management and care. Funding: EU Horizon 2020 Research and Innovation Programme

Metagenomic DNA sequencing for semi-quantitative pathogen detection from urine: a prospective, laboratory-based, proof-of-concept study

Background: Semi-quantitative bacterial culture is the reference standard to diagnose urinary tract infection, but culture is time-consuming and can be unreliable if patients are receiving antibiotics. Metagenomics could increase diagnostic accuracy and speed by sequencing the microbiota and resistome directly from urine. We aimed to compare metagenomics to culture for semi-quantitative pathogen and resistome detection from urine. Methods: In this proof-of-concept study, we prospectively included consecutive urine samples from a clinical diagnostic laboratory in Amsterdam. Urine samples were screened by DNA concentration, followed by PCR-free metagenomic sequencing of randomly selected samples with a high concentration of DNA (culture positive and negative). A diagnostic index was calculated as the product of DNA concentration and fraction of pathogen reads. We compared results with semi-quantitative culture using area under the receiver operating characteristic curve (AUROC) analyses. We used ResFinder and PointFinder for resistance gene detection and compared results to phenotypic antimicrobial susceptibility testing for six antibiotics commonly used for urinary tract infection treatment: nitrofurantoin, ciprofloxacin, fosfomycin, cotrimoxazole, ceftazidime, and ceftriaxone. Findings: We screened 529 urine samples of which 86 were sequenced (43 culture positive and 43 culture negative). The AUROC of the DNA concentration-based screening was 0·85 (95% CI 0·81–0·89). At a cutoff value of 6·0 ng/mL, culture positivity was ruled out with a negative predictive value of 91% (95% CI 87–93; 26 of 297 samples), reducing the number of samples requiring sequencing by 56% (297 of 529 samples). The AUROC of the diagnostic index was 0·87 (95% CI 0·79–0·95). A diagnostic index cutoff value of 17·2 yielded a positive predictive value of 93% (95% CI 85–97) and a negative predictive value of 69% (55–80), correcting for a culture-positive prevalence of 66%. Gram-positive pathogens explained eight (89%) of the nine false-negative metagenomic test results. Agreement of phenotypic and genotypic antimicrobial susceptibility testing varied between 71% (22 of 31 samples) and 100% (six of six samples), depending on the antibiotic tested. Interpretation: This study provides proof-of-concept of metagenomic semi-quantitative pathogen and resistome detection for the diagnosis of urinary tract infection. The findings warrant prospective clinical validation of the value of this approach in informing patient management and care. Funding: EU Horizon 2020 Research and Innovation Programme

Ecto-5′-Nucleotidase and Thiopurine Cellular Circulation: Association with CytotoxicityS⃞

Thiopurine drugs such as 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are used to treat acute lymphoblastic leukemia of childhood. To test the hypothesis that variation in the expression of genes within the “thiopurine pathway” might influence 6-MP and 6-TG sensitivity, we generated basal gene expression profiles and IC50 values for both of these thiopurine drugs using a model system consisting of 194 Human Variation Panel lymphoblastoid cell lines. Association analysis showed that thiopurine S-methyltransferase, ecto-5′-nucleotidase (NT5E), and multidrug resistance protein 4 (ABCC4) expression were correlated with thiopurine cytotoxicity. Those observations suggested the possible existence of a “thiopurine cellular circulation” involving nucleotide efflux by ABCC4, hydrolysis of thiopurine nucleotide monophosphates outside of the cell by NT5E, and subsequent transport of thiopurine nucleosides back into the cell by nucleoside transporters. The existence of this cellular circulation was confirmed by a series of functional experiments performed with cultured cells stably or transiently transfected with ABCC4 and/or NT5E. Because of the central role of NT5E in this cellular circulation, the NT5E gene was resequenced using 287 DNA samples from three ethnic groups, with the identification of 68 single nucleotide polymorphisms (SNPs), 46 of which were novel. Several SNPs in the 5′-flanking region of NT5E were highly correlated with expression, rs9450278 having the lowest p value (p = 2.4 × 10−10, R = −0.376). The thiopurine cellular circulation and genetic polymorphisms for genes encoding the proteins involved should be incorporated into future studies of thiopurine drug therapy and effect