Cross - fertilization between three different teaching modes for geo - informatics education

Objective of this study was to determine if the use and student appreciation of course materials differs for native materials (materials that were developed for that course type in which they are used) and foreign materials (materials that were developed for another course type) and if the way the materials are used, (compulsory versus optional, interchangeable versus the only source of information) affects the student appreciation. A comparison was made between a face-to-face course, a blended learning course and a distance course. The comparison was based on a questionnaire, the course evaluation and the statistics from the digital learning environments. Results show no difference between native and foreign course materials, but do however show the influence of the way the materials were used. Appreciation for compulsory, non-interchangeable materials is higher than for optional interchangeable ones, but even for this last category the general appreciation is high. Distance students have the highest overall appreciation for study materials, followed by the face-to-face students

TEACHING GEOGRAPHIC INFORMATION SCIENCE CONCEPTS WITH QGIS AND THE LIVING TEXTBOOK – TOWARDS A SUSTAINABLE AND INCLUSIVE DISTANCE EDUCATION

In 2020, many students could not travel due to the restrictions imposed by the COVID pandemic. In response, Faculty ITC of the University of Twente offered the online course Principles and Applications of Geographic Information Systems and Earth Observation as the first quartile of a full presential MSc. Programme. The course used the flipped classroom strategy to enhance student's ability to choose the learning strategy that best fitted their learning styles and was developed around four principles: (1) The course was Exercise led - students were introduced to concepts from the exercise descriptions; (2) Every concept taught was demonstrated and operationalized; (3) To emphasize the focus on concept learning, only two software tools were used - QGIS and the Living Textbook; (4) The software tools should be inclusive and encourage technological independence. The first three elements were evaluated by comparing the student feedback, the evaluation questionnaires and the academic attainment levels of the 2020 course with the in-house. The inclusiveness and technological independence were measured via the institutional impact. The results were positive for the new course setup, with students performing slightly better when compared with 2019 in-house edition of the course. The course had a significant institutional impact by contributing to a deeper commitment to open-source software tools. Open source is now the primary choice for teaching, with ITC becoming a QGIS-certified organization

TB Hackathon: Development and Comparison of Five Models to Predict Subnational Tuberculosis Prevalence in Pakistan

Pakistan’s national tuberculosis control programme (NTP) is among the many programmes worldwide that value the importance of subnational tuberculosis (TB) burden estimates to support disease control efforts, but do not have reliable estimates. A hackathon was thus organised to solicit the development and comparison of several models for small area estimation of TB. The TB hackathon was launched in April 2019. Participating teams were requested to produce district-level estimates of bacteriologically positive TB prevalence among adults (over 15 years of age) for 2018. The NTP provided case-based data from their 2010–2011 TB prevalence survey, along with data relating to TB screening, testing and treatment for the period between 2010–2011 and 2018. Five teams submitted district-level TB prevalence estimates, methodological details and programming code. Although the geographical distribution of TB prevalence varied considerably across models, we identified several districts with consistently low notification-to-prevalence ratios. The hackathon highlighted the challenges of generating granular spatiotemporal TB prevalence forecasts based on a cross-sectional prevalence survey data and other data sources. Nevertheless, it provided a range of approaches to subnational disease modelling. The NTP’s use and plans for these outputs shows that, limitations notwithstanding, they can be valuable for programme planning

Rectal microbiota are coupled with altered cytokine production capacity following community-acquired pneumonia hospitalization

Human studies describing the immunomodulatory role of the intestinal microbiota in systemic infections are lacking. Here, we sought to relate microbiota profiles from 115 patients with community-acquired pneumonia (CAP), both on hospital admission and following discharge, to concurrent circulating monocyte and neutrophil function. Rectal microbiota composition did not explain variation in cytokine responses in acute CAP (median 0%, IQR 0.0%-1.9%), but did one month following hospitalization (median 4.1%, IQR 0.0%-6.6%, p = 0.0035). Gene expression analysis of monocytes showed that undisrupted microbiota profiles following hospitalization were associated with upregulated interferon, interleukin-10, and G-protein-coupled-receptor-ligand-binding pathways. While CAP is characterized by profoundly distorted gut microbiota, the effects of these disruptions on cytokine responses and transcriptional profiles during acute infection were absent or modest. However, rectal microbiota were related to altered cytokine responses one month following CAP hospitalization, which may provide insights into potential mechanisms contributing to the high risk of recurrent infections following hospitalization.peer-reviewe

Spectrum of Phenotypic, Genetic, and Functional Characteristics in Patients With Epilepsy With KCNC2 Pathogenic Variants

Background and ObjectivesKCNC2 encodes Kv3.2, a member of the Shaw-related (Kv3) voltage-gated potassium channel subfamily, which is important for sustained high-frequency firing and optimized energy efficiency of action potentials in the brain. The objective of this study was to analyze the clinical phenotype, genetic background, and biophysical function of disease-associated Kv3.2 variants.MethodsIndividuals with KCNC2 variants detected by exome sequencing were selected for clinical, further genetic, and functional analysis. Cases were referred through clinical and research collaborations. Selected de novo variants were examined electrophysiologically in Xenopus laevis oocytes.ResultsWe identified novel KCNC2 variants in 18 patients with various forms of epilepsy, including genetic generalized epilepsy (GGE), developmental and epileptic encephalopathy (DEE) including early-onset absence epilepsy, focal epilepsy, and myoclonic-atonic epilepsy. Of the 18 variants, 10 were de novo and 8 were classified as modifying variants. Eight drug-responsive patients became seizure-free using valproic acid as monotherapy or in combination, including severe DEE cases. Functional analysis of 4 variants demonstrated gain of function in 3 severely affected DEE cases and loss of function in 1 case with a milder phenotype (GGE) as the underlying pathomechanisms.DiscussionThese findings implicate KCNC2 as a novel causative gene for epilepsy and emphasize the critical role of KV3.2 in the regulation of brain excitability

Intracellular pyruvate levels positively correlate with cytokine production capacity in tolerant monocytes from patients with pneumonia

Background: Community-acquired pneumonia (CAP) is responsible for a high morbidity and mortality worldwide. Monocytes are essential for pathogen recognition and the initiation of an innate immune response. Immune cells induce intracellular glycolysis upon activation to support several functions. Objective: To obtain insight in the metabolic profile of blood monocytes during CAP, with a focus on glycolysis and branching metabolic pathways, and to determine a possible association between intracellular metabolite levels and monocyte function. Methods: Monocytes were isolated from blood of patients with CAP within 24 h of hospital admission and from control subjects matched for age, sex and chronic comorbidities. Changes in glycolysis, oxidative phosphorylation (OXPHOS), tricarboxylic acid (TCA) cycle and the pentose phosphate pathway were investigated through RNA sequencing and metabolomics measurements. Monocytes were stimulated ex vivo with lipopolysaccharide (LPS) to determine their capacity to produce tumor necrosis factor (TNF), interleukin (IL)-1β and IL-10. Results: 50 patients with CAP and 25 non-infectious control subjects were studied. When compared with control monocytes, monocytes from patients showed upregulation of many genes involved in glycolysis, including PKM, the gene encoding pyruvate kinase, the rate limiting enzyme for pyruvate production. Gene set enrichment analysis of OXPHOS, the TCA cycle and the pentose phosphate pathway did not reveal differences between monocytes from patients and controls. Patients' monocytes had elevated intracellular levels of pyruvate and the TCA cycle intermediate α-ketoglutarate. Monocytes from patients were less capable of producing cytokines upon LPS stimulation. Intracellular pyruvate (but not α-ketoglutarate) concentrations positively correlated with IL-1β and IL-10 levels released by patients' (but not control) monocytes upon exposure to LPS. Conclusion: These results suggest that elevated intracellular pyruvate levels may partially maintain cytokine production capacity of hyporesponsive monocytes from patients with CAP.peer-reviewe

TB hackathon : development and comparison of five models to predict subnational tuberculosis prevalence in Pakistan

Pakistan's national tuberculosis control programme (NTP) is among the many programmes worldwide that value the importance of subnational tuberculosis (TB) burden estimates to support disease control efforts, but do not have reliable estimates. A hackathon was thus organised to solicit the development and comparison of several models for small area estimation of TB. The TB hackathon was launched in April 2019. Participating teams were requested to produce district-level estimates of bacteriologically positive TB prevalence among adults (over 15 years of age) for 2018. The NTP provided case-based data from their 2010-2011 TB prevalence survey, along with data relating to TB screening, testing and treatment for the period between 2010-2011 and 2018. Five teams submitted district-level TB prevalence estimates, methodological details and programming code. Although the geographical distribution of TB prevalence varied considerably across models, we identified several districts with consistently low notification-to-prevalence ratios. The hackathon highlighted the challenges of generating granular spatiotemporal TB prevalence forecasts based on a cross-sectional prevalence survey data and other data sources. Nevertheless, it provided a range of approaches to subnational disease modelling. The NTP's use and plans for these outputs shows that, limitations notwithstanding, they can be valuable for programme planning

Adaptation, spread and transmission of SARS-CoV-2 in farmed minks and associated humans in the Netherlands

In the first wave of the COVID-19 pandemic (April 2020), SARS-CoV-2 was detected in farmed minks and genomic sequencing was performed on mink farms and farm personnel. Here, we describe the outbreak and use sequence data with Bayesian phylodynamic methods to explore SARS-CoV-2 transmission in minks and humans on farms. High number of farm infections (68/126) in minks and farm workers (>50% of farms) were detected, with limited community spread. Three of five initial introductions of SARS-CoV-2 led to subsequent spread between mink farms until November 2020. Viruses belonging to the largest cluster acquired an amino acid substitution in the receptor binding domain of the Spike protein (position 486), evolved faster and spread longer and more widely. Movement of people and distance between farms were statistically significant predictors of virus dispersal between farms. Our study provides novel insights into SARS-CoV-2 transmission between mink farms and highlights the importance of combining genetic information with epidemiological information when investigating outbreaks at the animal-human interface

Effectiveness of Passive and Active Surveillance for Early Detection of SARS-CoV-2 in Mink during the 2020 Outbreak in the Netherlands

Starting December 2019, a novel coronavirus (SARS-CoV-2) spread among humans across the world. From 2020 onward, farmed mink were found susceptible to the virus. In this paper, we describe the Dutch surveillance system and the added surveillance components for early detection of SARS-CoV-2 outbreaks and their results in Dutch mink farms. In the Netherlands, a surveillance system was in place in which mink farmers could submit carcasses for postmortem evaluation and could contact a telephone helpdesk for veterinary advise. Through this system, the first SARS-CoV-2 outbreak in two mink farms was detected in April 2020. Immediately, the Dutch Ministry of Agriculture commissioned a consortium of statutory and research institutes to intensify the surveillance system. The program consisted of both passive surveillance, i.e., mandatory notifications and active surveillance components, i.e., serological screenings and weekly risk-based sampling of dead mink for early detection of new SARS-CoV-2 infections. When one of the surveillance components indicated a suspicion of a possible SARS-CoV-2 infection, follow-up samplings were conducted and at confirmation, all mink were culled. During 2020, 67 out of 124 mink farms that were under surveillance became infected with SARS-CoV-2 (54%). Of these, 31 were detected based on clinical signs (passive surveillance of clinical signs) and 36 were detected through active surveillance. From the mink farms with a new SARS-CoV-2 outbreak that was detected through the surveillance, in 19% of the farms (n = 7), the mink never showed any clinical signs of SARS-CoV-2 and might have been missed by the passive notification system. This study underlines the added value of a surveillance system that can quickly be intensified. The subsequent combination of both passive and active surveillance has shown to be effective in the early detection of emerging pathogens, which is important to minimize the risk of zoonotic spill-over