183 research outputs found
Critical reflection and dialogical learning design: moving MOOCs beyond unidirectional transmission of content
Distance education and e-learning has been around for some time now. The ubiquitous development of the internet (Sharples, 2007) has however made way for the emergence of new educational formats such as the much talked-about Massive Open Online Courses (MOOCs). Within MOOCs users have access to educational literature and tasks at all times, which allow users to fit the course into their own pace, place and Personal Learning Environment (Attwell 2007).Today MOOCs has spread across the globe, and in Denmark we now see institutions such as Aarhus University developing a new course with roots in the MOOC format, however without the âMassiveâ part (Aarhus University, 2016).Over a 5 week period we conducted a netnographic (Kozinet, 2015) mixed methods research of the MOOC Blended Learning Essentials (https://www.futurelearn.com/courses/blended-learning-gettingstarted/2). Contrary to the acclaimed potentials of MOOCs, our research showed a pronounced lack of dialogue and a high degree of what Freire (1996) calls âthe banking concept of education,â entailing a high amount of one-way knowledge transmission (Hoem, 2006). To circumvent these tendencies, the paper presents a case analysis and design framework for moving MOOCs beyond âthe banking concept of educationâ and towards dialogue in ways that support critical thinking; a high-level cognitive skill essential to higher education (Laurillard, 2012).
Social isolation and all-cause mortality: a population-based cohort study in Denmark.
Social isolation is associated with increased mortality. Meta-analytic results, however, indicate heterogeneity in effect sizes. We aimed to provide new evidence to the association between social isolation and mortality by conducting a population-based cohort study. We reconstructed the Berkman and Syme's social network index (SNI), which combines four components of social networks (partnership, interaction with family/friends, religious activities, and membership in organizations/clubs) into an index, ranging from 0/1 (most socially isolated) to 4 (least socially isolated). We estimated cumulative mortality and adjusted mortality rate ratios (MRR) associated with SNI. We adjusted for potential important confounders, including psychiatric and somatic status, lifestyle, and socioeconomic status. Cumulative 7-year mortality in men was 11% for SNI 0/1 and 5.4% for SNI 4 and in women 9.6% for SNI 0/1 and 3.9% for SNI 4. Adjusted MRRs comparing SNI 0/1 with SNI 4 were 1.7 (95% CI: 1.1-2.6) among men and 1.6 (95% CI: 0.83-2.9) among women. Having no partner was associated with an adjusted MRR of 1.5 (95% CI: 1.2-2.1) for men and 1.7 (95% CI: 1.2-2.4) for women. In conclusion, social isolation was associated with 60-70% increased mortality. Having no partner was associated with highest MRR
Hydronium-dominated ion transport in carbon-dioxide-saturated electrolytes at low salt concentrations in nanochannels
Nanochannel ion transport is known to be governed by surface charge at low ionic concentrations. In this paper, we show that this surface charge is typically dominated by hydronium ions arising from dissolution of ambient atmospheric carbon dioxide. Taking the hydronium ions into account, we model the nanochannel conductance at low salt concentrations and identify a conductance minimum before saturation at a value independent of salt concentration in the dilute limit. Via the Poisson-Boltzmann equation, our model self-consistently couples chemical-equilibrium dissociation models of the silica wall and of the electrolyte bulk, parametrized by the dissociation reaction constants. Experimental data with aqueous KCl solutions in 165-nm-high silica nanochannels are described well by our model, both with and without extra hydronium from added HCl
Evidence for More than One Parkinson's Disease-Associated Variant within the HLA Region
Parkinson's disease (PD) was recently found to be associated with HLA in a genome-wide association study (GWAS). Follow-up GWAS's replicated the PD-HLA association but their top hits differ. Do the different hits tag the same locus or is there more than one PD-associated variant within HLA? We show that the top GWAS hits are not correlated with each other (0.00â¤r2â¤0.15). Using our GWAS (2000 cases, 1986 controls) we conducted step-wise conditional analysis on 107 SNPs with P<10â3 for PD-association; 103 dropped-out, four remained significant. Each SNP, when conditioned on the other three, yielded PSNP1â=â5Ă10â4, PSNP2â=â5Ă10â4, PSNP3â=â4Ă10â3 and PSNP4â=â0.025. The four SNPs were not correlated (0.01â¤r2â¤0.20). Haplotype analysis (excluding rare SNP2) revealed increasing PD risk with increasing risk alleles from ORâ=â1.27, Pâ=â5Ă10â3 for one risk allele to ORâ=â1.65, Pâ=â4Ă10â8 for three. Using additional 843 cases and 856 controls we replicated the independent effects of SNP1 (Pconditioned-on-SNP4â=â0.04) and SNP4 (Pconditioned-on-SNP1â=â0.04); SNP2 and SNP3 could not be replicated. In pooled GWAS and replication, SNP1 had ORconditioned-on-SNP4â=â1.23, Pconditioned-on-SNP4â=â6Ă10â7; SNP4 had ORconditioned-on-SNP1â=â1.18, Pconditioned-on-SNP1â=â3Ă10â3; and the haplotype with both risk alleles had ORâ=â1.48, Pâ=â2Ă10â12. Genotypic OR increased with the number of risk alleles an individual possessed up to ORâ=â1.94, Pâ=â2Ă10â11 for individuals who were homozygous for the risk allele at both SNP1 and SNP4. SNP1 is a variant in HLA-DRA and is associated with HLA-DRA, DRB5 and DQA2 gene expression. SNP4 is correlated (r2â=â0.95) with variants that are associated with HLA-DQA2 expression, and with the top HLA SNP from the IPDGC GWAS (r2â=â0.60). Our findings suggest more than one PD-HLA association; either different alleles of the same gene, or separate loci
Epigenome-wide association study of peripheral immune cell populations in Parkinsonâs disease
Understanding the contribution of immune mechanisms to Parkinsonâs disease pathogenesis is an important challenge, potentially of major therapeutic implications. To further elucidate the involvement of peripheral immune cells, we studied epigenome-wide DNA methylation in isolated populations of CD14+ monocytes, CD19+ B cells, CD4+ T cells, and CD8+ T cells from Parkinsonâs disease patients and healthy control participants. We included 25 patients with a maximum five years of disease duration and 25 controls, and isolated four immune cell populations from each fresh blood sample. Epigenome-wide DNA methylation profiles were generated from 186 samples using the Illumina MethylationEpic array and association with disease status was tested using linear regression models. We identified six differentially methylated CpGs in CD14+ monocytes and one in CD8â+âT cells. Four differentially methylated regions were identified in monocytes, including a region upstream of RAB32, a gene that has been linked to LRRK2. Methylation upstream of RAB32 correlated negatively with mRNA expression, and RAB32 expression was upregulated in Parkinsonâs disease both in our samples and in summary statistics from a previous study. Our epigenome-wide association study of early Parkinsonâs disease provides evidence for methylation changes across different peripheral immune cell types, highlighting monocytes and the RAB32 locus. The findings were predominantly cell-type-specific, demonstrating the value of isolating purified cell populations for genomic studies
Breeding unicorns:Developing trustworthy and scalable randomness beacons
Randomness beacons are services that periodically emit a random number, allowing users to base decisions on the same random value without trusting anyone: ideally, the randomness beacon does not only produce unpredictable values, but is also of low computational complexity for the users, bias-resistant and publicly verifiable. Such randomness beacons can serve as an important primitive for smart contracts in a variety of contexts. This paper first presents a structured security analysis, based on which we then design, implement, and evaluate a trustworthy and efficient randomness beacon. Our approach does not require users to register or run any computationally intensive operations. We then compare different implementation and deployment options on distributed ledgers, and report on an Ethereum smart contract-based lottery using our beacon
The GBA variant E326K is associated with Parkinson's disease and explains a genome-wide association signal
Objective
Coding variants in the GBA gene have been identified as the numerically most important genetic risk factors for Parkinson's disease (PD). In addition, genome-wide association studies (GWAS) have identified associations with PD in the SYT11-GBA region on chromosome 1q22, but the relationship to GBA coding variants have remained unclear. The aim of this study was to sequence the complete GBA gene in a clinical cohort and to investigate whether coding variants within the GBA gene may be driving reported association signals.
Methods
We analyzed high-throughput sequencing data of all coding exons of GBA in 366 patients with PD. The identified low-frequency coding variants were genotyped in three Scandinavian case-controls series (786 patients and 713 controls). Previously reported risk variants from two independent association signals within the SYT11-GBA locus on chromosome 1 were also genotyped in the same samples. We performed association analyses and evaluated linkage disequilibrium (LD) between the variants.
Results
We identified six rare mutations (1.6%) and two low-frequency coding variants in GBA. E326K (rs2230288) was significantly more frequent in PD patients compared to controls (OR 1.65, p = 0.03). There was no clear association of T369M (rs75548401) with disease (OR 1.43, p = 0.24). Genotyping the two GWAS hits rs35749011 and rs114138760 in the same sample set, we replicated the association between rs35749011 and disease status (OR 1.67, p = 0.03), while rs114138760 was found to have similar allele frequencies in patients and controls. Analyses revealed that E326K and rs35749011 are in very high LD (r2 0.95).
Conclusions
Our results confirm that the GBA variant E326K is a susceptibility allele for PD. The results suggest that E326K may fully account for the primary association signal observed at chromosome 1q22 in previous GWAS of PD.acceptedVersio
Dopamine agonist serum concentrations and impulse control disorders in Parkinson's disease
Background and purpose: Impulse control disorders (ICDs) are common among Parkinson's
disease patients using dopamine agonists. We wanted to determine whether ICD patients
have higher dopamine agonist serum concentrations than those without any sign of ICD.
Methods: Patients who used either pramipexole or ropinirole depot once daily were
screened for ICDs using the validated Questionnaire for Impulsive-Compulsive Disorders
in Parkinson's DiseaseâRating Scale. Those who scored above the cut-off for one or more
of the four defined ICDs (gambling, compulsive sexual behavior, compulsive shopping,
and binge-eating) were compared in a caseâcontrol study to patients who scored zero
points (no evidence of ICD) on the same items. They were examined clinically and evaluated using relevant scales. Three blood samples were taken on the same day: before daily
dose, and then 6 and 12âh later.
Results: Forty-six patients were included: 19 ICD-positive and 27 controls. Ropinirole
serum concentrations 6âh after daily intake (Cmax) were higher in the case group compared
to the control group, as was the daily ropinirole dosage. No differences were observed in
serum concentrations, dosage or total drug exposure for pramipexole. Disease duration
and length of dopamine agonist treatment was significantly longer among ICD patients
for ropinirole, but not for pramipexole.
Conclusions: The use of pramipexole may in itself confer high ICD risk, whereas ICDs
among ropinirole users depend more on serum concentration and drug exposure. The
pharmacokinetic properties of ropinirole make it challenging to predict its effects on patients, which supports the need for therapeutic drug monitoring to reduce risk of ICD
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