23 research outputs found

    Når skolens børn evaluerer sig selv

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    I overensstemmelse med ideen om livslang læring forventes skolebørn i stigende grad at vurdere, hvad de har lært. Karakteristisk for disse selvevalueringspraksisser er, at de ikke kun knytter sig til børnenes faglige kompetencer. De går ofte også tæt på børnenes mere personlige forhold. Derudover er evaluering en del af den skolepolitiske dagsorden, hvor læreren er forpligtet på at dokumentere elevernes læring. I denne artikel går vi tæt på undervisningen og præsenterer eksempler på evalueringspraksisser, der skaber vidt forskellige deltagelsesmuligheder for børnene. Der er fokus på aktiviteter, hvor børnene skal vurdere, hvad de har lært, gennem brug af evalueringsværktøjer som portfolio og læringsplatforme. Vi diskuterer den udspændthed, som læreren befinder sig i mellem på den ene side at efterleve politiske krav om evaluering og på den anden side at praktisere evaluering, der kan udvikle undervisningen og styrke børnenes trivsel og læring samtidig med hensynet til børnenes behov og forudsætninger

    Causal inference for planning randomised critical care trials:Protocol for a scoping review

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    BACKGROUND: Randomised clinical trials in critical care are prone to inconclusiveness owing, in part, to undue optimism about effect sizes and suboptimal accounting for heterogeneous treatment effects. Planned predictive enrichment based on secondary critical care data (often very rich with respect to both data types and temporal granularity) and causal inference methods may help overcome these challenges, but no overview exists about their use to this end. METHODS: We will conduct a scoping review to assess the extent and nature of the use of causal inference from secondary data for planned predictive enrichment of randomised clinical trials in critical care. We will systematically search 10 general and specialty journals for reports published on or after 1 January 2018, of randomised clinical trials enrolling adult critically ill patients. We will collect trial metadata (e.g., recruitment period and phase) and, when available, information pertaining to the focus of the review (predictive enrichment based on causal inference estimates from secondary data): causal inference methods, estimation techniques and software used; types of patient populations; data provenance, types and models; and the availability of the data (public or not). The results will be reported in a descriptive manner. DISCUSSION: The outlined scoping review aims to assess the use of causal inference methods and secondary data for planned predictive enrichment in randomised critical care trials. This will help guide methodological improvements to increase the utility, and facilitate the use, of causal inference estimates when planning such trials in the future

    Reduced Alcohol Seeking and Withdrawal Symptoms in Mice Lacking the BDNF Receptor SorCS2

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    Alcohol use disorder (AUD) is characterized by repetitive and uncontrolled intake of alcohol with severe consequences for affected individuals, their families and society as a whole. Numerous studies have implicated brain-derived neurotrophic factor (BDNF) activity in the neurobiology underlying AUD. The BDNF signaling mechanism is complex and depends on two receptor systems, TrkB and p75NTR, which appear to have opposite effects on alcohol seeking behavior in animal models. We recently discovered that the sortilin-related receptor SorCS2 forms complexes with both TrkB and p75NTR and is important for BDNF activity in the developing and adult CNS. Moreover, the SORCS2 gene was recently identified as the top association signal for severity of alcohol withdrawal symptoms. Hence, we speculated that SorCS2 deficient mice would have an altered response to alcohol. The role of SorCS2 in the acute and adapted response to alcohol was therefore investigated by comparing SorCS2 knockout (Sorcs2−/−) mice to wild type (WT) mice in three paradigms modeling alcohol sensitivity and consumption; alcohol-induced conditioned place preference, two-bottle choice test as well as the behavioral response to alcohol withdrawal. We found that, when compared to the WT mice, (I) Sorcs2−/− mice displayed complete lack of alcohol-induced place preference, (II) when given free choice between water and alcohol, Sorcs2−/− mice consumed less alcohol, and (III) Sorcs2−/− mice showed no handling-induced convulsion in response to alcohol withdrawal following extended alcohol exposure. Taken together, these results show that lack of the alcohol withdrawal risk gene Sorcs2 results in abnormal behavioral response to alcohol in mice. Consequently, SorCS2 may play an important role in the molecular pathways underlying AUD and complications associated with alcohol withdrawal

    PCSK9 deficiency alters brain lipid composition without affecting brain development and function

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    PCSK9 induces lysosomal degradation of the low-density lipoprotein (LDL) receptor (LDLR) in the liver, hereby preventing removal of LDL cholesterol from the circulation. Accordingly, PCSK9 inhibitory antibodies and siRNA potently reduce LDL cholesterol to unprecedented low levels and are approved for treatment of hypercholesterolemia. In addition, PCSK9 inactivation alters the levels of several other circulating lipid classes and species. Brain function is critically influenced by cholesterol and lipid composition. However, it remains unclear how the brain is affected long-term by the reduction in circulating lipids as achieved with potent lipid lowering therapeutics such as PCSK9 inhibitors. Furthermore, it is unknown if locally expressed PCSK9 affects neuronal circuits through regulation of receptor levels. We have studied the effect of lifelong low peripheral cholesterol levels on brain lipid composition and behavior in adult PCSK9 KO mice. In addition, we studied the effect of PCSK9 on neurons in culture and in vivo in the developing cerebral cortex. We found that PCSK9 reduced LDLR and neurite complexity in cultured neurons, but neither PCSK9 KO nor overexpression affected cortical development in vivo. Interestingly, PCSK9 deficiency resulted in changes of several lipid classes in the adult cortex and cerebellum. Despite the observed changes, PCSK9 KO mice had unchanged behavior compared to WT controls. In conclusion, our findings demonstrate that altered PCSK9 levels do not compromise brain development or function in mice, and are in line with clinical trials showing that PCSK9 inhibitors have no adverse effects on cognitive function

    Expression analysis of asthma candidate genes during human and murine lung development

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    <p>Abstract</p> <p>Background</p> <p>Little is known about the role of most asthma susceptibility genes during human lung development. Genetic determinants for normal lung development are not only important early in life, but also for later lung function.</p> <p>Objective</p> <p>To investigate the role of expression patterns of well-defined asthma susceptibility genes during human and murine lung development. We hypothesized that genes influencing normal airways development would be over-represented by genes associated with asthma.</p> <p>Methods</p> <p>Asthma genes were first identified via comprehensive search of the current literature. Next, we analyzed their expression patterns in the developing human lung during the pseudoglandular (gestational age, 7-16 weeks) and canalicular (17-26 weeks) stages of development, and in the complete developing lung time series of 3 mouse strains: A/J, SW, C57BL6.</p> <p>Results</p> <p>In total, 96 genes with association to asthma in at least two human populations were identified in the literature. Overall, there was no significant over-representation of the asthma genes among genes differentially expressed during lung development, although trends were seen in the human (Odds ratio, OR 1.22, confidence interval, CI 0.90-1.62) and C57BL6 mouse (OR 1.41, CI 0.92-2.11) data. However, differential expression of some asthma genes was consistent in both developing human and murine lung, e.g. <it>NOD1, EDN1, CCL5, RORA </it>and <it>HLA-G</it>. Among the asthma genes identified in genome wide association studies, <it>ROBO1</it>, <it>RORA, HLA-DQB1, IL2RB </it>and <it>PDE10A </it>were differentially expressed during human lung development.</p> <p>Conclusions</p> <p>Our data provide insight about the role of asthma susceptibility genes during lung development and suggest common mechanisms underlying lung morphogenesis and pathogenesis of respiratory diseases.</p

    Platform trials

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    Platform trials focus on the perpetual testing of many interventions in a disease or a setting. These trials have lasting organizational, administrative, data, analytic, and operational frameworks making them highly efficient. The use of adaptation often increases the probabilities of allocating participants to better interventions and obtaining conclusive results. The COVID-19 pandemic showed the potential of platform trials as a fast and valid way to improved treatments. This review gives an overview of key concepts and elements using the Intensive Care Platform Trial (INCEPT) as an example.</p

    Når inklusionsbestræbelser ender i eksklusion:Lærerfaglige udfordringer i en tid med test, faglighed og evaluering

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    Denne artikel viser, at internationale dagsordener om test, faglighed og evaluering i skolen udfordrer mere etisk forankrede pædagogikker i praksis. Artiklen viser konsekvenserne heraf for skolens prak-sis. I det første empiriske nedslag (Hedegaard-Sørensen og Grumløse 2016) viser vi, hvordan et skolepolitisk fokus, ligesom internationale dagsordener, vægter en fag-faglig og læringsfokuseret tilgang, hvilket læreren må følge. I det andet empiriske nedslag (Grumløse, Kaas og Berg 2020) viser vi, hvordan forskellige evalueringsredskaber, med intentioner om at skabe trivsel og deltagelse for alle børn, ender med at fungere som ekskluderende teknologier
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