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BACKGROUND: Myopia prevalence has been increasing in the last decades, and its pathological consequences, including myopic maculopathy and high myopia-associated optic neuropathy, are now one of the most common causes of visual impairment. It is estimated that by 2050, more than 50% of Europeans and Americans will be myopes, which is alarming due to the high morbidity of myopes over - 6.00D. Once myopia has appeared, there are different options with scientific evidence to try to slow the axial length growth. Ophthalmic lenses are the less invasive treatment to control myopia, and there is evidence about the efficacy of different designs, mainly in the Asiatic population. However, new designs have been launched, and it is not known if efficacy is the same between Asiatic and European subjects. Thus, we have set up a randomized, controlled, double-blind, and multicenter trial to investigate the efficacy of a new design of ophthalmic lenses for myopia control in European children. METHODS: A 2-year prospective, multicenter, randomized controlled, and double-blind clinical trial is used to investigate the efficacy of a new design of ophthalmic lenses to slow the progression of myopia. Three hundred children aged from 6 to 13 years old will be recruited and randomly assigned to a study or control group. The study group will be composed of 150 children wearing MyoCare while the control group will be composed of 150 children wearing Clearview. The inclusion criteria will be myopia with a spherical equivalent between - 0.75D and - 5.00D, astigmatism < 1.50D, and anisometropia < 1.00D and having a historical evolution of at least - 0.50 The primary outcome is to compare the mean annual progression of the spherical equivalent between both groups. The secondary outcomes are axial length, choroidal thickness, phorias, and accommodative status of both groups. DISCUSSION: This study will be the first randomized and controlled clinical trial in European children with spectacle len

Masterarbeit Universität Innsbruck 2023

BACKGROUND: Immunoglobulin A nephropathy (IgAN) frequently leads to kidney failure. The urinary proteomics-based classifier IgAN237 may predict disease progression at the time of kidney biopsy. We studied whether IgAN237 also predicts progression later in the course of IgAN. METHODS: Urine from patients with biopsy-proven IgAN was analyzed using capillary electrophoresis-mass spectrometry at baseline (IgAN237-1, n = 103) and at follow-up (IgAN237-2, n = 89). Patients were categorized as "non-progressors" (IgAN237 ≤0.38) and "progressors" (IgAN237 >0.38). Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio slopes were calculated. RESULTS: Median age at biopsy was 44 years, interval between biopsy and IgAN237-1 was 65 months and interval between IgAN237-1 and IgAN237-2 was 258 days (interquartile range 71-531). IgAN237-1 and IgAN237-2 values did not differ significantly and were correlated (rho = 0.44, P < .001). Twenty-eight percent and 26% of patients were progressors based on IgAN237-1 and IgAN237-2, respectively. IgAN237 inversely correlated with chronic eGFR slopes (rho = -0.278, P = .02 for score-1; rho = -0.409, P = .002 for score-2) and with ±180 days eGFR slopes (rho = -0.31, P = .009 and rho = -0.439, P = .001, respectively). The ±180 days eGFR slopes were worse for progressors than for non-progressors (median -5.98 versus -1.22 mL/min/1.73 m2 per year for IgAN237-1, P < .001; -3.02 vs 1.08 mL/min/1.73 m2 per year for IgAN237-2, P = .0047). In multiple regression analysis baseline progressor/non-progressor according to IgAN237 was an independent predictor of eGFR180days-slope (P = .001). CONCLUSION: The urinary IgAN237 classifier represents a risk stratification tool in IgAN also later in the course of the dynamic disease. It may guide patient management in an individualized manner.

While agriculture is a major source of employment, it is notable that youths in developing countries are unemployed. In Kenya, agriculture is taught in the 8-4-4 syllabus and in the current competency-based curriculum. Despite the above facts, Kenya still requires human resources to drive the agricultural sector. The purpose of this study was to examine trends in progression in agriculture careers among students in tertiary institutions in Kakamega and Bungoma counties, Kenya, from 2016 to 2021. Correlational and cross-sectional research designs were used. Stratified random sampling was used to select agriculture students; purposive sampling was used to select universities, the Kenya Universities and Colleges Central Placement Service (KUCCPS), and technical and vocational education and training (TVET) institutions. Purposive sampling was used to select key informants, while quota sampling was employed to select focus group discussions. Using a pragmatic philosophical standing point as a lens, the study applied a mixed research strategy for data collection, coupled with mixed methods for triangulation. The sampling size was determined from Yamane (1967) formulae based on the study population. A sample size of (249) secondary school students, (24) university students, and (131) TVET institution students gives a sample size of 404 from a target population of 11928 students. A pilot study was done in Vihiga County. The data was collected using document content guides, questionnaires, focus group discussions, and interview guides. Due diligence was taken into consideration while collecting and processing the data to ensure both the reliability and validity of the study. Both descriptive and inferential techniques (trend analysis) were employed to analyze the data, which was presented using frequency tables and line graphs. The total KCSE agriculture enrolment in Kenya and total agriculture enrolment in TVET were strongly and positively correlated (r = 0.889, p = 0.018)

While agriculture is a major source of employment, it is notable that youths in developing countries are unemployed. In Kenya, agriculture is taught in the 8-4-4 syllabus and in the current competency-based curriculum. Despite the above facts, Kenya still requires human resources to drive the agricultural sector. The purpose of this study was to examine trends in progression in agriculture careers among students in tertiary institutions in Kakamega and Bungoma counties, Kenya, from 2016 to 2021. Correlational and cross-sectional research designs were used. Stratified random sampling was used to select agriculture students; purposive sampling was used to select universities, the Kenya Universities and Colleges Central Placement Service (KUCCPS), and technical and vocational education and training (TVET) institutions. Purposive sampling was used to select key informants, while quota sampling was employed to select focus group discussions. Using a pragmatic philosophical standing point as a lens, the study applied a mixed research strategy for data collection, coupled with mixed methods for triangulation. The sampling size was determined from Yamane (1967) formulae based on the study population. A sample size of (249) secondary school students, (24) university students, and (131) TVET institution students gives a sample size of 404 from a target population of 11928 students. A pilot study was done in Vihiga County. The data was collected using document content guides, questionnaires, focus group discussions, and interview guides. Due diligence was taken into consideration while collecting and processing the data to ensure both the reliability and validity of the study. Both descriptive and inferential techniques (trend analysis) were employed to analyze the data, which was presented using frequency tables and line graphs. The total KCSE agriculture enrolment in Kenya and total agriculture enrolment in TVET were strongly and positively correlated (r = 0.889, p = 0.018)

Aims: This post hoc analysis of the ATHENA trial (NCT00174785) assessed the effect of dronedarone on the estimated burden of atrial fibrillation (AF)/atrial flutter (AFL) progression to presumed permanent AF/AFL, and regression to sinus rhythm (SR), compared with placebo. Methods and results: The burden of AF/AFL was estimated by a modified Rosendaal method using available electrocardiograms (ECG). Cumulative incidence of permanent AF/AFL (defined as >= 6 months of AF/AFL until end of study) or permanent SR (defined as >= 6 months of SR until end of study) were calculated using Kaplan-Meier estimates. A log-rank test was used to assess statistical significance. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were estimated using a Cox model, adjusted for treatment group. Of the 4439 patients included in this analysis, 2208 received dronedarone, and 2231 placebo. Baseline and clinical characteristics were well balanced between groups. Overall, 304 (13.8%) dronedarone-treated patients progressed to permanent AF/AFL compared with 455 (20.4%) treated with placebo (P < 0.0001). Compared with those receiving placebo, patients receiving dronedarone had a lower cumulative incidence of permanent AF/AFL (log-rank P < 0.001; HR: 0.65; 95% CI: 0.56-0.75), a higher cumulative incidence of permanent SR (log-rank P < 0.001; HR: 1.19; 95% CI: 1.09-1.29), and a lower estimated AF/AFL burden over time (P < 0.01 from Day 14 to Month 21). Conclusion: These results suggest that dronedarone could be a useful antiarrhythmic drug for early rhythm control due to less AF/AFL progression and more regression to SR vs. placebo, potentially reflecting reverse remodeling.

Objectives: Periodontitis and underlying bacteria have been linked to the development of rheumatoid arthritis (RA). One suggested pathogen is Aggregatibacter actinomycetemcomitans (A.a.), which expresses leukotoxin A (LtxA) that can citrullinate human proteins, providing a possible trigger for the production of anti-citrullinated protein antibodies (ACPA). In this study, we seek to determine the presence of antibodies toward LtxA in patients at risk of developing RA. Methods: Two prospective observational patient cohorts (one Swedish and one British) with symptomatic at-risk patients were studied. Anti-LtxA antibodies were analyzed by a cell-based neutralization assay in baseline serum and compared to 100 Swedish blood donors that served as controls. Results: Serum anti-LtxA levels or positivity did not differ between patients and blood donors. In the British cohort, anti-LtxA was more prevalent among ACPA-positive arthralgia patients compared with ACPA-negative arthralgia cases (24% vs. 13%, p < 0.0001). In the Swedish at-risk cohort, anti-LtxA positive patients were at increased risk of progression to arthritis (hazard ratio (HR) 2.10, 95% CI 1.04–4.20), but this was not confirmed in the UK at-risk cohort (HR 0.99, CI 0.60–1.65). Conclusion: Serum anti-LtxA is not elevated before RA diagnosis, and associations with disease progression and ACPA levels differ between populations. Other features of the oral microbiome should be explored in upcoming periodontitis-related RA research.

BackgroundLower-grade IDH mutant glioma patients frequently undergo malignant transformation (MT), with apparent worse prognosis. Many studies examine MT in mixed IDH status cohorts and define MT using imaging, not histopathology. Our study examines the timing, predictors, and prognostic implications of pathologically determined MT in a large, exclusively IDH mutant cohort.MethodsWe identified 193 IDH mutant lower-grade glioma patients at UCLA who received multiple surgeries. We examined the outcomes of pathologically determined MT patients.ResultsTime to MT is longer in grade 2 oligodendroglioma (G2 Oligo) than in grade 2 astrocytoma (G2 Astro) (HR = 0.46, P = .0007). The grade 3 astrocytoma (G3 Astro) to grade 4 astrocytoma (G4 Astro) interval is shorter in stepwise MT (G2 to G3 to G4 Astro) patients than in initial G3 Astro patients (P = .03). Novel contrast enhancement had 65% positive predictivity, 67% negative predictivity, 75% sensitivity, and 55% specificity in indicating pathologically defined MT. In G2 Astro, initial gross total resection delayed MT (HR = 0.50, P = .02) and predicted better overall survival (OS) (HR = 0.34, P = .009). In G2 Oligo, spontaneous MT occurred earlier than treated MT (HR = 11.43, P = .0002), but treatment did not predict improved OS (P = .8). MT patients (n = 126) exhibited worse OS than non-MT patients (n = 67) in All (HR = 2.54, P = .0009) and G2 Astro (HR = 4.26, P = .02).ConclusionOur study expands the understanding of MT to improve IDH mutant lower-grade glioma management.

AimsAdvanced liver fibrosis can regress following the elimination of causative injuries. Trichrome (TC) stain has traditionally been used to evaluate the degree of fibrosis in liver, although it is rarely helpful in assessing quality of fibrosis (i.e. progression and regression). Orcein (OR) stain highlights established elastic fibres, but its use in examining fibrosis is not well recognised. This study assessed the potential utility of comparing OR and TC staining patterns to evaluate the quality of fibrosis in various settings of advanced fibrosis.Methods and resultsThe haematoxylin and eosin and TC stains of 65 liver resection/explant specimens with advanced fibrosis caused by different elements were reviewed. Twenty-two cases were scored as progressive (P), 16 as indeterminate (I) and 27 as regressive (R) using TC stain based on the Beijing criteria. The OR stains confirmed 18 of 22 P cases. The remaining P cases showed either stable fibrosis or mixed P and R. Of the 27 R cases, 26 were supported by OR stain, with many showing thin perforated septa typically seen in adequately treated viral hepatitis cases. The 16 I cases showed a variety of OR staining patterns, which allowed for further subclassification than using TC stain alone. Viral hepatitis cases were enriched for regressive features (17 of 27).ConclusionsOur data demonstrated the utility of OR as an adjunctive stain to evaluate the changes in fibrosis in cases of cirrhosis.

The latest and increasingly sophisticated digital simulations, often set in fantastical worlds, have become like laboratories in which players/ audiences can test their knowledge of culture, their ethical beliefs, interpretive skills, and anthropological imaginations. The article looks at games not just through the lens of their programmed poetics, but rather as laboratories in which experimentation becomes one of the elements of play, and gameplay touches the essence of the game – the activity, which is defined as dynamic competition within an adopted convention. One example of such experimentation is the transgressive way of conducting gameplay. However, creating a detailed typology of all possible transgressive gameplay is clearly not feasible, especially when taking into account accidental situations, such as when a player exploits a loophole or error in the programmed process without realizing that they are intentionally bypassing solutions designed by the creators. Nonetheless, intentional actions can be characterized in terms of three basic aspects – ingression (e.g., interference with computer programs), progression (e.g., fastrun, bypassing, etc.), and regression (transpositions, refunctionalizations, etc.). They concern both evidence of specific intentions and reveal ways of breaking rules, introducing one’s own rules, or forcing one’s own gameplay style., The latest and increasingly sophisticated digital simulations, often set in fantastical worlds, have become like laboratories in which players/ audiences can test their knowledge of culture, their ethical beliefs, interpretive skills, and anthropological imaginations. The article looks at games not just through the lens of their programmed poetics, but rather as laboratories in which experimentation becomes one of the elements of play, and gameplay touches the essence of the game – the activity, which is defined as dynamic competition within an adopted convention. One example of such experimentation is the transgressive way of conducting gameplay. However, creating a detailed typology of all possible transgressive gameplay is clearly not feasible, especially when taking into account accidental situations, such as when a player exploits a loophole or error in the programmed process without realizing that they are intentionally bypassing solutions designed by the creators. Nonetheless, intentional actions can be characterized in terms of three basic aspects – ingression (e.g., interference with computer programs), progression (e.g., fastrun, bypassing, etc.), and regression (transpositions, refunctionalizations, etc.). They concern both evidence of specific intentions and reveal ways of breaking rules, introducing one’s own rules, or forcing one’s own gameplay style.

Glaucoma is a group of progressive optic neuropathies characterized by loss of retinal ganglion cells and visual field deterioration. Despite the fact that the underlying pathophysiology of glaucoma remains unknown, elevated intraocular pressure (IOP) is a well-established risk factor, and the only factor that can be modified. Robust evidence from epidemiological studies and clinical trials has clearly demonstrated the benefits of IOP control in reducing the risk of glaucoma progression. IOP-lowering therapy by the means of eye drops remains a first-line treatment option. However, like other chronic and asymptomatic conditions, many patients with glaucoma have difficulties in maintaining high rates of adherence persistence to prescribed medications. On average, patients with chronic medical conditions take 30-70% of the prescribed medication doses, and on average 50% discontinue medications in the first months of therapy. The ophthalmic literature shows similarly low rates of adherence to treatment. Indeed, poor adherence is associated with disease progression and increased complication rates, as well as healthcare costs. The present review analyzes and discusses the causes of variability of the adherence to the prescribed drugs. The education of patients about glaucoma and the potential consequences of insufficient adherence and persistence seems fundamental to maximize the probability of treatment success and therefore prevent visual disability to avoid unnecessary healthcare costs.

BackgroundTo assign a course of secondary progressive multiple sclerosis (MS) (SPMS) may be difficult and the proportion of persons with SPMS varies between reports. An objective method for disease course classification may give a better estimation of the relative proportions of relapsing-remitting MS (RRMS) and SPMS and may identify situations where SPMS is under reported. Materials and methodsData were obtained for 61,900 MS patients from MS registries in the Czech Republic, Denmark, Germany, Sweden, and the United Kingdom (UK), including date of birth, sex, SP conversion year, visits with an Expanded Disability Status Scale (EDSS) score, MS onset and diagnosis date, relapses, and disease-modifying treatment (DMT) use. We included RRMS or SPMS patients with at least one visit between January 2017 and December 2019 if >= 18 years of age. We applied three objective methods: A set of SPMS clinical trial inclusion criteria ("EXPAND criteria") modified for a real-world evidence setting, a modified version of the MSBase algorithm, and a decision tree-based algorithm recently published. ResultsThe clinically assigned proportion of SPMS varied from 8.7% (Czechia) to 34.3% (UK). Objective classifiers estimated the proportion of SPMS from 15.1% (Germany by the EXPAND criteria) to 58.0% (UK by the decision tree method). Due to different requirements of number of EDSS scores, classifiers varied in the proportion they were able to classify; from 18% (UK by the MSBase algorithm) to 100% (the decision tree algorithm for all registries). Objectively classified SPMS patients were older, converted to SPMS later, had higher EDSS at index date and higher EDSS at conversion. More objectively classified SPMS were on DMTs compared to the clinically assigned. ConclusionSPMS appears to be systematically underdiagnosed in MS registries. Reclassified patients were more commonly on DMTs., QC 20230320

Objectives: Periodontitis and underlying bacteria have been linked to the development of rheumatoid arthritis (RA). One suggested pathogen is Aggregatibacter actinomycetemcomitans (A.a.), which expresses leukotoxin A (LtxA) that can citrullinate human proteins, providing a possible trigger for the production of anti-citrullinated protein antibodies (ACPA). In this study, we seek to determine the presence of antibodies toward LtxA in patients at risk of developing RA. Methods: Two prospective observational patient cohorts (one Swedish and one British) with symptomatic at-risk patients were studied. Anti-LtxA antibodies were analyzed by a cell-based neutralization assay in baseline serum and compared to 100 Swedish blood donors that served as controls. Results: Serum anti-LtxA levels or positivity did not differ between patients and blood donors. In the British cohort, anti-LtxA was more prevalent among ACPA-positive arthralgia patients compared with ACPA-negative arthralgia cases (24% vs. 13%, p < 0.0001). In the Swedish at-risk cohort, anti-LtxA positive patients were at increased risk of progression to arthritis (hazard ratio (HR) 2.10, 95% CI 1.04–4.20), but this was not confirmed in the UK at-risk cohort (HR 0.99, CI 0.60–1.65). Conclusion: Serum anti-LtxA is not elevated before RA diagnosis, and associations with disease progression and ACPA levels differ between populations. Other features of the oral microbiome should be explored in upcoming periodontitis-related RA research.

Aims: This post hoc analysis of the ATHENA trial (NCT00174785) assessed the effect of dronedarone on the estimated burden of atrial fibrillation (AF)/atrial flutter (AFL) progression to presumed permanent AF/AFL, and regression to sinus rhythm (SR), compared with placebo. Methods and results: The burden of AF/AFL was estimated by a modified Rosendaal method using available electrocardiograms (ECG). Cumulative incidence of permanent AF/AFL (defined as >= 6 months of AF/AFL until end of study) or permanent SR (defined as >= 6 months of SR until end of study) were calculated using Kaplan-Meier estimates. A log-rank test was used to assess statistical significance. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were estimated using a Cox model, adjusted for treatment group. Of the 4439 patients included in this analysis, 2208 received dronedarone, and 2231 placebo. Baseline and clinical characteristics were well balanced between groups. Overall, 304 (13.8%) dronedarone-treated patients progressed to permanent AF/AFL compared with 455 (20.4%) treated with placebo (P < 0.0001). Compared with those receiving placebo, patients receiving dronedarone had a lower cumulative incidence of permanent AF/AFL (log-rank P < 0.001; HR: 0.65; 95% CI: 0.56-0.75), a higher cumulative incidence of permanent SR (log-rank P < 0.001; HR: 1.19; 95% CI: 1.09-1.29), and a lower estimated AF/AFL burden over time (P < 0.01 from Day 14 to Month 21). Conclusion: These results suggest that dronedarone could be a useful antiarrhythmic drug for early rhythm control due to less AF/AFL progression and more regression to SR vs. placebo, potentially reflecting reverse remodeling.

Objectives: Periodontitis and underlying bacteria have been linked to the development of rheumatoid arthritis (RA). One suggested pathogen is Aggregatibacter actinomycetemcomitans (A.a.), which expresses leukotoxin A (LtxA) that can citrullinate human proteins, providing a possible trigger for the production of anti-citrullinated protein antibodies (ACPA). In this study, we seek to determine the presence of antibodies toward LtxA in patients at risk of developing RA. Methods: Two prospective observational patient cohorts (one Swedish and one British) with symptomatic at-risk patients were studied. Anti-LtxA antibodies were analyzed by a cell-based neutralization assay in baseline serum and compared to 100 Swedish blood donors that served as controls. Results: Serum anti-LtxA levels or positivity did not differ between patients and blood donors. In the British cohort, anti-LtxA was more prevalent among ACPA-positive arthralgia patients compared with ACPA-negative arthralgia cases (24% vs. 13%, p < 0.0001). In the Swedish at-risk cohort, anti-LtxA positive patients were at increased risk of progression to arthritis (hazard ratio (HR) 2.10, 95% CI 1.04-4.20), but this was not confirmed in the UK at-risk cohort (HR 0.99, CI 0.60-1.65). Conclusion: Serum anti-LtxA is not elevated before RA diagnosis, and associations with disease progression and ACPA levels differ between populations. Other features of the oral microbiome should be explored in upcoming periodontitis-related RA research.

Objectives: Periodontitis and underlying bacteria have been linked to the development of rheumatoid arthritis (RA). One suggested pathogen is Aggregatibacter actinomycetemcomitans (A.a.), which expresses leukotoxin A (LtxA) that can citrullinate human proteins, providing a possible trigger for the production of anti-citrullinated protein antibodies (ACPA). In this study, we seek to determine the presence of antibodies toward LtxA in patients at risk of developing RA. Methods: Two prospective observational patient cohorts (one Swedish and one British) with symptomatic at-risk patients were studied. Anti-LtxA antibodies were analyzed by a cell-based neutralization assay in baseline serum and compared to 100 Swedish blood donors that served as controls. Results: Serum anti-LtxA levels or positivity did not differ between patients and blood donors. In the British cohort, anti-LtxA was more prevalent among ACPA-positive arthralgia patients compared with ACPA-negative arthralgia cases (24% vs. 13%, p < 0.0001). In the Swedish at-risk cohort, anti-LtxA positive patients were at increased risk of progression to arthritis (hazard ratio (HR) 2.10, 95% CI 1.04–4.20), but this was not confirmed in the UK at-risk cohort (HR 0.99, CI 0.60–1.65). Conclusion: Serum anti-LtxA is not elevated before RA diagnosis, and associations with disease progression and ACPA levels differ between populations. Other features of the oral microbiome should be explored in upcoming periodontitis-related RA research.

Objectives: Periodontitis and underlying bacteria have been linked to the development of rheumatoid arthritis (RA). One suggested pathogen is Aggregatibacter actinomycetemcomitans (A.a.), which expresses leukotoxin A (LtxA) that can citrullinate human proteins, providing a possible trigger for the production of anti-citrullinated protein antibodies (ACPA). In this study, we seek to determine the presence of antibodies toward LtxA in patients at risk of developing RA. Methods: Two prospective observational patient cohorts (one Swedish and one British) with symptomatic at-risk patients were studied. Anti-LtxA antibodies were analyzed by a cell-based neutralization assay in baseline serum and compared to 100 Swedish blood donors that served as controls. Results: Serum anti-LtxA levels or positivity did not differ between patients and blood donors. In the British cohort, anti-LtxA was more prevalent among ACPA-positive arthralgia patients compared with ACPA-negative arthralgia cases (24% vs. 13%, p < 0.0001). In the Swedish at-risk cohort, anti-LtxA positive patients were at increased risk of progression to arthritis (hazard ratio (HR) 2.10, 95% CI 1.04–4.20), but this was not confirmed in the UK at-risk cohort (HR 0.99, CI 0.60–1.65). Conclusion: Serum anti-LtxA is not elevated before RA diagnosis, and associations with disease progression and ACPA levels differ between populations. Other features of the oral microbiome should be explored in upcoming periodontitis-related RA research.

Syftet med denna studie är att genom en kvalitativ innehållsanalys av böcker i sångmetodik undersöka hur olika aspekter kring övning och progression för sång och röstträning representeras. Innehållet i tre utvalda böcker analyserades med utgångspunkt i att sammanställa vad författarna nämner om övning och progression i förhållande till böckernas utformning av praktiska sång-och röstövningar. Resultatet visade att aspekterna kring övning är mångfacetterade och varierar utifrån författarnas olika bakgrund men att det ändå finns ett flertal gemensamma. De aspekter som framhävs i böckerna är att övning för att utveckla sångrösten handlar om regelbundenhet, repetition och variation. Resultatet visade även att progression i förhållande till hur sång-och röstövningarna var utformade i böckerna förekom i varierad utsträckning. I diskussionen diskuteras hur författarna på olika sätt kommunicerar övningsaspekter och progression i förhållande till sång- och röstträning.

Syftet med detta examensarbete är att undersöka och belysa hur formativ bedömning används i praktiken enligt verksamma mellanstadielärare. Ett delsyfte är även att undersöka hur den formativa bedömningen följs upp under elevernas skolgång. Undersökningen är kvalitativ och materialet samlades in via intervjuer med åtta legitimerade lärare som är behöriga i ämnet svenska och undervisar i årskurs 4–6. Det teoretiska perspektivet som studien vilar på är det sociokulturella perspektivet med fokus på begrepp som den proximala utvecklingszonen, scaffolding, mediering och appropriering. Resultatet av undersökningen visar att lärarna arbetar formativt i den utsträckning de kan för att nå elevernas fulla potential inom skrivutvecklingen. Lärarna berättar att återkopplingen ligger till grund för att ta elevernas lärande vidare. Vi fick ta del av både positiva och negativa aspekter av det formativa arbetet. Det positiva som lyfts är framförallt att eleverna genom formativ bedömning utvecklar sitt skrivande till det bättre. En negativ aspekt som lyfts är tidsbristen, lärarna anser att de inte har tillräckligt med tid till återkoppling. Vi fick även ta del av hur lärarna följer och synliggör elevernas progression. Avslutningsvis har studien samlat flera tillvägagångssätt för att arbeta formativt med skrivutveckling.

Studiens syfte är att synliggöra möjligheter och begränsningar för kontinuitet och progression i barns naturvetenskapliga lärande inför övergången från förskola till förskoleklass. Studiens teoretiska utgångspunkt är det sociokulturella perspektivet. För att identifiera möjligheter och begränsningar genomfördes intervjuer med barn, förskollärare och förskoleklasslärare. Resultatet i studien presenteras i fyra teman; barnens intressen, utmanande lärandeinnehåll och arbetssätt, samarbete och insyn samt prioriterade utvecklingsområden. Resultaten visade att barnen förväntar sig och önskar utmanande, nya innehåll och arbetssätt som inkluderar inslag av deras personliga intresseområden. Både förskolan och förskoleklassen behöver arbeta medvetet med naturvetenskap för att skapa möjligheter för kontinuitet och progression. Naturvetenskapsundervisning kan och bör utgå från barns intressen och kombineras med andra ämnesinnehåll i tema- och projektarbeten samt utformas med hänsyn till barns erfarenheter och proximala utvecklingszoner för att främja progression i barns naturvetenskapliga lärande. Detta skapar i sin tur tillfällen att beröra naturvetenskapen i samverkan mellan förskola och förskoleklass inför övergången. Resultaten har även visat att förskollärare ochförskoleklasslärare måste prioritera samverkan och skapa insyn i varandras verksamheter för att främja ett gott samarbete inför övergången till förskoleklass.

Syftet med denna studie var att belysa hur progression och färdighetnivåerna från den Gemensamma europeiska referensramen för språk (GERS) kan vara till stöd för lärare. Ett exempel kan vara att hjälpa lärare vid val av läromedel för att synliggöra hur läromedlen stöttar elevernas utveckling av förmågorna lyssna, skriva och tala. För att uppfylla detta syfte formulerades tre forskningsfrågor: 1. Vilket utrymme får förmågorna skriva, lyssna samt tala i respektive läromedel? 2. Vilken färdighetsnivå enligt GERS kräver övningarna för förmågorna skriva, lyssna och tala? och 3. Hur ser progressionen ut för förmågorna skriva, lyssna och tala i de granskade läromedlen i relation till nivåerna i GERS? Studien granskade två läromedel varav ett läromedel var helt digitalt och det andra var ett tryckt läromedel i bokform. I studien analyserades uppgifterna med hjälp av GERS och kategoriserades med hjälp av Littlejohns ramverk. Studien använde dessutom en metodkombination, där både kvalitativa och kvantitativa metoder brukades. Resultatet visade att det finns en skillnad vad gäller det utrymme förmågorna får, samt att övningarna i läromedlen kategoriserades inom olika färdighetsnivåer. Dessutom visade det ena läromedlet på en tydligare progression inom GERS färdighetsnivåer.

BackgroundIt is possible to calculate the number of years to the expected clinical onset (YECO) of autosomal-dominant Alzheimer's disease (adAD). A similar time scale is lacking for sporadic Alzheimer's disease (sAD). The purpose was to design and validate a time scale in YECO for patients with sAD in relation to CSF and PET biomarkers.MethodsPatients diagnosed with Alzheimer's disease (AD, n = 48) or mild cognitive impairment (MCI, n = 46) participated in the study. They underwent a standardized clinical examination at the Memory clinic, Karolinska University Hospital, Stockholm, Sweden, which included present and previous medical history, laboratory screening, cognitive assessment, CSF biomarkers (A beta(42), total-tau, and p-tau), and an MRI of the brain. They were also assessed with two PET tracers, C-11-Pittsburgh compound B and F-18-fluorodeoxyglucose. Assuming concordance of cognitive decline in sAD and adAD, YECO for these patients was calculated using equations for the relationship between cognitive performance, YECO, and years of education in adAD (Almkvist et al. J Int Neuropsychol Soc 23:195-203, 2017).ResultsThe mean current point of disease progression was 3.2 years after the estimated clinical onset in patients with sAD and 3.4 years prior to the estimated clinical onset in patients with MCI, as indicated by the median YECO from five cognitive tests. The associations between YECO and biomarkers were significant, while those between chronological age and biomarkers were nonsignificant. The estimated disease onset (chronological age minus YECO) followed a bimodal distribution with frequency maxima before (early-onset) and after (late-onset) 65 years of age. The early- and late-onset subgroups differed significantly in biomarkers and cognition, but after control for YECO, this difference disappeared for all except the APOE e4 gene (more frequent in early- than in late-onset).ConclusionsA novel time scale in years of disease progression based on cognition

Syftet med denna studie är att genom en kvalitativ innehållsanalys av böcker i sångmetodik undersöka hur olika aspekter kring övning och progression för sång och röstträning representeras. Innehållet i tre utvalda böcker analyserades med utgångspunkt i att sammanställa vad författarna nämner om övning och progression i förhållande till böckernas utformning av praktiska sång-och röstövningar. Resultatet visade att aspekterna kring övning är mångfacetterade och varierar utifrån författarnas olika bakgrund men att det ändå finns ett flertal gemensamma. De aspekter som framhävs i böckerna är att övning för att utveckla sångrösten handlar om regelbundenhet, repetition och variation. Resultatet visade även att progression i förhållande till hur sång-och röstövningarna var utformade i böckerna förekom i varierad utsträckning. I diskussionen diskuteras hur författarna på olika sätt kommunicerar övningsaspekter och progression i förhållande till sång- och röstträning.

Aims: This post hoc analysis of the ATHENA trial (NCT00174785) assessed the effect of dronedarone on the estimated burden of atrial fibrillation (AF)/atrial flutter (AFL) progression to presumed permanent AF/AFL, and regression to sinus rhythm (SR), compared with placebo. Methods and results: The burden of AF/AFL was estimated by a modified Rosendaal method using available electrocardiograms (ECG). Cumulative incidence of permanent AF/AFL (defined as >= 6 months of AF/AFL until end of study) or permanent SR (defined as >= 6 months of SR until end of study) were calculated using Kaplan-Meier estimates. A log-rank test was used to assess statistical significance. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were estimated using a Cox model, adjusted for treatment group. Of the 4439 patients included in this analysis, 2208 received dronedarone, and 2231 placebo. Baseline and clinical characteristics were well balanced between groups. Overall, 304 (13.8%) dronedarone-treated patients progressed to permanent AF/AFL compared with 455 (20.4%) treated with placebo (P < 0.0001). Compared with those receiving placebo, patients receiving dronedarone had a lower cumulative incidence of permanent AF/AFL (log-rank P < 0.001; HR: 0.65; 95% CI: 0.56-0.75), a higher cumulative incidence of permanent SR (log-rank P < 0.001; HR: 1.19; 95% CI: 1.09-1.29), and a lower estimated AF/AFL burden over time (P < 0.01 from Day 14 to Month 21). Conclusion: These results suggest that dronedarone could be a useful antiarrhythmic drug for early rhythm control due to less AF/AFL progression and more regression to SR vs. placebo, potentially reflecting reverse remodeling.

Objectives: Periodontitis and underlying bacteria have been linked to the development of rheumatoid arthritis (RA). One suggested pathogen is Aggregatibacter actinomycetemcomitans (A.a.), which expresses leukotoxin A (LtxA) that can citrullinate human proteins, providing a possible trigger for the production of anti-citrullinated protein antibodies (ACPA). In this study, we seek to determine the presence of antibodies toward LtxA in patients at risk of developing RA. Methods: Two prospective observational patient cohorts (one Swedish and one British) with symptomatic at-risk patients were studied. Anti-LtxA antibodies were analyzed by a cell-based neutralization assay in baseline serum and compared to 100 Swedish blood donors that served as controls. Results: Serum anti-LtxA levels or positivity did not differ between patients and blood donors. In the British cohort, anti-LtxA was more prevalent among ACPA-positive arthralgia patients compared with ACPA-negative arthralgia cases (24% vs. 13%, p < 0.0001). In the Swedish at-risk cohort, anti-LtxA positive patients were at increased risk of progression to arthritis (hazard ratio (HR) 2.10, 95% CI 1.04-4.20), but this was not confirmed in the UK at-risk cohort (HR 0.99, CI 0.60-1.65). Conclusion: Serum anti-LtxA is not elevated before RA diagnosis, and associations with disease progression and ACPA levels differ between populations. Other features of the oral microbiome should be explored in upcoming periodontitis-related RA research.

Aims: This post hoc analysis of the ATHENA trial (NCT00174785) assessed the effect of dronedarone on the estimated burden of atrial fibrillation (AF)/atrial flutter (AFL) progression to presumed permanent AF/AFL, and regression to sinus rhythm (SR), compared with placebo. Methods and results: The burden of AF/AFL was estimated by a modified Rosendaal method using available electrocardiograms (ECG). Cumulative incidence of permanent AF/AFL (defined as >= 6 months of AF/AFL until end of study) or permanent SR (defined as >= 6 months of SR until end of study) were calculated using Kaplan-Meier estimates. A log-rank test was used to assess statistical significance. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were estimated using a Cox model, adjusted for treatment group. Of the 4439 patients included in this analysis, 2208 received dronedarone, and 2231 placebo. Baseline and clinical characteristics were well balanced between groups. Overall, 304 (13.8%) dronedarone-treated patients progressed to permanent AF/AFL compared with 455 (20.4%) treated with placebo (P < 0.0001). Compared with those receiving placebo, patients receiving dronedarone had a lower cumulative incidence of permanent AF/AFL (log-rank P < 0.001; HR: 0.65; 95% CI: 0.56-0.75), a higher cumulative incidence of permanent SR (log-rank P < 0.001; HR: 1.19; 95% CI: 1.09-1.29), and a lower estimated AF/AFL burden over time (P < 0.01 from Day 14 to Month 21). Conclusion: These results suggest that dronedarone could be a useful antiarrhythmic drug for early rhythm control due to less AF/AFL progression and more regression to SR vs. placebo, potentially reflecting reverse remodeling.

Objectives: Periodontitis and underlying bacteria have been linked to the development of rheumatoid arthritis (RA). One suggested pathogen is Aggregatibacter actinomycetemcomitans (A.a.), which expresses leukotoxin A (LtxA) that can citrullinate human proteins, providing a possible trigger for the production of anti-citrullinated protein antibodies (ACPA). In this study, we seek to determine the presence of antibodies toward LtxA in patients at risk of developing RA. Methods: Two prospective observational patient cohorts (one Swedish and one British) with symptomatic at-risk patients were studied. Anti-LtxA antibodies were analyzed by a cell-based neutralization assay in baseline serum and compared to 100 Swedish blood donors that served as controls. Results: Serum anti-LtxA levels or positivity did not differ between patients and blood donors. In the British cohort, anti-LtxA was more prevalent among ACPA-positive arthralgia patients compared with ACPA-negative arthralgia cases (24% vs. 13%, p < 0.0001). In the Swedish at-risk cohort, anti-LtxA positive patients were at increased risk of progression to arthritis (hazard ratio (HR) 2.10, 95% CI 1.04-4.20), but this was not confirmed in the UK at-risk cohort (HR 0.99, CI 0.60-1.65). Conclusion: Serum anti-LtxA is not elevated before RA diagnosis, and associations with disease progression and ACPA levels differ between populations. Other features of the oral microbiome should be explored in upcoming periodontitis-related RA research.

Objectives: Periodontitis and underlying bacteria have been linked to the development of rheumatoid arthritis (RA). One suggested pathogen is Aggregatibacter actinomycetemcomitans (A.a.), which expresses leukotoxin A (LtxA) that can citrullinate human proteins, providing a possible trigger for the production of anti-citrullinated protein antibodies (ACPA). In this study, we seek to determine the presence of antibodies toward LtxA in patients at risk of developing RA. Methods: Two prospective observational patient cohorts (one Swedish and one British) with symptomatic at-risk patients were studied. Anti-LtxA antibodies were analyzed by a cell-based neutralization assay in baseline serum and compared to 100 Swedish blood donors that served as controls. Results: Serum anti-LtxA levels or positivity did not differ between patients and blood donors. In the British cohort, anti-LtxA was more prevalent among ACPA-positive arthralgia patients compared with ACPA-negative arthralgia cases (24% vs. 13%, p < 0.0001). In the Swedish at-risk cohort, anti-LtxA positive patients were at increased risk of progression to arthritis (hazard ratio (HR) 2.10, 95% CI 1.04-4.20), but this was not confirmed in the UK at-risk cohort (HR 0.99, CI 0.60-1.65). Conclusion: Serum anti-LtxA is not elevated before RA diagnosis, and associations with disease progression and ACPA levels differ between populations. Other features of the oral microbiome should be explored in upcoming periodontitis-related RA research.

Objectives: Periodontitis and underlying bacteria have been linked to the development of rheumatoid arthritis (RA). One suggested pathogen is Aggregatibacter actinomycetemcomitans (A.a.), which expresses leukotoxin A (LtxA) that can citrullinate human proteins, providing a possible trigger for the production of anti-citrullinated protein antibodies (ACPA). In this study, we seek to determine the presence of antibodies toward LtxA in patients at risk of developing RA. Methods: Two prospective observational patient cohorts (one Swedish and one British) with symptomatic at-risk patients were studied. Anti-LtxA antibodies were analyzed by a cell-based neutralization assay in baseline serum and compared to 100 Swedish blood donors that served as controls. Results: Serum anti-LtxA levels or positivity did not differ between patients and blood donors. In the British cohort, anti-LtxA was more prevalent among ACPA-positive arthralgia patients compared with ACPA-negative arthralgia cases (24% vs. 13%, p < 0.0001). In the Swedish at-risk cohort, anti-LtxA positive patients were at increased risk of progression to arthritis (hazard ratio (HR) 2.10, 95% CI 1.04–4.20), but this was not confirmed in the UK at-risk cohort (HR 0.99, CI 0.60–1.65). Conclusion: Serum anti-LtxA is not elevated before RA diagnosis, and associations with disease progression and ACPA levels differ between populations. Other features of the oral microbiome should be explored in upcoming periodontitis-related RA research.

Objectives: Periodontitis and underlying bacteria have been linked to the development of rheumatoid arthritis (RA). One suggested pathogen is Aggregatibacter actinomycetemcomitans (A.a.), which expresses leukotoxin A (LtxA) that can citrullinate human proteins, providing a possible trigger for the production of anti-citrullinated protein antibodies (ACPA). In this study, we seek to determine the presence of antibodies toward LtxA in patients at risk of developing RA. Methods: Two prospective observational patient cohorts (one Swedish and one British) with symptomatic at-risk patients were studied. Anti-LtxA antibodies were analyzed by a cell-based neutralization assay in baseline serum and compared to 100 Swedish blood donors that served as controls. Results: Serum anti-LtxA levels or positivity did not differ between patients and blood donors. In the British cohort, anti-LtxA was more prevalent among ACPA-positive arthralgia patients compared with ACPA-negative arthralgia cases (24% vs. 13%, p < 0.0001). In the Swedish at-risk cohort, anti-LtxA positive patients were at increased risk of progression to arthritis (hazard ratio (HR) 2.10, 95% CI 1.04-4.20), but this was not confirmed in the UK at-risk cohort (HR 0.99, CI 0.60-1.65). Conclusion: Serum anti-LtxA is not elevated before RA diagnosis, and associations with disease progression and ACPA levels differ between populations. Other features of the oral microbiome should be explored in upcoming periodontitis-related RA research.

Background: To assign a course of secondary progressive multiple sclerosis (MS) (SPMS) may be difficult and the proportion of persons with SPMS varies between reports. An objective method for disease course classification may give a better estimation of the relative proportions of relapsing–remitting MS (RRMS) and SPMS and may identify situations where SPMS is under reported. Materials and methods: Data were obtained for 61,900 MS patients from MS registries in the Czech Republic, Denmark, Germany, Sweden, and the United Kingdom (UK), including date of birth, sex, SP conversion year, visits with an Expanded Disability Status Scale (EDSS) score, MS onset and diagnosis date, relapses, and disease-modifying treatment (DMT) use. We included RRMS or SPMS patients with at least one visit between January 2017 and December 2019 if ≥ 18 years of age. We applied three objective methods: A set of SPMS clinical trial inclusion criteria (“EXPAND criteria”) modified for a real-world evidence setting, a modified version of the MSBase algorithm, and a decision tree-based algorithm recently published. Results: The clinically assigned proportion of SPMS varied from 8.7% (Czechia) to 34.3% (UK). Objective classifiers estimated the proportion of SPMS from 15.1% (Germany by the EXPAND criteria) to 58.0% (UK by the decision tree method). Due to different requirements of number of EDSS scores, classifiers varied in the proportion they were able to classify; from 18% (UK by the MSBase algorithm) to 100% (the decision tree algorithm for all registries). Objectively classified SPMS patients were older, converted to SPMS later, had higher EDSS at index date and higher EDSS at conversion. More objectively classified SPMS were on DMTs compared to the clinically assigned. Conclusion: SPMS appears to be systematically underdiagnosed in MS registries. Reclassified patients were more commonly on DMTs.

Background & Aims: Colonic adenomatous polyps, or adenomas, are frequent precancerous lesions and the origin of most cases of colorectal adenocarcinoma. However, we know from epidemiologic studies that although most colorectal cancers (CRCs) originate from adenomas, only a small fraction of adenomas (3%–5%) ever progress to cancer. At present, there are no molecular markers to guide follow-up surveillance programs. Methods: We profiled, by mass spectrometry–based proteomics combined with machine learning analysis, a selected cohort of formalin-fixed, paraffin-embedded high-grade (HG) adenomas with long clinical follow-up, collected as part of the Danish national screening program. We grouped subjects in the cohort according to their subsequent history of findings: a nonmetachronous advanced neoplasia group (G0), with no new HG adenomas or CRCs up to 10 years after polypectomy, and a metachronous advanced neoplasia group (G1) where individuals developed a new HG adenoma or CRC within 5 years of diagnosis. Results: We generated a proteome dataset from 98 selected HG adenoma samples, including 20 technical replicates, of which 45 samples belonged to the nonmetachronous advanced neoplasia group and 53 to the metachronous advanced neoplasia group. The clear distinction of these 2 groups seen in a uniform manifold approximation and projection plot indicated that the information contained within the abundance of the ∼5000 proteins was sufficient to predict the future occurrence of HG adenomas or development of CRC. Conclusions: We performed an in-depth analysis of quantitative proteomic data from 98 resected adenoma samples using various novel algorithms and statistical packages and found that their proteome can predict development of metachronous advanced lesions and progression several years in advance.

Background Early-life animal exposure has been associated with both protective and harmful effects on asthma and allergic disease. We aimed to explore factors that may modify associations of early-life animal exposure with asthma and allergic disease, so as to better understand these differences in findings. Methods We used data from ≤84 478 children from the Danish National Birth Cohort recruited during pregnancy between 1996 and 2002, and linked registry data up to the child’s 13th birthday. Adjusted Cox models were used to examine associations of early-life cat, dog, rabbit, rodent, bird and livestock exposure with atopic dermatitis, asthma and allergic rhinoconjunctivitis overall, and by source of exposure (domestic or occupation), parental history of asthma or allergy, maternal education level and timing of exposure. Results Overall, associations between animal exposure and the three outcomes of interest were weak. However, dog exposure was associated with marginally lower risk of atopic dermatitis and asthma [adjusted hazard ratio (aHR) = 0.81, 95% CI: 0.70–0.94 and 0.88, 95% CI: 0.82–0.94, respectively], whereas prenatal domestic bird exposure was associated with slightly increased risk of asthma (aHR = 1.18, 95% CI: 1.05–1.32). Source of exposure, parental history of asthma or allergy and timing of exposure modified associations. Early-life animal exposure did not appear to increase the risk of allergic rhinoconjunctivitis (aHR range = 0.88, 95% CI: 0.81–0.95 to 1.00, 95% CI: 0.91–1.10). Conclusions The overall weak associations observed between animal exposure and atopic dermatitis, asthma and allergic rhinoconjunctivitis were modified by type of animal, source of exposure, parental history of asthma or allergy and timing of exposure, suggesting that these factors should be considered when assessing the risks associated with early-life animal exposure., Background Early-life animal exposure has been associated with both protective and harmful effects on asthma and allergic disease. We aimed to explore factors that may modify associations of early-life animal exposure with asthma and allergic disease, so as to better understand these differences in findings. Methods We used data from

Background The Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial assessed dapagliflozin versus placebo, in addition to standard therapy, in patients with chronic kidney disease (CKD) and albuminuria, and was terminated prematurely due to overwhelming efficacy. The study objective was to model the long-term clinical outcomes of DAPA-CKD beyond the trial follow-up. Methods A Markov model extrapolated event incidence per 1000 patients and CKD progression rates for patients receiving dapagliflozin or placebo over a 10-year time horizon. We derived treatment-specific CKD stage transition matrices using DAPA-CKD trial data. We extrapolated relevant efficacy endpoints using parametric survival equations for all-cause mortality and generalized estimating equations for recurrent events. Results When extrapolated over a 10-year period, patients randomized to dapagliflozin spent more time in CKD stages 1-3 and less in stages 4-5 than placebo [0.65 (95% CrI 0.41, 0.90) and -0.23 (95% CrI -0.45, 0.00) years per patient, respectively]. Dapagliflozin prevented an estimated 83 deaths and 51 patients initiating kidney replacement therapy per 1000 patients over 10 years. Predicted rates of hospitalized heart failure and abrupt declines in kidney function were reduced (19 and 39 estimated events per 1000 patients, respectively). Conclusions Adding dapagliflozin to standard therapeutic management of CKD is expected to have long-term cardiorenal benefit beyond what has been demonstrated in the DAPA-CKD trial, with patients predicted to live longer with fewer complications.

The establishment of cellular identity is driven by transcriptional and epigenetic regulators of the chromatin proteome - the chromatome. Comprehensive analyses of the chromatome composition and dynamics can therefore greatly improve our understanding of gene regulatory mechanisms. Here, we developed an accurate mass spectrometry (MS)-based proteomic method called Chromatin Aggregation Capture (ChAC) followed by Data-Independent Acquisition (DIA) and analyzed chromatome reorganizations during major phases of pluripotency. This enabled us to generate a comprehensive atlas of proteomes, chromatomes, and chromatin affinities for the ground, formative and primed pluripotency states, and to pinpoint the specific binding and rearrangement of regulatory components. These comprehensive datasets combined with extensive analyses identified phase-specific factors like QSER1 and JADE1/2/3 and provide a detailed foundation for an in-depth understanding of mechanisms that govern the phased progression of pluripotency. The technical advances reported here can be readily applied to other models in development and disease.

Background/aims To investigate the natural history of PRPF31-related retinitis pigmentosa (RP11). Materials and methods We identified individuals with RP11 and collected retrospective data from disease onset to present date including genetics, demographic data, Goldmann visual field areas, and visual acuity measurements. Visual fields were evaluated as summed squared degrees and best-corrected visual acuity was converted to logMAR. We performed linear mixed model regression analysis to evaluate annual disease progression, and survival analysis to evaluate the age of legal blindness. Results We included 46 subjects with RP11. Median age of disease onset was 10 years (range 5–65). Follow-up spanned from 0 to 36 years with a median of 8 years. Median Goldmann visual field areas decreased by 10.0% per year (95% CI 7.5%−12.4%) with target IV4e, 7.9% (95% CI 4.5% − 11.2%) with target III4e, and 9.3% (95% CI: 7.0% −11.5%) when combining target sizes. Individuals with RP11 maintained good visual acuity until late stage of disease. Legal blindness was reached at a median age of 57 years (95% CI 50–75 years). Conclusions PRPF31 variants cause autosomal dominant retinitis pigmentosa that most commonly manifests in childhood with a variable disease progression. Visual field area deteriorates faster than visual acuity and was the major cause of legal blindness in our study population. This study characterizes disease progression in retinitis pigmentosa caused by PRPF31-variants and demonstrates the importance of differentiation between specific genotypes when counselling patients and conducting natural history studies of RP.

Background Vascular calcification is a known risk factor for cardiovascular events and mortality in patients with chronic kidney disease (CKD). However, since there is a lack of studies examining several arterial regions at a time, we aimed to evaluate the risk of major adverse cardiovascular events (MACE) and all-cause mortality according to calcium scores in five major arterial sites. Methods This was a prospective study of 580 patients from the Copenhagen CKD Cohort. Multidetector computed tomography of the coronary and carotid arteries, the thoracic aorta, the abdominal aorta and the iliac arteries was used to determine vascular calcification at baseline. Calcium scores were divided into categories: 0, 1-100, 101-400 and >400. Results During the follow-up period of 4.1 years a total of 59 cardiovascular events and 64 all-cause deaths occurred. In Cox proportional hazards models adjusted for age, sex, estimated glomerular filtration rate, hypertension, diabetes mellitus, hypercholesterolemia and smoking, only the coronary and carotid arteries, and the thoracic aorta were independent predictors of the designated endpoints. When examining the potential of calcification in the five arterial sites for predicting MACE, the difference in C-statistic was also most pronounced in these three sites, at 0.21 [95% confidence interval (CI) 0.16%-0.26%, P < .001], 0.26 (95% CI 0.22%-0.3%, P < .001) and 0.20 (95% CI 0.16%-0.24%, P < .001), respectively. This trend also applied to all-cause mortality. Conclusions The overall results, including data on specificity, suggest that calcium scores of the coronary and carotid arteries have the most potential for identifying patients with CKD at high cardiovascular risk and for evaluating new therapies.

Aims The recent 4S-AF (scheme proposed by the 2020 ESC AF guidelines to address stroke risk, symptom severity, severity of AF burden and substrate of AF to provide a structured phenotyping of AF patients in clinical practice to guide therapy and assess prognosis) scheme has been proposed as a structured scheme to characterize patients with atrial fibrillation (AF). We aimed to assess whether the 4S-AF scheme predicts AF progression in patients with self-terminating AF. Methods and results We analysed 341 patients with self-terminating AF included in the well-phenotyped Reappraisal of Atrial Fibrillation: Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilization in the Progression of AF (RACE V) study. Patients had continuous monitoring with implantable loop recorders or pacemakers. AF progression was defined as progression to persistent or permanent AF or progression of self-terminating AF with >3% burden increase. Progression of AF was observed in 42 patients (12.3%, 5.9% per year). Patients were given a score based on the components of the 4S-AF scheme. Mean age was 65 [interquartile range (IQR) 58-71] years, 149 (44%) were women, 103 (49%) had heart failure, 276 (81%) had hypertension, and 38 (11%) had coronary artery disease. Median CHA(2)DS(2)-VASc (the CHA(2)DS(2)-VASc score assesses thromboembolic risk. C, congestive heart failure/left ventricular dysfunction; H, hypertension; A(2), age >= 75 years; D, diabetes mellitus; S-2, stroke/transient ischaemic attack/systemic embolism; V, vascular disease; A, age 65-74 years; Sc, sex category (female sex)) score was 2 (IQR 2-3), and median follow-up was 2.1 (1.5-2.6) years. The average score of the 4S-AF scheme was 4.6 +/- 1.4. The score points from the 4S-AF scheme did not predict the risk of AF progression [odds ratio (OR) 1.1 95% CI 0.88-1.41, C-statistic 0.53]. However, excluding the symptoms domain, resulting in the 3S-AF (4S-AF scheme without the domain symptom severi

Background Chronic kidney disease (CKD) is a complication of type 2 diabetes (T2D) with high morbidity and mortality. The prevalence of CKD in T2D is increasing due to rising numbers of persons with T2D. Multiple clinical trials have been conducted testing novel therapies to reduce the progression of CKD, cardiovascular morbidity, in particular hospitalization for heart failure, and mortality. Results of these clinical trials have informed guidelines for the management of CKD in T2D. Methods The epidemiology of CKD in T2D and the process of guideline writing, including data gathering, grading and consensus development, were reviewed. Recent guidelines for the management of CKD in T2D that include recent renal outcome clinical trials are reported, along with supporting evidence. Results All current guidelines recommend annual screening for CKD, control of blood pressure and glucose, although the target levels and background therapy recommendations vary. Renin-angiotensin system (RAS) inhibition is uniformly recommended. Sodium-glucose cotransporter-2 (SGLT2) inhibition with proven agents is recommended by all guidelines, with minor variations in suggested estimated glomerular filtration rate and albuminuria levels. Finerenone, the first nonsteroidal mineralocorticoid receptor antagonist with renal outcome data, is recommended by the most recent guideline available. Conclusions Current guidelines continue to recommend screening for CKD, blood pressure control using RAS inhibition as first-line therapy, and glucose control. SGLT2 inhibition and finerenone are recent additions to current guidelines to improve CKD outcomes in T2D, based on robust clinical trial data.

Aims The recent 4S-AF (scheme proposed by the 2020 ESC AF guidelines to address stroke risk, symptom severity, severity of AF burden and substrate of AF to provide a structured phenotyping of AF patients in clinical practice to guide therapy and assess prognosis) scheme has been proposed as a structured scheme to characterize patients with atrial fibrillation (AF). We aimed to assess whether the 4S-AF scheme predicts AF progression in patients with self-terminating AF. Methods and results We analysed 341 patients with self-terminating AF included in the well-phenotyped Reappraisal of Atrial Fibrillation: Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilization in the Progression of AF (RACE V) study. Patients had continuous monitoring with implantable loop recorders or pacemakers. AF progression was defined as progression to persistent or permanent AF or progression of self-terminating AF with >3% burden increase. Progression of AF was observed in 42 patients (12.3%, 5.9% per year). Patients were given a score based on the components of the 4S-AF scheme. Mean age was 65 [interquartile range (IQR) 58-71] years, 149 (44%) were women, 103 (49%) had heart failure, 276 (81%) had hypertension, and 38 (11%) had coronary artery disease. Median CHA(2)DS(2)-VASc (the CHA(2)DS(2)-VASc score assesses thromboembolic risk. C, congestive heart failure/left ventricular dysfunction; H, hypertension; A(2), age >= 75 years; D, diabetes mellitus; S-2, stroke/transient ischaemic attack/systemic embolism; V, vascular disease; A, age 65-74 years; Sc, sex category (female sex)) score was 2 (IQR 2-3), and median follow-up was 2.1 (1.5-2.6) years. The average score of the 4S-AF scheme was 4.6 +/- 1.4. The score points from the 4S-AF scheme did not predict the risk of AF progression [odds ratio (OR) 1.1 95% CI 0.88-1.41, C-statistic 0.53]. However, excluding the symptoms domain, resulting in the 3S-AF (4S-AF scheme without the domain symptom severi

Syftet med detta examensarbete är att undersöka och belysa hur formativ bedömning används i praktiken enligt verksamma mellanstadielärare. Ett delsyfte är även att undersöka hur den formativa bedömningen följs upp under elevernas skolgång. Undersökningen är kvalitativ och materialet samlades in via intervjuer med åtta legitimerade lärare som är behöriga i ämnet svenska och undervisar i årskurs 4–6. Det teoretiska perspektivet som studien vilar på är det sociokulturella perspektivet med fokus på begrepp som den proximala utvecklingszonen, scaffolding, mediering och appropriering. Resultatet av undersökningen visar att lärarna arbetar formativt i den utsträckning de kan för att nå elevernas fulla potential inom skrivutvecklingen. Lärarna berättar att återkopplingen ligger till grund för att ta elevernas lärande vidare. Vi fick ta del av både positiva och negativa aspekter av det formativa arbetet. Det positiva som lyfts är framförallt att eleverna genom formativ bedömning utvecklar sitt skrivande till det bättre. En negativ aspekt som lyfts är tidsbristen, lärarna anser att de inte har tillräckligt med tid till återkoppling. Vi fick även ta del av hur lärarna följer och synliggör elevernas progression. Avslutningsvis har studien samlat flera tillvägagångssätt för att arbeta formativt med skrivutveckling.

Studiens syfte är att synliggöra möjligheter och begränsningar för kontinuitet och progression i barns naturvetenskapliga lärande inför övergången från förskola till förskoleklass. Studiens teoretiska utgångspunkt är det sociokulturella perspektivet. För att identifiera möjligheter och begränsningar genomfördes intervjuer med barn, förskollärare och förskoleklasslärare. Resultatet i studien presenteras i fyra teman; barnens intressen, utmanande lärandeinnehåll och arbetssätt, samarbete och insyn samt prioriterade utvecklingsområden. Resultaten visade att barnen förväntar sig och önskar utmanande, nya innehåll och arbetssätt som inkluderar inslag av deras personliga intresseområden. Både förskolan och förskoleklassen behöver arbeta medvetet med naturvetenskap för att skapa möjligheter för kontinuitet och progression. Naturvetenskapsundervisning kan och bör utgå från barns intressen och kombineras med andra ämnesinnehåll i tema- och projektarbeten samt utformas med hänsyn till barns erfarenheter och proximala utvecklingszoner för att främja progression i barns naturvetenskapliga lärande. Detta skapar i sin tur tillfällen att beröra naturvetenskapen i samverkan mellan förskola och förskoleklass inför övergången. Resultaten har även visat att förskollärare ochförskoleklasslärare måste prioritera samverkan och skapa insyn i varandras verksamheter för att främja ett gott samarbete inför övergången till förskoleklass.

Syftet med denna studie var att belysa hur progression och färdighetnivåerna från den Gemensamma europeiska referensramen för språk (GERS) kan vara till stöd för lärare. Ett exempel kan vara att hjälpa lärare vid val av läromedel för att synliggöra hur läromedlen stöttar elevernas utveckling av förmågorna lyssna, skriva och tala. För att uppfylla detta syfte formulerades tre forskningsfrågor: 1. Vilket utrymme får förmågorna skriva, lyssna samt tala i respektive läromedel? 2. Vilken färdighetsnivå enligt GERS kräver övningarna för förmågorna skriva, lyssna och tala? och 3. Hur ser progressionen ut för förmågorna skriva, lyssna och tala i de granskade läromedlen i relation till nivåerna i GERS? Studien granskade två läromedel varav ett läromedel var helt digitalt och det andra var ett tryckt läromedel i bokform. I studien analyserades uppgifterna med hjälp av GERS och kategoriserades med hjälp av Littlejohns ramverk. Studien använde dessutom en metodkombination, där både kvalitativa och kvantitativa metoder brukades. Resultatet visade att det finns en skillnad vad gäller det utrymme förmågorna får, samt att övningarna i läromedlen kategoriserades inom olika färdighetsnivåer. Dessutom visade det ena läromedlet på en tydligare progression inom GERS färdighetsnivåer.

Resit exams allow students who have failed a subject a second chance to demonstrate achievement of the academic standards required for program progression. Contrary to previous studies in this field, this paper reports on the value of resit exams with a comprehensive discussion of the lessons learned from the implementation of resits in different conditions and is intended to assist educators to decide whether such exams are a useful and fair way to promote student progression. The data were obtained from student academic performance metrics, a survey with a total of 444 students, six student focus group interviews with a total of 29 students, and three individual staff interviews. The study suggests the benefits of resit exams as a tool to improve student learning outcomes and progression, especially with the close relationship between resit exams and threshold and high-stakes assessment requirements. While the psychological and progression benefits of resit exams were acknowledged by the participants, concerns were expressed about some aspects of the way the school offered the resits and the issue of inequality. Alternatives were proposed to avoid unnecessary failure and promote learning.

Tydliga mål och förutsättningar för progression är avgörande för studenters lärande. För att stödja studenters lärandeprogression och måluppfyllelse har vi inom de naturvetenskapliga utbildningarna i Lund utvecklat så kallade progressionsplaner. Progressionsplanen konkretiserar varje examensmål i etappmål med gradvis stegrade krav. Utifrån etappmålen formuleras sedan kursmål, som tillsammans banar väg för progression mot examensmålen. Arbetet med progressionsplaner påbörjades 2017 och har lett till att 300 av fakultetens 400 kursplaner har reviderats fram till 2022.I denna rapport undersöker jag hur den förväntade progressionen i studenters lärande avspeglas i kursmålen inom kandidatutbildningens åtta huvudområden och sjukhusfysikerutbildningen. Syftet är att jämföra den förväntade progressionen 2017 och 2022 inom respektive område. För detta syfte inventerade och analyserade jag vid dessa båda tidpunkter områdenas obligatoriska kursmål och delade in dessa i tre etapper per examensmål. Sammantaget visar analyserna att examensmålen täcktes in i fler etapper 2022 än 2017. De visar också att sju av examensmålen, med enstaka undantag, representerades av kursmål i tre etapper 2022. Jämförelserna avspeglar därmed att den förväntade progressionen mot dessa mål hade stärkts mellan 2017 och 2022. När det gäller det åttonde, metakognitiva målet var den förväntade progressionen fortfarande svag inom flertalet områden.Min huvudsakliga slutsats är att arbetet med progressionsplaner över lag har skapat goda förutsättningar för lärandeprogression. Samtidigt har vi uppmärksammats på inom vilka delar av lärandet progressionen fortfarande behöver stärkas. I rapportens avslutande del diskuterar och föreslår jag åtgärder för hur detta kan gå till.

Objectives: The aim is to explore the trajectory of caregiver burden and how this relates to caregiver and contextual factors in community-dwelling dyads. Methods: At baseline, 201 family caregivers were included. The multidimensional construct of family caregiver burden and the effects of sense of competence, empathy, and quality of the relationship on this burden were assessed over 15 months using semi-structured interviews and questionnaires. Results: We found an increase of burden linked to disruptions in the caregiver’s own usual activities ( p = 0.002) and physical health complaints ( p = 0.001). Caregivers with a high sense of competence experienced lower caregiver burden during the entire caregiving process ( p < 0.001). Discussion: Healthcare professionals should alert family caregivers to the importance of taking care of themselves as early as possible in their new caregiver role. Caregiving is demanding and could negatively influence their own activities and physical health.

Resit exams allow students who have failed a subject a second chance to demonstrate achievement of the academic standards required for program progression. Contrary to previous studies in this field, this paper reports on the value of resit exams with a comprehensive discussion of the lessons learned from the implementation of resits in different conditions and is intended to assist educators to decide whether such exams are a useful and fair way to promote student progression. The data were obtained from student academic performance metrics, a survey with a total of 444 students, six student focus group interviews with a total of 29 students, and three individual staff interviews. The study suggests the benefits of resit exams as a tool to improve student learning outcomes and progression, especially with the close relationship between resit exams and threshold and high-stakes assessment requirements. While the psychological and progression benefits of resit exams were acknowledged by the participants, concerns were expressed about some aspects of the way the school offered the resits and the issue of inequality. Alternatives were proposed to avoid unnecessary failure and promote learning.

Background Despite renin-angiotensin-aldosterone system blockade and immunosuppressive treatment, focal segmental glomerulosclerosis (FSGS) often progresses to kidney failure. The objective of this prespecified analysis of the dapagliflozin and prevention of adverse outcomes in chronic kidney disease trial (DAPA-CKD) was to assess efficacy and safety of dapagliflozin in a small subgroup of participants with FSGS confirmed by kidney biopsy. Methods In DAPA-CKD, patients with an estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m(2) and urinary albumin:creatinine ratio (UACR) 200-5000 mg/g (22.6-565 mg/mol) were randomized to dapagliflozin 10 mg once daily or placebo as an adjunct to standard care and followed for median 2.4 years. The primary composite endpoint was sustained eGFR decline >= 50%, end-stage kidney disease, or kidney or cardiovascular death. The endpoint of interest for this analysis was eGFR slope (acute effects from baseline to Week 2 and chronic effects from Week 2 to end of treatment). Results Of 104 participants with biopsy-confirmed FSGS, 45 were randomized to dapagliflozin and 59 to placebo. Mean (standard deviation) age was 54.0 (14.3) years, mean eGFR 41.9 (11.5) mL/min/1.73 m(2) and median (interquartile range) UACR 1248 (749-2211) mg/g. The primary outcome occurred in 4 (8.9%) and 7 (11.9%) participants randomized to dapagliflozin and placebo, respectively [hazard ratio 0.62, 95% confidence interval (95% CI) 0.17, 2.17]. Dapagliflozin led to a larger acute reduction (standard error) in eGFR compared with placebo (-4.5, 95% CI -5.9 to -3.1 versus -0.9, -2.1 to 0.4 mL/min/1.73 m(2)/2 weeks). Thereafter, mean rates of chronic eGFR decline with dapagliflozin and placebo were -1.9 (-3.0, -0.9) and -4.0 (-4.9, -3.0) mL/min/1.73 m(2)/year, respectively (difference 2.0, 95% CI 0.6 to 3.5, mL/min/1.73 m(2)/year). Adverse events leading to study drug discontinuation were similar in both groups; there were fewer serious adverse events