Analysis of the use of time prepositions based on the Czech learner corpora

The bachelor thesis focuses on the analysis of the use of prepositions with temporal meaning by non-native speakers of Czech in written texts. The starting point of the thesis is the observation that the use of prepositions is very difficult for non-native speakers even at a high level of proficiency. In the theoretical part we outline the system of prepositions in contemporary Czech as described in Czech grammars, but also as reflected in theoretical works in the field of teaching prepositions to non-native speakers of Czech. The theoretical works describing methodological difficulties in teaching prepositions in the context of Czech as a foreign language are based on the authors' personal experiences with teaching. Based on the material of the CzeSL and Merlin learner corpora, we analyse the use of prepositions to confirm/disprove the difficulties in their use contained in the theoretical works. The aim of the bachelor's thesis is to quantitatively map the use of prepositions by non- native speakers in written works. Key words Czech as a foreign language, grammar, prepositions, error analysis, learner corpus CzeSL, MerlinBakalářská práce se zaměřuje na analýzu užití předložek s časovým významem nerodilými mluvčími češtiny v písemných textech. Východiskem práce je poznatek, že užívání předložek je pro nerodilé mluvčí velmi obtížné i na vysoké úrovni pokročilosti. V teoretické části nastíníme systém předložek v současné češtině, tak jak jej popisují české gramatiky, ale i jak je reflektován v teoretických pracích z oblasti výuky předložek pro nerodilé mluvčí češtiny. Teoretické práce popisující metodické obtíže při výuce předložek v rámci češtiny jako cizího jazyka vycházejí z osobních zkušeností autorů s výukou. Na základě materiálu žákovských korpusů CzeSL a Merlin provedeme analýzu užití předložek, abychom potvrdili / vyvrátili obtíže v jejich užití, obsažené v teoretických pracích. Cílem bakalářské práce je kvantitativně zmapovat užívání předložek nerodilými mluvčími v písemných pracích. Klíčová slova Čeština jako cizí jazyk, mluvnice, předložka, chybová analýza, žákovský korpus CzeSL, MerlinÚstav bohemistických studiíInstitute of Czech StudiesFaculty of ArtsFilozofická fakult

Analysis of the use of time prepositions based on the Czech learner corpora

The bachelor thesis focuses on the analysis of the use of prepositions with temporal meaning by non-native speakers of Czech in written texts. The starting point of the thesis is the observation that the use of prepositions is very difficult for non-native speakers even at a high level of proficiency. In the theoretical part we outline the system of prepositions in contemporary Czech as described in Czech grammars, but also as reflected in theoretical works in the field of teaching prepositions to non-native speakers of Czech. The theoretical works describing methodological difficulties in teaching prepositions in the context of Czech as a foreign language are based on the authors' personal experiences with teaching. Based on the material of the CzeSL and Merlin learner corpora, we analyse the use of prepositions to confirm/disprove the difficulties in their use contained in the theoretical works. The aim of the bachelor's thesis is to quantitatively map the use of prepositions by non- native speakers in written works. Key words Czech as a foreign language, grammar, prepositions, error analysis, learner corpus CzeSL, Merli

Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial

BackgroundSparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis.MethodsPROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850.FindingsBetween Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals.InterpretationOver 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics