Penerapan Engaged Learning Strategy dalam Menumbuhkembangkan Tanggung Jawab Belajar dan Kemampuan Koneksi Matematis Siswa Sekolah Menengah Atas

Penelitian ini bertujuan untuk mengungkap tanggungjawab belajar dan kemampuan koneksi matematis siswa pada materi Fungsi Logaritma di kelas X IPA SMA Negeri 3 Singkawang yang menerapkan Engaged Learning Strategy. Dalam penelitian ini yang dimaksud dengan tanggung jawab belajar adalah sikap dan perilaku siswa yang menunjukkan kepatuhan umum dengan standar perilaku yang diharapkan serta komitmen sehubungan dengan belajar akademik siswa, yang bisa dilihat dari aspek-aspek seperti: (1) Memiliki Inisiatif, Otonomi dan Kendali Belajar (2) Berpartisipasi Aktif dalam Pembelajaran, (3) Orientasi Positif terhadap Sekolah, (4) Mampu Memanajemen Sumber Belajar. Sedangkan kemampuan koneksi matematis adalah kemampuan siswa menemukan dan menggunakan keterkaitan antar konsep dalam matematika dan kemampuan siswa menemukan dan menggunakan keterkaitan konsep matematika dengan masalah dalam kehidupan sehari-hari. Metode penelitian yang digunakan adalah Quasi Experiment (Eksperimen Semu) dengan rancangan one-group pre-test post-test design, dimana kemampuan koneksi matematis 37 siswa dalam pembelajaran diukur sebelum dan setelah pembelajaran yang menerapkan Engaged Learning Strategy. Dalam penelitian ini, tanggung jawab belajar diukur dengan menggunakan kuesioner penilaian diri sedangkan kemampuan koneksi matematis siswa diukur dengan menggunakan tes uraian. Hasil penilaian diri kemudian diolah dengan skala Likert yang dikonversi menjadi data kuantitatif sementara hasil tes uraian diolah dengan mengacu pada pedoman penskoran. Hasil analisis data menunjukkan secara umum tanggung jawab belajar siswa meningkat sebesar 6 % dimana peningkatan terbesar adalah indikator Berpartisipasi Aktif dalam pembelajaran. Hal ini terjadi karena masalah nyata yang digunakan dalam pembelajaran sehingga dapat memotivasi siswa untuk menginvestasikan minatnya dalam belajar. Sedangkan untuk kemampuan koneksi matematis dibatasi dalam penelitian ini hanya untuk koneksi dengan kehidupan sehari-hari dan antar konsep matematika. Secara keseluruhan kemampuan koneksi matematis mengalami peningkatan skor rata-rata sebesar 1,5%

PENERAPAN ENGAGED LEARNING STRATEGY DALAM MENUMBUHKEMBANGKAN TANGGUNG JAWAB BELAJAR DAN KEMAMPUAN KONEKSI MATEMATIS SISWA SEKOLAH MENENGAH ATAS

Abstrak : Penelitian ini bertujuan untuk mengungkap tanggungjawab belajar dan kemampuan koneksi matematis siswa pada materi Fungsi Logaritma di kelas X IPA SMA Negeri 3 Singkawang yang menerapkan Engaged Learning Strategy. Metode penelitian yang digunakan adalah Quasi Experiment (Eksperimen Semu) dengan rancangan one-group pre-test post-test design, dimana kemampuan koneksi matematis 37 siswa dalam pembelajaran diukur sebelum dan setelah pembelajaran yang menerapkan Engaged Learning Strategy. Dalam penelitian ini siswa yang memiliki tanggung jawab belajar dicirikan dengan 4 indikator yaitu (1) Inisiatif, otonomi dan kendali belajar (2) Berpartisipasi Aktif, (3) Orientasi Positif terhadap Sekolah, (4) Manajemen Sumber Belajar. Hasil analisis data menunjukkan secara umum tanggung jawab belajar siswa meningkat sebesar 6 % dimana peningkatan terbesar adalah indikator Berpartisipasi Aktif. Sedangkan untuk kemampuan koneksi matematis dibatasi dalam penelitian ini hanya untuk koneksi dengan kehidupan sehari-hari dan antar konsep matematika. Secara keseluruhan kemampuan koneksi matematis mengalami peningkatan skor ratarata sebesar 1,5%.Kata Kunci : Engaged Learning Strategy, Tanggung Jawab Belajar, Koneksi MatematisAbstract : This study aims to investigate the responsibility of learning and the mathematical connections of students XIPA at SMAN 3 Singkawang learning that apply Engaged Learning Strategy. The study method is Quasi Experiment with one-group pre-test post-test design, where the learning responsibility and mathematical connections of 37 students are measured before and after applying Engaged Learning. In this study, students who have the learning responsibility characterized by four indicators: (1) Have initiative, autonomy and control of learning (2) Active Participation, (3) Have a positive orientation towards school, (4) Management of Learning Resources. The results showed that the learning responsibility has increased by 6% with largest contributions occurred in the Active Participation. As for the mathematical connections is limited in this study only for : (1) to connect with everyday life and (2) to connect between mathematical concepts. Overall the mathematical connections average scores increased of 1.5%.Keywords : Engaged Learning Strategy, Learning Responsibility, Mathematical Connection

Libri Kartika S, Edy Tandililing, Bistari Program Studi Pascasarjana Pendidikan Matematika FKIP Untan Email: [email protected]

Abstrak : Penelitian ini bertujuan untuk mengungkap tanggungjawab belajar dan kemampuan koneksi matematis siswa pada materi Fungsi Logaritma di kelas X IPA SMA Negeri 3 Singkawang yang menerapkan Engaged Learning Strategy. Metode penelitian yang digunakan adalah Quasi Experiment (Eksperimen Semu) dengan rancangan one-group pre-test post-test design, dimana kemampuan koneksi matematis 37 siswa dalam pembelajaran diukur sebelum dan setelah pembelajaran yang menerapkan Engaged Learning Strategy. Dalam penelitian ini siswa yang memiliki tanggung jawab belajar dicirikan dengan 4 indikator yaitu (1) Inisiatif, otonomi dan kendali belajar (2) Berpartisipasi Aktif, (3) Orientasi Positif terhadap Sekolah, (4) Manajemen Sumber Belajar. Hasil analisis data menunjukkan secara umum tanggung jawab belajar siswa meningkat sebesar 6 % dimana peningkatan terbesar adalah indikator Berpartisipasi Aktif. Sedangkan untuk kemampuan koneksi matematis dibatasi dalam penelitian ini hanya untuk koneksi dengan kehidupan sehari-hari dan antar konsep matematika. Secara keseluruhan kemampuan koneksi matematis mengalami peningkatan skor ratarata sebesar 1,5%.Kata Kunci : Engaged Learning Strategy, Tanggung Jawab Belajar, Koneksi MatematisAbstract : This study aims to investigate the responsibility of learning and the mathematical connections of students XIPA at SMAN 3 Singkawang learning that apply Engaged Learning Strategy. The study method is Quasi Experiment with one-group pre-test post-test design, where the learning responsibility and mathematical connections of 37 students are measured before and after applying Engaged Learning. In this study, students who have the learning responsibility characterized by four indicators: (1) Have initiative, autonomy and control of learning (2) Active Participation, (3) Have a positive orientation towards school, (4) Management of Learning Resources. The results showed that the learning responsibility has increased by 6% with largest contributions occurred in the Active Participation. As for the mathematical connections is limited in this study only for : (1) to connect with everyday life and (2) to connect between mathematical concepts. Overall the mathematical connections average scores increased of 1.5%.Keywords : Engaged Learning Strategy, Learning Responsibility, Mathematical Connection

Amniotic fluid absorption and growth functions in humans: what can we indirectly learn from congenital digestive atresias?

Background: Amniotic fluid (AF) was thought of just as a mechanical cushioning to the foetus. Nowadays, its role during pregnancy is getting more attention, suggesting hitherto unknown aspects. The aim of the study is to speculate on AF nutritional functions and its clinical repercussions based on what digestive tract (DT) atresias seem to suggest. Methods: A retrospective analysis of the patients admitted to our department for DT atresias between 2000 and 2020 was conducted. Patients’ birth weight (BW), gestational age (GA) at birth and diagnosis were recorded. The following were excluded from the study: oesophageal atresias (OA) with tracheoesophageal fistula (TOF), colonic and anal atresias and patients with associated major comorbidities. A control group was made of patients admitted to our ward in the same period for congenital pulmonary airway malformations (CPAM). To standardize the BW, it was coupled with birth GA calculating the newborn percentiles. The mean newborn percentiles of OAs, duodenal atresias (DAs), jejunal atresias (JAs), and ileal atresias (IAs) were independently compared with the control group using Student’s t-test. Lastly, the significance of the frequencies’ distribution of newborns born small for gestational age (SGA) between the DT atresias and the control group was evaluated with the χ2 test, and the OR were calculated. A p-value < 0.05 was considered statistically significant. Results: A total of 231 patients were eligible for the study: 36 OAs without TOF, mean BW 2488.8 ± 491 g (range 1630–3750 g), mean GA 36.8 ± 2.1 weeks (31–40 weeks), mean newborn percentile 18 ± 22 (1–75); 20 DAs, mean BW 2586.8 ± 577.9 g (1250–3462 g), mean GA 36.2 ± 2.5 weeks (31–40 weeks), mean newborn percentile 31 ± 23 (3–79); 17 JAs, mean BW 2483.5 ± 621.7 g (900–3205 g), mean GA 34.8 ± 2.1 weeks (30–38 weeks), mean newborn percentile 44 ± 28 (4–96); 17 IAs, mean BW 2646.1 ± 769.8 g (1162.0–3888 g), mean GA 35.9 ± 3.2 weeks (30–41 weeks), mean newborn percentile 44 ± 26 (1–82); and 141 CPAMs with mean BW 3287.4 ± 492.0 g (980–4580 g), mean GA 38.7 ± 1.8 weeks (26–41 weeks), mean newborn percentile 43 ± 26 (1–99). The number of SGA neonates was 18 between OA patients (50%), 4 between DAs (20%), 1 between JAs (6%), 2 between IAs (12%) and 11 between CPAMs (8%). The mean percentile of the OAs and DAs was lower than the control group with a p of < .01 and .03 while no statistical significance was found in the comparison between DAs, JAs, IAs and CPAMs with a p of .06, .86 and .59. The incidence of SGA in the control group resulted lower than the one in the DT atresias where it becomes higher the more proximal the atresia is (p < .05). The OR of SGA newborn in the OA group was 11.8, in DA 3.0, in JA 0.7 and in IA 1.6. Conclusion: AF showed to have a great impact on foetal growth, and its preferred site of absorption seemed to be the stomach and duodenum. Its nutritional role could have an important predictive value in diagnosing DT atresia both prenatally and postnatally

Prion protein monoclonal antibody (PRN100) therapy for Creutzfeldt–Jakob disease: evaluation of a first-in-human treatment programme

Background: Human prion diseases, including Creutzfeldt–Jakob disease (CJD), are rapidly progressive, invariably fatal neurodegenerative conditions with no effective therapies. Their pathogenesis involves the obligate recruitment of cellular prion protein (PrPC) into self-propagating multimeric assemblies or prions. Preclinical studies have firmly validated the targeting of PrPC as a therapeutic strategy. We aimed to evaluate a first-in-human treatment programme using an anti-PrPC monoclonal antibody under a Specials Licence. Methods: We generated a fully humanised anti-PrPC monoclonal antibody (an IgG4κ isotype; PRN100) for human use. We offered treatment with PRN100 to six patients with a clinical diagnosis of probable CJD who were not in the terminal disease stages at the point of first assessment and who were able to readily travel to the University College London Hospital (UCLH) Clinical Research Facility, London, UK, for treatment. After titration (1 mg/kg and 10 mg/kg at 48-h intervals), patients were treated with 80–120 mg/kg of intravenous PRN100 every 2 weeks until death or withdrawal from the programme, or until the supply of PRN100 was exhausted, and closely monitored for evidence of adverse effects. Disease progression was assessed by use of the Medical Research Council (MRC) Prion Disease Rating Scale, Motor Scale, and Cognitive Scale, and compared with that of untreated natural history controls (matched for disease severity, subtype, and PRNP codon 129 genotype) recruited between Oct 1, 2008, and July 31, 2018, from the National Prion Monitoring Cohort study. Autopsies were done in two patients and findings were compared with those from untreated natural history controls. Findings: We treated six patients (two men; four women) with CJD for 7–260 days at UCLH between Oct 9, 2018, and July 31, 2019. Repeated intravenous dosing of PRN100 was well tolerated and reached the target CSF drug concentration (50 nM) in four patients after 22–70 days; no clinically significant adverse reactions were seen. All patients showed progressive neurological decline on serial assessments with the MRC Scales. Neuropathological examination was done in two patients (patients 2 and 3) and showed no evidence of cytotoxicity. Patient 2, who was treated for 140 days, had the longest clinical duration we have yet documented for iatrogenic CJD and showed patterns of disease-associated PrP that differed from untreated patients with CJD, consistent with drug effects. Patient 3, who had sporadic CJD and only received one therapeutic dose of 80 mg/kg, had weak PrP synaptic labelling in the periventricular regions, which was not a feature of untreated patients with sporadic CJD. Brain tissue-bound drug concentrations across multiple regions in patient 2 ranged from 9·9 μg per g of tissue (SD 0·3) in the thalamus to 27·4 μg per g of tissue (1·5) in the basal ganglia (equivalent to 66–182 nM). Interpretation: Our academic-led programme delivered what is, to our knowledge, the first rationally designed experimental treatment for human prion disease to a small number of patients with CJD. The treatment appeared to be safe and reached encouraging CSF and brain tissue concentrations. These findings justify the need for formal efficacy trials in patients with CJD at the earliest possible clinical stages and as prophylaxis in those at risk of prion disease due to PRNP mutations or prion exposure. Funding: The Cure CJD Campaign, the National Institute for Health Research UCLH Biomedical Research Centre, the Jon Moulton Charitable Trust, and the UK MRC

Ambroxol for the Treatment of Patients With Parkinson Disease With and Without Glucocerebrosidase Gene Mutations: A Nonrandomized, Noncontrolled Trial

Importance: Mutations of the glucocerebrosidase gene, GBA1 (OMIM 606463), are the most important risk factor for Parkinson disease (PD). In vitro and in vivo studies have reported that ambroxol increases β-glucocerebrosidase (GCase) enzyme activity and reduces α-synuclein levels. These observations support a potential role for ambroxol therapy in modifying a relevant pathogenetic pathway in PD. Objective: To assess safety, tolerability, cerebrospinal fluid (CSF) penetration, and target engagement of ambroxol therapy with GCase in patients with PD with and without GBA1 mutations. / Interventions: An escalating dose of oral ambroxol to 1.26 g per day. Design, Setting, and Participants: This single-center open-label noncontrolled clinical trial was conducted between January 11, 2017, and April 25, 2018, at the Leonard Wolfson Experimental Neuroscience Centre, a dedicated clinical research facility and part of the University College London Queen Square Institute of Neurology in London, United Kingdom. Participants were recruited from established databases at the Royal Free London Hospital and National Hospital for Neurology and Neurosurgery in London. Twenty-four patients with moderate PD were evaluated for eligibility, and 23 entered the study. Of those, 18 patients completed the study; 1 patient was excluded (failed lumbar puncture), and 4 patients withdrew (predominantly lumbar puncture-related complications). All data analyses were performed from November 1 to December 14, 2018. / Main Outcomes and Measures: Primary outcomes at 186 days were the detection of ambroxol in the CSF and a change in CSF GCase activity. / Results: Of the 18 participants (15 men [83.3%]; mean [SD] age, 60.2 [9.7] years) who completed the study, 17 (8 with GBA1 mutations and 9 without GBA1 mutations) were included in the primary analysis. Between days 0 and 186, a 156-ng/mL increase in the level of ambroxol in CSF (lower 95% confidence limit, 129 ng/mL; P < .001) was observed. The CSF GCase activity decreased by 19% (0.059 nmol/mL per hour; 95% CI, -0.115 to -0.002; P = .04). The ambroxol therapy was well tolerated, with no serious adverse events. An increase of 50 pg/mL (13%) in the CSF α-synuclein concentration (95% CI, 14-87; P = .01) and an increase of 88 ng/mol (35%) in the CSF GCase protein levels (95% CI, 40-137; P = .002) were observed. Mean (SD) scores on part 3 of the Movement Disorders Society Unified Parkinson Disease Rating Scale decreased (ie, improved) by 6.8 (7.1) points (95% CI, -10.4 to -3.1; P = .001). These changes were observed in patients with and without GBA1 mutations. / Conclusions and Relevance: The study results suggest that ambroxol therapy was safe and well tolerated; CSF penetration and target engagement of ambroxol were achieved, and CSF α-synuclein levels were increased. Placebo-controlled clinical trials are needed to examine whether ambroxol therapy is associated with changes in the natural progression of PD. Trial Registration: ClinicalTrials.gov identifier: NCT02941822; EudraCT identifier: 2015-002571-24

Protocol of a randomized, double-blind, placebo-controlled, parallel-group, multicentre study of the efficacy and safety of nicotinamide in patients with Friedreich ataxia (NICOFA)

Introduction: Currently, no treatment that delays with the progression of Friedreich ataxia is available. In the majority of patients Friedreich ataxia is caused by homozygous pathological expansion of GAA repeats in the first intron of the FXN gene. Nicotinamide acts as a histone deacetylase inhibitor. Dose escalation studies have shown, that short term treatment with dosages of up to 4 g/day increase the expression of FXN mRNA and frataxin protein up to the levels of asymptomatic heterozygous gene carriers. The long-term effects and the effects on clinical endpoints, activities of daily living and quality of life are unknown. Methods: The aim of the NICOFA study is to investigate the efficacy and safety of nicotinamide for the treatment of Friedreich ataxia over 24 months. An open-label dose adjustment wash-in period with nicotinamide (phase A: weeks 1–4) to the individually highest tolerated dose of 2–4 g nicotinamide/day will be followed by a 2 (nicotinamide group): 1 (placebo group) randomization (phase B: weeks 5–104). In the nicotinamide group, patients will continue with their individually highest tolerated dose between 2 and 4 g/d per os once daily and the placebo group patients will be receiving matching placebo. Safety assessments will consist of monitoring and recording of all adverse events and serious adverse events, regular monitoring of haematology, blood chemistry and urine values, regular measurement of vital signs and the performance of physical examinations including cardiological signs. The primary outcome is the change in the Scale for the Assessment and Rating of Ataxia (SARA) over time as compared with placebo in patients with Friedreich ataxia based on the linear mixed effect model (LMEM) model. Secondary endpoints are measures of quality of life, functional motor and cognitive measures, clinician’s and patient’s global impression-change scales as well as the upregulation of the frataxin protein level, safety and survival/death. Perspective: The NICOFA study represents one of the first attempts to assess the clinical efficacy of an epigenetic therapeutic intervention for this disease and will provide evidence of possible disease modifying effects of nicotinamide treatment in patients with Friedreich ataxia