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Mathematics teacher candidates enter teacher education with knowledge that could support or limit their learning. It is therefore important to gain insights of this knowledge to inform teacher education. This paper offers such insights for prospective mathematics teachers' initial knowledge of problem solving (PS) for teaching at the beginning of their teacher education programme. It reports on a study that investigated three categories of problem-solving knowledge for teaching: problem characterization, the PS process, and PS disposition. Participants were 109 prospective primary teachers at a university in Spain. Data sources were questionnaires designed for the study to explore the initial knowledge held by the participants for three categories of problem-solving knowledge. Findings indicated that the participants' knowledge was stronger regarding the PS process and disposition than for problem characterization but had limitations that needed to be addressed in their teacher preparation programme.

Objective: To clinically and pathologically characterize a cohort of patients presenting with a novel form of distal myopathy and to identify the genetic cause of this new muscular dystrophy.Methods: We studied 4 families (3 from Spain and 1 from Sweden) suffering from an autosomal dominant distal myopathy. Affected members showed adult onset asymmetric distal muscle weakness with initial involvement of ankle dorsiflexion later progressing also to proximal limb muscles.Results: In all 3 Spanish families, we identified a unique missense variant in the ACTN2 gene cosegregating with the disease. The affected members of the Swedish family carry a different ACTN2 missense variant.Interpretation: ACTN2 encodes for alpha actinin2, which is highly expressed in the sarcomeric Z-disk with a major structural and functional role. Actininopathy is thus a new genetically determined distal myopathy. ANN NEUROL 2019;85:899-906. [ABSTRACT FROM AUTHOR]

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Research on mathematics teachers' knowledge has generally focused more on mathematics concepts than mathematical processes. This paper addresses the latter with a focus on mathematical problem solving (PS). It reports on a study that investigated the pedagogical knowledge for PS of prospective elementary school teachers of mathematics (PTs). Participants were 149 PTs at a university in Spain. They were at the end of their teacher education program. Data sources consisted of a questionnaire on knowledge of learning PS and a questionnaire on knowledge of teaching PS. Findings indicated that the PTs held combination of different levels of knowledge of PS learning and teaching. Many of them demonstrated appropriate knowledge of many characteristics for (1) PS learning consisting of student as a problem-solver, PS as a worthwhile task, non-cognitive factor related to PS, and (2) PS teaching consisting of PS teaching approaches, discourse in PS, intervention during stuck state in PS, PS assessment, and PS resources. However, there were also contradictions and limitations to their knowledge with implications for teacher education. These combination of appropriate and inappropriate knowledge resulted in some conflicts that are related to teaching actions and would limit student' learning of PS. [ABSTRACT FROM AUTHOR]

The term neuromuscular disorder (NMD) includes many genetic and acquired diseases and differential diagnosis can be challenging. Next-generation sequencing (NGS) is especially useful in this setting given the large number of possible candidate genes, the clinical, pathological, and genetic heterogeneity, the absence of an established genotype-phenotype correlation, and the exceptionally large size of some causative genes such as TTN, NEB and RYR1. We evaluated the diagnostic value of a custom targeted next-generation sequencing gene panel to study the mutational spectrum of a subset of NMD patients in Spain. In an NMD cohort of 207 patients with congenital myopathies, distal myopathies, congenital and adult-onset muscular dystrophies, and congenital myasthenic syndromes, we detected causative mutations in 102 patients (49.3%), involving 42 NMD-related genes. The most common causative genes, TTN and RYR1, accounted for almost 30% of cases. Thirty-two of the 207 patients (15.4%) carried variants of uncertain significance or had an unidentified second mutation to explain the genetic cause of the disease. In the remaining 73 patients (35.3%), no candidate variant was identified. In combination with patients' clinical and myopathological data, the custom gene panel designed in our lab proved to be a powerful tool to diagnose patients with myopathies, muscular dystrophies and congenital myasthenic syndromes. Targeted NGS approaches enable a rapid and cost-effective analysis of NMD- related genes, offering reliable results in a short time and relegating invasive techniques to a second tier. [ABSTRACT FROM AUTHOR]

Purpose: To present data on the late toxicity endpoints of a randomized trial (DART 01/05) conducted to determine whether long-term androgen deprivation (LTAD) was superior to short-term AD (STAD) when combined with high-dose radiation therapy (HDRT) in patients with prostate cancer (PCa).Patients and Methods: Between November 2005 and December 2010, 355 eligible men with cT1c-T3aN0M0 PCa and intermediate-risk and high-risk factors (2005 National Comprehensive Cancer Network criteria) were randomized to 4 months of AD combined with HDRT (median dose, 78 Gy) (STAD) or the same treatment followed by 24 months of AD (LTAD). Treatment-related complications were assessed using European Organization for Research and Treatment of Cancer-Radiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events v3.0 scoring schemes. Multivariate analyses for late toxicity were done using the Fine-Gray method.Results: The 5-year incidence of grade ≥2 rectal and urinary toxicity was 11.1% and 8.2% for LTAD and 7.6% and 7.3% for STAD, respectively. Compared with STAD, LTAD was not significantly associated with a higher risk of late grade ≥2 rectal toxicity (hazard ratio [HR] 1.360, 95% confidence interval [CI] 0.660-2.790, P=.410) or urinary toxicity (HR 1.028, 95% CI 0.495-2.130, P=.940). The multivariate analysis showed that a baseline history of intestinal comorbidity (HR 3.510, 95% CI 1.560-7.930, P=.025) and the rectal volume receiving >60 Gy (Vr60) (HR 1.030, 95% CI 1.001-1.060, P=.043) were the only factors significantly correlated with the risk of late grade ≥2 rectal complications. A history of previous surgical prostate manipulations was significantly associated with a higher risk of grade ≥2 urinary complications (HR 2.427, 95% CI 1.051-5.600, P=.038). Long-term AD (HR 2.090; 95% CI 1.170-3.720, P=.012) and a history of myocardial infarction (HR 2.080; 95% CI 1.130-3.810, P=.018) were significantly correlated with a higher probability of cardiovascular events.Conclusion: Long-term AD did not significantly impact urinary or rectal radiation-induced toxicity, although it was associated with a higher risk of cardiovascular events. Longer follow-up is needed to measure the impact of AD on late morbidity and non-PCa mortality. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): The optimal duration of androgen deprivation (AD) combined with high-dose radiotherapy (HDRT) in prostate cancer remains a matter of controversy. We did a phase 3 trial designed to determine whether long-term AD (LTAD) is superior to short-term AD (STAD) when combined with HDRT. In this report, we present the 10-year survival results. The hypothesis is that long-term AD (LTAD) compared to short-term AD (STAD) improves overall survival among high-risk patients receiving HDRT.Materials/methods: This open-label, phase 3 randomized controlled trial, recruited patients from ten university hospitals throughout Spain. Eligibility included patients with cT1c-T3aN0M0 adenocarcinoma of prostate with intermediate and high-risk factors according to NCCN criteria and PSA less than 100 ng/ml. All patients received 4 months of neoadjuvant and concomitant AD (STAD) + HDRT (median radiation dose 78 Gy) before randomization to adjuvant goserelin for two years (LTAD). Stratification was performed according to risk group (intermediate risk [IR] versus high risk [HR]). Study endpoints included overall survival (OS), metastasis free survival (MFS), disease free survival (DFS) and biochemical-disease free survival (bDFS). Survival analyses were done with Kaplan-Meier (KM) curves. Fine & Gray (F&G) regression was used for the adjusted analyses.Results: From 2005 to 2010, 355 patients were randomly assigned to the treatment groups and included in the analysis (178 to STAD and 177 to LTAD). The median follow-up was 119 months (IQR 101-124). The 10-year bDFS for LTAD and STAD was 70.2% and 62.3% respectively (hazard ratio [HR] 1.19, 95% CI, 0.71 to 2.01). The 10-year OS was 78.4% for LTAD and 73.3% for STAD (HR 1.20, 95% CI, 0.79 to 1.82), and the corresponding figure for MFS was 76.0% and 70.9% for LTAD and STAD respectively (HR 1.12, 95% CI, 0.46 to 2.73). For high-risk patients treated with LTAD, the 10-year bDFS was 67.2% compared to 53.7% for STAD (log rank P = 0.03; F&G P = 0.147, HR 1.12 95% CI 0.61 to 2.04). The 10-year OS was 78.5% compared to 67.0% for STAD (log rank, P = 0.056; F&G P = 0.786, HR, 1.18, 95% CI, 0.36 to 3.84) and the 10-year MFS was 76.6% versus 65.0% for LTAD and STAD respectively (log rank P = 0.069; F&G P = 0.057, HR, 1.12, 95% CI, 0.46 to 2.73). Only 11 patients died from PCa, all of them in the high-risk subgroup.Conclusion: Long term results failed to show a significant benefit with LTAD compared to STAD in patients treated with HDRT. The subgroup of patients with high-risk PCa treated with LTAD had a non-significant improvement in bDFS, MFS and OS compared with STAD. The relatively small simple size, a low number of events and an effective salvage treatment could be responsible for the lack of a statistical significance. The trial is registered at ClinicalTrials.gov, number NCT02175212. [ABSTRACT FROM AUTHOR]

Background: The optimum duration of androgen deprivation combined with high-dose radiotherapy in prostate cancer remains undefined. We aimed to determine whether long-term androgen deprivation was superior to short-term androgen deprivation when combined with high-dose radiotherapy., Methods: In this open-label, multicentre, phase 3 randomised controlled trial, patients were recruited from ten university hospitals throughout Spain. Eligible patients had clinical stage T1c-T3b N0M0 prostate adenocarcinoma with intermediate-risk and high-risk factors according to 2005 National Comprehensive Cancer Network criteria. Patients were randomly assigned (1:1) using a computer-generated randomisation schedule to receive either 4 months of androgen deprivation combined with three-dimensional conformal radiotherapy at a minimum dose of 76 Gy (range 76-82 Gy; short-term androgen deprivation group) or the same treatment followed by 24 months of adjuvant androgen deprivation (long-term androgen deprivation group), stratified by prostate cancer risk group (intermediate risk vs high risk) and participating centre. Patients assigned to the short-term androgen deprivation group received 4 months of neoadjuvant and concomitant androgen deprivation with subcutaneous goserelin (2 months before and 2 months combined with high-dose radiotherapy). Anti-androgen therapy (flutamide 750 mg per day or bicalutamide 50 mg per day) was added during the first 2 months of treatment. Patients assigned to long-term suppression continued with the same luteinising hormone-releasing hormone analogue every 3 months for another 24 months. The primary endpoint was biochemical disease-free survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02175212., Findings: Between Nov 7, 2005, and Dec 20, 2010, 178 patients were randomly assigned to receive short-term androgen deprivation and 177 to receive long-term androgen deprivation. After a median follow-up of 63 months (IQR 50-82), 5-year biochemical disease-free survival was significantly better among patients receiving long-term androgen deprivation than among those receiving short-term treatment (90% [95% CI 87-92] vs 81% [78-85]; hazard ratio [HR] 1·88 [95% CI 1·12-3·15]; p=0·01). 5-year overall survival (95% [95% CI 93-97] vs 86% [83-89]; HR 2·48 [95% CI 1·31-4·68]; p=0·009) and 5-year metastasis-free survival (94% [95% CI 92-96] vs 83% [80-86]; HR 2·31 [95% CI 1·23-3·85]; p=0·01) were also significantly better in the long-term androgen deprivation group than in the short-term androgen deprivation group. The effect of long-term androgen deprivation on biochemical disease-free survival, metastasis-free survival, and overall survival was more evident in patients with high-risk disease than in those with low-risk disease. Grade 3 late rectal toxicity was noted in three (2%) of 177 patients in the long-term androgen deprivation group and two (1%) of 178 in the short-term androgen deprivation group; grade 3-4 late urinary toxicity was noted in five (3%) patients in each group. No deaths related to treatment were reported., Interpretation: Compared with short-term androgen deprivation, 2 years of adjuvant androgen deprivation combined with high-dose radiotherapy improved biochemical control and overall survival in patients with prostate cancer, particularly those with high-risk disease, with no increase in late radiation toxicity. Longer follow-up is needed to determine whether men with intermediate-risk disease benefit from more than 4 months of androgen deprivation., Funding: Spanish National Health Investigation Fund, AstraZeneca., (Copyright © 2015 Elsevier Ltd. All rights reserved.)