Prevention of reading difficulties in children with and without familial risk:Short- and long-term effects of an early intervention

In a randomized-controlled trial we tested a computer-assisted intervention for the prevention of reading difficulties, delivered by nonprofessional tutors, running from kindergarten to halfway Grade 2. The full sample included 123 prereaders (M = 5; 6 years; 56 intervention; 67 controls) with low preliteracy skills. Parents were sent a questionnaire to assess family risk (FR) for reading difficulties. There was no intervention effect in the full sample, but, unexpectedly, the effect differed between subsamples that did and did not return the questionnaire. The intervention did not affect reading acquisition in the subsample (N = 49) without FR-data, mostly children from immigrant, non-Dutch speaking, low-socioeconomic status (SES) families, but had large effects in the subsample of Dutch-speaking, middle and high SES-parents with FR-data (N = 74). The latter subsample was followed until Grade 6, 4 years after the intervention, and included 36 intervention children and 38 controls. Long-lasting improvements were found in word-reading fluency, which transferred to reading fluency for pseudowords, English words: and texts, and to spelling. The intervention substantially reduced the need for remedial teaching and grade retention. On all measures, children with FR performed worse than children without FR. The intervention had similar effects on the progress of both groups, but the FR children needed more sessions. This study shows that a 2-year cost-effective early intervention can reduce the incidence of reading difficulties. However, it remains a challenge to make the intervention suited for children in which a lack of preliteracy skills merely seems to reflect a lack of learning opportunities

Isolation of peroxisome assembly mutants from Saccharomyces cerevisiae with different morphologies using a novel positive selection procedure.

We have developed a positive selection system for the isolation of Saccharomyces cerevisiae mutants with disturbed peroxisomal functions. The selection is based on the lethality of hydrogen peroxide (H2O2) that is produced in wild type cells during the peroxisomal beta-oxidation of fatty acids. In total, 17 mutants having a general impairment of peroxisome biogenesis were isolated, as revealed by their inability to grow on oleic acid as the sole carbon source and their aberrant cell fractionation pattern of peroxisomal enzymes. The mutants were shown to have monogenetic defects and to fall into 12 complementation groups. Representative members of each complementation group were morphologically examined by immunocytochemistry using EM. In one mutant the induction and morphology of peroxisomes is normal but import of thiolase is abrogated, while in another the morphology differs from the wild type: stacked peroxisomal membranes are present that are able to import thiolase but not catalase. These mutants suggest the existence of multiple components involved in peroxisomal protein import. Some mutants show the phenotype characteristic of glucose-repressed cells, an indication for the interruption of a signal transduction pathway resulting in organelle proliferation. In the remaining mutants morphologically detectable peroxisomes are absent: this phenotype is also known from fibroblasts of patients suffering from Zellweger syndrome, a disorder resulting from impairment of peroxisome

Acquiring reading and vocabulary in Dutch and English: the effect of concurrent instruction

To investigate the effect of concurrent instruction in Dutch and English on reading acquisition in both languages, 23 pupils were selected from a school with bilingual education, and 23 from a school with education in Dutch only. The pupils had a Dutch majority language background and were comparable with regard to social-economic status (SES). Reading and vocabulary were measured twice within an interval of 1 year in Grade 2 and 3. The bilingual group performed better on most English and some of the Dutch tests. Controlling for general variables and related skills, instruction in English contributed significantly to the prediction of L2 vocabulary and orthographic awareness at the second measurement. As expected, word reading fluency was easier to acquire in Dutch with its relatively transparent orthography in comparison to English with its deep orthography, but the skills intercorrelated highly. With regard to cross-linguistic transfer, orthographic knowledge and reading comprehension in Dutch were positively influenced by bilingual instruction, but there was no indication of generalization to orthographic awareness or knowledge of a language in which no instruction had been given (German). The results of the present study support the assumption that concurrent instruction in Dutch and English has positive effects on the acquisition of L2 English and L1 Dutch

Pathways Into Literacy:The Role of Early Oral Language Abilities and Family Risk for Dyslexia

The present study investigated the role of early oral language and family risk for dyslexia in the two developmental pathways toward reading comprehension, through word reading and through oral language abilities. The sample contained 237 children (164 at family risk for dyslexia) from the Dutch Dyslexia Program. Longitudinal data were obtained on seven occasions when children were between 4 and 12 years old. The relationship between early oral language ability and reading comprehension at the age of 12 years was mediated by preliteracy skills and word-decoding ability for the first pathway and by later language abilities for the second pathway. Family risk influenced literacy development through its subsequent relations with preliteracy skills, word decoding, and reading comprehension. Although performance on language measures was often lower for the family-risk group than for the no-family-risk group, family risk did not have a specific relation with either early or later oral language abilities

Telomere length in breast cancer patients before and after chemotherapy with or without stem cell transplantation

High-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT) may accelerate telomere length loss in haematopoietic stem cells. As data including pre-and post-treatment samples are lacking, we studied leukocyte telomere length and telomerase activity before and after treatment in breast cancer patients randomized to receive 5 adjuvant courses FEC (5-FU, epirubicin and cyclophosphamide) (n= 17), or 4 × FEC followed by high-dose cyclophosphamide, thiotepa, carboplatin and autologous PBSCT (n= 16). Haemoglobin, MCV, leukocyte-and platelet numbers were assessed prior to (t0), 5 months after (t1) and 9 months after chemotherapy (t2); these parameters were decreased at t1 and t2 compared to t0(high-dose: all parameters; standard-dose: leukocytes and platelets), and all parameters were lower after high-dose than standard-dose treatment at t1. Paired individual leukocyte samples of t0 and t1 showed telomere length change (determined by telomere restricted fragment (TRF) assay) ranging from +0.8 to –2.2 kb, with a decreased TRF length in 9 patients of both groups. Telomerase activity (determined by TRAP assay) was below detection limit in leukocyte samples of t0 and t1. Thus, standard-and high-dose chemotherapy negatively affect haematological reconstitution in this setting. In individual patients, telomere length can be remarkably changed following haematological proliferative stress after treatment. © 2001 Cancer Research Campaign www.bjcancer.co

Intravenous Thrombolysis Before Endovascular Treatment in Posterior Circulation Occlusions:A MR CLEAN Registry Study

BACKGROUND: The effectiveness of intravenous thrombolysis (IVT) before endovascular treatment (EVT) has been investigated in randomized trials and meta-analyses. These studies mainly concerned anterior circulation occlusions. We aimed to investigate clinical, technical, and safety outcomes of IVT before EVT in posterior circulation occlusions in a nationwide registry. METHODS: Patients were included from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), a nationwide, prospective, multicenter registry of patients with acute ischemic stroke due to a large intracranial vessel occlusion receiving EVT between 2014 and 2019. All patients with a posterior circulation occlusion were included. Primary outcome was a shift toward better functional outcome on the modified Rankin Scale at 90 days. Secondary outcomes were favorable functional outcome (modified Rankin Scale scores, 0–3), occurrence of symptomatic intracranial hemorrhages, successful reperfusion (extended Thrombolysis in Cerebral Ischemia ≥2B), first-attempt successful reperfusion, and mortality at 90 days. Regression analyses with adjustments based on univariable analyses and literature were applied. RESULTS: A total of 248 patients were included, who received either IVT (n=125) or no IVT (n=123) before EVT. Results show no differences in a shift on the modified Rankin Scale (adjusted common odds ratio, 1.04 [95% CI, 0.61–1.76]). Although symptomatic intracranial hemorrhages occurred more often in the IVT group (4.8% versus 2.4%), regression analysis did not show a significant difference (adjusted odds ratio, 1.65 [95% CI, 0.33–8.35]). Successful reperfusion, favorable functional outcome, first-attempt successful reperfusion, and mortality did not differ between patients treated with and without IVT. CONCLUSIONS: We found no significant differences in clinical, technical, and safety outcomes between patients with a large vessel occlusion in the posterior circulation treated with or without IVT before EVT. Our results are in line with the literature on the anterior circulation. GRAPHIC ABSTRACT: A graphic abstract is available for this article.</p

Endovascular Treatment for Posterior Circulation Stroke in Routine Clinical Practice:Results of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry

BACKGROUND AND PURPOSE: The benefit of endovascular treatment (EVT) for posterior circulation stroke (PCS) remains uncertain, and little is known on treatment outcomes in clinical practice. This study evaluates outcomes of a large PCS cohort treated with EVT in clinical practice. Simultaneous to this observational study, several intervention centers participated in the BASICS trial (Basilar Artery International Cooperation Study), which tested the efficacy of EVT for basilar artery occlusion in a randomized setting. We additionally compared characteristics and outcomes of patients treated outside BASICS in trial centers to those from nontrial centers. METHODS: We included patients with PCS from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry: a prospective, multicenter, observational study of patients who underwent EVT in the Netherlands between 2014 and 2018. Primary outcome was a score of 0 to 3 on the modified Rankin Scale at 90 days. Secondary outcomes included reperfusion status and symptomatic intracranial hemorrhage. For outcome comparison between patients treated in trial versus nontrial centers, we used ordinal logistic regression analysis. RESULTS: We included 264 patients of whom 135 (51%) had received intravenous thrombolysis. The basilar artery was most often involved (77%). Favorable outcome (modified Rankin Scale score 0-3) was observed in 115/252 (46%) patients, and 109/252 (43%) patients died. Successful reperfusion was achieved in 178/238 (75%), and symptomatic intracranial hemorrhage occurred in 9/264 (3%). The 154 nontrial patients receiving EVT in BASICS trial centers had similar characteristics and outcomes as the 110 patients treated in nontrial centers (modified Rankin Scale adjusted cOR: 0.77 [95% CI, 0.5-1.2]). CONCLUSIONS: Our study shows that high rates of favorable clinical outcome and successful reperfusion can be achieved with EVT for PCS, despite high mortality. Characteristics and outcomes of patients treated in trial versus nontrial centers were similar indicating that our cohort is representative of clinical practice in the Netherlands. Randomized studies using modern treatment approaches are needed for further insight in the benefit of EVT for PCS

Care after pancreatic resection according to an algorithm for early detection and minimally invasive management of pancreatic fistula versus current practice (PORSCH-trial):design and rationale of a nationwide stepped-wedge cluster-randomized trial

Background: Pancreatic resection is a major abdominal operation with 50% risk of postoperative complications. A common complication is pancreatic fistula, which may have severe clinical consequences such as postoperative bleeding, organ failure and death. The objective of this study is to investigate whether implementation of an algorithm for early detection and minimally invasive management of pancreatic fistula may improve outcomes after pancreatic resection. Methods: This is a nationwide stepped-wedge, cluster-randomized, superiority trial, designed in adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines. During a period of 22 months, all Dutch centers performing pancreatic surgery will cross over in a randomized order from current practice to best practice according to the algorithm. This evidence-based and consensus-based algorithm will provide daily multilevel advice on the management of patients after pancreatic resection (i.e. indication for abdominal imaging, antibiotic treatment, percutaneous drainage and removal of abdominal drains). The algorithm is designed to aid early detection and minimally invasive step-up management of postoperative pancreatic fistula. Outcomes of current practice will be compared with outcomes after implementation of the algorithm. The primary outcome is a composite of major complications (i.e. post-pancreatectomy bleeding, new-onset organ failure and death) and will be measured in a sample size of at least 1600 patients undergoing pancreatic resection. Secondary endpoints include the individual components of the primary endpoint and other clinical outcomes, healthcare resource utilization and costs analysis. Follow up will be up to 90 days after pancreatic resection. Discussion: It is hypothesized that a structured nationwide implementation of a dedicated algorithm for early detection and minimally invasive step-up management of postoperative pancreatic fistula will reduce the risk of major complications and death after pancreatic resection, as compared to current practice. Trial registration: Netherlands Trial Register: NL 6671. Registered on 16 December 2017

Care after pancreatic resection according to an algorithm for early detection and minimally invasive management of pancreatic fistula versus current practice (PORSCH-trial): design and rationale of a nationwide stepped-wedge cluster-randomized trial

BACKGROUND: Pancreatic resection is a major abdominal operation with 50% risk of postoperative complications. A common complication is pancreatic fistula, which may have severe clinical consequences such as postoperative bleeding, organ failure and death. The objective of this study is to investigate whether implementation of an algorithm for early detection and minimally invasive management of pancreatic fistula may improve outcomes after pancreatic resection. METHODS: This is a nationwide stepped-wedge, cluster-randomized, superiority trial, designed in adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines. During a period of 22 months, all Dutch centers performing pancreatic surgery will cross over in a randomized order from current practice to best practice according to the algorithm. This evidence-based and consensus-based algorithm will provide da