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

Miniforceps EBUS-guided lymph node biopsy: impact on diagnostic yield

Introduction: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the standard diagnostic method for sampling mediastinal and hilar lymph nodes. Non-diagnostic samples have led some pulmonologists to add a miniforceps biopsy (EBUS-TBFB) in order to increase diagnostic yield. Our study aims to analyze the impact of adding EBUS-TBFB to the EBUS-TBNA in cases where Rapid On-site Evaluation (ROSE) was negative for malignancy or was non-diagnostic.Material and methods: This retrospective chart review included 91 patients who were aged 18–90 years old and underwent EBUS with both TBNA and TBFB between January 1, 2013 and July 1, 2018.Results: There was no significant statistical difference in the diagnostic yield of TBNA vs TBFB with a McNemar value of 0.167, and this conclusion was the same when stratified by race, age and lymph node size. Using TBNA as a gold standard, the sensitivity and specificity of TBFB was 87% and 69%, respectively. Out of the non-diagnostic TBNA samples on ROSE and cell-block, subsequent TBFB resulted in additional pathologic diagnoses in 16% of cases, of which 67% were non-caseating granulomas. Furthermore, two additional malignant cases were identified by TBFB consisting of small cell carcinoma and non-Hodgkin’s lymphoma.Conclusion: In conclusion, TBFB is a useful adjunctive tool in the diagnosis of non-malignant conditions (i.e. granulomatous diseases) with the potential to spare the patient from more invasive surgical biopsies. Training of future fellows in performing TBFB in addition to TBNA should be strongly encouraged

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

Silencing of the FTO gene inhibits insulin secretion : An in vitro study using GRINCH cells

Expression of fat mass and obesity-associated gene (FTO) and ADP-ribosylation factor-like 15 (ARL15) in human islets is inversely correlated with HbA(1c). However, their impact on insulin secretion is still ambiguous. Here in, we investigated the role of FTO and ARL15 using GRINCH (Glucose-Responsive Insulin-secreting C-peptide-modified Human proinsulin) clonal rat beta-cells. GRINCH cells have inserted GFP into the human C-peptide insulin gene. Hence, secreted CpepGFP served to monitor insulin secretion. mRNA silencing of FTO in GRINCH cells showed a significant reduction in glucose but not depolarization-stimulated insulin secretion, whereas ARL15 silencing had no effect. A significant down-regulation of insulin mRNA was observed in FTO knockdown cells. Type-2 Diabetic islets revealed a reduced expression of FTO mRNA. In conclusion, our data suggest that fluorescent CpepGFP released from GRINCH cells may serve as a convenient marker for insulin secretion. Silencing of FTO expression, but not ARL15, inhibits insulin secretion by affecting metabolic signaling.Peer reviewe

Effectiveness of life skills training on increasing self-esteem of high school students

AbstractObjective This study designed to investigate effectiveness of training life skills on adolescents’ students. Method This study is a pseudo-experimental study which accomplished on 160 students in Karaj city. Subjects of the study selected randomly from list of students in all of the schools of Karaj; then they divided randomly in two groups. Trained counsellors taught the life skills to students of the study group, and 80 reminder subjects assigned as control group. After educating the training program, subjects administered Cooper Smith self-esteem questionnaire (58-items version). Results Findings of the study indicated that life skills training lead to significant increase of self-esteem in study group in contrast to control group subjects. Conclusion Psycho education and mental health programs such as life skills training could cause to increase the necessary skills in students and decline school and educational problems

The Sensitivity and Specificity of Loop-Mediated Isothermal Amplification (LAMP) Assay for Tuberculosis Diagnosis in Adults with Chronic Cough in Malawi.

BACKGROUND: Current tuberculosis diagnostics lack sensitivity, and are expensive. Highly accurate, rapid and cheaper diagnostic tests are required for point of care use in low resource settings with high HIV prevalence. OBJECTIVE: To investigate the sensitivity and specificity, and cost of loop-mediated isothermal amplification (LAMP) assay for tuberculosis diagnosis in adults with chronic cough compared to Xpert® MTB/RIF, fluorescence smear microscopy. METHODS: Between October 2013 and March 2014, consecutive adults at a primary care clinic were screened for cough, offered HIV testing and assessed for tuberculosis using LAMP, Xpert® MTB/RIF and fluorescence smear microscopy. Sensitivity and specificity (with culture as reference standard), and costs were estimated. RESULTS: Of 273 adults recruited, 44.3% (121/273) were HIV-positive and 19.4% (53/273) had bacteriogically confirmed tuberculosis. The sensitivity of LAMP compared to culture was 65.0% (95% CI: 48.3% to 79.4%) with 100% (95% CI: 98.0% to 100%) specificity. The sensitivity of Xpert® MTB/RIF (77.5%, 95% CI: 61.5% to 89.2%) was similar to that of LAMP, p = 0.132. The sensitivity of concentrated fluorescence smear microscopy with routine double reading (87.5%, 95% CI: 73.2% to 95.8%) was higher than that of LAMP, p = 0.020. All three tests had high specificity. The lowest cost per test of LAMP was at batch size of 14 samples (US$9.98); this was lower than Xpert® MTB/RIF (US$ 13.38) but higher than fluorescence smear microscopy (US$ 0.65). CONCLUSION: The sensitivity of LAMP was similar to Xpert® MTB/RIF but lower than fluorescence smear microscopy; all three tests had high specificity. These findings support the Malawi policy that recommends a combination of fluorescence smear microscopy and Xpert® MTB/RIF prioritised for people living with HIV, already found to be smear-negative, or being considered for retreatment of tuberculosis

Withdrawal from escalated cocaine self-administration impairs reversal learning by disrupting the effects of negative feedback on reward exploitation: a behavioral and computational analysis.

Addiction is regarded as a disorder of inflexible choice with behavior dominated by immediate positive rewards over longer-term negative outcomes. However, the psychological mechanisms underlying the effects of self-administered drugs on behavioral flexibility are not well understood. To investigate whether drug exposure causes asymmetric effects on positive and negative outcomes we used a reversal learning procedure to assess how reward contingencies are utilized to guide behavior in rats previously exposed to intravenous cocaine self-administration (SA). Twenty-four rats were screened for anxiety in an open field prior to acquisition of cocaine SA over six daily sessions with subsequent long-access cocaine SA for 7 days. Control rats (n = 24) were trained to lever-press for food under a yoked schedule of reinforcement. Higher rates of cocaine SA were predicted by increased anxiety and preceded impaired reversal learning, expressed by a decrease in lose-shift as opposed to win-stay probability. A model-free reinforcement learning algorithm revealed that rats with high, but not low cocaine escalation failed to exploit previous reward learning and were more likely to repeat the same response as the previous trial. Eight-day withdrawal from high cocaine escalation was associated, respectively, with increased and decreased dopamine receptor D2 (DRD2) and serotonin receptor 2C (HTR2C) expression in the ventral striatum compared with controls. Dopamine receptor D1 (DRD1) expression was also significantly reduced in the orbitofrontal cortex of high cocaine-escalating rats. These findings indicate that withdrawal from escalated cocaine SA disrupts how negative feedback is used to guide goal-directed behavior for natural reinforcers and that trait anxiety may be a latent variable underlying this interaction.Pinsent Darwin Studentship, Cambridge University Swedish Research Council AXA Research Fund National Health and MRC of Australia Cambridge Isaac Newton Trust Boehringer Ingelheim Pharma GmbH, German

Correction: Withdrawal from escalated cocaine self-administration impairs reversal learning by disrupting the effects of negative feedback on reward exploitation: a behavioral and computational analysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper