Ectrodactyly and lethal pulmonary acinar dysplasia associated with homozygous FGFR2 mutations identified by exome sequencing

First published: 11 July 2016Abstract not availableChristopher P. Barnett, Nathalie J. Nataren, Manuela Klingler-Hoffmann, Quenten Schwarz, Chan-Eng Chong, Young K. Lee, Damien L. Bruno, Jill Lipsett, Andrew J. McPhee, Andreas W. Schreiber, Jinghua Feng, Christopher N. Hahn, and Hamish S. Scot

Effect of treatment of gestational diabetes mellitus on pregnancy outcomes

Copyright © 2005 Massachusetts Medical Society.Background: We conducted a randomized clinical trial to determine whether treatment of women with gestational diabetes mellitus reduced the risk of perinatal complications. Methods: We randomly assigned women between 24 and 34 weeks’ gestation who had gestational diabetes to receive dietary advice, blood glucose monitoring, and insulin therapy as needed (the intervention group) or routine care. Primary outcomes included serious perinatal complications (defined as death, shoulder dystocia, bone fracture, and nerve palsy), admission to the neonatal nursery, jaundice requiring phototherapy, induction of labor, cesarean birth, and maternal anxiety, depression, and health status. Results: The rate of serious perinatal complications was significantly lower among the infants of the 490 women in the intervention group than among the infants of the 510 women in the routine-care group (1 percent vs. 4 percent; relative risk adjusted for maternal age, race or ethnic group, and parity, 0.33; 95 percent confidence interval, 0.14 to 0.75; P=0.01). However, more infants of women in the intervention group were admitted to the neonatal nursery (71 percent vs. 61 percent; adjusted relative risk, 1.13; 95 percent confidence interval, 1.03 to 1.23; P=0.01). Women in the intervention group had a higher rate of induction of labor than the women in the routine-care group (39 percent vs. 29 percent; adjusted relative risk, 1.36; 95 percent confidence interval, 1.15 to 1.62; P<0.001), although the rates of cesarean delivery were similar (31 percent and 32 percent, respectively; adjusted relative risk, 0.97; 95 percent confidence interval, 0.81 to 1.16; P=0.73). At three months post partum, data on the women’s mood and quality of life, available for 573 women, revealed lower rates of depression and higher scores, consistent with improved health status, in the intervention group. Conclusions: Treatment of gestational diabetes reduces serious perinatal morbidity and may also improve the woman’s health-related quality of life.Caroline A. Crowther, Janet E. Hiller, John R. Moss, Andrew J. McPhee, William S. Jeffries and Jeffrey S. Robinso

Polymeric peptide pigments with sequence-encoded properties

Melanins are a family of heterogeneous polymeric pigments that provide ultraviolet (UV) light protection, structural support, coloration, and free radical scavenging. Formed by oxidative oligomerization of catecholic small molecules, the physical properties of melanins are influenced by covalent and noncovalent disorder. We report the use of tyrosine-containing tripeptides as tunable precursors for polymeric pigments. In these structures, phenols are presented in a (supra-)molecular context dictated by the positions of the amino acids in the peptide sequence. Oxidative polymerization can be tuned in a sequence-dependent manner, resulting in peptide sequence–encoded properties such as UV absorbance, morphology, coloration, and electrochemical properties over a considerable range. Short peptides have low barriers to application and can be easily scaled, suggesting near-term applications in cosmetics and biomedicine

The GBT 350-MHz Drift Scan Pulsar Survey. III. Detection of a magnetic field in the eclipsing material of PSR J2256-1024

We present the first measurement of a non-zero magnetic field in the eclipsing material of a black widow pulsar. Black widows are millisecond pulsars which are ablating their companions; therefore they are often proposed as one potential source of isolated millisecond pulsars. PSR J2256-1024 is an eclipsing black widow discovered at radio wavelengths and later also observed in the X-ray and gamma parts of the spectrum. Here we present the radio timing solution for PSR J2256-1024, polarization profiles at 350, 820, and 1500~MHz and an investigation of changes in the polarization profile due to eclipsing material in the system. In the latter we find evidence of Faraday rotation in the linear polarization shortly after eclipse, measuring a rotation measure of 0.44(6) rad per meter squared and a corresponding line-of-sight magnetic field of 3.5(17) mG.Comment: 14 pages, 8 figure

Neurodevelopmental outcomes at 7 years’ corrected age in preterm infants who were fed high-dose docosahexaenoic acid to term equivalent: a follow-up of a randomised controlled trial

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work noncommercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http:// creativecommons.org/licenses/by-nc/4.0/OBJECTIVE: To determine if improvements in cognitive outcome detected at 18 months' corrected age (CA) in infants born <33 weeks' gestation receiving a high-docosahexaenoic acid (DHA) compared with standard-DHA diet were sustained in early childhood. DESIGN: Follow-up of a multicentre randomised controlled trial. Randomisation was stratified for sex, birth weight (<1250 vs ≥1250 g) and hospital. SETTING: Five Australian tertiary hospitals from 2008 to 2013. PARTICIPANTS: 626 of the 657 participants randomised between 2001 and 2005 were eligible to participate. INTERVENTIONS: High-DHA (≈1% total fatty acids) enteral feeds compared with standard-DHA (≈0.3% total fatty acids) from age 2-4 days until term CA. PRIMARY OUTCOME: Full Scale IQ of the Wechsler Abbreviated Scale of Intelligence (WASI) at 7 years CA. Prespecified subgroup analyses based on the randomisation strata (sex, birth weight) were conducted. RESULTS: 604 (92% of the 657 originally randomised) consented to participate (291 high-DHA, 313 standard-DHA). To address missing data in the 604 consenting participants (22 for primary outcome), multiple imputation was performed. The Full Scale IQ was not significantly different between groups (high-DHA 98.3, SD 14.0, standard-DHA 98.5, SD 14.9; mean difference adjusted for sex, birthweight strata and hospital -0.3, 95% CI -2.9 to 2.2; p=0.79). There were no significant differences in any secondary outcomes. In prespecified subgroup analyses, there was a significant sex by treatment interaction on measures of parent-reported executive function and behaviour. Scores were within the normal range but girls receiving the high-DHA diet scored significantly higher (poorer outcome) compared with girls receiving the standard-DHA diet. CONCLUSIONS: Supplementing the diets of preterm infants with a DHA dose of approximately 1% total fatty acids from days 2-4 until term CA showed no evidence of benefit at 7 years' CA. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry: ACTRN12606000327583

Challenging the 'New Professionalism': from managerialism to pedagogy?

In recent years there have been changes made to the conceptualisation of continuing professional development for teachers in both the Scottish and English systems of education. These changes have been instigated by successive UK governments (and more recently, by the Scottish Executive), together with the General teaching Council for Scotland (GTCS) and the General Teaching Council for England (GTCE). This paper argues that these changes have not provided a clear rationale for CPD, but instead have introduced tensions between the concept of teacher education and that of training. The need for a less confused understanding of CPD and its purposes is underlined, as is the need for school based approaches to continuing teacher education. Arguably, teacher education must move from technicist emphases to a model which integrates the social processes of change within society and schools with the individual development and empowerment of teachers

Daclatasvir in combination with asunaprevir and beclabuvir for hepatitis C virus genotype 1 infection with compensated cirrhosis

Importance Effective and well-tolerated, interferon-free regimens are needed for treatment of patients with chronic hepatitis C virus (HCV) infection and cirrhosis. Objective All-oral therapy with daclatasvir (nonstructural protein 5A [NS5A] inhibitor), asunaprevir (NS3 protease inhibitor), and beclabuvir (nonnucleoside NS5B inhibitor), with or without ribavirin, was evaluated in patients with HCV genotype 1 infection and compensated cirrhosis. Design, Setting, and Participants The UNITY-2 study was conducted between December 2013 and October 2014 at 49 outpatient sites in the United States, Canada, France, and Australia. Patients were treated for 12 weeks, with 24 weeks of follow-up after completion of treatment. Adult patients with cirrhosis were enrolled in 2 cohorts: HCV treatment-naive or HCV treatment-experienced. Statistical analyses were based on historical controls; there were no internal controls. Interventions All patients received twice-daily treatment with the fixed-dose combination of daclatasvir (30 mg), asunaprevir (200 mg), and beclabuvir (75 mg). In addition, patients within each cohort were stratified according to HCV genotype 1 subtype (1a or 1b) and randomly assigned (1:1) to receive double-blinded weight-based ribavirin (1000-1200 mg/d) or matching placebo. Main Outcomes and Measures Sustained virologic response at posttreatment week 12 (SVR12). Results One hundred twelve patients in the treatment-naive group and 90 patients in the treatment-experienced group were treated and included in the analysis. Enrolled patients were 88% white with a median age of 58 years (treatment-naive group) or 60 years (treatment-experienced group); 74% had genotype 1a infection. SVR12 rates were 98% (97.5% CI, 88.9%-100%) for patients in the treatment-naive group and 93% (97.5% CI, 85.0%-100.0%) for those in the treatment-experienced group when ribavirin was included in the regimen. With the fixed-dose combination alone, response rates were 93% (97.5% CI, 85.4%-100.0%) for patients in the treatment-naive group and 87% (97.5% CI, 75.3%-98.0%) for those in the treatment-experienced group. Three serious adverse events were considered to be treatment related and there were 4 adverse event–related discontinuations. Treatment-emergent grade 3 or 4 alanine aminotransferase elevations were observed in 4 patients, of which 1 had concomitant total bilirubin elevation. Conclusions and Relevance In this open-label uncontrolled study, patients with chronic HCV genotype 1 infection and cirrhosis who received a 12-week oral fixed-dose regimen of daclatasvir, asunaprevir, and beclabuvir, with or without ribavirin, achieved high rates of SVR12

The N3RO trial: a randomised controlled trial of docosahexaenoic acid to reduce bronchopulmonary dysplasia in preterm infants < 29 weeks’ gestation

Background: Bronchopulmonary dysplasia (BPD) is a major cause of mortality and long-term respiratory and neurological morbidity in very preterm infants. While survival rates of very preterm infants have increased over the past two decades there has been no decrease in the rate of BPD in surviving infants. Evidence from animal and human studies has suggested potential benefits of docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid, in the prevention of chronic lung disease. This randomised controlled trial aims to determine the effectiveness of supplementary DHA in reducing the rate of BPD in infants less than 29 weeks’ gestation. Methods/design: This is a multicentre, parallel group, randomised, blinded and controlled trial. Infants born less than 29 weeks’ gestation, within 3 days of first enteral feed and with parent informed consent are eligible to participate. Infants will be randomised to receive an enteral emulsion containing DHA or a control emulsion without DHA. The DHA emulsion will provide 60 mg/kg/day of DHA. The study emulsions will continue to 36 weeks’ postmenstrual age (PMA). The primary outcome is BPD as assessed by the requirement for supplemental oxygen and/or assisted ventilation at 36 weeks’ PMA. Secondary outcomes include the composite of death or BPD; duration of respiratory support and hospitalisation, major neonatal morbidities. The target sample size is 1244 infants (622 per group), which will provide 90 % power to detect a clinically meaningful absolute reduction of 10 % in the incidence of BPD between the DHA and control emulsion (two tailed α =0.05). Discussion: DHA supplementation has the potential to reduce respiratory morbidity in very preterm infants. This multicentre trial will provide evidence on whether an enteral DHA supplement reduces BPD in very preterm infants