International guidelines for the management and treatment of Morquio A syndrome.

Morquio A syndrome (mucopolysaccharidosis IVA) is a lysosomal storage disorder associated with skeletal and joint abnormalities and significant non-skeletal manifestations including respiratory disease, spinal cord compression, cardiac disease, impaired vision, hearing loss, and dental problems. The clinical presentation, onset, severity and progression rate of clinical manifestations of Morquio A syndrome vary widely between patients. Because of the heterogeneous and progressive nature of the disease, the management of patients with Morquio A syndrome is challenging and requires a multidisciplinary approach, involving an array of specialists. The current paper presents international guidelines for the evaluation, treatment and symptom-based management of Morquio A syndrome. These guidelines were developed during two expert meetings by an international panel of specialists in pediatrics, genetics, orthopedics, pulmonology, cardiology, and anesthesia with extensive experience in managing Morquio A syndrome

Quantification of massively parallel sequencing libraries - a comparative study of eight methods

Abstract Quantification of massively parallel sequencing libraries is important for acquisition of monoclonal beads or clusters prior to clonal amplification and to avoid large variations in library coverage when multiple samples are included in one sequencing analysis. No gold standard for quantification of libraries exists. We assessed eight methods of quantification of libraries by quantifying 54 amplicon, six capture, and six shotgun fragment libraries. Chemically synthesized double-stranded DNA was also quantified. Light spectrophotometry, i.e. NanoDrop, was found to give the highest concentration estimates followed by Qubit and electrophoresis-based instruments (Bioanalyzer, TapeStation, GX Touch, and Fragment Analyzer), while SYBR Green and TaqMan based qPCR assays gave the lowest estimates. qPCR gave more accurate predictions of sequencing coverage than Qubit and TapeStation did. Costs, time-consumption, workflow simplicity, and ability to quantify multiple samples are discussed. Technical specifications, advantages, and disadvantages of the various methods are pointed out

Mid-term results of a modified arterial switch operation using the direct reconstruction technique of the pulmonary artery

Background: There is ongoing discussion as to whether it is beneficial to avoid pulmonary sinus augmentation in the arterial switch operation. We report a single-surgeon series of mid-term results for direct pulmonary artery anastomosis during switch operation for transposition of the great arteries (TGA). Methods: This retrospective study includes 17 patients with TGA, combined with an atrial septal defect, patent foramen ovale or ventricular septal defect. Patient data was analyzed from hospital charts, including operative reports, post-operative course, and regular follow-up investigations. The protocol included cardiological examination by a single pediatric cardiologist. Echocardiographic examinations were performed immediately after arrival on the intensive unit, before discharge, and then after three, six, and 12 months, followed by yearly intervals. Pulmonary artery stenosis (PAS) was categorized into three groups according to the Doppler-measured pulmonary gradient: grade I (trivial stenosis) = increased pulmonary flow with a gradient below 25 mm Hg; grade II (moderate stenosis) = a gradient ranging from 25 to 49 mm Hg; and grade III (severe stenosis) = a gradient above 50 mm Hg. Follow-up data was available for all patients. The length of follow-up ranged from 1.2 to 9.7 years, median: 7.5 years (mean 6.1 years ± 14 months). Results: During follow-up, 12 patients (70.6%) had no (or only trivial) PAS, five patients (29.4%) had moderate stenosis without progress, and no patient had severe PAS. Cardiac catheterization after arterial switch operation was performed in 11 patients (64.7%) and showed a good correlation with echocardiographic findings. During follow-up there was no reintervention for PAS. Conclusions: Direct reconstruction of the neo-pulmonary artery is a good option in TGA with antero-posterior position of the great vessels, with very satisfactory mid-term results. (Cardiol J 2010; 17, 6: 574-579

Persistence of Nasopharyngeal Pneumococcal Vaccine Serotypes and Increase of Nonvaccine Serotypes Among Vaccinated Infants and Their Mothers 5 Years After Introduction of Pneumococcal Conjugate Vaccine 13 in The Gambia.

BACKGROUND: The widespread use of pneumococcal conjugate vaccine (PCV) has brought about a dramatic decrease in pneumococci of vaccine serotypes (VTs) but nonvaccine serotypes (NVTs) have emerged. METHODS: We conducted a cross-sectional survey (CSS) among infants who received 3 doses of 13-valent PCV (PCV13) and their mothers 5 years (CSS3) after PCV13 introduction. Nasopharyngeal swab samples were collected and cultured for isolation of Streptococcus pneumoniae. Whole-genome sequencing of the nontypeable strains was performed. Data were compared with those from 2 previous surveys conducted before PCV13 introduction (CSS1) and 1 year later (CSS2). RESULTS: Among infants, VT carriage decreased from 33.3% (113/339) in CSS1 to 11.4% (40/351) in CSS3 (P = .001) while NVTs increased from 53.1% (180/339) in CSS1 to 74.4% (261/351) in CSS3 (P < .001). Among mothers, there was a significant decrease in VTs between CSS2 8.4% (29/347) and CSS3 5.6% (19/342) (P = .006). NVTs increased from 16.6% (55/331) in CSS1 to 32.2% (110/342) in CSS3 (P < .001). In CSS3, the most prevalent VTs were 7F in infants and 3 in mothers, and the most prevalent NVTs were serogroup 16 and nontypeables, respectively. Genomic analysis showed that VTs were more likely than NVTs to lose their ability to express the capsule. CONCLUSIONS: Five years after PCV13 introduction, we show both direct (infants) and indirect effects (mothers) of the vaccine, while NVT replacement has occurred in both groups. Ongoing circulation of VTs warrants further study of their relevance in any consideration of a reduced dose schedule

Prevention of bacterial infections in the newborn by pre-delivery administration of azithromycin: Study protocol of a randomized efficacy trial.

BACKGROUND: Neonatal deaths, estimated at approximately 4 million annually, now account for almost 40% of global mortality in children aged under-five. Bacterial sepsis is a leading cause of neonatal mortality. Assuming the mother is the main source for bacterial transmission to newborns, the primary objective of the trial is to determine the impact of one oral dose of azithromycin, given to women in labour, on the newborn's bacterial carriage in the nasopharynx. Secondary objectives include the impact of the intervention on bacterial colonization in the baby and the mother during the first month of life. METHODS/DESIGN: This is a Phase III, double -blind, placebo controlled randomized clinical trial in which 830 women in labour were randomized to either a single dose of 2 g oral azithromycin or placebo (ratio 1:1). The trial included pregnant women in labour aged 18 to 45 years attending study health centres in the Western Gambia. A post-natal check of the mother and baby was conducted at the health centre by study clinicians before discharge and 8-10 days after delivery. Home follow up visits were conducted daily during the first week and then weekly until week 8 after delivery. Vaginal swabs and breast milk samples were collected from the mothers, and the pathogens Streptococcus pneumoniae, Group B Streptococcus (GBS) and Staphylococcus aureus were isolated from the study samples. For bacterial isolates, susceptibility pattern to azithromycin was determined using disk diffusion and E-test. Eye swabs were collected from newborns with eye discharge during the follow up period, and Chlamydial infection was assessed using molecular methods. DISCUSSION: This is a proof-of-concept study to assess the impact of antibiotic preventive treatment of women during labour on bacterial infections in the newborn. If the trial confirms this hypothesis, the next step will be to assess the impact of this intervention on neonatal sepsis. The proposed intervention should be easily implementable in developing countries. TRIAL REGISTRATION: ClinicalTrials.gov Identifier--NCT01800942--First received: February 26, 2013

Effect on nasopharyngeal pneumococcal carriage of replacing PCV7 with PCV13 in the Expanded Programme of Immunization in The Gambia.

INTRODUCTION: In 2011, two years after the introduction of 7-valent Pneumococcal conjugate vaccine (PCV7), the Gambian immunization programme replaced PVC7 with PCV13 (13-valent). Our objective was to assess the additional impact of PCV13 on prevalence of pneumococcal nasopharyngeal carriage. METHODS: We recruited healthy Gambian infants who had received three PCV doses. Nasopharyngeal swabs were collected from infants and their mothers during two cross-sectional surveys (CSS) conducted in infants vaccinated with PCV7 (CSS1) and vaccinated with PCV13 (CSS2). Pneumococci were isolated and serotyped following standardized methods. Whole genome sequencing was performed on non-typable pneumococcus isolated in CSS1 and CSS2. RESULTS: 339 and 350 infants and their mothers were recruited in CSS1 and CSS2, respectively. Overall prevalence of pneumococcal carriage was 85.4% in infants. Among infants, prevalence of vaccine type (VT) carriage was lower in CSS2 [9.4% versus 4.9% (p=0.025) for PCV7-VT; 33.3% versus 18.3% (p<0.001) for PCV13-VT and 23.9% versus 13.7% (p=0.001) for the 6 additional serotypes included in PCV13]. At CSS2, there was a decrease of serotypes 6A (from 15.3% to 5.7%, p<0.001) and 19F (from 5.6% to 1.7%, p=0.007), and an increase of non-typable pneumococci (0.3-6.0%, p<0.001), most of which (82.4%) were from typable serotype backgrounds that had lost the ability to express a capsule. Prevalence of overall and VT carriage in mothers was similar in CSS1 and CSS2. CONCLUSIONS: Replacing PCV7 for PCV13 rapidly decreased prevalence of VT carriage among vaccinated Gambian infants. An indirect effect in mothers was not observed yet. Vaccine-driven selection pressure may have been responsible for the increase of non-typable isolates

Reproducibility and Replicability of Web Measurement Studies

Web measurement studies can shed light on not yet fully understood phenomena and thus are essential for analyzing how the modern Web works. This often requires building new and adjusting existing crawling setups, which has led to a wide variety of analysis tools for different (but related) aspects. If these efforts are not sufficiently documented, the reproducibility and replicability of the measurements may suffer - two properties that are crucial to sustainable research. In this paper, we survey 117 recent research papers to derive best practices for Web-based measurement studies and specify criteria that need to be met in practice. When applying these criteria to the surveyed papers, we find that the experimental setup and other aspects essential to reproducing and replicating results are often missing. We underline the criticality of this finding by performing a large-scale Web measurement study on 4.5 million pages with 24 different measurement setups to demonstrate the influence of the individual criteria. Our experiments show that slight differences in the experimental setup directly affect the overall results and must be documented accurately and carefully

Measurement of Aerodynamically Induced Blade Distortion on a Shrouded Counter-Rotating Prop-Fan

Blade deformation on a 1 m diameter composite fan rotor is measured simultaneously using stereoscopic image pattern correlation technique (IPCT) and blade-tip imaging. Absolute referencing of the blades is made possible by simultaneously tracking a marker on the hub using a fourth camera. Illumination is provided by microsecond pulses of high-power LEDs. Rise and fall time in the 100ns regime are achieved using a self-designed high-current drive circuit. A high-speed microcontroller provides accurate, speed-independent angular delays to enable phase-locked triggering of cameras and LEDs. Mean and RMS deformation of the blade are acquired for different aerodynamic loading conditions induced by imposing a non-uniformity upstream of the rotor aimed at mimicking boundary layer ingestion