The Language Profile of Preschool Children With 22q11.2 Deletion Syndrome and the Relationship With Speech Intelligibility

Purpose: Young children with 22q11.2 deletion syndrome (22q11DS) often have impaired language development and poor speech intelligibility. Here, we report a comprehensive overview of standardized language assessment in a relatively large sample of preschool-aged children with 22q11DS. We furthermore explored whether speech ability explained variability in language skills. Method: Forty-four monolingual Dutch preschoolers (3–6 years) with a confirmed genetic 22q11DS diagnosis participated in this prospective cohort study. Standardized tests (Clinical Evaluation of Language Fundamentals Preschool-2-NL and Peabody Picture Vocabulary Test-III-NL) were administered. Speech intelligibility was rated by two expert speech and language therapists using a standardized procedure. Results: Most children had impaired language skills across all tested domains. The composite score for expressive language was significantly lower than that for receptive language, but the two were strongly correlated. Only small differences between the mean scores on the various subtests were observed, with the lowest scores for expressive morphosyntactic skills. Language scores showed a moderate positive relation with speech intelligibility, but language abilities varied greatly among the children with intelligible speech. Conclusions: We show that the majority of preschool children with 22q11DS have a broad range of language problems. Other than the relatively larger impairment in expressive than in receptive language skills, our results do not show a clearly delineated language profile. As many of the children with intelligible speech still had below-average language scores, we highlight that language problems require a broad assessment and care in all young children with 22q11DS. Future research using spontaneous language and detailed speech analysis is recommended, to provide more in-depth understanding of children's language profile and the relationship between speech and language in 22q11DS

Five-year safety and efficacy of leadless pacemakers in a Dutch cohort

BACKGROUND: Adequate real-world safety and efficacy of leadless pacemakers (LPs) have been demonstrated up to 3 years after implantation. Longer-term data are warranted to assess the net clinical benefit of leadless pacing.OBJECTIVE: The purpose of this study was to evaluate the long-term safety and efficacy of LP therapy in a real-world cohort.METHODS: In this retrospective cohort study, all consecutive patients with a first LP implantation from December 21, 2012, to December 13, 2016, in 6 Dutch high-volume centers were included. The primary safety endpoint was the rate of major procedure- or device-related complications (ie, requiring surgery) at 5-year follow-up. Analyses were performed with and without Nanostim battery advisory-related complications. The primary efficacy endpoint was the percentage of patients with a pacing capture threshold ≤2.0 V at implantation and without ≥1.5-V increase at the last follow-up visit.RESULTS: A total of 179 patients were included (mean age 79 ± 9 years), 93 (52%) with a Nanostim and 86 (48%) with a Micra VR LP. Mean follow-up duration was 44 ± 26 months. Forty-one major complications occurred, of which 7 were not advisory related. The 5-year major complication rate was 4% without advisory-related complications and 27% including advisory-related complications. No advisory-related major complications occurred a median 10 days (range 0-88 days) postimplantation. The pacing capture threshold was low in 163 of 167 patients (98%) and stable in 157 of 160 (98%).CONCLUSION: The long-term major complication rate without advisory-related complications was low with LPs. No complications occurred after the acute phase and no infections occurred, which may be a specific benefit of LPs. The performance was adequate with a stable pacing capture threshold.</p

Subsequent Event Risk in Individuals with Established Coronary Heart Disease:Design and Rationale of the GENIUS-CHD Consortium

BACKGROUND: The "GENetIcs of sUbSequent Coronary Heart Disease" (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185,614 participants with either acute coronary syndrome, stable CHD or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with duration of follow up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (HR 1.15 95% CI 1.14-1.16) per 5-year increase, male sex (HR 1.17, 95% CI 1.13-1.21) and smoking (HR 1.43, 95% CI 1.35-1.51) with risk of subsequent CHD death or myocardial infarction, and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and non-genetic determinants of subsequent event risk in individuals with established CHD, in order to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Measurement of charged jet production cross sections and nuclear modification in p-Pb collisions at root s(NN)=5.02 TeV

Charged jet production cross sections in p-Pb collisions at root s(NN) = 5.02 TeV measured with the ALICE detector at the LHC are presented. Using the anti-k(T) algorithm, jets have been reconstructed in the central rapidity region from charged particles with resolution parameters R = 0.2 and R = 0.4. The reconstructed jets have been corrected for detector effects and the underlying event background. To calculate the nuclear modification factor, R-pPb, of charged jets in p-Pb collisions, a pp reference was constructed by scaling previously measured charged jet spectra at root s = 7 TeV. In the transverse momentum range 20Peer reviewe