Complete genome sequences of six measles virus strains

Genetic characterization of wild-type measles virus (MV) strains is a critical component of measles surveillance and molecular epidemiology. We have obtained complete genome sequences of six MV strains belonging to different genotypes, using random-primed next generation sequencing

Fundamental Physical Constants: Looking from Different Angles

We consider fundamental physical constants which are among a few of the most important pieces of information we have learned about Nature after its intensive centuries-long studies. We discuss their multifunctional role in modern physics including problems related to the art of measurement, natural and practical units, origin of the constants, their possible calculability and variability etc

Neonatal critical illness and development: white matter and hippocampus alterations in school-age neonatal ECMO survivors

Aim: Examine the neurobiology of long-term neuropsychological deficits following neonatal extracorporeal membrane oxygenation (ECMO). Method: This cross-sectional study assessed white matter integrity and hippocampal volume of ECMO survivors (8-15yrs) and healthy controls (8-17yrs) using Diffusion Tensor Imaging and structural MRI, respectively. Neuropsychological outcome was evaluated in patients. Included clinical predictors of white matter integrity: age start ECMO, ECMO duration, highest oxygenation index before ECMO, highest mean airway pressure and mechanical ventilation duration. Results: Patients (n=23) had lower global fractional anisotropy than controls (n=54)(patients=.368; controls=.381; p=.02), but similar global mean diffusivity (p=.41). Patients had lower fractional anisotropy in the left cingulum bundle (patients=.345; controls=.399; p<.001) and higher mean diffusivity in a region of the left parahippocampal cingulum (patients=.916; controls=.871; p<.001). Higher global mean diffusivity predicted worse verbal memory in patients (n=17)(β=-.74, p=.01). Patients (n=23) had smaller bilateral hippocampal volume than controls (n=43)(left: p< .001; right: p< .001). In patients, this was related to worse verbal memory (left: β=.65, p=.02; right: β=.71, p=.01). Interpretation: Neonatal ECMO survivors are at risk for long-term brain alterations, which may partly explain long-term neuropsychological impairments. Neuroimaging may contribute to better risk stratification of long-term impairments

Long-term cognitive follow-up in children treated for Maroteaux-Lamy syndrome

Background: It remains unclear to what extent the brain is affected by Maroteaux-Lamy syndrome (MPS VI), a progressive lysosomal storage disorder. While enzyme replacement therapy (ERT) elicits positive effects, the drug cannot cross the blood–brain barrier. We therefore studied cognitive development and brain abnormalities in the Dutch MPS VI patient population treated with ERT. Methods: In a series of 11 children with MPS VI (age 2 to 20 years), we assessed cognitive functioning and brain magnetic resonance imaging prospectively at the start of ERT and at regular times thereafter up to 4.8 years. We also assessed the children’s clinical characteristics, their siblings’ cognitive development, and their parents’ educational levels. Results: The patients’ intelligence scores ranged from normal to mentally delayed (range test scores 52–131). In 90 %, their scores remained fairly stable during follow-up, generally lying in the same range as their siblings’ test scores (median for patients = 104, median for siblings = 88) and comparing well with the parental educational levels. Native-speaking patients had higher intelligence test scores than non-native-speaking patients. Two patients, both with high baseline glycosaminoglycan levels in their urine and severe mutations in the arylsulfatase B gene, scored clearly lower than expected. Patients with pY210C performed best. Brain abnormalities were aspecific, occurring more in patients with severe symptoms. Conclusion: Our study shows that cognitive development in MPS VI patients is determined not only by familial and social-background factors, but, in patients with a severe form of the disease, also by the disease itself. Therefore in patients with severe disease presentation cognition should be monitored carefully

A narrative analysis of career transition themes and outcomes using chaos theory as a guiding metaphor

In a rapidly changing world of work little research exists on mid-career transitions. We investigated these using the open-systems approach of chaos theory as a guiding metaphor and conducted interviews with seven mid-career individuals chosen for their experience of a significant mid-career transition. Four common themes were identified through narrative analysis, where ‘false starts’ to a career were a common experience prior to finding a career ‘fit’. Career transitions, precipitated by a trigger state and/or event such as a period of disillusionment, were an important part of this ‘finding a fit’ process. Overall, career success outcomes were shaped by a combination of chaos elements: chance, unplanned events, and non-linearity of resultant outcomes. We discuss implications for future research and for practice

Sensitivity Achieved by the LIGO and Virgo Gravitational Wave Detectors during LIGO's Sixth and Virgo's Second and Third Science Runs

See paper for full list of authors - Associated data products are publicly accessible here https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=63432We summarize the sensitivity achieved by the LIGO and Virgo gravitational wave detectors for low-mass compact binary coalescence (CBC) searches during LIGO's sixth science run and Virgo's second and third science runs. We present strain noise power spectral densities (PSDs) which are representative of the typical performance achieved by the detectors in these science runs. The data presented here and in the accompanying web-accessible data files are intended to be released to the public as a summary of detector performance for low-mass CBC searches during S6 and VSR2-3

Studies into the mechanism of measles-associated immune suppression during a measles outbreak in the Netherlands

Measles causes a transient immune suppression, leading to increased susceptibility to opportunistic infections. In experimentally infected non-human primates (NHPs) measles virus (MV) infects and depletes pre-existing memory lymphocytes, causing immune amnesia. A measles outbreak in the Dutch Orthodox Prote

Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appr

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk