Tract-Based Spatial Statistics in Preterm-Born Neonates Predicts Cognitive and Motor Outcomes at 18 Months.

BACKGROUND AND PURPOSE: Adverse neurodevelopmental outcome is common in children born preterm. Early sensitive predictors of neurodevelopmental outcome such as MR imaging are needed. Tract-based spatial statistics, a diffusion MR imaging analysis method, performed at term-equivalent age (40 weeks) is a promising predictor of neurodevelopmental outcomes in children born very preterm. We sought to determine the association of tract-based spatial statistics findings before term-equivalent age with neurodevelopmental outcome at 18-months corrected age. MATERIALS AND METHODS: Of 180 neonates (born at 24-32-weeks\u27 gestation) enrolled, 153 had DTI acquired early at 32 weeks\u27 postmenstrual age and 105 had DTI acquired later at 39.6 weeks\u27 postmenstrual age. Voxelwise statistics were calculated by performing tract-based spatial statistics on DTI that was aligned to age-appropriate templates. At 18-month corrected age, 166 neonates underwent neurodevelopmental assessment by using the Bayley Scales of Infant Development, 3rd ed, and the Peabody Developmental Motor Scales, 2nd ed. RESULTS: Tract-based spatial statistics analysis applied to early-acquired scans (postmenstrual age of 30-33 weeks) indicated a limited significant positive association between motor skills and axial diffusivity and radial diffusivity values in the corpus callosum, internal and external/extreme capsules, and midbrain (P \u3c .05, corrected). In contrast, for term scans (postmenstrual age of 37-41 weeks), tract-based spatial statistics analysis showed a significant relationship between both motor and cognitive scores with fractional anisotropy in the corpus callosum and corticospinal tracts (P \u3c .05, corrected). Tract-based spatial statistics in a limited subset of neonates (n = 22) scanned at CONCLUSIONS: The strength of the association between fractional anisotropy values and neurodevelopmental outcome scores increased from early-to-late-acquired scans in preterm-born neonates, consistent with brain dysmaturation in this population

Targeted next generation sequencing of pancreatic solid pseudopapillary neoplasms show mutations in Wnt signaling pathway genes.

Solid pseudopapillary neoplasms of the pancreas are rare neoplasms that have been shown to harbor recurrent somatic pathogenic variants in the beta-catenin gene, CTNNB1. Here, we used targeted next generation sequencing to analyze these tumors for other associated mutations. Six cases of solid pseudopapillary neoplasms were studied. DNA extracted from formalin-fixed paraffin embedded tissue blocks was analyzed using the Ion Torrent platform, with the 50-gene Ampliseq Cancer Hotspot Panel v2 (CHPv2), with further variant validation performed by Sanger sequencing. Four tumors (67%) were confirmed to harbor mutations within CTNNB1, two with c.109T > G p.(Ser37Ala) and two with c.94G > A p.(Asp32Asn). One case showed a frameshift deletion in the Adenomatous Polyposis Coli gene, APC c.3964delG p.(Glu1322Lysfs*93) with a variant allele frequency of 42.6%. Sanger sequencing on non-tumoral tissue confirmed the variant was somatic. The patient with the APC mutation developed metastasis and died. In addition to the four cases harboring CTNNB1 variants, we found a case characterized by poor outcome, showing a rare frameshift deletion in the APC gene. Since the APC product interacts with beta-catenin, APC variants may, in addition to CTNNB1, contribute to the pathogenesis of solid pseudopapillary neoplasms via the Wnt signaling pathway

Brain Injury Patterns in Hypoglycemia in Neonatal Encephalopathy

ABSTRACT BACKGROUND AND PURPOSE: Low glucose values are often seen in term infants with NE, including HIE, yet the contribution of hypoglycemia to the pattern of neurologic injury remains unclear. We hypothesized that MR features of neonatal hypoglycemia could be detected, superimposed on the predominant HIE injury pattern

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials

Impacts of the 2014-2015 Holuhraun eruption on the UK atmosphere

Volcanic emissions, specifically from Iceland, pose a pan-European risk and are on the UK National Risk Register due to potential impacts on aviation, public health, agriculture, the environment and the economy, both from effusive and explosive activity. During the 2014-2015 fissure eruption at Holuhraun in Iceland, the UK atmosphere was significantly perturbed. This study focuses one major incursion in September 2014, affecting the surface concentrations of both aerosols and gases across the UK, with sites in Scotland experiencing the highest sulfur dioxide (SO2) concentrations. The perturbation event observed was confirmed to originate from the fissure eruption using satellite data from GOME2B and the chemical transport model, EMEP4UK, which was used to establish the spatial distribution of the plume over the UK during the event of interest. At the two UK European Monitoring and Evaluation Program (EMEP) supersite observatories (Auchencorth Moss, SE Scotland and Harwell, SE England) significant alterations in sulfate (SO42-) content of PM10 and PM2.5 during this event, concurrently with evidence of an increase in ultrafine aerosol, most likely due to nucleation and growth of aerosol within the plume, were observed. At Auchencorth Moss, higher hydrochloric acid (HCl) concentrations during the September event (max = 1.21 µg m-3, c.f annual average 0.12 µg m-3 35 in 2013), were assessed to be due to acid displacement of chloride (Cl-) from sea salt (NaCl) to form HCl gas rather than due to primary emissions of HCl from Holuhraun. The gas and aerosol partioning at Auchencorth moss of inorganic species by thermodynamic modelling, confirmed the observed partioning of HCl. Using the data from the chemical thermodynamic model, ISORROPIA-II, there is evidence that the background aerosol, which is typically basic at this site, became acidic with an estimated pH of 3.8 during the peak of the event. Volcano plume episodes were periodically observed by the majority of the UK air quality monitoring networks during the first 4 months of the eruption (August – December 2014), at both hourly and monthly resolution. In the low resolution networks, which provide monthly SO2 averages, concentrations were found to be significantly elevated at remote “clean” sites in NE Scotland and SW England, with record high SO2 concentrations for some sites in September 2014. For sites which are regularly influenced by anthropogenic emissions, taking into account the underlying trends, the eruption led to statistically unremarkable SO2 concentrations (return probabilities >0.1, ~10 months). However for a few sites, SO2 concentrations were clearly much higher than has been previously observed (return probability 3000 months). The Holuhraun Icelandic eruption has resulted in a unique study providing direct evidence of atmospheric chemistry perturbation of both gases and aerosols in the UK background atmosphere. The measurements can be used to both challenge and verify existing atmospheric chemistry of volcano plumes, especially those originating from effusive eruptions, which have been under-explored, due to limited observations available in the literature. If all European data sets were collated this would allow improved model verification and risk assessments for future volcanic eruptions of this type

Two New Loci for Body-Weight Regulation Identified in a Joint Analysis of Genome-Wide Association Studies for Early-Onset Extreme Obesity in French and German Study Groups

Meta-analyses of population-based genome-wide association studies (GWAS) in adults have recently led to the detection of new genetic loci for obesity. Here we aimed to discover additional obesity loci in extremely obese children and adolescents. We also investigated if these results generalize by estimating the effects of these obesity loci in adults and in population-based samples including both children and adults. We jointly analysed two GWAS of 2,258 individuals and followed-up the best, according to lowest p-values, 44 single nucleotide polymorphisms (SNP) from 21 genomic regions in 3,141 individuals. After this DISCOVERY step, we explored if the findings derived from the extremely obese children and adolescents (10 SNPs from 5 genomic regions) generalized to (i) the population level and (ii) to adults by genotyping another 31,182 individuals (GENERALIZATION step). Apart from previously identified FTO, MC4R, and TMEM18, we detected two new loci for obesity: one in SDCCAG8 (serologically defined colon cancer antigen 8 gene; p = 1.85610 x 10(-8) in the DISCOVERY step) and one between TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase gene) and MSRA (methionine sulfoxide reductase A gene; p = 4.84 x 10(-7)), the latter finding being limited to children and adolescents as demonstrated in the GENERALIZATION step. The odds ratios for early-onset obesity were estimated at similar to 1.10 per risk allele for both loci. Interestingly, the TNKS/MSRA locus has recently been found to be associated with adult waist circumference. In summary, we have completed a meta-analysis of two GWAS which both focus on extremely obese children and adolescents and replicated our findings in a large followed-up data set. We observed that genetic variants in or near FTO, MC4R, TMEM18, SDCCAG8, and TNKS/MSRA were robustly associated with early-onset obesity. We conclude that the currently known major common variants related to obesity overlap to a substantial degree between children and adults

Drivers for spatial, temporal and long-term trends in atmospheric ammonia and ammonium in the UK

A unique long-term dataset from the UK National Ammonia Monitoring Network (NAMN) is used here to assess spatial, seasonal and long-term variability in atmospheric ammonia (NH3: 1998–2014) and particulate ammonium(NH4+: 1999–2014) across the UK. Extensive spatial heterogeneity in NH3 concentrations is observed, with lowest annual mean concentrations at remote sites (< 0.2 μg m-3 and highest in the areas with intensive agriculture (up to 22 μg m-3), while NH4+ concentrations show less spatial variability (e.g. range of 0.14 to 1.8 μg m-3 annual mean in 2005). Temporally, NH3 concentrations are influenced by environmental conditions and local emission sources. In particular, peak NH3 concentrations are observed in summer at background sites (defined by 5 km grid average NH3 emissions < 1 kg N ha-1 yr-1 and in areas dominated by sheep farming, driven by increased volatilization of NH3 in warmer summer temperatures. In areas where cattle, pig and poultry farming is dominant, the largest NH3 concentrations are in spring and autumn, matching periods of manure application to fields. By contrast, peak concentrations of NH4+ aerosol occur in spring, associated with long-range transboundary sources. An estimated decrease in NH3 emissions by 16%between 1998 and 2014 was reported by the UK National Atmospheric Emissions Inventory. Annually averaged NH3 data from NAMN sites operational over the same period (n=59)show an indicative downward trend, although the reduction in NH3 concentrations is smaller and non-significant: Mann–Kendall (MK), -6.3 %; linear regression(LR), -3.1 %. In areas dominated by pig and poultry farming, a significant reduction in NH3 concentrations between 1998 and 2014 (MK: -22 %; LR: -21 %, annually averaged NH3/ is consistent with, but not as large as the decrease in estimated NH3 emissions from this sector over the same period (-39 %). By contrast, in cattle-dominated areas there is a slight upward trend (non-significant) in NH3 concentrations (MK: +12 %; LR: +3.6 %, annually averaged NH3, despite the estimated decline in NH3 emissions from this sector since 1998 (-11 %). At background and sheep-dominated sites, NH3 concentrations increased over the monitoring period. These increases (non-significant) at background (MK: C17 %; LR: C13 %, annually averaged data) and sheep-dominated sites (MK: +15 %; LR: +19 %, annually averaged data) would be consistent with the concomitant reduction in SO2 emissions over the same period, leading to a longer atmospheric lifetime of NH3, thereby increasing NH3 concentrations in remote areas. The observations for NH3 concentrations not decreasing as fast as estimated emission trends are consistent with a larger downward trend in annual particulate NH4+ concentrations (1999–2014: MK: -47 %; LR: -49 %, p < 0.01, n=23), associated with a lower formation of particulate NH4+ in the atmosphere from gas phase NH3

Television viewing, food preferences, and food habits among children: A prospective epidemiological study

<p>Abstract</p> <p>Background</p> <p>Obesity has increased since the early 1980s, and despite numerous attempts, effective strategies to counter this worldwide epidemic are lacking. Food preferences are established early in life and are difficult to change later. There is therefore a need to identify factors that influence the development of food preferences. Our aim was therefore, to investigate cross-sectional and prospective associations between TV viewing habits and food preferences and habits, respectively. We hypothesized that more TV viewing was associated with less healthy concomitant and future food preferences and food habits.</p> <p>Methods</p> <p>Data are from the Danish part of European Youth Heart Study (EYHS) I and II, a prospective cohort study conducted among 8-10-year-old and 14-16-year-old Danes in 1997-98. Six years later 2003-04 the 8-10-year-olds were followed up at age 14-16 years, and a new group of 8-10-year olds were included. Data were analysed using mixed linear regression analysis. Cross-sectional analyses included 697 8-10-year-olds and 495 14-16-year-olds. Prospective analyses included 232 pupils with complete data at baseline and follow-up. Associations between TV viewing habits and the sum of healthy food preferences (ΣHFP), and the sum of healthy food habits (ΣHFH), respectively, were examined.</p> <p>Results</p> <p>Inverse cross-sectional associations between TV viewing (h/day) and both ΣHFP and ΣHFH were present for both the 8-10-year-old and the 14-16-year-old boys and girls. The frequency of meals in front of the TV (times/week) was also inversely associated with ΣHFP among 8-10-year-old boys, and with ΣHFH in all sex- and age groups. Among girls, baseline TV viewing (h/day) was directly associated with adverse development in the ΣHFP during follow-up. The concomitant 6-year changes in ΣHFH and TV viewing (h/day) were inversely associated in boys.</p> <p>Conclusions</p> <p>Long time spent on TV viewing, and possibly to a lesser degree, frequent consumption of meals during TV viewing, seem to be associated with generally having unhealthy food preferences and food habits among school-aged children. These associations, however, were not generally persistent after 6 years of follow-up.</p