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The Pediatric Heart Network Normal Echocardiogram Database Study had unanticipated challenges. We sought to describe these challenges and lessons learned to improve the design of future studies.
Challenges were divided into three categories: enrolment, echocardiographic imaging, and protocol violations. Memoranda, Core Lab reports, and adjudication logs were reviewed. A centre-level questionnaire provided information regarding local processes for data collection. Descriptive statistics were used, and chi-square tests determined differences in imaging quality.
For the 19 participating centres, challenges with enrolment included variations in Institutional Review Board definitions of “retrospective” eligibility, overestimation of non-White participants, centre categorisation of Hispanic participants that differed from National Institutes of Health definitions, and exclusion of potential participants due to missing demographic data. Institutional Review Board amendments resolved many of these challenges. There was an unanticipated burden imposed on centres due to high numbers of echocardiograms that were reviewed but failed to meet submission criteria. Additionally, image transfer software malfunctions delayed Core Lab image review and feedback. Between the early and late study periods, the proportion of unacceptable echocardiograms submitted to the Core Lab decreased (14 versus 7%, p < 0.01). Most protocol violations were from eligibility violations and inadvertent protected health information disclosure (overall 2.5%). Adjudication committee reviews led to protocol changes.
Numerous challenges encountered during the Normal Echocardiogram Database Study prolonged study enrolment. The retrospective design and flaws in image transfer software were key impediments to study completion and should be considered when designing future studies collecting echocardiographic images as a primary outcome.
The science of studying diamond inclusions for understanding Earth history has developed significantly over the past decades, with new instrumentation and techniques applied to diamond sample archives revealing the stories contained within diamond inclusions. This chapter reviews what diamonds can tell us about the deep carbon cycle over the course of Earth’s history. It reviews how the geochemistry of diamonds and their inclusions inform us about the deep carbon cycle, the origin of the diamonds in Earth’s mantle, and the evolution of diamonds through time.
This study investigates the pressure–strain tensor (
) in Langmuir turbulence. The pressure–strain tensor is determined from large-eddy simulations (LES), and is partitioned into components associated with the mean current shear (rapid), the Stokes shear and the turbulent–turbulent (slow) interactions. The rapid component can be parameterized using existing closure models, although the coefficients in the closure models are particular to Langmuir turbulence. A closure model for the Stokes component is proposed, and it is shown to agree with results from the LES. The slow component of
does not agree with existing ‘return-to-isotropy’ closure models for five of the six components of the Reynolds stress tensor, and a new closure model is proposed that accounts for these deviations which vary systematically with Langmuir number,
, and depth. The implications of these results for second- and first-order closures of Langmuir turbulence are discussed.
With the recent discovery of a dozen dusty star-forming galaxies and around 30 quasars at z > 5 that are hyper-luminous in the infrared (μ LIR > 1013 L⊙, where μ is a lensing magnification factor), the possibility has opened up for SPICA, the proposed ESA M5 mid-/far-infrared mission, to extend its spectroscopic studies toward the epoch of reionisation and beyond. In this paper, we examine the feasibility and scientific potential of such observations with SPICA’s far-infrared spectrometer SAFARI, which will probe a spectral range (35–230 μm) that will be unexplored by ALMA and JWST. Our simulations show that SAFARI is capable of delivering good-quality spectra for hyper-luminous infrared galaxies at z = 5 − 10, allowing us to sample spectral features in the rest-frame mid-infrared and to investigate a host of key scientific issues, such as the relative importance of star formation versus AGN, the hardness of the radiation field, the level of chemical enrichment, and the properties of the molecular gas. From a broader perspective, SAFARI offers the potential to open up a new frontier in the study of the early Universe, providing access to uniquely powerful spectral features for probing first-generation objects, such as the key cooling lines of low-metallicity or metal-free forming galaxies (fine-structure and H2 lines) and emission features of solid compounds freshly synthesised by Population III supernovae. Ultimately, SAFARI’s ability to explore the high-redshift Universe will be determined by the availability of sufficiently bright targets (whether intrinsically luminous or gravitationally lensed). With its launch expected around 2030, SPICA is ideally positioned to take full advantage of upcoming wide-field surveys such as LSST, SKA, Euclid, and WFIRST, which are likely to provide extraordinary targets for SAFARI.
We performed a new series of measurements on samples that were part of early measurements on radiocarbon (14C) dating made in 1948–1949. Our results show generally good agreement to the data published in 1949–1951, despite vast changes in technology, with only two exceptions where there was a discrepancy in the original studies. Our new measurements give calibrated ages that overlap with the known ages. We dated several samples at four different laboratories, and so we were also able to make a small intercomparison at the same time. In addition, new measurements on samples from other Egyptian materials used by Libby and co-workers were made at UC Irvine. Samples of tree rings used in the original studies (from Broken Flute Cave and Centennial Stump) were obtained from the University of Arizona Laboratory of Tree-Ring Research archive and remeasured. New data were compared to the original studies and other records.
The red algal genus Porphyra is sister to the genus Pyropia, the single most valuable marine crop in the Orient. We developed microsatellite loci for the red alga Porphyra umbilicalis, a widespread species in the Northern Atlantic. Enriched DNA libraries were constructed and 68 loci were screened for amplification and polymorphism. Seven polymorphic microsatellite markers were isolated using 44 individuals collected from four natural populations. The number of alleles per locus ranged from two to 12. Null alleles were detected in three loci. Among the markers reported, we tested also cross-amplification with two other Porphyra spp. These polymorphic microsatellite markers should be useful for investigating population genetic structure of P. umbilicalis in the North East Atlantic.
Our current knowledge of star formation and accretion luminosity at high redshift (z > 3–4), as well as the possible connections between them, relies mostly on observations in the rest-frame ultraviolet, which are strongly affected by dust obscuration. Due to the lack of sensitivity of past and current infrared instrumentation, so far it has not been possible to get a glimpse into the early phases of the dust-obscured Universe. Among the next generation of infrared observatories, SPICA, observing in the 12–350 µm range, will be the only facility that can enable us to trace the evolution of the obscured star-formation rate and black-hole accretion rate densities over cosmic time, from the peak of their activity back to the reionisation epoch (i.e., 3 < z ≲ 6–7), where its predecessors had severe limitations. Here, we discuss the potential of photometric surveys performed with the SPICA mid-infrared instrument, enabled by the very low level of impact of dust obscuration in a band centred at 34 µm. These unique unbiased photometric surveys that SPICA will perform will fully characterise the evolution of AGNs and star-forming galaxies after reionisation.
The Square Kilometre Array will be an amazing instrument for pulsar astronomy. While the full SKA will be sensitive enough to detect all pulsars in the Galaxy visible from Earth, already with SKA1, pulsar searches will discover enough pulsars to increase the currently known population by a factor of four, no doubt including a range of amazing unknown sources. Real time processing is needed to deal with the 60 PB of pulsar search data collected per day, using a signal processing pipeline required to perform more than 10 POps. Here we present the suggested design of the pulsar search engine for the SKA and discuss challenges and solutions to the pulsar search venture.
Elevated birth weight is linked to glucose intolerance and obesity health-related complications later in life. No studies have examined if infant birth weight is associated with gene expression markers of obesity and inflammation in a tissue that comes directly from the infant following birth. We evaluated the association between birth weight and gene expression on fetal programming of obesity. Foreskin samples were collected following circumcision, and gene expression analyzed comparing the 15% greatest birth weight infants (n=7) v. the remainder of the cohort (n=40). Multivariate linear regression models were fit to relate expression levels on differentially expressed genes to birth weight group with adjustment for variables selected from a list of maternal and infant characteristics. Glucose transporter type 4 (GLUT4), insulin receptor substrate 2 (IRS2), leptin receptor (LEPR), lipoprotein lipase (LPL), low-density lipoprotein receptor-related protein 1 (LRP1), matrix metalloproteinase 2 (MMP2), plasminogen activator inhibitor-1 (PAI-1) and transcription factor 7-like 2 (TCF7L2) were significantly upregulated and histone deacetylase 1 (HDAC1) and thioredoxin (TXN) downregulated in the larger birth weight neonates v. controls. Multivariate modeling revealed that the estimated adjusted birth weight group difference exceeded one standard deviation of the expression level for eight of the 10 genes. Between 25 and 50% of variation in expression level was explained by multivariate modeling for eight of the 10 genes. Gene expression related to glycemic control, appetite/energy balance, obesity and inflammation were altered in tissue from babies with elevated birth weight, and these genes may provide important information regarding fetal programming in macrosomic babies.
One of the difficulties in reporting accurate radiocarbon results from compound-specific radiocarbon analysis (CSRA) is the lack of suitable process standard materials to correct for the amount and 14C content of carbon added during extensive sample processing. We evaluated the use of n-alkanes extracted from modern grass material (1.224±0.006 fraction modern) as process standards for CSRA. The n-alkanes were isolated using preparative capillary gas chromatography (PCGC) from two independent chemical extraction methods applied to the grass. Since this was our first assessment of the 14C content of the grass n-alkanes, we corrected for extraneous carbon derived from PCGC isolation using commercially available single compounds of modern and 14C-free content. Results were consistent across the two extraction methods showing that the C29n-alkane has a fraction modern value that is within 1σ of the bulk value of the grass while C31n-alkane and less abundant n-alkanes have values within 2σ of the bulk value of the grass. C29 and C31n-alkanes were the most abundant n-alkanes in the grass and, as such, the more feasible for collection of sufficient amounts of carbon for accelerator mass spectrometry (AMS) analysis. Our results suggest that choosing a grass n-alkane with an elution time closest to that of the unknowns may be advisable due to possibly greater effect from GC column bleed (14C-free) at later elution times. We conclude that C29 and C31n-alkanes in modern grass of known 14C content can be used as in-house standards to correct for the addition of 14C-free carbon during sample preparation for 14C analysis of n-alkanes.
Potato, dry bean, and sugar beet production have increased markedly in recent years on irrigated cropland in Alberta, Canada. Concerns exist about declining soil quality and increased soil erosion when these low-residue crops are grown in sequence in short-duration rotations. A 12-yr rotation study was conducted to determine the merits of adopting various conservation practices (reduced tillage, cover crops, composted manure) and longer-duration rotations to develop a more sustainable production system for these row crops. This article reports on weed density and weed seedbank data collected in the study. Weed densities recorded prior to applying postemergence herbicides indicated that conservation compared with conventional management treatments had greater weed densities in 30 to 45% of the cases in 3-, 4-, and 5-yr rotations. In contrast, a 6-yr conservation rotation that included 2 yr of timothy forage resulted in similar or lower weed densities than rotations with conventional management practices. Residual weed densities recorded 4 wk after applying postemergence herbicides were only greater in conservation than conventional rotations in 2 of 12 yr, regardless of rotation length. Weed seedbank densities at the conclusion of the 12-yr study were similar for 3- to 6-yr rotations under either conservation or conventional management. These findings indicate that implementing a suite of conservation practices poses little risk of increased weed populations in the long term. This knowledge will facilitate grower adoption of more sustainable agronomic practices for irrigated row crops in this region.
The effects of fish oil (FO) supplementation on glycaemic control are unclear, and positive effects may occur only when the phospholipid content of tissue membranes exceeds 14 % as n-3 PUFA. Subjects (n 36, thirty-three completed) were paired based on metabolic parameters and allocated into a parallel double-blind randomised trial with one of each pair offered daily either 6 g of FO (3·9 g n-3 PUFA) or 6 g of maize oil (MO) for 9 months. Hyperinsulinaemic–euglycaemic–euaminoacidaemic (HIEGEAA) clamps (with [6,6 2H2 glucose]) were performed at the start and end of the intervention. Endogenous glucose production (EGP) and whole-body protein turnover (WBPT) were each measured after an overnight fast. The primary outcome involved the effect of oil type on insulin sensitivity related to glycaemic control. The secondary outcome involved the effect of oil type on WBPT. Subjects on FO (n 16) had increased erythrocyte n-3 PUFA concentrations >14 %, whereas subjects on MO (n 17) had unaltered n-3 PUFA concentrations at 9 %. Type of oil had no effect on fasting EGP, insulin sensitivity or total glucose disposal during the HIEGEAA clamp. In contrast, under insulin-stimulated conditions, total protein disposal (P=0·007) and endogenous WBPT (P=0·001) were both increased with FO. In an associated pilot study (n 4, three completed), although n-3 PUFA in erythrocyte membranes increased to >14 % with the FO supplement, the enrichment in muscle membranes remained lower (8 %; P<0·001). In conclusion, long-term supplementation with FO, at amounts near the safety limits set by regulatory authorities in Europe and the USA, did not alter glycaemic control but did have an impact on WBPT.
Episodes of depression and anxiety (D&A) during the transition from late adolescence to adulthood, particularly when persistent, are predictive of long-term disorders and associated public health burden. Understanding risk factors at this time is important to guide intervention. The current objective was to investigate the associations between maternal symptoms of D&A with offspring symptoms during their transition to adulthood.
Data from a large population-based birth cohort study, in South Brazil, were used. Prospective associations between maternal D&A and offspring risk of these symptoms during the transition to adulthood (18/19, 24 and 30 years) were estimated.
Maternal D&A in adolescence was associated with offspring symptoms across the transition to adulthood, associations were consistently stronger for females than for males. Daughters whose mothers reported D&A were 4.6 times (95% confidence interval 2.71–7.84) as likely to report D&A at all three time-points, than daughters of symptom-free mothers.
Maternal D&A is associated with persistent D&A during the daughter's transition to adulthood. Intervention strategies should consider the mother's mental health.
Generalized anxiety disorder (GAD) and panic disorder (PD) differ in their biology and co-morbidities. We hypothesized that GAD but not PD symptoms at the age of 15 years are associated with depression diagnosis at 18 years.
Using longitudinal data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort we examined relationships of GAD and PD symptoms (measured by the Development and Well-Being Assessment) at 15 years with depression at 18 years (by the Clinical Interview Schedule – Revised) using logistic regression. We excluded adolescents already depressed at 15 years and adjusted for social class, maternal education, birth order, gender, alcohol intake and smoking. We repeated these analyses following multiple imputation for missing data.
In the sample with complete data (n = 2835), high and moderate GAD symptoms in adolescents not depressed at 15 years were associated with increased risk of depression at 18 years both in unadjusted analyses and adjusting for PD symptoms at 15 years and the above potential confounders. The adjusted odds ratio (OR) for depression at 18 years in adolescents with high relative to low GAD scores was 5.2 [95% confidence interval (CI) 3.0–9.1, overall p < 0.0001]. There were no associations between PD symptoms and depression at 18 years in any model (high relative to low PD scores, adjusted OR = 1.3, 95% CI 0.3–4.8, overall p = 0.737). Missing data imputation strengthened the relationship of GAD symptoms with depression (high relative to low GAD scores, OR = 6.2, 95% CI 3.9–9.9) but those for PD became weaker.
Symptoms of GAD but not PD at 15 years are associated with depression at 18 years. Clinicians should be aware that adolescents with GAD symptoms may develop depression.
The Herschel Space Observatory was the fourth cornerstone mission in the European Space Agency (ESA) science programme with excellent broad band imaging capabilities in the sub-mm and far-infrared part of the spectrum. Although the spacecraft finished its observations in 2013, it left a large legacy dataset that is far from having been fully scrutinised and still has a large potential for new scientific discoveries. This is specifically true for the photometric observations of the PACS and SPIRE instruments. Some source catalogues have already been produced by individual observing programs, but there are many observations that risk to remain unexplored. To maximise the science return of the SPIRE and PACS data sets, we are in the process of building the Herschel Point Source Catalogue (HPSC) from all primary and parallel mode observations. Our homogeneous source extraction enables a systematic and unbiased comparison of sensitivity across the different Herschel fields that single programs will generally not be able to provide. The catalogue will be made available online through archives like the Herschel Science Archive (HSA), the Infrared Science Archive (IRSA), and the Strasbourg Astronomical Data Center (CDS).
Objective: Despite growing adoption, the impact of prehospital initiation of therapeutic hypothermia on outcomes of cardiac arrest patients is unknown. The objective of this study was to determine if prehospital administration of cold intravenous fluids improved the time-to-target temperature.
Methods: All patients enrolled in an institutional post– cardiac arrest treatment pathway were prospectively registered into a quality assurance database. Patients undergoing cooling induction on hospital arrival were compared to those receiving a new treatment protocol initiated during the study period involving prehospital cooling with 4°C (39.2°F) normal saline. The primary outcome was the time-to-target temperature. Secondary outcomes included emergency medicine system transport time metrics, mortality, and neurologic status at discharge and 1 year.
Results: One hundred thirty-two patients were enrolled during the study period. The initial rhythm was ventricular fibrillation/tachycardia in 63% and asystole/pulseless electrical activity in 36%. Eighty patients received prehospital cooling and 52 patients did not and comprised the historical control group. Time-to-target temperatures were not significantly different between prehospital and hospital cooled groups (256 v. 271 minutes, respectively, p=0.64), nor was there any improvement in hospital survival (54% v. 50%, p=0.67), good neurologic outcome (49% v. 44%, p=0.61), or 1- year survival (49% v. 42%, p=0.46) between the two groups. Transport times were longer in the prehospital cooled group.
Conclusions: Out-of-hospital cardiac arrest patients treated with prehospital cooling before arrival at our urban hospital did not have faster time-to-target temperature or improvement in outcomes compared to patients cooled immediately on emergency department arrival. Further research is needed to determine if any benefits exist from prehospital cooling prior to its widespread adoption.
Since mid-2007 we have carried out a dedicated long-term monitoring programme at 15 GHz using the Owens Valley Radio Observatory 40 meter telescope (OVRO 40m). One of the main goals of this programme is to study the relation between the radio and gamma-ray emission in blazars and to use it as a tool to locate the site of high energy emission. Using this large sample of objects we are able to characterize the radio variability, and study the significance of correlations between the radio and gamma-ray bands. We find that the radio variability of many sources can be described using a simple power law power spectral density, and that when taking into account the red-noise characteristics of the light curves, cases with significant correlation are rare. We note that while significant correlations are found in few individual objects, radio variations are most often delayed with respect to the gamma-ray variations. This suggests that the gamma-ray emission originates upstream of the radio emission. Because strong flares in most known gamma-ray-loud blazars are infrequent, longer light curves are required to settle the issue of the strength of radio-gamma cross-correlations and establish confidently possible delays between the two. For this reason continuous multiwavelength monitoring over a longer time period is essential for statistical tests of jet emission models.