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Optimal maternal long chain polyunsaturated fatty acid (LCPUFA) status is essential for the developing foetus. The fatty acid desaturase (FADS) genes are involved in the endogenous synthesis of LCPUFA. The minor allele of various FADS single nucleotide polymorphisms (SNPs) have been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), and lower concentrations of arachidonic acid (AA) and docosahexaenoic acid (DHA). There is limited research on the influence of FADS genotype on cord PUFA status. The current study investigated the influence of maternal and child genetic variation in FADS genotype on cord blood PUFA status in a high fish-eating cohort. Cord blood samples (n=1088) collected from the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2) were analysed for total serum PUFA. Of those with cord PUFA data available, maternal (n=1062) and child (n=916), FADS1 (rs174537, rs174561), FADS2 (rs174575), and FADS1-FADS2 (rs3834458) were determined. Regression analysis determined that maternal minor allele homozygosity was associated with lower cord blood concentrations of docosahexaenoic acid (DHA) and the sum of EPA+DHA. Lower cord blood AA concentrations were observed in children who were minor allele homozygous for rs3834458 (β=0.075; p=0.037). Children who were minor allele carriers for rs174537, rs174561, rs174575 and rs3834458 had a lower cord blood AA:LA ratio (p<0.05 for all). Both maternal and child FADS genotype were associated with cord LCPUFA concentrations, and therefore, the influence of FADS genotype was observed despite the high intake of preformed dietary LCPUFA from fish in this population.
To determine the false-positive rate of pulse oximetry screening at moderate altitude, presumed to be elevated compared with sea level values and assess change in false-positive rate with time.
We retrospectively analysed 3548 infants in the newborn nursery in Albuquerque, New Mexico, (elevation 5400 ft) from July 2012 to October 2013. Universal pulse oximetry screening guidelines were employed after 24 hours of life but before discharge. Newborn babies between 36 and 36 6/7 weeks of gestation, weighing >2 kg and babies >37 weeks weighing >1.7 kg were included in the study. Log-binomial regression was used to assess change in the probability of false positives over time.
Of the 3548 patients analysed, there was one true positive with a posteriorly-malaligned ventricular septal defect and an interrupted aortic arch. Of the 93 false positives, the mean pre- and post-ductal saturations were lower, 92 and 90%, respectively. The false-positive rate before April 2013 was 3.5% and after April 2013, decreased to 1.5%. There was a significant decrease in false-positive rate (p = 0.003, slope coefficient = −0.082, standard error of coefficient = 0.023) with the relative risk of a false positive decreasing at 0.92 (95% CI 0.88–0.97) per month.
This is the first study in Albuquerque, New Mexico, reporting a high false-positive rate of 1.5% at moderate altitude at the end of the study in comparison to the false-positive rate of 0.035% at sea level. Implementation of the nationally recommended universal pulse oximetry screening was associated with a high false-positive rate in the initial period, thought to be from the combination of both learning curve and altitude. After the initial decline, it remained steadily elevated above sea level, indicating the dominant effect of moderate altitude.
Although organizational climate may affect faculty’s mentoring behaviors, there has not been any way to measure that climate. The purpose of this study was to test the reliability and validity of two novel scales to measure organizational mentoring climate importance and availability at two public research universities.
We developed 36 content-valid mentoring climate items in four dimensions: Structure, Programs/Activities, Policies/Guidelines, and Values. In total, 355 faculty completed an anonymous, structured, online survey asking about the importance (very important to very unimportant) and availability (no, don’t know, yes) of each of the items. We conducted reliability analyses and construct validity testing using exploratory common factor analysis, principal axis factoring, and oblique rotation.
The majority of the predominantly female, White non-Hispanic, senior, tenure-track faculty were not currently mentoring another faculty or being mentored. Analyses demonstrated a 15-item solution for both the Organizational Mentoring Climate Importance (OMCI) and the Availability (OMCA) Scales, with three factors each: Organizational Expectations, Mentor–Mentee Relationships, and Resources. Standardized Cronbach alphas ranged from 0.74 to 0.90 for the subscales, and 0.94 (OMCI) and 0.87 (OMCA) for the full scales. Faculty rated all items as somewhat to very important; however, perceived availability was very low ranging from mentor training programs (40%) to guidelines for evaluating mentoring success or managing conflict (2.5%).
The scales will allow studying of how organizational climate may affect mentoring behavior and whether climate can be changed to improve faculty mentoring outcomes. We provide recommendations for furthering the science of organizational mentoring climate and culture.
We characterized the impact of removal of the ESBL designation from microbiology reports on inpatient antibiotic prescribing. Definitive prescribing of carbapenems decreased from 48.4% to 16.1% (P = .01) and β-lactam–β-lactamase inhibitor combination increased from 19.4% to 61.3% (P = .002). Our findings confirm the importance of collaboration between microbiology and antimicrobial stewardship programs.
The political underrepresentation of women and racial minorities in Canadian politics is well documented. One political arena that has yet to be examined in this respect, however, is school boards. Using data from a candidate survey conducted during the course of the 2018 Ontario school board elections, as well as demographic data collected on the entire population of school board candidates, we explore the unique characteristics of school board elections. The research note begins by describing the gender and racial composition of candidates and trustees in Canada's most populous province. It then considers the ways in which school board elections may serve as a launchpad to higher office for either of these two traditionally underrepresented groups, as we explore the features of progressive political ambition, recruitment into school board campaigns and the relative electoral success of racialized candidates and women in this local office. While women do very well in school board elections, they are significantly less likely than their male counterparts to have the desire to move up to provincial or federal politics. Meanwhile, racialized candidates contest school board election in significant numbers and report similar levels of progressive ambition relative to their white counterparts, but they fare exceptionally poorly in school board elections.
Optimal maternal polyunsaturated fatty acid (PUFA) status is essential for foetal development. The desaturase enzymes, encoded by the fatty acid desaturase (FADS) genes, are involved in the endogenous synthesis of long chain (LC)PUFA and influence maternal LCPUFA concentrations. The minor allele of various FADS SNPs has been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), and lower concentrations of the LCPUFA arachidonic acid (AA) and docosahexaenoic acid (DHA); however, there is limited research to date on the influence of FADS genotype on cord PUFA status. The aim of the current study was to investigate the influence of maternal and child genetic variation on cord blood PUFA status in a high fish-eating cohort.
Cord blood samples collected from mother-child pairs (n = 1088) taking part in the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2) were analysed for total serum PUFA. Maternal (n = 1088) and child genotype (n = 592) were determined for the FADS SNPs rs174537, rs174561, rs174575, and rs3834458. Regression analysis determined associations between maternal and child FADS genotype and cord PUFA status. In all regression models, the major allele homozygote genotype for each SNP was used as the reference group.
Directions of significant associations were as predicted. In mothers, the minor allele homozygote genotype for SNPs rs174537, rs174561 and rs3834458 was associated with lower cord DHA and lower total n-3 PUFA when compared to the major allele homozygous genotype (p < 0.05 for all). The heterozygous genotype was associated with increased concentrations of LA compared to the reference genotype for rs174561 (p = 0.021) and rs383448 (p = 0.023). In children, the heterozygous genotype was associated with lower AA concentrations and lower cord n-6:n-3 ratio for all SNPs (p < 0.05 for all) compared to those with the major allele homozygous genotype. A lower cord AA:LA ratio was also observed for children heterozygous for rs174547, rs174561 and rs174575 (p < 0.05 for all). Contrary to expected, there were no associations between cord PUFA concentrations and child minor allele homozygous genotype.
The current study indicates that variation in maternal and child FADS genotype influences cord PUFA concentrations, despite the high intake of preformed dietary LCPUFA from fish in this population. The sample size for minor allele homozygous children was likely too small to observe any statistically significant associations in the current analysis. Further research is needed to determine whether increased dietary intake can compensate for lower PUFA status as a result of FADS genotype.
Forty years ago, Knut Fladmark (1979) argued that the Pacific Coast offered a viable alternative to the ice-free corridor model for the initial peopling of the Americas—one of the first to support a “coastal migration theory” that remained marginal for decades. Today, the pre-Clovis occupation at the Monte Verde site is widely accepted, several other pre-Clovis sites are well documented, investigations of terminal Pleistocene subaerial and submerged Pacific Coast landscapes have increased, and multiple lines of evidence are helping decode the nature of early human dispersals into the Americas. Misconceptions remain, however, about the state of knowledge, productivity, and deglaciation chronology of Pleistocene coastlines and possible technological connections around the Pacific Rim. We review current evidence for several significant clusters of early Pacific Coast archaeological sites in North and South America that include sites as old or older than Clovis. We argue that stemmed points, foliate points, and crescents (lunates) found around the Pacific Rim may corroborate genomic studies that support an early Pacific Coast dispersal route into the Americas. Still, much remains to be learned about the Pleistocene colonization of the Americas, and multiple working hypotheses are warranted.
Project management expertise is employed across many professional sectors, including clinical research organizations, to ensure that efforts undertaken by the organization are completed on time and according to specifications and are capable of achieving the needed impact. Increasingly, project leaders (PLs) who possess this expertise are being employed in academic settings to support clinical and preclinical translational research team science. Duke University’s clinical and translational science enterprise has been an early adopter of project management to support clinical and preclinical programs. We review the history and evolution of project management and the PL role at Duke, examine case studies that illustrate their growing value to our academic research environment, and address challenges and solutions to employing project management in academia. Furthermore, we describe the critical role project leadership plays in accelerating and increasing the success of translational team science and team approaches frequently required for systems biology and “big data” scientific studies. Finally, we discuss perspectives from Duke project leadership professionals regarding the training needs and requirements for PLs working in academic clinical and translational science research settings.
The purpose of this study was to examine whether vehicle type based on size (car vs. other = truck/van/SUV) had an impact on the speeding, acceleration, and braking patterns of older male and female drivers (70 years and older) from a Canadian longitudinal study. The primary hypothesis was that older adults driving larger vehicles (e.g., trucks, SUVs, or vans) would be more likely to speed than those driving cars. Participants (n = 493) had a device installed in their vehicles that recorded their everyday driving. The findings suggest that the type of vehicle driven had little or no impact on per cent of time speeding or on the braking and accelerating patterns of older drivers. Given that the propensity for exceeding the speed limit was high among these older drivers, regardless of vehicle type, future research should examine what effect this behaviour has on older-driver road safety.
Background: Focal cortical dysplasias (FCDs) are congenital structural abnormalities of the brain, and represent the most common cause of medication-resistant focal epilepsy in children and adults. Recent studies have shown that somatic mutations (i.e. mutations arising in the embryo) in mTOR pathway genes underlie some FCD cases. Specific therapies targeting the mTOR pathway are available. However, testing for somatic mTOR pathway mutations in FCD tissue is not performed on a clinical basis, and the contribution of such mutations to the pathogenesis of FCD remains unknown. Aim: To investigate the feasibility of screening for somatic mutations in resected FCD tissue and determine the proportion and spatial distribution of FCDs which are due to low-level somatic mTOR pathway mutations. Methods: We performed ultra-deep sequencing of 13 mTOR pathway genes using a custom HaloPlexHS target enrichment kit (Agilent Technologies) in 16 resected histologically-confirmed FCD specimens. Results: We identified causal variants in 62.5% (10/16) of patients at an alternate allele frequency of 0.75–33.7%. The spatial mutation frequency correlated with the FCD lesion’s size and severity. Conclusions: Screening FCD tissue using a custom panel results in a high yield, and should be considered clinically given the important potential implications regarding surgical resection, medical management and genetic counselling.
We assessed whether paternal demographic, anthropometric and clinical factors influence the risk of an infant being born large-for-gestational-age (LGA). We examined the data on 3659 fathers of term offspring (including 662 LGA infants) born to primiparous women from Screening for Pregnancy Endpoints (SCOPE). LGA was defined as birth weight >90th centile as per INTERGROWTH 21st standards, with reference group being infants ⩽90th centile. Associations between paternal factors and likelihood of an LGA infant were examined using univariable and multivariable models. Men who fathered LGA babies were 180 g heavier at birth (P<0.001) and were more likely to have been born macrosomic (P<0.001) than those whose infants were not LGA. Fathers of LGA infants were 2.1 cm taller (P<0.001), 2.8 kg heavier (P<0.001) and had similar body mass index (BMI). In multivariable models, increasing paternal birth weight and height were independently associated with greater odds of having an LGA infant, irrespective of maternal factors. One unit increase in paternal BMI was associated with 2.9% greater odds of having an LGA boy but not girl; however, this association disappeared after adjustment for maternal BMI. There were no associations between paternal demographic factors or clinical history and infant LGA. In conclusion, fathers who were heavier at birth and were taller were more likely to have an LGA infant, but maternal BMI had a dominant influence on LGA.
We sought to define the prevalence of echocardiographic abnormalities in long-term survivors of paediatric hematopoietic stem cell transplantation and determine the utility of screening in asymptomatic patients. We analysed echocardiograms performed on survivors who underwent hematopoietic stem cell transplantation from 1982 to 2006. A total of 389 patients were alive in 2017, with 114 having an echocardiogram obtained ⩾5 years post-infusion. A total of 95 patients had echocardiogram performed for routine surveillance. The mean time post-hematopoietic stem cell transplantation was 13 years. Of 95 patients, 77 (82.1%) had ejection fraction measured, and 10/77 (13.0%) had ejection fraction z-scores ⩽−2.0, which is abnormally low. Those patients with abnormal ejection fraction were significantly more likely to have been exposed to anthracyclines or total body irradiation. Among individuals who received neither anthracyclines nor total body irradiation, only 1/31 (3.2%) was found to have an abnormal ejection fraction of 51.4%, z-score −2.73. In the cohort of 77 patients, the negative predictive value of having a normal ejection fraction given no exposure to total body irradiation or anthracyclines was 96.7% at 95% confidence interval (83.3–99.8%). Systolic dysfunction is relatively common in long-term survivors of paediatric hematopoietic stem cell transplantation who have received anthracyclines or total body irradiation. Survivors who are asymptomatic and did not receive radiation or anthracyclines likely do not require surveillance echocardiograms, unless otherwise indicated.
Successful organic farming requires crop varieties that are resilient to environmental variability. Assessing variety performance across the range of conditions represented on working farms is vital to developing such varieties; however, data collected from on-farm, participatory trials can be difficult to both collect and interpret. To assess the utility of data arising from participatory trialing efforts, we examined the performance of butternut squash (Cucurbita moschata L.), broccoli (Brassica oleracea L.) and carrot (Daucus carota L.) varieties grown in diverse organic production environments in participatory trials in Oregon, Washington, Wisconsin and New York using adaptability analysis (regression of variety means on environmental index). Patterns of adaptation varied across varieties, with some demonstrating broad adaptation and others showing specific adaptation to low- or high-yielding environments. Selection of varieties with broad vs specific adaptation should be guided by farmers’ risk tolerance and on-farm environmental variation. Adaptability analysis was appropriate for continuous variables (e.g., yield traits), but less so for ordinal variables and quality traits such as flavor and appearance, which can be vitally important in organic vegetable crop variety selection. The relative advantages of adaptability analysis and additive main effects and multiplicative interactions are also discussed in relation to on-farm trial networks. This work demonstrated the unique challenges presented by extensive participatory vegetable trialing efforts, which, as compared to grain crops, require novel approaches to facilitating farmer participation as well as data collection and analysis. Efficient, precise and reliable methods for evaluating quality related traits in these crops would allow researchers to assess stability and adaptation across a wider range of traits, providing advantages for effective plant breeding and trialing activities within the organic sector.
The burden of common perinatal mental disorders (CPMD) in low-and-middle-income countries is substantially higher than high-income countries, with low levels of detection, service provision and treatment in resource-constrained settings. We describe the development of an ultra-short screening tool to detect antenatal depression, anxiety disorders and maternal suicidal ideation.
A sample of 376 women was recruited at a primary-level obstetric clinic. Five depression and anxiety symptom-screening questionnaires, demographics and psychosocial risk questionnaires were administered. All participants were assessed with the Mini-International Neuropsychiatric Interview (MINI), a structured, diagnostic interview. Screening tool items were analysed against diagnostic data using multiple logistic regression and receiver operating curve (ROC) analysis.
The prevalence of MINI-defined major depressive episode (MDE) and/or anxiety disorders was 33%. Overall, 18% of participants expressed suicidal ideation and behaviour, 54% of these had no depression or anxiety diagnosis. Multiple logistic regression identified four screening items that were independently predictive of MDE and anxiety disorders, investigating depressed mood, anhedonia, anxiety symptoms and suicidal ideation. ROC analysis of these combined items yielded an area under the curve of 0.83 (95% CI 0.78–0.88). A cut-off score of 2 or more offered a sensitivity of 78% and specificity of 82%.
This novel screening tool is the first measure of CPMD developed in South Africa to include depressed mood, anxiety symptoms and suicidal ideation. While the tool requires further investigation, it may be useful for the early identification of mental health symptoms and morbidity in the perinatal period.