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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.
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.
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.
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.
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.
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.
Hemorrhage remains the major cause of preventable death after trauma. Recent data suggest that earlier blood product administration may improve outcomes. The purpose of this study was to determine whether opportunities exist for blood product transfusion by ground Emergency Medical Services (EMS).
This was a single EMS agency retrospective study of ground and helicopter responses from January 1, 2011 through December 31, 2015 for adult trauma patients transported from the scene of injury who met predetermined hemodynamic (HD) parameters for potential transfusion (heart rate [HR]≥120 and/or systolic blood pressure [SBP]≤90).
A total of 7,900 scene trauma ground transports occurred during the study period. Of 420 patients meeting HD criteria for transfusion, 53 (12.6%) had a significant mechanism of injury (MOI). Outcome data were available for 51 patients; 17 received blood products during their emergency department (ED) resuscitation. The percentage of patients receiving blood products based upon HD criteria ranged from 1.0% (HR) to 5.9% (SBP) to 38.1% (HR+SBP). In all, 74 Helicopter EMS (HEMS) transports met HD criteria for blood transfusion, of which, 28 patients received prehospital blood transfusion. Statistically significant total patient care time differences were noted for both the HR and the SBP cohorts, with HEMS having longer time intervals; no statistically significant difference in mean total patient care time was noted in the HR+SBP cohort.
In this study population, HD parameters alone did not predict need for ED blood product administration. Despite longer transport times, only one-third of HEMS patients meeting HD criteria for blood administration received prehospital transfusion. While one-third of ground Advanced Life Support (ALS) transport patients manifesting HD compromise received blood products in the ED, this represented 0.2% of total trauma transports over the study period. Given complex logistical issues involved in prehospital blood product administration, opportunities for ground administration appear limited within the described system.
MixFM, ZielinskiMD, MyersLA, BernsKS, LukeA, StubbsJR, ZietlowSP, JenkinsDH, SztajnkrycerMD. Prehospital Blood Product Administration Opportunities in Ground Transport ALS EMS – A Descriptive Study. Prehosp Disaster Med. 2018;33(3):230–236.
The Joint Commission Centre for Transforming Healthcare's Web-based Targeted Solutions Tool (TST) for improving hand hygiene was implemented to elucidate contributing factors to low compliance rates of hand hygiene. Monitoring of compliance was done by trained unknown and known observers and rates of hospital-acquired infections were tracked and correlated against the changes in hand hygiene compliance. In total, 5669 of hand hygiene observations were recorded by the secret observers. The compliance rate increased from 75·4% at baseline (May–August 2014) to 88·6% during the intervention (13 months) and the control periods (P < 0·0001). Reductions in healthcare-associated infection rates were recorded for Clostridium difficle infections from 7·95 (CI 0·8937–28·72) to 1·84 (CI 0·02411–10·26) infections per 10 000 patient-days (P = 0·23), central line-associated blood-stream infections from 5·9 (CI 1·194–17·36) to 2·9 (0·7856–7·475) per 1000 device days (P = 0·37) and catheter-associated urinary tract infections from 5·941 (CI 1·194–17·36) to 0 per 1000 device days (P = 0·42). The top contributing factors for non-compliance were: improper use of gloves, hands full of supplies or medications and frequent entry or exit in isolation areas. We conclude that the application of TST allows healthcare organisations to improve hand hygiene compliance and to identify the factors contributing to non-compliance.
The government publishes 3 different public report surgical site infection (SSI) metrics, all called standardized infection ratios (SIRs), that impact perceived hospital quality. We conducted a non-random cross-sectional observational pilot study of 20 California hospitals that voluntarily submitted colon surgery and SSI data. Discordant SIR values, leading to contradictory conclusions, occurred in 35% of these hospitals.
There is limited evidence on the acceptability, feasibility and cost-effectiveness of task-sharing interventions to narrow the treatment gap for mental disorders in sub-Saharan Africa. The purpose of this article is to describe the rationale, aims and methods of the Africa Focus on Intervention Research for Mental health (AFFIRM) collaborative research hub. AFFIRM is investigating strategies for narrowing the treatment gap for mental disorders in sub-Saharan Africa in four areas. First, it is assessing the feasibility, acceptability and cost-effectiveness of task-sharing interventions by conducting randomised controlled trials in Ethiopia and South Africa. The AFFIRM Task-sharing for the Care of Severe mental disorders (TaSCS) trial in Ethiopia aims to determine the acceptability, affordability, effectiveness and sustainability of mental health care for people with severe mental disorder delivered by trained and supervised non-specialist, primary health care workers compared with an existing psychiatric nurse-led service. The AFFIRM trial in South Africa aims to determine the cost-effectiveness of a task-sharing counselling intervention for maternal depression, delivered by non-specialist community health workers, and to examine factors influencing the implementation of the intervention and future scale up. Second, AFFIRM is building individual and institutional capacity for intervention research in sub-Saharan Africa by providing fellowship and mentorship programmes for candidates in Ethiopia, Ghana, Malawi, Uganda and Zimbabwe. Each year five Fellowships are awarded (one to each country) to attend the MPhil in Public Mental Health, a joint postgraduate programme at the University of Cape Town and Stellenbosch University. AFFIRM also offers short courses in intervention research, and supports PhD students attached to the trials in Ethiopia and South Africa. Third, AFFIRM is collaborating with other regional National Institute of Mental Health funded hubs in Latin America, sub-Saharan Africa and south Asia, by designing and executing shared research projects related to task-sharing and narrowing the treatment gap. Finally, it is establishing a network of collaboration between researchers, non-governmental organisations and government agencies that facilitates the translation of research knowledge into policy and practice. This article describes the developmental process of this multi-site approach, and provides a narrative of challenges and opportunities that have arisen during the early phases. Crucial to the long-term sustainability of this work is the nurturing and sustaining of partnerships between African mental health researchers, policy makers, practitioners and international collaborators.
The source of variability in people's response to stressful life events is poorly understood.
We examine the genetic and environmental underpinning of resilience (i.e. the difference between the twins' internalising symptoms and their predicted symptoms based on cumulative stressful life events).
Stressful life event exposure and internalising symptoms were assessed at two time points in 7500 adult twins. Using the residual between actual and predicted internalising symptom total score, twin modelling was conducted for each wave separately and longitudinally.
Resilience was found to have a moderate genetic heritability at each wave (~31%). Qualitative gender effects were found. Incorporating error of measurement into the model increased the estimated heritability for the latent construct of resilience (~50%). When measurement error and occasion-specific effects were removed, environmental influences contributed roughly equally to level of resilience.
Both genes and environment influence level of psychiatric resilience, and are largely stable over time. Environmental influences can have an enduring effect on resilience.
Choline is an essential nutrient that is found in many food sources and plays a critical role in the development of the central nervous system. Animal studies have shown that choline status pre- and postnatally can have long-lasting effects on attention and memory; however, effects in human subjects have not been well studied. The aim of the present study was to examine the association between plasma concentrations of free choline and its related metabolites in children and their neurodevelopment in the Seychelles Child Development Nutrition Study, an ongoing longitudinal study assessing the development of children born to mothers with high fish consumption during pregnancy. Plasma concentrations of free choline, betaine, dimethylglycine (DMG), methionine and homocysteine and specific measures of neurodevelopment were measured in 210 children aged 5 years. The children's plasma free choline concentration (9·17 (sd 2·09) μmol/l) was moderately, but significantly, correlated with betaine (r 0·24; P= 0·0006), DMG (r 0·15; P= 0·03), methionine (r 0·24; P= 0·0005) and homocysteine (r 0·19; P= 0·006) concentrations. Adjusted multiple linear regression revealed that betaine concentrations were positively associated with Preschool Language Scale – total language scores (β = 0·066; P= 0·04), but no other associations were evident. We found no indication that free choline concentration or its metabolites, within the normal physiological range, are associated with neurodevelopmental outcomes in children at 5 years of age. As there is considerable animal evidence suggesting that choline status during development is associated with cognitive outcome, the issue deserves further study in other cohorts.