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To develop a physiological data-driven model for early identification of impending cardiac arrest in neonates and infants with cardiac disease hospitalised in the cardiovascular ICU.
We performed a single-institution retrospective cohort study (11 January 2013–16 September 2015) of patients ≤1 year old with cardiac disease who were hospitalised in the cardiovascular ICU at a tertiary care children’s hospital. Demographics and diagnostic codes of cardiac arrest were obtained via the electronic health record. Diagnosis of cardiac arrest was validated by expert clinician review. Minute-to-minute physiological monitoring data were recorded via bedside monitors. A generalized linear model was used to compute a minute by minute risk score. Training and test data sets both included data from patients who did and did not develop cardiac arrest. An optimal risk-score threshold was derived based on the model’s discriminatory capacity for impending arrest versus non-arrest. Model performance measures included sensitivity, specificity, accuracy, likelihood ratios, and post-test probability of arrest.
The final model consisting of multiple clinical parameters was able to identify impending cardiac arrest at least 2 hours prior to the event with an overall accuracy of 75% (sensitivity = 61%, specificity = 80%) and observed an increase in probability of detection of cardiac arrest from a pre-test probability of 9.6% to a post-test probability of 21.2%.
Our findings demonstrate that a predictive model using physiologic monitoring data in neonates and infants with cardiac disease hospitalised in the paediatric cardiovascular ICU can identify impending cardiac arrest on average 17 hours prior to arrest.
We reviewed all patients who were supported with extracorporeal membrane oxygenation and/or ventricular assist device at our institution in order to describe diagnostic characteristics and assess mortality.
A retrospective cohort study was performed including all patients supported with extracorporeal membrane oxygenation and/or ventricular assist device from our first case (8 October, 1998) through 25 July, 2016. The primary outcome of interest was mortality, which was modelled by the Kaplan–Meier method.
A total of 223 patients underwent 241 extracorporeal membrane oxygenation runs. Median support time was 4.0 days, ranging from 0.04 to 55.8 days, with a mean of 6.4±7.0 days. Mean (±SD) age at initiation was 727.4 days (±146.9 days). Indications for extracorporeal membrane oxygenation were stratified by primary indication: cardiac extracorporeal membrane oxygenation (n=175; 72.6%) or respiratory extracorporeal membrane oxygenation (n=66; 27.4%). The most frequent diagnosis for cardiac extracorporeal membrane oxygenation patients was hypoplastic left heart syndrome or hypoplastic left heart syndrome-related malformation (n=55 patients with HLHS who underwent 64 extracorporeal membrane oxygenation runs). For respiratory extracorporeal membrane oxygenation, the most frequent diagnosis was congenital diaphragmatic hernia (n=22). A total of 24 patients underwent 26 ventricular assist device runs. Median support time was 7 days, ranging from 0 to 75 days, with a mean of 15.3±18.8 days. Mean age at initiation of ventricular assist device was 2530.8±660.2 days (6.93±1.81 years). Cardiomyopathy/myocarditis was the most frequent indication for ventricular assist device placement (n=14; 53.8%). Survival to discharge was 42.2% for extracorporeal membrane oxygenation patients and 54.2% for ventricular assist device patients. Kaplan–Meier 1-year survival was as follows: all patients, 41.0%; extracorporeal membrane oxygenation patients, 41.0%; and ventricular assist device patients, 43.2%. Kaplan–Meier 5-year survival was as follows: all patients, 39.7%; extracorporeal membrane oxygenation patients, 39.7%; and ventricular assist device patients, 43.2%.
This single-institutional 18-year review documents the differential probability of survival for various sub-groups of patients who require support with extracorporeal membrane oxygenation or ventricular assist device. The indication for mechanical circulatory support, underlying diagnosis, age, and setting in which cannulation occurs may affect survival after extracorporeal membrane oxygenation and ventricular assist device. The Kaplan–Meier analyses in this study demonstrate that patients who survive to hospital discharge have an excellent chance of longer-term survival.
Adverse psychosocial working environments characterized by job strain (the combination of high demands and low control at work) are associated with an increased risk of depressive symptoms among employees, but evidence on clinically diagnosed depression is scarce. We examined job strain as a risk factor for clinical depression.
We identified published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individual-level data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium. Summary estimates of the association were obtained using random-effects models. Individual-level data analyses were based on a pre-published study protocol.
We included six published studies with a total of 27 461 individuals and 914 incident cases of clinical depression. From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression. Job strain was associated with an increased risk of clinical depression in both published [relative risk (RR) = 1.77, 95% confidence interval (CI) 1.47–2.13] and unpublished datasets (RR = 1.27, 95% CI 1.04–1.55). Further individual participant analyses showed a similar association across sociodemographic subgroups and after excluding individuals with baseline somatic disease. The association was unchanged when excluding individuals with baseline depressive symptoms (RR = 1.25, 95% CI 0.94–1.65), but attenuated on adjustment for a continuous depressive symptoms score (RR = 1.03, 95% CI 0.81–1.32).
Job strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.
Bitter gourd (Momordica charantia L.) is an important market vegetable in the tropics. The objectives of this study were to (1) conduct a preliminary evaluation of genetic diversity in bitter gourd flesh (without seeds) for phytonutrient (carotenoid, ascorbic acid and tocopherol) contents with the aim to understand which phytonutrients might be increased through breeding, (2) assess the association between fruit traits and phytonutrient contents and (3) evaluate the effect of the fruit harvest stage on phytonutrient contents. A total of 17 diverse bitter gourd entries of various commercial market types were evaluated for fruit traits and phytonutrient contents for 2 years. Significant differences (P= 0.05) among the entries were detected for total carotenoids, total tocopherols, dry matter and fruit traits. Mean total carotenoid contents of the entries ranged from 10 to 1335 μg/100 g fresh weight in year 1 and 10 to 1185 μg/100 g fresh weight in year 2. Mean ascorbic acid contents were 69 and 61 mg/100 g fresh weight in year 1 and year 2, respectively. Total tocopherol contents among the entries ranged from 480 to 1345 and 445 to 2145 μg/100 g fresh weight in year 1 and year 2, respectively. Total carotenoid and ascorbic acid contents were highest at 12 days after fruit set (DAFS), but total tocopherol contents were highest from 14 to 20 DAFS. A 100 g portion of bitter gourd fruit can meet 190, 17 and 8% of the recommended daily allowances of vitamin C, vitamin E and vitamin A, respectively, for adults.
Both maternal 25-hydroxyvitamin D (25(OH)D) concentrations during pregnancy and
placental amino acid transporter gene expression have been associated with
development of the offspring in terms of body composition and bone structure.
Several amino acid transporter genes have vitamin D response elements in their
promoters suggesting the possible linkage of these two mechanisms. We aimed to
establish whether maternal 25(OH)D and vitamin D-binding protein (VDBP) levels
relate to expression of placental amino acid transporters. RNA was extracted
from 102 placental samples collected in the Southampton Women's Survey,
and gene expression was analysed using quantitative real-time PCR. Gene
expression data were normalised to the geometric mean of three housekeeping
genes, and related to maternal factors and childhood body composition. Maternal
serum 25(OH)D and VDBP levels were measured by radioimmunoassay. Maternal
25(OH)D and VDBP levels were positively associated with placental expression of
specific genes involved in amino acid transport. Maternal 25(OH)D and VDBP
concentrations were correlated with the expression of specific placental amino
acid transporters, and thus may be involved in the regulation of amino acid
transfer to the fetus. The positive correlation of VDBP levels and placental
transporter expression suggests that delivery of vitamin D to the placenta may
be important. This exploratory study identifies placental amino acid
transporters which may be altered in response to modifiable maternal factors and
provides a basis for further studies.
Poor nutrition during fetal development can permanently alter growth, cardiovascular physiology and metabolic function. Animal studies have shown that prenatal undernutrition followed by balanced postnatal nutrition alters deoxyribonucleic acid (DNA) methylation of gene promoter regions of candidate metabolic control genes in the liver. The aim of this study was to investigate whether methylation status of the proximal promoter regions of four candidate genes differed between individuals exposed to the Dutch famine in utero. In addition, we determined whether methylation status of these genes was associated with markers of metabolic and cardiovascular disease and adult lifestyle. Methylation status of the GR1-C (glucocorticoid receptor), PPARγ (peroxisome proliferator-activated receptor gamma), lipoprotein lipase and phosphatidylinositol 3 kinase p85 proximal promoters was investigated in DNA isolated from peripheral blood samples of 759 58-year-old subjects born around the time of the 1944–45 Dutch famine. We observed no differences in methylation levels of the promoters between exposed and unexposed men and women. Methylation status of PPARγ was associated with levels of high-density lipoprotein cholesterol and triglycerides as well as with exercise and smoking. Hypomethylation of the GR promoter was associated with adverse adult lifestyle factors, including higher body mass index, less exercise and more smoking. The previously reported increased risk of cardiovascular and metabolic disease after prenatal famine exposure was not associated with differences in methylation status across the promoter regions of these candidate genes measured in peripheral blood. The adult environment seems to affect GR and PPARγ promoter methylation.
Environmental exposures throughout the life course, including nutrition, may induce phenotypic and epigenetic changes. There is limited information about how timing affects the nature of such effects induced by a specific nutritional exposure. We investigated the effect of increased exposure to folic acid before birth or during the juvenile–pubertal period in rats on the epigenetic regulation of glucose homeostasis. Rats were fed either a folic acid-adequate (AF; 1 mg/kg feed) or a folic acid-supplemented (FS; 5 mg/kg feed) diet from conception until delivery and then an AF diet during lactation. Juvenile rats were fed either the AF or the FS diet from weaning for 28 d and then an AF diet. Liver and blood were collected after a 12 h fast between postnatal days 84 and 90. Maternal FS diet increased plasma glucose concentration significantly (P < 0·05) in females, but not in males. Post-weaning FS diet decreased glucose concentration significantly in females, but increased glucose concentration in males. There were no effects of the FS diet on phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression in males, while the pattern of expression was related to plasma glucose concentration in females. The FS diet induced specific changes in the methylation of individual CpG in females, but not in males, which were related to the time of exposure. Methylation of CpG − 248 increased the binding of CCAAT-enhancer-binding protein β to the PEPCK promoter. Together, these findings show that both the period during the life course and sex influence the effect of increased exposure to folic acid on the epigenetic regulation of PEPCK and glucose homeostasis.
This paper briefly describes the principle of operation and science goals of the AMANDA high energy neutrino telescope located at the South Pole, Antarctica. Results from an earlier phase of the telescope, called AMANDA-BIO, demonstrate both reliable operation and the broad astrophysical reach of this device, which includes searches for a variety of sources of ultrahigh energy neutrinos: generic point sources, Gamma-Ray Bursts and diffuse sources. The predicted sensitivity and angular resolution of the telescope were confirmed by studies of atmospheric muon and neutrino backgrounds. We also report on the status of the analysis from AMANDA-II, a larger version with far greater capabilities. At this stage of analysis, details of the ice properties and other systematic uncertainties of the AMANDA-II telescope are under study, but we have made progress toward critical science objectives. In particular, we present the first preliminary flux limits from AMANDA-II on the search for continuous emission from astrophysical point sources, and report on the search for correlated neutrino emission from Gamma Ray Bursts detected by BATSE before decommissioning in May 2000. During the next two years, we expect to exploit the full potential of AMANDA-II with the installation of a new data acquisition system that records full waveforms from the in-ice optical sensors.
The progress that has been made in SiC diodes and GTOs is reviewed. A 100 A/1000 V SiC pi- n diode package, the highest current rating reported for any SiC device, a 69 A conduction/ 11 A turn-off of a SiC GTO and MTOTM, as well as the first all-SiC, 3 phase Pulse Width Modulated (PWM) inverter are reported, herein, for the first time. The inverter achieves voltage controlled turn off with a high temperature capable, hybrid SiC JFET. Material and process technology issues that will need to be addressed before device commercialization can be realized are discussed.
Ondansetron 4 mg was compared with metoclopramide 10 mg for prevention of post-operative nausea and emesis in in-patients undergoing major gynaecological surgery in this double-blind, randomized, placebo-controlled, multicentre study. A total of 1044 patients received a single intravenous (i.v.) injection of study medication immediately before induction of anaesthesia. Nausea and emesis were assessed over the 24 h post-operative period. Significantly more patients who received ondansetron experienced no emetic episodes (44%) compared with those who received metoclopramide (37%, P=0.049) or placebo (25%, P<0.001). No nausea was experienced by significantly more patients who received ondansetron (32%) than with patients who received metoclopramide (24%, P=0.009) or placebo (16%, P<0.001). In addition, fewer emetic episodes, less severe nausea and a reduced need for rescue antiemetics were also observed with ondansetron (P<0.05 vs. metoclopramide and placebo). Metoclopramide and placebo-treated patients were also 1.5 times (95% CI 1.5–4.2) and 2.5 times (95% CI 1.1–2.0) more likely, respectively, to experience nausea post-operatively. Overall, ondansetron was the most effective antiemetic in this patient population.
Angora goats have been suggested as biological control agents for leafy spurge, especially in environmentally sensitive or limited access areas. Dietary preferences and dietary nutritive content of herded Angora goats were evaluated over a two-year period in North Dakota. Relative preferences of forages were evaluated by comparing botanical composition of diets as determined by microhistological analysis of fecal samples to forage availability in the field. Leafy spurge and shrubs comprised the largest percentage of goat diets throughout each grazing season. Goats preferred leafy spurge and shrubs at all times and avoided most cool-season grass species. The nutritional requirements of Angora goats nursing kids were met throughout the grazing season. Use of Angora goats is another tool available to land managers to manage leafy spurge infestations in the Northern Plains.
The effect of annual defoliation on leafy spurge-infested rangeland was investigated over a 5-yr period. Artificial defoliation was conducted once or twice annually at various phenological growth stages of leafy spurge to simulate grazing by herded Angora goats. Single defoliation treatments did not reduce total leafy spurge stem densities. Defoliation twice in a growing season for 4 consecutive yr reduced total leafy spurge stem densities by 55% over nondefoliated controls. Grass foliar cover and yield increased in all defoliation treatments. Despite the increased grass yield on single defoliation treatments, cattle use would likely be limited in these treatments due to the high density of leafy spurge stems. Stem densities of leafy spurge in twice-defoliated treatments should not deter cattle from grazing these sites, thereby increasing the available forage supply. The data suggest that repeated grazing of leafy spurge-infested rangeland within a growing season would be required to reduce stem densities adequately and increase cattle use and production from these sites.
Previous studies in foetal and growing sheep have shown that prolonged administration of β-agonist drugs leads to selective but marked attenuation of cardiovascular, metabolic and endocrine responses to the natural catecholamine hormones adrenaline and noradrenaline, as well as attenuation of responses to the drug itself. The experiment reported here was carried out to determine whether administration of the β-agonist drug, salbutamol, by twice-daily intramuscular injection at rates of 40 or 200 μ/kg per day, for a period long enough to result in substantial attenuation of its metabolic and endocrine effects, might also result in impairment in the ability of treated animals to respond to stressful husbandry procedures which disturb metabolic homeostasis and which depend on increased sympathetic nervous and adrenal activity for the restoration of homeostasis. Serial blood sampling on day 1 and day 14 of salbutamol treatment showed that the large increases in plasma lactate and glucose observed on the 1st day were absent on day 14, while the rapid increases in free fatty acids and insulin observed on day 1 were very greatly attenuated. Daily blood sampling also demonstrated that salbutamol, like cimaterol, significantly decreased both pre- and post-feeding plasma insulin and glucose concentrations.
Metabolic and endocrine changes consequent on herding and immersion of the lambs in a sheep-dip, were unaltered by 14 days of salbutamol treatment, even though the procedure resulted in activation of the pituitary-adrenal axis as evidenced by increased β-endorphin and cortisol concentrations, and a large increase in plasma lactate concentration. These results suggest β-agonist-treated animals can respond normally to physiological stresses but further investigations remain necessary to determine whether responses dependent on increased lipid mobilization and shivering, such as shearing or prolonged exposure to severe cold, remain normal in β-agonist treated animals.
Leaf proportions (LP) were determined in spring barley straws harvested at Cambridge in 1984 and 1985. Linear regression equations showed that a greater number of days to flowering increased LP whilst greater plant height decreased LP in spring barley straws. Plant height accounted for more than 70% of the variance in LP. By contrast, grain yield and stem diameter accounted for only a small percentage of the variance in LP. Straws from two-rowed winter barleys had slightly higher LP than six-rowed winter barleys but LP in winter and spring barleys were similar.
Leaf blade and leaf sheath fractions of the straws had lower acid detergent fibre and lignin contents and were more digestible than the stem fractions. Linear regression equations of straw digestibility in spring barleys on LP, grain yields, days to flowering and plant heights showed that LP accounted for a higher percentage of the variance in digestibility in 1984 than the other characteristics. In 1985, when harvesting conditions were unusually wet, grain yield accounted for the highest percentage of the variance in straw digestibility.
There were no differences in chemical composition and straw digestibility between two-rowed and six-rowed barleys, but winter barleys had higher straw digestibility than spring barleys. Date of sowing did not influence straw quality in two-rowed winter barleys.
The ranking of two-rowed spring barleys for LP, chemical composition and digestibility suggested that varieties with consistently better straw quality could be identified.
A technique commonly used as the final stage of cleaning gold electrode surfaces is to electrochemically form and reduce a monolayer of oxide on the surface. We have investigated the changes on the Au(111) surface during this procedure using in situ electrochemical scanning tunneling microscopy.
This evaluation of recent experience of hypoglossal-facial nerve anastomosis in ten patients who had undergone acoustic neuroma resection, indicates that this procedure may have a role to play in the treatment of this disfiguring condition. Facial symmetry at rest is satisfactory in the majority of patients, who suffered little long term deficit from the loss of their hypoglossal nerve. This procedure is ideally suited to otolaryngological practice.