Palmar Warming for Radial Artery Vasodilation to Facilitate Transradial Access: A Randomized Controlled Trial.

PURPOSE: To investigate the efficacy of palmar warming to induce radial artery vasodilation. MATERIALS AND METHODS: After informed consent was obtained, healthy volunteers (n = 45) were randomized 2:1 in palmar warming and control groups, respectively, for this prospective, randomized, single-blind clinical trial (NCT03620383). The palmar warming group was given a warm, commercially available, air-activated heat pack (Kobayashi Consumer Products LLC, Dalton, Georgia) to hold in the left hand for palmar warming. The control group was given a deactivated version of the same heat pack. Left radial artery cross-sectional area (CSA) measurements were obtained at baseline and in 5-minute intervals up to 20 minutes in both groups. Differences in the trends of changes in the radial artery CSA between palmar warming and control groups were examined with the age- and sex-adjusted repeated measure analysis of variance. Propensity score-matched treatment effect analysis was conducted to quantify the effect of heat on radial artery CSA. RESULTS: The palmar warming group and the control group were significantly different in terms of subject sex (males/females: 7/23 and 10/5, respectively; P = .005) and baseline CSA (2.5±0.2 mm2 vs 3.2±0.3 mm2, respectively; P = .014). Radial artery CSA showed an increasing trend over time in the palmar warming group compared to a stable trend over time in the control group (P < .0001). Propensity score-matched comparison showed a 43.9% increase (95% confidence interval: 34.1%-53.8%) in CSA in the palmar warming group compared to the control group (P < .0001). CONCLUSIONS: The palmar warming technique is effective at dilating the radial artery and may be a beneficial technique to facilitate transradial access.

Real-time characterization of the molecular epidemiology of an influenza pandemic.

Early characterization of the epidemiology and evolution of a pandemic is essential for determining the most appropriate interventions. During the 2009 H1N1 influenza A pandemic, public databases facilitated widespread sharing of genetic sequence data from the outset. We use Bayesian phylogenetics to simulate real-time estimates of the evolutionary rate, date of emergence and intrinsic growth rate (r0) of the pandemic from whole-genome sequences. We investigate the effects of temporal range of sampling and dataset size on the precision and accuracy of parameter estimation. Parameters can be accurately estimated as early as two months after the first reported case, from 100 genomes and the choice of growth model is important for accurate estimation of r0. This demonstrates the utility of simple coalescent models to rapidly inform intervention strategies during a pandemic.

Marginal iodide deficiency and thyroid function: dose-response analysis for quantitative pharmacokinetic modeling.

Severe iodine deficiency (ID) results in adverse health outcomes and remains a benchmark for understanding the effects of developmental hypothyroidism. The implications of marginal ID, however, remain less well known. The current study examined the relationship between graded levels of ID in rats and serum thyroid hormones, thyroid iodine content, and urinary iodide excretion. The goals of this study were to provide parametric and dose-response information for development of a quantitative model of the thyroid axis. Female Long Evans rats were fed casein-based diets containing varying iodine (I) concentrations for 8 weeks. Diets were created by adding 975, 200, 125, 25, or 0 µg/kg I to the base diet (~25 µg I/kg chow) to produce 5 nominal I levels, ranging from excess (basal+added I, Treatment 1: 1000 µg I/kg chow) to deficient (Treatment 5: 25 µg I/kg chow). Food intake and body weight were monitored throughout and on 2 consecutive days each week over the 8-week exposure period, animals were placed in metabolism cages to capture urine. Food, water intake, and body weight gain did not differ among treatment groups. Serum T4 was dose-dependently reduced relative to Treatment 1 with significant declines (19 and 48%) at the two lowest I groups, and no significant changes in serum T3 or TSH were detected. Increases in thyroid weight and decreases in thyroidal and urinary iodide content were observed as a function of decreasing I in the diet. Data were compared with predictions from a recently published biologically based dose-response (BBDR) model for ID. Relative to model predictions, female Long Evans rats under the conditions of this study appeared more resilient to low I intake. These results challenge existing models and provide essential information for development of quantitative BBDR models for ID during pregnancy and lactation.

Predictive modeling of a mixture of thyroid hormone disrupting chemicals that affect production and clearance of thyroxine.

Thyroid hormone (TH) disrupting compounds interfere with both thyroidal and extrathyroidal mechanisms to decrease circulating thyroxine (T(4)). This research tested the hypothesis that serum T(4) concentrations of rodents exposed to a mixture of both TH synthesis inhibitors (pesticides) and stimulators of T(4) clearance in the liver (polyhalogenated aromatic hydrocarbons, PHAHs) could be best predicted by an integrated addition model. Female Long-Evans rats, 23 days of age, were dosed with dilutions of a mixture of 18 PHAHs (2 dioxins, 4 dibenzofurans, and 12 PCBs, including dioxin-like and non-dioxin like PCBs) and a mixture of 3 pesticides (thiram, pronamide, and mancozeb) for four consecutive days. Serum was collected 24 hours after the last exposure and T(4) concentrations were measured by radioimmunoassay. Animals exposed to the highest dose of the mixture experienced a 45% decrease in serum T(4). Three additivity model predictions (dose addition, effect addition, and integrated addition) were generated based on single chemical data, and the results were compared. Effect addition overestimated the effect produced by the combination of all 21 chemicals. The results of the dose- and integrated-addition models were similar, and both provided better predictions than the effect-addition model. These results support the use of dose- and integrated additivity models in predicting the effects of complex mixtures.

In vivo acute exposure to polychlorinated biphenyls: effects on free and total thyroxine in rats.

Hypothyroxinemia in rats has been well documented as a result of exposure to polychlorinated biphenyls (PCBs). Hypothetical mechanisms include induction of hepatic catabolic enzymes and cellular hormone transporters, and/or interference with plasma transport proteins. We hypothesized that if thyroxine displacement from transport proteins by PCBs occurs in vivo, it would result in increased free thyroxine (FT4). This study investigates the effects of a single oral dose of 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153 at 60 mg/kg) or 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169 at 1 mg/kg) on rats at 28 or 76 days of age. Total thyroxine (TT4) and FT4 were measured at 0.5, 1, 2, 4, 8, 24, or 48 hours post-dosing. Microsomal ethoxy- and pentoxy-resorufin-O-deethylase (EROD and PROD) activity and uridine diphosphoglucuronosyl transferase (UGT) activity were determined. No significant increase in TT4 or FT4 concentrations was seen at any time point. PCB 153 significantly decreased TT4 and FT4 in young and adult rats, with young rats showing a time-by-treatment interaction from 2 to 48 hours post-dosing in serum FT4. With PCB 169 exposure, young rats showed a decrease in FT4 only, whereas adult rats showed decreases in TT4 only. Hepatic EROD and PROD activities were both dramatically increased following PCB 169 and 153, respectively. Uridine diphosphoglucuronosyl transferase activity was increased only after PCB 169 exposure. These data demonstrate that neither PCB 153 nor PCB169 increased FT4, which supports the conclusion that these PCBs do not displace thyroxine from serum TTR, or if it does occur, there is no subsequent increase in serum FT4 in vivo.

Influence of the drinking water disinfection by-product dibromoacetic acid on rat estrous cyclicity and ovarian follicular steroid release in vitro.

The drinking water disinfection by-product, dibromoacetic acid (DBA) has been reported to affect gonadal functions in the male rat. However, there is little information regarding the influence of DBA on female reproductive activity. Consequently, the present study investigated the effects of DBA on estrous cyclicity and the impact in vitro of DBA on ovarian follicular steroid secretion. Regularly cycling animals were dosed with DBA (0 to 270 mg/kg/day) for 14 days and estrous cyclicity was monitored during treatment and for an additional 2-week posttreatment interval. A dose-related alteration in cyclicity was observed at 90 and 270 mg/kg/day, which persisted through the posttreatment monitoring in the high dose group. An in vitro exposure of preovulatory follicles to DBA was then used to assess the influence of DBA on steroid release. To select a concentration for use, a single oral exposure to 270 mg/kg was administered, and the mean blood levels were determined over a 5-h interval. For this in vitro work, pairs of preovulatory follicles from PMSG-primed immature rats were exposed to 0 or 50 microg/mL DBA over a 24-h period and evaluated for estradiol and progesterone release under baseline and hCG-stimulated conditions. The influence of tumor necrosis factor (TNFalpha) exposures under these conditions was also determined. In the nonstimulated condition, DBA was found to increase the release of estradiol, but had no detectable effect in response to hCG. Progesterone, however, showed marked suppression under hCG stimulation following exposure to DBA, while nonstimulated secretion was unaffected. TNFalpha by itself also suppressed stimulated progesterone release, but had no additional effect in combination with DBA. The data suggest that one factor in the disruption in estrous cyclicity could be an alteration in steroid production, which was characterized by separate effects on both estradiol and progesterone secretion.

Selecting pilots with crew resource management skills.

For years, pilot selection has focused primarily on the identification of individuals with superior flying skills and abilities. More recently, the aviation community has become increasingly aware that successful completion of a flight or mission requires not only flying skills but the ability to work well in a crew situation. This project involved development and validation of a crew resource management (CRM) skills test for Air Force transport pilots. A significant relation was found between the CRM skills test and behavior-based ratings of aircraft commander CRM performance, and the implications of these findings for CRM-based selection and training are discussed.

Effect of prenatal exposure to TCDD on the promotion of endometriotic lesion growth by TCDD in adult female rats and mice.

Several lines of research led to our hypothesis that perinatal exposure to TCDD may alter the sensitivity of adult rodents to the promotional effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on endometriosis. Pregnant rats and mice were treated on gestation day (GD) 8 with either 1 (rats) or 3 (mice) microg TCDD/kg or vehicle. Female offspring were reared to adulthood, and endometriosis was induced surgically. All animals received 0, 3, or 10 microg TCDD/kg 3 weeks prior to surgery, at the time of surgery, and 3, 6, and 9 weeks after surgery. Necropsies were performed 12 weeks after surgery. Measurements at necropsy included the diameter of endometriotic lesions and body, uterine, ovarian and liver weights. While no effect of treatment on lesion diameter was found in rats, analyses revealed that perinatal plus adult exposure to TCDD can increase the size of endometriotic lesions surgically induced in mice. These and additional data on body and organ weights are consistent with previous work. These data confirm the sensitivity of mice to the promotion of endometriotic lesion growth by TCDD and indicate a perinatal effect of TCDD on this parameter when perinatal exposure on GD8 is supplemented with adult exposure to TCDD of female mice.

Dibromoacetic acid does not adversely affect early pregnancy in rats.

Dibromoacetic acid (DBA), a byproduct of water disinfection, has been shown to have adverse reproductive effects in male rodents. In light of the lack of data on potential effects on female reproduction, studies were initiated to evaluate the potential effect of the chemical on early pregnancy. Groups of mature Holtzman rats were used, and cycles were monitored in all animals by vaginal smears. The administration of DBA at 0, 62.5, 125, or 250 mg/kg/d to rats during the first 8 d of pregnancy had no effect on the number of implantation sites found on Day 9 nor any other progestational parameter, except for serum estradiol, which was elevated. When groups of pregnant rats treated with the same range of dosages of DBA during Days 1 through 8 of pregnancy were killed on Day 20, there was no effect of treatment on the number of pups/litter, number of resorptions, or mean pup weight. These data demonstrate that while DBA has serious adverse effects on reproduction in male rodents, the chemical does not affect early pregnancy in rats. Effects on ovarian function and latent fertility are not ruled out.

Comparison of 0.25% ropivacaine and bupivacaine for epidural analgesia for labor and vaginal delivery.

STUDY OBJECTIVE: Part 1: To measure ropivacaine levels in the mother and infant at delivery after continuous lumbar epidural infusion. Part 2: To compare epidural ropivacaine to epidural bupivacaine for labor analgesia in regard to effectiveness, motor blockade, and maternal and neonatal effects. DESIGN: Part 1: Open-labelled, non-blind study. Part 2: Randomized, double-blind study. SETTING: Labor and delivery units of two academic hospitals. PATIENTS: Part 1: 20 ASA physical status I and II parturients in active labor. Part 2: 81 ASA physical status I and II parturients in active labor. INTERVENTIONS: For Part 1, 8 to 12 ml of 0.25% ropivacaine was administered through a lumbar epidural catheter to achieve a T10 dermatomal sensory level. An infusion of 0.25% ropivacaine, 8 to 10 ml/hr, maintained this sensory level. Maternal and umbilical cord blood samples obtained at delivery were analyzed for ropivacaine concentration. For Part 2, anesthetic management was similar to that previously described except patients were randomized to receive either 0.25% ropivacaine or 0.25% bupivacaine. Onset, regression, maximal spread of sensory block, and onset and degree of motor blockade were measured. Contraction pain as assessed using a visual analog scale (VAS), maternal blood pressure, and heart rate were determined every 5 minutes until a stable VAS-contraction score was achieved, and every 30 minutes thereafter. Neonatal assessment included Apgar scores and neurologic and adaptive capacity scores (NACS) at 15 minutes, 2 hours, and 24 hours. MEASUREMENTS AND MAIN RESULTS: For Part 1, the total and free maternal arterial concentrations of ropivacaine at delivery were 0.64 +/- 0.14 microgram/ml and 0.10 +/- .02 microgram/ml, respectively; the umbilical venous total and free concentrations were 0.19 +/- 0.03 microgram/ml and 0.12 +/- 0.07 microgram/ml, respectively (n = 12). The umbilical arterial and venous concentrations did not differ for both the free and total concentrations. For Part 2, there was no difference between ropivacaine and bupivacaine in the variables measured. Umbilical cord gases and Apgar scores were not different between the two groups; NACS were higher at 15 minutes and 2 hours in the ropivacaine group (p < 0.05) than the bupivacaine group. CONCLUSION: Both ropivacaine and bupivacaine produced excellent analgesia for labor with no major adverse effect on the mother or neonate.

Personnel selection.

This chapter reviews literature from approximately mid-1993 through early 1996 in the areas of performance and criteria, validity, statistical and equal opportunity issues, selection for work groups, person-organization fit, applicant reactions to selection procedures, and research on predictors, including ability, personality, assessment centers, interviews, and biodata. The review revolves around three themes: (a) attention toward criteria and models of performance, (b) interest in personality measures as predictors of job performance, and (c) work on the person-organization fit selection model. In our judgment, these themes merge when it is recognized that development of performance models that differentiate criterion constructs reveal highly interpretable relationships between the predictor domain (i.e. ability, personality, and job knowledge) and the criterion domain (i.e. technical proficiency, extra-technical proficiency constructs such as prosocial organizational behavior, and overall job performance). These and related developments are advancing the science of personnel selection and should enhance selection practices in the future.

Ketoconazole impairs early pregnancy and the decidual cell response via alterations in ovarian function.

Ketoconazole (KCZ) is an imidazole antifungal agent that also affects P450 enzymes of the mammalian steroidogenic system. Several steps in the ovarian steroidogenesis pathway are known to be inhibited by KCZ, but previous work has failed to address the ramifications of such inhibition with respect to early pregnancy. In initial studies, Holtzman rats (8-10/group) were administered 10-100 mg/kg KCZ during days 1-8 of pregnancy. On day 9, evaluations revealed a reduction at both 75 and 100 mg KCZ/kg in the number of implantation sites and serum progesterone levels as well as an increase in ovarian weight. The decidual cell response (DCR) was blocked by KCZ in parallel with decreased serum progesterone and increased ovarian weight, indicating direct interference with uterine function. KCZ had no effect when given to long-term-ovariectomized rats that were hormone supplemented to permit the DCR, indicating that the ovary was at least one site of KCZ action on early pregnancy. Measurement of ovarian progesterone production in vitro from ovaries removed from rats treated in vivo with KCZ indicated a decline in progesterone production, suggesting a direct effect of KCZ on ovarian steroidogenesis. These data demonstrate that KCZ can compromise early pregnancy and appears to do so by inhibiting progesterone synthesis in the ovary.