Analysing how changes in the health status of healthcare workers affects epidemic outcomes.

During a disease outbreak, healthcare workers (HCWs) are essential to treat infected individuals. However, these HCWs are themselves susceptible to contracting the disease. As more HCWs get infected, fewer are available to provide care for others, and the overall quality of care available to infected individuals declines. This depletion of HCWs may contribute to the epidemic's severity. To examine this issue, we explicitly model declining quality of care in four differential equation-based susceptible, infected and recovered-type models with vaccination. We assume that vaccination, recovery and survival rates are affected by quality of care delivered. We show that explicitly modelling HCWs and accounting for declining quality of care significantly alters model-predicted disease outcomes, specifically case counts and mortality. Models neglecting the decline of quality of care resulting from infection of HCWs may significantly under-estimate cases and mortality. These models may be useful to inform health policy that may differ for HCWs and the general population. Models accounting for declining quality of care may therefore improve the management interventions considered to mitigate the effects of a future outbreak.

Mild hypoxic ischaemic encephalopathy and long term neurodevelopmental outcome - A systematic review.

AIMS: Hypoxic ischaemic encephalopathy (HIE) remains a significant cause of long term neurodisability despite therapeutic hypothermia (TH). Infants with mild HIE, representing 50% of those with HIE, are perceived as low risk and are currently not eligible for TH [1]. This review examines the available evidence of outcome in term infants with mild HIE. METHODS: Medline, Embase and Cochrane Clinical Trials databases were searched in March 2017. Studies with well-defined HIE grading at birth and standardised neurodevelopmental assessment at ≥18 months were included. Abnormal outcome was defined as death, cerebral palsy or standardised neurodevelopmental test score more than 1 standard deviation below the mean. RESULT: Twenty studies were included. Abnormal outcome was reported in 86/341 (25%) of infants. There was insufficient evidence to examine the effect of TH on outcome. CONCLUSION: A significant proportion of infants with mild HIE have abnormal outcome at follow up.

Steady-state carbamazepine pharmacokinetics following oral and stable-labeled intravenous administration in epilepsy patients: effects of race and sex.

Carbamazepine is a widely prescribed antiepileptic drug. Owing to the lack of an intravenous formulation, its absolute bioavailability, absolute clearance, and half-life in patients at steady state have not been determined. We developed an intravenous, stable-labeled (SL) formulation in order to characterize carbamazepine pharmacokinetics in patients. Ninety-two patients received a 100-mg infusion of SL-carbamazepine as part of their morning dose. Blood samples were collected up to 96 hours after drug administration. Plasma drug concentrations were measured with liquid chromatography-mass spectrometry, and concentration-time data were analyzed using a noncompartmental approach. Absolute clearance (l/hr/kg) was significantly lower in men (0.039 ± 0.017) than in women (0.049 ± 0.018; P = 0.007) and in African Americans (0.039 ± 0.017) when compared with Caucasians (0.048 ± 0.018; P = 0.019). Half-life was significantly longer in men than in women as well as in African Americans as compared with Caucasians. The absolute bioavailability was 0.78. Sex and racial differences in clearance may contribute to variable dosing requirements and clinical response.

Phenytoin half-life and clearance during maintenance therapy in adults and elderly patients with epilepsy.

BACKGROUND: Phenytoin (PHT) is widely used to treat epilepsy in elderly patients, but information on its pharmacokinetics in this population is limited. OBJECTIVE: The purpose of this study was to investigate the effects of age and sex on PHT pharmacokinetics using stable-labeled (SL) isotopes of PHT or fosphenytoin (FOS) administered IV or IM while patients remained on their oral maintenance regimen. METHODS: Subjects were patients 18 years or older with epilepsy, but otherwise healthy, on a maintenance regimen of PHT who were not taking interacting medications. Subjects were given a single injection of a 100 mg dose of SL-PHT or SL-FOS followed by their usual morning PHT dose less 100 mg. Serial blood samples were collected up to 196 hours after the SL dose. Plasma PHT and SL-PHT concentrations were measured by a gas chromatographic-mass spectrometric assay. PHT pharmacokinetics were characterized using a population-based, nonlinear, mixed-effects model. RESULTS: Sixty-three subjects completed the study, 45 of whom were 65 years or older. There was no difference between adult and elderly or men and women in PHT clearance, distribution volume, and elimination half-life. The mean elimination half-life was 40 hours. CONCLUSIONS: Healthy elderly adults appear to have the same phenytoin (PHT) pharmacokinetics as younger adults. Reduced PHT dosage requirements may be due to age-related changes in patients' sensitivity to the therapeutic and toxic effects of the drug. The prolonged elimination half-life suggests that most patients can take PHT once daily and the time to reach steady-state may extend to 2-3 weeks.

Can dual energy X-ray absorptiometry provide a valid assessment of changes in thigh muscle mass with strength training in older adults?

OBJECTIVE: To determine how dual-energy X-ray absorptiometry (DXA) compares to computed tomography (CT) for measuring changes in total thigh skeletal muscle (SM) mass with strength training (ST) in older adults. SUBJECTS: Fifty previously sedentary, relatively healthy older men (n=23, 60 (s.d.=7.5) years) and women (n=27, 60 (s.d.=9.3) years). RESULTS: Results indicate that there was a significant increase in thigh SM mass with ST measured by both CT (3.9+/-0.4%) and DXA (2.9+/-0.6%) methods (both P<0.001), and there was not a significant difference in percent change between the two methods, although there was a substantial absolute difference ( approximately 2 kg) at baseline between the two methods. Although Bland-Altman plots indicate overall agreement between the percent thigh SM mass changes of DXA vs CT methods, the 3.4% error associated with DXA was greater than the thigh SM mass change from DXA. However, the CT measured change in thigh SM mass was greater than its error (0.6%). CONCLUSIONS: DXA overestimates baseline and after ST thigh SM mass, and may not be able to detect small changes in thigh SM mass with ST due to its higher error. Although DXA has certain advantages that warrant is used in epidemiologic and intervention studies, improvements to DXA are needed for the accurate assessment of small changes in thigh SM mass.

AFLP-based assessment of genetic diversity among nine alfalfa germplasms using bulk DNA templates.

Improving commercial utilization of perennial Medicago collections requires developing approaches that can rapidly and accurately characterize genetic diversity among large numbers of populations. This study evaluated the potential of using amplified fragment length polymorphism (AFLP) DNA markers, in combination with DNA bulking over multiple genotypes, as a strategy for high-throughput characterization of genetic distances (D) among alfalfa (Medicago sativa L.) accessions. Bulked DNA templates from 30 genotypes within each of nine well-recognized germplasms (African, Chilean, Flemish, Indian, Ladak, Medicago sativa subsp. falcata, Medicago sativa subsp. varia, Peruvian, and Turkistan) were evaluated using 34 primer combinations. A total of 3754 fragments were identified, of which 1541 were polymorphic. The number of polymorphic fragments detected per primer combination ranged from 20 to 85. Pairwise D estimates among the nine germplasms ranged from 0.52 to 1.46 with M. sativa subsp. falcata being the most genetically dissimilar. Unweighted pair-group method arithmetic average (UPGMA) analysis of the marker data produced two main clusters, (i) M. sativa subsp. sativa and M. sativa subsp. varia, and (ii) M. sativa subsp. falcata. Cluster-analysis results and D estimates among the Chilean, Peruvian, Flemish, and M. sativa subsp. varia germplasms supported the hypothesis that Peruvian was more similar to original Spanish introductions into Central and South America than Chilean. Hierarchical arrangement of the nine germplasms was supported by their respective geographic, subspecific, and intersubspecific hybrid origins. Subsets of as few as seven highly informative primer pairs were identified that produced comparable D estimates and similar heirarchical arrangements compared with the complete dataset. The results indicate that use of primer-pair subsets for AFLP analysis of bulk DNA templates could serve as a high-throughput system for accurately characterizing genetic diversity among large numbers of alfalfa populations.

Variability of total phenytoin serum concentrations within elderly nursing home residents.

BACKGROUND: Approximately 6% of all elderly nursing home residents receive phenytoin. Phenytoin concentrations are often measured to guide therapy. OBJECTIVE: To evaluate the intraresident variability among multiple measurements of total phenytoin serum concentrations in nursing home residents. METHODS: This was an observational study of 56 elderly (>or=65 years) nursing home residents from 32 nursing homes who had at least 3 phenytoin concentrations measured while on the same dose of phenytoin for at least 4 weeks and who were not taking any interfering concomitant medications. These were a subset of 387 elderly nursing home residents from 112 nursing homes across the United States who had total phenytoin concentration measurements between June 1998 and December 2000. RESULTS: The mean age was 80.1 years (range, 65 to 100 years) and 58.9% were women. The mean daily dose of phenytoin per resident was 4.9 +/- 1.5 mg/kg. Total phenytoin concentrations within an elderly nursing home resident varied as much as two- to threefold, even though there was no change in dose. The person with the smallest variability had a minimum concentration of 10.0 micro g/mL and a maximum of 10.4 micro g/mL. The person with the largest variability had a minimum concentration of 9.7 micro g/mL and a maximum of 28.8 micro g/mL. CONCLUSIONS: There is considerable variability in the total phenytoin concentrations in the elderly nursing home resident and measurement of a single total phenytoin concentration should not be used to guide treatment.

A moderate carbohydrate and fat diet does not impair strength performance in moderately trained males.

BACKGROUND: The purpose of this investigation was to study the effects of varied levels of dietary carbohydrate and fat intake on exercise training and high intensity exercise performance in moderately strength trained, aerobic trained and untrained males. METHODS: Subjects (6 strength trained, 6 aerobically trained serving as an active control group, 6 sedentary) consumed isoenergetic diets considered either high CHO/low fat (HC/LF: total energy 62% CHO, 20% fat, 18% protein) or moderate CHO and fat (MC/MF: total energy 42% CHO, 40% fat, 18% protein) in a randomly assigned crossover design. Each dietary treatment was three weeks in length. Prior to the study and following each dietary treatment, muscular strength and endurance was determined (isokinetic knee extension and flexion, standard concentric free weight bench press). RESULTS: No differences as a result of the dietary treatment were seen in isokinetic peak torque, total work production, single repetition maximum (1 RM) bench press, or number of bench press repetitions at 80% 1 RM. Self-reported exercise log data showed no dietary effect on the subject's ability to maintain training level. CONCLUSIONS: These findings indicate that varying dietary macronutrient content (HC/LF or MC/MF) had no effect on exercise training or strength exercise performance in moderately trained (aerobic and strength) or sedentary males.

Identification and meta-analytic assessment of psychological constructs measured in employment interviews.

There has been a growing interest in understanding what constructs are assessed in the employment interview and the properties of those assessments. To address these issues, the authors developed a comprehensive taxonomy of 7 types of constructs that the interview could assess. Analysis of 338 ratings from 47 actual interview studies indicated that basic personality and applied social skills were the most frequently rated constructs in this taxonomy, followed by mental capability and job knowledge and skills. Further analysis suggested that high- and low-structure interviews tend to focus on different constructs. Taking both frequency and validity results into consideration, the findings suggest that at least part of the reason why structured interviews tend to have higher validity is because they focus more on constructs that have a stronger relationship with job performance. Limitations and directions for future research are discussed.

Estimation of energy expenditure from physical activity measures: determinants of accuracy.

OBJECTIVE: To describe the determinants, specifically age, body mass index, percentage of body fat, and physical activity (PA) level, associated with over- and underestimation of energy expenditure (EE) using PA records and the Stanford Seven-Day Physical Activity Recall (7DR) compared with doubly labeled water (DLW). RESEARCH METHODS AND PROCEDURES: We collected PA measures on 24 males eating a controlled diet designed to maintain body weight, and we determined EE from DLW and estimated EE from PA records and 7DR. RESULTS: Absolute differences in the estimation of EE between DLW and PA assessment methods were greater for the 7DR (30.6 +/- 9.9%) than PA records (7.9 +/- 3.2%). In PA records, overestimation of EE was greater with older age and higher body fatness; EE was overestimated by 16.7% among men 50 years and older compared with only 5.3% among men <40 years of age. For percentage of body fat, EE was overestimated by 19.7% among men with a percentage of body fat > or =30% compared with only 5.6% among men with a percentage of body fat <25%. A trend for less overestimation of EE with higher levels of PA (measured by DLW/basal metabolic rate [BMR]) also was observed in the PA records. In the 7DR, the estimates of EE varied widely and no trends were observed by age, percentage of body fat, and PA levels. DISCUSSION: Estimation of EE from the 7DR is considerably more variable than from PA records. Factors related to age and percentage of body fat influenced the accuracy of estimated EE in the PA record. Additional studies are needed to understand factors related to accurate reporting of PA behaviors, which are used to estimate EE in free-living adults.

Dimension and exercise variance in assessment center scores: a large-scale evaluation of multitrait-multimethod studies.

This study addresses 3 questions regarding assessment center construct validity: (a) Are assessment center ratings best thought of as reflecting dimension constructs (dimension model), exercises (exercise model), or a combination? (b) To what extent do dimensions or exercises account for variance? (c) Which design characteristics increase dimension variance? To this end, a large set of multitrait-multimethod studies (N = 34) were analyzed, showing that assessment center ratings were best represented (i.e., in terms of fit and admissible solutions) by a model with correlated dimensions and exercises specified as correlated uniquenesses. In this model, dimension variance equals exercise variance. Significantly more dimension variance was found when fewer dimensions were used and when assessors were psychologists. Use of behavioral checklists, a lower dimension-exercise ratio, and similar exercises also increased dimension variance.

Energy metabolism increases and regional body fat decreases while regional muscle mass is spared in humans climbing Mt. Everest.

The objectives of the study were to determine regional changes in body composition, energy expenditure by means of doubly labeled water, and net energy balance during exposure to high and extreme altitudes (5,300-8,848 m). This study focuses on a subset of subjects who consumed the doubly labeled water (three base camp personnel and seven climbers). Regional body composition was determined by measuring skinfold thicknesses and circumferences at 10 different sites on the body. Energy expenditure was measured by doubly labeled water excretion. Discrepancies between actual energy expenditure and data obtained from diet records and body weight changes suggested a chronic underreporting of dietary energy intake, especially by those subjects who reached the highest altitudes. This underreporting may be due in part to diminished cognition or to a preferential focus on survival, rather than on filling out diet records accurately. Mean adjusted dietary intakes were 10.50 +/- 0. 65 MJ/d (2510 +/- 155 kcal/d) for those who remained at base camp, and 20.63 +/- 6.56 MJ/d (4931 +/- 1568 kcal/d) for those who climbed above base camp. Energy expenditure averaged 2.5-3.0 times sea level resting energy expenditure. Differential changes in regional body composition suggested a preferential loss of fat mass and a relative sparing of muscle mass, despite insufficient energy intake to maintain body weight.

Relationship between overnight energy expenditure and BMR measured in a room-sized calorimeter.

OBJECTIVE: The purpose of this study was to determine if overnight energy expenditure, the lowest energy expenditure sustained for 60 min during the night, measured and predicted basal metabolic rate are equivalent. DESIGN: Overnight energy expenditure (ON-EE), the lowest energy expenditure sustained for 60 min during sleep (LS-EE) and basal metabolic rate (BMR) were measured two to seven times in a room-sized indirect calorimeter in 69 adult subjects. Subjects' gender, age, weight and height were also used to predict BMR (FAO/WHO/UNU, 1985) (BMR-WHO). SETTING: Beltsville Human Nutrition Research Center, Beltsville, MD, USA. RESULTS: The results from calorimetry measurements (mean +/- s.d.) included: ON-EE (6.87 +/- 0.99 MJ/d), LS-EE (6.18 +/- 0.94 MJ/d) and BMR (6.87 +/- 0.99 MJ/d). Predicted BMR mean was: BMR-WHO, 6.95 +/- 1.03. The mean within-subject difference for the calorimetry measurements were: ON-EE, 0.21 MJ/d; LS-EE, 0.16 MJ/d; and BMR, 0.34 MJ/d. Results indicate there was no significant difference between ON-EE, BMR and BMR-WHO. LS-EE was significantly lower (P < 0.0001) than ON-EE, BMR and BMR-WHO. CONCLUSION: These results indicate that while metabolic rate drops significantly below BMR during sleep, overnight metabolic rate and BMR are equivalent.

Body composition analysis of small pigs by dual-energy x-ray absorptiometry.

We evaluated the use of dual-energy x-ray absorptiometry (DXA) for measuring the gross body composition of small subjects in 97 pigs that ranged from 5 to 27 kg live body weight. Scans were performed using a Lunar DPXL densitometer in the pediatric mode (Version 3.8e). The DXA scans of the live pigs provided measurements of total fat, lean, and bone mineral content. After scanning, the pigs were killed, the entire body was ground, and samples were analyzed chemically (CHEM) for fat, protein, ash, and water content. We found that DXA significantly underestimated the percentage of fat in the body (DXA, 6.9+/-.33% vs CHEM, 10.9+/-.31%, P < .001). The correlation (r) between DXA and chemical measures of percentage fat was .86 and for grams of fat it was .96. Lean tissue mass measured by DXA was highly correlated with CHEM measurements of total grams of body water (r = .99), total grams of body protein (r = .94), and lean body mass (r = .99). The average DXA bone mineral content was within 2% of the amount estimated from total body ash and the correlation between the two values was .94. The relationships between DXA and CHEM measurements for percentages of body composition of pigs that weighed between 5 and 27 kg are described by the following regression equations: %fatCHEM = 5.22 + [.817.fatDXA], (r = .86, standard error of the estimate, SEE = 1.56); %proteinCHEM = -7.8 + [.256%leanDXA], (r = .35, SEE = 2.3); %waterCHEM = -5.2 + [.808-%leanDXA], (r = .59, SEE = 3.67). These results are consistent with previously reported results and suggest that even though direct use of DXA readings may not be sufficiently accurate, the high degree of correlation indicates that with proper calibration the DXA values can be used to predict body composition.

Brief paradoxical sleep deprivation impairs reference, but not working, memory in the radial arm maze task.

Selective deprivation of paradoxical sleep after learning results in memory deficits in a variety of tasks. The present experiment was designed to examine the effects of paradoxical sleep deprivation (PSD) upon spatial working and reference memory. Adult male Sprague-Dawley rats were trained for 10 days in an eight-arm radial maze. Food rewards were available in four of the arms, while the other four arms were never baited. After each daily training session, different groups of rats were given 4 h of PSD, beginning either immediately, 4 h, or 8 h after the training experience. An additional group received PSD during the period 13-24 h following daily training. The group that received PSD for 4 h immediately following daily training showed significant impairment compared to the other groups, but the deficit was limited to the reference component of the task. This result suggests that PSD causes deficits only in long-term forms of spatial memory.

Body composition analysis of pigs from 5 to 97 kg by dual energy X-ray absorptiometry.

A total of 231 pigs were anesthetized and then scanned by DXA using a Lunar DPXL instrument. The weight of the pigs ranged from 5 to 97 kg (av. = 37.7 kg). Of the total, 98 pigs were scanned using the pediatric mode and 133 pigs were scanned using the adult mode. After scanning, the pigs were euthanized, the entire body homogenized by grinding, and analyzed chemically for fat, water, protein and total body mineral content. The mean value for the DXA total tissue mass (37.1 kg) was not significantly (P > 0.05, n = 231) different from the mean body weight. The mean DXA value for percent fat was 14.6 and was significantly less (P < 0.05) than the mean value (17.6%) measured by CHEM analysis. The greatest discrepancy occurred in pigs with < 15% body fat. From a prediction equation using the DXA R value [% fat = 493-349(DXA R value)], the DXA estimated percent fat was 18.0%, compared to 17.6% by CHEM analysis (P > 0.05). Using a prediction equation [g protein = -1.062 + 0.22(g DXA lean)], the DXA estimate for body protein content was 17.8%, compared to 17.1% (P < 0.05, n = 131) by CHEM analysis. The DXA estimate for body water content [g water = 508 + 0.74 (g DXA lean)] was 63.8%, compared to 62.6% (P < 0.05, n = 231) by CHEM analysis. The bone mineral content of 83 of the pigs measured by DXA was 2.40%, compared to 2.54% (P < 0.05, n = 83) estimated from CHEM analysis of total body ash [g bone mineral = g total body ash -0.0085(g DXA lean)].

Intraabdominal adipose tissue and anthropometric surrogates in African American women with upper- and lower-body obesity.

It is well established that visceral adipose tissue (VAT) is associated with increased morbidity and mortality in white women. In a recent study, we found that African American women had smaller depots of VAT. To test the relation of VAT to the commonly used anthropometric surrogates for fat patterning, including waist-to-hip ratio (WHR), waist circumference, subscapular skinfold thickness, and ratio of triceps to subscapular skinfold thickness, we recruited 48 normotensive African American women > 120% of ideal body weight on the basis of WHRs > 0.85 [upper-body obesity (UBO); n = 23] and < 0.76 [lower-body obesity (LBO); n = 25]. There were no differences between groups in age, height, weight, body mass index, or percentage of body fat. VAT was determined by magnetic resonance imaging at L4-5; percentage of fat was determined by dual-energy X-ray absorptiometry. Women with UBO had significantly larger mean (+/- SEM) depots of VAT at L4-5 than did women with LBO (0.26 +/- 0.02 compared with 0.19 +/- 0.02 L). Waist circumference was the single best predictor of VAT at L4-5 in both groups of women whereas WHR was significantly associated with VAT at L4-5 only in women with UBO. In African American women, waist circumference is a better surrogate for VAT than is WHR.