Associations of burnout with awakening and diurnal cortisol among police officers.

The aim of this cross-sectional study was to assess the associations of burnout with cortisol parameters in 197 police officers from the Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) study (2010-2014). The Maslach Burnout Inventory-General Survey assessed depersonalization, exhaustion, and professional efficacy. Officers provided salivary cortisol samples collected upon awakening, and 15, 30, and 45 min thereafter as well as three additional samples at lunchtime, dinnertime, and bedtime. Total area under the curve with respect to increase (AUCWI for waking and AUCDI for diurnal), total area under the curve with respect to ground (AUCWG for waking and AUCDG for diurnal), and diurnal slope were determined and used in this study. Unadjusted and adjusted (age, sex, and race/ethnicity) associations were examined using linear regression. The mean age of the officers was 48 years and 72% were males. The depersonalization component of burnout was negatively associated with AUCDG (ß = -108.4; p = 0.036). Similarly, as exhaustion increased, AUCWI (ß = -9.58, p = 0.038), AUCDG (ß = -114.7, p = 0.029) and the diurnal slope (ß = -0.000038; p = 0.017) decreased. The Professional efficacy was not associated with any of the cortisol parameters. These results suggest that certain characteristics of burnout may be associated with diminished cortisol secretion in this group of urban police officers. Our findings add to previous studies examining associations of burnout with the cortisol awakening response. Future longitudinal studies are needed to evaluate the temporal relationship between burnout and these cortisol parameters.

Importance of dispersal routes that minimize open-ocean movement to the genetic structure of island populations.

Islands present a unique scenario in conservation biology, offering refuge yet imposing limitations on insular populations. The Kimberley region of northwestern Australia has more than 2500 islands that have recently come into focus as substantial conservation resources. It is therefore of great interest for managers to understand the driving forces of genetic structure of species within these island archipelagos. We used the ubiquitous bar-shouldered skink (Ctenotus inornatus) as a model species to represent the influence of landscape factors on genetic structure across the Kimberley islands. On 41 islands and 4 mainland locations in a remote area of Australia, we genotyped individuals across 18 nuclear (microsatellite) markers. Measures of genetic differentiation and diversity were used in two complementary analyses. We used circuit theory and Mantel tests to examine the influence of the landscape matrix on population connectivity and linear regression and model selection based on Akaike's information criterion to investigate landscape controls on genetic diversity. Genetic differentiation between islands was best predicted with circuit-theory models that accounted for the large difference in resistance to dispersal between land and ocean. In contrast, straight-line distances were unrelated to either resistance distances or genetic differentiation. Instead, connectivity was determined by island-hopping routes that allow organisms to minimize the distance of difficult ocean passages. Island populations of C. inornatus retained varying degrees of genetic diversity (NA = 1.83 - 7.39), but it was greatest on islands closer to the mainland, in terms of resistance-distance units. In contrast, genetic diversity was unrelated to island size. Our results highlight the potential for islands to contribute to both theoretical and applied conservation, provide strong evidence of the driving forces of population structure within undisturbed landscapes, and identify the islands most valuable for conservation based on their contributions to gene flow and genetic diversity.

Dimensional analysis of actigraphic derived sleep data.

Nonlinear dimensional analyses can be a useful tool in understanding the underlying behavior of dynamical systems, including biological systems. Many biological functions can be modeled as chaotic processes, including sleep. Sleep data can be obtained from several methods, such as electroencephalograms, polysomnography, and actigraph. Actigraphy, because of its low level of invasiveness, is an increasingly popular method of obtaining sleep data. This study analyzed actigraphy data with nonlinear dimensional analyses to determine if such analytic methods would be useful in sleep studies. Participants wore actigraphs on their wrists, which recorded movement for several days. Several sleep quality variables, such as movement during sleep and total sleep time, were derived from these sleep data. These variables were used to determine whether the quality of sleep was good or poor. Lagged phase space plots were graphed and nonlinear parameters for the fractal dimension and the correlation dimension were computed for each participant. Descriptive and inferential statistics were performed to determine if the nonlinear parameters showed significant differences with respect to sleep quality.

Estimation of the maximum flow-mediated brachial artery response using local regression methods.

We consider methods for estimating the maximum from a sequence of measurements of flow-mediated diameter of the brachial artery. Flow-mediated vasodilation (FMD) is represented using the maximum change from a baseline diameter measurement after the release of a blood pressure cuff that has been inflated to reduce flow in the brachial artery. The influence of the measurement error on the maximum diameter from raw data can lead to overestimation of the average maximum change from the baseline for a sample of individuals. Nonparametric regression models provide a potential means for dealing with this problem. When using this approach, it is necessary to make a judicious choice of regression methods and smoothing parameters to avoid overestimation or underestimation of FMD. This study presents results from simulation studies using kernel-based local linear regression methods that characterize the relationship between the measurement error, smoothing and bias in estimates of FMD. Comparisons between fixed or constant smoothing and automated smoothing parameter selection using the generalized cross validation (GCV) statistic are made, and it is shown that GCV-optimized smoothing may over-smooth or under-smooth depending on the heart rate, measurement error and measurement frequency. We also present an example using measured data from the Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) pilot study. In this example, smoothing resulted in lower estimates of FMD and there was no clear evidence of an optimal smoothing level. The choice to use smoothing and the appropriate smoothing level to use may depend on the application.

A new descriptor selection scheme for SVM in unbalanced class problem: a case study using skin sensitisation dataset.

A novel descriptor selection scheme for Support Vector Machine (SVM) classification method has been proposed and its utility demonstrated using a skin sensitisation dataset as an example. A backward elimination procedure, guided by mean accuracy (the average of specificity and sensitivity) of a leave-one-out cross validation, is devised for the SVM. Subsets of descriptors were first selected using a sequential t-test filter or a Random Forest filter, before backward elimination was applied. Different kernels for SVM were compared using this descriptor selection scheme. The Radial Basis Function (RBF) kernel worked best when a sequential t-test filter was adopted. The highest mean accuracy, 84.9%, was obtained using SVM with 23 descriptors. The sensitivity and the specificity were as high as 93.1% and 76.6%, respectively. A linear kernel was found to be optimal when a Random Forest filter was used. The performance using 24 descriptors was comparable with a RBF kernel with a sequential t-test filter. As a comparison, Fisher's linear discriminant analysis (LDA) under the same descriptor selection scheme was carried out. SVM was shown to outperform the LDA.

Molecular cloning and characterization of pig, cow and sheep MAdCAM-1 cDNA and the demonstration of cross-reactive epitopes amongst mammalian homologues.

Full-length cDNA clones for the pig, cow and sheep mucosal addressin cellular adhesion molecule (MAdCAM)-1 homologues were isolated from Peyer's patches by a combination of reverse transcription (RT)-polymerase chain reaction and 5' and 3' RACE strategies. Degenerate primers based on conserved amino acid (aa) sequences within the N-terminal immunoglobulin (Ig)-like domains of the human and rodent MAdCAM-1 molecules were used for initial sequencing of the Ig-like domains. MAdCAM-1 transcripts of 1425 bp, 1525 bp and 1510 bp obtained for the pig, cow and sheep contained an open-reading frame for proteins of 390, 424 and 418 aa, respectively. The pig and ruminant MAdCAM-1 had two N-terminal Ig-like domains, a mucin-like region and a third Ig-like domain found in rodent but not human MAdCAM-1. Antibodies raised against bacterially expressed N-terminal Ig-like domains of pig, human and sheep MAdCAM-1 demonstrated the existence of cross-reactive epitopes, raising the possibility of producing monoclonal antibodies which can be used as multi-species MAdCAM-1-targeting reagent for the development of mucosal vaccines.

A statistical test to determine the quality of accelerometer data.

Accelerometer data quality can be inadequate due to data corruption or to non-compliance of the subject with regard to study protocols. We propose a simple statistical test to determine if accelerometer data are of good quality and can be used for analysis or if the data are of poor quality and should be discarded. We tested several data evaluation methods using a group of 105 subjects who wore Motionlogger actigraphs (Ambulatory Monitoring, Inc.) over a 15 day period to assess sleep quality in a study of health outcomes associated with stress among police officers. Using leave-one-out cross-validation and calibration-testing methods of discrimination statistics, error rates for the methods ranged from 0.0167 to 0.4046. We found that the best method was to use the overall average distance between consecutive time points and the overall average mean amplitude of consecutive time points. These values gave us a classification error rate of 0.0167. The average distance between points is a measure of smoothness in the data, and the average mean amplitude between points gave an average reading. Both of these values were then normed to determine a final statistic, K, which was then compared to a cut-off value, K(C), to determine data quality.

Platelet aggregation in whole blood is a paradoxical predictor of ischaemic stroke: Caerphilly Prospective Study revisited.

The Caerphilly Prospective Study demonstrates a paradoxical association of increased ischaemic stroke risk with decreased whole blood adenosine diphosphate (ADP) induced platelet sensitivity. A reanalysis of this association examines whether other haematological indices and prevalent disease at baseline may explain this finding. There were 1506 men free of clinical cardiovascular disease at baseline, with 85 men manifesting a first ischaemic stroke event over 8.3 years of follow-up in this population-based prospective cohort study. Using two different approaches, the paradoxical findings are confirmed and associations are slightly stronger after accounting for red cell, platelet, and white cell indices. A U-shaped relation of stroke with platelet count is noted. These findings are consistent with the existence of sub-clinical endothelial disease and compensatory mechanisms down-regulating ADP-induced aggregation sensitivity. They support an allostasis model of causality for understanding the paradox. A public health approach to prevention could have measurable impact if intervention strategies can be developed to alter early stages of disease appropriate to such mechanisms of causation.

Thromboembolic disease and antithrombotic therapy in newborns.

This update uses an evidence based approach to analyze and present the epidemiology of neonatal thrombosis, etiologies, currently used techniques for diagnosis with their limitations, and current therapeutic approaches. In addition, the approaches to both prevention and optimal therapies are discussed. In Section I Dr. Paul Monagle addresses the epidemiology of neonatal thrombosis outside of the central nervous system in both arterial and venous locations, and those that occur in utero. The specific contributions of catheters and congenital prothrombotic disorders are delineated. Dr. Monagle also describes currently used techniques for the diagnosis of thrombotic events as well as their limitations and the current therapeutic approaches. In Section II, Dr. Gabrielle deVeber reviews the epidemiology of neonatal thrombosis within the central nervous system, in both arterial and venous locations and those that occur in utero. The neurological presentation, risk factors including congenital prothrombotic disorders, anatomical distribution, diagnostic tests, use of antithrombotic therapy and neurologic outcome of neonates with either sinovenous thrombosis or arterial ischemic stroke are discussed. In Section III, Dr. Anthony Chan reviews the current approaches to the prevention and treatment of neonatal thrombosis. Information on the differences in the response of neonates compared to adults to antithrombotic therapy and new approaches to the prevention and treatment of thrombosis in neonates are emphasized.

A prime-boost vaccination strategy using naked DNA followed by recombinant porcine adenovirus protects pigs from classical swine fever.

Weaned pigs (6-week-old) and 7-day-old pre-weaned piglets were vaccinated with naked plasmid DNA expressing the gp55/E2 gene from classical swine fever virus (CSFV). Both groups of pigs were then given a booster dose of recombinant porcine adenovirus expressing the gp55 gene (rPAV-gp55). Following challenge with CSFV, 100% of weaned pigs and 75% pre-weaned piglets were protected from disease. Weaned pigs given a single dose of rPAV-gp55 were also protected, but showed a slight increase in temperature immediately post-challenge. However, weaned animals given a DNA prime before rPAV-gp55 showed no fluctuation in body temperature following challenge and no pathology in spleen or lymph nodes upon post-mortem. In addition, no CSFV could be re-isolated from the rPAV vaccinated group and from only one pig in the prime-boost group following challenge, suggesting that both vaccination regimes have the potential to reduce or prevent virus shedding following experimental challenge.

Acquired activated protein C resistance is associated with lupus anticoagulants and thrombotic events in pediatric patients with systemic lupus erythematosus.

Acquired activated protein C resistance (APCR) has been hypothesized as a possible mechanism by which antiphospholipid antibodies (APLAs) cause thrombotic events (TEs). However, available evidence for an association of acquired APCR with APLAs is limited. More importantly, an association of acquired APCR with TEs has not been demonstrated. The objective of the study was to determine, in pediatric patients with systemic lupus erythematosus (SLE), whether (1) acquired APCR is associated with the presence of APLAs, (2) APCR is associated with TEs, and (3) there is an interaction between APCR and APLAs in association with TEs. A cross-sectional cohort study of 59 consecutive, nonselected children with SLE was conducted. Primary clinical outcomes were symptomatic TEs, confirmed by objective radiographic tests. Laboratory testing included lupus anticoagulants (LAs), anticardiolipin antibodies (ACLAs), APC ratio, protein S, protein C, and factor V Leiden. The results revealed that TEs occurred in 10 (17%) of 59 patients. Acquired APCR was present in 18 (31%) of 58 patients. Acquired APCR was significantly associated with the presence of LAs but not ACLAs. Acquired APCR was also significantly associated with TEs. There was significant interaction between APCR and LAs in the association with TEs. Presence of both APCR and LAs was associated with the highest risk of a TE. Protein S and protein C concentrations were not associated with the presence of APLAs, APCR, or TEs. Presence of acquired APCR is a marker identifying LA-positive patients at high risk of TEs. Acquired APCR may reflect interference of LAs with the protein C pathway that may represent a mechanism of LA-associated TEs. (Blood. 2001;97:844-849)

Rapid dissemination of intramuscularly inoculated DNA vaccines.

Deoxyribonucleic acid (DNA) vaccination offers the prospect of novel, safe vaccines that can stimulate cell-mediated immunity as well as antibody. An understanding of how and where transfection occurs in vivo will assist strategies to enhance their efficacy. Plasmid DNA encoding for the expression of firefly luciferase was injected intramuscularly into sheep. The DNA was rapidly disseminated and could be detected in efferent lymph within 5 min. At the earliest time that cells were tested separately from lymph plasma (1 h), DNA was found to be present in both the lymph plasma and within lymph cells. Although plasmid DNA could be detected intracellularly in lymph and in muscle tissue at the site of inoculation, no luciferase gene expression could be detected. The results suggest that, in addition to the internalization of plasmid DNA, other factors may limit gene expression, possibly the rate of DNA migration into the nucleus.

Addressing sexuality-related needs in practice: perspectives of maternal/child and women's health nurses.

A quantitative, descriptive survey was conducted using Waterhouse's instrument, Survey of Sexuality-Related Nursing Practice. The purpose of this study was to examine the extent to which maternal/child and women's health nurses address sexuality in their practice and to assess the influence of select variables on that practice. A sample of maternal/child and women's health registered nurses (n = 130) was systematically selected from the 1995 Association of Women's Health, Obstetric and Neonatal Nurses' (AWHONN) District VII mailing list. Findings reveal incongruities in maternal/child and women's health nurses' perspectives and the incorporation of sexuality-related nursing interventions into practice.

The immune response to a polyoma virus replicon-based DNA vaccine.

DNA vaccination has proven to be effective against a number of tumours and microbial diseases. As DNA vaccines are unable to replicate, plasmid copy number per cell is dependent on in vivo transfection efficiency, which is usually quite low. Consequently, immune responses generated are likely to be sub-optimal due to low antigen expression levels in transfected cells. During this study, replicating DNA vaccines delivered intra-epidermally by gene gun, were assessed for their ability to more efficiently generate immune responses in mice. The data demonstrate that, using a polyoma virus-based system of replication, 10-fold less DNA expressing the haemagglutinin gene of influenza virus, was required to stimulate a humoral immune response, compared to an equivalent non-replicating vaccine. This observation suggests that the use of replicating DNA vaccines in some delivery systems may enhance the effectiveness of immune responses.

Protection of pigs against classical swine fever with DNA-delivered gp55.

Classical swine fever virus causes significant mortality and morbidity in commercial piggeries in many countries in Europe and Asia. The protective antigen, gp55, is highly conformation-dependent and thus killed virus or bacterially produced proteins are not protective. This report demonstrates that DNA vaccination with the gene encoding gp55 can provide protective immunity with inoculation of two doses of 25 microg DNA or a single shot of 200 microg. Furthermore, the DNA can be delivered intramuscularly or by a simple spring-loaded needleless inoculator. In addition it is shown that inoculation of the DNA at a single site conveys the same level of immunity as division of the dose between two sites.

Avian cytokines - the natural approach to therapeutics.

While the effective use of antibiotics for the control of human disease has saved countless lives and has increased life expectancy over the past few decades, there are concerns arising from their usage in livestock. The use of antibiotic feed additives in food production animals has been linked to the emergence in the food chain of multiple drug-resistant bacteria that appear impervious to even the most powerful antimicrobial agents. Furthermore, the use of chemical antimicrobials has led to concerns involving environmental contamination and unwanted residues in food products. The imminent banning of antibiotic usage in livestock feed has intensified the search for environmentally-friendly alternative methods to control disease. Cytokines, as natural mediators and regulators of the immune response, offer exciting new alternatives to conventional chemical-based therapeutics. The utilisation of cytokines is becoming more feasible, particularly in poultry, with the recent cloning of a number of avian cytokine genes. Chickens offer an attractive small animal model system with which to study the effectiveness of cytokine therapy in the control of disease in intensive livestock. In this report we will review the status of avian cytokines and focus on our recent studies involving the therapeutic potential of chicken interferon gamma (ChIFN-gamma) as a vaccine adjuvant and a growth promoter.

Insertion sites for recombinant vaccinia virus construction: effects on expression of a foreign protein.

The expression of antigens or other molecules from recombinant vaccinia viruses requires the insertion of coding sequence at specific sites in the viral genome. Here we investigate the influence of two different sites on the level of protein expressed during a viral infection. The level of immune response in mice to vaccinia virus-expressed murine interleukin 2 (IL-2) or IL-4 varied depending on whether the coding sequence was inserted into the vaccinia virus thymidine kinase (tk) gene or into the HindIII F fragment of the viral genome where herpes simplex virus (HSV) tk was used as a selectable marker. In each case the intensity of the response was greater when the relevant gene was expressed from the HindIII F insertion site. In order to quantify these differences a series of recombinant viruses expressing luciferase was constructed. Luciferase activity from coding sequence inserted into the HindIII F fragment was significantly higher than that from the tk gene insertion, provided HSV tk(+) constructs were compared. Insertion of a marker gene (HSV tk) into the HindIII F site with disruption of the F7L open reading frame led to a reduced level of luciferase expressed from the tk insert, despite more than 45 kb of intervening sequence. In mice, luciferase expression was higher from the HindIII F inserted gene than from the tk insert in both lungs and ovaries.

Cytokine therapy: a natural alternative for disease control.

Disease control in food production animals is normally mediated through the use of vaccines, chemicals and antibiotics. However, the extensive use of antibiotics and chemicals in livestock has resulted in environmental and human health concerns, particularly with regard to the emergence of drug-resistant bacteria in the food chain. In fact, the World Health Organisation (WHO) has now urged meat producers to use environmentally-friendly alternative methods to control disease. Cytokines, as natural mediators of the immune response, offer exciting alternatives to conventional therapeutics. The utilisation of cytokines is becoming more feasible with the recent cloning of a number of cytokine genes. Since the chicken's immune system is similar to that of mammals, they offer an attractive model system with which to study the effectiveness of cytokine therapy in the control of disease in intensive livestock. In this report we will review our recent studies on the therapeutic potential of chicken interferon gamma (ChIFN-gamma) as a vaccine adjuvant and a growth promoter.

The ovine cytotoxic T lymphocyte responses to bluetongue virus.

This study uses recombinant vaccinia viruses expressing truncated or entire bluetongue virus (BTV) proteins to map the location of epitopes recognized by cytotoxic T lymphocytes (CTL) from Australian merino sheep. The non-structural protein, NS1, was recognised by CTL from all sheep, while VP2, VP3, VP5 and VP7 were recognised by CTL from only some sheep. The remaining proteins (except for VP1, which was not tested) did not contain CTL epitopes. When truncated genes were used to map the location of CTL epitopes, it was found that sheep often have CTL that recognise more than one epitope in NS1 or VP2. Overall there was considerable diversity in the CTL recognition patterns in the sheep tested.

Venous thromboembolic events in pediatric patients. Diagnosis and management.

Venous thromboembolism is a rapidly increasing secondary complication in children being treated for serious, life-threatening, primary diseases. Most current management guidelines and recommendations for imaging techniques have been extrapolated from the results of trials in adults. This may be less than optimal for children as there are important differences. The purpose of this article is to summarize the information on venous thromboembolism in children, and offer some guidelines for diagnosis, prophylaxis, and therapeutic intervention based on the best available evidence.