Characterization of tissue types in basal cell carcinoma images via generative modeling and concept vectors.

The promise of machine learning methods to act as decision support systems for pathologists continues to grow. However, central to their successful adoption must be interpretable implementations so that people can trust and learn from them effectively. Generative modeling, most notable in the form of adversarial generative models, is a naturally interpretable technique because the quality of the model is explicit from the quality of images it generates. Such a model can be further assessed by exploring its latent space, using human-meaningful concepts by defining concept vectors. Motivated by these ideas, we apply for the first time generative methods to histological images of basal cell carcinoma (BCC). By simultaneously learning to generate and encode realistic image patches, we extract feature rich latent vectors that correspond to various tissue morphologies, namely BCC, epidermis, keratin, papillary dermis and inflammation. We show that a logistic regression model trained on these latent vectors can achieve high classification accuracies across 6 binary tasks (86-98%). Further, by projecting the latent vectors onto learned concept vectors we can generate a score for the absence or degree of presence for a given concept, providing semantically accurate "conceptual summaries" of the various tissues types within a patch. This can be extended to generate multi-dimensional heat maps for whole-image specimens, which characterizes the tissue in a similar way to a pathologist. We additionally find that accurate concept vectors can be defined using a small labeled dataset.

Use of diagnostic reports to estimate prevalence and distribution of skeletal lesions in young Thoroughbreds.

Diagnostic reports written to assist stud managers in the sale of young Thoroughbreds have not previously been used as a data source for the study of skeletal lesions. However, analyses of these reports may provide efficient and cost-effective insights into the prevalence and distribution of skeletal lesions within a population. Diagnostic reports written by veterinarians were acquired from Thoroughbred stud managers in Australia and New Zealand. The reports were based on approximately 1300 sets of weanling and yearling radiographs taken between 2002 and 2007. The prevalence and anatomical distribution of skeletal lesions in weanlings (299 horses) and yearlings (1004 horses) were determined from these reports. Overall, 69.9% of weanlings and 64.5% of yearlings were reported as having one or more skeletal lesions. Diagnostic reports in weanlings were a strong indication of what was likely to be seen in subsequent yearling reports. These diagnostic reports are typically used by stud managers in the sales process and the potential drawback is that some categories of skeletal lesions may be under-reported. However, there was substantial agreement between the prevalence and distribution of several skeletal lesions reported in this study and those previously reported from direct evaluation of radiographs for Australian and New Zealand Thoroughbred yearlings. Strong agreement was found for osteophytes, enthesiophytes and other modelling in the hocks, and for lesions in the hind fetlocks and stifles. This indicates that written diagnostic reports are a useful and a reliable source of data for the study of some skeletal lesions in young Thoroughbred horses.

Heritability of racing durability traits in the Australian and Hong Kong Thoroughbred racing populations.

REASONS FOR PERFORMING STUDY: Many attempts have been made to improve the well-being of racing Thoroughbreds through improvements in management and veterinary care. However, these attempts are often limited by the industry's ability to regulate a large number of environmental variables and as a result have arguably had limited success in providing long-lasting change for the breed. OBJECTIVES: To identify heritable durability traits for Thoroughbred horses racing in Australia and Hong Kong. STUDY DESIGN: Heritability analysis of a longitudinal dataset. METHODS: Performance data on the Thoroughbred populations racing in Australia and Hong Kong between 2000 and 2011 (n = 168,993) were used to estimate the heritabilities and probability values of fixed effects and covariates for a range of racing durability traits. Heritabilities for all durability traits were estimated using a single trait animal model. Each model included, as a minimum, the effects of sex and trainer. RESULTS: Racing longevity (0.12 ± 0.01), racing persistence (0.10 ± 0.01), racing frequency (0.03 ± 0.01), spells (a time period between consecutive races, official trials and/or jump-outs greater than 90 days in length) per year (0.05 ± 0.01), spells per 10 starts (0.03 ± 0.01) and variation of days between races (0.08 ± 0.03) were all significantly heritable for horses racing in Australia. Racing longevity (0.08 ± 0.02), racing persistence (0.04 ± 0.02), spells per year (0.06 ± 0.02) and spells per 10 starts (0.11 ± 0.04) were significantly heritable for horses racing in Hong Kong. CONCLUSIONS: The heritabilities estimated for durability traits in this study provide support for the successful and practical application of genetic selection methodologies to improving the well-being of racing Thoroughbreds.

A spatially-averaged mathematical model of kidney branching morphogenesis.

Kidney development is initiated by the outgrowth of an epithelial ureteric bud into a population of mesenchymal cells. Reciprocal morphogenetic responses between these two populations generate a highly branched epithelial ureteric tree with the mesenchyme differentiating into nephrons, the functional units of the kidney. While we understand some of the mechanisms involved, current knowledge fails to explain the variability of organ sizes and nephron endowment in mice and humans. Here we present a spatially-averaged mathematical model of kidney morphogenesis in which the growth of the two key populations is described by a system of time-dependant ordinary differential equations. We assume that branching is symmetric and is invoked when the number of epithelial cells per tip reaches a threshold value. This process continues until the number of mesenchymal cells falls below a critical value that triggers cessation of branching. The mathematical model and its predictions are validated against experimentally quantified C57Bl6 mouse embryonic kidneys. Numerical simulations are performed to determine how the final number of branches changes as key system parameters are varied (such as the growth rate of tip cells, mesenchyme cells, or component cell population exit rate). Our results predict that the developing kidney responds differently to loss of cap and tip cells. They also indicate that the final number of kidney branches is less sensitive to changes in the growth rate of the ureteric tip cells than to changes in the growth rate of the mesenchymal cells. By inference, increasing the growth rate of mesenchymal cells should maximise branch number. Our model also provides a framework for predicting the branching outcome when ureteric tip or mesenchyme cells change behaviour in response to different genetic or environmental developmental stresses.

Heritability of racing performance in the Australian Thoroughbred racing population.

Performance data for 164,046 Thoroughbreds entered in a race or official barrier trial in Australia were provided by Racing Information Services Australia. Analyses estimating the heritability for a range of racing performance traits using a single-trait animal model were performed using ASREML-R. Log of cumulative earnings (LCE; 0.19 ± 0.01), log of earnings per race start (0.23 ± 0.02) and best race distance (0.61 ± 0.03) were all significantly heritable. Fixed effects for sex were significant (P < 0.001) for all performance traits aside from LCE (P = 0.382). With the exception of annual earnings, trainer was also significant for all performance traits. As the application of modern genetic selection methodologies continues to gain popularity in the racing industry, contemporary heritability estimates from the current population of Thoroughbreds will play a vital role in identifying which traits are better suited to selection and in the development of more accurate genomic evaluations for racing performance.

Performance selection for Thoroughbreds racing in Hong Kong.

REASONS FOR PERFORMING STUDY: Different indicators of racing performance are commonly used in the racing industry to assess the genetic superiority of racing Thoroughbreds. However, how well these indicators predict the performance of future progeny or siblings varies depending on the population and circumstances in which the indicators were recorded or achieved. OBJECTIVES: To identify heritable indicators of racing performance for horses racing in Hong Kong. STUDY DESIGN: Heritability analysis of racing performance traits. METHODS: Performance data on the population of Thoroughbreds racing in Hong Kong between 3 September 2000 and 12 March 2011 (n = 4947) were acquired and used to estimate the heritabilities and probability values of fixed effects and covariates for a range of racing performance traits. Heritabilities for all performance traits were estimated using a single trait animal model. Each model included, as a minimum, the effects of sex, region of origin and trainer. RESULTS: Heritability estimates for traits relating to finish position ranged from 0.01 to 0.06. Average handicap weight had a heritability of 0.07 ± 0.03. The effects of sex (fixed) and trainer (random) were significant (P<0.05) for all performance traits relating to earnings measures, handicap weights and finish positions. The heritability of win time at 1600 m was 0.52 ± 0.06 and was the only significant estimate of heritability for win time in the current study. CONCLUSIONS: Although significantly affected by multiple environmental factors, certain indicators of Hong Kong racing performance can be reliably used to predict the performance of the individual's progeny or siblings. However, despite Hong Kong's controlled racing environment, these indicators appear to be no more heritable than in other less controlled racing environments.

Heritability of epistaxis in the Australian Thoroughbred racehorse population.

Post exercise epistaxis, the manifestation of a severe form of exercise-induced pulmonary haemorrhage (EIPH), has been observed in many equine racing populations. Although multiple analyses have suggested that non-genetic factors may lead to the development of this condition, relatively little consensus has been reached regarding its genetic aetiology. The objective of this study was to provide insight into both genetic and non-genetic factors that may contribute to the expression of epistaxis in the Australian Thoroughbred racing population. Racing records and reported epistaxis occurrences were acquired for 117,088 horses entered in races and official barrier trials from 1 August 2000 until 22 February 2011. Heritability was estimated using two different logistic generalised linear mixed models (lifetime epistaxis risk h(2) = 0.27 and individual race epistaxis risk h(2) = 0.50). Sex, age, and year of birth were shown to be significant; however, trainer, jockey, race distance, condition of the track (i.e. 'going'), racecourse, track surface, number of race starters, year and month of race were not significant. Evidence suggests genetic and non-genetic links to EIPH expressed as epistaxis.

Handedness of whip use by Australian Jockeys.

OBJECTIVE: To compare handedness of whip use by Australian jockeys in Melbourne (where racing is counterclockwise) and Sydney (where racing is clockwise). METHODS: Photographs of finishes of Thoroughbred horse races in Melbourne and Sydney were examined. Where whip use was clearly visible, the venue, the hand in which the whip was held and the names of the jockey and the horse were determined. Comparisons of whip hand use between cities were made using the Chi-squared test. RESULTS: A total of 771 identifications were made, 328 from Melbourne and 443 from Sydney, representing 78 jockeys and 506 horses. Right-handed whip use was identified in 244 (74.39%) photographs of Melbourne races and in 313 (70.65%) photographs of Sydney races. There was no difference between right-handed whip use in Melbourne and Sydney (P = 0.53), nor in the handedness of whip use by individual jockeys (P = 0.74). Predominantly right-handed jockeys demonstrated significantly stronger dominance (84.51 ± 14.03%) compared with left-hand dominant riders (71.07 ± 9.40%; P = 0.01). A total of 84 horses were identified being ridden by the same jockey in different races. In 64 of the 84 cases, the whip was used in the same hand in all photographs. In the remaining instances, the whip was observed to be used in both hands by the one jockey. CONCLUSION: The findings support the view the whip can be used as an aid to steering during races.

Sequence analysis of the equine ACTN3 gene in Australian horse breeds.

The sarcomeric α-actinins, encoded by the genes ACTN2 and ACTN3, are major structural components of the Z-line and have high sequence similarity. α-Actinin-2 is present in all skeletal muscle fibres, while α-actinin-3 has developed specialized expression in only type 2 (fast, glycolytic) fibres. A common single nucleotide polymorphism (SNP) in the human ACTN3 gene (R577X) has been found to influence muscle performance in elite athletes and the normal population. For this reason, equine ACTN3 (eACTN3) is considered to be a possible candidate that may influence horse performance. In this study, the intron/exon boundaries and entire coding region of eACTN3 have been sequenced in five Australian horse breeds (Thoroughbred, Arabian, Standardbred, Clydsdale and Shire) and compared to the eACTN3 GenBank sequence. A total of 34 SNPs were identified, of which 26 were intronic and eight exonic. All exonic SNPs were synonymous; however, five intronic SNPs showed significant differences between breeds. A total of 72 horses were genotyped for a SNP located in the promoter region of the eACTN3 gene (g. 1104 G>A) which differed significantly between breed groups. We hypothesize that this polymorphism influences eACTN3 expression and with further studies may provide a novel marker of horse performance in the future.

Modelling cell turnover in a complex tissue during development.

The growth of organs results from proliferation within distinct cellular compartments. Organ development also involves transitions between cell types and variations in cell cycle duration as development progresses, and is regulated by a balance between entry into the compartment, proliferation of cells within the compartment, acquisition of quiescence and exit from that cell state via differentiation or death. While it is important to understand how environmental or genetic alterations can perturb such development, most approaches employed to date are descriptive rather than quantitative. This is because the identification and quantification of such parameters, while tractable in vitro, is challenging in the context of a complex tissue in vivo. Here we present a new framework for determining cell turnover in developing organs in vivo that combines cumulative cell-labelling and quantification of distinct cell-cycle phases without assuming homogeneity of behaviour within that compartment. A mathematical model is given that allows the calculation of cell cycle length in the context of a specific biological example and assesses the uncertainty of this calculation due to incomplete knowledge of cell cycle dynamics. This includes the development of a two population model to quantify possible heterogeneity of cell cycle length within a compartment and estimate the aggregate proliferation rate. These models are demonstrated on data collected from a progenitor cell compartment within the developing mouse kidney, the cap mesenchyme. This tissue was labelled by cumulative infusion, volumetrically quantified across time, and temporally analysed for the proportion of cells undergoing proliferation. By combining the cell cycle length predicted by the model with measurements of total cell population and mitotic rate, this approach facilitates the quantification of exit from this compartment without the need for a direct marker of that event. As a method specifically designed with assumptions appropriate to developing organs we believe this approach will be applicable to a range of developmental systems, facilitating estimations of cell cycle length and compartment behaviour that extend beyond simple comparisons of mitotic rates between normal and perturbed states.

Profiling the careers of Thoroughbred horses racing in Hong Kong between 2000 and 2010.

REASONS FOR PERFORMING STUDY: Research in Thoroughbred racehorses is often specific to horses from a given racing population or region. In order to investigate trends in racehorse careers across populations accurately, population-specific benchmarks for performance outcomes must be established. OBJECTIVES: To provide summary statistics for performance outcomes for Thoroughbreds racing in Hong Kong between 2000 and 2010 and to document and provide evidence on the current differences in racing careers across sexes and regions of origin for horses racing in Hong Kong. STUDY DESIGN: Performance data on the population of Thoroughbreds racing in Hong Kong between 3 September 2000 and 12 March 2011 (n = 4950) were acquired and used to describe and compare the careers of Thoroughbred racehorses in Hong Kong. METHODS: Career length, number of career starts and number of spells from racing per year were evaluated. Kaplan-Meier survival curves, stratified by sex, age group, country of origin and region of origin were produced for career length. A Cox's proportional hazards model was fitted to assess factors influencing the risk of retirement from racing in Hong Kong. RESULTS: Log-rank tests for equality of career length survivor functions showed significant differences (P<0.001) across sexes, age groups, countries of origin and regions of origin. An increased age at first start in Hong Kong tended to increase the hazard rate for retirement from racing in Hong Kong, whereas greater earnings per race and originating from Europe tended to reduce the hazard rate for racing retirement. CONCLUSIONS AND POTENTIAL RELEVANCE: Differences in career outcomes within a racing population appear to be influenced partly by the region from which a horse originates, with specific effects on each performance outcome also varying between regions. Future research should take into account these potential differences when comparing results across populations.

The association of age at first start with career length in the Australian Thoroughbred racehorse population.

REASONS FOR PERFORMING STUDY: Studies of Thoroughbred racing populations have provided evidence of a positive effect on racing careers for horses that commence racing as 2-year-olds. Currently, research investigating the presence of this effect in the Australian Thoroughbred racing population is limited. OBJECTIVES: To investigate the association between age at first start and career length in the Australian Thoroughbred population and estimate the risk of racing retirement for horses racing in Australia based on age at first start, career earnings, number of starts as a 2-year-old and distance raced. METHODS: Data were collected for Thoroughbreds, born on or after 1 January 1998, that had raced between 1 August 2000 and 22 February 2011 in Australia. A Kaplan-Meier survival curve, stratified by age group, was produced for career length. A Cox proportional hazard model was fitted to assess factors influencing the risk of retirement from racing. The model included sex, age at first start, career earnings, number of starts as a 2-year-old, distance raced and appropriate interaction terms. RESULTS: The study population included 117,088 horses. Geldings had significantly (P<0.001) longer careers than females and intact males, and females had significantly (P<0.001) longer careers than intact males. Risk of retirement from racing decreased with a younger age at first start, a higher number of starts as a 2-year-old, and a longer average distance raced. For intact males, the risk of retirement from racing increased as earnings increased, while for females and geldings the risk of retirement from racing decreased as earnings increased. CONCLUSIONS AND POTENTIAL RELEVANCE: The introduction of young Thoroughbreds to racing appears to have no apparent adverse effects on these horses racing in Australia. The impact of some risk factors associated with retirement from racing varied between sexes and should be considered when evaluating career outcomes.

Profiling the careers of Thoroughbred horses racing in Australia between 2000 and 2010.

REASONS FOR PERFORMING STUDY: Research investigating trends in racehorse careers require a benchmark for accurate comparison. Currently little whole population data exists for horses racing in Australia. OBJECTIVES: To determine the range and variation in career length and number of career starts for horses racing in Australia. To document and provide evidence regarding the current differences between the sexes for career length and careers starts. METHODS: Racing data were collected for Thoroughbreds over a 10-year period. Career length, number of career starts and spells per year were evaluated. Statistical analyses were performed using the statistical package R. RESULTS: A total of 2,782,774 performance records yielded career information for 164,046 horses. Median career length and number of career starts for the population were 14.7 months and 10 starts, respectively. Significant differences (P<0.001) were present between the sexes for all career outcomes. Between 2000 and 2010, the percentage of Thoroughbreds racing in Australia with careers longer than 12, 24, 36 and 48 months was 56.65, 32.35, 16.66 and 7.74, respectively. CONCLUSIONS AND POTENTIAL RELEVANCE: Clear differences in career outcomes exist between intact males, females and geldings racing in Australia. Future research should be conscious of these differences when analysing population data.

Recycling endosome-dependent and -independent mechanisms for IL-10 secretion in LPS-activated macrophages.

IL-10 is a key anti-inflammatory cytokine secreted by activated macrophages as a feedback control mechanism to prevent excessive inflammatory responses. Here, we define multiple intracellular trafficking pathways involved in the secretion of newly synthesized IL-10 from macrophages following TLR4 activation with LPS, and show how this relates to the previously defined trafficking pathways for IL-6 and TNF in macrophages simultaneously producing these proinflammatory cytokines. IL-10 exits the Golgi in multiple tubular carriers, including those dependent on p230GRIP. Some of the IL-10 is then delivered to recycling endosomes, where cytokine sorting may occur prior to its release. Another portion of the IL-10 is delivered to the cell surface in distinct vesicles colabeled for apoE. Thus, we show at least two post-Golgi pathways via which IL-10 is trafficked, ensuring its secretion from activated macrophages under different physiological conditions.

Histologic and biomechanical evaluation of a novel macroporous polytetrafluoroethylene knit mesh compared to lightweight and heavyweight polypropylene mesh in a porcine model of ventral incisional hernia repair.

PURPOSE: To evaluate the biocompatibility of heavyweight polypropylene (HWPP), lightweight polypropylene (LWPP), and monofilament knit polytetrafluoroethylene (mkPTFE) mesh by comparing biomechanics and histologic response at 1, 3, and 5 months in a porcine model of incisional hernia repair. METHODS: Bilateral full-thickness abdominal wall defects measuring 4 cm in length were created in 27 Yucatan minipigs. Twenty-one days after hernia creation, animals underwent bilateral preperitoneal ventral hernia repair with 8 × 10 cm pieces of mesh. Repairs were randomized to Bard(®)Mesh (HWPP, Bard/Davol, http://www.davol.com), ULTRAPRO(®) (LWPP, Ethicon, http://www.ethicon.com), and GORE(®)INFINIT Mesh (mkPTFE, Gore & Associates, http://www.gore.com). Nine animals were sacrificed at each timepoint (1, 3, and 5 months). At harvest, a 3 × 4 cm sample of mesh and incorporated tissue was taken from the center of the implant site and subjected to uniaxial tensile testing at a rate of 0.42 mm/s. The maximum force (N) and tensile strength (N/cm) were measured with a tensiometer, and stiffness (N/mm) was calculated from the slope of the force-versus-displacement curve. Adjacent sections of tissue were stained with hematoxylin and eosin (H&E) and analyzed for inflammation, fibrosis, and tissue ingrowth. Data are reported as mean ± SEM. Statistical significance (P < 0.05) was determined using a two-way ANOVA and Bonferroni post-test. RESULTS: No significant difference in maximum force was detected between meshes at any of the time points (P > 0.05 for all comparisons). However, for each mesh type, the maximum strength at 5 months was significantly lower than that at 1 month (P < 0.05). No significant difference in stiffness was detected between the mesh types or between timepoints (P > 0.05 for all comparisons). No significant differences with regard to inflammation, fibrosis, or tissue ingrowth were detected between mesh types at any time point (P > 0.09 for all comparisons). However, over time, inflammation decreased significantly for all mesh types (P < 0.001) and tissue ingrowth reached a slight peak between 1 and 3 months (P = 0.001) but did not significantly change thereafter (P > 0.09). CONCLUSIONS: The maximum tensile strength of mesh in the abdominal wall decreased over time for HWPP, LWPP, and mkPTFE mesh materials alike. This trend may actually reflect inability to adequately grip specimens at later time points rather than any mesh-specific trend. Histologically, inflammation decreased with time (P = 0.000), and tissue ingrowth increased (P = 0.019) for all meshes. No specific trends were observed between the polypropylene meshes and the monofilament knit PTFE, suggesting that this novel construction may be a suitable alternative to existing polypropylene meshes.

Early biocompatibility of crosslinked and non-crosslinked biologic meshes in a porcine model of ventral hernia repair.

PURPOSE: Biologic meshes have unique physical properties as a result of manufacturing techniques such as decellularization, crosslinking, and sterilization. The purpose of this study is to directly compare the biocompatibility profiles of five different biologic meshes, AlloDerm(®) (non-crosslinked human dermal matrix), PeriGuard(®) (crosslinked bovine pericardium), Permacol(®) (crosslinked porcine dermal matrix), Strattice(®) (non-crosslinked porcine dermal matrix), and Veritas(®) (non-crosslinked bovine pericardium), using a porcine model of ventral hernia repair. METHODS: Full-thickness fascial defects were created in 20 Yucatan minipigs and repaired with the retromuscular placement of biologic mesh 3 weeks later. Animals were euthanized at 1 month and the repair sites were subjected to tensile testing and histologic analysis. Samples of unimplanted (de novo) meshes and native porcine abdominal wall were also analyzed for their mechanical properties. RESULTS: There were no significant differences in the biomechanical characteristics between any of the mesh-repaired sites at 1 month postimplantation or between the native porcine abdominal wall without implanted mesh and the mesh-repaired sites (P > 0.05 for all comparisons). Histologically, non-crosslinked materials exhibited greater cellular infiltration, extracellular matrix (ECM) deposition, and neovascularization compared to crosslinked meshes. CONCLUSIONS: While crosslinking differentiates biologic meshes with regard to cellular infiltration, ECM deposition, scaffold degradation, and neovascularization, the integrity and strength of the repair site at 1 month is not significantly impacted by crosslinking or by the de novo strength/stiffness of the mesh.

Correlates of distress in children at risk for affective disorder: exploring predictors in the offspring of depressed and nondepressed mothers.

BACKGROUND: Efforts to understand the correlates of psychological distress in children frequently examine possible correlates in samples of children who are selected for high levels of distress. The propose of this study was to compare distress correlates in a sample with depressed mothers, and thus at high-risk for distress, to a low-risk sample. METHODS: Examining data from part of a larger project, the association of children's depressive symptoms and internalizing and externalizing problems to maternal depression level, life stress, verbal ability, and the experience of a traumatic event were examined in a series of regression equations. RESULTS: Results indicated that children's depressive symptoms, rather than internalizing and externalizing problems, tended to be most consistently related to maternal variables, and also suggested that any experience of maternal depressive symptoms was associated with child problems. It was also found that child depressive symptoms were correlated with life events, but only for nondepressed mothers, and that at-risk children with higher levels of verbal ability were significantly less likely to report experiencing depressive symptoms and internalizing problems than were those with lower levels of verbal ability. LIMITATIONS: Because these data are preliminary, further research examining a broader array of variables is important. CONCLUSIONS: These results suggest the need for different models of these processes in different populations of children.

Field research on the relationship between stress and disease activity in rheumatoid arthritis.

We review empirical evidence from two field studies for the role of stressful life events in disease flare-ups among patients with rheumatoid arthritis (RA). RA patients were expected to be more vulnerable psychologically, and physiologically, to stressful events in their everyday lives than other arthritis patients without an autoimmune disease. Findings from two studies are reviewed both for their substantive contribution, but also to provide guidance on measurement issues in future field research of this kind. One study included 41 patients with RA, who were interviewed weekly and called to a clinic for blood work and joint examinations when their levels of interpersonal stress increased significantly. A second study used a similar design but included comparison samples of patients with osteoarthritis (OA) and healthy controls of similar age and the same gender as the RA sample. The findings provided support for the proposition that interpersonal stressors are predictive of increases in disease activity. Not all RA patients, however, showed these relationships, and there was evidence that some participants with OA who were depressed also showed higher disease activity following interpersonal stressors. Significant individual differences in the stress-disease relationship were uncovered that deserve greater attention in future studies. Important improvements in the assessment of stressful events and refinements in panel study design are also presented as guides to research on the role of stress in disease processes.

Body fat distribution and hemodynamic stress responses in premenopausal obese women: a preliminary study.

To examine the relationship between body fat distribution and hemodynamic stress responses, cardiovascular responses to a speech task and a forehead cold pressor task were evaluated with 24 premenopausal women classified a priori as either centrally or peripherally obese. Results showed that women with central adiposity exhibited greater stress-related increases in diastolic blood pressure and total peripheral resistance, whereas women with peripheral adiposity exhibited greater stress-related increases in cardiac output. Depression, self-consciousness, hostility, and mood scores did not explain significant variance in the stress response differences between regional adiposity groups. The findings suggest that central adiposity may increase the risk of cardiovascular disease in women at least in part by enhancing vascular responses to stress.

Development of ultrasonic vocalization responses in genetically heterogeneous National Institute of Health (N:NIH) rats. I. Influence of age, testing experience, and associated factors.

The N:NIH strain of rats was developed by the National Institutes of Health to provide a maximally heterogeneous population as a base for selective breeding (Hansen & Spuhler, 1984). Using the N:NIH strain, this laboratory will selectively breed adult animals that exhibited extremes of high or low ultrasonic vocalization (USV) rates as infants. Because nothing was known about USV in N:NIH rats, we characterized the development of isolation-induced USV in the first generation of this strain born in our laboratory. In a longitudinal/cross-sectional study of pups tested at 3, 10, 15, and 18 days postnatally, N:NIH pups emitted their highest rates of USV at 3-4 days postnatally and calling remained high for 10 days before declining. USV rates were found to be a relatively environmentally stable behavioral trait in that repeated testing did not significantly affect the calling rates of either individuals or litters, and only at 3 days postnatal age did naturally occurring ambient temperature variations (6 degrees C range) significantly affect USV responses. Individual differences in USV responses emerged by 10 days of age that were not simply correlations of body weight or rectal temperature, and pups at that age showed isolation calling rates that were highly predictive of their response levels 5 days later.