The evolution of highly variable immunity genes across a passerine bird radiation.

To survive, individuals must be able to recognize and eliminate pathogens. The genes of the major histocompatibility complex (MHC) play an essential role in this process in vertebrates as their diversity affects the repertoire of pathogens that can be recognized by the immune system. Emerging evidence suggests that birds within the parvorder Passerida possess an exceptionally high number of MHC genes. However, this has yet to be directly investigated using a consistent framework, and the question of how this MHC diversity has evolved has not been addressed. We used next-generation sequencing to investigate how MHC class I gene copy number and sequence diversity varies across the Passerida radiation using twelve species chosen to represent the phylogenetic range of this group. Additionally, we performed phylogenetic analyses on this data to identify, for the first time, the evolutionary model that best describes how MHC class I gene diversity has evolved within Passerida. We found evidence of multiple MHC class I genes in every family tested, with an extremely broad range in gene copy number across Passerida. There was a strong phylogenetic signal in MHC gene copy number and diversity, and these traits appear to have evolved through a process of Brownian motion in the species studied, that is following the pattern of genetic drift or fluctuating selection, as opposed to towards a single optimal value or through evolutionary 'bursts'. By characterizing MHC class I gene diversity across Passerida in a systematic framework, this study provides a first step towards understanding this huge variation.

Factitious hand disorders: review of 29 years of multidisciplinary care.

PURPOSE: To improve our understanding of factitious hand disorders with a review of our experience over 29 years in a multidisciplinary hand center. METHODS: A retrospective chart review was performed to identify workers' compensation patients treated for factitious hand disorders in the multidisciplinary hand center between January 1981 and September 2010. Multidisciplinary evaluation at this center involved evaluation by hand surgeons, occupational therapists, and psychologists. Data collected include age, sex, race, educational level, clinical presentation, number of diagnostic tests, number of surgeries, time to referral to the multidisciplinary center, direct cost of care, psychological diagnosis, Minnesota Multiphasic Personality Inventory, treatment modalities, and work status. RESULTS: We identified 174 workers' compensation patients with factitious hand disorders. Presentation was used to classify patients into 1 of 4 categories: psychopathological dystonia, factitious edema, psychopathological complex regional pain syndrome, and factitious wound creation and manipulation. There were statistically significant differences between the 4 categories in demographics, utilization of medical resources, psychopathology, treatment modalities, and return-to-work status. Patients with factitious wounds were more educated, used more medical resources, demonstrated an angry or hostile profile, and experienced a lower return-to-work rate. Patients with dystonia were less educated, used less medical resources, demonstrated a hypochondriasis or depressed profile, and experienced a higher return-to-work rate. CONCLUSIONS: Treatment of factitious hand disorders remains frustrating and costly due to failure or recurrence after traditional approaches. This review is a large-scale examination of the factitious hand disorder population that demonstrates the unique pathology involved in each of the 4 categories. There is a specific association between the category of hand disorder and the underlying pathology and prognosis. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Effect of low light and high noise on behavioural activity, physiological indicators of stress and production in laying hens.

1. Commercial laying hens are commonly housed in noisy and dim environments, yet relatively little is known about whether these conditions, particularly in combination, have any effect on welfare or egg production. 2. The study was designed to investigate whether chronic exposure to continuous noise (60 dB(A) vs. 80 dB(A)) and/or light intensity (150 lux vs. 5 lux) during the critical period of coming into lay (16-24 weeks of age) influenced behaviour (activity, resting and feather maintenance), physiological stress (plasma corticosterone and heterophil to lymphocyte ratio) and production (number and weight of eggs laid) in laying hens. 3. Hens in the low light pens were less active and preened and dust-bathed more than those housed in 150 lux; hens in the high noise pens rested more frequently than those in quieter pens. 4. There was no evidence that chronic exposure to low light or high noise caused appreciable physiological stress but egg production was affected by these conditions. Hens kept in pens with low light or high noise laid fewer eggs per day than those kept in high light or low noise pens. These effects were additive, so that the fewest eggs were laid by hens subject to both low light and high noise. 5. These results show that low light intensity and continual high background noise have a detrimental effect on egg production in the early laying phase as well as influencing the time allocated to different behaviours. However there was no strong evidence for a physiological stress response to either of these conditions or their combination.

The effects of acute and chronic hypoxia on cortisol, glucose and lactate concentrations in different populations of three-spined stickleback.

The response of individuals from three different populations of three-spined sticklebacks to acute and chronic periods of hypoxia (4.4 kPa DO, 2.2 mg l⁻¹) was tested using measures of whole-body cortisol, glucose and lactate. Although there was no evidence of a neuroendocrine stress response to acute hypoxia, fish from the population least likely to experience hypoxia in their native habitat had the largest response to low oxygen, with significant evidence of anaerobic glycolysis after 2 h of hypoxia. However, there was no measurable effect of a more prolonged period (7 days) of hypoxia on any of the fish in this study, suggesting that they acclimated to this low level of oxygen over time. Between-population differences in the analytes tested were observed in the control fish of the acute hypoxia trial, which had been in the laboratory for 16 days. These differences were not apparent among the control fish in the chronic exposure groups that had been held in the laboratory for 23 days, suggesting that these site-specific trends in physiological status were acclimatory. Overall, the results of this study suggest that local environmental conditions may shape sticklebacks' general physiological profile as well as influencing their response to hypoxia.

Mediastinoscopy in patients with presumptive stage I sarcoidosis: a risk/benefit, cost/benefit analysis.

STUDY OBJECTIVE: To determine whether persons with asymptomatic bilateral hilar lymphadenopathy (ABHL) and normal results of a physical examination should be observed with a presumptive diagnosis of stage 1 sarcoidosis (S1S) (ABHLps), its most frequent cause, or undergo mediastinoscopy to avoid overlooking an alternative diagnosis (AD) requiring treatment. DESIGN: We surveyed the English-language medical literature to estimate the proportion of persons with tuberculosis (TB), Hodgkin's disease (HD), and non-Hodgkin's lymphoma (NHL) who present with ABHL and calculated the number of mediastinoscopies required to identify each AD by computing the following ratio: incidence S1S/incidence of each AD presenting as ABHL (I(S1S)/I[ABHL-AD]). Risks of mediastinoscopy and benefits of earlier ascertainment of AD were derived from the published literature. Cost estimates were based on institutional charges. We conducted a regional survey of practicing pulmonologists to ascertain their diagnostic preferences. RESULTS: We estimate that if 33,000 persons with ABHL underwent mediastinoscopy, 32,982 (99.95%) would be found to have S1S or, very rarely, a disorder not requiring intervention; 407 would require hospitalization for complications at a cost in excess of $1 million; and 204 would experience major morbidity; 8 persons with TB, 9 with HD, and 1 with NHL would be identified at a cost of $100 to $200 million. The benefit for persons diagnosed as having AD would be minimal and likely offset by the procedural mortality. Seventy percent of pulmonologists responding to the survey favored observation over transbronchial lung biopsy or mediastinoscopy in patients with ABHL. CONCLUSION: A policy of continued observation of patients presenting with ABHL is preferable to diagnostic mediastinoscopy from both the risk/benefit and cost/benefit standpoint.

Gender and smoking cessation: a factor structure comparison of processes of change.

This study examined gender differences in the pattern of process use for smoking cessation using the Processes of Change Questionnaire (J. O. Prochaska, W. F. Velicer, C. C. DiClemente, & J. Fava, 1988). The goals were (a) to determine the degree to which the covariance structure of the Processes of Change Questionnaire is invariant across gender, (b) to test the existence of the theoretical 2-factor process model using confirmatory factor analysis, and (c) to explore mean differences, if found, in the use of the 10 processes of change across 4 stages of change (precontemplation, contemplation, preparation, and action). The sample (N = 516) had an equal distribution of men and women across the stages of change. Results demonstrated that the structure of the measure for men and women was invariant at the level of the variance-covariance matrices and that the hypothesized 2-factor model fit the data. Only stage of change predicted the experiential and behavioral process factors.

Comparison of 4 nutrient databases with chemical composition data from the Dietary Approaches to Stop Hypertension trial. DASH Collaborative Research Group.

Accuracy of computerized nutrient databases is an important consideration in selecting a nutrient analysis system. We project compared the nutrient content of daily menus calculated from 4 microcomputer programs to chemical analysis of menus analyzed for the Dietary Approaches to Stop Hypertension (DASH) trial. Thirty-six menus were entered at 2 independent DASH sites using the ESHA Food Processor, Minnesota Nutrition Data System, Moore's Extended Nutrient Database, and Nutritionist IV databases. Food prepared according to these menus was chemically analyzed at the Food Analysis Laboratory Control Center at Virginia Polytechnic Institute and State University, Department of Biochemistry, Blacksburg. Estimates for 13 nutrients were compared: energy, total fat, saturated fat, monounsaturated fat, polyunsaturated fat, carbohydrate, protein, cholesterol, calcium, potassium, magnesium, iron, and sodium. The overall intraclass correlation between the 2 sites' data entry was 0.998; thus, values were averaged for analyses. Databases varied significantly in their mean deviations from chemical analyses values for saturated, monounsaturated, and polyunsaturated fatty acids, potassium, magnesium, and iron (P < .05); however, these differences were small (< 10%). Absolute deviations, which estimate the combined effect of bias and precision, were significantly different among databases for energy, saturated fatty acids, and polyunsaturated acids. Absolute differences from the laboratory values varied by < 15%, except for iron. All 4 databases were comparable in accuracy and precision and performed well. Criteria for database selection depends not only on overall database accuracy, especially for nutrients of interest, but also on the ease of use of the program, relevant features of the associated software; and cost.

Social reinforcement of substance abuse aftercare group therapy attendance.

Although adherence to aftercare therapy in substance abuse treatment is associated with improved treatment outcome, relatively little research has explored methods of improving aftercare adherence. To improve on established methods of promoting aftercare adherence, 43 graduates of the 28-day intensive substance abuse treatment program at the Salem Veteran's Affairs Medical Center who received standard aftercare orientation are compared to 38 graduates who received the standard intervention plus social reinforcement of aftercare group therapy attendance. Clients who received social reinforcement attended more aftercare group sessions than did clients who received the standard treatment during the 8-week intervention (68.8% vs. 49.4% of sessions attended), and during the 4-week follow-up period (41.5% vs. 31.4% of sessions). These findings are noteworthy since the standard treatment had been shown to be effective in increasing aftercare adherence in prior studies (Lash, 1998; Lash & Blosser, 1999). Areas for future research are discussed.

Chronic ammonia exposure does not influence hepatic gene expression in growing pigs.

Housed pigs are often exposed to elevated concentrations of atmospheric ammonia. This aerial pollutant is widely considered to be an environmental stressor that also predisposes to reduced growth rates and poor health, although evidence to support this view is limited. Hepatic gene expression is very responsive to stress and metabolic effects. Two batches of growing pigs were therefore exposed to a nominal concentration of atmospheric ammonia of either 5 ppm (low) or 20 ppm (high) from 4 weeks of age for 15 weeks. Growth rates were monitored. Samples of liver were taken after slaughter (at ∼19 weeks of age). Samples from the second batch were analysed for global gene expression using 23 K Affymetrix GeneChip porcine genome arrays. Samples from both batches were subsequently tested for five candidate genes using quantitative real-time PCR (qPCR). The array analysis failed to detect any significant changes in hepatic gene expression following chronic exposure to atmospheric ammonia. Animals clustered into two main groups but this was not related to the experimental treatment. There was also no difference in growth rates between groups. The qPCR analyses validated the array results by showing similar fold changes in gene expression to the arrays. They revealed a significant batch effect in expression of lipin 1 (LPIN1), Chemokine (C-X-C motif) ligand 14 (CXCL14), serine dehydratase (SDS) and hepcidin antimicrobial peptide (HAMP). Only CXCL14, a chemotactic cytokine for monocytes, was significantly down-regulated in response to ammonia. As chronic exposure to atmospheric ammonia did not have a clear influence on hepatic gene expression, this finding implies that 20 ppm of atmospheric ammonia did not pose a significant material risk to the health or metabolism of housed pigs.

The impact of chronic environmental stressors on growing pigs, Sus scrofa (Part 1): stress physiology, production and play behaviour.

Commercially farmed animals are frequently housed in conditions that impose a number of concurrent environmental stressors. For pigs housed indoors, elevated levels of mechanical noise, atmospheric ammonia and low light intensities are commonplace. This experiment examined the effects on growing pigs of chronic exposure to combinations of commercially relevant levels of these potential stressors. Four-week-old hybrid female pigs (n = 224) were housed under experimentally manipulated conditions of nominally either <5 or 20 ppm atmospheric concentration of ammonia (24 h), a light intensity of 40 lux or 200 lux (12 h) and mechanical noise at either ⩽60 or 80 dB(A) (24 h) for 15 weeks in a fully factorial arrangement (23) of treatments. The response of pigs to these environmental factors was assessed using a suite of physiological, production and behavioural measures. These included indicators of hypothalamic-pituitary-adrenal (HPA) axis activation such as salivary cortisol and adrenal morphometry, as well as body weight, food conversion efficiency and general health scores. Play behaviour was recorded as it is thought to be inversely related to stress. Chronic exposure to ammonia produced the strongest effect, shown by lower concentrations of salivary cortisol and larger adrenal cortices in the pigs reared under 20 ppm ammonia, which may have been indicative of a period of HPA activation leading to a downregulation of cortisol production. The pigs in the ammoniated rooms also performed less play behaviour than pigs in non-ammoniated rooms. There was evidence for an interaction between high noise and ammonia on the health scores of pigs and for brighter light to ameliorate the effect of ammonia on salivary cortisol. However, there was no measurable impact of these potential stressors on the productivity of the pigs or any of the other physiological parameters measured. We conclude that there should be little concern in terms of performance about the physical stressors tested here, within current European Union legal limits. However, 20 ppm ammonia may have had an adverse influence on the well-being of growing pigs. In this study, all other aspects of the pigs' husbandry were optimal; therefore, it is possible that under less favourable conditions, more pronounced effects of ammonia, noise and dim light would be observed.

The impact of chronic environmental stressors on growing pigs, Sus scrofa (Part 2): social behaviour.

The effects of common and concurrent environmental stressors on the social behaviour of farm animals are poorly understood. Here, we report the results of a multifactorial experiment designed specifically to examine the individual, additive or interactive effects of elevated ammonia, noise and low light (LL) levels on the social behaviour of growing pigs. Social behaviour was measured in terms of the nature, frequency and duration of both initiated and response behaviours for 4 weeks following mixing of the groups. General activity patterns, group cohesion and social discrimination were also examined as a function of the environmental treatments. Elevated concentrations of atmospheric ammonia (∼20 v. <5 ppm) and LL intensity (∼40 v. 200 lux) had the most pronounced effects, particularly on the nature of social interactions, with pigs under these conditions showing more aggression in the early stages of the experiment. In addition, pigs exposed to a high level of mechanical noise representative of artificial ventilation (∼80 v. 40 dB [A]) were less submissive to aggressive acts, while pigs in ∼20 ppm ammonia showed more reciprocated aggression when in coincident LL (<40 lux). The results indicate that atmospheric ammonia at commonly experienced concentrations may undermine social stability, particularly in the presence of low lighting, though the mechanisms are currently unknown. These findings have implications for the welfare of growing pigs and hence policy makers and farmers alike, with respect to the improvement of welfare in intensive pig farming.

Caesarean section delivery and the risk of allergic disorders in childhood.

BACKGROUND: The composition of the intestinal flora in young children, if unfavourable, may increase the susceptibility to allergic disorders. Beneficial intestinal microbes originate from the maternal vaginal tract and thus are more likely to be transferred during vaginal births than during Caesarean sections (C-sections). OBJECTIVE: To determine whether children born by C-section have a different risk of allergic disorders compared with those delivered vaginally. We also tested the hypothesis that the risk of allergic disorders is highest for children born after 'repeat C-sections'. METHODS: A retrospective cohort study of 8,953 children aged 3-10 years. Children diagnosed with allergic rhinoconjunctivitis (AR), asthma, atopic dermatitis (AD), or food allergies were identified from the Kaiser Permanente Northwest Region electronic records. The children's sex, birth weight, birth order, postnatal exposure to antibiotics as well as the mothers' age, ethnicity, education, marital status, smoking status during pregnancy, and use of asthma or hayfever medications were identified through the mothers' medical records or through the Oregon Birth Registry. RESULTS: The risk of being diagnosed with AR was significantly higher in the children born by C-section than in those delivered vaginally: adjusted odds ratio (OR)=1.37%, 95% confidence interval (CI)=1.14-1.63. Delivery by C-section was also associated with the subsequent diagnosis of asthma (OR=1.24%, 95% CI=1.01-1.53); this association was gender specific, with a positive association restricted to girls (OR for asthma in girls: OR=1.53%, 95% CI=1.11-2.10; in boys: OR=1.08%, 95% CI=0.81-1.43). There was no significant association between mode of delivery and AD. If children born in a 'repeat C-section' were considered separately the risk of being diagnosed with AR increased further (OR=1.78%, 95% CI=1.34-2.37). The same increase was noted for asthma in girls (OR=1.83%, 95% CI=1.13-2.97) but not in boys. CONCLUSION: Caesarean sections may be associated with an increased risk of developing AR in childhood.

Adolescent health care visits: opportunities for brief prevention messages.

CONTEXT: It has been suggested that clinicians should increase efforts to modify and prevent risky behavior in adolescents. Professional organizations have proposed recommendations about access to care and preventive services, but it is difficult to know where and how to most effectively deliver such services. PRACTICE PATTERN EXAMINED: Clinic visits among adolescent HMO members (14 to 17 years of age). SETTING: Kaiser Permanente Northwest Division, a medium-sized, nonprofit, group-model HMO in the Pacific Northwest. DATA SOURCES: Two administrative databases (one for membership and one for outpatient utilization). RESULTS: A total of 22,626 adolescents who met the inclusion criteria were identified. Of these, 62% (more than 14,000 adolescents) were seen in a primary care clinic within 1 year; almost 83% (more than 18,000 adolescents) were seen within 2 years. There were several opportunities for follow-up for adolescents who had at least one visit in 1995: 60% had more than one visit during 1995, and 80% had more than one visit over the 2-year span of 1995 and 1996. The largest number of adolescent visits occurred in August through November, and most visits took place in the afternoon. CONCLUSIONS: Primary care visits in an HMO present an excellent opportunity to reach many teenagers outside of a school setting. Short-term educational or prevention programs would be optimal during late summer and fall; additional staff members may be able to present these programs after school once school begins.

Improving the E coding of hospitalizations for injury: do hospital records contain adequate documentation?

OBJECTIVES: Incomplete external cause of injury (E) coding limits the usefulness of hospital discharge data sets for injury surveillance and research. Hospital medical records were examined to determine whether they contained adequate cause of injury documentation to allow for more complete E coding of injury discharges. METHODS: Medical records for a sample of discharges involving a principal diagnosis of injury from the Uniform Hospital Discharge Data Set for Rhode Island were selected. We assigned E codes to these discharges and compared our E codes with those of the discharge data set. RESULTS: Documentation of cause of injury in the medical records was sufficient to allow assignment of a specific E code to 70% of the injuries for which no E codes or vague E codes were submitted on the Uniform Hospital Discharge Data Set. It was estimated that specific cause of injury documentation is available in the medical records of 80% of all injury discharges in Rhode Island; for approximately 90%, an E code describing at least the broad cause of injury could be assigned. CONCLUSIONS: Rates of E coding can be substantially increased by making better use of existing documentation in medical records.

Rapid isolation of cDNA by hybridization.

The isolation of genes from a given genomic region can be a rate-limiting step in the discovery of disease genes. We describe an approach to the isolation of cDNAs that have sequences in common with large genomic clones such as bacterial artificial chromosomes. We applied this method to loci both amplified and deleted in cancer, illustrating its usage in the identification of both oncogenes and tumor suppressor genes, respectively. The method, called rapid isolation of cDNAs by hybridization (RICH), depends on solution hybridization, enzymatic modification, and amplification/selection of sequences present in both cDNA populations and the genomic clones. The method should facilitate the development of transcription maps for large genomic clones, possibly even yeast artificial chromosomes.