Applying the adverse outcome pathway concept for assessing non-monotonic dose responses: biphasic effect of bis(2-ethylhexyl) phthalate (DEHP) on testosterone levels.

Male reproduction is one of the primary health endpoints identified in rodent studies for some phthalates, such as DEHP (Bis(2-ethylhexyl) phthalate), DBP (Dibutyl phthalate), and BBP (Benzyl butyl phthalate). The reduction in testosterone level was used as an intermediate key event for grouping some phthalates and to establish a reference point for risk assessment. Phthalates, and specifically DEHP, are one of the chemicals for which the greatest number of non-monotonic dose responses (NMDRs) are observed. These NMDRs cover different endpoints and situations, often including testosterone levels. The presence of NMDR has been the subject of some debate within the area of chemical risk assessment, which is traditionally anchored around driving health-based guidance values for apical endpoints that typically follow a clear monotonic dose-response. The consequence of NMDR for chemical risk assessment has recently received considerable attention amongst regulatory agencies, which confirmed its relevance particularly for receptor-mediated effects. The present review explores the relationship between DEHP exposure and testosterone levels, investigating the biological plausibility of the observed NMDRs. The Adverse Outcome Pathway (AOP) concept is applied to integrate NMDRs into Key Event Relationships (KERs) for exploring a mechanistic understanding of initial key events and possibly associated reproductive and non-reproductive adverse outcomes.

Frequently repeated measurements -our experience of collecting data with SMS.

BACKGROUND: As technology is advancing, so are the possibilities for new data collection methods in research, potentially improving data quality and validity of the results. In Sweden, a system using frequent repeated data collection using text messages, SMS Track, has been used in clinical research for more than a decade. In this paper, compliance with repeated text message questions was examined across five different studies, i.e. if compliance was 1: associated with study-specific factors (age or gender of the subjects, the condition, its' severity or course, i.e. improvement, relapse or steady state) and/or. 2: associated with the methodology itself (the question being asked, the frequency and number of questions, duration of data collection, initial compliance or the management of the system). METHODS: Descriptive comparisons were done across five studies. Three studies were collecting weekly responses over at least 52 weeks ("Weekly studies") and were used to investigate the effect of age, sex and pain severity on compliance, the effect of early compliance for late compliance, and finally the early occurrence of two successive weeks with non-compliance. RESULT: Compliance was excellent across all five studies, and only influenced somewhat by age, sex and pain-level. The factor "study" remained significant in the final model thus the observed differences may be a result of the conditions studied but does not seem to be attributable to severity or development of these conditions. Number and frequency of questions did not influence compliance, nor did study duration. CONCLUSIONS: Compliance was excellent in the included studies and was not affected by population factors. However, differences in compliance were observed that cannot be easily explained and warrant further investigation. In particular, the nature of the variables or the management of the study are potential areas for further investigations.

Dietary methionine deficiency reduces laying performances of female common ducks and impacts traits of interest of their mule ducklings.

The effects of maternal nutrition on offspring phenotypes have been mainly documented over the past years in mammals, and are now studied in poultry as well. In the present study, we investigated the effects of a reduced level of dietary Methionine (Met) on laying performances of common laying ducks and their impacts on the phenotype of their mule ducklings. A total of 60 female laying ducks were divided into 2 dietary treatments at 10 wk of age. The restricted group received Met-restricted diets (R group) containing 0.25% of Met whereas the control group received control diets (C group) containing 0.40% of Met that meets Met requirements. The restriction was applied during the growing and laying periods, from 10 to 51 wk of age and a particular focus was put on female breeder traits that might be affected by the Met restriction. Plasma parameters of hepatic and lipid metabolisms were recorded in ducklings. Total weight (P < 0.001), albumen weight (P < 0.001) and albumen percentage of dry matter (P < 0.01) were decreased for eggs laid by female breeders from the R group. Both male and female ducklings from the R group of female breeders showed a reduced BW at hatching (P < 0.001) and a tendency to an increased proportional liver weight (P = 0.07). Finally, the maternal low dietary Met level modified plasma parameters in newborn ducklings regardless of sex: alkaline phosphatase (ALP) and alanine transaminase (ALT) activities were reduced (P = 0.07 and P = 0.002, respectively), levels of glucose (P = 0.03) and triglycerides (P = 0.01) were higher whereas level of free fatty acids decreased (P = 0.01). It was concluded that feeding female laying ducks with a restricted dietary Met content during the growing and laying periods has a negative effect on egg weight and composition. The ducklings that were restricted in nutrients during their early development, have a reduced BW, and altered lipid and hepatic metabolisms.

Evaluating the evidence for non-monotonic dose-response relationships: A systematic literature review and (re-)analysis of in vivo toxicity data in the area of food safety.

This study aims to evaluate the evidence for the existence of non-monotonic dose-responses (NMDRs) of substances in the area of food safety. This review was performed following the systematic review methodology with the aim to identify in vivo studies published between January 2002 and February 2015 containing evidence for potential NMDRs. Inclusion and reliability criteria were defined and used to select relevant and reliable studies. A set of six checkpoints was developed to establish the likelihood that the data retrieved contained evidence for NMDR. In this review, 49 in vivo studies were identified as relevant and reliable, of which 42 were used for dose-response analysis. These studies contained 179 in vivo dose-response datasets with at least five dose groups (and a control group) as fewer doses cannot provide evidence for NMDR. These datasets were extracted and analyzed using the PROAST software package. The resulting dose-response relationships were evaluated for possible evidence of NMDRs by applying the six checkpoints. In total, 10 out of the 179 in vivo datasets fulfilled all six checkpoints. While these datasets could be considered as providing evidence for NMDR, replicated studies would still be needed to check if the results can be reproduced to rule out that the non-monotonicity was caused by incidental anomalies in that specific study. This approach, combining a systematic review with a set of checkpoints, is new and appears useful for future evaluations of the dose response datasets regarding evidence of non-monotonicity.

Preventing sickness absenteeism among employees with common mental disorders or stress-related symptoms at work: Design of a cluster randomized controlled trial of a problem-solving based intervention versus care-as-usual conducted at the Occupational Health Services.

BACKGROUND: Common mental disorders (CMDs) are among the leading causes of sick leave in Sweden and other OECD countries. They result in suffering for the individual and considerable financial costs for the employer and for society at large. The occupational health service (OHS) can offer interventions in which both the individual and the work situation are taken into account. The aim of this paper is to describe the design of a study evaluating the effectiveness of an intervention given at the OHS to employees with CMDs or stress-related symptoms at work. In addition, intervention fidelity and its relation to the outcome will be assessed in a process analysis. METHODS: The study is designed as a cluster randomized trial in which the participating OHS consultants are randomized into either delivering the intervention or performing care as usual. Employees with CMDs or stress-related symptoms at work are recruited consecutively by the OHS consultants. The intervention aims to improve the match between the employee and the job situation. Interviews are held individually with the employee and the nearest supervisor, after which a joint meeting with both the employee and the supervisor takes place. A participatory approach is applied by which the supervisor and the employee are guided by the OHS consultant and encouraged to actively take part in problem solving concerning the work situation. Outcomes will be assessed at baseline and at six and 12 months. A long-term follow-up at 3 years will also be performed. The primary outcome is registered sickness absence during a 1-year period after study inclusion. Secondary outcomes are mental health and work ability. The intervention's cost effectiveness, compared to treatment as usual, both for society and for the employer will be evaluated. A process evaluation by both the OHS consultants and the employee will be carried out. DISCUSSION: The study includes analyses of the effectiveness of the intervention (clinical and economic) as well as an analysis of its implementation at the participating OHSs. Possible methodological challenges such as selection bias and risk of contamination between OHS consultants delivering the experimental condition and consultants giving usual care are discussed. TRIAL REGISTRATION: ClinicalTrials NCT02563743 Sep 28 2015.

Genetic and non-genetic factors related to the success of artificial insemination in dairy goats.

The objective of this study was to evaluate genetic and non-genetic factors influencing artificial insemination (AI) success in French dairy goats. Data analysis, on a total of 584 676 and 386 517 AI records for Alpine and Saanen breed, respectively, collected from 1992 to 2009, was conducted separately on each breed. We used a linear simple repeatability animal model which combined male and female random effect and environmental fixed effects. The most important environmental factor identified was the period within year effect due to the European heat wave of 2003. The estimated values of the annual fertility exhibited a negative trend of 1% loss of AI success per 10 years for Alpine breed only. The range of variation for the flock×within years random effect was 70% and 65% for Alpine and Saanen breeds. The negative effect on AI success of antibody production after repetitive hormonal treatment was confirmed. We observed an important positive relationship between fertility and protein yield expressed as quartile within flock×years of protein 250-day yield for female with lactation number over 1, while this trend was negative for primiparous females. We detected a negative effect of the duration of conservation of semen with a difference of about 4% of AI success between extreme values (2 to 8+ or 9+ years). Heritability estimates for male fertility were 0.0037 and 0.0043 for Alpine and Saanen breed respectively, while estimates for female fertility was 0.040 and 0.049. Repeatability estimates for males were 0.008 and 0.010 for Alpine and Saanen, respectively, and 0.097 and 0.102 for females. With such low values of heritability, selection can hardly affect fertility.

Improving residual feed intake of mule progeny of Muscovy ducks: genetic parameters and responses to selection with emphasis on carcass composition and fatty liver quality.

In France, about 95% of the fatty liver production comes from mule ducks, an infertile hybrid cross between female common ducks (Anas platyrhynchos) and Muscovy drakes (Cairina moschata). As a hybrid, genetic improvement of the performance of mule ducks is achieved by selection of the parental populations. Feed represents two-thirds of the total costs of duck production; thus, the breeders' main concern is to improve the birds' feed efficiency without impairing their capacity to be overfed after the growing period. To obtain insight into this economically important trait, we designed a divergent selection experiment for Muscovy sires on the basis of the residual feed intake (RFI) of their male mule progeny. Residual feed intake represents the fraction of feed intake that cannot be explained by maintenance and production requirements. Data comprised records from generations 0 to 2 with 227 Muscovy sires of 2,016 mule ducks. Growth and fat deposition were measured individually for all mule ducks. Half-sib mule ducks were placed together in 1 small pen, and the feed consumption was recorded for each pen; all half-sibs therefore had the same feed intake estimates. Heritability of RFI was high (0.83 ± 0.42), and after 2 generations of selection, the differences between lines in terms of RFI (contrast of 9.13 g/d, representing 0.76 phenotypic standard deviation; P < 0.0001) and feed conversion ratio (contrast of 0.08, representing 0.28 phenotypic standard deviation; P = 0.0003) were marked. In regard to carcass traits, the low-RFI line (high-efficiency animals) had heavier legs (476 vs. 463 g; P < 0.0001) and magret muscles (268 vs. 262 g; P = 0.001) than the high-RFI line (low-efficiency animals). No differences were observed for either the liver weight or the melting rate between the 2 lines (P > 0.46). Selection on RFI thus improves the feed efficiency of animals without impairing their capacity to produce fatty liver.

Using the product threshold model for estimating separately the effect of temperature on male and female fertility.

Animals under environmental thermal stress conditions have reduced fertility due to impairment of some mechanisms involved in their reproductive performance that are different in males and females. As a consequence, the most sensitive periods of time and the magnitude of effect of temperature on fertility can differ between sexes. The objective of this study was to estimate separately the effect of temperature in different periods around the insemination time on male and on female fertility by using the product threshold model. This model assumes that an observed reproduction outcome is the result of the product of 2 unobserved variables corresponding to the unobserved fertilities of the 2 individuals involved in the mating. A total of 7,625 AI records from rabbits belonging to a line selected for growth rate and indoor daily temperature records were used. The average maximum daily temperature and the proportion of days in which the maximum temperature was greater than 25°C were used as temperature descriptors. These descriptors were calculated for several periods around the day of AI. In the case of males, 4 periods of time covered different stages of the spermatogenesis, the transit through the epididymus of the sperm, and the day of AI. For females, 5 periods of time covered the phases of preovulatory follicular maturation including day of AI and ovulation, fertilization and peri-implantational stage of the embryos, embryonic and early fetal periods of gestation, and finally, late gestation until birth. The effect of the different temperature descriptors was estimated in the corresponding male and female liabilities in a set of threshold product models. The temperature of the day of AI seems to be the most relevant temperature descriptor affecting male fertility because greater temperature records on the day of AI caused a decrease in male fertility (-6% in male fertility rate with respect to thermoneutrality). Departures from the thermal zone in temperature descriptors covering several periods before AI until early gestation had a negative effect on female fertility, with the pre- and peri-implantational period of the embryos being especially sensitive (from -5 to -6% in female fertility rate with respect to thermoneutrality). The latest period of gestation was unaffected by the temperature. Overall, magnitude and persistency of the temperatures reached in the conditions of this study do not seem to be great enough to have a large effect on male and female rabbit fertility.

Child's positive and negative impacts on parents--a person-oriented approach to understanding temperament in preschool children with intellectual disabilities.

BACKGROUND: Despite previous efforts to understand temperament in children with intellectual disability (ID), and how child temperament may affect parents, the approach has so far been unidimensional. Child temperament has been considered in relation to diagnosis, with the inherent risk of overlooking individual variation of children's temperament profiles within diagnostic groups. The aim of the present study was to identify temperamental profiles of children with ID, and investigate how these may affect parents in terms of positive and negative impacts. METHOD: Parent-rated temperament in children with ID was explored through a person-oriented approach (cluster analysis). Children with ID (N=49) and typically developing (TD) children (N=82) aged between 4 and 6 years were clustered separately. RESULTS: Variation in temperament profiles was more prominent among children with ID than in TD children. Out of the three clusters found in the ID group, the disruptive, and passive/withdrawn clusters were distinctly different from clusters found in the TD group in terms of temperament, while the cluster active and outgoing was similar in shape and level of temperament ratings of TD children. Children within the disruptive cluster were described to have more negative and less positive impacts on mothers compared to children within the other clusters in the ID group. CONCLUSIONS: Mothers who describe their children as having disruptive temperament may be at particular risk for experiencing higher parenting stress as they report that the child has higher negative and lower positive impacts than other parents describe. The absence of a relationship between child temperament profile and positive or negative impact on fathers may indicate that fathers are less affected by child temperament. However, this relationship needs to be further explored.

Product versus additive model for studying artificial insemination results in several livestock populations.

Two models can be used for studying binary results of AI. The additive threshold model proposes an underlying variable as summing the environmental and genetic effects from the 2 individuals involved in the mating, and the product threshold model assumes that the conditional probability of AI success is the product of the probabilities of success of 2 unobserved binary phenotypes (one is the male fertility; the other is the female fertility). The purpose of this paper is to compare the predictive ability of the product and the additive threshold models for studying AI results and to compare results obtained with the 2 models in 3 different species: cattle, sheep, and rabbits. Results showed that the predictive ability of the product model is similar to the additive model in sheep and rabbits but worst in cattle (percentage of wrong prediction = 42, 27, and 35% in the additive model; 43, 28, and 47% in the product model in sheep, rabbits, and cattle, respectively). Even when the 2 models have similar performance, they differed in their EBV (for instance, Pearson correlation between EBV predicted with the 2 models = 0.46 in sheep for male fertility). The product model can determine which sex is responsible for an AI failure. In sheep, the female was the responsible in 94% of the cases and male in 2% of them; in rabbits, the female was the responsible in 54% of the cases and the male in 39% of them. Different estimates of probabilities for male and female fertility success obtained with the product model in the 3 species suggest that male and female fertilities behave differently depending on the species and the uniqueness of the data sets. Although product model seems to provide additional information in the fertility process, further research is needed to understand the worst performance of the product model in cattle.

Expression of seasonality in Merinos d'Arles ewes of different genotypes at the MT1 melatonin receptor gene.

Spontaneous ovulatory activity (SOA) in spring has been used to study the out-of-season breeding ability of Merinos d'Arles (MA) ewes. Within this breed, an association was found between more intense seasonality and genotype -/- at a MnlI restriction site (allele - for its absence v. + for its presence) in Exon II of the MT1 receptor gene. This study was designed to ascertain whether this association results in a direct effect of the MT1 genotype on the expression of seasonality in MA ewes. In the first year of the study, genotyping of 314 MA ewes at locus MnlI was carried out and resulted in frequencies of 43.0%, 44.9% and 12.1% for genotypes +/+, +/- and -/-, respectively. The SOA of these ewes was determined in early April of two consecutive years by assaying plasma progesterone concentrations in two blood samples taken 9 days apart. Groups of 30 ewes of each homozygous genotype (+/+ and -/-) were identified from this population and their SOA was followed by taking blood samples at regular intervals between January and mid-April of the second and third year of the study. In the second year, groups of ewes were managed together on rangelands, whereas in the third year each group was split into two subgroups given differential feed levels. The results clearly showed that genotype had no significant effect on SOA during the 2- to 3-month period preceding the introduction of rams for spring mating. In the second year of the study, in which the experimental procedure allowed a fair comparison of the fertility of ewes in spring mating, fertility was similar for both genotypes. The reciprocity of the association was not demonstrated and the MnlI polymorphic site could not be used as a genetic marker of selection for out-of-season breeding ability, at least not in the MA breed. The percentage of cycling ewes significantly decreased between January and April, and older ewes (5 or 6 years old depending on the year of the study) were more cyclic than younger ones (2 and 3 years old, respectively). The differential feeding level of ewes from early February did not significantly affect their SOA during the time period studied in the third year of the study.

Child dental fear as measured with the Dental Subscale of the Children's Fear Survey Schedule: the impact of referral status and type of informant (child versus parent).

OBJECTIVES: The first aim of this methodological study was to investigate the agreement between self-ratings of Children's Fear Survey Schedule (CFSS-DS). The second aim was to explore using differentiated cut-off scores, and to compare these cut-off scores with those commonly used. METHODS: Three different data collections included study groups (n = 497) of children and adolescents who had been referred to specialized pediatric dentistry clinics, and reference groups (n = 499) of dental patients and children rating the analyses were limited to the Östergötland sample (n = 210 + 228). Patients and their accompanying parents (mainly mothers) were asked to fill in the CFSS-DS independently. Cut-off scores on the CFSS-DS scale were determined using receiver-operating characteristic analysis; patient-parent agreement was illustrated with Bland-Altman plots. RESULTS: The patient-parent agreement was modest, particularly among those who were referred because of dental behaviour management problems (DBMP). Cut-off scores differentiated by age and gender, suggested by exploration according to two different methods, were with few exceptions clearly below the standard cut-off score. CONCLUSION: [corrected] The validity of parental ratings of their children dental fear should be questioned, particularly in high-fear populations. Self-ratings should, as far as possible, be used to complement parental ratings. One consequence of using the standard cut-off score is the risk of overlooking some patients needs for special attention. Further research is needed to establish and validate age-and gender-differentiated cut-off scores on the CFSS-DS.

Heritability of dental fear.

The objective was to test a hypothesized genetic component (i.e., monozygotic being more similar compared with dizygotic twins) in dental fear/anxiety by comparing the probandwise concordance. We analyzed data based on a dichotomous measure of Dental Fear/Anxiety and a continuous measure of Dental Fear Intensity from over 2000 twins, collected when participants were 13-14 years old and once again three years later. The hypothesis was confirmed, but heritability of Dental Fear/Anxiety was estimated to be higher for girls (0.77 at time 1 and 0.55 at time 2) than for boys (0.14 and 0.0 at times 1 and 2, respectively). Heritability of Dental Fear Intensity, however, was similar for girls (0.30 and 0.40 at times 1 and 2, respectively) and boys (0.47, 0.44). Studies of the etiology of dental fear/anxiety should take genetic vulnerability into account and include molecular biology measures. Possible heritability differences between girls and boys need attention.

Neuroendocrine and genetic control of seasonal reproduction in sheep and goats.

Goats and sheep generally express seasonal variations in their sexual behaviour, spermatogenic activity (from moderate decrease to very low sperm production), gamete quality (variations in fertilization rates and embryo survival), ovulation frequency (presence or absence of ovulation), and ovulation rate (number of eggs shed per ovulation period). This induces seasonal availability of derived, fresh animal products (meat, milk and cheese) because of a more or less marked seasonal distribution of births. A complex combination of an endogenous circannual rhythm driven and synchronized by light and melatonin, which controls the pulsatile activity of GnRH neurons in the preoptic-mediobasal hypothalamus, is responsible for these changes. Dramatic and long-term neuroendocrine changes, involving different neuromediator systems and neuronal plasticity, have been shown to play a role in these processes. A strong variability between breeds exists in both species regarding the dates of onset and end of the breeding season, with a gradient of seasonality from southern to northern latitudes. Within a breed, seasonal traits are heritable; thus, genetic selection could be one way to decrease seasonality in sheep and goats in the future.

Fine mapping of the FecL locus influencing prolificacy in Lacaune sheep.

In the Lacaune sheep population, two major loci influencing ovulation rate are segregating: FecX and FecL. The FecX(L) mutation is a non-conservative substitution (p.Cys53Tyr) in BMP15 that prevents the processing of the protein. Using a statistical approach, FecL has been shown to be an autosomal major gene. A full genome scan localized the FecL locus on sheep chromosome 11. Fine mapping reduced the interval containing FecL to markers BM17132 and FAM117A, corresponding to a synteny block of 1.1 megabases on human chromosome 17, which encompasses 20 genes. The expression of 16 genes from this interval was observed in tissues of the reproductive axis, but expression was not affected in homozygous FecL(L) females. In this interval, a unique haplotype was associated with the FecL(L) mutation. This particular haplotype could be predicted by the DLX3:c.*803A>G SNP in the 3' UTR sequence of the DLX3 gene. This SNP provided accurate classification of animals (99.5%) as carriers or non-carriers of the mutation and therefore maybe useful in marker assisted selection. A synergistic action of FecL(L) and FecX(L) mutations on both ovulation rate and litter size was demonstrated. Until now, all the Fec genes identified in sheep belong to the bone morphogenetic protein (BMP) system. Based on the human orthologous region, none of the 20 genes in the FecL region corresponds to known molecules in the BMP system. The identification of the FecL(L) mutation could lead to the discovery of a new pathway involved in the regulation of ovulation rate.

Product versus additive threshold models for analysis of reproduction outcomes in animal genetics.

The phenotypic observation of some reproduction traits (e.g., insemination success, interval from lambing to insemination) is the result of environmental and genetic factors acting on 2 individuals: the male and female involved in a mating couple. In animal genetics, the main approach (called additive model) proposed for studying such traits assumes that the phenotype is linked to a purely additive combination, either on the observed scale for continuous traits or on some underlying scale for discrete traits, of environmental and genetic effects affecting the 2 individuals. Statistical models proposed for studying human fecundability generally consider reproduction outcomes as the product of hypothetical unobservable variables. Taking inspiration from these works, we propose a model (product threshold model) for studying a binary reproduction trait that supposes that the observed phenotype is the product of 2 unobserved phenotypes, 1 for each individual. We developed a Gibbs sampling algorithm for fitting a Bayesian product threshold model including additive genetic effects and showed by simulation that it is feasible and that it provides good estimates of the parameters. We showed that fitting an additive threshold model to data that are simulated under a product threshold model provides biased estimates, especially for individuals with high breeding values. A main advantage of the product threshold model is that, in contrast to the additive model, it provides distinct estimates of fixed effects affecting each of the 2 unobserved phenotypes.

Nasal hyperresponders and atopic subjects report different symptom intensity to air quality: a climate chamber study.

UNLABELLED: Short-term exposure to dust and dust added with beta-(1,3)-d-glucan or aldehydes may cause sensory reactions. In random order, we exposed 36 volunteers in a climate chamber to clean air, office dust, dust with glucan, and dust with aldehydes. Three groups of subjects were exposed, eleven were non-atopic with nasal histamine hyperreactivity, 13 were non-atopic, and 12 were atopic. Subjective ratings of symptoms and general health were registered four times during four 6-h exposure sessions. Six symptom intensity indices were constructed. The nasal hyperreactive group had a high and time-dependent increase of mucous membrane irritations, whereas the atopic group had a low and stable rate of irritations with exposure time, close to the reference group (P = 0.02 for differences between the groups with respect to time under exposure for Weak Inflammatory Responses and P = 0.05 for Irritative Body Perception, significance mainly because of the nasal hyperreactive group). Exposure to dust, with or without glucan or aldehydes, showed increased discomfort measured by the index for Constant Indoor Climate, and dust with glucan had a similar effect for the index for Lower Respiratory Effects. For Psychological and Neurological Effects these were dependent on group affiliation, thus preventing a uniform statement of exposure effects for all three investigated groups. PRACTICAL IMPLICATIONS: Opportunities for identifying persons with high or low sensitivity to low-level exposures are important in preventive medicine and will reduce intra-group variability and thus increase the power of experimental and epidemiological studies searching for correlations between exposures and health effects. The contrast between nasal hyperreactive on one side and atopic and reference subjects on the other side is particularly important. The atopic group indicated a non-homogenous reaction depending on their hyperreactive status, a finding that could be important but needs further confirmation.

Cost effectiveness of two rehabilitation programmes for neck and back pain patients: A seven year follow-up.

The cost effectiveness of work-oriented rehabilitation for persons on long-term sick leave needs to be assessed. This prospective observational study presents a follow-up seven years after rehabilitation using two different evidence-based work-oriented regimens. Individuals on sick leave for neck and back pain were referred to two rehabilitation programmes in Sweden. The first programme was a relatively low-intensity programme based on orthopaedic manual therapy and exercise programme (OMTP). The second programme was a full-time multidisciplinary programme (MDP). The primary outcome was sickness absence seven years after intervention. Cost effectiveness was calculated on the basis of loss of production due to sickness absence. The results show that participants referred to MDP and with less than 60 sick days before rehabilitation have reduced sickness absence after intervention as compared to matched controls. This corresponds to a cost reduction of about 94,494 EUR per referred individual. Further, the results indicate that participants of the OMTP who have more than 60 sick days before rehabilitation have a statistically significant increased risk of disability pension. This means increased cost in terms of loss of production of 44,593 EUR per referred individual. The results of this study show that MPD but not OMTP achieves the goal of working life-oriented rehabilitation. A direct comparison between the rehabilitation programmes strengthened the assumption that long-term sickness absence prior to rehabilitation is associated with more days on sick leave after rehabilitation. This analysis also indicated the importance of participants' pain self-efficacy beliefs and recovery beliefs on rehabilitation outcome.

Genetic and non-genetic parameters of several characteristics of production and semen quality in young bucks.

The objective of this study was to evaluate genetic and non-genetic factors influencing characteristics of young buck semen production using a multivariate model that takes into account the longitudinal structure of data. Data were collected from 1989 to 2002 at two French A.I. centres. The data corresponded to 13151 and 9206 ejaculates of 758 Alpine and 535 Saanen bucks respectively, collected at the beginning of the first breeding season (September-December). The semen volume, the total number of spermatozoa, the concentration, the motility score of spermatozoa after freezing and the percentage of motile spermatozoa after freezing were registered for each ejaculate. Within-breed heritabilities and repeatabilities were estimated using a multivariate animal model using a power spatial covariance structure for environmental effect. For all characteristics and the two breeds, the main source of variation was the year-month interaction that interacted with the centre. We observed a decrease in years of motility score after freezing. Age and frequency of collection had a significant effect on semen volume and number of spermatozoa for both breeds, and on concentration of spermatozoa for the Alpine breed. No effect of these factors was found on the characteristics observed after freezing. Heritabilities for concentration, number of spermatozoa, semen volume, motility score after freezing and percentage of motile spermatozoa after freezing per ejaculate were respectively, 0.32, 0.15, 0.25, 0.12 and 0.05 for the Saanen breed and 0.34, 0.25, 0.29, 0.17 and 0.03 for the Alpine breed. Genetic correlations between volume and number of spermatozoa were respectively, 0.74 for the Alpine breed and 0.86 for the Saanen breed. Further study is required to compare the semen characteristics of young bucks with their mature production.

Effects on human eyes caused by experimental exposures to office dust with and without addition of aldehydes or glucan.

UNLABELLED: Thirty-six volunteers (in three susceptibility groups: 11 subjects were non-allergic with nasal histamine hypersensitivity, 13 were non-allergic with normal sensitivity, and 12 were pollen allergic with or without nasal hypersensitivity) were exposed for three and a half hours in a climate chamber. Each subject was exposed to clean air (dust 45 +/- 38 microg/m(3) total suspended particle, TSP), house dust at 357 +/- 180 microg/m(3) TSP, house dust 382 +/- 175 microg/m(3) TSP with added glucan (50 ng/m(3)) and house dust 394 +/- 168 microg/m(3) TSP with added aldehydes corresponding to a gaseous phase of 300 microg/m(3) in the air. The study was explorative by nature. No significant effects of exposures as such were seen on break-up time, conjunctival epithelial damage score and Trolox Equivalent Antioxidant Capacity (TEAC) in tear film and subjective ratings. However, in TEAC a significant different time course was seen during exposures to aldehyde-containing dust indicating a subacute and late response to the exposures. Perceived eye irritation increased significantly during exposures to normal dust. The perception ratings were highly correlated, whereas no correlation was found between the subjective responses and the objective measurements. PRACTICAL IMPLICATIONS: The findings indicate that measurement effects on the eyes are rather insensitive measures of short time effects of office dust exposures.