Prevalence, age at onset, and risk factors of self-reported asthma among Swedish adolescent elite cross-country skiers.

The objective of the study was to compare the prevalence of self-reported physician-diagnosed asthma and age at asthma onset between Swedish adolescent elite skiers and a reference group and to assess risk factors associated with asthma. Postal questionnaires were sent to 253 pupils at the Swedish National Elite Sport Schools for cross-country skiing, biathlon, and ski-orienteering ("skiers") and a random sample of 500 adolescents aged 16-20, matched for sport school municipalities ("reference"). The response rate was 96% among the skiers and 48% in the reference group. The proportion of participants with self-reported physician-diagnosed asthma was higher among skiers than in the reference group (27 vs 19%, P=.046). Female skiers reported a higher prevalence of physician-diagnosed asthma compared to male skiers (34 vs 20%, P=.021). The median age at asthma onset was higher among skiers (12.0 vs 8.0 years; P<.001). Female sex, family history of asthma, nasal allergy, and being a skier were risk factors associated with self-reported physician-diagnosed asthma. Swedish adolescent elite cross-country skiers have a higher asthma prevalence and later age at asthma onset compared to a reference population. Being an adolescent, elite skier is an independent risk factor associated with asthma.

Automatic detection and analysis of cell motility in phase-contrast time-lapse images using a combination of maximally stable extremal regions and Kalman filter approaches.

Phase-contrast illumination is simple and most commonly used microscopic method to observe nonstained living cells. Automatic cell segmentation and motion analysis provide tools to analyze single cell motility in large cell populations. However, the challenge is to find a sophisticated method that is sufficiently accurate to generate reliable results, robust to function under the wide range of illumination conditions encountered in phase-contrast microscopy, and also computationally light for efficient analysis of large number of cells and image frames. To develop better automatic tools for analysis of low magnification phase-contrast images in time-lapse cell migration movies, we investigated the performance of cell segmentation method that is based on the intrinsic properties of maximally stable extremal regions (MSER). MSER was found to be reliable and effective in a wide range of experimental conditions. When compared to the commonly used segmentation approaches, MSER required negligible preoptimization steps thus dramatically reducing the computation time. To analyze cell migration characteristics in time-lapse movies, the MSER-based automatic cell detection was accompanied by a Kalman filter multiobject tracker that efficiently tracked individual cells even in confluent cell populations. This allowed quantitative cell motion analysis resulting in accurate measurements of the migration magnitude and direction of individual cells, as well as characteristics of collective migration of cell groups. Our results demonstrate that MSER accompanied by temporal data association is a powerful tool for accurate and reliable analysis of the dynamic behaviour of cells in phase-contrast image sequences. These techniques tolerate varying and nonoptimal imaging conditions and due to their relatively light computational requirements they should help to resolve problems in computationally demanding and often time-consuming large-scale dynamical analysis of cultured cells.

Genetic analyses of pathogen-specific mastitis.

The aims of this study were to investigate the presence of genetic variation for susceptibility to pathogen-specific mastitis and to examine whether haplotypes of an identified quantitative trait locus with effect on unspecific mastitis resistance had different effects on specific mastitis pathogens. Bacteriological data on mastitis pathogens were obtained from the diagnostic laboratory at the Swedish National Veterinary Institute. The data were mainly from subclinical cases of mastitis but also clinical cases were included. Variance components were estimated for incidence of the six most frequent pathogens using Markov Chain Monte Carlo methodology via Gibbs sampling. Genetic variation for susceptibility to pathogen-specific mastitis was higher compared to estimates of general resistance to clinical mastitis in most other studies. However, because of the non-random nature of data collection, comparisons to other studies should be made by caution. The effect of haplotype on the risk of being infected by a given mastitis pathogen, relative to other pathogens, was studied using an allele substitution model. Although there were no significant haplotype substitution effects on the resistance to any of the six mastitis pathogens, there was a significant difference between the effects of two of the haplotypes regarding the risk of acquiring a Streptococcus dysgalactiae infection.

Using geographical information systems to analyse accessibility to health services in the West Bank, occupied Palestinian territory.

Accessibility to adequate health services is a basic human right. Israeli road blocks and checkpoints inhibit access to health care for the Palestinian population. While other studies have dealt with the impact of the barriers, few are based on actual measurements of transport times between locations. Geographical information systems (GIS) and network analysis were used to generate different estimations of accessibility based on the existing road network and transport barriers. The population negatively affected were mainly people living outside urban centres and in governorates with no general hospital. Quantitative measurements using GIS can be used to confirm qualitative studies based on interviews and questionnaires and improve the understanding of the results. Working with a spatial analysis tool also helps to pinpoint weaknesses in the current infrastructure, thus improving the efficiency of future investments to improve health care in the West Bank.

Genetic mapping of quantitative trait loci for growth and fatness in pigs.

The European wild boar was crossed with the domesticated Large White pig to genetically dissect phenotypic differences between these populations for growth and fat deposition. The most important effects were clustered on chromosome 4, with a single region accounting for a large part of the breed difference in growth rate, fatness, and length of the small intestine. The study is an advance in genome analyses and documents the usefulness of crosses between divergent outbred populations for the detection and characterization of quantitative trait loci. The genetic mapping of a major locus for fat deposition in the pig could have implications for understanding human obesity.

Fine mapping of quantitative trait loci for mastitis resistance on bovine chromosome 11.

Quantitative trait loci (QTL) affecting clinical mastitis (CM) and somatic cell score (SCS) were mapped on bovine chromosome 11. The mapping population consisted of 14 grandsire families belonging to three Nordic red cattle breeds: Finnish Ayrshire (FA), Swedish Red and White (SRB) and Danish Red. The families had previously been shown to segregate for udder health QTL. A total of 524 progeny tested bulls were included in the analysis. A linkage map including 33 microsatellite and five SNP markers was constructed. We performed combined linkage disequilibrium and linkage analysis (LDLA) using the whole data set. Further analyses were performed for FA and SRB separately to study the origin of the identified QTL/haplotype and to examine if it was common in both populations. Finally, different two-trait models were fitted. These postulated either a pleiotropic QTL affecting both traits; two linked QTL, each affecting one trait; or one QTL affecting a single trait. A QTL affecting CM was fine-mapped. In FA, a haplotype having a strong association with a high negative effect on mastitis resistance was identified. The mapping precision of an earlier detected SCS-QTL was not improved by the LDLA analysis because of lack of linkage disequilibrium between the markers used and the QTL in the region.

Fine-mapping QTL for mastitis resistance on BTA9 in three Nordic red cattle breeds.

A QTL affecting clinical mastitis and/or somatic cell score (SCS) has been reported previously on chromosome 9 from studies in 16 families from the Swedish Red and White (SRB), Finnish Ayrshire (FA) and Danish Red (DR) breeds. In order to refine the QTL location, 67 markers were genotyped over the whole chromosome in the 16 original families and 18 additional half-sib families. This enabled linkage disequilibrium information to be used in the analysis. Data were analysed by an approach that combines information from linkage and linkage disequilibrium, which allowed the QTL affecting clinical mastitis to be mapped to a small interval (<1 cM) between the markers BM4208 and INRA084. This QTL showed a pleiotropic effect on SCS in the DR and SRB breeds. Haplotypes associated with variations in mastitis resistance were identified. The haplotypes were predictive in the general population and can be used in marker-assisted selection. Pleiotropic effects of the mastitis QTL were studied for three milk production traits and eight udder conformation traits. This QTL was also associated with yield traits in DR but not in FA or SRB. No QTL were found for udder conformation traits on chromosome 9.

Joint analysis of quantitative trait loci for clinical mastitis and somatic cell score on five chromosomes in three Nordic dairy cattle breeds.

Five chromosomes were selected for joint quantitative trait loci (QTL) analyses for clinical mastitis (CM) and somatic cell score (SCS) in 3 breeds: Finnish Ayrshire (FA), Swedish Red and White (SRB), and Danish Red (DR). In total, 19 grandsires and 672 sons in FA, 19 grandsires and 499 sons in SRB, and 8 grandsires and 258 sons in DR were used in the study. These individuals were genotyped with the 61 microsatellite markers used in any of the previous QTL scans on the selected chromosomes. Within-family QTL analyses based on linear regression models were carried out for CM and SCS to identify the segregating sires for each region. On the segregating families, joint single-trait and 2-trait analyses were performed using variance components models. The analyses confirmed that QTL affecting CM or SCS, or both, segregate on Bos taurus autosomes (BTA) 9, 11, 14, and 18, whereas a QTL on BTA29 could not be confirmed. Our results indicate that there may be at least 2 linked QTL on BTA9, one that primarily affects CM and a second that primarily affects SCS. On chromosomes BTA11, 14, and 18, the joint analyses were only significant for SCS.

Quantitative trait loci affecting fertility and calving traits in Swedish dairy cattle.

Impaired fertility is the main reason for involuntary culling of dairy cows in Sweden. The objective of this study was to map quantitative trait loci (QTL) influencing fertility and calving traits in the Swedish dairy cattle population. The traits analyzed were number of inseminations, 56-d nonreturn rate, interval from calving to first insemination, fertility treatments, heat intensity score, stillbirth, and calving performance. A genome scan covering 20 bovine chromosomes was performed using 145 microsatellite markers. The mapping population consisted of 10 sires and their 417 sons in a granddaughter design. Nine of the sires were of the Swedish Red Breed, and one was a Swedish Holstein. Least squares regression was used to map loci affecting the analyzed traits, and permutation tests were used to set significance thresholds. Cofactors were used in the analyses of individual chromosomes to adjust for QTL found on other chromosomes. The use of cofactors increased both the number of QTL found and the significance level. In the initial analysis, we found 13 suggestive QTL that were mapped to chromosomes 6, 7, 9, 11, 13, 15, 20, and 29. When cofactors were included, 30 QTL were detected on chromosomes 1, 3, 4, 18, 19, 22, and 25, in addition to the 8 previously mentioned chromosomes. Some of the results from the cofactor analysis may be false positives and require further validation. In conclusion, we were able to map several QTL affecting fertility and calving traits in Swedish dairy cattle.

Allelotype analysis of 2',3'-dideoxycytidine- and 1,3-butadiene-induced lymphomas in B6C3F1 mice.

To identify potential tumor suppressor genes involved in lymphoma development, we generated allelotypes of 16 2',3'-dideoxycytidine (ddC and 31 1,3-butadiene (BD)-induced lymphomas from C57BL/6 x C3H/He F1 (hereafter called B6C3F1) mice. Two or more anonymous simple sequence length polymorphisms per autosome were examined for loss of heterozygosity (LOH). Allelic losses throughout the genome were generally infrequent, except for markers on chromosome 2, 4, 11 and 12. The highest frequency of allelic losses was observed on chromosome 12, with 38 and 39% in ddC and BD-induced lymphomas, respectively. The most prevalent LOH was localized to the distal region bounded by markers D12Mit263 and D12Nds2. No known tumor suppressor genes have been mapped to this region, and no obvious candidates could be identified, suggesting the presence of novel suppressor gene(s). LOH on chromosome 2 was observed in 31% of ddC-induced lymphomas but in only 3% (1/31) of BD-induced lymphomas, suggesting a ddC-specific genetic effect. Detailed analysis localized a potential tumor suppressor gene residing on the distal region of chromosome 2, between markers D2Mit147 and D2Mit148. Twenty-five % of ddC-induced and 23% of BD-induced lymphomas showed LOH on chromosome 4, and two discrete regions were identified. One of the regions includes the IFN gene cluster and is syntenic to human chromosome 9p2l-22. Candidate tumor suppressor genes, Mts1 (multiple tumor suppressor 1) and Mts2 have been mapped to this region. The second region is located on the distal part of chromosome 4, which is homologous to human chromosome 1p35-36, a region that is frequently deleted in various types of human tumors. Finally, 19% of ddC-induced and 29% of BD-induced lymphomas revealed LOH on chromosome 11 at the Acrb locus, which lies within 1 cM of p53, suggesting that the p53 tumor suppressor gene also plays a role in lymphomagenesis. These results suggest that multiple potential suppressor loci contribute to lymphoma development in B6C3F1 mice.

Effects of hyperglycemia on in vivo adipose tissue metabolism studied with microdialysis in IDDM subjects.

The effect of hyperglycemia on in vivo adipose tissue metabolism was studied with microdialysis in seven lean patients with insulin-dependent diabetes mellitus (IDDM) receiving a constant infusion of insulin (36 pmol.m-2.min-1). Glucose was infused in a randomized fashion to maintain either a lower glucose level (6.6 +/- 0.3 mM, mean +/- SE) or hyperglycemia (11.8 +/- 0.8 mM) for 3 h. For insulin concentrations of 84 +/- 12 and 96 +/- 12 pM, hyperglycemia (11.8 +/- 0.8 mM) did not alter the plasma glycerol or lactate levels significantly but resulted in a significant (P < 0.0001) increase in plasma free fatty acid levels (0.49 +/- 0.13 vs. 0.32 +/- 0.08 mM). Plasma catecholamine levels were unchanged during hyperglycemia. Interstitial glycerol concentrations, measured in abdominal subcutaneous adipose tissue as an index of lipolysis, were not significantly influenced by hyperglycemia when compared with concentrations at the lower glucose level (92 +/- 30 vs. 106 +/- 18 microM). Moreover, hyperglycemia did not change abdominal adipose interstitial lactate levels significantly (1,248 +/- 174 vs. 1,351 +/- 159 microM during euglycemia). It may be concluded that hyperglycemia has no independent antilipolytic effect in IDDM subjects. Furthermore, in these patients, hyperglycemia gives no further lactate production in the subcutaneous adipose tissue in the presence of low physiological insulin levels.

Structure of the mouse type XV collagen gene, Col15a1, comparison with the human COL15A1 gene and functional analysis of the promoters of both genes.

Isolation and characterization of the mouse gene for the alpha1 chain of type XV collagen (Col15a1) revealed it to be approximately 110 kb in length and contain 40 exons. Analysis of the proximal 5'-flanking region showed properties characteristic of a housekeeping gene promoter, such as an absence of TATA and CAAT boxes, the presence of several transcriptional start sites and a high G+C content. The general organization of the mouse Col15a1 gene was found to be highly similar to that of its human homologue, but the genomic area encoding the end of the N-terminal non-collagenous domain showed marked divergence from the human form. Furthermore, two exons coding for the N-terminal collagenous domain of the human alpha1(XV) chain are lacking in the mouse Col15a1 gene. Due to the lack of two exons and a codon divergence in one exon, the mouse alpha1(XV) chain contains seven collagenous domains, whereas the human equivalent contains nine. Comparison of 5'-flanking sequences indicated four domains that were conserved between the mouse and human genes. Functional analysis of the mouse promoter identified cis-acting elements for both positive and negative regulation of Col15a1 gene expression in mouse NIH/3T3 cells.

Regional mapping of suppressor loci for anchorage independence and tumorigenicity on human chromosome 9.

By microcell-mediated chromosome transfer to the malignant Syrian hamster cell line BHK-191-5C, we previously identified two suppressor functions on human chromosome 9 (HSA9), one for anchorage independence and another for tumorigenicity. However, the precise chromosomal locations of these suppressor functions were not determined. The present study was undertaken to define the regional location of these suppressor loci using a panel of microcell hybrids containing structurally altered HSA9 with different deleted regions in the BHK-191-5C background. DNA derived from the cell hybrids was analyzed by PCR for verification of the presence of HSA9 genetic material by amplifying 62 microsatellite markers and 13 genes, covering the entire length of HSA9. Our deletion mapping data on anchorage independent and tumorigenic hybrids suggest that the suppressor function for anchorage independence is located in the region between 9q32 to 9qter. The suppressor for tumorigenicity may be located in one of three deleted regions on HSA9, the first one between the markers D9S162 and D9S1870, the second one between the markers D9S1868 and TIGRA002I21, and the third one between the markers D9S59 and D9S155.

The salt output of a nebulizer--a comparison between two nebulizer types.

The output of a nebulizer is generally defined as its weight loss during 1 min of nebulization. This mass output includes the weight loss due to evaporation of the solution required to moisten the dry air that is fed through the nebulizer. In order to compare results obtained from studies using different nebulizers we introduce the salt output as the amount of the solution that actually leaves the liquid phase as droplets and not by evaporation. The performance characteristics of a standard jet nebulizer (MA2) and a Sidestream jet neublizer were compared. Mass output was determined at different methacholine concentrations. Salt output was assessed by analysing the remaining salt in the nebulizers after 1 min of nebulization. Overall system performance in terms of forced expiratory volume in 1 sec (FEV1) reduction after 1 min of exposure to individually selected concentrations of methacholine were studied in 15 healthy, non-smoking subjects. Both nebulizer types showed a moderate linear increase of mass output with methacholine concentration. The efficiency coefficient, the quotient between salt output and mass output, was found to be 0.93 and 0.75 for the MA2 and Sidestream nebulizer respectively. These findings were explained by differences in airflow through, and temperature inside, the nebulizers. The salt output of the nebulizers proved to be better correlated to the FEV1-reduction following methacholine inhalation than did the mass output. The relative amount of the salt output that adhered to the acrylic walls of the Sidestream nebulizer drying tower was found to be 9%. We conclude that it is more appropriate to use salt output than mass output as a nebulizer performance descriptor. The study also shows the importance of determining nebulizer system performance under conditions as similar to true provocations as possible.

Mapping quantitative trait loci for carcass and meat quality traits in a wild boar x Large White intercross.

An intercross between wild boar and a domestic Large White pig population was used to map quantitative trait loci (QTL) for body proportions, weight of internal organs, carcass composition, and meat quality. The results concerning growth traits and fat deposition traits have been reported elsewhere. In the present study, all 200 F2 animals, their parents, and their grandparents were genotyped for 236 markers. The marker genotypes were used to calculate the additive and dominance coefficients at fixed positions in the genome of each F2 animal, and the trait values were regressed onto these coefficients in intervals of 1 cM. In addition, the effect of proportion of wild boar alleles was tested for each chromosome. Significant QTL effects were found for percentage lean meat and percentage lean meat plus bone in various cuts, proportion of bone in relation to lean meat in ham, muscle area, and carcass length. The significant QTL were located on chromosomes 2, 3, 4, and 8. Each QTL explained 9 to 16% of the residual variance of the traits. Gene action for most QTL was largely additive. For meat quality traits, there were no QTL that reached the significance threshold. However, the average proportion of wild boar alleles across the genome had highly significant effects on reflectance and drip loss. The results show that there are several chromosome regions with a considerable effect on carcass traits in pigs.

Vibration in car repair work.

The main objective of the study was to find efficient hand tools which caused only minor vibration loading. Vibration measurements were carried out under standardised working conditions. The time during which car body repairers in seven companies were exposed to vibration was determined. Chisel hammers, impact wrenches, sanders and saws were the types of tools which generated the highest vibration accelerations. The average daily exposure at the different garages ranged from 22 to 70 min. The risk of vibration injury is currently rated as high. The difference between the highest and lowest levels of vibration was considerable in most tool categories. Therefore the choice of tool has a major impact on the magnitude of vibration exposure. The importance of choosing the right tools and working methods is discussed and a counselling service on vibration is proposed.