The Norwegian Healthier Goats program--modeling lactation curves using a multilevel cubic spline regression model.

In 2001, the Norwegian Goat Health Service initiated the Healthier Goats program (HG), with the aim of eradicating caprine arthritis encephalitis, caseous lymphadenitis, and Johne's disease (caprine paratuberculosis) in Norwegian goat herds. The aim of the present study was to explore how control and eradication of the above-mentioned diseases by enrolling in HG affected milk yield by comparison with herds not enrolled in HG. Lactation curves were modeled using a multilevel cubic spline regression model where farm, goat, and lactation were included as random effect parameters. The data material contained 135,446 registrations of daily milk yield from 28,829 lactations in 43 herds. The multilevel cubic spline regression model was applied to 4 categories of data: enrolled early, control early, enrolled late, and control late. For enrolled herds, the early and late notations refer to the situation before and after enrolling in HG; for nonenrolled herds (controls), they refer to development over time, independent of HG. Total milk yield increased in the enrolled herds after eradication: the total milk yields in the fourth lactation were 634.2 and 873.3 kg in enrolled early and enrolled late herds, respectively, and 613.2 and 701.4 kg in the control early and control late herds, respectively. Day of peak yield differed between enrolled and control herds. The day of peak yield came on d 6 of lactation for the control early category for parities 2, 3, and 4, indicating an inability of the goats to further increase their milk yield from the initial level. For enrolled herds, on the other hand, peak yield came between d 49 and 56, indicating a gradual increase in milk yield after kidding. Our results indicate that enrollment in the HG disease eradication program improved the milk yield of dairy goats considerably, and that the multilevel cubic spline regression was a suitable model for exploring effects of disease control and eradication on milk yield.

The impact of contracts on outsourcing computed tomography examinations from a Swedish public university hospital to a private radiology unit.

INTRODUCTION: After years of outsourcing without detailed contracts from one of Sweden's largest university hospitals to external radiology units, the hospital started to use a specific contract for outsourcing computed tomography (CT) examinations. The purpose of this study was to compare the cost-effectiveness of two outsourcing approaches, where examinations were performed either with a detailed, specific contract (with-contract) or without (no-contract), between a hospital radiology department and private external units. METHODS: This retrospective study included a group of electively outsourced CT-examinations (n = 132) and a control group of in-house CT-examinations (n = 132), selected from the three different types of CT-examinations referred from the Departments of Oncology and Hematology. These examinations were randomly selected from four different groups over two time periods of one year each, one being outsourcing without a contract (no-contract, during 2013), one time period with a specific contract (with-contract, during 2014) and two control groups of examinations performed in-house within both these time periods. We compared outsourced examinations (both no-contract and with-contract groups) and in-house examinations. The comparison of these groups include five parameters; management-time, patient waiting-time, the quality of the examinations, - image interpretations and costs. RESULTS: During 2013, management-time for CT-examinations was longer in the outsourced group (no-contract) than in the in-house group, with a statistical significance (P = 0.002). Fewer examinations performed in-house and in the with-contract group needed re-interpretation than in the no-contract group. CT-examinations in the with-contract group were associated with shorter overall management-time, patient waiting time and lower costs compared to the no-contract group. CONCLUSION: Using a contract with detailed specifications for outsourcing CT-examinations may be an effective way of reducing patient waiting time. Outsourcing based on a well-founded contract can be cost-effective, compared with outsourcing without a detailed plan for the services required.

Effects of subclinical footpad dermatitis and emotional arousal on surface foot temperature recorded with infrared thermography in turkey toms (Meleagris gallopavo).

Footpad dermatitis is a condition that causes lesions on the plantar surface of the footpads in growing turkeys. Potential inflammatory processes and pain associated with increasing severity of footpad dermatitis raise animal welfare concerns. This study investigated whether the temperature of the plantar surface of the foot (the footpads and the entire plantar foot including interdigital membranes) assessed with infrared thermography reflects severity of mild footpad dermatitis as assessed with a Visual Analogue Scale in 80 turkey toms at 10 weeks of age. In order to study effects of a potential emotional arousal due to the testing procedures, effects of sequential testing order and duration of handling of the turkeys was included in the model. Footpad temperatures were significantly lower than foot temperatures (P < 0.001, R2 = 0.57, -3.36°C ± 0.28°C), and higher visual analogue scale scores were anti-correlated with footpad (-0.06°C ± 0.037°C) and foot temperatures (-0.07°C ± 0.066°C). Furthermore, a negative association between footpad temperature and handling time (-0.02 ± 0.0227, P = 0.048), and a non-linear association between foot and footpad temperatures and sequential testing order, were found (P<0.001). The results indicate that severity of mild footpad dermatitis as scored visually was associated with the temperatures of the plantar surface of the foot and footpads, and that thermal imaging therefore represents a novel tool for the reliable and non-invasive early detection of subclinical foot pathologies in turkeys. The association was negative, and the findings therefore indicate that potential inflammatory processes in the epidermis at this early stage of footpad dermatitis are negligible, and/or that the hyperkeratosis of the surface keratin shielded heat emission from the footpads. The associations between surface temperatures, handling time, and sequential testing order suggest an emotional arousal in response to the experimental procedures, and these factors need to be considered when applying infrared thermography in future studies of leg health in turkeys.

Bioinspired coupled helical coils for soft tissue engineering of tubular structures - Improved mechanical behavior of tubular collagen type I templates.

The design of constructs for tubular tissue engineering is challenging. Most biomaterials need to be reinforced with supporting structures such as knittings, meshes or electrospun material to comply with the mechanical demands of native tissues. In this study, coupled helical coils (CHCs) were manufactured to mimic collagen fiber orientation as found in nature. Monofilaments of different commercially available biodegradable polymers were wound and subsequently fused, resulting in right-handed and left-handed polymer helices fused together in joints where the filaments cross. CHCs of different polymer composition were tested to determine the tensile strength, strain recovery, hysteresis, compressive strength and degradation of CHCs of different composition. Subsequently, seamless and stable hybrid constructs consisting of PDSII® USP 2-0 CHCs embedded in porous collagen type I were produced. Compared to collagen alone, this hybrid showed superior strain recovery (93.5±0.9% vs 71.1±12.6% in longitudinal direction; 87.1±6.6% vs 57.2±4.6% in circumferential direction) and hysteresis (18.9±2.7% vs 51.1±12.0% in longitudinal direction; 11.5±4.6% vs 46.3±6.3% in circumferential direction). Furthermore, this hybrid construct showed an improved Young's modulus in both longitudinal (0.5±0.1MPavs 0.2±0.1MPa; 2.5-fold) and circumferential (1.65±0.07MPavs (2.9±0.3)×10-2MPa; 57-fold) direction, respectively, compared to templates created from collagen alone. Moreover, hybrid template characteristics could be modified by changing the CHC composition and CHCs were produced showing a mechanical behavior similar to the native ureter. CHC-enforced templates, which are easily tunable to meet different demands may be promising for tubular tissue engineering. STATEMENT OF SIGNIFICANCE: Most tubular constructs lack sufficient strength and tunability to comply with the mechanical demands of native tissues. Therefore, we embedded coupled helical coils (CHCs) produced from biodegradable polymers - to mimic collagen fiber orientation as found in nature - in collagen type I sponges. We show that the mechanical behavior of CHCs is very similar to native tissue and strengths structurally weak tubular constructs. The production procedure is relatively easy, reproducible and mechanical features can be controlled to meet different mechanical demands. This is promising in template manufacture, hence offering new opportunities in tissue engineering of tubular organs and preventing graft failure.

Prediction of gestational age based on genome-wide differentially methylated regions.

BACKGROUND: We explored the association between gestational age and cord blood DNA methylation at birth and whether DNA methylation could be effective in predicting gestational age due to limitations with the presently used methods. We used data from the Norwegian Mother and Child Birth Cohort study (MoBa) with Illumina HumanMethylation450 data measured for 1753 newborns in two batches: MoBa 1, n = 1068; and MoBa 2, n = 685. Gestational age was computed using both ultrasound and the last menstrual period. We evaluated associations between DNA methylation and gestational age and developed a statistical model for predicting gestational age using MoBa 1 for training and MoBa 2 for predictions. The prediction model was additionally used to compare ultrasound and last menstrual period-based gestational age predictions. Furthermore, both CpGs and associated genes detected in the training models were compared to those detected in a published prediction model for chronological age. RESULTS: There were 5474 CpGs associated with ultrasound gestational age after adjustment for a set of covariates, including estimated cell type proportions, and Bonferroni-correction for multiple testing. Our model predicted ultrasound gestational age more accurately than it predicted last menstrual period gestational age. CONCLUSIONS: DNA methylation at birth appears to be a good predictor of gestational age. Ultrasound gestational age is more strongly associated with methylation than last menstrual period gestational age. The CpGs linked with our gestational age prediction model, and their associated genes, differed substantially from the corresponding CpGs and genes associated with a chronological age prediction model.

25-Hydroxyvitamin D in pregnancy and genome wide cord blood DNA methylation in two pregnancy cohorts (MoBa and ALSPAC).

The aim of the study was to investigate whether maternal mid-pregnancy 25-hydroxyvitamin D concentrations are associated with cord blood DNA methylation. DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip, and maternal plasma 25-hydroxyvitamin D was measured in 819 mothers/newborn pairs participating in the Norwegian Mother and Child Cohort (MoBa) and 597 mothers/newborn pairs participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Across 473,731CpG DNA methylation sites in cord blood DNA, none were strongly associated with maternal 25-hydroxyvitamin D after adjusting for multiple tests (false discovery rate (FDR)>0.5; 473,731 tests). A meta-analysis of the results from both cohorts, using the Fisher method for combining p-values, also did not strengthen findings (FDR>0.2). Further exploration of a set of CpG sites in the proximity of four a priori defined candidate genes (CYP24A1, CYP27B1, CYP27A1 and CYP2R1) did not result in any associations with FDR<0.05 (56 tests). In this large genome wide assessment of the potential influence of maternal vitamin D status on DNA methylation, we did not find any convincing associations in 1416 newborns. If true associations do exist, their identification might require much larger consortium studies, expanded genomic coverage, investigation of alternative cell types or measurements of 25-hydroxyvitamin D at different gestational time points.

Development and maintenance of guideline-based decision support for pharmacological treatment of hypertension.

The objective was to build a computer-based decision support system (DSS), which could apply the formal rules embedded in guidelines regarding pharmacological treatment of hypertension. The aim was also to test VISUAL BASIC as a development tool for DSS's in health care. From the Swedish guidelines for treatment of hypertension, the most widely accepted and scientifically best proved treatment strategies were chosen and implemented as rules. A DSS that is capable of applying the evidence-based rules extracted from guidelines regarding drug treatment of hypertension, to any patient's medical profile, was constructed. The output consists of a recommendation regarding preferred generic drug class and also a written report, reflecting decision steps provided by the rule-base and inference engine. We also provide methods for formalising an implementable language of guidelines. A mainstream programming language like VISUAL BASIC can be an alternative when building complicated decision support systems. A logic formal notation can facilitate communication between the expert and the programmer. The program is a stand-alone product independent of computerized medical records and thereby easy to install and maintain.

Genome comparison of bacterial pathogens.

Bacterial pathogens are being sequenced at an increasing rate. To many microbiologists, it appears that there simply is not enough time to digest all the information suddenly available. In this chapter we present several tools for comparison of sequenced pathogenic genomes, and discuss differences between pathogens and non-pathogens. The presented tools allow comparison of large numbers of genomes in a hypothesis-driven manner. Visualization of the results is very important for clear presentation of the results and various ways of graphical representation are introduced.

The genus burkholderia: analysis of 56 genomic sequences.

The genus Burkholderia consists of a number of very diverse species, both in terms of lifestyle (which varies from category B pathogens to apathogenic soil bacteria and plant colonizers) and their genetic contents. We have used 56 publicly available genomes to explore the genomic diversity within this genus, including genome sequences that are not completely finished, but are available from the NCBI database. Defining the pan- and core genomes of species results in insights in the conserved and variable fraction of genomes, and can verify (or question) historic, taxonomic groupings. We find only several hundred genes that are conserved across all Burkholderia genomes, whilst there are more than 40,000 gene families in the Burkholderia pan-genome. A BLAST matrix visualizes the fraction of conserved genes in pairwise comparisons. A BLAST atlas shows which genes are actually conserved in a number of genomes, located and visualized with reference to a chosen genome. Genomic islands are common in many Burkholderia genomes, and most of these can be readily visualized by DNA structural properties of the chromosome. Trees that are based on relatedness of gene family content yield different results depending on what genes are analyzed. Some of the differences can be explained by errors in incomplete genome sequences, but, as our data illustrate, the outcome of phylogenetic trees depends on the type of genes that are analyzed.

Genetic variability of Campylobacter jejuni isolated from fresh and frozen broiler carcasses.

AIMS: The aim of this study was to determine the genetic variability of Campylobacter jejuni isolates from poultry before and after freezing treatment in order to identify genotypes that would survive the treatment. METHODS AND RESULTS: C. jejuni was isolated from both fresh and frozen halves of the same carcass after freezing for 2 or more than 20 days at -20 degrees C. From 36 carcasses, representing five unrelated flocks in Norway, a total of 209 isolates were included in the study. Thirty-two of the isolates were recovered with a qualitative method while the remaining 177 were isolated using a quantitative method. Isolates were genotyped with fluorescent amplified fragment length polymorphism using MfeI and BglII restriction enzymes. Nine different genotypes were identified, however, one genotype was shown to be dominant in three different flocks. This genotype and the dominant genotype of another flock were found among isolates from fresh and frozen broiler halves. They were also shown to be identical to genotypes frequently identified among strains isolated from humans, cattle and poultry flocks in previous years. CONCLUSIONS: Freezing treatment or isolation method appeared not to select for a particular genotype. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of the present study indicate that the freezing tolerance of strains is not genotype dependent.

Evaluation of a computer-based decision support system for treatment of hypertension with drugs: retrospective, nonintervention testing of cost and guideline adherence.

OBJECTIVE: To evaluate a computerized decision support system (DSS) for drug treatment of hypertension, regarding quality, safety, and cost compared to actual antihypertensive drug treatment. DESIGN: The medical profiles of 338 hypertensive patients treated with drugs against hypertension were processed by the DSS. The drug treatment proposed by the system was then compared to actual treatment given by their physician. SETTING: Four health centres in the county of Västerbotten, in Sweden. SUBJECTS: A list of hypertensive patients was extracted from the computerized medical records of each health centre and every fifth patient's medical profile was assessed by the system. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Drug used, drug used in relation to certain major diseases such as diabetes mellitus, asthma, ischaemic heart disease (IHD), and previous myocardial infarction. Adherence to hypertension guidelines, safety, and cost. RESULTS: The DSS suggested significantly more thiazides and significantly fewer calcium antagonists than the physicians had prescribed, with a total cost reduction of 33-40%, depending on doses chosen. The DSS drug profile was more adherent to guidelines in patients with major complicating diseases, suggesting an improvement in treatment quality for these patients by the DSS. CONCLUSION: The DSS which fully implements current guidelines may improve the quality of antihypertensive treatment, concurrently leading to a considerable reduction in drug costs.