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Biomedical subjects

P Olson

Publications and source records attributed to P Olson.

At least 19 recordsLinked to original sources

Mortality of Swedish horses with complete life insurance between 1997 and 2000: variations with sex, age, breed and diagnosis.

The aim of this study was to evaluate the potential usefulness of the database maintained by the Swedish insurance company Agria for providing mortality statistics on Swedish horses. Mortality statistics (incidence rates and survival) were calculated, both crudely and stratified by sex, age, breed, breed group and diagnosis, for the horses with complete life insurance, which covers most health problems. The total mortality was 415 (95 per cent confidence interval [CI] 399 to 432) deaths per 10,000 horse-years at risk, and the diagnostic mortality, including only deaths with an assigned diagnosis, was 370 (95 per cent CI 355 to 386) deaths per 10,000 horse-years at risk. The diagnostic mortality of geldings was 459 (95 per cent CI 431 to 487), of mares 345 (95 per cent CI 322 to 365) and of stallions 214 (95 per cent CI 182 to 247) deaths per 10,000 horse-years at risk. The mortality rates increased with age and differed widely between breeds. Survival analysis showed that the median age at death of the horses enrolled before they were one year of age was 18.8 years. The most common cause of death or euthanasia was joint problems, which were responsible for 140 (95 per cent CI 130 to 149) deaths per 10,000 horse-years at risk. The results of multivariable models developed by using Poisson regression generally agreed well with the crude results.

Age Distribution↗

Specific causes of morbidity among Swedish horses insured for veterinary care between 1997 and 2000.

The principal aim of this study was to analyse the incidence of disease due to general and more specific causes among over 100,000 horses covered by complete insurance for veterinary care by a Swedish insurance company during 1997 to 2000. The database was used to calculate the rate of cause-specific morbidity in horses of different ages, sexes and breed groups kept in different regions with different human population densities. The joints were the most commonly affected part of the body, followed by unspecified/whole body, the skin and the digestive system. The most common specific diagnosis was fetlock arthritis, followed by lameness of undefined origin, other locomotor problems, traumatic injuries to the skin, arthritis in several joints, and colic. Geldings had the highest rate of at least one disease event in the joints, unspecified/whole body, skeletal or respiratory system, whereas in the other four major systems the difference between the sexes was marginal.

Age Distribution↗

Morbidity of Swedish horses insured for veterinary care between 1997 and 2000: variations with age, sex, breed and location.

The aim of this study was to evaluate the potential usefulness of the database maintained by the Swedish insurance company Agria for providing disease statistics on Swedish horses. The demography of the horses insured for veterinary care during the period 1997 to 2000 was recorded and the incidence of morbidity, defined as horses that required veterinary care that cost more than the policy excess, was calculated. Yearly incidences were calculated for horses that required veterinary care at least once, first overall, and then for horses with complete insurance, by sex, age, breed group, breed, location and human population density. Poisson regression was applied to a multivariable model to produce estimates of relative risk adjusted for other factors in the model, such as age. The total number of horse-years at risk for those with complete insurance was over 72,000 each year. The annual incidence rate for horses that required veterinary care at least once varied from 1080 to 1190 events per 10,000 horse-years at risk; for geldings the averaged incidence rate was 1398 events, for mares it was 1042 events, and for stallions it was 780 events per 10,000 horse-years at risk. There were considerable variations in incidence rate between breeds.

Age Distribution↗

Mortality in over 350,000 insured Swedish dogs from 1995-2000: I. Breed-, gender-, age- and cause-specific rates.

This study presents data on over 350,000 insured Swedish dogs up to 10 years of age contributing to over one million dog-years at risk (DYAR) during 1995-2000. A total of 43,172 dogs died or were euthanised and of these 72% had a claim with a diagnosis for the cause of death. The overall total mortality was 393 deaths per 10,000 DYAR. Mortality rates are calculated for the 10 most common breeds, 10 breeds with high mortality and a group including all other breeds, crudely and for general causes of death. Proportional mortality is presented for several classifications. Five general causes accounted for 62% of the deaths with a diagnosis (i.e. tumour (18%), trauma (17%), locomotor (13%), heart (8%) and neurological (6%)). Mortality rates for the five most common diagnoses within the general causes of death are presented. These detailed statistics on mortality can be used in breed-specific strategies as well as for general health promotion programs. Further details on survival and relative risk by breed and age are presented in the companion paper (Egenvall et al. 2005).

Age Factors↗

Mortality in over 350,000 insured Swedish dogs from 1995-2000: II. Breed-specific age and survival patterns and relative risk for causes of death.

This study continues analysis from a companion paper on over 350,000 insured Swedish dogs up to 10 years of age contributing to more than one million dog-years at risk during 1995-2000. The age patterns for total and diagnostic mortality and for general causes of death (trauma, tumour, locomotor, heart and neurological) are presented for numerous breeds. Survival estimates at five, eight and 10 years of age are calculated. Survival to 10 years of age was 75% or more in Labrador and golden retrievers, miniature and toy poodles and miniature dachshunds and lowest in Irish wolfhounds (91% dead by 10 years). Multivariable analysis was used to estimate the relative risk for general and more specific causes of death between breeds accounting for gender and age effects, including two-way interactions. Older females had tumour as a designated cause of death more often than males in most breeds, but not in the Bernese mountain dog. Information presented in this and the companion paper inform our understanding of the population level burden of disease, and support decision-making at the population and individual level about health promotion efforts and treatment and prognosis of disease events.

Age Factors↗

Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST).

Sclerosteosis is a progressive sclerosing bone dysplasia with an autosomal recessive mode of inheritance. Radiologically, it is characterized by a generalized hyperostosis and sclerosis leading to a markedly thickened and sclerotic skull, with mandible, ribs, clavicles and all long bones also being affected. Due to narrowing of the foramina of the cranial nerves, facial nerve palsy, hearing loss and atrophy of the optic nerves can occur. Sclerosteosis is clinically and radiologically very similar to van Buchem disease, mainly differentiated by hand malformations and a large stature in sclerosteosis patients. By linkage analysis in one extended van Buchem family and two consanguineous sclerosteosis families we previously mapped both disease genes to the same chromosomal 17q12-q21 region, supporting the hypothesis that both conditions are caused by mutations in the same gene. After reducing the disease critical region to approximately 1 Mb, we used the positional cloning strategy to identify the SOST gene, which is mutated in sclerosteosis patients. This new gene encodes a protein with a signal peptide for secretion and a cysteine-knot motif. Two nonsense mutations and one splice site mutation were identified in sclerosteosis patients, but no mutations were found in a fourth sclerosteosis patient nor in the patients from the van Buchem family. As the three disease-causing mutations lead to loss of function of the SOST protein resulting in the formation of massive amounts of normal bone throughout life, the physiological role of SOST is most likely the suppression of bone formation. Therefore, this gene might become an important tool in the development of therapeutic strategies for osteoporosis.

Adaptor Proteins, Signal Transducing↗

Sentinel lymph node biopsy after neoadjuvant chemotherapy for breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a developing alternative to axillary dissection and may prove to be accurate in the detection of micrometastases in lymph nodes of breast cancer patients. Limited studies exist in the use of SLNB after neoadjuvant therapy. This study was undertaken to determine the accuracy of SLNB after neoadjuvant chemotherapy. METHODS: Thirty-one patients with stage I or II breast cancer underwent SLNB after neoadjuvant chemotherapy. RESULTS: Lymphatic mapping was performed by radioisotope, blue dye, or both techniques. Sentinel nodes (SN) were identified in 29 patients (93.5%). The SN was positive in 11 patients (38.0%), and was the only positive node in 5 patients (45.5%). There were no false negative SN by hematoxyin and eosin stain or immunohistochemistry (IHC) studies. CONCLUSIONS: Sentinel node identification rate is similar to that in nonneoadjuvant studies. The sentinel node accurately predicted metastatic disease in the axilla. IHC studies failed to detect any additional micrometastases. This diagnostic technique may provide treatment guidance for patients after neoadjuvant therapy.

Axilla↗

Age pattern of mortality in eight breeds of insured dogs in Sweden.

The objective of this study was to use several methods to describe the age patterns for risk of death in selected breeds of dogs insured for life in a Swedish animal-insurance company in 1996. Data on eight breeds were analyzed for age at death (including euthanasia). If dogs left the insurance for reasons other than death, they were regarded as censored. Dogs were only insured up to 10 years of age. Four analytical approaches were used. First, descriptive statistics of age distributions (e.g. breed-specific median ages at death, breed- and age-specific mortality risks) were computed. Second, age-specific estimates of survival were calculated using the formula: survival=(1-risk(age<1 year))(1-risk(age 1<2 year))... (1-risk(age 9<1 0 year)). Third, Cox regression (proportional-hazards model) was used to estimate survival and hazard functions. Finally, hierarchically coded Poisson regression was used to determine age-specific cut-points in the risk of death. The hazards from Cox and the incidence-density rates from the hierarchically coded models were transformed to estimates of risk: risk=1-exp¿-(hazard)¿ or 1-exp¿-(incidence-density rate)¿. The breeds studied were Beagle, Bernese mountain dog, Boxer, Cavalier King Charles spaniel, Drever, German shepherd dog, Mongrel and Poodle, together representing over 50000 dogs each year. The yearly breed-specific mortality risk varied between 1.7% (Poodle) and 6.5% (Bernese mountain dog). In all breeds, the risk of death increased with age but the pattern varied by breed. The probability of survival at 5 years of age varied between 94% (Cavalier King Charles spaniel and Poodle) and 83% (Bernese mountain dog, Drever, German shepherd dog) and the survival at 10 years between 83% (Poodle) and 30% (Bernese mountain dog). The survival estimates from Cox and those derived using the combined-risk formula were similar. The cut-point risk estimates provided a simplified picture of when the risk of death changed significantly compared to previous age categories. As anticipated, breeds differed widely in survival up to 10 years of age and there were marked differences in age patterns of mortality. The implications of these findings should be considered in multivariable analyses, where the confounding effect of age is often controlled for using a single age variable common to several breeds.

Age Distribution↗

Gender, age and breed pattern of diagnoses for veterinary care in insured dogs in Sweden during 1996.

More than 200,000 dogs insured for veterinary care by one Swedish company at the beginning of 1996 were included in a retrospective cross-sectional study. Data from receipts for visits to veterinarians that were part of reimbursed veterinary care events, whose cost exceeded the deductible cost, were used to calculate the risk of cause-specific morbidity, both in total and stratified by gender, age and breed. Diagnoses were described by organic system, for example, cardiovascular, and by disease process, for example, neoplastic The most commonly affected system was the integument followed by the gastrointestinal and genital systems. The genital system was the most commonly affected system in females, within which 50 per cent of the affected bitches had pyometra. Inflammatory processes were most common, followed by symptomatic conditions, traumatic injuries and neoplastic conditions.

Age Factors↗

Gender, age, breed and distribution of morbidity and mortality in insured dogs in Sweden during 1995 and 1996.

More than 200,000 dogs insured by one Swedish company at the beginning of either 1995 or 1996 were included in a retrospective, cross-sectional study. They could be covered for veterinary care at any age, but were eligible for life insurance only up to 10 years of age. Accessions for veterinary care that exceeded the deductible cost were used to calculate the risk of morbidity. The morbidity and mortality data have been stratified by gender, age, breed, location and human population density. In each year, 13 per cent of the dogs experienced at least one veterinary care event and the mortality risk was 3.0 per cent. The risk of morbidity varied with age, gender, breed, and location. The risk of mortality increased principally with age. It was possible to derive population-based risks of morbidity and mortality from these insurance data.

Age Distribution↗

A Laboratory Model for Convection in Earth's Core Driven by a Thermally Heterogeneous Mantle.

Thermal convection experiments in a rapidly rotating hemispherical shell suggest a model in which the convection in Earth's liquid outer core is controlled by a thermally heterogeneous mantle. Experiments show that heterogeneous boundary heating induces an eastward flow in the core, which, at a sufficiently large magnitude, develops into a large-scale spiral with a sharp front. The front separates the warm and cold regions in the core and includes a narrow jet flowing from the core-mantle boundary to the inner-core boundary. The existence of this front in the core may explain the Pacific quiet zone in the secular variation of the geomagnetic field and the longitudinally heterogeneous structure of the solid inner core.

Journal Article↗

A cytosine analog that confers enhanced potency to antisense oligonucleotides.

Antisense technology is based on the ability to design potent, sequence-specific inhibitors. The G-clamp heterocycle modification, a cytosine analog that clamps on to guanine by forming an additional hydrogen bond, was rationally designed to enhance oligonucleotide/RNA hybrid affinity. A single, context-dependent substitution of a G-clamp heterocycle into a 15-mer phosphorothioate oligodeoxynucleotide (S-ON) targeting the cyclin-dependent kinase inhibitor, p27(kip1), enhanced antisense activity as compared with a previously optimized C5-propynyl-modified p27(kip1) S-ON and functionally replaced 11 C5-propynyl modifications. Dose-dependent, sequence-specific antisense inhibition was observed at nanomolar concentrations of the G-clamp S-ONs. A single nucleotide mismatch between the G-clamp S-ON and the p27(kip1) mRNA reduced the potency of the antisense ON by five-fold. A 2-base-mismatch S-ON eliminated antisense activity, confirming the sequence specificity of G-clamp-modified S-ONs. The G-clamp-substituted p27(kip1) S-ON activated RNase H-mediated cleavage and demonstrated increased in vitro binding affinity for its RNA target compared with conventional 15-mer S-ONs. Furthermore, incorporation of a single G-clamp modification into a previously optimized 20-mer phosphorothioate antisense S-ON targeting c-raf increased the potency of the S-ON 25-fold. The G-clamp heterocycle is a potent, mismatch-sensitive, automated synthesizer-compatible antisense S-ON modification that will have important applications in the elucidation of gene function, the validation of gene targets, and the development of more potent antisense-based pharmaceuticals.

Animals↗

Long-term follow-up post-cryosurgery in a sheep breast model.

This study constitutes the advanced stage of an ongoing project for the development of cryosurgical devices and techniques for breast cryosurgery. The current study focuses on the long-term follow-up post-cryosurgery in a sheep breast model. Results of this study indicate that the cryotreatment site in a sheep breast model cannot be identified up to 5 months post-cryosurgery by means of ultrasound, mammography, or MRI. Histology findings of this study further indicate that there is no gross or microscopic difference between lesions that have been subject to one versus three freeze/thaw cycles. Under either cryosurgical protocol, there is a main cryoinjured region that has uniform destruction of epithelium and healing scar formation and a transition zone of damaged lobules without acini, surrounded by healthy tissues. The cryoinjured region at 5 months post-cryosurgery was found to be about half the diameter of the ultrasound-imaged frozen region during the cryoprocedure. This study shows that, in terms of recovery and regeneration, surgical excision appears to have an advantage over cryosurgery, which results in a more rapid healing process. Based on observations that the cryoinjured region is no smaller than the ultrasound-imaged ice-ball and that the typical thickness of the transition zone is up to 5 mm, a conservative use of the cryosurgical device developed for the current study in an ultrasound-monitored cryoprocedure requires at least 5 mm safety margins of the frozen region radius around the target region.

Animals↗

Capture of a recombination activating sequence from mammalian cells.

We have developed a genetic trap for identifying sequences that promote homologous DNA recombination. The trap employs a retroviral vector that normally disables itself after one round of replication. Insertion of defined DNA sequences into the vector induced the repair of a 300 base pair deletion, which restored its ability to replicate. Tests of random sequence libraries made in the vector revealed a putative recombination signal (CCCACCC). When this heptamer or an abbreviated form (CCCACC) were reinserted into the vector, they stimulated vector repair and other DNA rearrangements. Mutant forms of these oligomers (eg CCCAACC or CCWACWS) did not. Our data suggest that the recombination events occurred within 48 h after transfection.

Animals↗

Survey of the Swedish dog population: age, gender, breed, location and enrollment in animal insurance.

A sample of the Swedish population was surveyed by interviewing households by telephone. The number interviewed was 11,762, of which 15.5% owned dogs, and of these, 77.9% had one dog. The estimated total population of dogs in Sweden was just over 800,000. Dog-owning was more common in more rural areas compared to larger cities. The numbers of male and female dogs were similar and few dogs were neutered. Mean age was 5.7 years with median 5 years. Mongrels comprised 13.3% and the most common breed was the dachshund (7.4%). Of dogs with information on insurance status, 68.4% of the dogs were insured for veterinary care and 58.3% were life insured.

Age Factors↗

Validation of computerized Swedish dog and cat insurance data against veterinary practice records.

Large computerized medical databases offer great potential for epidemiological research. However, data-quality issues must be addressed. This study evaluated the agreement between veterinary practice records and computerized insurance data in a large Swedish claims database. For the year 1995, the company insured over 320,000 dogs and cats. A total of 470 hard-copy records were sampled from claims for health care (n = 236) and life insurance (n = 234). Computerized insurance data for these claims were accessed and records from the attending veterinary practices were collected. For health and life claims, respectively, 79.2 and 72.8% of practice records were retrieved. Variables compared between the computer and practice records were breed, sex, date of birth and diagnosis for the claim. The degree of agreement was categorized as agreement, minor disagreement, major disagreement or data missing. Multivariable logistic regression was used to examine factors associated with errors. The observed agreement for breed and sex was excellent. There was 28.9 and 33.8% minor disagreement for the date of birth for health and life claims, respectively. This was mainly because, prior to 1993, the date of birth was coded as the first of January when more complete information was unavailable. Major disagreement (different year of birth) was low for both health and life claims. For health and life claims, the observed agreement for diagnosis was 84.0 and 84.9%, minor disagreement was 6.4 and 4.3%, and major disagreement 5.9 and 9.4%, respectively. Although there was no difference based on size of the veterinary clinic involved, there was a tendency for better agreement between the practice record and the computerized insurance data for claims from clinics with computerized practice records (n = 40) than for clinics with manual practice records (n = 286). Rates of discrepancy were affected by the clerk who processed the claims. Records processed by two of the 21 clerks had significantly more disagreements. Given the nature of the data, it was only possible to calculate a measure of observed agreement. In general, the agreement between data in the insurance-company database and from the practice records was excellent for demographic data such as breed and sex and fair for diagnostic information and date of birth. In general, the data are adequate to support ongoing research with due considerations of certain limitations.

Animals↗

High-level expression of eukaryotic polypeptides from bacterial chromosomes.

Attractive economics and short development timelines have often been cited as reasons for using bacteria to express eukaryotic proteins on a commercial scale. Nevertheless, routine techniques for bacterial expression of heterologous proteins are beset by a variety of technical and legal difficulties. In particular, the use of plasmids to express foreign proteins, popular promoter systems, protein fusion partners, and histidine tags and the recovery of proteins from inclusion bodies are affected by a host of issued patents. Chromosomally encoded leaderless fusions (CELF) offer a variety of technical and legal advantages over existing bacterial expression systems. In this study, we show that CELF can be used to produce a wide assortment of eukaryotic proteins at 10-liter fermentation scale.

Bacteriophage T7↗

Mortality in insured Swedish dogs: rates and causes of death in various breeds.

Data on over 222,000 Swedish dogs enrolled in life insurance in 1992 and 1993 were analysed. There were approximately 260 deaths per 10,000 dog-years at risk. Breed-specific mortality rates and causes of death are presented for breeds with more than 500 dogs at risk that had consistently high or low rates. Breed-specific mortality ranged from less than 1 per cent to more than 11 per cent. True rates and proportional statistics for the cause of death were calculated for the entire insured population (250 breeds) and cause-specific mortality rates were calculated for the breeds with the highest risk of dying of the most common causes. Trauma, tumours and problems related to the locomotor system together accounted for more than 40 per cent of all deaths or euthanasias. Although limited to insured dogs, these data cover approximately one-third of all Swedish dogs and provide baseline mortality data for further population-based studies on health and disease.

Animals↗