Using a chain of models to predict health and environmental impacts in Norway from a hypothetical nuclear accident at the Sellafield site.

When a nuclear accident occurs, decision makers in the affected country/countries would need to act promptly to protect people, the environment and societal interests from harmful impacts of radioactive fallout. The decisions are usually based on a combination of model prognoses, measurements, and expert judgements within in an emergency decision support system (DSS). Large scale nuclear accidents would need predictive models for the atmospheric, terrestrial, freshwater, and marine ecosystems, for the connections between these in terms of radionuclide fluxes, and for the various exposure pathways to both humans and biota. Our study showed that eight different models and DSS modules could be linked to assess the total human and environmental consequences in Norway from a hypothetical nuclear accident, here chosen to be the Sellafield nuclear reprocessing plant. Activity concentrations and dose rates from 137Cs for both humans and the environment via various exposure routes were successfully modelled. The study showed that a release of 1% of the total inventory of 137Cs in the Highly Active Liquor Tanks at Sellafield Ltd is predicted to severely impact humans and the environment in Norway if strong winds are blowing towards the country at the time of an accidental atmospheric release. Furthermore, since the models did not have built-in uncertainty ranges when this Sellafield study was performed, investigations were conducted to identify the key factors contributing to uncertainty in various models and prioritise the ones to focus on in future research.

The influence of unilateral oophorectomy on the age of menopause.

OBJECTIVE: To determine the age of menopause after premenopausal unilateral oophorectomy (UO) and to establish whether UO at a young age leads to menopause at a younger age than if UO occurs at an older age. METHODS: A cohort of 28 731 women, of whom 17 781 (62%) were menopausal, was investigated. Information on menopause was obtained from self-reported questionnaires. Surgical data were obtained from the National Patient Register to avoid recollection bias. Age of menopause after UO/not UO was determined using Kaplan-Meier curves. Cox regression was used to identify factors of importance for early menopause. RESULTS: UO was performed in 1148 women. Women with UO after the age of 45 years, premenopausal hysterectomy, bilateral oophorectomy and cancer were excluded, leaving 236 in the analysis. Menopause occurred 1.8 years earlier after UO compared to women with two intact ovaries (mean 49.5 vs. 51.3 years), and younger age at UO was significantly linearly correlated to younger age at menopause. UO (hazard ratio 1.23) and smoking (hazard ratio 1.12) significantly decreased the age of menopause. CONCLUSIONS: Premenopausal unilateral oophorectomy significantly reduces the age of menopause by 1.8 years. Younger age at UO leads to significantly younger age at menopause.

Chronic non-cancer pain and the epidemic prescription of opioids in the Danish population: trends from 2000 to 2013.

BACKGROUND: Chronic pain has serious consequences for individuals and society. In addition, opioid prescription for chronic non-cancer pain (CNCP) has become more frequent. This study aims to examine the trends regarding the prevalence of CNCP, dispensed opioids, and concurrent use of benzodiazepine (BZD)/BZD-related drugs in the Danish population. METHODS: Data from the cross-sectional national representative Danish Health and Morbidity Surveys (2000, 2005, 2010, and 2013) were combined with The Danish National Prescription Registry at an individual level. The study populations varied between 5000 and 13,000 individuals ≥16 years (response rates: 51-63%). Respondents completed a self-administered questionnaire, which included the analyzed items on identification of chronic pain (≥6 months). RESULTS: From 2000 to 2013, the prevalence of CNCP increased and subsequently the annual prevalence of opioid use from 4.1% to 5.7% among CNCP individuals. Higher CNCP prevalence was related to female gender, no cohabitation partner, short education, non-Western origin, and overweight/obesity. In addition, women with CNCP, especially >65 years, became more frequent users of opioids and used higher doses than men. Concurrent use of BZD/BZD-related drugs decreased (13%) from 2010 to 2013, still one-third of long-term opioid user were co-medicated with these drugs. CONCLUSIONS: The use of opioids has increased in Denmark, especially among elderly women. The concurrent use of BZD/BZD-related drugs has decreased from 2010 to 2013, but still one-third of long-term opioid users were co-medicated.

[Fatal ecstasy intoxication]. / Letalt forløbende ecstasyforgiftning.

A case of full-blown, lethal MDMA intoxication, owing to abuse of ecstasy is described. The increasing popularity of ecstasy among young, otherwise healthy, people prompts health care providers to recognise better the symptoms of systemic intoxication in order to initiate early treatment, such as rehydration, cooling in cases of hyperthermia, seizure treatment, correction of cardiac arrhythmia, and metabolic and electrolyte abnormalities.

Cost consciousness among anaesthetic staff.

BACKGROUND: Anaesthetists, like all other specialists, need to be aware of the costs of drugs, fluids and disposables commonly used in their clinical practice so that excessive costs and waste can be minimized without compromising patient care or safety. The present study describes cost consciousness among 120 anaesthetic staff members in two Danish anaesthetic departments. METHOD: A prospective study questioning 120 anaesthetic staff members (69 anaesthetic nurses, 35 senior anaesthetists and 16 junior anaesthetists) about the costs of 29 drugs, fluids and disposable used in routine anaesthetic practice. RESULTS: After the study period 107 questionnaires (90%) were available for analysis. Thirty-eight percent of all estimated costs were within 50% of the actual costs and 85% were within 100%. The costs of relatively expensive items such as isoflurane, enflurane, sevoflurane and hydroxyethyl starch were consistently underestimated, whereas cheaper items such as narcotic drugs, endotracheal tubes, intravenous tubing, plastic syringes and Quincke spinal needle were consistently overestimated. In general, the anaesthetic staff overestimated the costs by 69% (range -24% to 270%). The anaesthetic nursing group overestimated the costs by 49% (range -24% to 270%), junior anaesthetists by 94% (range 25% to 226%) and senior anaesthetists by 72% (range -14% to 135%). CONCLUSION: This study shows that the overall consciousness of the costs of anaesthetic drugs, fluids and disposables has to be improved in order to permit the staff to optimize resources.

[Fiber optic tracheoscopy in percutaneous dilation tracheostomy]. / Fiberoptisk trakeoskopi ved perkutan dilatationstrakeostomi.

Percutaneous dilatational tracheostomy (PDT) was performed on a 64 year-old female multitraumatised patient. Because of difficulties during the procedure, fiberoptic tracheoscopy was carried out and revealed perforation and dilatation of the endotracheal tube. The error was corrected with little loss of time, and no complications were observed after finishing the procedure. We recommend the use of routine fiberoptic tracheoscopy during and after percutaneous dilatational tracheostomy as suggested by Ciaglia et al (2).

Effects of nonverbal behavior on perceptions of power bases.

Among a sample of U.S. students, the effects of 3 forms of nonverbal behavior (facial expression, visual behavior, and body posture) on perceptions of power bases (reward, coercive, legitimate, referent, expert, and credibility) were investigated. In contrast to previous investigations of nonverbal behavior and power, a precise construct definition and reliable and valid operational definitions of power were used, and specific perceptions of power bases were examined. A relaxed facial expression, compared with a nervous facial expression, increased the ratings for referent, reward, legitimate, expert, and credibility power bases. Also, direct eye contact yielded higher credibility ratings than indirect eye contact.

Semen analysis performed by different laboratory teams: an intervariation study.

Some recent studies have indicated that sperm concentration has decreased during the last 50 years. However, comparisons between laboratories have revealed that geographical differences seem to exist and that any decrease may not be global. One point of criticism concerning comparison of results from different laboratories has been that some of the discrepancies detected could reflect the lack of standardized methods used in the different laboratories. Four teams, each consisting of one physician and one technician from groups which have recently published data on semen quality, met in order to evaluate the variability between their laboratories on semen analysis. Twenty-six fresh semen samples from unselected men were analysed. The groups analysed the samples according to the normal practice in their laboratories, using their own equipment. The variation between laboratories was estimated through a random effects model. For sperm concentration and semen volume assessment a remarkable consistency between laboratories was detected, in contrast to the very considerable inter-individual variation. For sperm motility and morphology assessments interlaboratory consistency was much poorer. In conclusion, evaluation of sperm motility and morphology characteristics requires further standardization in order to achieve comparable data from different laboratories. However, semen volume and sperm concentration are characteristics which can be compared reliably between laboratories, when similar methodologies are used.

Gamma delta T cells are secondary participants in acute graft-versus-host reactions initiated by CD4+ alpha beta T cells.

To examine the role of T cell subpopulations in an acute graft-versus-host (GVH) reaction, gamma delta T cells and alpha beta T cells expressing one of the two prototypic V beta families were negatively isolated from adult blood samples and injected into allogeneic chick embryos. CD4+ alpha beta T cells expressing either V beta 1 or V beta 2 receptors were equally capable of inducing acute GVH reactions, consistent with the idea that alpha beta T cell alloreactivity is determined by CDR3 variability. By themselves, the gamma delta T cells were incapable of inducing GVH reactions. However, host gamma delta T cells were recruited into the donor alpha beta T cell-initiated lesions, where they were activated and induced to proliferate. The data suggest that gamma delta T cells may play a secondary role in GVH reactions.

Restriction fragment length polymorphism analysis of the chicken B-F and B-L genes and their association with serologically defined B haplotypes.

Seven serologically defined chicken haplotypes have been analysed by restriction fragment length polymorphism (RFLP) with chicken cDNA probes specific for MHC class I and II. The results demonstrate an excellent correlation between the observed RFLP banding patterns in the investigated haplotypes and the serological B-typing. In future, RFLP analysis in addition to serological B-typing may sharpen the tools in the search for recombinant chromosomes separating B-F and B-L.

MHC class II beta-chain expression in the rainbow trout.

A cDNA clone corresponding to the MHC class II beta-chain of the rainbow trout (Oncorhynchus mykiss) has been isolated and used in restriction fragment length polymorphism (RFLP) studies in a family of full siblings of rainbow trout. A very simple RFLP pattern was detected, suggesting segregation of a homozygote AA genotype and a heterozygote AB genotype. The MHC class II beta-chain of the rainbow trout seems to be transcribed in the same type of cells as class II genes of higher vertebrates even though the cDNA clone recognizes atypical messenger sizes of 2.2 kb and 3.6 kb in the analysed family. Surprisingly the transcripts seem to be allele-specific for the assigned genotypes.

Kinetics and mechanism of proteinase-binding of pregnancy zone protein (PZP). Appearance of sulfhydryl groups in reactions with proteinases.

Proteinase binding by pregnancy zone protein (PZP), an alpha-macroglobulin involves bait region cleavages, association of dimeric-PZP into tetrameric and reaction of internal gamma-glutamyl-beta-cysteinyl thiol esters of PZP with proteinase side chains. The product is an equimolar enzyme-PZP(tetramer) covalently linked complex with four free sulfhydryl groups. The kinetics of the appearances of sulfhydryl groups during the reaction of PZP with chymotrypsin has been investigated using stopped-flow and conventional mixing techniques over a broad concentration range. Thiol ester cleavages followed double exponential decays corresponding with two steps. The faster one resulted in the appearance of three sulfhydryl groups with an observed rate constant, k(obs) = k1.1 + k1.2 delta E, dependent on the excess concentration of chymotrypsin, delta E, and k1.1 = 0.03 s-1 and k1.2 = 4 x 10(4) M-1 s-1. The last sulfhydryl group appeared in a slower step, with similar concentration dependence and k2.1 approximately 0.003 s-1 and k2.2 approximately 5 x 10(3) M-1s-1. Covalent binding of the enzyme apparently was simultaneous with the faster thiol ester cleavage step. Based on these and previous results a model of the reaction mechanism of the proteinase binding reaction of PZP is proposed. It consists of four major steps: (i) Bait region cleavage of PZP-dimers by the enzyme, (ii) fast association of enzyme-PZP(dimer) species with native PZP or with another enzyme-PZP(dimer) compound resulting in release of one of the associated enzyme molecules (iii) reaction of an average of three thiol esters of the enzyme-PZP(tetramer) intermediate with the associated internal enzyme molecule or with an external one. In this step one enzyme molecule becomes covalently linked to the PZP-(tetramer), three sulfhydryl groups appear and the enzymic activity of the bound enzyme molecule decreases to the level of that of the final complex. (iv) Hydrolysis of the last thiol ester and in the presence of excess enzyme, degradation of enzyme-PZP(tetramer) complexes and formation of fragments some of which are the size of PZP(dimer) with enzyme bound.

Automated image-based cytometry with fluorescence-stained specimens.

The combination of digitized microscopy, algorithms for object recognition and fluorescent labeling is a promising approach for reliable, quick, automated and cost-effective screening of clinical specimens. We describe two conceptually different algorithms for detecting objects in fluorescence microscopic images. One, which is partially automated, compares a mask that represents a typical object with every position in the image; the other, which is fully automated, calculates threshold intensities to segment the image into regions of objects and background. Applications of the algorithms in conjunction with a prototype image-based cytometer are demonstrated for determining the DNA ploidy distribution of cultured human endometrial cells and determining the DNA ploidy distribution and the fraction of cells expressing the E6 antigen of human papilloma virus serotypes 16 and 18 in a PAP smear. The encouraging results from this study suggest that automated image-based cytometry utilizing fluorescent stains will be a valuable asset for clinical screening.

The "adjuvant effect" of the polymorphic B-G antigens of the chicken major histocompatibility complex analyzed using purified molecules incorporated in liposomes.

The polymorphic B-G region of the chicken major histocompatibility complex has previously been shown to mediate an "adjuvant effect" on the humoral response to other erythrocyte alloantigens. We demonstrate here that B-G molecules purified with monoclonal antibodies exert this adjuvant effect on the production of alloantibodies to chicken class I (B-F) molecules, when the two are in the same liposome. The adjuvant effect may in part be mediated by antibodies, since the antibody response to B-G molecules occurs much faster than the response to B-F molecules, and conditions in which antibodies to B-G are present increase the speed of the response to B-F molecules. We also found that the presence of B-G molecules in separate liposomes results in a lack of response to B-F molecules. In the light of this and other data, we consider the possible roles for the polymorphic B-G molecules, particularly for the generation of B cell diversity, in the immune systems of birds and other animals.

Increased angiogenesis in diabetes.

Rats with streptozotocin-induced diabetes mellitus showed a 3.4-4.5 times increased angiogenic response following mast-cell activation in situ as compared with age-matched normal controls. The test tissue used was the mesenteric window, which we have previously exploited as a quantitative angiogenesis assay. In the present study two independent techniques for quantifying the angiogenic response showed essentially the same result. The finding of a pathologically increased angiogenic reaction in the diabetic animals is noteworthy since some of the most harmful complications of diabetes in man relate to proliferative vascular lesions.

MHC-like molecules in some nonmammalian vertebrates can be detected by some cross-reactive xenoantisera.

Rabbit antisera raised to human and chicken MHC molecules were used to immunoprecipitate cross-reactive molecules from biosynthetically and cell surface-labeled spleen and/or blood cells of representative vertebrate species. Five major points emerged: 1) There were many nonspecific cross-reactions using these techniques, so various criteria were developed to distinguish these from true MHC-like molecules. 2) Only very small subpopulations of immunogen-specific antibodies cross-reacted with MHC-like molecules in other nonmammalian species. These subpopulations were different for each species and even within a species, sometimes being so limited as to behave like alloantisera. This led to a very scattered pattern of true cross-reactions that sometimes failed to reflect the properties of the bulk antibody population. 3) Antisera containing antibodies to class II beta- and class I alpha-chains cross-reacted better and more widely than those to B-G, class II alpha and, in general, beta 2-microglobulin. 4) Some cross-reactive antibodies were clearly directed to epitopes on the surface of the mature heterodimers, but many seemed to recognize nonlinear cryptic determinants, presumably in the contact regions between the chains. These latter antibodies recognized biosynthetic intermediates and also a variety of unusual cell surface MHC-like molecules present in reptile and amphibian, but absent in the mammal and chicken cells tested. These included E homodimers whose relationship to chicken B-G molecules is unknown. 5) MHC-like molecules were identified in a bird, three reptiles, and two amphibians, but no molecules with the expected properties were found with these reagents in any of the fish tested.