Trabecular Bone Score Improves Early After Successful Kidney Transplantation Irrespective of Antiresorptive Therapy and Changes in Bone Mineral Density.

Background: Trabecular bone score (TBS) is a new tool to assess trabecular bone microarchitecture based on standard dual-energy x-ray absorptiometry (DXA) of lumbar spine images. TBS may be important to assess bone quality and fracture susceptibility in kidney transplant recipients (KTRs). This study aimed to investigate the effect of different bone therapies on TBS in KTRs. Methods: We reanalyzed DXA scans to assess TBS in 121 de novo KTRs at baseline, 10 wk, and 1 y. This cohort, between 2007 and 2009, participated in a randomized, placebo-controlled trial evaluating the effect of ibandronate versus placebo in addition to vitamin D and calcium. Results: Although bone mineral density (BMD) Z scores showed a subtle decrease in the first weeks, TBS Z scores increased from baseline to 10 wk for both treatment groups, followed by a slight decline at 12 mo. When comparing treatment groups and adjusting for baseline TBS, there were no differences found in TBS at 12 mo (P = 0.419). Correlation between TBS and BMD at baseline was weak (Spearman's ρ = 0.234, P = 0.010), and change in TBS was not correlated with changes in lumbar spine BMD in either of the groups (ρ = 0.003, P = 0.973). Conclusions: Treatment with ibandronate or vitamin D and calcium did not affect bone quality as measured by TBS in de novo KTRs, but TBS increased early, irrespective of intervention. Changes in TBS and BMD during the study period were not correlated, indicating that these measurements reflect different aspects of bone integrity. TBS may complement BMD assessment in identifying KTRs with a high fracture risk.

Description of the prehospital emergency healthcare system in Norway.

Background: Norway has a long coastline, steep mountains, and wide fjords, which presents some challenges to the prehospital emergency healthcare system. In recent years, the prehospital emergency medical services (EMS) have undergone significant changes, structurally, in terms of professionalisation of the services and in the education level of the personnel. In this article, we aim to describe the current structure for handling prehospital medical emergencies. Methods: For healthcare, Norway is divided into four Regional Health Authorities, consisting of 19 Health Trusts, where 18 have an EMS. There is a dedicated medical emergency number, 113, that terminates in 16 emergency medical communication centres. The use of air and boat ambulances, in addition to traditional ambulances, seeks to meet the challenges in the EMS system. Strengths and limitations: The Norwegian EMS is an advanced system with highly educated staff; however, this level of care comes with an equally high cost. Conclusion: The Norwegian EMS can handle emergencies nationwide, providing advanced care at the scene and during transport. The geography and demography challenge the idea of equal care, but the open publishing of data from national quality registries seeks to identify and address potential differences.

Alkyl-phenanthrenes in early life stage fish: differential toxicity in Atlantic haddock (Melanogrammus aeglefinus) embryos.

Tricyclic polycyclic aromatic hydrocarbons (PAHs) are believed to be the primary toxic components of crude oil. Such compounds including phenanthrene are known to have direct effects on cardiac tissue, which lead to malformations during organogenesis in early life stage fish. We tested a suite of 13 alkyl-phenanthrenes to compare uptake and developmental toxicity in early life stage haddock (Melanogrammus aeglefinus) embryos during gastrulation/organogenesis beginning at 2 days post fertilization via passive dosing. The alkyl-phenanthrenes were tested at their solubility limits, and three of them also at lower concentrations. Measured body burdens were linearly related to measured water concentrations. All compounds elicited one or more significant morphological defects or functional impairment, such as decreased length, smaller eye area, shorter jaw length, and increased incidence of body axis deformities and eye deformities. The profile of developmental toxicities appeared unrelated to the position of alkyl substitution, and gene expression of cytochrome 1 a (cyp1a) was low regardless of alkylation. Mortality and sublethal effects were observed below the expected range for baseline toxicity, thus indicating excess toxicity. Additionally, PAH concentrations that resulted in toxic effects here were far greater than when measured in whole crude oil exposures that cause toxicity. This work demonstrates that, while these phenanthrenes are toxic to early life stage fish, they cannot individually account for most of the developmental toxicity of crude oil, and that other compounds and/or mixture effects should be given more consideration.

The impact of demographic and clinical characteristics on the trajectories of health-related quality of life among patients with Fabry disease.

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder characterized by multiorgan dysfunction. Since individuals with FD usually experience progressive clinical disease manifestations, their health-related quality of life (HRQOL) is expected to change over time. However, there is limited longitudinal research examining HRQOL outcomes in individuals with FD. We aimed to: assess longitudinal outcomes in HRQOL in adults with FD; examine the physical- and mental HRQOL trajectories at the initial registration (baseline), 3-5 year, and 7-13 year follow-ups; and evaluate the possible associations of age, sex and medical complications with the physical- and mental HRQOL trajectories. METHODS: Forty-three individuals with FD (53% female) who were aged 18 to 81 years at baseline attended clinical follow-up visits between 2006 and 2020. Medical records were extracted retrospectively. Demographics and the 36-item Short-Form Health Survey (SF-36) were recorded at scheduled visits, except for the last data collection which was prospectively obtained in 2020. The physical (PCS) and mental (MCS) composite scores (SF-36) were chosen as outcome measures. RESULTS: The eight SF-36 domain scores were stable over a span of 13 years, and only physical- and social functioning domains worsened clinically over this follow-up period. Mean baseline SF-36 domain scores were all significantly lower (decreased HRQOL) in the FD sample compared with Norwegian population norms. Two hierarchical linear models were run to examine whether demographics and medical complications (measured at the last clinical visit) predicted physical and mental HRQOL trajectories. Age above 47 years (p < 0.001), male sex (p = 0.027), small fibre neuropathy (p < 0.001), renal dysfunction (p < 0.001), and cerebrovascular events (p = 0.003) were associated with lower HRQOL over time. No significant interactions were found between the time of follow up and the abovementioned predictors of HRQOL. CONCLUSIONS: Overall HRQOL trajectories remained stable between baseline, 3-5 year, and 7-13 year follow-ups, with the majority of individuals reporting decreased physical and mental HRQOL. Medical complications in combination with older age and male sex are important predictors of lower HRQOL in FD. Awareness of this relationship is valuable both for health care providers and for patients. The findings provide indicators that can guide treatment decisions to improve physical and mental HRQOL outcomes.

Genetic markers associated with long-term cardiovascular outcome in kidney transplant recipients.

There is a clear genetic contribution to the risk of cardiovascular diseases, and a composite genetic risk score (GRS) based on 27 single nucleotide polymorphisms (SNPs) was reported to predict risk of cardiovascular events in the general population. We aimed to evaluate this risk score in renal transplant recipients, a population with heightened cardiovascular risk, with a yet unknown genetic contribution. A total of 1640 participants from the ALERT trial (Assessment of Lescol in Renal Transplantation), a study comparing fluvastatin with placebo in stable renal transplant recipients, were genotyped for all SNPs making up the GRS. Risk alleles were weighted by the log of odds ratios reported in genome wide association studies and summed. Associations between GRS and time from study inclusion to first major cardiovascular event (MACE) were analyzed by Cox regression. In analyses adjusted for cardiovascular risk factors, GRS was significantly associated with MACE (hazard ratio [HR] 1.81, P = .006) when comparing genetic high-risk patients (quartile 4) with genetic low-risk participants (quartile 1). A 27-SNP GRS, which predicted cardiovascular events in the nontransplant population, appears to have predictive value also in kidney allograft recipients. Refining the score to better fit the transplant population seems feasible.

Digitized patient-provider interaction: How does it matter? A qualitative meta-synthesis.

Sociological interest in the digitization of health has predominantly been studied using qualitative approaches. Research in this field has grown steadily since the late 1990's but to date, no synthesis has been conducted to integrate this now rather comprehensive corpus of data. In this paper we present a meta-ethnography of 15 papers reporting qualitative studies of digitally mediated patient - professional interactions. By dissecting the detailed descriptions of digitized practices in this most basic relationship in health care, we explore how these studies can illuminate important aspects of social relations in contemporary society. Our interpretative synthesis enables us to reassert a sociological view that places changes in social structures and interaction at the core of questions about the digitization of health care. Our synthesis of this literature identifies four key concepts that point at structural processes of change. We argue that when patient-professional interactions are digitized, relations are respatialized, and there are reconnections of relational components. These lead to empirically specific reactions, which can be characterized as reconstitutions and renegotiations of social practices which in turn are related to the reconfiguration of basic social institutions. We propose a new direction for exploring the digitalization of health care to illuminate how digital health is related to contemporary social change.

Monitoring and Benchmarking eHealth in the Nordic Countries.

The Nordic eHealth Research Network, a subgroup of the Nordic Council of Ministers eHealth group, is working on developing indicators to monitor progress in availability, use and outcome of eHealth applications in the Nordic countries. This paper reports on the consecutive analysis of National eHealth policies in the Nordic countries from 2012 to 2016. Furthermore, it discusses the consequences for the development of indicators that can measure changes in the eHealth environment arising from the policies. The main change in policies is reflected in a shift towards more stakeholder involvement and intensified focus on clinical infrastructure. This change suggests developing indicators that can monitor understandability and usability of eHealth systems, and the use and utility of shared information infrastructure from the perspective of the end-users - citizens/patients and clinicians in particular.

Systematic screening for atrial fibrillation in a 65-year-old population with risk factors for stroke: data from the Akershus Cardiac Examination 1950 study.

Aims: To investigate the yield of screening for atrial fibrillation (AF) in a cohort of 65-year-old individuals from the general population with additional risk factors for stroke. Methods and results: We invited participants with additional risk factors for stroke (CHA2DS2-VASc score ≥2 for men or ≥ 3 for women) without previously known AF from a population-based study in Norway to participate in a 2-week screening for AF. Screening was performed by one-lead 'thumb electrocardiography (ECG)' recordings of 30 s twice daily or when the participants experienced symptoms. In total, 1742 (47.0%) participants of the Akershus Cardiac Examination (ACE) 1950 study had at least one additional risk factor for stroke. Of these, 123 cases reported a history of AF and 101 (5.8%) cases were ECG validated. Eight [0.5%, 95% confidence interval (CI) 0.2-0.9] new AF cases were diagnosed by 12-lead ECG at baseline, and 10 additional participants were diagnosed with AF before screening commenced. We invited all 1601 participants who met the inclusion criteria for screening, of which 1510 (94.3%) participants were included (44% women and 56% men). The screening revealed AF in 13 (0.9%, 95% CI 0.5-1.5) participants. The total prevalence of ECG-validated AF after screening among the 65-year-olds with risk factors for stroke was 7.6% (95% CI 6.4-8.9), in men 10.0% (95% CI 8.2-12.0), and in women 4.3% (95% CI 3.0-6.1) (P < 0.001). Conclusion: In a group of 1510 well-characterized 65-year-olds with risk factors for stroke, 2-week intermittent ECG screening identified undiagnosed AF in 0.9%. The total prevalence of AF was 7.6%.

Tumour-associated glial host cells display a stem-like phenotype with a distinct gene expression profile and promote growth of GBM xenografts.

BACKGROUND: Little is known about the role of glial host cells in brain tumours. However, supporting stromal cells have been shown to foster tumour growth in other cancers. METHODS: We isolated stromal cells from patient-derived glioblastoma (GBM) xenografts established in GFP-NOD/scid mice. With simultaneous removal of CD11b+ immune and CD31+ endothelial cells by fluorescence activated cell sorting (FACS), we obtained a population of tumour-associated glial cells, TAGs, expressing markers of terminally differentiaed glial cell types or glial progenitors. This cell population was subsequently characterised using gene expression analyses and immunocytochemistry. Furthermore, sphere formation was assessed in vitro and their glioma growth-promoting ability was examined in vivo. Finally, the expression of TAG related markers was validated in human GBMs. RESULTS: TAGs were highly enriched for the expression of glial cell proteins including GFAP and myelin basic protein (MBP), and immature markers such as Nestin and O4. A fraction of TAGs displayed sphere formation in stem cell medium. Moreover, TAGs promoted brain tumour growth in vivo when co-implanted with glioma cells, compared to implanting only glioma cells, or glioma cells and unconditioned glial cells from mice without tumours. Genome-wide microarray analysis of TAGs showed an expression profile distinct from glial cells from healthy mice brains. Notably, TAGs upregulated genes associated with immature cell types and self-renewal, including Pou3f2 and Sox2. In addition, TAGs from highly angiogenic tumours showed upregulation of angiogenic factors, including Vegf and Angiopoietin 2. Immunohistochemistry of three GBMs, two patient biopsies and one GBM xenograft, confirmed that the expression of these genes was mainly confined to TAGs in the tumour bed. Furthermore, their expression profiles displayed a significant overlap with gene clusters defining prognostic subclasses of human GBMs. CONCLUSIONS: Our data demonstrate that glial host cells in brain tumours are functionally distinct from glial cells of healthy mice brains. Furthermore, TAGs display a gene expression profile with enrichment for genes related to stem cells, immature cell types and developmental processes. Future studies are needed to delineate the biological mechanisms regulating the brain tumour-host interplay.

Association Between Pretransplant Cancer and Survival in Kidney Transplant Recipients.

BACKGROUND: Kidney transplantation in recipients with a previous malignancy is often deferred 2 to 5 years after cancer treatment due to fear of cancer recurrence. In Norway, the required waiting period has been 1 year. METHODS: We compared patient and graft survival of recipients with pretransplant cancer to the outcomes of matched recipients without such cancer (comparators) using Cox regression. RESULTS: From 1963 to 2010, 377 (6.4%) of 5867 recipients had a pretransplant cancer. During a median follow-up of 6.8 years, 256 recipients died, 35 (13.7%) from recurrent cancer and 27 (10.5%) from de novo cancer. Uncensored and death-censored graft loss occurred in 263 and 46 recipients, respectively. All-cause mortality was similar as in comparators (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.93-1.20]; P = 0.40), death-censored graft loss was lower (HR, 0.63; 95% CI, 0.47-0.84; P = 0.002), and uncensored graft loss was similar (HR, 0.99; 95% CI, 0.87-1.12; P = 0.87). Cancer mortality was higher than in comparators (HR, 1.97; 95% CI, 1.51-2.56; P < 0.001), particularly during the first 5 years of follow-up (HR, 3.44; 95% CI, 2.36-5.03; P < 0.01). Waiting period was not associated with recurrent cancer mortality or all-cause mortality (both P > 0.45). Results were similar within cancer subgroups, with most data in patients with a history of kidney cancer, prostate cancer, urothelial cancer, and skin squamous cell carcinoma. CONCLUSIONS: Kidney transplant recipients with a pretransplant cancer had a similar overall patient and graft survival as recipients without such cancer. Cancer mortality was increased, particularly during the first 5 years after transplantation. A short waiting period was not associated with mortality.

Using the Internet to Support Exercise and Diet: A Stratified Norwegian Survey.

BACKGROUND: Internet is used for a variety of health related purposes. Use differs and has differential effects on health according to socioeconomic status. OBJECTIVE: We investigated to what extent the Norwegian population use the Internet to support exercise and diet, what kind of services they use, and whether there are social disparities in use. We expected to find differences according to educational attainment. METHODS: In November 2013 we surveyed a stratified sample of 2196 persons drawn from a Web panel of about 50,000 Norwegians over 15 years of age. The questionnaire included questions about using the Internet, including social network sites (SNS), or mobile apps in relation to exercise or diet, as well as background information about education, body image, and health. The survey email was opened by 1187 respondents (54%). Of these, 89 did not click on the survey hyperlink (declined to participate), while another 70 did not complete the survey. The final sample size is thus 1028 (87% response rate). Compared to the Norwegian census the sample had a slight under-representation of respondents under the age of 30 and with low education. The data was weighted accordingly before analyses. RESULTS: Sixty-nine percent of women and 53% of men had read about exercise or diet on the Internet (χ(2)= 25.6, P<.001). More people with higher education (71%, χ(2)=19.1, P<.001), reported this. The same gender difference was found for using Internet-based interventions with 20% of women compared to14% of men reporting having used these interventions (χ(2)=7.9, P= .005), for having posted a status about exercise or diet on Facebook or other SNS (23% vs 12%, χ(2)=18.8, P<.001), and for having kept an online exercise or diet journal (21% vs 15%, χ(2)=7.0, P=.008). Evaluations of own physical appearance accounted for some of the gender differences in using online exercise or diet journals. Seven percent of the total sample reported having used electronic communication to ask professionals about exercise or diet, while a few more had discussed online with peers (10%). Asking professionals online was more common amongst those with only primary education (13%, χ(2)<10.5, P=.005).  CONCLUSIONS: Gender and education are related to how the Internet is used to support health behaviors. We should be aware of the potential role of the Internet in accelerating social disparities in health, and continue to monitor population use. For Internet- and mobile-based interventions to support health behaviors, this study provides information relevant to tailoring of delivery media and components to user.

Survival of the project: a case study of ICT innovation in health care.

From twenty years of information and communication technology (ICT) projects in the health sector, we have learned one thing: most projects remain projects. The problem of pilotism in e-health and telemedicine is a growing concern, both in medical literature and among policy makers, who now ask for large-scale implementation of ICT in routine health service delivery. In this article, we turn the question of failing projects upside down. Instead of investigating the obstacles to implementing ICT and realising permanent changes in health care routines, we ask what makes the temporary ICT project survive, despite an apparent lack of success. Our empirical material is based on Norwegian telemedicine. Through a case study, we take an in-depth look into the history of one particular telemedical initiative and highlight how ICT projects matter on a managerial level. Our analysis reveals how management tasks were delegated to the ICT project, which thus contributed to four processes of organisational control: allocating resources, generating and managing enthusiasm, system correction and aligning local practice and national policies. We argue that the innovation project in itself can be considered an innovation that has become normalised in health care, not in clinical, but in management work. In everyday management, the ICT project appears to be a convenient tool suited to ease the tensions between state regulatory practices and claims of professional autonomy that arise in the wake of new public management reforms. Separating project management and funding from routine practice handles the conceptualised heterogeneity between innovation and routine within contemporary health care delivery. Whilst this separation eases the execution of both normal routines and innovative projects, it also delays expected diffusion of technology.

Does insulin impact cold-induced fluid- and protein-extravasation?

BACKGROUND: Insulin has been shown to stabilize the endothelial barrier via inactivation of the endothelial contractile machinery and enhancement of cell-cell adhesions. Here we explored if insulin by its endothelial-stabilizing and anti-inflammatory properties could influence the increase of fluid- and protein-extravasation during hypothermia. METHODS: Two groups of animals (n=10, each) were cooled to 28°C, with insulin-infusion (I-group) or without (C-group), in a randomly controlled study. Fluid balance, hemodynamics, plasma volume (PV), colloid osmotic pressures in plasma (COPp) and interstitial fluid (COPi), hematocrit (Hct), cytokine profiles, serum-albumin- and protein-concentrations were measured and fluid extravasation rate (FER) and albumin-and protein-masses calculated. RESULTS: During 240 min of hypothermia the albumin- and protein-masses together with COPp decreased significantly in both groups. COPi remained essentially unchanged. Plasma volume decreased significantly in the C-group, whereas only a decreasing trend was present in the I-group. Hemoconcentration was significant in both study groups reflected by the Hct-values. A slight increasing trend of FER was seen in both groups from 0.10 (0.04) ml/kg/min and 0.09 (0.05) mg/kg/min, C-group and I-group, respectively, to 0.14 (0.05) mg/kg/min and 0.12 (0.03) mg/kg/min, during the hypothermic period. Between-group differences were absent for all listed parameters including FER. CONCLUSION: Insulin administration does not impact fluid and protein extravasation significantly in animals undergoing cooling and prolonged hypothermia.

Risk factors for hip-related clinical signs in a prospective cohort study of four large dog breeds in Norway.

We conducted a prospective cohort study including privately owned dogs from the breeds Newfondland (NF), Labrador Retriever (LR), Leonberger (LEO), and Irish Wolfhound (IW) followed from birth until age 9 yrs. We wanted to investigate whether radiological hip dysplasia status given at approximately age 12-18 mos and other factors during growth influenced development of clinical signs due to hip-joint disease necessitating veterinary consultation. Whether or not such signs occurred due to hip dysplasia or due to secondary or primary DJD could not be distinguished, and we therefore used the term "owner-reported veterinary-diagnosed hip-related clinical signs" ("the event"). The included dogs were followed from birth to the event or until a maximum of 9 yrs of age. Our objectives were to describe breed differences in time to incidence and to evaluate potential risk factors for the time to event. We used Kaplan-Meier curves to describe time to incidence, and potential risk factors were assessed by use of a Cox proportional-hazards model. We enrolled 494 dogs from 103 litters, and 46 dogs were reported as having had the event during the observation period. We observed a significant time-varying effect (TVE): LR and LEO developed clinical signs later in life than NF. If the radiological hip status was either mild, moderate, or severe the hazard of experiencing the event was significantly increased. Access to off-leash exercise at age 12 mos decreased the hazard of the event, and the hazard varied by litter. The findings supported the hypothesis that radiological hip status at screening and exercise conditions during growth influenced the time to incidence of the event and that there were breed differences in time to the event.

Hippocampal and ventricular changes in Parkinson's disease mild cognitive impairment.

We analyzed T1-weighted brain magnetic resonance imaging data of 100 cognitively normal elderly controls (NC), 127 cognitively normal Parkinson's disease (PD; PDCN) and 31 PD-associated mild cognitive impairment (PDMCI) subjects from the Norwegian ParkWest study. Using automated segmentation methods, followed by the radial distance technique and multiple linear regression we studied the effect of clinical diagnosis on hippocampal and ventricular radial distance while adjusting for age, education, and scanning site. PDCN subjects had significantly smaller bilateral hippocampal radial distance relative to NC. Nonamnestic PDMCI subjects showed smaller right hippocampal radial distance relative to NC. PDMCI subjects showed significant enlargement of all portions of the lateral ventricles relative to NC and significantly larger bilateral temporal and occipital and left frontal lateral ventricular expansion relative to PDCN subjects. Nonamnestic PDMCI subjects showed significant ventricular enlargement spanning all parts of the lateral ventricle while those with amnestic PDMCI showed changes localized to the left occipital horn. Hippocampal atrophy and lateral ventricular enlargement show promise as structural biomarkers for PD.

What does an e-mail address add? - Doing health and technology at home.

There is increasing interest in using electronic mail and other electronic health technologies (e-health technologies) in patient follow-ups. This study sheds light on patients' reception of provider-initiated e-health in their everyday environments. In a research project carried out in Norway (2005-2007), an electronic address for a hospital dermatology ward was offered to 50 patient families for improved access to expert advice from the patients' homes. Drawing on semi-structured interviews with 12 families, this paper explores how the electronic address was integrated into everyday health practice. The research illuminates how the electronic address did not only represent changes related to treatment procedures and frequency or nature of expert contact; it was also important to other practices in the everyday lives of the families of patients with chronic illness. Once in place on the patients' computers, the electronic address was ascribed at least four different roles: it was used as the intended riverbed for a flow of information, but also as a safety alarm, as a shield to the medical gaze and as a token of competence in care and parenting. The multiplicity in use and reception of an electronic address in patient settings illustrates the need to include patients' everyday practices in current professional and political discussions of e-mail and other e-health technologies. Thus this paper argues that there is a need for research on electronic patient-provider communication that moves beyond frequency of use and questions on how technology will affect medical encounters. Social science equally needs to investigate how provider-initiated e-health technologies gets involved in patients' moral and social performance of health and illness in everyday life.

A prospective study on canine hip dysplasia and growth in a cohort of four large breeds in Norway (1998-2001).

The study-objective was to measure the effect of weight and growth related parameters on the risk of development of Canine Hip Dysplasia (CHD). The hypothesis was that heavy and fast growing dogs of large sized breeds were at increased risk of development of CHD compared to lighter and slower growing dogs. A prospective cohort study was conducted among dogs of four large breeds: Newfoundland (NF), Leonberger (LEO), Labrador retriever (LR), and Irish wolfhound (IW). The dogs were privately owned with individualized nutrition and environment, and they were followed from birth and throughout the growth period until the official screening for CHD was performed. The study sample consisted of 501 dogs from 103 litters, with the breed distribution 125 NF, 180 LEO, 133 LR, and 63 IW. Because the dogs were clustered in litters a multivariable random effects logistic regression model was used to assess statistically significant growth-related risk factors for CHD. The estimated incidence risk of CHD was 36% in NF, 25% in LEO, 20% in LR, and 10% in IW. Based upon the final multilevel model it appears that the odds of CHD among both LR and IW (odds ratio (OR) 0.22) are about one-fifth of the odds for NF. The odds for LEO (OR 0.60) are not significantly different from NF. There appeared to be an inverse relationship between body weight at 3 months of age and odds of CHD, with an OR of 0.89 (P=0.044). The degree of clustering at the litter-level was high (22.6%) and highly significant (P<0.001). Findings failed to support the hypothesis that heavy and fast growing dogs from four large sized breeds were at increased risk for development of CHD. There might be other unmeasured environmental risk factors for CHD in this cohort of dogs, although the contribution of the genetic variance to the litter-level clustering also needs further investigation.

Adaptive radiotherapy based on contrast enhanced cone beam CT imaging.

Cone beam CT (CBCT) imaging has become an integral part of radiation therapy, with images typically used for offline or online patient setup corrections based on bony anatomy co-registration. Ideally, the co-registration should be based on tumor localization. However, soft tissue contrast in CBCT images may be limited. In the present work, contrast enhanced CBCT (CECBCT) images were used for tumor visualization and treatment adaptation. Material and methods. A spontaneous canine maxillary tumor was subjected to repeated cone beam CT imaging during fractionated radiotherapy (10 fractions in total). At five of the treatment fractions, CECBCT images, employing an iodinated contrast agent, were acquired, as well as pre-contrast CBCT images. The tumor was clearly visible in post-contrast minus pre-contrast subtraction images, and these contrast images were used to delineate gross tumor volumes. IMRT dose plans were subsequently generated. Four different strategies were explored: 1) fully adapted planning based on each CECBCT image series, 2) planning based on images acquired at the first treatment fraction and patient repositioning following bony anatomy co-registration, 3) as for 2), but with patient repositioning based on co-registering contrast images, and 4) a strategy with no patient repositioning or treatment adaptation. The equivalent uniform dose (EUD) and tumor control probability (TCP) calculations to estimate treatment outcome for each strategy. Results. Similar translation vectors were found when bony anatomy and contrast enhancement co-registration were compared. Strategy 1 gave EUDs closest to the prescription dose and the highest TCP. Strategies 2 and 3 gave EUDs and TCPs close to that of strategy 1, with strategy 3 being slightly better than strategy 2. Even greater benefits from strategies 1 and 3 are expected with increasing tumor movement or deformation during treatment. The non-adaptive strategy 4 was clearly inferior to all three adaptive strategies. Conclusion. CECBCT may prove useful for adaptive radiotherapy.

Maternal angiotensinogen (AGT) haplotypes, fetal renin (REN) haplotypes and risk of preeclampsia; estimation of gene-gene interaction from family-triad data.

BACKGROUND: Preeclampsia is a debilitating disorder affecting approximately 3% of pregnant women in the Western world. Although inconclusive, current evidence suggests that the renin-angiotensin system may be involved in hypertension. Therefore, our objective was to determine whether the genes for placental renin (REN) and maternal angiotensinogen (AGT) interact to influence the risk of preeclampsia. METHODS: Three haplotype-tagging SNPs (htSNPs) covering REN (rs5705, rs1464818, and rs3795575) and another three covering AGT (rs2148582, rs2478545 and rs943580) were genotyped in 99 mother-father-child triads of preeclampsia pregnancies. We estimated relative risks (RR) conferred by maternal AGT and fetal REN haplotypes using HAPLIN, a statistical software designed to detect multi-marker transmission distortion among triads. To assess a combined effect of maternal AGT and fetal REN haplotypes, the preeclamptic triads were first stratified by presence/absence of maternal AGT haplotype C-T-A and tested for an effect of fetal REN across these strata. RESULTS: We found evidence that mothers carrying the most frequent AGT haplotype, C-T-A, had a reduced risk of preeclampsia (RR of 0.4, 95% CI = 0.2-0.8 for heterozygotes and 0.6, 95% CI = 0.2-1.5 for homozygotes). Mothers homozygous for AGT haplotypes t-c-g and C-c-g appeared to have a higher risk, but only the former was statistically significant. We found only weak evidence of an overall effect of fetal REN haplotypes and no support for our hypothesis that an effect of REN depended on whether the mother carried the C-T-A haplotype of AGT (p = 0.33). CONCLUSION: Our findings indicate that the mother's AGT haplotypes affect her risk for developing preeclampsia. However, this risk is not influenced by fetal REN haplotypes.

Genomic aberrations in borderline ovarian tumors.

BACKGROUND: According to the scientific literature, less than 30 borderline ovarian tumors have been karyotyped and less than 100 analyzed for genomic imbalances by CGH. METHODS: We report a series of borderline ovarian tumors (n = 23) analyzed by G-banding and karyotyping as well as high resolution CGH; in addition, the tumors were analyzed for microsatellite stability status and by FISH for possible 6q deletion. RESULTS: All informative tumors were microsatellite stable and none had a deletion in 6q27. All cases with an abnormal karyotype had simple chromosomal aberrations with +7 and +12 as the most common. In three tumors with single structural rearrangements, a common breakpoint in 3q13 was detected. The major copy number changes detected in the borderline tumors were gains from chromosome arms 2q, 6q, 8q, 9p, and 13q and losses from 1p, 12q, 14q, 15q, 16p, 17p, 17q, 19p, 19q, and 22q. The series included five pairs of bilateral tumors and, in two of these pairs, informative data were obtained as to their clonal relationship. In both pairs, similarities were found between the tumors from the right and left side, strongly indicating that bilaterality had occurred via a metastatic process. The bilateral tumors as a group showed more aberrations than did the unilateral ones, consistent with the view that bilaterality is a sign of more advanced disease. CONCLUSION: Because some of the imbalances found in borderline ovarian tumors seem to be similar to imbalances already known from the more extensively studied overt ovarian carcinomas, we speculate that the subset of borderline tumors with detectable imbalances or karyotypic aberrations may contain a smaller subset of tumors with a tendency to develop a more malignant phenotype. The group of borderline tumors with no imbalances would, in this line of thinking, have less or no propensity for clonal evolution and development to full-blown carcinomas.