Early synapsids neurosensory diversity revealed by CT and synchrotron scanning.

Non-mammaliaform synapsids (NMS) represent the closest relatives of today's mammals among the early amniotes. Exploring their brain and nervous system is key to understanding how mammals evolved. Here, using CT and Synchrotron scanning, we document for the first time three extreme cases of neurosensory and behavioral adaptations that probe into the wide range of unexpected NMS paleoneurological diversity. First, we describe adaptations to low-frequency hearing and low-light conditions in the non-mammalian cynodont Cistecynodon parvus, supporting adaptations to an obligatory fossorial lifestyle. Second, we describe the uniquely complex and three-dimensional maxillary canal morphology of the biarmosuchian Pachydectes elsi, which suggests that it may have used its cranial bosses for display or low-energy combat. Finally, we introduce a paleopathology found in the skull of Moschognathus whaitsi. Since the specimen was not fully grown, this condition suggests the possibility that this species might have engaged in playful fighting as juveniles-a behavior that is both social and structured. Additionally, this paper discusses other evidence that could indicate that tapinocephalid dinocephalians were social animals, living and interacting closely with one another. Altogether, these examples evidence the wide range of diversity of neurological structures and complex behavior in NMS.

Phosphorus-31: A table-top method for 3D B1-field amplitude and phase measurements.

A novel method of high-spatial-resolution, 3D B1-field distribution measurements is presented. The method is independent of the MR-scanner, and it allows for automated acquisitions of complete maps of all magnetic field vector components for both proton and heteronuclear MR coils of arbitrary geometrical shapes. The advantage of the method proposed here, compared with methods based on measurements with an MR-scanner, is that a complete image of both receive and transmit B1-fields, including the phase of the B1-field, can be acquired. The B1 field maps obtained in this manner can be used for absolute quantification of metabolites in MRS experiments, as well as for intensity compensations in imaging experiments, both of which are important concepts in biological and medical MR applications. Another use might be in coil development and testing. A comparison with B1 field magnitude maps obtained with an MR-scanner was included to validate the accuracy of the proposed method.

Reproductive factors and risk of melanoma: a population-based cohort study.

BACKGROUND: The association between reproductive factors and risk of cutaneous melanoma (CM) is unclear. We investigated this issue in the Norwegian Women and Cancer cohort study. OBJECTIVES: To examine the association between the reproductive factors age at menarche, menstrual cycle length, parity, age at first and last birth, menopausal status, breastfeeding duration and length of ovulatory life, and CM risk, overall and by histological subtypes and anatomical site. METHODS: We followed 165 712 women aged 30-75 years at inclusion from 1991-2007 to the end of 2015. Multivariable Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The mean age at cohort enrolment was 49 years. During a median follow-up of 18 years, 1347 cases of CM were identified. No reproductive factors were clearly associated with CM risk. When stratifying by histological subtype we observed significant heterogeneity (P = 0·01) in the effect of length of ovulatory life on the risk of superficial spreading melanoma (HR 1·02, 95% CI 1·01-1·04 per year increase) and nodular melanoma (HR 0·97, 95% CI 0·94-1·01 per year increase). When stratifying by anatomical site, menopausal status (HR 0·54, 95% CI 0·31-0·92, postmenopausal vs. premenopausal) and menstrual cycle length (HR 1·07, 95% CI 1·01-1·13, per day increase) were associated with CM of the trunk, and significant heterogeneity between anatomical sites was observed for menopausal status (P = 0·04). CONCLUSIONS: In this large population-based Norwegian cohort study, we did not find convincing evidence of an association between reproductive factors and risk of CM.

CHARACTERIZATION OF A LITHIUM FORMATE EPR-DOSIMETRY SYSTEM FOR PROTON RADIATION THERAPY.

The specific aim for the characterization of the lithium formate dosimetry system is to determine response and stability in a proton beam. The long-term goal for this investigation is an audit system for proton therapy like the end-to-end dose determinations performed for radiotherapy with photons. For a 150-MeV proton beam, the dose response was found to be linear in the dose interval 0-8.8 Gy. The accuracy of dose reconstruction was controlled in a blind test, in which the dose of 6.63 Gy was measured in samples irradiated with a real dose of 6.70 Gy. The stability was determined by irradiations of sets of four dosimeters every week during 1 month and analyzed at the same day thereafter. The fitting of the fading curve was done with a second-order polynomial resulting in a 6.6% lower value compared to the reference after 31 d.

Obesity and Associated Comorbidities in People and Companion Animals: A One Health Perspective.

This article reviews the biology, prevalence and risks for obesity in people and companion dogs and cats, and explores the links between obesity and diabetes mellitus and cancer across these species. Obesity is a major healthcare problem in both human and veterinary medicine and there is an increasing prevalence of obesity in people and pets. In people and animals, obesity is a complex disorder involving diet, level of physical activity, behavioural factors, socioeconomic factors, environment exposures, genetics, metabolism and the microbiome. Pets and people share a number of obesity-related comorbidities. Obesity is a major risk factor for type 2 diabetes mellitus in people and in cats, but this association is not recognized in dogs. Obesity is a recognized risk factor for a number of human cancers, but there are fewer data available describing this association with canine neoplastic disease. One approach to addressing the problem of obesity is by taking a 'One Health' perspective. Comparative clinical research examining shared lifestyle and environmental risk factors and the reasons underlying species differences should provide new perspectives on the fundamental biology of obesity. One Health programmes involving human healthcare professionals and veterinarians could help address obesity with simple interventions at the community level.

Passing a seawater challenge test is not indicative of hatchery-reared Atlantic salmon Salmo salar smolts performing as well at sea as their naturally produced conspecifics.

Despite satisfactory reactions to seawater challenge tests indicative of appropriate physiological state, hatchery-reared Atlantic salmon Salmo salar smolts stocked in the Eira River in Norway between 2001 and 2011 performed less well at sea in terms of growth, age at maturity and survival than smolts of natural origin. The mean rates of return to the river for hatchery-reared and naturally produced S. salar were 0·98 and 2·35%. In the Eira River, c. 50 000 hatchery-reared S. salar smolts of local origin were stocked annually to compensate for reduced natural smolt production following regulation for hydroelectric purposes, while a mean of 17 262 smolts were produced naturally in the river. This study demonstrates that, although captive S. salar perform well in seawater challenge tests, hatchery-reared smolts are not necessarily as adaptable to marine life as their naturally produced counterparts. These findings suggest that production of hatchery-reared smolts more similar to naturally produced individuals in morphology, physiology and behaviour will be necessary to improve success of hatchery releases. Where possible, supplementary or alternative measures, including habitat restoration, could be implemented to ensure the long-term viability of wild stocks.

Prevalence and trends of sunscreen use and sunburn among Norwegian women.

BACKGROUND: Sunscreen is recommended to prevent sunburn and skin cancer. OBJECTIVES: To investigate sunscreen use in relation to demographic and phenotypic characteristics among women in Norway, as well as solar UV exposure, sunburn experience in different decades of life, and temporal trends in sunscreen use. METHODS: We used data from the Norwegian Women and Cancer Study, a large population-based prospective cohort study. Log-binomial regression was used to estimate the association between sunscreen use and personal characteristics. Results are presented as prevalence ratios (PRs) and 99% confidence intervals (CIs). RESULTS: The study sample consisted of 148,869 women, with a mean age, when answering the questionnaire, of 53 years (range 41-75). Sixty-five per cent of the women used sunscreen during the Easter holiday, 73% in northern latitudes and 87% in bathing vacations in southern latitudes. Sunscreen with sun protection factor (SPF) ≥ 15 was used by 25,156 (18%) at Easter, 18,118 (13%) in northern latitudes and 22,678 (30%) in southern latitudes. The prevalence of sunscreen use increased from 1997 to 2007, and this increase was associated with age. In 1997, 39% of women reported at least one sunburn per year in the recent decade, compared with 46% in 2007 (Ptrend = 0·001). Women who experienced at least four sunburns per year during adolescence reported more sunscreen use in adulthood (PREaster 1·54, 99% CI 1·30-1·83; PRnorthern latitudes 1·49, 99% CI 1·20-1·84; PRsouthern latitudes 1·37, 99% CI 1·14-1·65). CONCLUSIONS: The prevalence of sunscreen use increased from 1997 to 2007. However, this increase has not been accompanied by a decrease in sunburn. Moreover, use of sunscreen with the recommended SPF was not common among Norwegian women.

CLIPPERS among patients diagnosed with non-specific CNS neuroinflammatory diseases.

Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) is an inflammatory CNS disorder characterized by 1) subacute onset of cerebellar and brainstem symptoms, 2) peripontine contrast-enhancing perivascular lesions with a "salt-and-pepper" appearance on MRI, and 3) angiocentric, predominantly T-lymphocytic infiltration as revealed by brain biopsy. Inflammatory diseases including neuroinfections, CNS lymphoma and neurosarcoidosis must be excluded. Since CLIPPERS was described in 2010, many patients might have been misdiagnosed in the past. We therefore searched medical records from a large tertiary neurological center, the Department of Neurology at Rigshospitalet, Copenhagen University Hospital, for patients discharged between 1999 and 2013 with a diagnosis of "sarcoidosis with other localization", "other acute disseminating demyelination", "other demyelinating disease in the CNS" or "encephalitis, myelitis or encephalomyelitis". Of 206 identified patients, 24 had been examined by brain biopsy and were included for further evaluation. Following clinical, neuroradiological and neuropathological review, 3 patients (12.5%) were reclassified as having CLIPPERS. Median long-term follow-up was 75 months. The present results suggest that clinical re-evaluation of patients previously diagnosed with unspecified inflammatory demyelinating CNS disease or atypical neurosarcoidosis may increase the detection rate of CLIPPERS. Further, potentially severe neurological deficits and progressive parenchymal atrophy on MRI may suggest neurodegenerative features, which emphasizes the need for early immunomodulatory treatment.

High-resolution mapping of 1D and 2D dose distributions using X-band electron paramagnetic resonance imaging.

Electron paramagnetic resonance imaging (EPRI) was performed to visualise 2D dose distributions of homogenously irradiated potassium dithionate tablets and to demonstrate determination of 1D dose profiles along the height of the tablets. Mathematical correction was applied for each relative dose profile in order to take into account the inhomogeneous response of the resonator using X-band EPRI. The dose profiles are presented with the spatial resolution of 0.6 mm from the acquired 2D images; this value is limited by pixel size, and 1D dose profiles from 1D imaging with spatial resolution of 0.3 mm limited by the intrinsic line-width of potassium dithionate. In this paper, dose profiles from 2D reconstructed electron paramagnetic resonance (EPR) images using the Xepr software package by Bruker are focussed. The conclusion is that using potassium dithionate, the resolution 0.3 mm is sufficient for mapping steep dose gradients if the dosemeters are covering only ±2 mm around the centre of the resonator.

EPR imaging of dose distributions aiming at applications in radiation therapy.

A one-dimensional electron paramagnetic resonance (EPR) imaging method for visualisation of dose distributions in photon fields has been developed. Pressed pellets of potassium dithionate were homogeneously irradiated in a (60)Co radiation field to 600 Gy. The EPR analysis was performed with an X-Band (9.6 GHz) Bruker E540 EPR and EPR imaging spectrometer equipped with an E540 GC2X two-axis X-band gradient coil set with gradients along the y axis (along the sample tube) and z axis (along B0) and an ER 4108TMHS resonator. Image reconstruction, including deconvolution, baseline corrections and corrections for the resonator sensitivity, was performed using an in-house-developed Matlab code for the purpose to have a transparent and complete algorithm for image reconstruction. With this method, it is possible to visualise a dose distribution with an accuracy of ∼5 % within ±5 mm from the centre of the resonator.

Plasma 25 hydroxyvitamin D level and blood gene expression profiles: a cross-sectional study of the Norwegian Women and Cancer Post-genome Cohort.

BACKGROUND/OBJECTIVES: Vitamin D deficiency has been associated with increased risk of developing several diseases, but much is unknown about the molecular effects involved. Gene expression technology is increasingly being used to elucidate molecular mechanisms related to nutritional factors, and in this study of free-living, middle-aged Norwegian women, we aimed at identifying gene expression pathways in the blood associated with vitamin D status. SUBJECTS/METHODS: Blood samples and questionnaires were collected as a part of the Norwegian Women and Cancer Post-genome Cohort (500 invited subjects, 218 included). Plasma 25 hydroxyvitamin D (25(OH)D) concentrations were measured using high-performance liquid chromatography, and we compared groups with sufficient versus deficient vitamin D status (25(OH)D >50 nmol/l (n=66) versus <37.5 nmol/l (n=83)), to identify differences in gene expression profiles obtained using full-genome microarrays. RESULTS: In a targeted pathway-level analysis, several immunological processes, immune cell functions and major signaling pathways were differentially regulated according to vitamin D status (P<0.01). To a certain degree, results from in vitro studies reported in the literature were reflected in this population setting. CONCLUSIONS: We conclude that vitamin D status measured as 25(OH)D was associated with molecular pathways that may ultimately affect the potential onset of diseases. The use of gene expression analysis in a population setting may give valuable input to the study of effects of nutritional factors.

Decreased muscle concentrations of ATP and PCR in the quadriceps muscle of fibromyalgia patients--a 31P-MRS study.

BACKGROUND AND METHODS: Fibromyalgia (FMS) has a prevalence of approximately 2% in the population. Central alterations have been described in FMS, but there is not consensus with respect to the role of peripheral factors for the maintenance of FMS. 31P magnetic resonance spectroscopy (31P-MRS) has been used to investigate the metabolism of phosphagens in muscles of FMS patients, but the results in the literature are not in consensus. The aim was to investigate the quantitative content of phosphagens and pH in resting quadriceps muscle of patients with FMS (n = 19) and in healthy controls (CONTROLS; n = 14) using (31) P-MRS. It was also investigated whether the concentrations of these substances correlated with measures of pain and/or physical capacity. RESULTS: Significantly lower concentrations of adenosine triphosphate (ATP) and phosphocreatinine (PCr; 28-29% lower) were found in FMS. No significant group differences existed with respect to inorganic phosphate (Pi), Pi/PCr and pH. The quadriceps muscle fat content was significantly higher in FMS than in CONTROLS [FMS: 9.0 ± 0.5% vs. CONTROLS: 6.6 ± 0.6%; (mean ± standard error); P = 0.005]. FMS had significantly lower hand and leg capacity according to specific physical test, but there were no group differences in body mass index, subjective activity level and in aerobic fitness. In FMS, the specific physical capacity in the leg and the hand correlated positively with the concentrations of ATP and PCr; no significant correlations were found with pain intensities. CONCLUSIONS: Alterations in intramuscular ATP, PCr and fat content in FMS probably reflect a combination of inactivity related to pain and dysfunction of muscle mitochondria.

Mediterranean diet and incidence of hip fractures in a European cohort.

UNLABELLED: Prevention of hip fractures is of critical public health importance. In a cohort of adults from eight European countries, evidence was found that increased adherence to Mediterranean diet, measured by a 10-unit dietary score, is associated with reduced hip fracture incidence, particularly among men. INTRODUCTION: Evidence on the role of dietary patterns on hip fracture incidence is scarce. We explored the association of adherence to Mediterranean diet (MD) with hip fracture incidence in a cohort from eight European countries. METHODS: A total of 188,795 eligible participants (48,814 men and 139,981 women) in the European Prospective Investigation into Cancer and nutrition study with mean age 48.6 years (±10.8) were followed for a median of 9 years, and 802 incident hip fractures were recorded. Diet was assessed at baseline through validated dietary instruments. Adherence to MD was evaluated by a MD score (MDs), on a 10-point scale, in which monounsaturated were substituted with unsaturated lipids. Association with hip fracture incidence was assessed through Cox regression with adjustment for potential confounders. RESULTS: Increased adherence to MD was associated with a 7 % decrease in hip fracture incidence [hazard ratio (HR) per 1-unit increase in the MDs 0.93; 95 % confidence interval (95 % CI) = 0.89-0.98]. This association was more evident among men and somewhat stronger among older individuals. Using increments close to one standard deviation of daily intake, in the overall sample, high vegetable (HR = 0.86; 95 % CI = 0.79-0.94) and high fruit (HR = 0.89; 95 % CI = 0.82-0.97) intake was associated with decreased hip fracture incidence, whereas high meat intake (HR = 1.18; 95 % CI = 1.06-1.31) with increased incidence. Excessive ethanol consumption (HR high versus moderate = 1.74; 95 % CI = 1.32-2.31) was also a risk factor. CONCLUSIONS: In a prospective study of adults, increased adherence to MD appears to protect against hip fracture occurrence, particularly among men.

Adherence to the mediterranean diet and risk of breast cancer in the European prospective investigation into cancer and nutrition cohort study.

Epidemiological evidence suggests that the Mediterranean diet (MD) could reduce the risk of breast cancer (BC). As evidence from the prospective studies remains scarce and conflicting, we investigated the association between adherence to the MD and risk of BC among 335,062 women recruited from 1992 to 2000, in ten European countries, and followed for 11 years on average. Adherence to the MD was estimated through an adapted relative Mediterranean diet (arMED) score excluding alcohol. Cox proportional hazards regression models were used while adjusting for BC risk factors. A total of 9,009 postmenopausal and 1,216 premenopausal first primary incident invasive BC were identified (5,862 estrogen or progesterone receptor positive [ER+/PR+] and 1,018 estrogen and progesterone receptor negative [ER-/PR-]). The arMED was inversely associated with the risk of BC overall and in postmenopausal women (high vs. low arMED score; hazard ratio [HR] = 0.94 [95% confidence interval [CI]: 0.88, 1.00] ptrend = 0.048, and HR = 0.93 [95% CI: 0.87, 0.99] ptrend = 0.037, respectively). The association was more pronounced in ER-/PR- tumors (HR = 0.80 [95% CI: 0.65, 0.99] ptrend = 0.043). The arMED score was not associated with BC in premenopausal women. Our findings show that adherence to a MD excluding alcohol was related to a modest reduced risk of BC in postmenopausal women, and this association was stronger in receptor-negative tumors. The results support the potential scope for BC prevention through dietary modification.

Dose response of xylitol and sorbitol for EPR retrospective dosimetry with applications to chewing gum.

The purpose of this investigation was to study the radiation-induced electron paramagnetic resonance signal in sweeteners xylitol and sorbitol for use in retrospective dosimetry. For both sweeteners and chewing gum, the signal changed at an interval of 1-84 d after irradiation with minimal changes after 4-8 d. A dependence on storage conditions was noticed and the exposure of the samples to light and humidity was therefore minimised. Both the xylitol and sorbitol signals showed linearity with dose in the measured dose interval, 0-20 Gy. The dose-response measurements for the chewing gum resulted in a decision threshold of 0.38 Gy and a detection limit of 0.78 Gy. A blind test illustrated the possibility of using chewing gums as a retrospective dosemeter with an uncertainty in the dose determination of 0.17 Gy (1 SD).