Structural phase transitions in synthetic analogues of the titanite structure type

The aim of the work presented here is to contribute to the understanding of the driving forces behind displacive phase transitions in transition metal oxides. Towards this aim, synthetic derivatives of the mineral titanite, CaTiOSiO4, are used as model compounds. The study is focusing on the occurrence of displacive phase transitions in compounds with the 2:4:4 cation charge combination: SrTiOGeO4, CaTiOGeO4, CaZrOGeO4 and the binary solid solutions CaTiO(GexSi1-x)O4, (CaxSr1-x)TiOGeO4 and Ca(TixZr1-x)OGeO4. All experiments have been performed on synthetic materials obtained by solid state synthesis from the respective oxides. In the case of the end-member composition CaTiOGeO4 single crystals have been grown from the melt. As the phase transitions encountered in these compounds are of a displacive nature and therefore non-quenchable their observation requires in situ measurements at elevated temperatures. This applies to electron microscopy as well as to X-ray diffraction. In the case of CaTiOGeO4, single crystals have been studied in order to examine the distribution and temperature dependence of diffuse scattering associated with the displacive phase transitions in this material. X-ray powder diffraction measurements at ambient and at elevated temperatures have been used to characterize the temperature evolution of the crystal lattices in the solid solutions as well as in the endmembers. The observed structural phase transitions occur both as a function of temperature and of composition and are identified based on the determination of spontaneous strain. CaTiOGeO4 and SrTiOGeO4 behave in analogy to the well known P21/a – A2/a transition observed in titanite, CaTiOSiO4. While the transition temperature across (CaxSr1-x)TiOGeO4 stays constant near Tc = 590 K, it increases linearly from Tc = 487 K in titanite, to Tc = 588 K in CaTiOGeO4. Phase transitions across the solid solution Ca(TixZr1-x)OGeO4 additionally occur as a function of composition. The transition P21/a – A2/a is not observable above ambient temperature in samples with extrapolated Zr concentration in excess of 18 %. The aristotype structure of titanite (space group symmetry A2/a) is observed for intermediate compounds. CaZrOGeO4 and compounds with high Zr content exhibit a distorted titanite structure of space group symmetry A . This triclinic form transforms to the monoclinic titanite aristotype structure at elevated temperature and with increasing Ti content. The critical temperature is 488 K for the Zr-endmember and the critical composition at ambient temperature is at about 30% Ti-concentration

Family studies to find rare high risk variants in migraine

INTRODUCTION: Migraine has long been known as a common complex disease caused by genetic and environmental factors. The pathophysiology and the specific genetic susceptibility are poorly understood. Common variants only explain a small part of the heritability of migraine. It is thought that rare genetic variants with bigger effect size may be involved in the disease. Since migraine has a tendency to cluster in families, a family approach might be the way to find these variants. This is also indicated by identification of migraine-associated loci in classical linkage-analyses in migraine families. A single migraine study using a candidate-gene approach was performed in 2010 identifying a rare mutation in the TRESK potassium channel segregating in a large family with migraine with aura, but this finding has later become questioned. The technologies of next-generation sequencing (NGS) now provides an affordable tool to investigate the genetic variation in the entire exome or genome. The family-based study design using NGS is described in this paper. We also review family studies using NGS that have been successful in finding rare variants in other common complex diseases in order to argue the promising application of a family approach to migraine. METHOD: PubMed was searched to find studies that looked for rare genetic variants in common complex diseases through a family-based design using NGS, excluding studies looking for de-novo mutations, or using a candidate-gene approach and studies on cancer. All issues from Nature Genetics and PLOS genetics 2014, 2015 and 2016 (UTAI June) were screened for relevant papers. Reference lists from included and other relevant papers were also searched. For the description of the family-based study design using NGS an in-house protocol was used. RESULTS: Thirty-two successful studies, which covered 16 different common complex diseases, were included in this paper. We also found a single migraine study. Twenty-three studies found one or a few family specific variants (less than five), while other studies found several possible variants. Not all of them were genome wide significant. Four studies performed follow-up analyses in unrelated cases and controls and calculated odds ratios that supported an association between detected variants and risk of disease. Studies of 11 diseases identified rare variants that segregated fully or to a large degree with the disease in the pedigrees. CONCLUSION: It is possible to find rare high risk variants for common complex diseases through a family-based approach. One study using a family approach and NGS to find rare variants in migraine has already been published but with strong limitations. More studies are under way. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s10194-017-0729-y) contains supplementary material, which is available to authorized users

General practitioner characteristics and delay in cancer diagnosis. a population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Delay in cancer diagnosis may have serious prognostic consequences, and some patients experience delays lasting several months. However, we have no knowledge whether such delays are associated with general practitioner (GP) characteristics. The aim of the present study was to analyse whether GP and practice characteristics are associated with the length of delay in cancer diagnosis.</p> <p>Methods</p> <p>The study was designed as a population-based cohort study. The setting was the County of Aarhus, Denmark (640,000 inhabitants). Participants include 334 GPs and their 1,525 consecutive, newly diagnosed cancer patients. During one year (September 2004 to August 2005), patients with incident cancer were enrolled from administrative registries. GPs completed questionnaires on the patients' diagnostic pathways and on GP and practice characteristics. Delay was categorised as patient-related (more than 60 days), doctor-related (more than 30 days) and system-related (more than 90 days). The associations between delay and characteristics were assessed in a logistic regression model using odds ratios (ORs).</p> <p>Results</p> <p>No GP characteristics (seniority, practice organization, list size, participation in continuing medical education, job satisfaction and level of burnout) were associated with doctor delay. Patients of female GPs more often had a short <it>patient delay </it>than patients of male GPs (OR 0.44, 95% confidence interval (95%CI) 0.28 to 0.71). Patients whose GPs provided many services (OR 0.66, 95%CI 0.44 to 0.95) and patients attending GPs with little former knowledge of their patients (OR 0.68, 95%CI 0.47 to 0.99) more often experienced a short <it>system delay </it>than patients attending GPs with less activity and more knowledge of their patients. Patients listed with a female GP more often experienced a long system delay than patients of male GPs (OR 1.50, 95%CI 1.02 to 2.21). Finally, patients with low GP-reported compliance more often experienced a long system delay (OR 1.73, 95%CI 1.07 to 2.80) than patients with higher compliance.</p> <p>Conclusions</p> <p>GP characteristics were not statistically significantly associated with doctor delay. However, some GP characteristics were associated with patient and system delay, which indicates that these factors may be important for understanding patient delay (e.g. perceived GP accessibility and the GP-patient relationship) and system delay (e.g. the GP's experience and opportunities for referring and coordinating diagnostic work-up).</p

Patient delay in cancer studies: a discussion of methods and measures

<p>Abstract</p> <p>Background</p> <p>There is no validated way of measuring the prevalence and duration of patient delay, and we do not know how people perceive and define the time intervals they are asked to report in patient delay studies. This lack of a validated measure hampers research in patient delay and is counterproductive to efforts directed at securing early diagnosis of cancer.</p> <p>Discussion</p> <p>The main argument of the present paper is that current studies on patient delay do not sufficiently consider existing theories on symptom interpretation. It is illustrated that the interpretation of bodily sensations as symptoms related to a specific cancer diagnosis is embedded within a social and cultural context. We therefore cannot assume that respondents define delay periods in identical ways.</p> <p>Summary</p> <p>In order to improve the validity of patient delay studies, it is suggested that research be strengthened on three counts: More research should be devoted to symptom interpretation processes, more research should seek to operationalise patient delay, and, importantly, more research is needed to develop valid instruments for measuring patient delay.</p

Socioeconomic patient characteristics predict delay in cancer diagnosis: a Danish cohort study

<p>Abstract</p> <p>Background</p> <p>Delay in cancer diagnosis may be important for cancer prognosis. Large individual variations in the duration of delay have been observed. This study examines whether patients' socioeconomic characteristics are predictors of long patient-, doctor- and system-related delay in cancer diagnosis.</p> <p>Methods</p> <p>Danish population-based cohort study. From September 2004 to September 2005, newly diagnosed cancer patients were enrolled from administrative registries. A total of 467 general practitioners in the County of Aarhus, Denmark, completed questionnaires on 2,212 cancer patients' diagnostic pathways. A total of 1,252 cancer patients filled in questionnaires on their socioeconomic characteristics (e.g. marital status, education, occupation, household income and fortune). Delay was categorised as short or long based on quartiles. Predictors of long delay were assessed in a logistic regression model using odds ratios (ORs) as a proxy of relative risks.</p> <p>Results</p> <p>In regard to <it>patient delay</it>, retired female patients experienced shorter delays (OR 0.35, 95% confidence interval (95%CI) 0.13 to 0.98) than employed female patients, while female smokers experienced longer delays (OR 2.42, 95%CI 1.21 to 4.85) than female non-smokers.</p> <p>In regard to <it>doctor delay</it>, female patients with a large household fortune experienced shorter delays (OR 0.07, 95%CI 0.01 to 0.45) than economically less privileged female patients. Well-educated men experienced shorter delays (OR 0.40, 95%CI 0.16 to 1.00) than men with short education. Male patients experienced longer doctor delays (OR 2.11, 95%CI 1.11 to 4.02) than women when gender-specific cancers were excluded.</p> <p>In regard to <it>system delay</it>, female patients with a large household fortune experienced shorter delays (OR 0.46, 95%CI 0.21 to 0.99) than economically less privileged women, while female patients with a high alcohol intake experienced longer delays (OR 2.82, 95%CI 1.18 to 6.72) than women with an average intake.</p> <p>Conclusion</p> <p>We found socioeconomic predictors of delay that allow us to hypothesize social inequalities in the distribution of delay, but, in general, only a few socioeconomic variables predicted delay in cancer diagnosis. Future research should examine a broader array of patients' personal characteristics.</p

Associations between follow-up screening after gestational diabetes and early detection of diabetes:a register based study

BACKGROUND: Women whose pregnancy was complicated by gestational diabetes have a 7-fold higher risk of developing diabetes, primarily type 2. Early detection can prevent or delay the onset of late complications, for which follow-up screening is important. This study investigated the extent of participation in follow-up screening and the possible consequences of nonattendance in the Region of North Jutland, Denmark. METHOD: In Danish national registers covering the years 1994–2011 we identified 2171 birthing women whose pregnancy was complicated by first-time gestational diabetes. Control visits to general practitioners and biochemical departments after giving birth were charted. Following national guidelines we defined four intervals for assessment of participation in follow-up screening. Diagnosis of diabetes or treatment with glucose-lowering agents after giving birth were also identified. Participation in follow-up screening and risk of diabetes was calculated. Time to obtaining diagnosis of diabetes or initiating treatment was analysed by Cox regression models. All models were adjusted for age, ethnicity and income. RESULTS: High attendance was found during the first control interval, after which attendance decreased with time after giving birth for both controls at general practitioners and biochemical departments. All differences in proportions were statistically significant. Women attending controls at general practitioners had a significantly higher risk of diabetes diagnosis and treatment after gestational diabetes than women not attending. The results for women attending testing at biochemical departments also showed an increased risk of initiation of treatment. Women attending at least one general practitioners control had a significantly higher risk of early diabetes diagnosis or treatment. Time to initiation of treatment was significantly higher for testing at biochemical departments. Women with high incomes had a significantly lower risk of diabetes diagnosis or initiation of treatment compared to low-income women. CONCLUSION: Participation in follow-up screening after gestational diabetes is low in the North Denmark Region. Follow-up screening ensures early detection of diabetes and initiation of treatment. Our results emphasize the importance of development of interventions to improve early detection and prevention of diabetes after gestational diabetes