Recommendation report for the implementation of research data management policy and for a sustainable research data management service at the University of Exeter

This is the Open Access and Research Data Management Policy Task and Finish Group's recommendation report for the implementation of research data management policy and a sustainable research data management service at the University of Exeter.JIS

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy

BACKGROUND Bleeding in early pregnancy is strongly associated with pregnancy loss. Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone therapy may improve pregnancy outcomes in women who have bleeding in early pregnancy. METHODS We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate progesterone, as compared with placebo, in women with vaginal bleeding in early pregnancy. Women were randomly assigned to receive vaginal suppositories containing either 400 mg of progesterone or matching placebo twice daily, from the time at which they presented with bleeding through 16 weeks of gestation. The primary outcome was the birth of a live-born baby after at least 34 weeks of gestation. The primary analysis was performed in all participants for whom data on the primary outcome were available. A sensitivity analysis of the primary outcome that included all the participants was performed with the use of multiple imputation to account for missing data. RESULTS A total of 4153 women, recruited at 48 hospitals in the United Kingdom, were randomly assigned to receive progesterone (2079 women) or placebo (2074 women). The percentage of women with available data for the primary outcome was 97% (4038 of 4153 women). The incidence of live births after at least 34 weeks of gestation was 75% (1513 of 2025 women) in the progesterone group and 72% (1459 of 2013 women) in the placebo group (relative rate, 1.03; 95% confidence interval [CI], 1.00 to 1.07; P=0.08). The sensitivity analysis, in which missing primary outcome data were imputed, resulted in a similar finding (relative rate, 1.03; 95% CI, 1.00 to 1.07; P=0.08). The incidence of adverse events did not differ significantly between the groups. CONCLUSIONS Among women with bleeding in early pregnancy, progesterone therapy administered during the first trimester did not result in a significantly higher incidence of live births than placebo. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment program; PRISM Current Controlled Trials number, ISRCTN14163439. opens in new tab.

Diopside, enstatite and forsterite solubilities in H2O and H2O-NaCl solutions at lower crustal and upper mantle conditions

The interaction of fluids with rock-forming minerals plays an important role in the chemical evolution of mafic and ultramafic rocks in the lower crust and upper mantle. Recent work highlights the importance of salt-rich fluids in element transport in settings such as the mantle wedge above subduction zones and high-grade granulite facies metamorphism. Forsterite (Mg2SiO4), enstatite (MgSiO3) and diopside (CaMgSi2O6) are key rock-forming minerals in these settings in the system CaO-MgO-SiO2. We determined experimentally the solubilities of diopside, enstatite and forsterite in H2O-NaCl fluids at a range of pressures and temperatures. Forsterite solubility was determined at 1 GPa, 800 and 900 °C, in pure H2O and in H2O-NaCl solutions. Forsterite dissolved congruently at nearly all conditions. Its solubility in pure H2O is low, but increases greatly with rising NaCl concentration in the fluid. Enstatite solubility was investigated in H2O-NaCl solutions at 1 GPa, 800 and 900 °C. Enstatite dissolved incongruently to yield forsterite at all conditions. Addition of excess silica led to suppression of forsterite and showed that fluids in equilibrium with enstatite with or without forsterite are strongly enriched in Si relative to Mg, though Mg solubility is significant at high salinity. Diopside solubility was determined in pure H2O at 650–900 °C and 0.7–1.5 GPa, and in H2O-NaCl solutions at 800 °C and 1 GPa, with NaCl concentrations approaching halite saturation. Diopside dissolves incongruently yielding residual forsterite at all conditions investigated. The solubility of diopside in pure H2O increases with increasing pressure, temperature and salinity. Diopside dissolution in H2O-NaCl solutions displays a dependence on fluid salinity similar to that of forsterite and wollastonite. The results of forsterite solubility experiments in H2O-NaCl solutions were used to calculate the compositions of fluid coexisting with enstatite or diopside where forsterite was present. The concentration of solutes coexisting with enstatite decreases with rising NaCl, similar to quartz. In contrast, bulk solutes coexisting with diopside increase with NaCl, similar to wollastonite and forsterite. These patterns imply complexing among rock-forming components and fluid components, that Ca-chloride species are substantially more stable than Mg-chloride species, and that hydrous Na-silicate complexes are important components of deep H2O-NaCl fluids. The results show that salt-bearing brines have substantial metasomatic power and may exert significant control on the chemical evolution of lower crustal and upper mantle mafic and ultramafic rocks