Closed-system behaviour of the Re-Os isotope system recorded in primary and secondary platinum-group mineral assemblages : evidence from a mantle chromitite at Harold's Grave (Shetland ophiolite complex, Scotland)

This study evaluates in detail the mineral chemistry, wholerock and mineral separate Os-isotope compositions of distinct platinumgroup mineral (PGM) assemblages in an isolated chromitite pod at Harold's Grave which occurs in mantle tectonite in the Shetland Ophiolite Complex (SOC), Scotland. This was the first ophiolite sequence worldwide that was shown to contain ppm levels of all six platinum-group elements (PGE) in podiform chromitite, including the contrasting type localities found here and at Cliff. At Harold's Grave the primary PGM assemblage is composed mainly of laurite and/or Os-rich iridium and formed early together with chromite, whereas the secondary PGM assemblage dominated by laurite, Osrich laurite, irarsite, native osmium and Ru-bearing pentlandite is likely to reflect processes including in-situ serpentinization, alteration during emplacement and regional greenschist metamorphism. The osmium isotope data define a restricted range of 'unradiogenic' 187Os/188Os values for coexisting laurite and Os-rich alloy pairs from 'primary' PGM assemblage (0.12473-0.12488) and similar 'unradiogenic' 187Os/188Os values for both 'primary' and 'secondary' PGM assemblages (0.1242±0.0008 and 0.1245±0.0006, respectively), which closely match the bulk 187Os/188Os value of their host chromitite (0.1240±0.0006). The unprecedented isotopic similarity between primary or secondary PGM assemblages and chromitite we report suggests that the osmium isotope budget of chromitite is largely controlled by the contained laurite and Os-rich alloy. This demonstrates that closed system behaviour of the Re- Os isotope system is possible, even during complex postmagmatic hydrothermal and/or metamorphic events. The preserved mantle Os-isotope signatures provide further support for an Enstatite Chondrite Reservoir (ECR) model for the convective upper mantle and are consistent with origin of the complex as a Caledonian ophiolite formed in a suprasubduction zone setting shortly before obduction

Four-year update of the EXIST-2 study

Objectives We examined the long-term effects of everolimus in patients with renal angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. Methods Following favorable results from the double- blind core phase of EXIST-2 (NCT00790400), patients were allowed to receive open-label everolimus (extension phase). Patients initially randomly assigned to everolimus continued on the same dose; those who were receiving placebo crossed over to everolimus 10 mg/day. Dose modifications were based on tolerability. The primary end point was angiomyolipoma response rate, defined as a ≥50% reduction from baseline in the sum volume of target renal angiomyolipomas in the absence of new target angiomyolipomas, kidney volume increase of >20% from nadir, and angiomyolipoma-related bleeding grade ≥2. The key secondary end point was safety. Results Of the 112 patients who received ≥1 dose of everolimus, 58% (95% CI, 48.3% to 67.3%) achieved angiomyolipoma response. Almost all patients (97%) experienced reduction in renal lesion volumes at some point during the study period. Median duration of everolimus exposure was 46.9 months. Sixteen (14.3%) patients experienced angiomyolipoma progression at some point in the study. No angiomyolipoma-related bleeding or nephrectomies were reported. One patient on everolimus underwent embolization for worsening right flank pain. Subependymal giant cell astrocytoma lesion response was achieved in 48% of patients and skin lesion response in 68% of patients. The most common adverse events suspected to be treatment-related were stomatitis (42%), hypercholesterolemia (30.4%), acne (25.9%), aphthous stomatitis and nasopharyngitis (each 21.4%). Ten (8.9%) patients withdrew because of an adverse event. Renal function remained stable, and the frequency of emergent adverse events generally decreased over time. Conclusions Everolimus treatment remained safe and effective over approximately 4 years. The overall risk/benefit assessment supports the use of everolimus as a viable treatment option for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. Trial registration ClinicalTrials.gov NCT0079040

Lung Function Is Associated with Arterial Stiffness in Children

BACKGROUND: In older adults, an independent association exists between impaired lung function and cardiovascular disease. This interaction might be related to the effects of aging and/or smoking. In order to explore possible childhood antecedents to this association, we hypothesized that decreased lung function and vascular stiffness might be related, in early life. OBJECTIVE: To determine the relationship between lung function and carotid augmentation index (AIx), a measure of vascular stiffness, in 8-year old children. METHODS: Data on brachial blood pressure, lung function (FEV(1), FVC, FEV(1)/FVC, obtained by spirometry) and carotid AIx75 (AIx standardised to an arbitrary heart rate of 75 beats per minute, obtained by applanation tonometry) was available in 249 community-based 8-year old children. These healthy children had been subjects in a randomised controlled trial of two interventions (omega-3 fatty acid supplementation and house-dust mite avoidance) to prevent asthma. Smoking in pregnancy and childhood environmental tobacco smoke (ETS) exposure was prospectively collected by questionnaire. The association between lung function and carotid AIx75 was assessed in multivariate models that included sex, height, smoking status during pregnancy, ETS exposure and randomisation groups (house dust mite avoidance and dietary intervention) as covariates. RESULTS: In the fully adjusted models, Carotid AIx75 was independently associated with FEV1 (standardised β = -0.17,b = -6.72, partial R(2) = .02, p = 0.03), FVC (standardised β = -0.29, b = -9.31, partial R(2) = 0.04, p<0.001) and FEV1/FVC (standardised β = .13, b = 18.4, partial R(2) = 0.02, p = 0.04). CONCLUSION: Lower lung volumes are associated with increased vascular stiffness at an early age. The interaction between lung function and vascular stiffness may thus represent more than just age-related alterations in both the pulmonary and vascular systems

Dividend Payments and Cross-country Differences in the Choice of Dividend

One of the hallmarks of good corporate governance is a well built and complies with the dividend policy, taking into account the interests of both the majority and minority shareholders, companies need to preserve and accrued competitive position in the market. Companies that pay dividends pay attention to credit rating agencies. A comparative analysis of the main indicators of dividend in the emerging markets of Russia and Poland with the performance of the developed markets of France and Germany. In the Russian data tested Lintner model describes well the trajectory of dividend payments in the developed markets. Isolated set of financial results of Russian companies that have an impact on their decision to pay dividends on the selected size of payments, revealed differences in dividend-making companies that have carried out cross-listing from making dividend companies whose shares are listed in Russia. This paper discusses mainly observed the company's decision to pay or not to pay dividends and the establishment of the amount of dividends in each year separately. For a description of such decisions used the term “dividend of choice” or “dividend decisions”. It also shows that dividend decisions of companies can vary significantly in different countries. Keywords: Financial capital structure, dividend policy, financial markets, dividend option JEL Classifications: G32, F62, D5

A New Reconstruction for Permian East Gondwana Based on Zircon Data From Ophiolite of the East Australian Great Serpentinite Belt

The Great Serpentinite Belt of eastern Australia is a similar to 1500 km long dismembered ophiolite assumed to be Cambrian based on studies of small (typically <50 m(2)) exotic meta-igneous inclusions despite contrasting ages (Cambrian-Devonian) and complex P-T histories. To overcome these issues, we studied a similar to 18 km(2) coherent block of dismembered ophiolite that provides robust geological context to sampling the ophiolite. Zircon U-Pb-Hf-O isotope and trace analyses from three plagiogranite dykes cutting massive gabbro confirm similar to 283-277 Ma ages and a mantle source. As a result, we argue older Cambrian to Devonian plagiogranite and subducted blocks were inherited from previous subduction events in eastern Australia. These findings allow us to match the Great Serpentinite Belt with the contemporary Dun Mountain ophiolite (New Zealand) and the Koh ophiolite (New Caledonia), thus supporting a new, integrated Pacific Gondwana margin paleogeography involving multiple arcs and subduction zones. Plain Language Summary Ophiolites are fragments of oceanic crust and mantle that have been thrusted onto continents by tectonics. Ophiolites provide important records of oceanic lithosphere and for assessing the timing of significant tectonic events. Previous studies of the Great Serpentinite Belt of eastern Australia, established a similar to 530 Myr age. However, studies focused on small (typically < 50 m(2)) exotic fault bounded blocks of ophiolitic material of varying geological ages and complex metamorphic histories. By focusing on an intact 18 km(2) fragment of oceanic crust with reliable geological relationships and low degrees of metamorphism, our results show this ophiolite is far younger (similar to 280 Myr old). This age overlaps with ophiolites in New Caledonia and New Zealand on what was the paleo-Pacific Gondwana margin. This new discovery leads to a new paleogeography for this period and improves geological links between eastern Australia, New Zealand, and New Caledonia.Funding was provided by UNE IRG funds to Milan and Australian Research Council Grants (Belousova, FT110100685). J. Kalmbach was sup-ported by the DAAD Rise Worldwide progra

The recycling of chromitites in ophiolites from southwestern North America

Podiform chromitites occur in mantle peridotites of the Late Triassic Puerto Nuevo Ophiolite, Baja California Sur State, Mexico. These are high-Cr chromitites [Cr# (Cr/Cr + Al atomic ratio = 0.61–0.69)] that contain a range of minor- and trace-elements and show whole-rock enrichment in IPGE (Os, Ir, Ru). That are similar to those of high-Cr ophiolitic chromitites crystallised from melts similar to high-Mg island-arc tholeiites (IAT) and boninites in supra-subduction-zone mantle wedges. Crystallisation of these chromitites from S-undersaturated melts is consistent with the presence of abundant inclusions of platinum-group minerals (PGM) such as laurite (RuS)-erlichmanite (OsS), osmium and irarsite (IrAsS) in chromite, that yield T ≈ T model ages peaking at ~ 325 Ma. Thirty-three xenocrystic zircons recovered from mineral concentrates of these chromitites yield ages (2263 ± 44 Ma to 278 ± 4 Ma) and Hf-O compositions [ɛ(t) = − 18.7 to + 9.1 and O values < 12.4‰] that broadly match those of zircons reported in nearby exposed crustal blocks of southwestern North America. We interpret these chromitite zircons as remnants of partly digested continental crust or continent-derived sediments on oceanic crust delivered into the mantle via subduction. They were captured by the parental melts of the chromitites when the latter formed in a supra-subduction zone mantle wedge polluted with crustal material. In addition, the Puerto Nuevo chromites have clinopyroxene lamellae with preferred crystallographic orientation, which we interpret as evidence that chromitites have experienced high-temperature and ultra high-pressure conditions (< 12 GPa and ~ 1600 °C). We propose a tectonic scenario that involves the formation of chromitite in the supra-subduction zone mantle wedge underlying the Vizcaino intra-oceanic arc ca. 250 Ma ago, deep-mantle recycling, and subsequent diapiric exhumation in the intra-oceanic basin (the San Hipólito marginal sea) generated during an extensional stage of the Vizcaino intra-oceanic arc ca. 221 Ma ago. The T ages at ~ 325 Ma record a partial melting event in the mantle prior to the construction of the Vizcaino intra-oceanic arc, which is probably related to the Permian continental subduction, dated at ~ 311 Ma.Funding for this research was provided through the CONACyT research project number 155662 and internal budget of the Instituto de Geología (UNAM) to AC, the Ramón y Cajal Fellowship RYC-2015-17596 to JMGJ, and by the project CGL2015-65824-P granted by the Spanish “Ministerio de Economía y Competitividad” to JAP. Additional funding for chromite microanalyses were provided by the DGAPA-UNAM postdoctoral fellowship to VC. This is also a contribution from the ARC National Key Centre for Geochemical Evolution and Metallogeny of Continents ( www.es.mq.edu.au /GEMOC) and the ARC Centre of Excellence for Core to Crust Fluid Systems. The SHRIMP facility lab and technical staff at Curtin University are also thanked for their support in the data acquisition. We also thank to Carlos Linares (Petrology Laboratory of the, UNAM, Mexico) for his help with the EMPA analyses on chromite. Michelangelo Martini, Luis Abel Jiménez-Galindo and all the personnel at the Fishermen's Cooperative Society at Bahía Tortugas (Baja California Sur) are wholeheartedly thanked for their kind assistance during our fieldwork

The TOSCA Registry for Tuberous Sclerosis-Lessons Learnt for Future Registry Development in Rare and Complex Diseases.

Introduction: The TuberOus SClerosis registry to increase disease Awareness (TOSCA) is an international disease registry designed to provide insights into the clinical characteristics of patients with Tuberous Sclerosis Complex (TSC). The aims of this study were to identify issues that arose during the design, execution, and publication phases of TOSCA, and to reflect on lessons learnt that may guide future registries in rare and complex diseases. Methods: A questionnaire was designed to identify the strengths, weaknesses, and issues that arose at any stage of development and implementation of the TOSCA registry. The questionnaire contained 225 questions distributed in 7 sections (identification of issues during registry planning, during the operation of the registry, during data analysis, during the publication of the results, other issues, assessment of lessons learnt, and additional comments), and was sent by e-mail to 511 people involved in the registry, including 28 members of the Scientific Advisory Board (SAB), 162 principal investigators (PIs), and 321 employees of the sponsor belonging to the medical department or that were clinical research associate (CRA). Questionnaires received within the 2 months from the initial mailing were included in the analysis. Results: A total of 53 (10.4%) questionnaires were received (64.3% for SAB members, 12.3% for PIs and 4.7% for employees of the sponsor), and the overall completeness rate for closed questions was 87.6%. The most common issues identified were the limited duration of the registry (38%) and issues related to handling of missing data (32%). In addition, 25% of the respondents commented that biases might have compromised the validity of the results. More than 80% of the respondents reported that the registry improved the knowledge on the natural history and manifestations of TSC, increased disease awareness and helped to identify relevant information for clinical research in TSC. Conclusions: This analysis shows the importance of registries as a powerful tool to increase disease awareness, to produce real-world evidence, and to generate questions for future research. However, there is a need to implement strategies to ensure patient retention and long-term sustainability of patient registries, to improve data quality, and to reduce biases

Angiomyolipoma rebound tumor growth after discontinuation of everolimus in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis

Introduction The EXIST-2 (NCT00790400) study demonstrated the superiority of everolimus over placebo for the treatment of renal angiomyolipomas associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (LAM). This post hoc analysis of EXIST-2 study aimed to assess angiomyolipoma tumor behavior among patients who submitted to continued radiographic examination following discontinuation of everolimus in the noninterventional follow-up phase. Methods For patients who discontinued everolimus at the completion of extension phase for reasons other than angiomyolipoma progression, a single CT/MRI scan of the kidney was collected after 1 year of treatment discontinuation. Changes from baseline and from the time of everolimus discontinuation in the sum of volumes of target angiomyolipoma lesions were assessed in the non-interventional follow-up phase (data cutoff date, November 6, 2015). Results Of the 112 patients who received >= 1 dose of everolimus and discontinued treatment by the end of extension phase, 34 (30.4%) were eligible for participation in the non-interventional follow-up phase. Sixteen of 34 patients were evaluable for angiomyolipoma tumor behavior as they had at least one valid efficacy assessment (i.e. kidney CT/MRI scan) after everolimus discontinuation. During the non-interventional follow-up phase, compared with baseline, two patients (12.5%) experienced angiomyolipoma progression (angiomyolipoma-related bleeding [n = 1], increased kidney volume [n = 1]). Five patients out of 16 (31.3%) experienced angiomyolipoma progression when compared with the angiomyolipoma tumor assessment at everolimus discontinuation. The median (range) percentage change in angiomyolipoma tumor volume (cm 3) from baseline was -70.56 (-88.30;-49.64) at time of everolimus discontinuation (n = 11), and -50.55 (-79.40;-23.16) at week 48 (n = 7) after discontinuation of everolimus. One patient death was reported due to angiomyolipoma hemorrhage. Conclusions Angiomyolipoma lesions displayed an increase in volume following discontinuation of everolimus in patients with renal angiomyolipoma or sporadic LAM associated with TSC, but there was no evidence of rapid regrowth

Newly Diagnosed and Growing Subependymal Giant Cell Astrocytoma in Adults With Tuberous Sclerosis Complex: Results From the International TOSCA Study.

The onset and growth of subependymal giant cell astrocytoma (SEGA) in tuberous sclerosis complex (TSC) typically occurs in childhood. There is minimal information on SEGA evolution in adults with TSC. Of 2,211 patients enrolled in TOSCA, 220 of the 803 adults (27.4%) ever had a SEGA. Of 186 patients with SEGA still ongoing in adulthood, 153 (82.3%) remained asymptomatic, and 33 (17.7%) were reported to ever have developed symptoms related to SEGA growth. SEGA growth since the previous scan was reported in 39 of the 186 adults (21%) with ongoing SEGA. All but one patient with growing SEGA had mutations in TSC2. Fourteen adults (2.4%) were newly diagnosed with SEGA during follow-up, and majority had mutations in TSC2. Our findings suggest that surveillance for new or growing SEGA is warranted also in adulthood, particularly in patients with mutations in TSC2