Database of multiparametric geophysical data from the TOMO-DEC experiment on Deception Island, Antarctica

We are grateful to the officers and crew of the Spanish vessels 'R/V Hesperides' and 'R/V Las Palmas', the personnel of the Marine Technology Unit (UTM), the military personnel of the 'Gabriel de Castilla' Spanish base, and the members of the TOMODEC Working Group. This manuscript has been partially funded by the following research projects: the Spanish project TEC2015-68752-R (MINECO/FEDER); KNOWAVES; the Spanish Education and Research Ministry grants REN 2001-3833, CGL2005-05789-C02-02/ANT, POL2006-08663, and CGL2008-01660; the U.S. National Science Foundation grant ANT-0230094; the European project MED-SUV funded by the European Union's Seventh Framework Program for research, technological development and demonstration under grant agreement No 308665; the European project EPOS; the European Union's Horizon 2020 research and innovation programme under grant agreement No 676564; and the U.S. National Science Foundation grant NSF-1521855 Hazard SEES project. Ocean bottom seismometers were provided by the U.S National Oceanographic Instrument Pool. This publication reflects only the authors' views. The European Commission is not responsible for any use that may be made of the information it contains.Deception Island volcano (Antarctica) is one of the most closely monitored and studied volcanoes on the region. In January 2005, a multi-parametric international experiment was conducted that encompassed both Deception Island and its surrounding waters. We performed this experiment from aboard the Spanish oceanographic vessel 'Hesperides', and from five land-based locations on Deception Island (the Spanish scientific Antarctic base 'Gabriel de Castilla' and four temporary camps). This experiment allowed us to record active seismic signals using a large network of seismic stations that were deployed both on land and on the seafloor. In addition, other geophysical data were acquired, including bathymetric high precision multi-beam data, and gravimetric and magnetic profiles. To date, the seismic and bathymetric data have been analysed but the magnetic and gravimetric data have not. We provide P-wave arrival-time picks and seismic tomography results in velocity and attenuation. In this manuscript, we describe the main characteristics of the experiment, the instruments, the data, and the repositories from which data and information can be obtained.MINECO/FEDER TEC2015-68752-RKNOWAVESSpanish Education and Research Ministry REN 2001-3833 CGL2005-05789-C02-02/ANT POL2006-08663 CGL2008-01660National Science Foundation (NSF) ANT-0230094 NSF-1521855European project MED-SUV - European Union's Seventh Framework Program 308665European project EPOSEuropean Union (EU) 67656

The Familial Clustering of Age at Menarche in Extended Twin Families

The timing of puberty is complex, possibly involving many genetic factors that may interact with environmental influences. Familial resemblance for age at menarche was studied in a sample of 4,995 female twins, 1,296 sisters, 2,946 mothers and 635 female spouses of male twins. They had indicated their age at menarche as part of a larger longitudinal survey. We assessed assortative mating for age at menarche, gene–environment interaction effects and estimated the heritability of individual differences in pubertal timing. There was significant evidence of gene–environment interaction, accounting for 1.5% of the variance. There was no indication of consistent mate assortment on age at menarche. Individual differences in age at menarche are highly heritable, with additive genetic factors explaining at least 70% of the true variation. An additional 1.5% of the variation can be explained by a genotype–environment interaction effect where environmental factors are more important in individuals genetically predisposed for late menarche

Metabolism of ticagrelor in patients with acute coronary syndromes.

© The Author(s) 2018Ticagrelor is a state-of-the-art antiplatelet agent used for the treatment of patients with acute coronary syndromes (ACS). Unlike remaining oral P2Y12 receptor inhibitors ticagrelor does not require metabolic activation to exert its antiplatelet action. Still, ticagrelor is extensively metabolized by hepatic CYP3A enzymes, and AR-C124910XX is its only active metabolite. A post hoc analysis of patient-level (n = 117) pharmacokinetic data pooled from two prospective studies was performed to identify clinical characteristics affecting the degree of AR-C124910XX formation during the first six hours after 180 mg ticagrelor loading dose in the setting of ACS. Both linear and multiple regression analyses indicated that ACS patients presenting with ST-elevation myocardial infarction or suffering from diabetes mellitus are more likely to have decreased rate of ticagrelor metabolism during the acute phase of ACS. Administration of morphine during ACS was found to negatively influence transformation of ticagrelor into AR-C124910XX when assessed with linear regression analysis, but not with multiple regression analysis. On the other hand, smoking appears to increase the degree of ticagrelor transformation in ACS patients. Mechanisms underlying our findings and their clinical significance warrant further research.Peer reviewedFinal Published versio

State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS)

PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy

The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury

Cross-cultural neuropsychological assessment in Europe: Position statement of the European Consortium on Cross-Cultural Neuropsychology (ECCroN)

Over the past decades European societies have become increasingly diverse. This diversity in culture, education, and language significantly impacts neuropsychological assessment. Although several initiatives are under way to overcome these barriers - e.g. newly developed and validated test batteries - there is a need for more collaboration in the development and implementation of neuropsychological tests, such as in the domains of social cognition and language. To address these gaps in cross-cultural neuropsychological assessment in Europe, the European Consortium on Cross-Cultural Neuropsychology (ECCroN) was established in 2019. ECCroN recommends taking a broad range of variables into account, such as linguistic factors, literacy, education, migration history, acculturation and other cultural factors. We advocate against race-based norms as a solution to the challenging interpretation of group differences on neuropsychological tests, and instead support the development, validation, and standardization of more widely applicable/cross-culturally applicable tests that take into account interindividual variability. Last, ECCroN advocates for an improvement in the clinical training of neuropsychologists in culturally sensitive neuropsychological assessment, and the development and implementation of guidelines for interpreter-mediated neuropsychological assessment in diverse populations in Europe. ECCroN may impact research and clinical practice by contributing to existing theoretical frameworks and by improving the assessment of diverse individuals across Europe through collaborations on test development, collection of normative data, cross-cultural clinical training, and interpreter-mediated assessment

Metabolomics Reveals Reduction of Metabolic Oxidation in Women with Polycystic Ovary Syndrome after Pioglitazone-Flutamide-Metformin Polytherapy

Polycystic ovary syndrome (PCOS) is a variable disorder characterized by a broad spectrum of anomalies, including hyperandrogenemia, insulin resistance, dyslipidemia, body adiposity, low-grade inflammation and increased cardiovascular disease risks. Recently, a new polytherapy consisting of low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen resulted in the regulation of endocrine clinical markers in young and non-obese PCOS women. However, the metabolic processes involved in this phenotypic amelioration remain unidentified. In this work, we used NMR and MS-based untargeted metabolomics to study serum samples of young non-obese PCOS women prior to and at the end of a 30 months polytherapy receiving low-dose flutamide, metformin and pioglitazone in combination with an estro-progestagen. Our results reveal that the treatment decreased the levels of oxidized LDL particles in serum, as well as downstream metabolic oxidation products of LDL particles such as 9- and 13-HODE, azelaic acid and glutaric acid. In contrast, the radiuses of small dense LDL and large HDL particles were substantially increased after the treatment. Clinical and endocrine-metabolic markers were also monitored, showing that the level of HDL cholesterol was increased after the treatment, whereas the level of androgens and the carotid intima-media thickness were reduced. Significantly, the abundance of azelaic acid and the carotid intima-media thickness resulted in a high degree of correlation. Altogether, our results reveal that this new polytherapy markedly reverts the oxidant status of untreated PCOS women, and potentially improves the pro-atherosclerosis condition in these patients

MFV Reductions of MSSM Parameter Space

The 100+ free parameters of the minimal supersymmetric standard model (MSSM) make it computationally difficult to compare systematically with data, motivating the study of specific parameter reductions such as the cMSSM and pMSSM. Here we instead study the reductions of parameter space implied by using minimal flavour violation (MFV) to organise the R-parity conserving MSSM, with a view towards systematically building in constraints on flavour-violating physics. Within this framework the space of parameters is reduced by expanding soft supersymmetry-breaking terms in powers of the Cabibbo angle, leading to a 24-, 30- or 42-parameter framework (which we call MSSM-24, MSSM-30, and MSSM-42 respectively), depending on the order kept in the expansion. We provide a Bayesian global fit to data of the MSSM-30 parameter set to show that this is manageable with current tools. We compare the MFV reductions to the 19-parameter pMSSM choice and show that the pMSSM is not contained as a subset. The MSSM-30 analysis favours a relatively lighter TeV-scale pseudoscalar Higgs boson and $\tan \beta \sim 10$ with multi-TeV sparticles.Comment: 2nd version, minor comments and references added, accepted for publication in JHE

Tetraspanin (TSP-17) Protects Dopaminergic Neurons against 6-OHDA-Induced Neurodegeneration in <i>C. elegans</i>

Parkinson's disease (PD), the second most prevalent neurodegenerative disease after Alzheimer's disease, is linked to the gradual loss of dopaminergic neurons in the substantia nigra. Disease loci causing hereditary forms of PD are known, but most cases are attributable to a combination of genetic and environmental risk factors. Increased incidence of PD is associated with rural living and pesticide exposure, and dopaminergic neurodegeneration can be triggered by neurotoxins such as 6-hydroxydopamine (6-OHDA). In C. elegans, this drug is taken up by the presynaptic dopamine reuptake transporter (DAT-1) and causes selective death of the eight dopaminergic neurons of the adult hermaphrodite. Using a forward genetic approach to find genes that protect against 6-OHDA-mediated neurodegeneration, we identified tsp-17, which encodes a member of the tetraspanin family of membrane proteins. We show that TSP-17 is expressed in dopaminergic neurons and provide genetic, pharmacological and biochemical evidence that it inhibits DAT-1, thus leading to increased 6-OHDA uptake in tsp-17 loss-of-function mutants. TSP-17 also protects against toxicity conferred by excessive intracellular dopamine. We provide genetic and biochemical evidence that TSP-17 acts partly via the DOP-2 dopamine receptor to negatively regulate DAT-1. tsp-17 mutants also have subtle behavioral phenotypes, some of which are conferred by aberrant dopamine signaling. Incubating mutant worms in liquid medium leads to swimming-induced paralysis. In the L1 larval stage, this phenotype is linked to lethality and cannot be rescued by a dop-3 null mutant. In contrast, mild paralysis occurring in the L4 larval stage is suppressed by dop-3, suggesting defects in dopaminergic signaling. In summary, we show that TSP-17 protects against neurodegeneration and has a role in modulating behaviors linked to dopamine signaling