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The Powell Basin is a small oceanic basin bounded by continental blocks that fragmented during drifting of South America from Antarctica. The basin is limited to the east by the South Orkney Microcontinent, to the north by the South Scotia Ridge, and to the west by the Antarctic Peninsula. The timing of its opening is poorly constrained due to low amplitude magnetic anomalies which hampers their identification and cause large uncertainties in proposed ages that range from the Late Eocene to Early Miocene. The Powell basin has been extensively studied using a variety of geophysical methods including seismic, gravity and magnetic surveys intended to unveil the tectonic domains. The magnetic anomalies and the thermal regime of the basin are of particular interest, as some of these studies have suggested that the absence of clear seafloor magnetic anomalies is the result of impermeable layers that prevent the venting of hot fluids into the water column. Using new magnetic and heat flow data together with geophysical data from international databases, weanalyze the thermal structure of the Powell Basin its lithosphere and the upper mantle dynamics and discuss the probable causes of the abnormally small amplitudes of magnetic anomalies., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Ringvent is a young shallow saucer-shaped sill intrusion emplaced in the Guaymas Basin in the Gulf of California, Mexico. It is an active hydrothermal cooling magmatic intrusion that allows the evaluation of thermomechanical processes involved in the emplacement of these structures in rift environments, practically in real-time.This study aims to provide information about the mechanisms involved in sill emplacement by characterizing the physical properties in the contact zone between the sill and the host rock. The physical data used in this project was taken from ten logs and core samples drilled at the Ringvent site by the IODP 385 expedition. The data set includes measurements of density, permeability, p-wave velocities, and magnetic susceptibility that was analyzed, cleaned and plotted to find patterns in the sediment´s behavior around the sill contact area.As a result of the analysis, we found that some of the factors that contribute to the emplacement of Ringvent are a porosity reduction above the sill, a decrease in the speed of the P-wave velocity, a slight decay in magnetic susceptibility, and the existence of a high-stress resistance layer above the sill.These results were compared to another site in the Guaymas basin, where an older and deeper sill was emplaced, finding similar patterns. This correlation allows us to contribute to the discussion about the factors involved in sill emplacement and argue about if these observed changes are a result of thermal alteration by the sill, or in contrast, they are what determine the depth and shape of the sill., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

The data publication contains the compilation of global heat-flow data by the International Heat Flow Commission (IHFC; www.ihfc-iugg.org) of the International Association of Seismology and Physics of the Earth's Interior (IASPEI). The presented data update 2023 contains data generated between 1939 and 2022 and constitutes the first intermediate update benefiting from the global collaborative assessment and quality control of the Global Heat Flow Database running since May 2021 (http://assessment.ihfc-iugg.org).

OBJETIVOS DE LA GUÍA CLÍNICA 1. Conocer la epidemiología, fisiopatología y factores de riesgo asociados al cáncer cervicouterino. 2. Aplicar las medidas de prevención secundaria de lesiones preinvasoras y cáncer cervicouterino. 3. Aplicar las estrategias de screening de VPH para lesiones preinvasoras y cáncer cervicouterino. 4. Conocer las proyecciones epidemiológicas de cáncer cervicouterino, entregadas por organismos internacionales, posterior a la vacunación universal y las estrategias de screening VPH.

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Myocardial revascularisation represents the most frequently performed therapeutic intervention worldwide. Current percutaneous and surgical revascularisation techniques provide excellent short- and long-term clinical outcomes. However, despite the technological and procedural advances with the widespread use of drug-eluting stents and arterial bypass grafts in contemporary practice, a considerable proportion of patients require repeat revascularisation procedures during long-term follow-up. The need for repeat revascularisation has a major impact on patients' quality of life and is associated with a significant economic burden. This consensus document summarises the views on the management of myocardial revascularisation failure of an expert panel of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). The present document provides a broad and pragmatic overview of the clinical management of myocardial revascularisation failure with a focus on the three key underlying mechanisms leading to repeat revascularisation: 1) failure of percutaneous coronary interventions, 2) failure of coronary artery bypass grafting, and 3) progression of coronary artery disease in native coronary segments previously untreated. The aim of the present position document is to provide a patient-oriented approach for the management of myocardial revascularisation failure.

International Ocean Discovery Program (IODP) Expedition 385 drilled organic-rich sediments with sill intrusions on the flanking regions and in the northern axial graben in Guaymas Basin, a young marginal rift basin in the Gulf of California. Guaymas Basin is characterized by a widely distributed, intense heat flow and widespread off-axis magmatism expressed by a dense network of sill intrusions across the flanking regions, which is in contrast to classical mid-ocean ridge spreading centers. The numerous off-axis sills provide multiple transient heat sources that mobilize buried sedimentary carbon, in part as methane and other hydrocarbons, and drive hydrothermal circulation. The resulting thermal and geochemical gradients shape abundance, composition, and activity of the deep subsurface biosphere of the basin. Drill sites extend over the flanking regions of Guaymas Basin, covering a distance of ~81 km from the from the northwest to the southeast. Adjacent Sites U1545 and U1546 recovered the oldest and thickest sediment successions (to ~540 meters below seafloor [mbsf]; equivalent to the core depth below seafloor, Method A [CSF-A] scale), one with a thin sill (a few meters in thickness) near the drilled bottom (Site U1545), and one with a massive, deeply buried sill (~356–430 mbsf) that chemically and physically affects the surrounding sediments (Site U1546). Sites U1547 and U1548, located in the central part of the northern Guaymas Basin segment, were drilled to investigate a 600 m wide circular mound (bathymetric high) and its periphery. The dome-like structure is outlined by a ring of active vent sites called Ringvent. It is underlain by a remarkably thick sill at shallow depth (Site U1547). Hydrothermal gradients steepen at the Ringvent periphery (Holes U1548A–U1548C), which in turn shifts the zones of authigenic carbonate precipitation and of highest microbial cell abundance toward shallower depths. The Ringvent sill was drilled several times and yielded remarkably diverse igneous rock textures, sediment–sill interfaces, and hydrothermal alteration, reflected by various secondary minerals in veins and vesicles. Thus, the Ringvent sill became the target of an integrated sampling and interdisciplinary research effort that included geological, geochemical, and microbiological specialties. The thermal, lithologic, geochemical, and microbiological contrasts between the two deep northwestern sites (U1545 and U1546) and the Ringvent sites (U1547 and U1548) form the scientific centerpiece of the expedition. These observations are supplemented by results from sites that represent attenuated cold seepage conditions in the central basin (Site U1549), complex and disturbed sediments overlying sills in the northern axial trough (Site U1550), terrigenous sedimentation events on the southeastern flanking regions (Site U1551), and hydrate occurrence in shallow sediments proximal to the Sonora margin (Site U1552). The scientific outcomes of Expedition 385 will (1) revise long-held assumptions about the role of sill emplacement in subsurface carbon mobilization versus carbon retention, (2) comprehensively examine the subsurface biosphere of Guaymas Basin and its responses and adaptations to hydrothermal conditions, (3) redefine hydrothermal controls of authigenic mineral formation in sediments, and (4) yield new insights into many geochemical and geophysical aspects of both architecture and sill–sediment interaction in a nascent spreading center. The generally high quality and high degree of completeness of the shipboard datasets present opportunities for interdisciplinary and multidisciplinary collaborations during shore-based studies. In comparison to Deep Sea Drilling Project Leg 64 to Guaymas Basin in 1979, sophisticated drilling strategies (for example, the advanced piston corer [APC] and half-length APC systems) and numerous analytical innovations have greatly improved sample recovery and scientific yield, particularly in the areas of organic geochemistry and microbiology. For example, microbial genomics did not exist 40 y ago. However, these technical refinements do not change the fact that Expedition 385 will in many respects build on the foundations laid by Leg 64 for understanding Guaymas Basin, regardless of whether adjustments are required in the near future.

The concept of arming antibodies with bioactive payloads for a site-specific therapy of cancer has gained considerable interest in recent years. However, a successful antibody-based targeting approach critically relies on the availability of a tumor-associated target that is not only preferentially expressed in the tumor tissue but is also easily accessible for antibody therapeutics coming from the bloodstream. Here, we perfused the vasculature of healthy and acute myeloid leukemia (AML)-bearing rats with a reactive ester derivative of biotin and subsequently quantified the biotinylated proteins to identify AML-associated bone marrow (BM) antigens accessible from the bloodstream. In total, >1400 proteins were identified. Overall, 181 proteins were >100-fold overexpressed in AML as compared with normal BM. Eleven of the most differentially expressed proteins were further validated by immunohistochemistry and confocal microscopic analyses, including novel antigens highly expressed in AML cells (for example, adaptor-related protein complex 3 β2) and in the leukemia-modified extracellular matrix (ECM) (for example, collagen-VI-α-1). The presented atlas of targetable AML-associated BM proteins provides a valuable basis for the development of monoclonal antibodies that could be used as carriers for a site-specific pharmacodelivery of cytotoxic drugs, cytokines or radionuclides to the BM in AML.

The immediate effect of coronary artery bypass grafting on global and regional myocardial function was studied by means of epicardial two-dimensional echocardiography during operations in 20 patients. Echocardiograms were recorded before cardiopulmonary bypass and 5 and 30 minutes after bypass. Global left ventricular function was expressed as percent short-axis area change and regional function as percent fractional area change. Segments were classified according to their baseline function as normal (percent fractional area change greater than 40%), moderately hypokinetic (percent fractional area change 21% to 40%), or severely dysfunctional (percent fractional area change less than 20%). Percent short-axis area change was significantly reduced immediately after cardiopulmonary bypass (from 42.0% +/- 4.6% to 34.9% +/- 3.0%, p less than 0.05) but had returned to baseline 30 minutes after bypass (42.6% +/- 4.0%). Similarly, function of normal and moderately hypokinetic segments decreased significantly immediately after cardiopulmonary bypass (normal segments: percent fractional area change 56% +/- 0.9% before bypass to 42.3% +/- 1.5% after bypass, p less than 0.0001; moderately hypokinetic segments: 31.0% +/- 0.9% to 25.1% +/- 1.4%, p less than 0.002). Both normal and moderately hypokinetic areas regained baseline function by 30 minutes after bypass (normal segments: 53.4% +/- 1.6%; moderately hypokinetic segments: 35.4% +/- 2.0%). In contrast, severely dysfunctional segments were found to be significantly improved immediately after bypass (14.7% +/- 0.9% before bypass to 27.7% +/- 2.1% after bypass, p less than 0.0001). This improvement was maintained 30 minutes after bypass (22.8% +/- 1.5%, p less than 0.001). We conclude that coronary revascularization exhibits an immediate beneficial effect on chronically underperfused myocardium having severely depressed baseline function. However, in normal and moderately hypokinetic areas, the depressant effects of global ischemia and reperfusion prevail in the immediate postbypass period, leading to a global depression of cardiac function.

Publisher Summary This chapter elaborates the importance of animal models in the study of antiprostatic drugs. The size of the prostate is species-specific being related to that of the testis as it compares to the body size of the respective species. The growth and function of the normal prostate are androgen dependent. The indirect effect of estrogens on the prostate, that is, the inhibition of testicular androgen biosynthesis, causes regressive changes similar in part to those that occur after castration. The weight decreases, there is involution of the epithelium, and the prostate ceases its secretory activity. Mastomys might be a suitable model for the investigation of substances in respect of their effect in prostatic carcinoma. Studies on the hormone dependency or, even better, suppressibility of adenoma tissue have produced some interesting results. The adenoma tissue was influenced neither by estrogens nor by treatment with anti-androgens. The metaplastically changed epithelium behaved differently. It is found that both estrogen and cyproterone acetate treatment led to hydropic vacuolar degeneration.

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Cyproterone acetate (6-chloro-17-acetoxy -1Α,2Α- methylene – 4,6-pregnadiene-3,20-dione) is the strongest antiandrogen known. Beside its androgenicity, this steroid has a strong progestational and thereby a partial antigonadotropic effect. There is vast evidence that the antiandrogenic effect is mainly due to competitive antagonism with androgens at the receptor sites of target organs. Experimental efforts aimed at two directions: (1) Possibilities for clinical use were evaluated and (2) cyproterone acetate was used as a tool for further investigation of testosterone-dependent events, e.g. androgen-dependent processes in the course of sexual differentiation. Almost all androgen-dependent organs and organ systems are affected by cyproterone acetate. Its most important effects in animals and humans are summarized in the following table: Since cyproterone acetate is also a potent progestagen, it could be used in combination with an estrogen as a hormonal contraceptive for women. Its antiandrogenicity would have positive effects in the so-called gestagen/androgen type of women. For use in men, only those antiandrogens would be suitable that have not only antiandrogenic but also gestagenic, hence antigonadotropic properties like cyproterone acetate. ‘Pure’ antiandrogens lacking these partial effects stimulate the secretion of gonadotropins and cause thereby enhanced synthesis and secretion of androgens which would compensate for antiandrogenic effects.

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This paper presents the power performance of the Oscillating Water Column (OWC) wave energy converter installed on the Island of Pico. The performance assessment of the device is based on real performance data gathered over the last years during normal operation. In addition to the estimation and assessment of the wave energy converting capabilities, an investigation has also been made on the transmission of the wave power through the conversion chain.

We contribute to the theoretical understanding of evolutionary algorithms and carry out a parameterized analysis of evolutionary algorithms for the Euclidean traveling salesperson problem (Euclidean TSP). We exploit structural properties related to the optimization process of evolutionary algorithms for this problem and use them to bound the runtime of evolutionary algorithms. Our analysis studies the runtime in dependence of the number of inner points $k$ and shows that simple evolutionary algorithms solve the Euclidean TSP in expected time O(nk(2k-1)!). Moreover, we show that, under reasonable geometric constraints, a locally optimal 2-opt tour can be found by randomized local search in expected time $O(n2kk!).

Platelets and mural thrombus at the lesion site may play a key role in initiating the restenosis process after coronary interventions. The ISAR Trial provides a comparison of the outcomes of patients randomized to two different antithrombotic regimens administered for 4 weeks after successful coronary stent placement: combined antiplatelet therapy (aspirin plus ticlopidine) or a conventional anticoagulant regimen (phenprocoumon with initial overlapping heparin plus aspirin). Within the first 4 weeks after stent placement, combined antiplatelet therapy has been associated with a significant reduction of ischemic complications. In the present study, we examined whether combined antiplatelet therapy administered for 4 weeks after stent placement is able to reduce the process of restenosis at 6 months.Of 517 patients initially randomized, 496 were eligible for 6-month angiographic follow-up. Scheduled angiography was performed in 432 of the eligible patients (87.1%), 216 in each group. In a comparison of the two groups, there were no significant differences in clinical and procedural variables or in qualitative and quantitative lesion characteristics before and after stenting. At 6 months, minimal luminal diameter was 1.95+/-0.86 mm in the group with initial combined antiplatelet therapy and 1.90+/-0.87 mm in the group with initial anticoagulant therapy (P=.55). Late lumen loss was 1.10+/-0.81 and 1.15+/-0.75 mm (P=.54), and the restenosis rate was 26.8% and 28.9%, respectively (P=.70). Target lesion revascularization rate was 14.6% in the antiplatelet therapy group and 15.6% in the anticoagulant therapy group (P=.85).This study shows that combined antiplatelet therapy (aspirin plus ticlopidine) administered for 4 weeks after coronary Palmaz-Schatz stent placement does not result in a detectable benefit for the prevention of restenosis compared with conventional anticoagulant therapy (phenprocoumon with initial overlapping heparin plus aspirin).

SUMMARY Progestogens administered to pregnant mice during the initial period of differentiation of the mammary gland rudiment produced various morphological changes in the mammary rudiments of both male and female foetuses. Norethisterone (17α-ethynyl-Δ4-oestrene-17β-ol-3-one) caused virilization of the rudiments in female foetuses. Medroxyprogesterone acetate (6α-methyl-Δ4-pregnene-17α-ol-3,20-dione-17α-acetate) produced virilization of the rudiments in female and feminization in male foetuses. Gestonorone caproate (19-nor-Δ4-pregnene-17α-ol-3,20-dione-17α-caproate) and allyloestrenol (17α-allyl-Δ4-oestren-17β-ol) tended to cause feminization of some of the mammary rudiments. Androgenic, anti-androgenic or anti-gonadotrophic effects of the investigated substances are considered as possible mechanisms involved in the present findings.

The coronavirus disease 2019 (COVID-19) pandemic poses an unprecedented challenge to healthcare worldwide. The infection can be life threatening and require intensive care treatment. The transmission of the disease poses a risk to both patients and healthcare workers. The number of patients requiring hospital admission and intensive care may overwhelm health systems and negatively affect standard care for patients presenting with conditions needing emergency interventions. This position statements aims to assist cardiologists in the invasive management of acute coronary syndrome (ACS) patients in the context of the COVID-19 pandemic. To that end, we assembled a panel of interventional cardiologists and acute cardiac care specialists appointed by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) and from the Acute Cardiovascular Care Association (ACVC) and included the experience from the first and worst affected areas in Europe. Modified diagnostic and treatment algorithms are proposed to adapt evidence-based protocols for this unprecedented challenge. Various clinical scenarios, as well as management algorithms for patients with a diagnosed or suspected COVID-19 infection, presenting with ST- and non-ST-segment elevation ACS are described. In addition, we address the need for re-organization of ACS networks, with redistribution of hub and spoke hospitals, as well as for in-hospital reorganization of emergency rooms and cardiac units, with examples coming from multiple European countries. Furthermore, we provide a guidance to reorganization of catheterization laboratories and, importantly, measures for protection of healthcare providers involved with invasive procedures.

TLRs, including TLR4, have been shown to play a crucial role in cardiovascular inflammatory-based diseases. The main goal of this study was to determine the potential of FP7, a synthetic glycolipid active as a TLR4 antagonist, to modulate haematopoietic and non-haematopoietic vascular TLR4 pro-inflammatory signalling. HUVEC, human THP-1 monocytes, THP-1-derived macrophages, mouse RAW-264.7 macrophages and Angiotensin II-infused apolipoprotein E-deficient mice were in vitro and in vivo models, respectively. Western blotting, Ab array and ELISA approaches were used to explore the effect of FP7 on TLR4 functional activity in response to bacterial LPS ( in vitro) and endogenous ligands of sterile inflammation ( in vitro and in vivo). Following activation of TLR4, in vitro and in vivo data revealed that FP7 inhibited p38 MAPK and p65 NF-kB phosphorylation associated with down-regulation of a number of TLR4-dependent pro-inflammatory proteins. In addition to inhibition of LPS-induced TLR4 signalling, FP7 negatively regulated TLR4 activation in response to ligands of sterile inflammation (hydroperoxide-rich oxidised LDL, in vitro and Angiotensin II infusion, in vivo). These results demonstrate the ability of FP7 to negatively regulate in vitro and in vivo haematopoietic and non-haematopoietic vascular TLR4 signalling both in humans and mice, suggesting the potential therapeutic use of this TLR4 antagonist for pharmacological intervention of vascular inflammatory diseases.

Background We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens. Methods GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75-100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75-100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with followup completed. Findings Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3.81%) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4.37%) participants in the control group (rate ratio 0.87 [95% CI 0. 75-1. 01]; p=0.073]). There was no evidence for a difference in treatment effects for the primary endpoint across prespecified subgroups of acute coronary syndromes and stable coronary artery disease (p=0.93). Grade 3 or 5 bleeding occurred in 163 participants in the experimental group and 169 in the control group (2.04% vs 2.12%; rate ratio 0.97 [95% CI 0. 78-1. 20]; p=0.77). Interpretation Ticagrelor in combination with aspirin for 1 month followed by ticagrelor alone for 23 months was not superior to 12 months of standard dual antiplatelet therapy followed by 12 months of aspirin alone in the prevention of all-cause mortality or new Q-wave myocardial infarction 2 years after percutaneous coronary intervention. Copright (C) 2018 Elsevier Ltd. All rights reserved. European Clinical Research Institute; Biosensors International; AstraZeneca; Medicines Company; Canada Research Chairs Programme

Objectives:\ud The toll-like receptors (TLRs), including TLR4, have been shown to play a crucial role in vascular inflammatory diseases, such as atherosclerosis and aneurysm. The main goal of this study was to determine the potential of IAXO-102 (Innaxon, Tewkesbury), a novel small molecule TLR4 antagonist, to modulate non-hematopoietic TLR4 proinflammatory signalling and inhibit experimental abdominal aortic aneurysm (AAA) development.\ud \ud Methods:\ud Human umbilical vein endothelial cells (HUVEC) and Angiotensin II-induced experimental AAA development were our in vitro and in vivo models respectively. Western blotting, antibody array and ELISA approaches were used to explore the effect of IAXO-102 on TLR4 functional activity on two levels: modulation of TLR4-induced mitogen activated protein kinases (MAPK) and p65 NF-kB phosphorylation and expression of TLR4 dependent proinflammatory proteins.\ud \ud Results:\ud Following activation of TLR4, in vitro/in vivo data revealed that IAXO-102 inhibited MAPK and p65 NF-kB phosphorylation associated with down regulation of the expression of TLR4 and TLR4 dependent proinflammatory proteins. Furthermore, IAXO-102 decreased Angiotensin II-induced aortic expansion, rupture and incidence of AAA.\ud \ud Conclusions:\ud These results demonstrate the ability of IAXO-102 to negatively regulate TLR4 signalling and to inhibit experimental AAA development, suggesting the potential therapeutic use of this TLR4 antagonist for pharmacological intervention of AAA.