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Immune thrombocytopenia (ITP) is a disease characterized by platelet destruction, presenting substantial challenges in clinical practice. The classic first line therapeutic management includes corticosteroids and intravenous immunoglobulins. Although it is less frequent in children than in adults, there is a significant percentage of patients, up to 47% according to the Pediatric and Adult Registry on Chronic ITP, who require second-line or further treatment, due to non-response to the first line treatment or persistence of disease, among other reasons. Several second line approaches for its treatment are currently in use, including increasing platelet production with thrombopoietin receptor agonists. We report the case of a 16-year-old patient with ITP and alopecia areata successfully treated with baricitinib, a reversible and selective JAK 1/2 inhibitor. Baricitinib is currently in use for the treatment of several autoimmune conditions and has been shown to increase platelet counts in these patients. This phenomenon has been linked to increased TPO signaling and reduced platelet destruction. There are promising preliminary results of adult ITP patients treated with baricitinib. This case report is the first reported use of baricitinib in ITP in the pediatric and adolescent setting, potentially leading to its use in this condition.

Abstract We quantify the effect of dust accumulation at Jezero crater by means of a Dust Correction Factor (DCF) for the solar radiation measured by the photodiodes of the Radiation and Dust Sensor of the Mars 2020 mission. After one Mars Year, dust on the photodiode surface attenuated 25%–30% of the incoming solar radiation. The DCF did not decrease monotonically; we use a model to reproduce its evolution and to derive dust deposition and lifting rates, showing that dust removal is 9 times larger at Jezero crater than at InSight's location in western Elysium Planitia. The model fit obtained using observed opacities is further improved when fed with dust sedimentation rates simulated by a GCM that considers a particle size distrtibution. Projections show seasonal net dust removal, being encouraging for the long‐term survival of solar‐powered missions to Jezero or similarly active dust lifting regions.

Abstract Background For soaring birds, the ability to benefit from variable airflow dynamics is crucial, especially while crossing natural barriers such as vast water bodies during migration. Soaring birds also take advantage of warm rising air, so-called thermals, that allow birds to ascend passively to higher altitudes with reduced energy costs. Although it is well known that soaring migrants generally benefit from supportive winds and thermals, the potential of uplifts and other weather factors enabling soaring behavior remains unsolved. Methods In this study, we GPS-tracked 19 Red Kites, Milvus milvus, from the Central European population that crossed the Adriatic Sea on their autumn migration. Migratory tracks were annotated with weather data (wind support, side wind, temperature difference between air and surface—proxy for thermal uplift, cloud cover, and precipitation) to assess their effect on Red Kites' decisions and soaring performance along their migration across the Adriatic Sea and land. Results Wind support affected the timing of crossing over the Adriatic Sea. We found that temperature differences and horizontal winds positively affected soaring sea movement by providing lift support in otherwise weak thermals. Furthermore, we found that the soaring patterns of tracked raptors were affected by the strength and direction of prevailing winds. Conclusion Thanks to modern GPS–GSM telemetry devices and available data from online databases, we explored the effect of different weather variables on the occurrence of soaring behavior and soaring patterns of migratory raptors. We revealed how wind affected the soaring pattern and that tracked birds could soar in weak thermals by utilizing horizontal winds, thus reducing energy costs of active flapping flight over vast water bodies.

La realización de estudios sobre el estado de conservación previo a las intervenciones rehabilitadoras y restauradoras permite conocer y actuar de forma coherente sobre el patrimonio arquitectónico. En esta línea se ha llevado a cabo la investigación de localización gráfica de alteraciones, estudio puntual de materiales de alteración y medición de parámetros ambientales (T y H) en las yeserías del Oratorio de la Madraza de Granada, espacio singular por sus antecedentes históricos y constructivos. Los resultados obtenidos determinan el nivel de alteración y presencia de los diferentes deterioros, así como la justificación de las causas de alteración que los han motivado. Igualmente se valida la metodología seguida en este estudio, consistente en diversos protocolos sucesivos que facilitan la determinación de las intervenciones restauradoras. De igual manera este método puede ser extrapolable a otros edificios con alto nivel de protección patrimonial.

Santa Pudia limestone, a biocalcarenite highly sensitive to decay, is one of the most commonly used building materials in historical monuments in the city of Granada, Spain. The compatibility between a variety of stone treatments (consolidants and/or water repellents) and this calcarenite was analyzed and the resulting improvement in durability assessed. To this end, a two-stage accelerated ageing process was implemented. In the first, freshly quarried, undamaged specimens were altered to resemble the weathered stone in buildings. The second was conducted after applying the various treatments to the artificially aged stone to test their effectiveness. While all the treatments studied (Tegosivin HL100, Silo 111, Estel 1100 and Tegovakon V) enhanced stone resistance to decay while barely affecting chromatic parameters, the most effective was Tegowakon V, as it provided the best results in the hydric tests on the limestone.

“Sierra Elvira stone” is one of the ornamental building stones most widely used in the historical monuments of eastern Andalusia. A Liassic age limestone, it appears in the central section of the Baetic Mountains and more specifically in the Middle Subbaetic domain. While the most common variety is a crinoid limestone, a micritic limestone of the same age has also been quarried, albeit in much smaller quantities. These stones form very thick beds, up to nearly 5 m deep, that run in consistently parallel lines and have a dip angle that facilitates quarrying. With petrographic, physical and mechanical properties that ensure stone strength and durability, it is a high quality building material suitable for both structural and ornamental purposes. These properties can be attributed to the minimal open porosity and concomitant excellent water resistance that characterize the stone, as well as to its high mechanical strength and low textural anisotropy, both elastic and mechanical. With such attributes, the stone can be successfully used for any number of purposes, including decorative stonework (portals, fountains, plinths), structural members (column shafts and bases) or urban curbing and paving. Intervention on Sierra de Elvira limestone structures should be limited to cleaning or repair, for consolidating or protective materials are scantly effective.

This work focuses on the chemical-mineralogical, textural and physical-mechanical properties of hydraulic lime mortars made with siliceous and calcareous aggregate. Mortars were cured at 60% and 90% of relative humidity, so as to assess the variability of mortar petrophysical properties in the hardened state due to the moisture conditions. The final aim was to determine the most adequate moisture conditions to be maintained during application and hardening of hydraulic mortars intended for repair interventions. We found out that using a calcareous aggregate and curing mortar at 90% of relative humidity give place to better textural and mechanical properties. However, these characteristics mostly depend on the maximum size of the aggregate grains, which should be smaller than 6 mm, in order to avoid the occurrence of mechanical discontinuities in the mortar.

We have studied the physical-mechanical behaviour of solid bricks treated with consolidants and/or water-repellents in accelerated aging tests to determine their durability. The bricks were manufactured with a quartz-rich clay lacking in carbonates to which was added small amounts of different additives (calcite, dolomite or sodium chloride). During the manufacturing process, we attempted to replicate solid bricks similar to those used in many Cultural Heritage buildings. We have concluded that silicon resin gives the best results, whatever the additive used, whereas acrylic resin gives the least satisfactory results.

Se ha realizado un estudio geoquímico de la fracción arcillosa de los sedimentos miopliocenos y de la muestra total de rocas metamórficas de los relieves adyacentes con el fin de determinar las características geoquímicas del medio de sedimentación y la influencia de las rocas circundantes sobre los sedimentos. Tras relacionar elementos químicos con rocas y minerales mediante un (ACP), se ha realizado una clasificación jerárquica ascendente (CJA), que ha reagrupado las muestras con características geoquímicas similares en 8 clases. La comparación gráfica de su composición geoquímica media pone de manifiesto una clara relación genética entre los sedimentos y las rocas metapelíticas de la Cordillera Bética oriental, siendo la influencia de gneises, rocas carbonatadas metamórficas y metabasitas muy localizada o inexistente. Finalmente, los contenidos de B y Mg nos han permitido distinguir varios tipos de medios de depósito que presentan diferentes grados de confinamiento y que, en relación con los cambios del nivel del mar producidos durante la crisis messiniense, se han visto influenciados sucesivamente por aguas marinas y continentales.

Synthetic biology (SynBio) is a rapidly advancing multidisciplinary field in which South American countries such as Chile, Argentina, and Brazil have made notable contributions and have established leadership positions in the region. In recent years, efforts have strengthened SynBio in the rest of the countries, and although progress is significant, growth has not matched that of the aforementioned countries. Initiatives such as iGEM and TECNOx have introduced students and researchers from various countries to the foundations of SynBio. Several factors have hindered progress in the field, including scarce funding from both public and private sources for synthetic biology projects, an underdeveloped biotech industry, and a lack of policies to promote bio-innovation. However, open science initiatives such as the DIY movement and OSHW have helped to alleviate some of these challenges. Similarly, the abundance of natural resources and biodiversity make South America an attractive location to invest in and develop SynBio projects.

Background and aims: We aimed to determine the association of carotid intima media thickness (CIMT), carotid plaques, and heart function with peak systolic velocity (PSV) of the common (CCA) and internal carotid artery (ICA) in a cross-sectional study. Methods: In the population-based Hamburg-City-Health-Study participants between 45 and 74 years were recruited. Cardio-vascular risk factors were assessed by history, blood samples, and clinical examination. CIMT, plaques, and PSV were determined by carotid ultrasound. Serum N-terminal brain natriuretic peptide (NT-proBNP) was determined as a biomarker for cardiac dysfunction, and left ventricular ejection fraction (LVEF) was quantified by echocardiography. Participants with carotid stenosis were excluded. Data were analyzed by multivariate linear regression. Results: We included 8567 participants, median age was 62 years, 51.8% were women. Median CIMT was 0.75 mm, NT-proBNP 80 pg/ml, LVEF 58.5%, and 30.4% had carotid plaques. For women PSV decreased in decades from 89 to 73 cm/s in CCAs and 78 to 66 cm/s in ICAs, and for men from 91 to 76 cm/s in CCAs and from 70 to 66 cm/s in ICAs. Corrected for age, sex, red blood cell count, and blood pressure, in CCAs lower PSV was associated with carotid plaques (p

Abstract Background Heparin is used worldwide for 70 years during all non-cardiac arterial procedures (NCAP) to reduce thrombo-embolic complications (TEC). But heparin also increases blood loss causing possible harm for the patient. Heparin has an unpredictable effect in the individual patient. The activated clotting time (ACT) can measure the effect of heparin. Currently, this ACT is not measured during NCAP as the standard of care, contrary to during cardiac interventions, open and endovascular. A RCT will evaluate if ACT-guided heparinization results in less TEC than the current standard: a single bolus of 5000 IU of heparin and no measurements at all. A goal ACT of 200–220 s should be reached during ACT-guided heparinization and this should decrease (mortality caused by) TEC, while not increasing major bleeding complications. This RCT will be executed during open abdominal aortic aneurysm (AAA) surgery, as this is a standardized procedure throughout Europe. Methods Seven hundred fifty patients, who will undergo open AAA repair of an aneurysm originating below the superior mesenteric artery, will be randomised in 2 treatment arms: 5000 IU of heparin and no ACT measurements and no additional doses of heparin, or a protocol of 100 IU/kg bolus of heparin and ACT measurements after 5 min, and then every 30 min. The goal ACT is 200–220 s. If the ACT after 5 min is < 180 s, 60 IU/kg will be administered; if the ACT is between 180 and 200 s, 30 IU/kg. If the ACT is > 220 s, no extra heparin is given, and the ACT is measured after 30 min and then the same protocol is applied. The expected incidence for the combined endpoint of TEC and mortality is 19% for the 5000 IU group and 11% for the ACT-guided group. Discussion The ACTION-1 trial is an international RCT during open AAA surgery, designed to show superiority of ACT-guided heparinization compared to the current standard of a single bolus of 5000 IU of heparin. A significant reduction in TEC and mortality, without more major bleeding complications, must be proven with a relevant economic benefit. Trial registration {2a} NTR NL8421 ClinicalTrials.gov NCT04061798 . Registered on 20 August 2019 EudraCT 2018-003393-27 Trial registration: data set {2b} Data category Information Primary registry and trial identifying number ClinicalTrials.gov : NCT04061798 Date of registration in primary registry 20-08-2019 Secondary identifying numbers NTR: NL8421 EudraCT: 2018-003393-27 Source(s) of monetary or material support ZonMw: The Netherlands Organisation for Health Research and Development Dijklander Ziekenhuis Amsterdam UMC Primary sponsor Dijklander Ziekenhuis Secondary sponsor(s) N/A Contact for public queries A.M. Wiersema, MD, PhD Arno@wiersema.nu 0031-229 208 206 Contact for scientific queries A.M. Wiersema, MD, PhD Arno@wiersema.nu 0031-229 208 206 Public title ACT Guided Heparinization During Open Abdominal Aortic Aneurysm Repair (ACTION-1) Scientific title ACTION-1: ACT Guided Heparinization During Open Abdominal Aortic Aneurysm Repair, a Randomised Trial Countries of recruitment The Netherlands. Soon the recruitment will start in Germany Health condition(s) or problem(s) studied Abdominal aortic aneurysm, arterial disease, surgery Intervention(s) ACT-guided heparinization 5000 IU of heparin Key inclusion and exclusion criteria Ages eligible for the study: ≥18 years Sexes eligible for the study: both Accepts healthy volunteers: no Inclusion criteria: Study type Interventional Allocation: randomized Intervention model: parallel assignment Masking: single blind (patient) Primary purpose: treatment Phase IV Date of first enrolment March 2020 Target sample size 750 Recruitment status Recruiting Primary outcome(s) The primary efficacy endpoint is 30-day mortality and in-hospital mortality during the same admission. The primary safety endpoint is the incidence of bleeding complications according to E-CABG classification, grade 1 and higher. Key secondary outcomes Serious complications as depicted in the Suggested Standards for Reports on Aneurysmal disease: all complications requiring re-operation, longer hospital stay, all complications

Abstract Dynamic parameters of preload have been widely recommended to guide fluid therapy based on the principle of fluid responsiveness and with regard to cardiac output. An equally important aspect is however to also avoid volume-overload. This accounts particularly when capillary leakage is present and volume-overload will promote impairment of microcirculatory blood flow. The aim of this study was to evaluate, whether an impairment of intestinal microcirculation caused by volume-load potentially can be predicted using pulse pressure variation in an experimental model of ischemia/reperfusion injury. The study was designed as a prospective explorative large animal pilot study. The study was performed in 8 anesthetized domestic pigs (German landrace). Ischemia/reperfusion was induced during aortic surgery. 6 h after ischemia/reperfusion-injury measurements were performed during 4 consecutive volume-loading-steps, each consisting of 6 ml kg−1 bodyweight−1. Mean microcirculatory blood flow (mean Flux) of the ileum was measured using direct laser-speckle-contrast-imaging. Receiver operating characteristic analysis was performed to determine the ability of pulse pressure variation to predict a decrease in microcirculation. A reduction of ≥ 10% mean Flux was considered a relevant decrease. After ischemia–reperfusion, volume-loading-steps led to a significant increase of cardiac output as well as mean arterial pressure, while pulse pressure variation and mean Flux were significantly reduced (Pairwise comparison ischemia/reperfusion-injury vs. volume loading step no. 4): cardiac output (l min−1) 1.68 (1.02–2.35) versus 2.84 (2.15–3.53), p = 0.002, mean arterial pressure (mmHg) 29.89 (21.65–38.12) versus 52.34 (43.55–61.14), p

Background Despite high female prevalence of peripheral artery disease (PAD), little is known about sex‐based outcomes after lower extremity revascularization (LER) for symptomatic PAD. The effects of rivaroxaban according to sex following LER have not been fully reported. Methods and Results In VOYAGER PAD (Vascular Outcomes Study of ASA [acetylsalicylic acid] Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease), low‐dose rivaroxaban versus placebo on a background of aspirin reduced the composite primary efficacy outcome of cardiovascular and limb events in patients with PAD undergoing LER. Unplanned index limb revascularization was prespecified and prospectively ascertained. The primary safety outcome was Thrombolysis in Myocardial Infarction major bleeding. Analyses of outcomes and treatment effects by sex were performed using Cox proportional hazards models. Among 6564 randomly assigned patients followed for a median of 28 months, 1704 (26.0%) were women. Among patients administered placebo, women were at similar risk for the primary efficacy outcome (hazard ratio [HR], 0.90; [95% CI, 0.74–1.09]; P=0.29) as men, while female sex was associated with a trend toward higher risk of unplanned index limb revascularization (HR, 1.18; [95% CI, 1.00–1.40]; P=0.0499). Irrespective of sex, effects of rivaroxaban were consistent for the primary efficacy outcome (P‐interaction=0.22), unplanned index limb revascularization (P‐interaction=0.64), and bleeding (P‐interaction=0.61). Women were more likely than men to discontinue study treatment (HR, 1.13; [95% CI, 1.03–1.25]; P=0.0099). Conclusions Among >1700 women with PAD undergoing LER, women and men were at similar risk for the primary outcome, but a trend for greater risk of unplanned index limb revascularization among women was observed. Effects of rivaroxaban were consistent by sex, though women more often discontinued treatment. Better understanding of sex‐based outcomes and treatment adherence following LER is needed. Registration URL: http://clinicaltrials.gov; Unique identifier: NCT02504216.

Este documento deve ser referenciado citando também a versão original em Inglês: Björck M, Earnshaw JJ, Acosta S, Bastos Gonçalves F, Cochennec F, Debus ES, Hinchliffe R, Jongkind V, Koelemay MJW, Menyhei G, Svetlikov AV, Tshomba Y, Van Den Berg JC, Esvs Guidelines Committee, de Borst GJ, Chakfé N, Kakkos SK, Koncar I, Lindholt JS, Tulamo R, Vega de Ceniga M, Vermassen F, Document Reviewers, Boyle JR, Mani K, Azuma N, Choke ETC, Cohnert TU, Fitridge RA, Forbes TL, Hamady MS, Munoz A, Müller-Hülsbeck S, Rai K. Editor's Choice - European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Acute Limb Ischaemia. Eur J Vasc Endovasc Surg. 2020 Feb;59(2):173-218. Epub 2019 Dec 31. PMID: 31899099. Published by Elsevier B.V. on behalf of European Society for Vascular Surgery. https://doi.org/10.1016/j.ejvs.2019.09.006

Background An increasing number of patients with a peripheral arterial occlusive disease were put on statins during the past years. This study assessed whether statin therapy was effective and safe for these new users. Methods and Results Using health insurance claims data from Germany’s second‐largest insurance fund, BARMER, we identified patients with peripheral arterial occlusive disease who had index revascularization between 2008 and 2018 without prior statin therapy. We compared patients with and without statin therapy in addition to antithrombotics during the first quarter after discharge (new users versus nonusers). Outcomes were all‐cause mortality, cardiovascular events, and incident major amputation for effectiveness and incident diabetes mellitus and incident myopathy for safety. Propensity score matching was used to balance the study groups. All analyses were stratified into patients with chronic limb‐threatening ischemia and intermittent claudication. A total of 22 208 patients (mean age 71.1 years and 50.3% women) were included in the study. In 10 922 matched patients, statin initiation was associated with lower all‐cause mortality (chronic limb‐threatening ischemia: hazard ratio [HR], 0.75 [95% CI, 0.68–0.84]; intermittent claudication: HR, 0.80 [95% CI, 0.70–0.92]), lower risk of major amputation in patients with chronic limb‐threatening ischemia (HR, 0.73; 95% CI, 0.58–0.93) and lower risk of cardiovascular events (hazard ratio, 0.80; 95% CI, 0.70–0.92) in patients with intermittent claudication during 5 years of follow‐up. Safety outcomes did not differ among the study groups. Conclusions Initiating statin therapy in patients with peripheral arterial occlusive disease after index revascularization is efficient and safe with an effect size comparable to earlier studies. Awareness campaigns for evidence‐based optimal pharmacological treatment among patients are recommended.

Introduction: Quality registries can be used to study treatment patterns and changes in trends of complications related to procedures and devices. To ensure that such study is possible in registries, there is a need to use standardised variables and the registry must have high internal and external validity. This study was an international external and internal validation of the newly initiated Maltese Vascular Registry. Report: Two international vascular registry consultants visited the Maltese Vascular Registry (MVR), and conducted an external validation on all carotid and aortic aneurysm repairs performed in 2017–18. The external validation was conducted by comparing hospital administration lists with the MVR list. Using randomly chosen numbers, an internal validation was conducted of 20 random cases of carotid and 20 aortic aneurysms, 10 from 2017 and 10 from 2018, to validate date of operation and procedure against the patient's medical record. The registry is built as a database using national personal identifier codes, with variables for date and type of procedure, and anaesthetic method used, to which a note is attached describing the indication, intervention, and follow up. Between the hospital registry and the MVR, 111 of 115 cases could be identified correctly, corresponding to 97% external validity. Between the patient case records and the MVR, the dates and procedures of 20/20 carotid and 20/20 aortic aneurysm procedure were identical, indicating 100% internal validity. Discussion: The MVR showed an external validity of 97% and internal validity of 100%. Future work should incorporate specific variables for comorbidity, procedures, and outcomes, with the registry aiming to incorporate international recommended variables for comorbidity, procedure, and outcome.

(1) Background: Difficulty hearing in noise is exacerbated in older adults. Older adults are more likely to have audiometric hearing loss, although some individuals with normal pure-tone audiograms also have difficulty perceiving speech in noise. Additional variables also likely account for speech understanding in noise. It has been suggested that one important class of variables is the ability to process auditory information once it has been detected. Here, we tested a set of these “suprathreshold” auditory processing abilities and related them to performance on a two-part test of speech understanding in competition with and without spatial separation of the target and masking speech. Testing was administered in the Portable Automated Rapid Testing (PART) application developed by our team; PART facilitates psychoacoustic assessments of auditory processing. (2) Methods: Forty-one individuals (average age 51 years), completed assessments of sensitivity to temporal fine structure (TFS) and spectrotemporal modulation (STM) detection via an iPad running the PART application. Statistical models were used to evaluate the strength of associations between performance on the auditory processing tasks and speech understanding in competition. Age and pure-tone-average (PTA) were also included as potential predictors. (3) Results: The model providing the best fit also included age and a measure of diotic frequency modulation (FM) detection but none of the other potential predictors. However, even the best fitting models accounted for 31% or less of the variance, supporting work suggesting that other variables (e.g., cognitive processing abilities) also contribute significantly to speech understanding in noise. (4) Conclusions: The results of the current study do not provide strong support for previous suggestions that suprathreshold processing abilities alone can be used to explain difficulties in speech understanding in competition among older adults. This discrepancy could be due to the speech tests used, the listeners tested, or the suprathreshold tests chosen. Future work with larger numbers of participants is warranted, including a range of cognitive tests and additional assessments of suprathreshold auditory processing abilities.

Background and aim. The occurrence of malignant pleural mesothelioma (MPM) has been reported among population groups with no documented professional exposure to asbestos fibres living in different geographic areas. This paper reviews existing data related to non occupational MPM including its occurrence in the province of Catania (Sicily, Italy). Methods. An electronic search of literature related to non occupational MPM was performed including the year 2005. Results. Non occupational MPM in subjects living in areas contaminated by a variety of asbestos and non asbestos fibres has been well documented through a number of epidemiologic studies including cases series, case-control studies, and a cohort study. In addition, the observation of familial clustering of MPM, suggests that genetic factors may play a role in the pathogenesis of this malignancy. The epidemiological evidence also suggests that MPM may occur as a result of the interaction between environmental carcinogens, genetic factors, and virus infection. Conclusion. It is likely that genetic predisposition and non-occupational exposure to low doses of asbestos and asbestos- like fibres may concur to the development of malignant mesothelioma. However, additional epidemiological and laboratory studies are needed to further understand the relationship between environmental exposure and individual susceptibility to this malignancy.

En nuestro país, el grupo de pacientes Adultos Mayores (sobre 65 años) ha tenido un crecimiento explosivo en los últimos años, reflejo de la expectativa de vida que ha aumentado casi 10 años desde 1981 a la fecha. Con mayor frecuencia, el grupo etario en cuestión requiere ingreso a Unidades más complejas. Estudios internacionales estiman que los adultos mayores ocupan en promedio más de la mitad de los días cama de las Unidades de Tratamiento Intensivo (UTI) a nivel mundial y están cobrando relevancia en la Medicina Intensiva dada particularidades específicas que presentan para su manejo en estas unidades. En Chile, existen escasos datos acerca de ingresos y mortalidad en este grupo de pacientes en las UTI. El objetivo de esta revisión es mostrar datos epidemiológicos de la realidad local en relación a pacientes admitidos en la UTI del Centro de Pacientes Críticos (CPC) de Clínica Las Condes (CLC).