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Abstract Sclerocorneal grafts are procedures considered in cases with extensive corneal and scleral tissue destruction. The study aims to describe sclerokeratoplasty outcomes in severely diseased eyes. We performed a retrospective review of clinical records. Demographic characteristics, medical history, surgical indications, aetiology of perforation, visual outcomes, complications associated with the surgical procedure, and ocular integrity at the end of the follow-up were obtained. Wilcoxon-signed rank tests and Mann-Whitney tests were used to compare complications between groups and outcomes at final follow-up. Survival analysis was performed to analyse vision preservation and global integrity and presented in Kaplan-Meier curves. 40 eyes from 40 patients with a mean age of 48.83 ± 18.85 years and a mean follow-up of 21.13 ± 33.92 months were included in the study. Median corrected visual acuity before and after the procedure remained at 2.8 logMAR. Twenty-seven eyes presented complications. The most common complications were a persistent epithelial defect in 11, hypertension in 10, and perforation in 8 eyes. More than half of the eyes (67.5%) presented with either one or more of all complications after corneoscleral graft. No significant differences were found regarding age, gender, or DM history. Concerning perforation, a significant difference was found between infectious and non-infectious only in the presentation of ocular hypertension (p = 0.048). Vision was preserved in 72.5% of the eyes, with a median survival probability of 4.12 years. Preservation of the ocular integrity was achieved in 85% of the eyes, with a median survival probability of 12 years. Sclerokeratoplasty despite being challenging and technically demanding followed by defiant complications, in some situations such as infectious keratitis and autoimmune diseases, is likely a procedure that salvages the eye and preserves vision.

Abstract: Introduction: Psychological treatments are becoming an increasingly important component of medical healthcare, as a growing number of people seek treatment for a wide range of mental health problems. While these treatments are known to be effective, much remains to be understood about their mechanisms and reasons for effectiveness. The study of statistical mediators is crucial in psychological research, as it is fundamental to understanding how psychological factors influence health, well-being, and human behavior, and thus to designing effective psychological interventions. Aim: This study investigates the role of resilience as a treatment mediator in PROCARE+, a brief transdiagnostic, personalized protocol for the selective prevention of emotional disorders in adolescents. This approach has proven effective for young people at risk of developing emotional issues. Method: We used simple mediation models in a sample of 153 adolescents to assess the impact of interventions on resilience. Outcome variables included self-reported and parent-reported emotional risk, mood, anxiety symptoms, and quality of life. Discussion: The results of this study provide valuable information on how PROCARE+ works and how to improve its effectiveness, pointing to resilience as a key mediator in reducing the risk of developing emotional disorders and improving quality of life.

Large vesicle extrusion from neurons may contribute to spreading pathogenic protein aggregates and promoting inflammatory responses, two mechanisms leading to neurodegenerative disease. Factors that regulate the extrusion of large vesicles, such as exophers produced by proteostressed C. elegans touch neurons, are poorly understood. Here, we document that mechanical force can significantly potentiate exopher extrusion from proteostressed neurons. Exopher production from the C. elegans ALMR neuron peaks at adult day 2 or 3, coinciding with the C. elegans reproductive peak. Genetic disruption of C. elegans germline, sperm, oocytes, or egg/early embryo production can strongly suppress exopher extrusion from the ALMR neurons during the peak period. Conversely, restoring egg production at the late reproductive phase through mating with males or inducing egg retention via genetic interventions that block egg-laying can strongly increase ALMR exopher production. Overall, genetic interventions that promote ALMR exopher production are associated with expanded uterus lengths and genetic interventions that suppress ALMR exopher production are associated with shorter uterus lengths. In addition to the impact of fertilized eggs, ALMR exopher production can be enhanced by filling the uterus with oocytes, dead eggs, or even fluid, supporting that distention consequences, rather than the presence of fertilized eggs, constitute the exopher-inducing stimulus. We conclude that the mechanical force of uterine occupation potentiates exopher extrusion from proximal proteostressed maternal neurons. Our observations draw attention to the potential importance of mechanical signaling in extracellular vesicle production and in aggregate spreading mechanisms, making a case for enhanced attention to mechanobiology in neurodegenerative disease.

This research article presents a comparison between two mainstream Deep Reinforcement Learning (DRL) algorithms, Asynchronous Advantage Actor-Critic (A3C) and Proximal Policy Optimization (PPO), in the context of two diverse environments: CartPole and Lunar Lander. DRL algorithms are widely known for their effectiveness in training agents to navigate complex environments and achieve optimal policies. Nevertheless, a methodical assessment of their effectiveness in various settings is crucial for comprehending their advantages and disadvantages. In this study, we conduct experiments on the CartPole and Lunar Lander environments using both A3C and PPO algorithms. We compare their performance in terms of convergence speed and stability. Our results indicate that A3C typically achieves quicker training times, but exhibits greater instability in reward values. Conversely, PPO demonstrates a more stable training process at the expense of longer execution times. An evaluation of the environment is needed in terms of algorithm selection, based on specific application needs, balancing between training time and stability. A3C is ideal for applications requiring rapid training, while PPO is better suited for those prioritizing training stability.

This perspective paper introduces a novel framework for container orchestration called CODECO. The CODECO orchestration framework relies on a data-network-computing approach to define the best infrastructure that can support the operation of next-generation Internet applications across a mobile, heterogeneous Edge-Cloud continuum. The selection of such an infrastructure is aligned with target performance profiles defined by the user, such as resilience or greenness. CODECO proposes to rely on decentralized Artificial Intelligence approaches to provide the most suitable infrastructure to an application deployment, considering infrastructural challenges, such as intermittent connectivity and node failure. This paper explains the current CODECO framework and gives insight into operational use-cases where CODECO is being deployed, as relevant examples of application for such a framework. Recent developments in the creation of the open-source CODECO framework are described and explained, allowing the use of the framework by the research community. The paper then provides a thorough analysis of CODECO’s features in comparison with existing orchestration frameworks, explaining the benefits introduced with this dynamic orchestration approach.

No-Reference video quality assessment has become a trending and challenging hot topic in estimating perceived quality in audiovisual content. In this paper, we present a proposal to considerably reduce the computational cost of video processing without losing accuracy in QoE estimation. Tests have been performed using the Video-MOS SaaS solution, a hybrid NR-VQA solution based on perceptible video distortions and a machine learning approach. After exploring the spatial and temporal redundancy present in a video sequence, the final approach combines video metric feature extraction in both high and low video resolution, together with a specific frame selection based on a uniform temporal sampling and frame type at the video coding level. An extensive validation with more than 144 hours of audiovisual content from six of the most important HD channels of DTT in Spain demonstrates the validity of the approach, ensuring real-time application on the test device, with computational cost savings of 94.96% and an obtained MOS error of 0.1144, in more than 174000 3-second measurements.

Objectives The core objectives of this study centre on enhancing the quality of life and well-being of individuals diagnosed with Parkinson’s and Alzheimer’s diseases. Our aim is to facilitate the monitoring of patient information, benefiting both caregivers and healthcare professionals. Methods As part of the PROCare4Life platform sensorial ecosystem, a web application with six engaging cognitive games focusing on developing cognitive training and stimulating brain activity are developed. A set of metrics calculated by the application feed machine learning predictive models to evaluate the cognitive status and evolution over time. Long-term analysis of the daily cognitive ability information is used to generate high-level outcomes and identify deviations for each patient from the multimodal fusion engine. And based on these results, a recommender system provides a set of personalized notifications. Results A 3-month pilot study that took place in five different countries shows the results obtained from 93 patients. An average of 22.4 games were completed per day and the recommender system generated a total of 260 game notifications, 37.7% of them were marked as read by the patients. The Cognitive State Score and the Deviations in Cognitive Abilities measurement, calculated by the multimodal fusion engine, when used in conjunction present a good overview of the patient’s current state and potential deviations. Conclusion The cognitive games application was well-received by elderly individuals who took part in the study. This tool can be valuable for caregivers and healthcare providers in assessing the cognitive function of patients through engaging in cognitive games.

Abstract Significant evidence does exist on the effectiveness of transdiagnostic interventions to improve emotional problems in clinical populations, and their application as universal and indicated prevention programs. However, no randomized controlled trials (RCT) studying selective transdiagnostic prevention intervention have been published. This is the first known RCT to evaluate the efficacy/effectiveness of an evidence-based selective prevention transdiagnostic program for emotional problems in adolescents. The impact of three different interventions was evaluated: (1) PROCARE (Preventive transdiagnostic intervention for Adolescents at Risk for Emotional disorders), which is a group-based, abbreviated version of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A), along with adding a booster session to reduce risk of onset of anxiety and depression, (2) PROCARE + , which includes the PROCARE protocol along with personalized add-on modules tailored to match adolescents’ risk factors, and (3) an active control condition (ACC) based on emotional psychoeducation. In total, 208 adolescents (48.5% girls) evidencing high risk and low protective factors were randomized and allocated to PROCARE, PROCARE + or ACC. Data from 153 adolescents who completed all assessments in the different phases of the study were analyzed. Self- and parent-reported measures were taken at baseline, as well as after the intervention, a 6 month follow-up was carried out, together with a 1 month follow-up after the booster session. Differences between conditions were significant on most of the outcome measures, with superior effect sizes for PROCARE + in the short and long term. Interventions were acceptable in terms of acceptability, with good satisfaction rates. Tailored targeted selective transdiagnostic interventions focused on mitigating risk factors and promoting protective factors in vulnerable adolescents are promising.

Abstract Introduction Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. Biologic drugs have a key role in the long-term anti-inflammatory treatment of moderate to severe patients due to their immunomodulatory properties. The aim of this study is to evaluate the effectiveness and safety of secukinumab in patients with moderate to severe HS after 16 weeks of treatment, and to explore potential predictors of clinical response to the drug. Methods Multicenter observational retrospective study. Patients treated with secukinumab 300 mg every 2 or 4 weeks who had completed at least 16 weeks of follow-up from nine hospitals based in southern Spain (Andalusia) were included in this study. Treatment effectiveness was assessed using the Hidradenitis Suppurativa Clinical Response (HiSCR). Information about adverse events was collected, the therapeutic burden of the patients was calculated as the summation of systemic medical treatments and surgical interventions (excluding incision and drainage) experienced until the start of secukinumab treatment. Results Forty-seven patients with severe HS were included for analysis. At week 16, 48.9% (23/47) of patients achieved HiSCR. Adverse events were present in 6.4% (3/47) of the patients. The multivariate analysis showed that female sex and, to a lesser extent, lower body mass index (BMI) and a lower therapeutic burden were potentially associated with a higher probability of HiSCR achievement. Conclusions Favorable short-term effectiveness and safety of secukinumab in the treatment of severe HS patients were observed. Female sex, lower BMI and a lower therapeutic burden may be associated with a higher probability of achieving HiSCR.

In this study, we investigate the impact of COVID-19 on academic achievement in Texas public schools. Demographic and Grade 5 STAAR test data were collected from 1155 public school districts for 2018–2019 and 2020–2021. Multiple regression was adopted to analyze the differences between rural and non-rural districts, as well as the impact of demographic characteristics on students’ achievement. The results reveal significant differences in demographic characteristics between the two academic years, with non-rural districts exhibiting a greater decline in academic achievement than rural districts. Additionally, the findings suggest that higher teacher salaries correlate with better academic performance across various subjects and that English learners require additional support to acquire content knowledge and skills. We further confirm that the COVID-19 pandemic has disrupted the academic learning experience of Texas students, with rural districts displaying more resilience than non-rural districts.

A first modeling approximation of the general performance of radiofrequency (RF) switches based on hexagonal boron nitride (hBN), a two-dimensional (2D) dielectric material is presented. The I-V characteristics intrinsic and extrinsic impedance parameters, the return loss, insertion loss and isolation of RF 2D switches fabricated with hBN are described here by a equivalent circuit models. Straightforward analytical expressions are obtained. In contrast to conventional switches, the unique RF performance of the hBN switch, at ON-state, i.e., a direct improvement with frequency of the insertion loss, is accurately described by considering a capacitor in the intrinsic part of the model. The latter is suggested to be related to storaged charge during the resistive switching mechanism. The highest mean relative error obtained between modeling and measurements of the return loss is of 7.6% with the approach presented here which overcomes the 42.5% of difference obtained with a previous model with an incomplete intrinsic device description.

Introduction: Right ventricular dysfunction (RVD) is a key component in the process of risk stratification in patients with acute pulmonary embolism (PE). Echocardiography remains the gold standard for RVD assessment, however, measures of RVD may be seen on CTPA imaging, including increased pulmonary artery diameter (PAD). The aim of our study was to evaluate the association between PAD and echocardiographic parameters of RVD in patients with acute PE. Methods: Retrospective analysis of patients diagnosed with acute PE was conducted at large academic center with an established pulmonary embolism response team (PERT). Patients with available clinical, imaging, and echocardiographic data were included. PAD was compared to echocardiographic markers of RVD. Statistical analysis was performed using the Student's t test, Chi-square test, or one-way analysis of variance (ANOVA); P < 0.05 was considered statistically significant. Results: 270 patients with acute PE were identified. Patients with a PAD >30 mm measured on CTPA had higher rates of RV dilation (73.1% vs 48.7%, P < 0.005), RV systolic dysfunction (65.4% vs 43.7%, P < 0.005), and RVSP >30 mmHg (90.2% vs 68%, P = 0.004), but not TAPSE ≤1.6 cm (39.1% vs 26.1%, P = 0.086). A weak increasing linear relationship between PAD and RVSP was noted (r = 0.379, P = 0.001). Conclusions: Increased PAD in patients with acute PE was significantly associated with echocardiographic markers of RVD. Increased PAD on CTPA in acute PE can serve as a rapid prognostic tool and assist with PE risk stratification at the time of diagnosis, allowing rapid mobilization of a PERT team and appropriate resource utilization.

Abstract Significant evidence does exist on the effectiveness of transdiagnostic interventions to improve emotional problems in clinical populations, and their application as universal and indicated prevention programs. However, no randomized controlled trials (RCT) studying selective transdiagnostic prevention intervention have been published. This is the first known RCT to evaluate the efficacy/effectiveness of an evidence-based selective prevention transdiagnostic program for emotional problems in adolescents. The impact of three different interventions was evaluated: (1) PROCARE (Preventive transdiagnostic intervention for Adolescents at Risk for Emotional disorders), which is a group-based, online-delivered, abbreviated version of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Adolescents (UP-A), along with adding a booster session, to reduce risk of onset of anxiety and depression, (2) PROCARE + , which includes the PROCARE protocol along with personalized add-on modules tailored to match adolescents’ risk factors, and (3) an active control condition (ACC) based on emotional psychoeducation. In total, 286 adolescents (53.3% girls) evidencing high risk and low protective factors were randomized and allocated to PROCARE, PROCARE + or ACC. Self- and parent-reported measures were taken at baseline, as well as after the intervention, a 6-month follow-up was carried out, together with a 1-month follow-up after the booster session. Differences between conditions were significant on most of the outcome measures, with superior effect sizes for PROCARE +. Interventions were excellent in terms of acceptability, with good satisfaction rates. Tailored selective transdiagnostic interventions focused on mitigating risk factors and promoting protective factors in vulnerable adolescents are promising.

The digitalization of the road transport sector necessitates the exploration of new sensing technologies that are cost-effective, high-performing, and durable. Traditional sensing systems suffer from limitations, including incompatibility with asphalt mixtures and low durability. To address these challenges, the development of self-sensing asphalt pavements has emerged as a promising solution. These pavements are composed of stimuli-responsive materials capable of exhibiting changes in their electrical properties in response to external stimuli such as strain, damage, temperature, and humidity. Self-sensing asphalt pavements have numerous applications, including in relation to structural health monitoring (SHM), traffic monitoring, Digital Twins (DT), and Vehicle-to-Infrastructure Communication (V2I) tools. This paper serves as a foundation for the advancement of self-sensing asphalt pavements by providing a comprehensive review of the underlying principles, the composition of asphalt-based self-sensing materials, laboratory assessment techniques, and the full-scale implementation of this innovative technology.

There is a genetic component to the risk of severe COVID-19, but the genetic effects are difficult to separate from social constructs that covary with genetic ancestry. To address this, the authors identify determinants of COVID-19 severity using admixture mapping, viral phylodynamics, and host immune and metagenomic sequencing.

Abstract Background Growing evidence suggests the relationship between obstructive sleep apnea (OSA) and venous thromboembolism (VTE). Few studies focused on VTE recurrence risk associated with OSA after anticoagulation cessation. Methods In a prospective cohort study, patients with documented VTE, were followed for an indefinite length of time and VTE recurrence were documented and adjudicated. The primary outcome was recurrent VTE after anticoagulation discontinuation. Secondary outcomes included all-cause mortality and the clinical presentation of VTE. Univariable and multivariable analyses were performed to identify risk factors for recurrence and mortality. Results Among the 2109 patients with documented VTE included, 74 patients had moderate to severe OSA diagnosis confirmed by home sleep test or polysomnography. During a median follow-up of 4.8 (interquartile range 2.5–8.0) years recurrent VTE occurred in 252 patients (9 with OSA and 243 without OSA). The recurrence risk in the univariable and multivariable analysis was not increased in patients with OSA, regardless of the time of diagnosis (before or after index VTE or pooled). VTE phenotype was significantly more often PE with or without associated deep vein thrombosis in the first event and recurrence for OSA patients compared to non-OSA patients. The risk of death was not increased in the OSA population compared to non-OSA patients in multivariable analysis. Conclusions In patients with OSA and VTE, the risk of all-cause mortality and VTE recurrence after anticoagulation discontinuation was not increased compared to non-OSA patients.

Zika virus (ZIKV) infects fetal neural progenitor cells (NPCs) causing severe neurodevelopmental disorders in utero. Multiple pathways involved in normal brain development are dysfunctional in infected NPCs but how ZIKV centrally reprograms these pathways remains unknown. Here we show that ZIKV infection disrupts subcellular partitioning of host transcripts critical for neurodevelopment in NPCs and functionally link this process to the up-frameshift protein 1 (UPF1). UPF1 is an RNA-binding protein known to regulate decay of cellular and viral RNAs and is less expressed in ZIKV-infected cells. Using infrared crosslinking immunoprecipitation and RNA sequencing (irCLIP-Seq), we show that a subset of mRNAs loses UPF1 binding in ZIKV-infected NPCs, consistent with UPF1's diminished expression. UPF1 target transcripts, however, are not altered in abundance but in subcellular localization, with mRNAs accumulating in the nucleus of infected or UPF1 knockdown cells. This leads to diminished protein expression of FREM2, a protein required for maintenance of NPC identity. Our results newly link UPF1 to the regulation of mRNA transport in NPCs, a process perturbed during ZIKV infection.

Abstract We determined sex differences in the prevalence of obstructive sleep apnea (OSA) among patients hospitalized with pulmonary embolism (PE) in Spain (2016–2018). We also compared outcomes according to the presence of OSA, and identified variables associated with in-hospital-mortality (IHM) after PE using the Spanish National Hospital Discharge Database. We identified 46,794 hospital admissions for PE; of these, 5.47% had OSA. OSA was more prevalent among men than women (7.57% vs. 3.65%, p 0.05). Older age, cancer, atrial fibrillation, non-septic shock, and need for mechanical ventilation increased IHM in men and women with OSA hospitalized with PE. The logistic regression model showed no sex differences in IHM among patients with OSA.

In vitro fertilization (IVF) has resulted in the birth of over 8 million children. Although most IVF-conceived children are healthy, several studies suggest an increased risk of altered growth rate, cardiovascular dysfunction, and glucose intolerance in this population compared to naturally conceived children. However, a clear understanding of how embryonic metabolism is affected by culture condition and how embryos reprogram their metabolism is unknown. Here, we studied oxidative stress and metabolic alteration in blastocysts conceived by natural mating or by IVF and cultured in physiologic (5%) or atmospheric (20%) oxygen. We found that IVF-generated blastocysts manifest increased reactive oxygen species, oxidative damage to DNA/lipid/proteins, and reduction in glutathione. Metabolic analysis revealed IVF-generated blastocysts display decreased mitochondria respiration and increased glycolytic activity suggestive of enhanced Warburg metabolism. These findings were corroborated by altered intracellular and extracellular pH and increased intracellular lactate levels in IVF-generated embryos. Comprehensive proteomic analysis and targeted immunofluorescence showed reduction of lactate dehydrogenase-B and monocarboxylate transporter 1, enzymes involved in lactate metabolism. Importantly, these enzymes remained downregulated in the tissues of adult IVF-conceived mice, suggesting that metabolic alterations in IVF-generated embryos may result in alteration in lactate metabolism. These findings suggest that alterations in lactate metabolism are a likely mechanism involved in genomic reprogramming and could be involved in the developmental origin of health and disease.

The digital transition that drives the new industrial revolution is largely driven by the application of intelligence and data. This boost leads to an increase in energy consumption, much of it associated with computing in data centers. This fact clashes with the growing need to save and improve energy efficiency and requires a more optimized use of resources. The deployment of new services in edge and cloud computing, virtualization, and software-defined networks requires a better understanding of consumption patterns aimed at more efficient and sustainable models and a reduction in carbon footprints. These patterns are suitable to be exploited by machine, deep, and reinforced learning techniques in pursuit of energy consumption optimization, which can ideally improve the energy efficiency of data centers and big computing servers providing these kinds of services. For the application of these techniques, it is essential to investigate data collection processes to create initial information points. Datasets also need to be created to analyze how to diagnose systems and sort out new ways of optimization. This work describes a data collection methodology used to create datasets that collect consumption data from a real-world work environment dedicated to data centers, server farms, or similar architectures. Specifically, it covers the entire process of energy stimuli generation, data extraction, and data preprocessing. The evaluation and reproduction of this method is offered to the scientific community through an online repository created for this work, which hosts all the code available for its download.

PurposeTo evaluate repeatability, reproducibility, and accordance between ocular surface measurements within three different imaging devices.MethodsWe performed an observational study on 66 healthy eyes. Tear meniscus height, non-invasive tear break-up time (NITBUT) and meibography were measured using three corneal imaging devices: Keratograph 5M (Oculus, Wetzlar, Germany), Antares (Lumenis, Sidney, Australia), and LacryDiag (Quantel Medical, Cournon d’Auvergne, France). One-way ANOVAs with post hoc analyses were used to calculate accordance between the tear meniscus and NITBUT. Reproducibility was assessed through coefficients of variation and repeatability with intraclass correlation coefficients (ICC). Reliability of meibography classification was analyzed by calculating Fleiss’ Kappa Index and presented in Venn diagrams.ResultsCoefficients of variation were high and differed greatly depending on the device and measurement. ICCs showed moderate reliability of NITBUT and tear meniscus height measurements. We observed discordance between measurements of tear meniscus height between the three devices, F2, 195 = 15.24, p < 0.01. Measurements performed with Antares were higher; 0.365 ± 0.0851, than those with Keratograph 5M and LacryDiag; 0.293 ± 0.0790 and 0.306 ± 0.0731. NITBUT also showed discordance between devices, F2, 111 = 13.152, p < 0.01. Measurements performed with LacryDiag were lower (10.4 ± 1.82) compared to those of Keratograph 5M (12.6 ± 4.01) and Antares (12.6 ± 4.21). Fleiss’ Kappa showed a value of -0.00487 for upper lid and 0.128 for inferior lid Meibography classification, suggesting discrete to poor agreement between measurements.ConclusionDepending on the device used and parameter analyzed, measurements varied between each other, showing a difference in image processing.

The presence of spiny butterfly rays, Gymnura altavela, in waters less than 20 m deep off the Canary Islands shows marked seasonality, with relatively high abundances in the summer and autumn. Large aggregations of sometimes hundreds of individuals, primarily females, appear in specific shallow areas of the archipelago and seem to be associated with the seasonal variation in water temperature. This seasonal pattern of presence or absence in shallow areas suggests that spiny butterfly rays migrate into deeper waters or other unknown areas during the rest of the year. G. altavela shows sexual dimorphism; in our study, females were larger and more abundant than males, with a sex ratio of 1:18.9. The species’ estimated asymptotic length, L∞, was 183.75 cm and thus close to the common length reported for the species (200 cm). The von Bertalanffy growth constant (k) oscillated between 0.210 and 0.310 year−1, as similarly described for the species in the Western North Atlantic off the U.S. coast. From June to November, the seawater temperature oscillated between 19 and 24 °C, and massive aggregations of females occurred at 22–24 °C and in a few specific sandy beaches on the islands. Spiny butterfly rays, mostly females, show a preference for aggregating in shallow waters during summertime, probably conditionate to mating or breeding behaviour.

Abstract Background Renal dysfunction influences outcomes after pulmonary embolism (PE). We aimed to determine the incremental value of adding renal dysfunction, defined by estimated glomerular filtration rate (eGFR), on top of the European Society of Cardiology (ESC) prognostic model, for the prediction of 30-day mortality in acute PE patients, which in turn could lead to the optimization of acute PE management. Methods We performed a multicenter, non-interventional retrospective post hoc analysis based on a prospectively collected cohort including consecutive confirmed acute PE stratified per ESC guidelines. We first identified which of three eGFR formulae most accurately predicted death. Changes in global model fit, discrimination, calibration and reclassification parameters were evaluated with the addition of eGFR to the prognostic model. Results Among 1943 patients (mean age 67.3 (17.1), 50.4% women), 107 (5.5%) had died at 30 days. The 4-variable Modification of Diet in Renal Disease (eGFRMDRD4) formula predicted death most accurately. In total, 477 patients (24.5%) had eGFRMDRD4

Abstract Background The treatment of venous thromboembolic disease the treatment of choice is systemic anticoagulation. However, the interruption of the inferior vena cava with filters has been recommended when anticoagulation fails or there is a contraindication. Due to the rising inferior vena cava filter (IVCF) complications, physicians are encouraged to retrieve them when there is no longer recommended. In daily practice, it may be a difficult close follow-up of these patients. In this study, the primary objective was to evaluate the IVCF retrieval rate of all implanted filters in a Spanish registry. Secondary objectives were to analyze the causes of failed retrieval, procedure-related complications, and outcomes at a 12-month follow-up. Results Three hundred fifty-six vena cava filters were implanted in 355 patients. The types of filter were: Gunther Tulip (Cook Medical) 160 (44.9%), Optease (Cordis) 77 (21.6%), Celect (Cook Medical) 49 (13, 7%), Aegisy (Lifetech Scientific) 33 (9.2%), Option ELITE (Argon Medical devices) 16 (4.4%), Denali filter (BD Bard) 11 (3.08%), ALN filter (ALN) 10 (2.8%). Removal was achieved in 274/356 (76,9%). eighty-two (23,1%) IVCF were not retrieved due to the following: 41 (11,5%) patients required ongoing filtration, 24 IVCF (6,7%) patients died before retrieval, and 17 (4,7%) impossibility of retrieval because of a tilted and embedded filter apex. There were no major complications observed. Conclusions The global retrieval rate of IVCF was achieved in 76.9%, and the adjusted retrieval rate was of 94.15% with no major complications. IVCF tilting was associated with failure of filter removal in less than 5% of cases. This study demonstrates that the retrieval procedure of IVCF is controlled by the clinician and not by the interventional radiologist.

We present a graphene-based phase shifter for radio-frequency (RF) phase-array applications. The core of the designed phase-shifting system consists of a graphene field-effect transistor (GFET) used in a common source amplifier configuration. The phase of the RF signal is controlled by exploiting the quantum capacitance of graphene and its dependence on the terminal transistor biases. In particular, by independently tuning the applied gate-to-source and drain-to-source biases, we observe that the phase of the signal, in the super-high frequency band, can be varied nearly 200° with a constant gain of 2.5 dB. Additionally, if only the gate bias is used as control signal, and the drain is biased linearly dependent on the former (i.e., in a completely analogue operation), a phase shift of 85° can be achieved making use of just one transistor and keeping a gain of 0 dB with a maximum variation of 1.3 dB. The latter design can be improved by applying a balanced branch-line configuration showing to be competitive against other state-of-the-art phase shifters. This work paves the way towards the exploitation of graphene technology to become the core of active analogue phase shifters for high-frequency operation.

ABSTRACT Ceragenins are a family of synthetic amphipathic molecules designed to mimic the properties of naturally occurring cationic antimicrobial peptides (CAMPs). Although ceragenins have potent antimicrobial activity, whether their mode of action is similar to that of CAMPs has remained elusive. Here, we reported the results of a comparative study of the bacterial responses to two well-studied CAMPs, LL37 and colistin, and two ceragenins with related structures, CSA13 and CSA131. Using transcriptomic and proteomic analyses, we found that Escherichia coli responded similarly to both CAMPs and ceragenins by inducing a Cpx envelope stress response. However, whereas E. coli exposed to CAMPs increased expression of genes involved in colanic acid biosynthesis, bacteria exposed to ceragenins specifically modulated functions related to phosphate transport, indicating distinct mechanisms of action between these two classes of molecules. Although traditional genetic approaches failed to identify genes that confer high-level resistance to ceragenins, using a Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) approach we identified E. coli essential genes that when knocked down modify sensitivity to these molecules. Comparison of the essential gene-antibiotic interactions for each of the CAMPs and ceragenins identified both overlapping and distinct dependencies for their antimicrobial activities. Overall, this study indicated that, while some bacterial responses to ceragenins overlap those induced by naturally occurring CAMPs, these synthetic molecules target the bacterial envelope using a distinctive mode of action. IMPORTANCE The development of novel antibiotics is essential because the current arsenal of antimicrobials will soon be ineffective due to the widespread occurrence of antibiotic resistance. The development of naturally occurring cationic antimicrobial peptides (CAMPs) for therapeutics to combat antibiotic resistance has been hampered by high production costs and protease sensitivity, among other factors. The ceragenins are a family of synthetic CAMP mimics that kill a broad spectrum of bacterial species but are less expensive to produce, resistant to proteolytic degradation, and seemingly resistant to the development of high-level resistance. Determining how ceragenins function may identify new essential biological pathways of bacteria that are less prone to the development of resistance and will further our understanding of the design principles for maximizing the effects of synthetic CAMPs.

Resumen: La economía del comportamiento (que aúna economía y psicología) ofrece claves para entender las decisiones tomadas por dirigentes políticos y por la ciudadanía durante la pandemia de COVID-19 a través de los llamados sesgos cognitivos. Estos sesgos pueden ser contrarrestados mediante intervenciones conductuales, denominadas nudges, para promocionar conductas responsables en la «nueva normalidad». Además de repasar, desde la óptica de la economía del comportamiento, el pasado, el presente y el futuro de los elementos conductuales que rodean a la pandemia y su gestión, este artículo propone la formalización jurídica de los nudges, para lo cual deben cumplirse tres estándares mínimos: la exigencia de transparencia, la proscripción de la arbitrariedad y la puesta en valor de su eficiencia. Sugerimos, de igual forma, diseñar protocolos para futuras pandemias, de suerte que los nudges y las medidas legislativas duras puedan complementarse de una manera armónica y escalonada. Los nudges se prestan a una implementación rápida y poco coercitiva, por lo que resultan especialmente apropiados en orden al encauzamiento de las conductas más leves, pudiendo así reservarse otras medidas, como las sanciones, para las situaciones más graves. Abstract: Behavioural economics (a combination of economics and psychology) provides keys to understand decisions made by politicians and citizens along the COVID-19 pandemic through the so-called cognitive biases. These biases can be offset by implementing behavioural interventions named “nudges” in order to promote responsible behaviours in the “new normality”. This paper analyses, from a behavioural economics perspective, past, present and future of behavioural aspects surrounding the pandemic. Besides, this paper proposes different ways to formalize nudges according to law, which needs the fulfilment of three minimum requirements, namely: transparency, non-arbitrariness and efficiency. Furthermore, it is also suggested that protocols and contingency plans are set up to face future pandemics, in which both soft (nudge-type) interventions and hard legal regulations play different roles but complementary ones. Nudges can be implemented in a fast and less coercive way, so they are particularly suitable for changing mild misbehaviour, reserving legal sanctions for the more serious ones.

Different hip pathologies can cause geometric variation of the acetabulum and femoral head. These variations have been considered as an underlying mechanism that affects the tribology of the natural hip joint and changes the stress distribution on the articular surface, potentially leading to joint degradation. To improve understanding of the damage mechanisms and abnormal mechanics of the hip joint, a reliable in-vitro methodology that represents the in vivo mechanical environment is needed where the position of the joint, the congruency of the bones and the loading and motion conditions are clinically relevant and can be modified in a controlled environment. An in vitro simulation methodology was developed and used to assess the effect of loading on a natural hip joint. Porcine hips were dissected and mounted in a single station hip simulator and tested under different loading scenarios. The loading and motion cycle consisted of a simplified gait cycle and three peak axial loading conditions were assessed (Normal, Overload and Overload Plus). Joints were lubricated with Ringer's solution and tests were conducted for 4 hours. Photographs were taken and compared to characterise cartilage surface and labral tissue pre, during and post simulation. The results showed no evidence of damage to samples tested under normal loading conditions, whereas the samples tested under overload and overload plus conditions exhibited different severities of tears and detachment of the labrum at the antero-superior region. The location and severity of damage was consistent for samples tested under the same conditions; supporting the use of this methodology to investigate further effects of altered loading and motion on natural tissue.

Nowadays the rationalization of electrical energy consumption is a serious concern worldwide. Energy consumption reduction and energy efficiency appear to be the two paths to addressing this target. To achieve this goal, many different techniques are promoted, among them, the integration of (artificial) intelligence in the energy workflow is gaining importance. All these approaches have a common need: data. Data that should be collected and provided in a reliable, accurate, secure, and efficient way. For this purpose, sensing technologies that enable ubiquitous data acquisition and the new communication infrastructure that ensure low latency and high density are the key. This article presents a sensing solution devoted to the precise gathering of energy parameters such as voltage, current, active power, and power factor for server farms and datacenters, computing infrastructures that are growing meaningfully to meet the demand for network applications. The designed system enables disaggregated acquisition of energy data from a large number of devices and characterization of their consumption behavior, both in real time. In this work, the creation of a complete multiport power meter system is detailed. The study reports all the steps needed to create the prototype, from the analysis of electronic components, the selection of sensors, the design of the Printed Circuit Board (PCB), the configuration and calibration of the hardware and embedded system, and the implementation of the software layer. The power meter application is geared toward data centers and server farms and has been tested by connecting it to a laboratory server rack, although its designs can be easily adapted to other scenarios where gathering the energy consumption information was needed. The novelty of the system is based on high scalability built upon two factors. Firstly, the one-on-one approach followed to acquire the data from each power source, even if they belong to the same physical equipment, so the system can correlate extremely well the execution of processes with the energy data. Thus, the potential of data to develop tailored solutions rises. Second, the use of temporal multiplexing to keep the real-time data delivery even for a very high number of sources. All these ensure compatibility with standard IoT networks and applications, as the data markup language is used (enabling database storage and computing system processing) and the interconnection is done by well-known protocols.

Summary: Cold-induced thermogenesis in endotherms demands adaptive thermogenesis fueled by mitochondrial respiration and Ucp1-mediated uncoupling in multilocular brown adipocytes (BAs). However, dietary regulation of thermogenesis in BAs isn’t fully understood. Here, we describe that the deficiency of Leucine-rich pentatricopeptide repeat containing-protein (Lrpprc) in BAs reduces mtDNA-encoded ETC gene expression, causes ETC proteome imbalance, and abolishes the mitochondria-fueled thermogenesis. BA-specific Lrpprc knockout mice are cold resistant in a 4°C cold-tolerance test in the presence of food, which is accompanied by the activation of transcription factor 4 (ATF4) and proteome turnover in BAs. ATF4 activation genetically by BA-specific ATF4 overexpression or physiologically by a low-protein diet feeding can improve cold tolerance in wild-type and Ucp1 knockout mice. Furthermore, ATF4 activation in BAs improves systemic metabolism in obesogenic environment regardless of Ucp1’s action. Therefore, our study reveals a diet-dependent but Ucp1-independent thermogenic mechanism in BAs that is relevant to systemic thermoregulation and energy homeostasis.

Media applications are amongst the most demanding services. They require high amounts of network capacity as well as computational resources for synchronous high-quality audio–visual streaming. Recent technological advances in the domain of new generation networks, specifically network virtualization and Multiaccess Edge Computing (MEC) have unlocked the potential of the media industry. They enable high-quality media services through dynamic and efficient resource allocation taking advantage of the flexibility of the layered architecture offered by 5G. The presented work demonstrates the potential application of Artificial Intelligence (AI) capabilities for multimedia services deployment. The goal was targeted to optimize the Quality of Experience (QoE) of real-time video using dynamic predictions by means of Deep Reinforcement Learning (DRL) algorithms. Specifically, it contains the initial design and test of a self-optimized cloud streaming proof-of-concept. The environment is implemented through a virtualized end-to-end architecture for multimedia transmission, capable of adapting streaming bitrate based on a set of actions. A prediction algorithm is trained through different state conditions (QoE, bitrate, encoding quality, and RAM usage) that serves the optimizer as the encoding values of the environment for action prediction. Optimization is applied by selecting the most suitable option from a set of actions. These consist of a collection of predefined network profiles with associated bitrates, which are validated by a list of reward functions. The optimizer is built employing the most prominent algorithms in the DRL family, with the use of two Neural Networks (NN), named Advantage Actor–Critic (A2C). As a result of its application, the ratio of good quality video segments increased from 65% to 90%. Furthermore, the number of image artifacts is reduced compared to standard sessions without applying intelligent optimization. From these achievements, the global QoE obtained is clearly better. These results, based on a simulated scenario, increase the interest in further research on the potential of applying intelligence to enhance the provisioning of media services under real conditions.

Ancient ecological legacies and past land use changes may inform on the present structure of biological communities. However, regions providing such successive ecosystems are scarce. In France, the ‘Landes de Gascogne’ area provides such ecological shifts since a few ancient moorland, peatland and oak areas prior the afforestation with maritime pine (Pinus pinaster) 160 years ago still remain. Focusing on soil-borne parasites such as plant-parasitic nematodes (PPN), because forests were recently increasingly impacted by the introduction of intensive agriculture, this study is therefore aimed at comparing the diversity and the community patterns of these organisms at different scales (intra- and intersites) and between different successive ecosystems. The understory vegetation as well as the pedo-climatic characterization of the sampled sites were also considered. Common diversity indices were not impacted by this transition from ancient to past ecosystems. Although the most colonizer nematodes prevailed in all the ecosystems, PPN community structures significantly diverged between both ecosystems. In the logged pine forests, the sediment legacy could have primarily impacted the diversity. Moreover, the PPN diversity would mainly respond to the soil hydromorphicity that determined the associated understory vegetation. Consequently, a significant shift in community structure from moorlands to logged pine to logged pine forests was observed, regarding especially high pathogenic species such as Pratylenchus spp. Thus, analyzing PPN community structure highlights the PPN potential risk to consider during the introduction of intensive cropping systems.

Most countries affected by the COVID-19 pandemic have repeatedly restricted public life to control the contagion. However, the health impact of confinement measures is hitherto unclear. We performed a multinational survey investigating changes in mental and physical well-being (MWB/PWB) during the first wave of the pandemic. A total of 14,975 individuals from 14 countries provided valid responses. Compared to pre-restrictions, MWB, as measured by the WHO-5 questionnaire, decreased considerably during restrictions (68.1 ± 16.9 to 51.9 ± 21.0 points). Whereas 14.2% of the participants met the cutoff for depression screening pre-restrictions, this share tripled to 45.2% during restrictions. Factors associated with clinically relevant decreases in MWB were female sex (odds ratio/OR = 1.20, 95% CI: 1.11–1.29), high physical activity levels pre-restrictions (OR = 1.29, 95% CI 1.16–1.42), decreased vigorous physical activity during restrictions (OR = 1.14, 95% CI: 1.05–1.23), and working (partially) outside the home vs. working remotely (OR = 1.29, 95% CI: 1.16–1.44/OR = 1.35, 95% CI: 1.23–1.47). Reductions, although smaller, were also seen for PWB. Scores in the SF-36 bodily pain subscale decreased from 85.8 ± 18.7% pre-restrictions to 81.3 ± 21.9% during restrictions. Clinically relevant decrements of PWB were associated with female sex (OR = 1.62, 95% CI: 1.50–1.75), high levels of public life restrictions (OR = 1.26, 95% CI: 1.18–1.36), and young age (OR = 1.10, 95% CI: 1.03–1.19). Study findings suggest lockdowns instituted during the COVID-19 pandemic may have had substantial adverse public health effects. The development of interventions mitigating losses in MWB and PWB is, thus, paramount when preparing for forthcoming waves of COVID-19 or future public life restrictions.

High-intensity interval training (HIIT) has numerous external load control variables. The management of these variables makes the physiological responses and performance presented by athletes also modify. The present study aimed to assess the activity of CK and LDH enzymes, performance and metabolic responses caused by two HIIT protocols above the maximum in male recreational runners. Fifteen recreational male runners performed two HIIT protocols in randomized order with multiple conditions: 1) H15 (n = 15), with a HIIT protocol of 15:15 work-recovery duration, and 2) H30 (n = 15) with a HIIT protocol of 30:30 work-recovery duration. Both protocols were performed at similar intensity (130% vV̇O2max), one set until voluntary exhaustion. Blood samples were collected and used to capture the levels and activities of blood lactate (BLac: mmol⋅L–1), glucose (GLU: mg⋅dL–1), creatine kinase (CK: U⋅L–1), and lactate dehydrogenase (LDH: U⋅L–1). BLac and GLU were collected at pre, five, and ten minutes after the H15 and H30 protocols were performed. Blood samples were used to measure the activities of CK and LDH enzymes, which were verified 24 h before and 48 h after the protocols. The distance traveled (m), total time (s), and bouts performed (rep) were also registered. Significant differences between conditions H15 and H30 were observed in the bouts performed (p = 0.001; ES = 1.19). Several statistical differences were found over time for BLac [pre vs. post 5 (both conditions: p = 0.001), pre vs. post 10 (both conditions: p = 0.001), and post 5 vs. post 10 (H30: p = 0.004)], CK [pre vs. post 24 (H15: p < 0.001; ES = 0.97 and H30: p = 0.001; ES = 0.74) post 24 vs. post 48 (H30: p = 0.03; ES = 0.56)], and LDH [pre vs. post24 (H15: p = 0.008; ES = 1.07 and H30: p = 0.022; ES = 0.85). No statistical differences between conditions were observed for any blood parameter. Thus, the volunteers exhibited equal performance in both protocols, which resulted in a similar physiological response. Despite this similarity, in comparison to H15, the H30 protocol presented lower CK activity post 48 and lactate levels after 10 min post protocol.

In the current era of patient empowerment and precision medicine, access to timely information is critical to decision-making. Unfortunately, we currently lack patient-specific, real-time data about clinical presentation, risk of thrombotic or hemorrhagic events, key risk factors, and adverse outcomes in patients with venous thromboembolism (VTE). Accordingly, the R egistro I nformatizado E nfermedad T rombo E mbólica (RIETE) investigators developed a tool to provide an open-source, real-time graphic representation of VTE-related data derived from over 90 000 patients with confirmed VTE. This information is intended to facilitate discussion in the informed decision-making process. The current article describes the aims, rationale, methods, and ongoing and future efforts of the real-time VTE infographics developed by the RIETE registry collaborators.

Macrophages are highly plastic cells with critical roles in immunity, cancer, and tissue homeostasis, but how these distinct cellular fates are triggered by environmental cues is poorly understood. To uncover how primary murine macrophages respond to bacterial pathogens, we globally assessed changes in post-translational modifications of proteins during infection with Mycobacterium tuberculosis, a notorious intracellular pathogen. We identified hundreds of dynamically regulated phosphorylation and ubiquitylation sites, indicating that dramatic remodeling of multiple host pathways, both expected and unexpected, occurred during infection. Most of these cellular changes were not captured by mRNA profiling, and included activation of ubiquitin-mediated autophagy, an evolutionarily ancient cellular antimicrobial system. This analysis also revealed that a particular autophagy receptor, TAX1BP1, mediates clearance of ubiquitylated Mtb and targets bacteria to LC3-positive phagophores. These studies provide a new resource for understanding how macrophages shape their proteome to meet the challenge of infection.

The construction of the Linear IFMIF Prototype Accelerator (LIPAc) is in progress in order to demonstrate the feasibility of the low energy section of an IFMIF deuteron accelerator up to 9 MeV with a beam current of 125 mA in CW. The next milestone of the project is the so-called Phase-B beam commissioning, and one of the missions is to demonstrate the acceleration of the proton beam up to 2.5 MeV or the deuteron beam up to 5.0 MeV in pulsed mode with a low duty cycle of 0.1% through RFQ. Most of the components and subsystems necessary for Phase-B were delivered by 2016 under the responsibility of Fusion for Energy (F4E) as in-kind contributions of several European institutes, namely CEA (France), CIEMAT (Spain), INFN (Italy), and SCK-CEN (Belgium), and QST is in charge of the installation of the delivered equipment. The installation and check-out of the RFQ subsystem and the RF power system was completed by July 2017, and the RF conditioning of the RFQ cavity started. Also, the installation and the check-out of the important sub-systems for Phase-B, namely MEBT and beam diagnostics, have been completed. Keywords: IFMIF, LIPAc, RFQ, Accelerator, Deuteron, Neutron source

Vitamin D level is known to be a factor potentially influencing physical fitness, but few studies have examined this phenomenon among youth athletes. We aimed to evaluate the associations of vitamin D levels (as measured by 25-hydroxyvitamin D concentrations—25(OH)D) with various physical fitness and motor performance tests in youth football (soccer) players. This cross-sectional study included a total of 52 youth soccer players (15.98 ± 2.26 years old) from Southern Croatia. The participants were evaluated at the end of the winter period and data were collected of anthropometric measures (body mass and body height), vitamin D status (25(OH)D levels), physical fitness tests (sprints of 10 and 20 m, 20 yards test, the countermovement jump, the reactive strength index (RSI)) and motor performance tests (the soccer-specific CODS, the soccer-specific agility, and static balance). Among the studied players, 54% had 25(OH)D insufficiency/deficiency, showing a lack of 25(OH)D is widespread even in youth athletes living at a southern latitude. The 25(OH)D level was correlated with sprint 20 m, 20 yards tests, and RSI, showing a greater role of 25(OH)D in physical fitness tests where energetic capacity is essential than in sport-related motor performance tests where skills are crucial. Our results support the idea that vitamin D can play a determinant role in physical fitness tests with a clear physiological component, but is not crucial in motor performance tests related to specific sports where skills are a key component. Future studies should investigate the effects of vitamin D supplementation on the performance in physical fitness and motor performance tests among youth athletes.

The 2018 European Respiratory Society (ERS) International Congress in Paris, France, highlighted the subject of pulmonary vascular disease (PVD). 2018 was an exciting year for the PVD community as it was the first ERS International Congress since the formation of Assembly 13, which is dedicated to PVD, pulmonary embolism and the right ventricle. This article aims to summarise the high-quality studies presented at the 2018 Congress into four subject areas: the use of risk stratification in pulmonary arterial hypertension, the molecular mechanisms and treatment of pulmonary hypertension (PH), understanding and improving the right ventricle in PH, and finally, advances in the field of acute pulmonary embolus.

ABSTRACT Zika virus (ZIKV) infection of neural progenitor cells (NPCs) in utero is associated with neurological disorders, such as microcephaly, but a detailed molecular understanding of ZIKV-induced pathogenesis is lacking. Here we show that in vitro ZIKV infection of human cells, including NPCs, causes disruption of the nonsense-mediated mRNA decay (NMD) pathway. NMD is a cellular mRNA surveillance mechanism that is required for normal brain size in mice. Using affinity purification-mass spectrometry, we identified multiple cellular NMD factors that bind to the viral capsid protein, including the central NMD regulator up-frameshift protein 1 (UPF1). Endogenous UPF1 interacted with the ZIKV capsid protein in coimmunoprecipitation experiments, and capsid expression posttranscriptionally downregulated UPF1 protein levels, a process that we confirmed occurs during ZIKV infection. Cellular fractionation studies show that the ZIKV capsid protein specifically targets nuclear UPF1 for degradation via the proteasome. A further decrease in UPF1 levels by RNAi significantly enhanced ZIKV infection in NPC cultures, consistent with a model in which NMD restricts ZIKV infection in the fetal brain. We propose that ZIKV, via the capsid protein, has evolved a strategy to lower UPF1 levels and dampen antiviral activities of NMD, which in turn contributes to neuropathology in vivo. IMPORTANCE Zika virus (ZIKV) is a significant global health threat, as infection has been linked to serious neurological complications, including microcephaly. Using a human stem cell-derived neural progenitor model system, we find that a critical cellular quality control process called the nonsense-mediated mRNA decay (NMD) pathway is disrupted during ZIKV infection. Importantly, disruption of the NMD pathway is a known cause of microcephaly and other neurological disorders. We further identify an interaction between the capsid protein of ZIKV and up-frameshift protein 1 (UPF1), the master regulator of NMD, and show that ZIKV capsid targets UPF1 for degradation. Together, these results offer a new mechanism for how ZIKV infection can cause neuropathology in the developing brain.

In the present viewpoint, the authors provide an overview of the current evidence supporting the positive influence of practicing physical activity regularly and improving physical fitness, mainly cardiorespiratory fitness and muscular strength, on metabolic and overall health. The evidence on this regard is strong and consistent, and in the different age groups. Likewise, enhancing cardiorespiratory fitness by means of physical activity has the potential of attenuating the negative effect of obesity on future health, as well as improving the prognosis of the metabolically healthy obesity phenotype. Collectively, the existing evidence strongly supports the recommendation of being active and enhancing cardiorespiratory fitness and muscular strength as a powerful public health strategy.

I develop a dynamic model with forward looking agents, and show that social pressure is effective in generating provision in a public good game: after a small group of agents start contributing to the public good, other agents decide to contribute as well due to a fear of being punished, and this generates contagion in the network. In contrast to earlier models in the literature, contagion happens fast, as part of the best response of fully rational individuals. The network topology has implications for whether contagion starts and the extent to which it spreads. I find conditions under which an agent decides to be the first to contribute in order to generate contagion in the network, as well as conditions for contribution due to a self-fulfilling fear of social pressure.

Abstract. Current guidelines recommend low-molecular-weight-heparins (LMWH) monotherapy for 3 to 6 months as first-line treatment for cancer-associated venous thromboembolism (VTE). In clinical practice, enoxaparin and nadroparin are common agents used. However, differences in therapy adherence between these LMWHs have never been reported. Therefore, our aim was to compare adherence to enoxaparin and nadroparin in patients with cancer-associated VTE. Consecutive patients with active cancer and objectively confirmed VTE, treated at a Dutch or a Spanish hospital, were followed during LMWH therapy with a maximum of 180 days. Cumulative incidences of discontinuation of both LMWHs were estimated and compared according to the Kaplan-Meier method, applying a competing risk analysis to correct for mortality. A total of 366 patients were analyzed during LMWH treatment, of whom 284 patients (78%) were treated with enoxaparin and 82 (22%) with nadroparin. The cumulative incidence of discontinuation of enoxaparin and nadroparin treatment because of side effects was 30% (95% confidence interval [CI] 24–36) and 8.8% (95% CI 1.1–15), respectively. Competing risk analysis revealed a higher number of patients discontinuing enoxaparin due to side effects (adjusted hazard ratio [HR]: 2.8; 95% CI 1.06–7.2). Pain at the injection site was the most common reason of discontinuation in patients using enoxaparin, occurring in 32 patients, while it occurred in 1 patient using nadroparin (adjusted HR: 4.0; 95% CI 0.52–31). This analysis reveals that enoxaparin was associated with a higher risk of discontinuation because of side effects compared to nadroparin. However, given the nature of the patient groups, these findings should be followed by future studies.

The usefulness of a diagnostic workup for occult cancer in patients with venous thromboembolism (VTE) is controversial. We used the RIETE (Registro Informatizado Enfermedad Trombo Embólica) database to perform a nested case-control study to validate a prognostic score that identifies patients with unprovoked VTE at increased risk for cancer. We dichotomized patients as having low- (≤2 points) or high (≥3 points) risk for cancer, and tried to validate the score at 12 and 24 months. From January 2014 to October 2016, 11,695 VTE patients were recruited. Of these, 1,360 with unprovoked VTE (11.6%) were eligible for the study. At 12 months, 52 patients (3.8%; 95%CI: 2.9-5%) were diagnosed with cancer. Among 905 patients (67%) scoring ≤2 points, 22 (2.4%) had cancer. Among 455 scoring ≥3 points, 30 (6.6%) had cancer (hazard ratio 2.8; 95%CI 1.6-5; p

We sought to examine sex-related differences in the characteristics and outcome in patients presenting with acute symptomatic pulmonary embolism (PE).We conducted a retrospective cohort study of 2,096 patients diagnosed with acute PE. The characteristics were recorded at presentation. Treatment was at the discretion of patients' physicians. The primary study outcome, all-cause mortality, and the secondary outcomes of PE-specific mortality, recurrent venous thromboembolism, and major bleeding were assessed during the first month of follow-up after PE diagnosis.Overall, the women were older than the men and had significantly higher rates of immobilization. They had significantly lower rates of chronic obstructive pulmonary disease and cancer. Women had a higher prevalence of syncope and elevated brain natriuretic peptide levels. Thirty-day all-cause mortality was similar between women and men (7.1% versus 6.2%; P = 0.38). Male gender was not independently significantly associated with PE-related death (adjusted odds ratio [OR] 1.02; 95% CI, 0.50 to 2.07; P = 0.96). Restricting the analyses to haemodynamically stable patients (n = 2,021), female gender was an independent predictor of all-cause (adjusted OR 1.56; 95% CI, 1.07 to 2.28; P = 0.02) and PE-specific mortality (adjusted OR 1.85; 95% CI, 1.02 to 3.33; P = 0.04). Compared with men, women were 2.05 times more likely to experience a major bleed.Women and men with PE had different clinical characteristics, presentation, and outcomes. Women receiving anticoagulation have a significantly higher risk of major bleeding, suggesting the need for careful monitoring of anticoagulant intensity in women.

Correction to: Thrombosis Journal (2018) 16:9 DOI 10.1186/s12959-018-0163-7