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Abstract This study evaluates whether exchange traded funds (ETFs) threaten financial market stability by testing two hypotheses relating the growing importance of ETFs to increased market volatility and rising equity valuations. We estimate quantile cointegration models using Standard & Poor's 500 Index (S&P 500) and Chicago Board Options Exchange volatility Index (VIX) data for 1994–2020. We found that an increase in ETFs is positively and significantly related to the long-term valuation of the S&P 500 for quantile values above the median. By contrast, ETFs have only a negative and significant effect on the VIX for quantiles around the median. Ultimately, two novel results were obtained. First, the distortion in the value of the S&P 500 relative to its fundamentals is driven by investor flow into ETFs during a bull market. Second, the impact of equity ETFs on the VIX is only affected when fundamental factors are in play, decreasing it. Therefore, ETFs contribute to forming equity bubbles and support valuation market dynamics. Both regulators and policymakers should consider these conclusions.

Introduction In light of the burden of traumatic brain injury (TBI) in children and the excessive number of unnecessary CT scans still being performed, new strategies are needed to limit their use while minimising the risk of delayed diagnosis of intracranial lesions (ICLs). Identifying children at higher risk of poor outcomes would enable them to be better monitored. The use of the blood-based brain biomarkers glial fibrillar acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) could help clinicians in this decision. The overall aim of this study is to provide new knowledge regarding GFAP and UCH-L1 in order to improve TBI management in the paediatric population.Methods and analysis We will conduct a European, prospective, multicentre study, the BRAINI-2 paediatric study, in 20 centres in France, Spain and Switzerland with an inclusion period of 30 months for a total of 2880 children and adolescents included. To assess the performance of GFAP and UCH-L1 used separately and in combination to predict ICLs on CT scans (primary objective), 630 children less than 18 years of age with mild TBI, defined by a Glasgow Coma Scale score of 13–15 and with a CT scan will be recruited. To evaluate the potential of GFAP and UCH-L1 in predicting the prognosis after TBI (secondary objective), a further 1720 children with mild TBI but no CT scan as well as 130 children with moderate or severe TBI will be recruited. Finally, to establish age-specific reference values for GFAP and UCH-L1 (secondary objective), we will include 400 children and adolescents with no history of TBI.Ethics and dissemination This study has received ethics approval in all participating countries. Results from our study will be disseminated in international peer-reviewed journals. All procedures were developed in order to assure data protection and confidentiality.Trial registration number NCT05413499.

Nosocomial infections are a frequent and serious problem in extremely low birth weight (ELBW) infants. Donor human milk (DHM) is the best alternative for feeding these babies when mother’s own milk (MOM) is not available. Recently, a patented prototype of a High-Temperature Short-Time (HTST) pasteurizer adapted to a human milk bank setting showed a lesser impact on immunologic components. We designed a multicentre randomized controlled trial that investigates whether, in ELBW infants with an insufficient MOM supply, the administration of HTST pasteurized DHM reduces the incidence of confirmed catheter-associated sepsis compared to DHM pasteurized with the Holder method. From birth until 34 weeks postmenstrual age, patients included in the study received DHM, as a supplement, pasteurized by the Holder or HTST method. A total of 213 patients were randomized; 79 (HTST group) and 81 (Holder group) were included in the analysis. We found no difference in the frequency of nosocomial sepsis between the patients of the two methods—41.8% (33/79) of HTST group patients versus 45.7% (37/81) of Holder group patients, relative risk 0.91 (0.64–1.3), p = 0.62. In conclusion, when MOM is not available, supplementing during admission with DHM pasteurized by the HTST versus Holder method might not have an impact on the incidence of catheter-associated sepsis.

Immunoparesis (IP) in multiple myeloma (MM) patients can be measured by classic assessment of immunoglobulin (Ig) levels or by analysis of the uninvolved heavy/light chain pair of the same immunoglobulin (uHLC) by the Hevylite® assay. In this study we evaluate the prognostic value of recovery from IP measured by classic total Ig and uHLC assessment in newly diagnosed MM transplant-eligible (NDMM-TE) patients with intensive treatment and its association with minimal residual disease (MRD). Patients were enrolled and treated in the PETHEMA/GEM2012MENOS65 trial and continued in the PETHEMA /GEM2014MAIN trial. Total Ig (IgG, IgA and IgM) and uHLC were analyzed in a central laboratory at diagnosis, after consolidation treatment and after the first year of maintenance. MRD was analyzed by next-generation flow cytometry after consolidation (sensitivity level 2x10-6). We found no differences in progression-free survival (PFS) between patients who recovered and patients who didn’t recover from IP after consolidation when examining classic total Ig and uHLC. However, after the first year of maintenance, in contrast to patients with classic IP, patients with recovery from uHLC IP had longer PFS than patients without recovery, with hazard ratio of 0.42 (95% confidence interval [CI]: 0.21-0.81; P=0.008). Multivariate analysis with Cox proportional-hazards regression models confirmed recovery from uHLC IP after the first year of maintenance as an independent prognostic factor for PFS, with an increase in C-statistic of 0.05 (95% CI: -0.04 to 0.14; P

A greater understanding of clinical trends in COVID-19 outcomes among patients with hematologic malignancies (HM) over the course of the pandemic, particularly the Omicron era, is needed. This ongoing, observational, and registry-based study with prospective data collection evaluated COVID-19 clinical severity and mortality in 1818 adult HM patients diagnosed with COVID-19 between 27 February 2020 and 1 October 2022, at 31 centers in the Madrid region of Spain. Of these, 1281 (70.5%) and 537 (29.5%) were reported in the pre-Omicron and Omicron periods, respectively. Overall, patients aged ≥70 years (odds ratio 2.16, 95% CI 1.64–2.87), with >1 comorbidity (2.44, 1.85–3.21), or with an underlying HM of chronic lymphocytic leukemia (1.64, 1.19–2.27), had greater odds of severe/critical COVID-19; odds were lower during the Omicron BA.1/BA.2 (0.28, 0.2–0.37) or BA.4/BA.5 (0.13, 0.08–0.19) periods and among patients vaccinated with one or two (0.51, 0.34–0.75) or three or four (0.22, 0.16–0.29) doses. The hospitalization rate (75.3% [963/1279], 35.7% [191/535]), rate of intensive care admission (30.0% [289/963], 14.7% [28/191]), and mortality rate overall (31.9% [409/1281], 9.9% [53/536]) and in hospitalized patients (41.3% [398/963], 22.0% [42/191]) decreased from the pre-Omicron to Omicron period. Age ≥70 years was the only factor associated with higher mortality risk in both the pre-Omicron (hazard ratio 2.57, 95% CI 2.03–3.25) and Omicron (3.19, 95% CI 1.59–6.42) periods. Receipt of prior stem cell transplantation, COVID-19 vaccination(s), and treatment with nirmatrelvir/ritonavir or remdesivir were associated with greater survival rates. In conclusion, COVID-19 mortality in HM patients has decreased considerably in the Omicron period; however, mortality in hospitalized HM patients remains high. Specific studies should be undertaken to test new treatments and preventive interventions in HM patients.

Introduction Two blood brain-derived biomarkers, glial fibrillar acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), can rule out intracranial lesions in patients with mild traumatic brain injury (mTBI) when assessed within the first 12 hours. Most elderly patients were excluded from previous studies due to comorbidities. Biomarker use in elderly population could be affected by increased basal levels. This study will assess the performance of an automated test for measuring serum GFAP and UCH-L1 in elderly patients to predict the absence of intracranial lesions on head CT scans after mTBI, and determine both biomarkers reference values in a non-TBI elderly population.Methods and analysis This is a prospective multicentre observational study on elderly patients (≥65 years) that will be performed in Spain, France and Germany. Two patient groups will be included in two independent substudies. (1) A cohort of 2370 elderly patients (1185

The objective of this study was to evaluate the application of hot water treatment to tomato fruits (Solanum lycopersicum cv. TA234) genetically modified with silencing of the TomloxB gene. Unmodified and genetically modified tomato fruits were immersed in water at 40°C for 10, 20 and 30 seconds. Subsequently, fruits were stored at 25°C for 18 days. Physiology was assessed and electrolyte leakage, lipoxygenase and polygalacturonase activities were monitored. Treatment applied to the genetically modified tomatoes at 40°C for 30 seconds, resulted in slower ripening, decreased metabolic activity and maintained the attributes in optimal conditions for longer time, increased the postharvest life of the genetically modified tomatoes until 18 days. Lipoxygenase and polygalacturonase activities were partially inhibited.

Objective: To identify the use of social media as an influencing factor of the orthodontic patient’s preferences regarding the lip profile protrusion. Methods: A two-part cross-sectional questionnaire was distributed to orthodontic patients in Spain and The Netherlands. The first part collected general data and frequency of use of different social media. The second part consisted of a series of modified female and male silhouettes presenting different lip profile positions. Each participant was required to choose both the (male and female) most attractive silhouette and the least attractive one.Student t-test, one-way ANOVA and Chi-square test were performed. Effect sizes were calculated to express the magnitude of differences between samples. Results: The Spanish sample resulted in a moderate higher tendency (R2 = 0.060) to choose protrusive lips as the most attractive lip profile for females, on subjects with more frequent use of social media. A medium tendency (R2=0,26) was observed as result of low users of social media choosing and ideal lip profile for men.The Dutch sample showed that high users of social media tended to choose as attractive a more protrusive female lip profile versus low users (p

Introduction Digital technologies can be used as part of paediatric motor rehabilitation to remediate impairment, promote recovery and improve function. However, the uptake of digital technologies in this clinical field may be limited.The aim of this study is to describe and explain digital technology use for paediatric motor rehabilitation. The specific objectives will be: (1) to describe the access to, acceptance of and use of digital technologies as a function of individual factors related to professionals practicing motor rehabilitation with children, and of environmental factors related to paediatric rehabilitation practice and (2) to explain digital technology use with a causal model based on the ‘unified theory of acceptance and use of technology’.Methods and analysis RehaTech4child (Rehabilitation Technologies For children) is a cross-sectional study involving an online survey, that is sponsored by the European Academy of Childhood Disability (EACD). The survey protocol follows the Strengthening the Reporting of Observational Studies in Epidemiology and CHERRIES (Checklist for Reporting Results of Internet E-Surveys) guidelines. The survey includes 43 questions about (1) respondents’ individual and environmental characteristics; (2) the ease of access to digital technologies, and the frequency, type and purpose of use of those technologies and (3) acceptance of technologies and barriers to their use. The survey is intended for professionals involved in paediatric motor rehabilitation. It is disseminated across Europe by the EACD network in 20 languages. Participation is anonymous and voluntary. We aim to include 500 respondents to ensure sufficient precision for the description of study outcomes and to perform stratified analyses by the main determinants.Ethics and dissemination Ethics approval was waived by the Brest CHRU Institutional Review Board. The study is conducted according to current French legislation (loi Jardé (n°2012-300)) and the survey is GDPR compliant. Study findings will be presented at national and international meetings and submitted for publication in a peer-reviewed journal.Trial registration number NCT05176522.

Antibiotic burden is a critical issue in neonatal intensive care units (NICU) and antibiotic use is considered a quality indicator of neonatal care. Our aim was to optimize antibiotic use through a quality improvement (QI) initiative that included revision of departmental protocols and implementation of a surveillance system based on process indicators.MethodsThis is descriptive study of a cohort of all very low birth weight (VLBW) infants admitted to the NICU from 2014 to 2019. A series of QI interventions were made during the study period and included departmental protocols and the implementation of a surveillance system based on process indicators. The primary outcome was the percentage of VLBW infants who had received early antibiotics (ampicillin, gentamicin, or cefotaxime on the day of birth or day 1 or 2 after birth), antibiotics for longer than 3 days (despite negative blood culture), or no antibiotics.ResultsDuring the study period, a significant relative reduction was seen in the proportion of VLBW infants administered early antibiotics (46%; p < 0.01) and in infants provided antibiotics for longer than 3 days (90%; p < 0.01). Additionally, the percentage of VLBW with “no antibiotics” during their NICU stay increased fivefold (6 to 30%; p < 0.001).ConclusionsIn our NICU, the implementation of a QI initiative that is based on affordable methods to track process indicators and evaluate the results led into a significant reduction in antibiotic exposure in VLBW infants. This approach is easy to implement in other NICUs as well.

BackgroundDuring early skin-to-skin contact (ESSC), alterations in peripheral oxygen saturation (SpO2) and heart rate (HR) have been frequently observed.ObjectivesThis study aimed to determine the incidence of cardiorespiratory events (CREs) during ESSC in healthy term newborns (HTNs) and estimate the association of maternal and neonatal prognostic factors with the risk of CREs.MethodsA pooled analysis of the cohort from a clinical trial involving healthy mother–child dyads during ESSC was performed. Pulse oximetry was employed to continuously monitor SpO2 and HR within 2 h after birth. The individual and combined prognostic relevance of the demographic and clinical characteristics of dyads for the occurrence of a CRE (SpO2 180 bpm) was analyzed through logistic regression models.ResultsOf the 254 children assessed, 169 [66.5%; 95% confidence interval (95% CI), 60.5–72.5%] had at least one CRE. The characteristics that increased the risk of CRE were maternal age ≥35 years (odds ratio, 2.21; 95% CI, 1.19–4.09), primiparity (1.96; 1.03–3.72), gestational body mass index (BMI) >25 kg/m2 (1.92; 1.05–3.53), and birth time between 09:00 p.m. and 08:59 a.m. (2.47; 1.02–5.97).ConclusionCREs were more frequent in HTNs born during nighttime and in HTNs born to first-time mothers, mothers ≥35 years, and mothers with a gestational BMI >25 kg/m2. These predictor variables can be determined during childbirth. Identification of neonates at higher risk of developing CREs would allow for closer surveillance during ESSC.

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February–June 2020; n = 769 (66%)) and later (July 2020–February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11–0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01–3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22–0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81–1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.

Background and AimsThe provision of coordinated and multidisciplinary rehabilitation programs that adapt to the individual with cerebral palsy (CP) evolving rehabilitation needs throughout the different phases of life is highly challenging for healthcare systems. The aim of this study was to report the changes in motor rehabilitation (MR) environmental factors, service use and patient outcomes between children and adults with cerebral palsy and to identify if changes took place earlier or later than the standard division between pediatric and adult healthcare systems at 18 years.MethodsWe used data from the French ESPaCe survey to select a set of indicators for MR environmental factors, service use and patient outcomes, highlighted by patients and families in previous studies. We then compared the distribution of the indicator data between children and adults, as well as between four transition age groups: children under 12, adolescents up to 17 years, young adults, and adults over 25 years of age. We estimated odds ratios adjusted for motor involvement, associated impairments and informant type.ResultsA total of 997 respondents over 2 years of age were included in this study (484 children and 513 adults). Finding an available physiotherapist was very difficult for almost half of the children, and a greater proportion of adolescents and adults. Physiotherapy was provided in a private outpatient practice for twice as many adults over 25 years as children and adolescents. The weekly amount of physical therapy decreased as outpatient practice increased. Multidisciplinary rehabilitation decreased sharply from adolescence and was halved at adulthood. Satisfaction with the MR program decreased from childhood into adolescence and adulthood. Perceived impact of physiotherapy on people with CP and their main carers were less positive in adolescents.ConclusionsHealthcare policies should focus on accessibility issues at all ages, consider adolescents as a specific population, consider a wide transition phase (12–25 yo) and maintain a multidisciplinary approach at adulthood. There is a strong need for national rehabilitation strategies for individuals with CP.

Introduction: Heart transplant (HT) survival has barely improved in the last decades, which is unsatisfactory for many HT recipients. The development of anti-human leukocyte antigen (anti-HLA) antibodies in HT patients is associated with a cardiac allograft dysfunction. The mechanisms leading to this damage are unclear. The Multimodality Evaluation Of Antibody-Mediated Injury In Heart Transplantation (LEONE-HT) study aimed to thoroughly describe the damage inflicted on the myocardium by anti-HLA antibodies. Methods and analysis: The LEONE-HT study is a cohort study with a cross-sectional approach in which HT patients with positive anti-HLA antibodies are compared with coetaneous HT patients with negative anti-HLA antibodies. All patients will undergo a state-of-the-art multimodal assessment, including imaging techniques, coronary anatomy and physiology evaluations and histological and immunological analyses. The individual and combined primary outcomes of structural graft injuries and longitudinal secondary outcomes are to be compared between the exposed and non-exposed groups with univariate and multivariable descriptive analyses. Ethics and dissemination: The LEONE-HT study is carried out in accordance with the principles set out in the Declaration of Helsinki and the International Conference on Harmonization guidelines for good clinical practice and following national laws and regulations. The study design, objectives and participant centers have been communicated to clinicaltrials.gov (NCT05184426). The LEONE-HT study counts on the support of patient associations to disseminate the objectives and results of the research. This study was funded by the Spanish Ministry of Science and Innovation and the Spanish Society of Cardiology.

This paper introduces skew dihedral group rings and their applications for public-key cryptography. We present a specific skew group ring that is the underlying algebraic platform for our cryptographic constructions. We then build a two-party key exchange protocol and present an analysis of its security. We then exploit it to derive a group key agreement protocol, a probabilistic public-key scheme, and a key encapsulation mechanism. In addition to the security analysis of our cryptographic constructions, we present a proof-of-concept implementation.

Today, there are new technologies to produce bioethanol: one of them is the Pressure Swing Adsorption (PSA) process. This process has displaced other separation technologies due to the use of natural adsorbents and its methodology to obtain high purities with a lower energy cost. The aim of this work focuses on the optimization of the PSA process (experimental case) to obtain a higher recovery and production of bioethanol using lower energy consumption. The results are favorable since the energy cost is reduced to a range of 60% and 62%, obtaining purities above 99% wt of ethanol and recovery between 75% and 77.41%. The bioethanol produced and purified in the different scenarios meets international standards to be used as a fuel or oxygenating additive.

Small wind turbines (SWTs) have been a common option for rural electrification during recent decades. Recently, an application for connecting these devices to the grid was proposed. This requires an AC-coupled configuration, which brings the need for a power converter necessary for connection to the AC bus. This publication analyzes the requirements and commercial availability of such power converters, coming first to a conclusion on the lack of existing electronic power converters for SWTs, mainly in the lowest power range (

In this paper, all extremal Type I and Type III codes of length 60 with an automorphism of order 29 are classified up to equivalence. In both cases, it has been proven that there are three inequivalent codes. In addition, a new family of self-dual codes over non-binary fields is presented.

(1) Background: Clinical presentation, disease distribution, or treatment received may provide insights into the reasons contributing to sex differences in chronic thromboembolic pulmonary hypertension (CTEPH). (2) Methods: We evaluated 453 patients (56% women) between 2007–2019. Data was collected from REHAP (Registro Español de Hipertensión Arterial Pulmonar) registry. Two time periods were selected to evaluate the influence of new treatments over time. (3) Results: Women were older. Baseline functional class was worse, and distance walked shorter in women compared with men. Women had higher pulmonary vascular resistances. Despite this, pulmonary endarterectomy (PEA) was carried out in more men, and women received more frequently pulmonary vasodilators exclusively. The 2014–2019 interval was associated with a better survival only among women. Interestingly, women had a more distal disease during this second period of time. (4) Conclusions: Even though women were older, and received invasive treatments less frequently, mortality was similar in both sexes. The introduction of balloon pulmonary angioplasty and the improvement of pulmonary endarterectomy, especially during the last years, could be associated with a survival benefit among women.