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In this work, we study a Buckley–Leverett equation of two-phase flow in porous media from the point of view of the Lie theory. We find that for some functions the equation has abundant exact solutions expressible in terms of Jacobi elliptic functions and consequently has many solutions in the form of periodic waves or solitary waves. We determine low-order conservation laws by using the multiplier method. From conservations laws, we construct the potential systems. From these systems we deduce potential equations. We study these equations from the point of view of Lie theory. Moreover, for these equations some nontrivial conservation laws are constructed by using the multipliers method.

This paper considers a generalized (2+1) dimensional nonlinear evolution equation depending on two nonzero arbitrary constants. We derive the Lie point symmetry generators and Lie symmetry groups. This symmetry analysis leads us the reductions equations, through one of which we obtain solutions. We also get the low-order conservation laws of the equation that have been obtained using the corresponding symmetries of the family. We will present a classification of conservation laws for this equation and we will apply Lie symmetry analysis to the equation in order to obtain exact solutions.

This express brief addresses the voltage collapse problem in direct-current (dc) networks by using a recursive heuristic search algorithm based on the Newton-Raphson method. The determinant of the Jacobian matrix in the Newton-Raphson method is used as a sensitivity index to determine the maximum power consumption of the dc network. The recursive solution approach corresponds to a sequential power flow approach by incrementing all values of the power consumptions uniformly. Simulation results validate the efficiency of the proposed method in comparison to the large-scale nonlinear solvers available in the general algebraic modeling system optimization package. The MATLAB programming environment was employed for implementing the proposed recursive Newton-Raphson method.

The Foundations for Evidence-Based Policymaking Act of 2018 requires cabinet-level agencies to use evidence to justify and support budget and policy making. As investigators from the Quality Enhancement Research Initiative (QUERI) program, we were tasked with assisting Veterans Health Administration (VHA) leadership with the implementation of the Evidence-Based Policymaking Act of 2018. Through meetings with stakeholders, we identified a gap in the review process for legislative and budget proposals; no systematic process existed to evaluate the supporting evidence base for proposals.Here, we describe the development, refinement, and use of a checklist to assess the strength of evidence included in VHA legislative and budget proposals for changes to care delivery; clinical, research, and administrative operations; and staffing and workforce issues.The evidence assessment checklist is now part of the regular review process for VHA legislative and budget proposals. It is also being adapted for use elsewhere within the Department of Veterans Affairs. The checklist has provided a framework for briefings and training on best practices for using evidence to guide policy and budget decisions.Including evidence reviews in the legislative and budget proposal prioritization process may be an effective institutional arrangement to promote the use of evidence to inform high-level health policy decisions and to build a "culture of evidence" within the government.

The Veterans Health Administration (VHA) implemented the Stratification Tool for Opioid Risk Mitigation (STORM) to reduce the risk of serious adverse events (SAE) among patients with opioid analgesic prescriptions. VHA facilities were mandated to case review patients identified as high-risk by STORM. The aim of this study was to measure the effect of this mandate on all-cause mortality and SAEs among VHA patients newly-diagnosed with opioid use disorder (OUD).Secondary analysis of a stepped-wedged cluster randomized controlled trial conducted at all 140 VHA facilities, with facility as the unit of randomization, from 2018-2020. Setting and Participants United States VHA facilities were randomized to case review the top 1% or 5% of high-risk patients prescribed opioid analgesics identified by STORM. 28,251 patients were diagnosed with OUD during the trial, and were considered control or treatment depending on the status of the facility where they received their OUD diagnosis. Post-hoc analyses among patients who had at least one opioid analgesic prescription in the 90 days prior to diagnosis were conducted, and were then stratified by receipt of a prescription in the 90 days following diagnosis to assess the sensitivity of results to opioid discontinuation.All-cause mortality and opioid-related, drug-related, suicide-related, and other SAEs within 90-days of OUD diagnosis.Mandated case review increased the odds of 90-day mortality (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.06, 2.87), but did not significantly change the odds of SAEs. Among patients who received an opioid prescription prior to but not after OUD diagnosis, the odds of all-cause mortality within 90 days was 5.87 (95% CI 1.85, 18.58) relative to control patients.Veterans Health Administration patients newly-diagnosed with opioid use disorder experienced increased all-cause mortality following expansion of a case-review mandate for high-risk patients prescribed opioids.

The datasets supporting this article are reported in the supplementary material Tables S1-S4., The contribution of wildlife species to pathogen maintenance in multi-host communities has seldom been quantified. To assess the relative contribution of the main wildlife hosts of animal tuberculosis (TB) to its maintenance, we estimated the basic reproduction number (R0) of Mycobacterium tuberculosis complex in wild boar and red deer at 29 sites in the Iberian Peninsula. Host abundance and true TB prevalence were estimated for each species at each site by sampling from distributions incorporating the uncertainty in the proportion of the population harvested each year, sensitivity, and specificity of the diagnostic methods, while excretion of mycobacteria was estimated using site-occupancy models. The distributions of these parameters were then used to estimate, at each site, the R0,wild boar (range 0.1 – 55.9, average 8.7, standard deviation 11.8), and the R0,red deer (0.1 – 18.9, 2.2, 3.9). Animal TB is maintained in epidemiological scenarios ranging from any single species acting as a maintenance host (the wild boar in 18 sites and the red deer in 5), to facultative multi-host disease (6 sites). The prevalence of TB in the red deer is likely an important driver of the epidemiology in multi-host communities. The wild boar was the main maintenance host of TB in most of the study sites and could have an epidemiological role linking the wildlife multi-host community and livestock., This work was supported by Fundação para a Ciência e Tecnologia [project grant EXPL/CVT-CVT/1525/2021 and fellowship SFRH/BPD/116596/2016 to N.S.]. FCT/MCTES for the financial support to CESAM (UIDP/50017/2020 +UIDB/50017/2020), through national funds.

Lung cancer is the leading cause of cancer mortality worldwide, with non-small cell lung cancer (NSCLC) being the most prevalent histology. While immunotherapy with checkpoint inhibitors has shown outstanding results in NSCLC, the precise identification of responders remains a major challenge. Most studies attempting to overcome this handicap have focused on adenocarcinomas or squamous cell carcinomas. Among NSCLC subtypes, the molecular and immune characteristics of lung large cell carcinoma (LCC), which represents 10% of NSCLC cases, are not well defined. We hypothesized that specific molecular aberrations may impact the immune microenvironment in LCC and, consequently, the response to immunotherapy. To that end, it is particularly relevant to thoroughly describe the molecular genotype–immunophenotype association in LCC–to identify robust predictive biomarkers and improve potential benefits from immunotherapy. We established a cohort of 18 early-stage, clinically annotated, LCC cases. Their molecular and immune features were comprehensively characterized by genomic and immune-targeted sequencing panels along with immunohistochemistry of immune cell populations. Unbiased clustering defined two novel subgroups of LCC. Pro-immunogenic tumors accumulated certain molecular alterations, showed higher immune infiltration and upregulated genes involved in potentiating immune responses when compared to pro-tumorigenic samples, which favored tumoral progression. This classification identified a set of biomarkers that could potentially predict response to immunotherapy. These results could improve patient selection and expand potential benefits from immunotherapy.

BACKGROUND: Rural residents face more barriers to healthcare access, including challenges in receiving home- and community-based long-term services, compared to urban residents. Self-directed services provide flexibility and choice in care options and may be particularly well suited to help older adults with multiple chronic conditions and functional limitations who reside in rural areas remain independent and live in the community. METHODS: We conducted a retrospective observational study to understand whether differences in health outcomes between Veteran-Directed Care (VDC), a self-directed Veterans Health Administration (VHA)-paid care program, and other VHA-paid home- and community-based personal care services vary in rural/urban location. The sample included 37,395 Veterans receiving VHA-paid home- and community-based long-term care services in FY17. Our primary outcomes were changes in monthly incidence of VHA or VHA-paid community acute care admissions, nursing home admissions, and emergency department (ED) visits. We used fixed effects logistic regression models on unmatched and coarsened exact matched cohorts, stratified by rural/urban location. RESULTS: Both urban and rural VDC recipients were significantly less likely to be admitted to VHA-paid nursing homes, compared to those receiving other VHA-paid personal care services (rural: incremental effect = −0.22, [ −0.30, −0.14]; urban: incremental effect = −0.14, [−0.20, −0.07]). Rural, but not urban, VDC enrollees had significantly fewer VHA-paid acute care admissions and ED visits, relative to recipients of other VHA-paid personal care services (acute care, rural: incremental effect = −0.07, 95% CI = [−0.14, −0.01], urban: incremental effect = −0.01, [−0.06, 0.03]; ED, rural: incremental effect = −0.08, [−0.14, −0.02], urban: incremental effect = 0.01, [−0.03, 0.05]). CONCLUSIONS: VDC recipients had fewer incidents of potentially avoidable VHA-paid health care use, compared to similar Veterans receiving other VHA-paid personal care services. These differences were more pronounced among rural VDC recipients than urban VDC recipients.

Tick vaccines are necessary as part of a One Health approach for the control of tick infestations and tick-borne diseases. Subolesin (SUB, also known as 4D8) is a tick protective antigen that has shown efficacy in vaccine formulations for the control of ectoparasite infestations and pathogen infection/transmission. A recent proof-of-concept study reported oral vaccination combining Rhipicephalus microplus SUB with heat inactivated Mycobacterium bovis (IV) as an immunostimulant for the control of cattle tick infestations. Based on the efficacy of Rhipicephalus decoloratus SUB for the control of multiple cattle tick species in Uganda, herein we design a controlled pen trial using an oral formulation combining R. decoloratus SUB with IV for the control of R. decoloratus and Rhipicephalus appendiculatus cattle tick infestations. Vaccine efficacy (E) of SUB + IV on tick life cycle was compared with IV and SUB alone and with PBS as control. The IgG antibody titers against SUB and M. bovis P22 and the serum levels of selected protein immune biomarkers (IL-1beta, TNF-alpha, C3) were determined and analyzed as possible correlates of protection. Oral immunization with IV and SUB alone and in SUB + IV combination were effective for the control of tick infestations (E = 71–96% for R. decoloratus and 87–99% for R. appendiculatus) with highest E (higher than 95%) for SUB + IV. The results demonstrated that oral immunization with the SUB + IV formulation resulted in effective control of cattle tick infestations through the activation of multiple immune mechanisms. These results support the application of oral vaccine formulations with SUB + IV for the control of cattle infestations with Rhipicephalus species towards improving animal health., This research was financially supported by the National Agricultural Research Organization (NARO) of Uganda. The IV research was also funded by Junta de Castilla-La Mancha, Spain, project MYCOTRAINING SBPLY/19/180501/000174 and the State Research Agency, Spain, project BIOGAL [PID2020-116761 GB-I00].

© 2010 College of American Pathologists. Permission to use figures, tables, and brief excerpts from this work in scientific and educational works is hereby granted provided that the source is acknowledged. Any use of material in this work that is determined to be "fair use" under Section 107 or that satisfies the conditions specified in Section 108 of the U.S. copyright Law (17 USC, as revised by P.L. 94-553) does not require the society's permission. Republication, systematic reproduction, posting in electronic form on servers, or other uses of this material, except as exempted by the above statements, requires written permission or license from College of American Pathologists., Context.—: There is a need to avoid the overdiagnosis of prostate cancer (PCa) and to find more specific biomarkers. Objective.—: To evaluate the clinical utility of [-2]pro-prostate-specific antigen ([-2]proPSA) derivatives in detecting clinically significant PCa (csPCa) and to compare it with prostate-specific antigen (PSA) and with the percentage of free PSA (%fPSA). Design.—: Two hundred thirty-seven men (PSA: 2-10 ng/mL) scheduled for a prostate biopsy were enrolled. Parametric and nonparametric tests, receiver operating characteristic curves, and logistic regression analysis were applied. Outcomes were csPCa and overall PCa. Results.—: Both [-2]proPSA derivatives were significantly higher in csPCa and overall PCa (P < .001). The areas under the curves for the prediction of csPCa were higher for the percentage of [-2]proPSA (%[-2]proPSA) (0.781) and the prostate health index (PHI) (0.814) than for PSA (0.651) and %fPSA (0.724). There was a gain of 11% in diagnostic accuracy when %[-2]proPSA or PHI were added to a base model with PSA and %fPSA. Twenty-five percent to 29% of biopsies could have been spared with %[-2]proPSA (cutoff: ≥1.25%) and PHI (cutoff: ≥27), missing 10% of csPCas. The same results could have been achieved by using [-2]proPSA as a reflex test, when %fPSA was 25% or less (cutoffs: ≥1.12% and ≥24 for %[-2]proPSA and PHI, respectively). Conclusions.—: The [-2]proPSA derivatives improve the diagnostic accuracy of csPCa when the PSA value is between 2 and 10 ng/mL, sparing unnecessary biopsies and selecting patients for active surveillance. [-2]proPSA can be used as a reflex test when %fPSA is 25% or less, without reducing the diagnostic accuracy for csPCa and the number of spared biopsies.

Storylines of atmospheric circulation change, or physically self-consistent narratives of plausible future events, have recently been proposed as a non-probabilistic means to represent uncertainties in climate change projections. Here, we apply the storyline approach to 21st century projections of summer air stagnation over Europe and the United States. We use a Climate Model Intercomparison Project Phase 6 (CMIP6) ensemble to generate stagnation storylines based on the forced response of three remote drivers of the Northern Hemisphere mid-latitude atmospheric circulation: North Atlantic warming, North Pacific warming, and tropical versus Arctic warming. Under a high radiative forcing scenario (SSP5-8.5), models consistently project increases in stagnation over Europe and the U.S., but the magnitude and spatial distribution of changes vary substantially across CMIP6 ensemble members, suggesting that future projections are not well-constrained when using the ensemble mean alone. We find that the diversity of projected stagnation changes depends on the forced response of remote drivers in individual models. This is especially true in Europe, where differences of ~2 summer stagnant days per degree of global warming are found amongst the different storyline combinations. For example, the greatest projected increase in stagnation for most European regions leads to the smallest increase in stagnation for southwestern Europe; i.e. limited North Atlantic warming combined with near-equitable tropical and Arctic warming. In the U.S., only the atmosphere over the northern Rocky Mountain states demonstrates comparable stagnation projection uncertainty, due to opposite influences of remote drivers on the meteorological conditions that lead to stagnation, This work was supported by the Spanish Ministerio de Educación, Cultura y Deporte [Grant Number FPU16/01972]; the Spanish Ministerio de Economía y Competitividad [Grant NumberRYC-2014-15036]; and the Spanish Ministerio de Economía, Industria y Competitividad [Grant Numbers CGL2017-83198-R and RTI2018-096402-B-I00]. J L S was supported by the Ubben Program for Carbon and Climate Science while a postdoctoral researcher at Northwestern. D E H was supported by U.S. National Science Foundation grant CBET-1848683. ERA5 data provided courtesy ECMWF. The authors are also grateful to the World Climate Research Programme’s Working Group on Coupled Modelling, which is responsible for CMIP, and the modelling groups for producing and makingavailable their model outputs. Theauthorsthanktwoanonymousreviewersfortheir useful comments.

Non-tuberculous mycobacteria (NTM) circulate between the environment, animals and humans entailing a double concern: their ability to interfere with tuberculosis diagnosis and their potential to cause infections in their hosts. However, published records on NTM infections in animals are still scarce. The aims of the present study were to describe the diversity of NTM circulating among wild and domestic species from Spain and to analyze their implications as potential pathogenic microorganisms or as sources of interferences in the diagnosis of bovine tuberculosis. Overall, 293 NTM isolates of 277 animals were obtained from tissue samples collected between 2012 and 2019, and analyzed through a multigene approach for mycobacteria identification. Thirty-one species were identified, being Mycobacterium avium subsp. avium (Maa) and M. avium subsp. hominissuis (Mah), but also M. bouchedurhonense, M. nonchromogenicum and M. lentiflavum, the most abundant ones. Maa and M. lentiflavum were isolated in several animals showing tuberculosis-like lesions. Maa, Mah and M. nonchromogenicum were recovered from many cattle that had reacted to the tuberculin skin test. Other NTM were also associated to these phenomena. These four mycobacterial species were geographically associated between wild boar and other hosts. The findings of the present study suggest that a high diversity of NTM circulates among wildlife and livestock. Wild boar and M. avium seem to play a relevant role in this epidemiological scenario.

Two aspects of a widely used 1D model of blood flow in a single blood vessel are studied by symmetry analysis, where the variables in the model are the blood pressure and the cross-section area of the blood vessel. As one main result, all travelling wave solutions are found by explicit quadrature of the model. The features, behaviour, and boundary conditions for these solutions are discussed. Solutions of interest include shock waves and sharp wave-front pulses for the pressure and the blood flow. Another main result is that three new conservation laws are derived for inviscid flows. Compared to the well-known conservation laws in 1D compressible fluid flow, they describe generalized momentum and generalized axial and volumetric energies. For viscous flows, these conservation laws get replaced by conservation balance equations which contain a dissipative term proportional to the friction coefficient in the model., Comment: 23 pages; 9 figures

Purpose: Ascending aorta (AAo) acute pathology still has an open-surgery indication with a high mortality rate associated to cardiopulmonary bypass and circulatory arrest. In these cases, the endovascular aortic approach could be an excellent option. The aim of the present study is to detail an optimized technique for the endovascular treatment of AAo diseases, based on thoracic endovascular aortic repair (TEVAR) and transcatheter aortic valve implantation (TAVI) procedures. Technique: The procedure implies the usual preparation for TEVAR and TAVI implants. A transient pacemaker lead is necessary to deliver the prosthesis under “rapid pacing.” As in the TAVI technique, a final high-support guidewire is placed at the left ventricle. The proximal landing zone is the sinotubular junction (zone 0B). Transesophageal echocardiography is essential to ensure aortic valve function and patency in coronary arteries during the delivery. To assess a potential occlusion of the brachiocephalic artery, a guidewire is positioned in the descending aorta from the axillary artery. Finally, a noncovered stent is implanted to stabilize the AAo prosthesis. Conclusion: The technique presented here can standardize a safe and reproducible procedure to endovascular repair of AAo diseases. However, new devices specifically designed for the AAo could facilitate the transcatheter approach. Clinical Impact Ascending aorta acute pathology still has an open-surgery indication with high mortality rate associated to cardiopulmonary bypass and circulatory arrest. Moreover, near 30% of patients are not considered suitable for surgery because of age, critical situation or the presence of severe comorbidities. The present study provides a detailed and optimized technique for the endovascular treatment of ascending aorta disease, based on TEVAR and TAVI procedures.

ContextInvestigators in palliative care rely heavily on routinely collected data, which carry risk of unobserved confounding and selection bias. ‘Natural experiments’ offer opportunities to generate credible causal treatment effect estimates from observational data.ObjectivesWe aimed first to review studies that employed ‘natural experiments’ to evaluate palliative care, and second to consider implications for expanding use of these methods.MethodsWe searched systematically seven databases to identify studies using ‘natural experiments’ to evaluate palliative care’s effect on outcomes and costs. We searched three grey literature repositories, and hand-searched journals and prior systematic reviews. We assessed reporting using the Strengthening the Reporting of Observational Studies in Epidemiology checklist and a bespoke methodological quality tool, using two reviewers at each stage. We combined results in a narrative synthesis.ResultsWe included 17 studies, which evaluated a wide range of interventions and populations. Seven studies employed a difference-in-differences design; five each used instrumental variables and interrupted time series analysis. Outcomes of interest related mostly to healthcare use. Reporting quality was variable. Most studies reported lower costs and improved outcomes associated with palliative care, but a third of utilisation and place of death evaluations found no effect.ConclusionAmong the large number of observational studies in palliative care, a small minority have employed causal mechanisms. High-volume routine data collection, the expansion of palliative care services worldwide and recent methodological advances offer potential for increased use of ‘natural experiments’. Such studies would improve the quality of the evidence base.

A concise review covering updated presence and role of 2-phenethylamines in medicinal chemistry is presented. Open-chain, flexible alicyclic amine derivatives of this motif are enumerated in key therapeutic targets, listing medicinal chemistry hits and appealing screening compounds. Latest reports in discovering new bioactive 2-phenethylamines by research groups are covered too.

(S)-N1,N3-dibenzyl-1-cyclohexyl-N1,N3-bis((R)-1-phenylethyl)propane-1,3-diamine was prepared in good yield by the reduction of the corresponding amide, which was obtained by the addition of a chiral lithium amide to an α,β-unsaturated ester. The target compound was fully characterized by NMR (1H and 13C), high-resolution mass spectrometry and polarimetry.

BACKGROUND: Previous studies have demonstrated that Hospital at Home (HaH) care is associated with lower costs than traditional hospital care. Most prior studies were small, not U.S.-focused, or did not include post-acute costs in their analyses. Our objective was to determine if combined acute and 30-day post-acute costs of care were lower for HaH patients compared to inpatient comparisons in a Center for Medicare and Medicaid Innovation Center demonstration of HaH. METHODS: A single-center New York City retrospective observational cohort study of patients admitted to either HaH or inpatient care from Sept 1, 2014 through Aug 31, 2017. Eligible patients were 18 years or older, required inpatient admission, lived in Manhattan, and met home safety requirements. Comparison individuals met the same criteria and were included if they refused HaH care or were admitted when HaH was not available. HaH care was substitutive hospital-level care and 30-days of post-acute transitional care. Main outcomes were costs of care of the acute and post-acute 30-day episodes. We matched subjects on age, sex, and insurance and conducted regression analyses using an unadjusted model followed by one adjusted for several patient characteristics. RESULTS: Of 523 Medicare beneficiaries admitted, data were available for 201 patients in the HaH arm and 101 patients receiving usual care. HaH patients were older (81.6 [SD=12.3] yrs. vs 74.6 [SD=14.0], p

COVID-19 coronavirus disease is an often-severe illness caused by the SARS-CoV-2 virus. The pandemic has demanded a great organization and redistribution of infrastructure and medical resources for the care of patients with cancer. The Gynecology service of the Oncology Hospital of the City of Buenos Aires is a monovalent center dependent on the City of Buenos Aires. It is part of the network of 33 public hospitals in the City of Buenos Aires and receives referrals from other hospitals in the network and from hospitals in the Province of Buenos Aires. As of March 20, 2020, when decree 260/20 came into force, which established social, preventive and compulsory isolation, a new modality was started for the care and benefits of our hospital. In our Service of the Hospital de Oncología de la Ciudad de Buenos Aires we have developed recommendations for the management of gynecological tumors during the COVID-19. The guide we developed is based on up-to-date data and available resources and provides suggestions and tools for decision-making in order to reduce the morbidity and mortality of patients with gynecological cancer during the Coronavirus pandemic (COVID-19).La enfermedad por coronavirus COVID-19 causada por el virus SARS-CoV-2 es en muchos casos grave. La pandemia ha demandado una gran organización y redistribución de infraestructura y recursos médicos para la atención de pacientes con cáncer. El servicio de Ginecología del Hospital de Oncología Marie Curie es un centro monovalente dependiente del Gobierno de la Ciudad de Buenos Aires. Forma parte de la red de 33 hospitales públicos de la Ciudad y recibe derivaciones de otros hospitales de la red y de hospitales de la Provincia de Buenos Aires. A partir del 20 de marzo de 2020, cuando entró en vigor el decreto 260/20 que dispuso el aislamiento social, preventivo y obligatorio, se inició una nueva modalidad para la atención y prestaciones de nuestro hospital. En el Servicio de Ginecología del Hospital Marie Curie hemos desarrollado recomendaciones para el manejo de los tumores ginecológicos durante la pandemia por COVID-19. Elaboramos una guía basada en los datos actualizados y recursos disponibles entre los que se encuentran la guía del International Journal of Gynecological Cancer, la guía de la Sociedad Británica del Cáncer Ginecológico, las recomendaciones de la Asociación Argentina de Ginecología Oncológica, y la Guía de la Sociedad de Ginecología Oncológica Americana que proveen sugerencias y herramientas para la toma de decisiones con el objeto de reducir la morbilidad y mortalidad de las pacientes con cáncer ginecológico durante la pandemia por Coronavirus (COVID-19).

Ecosystem anthropization is a main driver of biodiversity loss, but not all species are equally susceptible. Understanding and preventing biodiversity loss is particularly important in rapidly changing and biodiversity-rich areas like the Neotropics and requires exploring the role of both intrinsic and extrinsic vulnerability drivers. Here, we test how multiple potential intrinsic and extrinsic factors explain vulnerability to extinction in neotropical birds to provide a first insight of what makes these species susceptible to extinction and how they are responding to anthropization. Our analyses included data for 2268 neotropical birds. We characterized extinction risk based on the IUCN Red List categorization and tested the predictive value of seven intrinsic and four extrinsic variables using Bayesian MCMC Phylogenetic Generalized Least-Squares (PGLS) models. As hypothesized, we found higher intrinsic vulnerability to extinction among bigger and more specialized species which have low reproductive output and occupy smaller distribution ranges. Extrinsic drivers were also relevant predictors with more threatened species overlapping largely area with fewer human activities (lower night light levels and lower human population densities). Our results show that the extinction risk of neotropical birds is correlated with both intrinsic and extrinsic factors. Intrinsic vulnerabilities were as expected associated with narrower, specialized niches and slower life-histories. However, risk was not higher in more humanized environments, but instead more at-risk species were found in less disturbed areas that we suggest may represent refuges for birds that previously occurred in wider ranges and have now been excluded from the more anthropized regions. Our results contribute to our understanding of vulnerability predictors in birds and provide a first evaluation of neotropical birds that highlights the complex relationship between human pressure and biodiversity loss.

This paper proposes a quadratic convex model for optimal operation of battery energy storage systems in a direct current (DC) network that approximates the original nonlinear non-convex one. The proposed quadratic convex model uses Taylor’s series expansion to transform the product between voltage variables in the power balance equations into a linear combination of them. Numerical simulations in the general algebraic modeling system (GAMS) for both models show small diferences in the daily energy losses, which are lower than 3.00%. The main advantage of the proposed quadratic model is that its optimal solution is achievable with interior point methods guaranteeing its uniqueness (convexity properties of the solution space and objective function), which is not possible to guarantee with the exact nonlinear non-convex model. The 30-bus DC test feeder with four distributed generators (with power generation forecast via artifcial neural networks with errors lower than 1% between real and predicted generation curves) and three batteries is used to validate the proposed convex and exact models. Numerical results obtained by GAMS show the efectiveness of the proposed quadratic convex model for diferent simulation scenarios tested, which was confrmed by the CVX tool for convex optimization in MATLAB

The management of hemorrhoidal disease (HD) in patients with bleeding disorders (BD) is challenging. Polidocanol foam sclerotherapy (PFS) is associated with a low rate of bleeding complications. The aim of this study was to compare the efficacy and safety of PFS in the treatment of HD in patients with and without BD.This prospective, multicenter, cohort study enrolled patients with (group B) and without (group A) BD, with symptomatic internal HD grades I-III over an 18-month period. All patients were treated with PFS. Patients with congenital BD did not undergo prior replacement therapy and those with acquired BD due to antithrombotic drugs, did not discontinue therapy. Efficacy outcomes included therapeutic success and HD recurrence during a 1-year follow-up period. To evaluate safety the complications related to PFS were recorded.We included 228 patients (group A: 155, group B: 73; male/female: 114/114; mean age: 59.4 ± 15.9 years). The baseline hemorrhoidal disease bleeding grade (p 0.001) and Sodergren hemorrhoidal symptom severity score (p = 0.019) were higher for group B. The overall therapeutic success rate was 93.4% with an average number of sessions of 1.51 ± 0.74, significantly higher for group B (1.68 ± 0.86 vs 1.43 ± 0.65, p = 0.013). Complications occurred in 11.4% of the patients, with bleeding reported in 4.8%. The majority of complications were mild (96.2%). No significant differences between the two groups were observed for therapeutic success, recurrence, or complication rate.Patients with BD may have more symptomatic HD at baseline. Even so, PSF showed similar effectiveness and safety in patients with BD compared to patients without BD.

Background/Aim: Lack of interchangeability between prostate-specific antigen (PSA) assays could have a clinical impact. We compared PSA assays from different manufacturers and calibrations. Patients and Methods: A total of 233 men who underwent prostate biopsy (PSA: 2-10 ng/ml; Beckman Coulter Access(®) Hybritech(®) as reference) were enrolled. Total (tPSA) and free PSA (fPSA) were also measured using the Roche cobas(®) and the Abbott Architect(®) methods. Results: Roche tPSA values were ≈1% higher than Beckman, while Abbott values were ≈5% lower. Roche had the highest diagnostic sensitivity (92%) compared to Beckman Coulter (87%) and Abbott (85%). Roche fPSA was ≈3% lower and Abbott ≈17% higher than that of Beckman. For the percentage of fPSA, Roche had the highest sensitivity (98%). Conclusion: Roche cobas(®) and Beckman Coulter Access(®) Hybritech(®) tPSA were almost interchangeable. While the agreement was acceptable for tPSA, this did not happen with fPSA and greater efforts for harmonization are required.

BACKGROUND: One in twenty older adults in the United States is homebound and rarely/never leaves home. Although being homebound decreases the quality of the lived experience of individuals with serious illnesses, little is known about the frequency or likelihood of transitions in or out of homebound status. The objective of this study was to characterize the probability of transitions to and from homebound status among older adults and examine the relationship between dementia status and homebound transitions. METHODS: Using 2011–2018 data from the National Health and Aging Trends Study (NHATS), a nationally-representative longitudinal study of aging in the US, we identified 6,375 community-dwelling Medicare beneficiaries. Homebound status (independent, semi-homebound (leaving home but with difficulty or help), homebound (rarely or never leaving home), nursing home resident, dead) was assessed annually via self-report. Transition probabilities across states was assessed using a multistate Markov model. RESULTS: Less than half of homebound individuals remain homebound (probability = 41.5% [95% CI: 39.2%, 43.5%]) after one year. One out of four die (24% [22.3%, 26.0%]) and there is a low probability (3.2% [2.5%, 4.1%]) of transition to a nursing home. Dementia status was associated with increased risk of progression from independence to homebound status (HR: 1.83 [1.01, 3.34]). Dementia was consistently associated with increased probabilities of transitions to death including a two-fold increased hazards of progression from homebound to death (HR: 2.18 [1.69, 2.81]). Homebound individuals with dementia have a 34.2% [25.8%, 48.1%] probability of death in 5 years, compared to 17.4% [13.7%, 24.3%] among those without dementia. DISCUSSION: Dementia is associated with greater risk of transitioning across homebound states. There is a greater need to support home-based care for patients with dementia, especially as the ongoing COVID pandemic has raised concerns about the need to invest in alternative models to nursing home care.

Insurance disruptions before, during, and after pregnancy are common in the United States, but little is known about the enrollment patterns of pregnant people in the Affordable Care Act Marketplaces. Data from the Pregnancy Risk Assessment Monitoring System from the period 2016-18 show that among respondents enrolled in Marketplace coverage, approximately one-third reported continuous Marketplace enrollment from preconception through the postpartum period. Compared with respondents who were continuously enrolled in Marketplace coverage from preconception through postpartum, respondents who enrolled in Marketplace plans during pregnancy had a 10.8 percent lower rate of adequate prenatal care, a 6.4 percent lower rate of timely prenatal care initiation, and a 13.2 percent lower rate of having twelve or more prenatal care visits. Policies that promote continuity of coverage during pregnancy, such as designating pregnancy as a qualifying event for a Marketplace open enrollment period, may enable pregnant people to enroll in Marketplace coverage early in their pregnancies and thus enhance access to prenatal care.

Homebound persons living with dementia may have increased difficulty accessing needed care in the community. This study identifies factors associated with becoming homebound among a national sample of Medicare beneficiaries with newly identified dementia.Prospective cohort analysis.We used the National Health and Aging Trends Study (NHATS) 2011-2018 to identify community-dwelling older adults at the time of a new dementia diagnosis (n = 939). Dementia status was determined based on cognitive testing and self and proxy reporting.We compared characteristics of homebound (ie, those who never or rarely left home) and non-homebound participants at the time of dementia identification. Among non-homebound participants, we used a Fine-Gray subdistribution hazard model to identify factors associated with becoming homebound over follow-up (median follow-up 4 years), accounting for competing risks of death and moving to a nursing home.20% of individuals with newly identified dementia were homebound and this group was more functionally impaired, medically complex, and socioeconomically disadvantaged as compared to the non-homebound. Over time, depression [subhazard ratio (SHR) 2.19, 95% CI 1.36, 3.54], living in an assisted living facility (SHR 2.60, 95% CI 1.35, 4.97), and Hispanic ethnicity (SHR 1.91, 95% CI 1.05, 3.47) were associated with becoming homebound.Most adults are not homebound at the time of dementia diagnosis. Identifying and addressing modifiable factors like depression may slow progression to homebound status and enable persons living with dementia to access needed care in the community. In order to accommodate diverse individual and family preferences for long-term care, robust systems of home-based clinical and long-term care are necessary for those who do become homebound.

BackgroundThe COVID-19 pandemic has introduced significant changes in the workplace, implementing teleworking as an effective solution to reduce contagionObjectivesWe sought to explore the impact of working from home on people with rheumatic and musculoskeletal diseases (RMDs) in Europe during the COVID-19 pandemic.MethodsREUMAVID is an international cross-sectional study collecting data through an online survey in seven European countries led by the Health & Territory Research group of the University of Seville, together with a multidisciplinary team including patient representatives, rheumatologists, and health researchers. Data were collected in two phases, the first (P1) between April-July 2020 and the second (P2) between February-April 2021. Demographics, health behaviors, employment status, access to healthcare services, disease characteristics, WHO-5 Well-Being Index and Hospital Anxiety and Depression Scale (HADS) were collected. Workplace conditions including internet connection, computer, workstation, webcam, telephone, light, noise, calmness, and temperature were assessed (on a scale of 0 to 5, being 5 the best condition). Pearson’s Chi-square test, Kruskal-Wallis and Mann-Whitney test were used to explore association with working from home.ResultsThere were a total of 3,802 participants across both phases (mean age 52.6 (P1) vs. 55.0 years (P2); 80.2% female (P1) vs 83.7% (P2); 69.6% married (P1) vs 68.3% (P2), 48.6% university educated (P1) vs 47.8% (P2), 34.7% employed (P1) vs 38.1 (P2)). Most prevalent RMD was axial spondyloarthritis in P1 (37.2%), and rheumatoid arthritis in P2 (53.1%). Rates of working from home were consistent (P1: 39.8% vs P2: 39.9%).In P2, 37.4% of those working from home had a home office, while 38.5% worked from their living room or kitchen. Work-related aspects at home were assessed, with the worst rated being the workplace (3.2) and the best being the computer (4.0). Compared to patients with good well-being and without anxiety and depression, patients with poorer well-being and at higher risk of anxiety or depression reported more frequently poorer rating of work from home issues, such as workplace (3.0 vs. 3.5; 2.9 vs. 3.6; 2.9 vs. 3.4; pTable 1.Bivariate analysis of aspect related to work from home and well-being, anxiety and depression in the second REUMAVID phaseMean ± SD or n (%)Poor well-beingGood well-beingP-valueRisk of anxietyNo risk of anxietyP-valueRisk of depressionNo risk of depressionP-valueWIFI N: 3543.8 ± 1.13.9 ± 1.10.5343.8 ± 1.23.9 ± 1.00.1933.8 ± 1.13.9 ± 1.10.264Computer or laptop N: 3523.9 ± 1.14.1 ± 1.00.0313.8 ± 1.24.2 ± 0.90.0023.9 ± 1.14.1 ± 1.10.049Workstation N: 3473.0 ± 1.43.5 ± 1.32.9 ± 1.43.6 ± 1.22.9 ± 1.43.4 ± 1.3Webcam N: 3423.4 ± 1.53.7 ± 1.40.0693.4 ± 1.53.7 ± 1.40.0433.4 ± 1.33.6 ± 1.50.055Telephone2 N: 3503.9 ± 1.24.0 ± 1.30.2893.9 ± 1.34.0 ± 1.20.4843.8 ± 1.24.0 ± 1.30.034Light N: 3543.6 ± 1.24.0 ± 1.13.6 ± 1.24.0 ± 1.10.0013.5 ± 1.24.0 ± 1.1Noise N: 3533.3 ± 1.33.8 ± 1.43.2 ± 1.43.9 ± 1.23.2 ± 1.43.8 ± 1.3Calmness N: 3533.3 ± 1.44.0 ± 1.23.2 ± 1.44.0 ± 1.13.1 ± 1.43.9 ± 1.3Temperature N: 3533.6 ± 1.23.8 ± 1.20.0533.5 ± 1.33.9 ± 1.10.0083.5 ± 1.23.8 ± 1.20.039ConclusionPatients with poorer well-being, at higher risk of anxiety or depression reported poorer ratings of workspace-related aspects. Therefore, although work from home has helped to reduce the spread of the COVID-19 pandemic, the conditions under which RMD patients work from home must be considered, as these may affect the well-being and mental health of an already vulnerable group. It is necessary to assess the conditions of home-based workspaces - especially for workers with chronic diseases such as RMD patients - to ensure that it is feasible to work from home and that employers provide the necessary equipment for healthy work.AcknowledgementsThis study was supported by Novartis Pharma AG. We would like to thank all patients that completed the survey as well as all of the patient organisations that participated in the REUMAVID study including: the Cyprus League for People with Rheumatism (CYLPER) from Cyprus, the Association Française de Lutte Anti-Rhumatismale (AFLAR) from France, the Hellenic League Against Rheumatism (ELEANA) from Greece, the Associazione Nazionale Persone con Malattie Reumatologiche e Rare (APMARR) from Italy, the Portuguese League Against Rheumatic Diseases (LPCDR), from Portugal, the Spanish Federation of Spondyloarthritis Associations (CEADE), the Spanish Patients’ Forum (FEP), UNiMiD, Spanish Rheumatology League (LIRE), Andalusian Rheumatology League (LIRA), Catalonia Rheumatology League and Galician Rheumatology League from Spain, and the National Axial Spondyloarthritis Society (NASS), National Rheumatoid Arthritis (NRAS) and Arthritis Action from the United Kingdom.Disclosure of InterestsMarco Garrido-Cumbrera Grant/research support from: has a research collaboration with and provides services to Novartis Pharma AG, Victoria Navarro-Compán Grant/research support from: AbbVie, BMS, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Laura Christen Employee of: Novartis Pharma AG, José Correa-Fernández: None declared, Helena Marzo-Ortega Speakers bureau: AbbVie, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Takeda and UCB, Consultant of: AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer and UCB, Grant/research support from: Janssen and Novartis

Even though enormous efforts and control strategies have been implemented, bovine tuberculosis (TB) remains a significant source of health and socioeconomic concern. The standard method used in TB eradication programs for in vivo detection is the tuberculin skin test. However, the specificity of the tuberculin skin test is affected by infection with non-tuberculous mycobacteria or by vaccination. Thus, some animals are not correctly diagnosed. This study aimed firstly to identify a plasma metabolic TB profile by high-field (HF) nuclear magnetic resonance spectroscopy (NMR), and secondly measure this characteristic TB metabolic profile using low-field benchtop (LF) NMR as an affordable molecular technology for TB diagnosis. Plasma samples from cattle diagnosed with TB (derivation set, n = 11), diagnosed with paratuberculosis (PTB, n = 10), PTB-vaccinated healthy control (n = 10), and healthy PTB- unvaccinated control (n = 10) were analyzed by NMR. Unsupervised Principal Component Analysis (PCA) was used to identify metabolic differences between groups. We identified 14 metabolites significantly different between TB and control animals. The second group of TB animals was used to validate the results (validation set, n = 14). Predictive models based on metabolic fingerprint acquired by both HF and LF NMR spectroscopy successfully identified TB versus control subjects (Area Under the Curve of Receiver Operating Characteristic over 0.92 -in both models; Confidence Interval 0.77-1). In summary, plasma fingerprinting using HF and LF-NMR differentiated TB subjects from uninfected animals, and paratuberculosis and PTB-vaccinated subjects that may provide a TB false positive, highlighting the use of LF-NMR based metabolomics as a complementary or alternative diagnostic tool to the current diagnostic methods. This article is protected by copyright. All rights reserved.

Bovine paratuberculosis (PTB) is a chronic inflammatory disease caused by Mycobacterium avium susbp. paratuberculosis (MAP). Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) significantly associated with susceptibility to bovine PTB. The main objective of this study was to identify quantitative trait loci (QTLs) associated with MAP infection in Spanish Holstein cows (N = 983) using combinations of diagnostic tests and imputed whole-genome sequence (WGS) data. The infection status of these animals was defined by three diagnostic methods including ELISA for MAP-antibodies detection, and tissue culture and PCR for MAP detection. The 983 cows included in this study were genotyped with the Bovine MD SNP50 Bead Chip, and the corresponding genotypes were imputed to WGS using the 1,000 Bull genomes reference population. In total, 33.77 million SNP variants per animal were identified across the genome. Linear mixed models were used to calculate the heritability (h2) estimates for each diagnostic test and test combinations. Next, we performed a case-control GWAS using the imputed WGS datasets and the phenotypes and combinations of phenotypes with h2 estimates > 0.080. After performing the GWAS, the test combinations that showed SNPs with a significant association (PFDR ≤ 0.05), were the ELISA-tissue PCR-tissue culture, ELISA-tissue culture, and ELISA-tissue PCR. A total of twelve quantitative trait loci (QTLs) highly associated with MAP infection status were identified on the Bos taurus autosomes (BTA) 4, BTA5, BTA11, BTA12, BTA14, BTA23, BTA24, and BTA28, and some of these QTLs were linked to immune-modulating genes. The identified QTLs on BTA23 spanning from 18.81 to 22.95 Mb of the Bos taurus genome overlapped with several QTLs previously found to be associated with PTB susceptibility, bovine tuberculosis susceptibility, and clinical mastitis. The results from this study provide more clues regarding the molecular mechanisms underlying susceptibility to PTB infection in cattle and might be used to develop national genetic evaluations for PTB in Spain. Financial support for this study was provided by a grant from the Spanish Ministry of Science, Innovation, and Universities (MICINN, project code: RTI2018-094192-R-C21) and by European Regional Development Funds (FEDER) to MAH. MC and GBB have been awarded fellowships from the National Institute for Agricultural Research (INIA) and MICINN, respectively

The sustainable management of coastal lagoon hydrosystems is a key issue for the socio-economic and environmental development of many coastal areas worldwide. Often maintained by direct or indirect groundwater supplies, they provide a large range of ecosystem services, from which human societies take advantage. Twenty years after its implementation, a large majority of the Mediterranean lagoons have still not reached the "good status" required by the WFD. Several questions then arise as to the representativeness of the WFD indicators or the relevance of the restoration objectives considering the complexity, evolutionary and unpredictable nature of lagoon hydrosystems. This study proposes an innovative, multidisciplinary, long-term approach to define the proper functioning conditions of a costal lagoon hydrosystems, i.e. all the factors that contribute to the functioning of coastal lagoon hydrosystems and the connectivity with other biodiversity reservoirs, be they ecological, hydrological, social or political. By considering the lagoons and all its hydrological, ecological and societal proper functioning conditions over almost 200 years, this approach makes it possible to assess the influence of past natural and anthropogenic disturbances and support the implementation of future relevant hydrosystem-based management plans which have to be coordinated and politically driven. Defining proper restoration and management objectives should ensure that ecological functions are maintained based on current and future ecosystem benefits and uses. Considering the highly unpredictable nature of coastal hydrosystems, the state of an ecosystem should not only be evaluated on ecological or chemical criteria but also take into account socio-economic and political indicators. The implementation of the 3rd river basin management plan of the WFD as soon as 2022 could be the appropriate occasion to reassess the restoration objectives towards more realistic goals and to give more significance to the definition of the "resilience capacity" of water bodies in place of inappropriate restricted restauration objectives.

Bovine paratuberculosis (PTB), caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic granulomatous enteritis that affects cattle worldwide. According to their severity and extension, PTB-associated histological lesions have been classified into the following groups; focal, multifocal, and diffuse. It is unknown whether these lesions represent sequential stages or divergent outcomes. In the current study, the associations between host genetics and pathology were explored by genotyping 813 Spanish Holstein cows with no visible lesions (N= 373) and with focal (N=371), multifocal (N=33), and diffuse (N=33) lesions in gut tissues and regional lymph nodes. DNA from peripheral blood samples of these animals was genotyped with the Bovine EuroG MD Bead Chip, and the corresponding genotypes were imputed to whole-genome sequencing (WGS) data using the 1,000 Bull genomes reference population. A genome-wide association study (GWAS) was performed using the WGS data and the presence or absence of each type of histological lesion in a case-control approach. No overlap was seen in the SNPs controlling the three PTB-associated lesions. A total of 192 and 92 SNPs defining 13 and 9 distinct quantitative trait loci (QTLs) were highly-associated (P ≤ 5 x 10-7) with the multifocal (heritability= 0.075) and the diffuse (heritability= 0.189) lesions, respectively. Some of the identified QTLs overlapped with QTLs previously associated with PTB, bovine tuberculosis, mastitis, and IgG levels. Pathway analysis with candidate genes overlapping the identified QTLs revealed a significant enrichment of the keratinization pathway and cholesterol metabolism in the animals with multifocal and diffuse lesions, respectively. While keratin variants may predispose cows to the development of multifocal lesions, cholesterol variants associate with the more severe lesions. Taken together, these findings suggest that the variation in MAP-associated pathological outcomes might be genetically determined and indicative of distinct host responses in genetically predisposed individuals.

The Human Variome Project (HVP) is an international effort aiming systematically to collect and share information on all human genetic variants. It has been working for years in collaboration with local scientific societies by establishing systems to collect every genetic variant reported in a country and to store these variants within a database repository: LOVD (Argentinian chapter: ar.lovd.org). Formally established in 2017 in the Argentinian Node, up to June 2019 we collected more than 25,000 genetic variants deposited by 17 different laboratories. Nowadays the HVP country nodes represent more than 30 countries. In Latin America there are four country nodes: Argentina, Brazil, Mexico and Venezuela; the first two interacted recently launching the LatinGen database. In the present work we want to share our experience in applying the HVP project focusing on its organization, rules and nomenclature to reach the goal of sharing genetic variants and depositing them in the Leiden Open Variation Database. Contributing laboratories are seeking to share variant data to gain access all over the country. It is one of our goals to stimulate the highest quality by organizing courses, applying current nomenclature rules, sponsoring lectures in national congresses, distributing newsletter to serve the Argentinian genomics community and to stimulate the interaction among Latin America countries. El Proyecto Varioma Humano (HVP) es un esfuerzo internacional que tiene como objetivo recopilar y compartir sistemáticamente información sobre todas las variantes genéticas humanas. Hemos estado trabajando durante tres años en colaboración con sociedades científicas locales, mediante el establecimiento de sistemas para recolectar todas las variantes genéticas reportadas en el país y almacenarlas dentro de la base de datos LOVD (capítulo argentino: ar.lovd.org). En el año 2017 fue establecido formalmente el Nodo Argentino del HVP, habiéndose recolectado más de 25.000 variantes genéticas depositadas por 17 laboratorios diferentes hasta junio de 2019. Hoy en día existen al menos 30 nodos del HVP, correspondientes a diferentes países. En América Latina hay cuatro nodos: Argentina, Brasil, México y Venezuela; Los dos primeros interactuaron recientemente lanzando la base de datos LatinGen. En el presente trabajo queremos compartir nuestra experiencia en la aplicación del proyecto HVP centrándonos en su organización, reglas y nomenclatura para alcanzar el objetivo de compartir variantes genéticas y depositarlas en la base de datos de variaciones abiertas de Leiden (LOVD). Es uno de nuestros objetivos estimular la más alta calidad mediante la organización de cursos, aplicación de las reglas de nomenclatura actuales, patrocinio de conferencias en congresos nacionales, distribución de boletines informativos para la comunidad de genómica argentina, y estimulación de la interacción entre los países de América Latina.

Even though sympathetic dominance during the daytime period is well known, currently, scarce data exist on autonomic nervous system (ANS) regulation during sleep in pediatric obesity. We aimed to evaluate sleep cardiac ANS regulation in normal-weight (NW) and overweight and obese (OW) adolescents.In this study, 60 healthy adolescents (15.7 ± 0.7 years) belonging to a birth cohort since infancy were classified based on body mass index percentiles criteria as: OW (N = 27) or NW (N = 33). Sleep was evaluated by polysomnography (PSG) during two consecutive in-lab overnight sessions. Non-rapid eye movement (non-REM) sleep stages (stages 1, 2, and slow-wave sleep [SWS]), rapid eye movement (REM) sleep, and wakefulness (Wake) were scored. R-waves were detected automatically in the electrocardiographic (ECG) signal. An all-night heart rate variability analysis was conducted in the ECG signal, with several time- and frequency-domain measures calculated for each sleep-wake stage. Sleep time was divided into thirds (T1, T2, T3). The analysis was performed using a mixed-effects linear regression model.Sleep organization was comparable except for reduced REM sleep percentage in the OW group (p 0.04). Shorter R-R intervals were found for all sleep stages in the OW group; time-domain measured standard deviation of all R-R intervals (RRSD) was lower during stage 2, SWS and REM sleep (all p 0.05). The square root of the mean of the sum of the squares of differences between adjacent R-R intervals (RMSSD) was also lower only during wake after sleep onset (WASO) in T1 and T3 (p 0.05). The OW group had increased very low- and low-frequency (LF) power during WASO (in T1 and T2), and LF power during stage 2 and REM sleep (in T2). During WASO in the OW group, high-frequency (HF) power was lower (in T1 and T2), and LF/HF ratio was higher (in T2, p 0.007).Several sleep-stage-dependent changes in cardiac autonomic regulation characterized the OW group. As sleep-related ANS balance was disturbed in the absence of concomitant metabolic alterations in this sample of otherwise healthy OW adolescents, their relevance for pediatric obesity should be further explored throughout development.

Introduction: Collecting duct carcinomas (CDC), also known as Bellini’s tumors, are a rare and aggressive subtype of renal cell carcinoma. Therefore, there are very few data about their management, and there is no standard therapy for this malignancy. We report the outcome of CDC patients treated on institutions belonging to the ‘Grupo Centro’ of Genitourinary Tumors, a novel networking cooperative group in Spain. Material and Methods: Patients with CDC diagnosed between 1995 and 2015 were included. They had to have an appropriate follow-up, as well as available tissue for further correlative studies. Demographic baseline features and therapy outcomes were collected in a retrospective fashion. Approval for this data collection was obtained from a central ethical committee. Results: A total of 43 patients were analysed, with a median overall survival (OS) of 14 months (95% CI: 9.2–18.8 months). 29 of them (67.4%) were diagnosed as localized disease, and 14 (32.6%) as metastatic disease. For the subgroup of patients diagnosed without metastases, median relapse-free survival (RFS) is 22 months (95% CI: 12.4–35.6 months), and median OS, 53 months (95% CI: 35.5–84.3 months). For the subgroup of patients with metastatic disease, median OS is 6 months (95% CI: 4.1–7.8 months). 16 patients (55.2%) with stage IV disease received systemic therapy, mainly platinum-based chemotherapy, with a response rate of 12.5% and a median progression-free survival (PFS) of 2 months. Conclusions: CDC of the kidney is a malignancy with poor prognosis and few responses to therapy. Median OS of our group in the metastatic setting is similar to what has been observed in previous series. There is a clear need to improve the armamentarium we have for the systemic approach of patients with advanced CDC.

Background: US health care systems face a growing demand to incorporate innovations that improve patient outcomes at a lower cost. Funding agencies increasingly must demonstrate the impact of research investments on public health. The Learning Health System promotes continuous institutional innovation, yet specific processes to develop innovations for further research and implementation into real-world health care settings to maximize health impacts have not been specified. Objective: We describe the Research Lifecycle and how it leverages institutional priorities to support the translation of research discoveries to clinical application, serving as a broader operational approach to enhance the Learning Health System. Methods: Developed by the US Department of Veterans Affairs Office of Research and Development Research-to-Real-World Workgroup, the Research Lifecycle incorporates frameworks from product development, translational science, and implementation science methods. The Lifecycle is based on Workgroup recommendations to overcome barriers to more direct translation of innovations to clinical application and support practice implementation and sustainability. Results: The Research Lifecycle posits 5 phases which support a seamless pathway from discovery to implementation: prioritization (leadership priority alignment), discovery (innovation development), validation (clinical, operational feasibility), scale-up and spread (implementation strategies, performance monitoring), and sustainability (business case, workforce training). An example of how the Research Lifecycle has been applied within a health system is provided. Conclusions: The Research Lifecycle aligns research and health system investments to maximize real-world practice impact via a feasible pathway, where priority-driven innovations are adapted for effective clinical use and supported through implementation strategies, leading to continuous improvement in real-world health care.

A convenient asymmetric synthesis of methyl (2S,3S,6R)-6-(4-fluorophenyl)-2-(4-hydroxyphenyl)-piperidine-3-carboxylate is described, starting from Baylis–Hillman adducts. The route involves a domino process: allylic acetate rearrangement, stereoselective Ireland–Claisen rearrangement and asymmetric Michael addition, which provides a δ-amino acid derivative with full stereochemical control. A subsequent chemoselective transformation of one of the side-chain groups allows an effective cyclization leading to biologically interesting polysubstituted piperidines in which the 2,6-aryl groups could be attached sequentially.

In this paper, by applying the multiplier method we obtain a complete classification of low-order local conservation laws for a generalized seventh-order KdV equation depending on seven arbitrary nonzero parameters. We apply the Lie method in order to classify all point symmetries admitted by the equation in terms of the arbitrary parameters. We find that there are no special cases of the parameters for which the equation admits extra symmetries, other than those that can be found by inspection (scaling symmetry and space and time translation symmetries). We consider the reduced ordinary differential equations and we determined all integrating factors of the reduced equation from the combined x - and t - translation symmetries. Finally, we observe that all integrating factors arise by reduction of the low-order multipliers of the generalized seventh-order KdV equation.

The use of a hybrid membrane bioreactor (MBR) post-treatment system is proposed as a cost-efficient technology in order to minimize the environmental impact of anaerobic effluents, treating low-strength sewage at room temperature, such as their high nitrogen content and the presence of dissolved methane. In this research, nitrite was externally added at different concentrations into the anoxic compartment, providing an extra electron acceptor besides the existing nitrate, to evaluate its effect on denitrification, methane oxidation and OMPs removal processes. The nitrite addition significantly improved the denitrification potential of the system, achieving nitrogen removals up to 35 mg TN L−1. Moreover, higher nitrite concentrations clearly promoted an increase in the removal of some organic micropollutants (OMPs) such as diclofenac (DCF), ethinylestradiol (EE2), triclosan (TCS) and ibuprofen (IBP). Nevertheless, methane removal efficiencies or rates were not affected by this fact. Finally, COD and ammonium removals higher than 99 and 91% were observed during the entire operation, respectively. Based on the results, a future strategy in which ammonium is partially oxidized to nitrite could result in better nitrogen and OMPs removals for the proposed technology.

In this paper, symmetry groups are used to obtain symmetry reductions of (2+1)-dimensional KdV equations with variable coefficients. Despite the fact that these equations emerge in a nonlocal form,...

Resumen: La cirugía cardiovascular es la especialidad médica que se ocupa de la prevención, diagnóstico y tratamiento quirúrgico de los trastornos y enfermedades del sistema cardiocirculatorio. Los continuos y rápidos avances en el diagnóstico y tratamiento de las enfermedades cardiovasculares justifican la necesidad de llevar a cabo una actualización de los principales aspectos definitorios y organizativos de la especialidad, relacionados con la profesión (de la práctica, calidad asistencial), con el programa docente de la especialidad, la formación continuada de los cirujanos, los procesos de acreditación desde la Sociedad Española de Cirugía Torácica-Cardiovascular, entre otros.Este documento, elaborado por expertos de la cirugía cardiovascular, representa la opinión de la Sociedad Española de Cirugía Torácica-Cardiovascular y actualiza los principales aspectos de la especialidad en nuestro país. Abstract: Cardiovascular surgery is the medical specialty that deals with the prevention, diagnosis, and surgical treatment of disorders and diseases of the circulatory system. The continuous and rapid advances in the diagnosis and treatment of cardiovascular diseases justify the need to update the main, defining, and organisational aspects of the specialty, related to the profession (its practice, quality care), aspects on the teaching program of the specialty, the continuing education program of the surgeons, the processes of accreditation from the Spanish Society of Thoracic-Cardiovascular Surgery, etc.This document, prepared by experts in cardiovascular surgery, represents the opinion of the Spanish Society of Thoracic-Cardiovascular surgery and updates the main aspects of the specialty in our country. Palabras clave: Cirugía cardiovascular, Cirugía cardíaca, Cirugía torácica, Cirugía vascular, Recomendaciones, Keywords: Cardiovascular surgery, Cardiac surgery, Thoracic surgery, Vascular surgery, Recommendations