La ecuación de Ince-Hill

RESUMEN La ecuación de Ince-Hill es una ecuación diferencial lineal de segundo orden con coecientes periódicos que depende de 4 parámetros a; b; c y d (1 + a cos 2x) d2y dx2 + b sen 2x dy dx + (c + d cos 2x)y = 0 (1) Uno de los motivos de interés de esta ecuación reside en aparecer en ecuaciones variacionales ligadas a problemas de Mecánica Celeste. Con frecuencia el parámetro a representa ¡e, siendo e la excentricidad. Precisamente, una de las motivaciones iniciales de esta tesis es el estudio de la estabilidad de la solución trivial de (1) para los numerosos problemas de mecánica a los que se aplica. Este estudio no resulta nada sencillo desde el punto de vista analítico. Observar que la ecuación de Ince-Hill es una ecuación diferencial lineal de segundo orden que posee singularidades regulares, también llamadas de tipo Fuchs, es por ello que la tesis está dividida endos partes. Una primera, más general, que comprende los 2 primeros capítulos, dedicada al estudio local de los sistemas de ecuaciones diferenciales lineales con una singularidad de Fuchs, representa un marco general para este tipo de ecuaciones. En esta primera parte, en el Capítulo 2, realizamos el estudio local de la foliación denida por un sistema lineal complejo en un entorno de una singularidad de Fuchs. Este estudio general representa uno de los resultados más destacados de la tesis, ya que, aunque las ecuaciones lineales con coecientes holomorfos han sido abordadas usualmente desde el punto de vista analítico, su consideración como sistema dinámico, y la introducción de métodos algebraicos ha sido más reciente. Así la foliación para sistemas lineales ha sido realizada por Camacho, C., H. Kuiper, N., Palis, J. En nuestro caso se trata del estudio de sistemas con singularidades tipo Fuchs. A diferencia de Camacho, C., H. Kuiper, N., Palis, J. en el que se realiza un estudio de la foliación realizado mediante métodos con independencia de las coordenadas, la presencia de singularidades nos obligada a basarnos en ellas. Como resultado obtenemos una caracterización de la foliación determinada por el campo vectorial. Continuando con la analogía entre Camacho, C., H. Kuiper, N., Palis, J. y el caso con un sistema con singularidades, en el Capítulo 3 vemos como se puede llevar el estudio realizado en el Capítulo 2 a los campos vectoriales en CPn. Generalizando los trabajos de Zakeri, S. obtenemos una relación entre los campos vectoriales lineales en Cn+1 y los campos vectoriales en CPn con una singularidad de Fuchs. La segunda parte de la tesis, que comprende el Capítulo 4, la dedicamos al estudio particular de la ecuación de Ince-Hill. Se clasica en función del tipo de singularidades que posee para los distintos valores de los parámetros, para lo cual analizamos la forma algebraica de la ecuación. Finalmente, realizamos un estudio de la misma en el caso en el que la ecuación se puede expresar como un sistema Hamiltoniano y realizamos el estudio de la estabilidad para algunos casos concretos de los parámetros, siguiendo uno de los objetivos señalados anteriormente. ____________________________________________________________________________________________________The Ince-Hill's equation is a linear dierential equation of second degree with periodic coecients that depends on four parameters a; b; c and d (1 + a cos 2x) d2y dx2 + b sin 2x dy dx + (c + d cos 2x) y = 0 (1) The interest of (1) is that all the known cases of equations of Hill's kind with analytic coecients and solved problems of coexistence are particular cases of this equation with four parameters. (1) is in general no much studied, but particular cases of this equation appears on variational equations associated to problems of Celestial Mechanics. Frequently the parameter a denotes ¡e, where e is the eccentricity. Precisely, one of the initial motivations of this thesis is the study of the stability of the trivial solution of (1) for the numerous problems of mechanics that is applied. This study is not easy from the analysis viewpoint. Note that the Ince-Hill's equation is a linear dierential equation of second degree with regular singularities, this singularities are namely singularities of Fuchs kind. So the thesis is divided in two parts. The rst, more general, includes the two rst chapters and it is dedicated to local study of linear dierential equations systems with a singularity of Fuchs. In this part, in chapter 2, we make a local study of the foliation dened for a complex linear system in a neighbourhood of a singularity of Fuchs. This general study is one of the more emphasized results of the thesis is due to that although the linear equations with holomorphic coecients usually have been analyze from the analysis viewpoint, its consideration such us dynamical system and the introduction of algebraic methods is more recent. So the foliation for linear systems has been realized for Camacho, C., H. Kuiper, N., Palis, J. Our case is about the study of systems with singularities of Fuchs. In contrast to Camacho, C., H. Kuiper, N., Palis, J. which is realized an study of the foliation with methods independents of the coordinates, the existence of singularities forces to work with these. As a result we get a characterization of the foliation determined from the vectorial eld. Continue with the analogy between Camacho, C., H. Kuiper, N., Palis, J. and the case of a system with singularities, in chapter 3 we study about the generalization of the results in chapter 2 to vectorial elds in CPn. We generalize the work of Zakeri, S. and obtain a relation between the linear vectorial elds in Cn+1 and the vectorial elds in CPn with a singularity of Fuchs. The second part of the thesis, that includes the chapter 4 is dedicated to particular study of the Ince-Hill's equation. One of the results that we obtain is the classication of the equation in function of the kind of the singularities for the dierent values of the parameters, for this we analyze the algebraic form of the equation. Finally, we make an study of the equation in the case that the equation maybe expressed like a hamiltonian system and we study the stability for some concreted cases of the parameters

Patient engagement and patient support programs in allergy immunotherapy: A call to action for improving long-term adherence

Allergy immunotherapy (AIT) is acknowledged to produce beneficial mid- and long-term clinical and immunologic effects and increased quality of life in patients with allergic respiratory diseases (such as allergic rhinoconjunctivitis and allergic asthma). However, poor adherence to AIT (due to intentional and/or non-intentional factors) is still a barrier to achieving these benefits. There is an urgent need for patient support programs (PSPs) that encompass communication, educational and motivational components. In the field of AIT, a PSP should be capable of (1) improving adherence, (2) boosting patient engagement, (3) explaining how AIT differs from pharmacological allergy treatments; (4) increasing health literacy about chronic, progressive, immunoglobulin-E-mediated immune diseases, (5) helping the patient to understand and manage local or systemic adverse events, and (6) providing and/or predicting local data on aeroallergen levels. We reviewed the literature in this field and have identified a number of practical issues to be addressed when implementing a PSP for AIT: the measurement of adherence, the choice of technologies, reminders, communication channels and content, the use of "push" messaging and social networks, interactivity, and the involvement of caregivers and patient leaders. A key issue is "hi-tech" (i.e. approaches based mainly on information technology) vs. "hi-touch" (based mainly on interaction with humans, i.e. family members, patient mentors and healthcare professionals). We conclude that multistakeholder PSPs (combining patient-, provider and society-based actions) must now be developed and tested with a view to increasing adherence, efficacy and safety in the field of AIT

Experimental evaluation into novel, low cost, modular PEMFC stack

Attribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND 3.0)The Polymer Electrolyte Membrane Fuel Cell (PEMFC), despite being regarded as an ideal replacement to the internal combustion engine, is still not an economically attractive pri-mover due to a number of key challenges that have yet to be fully resolved; some of which include degradation to cell components resulting in inadequate lifetimes, specialised and costly manufacturing processes and poor gravimetric/volumetric energy densities. This paper presents a novel stack concept which removes the conventional bi polar plate (BPP), a component that is responsible for up to 80% of total stack weight and 90+% of stack volume in some designs. The removal of said component not only improves the volumetric and gravimetric energy density of the PEMFC stack but drastically reduces the cost of the stack by removing all costly manufacturing processes associated with PEMFC component machining while the functionality of the traditional BPP is still retained by the unique stack design. The stack architecture is first presented and then the characterisation of the PEMFC is shown over a wide range of operating scenarios. The experimental studies suggest that the performance of the new design is comparable to that of traditional stacks but at significantly less cost price.Final Published versio

Consensus on the Clinical Approach to Moderate-to-Severe Atopic Dermatitis in Spain: A Delphi Survey

Background. The purpose of this study was to gather information on the current assessment and management of patients with moderate-to-severe AD in routine daily practice. Methods. A cross-sectional two-round Delphi survey with the participation of dermatologists and allergologists throughout Spain was conducted. They completed a 46-item questionnaire, and consensus was defined when responses of >= 80% of participants coincided in the categories of a 5-point Likert scale for that item. Results. A total of 105 specialists (aged 40-59 years) completed the two rounds. Participants agreed regarding the consideration of AD as a multifaceted disease and the differences in clinical presentation of AD according to the patient's age. It is recommendable to perform a skin biopsy to exclude early stage T-cell cutaneous lymphoma, psoriasis, or dermatitis herpetiformis, among others (99.1%). Also, consensus was reached regarding the use of the SCORAD index to quantify the severity of the disease (86.7%), the use of wet wraps to increase the effect of topical corticosteroids (90.4%), the usefulness of proactive treatment during follow-up (85.6%) and tacrolimus ointment (91.2%) to reduce new flares, and the fact that crisaborole is not the treatment of choice for severe AD (92.4%). AD was not considered a contraindication for immunotherapy in patients with allergic respiratory diseases (92.4%). In patients with severe AD, the use of immune response modifier drugs (97.6%) or phototherapy (92.8%) does not sufficiently cover their treatment needs. Consensus was also obtained regarding the role of the new biologic drugs (93.6%) targeting cytokines involved in the Th2 inflammatory pathway (92.0%) and the potential role of dupilumab as first-line treatment (90.4%) in moderate-to-severe AD patients. Conclusion. This study contributes a reference framework to the care of AD patients. There is no diagnostic test or biomarkers to direct treatment or to assess the severity of the disease, and many therapeutic challenges remain

Analysis of microstructure and defects in 17-4 PH stainless steel sample manufactured by Selective Laser Melting

n/

変質花崗岩を配合した粘土瓦成形体の変形要因に関する研究

Although not yet widely implemented, fraction of exhaled nitric oxide (FeNO) has emerged in recent years as a potentially useful biomarker for the assessment of airway inflammation both in undiagnosed patients with non-specific respiratory symptoms and in those with established airway disease. Research to date essentially suggests that FeNO measurement facilitates the identification of patients exhibiting T-helper cell type 2 (Th2)-mediated airway inflammation, and effectively those in whom anti-inflammatory therapy, particularly inhaled corticosteroids (ICS), is beneficial. In some studies, FeNO-guided management of patients with established airway disease is associated with lower exacerbation rates, improvements in adherence to anti-inflammatory therapy, and the ability to predict risk of future exacerbations or decline in lung function. Despite these data, concerns regarding the applicability and utility of FeNO in clinical practice still remain. This article reviews the current evidence, both supportive and critical of FeNO measurement, in the diagnosis and management of asthma and other inflammatory airway diseases. It additionally provides suggestions regarding the practical application of FeNO measurement: how it could be integrated into routine clinical practice, how its utility could be assessed and its true value to both clinicians and patients could be established. Although some unanswered questions remain, current evidence suggests that FeNO is potentially a valuable tool for improving the personalised management of inflammatory airway diseases.<br/

Point-of-care biomarkers in asthma management : time to move forward

Peer reviewedPostprin

Optic Nerve Topography in Multiple Sclerosis Diagnosis

To assess the added value of the optic nerve region (by using visual evoked potentials [VEPs]) to the current diagnostic criteria. From the Barcelona clinically isolated syndrome (CIS) cohort, patients with complete information to assess dissemination in space (DIS), the optic nerve region, and dissemination in time at baseline (n = 388) were selected. Modified DIS (modDIS) criteria were constructed by adding the optic nerve to the current DIS regions. The DIS and modDIS criteria were evaluated with univariable Cox proportional hazard regression analyses with the time to the second attack as the outcome. A subset of these patients who had at least 10 years of follow-up or a second attack occurring within 10 years (n = 151) were selected to assess the diagnostic performance. The analyses were also performed according to CIS topography (optic neuritis vs non-optic neuritis). The addition of the optic nerve as a fifth region improved the diagnostic performance by slightly increasing the accuracy (2017 DIS 75.5%, modDIS 78.1%) and the sensitivity (2017 DIS 79.2%, modDIS 82.3%) without lowering the specificity (2017 DIS 52.4%, modDIS 52.4%). When the analysis was conducted according to CIS topography, the modDIS criteria performed similarly in both optic neuritis and non-optic neuritis CIS. The addition of the optic nerve, assessed by VEP, as a fifth region in the current DIS criteria slightly improves the diagnostic performance because it increases sensitivity without losing specificity

Endoglin and MMP14 contribute to Ewing sarcoma spreading by modulation of cell-matrix interactions

Endoglin (ENG) is a mesenchymal stem cell (MSC) marker typically expressed by active endothelium. This transmembrane glycoprotein is shed by matrix metalloproteinase 14 (MMP14). Our previous work demonstrated potent preclinical activity of first-in-class anti-ENG antibody-drug conjugates as a nascent strategy to eradicate Ewing sarcoma (ES), a devastating rare bone/soft tissue cancer with a putative MSC origin. We also defined a correlation between ENG and MMP14 expression in ES. Herein, we show that ENG expression is significantly associated with a dismal prognosis in a large cohort of ES patients. Moreover, both ENG/MMP14 are frequently expressed in primary ES tumors and metastasis. To deepen in their functional relevance in ES, we conducted transcriptomic and proteomic profiling of in vitro ES models that unveiled a key role of ENG and MMP14 in cell mechano-transduction. Migration and adhesion assays confirmed that loss of ENG disrupts actin filament assembly and filopodia formation, with a concomitant effect on cell spreading. Furthermore, we observed that ENG regulates cell-matrix interaction through activation of focal adhesion signaling and protein kinase C expression. In turn, loss of MMP14 contributed to a more adhesive phenotype of ES cells by modulating the transcriptional extracellular matrix dynamics. Overall, these results suggest that ENG and MMP14 exert a significant role in mediating correct spreading machinery of ES cells, impacting the aggressiveness of the disease.E.A.’s laboratory is supported by ISCIII-FEDER (PI20/00003), CIBERONC (CB16/12/00361), PAIDI-Junta de Andalucía (P18-RT-735), Fundación CRIS Contra el Cáncer, Asociación Candela Riera and Asociación Pablo Ugarte. A.T.A. is supported by Juan de la Cierva Incorporación fellowship (IJC-2018-036767-I); P.P.-C. is sponsored by the Fundación María García Estrada. J.O.-P is supported by Ph.D. Grant Plan Propio from the University of Seville. J.D.-M is supported by CIBERONC (CB16/12/00361). C.S.-A. is supported by the European Social Fund and the Junta de Andalucía (Talento Doctores 2020, DOC_01473). This work was supported by grants from the Consejería de Salud (Junta de Andalucía, grants No PI-0036-2017, PI-0040-2017, and PI-0061-2020) awarded to J.D.-M, A.T.A. and C. S.-A., respectively. This work was also supported by the GEIS-Fundación Mari Paz Jiménez Casado (IV beca trienal) granted to J.D.-M, the 13ª GEIS-Beca Buesa granted to A.T.A. and CRIS (Cancer Research Innovation Spain) granted to J.D.-M and E.A. The laboratory of T.G.P.G. is supported by the Barbara and Wilfried Mohr Foundation. The lab of J.A. is supported by the Instituto de Salud Carlos III (ISCIII), grant number PI20CIII/00020; Asociación Pablo Ugarte, grant numbers TRPV205/18, TPI-M 1149/13; Asociación Candela Riera; Asociación Todos Somos Iván & Fundación Sonrisa de Alex, grant reference: TVP333-19.S

Oral contraceptives do not modify the risk of a second attack and disability accrual in a prospective cohort of women with a clinically isolated syndrome and early multiple sclerosis

Cohort study; Oral contraceptives; Second relapseEstudio de cohorte; Anticonceptivos orales; Segunda recaídaEstudi de cohorts; Anticonceptius orals; Segona recaigudaObjective: To evaluate whether oral contraceptive (OC) use is associated with the risk of a second attack and disability accrual in women with a clinically isolated syndrome (CIS) and early multiple sclerosis (MS). Methods: Reproductive information from women included in the Barcelona CIS prospective cohort was collected through a self-reported cross-sectional survey. We examined the relationship of OC exposure with the risk of a second attack and confirmed Expanded Disability Status Scale of 3.0 using multivariate Cox regression models, adjusted by age, topography of CIS, oligoclonal bands, baseline brain T2 lesions, body size at menarche, smoking, and disease-modifying treatment (DMT). OC and DMT exposures were considered as time-varying variables. Findings were confirmed with sensitivity analyses using propensity score models. Results: A total of 495 women were included, 389 (78.6%) referred to ever use OC and 341 (68.9%) started OC before the CIS. Exposure to OC was not associated with a second attack (adjusted hazard ratio (aHR) = 0.73, 95% confidence interval (CI) = 0.33–1.61) or disability accrual (aHR = 0.81, 95% CI = 0.17–3.76). Sensitivity analyses confirmed these results. Conclusion: OC use does not modify the risk of second attack or disability accrual in patients with CIS and early MS, once considered as a time-dependent exposure and adjusted by other potential confounders.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was supported by FIS PI15/0070 from Ministry of Economy and Competitiveness of Spain