Laser shock processing: an emerging technique for the mechanical and surface properties enhancement of metallic materials

Laser Shock Processing (LSP) is as an effective technology for the improvement of surface and mechanical properties of metallic alloys and is an emerging technology in its way to production engineering in direct competence with other well established technologies as, i.e. shot peening. The technique is based on the application of a high intensity pulsed laser beam on a metallic target forcing a sudden vaporization of its surface into a high temperature and density plasma that immediately develops inducing a shock wave propagating into the material. The main advantage of this technique consists on its capability of inducing a relatively deep compression residual stresses field into metallic alloy pieces allowing an improved mechanical behaviour, explicitly, the life improvement under cyclic load connected with improved wear and corrosion resistance. The laser shock effects achieved by this method are comparable to those of shot-peening: that is, a local material compression linked to the generation and displacement of defects, surface state modification and, most important, a compressing residual stress field whose magnitude and depth into the material is generally associated with large improvements in fatigue resistance. Along with a description of the theoretical/computational and experimental methods developed by the authors for the predictive assessment and experimental implementation of LSP treatments, experimental results on the residual stress profiles and associated surface properties modification successfully reached under different LSP irradiation conditions in typical high strength materials will be presented in this paper

Cancer Immunotherapy of TLR4 Agonist-Antigen Constructs Enhanced with Pathogen-Mimicking Magnetite Nanoparticles and Checkpoint Blockade of PD-L1

Despite the tremendous potential of Toll-like receptor 4 (TLR4) agonists in vaccines, their efficacy as monotherapy to treat cancer has been limited. Only some lipopolysaccharides (LPS) isolated from particular bacterial strains or structures like monophosphoryl lipid A (MPLA) derived from lipooligosaccharide (LOS), avoid toxic overactivation of innate immune responses while retaining adequate immunogenicity to act as adjuvants. Here, different LOS structures are incorporated into nanoparticle-filled phospholipid micelles for efficient vaccine delivery and more potent cancer immunotherapy. The structurally unique LOS of the plant pathogen Xcc is incorporated into phospholipid micelles encapsulating iron oxide nanoparticles, producing stable pathogen-mimicking nanostructures suitable for targeting antigen presenting cells in the lymph nodes. The antigen is conjugated via a hydrazone bond, enabling rapid, easy-to-monitor and high-yield antigen ligation at low concentrations. The protective effect of these constructs is investigated against a highly aggressive model for tumor immunotherapy. The results show that the nanovaccines lead to a higher-level antigen-specific cytotoxic T lymphocyte (CTL) effector and memory responses, which when combined with abrogation of the immunosuppressive programmed death-ligand 1 (PD-L1), provide 100% long-term protection against repeated tumor challenge. This nanovaccine platform in combination with checkpoint inhibition of PD-L1 represents a promising approach to improve the cancer immunotherapy of TLR4 agonists

Diseño y elaboración de herramientas metodológicas para incorporar contenidos de ciencia y técnicas en el aula.

Depto. de Investigación y Psicología en EducaciónFac. de EducaciónFALSEsubmitte

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Gestión del conocimiento. Perspectiva multidisciplinaria. Volumen 9

El libro “Gestión del Conocimiento. Perspectiva Multidisciplinaria”, volumen 9, de la Colección Unión Global, es resultado de investigaciones. Los capítulos del libro, son resultados de investigaciones desarrolladas por sus autores. El libro es una publicación internacional, seriada, continua, arbitrada de acceso abierto a todas las áreas del conocimiento, que cuenta con el esfuerzo de investigadores de varios países del mundo, orientada a contribuir con procesos de gestión del conocimiento científico, tecnológico y humanístico que consoliden la transformación del conocimiento en diferentes escenarios, tanto organizacionales como universitarios, para el desarrollo de habilidades cognitivas del quehacer diario. La gestión del conocimiento es un camino para consolidar una plataforma en las empresas públicas o privadas, entidades educativas, organizaciones no gubernamentales, ya sea generando políticas para todas las jerarquías o un modelo de gestión para la administración, donde es fundamental articular el conocimiento, los trabajadores, directivos, el espacio de trabajo, hacia la creación de ambientes propicios para el desarrollo integral de las instituciones

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Tratamiento médico versus quirúrgico en el esófago de Barrett : resultados clínicos, histológicos y moleculares (ki-67, p53 y apoptosis) a largo plazo, de un estudio prospectivo y randomizado

Introducción El esófago de Barrett es la única lesión conocida en la actualidad que predispone a padecer un adenocarcinoma de esófago, enfermedad que asocia una baja supervivencia a los 5 años y cuya incidencia está aumentando en los países desarrollados. La metaplasia que representa el esófago de Barrett se produce como consecuencia de una exposición continuada de la mucosa esofágica a un excesivo reflujo gastroesofágico tanto ácido como biliar. Las dos principales opciones de tratamiento en el esófago de Barrett son el tratamiento médico de por vida, principalmente con inhibidores de la bomba de protones, y el tratamiento quirúrgico mediante la práctica de técnicas antireflujo, siendo la más importante la fundoplicatura de Nissen. Por otra parte, existen determinados biomarcadores moleculares, como Ki-67, p53 y el índice de apoptosis, que intervienen en la tumorogénesis y cuya cuantificación indica el grado de inestabilidad de un epitelio. Objetivos 1. Determinar qué tipo de tratamiento, médico o quirúrgico, es más eficaz no solo en el control de los síntomas de reflujo en los pacientes con esófago de Barrett sino también en prevenir su progresión a displasia y adenocarcinoma. 2. Estudiar el grado de apoptosis, el índice de proliferación celular (Ki-67) y la expresión de proto-oncogenes (p53) en las biopsias de los pacientes con esófago de Barrett y observar su evolución en el tiempo tras la aplicación del tratamiento médico o quirúrgico, para determinar si alguno de los dos estabiliza el epitelio metaplásico disminuyendo en mayor medida la probabilidad de sufrir transformación maligna. Pacientes y Método Desde 1982 hasta 2012, 161 pacientes con esófago de Barrett fueron incluidos en el estudio asignando de manera aleatoria uno de los dos tratamientos (40 mg de omeprazol al día o una fundoplicatura de Nissen). La valoración inicial de todos los sujetos (75 bajo tratamiento médico y 86 bajo tratamiento quirúrgico) así como durante el seguimiento periódico incluye una entrevista clínica, una endoscopia digestiva alta con toma múltiple de biopsias, un tránsito baritado y pruebas funcionales esofágicas (manometría intraluminal estacionaria, pH-metría ambulatoria de 24 horas y Bilitec). Resultados Ambos tipos de tratamiento resultaron igualmente eficaces tanto en el control de síntomas como en su capacidad protectora respecto a la malignización. No obstante, cuando la fundoplicatura es competente (74 pacientes), protege en mayor medida de la progresión a displasia de bajo grado. La cirugía eficaz no eliminó la posibilidad de malignización en todos los casos ya que 3 sujetos con una fundoplicatura competente sufrieron malignización. Dos de estos pacientes pertenecen a familias con alta prevalencia de Barrett y adenocarcinoma y el otro paciente padece esclerodermia, enfermedad refluxógena. Observamos que los niveles de Ki-67 y p53 se estabilizaron tras la fundoplicatura de Nissen mientras que sufrieron un aumento progresivo en los sujetos sometidos a tratamiento médico. Al contrario sucedió con el índice apoptótico que aumentó tras la cirugía y continuó disminuyendo tras la aplicación de los inhibidores de la bomba de protones. Estas diferencias se mantuvieron al comparar dos grupos de tratamiento quirúrgico y médico eficaces, es decir, con pH-metrías negativas. SUMMARY OF THE THESIS Introduction Barrett's esophagus is the only currently known lesion that predisposes to suffer an adenocarcinoma of the esophagus, a condition associated with poor survival at 5 years and whose incidence is increasing in developed countries. The metaplasia representing Barrett's esophagus occurs as a result of continued exposure of the esophageal mucosa to both excessive acid reflux biliary. The two main treatment options for Barrett's esophagus include medical treatment for life, mainly inhibitors proton pump, and surgical treatment by practicing antireflux techniques, the most important is Nissen fundoplication. Moreover, certain molecular biomarkers, such as Ki-67, p53 and apoptosis index, involved in tumorigenesis which quantification and indicates the degree of instability of an epithelium. Objectives 1. Determine what type of treatment, medical or surgical, is more effective not only in controlling reflux symptoms in patients with Barrett´s esophagus but also prevent progression to dysplasia and adenocarcinoma. 2. To study the degree of apoptosis, cell proliferation index (Ki-67) and the expression of proto-oncogenes (p53) in biopsies of patients with Barrett´s esophagus and observe their evolution over time after application of medical treatment or surgical, to determine if any of the two stabilizes the metaplastic epithelium further decreasing the likelihood of malignant transformation. Patients and Methods From 1982-2012, 161 patients with Barrett's esophagus were included in the study randomly assigned one of two treatments (40 mg omeprazole daily or Nissen fundoplication). The initial assessment of all subjects (75 medical and 86 surgical) as well as during the periodic monitoring includes a clinical interview, an upper endoscopy with multiple biopsies a barium swallow and esophageal function tests (stationary intraluminal manometry , ambulatory pH monitoring 24 hours and Bilitec). Results Both types of treatment both were equally effective in controlling symptoms such as in its protective capacity with respect to malignancy. However, when the fundoplication is competent (74 patients), protects more on the progression to low-grade dysplasia. Effective surgery did not eliminate the possibility of malignancy in all cases because 3 patients with malignant suffered a competent fundoplication. Two of these patients from families with high prevalence and Barrett's adenocarcinoma and one patient suffering from scleroderma, pro-reflux disease. We observed that the levels of Ki-67 and p53 stabilized after Nissen fundoplication while suffered a progressive increase in subjects undergoing medical treatment. Unlike happened with the apoptotic index increased after surgery and continued to decline after application of inhibitors of proton pump. These differences remained when comparing two groups effective surgical and medical treatment, ie pH-negative asymmetries

A path planning approach for computing large-amplitude motions of flexible molecules

International audienceMotivation: Motion is inherent in molecular interactions. Molecular flexibility must be taken into account in order to develop accurate computational techniques for predicting interactions. Energy-based methods currently used in molecular modeling (i.e. molecular dynamics, Monte Carlo algorithms) are, in practice, only able to compute local motions while accounting for molecular flexibility. However, large-amplitude motions often occur in biological processes. We investigate the application of geometric path planning algorithms to compute such large motions in flexible molecular models. Our purpose is to exploit the efficacy of a geometric conformational search as a filtering stage before subsequent energy refinements. Results: In this paper two kinds of large-amplitude motion are treated: protein loop conformational changes (involving protein backbone flexibility) and ligand trajectories to deep active sites in proteins (involving ligand and protein side-chain flexibility). First studies performed using our two-stage approach (geometric search followed by energy refinements) show that, compared to classical molecular modeling methods, quite similar results can be obtained with a performance gain of several orders of magnitude. Furthermore, our results also indicate that the geometric stage can provide highly valuable information to biologists. Availability: The algorithms have been implemented in the general-purpose motion planning software Move3D, developed at LAAS-CNRS. We are currently working on an optimized stand-alone library that will be available to the scientific community