Sistema de Vigilancia en Chagas facilitado por tecnologías de información y comunicación

La aplicación de las tecnologías de información y comunicación para los sistemas de vigilancia especializados en enfermedades prioritarias en América Latina como la enfermedad de Chagas, constituye un nuevo y valioso aporte para el control de la enfermedad que representa un grave problema de salud pública. El objetivo del presente trabajo fue evaluar un sistema de vigilancia epidemiológica y atención médica con el apoyo de tecnologías de información y comunicación (TICs), con la finalidad de detectar e introducir precozmente al sistema de salud a los individuos seropositivos para Chagas en un área endémica del interior de Argentina. Para ello se planificaron las acciones en función de dos Flujogramas de Atención, incorporando dos poblaciones objetivos (menores de 15 años y mujeres embarazadas), de tres Departamentos del interior de Córdoba y las acciones desarrolladas fueron: desarrollo del software del Sistema de Vigilancia para Chagas facilitado por TICs, acuerdos con autoridades gubernamentales y educativas, capacitación de agentes de terreno y equipo de salud de las zonas que efectuaron el tamizaje y posterior incorporación de datos y seguimiento de pacientes a partir del SVC-TICs. Los registros pre y post intervención fueron analizados estadísticamente. El número de población total incluida para este análisis fue de 11.585 menores de 15 años (Grupo TICs n= 5719 y Grupo Control n= 5866, obtenido de fuente de datos secundarios correspondiente a los registros del Ministerio de Salud de la Provincia).En el Grupo TICs se obtuvieron mayores frecuencias de registros, y en el 50% de las variables consideradas el Grupo Control no contenían información. El SVC-TICs, fue incorporado a los Sistemas de Vigilancia de los Ministerios de Salud de las zonas involucradas en el estudio, con un fuerte compromiso del equipo de salud a niveles locales y gubernamentales

Indirect Impact of PD-1/PD-L1 Blockade on a Murine Model of NK Cell Exhaustion

The induction of exhaustion on effector immune cells is an important limiting factor for cancer immunotherapy efficacy as these cells undergo a hierarchical loss of proliferation and cytolytic activity due to chronic stimulation. Targeting PD-1 has shown unprecedented clinical benefits for many cancers, which have been attributed to the prevention of immune suppression and exhaustion with enhanced anti-tumor responses. In this study, we sought to evaluate the role of the PD-1/PD-L1 pathway in murine natural killer (NK) cell activation, function, and exhaustion. In an in vivo IL-2-dependent exhaustion mouse model, neutralization of the PD-1/PD-L1 pathway improved NK cell activation after chronic stimulation when compared to control-treated mice. These cells displayed higher proliferative capabilities and enhanced granzyme B production. However, the blockade of these molecules during long-term in vitro IL-2 stimulation did not alter the progression of NK cell exhaustion (NCE), suggesting an indirect involvement of PD-1/PD-L1 on NCE. Given the expansion of CD8 T cells and regulatory T cells (Tregs) observed upon acute and chronic stimulation with IL-2, either of these two populations could influence NK cell homeostasis after PD-L1/PD-1 therapy. Importantly, CD8 T cell activation and functional phenotype were indeed enhanced by PD-1/PD-L1 therapy, particularly with anti-PD-1 treatment that resulted in the highest upregulation of CD25 during chronic stimulation and granted an advantage for IL-2 over NK cells. These results indicate a competition for resources between NK and CD8 T cells that arguably delays the onset of NCE rather than improving its activation during chronic stimulation. Supporting this notion, the depletion of CD8 T cells reversed the benefits of PD-1 therapy on chronically stimulated NK cells. These data suggest a bystander effect of anti-PD1 on NK cells, resulting from the global competition that exists between NK and CD8 T cells for IL-2 as a key regulator of these cells’ activation. Thus, achieving an equilibrium between these immune cells might be important to accomplish long-term efficacy during anti-PD-1/IL-2 therapy

Correlations of azimuthal anisotropy Fourier harmonics with subevent cumulants in pPb collisions at root s(NN)=8.16 TeV

Event-by-event long-range correlations of azimuthal anisotropy Fourier coefficients (vn) in 8.16 TeV pPb data, collected by the CMS experiment at the CERN Large Hadron Collider, are extracted using a subevent four-particle cumulant technique applied to very low multiplicity events. Each combination of four charged particles is selected from either two, three, or four distinct subevent regions of a pseudorapidity range from -2.4 to 2.4 of the CMS tracker, and with transverse momentum between 0.3 and 3.0 GeV. Using the subevent cumulant technique, correlations between vn of different orders are measured as functions of particle multiplicity and compared to the standard cumulant method without subevents over a wide event multiplicity range. At high multiplicities, the v2 and v3 coefficients exhibit an anticorrelation; this behavior is observed consistently using various methods. The v2 and v4 correlation strength is found to depend on the number of subevents used in the calculation. As the event multiplicity decreases, the results from different subevent methods diverge because of different contributions of noncollective or few-particle correlations. Correlations extracted with the four-subevent method exhibit a tendency to diminish monotonically toward the lowest multiplicity region (about 20 charged tracks) investigated. These findings extend previous studies to a significantly lower event multiplicity range and establish the evidence for the onset of long-range collective multiparticle correlations in small system collision

Effective Lagrangian for strongly coupled domain wall fermions

We derive the effective Lagrangian for mesons in lattice gauge theory with domain-wall fermions in the strong-coupling and large-N_c limits. We use the formalism of supergroups to deal with the Pauli-Villars fields, needed to regulate the contributions of the heavy fermions. We calculate the spectrum of pseudo-Goldstone bosons and show that domain wall fermions are doubled and massive in this regime. Since we take the extent and lattice spacing of the fifth dimension to infinity and zero respectively, our conclusions apply also to overlap fermions.Comment: 26 pp. RevTeX and 3 figures; corrected error in symmetry breaking scheme and added comments to discussio

Priority Needs for Conducting Pandemic-Relevant Clinical Research With Children in Europe : A Consensus Study With Pediatric Clinician-Researchers

Background: Infectious disease pandemics (IDP) pose a considerable global threat and can disproportionately affect vulnerable populations including children. Pediatric clinical research in pandemics is essential to improve children’s healthcare and minimize risks of harm by interventions that lack an adequate evidence base for this population. The unique features of IDPs require consideration of special processes to facilitate clinical research. We aimed to obtain consensus on pediatric clinician-researchers’ perceptions of the priorities to feasibly conduct clinical pediatric pandemic research in Europe.Methods: Mixed method study in 2 stages, recruiting pediatric clinician-researchers with experience of conducting pediatric infectious disease (ID) research in clinical settings in Europe. Stage one was an expert stakeholder workshop and interviews. Discussions focused on participant’s experience of conducting pediatric ID research and processes to facilitate pandemic research. Information informed stage two; an on-line consensus survey to identify pediatric clinician-researchers priorities to enable IDP research.Results: Twenty-three pediatric clinician-researchers attended the workshop and thirty-nine completed the survey. Priorities were primarily focused on structural and operational requirements of research design and regulation: 1) Clarity within the European Clinical Trials Directive for pediatric pandemic research; 2) Simplified regulatory processes for research involving clinical samples and data; and 3) Improved relationships between regulatory bodies and researchers.Conclusions: Results suggest that changes need to be made to the current regulatory environment to facilitate and improve pediatric research in the pandemic context. These findings can provide expert evidence to research policy decision makers and regulators and to develop a strategy to lobby for change.</p

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems

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

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

Glass-ceramic seal to join Crofer 22 APU alloy to YSZ ceramic in planar SOFCs

This work describes the design and development of a glass-ceramic seal to produce a hermetic joint between the ceramic electrolyte and the metallic interconnect of planar SOFC stacks. The glass-ceramic composition was designed considering the chemical compatibility with the ceramic electrolyte (yttria stabilized zirconia) and the oxidation resistant metal alloy interconnect (Crofer 22 APU), the thermo-mechanical properties (characteristic temperatures, thermal expansion coefficient), and the wettability on the substrates. The designed glass-ceramic seal is a barium-free silica-based glass, which partially crystallizes during the heat treatment after being deposited on Crofer 22 APU substrate by slurry coating or by electrophoretic deposition. The sealing process of the glass-ceramic was optimized, also taking into account that the maximum processing temperature should be lower than 950 ◦C (upper limit for the metallic interconnect) and the maximum heating rate of about 5 ◦C/min (limit for ceramic components). The joined ceramic/seal/metal samples were morphologically characterized and preliminary tested for 400 h in air atmosphere at the fuel cell operating temperature of 800 ◦C. Thermal ageing in air caused a Cr-diffusion from Crofer 22 APU alloy to the seal only when the alloy was used in the as-received condition. The preoxidised one did not diffuse Cr ions through the seal under the same ageing condition