Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Influencia de polimorfismos genéticos, variables analíticas y ambientales en las concentraciones valle de terapia anti-TNF de pacientes con enfermedad inflamatoria intestinal

OBJETIVOS La terapia anti-TNF-alfa está indicada en el tratamiento de las enfermedades inflamatorias crónicas. Cuando la respuesta es inadecuada se recomienda la intensificación de la dosis. Sin embargo, ni las razones para esta recomendación, ni los múltiples mecanismos implicados son bien conocidos. Nuestro objetivo principal es investigar si polimorfismos en los genes FCGRT, FCGR2A y FCGR3A (relacionados con el metabolismo y eliminación de inmunoglobulinas) ejercen una influencia en la concentración valle de IFX y adalimumab ADM en EII. Nuestros objetivos secundarios son: estudiar la influencia de dichos polimorfismos, inmunomoduladores, tipo de enfermedad y tiempo en tratamiento anti-TNF en la formación de ADAs. Estudiar la influencia de los polimorfismos en los tres genes en las concentraciones de TNF-alfa, y la influencia del polimorfismo VNTR en el gen FCGRT en las concentraciones de albúmina. Valorar la distribución de los genotipos de los tres genes en EII. Investigar la influencia en las concentraciones valle de anti-TNF de las covariables: concentraciones de TNF-alfa, PCR y albúmina, tipo de enfermedad, peso y sexo del paciente, tiempo en tratamiento anti-TNF, tipo de anti-TNF, presencia de ADAs y uso concomitante de inmunomoduladores. Finalmente, evaluar si existen diferencias en los genotipos, concentraciones de TNF-alfa y concentraciones valle de anti-TNF entre los pacientes a dosis intensificada y estándar y si el tiempo de pérdida de respuesta a los dos anti-TNF es diferente. METODOLOGIA Se trata de un estudio prospectivo, consecutivo de valoración transversal. Se han incluido 80 pacientes con EC y 23 con CU (mayores de 18 años previo consentimiento informado) de la consulta monográfica de EII del H. U. Santa Lucía de Cartagena en tratamiento con IFX o ADM en fase de mantenimiento. Se han estudiado los polimorfismos genéticos VNTR en el gen FCGRT, rs1801274 (H131R) en el gen FCGR2A y rs396991 (V158F) en el gen FCGR3A mediante reacción en cadena de la polimerasa. Se han medido las concentraciones valle de IFX y ADM y el título de ADAs (de forma cuantitativa mediante ELISA), concentraciones de TNF-alfa, PCR y albúmina. Las variables clínicas de los pacientes (peso, sexo, uso de inmunomoduladores y tiempo en tratamiento anti-TNF) se han extraído de las historias clínicas. El análisis estadístico se ha realizado con el programa SPSS versión 19.0. Para las variables continuas se ha realizado el test de Student (en caso de normalidad de la variable) y test U-Mann-Whitney (en caso contrario). Las variables cualitativas se han analizado mediante el test de Chi-cuadrado. Para el análisis de correlación entre variables continuas se han realizado los test de Spearman (para las no lineales) y de Pearson (para las lineales). RESULTADOS Y CONCLUSIONES Los polimorfismos estudiados en los genes FCGRT, FCGR2A y FCGR3A no influyen en las concentraciones valle de IFX y ADM en EII, por lo que no deben ser considerados biomarcadores para planificar el tratamiento con estas terapias. Los pacientes portadores del genotipo VV del polimorfismo V158F en el gen FCGR3A tienen mas riesgo de desarrollar ADAs (6 de los 16 pacientes portadores de este genotipo, p=0.004) y de perder la respuesta al anti-TNF ya que esos pacientes han precisado, en mayor proporción, un ajuste de la dosis (9 de los 16 pacientes con este genotipo estaban a dosis intensificada, p=0.03). El porcentaje de pacientes que desarrollo ADAs fue mayor entre los pacientes sin inmunomoduladores asociados, aunque sin alcanzar diferencias significativas (10 de los 13 pacientes con ADAs + estaban en monoterapia anti-TNF). Del análisis de las covariables que podrían influir en las concentraciones valle de anti-TNF hemos hallado que los pacientes con ADAs tenían menores concentraciones de IFX (0.61 μg/mL vs 3.24 μg/mL, p=0.009), la proporción de pacientes dentro de rango terapéutico fue mayor para el grupo ADM que IFX (86.5% vs 18.2%,p=0.001), y que los pacientes en tratamiento combinado ADM-inmunomodulador tenían mayores concentraciones de ADM que los que estaban en monoterapia con ADM (7.71 μg/mL vs4.54 μg/mL, p=0-009). Hemos hallado correlación directa entre las concentraciones de TNF-alfa e IFX e indirecta entre la albúmina y ADM, PCR e IFX y el peso y ADM. El porcentaje de pacientes dentro de rango terapéutico fue mayor para el grupo ADM que IFX (86.5% vs 18.2%, p=0.001). Como conclusión final, la monitorización de las concentraciones de anti-TNF y ADAs debería incluirse en práctica clínica para un manejo individualizado de estas terapias. ABREVIATURAS ADM: adalimumab, ADAs: anticuerpos antifármaco, CU: colitis ulcerosa, EC: enfermedad de Crohn, EII: enfermedad inflamatoria intestinal, IFX: infliximab, PCR: proteína c reactiva, TNF-alfa: factor de necrosis tumoral alfa. AIMS Anti-TNF therapy is used in the treatment of inflammatory chronic diseases. Intensification of the regimen is recommended if the treatment effect is inadequate. However, the rationale for this is not well defined, as there are also a considerable number of unknown underlying mechanisms. The aim of this study was to investigate whether polymorphisms in FCGRT, FCGR2A and FCGR3A genes (related with the metabolism and elimination of immunoglobulins) exert influence on the trough concentractions of IFX and adalimumab ADM in inflammatory bowel disease IBD. We also studied the influence of these polymorphisms, immunomodulators, type of disease and time under anti-TNF therapy in the development of ADAs as well as the influence of these polymorphisms in the concentrations of TNF-alpha, and the influence of VNTR polymorphism in the gene FCGRT in albumin concentractions. We assessed the differences in the distribution of genotypes between CD and UC. We Investigated the influence of covariates in the trough concentrations of IFX and ADM: TNF-alpha, CRP and albumin concentrations, type of disease, weight, sex, time under anti-TNF therapy, type of anti-TNF, presence of ADAs and immunomodulators. Finally, we assessed whether there are differences in the genotypes studied, TNF-alpha concentrations and trough concentrations of IFX and ADM between patients under standard and intensified dose and whether the time in loosing response to both anti-TNF is different. METHODS We performed a prospective, consecutive, cross-evaluation study. We included 80 CD and 23 UC patients (over 18 years prior informed consent) of the IBD unit of Santa Lucía University Hospital of Cartagena under treatment with IFX or ADM in maintenance phase. We studied the genetic polymorphisms VNTR in FCGRT gene, rs1801274 (H131R) in FCGR2A gene and rs396991 (V158F) in FCGR3A gene by polymerase chain reaction. We measured trough concentrations of IFX and ADM, ADAs titters (quantitatively by ELISA), and TNF-alpha, CRP and albumin concentrations. Clinical patient variables (weight, sex, immunomodulators and time under anti-TNF therapy) were analysed from medical records. The statistical analysis was performed using SPSS version 19.0. Student´s t test was performed for continuous variables (if normality of the variable) and U-Mann-Whitney test (otherwise). The qualitative variables were analyzed using the chi-square test. For the analysis of correlation between continuous variables we used Spearman test (for non-linear) and Pearson test (for linear). RESULTS AND CONCLUSIONS Polymorphisms in FCGRT, FCGR2A and FCGR3A genes do not influence trough concentrations of IFX and ADM in IBD, therefore, cannot be considered biomarkers to manage these therapies. Patients carrying VV genotype of V158F polymorphism in FCGR3A gene have more risk of developing ADAs (6 out of 16 patients, p=0.004) and loosing response to anti -TNF since these patients required, in a greater proportion, dose intensification (9 out of 16 patients, p=0.03). The risk of developing ADAs is higher among patients on anti-TNF monotherapy, as the number of patients who developed ADAs was greater in this group without statistically significant differences (10 out of 13 patients). In the analysis of covariates that could influence trough concentrations of anti-TNF we found that ADAs have a direct impact on IFX trough concentrations (0.61 μg/mL vs 3.24 μg/mL, p=0.009) as well as the type of anti-TNF because the percentage of patients treated with ADM with trough concentrations within cutt-off levels was higher (86.5% vs 18.2%, p=0.001). ADM trough concentrations were higher in patients on combination ADM-immunomodulator (7.71 μg/mL vs4.54 μg/mL, p=0-009). We found a direct correlation between the concentrations of TNF-alpha and IFX and indirect between albumin and ADM, PCR and IFX and weight and ADM. As a final conclusion, we would like to state that monitoring the concentrations of anti-TNF and immunogenicity (ADAs) should be included in clinical practice for individualized management. ABBREVIATIONS ADM: adalimumab, ADAs: anti-drug antibodies,, CD: Crohn´s disease, CRP: c reactive protein, IBD: inflammatory bowel disease, IFX: infliximab, TNF-alpha: tumoral necrosis factor, UC: ulcerative coliti

Gastric varicella: two cases in cancer patients

Gastric involvement with the varicella-zoster virus is an uncommon clinical condition where early suspicion and diagnosis are important to prevent the consequences deriving from its high morbidity and mortality, which in immunocompromised patients oscillate between 9% and 41% according to the various series. Two cases of gastric involvement with the varicella-zoster virus (VZV) in two patients with blood cancer are reported below. Gastric lesions are usually preceded by typical papulovesicular skin lesions. When gastric involvement is the first symptom of the disease its diagnosis and management may be delayed, which may entail severe consequences for immunocompromised patients. It is therefore that we suggest its inclusion in the algorithm for immunocompromised patients with abdominal pain and ulcer-like endoscopic lesions

Multi-phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations

Multi-phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes. To discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events. Methods: Summary statistics from genome wide-association studies (GWAS) from seven hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen activator inhibitor 1 [PAI-1]) and three major cardiovascular (CV) events (venous thromboembolism [VTE], coronary artery disease [CAD], ischemic stroke [IS]), were combined in 27 multi-trait combinations using metaUSAT. Genetic correlations between phenotypes were calculated using Linkage Disequilibrium Score Regression (LDSC). Newly associated loci were investigated for colocalization. We considered a significance threshold of 1.85 × 10 obtained after applying Bonferroni correction for the number of multi-trait combinations performed (n = 27). Across the 27 multi-trait analyses, we found 4 novel pleiotropic loci (XXYLT1, KNG1, SUGP1/MAU2, TBL2/MLXIPL) that were not significant in the original individual datasets, were not described in previous GWAS for the individual traits, and that presented a common associated variant between the studied phenotypes. The discovery of four novel loci contributes to the understanding of the relationship between hemostasis and CV events and elucidate common genetic factors between these traits

Multi-phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations

Background: Multi-phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes. Objectives: To discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events. Methods: Summary statistics from genome wide-association studies (GWAS) from seven hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen activator inhibitor 1 [PAI-1]) and three major cardiovascular (CV) events (venous thromboembolism [VTE], coronary artery disease [CAD], ischemic stroke [IS]), were combined in 27 multi-trait combinations using metaUSAT. Genetic correlations between phenotypes were calculated using Linkage Disequilibrium Score Regression (LDSC). Newly associated loci were investigated for colocalization. We considered a significance threshold of 1.85 × 10−9 obtained after applying Bonferroni correction for the number of multi-trait combinations performed (n = 27). Results: Across the 27 multi-trait analyses, we found 4 novel pleiotropic loci (XXYLT1, KNG1, SUGP1/MAU2, TBL2/MLXIPL) that were not significant in the original individual datasets, were not described in previous GWAS for the individual traits, and that presented a common associated variant between the studied phenotypes. Conclusions: The discovery of four novel loci contributes to the understanding of the relationship between hemostasis and CV events and elucidate common genetic factors between these traits

Coronal Heating as Determined by the Solar Flare Frequency Distribution Obtained by Aggregating Case Studies

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counter-intuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfv\'en waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, $\alpha=2$ as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed $>$600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: pre-flare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that $\alpha = 1.63 \pm 0.03$. This is below the critical threshold, suggesting that Alfv\'en waves are an important driver of coronal heating.Comment: 1,002 authors, 14 pages, 4 figures, 3 tables, published by The Astrophysical Journal on 2023-05-09, volume 948, page 7