Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease

Parasitemia; Parasitic diseases; Bloodstream infectionsParasitemia; Enfermedades parasitarias; Infecciones del torrente sanguíneoParasitèmia; Malalties parasitàries; Infeccions del torrent sanguiniCurrently available drugs against Trypanosoma cruzi infection, which causes 12000 deaths annually, have limitations in their efficacy, safety and tolerability. The evaluation of therapeutic responses to available and new compounds is based on parasite detection in the bloodstream but remains challenging because a substantial proportion of infected individuals have undetectable parasitemia even when using diagnostic tools with the highest accuracy. We characterize parasite dynamics which might impact drug efficacy assessments in chronic Chagas by analyzing pre- and post-treatment quantitative-PCR data obtained from blood samples collected regularly over a year. We show that parasitemia remains at a steady-state independently of the diagnostic sensitivity. This steady-state can be probabilistically quantified and robustly predicted at an individual level. Furthermore, individuals can be assigned to categories with distinct parasitological status, allowing a more detailed evaluation of the efficacy outcomes and adjustment for potential biases. Our analysis improves understanding of parasite dynamics and provides a novel background for optimizing future drug efficacy trials in Chagas disease

Evaluation of Microstructural and Mechanical Behavior of AHSS CP780 Steel Welded by GMAW-Pulsed and GMAW-Pulsed-Brazing Processes

Joints of complex phase 780 (CP-780) advanced high strength steel (AHSS) were carried out by using an ER-CuAl-A2 filler metal for the gas metal arc welding pulsed brazing (GMAW-P- brazing) process and the ER-80S-D2 for the GMAW-P process employing two levels of heat input. The phases in the weld bead and HAZ were analyzed, and the evaporation of zinc by means of scanning electron microscopy (SEM) was also monitored. The mechanical properties of the welded joints were evaluated by tension, microhardness and vertical impact tests. It was found that there was greater surface Zn evaporation in the joints welded with the GMAW-P process as compared to the GMAW-P-brazing process. The best results in tensile strength were observed in the joints welded with GMAW-P-brazing process, which increased by ~68% with respect to those of the GMAW-P. This behavior can be attributed to the formation of an intermetallic complex compound Cu-Al-Fe in the fusion line

La Imagen y la Narrativa como Herramientas para el Abordaje Psicosocial en Escenarios de Violencia. Departamento Valle del Cauca

En el siguiente trabajo se abordan contextos de hechos violentos a causa del conflicto sociopolítico interno en Colombia, desde un enfoque narrativo, cuya finalidad es analizar los eventos psicosociales traumáticos desde una postura psicológica. Además de ser un ejercicio educativo también nos permite acercarnos desde diferentes puntos de vista al conflicto armado que vivió nuestro país y del cual todavía quedan algunos focos de violencia así mismo consecuencias presentes en buena parte de la sociedad. El enfoque narrativo se presenta como un marco integrador, que tiene como objeto la comprensión de las experiencias humanas, re expresadas por medio de la exposición de los hechos relatados por algunas víctimas del conflicto armado. Por tanto, para el desarrollo de esta actividad, se realizara un análisis a los relatos y vivencias de víctimas de la violencia y el conflicto armado, desde una mirada psicológica teniendo en cuenta los impactos psicosociales por este flagelo y resaltando el sentido de fortaleza, resistencia y el esfuerzo de cada individuo, familia y comunidad para enfrentar de manera positiva las situaciones adversas, así como la superación y el rompimiento de ciclos de dolor desde una postura de empoderamiento y Resiliencia.The following paper deals with contexts of violent events due to the internal socio-political conflict in Colombia, from a narrative approach, which aims to analyze traumatic psychosocial events from a psychological perspective. In addition to being an educational exercise, it also allows us to approach the armed conflict that our country experienced from different points of view, and from which there are still some pockets of violence, as well as consequences present in a large part of society. The narrative approach is presented as an integrative framework, which aims at understanding human experiences, expressed through the exposure of the facts reported by some victims of the armed conflict. Therefore, for the development of this activity, an analysis will be made of the stories and experiences of victims of violence and armed conflict, from a psychological perspective taking into account the psychosocial impacts of this scourge and highlighting the sense of strength, resistance and the effort of each individual, family and community to positively face adverse situations, as well as overcoming and breaking cycles of pain from a position of empowerment and resilience

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

METODOLOGÍA DE SELECCIÓN DE POZOS CANDIDATOS PARA TRATAMIENTOS DE CONFORMANCE QUÍMICO

La canalización generalmente es consecuencia de la heterogeneidad del yacimiento, especialmente por grandes variaciones de permeabilidad, ocasionando reducción en la eficiencia volumétrica como producto de la recirculación del fluido inyectado en procesos de recobro secundario y/o mejorado (EOR). Con el objetivo de mejorar el perfil vertical de inyección y reducir la recirculación de agua inyectada, en Colombia se han implementado, desde el año 2008 a 2020, 33 tratamientos de control de canalización y conformance químico profundo en nueve campos con el objetivo de aumentar la eficiencia de barrido volumétrico para incrementar el factor de recuperación de petróleo. El resultado de los tratamientos reportados es de hasta 3 barriles de petróleo incremental por cada barril de gel rígido inyectado. Sin embargo, la cantidad de tratamientos de conformance es baja en comparación con el número de pozos inyectores en el país de aproximadamente 1400). Por lo tanto, Ecopetrol adaptó una metodología de selección de pozos candidatos para tratamientos de conformance químico que tiene en cuenta continuidad de los yacimientos, determinación y caracterización de la heterogeneidad, estudio de movimiento de fluidos, determinación de conectividad del patrón de inyección, distribución vertical y areal de los fluidos inyectados y producidos, generación de gráficos diagnósticos en software Sahara para finalmente identificar los pozos candidatos y realizar el diseño del tratamiento de conformance. La generación de los gráficos diagnóstico base de la metodología tiene como punto de partida la distribución vertical de producción secundaria realizada por el método IWR de alocación de producciones de malla ponderando caudales, en el cual la producción de un pozo es distribuida entre los inyectores que lo afectan, y esta producción es asociada a cada inyector. Con respecto a la distribución areal se toman elementos de flujo creando mallas dinámicas centradas en inyector y se pondera utilizando la distribución angular. La distribución de producción secundaria tiene en cuenta los ILT/PLT realizados históricamente en los pozos inyectores/ productores, mallado y coeficientes de distribución de los patrones de inyección en el tiempo. En el presente trabajo se hace una descripción y aplicación de la metodología integrada que permite identificar la producción de petróleo y agua por yacimiento en cada patrón de inyección, así como la eficiencia del agua inyectada para mapear acciones de mejoramiento de la producción de petróleo y disminución de la producción de agua, con el objetivo de identificar los sectores con menor desempeño y que requieren optimización del proceso secundario y/o mejorado. La metodología se validó y complementó con información de trazadores interwell (IWTT) y simulación numérica en líneas de flujo (streamline). En ese sentido, se vienen aplicando tratamientos de conformance desde el año 2021 en 23 nuevos pozos con resultados prometedores de producción incremental de petróleo. La selección de pozos candidatos para tratamientos de conformance químico amplían las expectativas de masificación de estas tecnologías en diferentes campos del país y se convierten en pieza fundamental para apalancar la consecución de reservas y una disminución de la huella de carbono debido principalmente a que con el mismo caudal de fluido inyectado se incrementa la producción de petróleo y en algunos tratamientos puede disminuir la producción de agua, asegurando menor consumo de energía (CO2) por cada barril de petróleo extraído

PCSK6 and Survival in Idiopathic Pulmonary Fibrosis

Rationale: Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by limited treatment options and high mortality. A better understanding of the molecular drivers of IPF progression is needed. Objectives: To identify and validate molecular determinants of IPF survival. Methods: A staged genome-wide association study was performed using paired genomic and survival data. Stage I cases were drawn from centers across the United States and Europe and stage II cases from Vanderbilt University. Cox proportional hazards regression was used to identify gene variants associated with differential transplantation-free survival (TFS). Stage I variants with nominal significance (P < 5 x 10(-5)) were advanced for stage II testing and meta-analyzed to identify those reaching genome-wide significance (P < 5 x 10(-8)). Downstream analyses were performed for genes and proteins associated with variants reaching genome-wide significance. Measurements and Main Results: After quality controls, 1,481 stage I cases and 397 stage II cases were included in the analysis. After filtering, 9,075,629 variants were tested in stage I, with 158 meeting advancement criteria. Four variants associated with TFS with consistent effect direction were identified in stage II, including one in an intron of PCSK6 (proprotein convertase subtilisin/kexin type 6) reaching genome-wide significance (hazard ratio, 4.11 [95% confidence interval, 2.54-6.67]; P = 9.45 x 10(-9)). PCSK6 protein was highly expressed in IPF lung parenchyma. PCSK6 lung staining intensity, peripheral blood gene expression, and plasma concentration were associated with reduced TFS. Conclusions: We identified four novel variants associated with IPF survival, including one in PCSK6 that reached genome-wide significance. Downstream analyses suggested that PCSK6 protein plays a potentially important role in IPF progression

Phylogeography and Genetic Variation of Triatoma dimidiata, the Main Chagas Disease Vector in Central America, and Its Position within the Genus Triatoma

Chagas disease is a serious parasitic disease of Latin America. Human contamination in poor rural or periurban areas is mainly attributed to haematophagous triatomine insects. Triatoma includes important vector species, as T. dimidiata in Central and Meso-America. DNA sequences, phylogenetic methods and genetic variation analyses are combined in a large interpopulational approach to investigate T. dimidiata and its closest relatives within Triatoma. The phylogeography of Triatoma indicates two colonization lineages northward and southward of the Panama isthmus during ancient periods, with T. dimidiata presenting a large genetic variability related to evolutionary divergences from a Mexican-Guatemalan origin. One clade remained confined to Yucatan, Chiapas, Guatemala and Honduras, with extant descendants deserving species status: T. sp. aff. dimidiata. The second clade gave rise to four subspecies: T. d. dimidiata in Guatemala and Mexico (Chiapas) up to Honduras, Nicaragua, Providencia island, and introduced into Ecuador; T. d. capitata in Panama and Colombia; T. d. maculipennis in Mexico and Guatemala; and T. d. hegneri in Cozumel island. This taxa distinction may facilitate the understanding of the diversity of vectors formerly included under T. dimidiata, their different transmission capacities and the disease epidemiology. Triatoma dimidiata will offer more problems for control than T. infestans in Uruguay, Chile and Brazil, although populations in Ecuador are appropriate targets for insecticide-spraying