WASP-4b Arrived Early for the TESS Mission

The Transiting Exoplanet Survey Satellite (TESS) recently observed 18 transits of the hot Jupiter WASP-4b. The sequence of transits occurred 81.6 $\pm$ 11.7 seconds earlier than had been predicted, based on data stretching back to 2007. This is unlikely to be the result of a clock error, because TESS observations of other hot Jupiters (WASP-6b, 18b, and 46b) are compatible with a constant period, ruling out an 81.6-second offset at the 6.4$\sigma$ level. The 1.3-day orbital period of WASP-4b appears to be decreasing at a rate of $\dot{P} = -12.6 \pm 1.2$ milliseconds per year. The apparent period change might be caused by tidal orbital decay or apsidal precession, although both interpretations have shortcomings. The gravitational influence of a third body is another possibility, though at present there is minimal evidence for such a body. Further observations are needed to confirm and understand the timing variation.Comment: AJ accepte

Case-Control Pilot Study on Acute Diarrheal Disease in a Geographically Defined Pediatric Population in a Middle Income Country

Introduction. Acute diarrheal disease (ADD) is a common cause of morbidity and mortality in children under 5 years of age. Understanding of the etiology of ADD is lacking in most low and middle income countries because reference laboratories detect limited number of pathogens. The objective of this study was to determine the feasibility to conduct a comprehensive case-control study to survey diarrheal pathogens among children with and without moderate-to-severe ADD. Materials and Methods. Microbiology and molecular-based techniques were used to detect viral, bacterial, and parasitic enteropathogens. The study was conducted in Bucaramanga, Colombia, after Institutional Review Board approval was obtained. Results. Ninety children less than 5 years of age were recruited after a written informed consent was obtained from parents or guardians. Forty-five subjects served as cases with ADD and 45 as controls. Thirty-six subjects out of 90 (40.0%) were positive for at least one enteropathogen, that is, 20 (44.4%) cases and 16 (35.5%) controls. Conclusions. The three most common enteric pathogens were enteroaggregative E. coli (10.0%), Norovirus (6.7%), and Salmonella spp. (5.6%). The E. coli pathogens were 18.8% of all infections making them the most frequent pathogens. Half of ADD cases were negative for any pathogens

Toll-like receptor 2/MyD88 signaling mediates zymosan-induced joint hypernociception in mice: Participation of TNF-alpha, IL-1 beta and CXCL1/KC

Arthritic pain is a serious health problem that affects a large number of patients. Toll-like receptors (TLRs) activation within the joints has been implicated in pathophysiology of arthritis. However, their role in the genesis of arthritic pain needs to be demonstrated. In the present study, it was addressed the participation of TLR2 and TLR4 and their adaptor molecule MyD88 in the genesis of joint hypernociception (a decrease in the nociceptive threshold) during zymosan-induced arthritis. Zymosan injected in the tibio-tarsal joint induced mechanical hypernociception in C57BL/6 wild type mice that was reduced in TLR2 and MyD88 null mice. On the other hand, zymosan-induced hypernociception was similar in C3H/HePas and C3H/Hej mice (TLR4 mutant mice). Zymosan-induced joint hypernociception was also reduced in TNFR1 null mice and in mice treated with IL-1 receptor antagonist or with an antagonist of CXCR1/2. Moreover, the joint production of TNF-alpha, IL-1 beta and CXCL1/KC by zymosan was dependent on TLR2/MyD88 signaling. Investigating the mechanisms by which TNF-alpha, IL-1 beta and CXCL1/KC mediate joint hypernociception, joint administration of these cytokines produced mechanical hypernociception, and they act in an interdependent manner. In last instance, their hypernociceptive effects were dependent on the production of hypernociceptive mediators, prostaglandins and sympathetic amines. These results indicate that in zymosan-induced experimental arthritis, TLR2/MyD88 is involved in the cascade of events of joint hypernociception through a mechanism dependent on cytokines and chemokines production. Thus, TLR2/MyD88 signaling might be a target for the development of novel drugs to control pain in arthritis. (C) 2011 Elsevier B.V. All rights reserved.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Pesquisa (CNPq)Coordenadoria de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Programa de Nucleos de Excelencia (PRONEX), Brazi

High Mitochondrial DNA Stability in B-Cell Chronic Lymphocytic Leukemia

BACKGROUND: Chronic Lymphocytic Leukemia (CLL) leads to progressive accumulation of lymphocytes in the blood, bone marrow, and lymphatic tissues. Previous findings have suggested that the mtDNA could play an important role in CLL. METHODOLOGY/PRINCIPAL FINDINGS: The mitochondrial DNA (mtDNA) control-region was analyzed in lymphocyte cell DNA extracts and compared with their granulocyte counterpart extract of 146 patients suffering from B-Cell CLL; B-CLL (all recruited from the Basque country). Major efforts were undertaken to rule out methodological artefacts that would render a high false positive rate for mtDNA instabilities and thus lead to erroneous interpretation of sequence instabilities. Only twenty instabilities were finally confirmed, most of them affecting the homopolymeric stretch located in the second hypervariable segment (HVS-II) around position 310, which is well known to constitute an extreme mutational hotspot of length polymorphism, as these mutations are frequently observed in the general human population. A critical revision of the findings in previous studies indicates a lack of proper methodological standards, which eventually led to an overinterpretation of the role of the mtDNA in CLL tumorigenesis. CONCLUSIONS/SIGNIFICANCE: Our results suggest that mtDNA instability is not the primary causal factor in B-CLL. A secondary role of mtDNA mutations cannot be fully ruled out under the hypothesis that the progressive accumulation of mtDNA instabilities could finally contribute to the tumoral process. Recommendations are given that would help to minimize erroneous interpretation of sequencing results in mtDNA studies in tumorigenesis

Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate

PURPOSE: The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods. MATERIALS AND METHODS: Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed. RESULTS: Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendall's tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively. CONCLUSION: BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.</p

Spatial and temporal facies evolution of a Lower Jurassic carbonate platform, NW Tethyan margin (Mallorca, Spain)

The variety of depositional facies of a Lower Jurassic carbonate platform has been investigated on the island of Mallorca along a transect comprising six stratigraphic profiles. Twenty-nine facies and sub-facies have been recognized, grouped into seven facies associations, ranging in depositional environment from supratidal/terrestrial and peritidal to outer platform. Spatial and temporal (2D) facies distribution along the transect reflects the evolution of the carbonate platform with time showing different facies associations, from a broad peritidal platform (stage 1) to a muddy open platform (stage 2), and finally to a peritidal to outer carbonate platform (stage 3). Stage 1 (early Sinemurian to earliest late Sinemurian) corresponds to a nearly-flat peritidal-shallow subtidal epicontinental platform with facies belts that shifted far and fast over the whole study area. The evolution from stage 1 to stage 2 (late Sinemurian) represents a rapid flooding of the epicontinental shallow platform, with more open-marine conditions, and the onset of differential subsidence. During stage 3 (latest Sinemurian), peritidal and shallow-platform environments preferentially developed to the northeast (Llevant Mountains domain) with a rapid transition to middle-outer platform environments toward the northwest (Tramuntana Range domain). Stages 1 and 3 present facies associations typical of Bahamian-type carbonates, whereas stage 2 represents the demise of the Bahamian-type carbonate factory and proliferation of muddy substrates with suspension-feeders. The described platform evolution responded to the interplay between the initial extensional tectonic phases related to Early Jurassic Tethyan rifting, contemporaneous environmental perturbations, and progressive platform flooding related to the Late Triassic–Early Jurassic worldwide marine transgression and associated accommodation changes

Hilando generaciones y moda

En el proyecto PAP llamado Hilando Generaciones y Moda del cual se presenta este reporte del periodo otoño 2022, el propósito general fue el de crear espacios en los cuales se diera paso a la colaboración intergeneracional e intercultural a través de la capacitación en costura y diseño de modas. Un espacio en donde los participantes pudieran intercambiar conocimientos, diálogos y trabajar en equipo, pero, sobre todo, mostrando empatía, confianza e interactuando mientas se conocen los estudiantes y las personas mayores. En este periodo escolar se elaboraron prendas de vestir para el uso personal y familiar de las personas mayores, se llevó a cabo una sesión fotográfica con las personas mayores, una pasarela para la exposición de las prendas, un documental y una revistacatálogo con las prendas. Las primeras sesiones se dedicaron a la sensibilización de los alumnos para con la población de personas mayores y con esto se dio pie para la interacción y convivencia entre los estudiantes y personas mayores, principalmente en las instalaciones del Centro Tapatío de atención al Adulto Mayor (CETAM) y en uno de los centros de día del DIF. Los estudiantes estuvieron interactuando con las personas mayores, en los que se generó una relación profunda de comprensión y empatía, y se crearon importantes resultados como las prendas, una capa tejida por alumnos y personas mayores, revistacatálogo, pasarela y un visible entramado entre las dos generaciones: jóvenes y personas mayores.ITESO, A.C

Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate

PURPOSE: The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods. MATERIALS AND METHODS: Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the R2). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed. RESULTS: Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendall's tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively. CONCLUSION: BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events

Design of bio-nanosystems for oral delivery of functional compounds

Nanotechnology has been referred to as one of the most interesting topics in food technology due to the potentialities of its use by food industry. This calls for studying the behavior of nanosystems as carriers of biological and functional compounds aiming at their utilization for delivery, controlled release and protection of such compounds during food processing and oral ingestion. This review highlights the principles of design and production of bio-nanosystems for oral delivery and their behavior within the human gastrointestinal (GI) tract, while providing an insight into the application of reverse engineering approach to the design of those bio-nanosystems. Nanocapsules, nanohydrogels, lipid-based and multilayer nanosystems are discussed (in terms of their main ingredients, production techniques, predominant forces and properties) and some examples of possible food applications are given. Phenomena occurring in in vitro digestion models are presented, mainly using examples related to the utilization of lipid-based nanosystems and their physicochemical behavior throughout the GI tract. Furthermore, it is shown how a reverse engineering approach, through two main steps, can be used to design bio-nanosystems for food applications, and finally a last section is presented to discuss future trends and consumer perception on food nanotechnology.Miguel A. Cerqueira, Ana C. Pinheiro, Helder D. Silva, Philippe E. Ramos, Ana I. Bourbon, Oscar L. Ramos (SFRH/BPD/72753/2010, SFRH/BD/48120/2008, SFRH/BD/81288/2011, SFRH/BD/80800/2011, SFRH/BD/73178/2010 and SFRH/BPD/80766/2011, respectively) are the recipients of a fellowship from the Fundacao para a Ciencia e Tecnologia (FCT, POPH-QREN and FSE Portugal). Maria L. Flores-Lopez thanks Mexican Science and Technology Council (CONACYT, Mexico) for PhD fellowship support (CONACYT Grant number: 215499/310847). The support of EU Cost Actions FA0904 and FA1001 is gratefully acknowledged