Limits to Gauge Coupling in the Dark Sector Set by the Nonobservation of Instanton-Induced Decay of Super-Heavy Dark Matter in the Pierre Auger Observatory Data.

Instantons, which are nonperturbative solutions to Yang-Mills equations, provide a signal for the occurrence of quantum tunneling between distinct classes of vacua. They can give rise to decays of particles otherwise forbidden. Using data collected at the Pierre Auger Observatory, we search for signatures of such instanton-induced processes that would be suggestive of super-heavy particles decaying in the Galactic halo. These particles could have been produced during the post-inflationary epoch and match the relic abundance of dark matter inferred today. The nonobservation of the signatures searched for allows us to derive a bound on the reduced coupling constant of gauge interactions in the dark sector: α_{X}≲0.09, for 10^{9}≲M_{X}/GeV<10^{19}. Conversely, we obtain that, for instance, a reduced coupling constant α_{X}=0.09 excludes masses M_{X}≳3×10^{13} GeV. In the context of dark matter production from gravitational interactions alone, we illustrate how these bounds are complementary to those obtained on the Hubble rate at the end of inflation from the nonobservation of tensor modes in the cosmological microwave background.

[Assessment of the impact of pharmaceutical consultations at initiation of a treatment with emicizumab in patients with severe hemophilia A without inhibitors]. / Évaluation de l'impact de consultations pharmaceutiques à l'instauration d'un traitement par émicizumab chez les patients hémophiles A sévères sans inhibiteurs.

Since 2019, severe haemophilia A without inhibitors can be treated with emicizumab. Its action, route of administration and management justified the creation of new tools for therapeutic education sessions addressed to patients. The main objective of our work was to assess the knowledge and skills acquired by patients after therapeutic education. The various documents created were a video, a slideshow, clinical cases in form of cards, and summary sheets intended for patients. At treatment beginning, a pharmaceutical consultation was proposed to all patients. Two months later, an evaluation was carried out and a second pharmaceutical consultation aimed to consolidate the achievements of patients. Simultaneously, a clinical self-evaluation by the patients was carried out. Thirty-six patients were included in the study. Theoretical items: method of manufacture, mechanism of action and regimen, are known for more than ¾ of patients. Practical skills, such as administration modalities, management of missed doses or bleeding, are familiar for more than 8 out of 10 patients. Sixteen (44.4%) patients presented an up-to-date haemophilia card. The assessment of the knowledge and skills of patients is encouraging since most of the items are acquired. These result highlights the interest of the new tools developed for the therapeutic education sessions.

Measurement of the Fluctuations in the Number of Muons in Extensive Air Showers with the Pierre Auger Observatory.

We present the first measurement of the fluctuations in the number of muons in extensive air showers produced by ultrahigh energy cosmic rays. We find that the measured fluctuations are in good agreement with predictions from air shower simulations. This observation provides new insights into the origin of the previously reported deficit of muons in air shower simulations and constrains models of hadronic interactions at ultrahigh energies. Our measurement is compatible with the muon deficit originating from small deviations in the predictions from hadronic interaction models of particle production that accumulate as the showers develop.

Potassium reduction in food by preparation technique for the dietetic management of patients with chronic kidney disease: a review.

BACKGROUND: Chronic kidney disease patients often use food preparation techniques to reduce potassium intake. However, the most effective techniques have not yet been determined for all food groups. The present study aimed to analyse all of the available information on potassium reduction in the food and identify the best preparation techniques by comparing the trend of change in potassium level. METHODS: Nine databases were searched from 1976 to May 2020, according to the PRISMA Statement. We included all articles reporting the amount of potassium before and after the application of food preparation techniques. Data were analysed using the Wilcoxon test and statistical simulation. RESULTS: A wide variety of food and culinary processes was observed in the 65 included articles. Cooking in water, pressure cooking and cooking in a microwave oven reduced potassium levels in all food groups, particularly in cereals and derivatives, fruits and derivatives, meats and derivatives, legumes, and leafy and cruciferous vegetables. Soaking food significantly reduced the potassium content in tubers and roots and leafy and cruciferous vegetables. Steam cooking and dry heating cooking also reduced potassium, although at a level lower than the other techniques. CONCLUSIONS: The present review shows that, in general, all food preparation techniques can reduce the potassium content, although cooking in water and soaking promotes a greater reduction; however, more studies with standardised techniques and complete data are necessary.

Features of the Energy Spectrum of Cosmic Rays above 2.5×10

We report a measurement of the energy spectrum of cosmic rays above 2.5×10^{18} eV based on 215 030 events. New results are presented: at about 1.3×10^{19} eV, the spectral index changes from 2.51±0.03(stat)±0.05(syst) to 3.05±0.05(stat)±0.10(syst), evolving to 5.1±0.3(stat)±0.1(syst) beyond 5×10^{19} eV, while no significant dependence of spectral features on the declination is seen in the accessible range. These features of the spectrum can be reproduced in models with energy-dependent mass composition. The energy density in cosmic rays above 5×10^{18} eV is [5.66±0.03(stat)±1.40(syst)]×10^{53} erg Mpc^{-3}.

[Antagonistic function of the heart muscle : Part II: Clinical implications]. / Die antagonistische Funktion des Herzmuskels : Teil II: Klinische Auswirkungen.

In the hypertrophic heart the myostructural afterload in the form of endoepicardial networks is predominant, which enhances myocardial hypertrophy. The intrinsic antagonism is derailed. Likewise, the connective tissue scaffold, i.e. the stromatogenic afterload, is enriched in the response to the derailment of antagonism in a hypertrophic heart up to regional captivation of the heart musculature. Due to the selective susceptibility of the auxotonic, contracting oblique transmural myocardial network for low dose negative inotropic medication, this promises to attenuate progress in myocardial hypertrophy. Volume reduction surgery is most effective in reducing wall stress as long as the myocardium is not critically fettered by fibrosis. The use of external mechanical circulatory support is then effective if the heart is supported in its resting mode, which means around a middle width and at minimal amplitude of motion. The takotsubo cardiomyopathy might possibly reflect an isolated, extreme stimulation of the intrinsic antagonism as a response to hormonally induced sensitization of the myocardium to catecholamine. A particular significant conclusion with respect to the diseased heart is that clinical diagnostics need new impulses with a focus on the analysis of local motion patterns and on myocardial stiffness reflecting disease-dependent antagonistic intensity. This would become a relevant diagnostic marker if corresponding (noninvasive) measurement techniques would become available.

Analysis of the mortality trend in the indigenous population of Brazil, 2000-2016.

OBJECTIVES: The objective of the study is to analyze the mortality trend in indigenous peoples in Brazil. STUDY DESIGN: The study design used is an ecological study. METHODS: A study carried out with data from the indigenous deaths recorded on the Mortality Information System in Brazil between 2000 and 2016. The Prais Winsten regression was used to analyze the trend of overall mortality in the country and in its geopolitical regions, in addition to the trend by sex, age groups, and groups of basic causes of death. RESULTS: Of all deaths, 47,806 indigenous deaths were recorded between 2000 and 2016. The majority was male (56.5%) and 27.2% in children aged younger than 5 years. The major groups of causes of death were the circulatory diseases (15.8%) and external causes (14.9%). The affections of the perinatal period (23.7%) and infectious and parasitic diseases (18.5%) were the main causes in children aged younger than 5 years. The indigenous mortality rates showed an increasing trend in the country (annual percent change [APC] = 2.37%). There was growth in both sexes and in most age ranges. Mortality from external causes (APC = 4.71%), neoplasms (APC = 4.67%), and respiratory causes (APC = 4.14%) also presented growth. The infectious and parasitic causes and genitourinary causes showed a stable trend in the studied period. CONCLUSIONS: The increasing trend of mortality in the analyzed variables showed disparities between indigenous and non-indigenous peoples in Brazil, pointing to the need for greater investment in basic social sectors, such as health, education, housing, and sanitation.

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±0.7(stat)±6.7(syst) 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-principles 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.

Morphoagronomic characterization and genetic diversity of a common bean RIL mapping population derived from the cross Rudá x AND 277.

Recombinant inbred lines (RILs) are a valuable resource for building genetic linkage maps. The presence of genetic variability in the RILs is essential for detecting associations between molecular markers and loci controlling agronomic traits of interest. The main goal of this study was to quantify the genetic diversity of a common bean RIL population derived from a cross between Rudá (Mesoamerican gene pool) and AND 277 (Andean gene pool). This population was developed by the single seed descent method from 500 F2 plants until the F10 generation. Seven quantitative traits were evaluated in the field in 393 RILs, the parental lines, and five control cultivars. The plants were grown using a randomized block design with additional controls and three replicates. Significant differences were observed among the RILs for all evaluated traits (P < 0.01). A comparison of the RILs and parental lines showed significant differences (P < 0.01) for the number of days to flowering (DFL) and to harvest (DH), productivity (PROD) and mass of 100 beans (M100); however, there were no significant differences for plant architecture, degree of seed flatness, or seed shape. These results indicate the occurrence of additive x additive epistatic interactions for DFL, DH, PROD, and M100. The 393 RILs were shown to fall into 10 clusters using Tocher's method. This RIL population clearly contained genetic variability for the evaluated traits, and this variability will be crucial for future studies involving genetic mapping and quantitative trait locus identification and analysis.

Loss of mitochondrial SDHB expression: what is its role in diffuse thyroid lipomatosis?

Diffuse lipomatosis of the thyroid gland is a very rare disease, characterized by extensive infiltration of thyroid parenchyma by mature adipose tissue, usually not accompanied by amyloid fibrils deposition. The pathophysiology of adipose tissue infiltration in the thyroid gland remains unknown. We report a clinical case of a diffuse thyroid lipomatosis, whose immunohistochemical study of succinate dehydrogenase - subunit B (SDHB) revealed loss of expression of this protein in the follicular or adipose cells. We detected the presence of a recently described SDHB gene large deletion. Loss of mitochondrial SDHB expression may have a key role in understanding the pathophysiology of thyrolipomatosis, by regulating status of lipid metabolism.

Effects of a high-energy diet on oocyte quality and in vitro embryo production in Bos indicus and Bos taurus cows.

The effects of different dietary energy levels [100 and 170% for maintenance (M) and high energy (1.7M), respectively] on metabolic, endocrine, and reproductive parameters were evaluated in nonlactating Bos indicus (Gir; n=14) and Bos taurus (Holstein; n=14) cows submitted to ultrasound-guided ovum pick-up followed by in vitro embryo production. The oocyte donor cows were housed in a tiestall system and fed twice daily (0800 and 1600 h). Twenty-one days before the beginning of the experiment, the animals were fed with a maintenance diet for adaptation followed by the experimental diets (M and 1.7M), and each cow underwent 9 ovum pick-up procedures 14 d apart. The recovered oocytes were cultured in vitro for 7 d. We measured glucose and insulin concentrations and performed glucose tolerance tests and the relative quantification of transcripts (PRDX1, HSP70.1, GLUT1, GLUT5, IGF1R, and IGF2R) from the oocytes recovered at the end of the experimental period. No interactions were observed between the effects of genetic groups and dietary energy level on the qualitative (viable oocytes, quality grade, and oocyte quality index) and quantitative (oocytes recovered) oocyte variables. There were no effects of dietary energy level on the qualitative and quantitative oocyte variables. However, Bos indicus cows had greater numbers of recovered structures, viable oocytes, and A and B oocyte grades as well as better oocyte quality index scores and lower DNA fragmentation rates compared with Bos taurus donors. In vitro embryo production (cleavage and blastocyst rates and number of embryos) was similar between diets, but the 1.7M diet reduced in vitro embryo production in Bos indicus cows after 60 d of treatment. Moreover, Bos indicus cows on the 1.7M diet showed lower transcript abundance for the HSP70.1, GLUT1, IGF1R, and IGF2R genes. All cows fed 1.7M diets had greater glucose and insulin concentrations and greater insulin resistance according to the glucose tolerance test. In conclusion, increasing dietary energy did not interfere with oocyte numbers and quality, but the 1.7M diet reduced in vitro embryo production in Bos indicus cows after 60 d of treatment. Finally, Bos indicus cows had greater oocyte quality, greater numbers of viable oocytes and greater in vitro embryo yield than Bos taurus.

Potential of hypocotyl diameter in family selection aiming at plant architecture improvement of common bean.

Cultivars of common bean with more erect plant architecture and greater tolerance to degree of lodging are required by producers. Thus, to evaluate the potential of hypocotyl diameter (HD) in family selection for plant architecture improvement of common bean, the HDs of 32 F2 plants were measured in 3 distinct populations, and the characteristics related to plant architecture were analyzed in their progenies. Ninety-six F2:3 families and 4 controls were evaluated in a randomized block design, with 3 replications, analyzing plant architecture grade, HD, and grain yield during the winter 2010 and drought 2011 seasons. We found that the correlation between the HD of F2 plants and traits related to plant architecture of F2:3 progenies were of low magnitude compared to the estimates for correlations considering the parents, indicating a high environmental influence on HD in bean plants. There was a predominance of additive genetic effects on the determination of hypocotyl diameter, which showed higher precision and accuracy compared to plant architecture grade. Thus, this characteristic can be used to select progenies in plant architecture improvement of common beans; however, selection must be based on the means of at least 39 plants in the plot, according to the results of repeatability analysis.

Adaptability and stability of soybean genotypes in off-season cultivation.

The oil and protein contents of soybean grains are important quantitative traits for use in breeding. However, few breeding programs perform selection based on these traits in different environments. This study assessed the adaptability and stability of 14 elite early soybean breeding lines in off-season cultivation with respect to yield, and oil and protein contents. A range of statistical methods was applied and these analyses indicated that for off-season cultivation, the lines UFUS 5 and UFUS 10 could be recommended due to their superior performance in grain yield, oil content, and specific adaptability to unfavorable environments along with high stability in these characteristics. Also recommended were UFUS 06, which demonstrated superior performance in all three tested characteristics and showed adaptation to favorable environments, and UFUS 13, which showed high adaptability and stability and a superior performance for protein content.

Evaluation of soybean lines and environmental stratification using the AMMI, GGE biplot, and factor analysis methods.

In the final phases of new soybean cultivar development, lines are cultivated in several locations across multiple seasons with the intention of identifying and selecting superior genotypes for quantitative traits. In this context, this study aimed to study the genotype-by-environment interaction for the trait grain yield (kg/ha), and to evaluate the adaptability and stability of early-cycle soybean genotypes using the additive main effects and multiplicative interaction (AMMI) analysis, genotype main effects and genotype x environment interaction (GGE) biplot, and factor analysis methods. Additionally, the efficiency of these methods was compared. The experiments were carried out in five cities in the State of Mato Grosso: Alto Taquari, Lucas do Rio Verde, Sinop, Querência, and Rondonópolis, in the 2011/2012 and 2012/2013 seasons. Twenty-seven early-cycle soybean genotypes were evaluated, consisting of 22 lines developed by Universidade Federal de Uberlândia (UFU) soybean breeding program, and five controls: UFUS Carajás, MSOY 6101, MSOY 7211, UFUS Guarani, and Riqueza. Significant and complex genotype-by-environment interactions were observed. The AMMI model presented greater efficiency by retaining most of the variation in the first two main components (61.46%), followed by the GGE biplot model (57.90%), and factor analysis (54.12%). Environmental clustering among the methodologies was similar, and was composed of one environmental group from one location but from different seasons. Genotype G5 presented an elevated grain yield, and high adaptability and stability as determined by the AMMI, factor analysis, and GGE biplot methodologies.

Comparative analysis of laparoscopic and ultrasound-guided biopsy methods for gene expression analysis in transgenic goats.

The present study aimed to compare laparoscopic (LP) and ultrasound-guided (US) biopsy methods to obtain either liver or splenic tissue samples for ectopic gene expression analysis in transgenic goats. Tissue samples were collected from human granulocyte colony stimulating factor (hG-CSF)-transgenic bucks and submitted to real-time PCR for the endogenous genes (Sp1, Baff, and Gapdh) and the transgene (hG-CSF). Both LP and US biopsy methods were successful in obtaining liver and splenic samples that could be analyzed by PCR (i.e., sufficient sample sizes and RNA yield were obtained). Although the number of attempts made to obtain the tissue samples was similar (P > 0.05), LP procedures took considerably longer than the US method (P = 0.03). Finally, transgene transcripts were not detected in spleen or liver samples. Thus, for the phenotypic characterization of a transgenic goat line, investigation of ectopic gene expression can be made successfully by LP or US biopsy, avoiding the traditional approach of euthanasia.

[Fecal microbiota transplantation in recurrent Clostridium difficile infections. Framework and pharmaceutical preparation aspects]. / Le transfert de microbiote fécal lors d'infections récidivantes à Clostridium difficile. Cadre et aspects pharmacotechniques.

The fecal microbiota transplantation consists in introducing a preparation constituted by a dilution of stools of a healthy donor in the digestive tract of a patient recipient, to restore his intestinal physiological balance. This therapeutic approach was the subject of numerous studies showing its efficiency in the treatment of the recurrent infections with Clostridium difficile. The fecal microbiota transplantation has now a high level of clinical evidence, which explains that it appears in various international recommendations. In France, the fecal microbiota transplantation responds to the definition of a medication and can be executed as a pharmaceutical preparation or as an experimental drug for clinical trials under the responsibility of a hospital pharmacy. The objective of this paper is to propose a definition of a framework and to describe the methods of preparation of the fecal microbiota transplantation in the treatment of the recurrent infections with C. difficile and the interactions to consider for hospital pharmacies that do not have technical means to operate this technique.

Treatment of childhood acute lymphoblastic leukemia in central America: a lower-middle income countries experience.

BACKGROUND: Five Asociación de Hemato-Oncología de Centroamérica (AHOPCA) countries have used an adapted BFM-based protocol for childhood acute lymphoblastic leukemia (ALL). PROCEDURE: In the AHOPCA-ALL 2008 protocol, patients were stratified by age, white blood cell count, immunophenotype, central nervous system involvement, day 8 prednisone response, and morphologic bone marrow response to induction therapy. Patients at Standard Risk (SR) received a three-drug induction regimen, a reinduction phase, and maintenance with protracted intrathecal therapy. Those at Intermediate (IR) and High Risk (HR) received, in addition, daunorubicin during induction therapy, a consolidation phase and two or three reinduction phases respectively. RESULTS: From August 2008 through July 2012, 1,313 patients were enrolled: 353 in SR, 548 in IR, 412 in HR. During induction therapy, 3.0% of patients died, 2.7% abandoned treatment, 1.1% had resistant ALL, and 93.2% achieved morphological complete remission (CR). Deaths and abandonment in first CR occurred in 2.7% and in 7.0% of patients, respectively. The relapse rate at a median observation time of 2.1 years was 15.0%. At 3 years, the event-free survival (EFS) and overall survival (OS), with abandonment considered as an event, were 59.4% (SE 1.7) and 68.2% (SE 1.6). Three-year EFS was 68.5% (SE 3.0), 62.1% (SE 2.6), and 47.8% (SE 3.2) for SR, IR, and HR groups. Adolescents had a significantly higher relapse rate (P = 0.001). CONCLUSIONS: This experience shows that common international studies are feasible in lower-middle income countries. Toxic deaths, abandonment of treatment, and relapses remain major obstacles to the successful treatment. Alternative treatment strategies may be beneficial.

In situ atomic force microscopy tip-induced deformations and Raman spectroscopy characterization of single-wall carbon nanotubes.

In this work, an atomic force microscope (AFM) is combined with a confocal Raman spectroscopy setup to follow in situ the evolution of the G-band feature of isolated single-wall carbon nanotubes (SWNTs) under transverse deformation. The SWNTs are pressed by a gold AFM tip against the substrate where they are sitting. From eight deformed SWNTs, five exhibit an overall decrease in the Raman signal intensity, while three exhibit vibrational changes related to the circumferential symmetry breaking. Our results reveal chirality dependent effects, which are averaged out in SWNT bundle measurements, including a previously elusive mode symmetry breaking that is here explored using molecular dynamics calculations.

Thermodynamic uncertainty relations in mesoscopic devices.

We investigate the thermodynamic uncertainty relations (TURs) in mesoscopic devices for all universal symmetry classes of Wigner-Dyson and Dirac (chiral). The observables of interest include the TUR (MS), which is defined in terms of the ratio between the mean noise and mean conductance, as well as a new TUR (R) proposed in this article, which is based on the ensemble mean of the noise-to-conductance ratio. A detailed study is made on the quantum interference corrections associated with the TURs. We also analyze the influence of orbital and sublattice/chiral degrees of freedom for the validity of the observables in these chaotic mesoscopic billiards. Our investigation is based on the concatenation between the Landauer-Büttiker theory, the Mahaux-Wendeinmüller theory, and the TURs. We simulate the universal mesoscopic chaotic quantum dots using the random-matrix theory and compare our numerical results with the pertinent experimental data. The results were obtained for a different number of channels and tunneling rates that vary from the opaque to the ideal regime and, in all cases, demonstrate a clear phenomenological distinction between the TURs. In particular, the opaque regime engenders remarkable differences between the observables, even in the semiclassical regime, which characterizes a clear violation of the central limit theorem. Furthermore, we show that the phenomenology of the quantum interference corrections is strikingly robust, surprisingly exhibiting an order of magnitude greater than the supposedly leading semiclassical term for the TUR (R).