Clarifying the Hubble constant tension with a Bayesian hierarchical model of the local distance ladder

Estimates of the Hubble constant, H0, from the local distance ladder and from the cosmic microwave background (CMB) are discrepant at the ∼3-σ level, indicating a potential issue with the standard ΛCDM cosmology. A probabilistic (i.e., Bayesian) interpretation of this tension requires a model comparison calculation, which in turn depends strongly on the tails of the H₀ likelihoods. Evaluating the tails of the local H₀ likelihood requires the use of non-Gaussian distributions to faithfully represent anchor likelihoods and outliers, and simultaneous fitting of the complete distance ladder dataset to ensure correct uncertainty propagation. We have hence developed a Bayesian hierarchical model of the full distance ladder that does not rely on Gaussian distributions and allows outliers to be modelled without arbitrary data cuts. Marginalizing over the full ∼3000-parameter joint posterior distribution we find H0 = (72.72 ± 1.67) km s¯¹ Mpc¯¹ when applied to the outlier-cleaned Riess et al. (2016) data, and (73.15 ± 1.78) km s¯¹ Mpc¯¹ with SN outliers reintroduced (the pre-cut Cepheid dataset is not available). Using our precise evaluation of the tails of the H0 likelihood, we apply Bayesian model comparison to assess the evidence for deviation from ΛCDM given the distance-ladder and CMB data. The odds against ΛCDM are at worst ∼10:1 when considering the Planck Collaboration (2016b) data, regardless of outlier treatment, considerably less dramatic than naïvely implied by the 2.8-σ discrepancy. These odds become ∼60:1 when an approximation to the more-discrepant Planck Collaboration (2016c) likelihood is included

Virulence Gene Sequencing Highlights Similarities and Differences in Sequences in Listeria monocytogenes Serotype 1/2a and 4b Strains of Clinical and Food Origin From 3 Different Geographic Locations

peer-reviewedThe Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmicb.2018.01103/full#supplementary-materialThe prfA-virulence gene cluster (pVGC) is the main pathogenicity island in Listeria monocytogenes, comprising the prfA, plcA, hly, mpl, actA, and plcB genes. In this study, the pVGC of 36 L. monocytogenes isolates with respect to different serotypes (1/2a or 4b), geographical origin (Australia, Greece or Ireland) and isolation source (food-associated or clinical) was characterized. The most conserved genes were prfA and hly, with the lowest nucleotide diversity (π) among all genes (P < 0.05), and the lowest number of alleles, substitutions and non-synonymous substitutions for prfA. Conversely, the most diverse gene was actA, which presented the highest number of alleles (n = 20) and showed the highest nucleotide diversity. Grouping by serotype had a significantly lower π value (P < 0.0001) compared to isolation source or geographical origin, suggesting a distinct and well-defined unit compared to other groupings. Among all tested genes, only hly and mpl were those with lower nucleotide diversity in 1/2a serotype than 4b serotype, reflecting a high within-1/2a serotype divergence compared to 4b serotype. Geographical divergence was noted with respect to the hly gene, where serotype 4b Irish strains were distinct from Greek and Australian strains. Australian strains showed less diversity in plcB and mpl relative to Irish or Greek strains. Notable differences regarding sequence mutations were identified between food-associated and clinical isolates in prfA, actA, and plcB sequences. Overall, these results indicate that virulence genes follow different evolutionary pathways, which are affected by a strain's origin and serotype and may influence virulence and/or epidemiological dominance of certain subgroups.This study was supported by the 7th Framework Programme projects PROMISE, contract number 265877

Pregnancy Protects Hyperandrogenemic Female Rats from Postmenopausal Hypertension

Polycystic ovary syndrome, the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenemia, obesity, insulin resistance, and elevated blood pressure. However, few studies have focused on the consequences of pregnancy on postmenopausal cardiovascular disease and hypertension in polycystic ovary syndrome women. In hyperandrogenemic female (HAF) rats, the hypothesis was tested that previous pregnancy protects against age-related hypertension. Rats were implanted with dihydrotestosterone (7.5 mg/90 days, beginning at 4 weeks and continued throughout life) or placebo pellets (controls), became pregnant at 10 to 15 weeks, and pups were weaned at postnatal day 21. Dams and virgins were then aged to 10 months (still estrous cycling) or 16 months (postcycling). Although numbers of offspring per litter were similar for HAF and control dams, birth weights were lower in HAF offspring. At 10 months of age, there were no differences in blood pressure, proteinuria, nitrate/nitrite excretion, or body composition in previously pregnant HAF versus virgin HAF. However, by 16 months of age, despite no differences in dihydrotestosterone, fat mass/or lean mass/body weight, previously pregnant HAF had significantly lower blood pressure and proteinuria, higher nitrate/nitrite excretion, with increased intrarenal mRNA expression of endothelin B receptor and eNOS (endothelial nitric oxide synthase), and decreased ACE (angiotensin-converting enzyme), AT1aR (angiotensin 1a receptor), and endothelin A receptor than virgin HAF. Thus, pregnancy protects HAF rats against age-related hypertension, and the mechanism(s) may be due to differential regulation of the nitric oxide, endothelin, and renin-angiotensin systems. These data suggest that polycystic ovary syndrome women who have experienced uncomplicated pregnancy may be protected from postmenopausal hypertension.Fil: Shawky, Noha M.. University Of Mississippi Medical Center; Estados UnidosFil: Patil, Chetan N.. Medical College Of Wisconsin; Estados UnidosFil: Dalmasso, Carolina. University of Kentucky; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa | Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa | Instituto de Investigación Médica Mercedes y Martín Ferreyra. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa; ArgentinaFil: Marañón, Rodrigo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina. Universidad Nacional de Tucumán. Facultad de Medicina; ArgentinaFil: Romero, Damián Gastón. University Of Mississippi Medical Center; Estados UnidosFil: Drummond, Heather. University Of Mississippi Medical Center; Estados UnidosFil: Reckelhoff, Jane F.. University Of Mississippi Medical Center; Estados Unido

Need for psychological support and disability management programs during and after the COVID-19 pandemic in Italy: Preliminary findings from a hospital-based occupational health surveillance program

Introduction: Since the beginning of COVID-19 pandemic, healthcare workers (HCWs) have undoubtedly experienced overwhelming levels of strain associated with social and occupational stressors. This study aimed to investigate the potential psychological effects experienced by hospital workers and HCWs and their associated demographical and occupational characteristics during the COVID-19 pandemic. Methods: A cross-sectional study was carried out in a public hospital in Rome, Italy, from June 2020 to July 2021. 635 hospital workers (HCWs, administrative and technicians) were enrolled in the study. The “Psychological Injury Risk Indicator” questionnaire was used. Statistical analyses have been made using Student’s T test for categorical binomial variables and analysis of variance for multi-categorical variables. Logistic regression analysis was then performed. Results: 30.6% of the sample was at risk for general psychological impairment; reduced energy recovery was found in 48.0% and sleep problems in 44.7% of them. Female workers reported a two-fold risk for potential psychological impairment compared to male colleagues. Nurses presented a three-fold risk while physicians a two-fold risk for the overall score. Additionally, physicians had a four-fold risk to develop a lack of energy recovery and a three-fold risk for chronic fatigue. Technicians showed a significant double risk for sleep problems and chronic fatigue as well as a three-fold risk for reduced energy recovery. Administrative personnel reported a tendency on sleep problems. Interestingly, agile working was a two-fold protecting factor. No-night shifters have a half risk for reporting problems in energy recovery. Discussion and Conclusion: The measure of agile working is effective to mitigate the impacts of COVID-19 on mental health by protecting and promoting the psychological wellbeing of HCWs during and after the outbreak

Effectiveness of psychological support to healthcare workers by the occupational health service: a pilot experience

Work-related stress is a significant risk for healthcare workers (HCWs). This study aims aevaluating the effectiveness of an individual psychological support programme for hospital workersIn all, 35 workers participated (n). A control group of 245 workers (7n) was set. Occupationadistress was measured by the General Health Questionnaire, (GHQ-12), the quality of life by the Short Form-36 health survey, (SF-36), and sickness absence was recorded. Costs and benefits of the service were evaluated and the return on investment (ROI) was calculated. The level of distress was significantly reduced in the treated group at the end of the follow-up (p &lt; 0.001). Quality of life had significantly improved (p &lt; 0.003). A 60% reduction of sickness absence days (SADs) following the intervention was recorded. After the treatment, absenteeism in cases was significantly lower than in controls (p &lt; 0.02). The individual improvement of mental health and quality of life was significantly correlated with the number of meetings with the psychologist (p &lt; 0.01 and p &lt; 0.03, respectively)The recovery of direct costs due to reduced sick leave absence was significantly higher than the costs of the programme; ROI was 2.73. The results must be examined with caution, given the very limited number of workers treated; this first study, however, encouraged us to continue the experience

Reproducible protocols for metagenomic analysis of human faecal phageomes

peer-reviewedAll sequence data used in the analyses were deposited in the Sequence read Archive (SRA) (http://www.ncbi.nlm.nih.gov/sra) under BioProject PRJNA407341. Sample IDs, meta data and corresponding accession numbers are summarised in Additional file 2: Table S2. All raw count tables, 16S taxonomic assignments, BLAST top hits for viral contigs and R code used for the analysis are available at (https://figshare.com/s/71163558b4f78e3e7ed6).Background Recent studies have demonstrated that the human gut is populated by complex, highly individual and stable communities of viruses, the majority of which are bacteriophages. While disease-specific alterations in the gut phageome have been observed in IBD, AIDS and acute malnutrition, the human gut phageome remains poorly characterised. One important obstacle in metagenomic studies of the human gut phageome is a high level of discrepancy between results obtained by different research groups. This is often due to the use of different protocols for enriching virus-like particles, nucleic acid purification and sequencing. The goal of the present study is to develop a relatively simple, reproducible and cost-efficient protocol for the extraction of viral nucleic acids from human faecal samples, suitable for high-throughput studies. We also analyse the effect of certain potential confounding factors, such as storage conditions, repeated freeze-thaw cycles, and operator bias on the resultant phageome profile. Additionally, spiking of faecal samples with an exogenous phage standard was employed to quantitatively analyse phageomes following metagenomic sequencing. Comparative analysis of phageome profiles to bacteriome profiles was also performed following 16S rRNA amplicon sequencing. Results Faecal phageome profiles exhibit an overall greater individual specificity when compared to bacteriome profiles. The phageome and bacteriome both exhibited moderate change when stored at + 4 °C or room temperature. Phageome profiles were less impacted by multiple freeze-thaw cycles than bacteriome profiles, but there was a greater chance for operator effect in phageome processing. The successful spiking of faecal samples with exogenous bacteriophage demonstrated large variations in the total viral load between individual samples. Conclusions The faecal phageome sequencing protocol developed in this study provides a valuable additional view of the human gut microbiota that is complementary to 16S amplicon sequencing and/or metagenomic sequencing of total faecal DNA. The protocol was optimised for several confounding factors that are encountered while processing faecal samples, to reduce discrepancies observed within and between research groups studying the human gut phageome. Rapid storage, limited freeze-thaw cycling and spiking of faecal samples with an exogenous phage standard are recommended for optimum results

Five types of blow-up in a semilinear fourth-order reaction-diffusion equation: an analytic-numerical approach

Five types of blow-up patterns that can occur for the 4th-order semilinear parabolic equation of reaction-diffusion type u_t= -\Delta^2 u + |u|^{p-1} u \quad {in} \quad \ren \times (0,T), p>1, \quad \lim_{t \to T^-}\sup_{x \in \ren} |u(x,t)|= +\iy, are discussed. For the semilinear heat equation $u_t= \Delta u+ u^p$, various blow-up patterns were under scrutiny since 1980s, while the case of higher-order diffusion was studied much less, regardless a wide range of its application.Comment: 41 pages, 27 figure

The five dimensions of B cell tolerance

B cell tolerance has been generally understood to be an acquired property of the immune system that governs antibody specificity in ways that avoid auto‐toxicity. As useful as this understanding has proved, it fails to fully explain the existence of auto‐reactive specificities in healthy individuals and contribution these may have to health. Mechanisms underlying B cell tolerance are considered to select a clonal repertoire that generates a collection of antibodies that do not bind self, ie tolerance operates more or less in three dimensions that largely spare autologous cells and antigens. Yet, most B lymphocytes in humans and probably in other vertebrates are auto‐reactive and absence of these auto‐reactive B cells is associated with disease. We suggest that auto‐reactivity can be embodied by extending the concept of tolerance by two further dimensions, one of time and circumstance and one that allows healthy cells to actively resist injury. In this novel concept, macromolecular recognition by the B cell receptor leading to deletion, anergy, receptor editing or B cell activation is extended by taking account of the time of development of normal immune responses (4th dimension) and the accommodation (or tolerance) of normal cells to bound antibody, activation of complement, and interaction with inflammatory cells (fifth dimension). We discuss how these dimensions contribute to understanding B cell biology in health or disease.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153034/1/imr12813.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153034/2/imr12813_am.pd

Síntesis green y caracterización biológica de AgNPs empleando extracto de alcaparras

La búsqueda de procesos sintéticos «verde» que se valgan de la biotecnología como una opción viable para la síntesis de nanopartículas metálicas y el interés por extractos vegetales acuosos como «fábrica de materiales nanoestructurados» han recibido enorme atención durante la última década. Ello es en respuesta a las innumerables y particulares propiedades fisicoquímicas de estos nanomateriales y sus consecuentes aplicaciones en diferentes sectores económicos, como la catálisis, la electrónica, la tecnología analítica, la ingeniería de alimentos, médica y farmacéutica. En el presente trabajo se describe la novedosa biosíntesis de nanopartículas de plata (AgNPs) a partir de la reducción de iones Ag+ con el extracto acuoso de hojas frescas de alcaparra (Capparis spinosa L). El proceso de síntesis se llevó a cabo adicionando 2 mL del extracto a 25 mL de solución de AgNO3 10 mM y llegando luego a microondas por 2 minutos. La formación de las AgNPs fue visualizada por el cambio de color de la solución de AgNO3 de incolora a marrón amarillento luego del agregado del extracto acuoso y confirmada vía espectrocopia UV-vis por la presencia de un pico de absorción de SPR a ~425 nm. Las características morfológicas de las AgNPs biosintetizadas fueron analizadas por microscopía electrónica de transmisión y su estabilidad electrostática por análisis de potencial Zeta. Si bien las AgNPs biosintetizadas no fijaron actividad antioxidante, ellas mostraron actividad biológica como potencial agente antibacteriano no convencional debido a su destacada actividad bactericida de amplio espectro, siendo la dosis a emplear del orden del picomolar. Además, este trabajo permitió dar valor agregado a residuos agroindustriales como fuente de compuestos bioactivos con propiedades reductoras y estabilizantes, los cuales propiciaron la síntesis sencilla y verde de nanomateriales de naturaleza metálica.Ibero-American Science and Technology Education Consortiu