Decision Making for Inconsistent Expert Judgments Using Negative Probabilities

In this paper we provide a simple random-variable example of inconsistent information, and analyze it using three different approaches: Bayesian, quantum-like, and negative probabilities. We then show that, at least for this particular example, both the Bayesian and the quantum-like approaches have less normative power than the negative probabilities one.Comment: 14 pages, revised version to appear in the Proceedings of the QI2013 (Quantum Interactions) conferenc

CO2 signaling mediates neurovascular coupling in the cerebral cortex

Neurovascular coupling is a fundamental brain mechanism that regulates local cerebral blood flow (CBF) in response to changes in neuronal activity. Functional imaging techniques are commonly used to record these changes in CBF as a proxy of neuronal activity to study the human brain. However, the mechanisms of neurovascular coupling remain incompletely understood. Here we show in experimental animal models (laboratory rats and mice) that the neuronal activity-dependent increases in local CBF in the somatosensory cortex are prevented by saturation of the CO2-sensitive vasodilatory brain mechanism with surplus of exogenous CO2 or disruption of brain CO2/HCO3− transport by genetic knockdown of electrogenic sodium-bicarbonate cotransporter 1 (NBCe1) expression in astrocytes. A systematic review of the literature data shows that CO2 and increased neuronal activity recruit the same vasodilatory signaling pathways. These results and analysis suggest that CO2 mediates signaling between neurons and the cerebral vasculature to regulate brain blood flow in accord with changes in the neuronal activity

Identification of novel imidazo[1,2-a]pyridine inhibitors targeting M. tuberculosis QcrB.

Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. Through the use of high throughput whole cell screening of an extensive compound library a number of imidazo[1,2-a]pyridine (IP) compounds were obtained as potent lead molecules active against M. tuberculosis and Mycobacterium bovis BCG. The IP inhibitors (1–4) demonstrated minimum inhibitory concentrations (MICs) in the range of 0.03 to 5 µM against a panel of M. tuberculosis strains. M. bovis BCG spontaneous resistant mutants were generated against IP 1, 3, and 4 at 5× MIC and subsequent whole genome sequencing identified a single nucleotide polymorphism 937ACC>937GCC (T313A) in qcrB, which encodes the b subunit of the electron transport ubiquinol cytochrome C reductase. This mutation also conferred cross-resistance against IP 1, 3 and 4 demonstrating a common target. Gene dosage experiments confirmed M. bovis BCG QcrB as the target where over-expression in M. bovis BCG led to an increase in MIC from 0.5 to >8 µM for IP 3. An acute murine model of TB infection established bacteriostatic activity of the IP series, which await further detailed characterization

Bayesian Inference For The Segmented Weibull Distribution

In this paper, we introduce a Bayesian approach for segmented Weibull distributions which could be a good alternative to analyze medical survival data in the presence of censored observations and covariates. With the obtained Bayesian estimated change-points we could get an excellent fit of the proposed model to any data sets. With the proposed methodology, it is also possible to identify survival times intervals where a covariate could have significantly different effects when compared to other lifetime intervals, an important point under a clinical view. The obtained Bayesian estimates are obtained using standard Markov Chain Monte Carlo methods. Some examples with real data sets illustrate the proposed methodology and its potential clinical value

Transit Timing and Duration Variations for the Discovery and Characterization of Exoplanets

Transiting exoplanets in multi-planet systems have non-Keplerian orbits which can cause the times and durations of transits to vary. The theory and observations of transit timing variations (TTV) and transit duration variations (TDV) are reviewed. Since the last review, the Kepler spacecraft has detected several hundred perturbed planets. In a few cases, these data have been used to discover additional planets, similar to the historical discovery of Neptune in our own Solar System. However, the more impactful aspect of TTV and TDV studies has been characterization of planetary systems in which multiple planets transit. After addressing the equations of motion and parameter scalings, the main dynamical mechanisms for TTV and TDV are described, with citations to the observational literature for real examples. We describe parameter constraints, particularly the origin of the mass/eccentricity degeneracy and how it is overcome by the high-frequency component of the signal. On the observational side, derivation of timing precision and introduction to the timing diagram are given. Science results are reviewed, with an emphasis on mass measurements of transiting sub-Neptunes and super-Earths, from which bulk compositions may be inferred.Comment: Revised version. Invited review submitted to 'Handbook of Exoplanets,' Exoplanet Discovery Methods section, Springer Reference Works, Juan Antonio Belmonte and Hans Deeg, Eds. TeX and figures may be found at https://github.com/ericagol/TTV_revie

Inequities in maternal postnatal visits among public and private patients: 2004 Pelotas cohort study

<p>Abstract</p> <p>Background</p> <p>The postnatal period is the ideal time to deliver interventions to improve the health of both the newborn and the mother. However, postnatal care shows low-level coverage in a large number of countries. The objectives of this study were to: 1) investigate inequities in maternal postnatal visits, 2) examine differences in postnatal care coverage between public and private providers and 3) explore the relationship between the absence of maternal postnatal visits and exclusive breastfeeding, use of contraceptive methods and maternal smoking three months after birth.</p> <p>Methods</p> <p>In the calendar year of 2004 a birth cohort study was started in the city of Pelotas, Brazil. Mothers were interviewed soon after delivery and at three months after birth. The absence of postnatal visits was defined as having no consultations between the time of hospital discharge and the third month post-partum. Logistic regression analysis was used to estimate the association between absence of postnatal visits and type of insurance scheme adjusting for potential confounding factors.</p> <p>Results</p> <p>Poorer women, black/mixed, those with lower level of education, single mothers, adolescents, multiparae, smokers, women who delivered vaginally and those who were not assisted by a physician were less likely to attend postnatal care. Postnatal visits were also less frequent among women who relied in the public sector than among private patients (72.4% vs 96% among public and private patients, respectively, <it>x</it>²p < 0.001) and this difference was not explained either by maternal characteristics or by health care utilization patterns. Women who attended postnatal visits were more likely to exclusively breastfeed their infants, to use contraceptive methods and to be non-smokers three months after birth.</p> <p>Conclusion</p> <p>Postpartum care is available for every woman free of charge in the Brazilian Publicly-funded health care system. However, low levels of postpartum care were seen in the study (77%). Efforts should be made to increase the percentage of women receiving postpartum care, particularly those in socially disadvantaged groups. This could include locally-adapted health education interventions that address women's beliefs and attitudes towards postpartum care. There is a need to monitor postpartum care and collected data should be used to guide policies for health care systems.</p

Predictors of and reasons for pacifier use in first-time mothers: an observational study

Background: The use of pacifiers is commonplace in Australia and has been shown to be negatively associated with breastfeeding duration. In order to influence behaviour related to the use of pacifiers it is important to understand the reasons for their use. The primary aim of this observational study was to investigate who (if anyone) advises first-time mothers to give a pacifier and the reasons for which they first give (or try to give) a pacifier to their infant. Additionally, this study investigated the predictors of pacifier use and the relationship between pacifier use and breastfeeding duration. Methods: In total, 670 Australian first-time mothers recruited as part of the NOURISH trial completed a questionnaire regarding infant feeding and pacifier use. Results: Pacifiers were introduced by 79% of mothers, of whom 28.7% were advised to use a pacifier by their mother/mother-in-law with a further 22.7% being advised by a midwife. The majority of mothers used a pacifier in order to soothe their infant (78.3%), to help put them to sleep (57.4%) and to keep them comforted and quiet (40.4%). Pacifiers given to infants before four weeks (adjHR 3.67; 95%CI 2.14–6.28) and used most days (adjHR 3.28; 95%CI 1.92–5.61) were significantly associated with shorter duration of breastfeeding. Conclusions: This study identifies an opportunity for educating new mothers and their support network, particularly their infant’s grandmothers, with regards to potential risks associated with the early and frequent use of a pacifier, and alternative methods for soothing their infant, in order to reduce the use of pacifiers and their potentially negative effect on breastfeeding duratio

Tetrahydropyrazolo[1,5-a]Pyrimidine-3-Carboxamide and N-Benzyl-6′,7′-Dihydrospiro[Piperidine-4,4′-Thieno[3,2-c]Pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3

Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. As part of our efforts towards the discovery of new anti-tubercular leads, a number of potent tetrahydropyrazolo[1,5-a]pyrimidine-3-ca​rboxamide(THPP) and N-benzyl-6′,7′-dihydrospiro[piperidine-4,​4′-thieno[3,2-c]pyran](Spiro) analogues were recently identified against Mycobacterium tuberculosis and Mycobacterium bovis BCG through a high-throughput whole-cell screening campaign. Herein, we describe the attractive in vitro and in vivo anti-tubercular profiles of both lead series. The generation of M. tuberculosis spontaneous mutants and subsequent whole genome sequencing of several resistant mutants identified single mutations in the essential mmpL3 gene. This ‘genetic phenotype’ was further confirmed by a ‘chemical phenotype’, whereby M. bovis BCG treated with both the THPP and Spiro series resulted in the accumulation of trehalose monomycolate. In vivo efficacy evaluation of two optimized THPP and Spiro leads showed how the compounds were able to reduce >2 logs bacterial cfu counts in the lungs of infected mice