Dilaton Quantum Cosmology with a Schrodinger-like equation

A quantum cosmological model with radiation and a dilaton scalar field is analysed. The Wheeler-deWitt equation in the mini-superspace induces a Schr\"odinger equation, which can be solved. An explicit wavepacket is constructed for a particular choice of the ordering factor. A consistent solution is possible only when the scalar field is a phantom field. Moreover, although the wavepacket is time dependent, a Bohmian analysis allows to extract a bouncing behaviour for the scale factor.Comment: 14 pages, 3 figures in eps format. Minors corrections, new figure

Imaging of Disease Dynamics during Meningococcal Sepsis

Neisseria meningitidis is a human pathogen that causes septicemia and meningitis with high mortality. The disease progression is rapid and much remains unknown about the disease process. The understanding of disease development is crucial for development of novel therapeutic strategies and vaccines against meningococcal disease. The use of bioluminescent imaging combined with a mouse disease model allowed us to investigate the progression of meningococcal sepsis over time. Injection of bacteria in blood demonstrated waves of bacterial clearance and growth, which selected for Opa-expressing bacteria, indicating the importance of this bacterial protein. Further, N. meningitidis accumulated in the thyroid gland, while thyroid hormone T4 levels decreased. Bacteria reached the mucosal surfaces of the upper respiratory tract, which required expression of the meningococcal PilC1 adhesin. Surprisingly, PilC1 was dispensable for meningococcal growth in blood and for crossing of the blood-brain barrier, indicating that the major role of PilC1 is to interact with mucosal surfaces. This in vivo study reveals disease dynamics and organ targeting during meningococcal disease and presents a potent tool for further investigations of meningococcal pathogenesis and vaccines in vivo. This might lead to development of new strategies to improve the outcome of meningococcal disease in human patients

The Completed SDSS-IV extended Baryon Oscillation Spectroscopic Survey: Measurement of the BAO and growth rate of structure of the luminous red galaxy sample from the anisotropic power spectrum between redshifts 0.6 and 1.0

We analyse the clustering of the Sloan Digital Sky Survey IV extended Baryon Oscillation Spectroscopic Survey Data Release 16 luminous red galaxy sample (DR16 eBOSS LRG) in combination with the high redshift tail of the Sloan Digital Sky Survey III Baryon Oscillation Spectroscopic Survey Data Release 12 (DR12 BOSS CMASS).We measure the redshift space distortions (RSD) and also extract the longitudinal and transverse baryonic acoustic oscillation (BAO) scale from the anisotropic power spectrum signal inferred from 377 458 galaxies between redshifts 0.6 and 1.0, with the effective redshift of zeff = 0.698 and effective comoving volume of 2.72 Gpc3. After applying reconstruction, we measure the BAO scale and infer DH(zeff)/rdrag = 19.30 ± 0.56 and DM(zeff)/rdrag = 17.86 ± 0.37. When we perform an RSD analysis on the pre-reconstructed catalogue on the monopole, quadrupole, and hexadecapole we find, DH(zeff)/rdrag = 20.18 ± 0.78, DM(zeff)/rdrag = 17.49 ± 0.52 and fσ8(zeff) = 0.454 ± 0.046. We combine both sets of results along with the measurements in configuration space and report the following consensus values: DH(zeff)/rdrag = 19.77 ± 0.47, DM(zeff)/rdrag = 17.65 ± 0.30 and fσ8(zeff) = 0.473 ± 0.044, which are in full agreement with the standard CDM and GR predictions. These results represent the most precise measurements within the redshift range 0.6 ≤ z ≤ 1.0 and are the culmination of more than 8 yr of SDSS observations

Abnormal accumulation of autophagic vesicles correlates with axonal and synaptic pathology in young Alzheimer’s mice hippocampus

Dystrophic neurites associated with amyloid plaques precede neuronal death and manifest early in Alzheimer’s disease (AD). In this work we have characterized the plaque-associated neuritic pathology in the hippocampus of young (4- to 6-month-old) PS1M146L/APP751SL mice model, as the initial degenerative process underlying functional disturbance prior to neuronal loss. Neuritic plaques accounted for almost all fibrillar deposits and an axonal origin of the dystrophies was demonstrated. The early induction of autophagy pathology was evidenced by increased protein levels of the autophagosome marker LC3 that was localized in the axonal dystrophies, and by electron microscopic identification of numerous autophagic vesicles filling and causing the axonal swellings. Early neuritic cytoskeletal defects determined by the presence of phosphorylated tau (AT8-positive) and actin–cofilin rods along with decreased levels of kinesin-1 and dynein motor proteins could be responsible for this extensive vesicle accumulation within dystrophic neurites. Although microsomal Aβ oligomers were identified, the presence of A11-immunopositive Aβ plaques also suggested a direct role of plaque-associated Aβ oligomers in defective axonal transport and disease progression. Most importantly, presynaptic terminals morphologically disrupted by abnormal autophagic vesicle buildup were identified ultrastructurally and further supported by synaptosome isolation. Finally, these early abnormalities in axonal and presynaptic structures might represent the morphological substrate of hippocampal dysfunction preceding synaptic and neuronal loss and could significantly contribute to AD pathology in the preclinical stages

Clinical Audits in Outpatient Clinics for Chronic Obstructive Pulmonary Disease: Methodological Considerations and Workflow

Objectives: Previous clinical audits for chronic obstructive pulmonary disease (COPD) have provided valuable information on the clinical care delivered to patients admitted to medical wards because of COPD exacerbations. However, clinical audits of COPD in an outpatient setting are scarce and no methodological guidelines are currently available. Based on our previous experience, herein we describe a clinical audit for COPD patients in specialized outpatient clinics with the overall goal of establishing a potential methodological workflow.Methods: A pilot clinical audit of COPD patients referred to respiratory outpatient clinics in the region of Andalusia, Spain (over 8 million inhabitants), was performed. The audit took place between October 2013 and September 2014, and 10 centers (20% of all public hospitals) were invited to participate. Cases with an established diagnosis of COPD based on risk factors, clinical symptoms, and a post-bronchodilator FEV1/FVC ratio of less than 0.70 were deemed eligible. The usefulness of formally scheduled regular follow-up visits was assessed. Two different databases (resources and clinical database) were constructed. Assessments were planned over a year divided by 4 three-month periods, with the goal of determining seasonal-related changes. Exacerbations and survival served as the main endpoints.Conclusions: This paper describes a methodological framework for conducting a clinical audit of COPD patients in an outpatient setting. Results from such audits can guide health information systems development and implementation in real-world settings.This study was financially supported by an unrestricted grant from Laboratorios Menarini, SA (Barcelona, Spain)

Intrauterine Growth Restriction Is a Direct Consequence of Localized Maternal Uropathogenic Escherichia coli Cystitis

Despite the continually increasing rates of adverse perinatal outcomes across the globe, the molecular mechanisms that underlie adverse perinatal outcomes are not completely understood. Clinical studies report that 10% of pregnant women will experience a urinary tract infection (UTI) and there is an association of UTIs with adverse perinatal outcomes. We introduced bacterial cystitis into successfully outbred female mice at gestational day 14 to follow pregnancy outcomes and immunological responses to determine the mechanisms that underlie UTI-mediated adverse outcomes. Outbred fetuses from mothers experiencing localized cystitis displayed intrauterine growth restriction (20–80%) as early as 48 hours post-infection and throughout the remainder of normal gestation. Robust infiltration of cellular innate immune effectors was observed in the uteroplacental tissue following introduction of UTI despite absence of viable bacteria. The magnitude of serum proinflammatory cytokines is elevated in the maternal serum during UTI. This study demonstrates that a localized infection can dramatically impact the immunological status as well as the function of non-infected distal organs and tissues. This model can be used as a platform to determine the mechanism(s) by which proinflammatory changes occur between non-contiguous genitourinary organ

Completed SDSS-IV extended Baryon Oscillation Spectroscopic Survey: Cosmological implications from two decades of spectroscopic surveys at the Apache Point Observatory

We present the cosmological implications from final measurements of clustering using galaxies, quasars, and Ly α forests from the completed Sloan Digital Sky Survey (SDSS) lineage of experiments in large-scale structure. These experiments, composed of data from SDSS, SDSS-II, BOSS, and eBOSS, offer independent measurements of baryon acoustic oscillation (BAO) measurements of angular-diameter distances and Hubble distances relative to the sound horizon, r_{d}, from eight different samples and six measurements of the growth rate parameter, fσ_{8}, from redshift-space distortions (RSD). This composite sample is the most constraining of its kind and allows us to perform a comprehensive assessment of the cosmological model after two decades of dedicated spectroscopic observation. We show that the BAO data alone are able to rule out dark-energy-free models at more than eight standard deviations in an extension to the flat, Λ CDM model that allows for curvature. When combined with Planck Cosmic Microwave Background (CMB) measurements of temperature and polarization, under the same model, the BAO data provide nearly an order of magnitude improvement on curvature constraints relative to primary CMB constraints alone. Independent of distance measurements, the SDSS RSD data complement weak lensing measurements from the Dark Energy Survey (DES) in demonstrating a preference for a flat Λ CDM cosmological model when combined with Planck measurements. The combined BAO and RSD measurements indicate σ_{8} = 0.85 ± 0.03, implying a growth rate that is consistent with predictions from Planck temperature and polarization data and with General Relativity. When combining the results of SDSS BAO and RSD, Planck, Pantheon Type Ia supernovae (SNe Ia), and DES weak lensing and clustering measurements, all multiple-parameter extensions remain consistent with a Λ CDM model. Regardless of cosmological model, the precision on each of the three parameters, Ω_{Λ}, H_{0}, and σ_{8}, remains at roughly 1%, showing changes of less than 0.6% in the central values between models. In a model that allows for free curvature and a time-evolving equation of state for dark energy, the combined samples produce a constraint Ω_{k} = −0.0022 ± 0.0022. The dark energy constraints lead to w_{0} = −0.909 ± 0.081 and w_{a} = −0.49^{+0.35}_{-0.30}, corresponding to an equation of state of w_{p} = 1.018 ± 0.032 at a pivot redshift z_{p} = 0.29 and a Dark Energy Task Force Figure of Merit of 94. The inverse distance ladder measurement under this model yields H_{0} = 68.18 ± 0.79 km s^{-1} Mpc^{-1}, remaining in tension with several direct determination methods; the BAO data allow Hubble constant estimates that are robust against the assumption of the cosmological model. In addition, the BAO data allow estimates of H_{0} that are independent of the CMB data, with similar central values and precision under a Λ CDM model. Our most constraining combination of data gives the upper limit on the sum of neutrino masses at ∑m_{v} < 0.115 eV (95% confidence). Finally, we consider the improvements in cosmology constraints over the last decade by comparing our results to a sample representative of the period 2000–2010. We compute the relative gain across the five dimensions spanned by w, Ω_{k}, ∑m_{v}, H_{0}, H_{0}, and σ_{8} and find that the SDSS BAO and RSD data reduce the total posterior volume by a factor of 40 relative to the previous generation. Adding again the Planck, DES, and Pantheon SN Ia samples leads to an overall contraction in the five-dimensional posterior volume of 3 orders of magnitude

Spike-Timing Precision and Neuronal Synchrony Are Enhanced by an Interaction between Synaptic Inhibition and Membrane Oscillations in the Amygdala

The basolateral complex of the amygdala (BLA) is a critical component of the neural circuit regulating fear learning. During fear learning and recall, the amygdala and other brain regions, including the hippocampus and prefrontal cortex, exhibit phase-locked oscillations in the high delta/low theta frequency band (∼2–6 Hz) that have been shown to contribute to the learning process. Network oscillations are commonly generated by inhibitory synaptic input that coordinates action potentials in groups of neurons. In the rat BLA, principal neurons spontaneously receive synchronized, inhibitory input in the form of compound, rhythmic, inhibitory postsynaptic potentials (IPSPs), likely originating from burst-firing parvalbumin interneurons. Here we investigated the role of compound IPSPs in the rat and rhesus macaque BLA in regulating action potential synchrony and spike-timing precision. Furthermore, because principal neurons exhibit intrinsic oscillatory properties and resonance between 4 and 5 Hz, in the same frequency band observed during fear, we investigated whether compound IPSPs and intrinsic oscillations interact to promote rhythmic activity in the BLA at this frequency. Using whole-cell patch clamp in brain slices, we demonstrate that compound IPSPs, which occur spontaneously and are synchronized across principal neurons in both the rat and primate BLA, significantly improve spike-timing precision in BLA principal neurons for a window of ∼300 ms following each IPSP. We also show that compound IPSPs coordinate the firing of pairs of BLA principal neurons, and significantly improve spike synchrony for a window of ∼130 ms. Compound IPSPs enhance a 5 Hz calcium-dependent membrane potential oscillation (MPO) in these neurons, likely contributing to the improvement in spike-timing precision and synchronization of spiking. Activation of the cAMP-PKA signaling cascade enhanced the MPO, and inhibition of this cascade blocked the MPO. We discuss these results in the context of spike-timing dependent plasticity and modulation by neurotransmitters important for fear learning, such as dopamine