Endothelial dysfunction and lung capillary injury in cardiovascular diseases

Cardiac dysfunction of both systolic and diastolic origins leads to increased left atrial pressure, lung capillary injury and increased resistance to gas transfer. Acutely, pressure-induced trauma disrupts the endothelial and alveolar anatomical configuration and definitively causes an impairment of cellular pathways involved in fluid-flux regulation and gas exchange efficiency, a process well identified as stress failure of the alveolar-capillary membrane. In chronic heart failure (HF), additional stimuli other than pressure may trigger the true remodeling process of capillaries and small arteries characterized by endothelial dysfunction, proliferation of myofibroblasts, fibrosis and extracellular matrix deposition. In parallel there is a loss of alveolar gas diffusion properties due to the increased path from air to blood (thickening of extracellular matrix) and loss of fine molecular mechanism involved in fluid reabsorption and clearance. Deleterious changes in gas transfer not only reflect the underlying lung tissue damage but also portend independent prognostic information and may play a role in the pathogenesis of exercise limitation and ventilatory abnormalities observed in these patients. Few currently approved treatments for chronic HF have the potential to positively affect structural remodeling of the lung capillary network; angiotensin-converting enzyme inhibitors are one of the few currently established options. Recently, more attention has been paid to novel therapies specifically targeting the nitric oxide pathway as a suitable target to improve endothelial function and permeability as well as alveolar gas exchange properties

Mechanisms for the disaggregation of soil cuttings in slurries

A series of tests has been undertaken on a variety of different soils to understand how soil cuttings disaggregate when pumped from the tunnel face to the separation plant during slurry tunnelling for pipe jacked tunnels. It is important to understand this process to ensure that the separation plant can be optimised to remove the maximum amount of soil from the slurry prior to the reuse of the liquid. In pipe-jacking operations this liquid is normally water, which is recirculated after the soil has been re-moved to minimise and if possible eliminate the production of liquid waste. The paper will present results from a series of “mixing tests”, devised by the authors to investigate disaggregation, and also from standard laboratory tests undertaken to establish basic soil properties such as soil strength. The “mixing tests” simulate the softening of the cuttings due to the presence of water and the shear forces applied to the slurry by the pumps and have al-ready allowed the effect of these factors to be quantified. This series of tests will demonstrate how the mechanism of disaggregation varies with strength resulting in different proportions of disaggregated soil particles in slurries subjected to the same mixing time and shear forces

Analysis of three-nucleon forces effects in the A=3A=3 system

Using modern nucleon-nucleon interactions in the description of the $A=3,4$ nuclear systems the $\chi^2$ per datum results to be much bigger than one. In particular it is not possible to reproduce the three- and four-nucleon binding energies and the $n-d$ scattering length simultaneously. This is one manifestation of the necessity of including a three-nucleon force in the nuclear Hamiltonian. In this paper we perform an analysis of some, widely used, three-nucleon force models. We analyze their capability to describe the aforementioned quantities and, to improve their description, we propose modifications in the parametrization of the models. The effects of these new parametrization are studied in some polarization observables at low energies.Comment: 10 pages, to be published in Few-Body Systems. Presented at the workshop on "Relativistic Description of Two- and Three-body Systems in Nuclear Physics" ECT* Trento, 19 - 23 October 200

The niche construction perspective: A critical appraisal

Niche construction refers to the activities of organisms that bring about changes in their environments, many of which are evolutionarily and ecologically consequential. Advocates of niche construction theory (NCT) believe that standard evolutionary theory fails to recognize the full importance of niche construction, and consequently propose a novel view of evolution, in which niche construction and its legacy over time (ecological inheritance) are described as evolutionary processes, equivalent in importance to natural selection. Here, we subject NCT to critical evaluation, in the form of a collaboration between one prominent advocate of NCT, and a team of skeptics. We discuss whether niche construction is an evolutionary process, whether NCT obscures or clarifies how natural selection leads to organismal adaptation, and whether niche construction and natural selection are of equivalent explanatory importance. We also consider whether the literature that promotes NCT overstates the significance of niche construction, whether it is internally coherent, and whether it accurately portrays standard evolutionary theory. Our disagreements reflect a wider dispute within evolutionary theory over whether the neo-Darwinian synthesis is in need of reformulation, as well as different usages of some key terms (e.g. evolutionary process)

Modern nuclear force predictions for the neutron-deuteron scattering lengths

The nd doublet and quartet scattering lengths have been calculated based on the modern NN and 3N interactions. We also studied the effect of the electromagnetic interactions in the form introduced in AV18. Switching them off for the various nuclear force models leads to shifts of up to +0.04 fm for doublet scattering length, which is significant for present day standards. The electromagnetic effects have also a noticeable effect on quartet scattering length, which otherwise is extremely stable under the exchange of the nuclear forces. For the current nuclear force models there is a strong scatter of the 3H binding energy and the doublet scattering length values around an averaged straight line (Phillips line). This allows to use doublet scattering length and the 3H binding energy as independent low energy observables.Comment: 16 pages, 1 table, 4 ps figure

Association of Primary Care Physician Supply with Population Mortality in the United States, 2005-2015

Importance: Recent US health care reforms incentivize improved population health outcomes and primary care functions. It remains unclear how much improving primary care physician supply can improve population health, independent of other health care and socioeconomic factors. Objectives: To identify primary care physician supply changes across US counties from 2005-2015 and associations between such changes and population mortality. Design, Setting, and Participants: This epidemiological study evaluated US population data and individual-level claims data linked to mortality from 2005 to 2015 against changes in primary care and specialist physician supply from 2005 to 2015. Data from 3142 US counties, 7144 primary care service areas, and 306 hospital referral regions were used to investigate the association of primary care physician supply with changes in life expectancy and cause-specific mortality after adjustment for health care, demographic, socioeconomic, and behavioral covariates. Analysis was performed from March to July 2018. Main Outcomes and Measures: Age-standardized life expectancy, cause-specific mortality, and restricted mean survival time. Results: Primary care physician supply increased from 196014 physicians in 2005 to 204419 in 2015. Owing to disproportionate losses of primary care physicians in some counties and population increases, the mean (SD) density of primary care physicians relative to population size decreased from 46.6 per 100000 population (95% CI, 0.0-114.6 per 100000 population) to 41.4 per 100000 population (95% CI, 0.0-108.6 per 100000 population), with greater losses in rural areas. In adjusted mixed-effects regressions, every 10 additional primary care physicians per 100000 population was associated with a 51.5-day increase in life expectancy (95% CI, 29.5-73.5 days; 0.2% increase), whereas an increase in 10 specialist physicians per 100000 population corresponded to a 19.2-day increase (95% CI, 7.0-31.3 days). A total of 10 additional primary care physicians per 100000 population was associated with reduced cardiovascular, cancer, and respiratory mortality by 0.9% to 1.4%. Analyses at different geographic levels, using instrumental variable regressions, or at the individual level found similar benefits associated with primary care supply. Conclusions and Relevance: Greater primary care physician supply was associated with lower mortality, but per capita supply decreased between 2005 and 2015. Programs to explicitly direct more resources to primary care physician supply may be important for population health

A rapid allele-specific assay for HLA-A*32:01 to identify patients at risk for vancomycin-induced Drug Reaction with Eosinophilia and systemic symptoms

Human leukocyte antigen (HLA) alleles have been implicated as risk factors for immune-mediated adverse drug reactions. We recently reported a strong association between HLA-A*32:01 and vancomycin-induced drug reaction with eosinophilia and systemic symptoms (DRESS). Identification of individuals with the risk allele prior to or shortly after the initiation of vancomycin therapy is of great clinical importance to prevent morbidity and mortality, improve drug safety and antibiotic treatment options. A prerequisite to the success of a pharmacogenetic screening tests is the development of simple, robust, cost-effective single HLA allele test that can be implemented in routine diagnostic laboratories. In this study, we developed a simple, real-time allele-specific PCR for typing the HLA-A*32:01 allele. Four-hundred and fifty-eight DNA samples including thirty HLA-A*32:01-positive samples were typed by allele-specific PCR. Compared to ASHI accredited sequence-based high-resolution, full allelic HLA typing, this assay demonstrates 100% accuracy, sensitivity of 100% (95% CI: 88.43% to 100%) and specificity of 100% (95% CI: 99.14% to 100%). The lowest limit of detection of this assay using the Power Up SYBR Green is 10 ng of template DNA. The assay demonstrates a sensitivity and specificity to differentiate HLA-A*32:01 allele from closely related non-HLA-A*32 alleles and may be used in clinical settings to identify individuals with the risk allele prior or during the course of vancomycin therapy

Magnetic field effect on the dielectric constant of glasses: Evidence of disorder within tunneling barriers

The magnetic field dependence of the low frequency dielectric constant $e_r$(H) of a structural glass a - SiO2 + xCyHz was studied from 400 mK to 50 mK and for H up to 3T. Measurement of both the real and the imaginary parts of $e_r$ is used to eliminate the difficult question of keeping constant the temperature of the sample while increasing H: a non-zero $e_r$(H) dependence is reported in the same range as that one very recently reported on multicomponent glasses. In addition to the recently proposed explanation based on interactions, the reported $e_r$(H) is interpreted quantitatively as a consequence of the disorder lying within the nanometric barriers of the elementary tunneling systems of the glass.Comment: latex Bcorrige1.tex, 5 files, 4 figures, 7 pages [SPEC-S02/009

Selected Topics in Three- and Four-Nucleon Systems

Two different aspects of the description of three- and four-nucleon systems are addressed. The use of bound state like wave functions to describe scattering states in $N-d$ collisions at low energies and the effects of some of the widely used three-nucleon force models in selected polarization observables in the three- and four-nucleon systems are discussed.Comment: Presented at the 21st European Conference on Few-Body Problems in Physics, Salamanca, Spain, 30 August - 3 September 201

Moving Atom-Field Interaction: Correction to Casimir-Polder Effect from Coherent Back-action

The Casimir-Polder force is an attractive force between a polarizable atom and a conducting or dielectric boundary. Its original computation was in terms of the Lamb shift of the atomic ground state in an electromagnetic field (EMF) modified by boundary conditions along the wall and assuming a stationary atom. We calculate the corrections to this force due to a moving atom, demanding maximal preservation of entanglement generated by the moving atom-conducting wall system. We do this by using non-perturbative path integral techniques which allow for coherent back-action and thus can treat non-Markovian processes. We recompute the atom-wall force for a conducting boundary by allowing the bare atom-EMF ground state to evolve (or self-dress) into the interacting ground state. We find a clear distinction between the cases of stationary and adiabatic motions. Our result for the retardation correction for adiabatic motion is up to twice as much as that computed for stationary atoms. We give physical interpretations of both the stationary and adiabatic atom-wall forces in terms of alteration of the virtual photon cloud surrounding the atom by the wall and the Doppler effect.Comment: 16 pages, 2 figures, clarified discussions; to appear in Phys. Rev.