229 research outputs found
Climate-informed stochastic hydrological modeling: Incorporating decadal-scale variability using paleo data
A hierarchical framework for incorporating modes of climate variability into stochastic simulations of hydrological data is developed, termed the climate-informed multi-time scale stochastic (CIMSS) framework. A case study on two catchments in eastern Australia illustrates this framework. To develop an identifiable model characterizing long-term variability for the first level of the hierarchy, paleoclimate proxies, and instrumental indices describing the Interdecadal Pacific Oscillation (IPO) and the Pacific Decadal Oscillation (PDO) are analyzed. A new paleo IPO-PDO time series dating back 440 yr is produced, combining seven IPO-PDO paleo sources using an objective smoothing procedure to fit low-pass filters to individual records. The paleo data analysis indicates that wet/dry IPO-PDO states have a broad range of run lengths, with 90% between 3 and 33 yr and a mean of 15 yr. The Markov chain model, previously used to simulate oscillating wet/dry climate states, is found to underestimate the probability of wet/dry periods >5 yr, and is rejected in favor of a gamma distribution for simulating the run lengths of the wet/dry IPO-PDO states. For the second level of the hierarchy, a seasonal rainfall model is conditioned on the simulated IPO-PDO state. The model is able to replicate observed statistics such as seasonal and multiyear accumulated rainfall distributions and interannual autocorrelations. Mean seasonal rainfall in the IPO-PDO dry states is found to be 15%-28% lower than the wet state at the case study sites. In comparison, an annual lag-one autoregressive model is unable to adequately capture the observed rainfall distribution within separate IPO-PDO states. Copyright © 2011 by the American Geophysical Union.Benjamin J. Henley, Mark A. Thyer, George Kuczera and Stewart W. Frank
Climate-informed stochastic hydrological modeling: Incorporating decadal-scale variability using paleo data
A hierarchical framework for incorporating modes of climate variability into stochastic simulations of hydrological data is developed, termed the climate-informed multi-time scale stochastic (CIMSS) framework. A case study on two catchments in eastern Australia illustrates this framework. To develop an identifiable model characterizing long-term variability for the first level of the hierarchy, paleoclimate proxies, and instrumental indices describing the Interdecadal Pacific Oscillation (IPO) and the Pacific Decadal Oscillation (PDO) are analyzed. A new paleo IPO-PDO time series dating back 440 yr is produced, combining seven IPO-PDO paleo sources using an objective smoothing procedure to fit low-pass filters to individual records. The paleo data analysis indicates that wet/dry IPO-PDO states have a broad range of run lengths, with 90% between 3 and 33 yr and a mean of 15 yr. The Markov chain model, previously used to simulate oscillating wet/dry climate states, is found to underestimate the probability of wet/dry periods >5 yr, and is rejected in favor of a gamma distribution for simulating the run lengths of the wet/dry IPO-PDO states. For the second level of the hierarchy, a seasonal rainfall model is conditioned on the simulated IPO-PDO state. The model is able to replicate observed statistics such as seasonal and multiyear accumulated rainfall distributions and interannual autocorrelations. Mean seasonal rainfall in the IPO-PDO dry states is found to be 15%-28% lower than the wet state at the case study sites. In comparison, an annual lag-one autoregressive model is unable to adequately capture the observed rainfall distribution within separate IPO-PDO states. Copyright © 2011 by the American Geophysical Union.Benjamin J. Henley, Mark A. Thyer, George Kuczera and Stewart W. Frank
Effect of temperature anisotropy on various modes and instabilities for a magnetized non-relativistic bi-Maxwellian plasma
Using kinetic theory for homogeneous collisionless magnetized plasmas, we
present an extended review of the plasma waves and instabilities and discuss
the anisotropic response of generalized relativistic dielectric tensor and
Onsager symmetry properties for arbitrary distribution functions. In general,
we observe that for such plasmas only those electromagnetic modes whose
magnetic field perturbations are perpendicular to the ambient magneticeld,
i.e.,B1 \perp B0, are effected by the anisotropy. However, in oblique
propagation all modes do show such anisotropic effects. Considering the
non-relativistic bi-Maxwellian distribution and studying the relevant
components of the general dielectric tensor under appropriate conditions, we
derive the dispersion relations for various modes and instabilities. We show
that only the electromagnetic R- and L- waves, those derived from them and the
O-mode are affected by thermal anisotropies, since they satisfy the required
condition B1\perpB0. By contrast, the perpendicularly propagating X-mode and
the modes derived from it (the pure transverse X-mode and Bernstein mode) show
no such effect. In general, we note that the thermal anisotropy modifies the
parallel propagating modes via the parallel acoustic effect, while it modifies
the perpendicular propagating modes via the Larmor-radius effect. In oblique
propagation for kinetic Alfven waves, the thermal anisotropy affects the
kinetic regime more than it affects the inertial regime. The generalized fast
mode exhibits two distinct acoustic effects, one in the direction parallel to
the ambient magnetic field and the other in the direction perpendicular to it.
In the fast-mode instability, the magneto-sonic wave causes suppression of the
firehose instability. We discuss all these propagation characteristics and
present graphic illustrations
Different atmospheric moisture divergence responses to extreme and moderate El Niños
On seasonal and inter-annual time scales, vertically integrated moisture divergence provides a useful measure of the tropical atmospheric hydrological cycle. It reflects the combined dynamical and thermodynamical effects, and is not subject to the limitations that afflict observations of evaporation minus precipitation. An empirical orthogonal function (EOF) analysis of the tropical Pacific moisture divergence fields calculated from the ERA-Interim reanalysis reveals the dominant effects of the El Niño-Southern Oscillation (ENSO) on inter-annual time scales. Two EOFs are necessary to capture the ENSO signature, and regression relationships between their Principal Components and indices of equatorial Pacific sea surface temperature (SST) demonstrate that the transition from strong La Niña through to extreme El Niño events is not a linear one. The largest deviation from linearity is for the strongest El Niños, and we interpret that this arises at least partly because the EOF analysis cannot easily separate different patterns of responses that are not orthogonal to each other. To overcome the orthogonality constraints, a self-organizing map (SOM) analysis of the same moisture divergence fields was performed. The SOM analysis captures the range of responses to ENSO, including the distinction between the moderate and strong El Niños identified by the EOF analysis. The work demonstrates the potential for the application of SOM to large scale climatic analysis, by virtue of its easier interpretation, relaxation of orthogonality constraints and its versatility for serving as an alternative classification method. Both the EOF and SOM analyses suggest a classification of “moderate” and “extreme” El Niños by their differences in the magnitudes of the hydrological cycle responses, spatial patterns and evolutionary paths. Classification from the moisture divergence point of view shows consistency with results based on other physical variables such as SST
Excess Mucin Impairs Subglottic Epithelial Host Defense in Mechanically Ventilated Patients
Rationale:
Aspiration of infective subglottic secretions causes ventilator-associated pneumonia (VAP) in mechanically ventilated patients. Mechanisms underlying subglottic colonization in critical illness have not been defined, limiting strategies for targeted prevention of VAP.
Objectives:
To characterize subglottic host defense dysfunction in mechanically ventilated patients in the intensive care unit (ICU). To determine whether subglottic mucin contributes to neutrophil phagocytic impairment and bacterial growth.
Methods:
Prospective subglottic sampling in mechanically ventilated patients (intubated for four or more days), and newly intubated control patients (intubated for less than 30 minutes). Isolation and culture of primary subglottic epithelial cells from controls. Laboratory analysis of host innate immune defenses.
Measurements and Main Results:
Twenty-four patients in the ICU and 27 newly intubated control patients were studied. Subglottic ICU samples had significantly reduced microbiological diversity and contained potential respiratory pathogens. The subglottic microenvironment in ICU was characterized by neutrophilic inflammation, significantly increased pro-inflammatory cytokines and neutrophil proteases, and altered physical properties of subglottic secretions, including accumulation of mucins. Subglottic mucin from ICU patients impaired the capacity of neutrophils to phagocytose and kill bacteria. Phagocytic function was reversible upon treatment with a mucolytic agent. Subglottic mucus promoted growth and invasion of bacterial pathogens in a novel air-liquid interface model of primary human subglottic epithelium.
Conclusions:
Mechanical ventilation in ICU is characterized by substantial mucin secretion and neutrophilic inflammation. Mucin impairs neutrophil dysfunction and promotes bacterial growth. Mucolytic agents reverse mucin-mediated neutrophil dysfunction. Enhanced mucus disruption and removal has potential to augment preventive benefits of subglottic drainage
The prognosis of allocentric and egocentric neglect : evidence from clinical scans
We contrasted the neuroanatomical substrates of sub-acute and chronic visuospatial deficits associated with different aspects of unilateral neglect using computed tomography scans acquired as part of routine clinical diagnosis. Voxel-wise statistical analyses were conducted on a group of 160 stroke patients scanned at a sub-acute stage. Lesion-deficit relationships were assessed across the whole brain, separately for grey and white matter. We assessed lesions that were associated with behavioural performance (i) at a sub-acute stage (within 3 months of the stroke) and (ii) at a chronic stage (after 9 months post stroke). Allocentric and egocentric neglect symptoms at the sub-acute stage were associated with lesions to dissociated regions within the frontal lobe, amongst other regions. However the frontal lesions were not associated with neglect at the chronic stage. On the other hand, lesions in the angular gyrus were associated with persistent allocentric neglect. In contrast, lesions within the superior temporal gyrus extending into the supramarginal gyrus, as well as lesions within the basal ganglia and insula, were associated with persistent egocentric neglect. Damage within the temporo-parietal junction was associated with both types of neglect at the sub-acute stage and 9 months later. Furthermore, white matter disconnections resulting from damage along the superior longitudinal fasciculus were associated with both types of neglect and critically related to both sub-acute and chronic deficits. Finally, there was a significant difference in the lesion volume between patients who recovered from neglect and patients with chronic deficits. The findings presented provide evidence that (i) the lesion location and lesion size can be used to successfully predict the outcome of neglect based on clinical CT scans, (ii) lesion location alone can serve as a critical predictor for persistent neglect symptoms, (iii) wide spread lesions are associated with neglect symptoms at the sub-acute stage but only some of these are critical for predicting whether neglect will become a chronic disorder and (iv) the severity of behavioural symptoms can be a useful predictor of recovery in the absence of neuroimaging findings on clinical scans. We discuss the implications for understanding the symptoms of the neglect syndrome, the recovery of function and the use of clinical scans to predict outcome
Proliferating macrophages in human tumours show characteristics of monocytes responding to myelopoietic growth factors
Macrophages play essential roles in maintaining tissue homeostasis and immune defence. However, their extensive infiltration into tumours has been linked to adverse outcomes in multiple human cancers. Within the tumour microenvironment (TME), tumour-associated macrophages (TAMs) promote tumour growth and metastasis, making them prime targets for cancer immunotherapy. Recent single-cell analysis suggest that proliferating TAMs accumulate in human cancers, yet their origins and differentiation pathways remain uncertain. Here, we show that a subpopulation of CD163+ TAMs proliferates in situ within the TME of melanoma, lung cancer, and breast cancer. Consistent with their potential role in suppressing anti-tumour activities of T cells, CD163+ TAMs express a range of potent immunosuppressive molecules, including PD-L1, PD-L2, IL-10, and TGF-β. Other phenotypic markers strongly suggested that these cells originate from CD14+ CCR2+ monocytes, a cell population believed to have minimal capacity for proliferation. However, we demonstrate in vitro that certain myelopoietic cytokines commonly available within the TME induce robust proliferation of human monocytes, especially the combination of interleukin 3 (IL-3) and Macrophage Colony-Stimulating Factor 1 (M-CSF). Monocytic cells cultured with these cytokines efficiently modulate T cell proliferation, and their molecular phenotype recapitulates that of CD163+ TAMs. IL-3-driven proliferation of monocytic cells can be completely blocked by IL-4, associated with the induction of CDKN1A, alongside the upregulation of transcription factors linked to dendritic cell function, such as BATF3 and IRF4. Taken together, our work suggests several novel therapeutic routes to reducing immunosuppressive TAMs in human tumours, from blocking chemokine-mediated recruitment of monocytes to blocking their proliferation
Patients presenting with somatic complaints in general practice: depression, anxiety and somatoform disorders are frequent and associated with psychosocial stressors
Mental disorders in primary care patients are frequently associated with physical complaints that can mask the disorder. There is insufficient knowledge concerning the role of anxiety, depression, and somatoform disorders in patients presenting with physical symptoms. Our primary objective was to determine the prevalence of depression, anxiety, and somatoform disorders among primary care patients with a physical complaint. We also investigated the relationship between cumulated psychosocial stressors and mental disorders.
We conducted a multicentre cross-sectional study in twenty-one private practices and in one academic primary care centre in Western Switzerland. Randomly selected patients presenting with a spontaneous physical complaint were asked to complete the self-administered Patient Health Questionnaire (PHQ) between November 2004 and July 2005. The validated French version of the PHQ allowed the diagnosis of mental disorders (DSM-IV criteria) and the analyses of exposure to psychosocial stressors.
There were 917 patients exhibiting at least one physical symptom included. The rate of depression, anxiety, and somatoform disorders was 20.0% (95% confidence interval [CI] = 17.4% to 22.7%), 15.5% (95% CI = 13.2% to 18.0%), and 15.1% (95% CI = 12.8% to 17.5%), respectively. Psychosocial stressors were significantly associated with mental disorders. Patients with an accumulation of psychosocial stressors were more likely to present anxiety, depression, or somatoform disorders, with an increase of 2.2 fold (95% CI = 2.0 to 2.5) for each additional stressor.
The investigation of mental disorders and psychosocial stressors among patients with physical complaints is relevant in primary care. Psychosocial stressors should be explored as potential epidemiological causes of mental disorders
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Direct-drive laser fusion: status and prospects
Techniques have been developed to improve the uniformity of the laser focal profile, to reduce the ablative Rayleigh-Taylor instability, and to suppress the various laser-plasma instabilities. There are now three direct-drive ignition target designs that utilize these techniques. Evaluation of these designs is still ongoing. Some of them may achieve the gains above 100 that are necessary for a fusion reactor. Two laser systems have been proposed that may meet all of the requirements for a fusion reactor
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