Reorganization of Atlantic Waters at sub-polar latitudes linked to deep-water overflow in both glacial and interglacial climate states

While a large cryosphere may be a necessary boundary condition for millennial-scale events to persist, a growing body of evidence from previous interglacial periods suggests that high-magnitude climate events are possible during low-cryosphere climate states. However, the full spectrum of variability, and the antecedent conditions under which such variability can occur, have not been fully described. As a result, the mechanisms generating high-magnitude climate variability during low-cryosphere boundary conditions remain unclear. In this study, high-resolution climate records from Deep Sea Drilling Project (DSDP) site 610 are used to portray the North Atlantic climate's progression through low ice, boundary conditions of Marine Isotope Stage (MIS) 11c into the glacial inception. We show that this period is marked by two climate events displaying rapid shifts in both deep overflow and surface climate. The reorganization between Polar Water and Atlantic Water at subpolar latitudes appears to accompany changes in the flow of deep water emanating from the Nordic Seas, regardless of magnitude or boundary conditions. Further, during both intermediate and low ice boundary conditions, we find that a reduction in deep water precedes surface hydrographic change. The existence of surface and deep-ocean events, with similar magnitudes, abruptness, and surface–deep phasing, advances our mechanistic understanding of, and elucidates antecedent conditions that can lead to, high-magnitude climate instability.publishedVersio

Reorganization of Atlantic Waters at sub-polar latitudes linked to deep-water overflow in both glacial and interglacial climate states

While a large cryosphere may be a necessary boundary condition for millennial-scale events to persist, a growing body of evidence from previous interglacial periods suggests that high-magnitude climate events are possible during low-cryosphere climate states. However, the full spectrum of variability, and the antecedent conditions under which such variability can occur, have not been fully described. As a result, the mechanisms generating high-magnitude climate variability during low-cryosphere boundary conditions remain unclear. In this study, high-resolution climate records from Deep Sea Drilling Project (DSDP) site 610 are used to portray the North Atlantic climate's progression through low ice, boundary conditions of Marine Isotope Stage (MIS) 11c into the glacial inception. We show that this period is marked by two climate events displaying rapid shifts in both deep overflow and surface climate. The reorganization between Polar Water and Atlantic Water at subpolar latitudes appears to accompany changes in the flow of deep water emanating from the Nordic Seas, regardless of magnitude or boundary conditions. Further, during both intermediate and low ice boundary conditions, we find that a reduction in deep water precedes surface hydrographic change. The existence of surface and deep-ocean events, with similar magnitudes, abruptness, and surface–deep phasing, advances our mechanistic understanding of, and elucidates antecedent conditions that can lead to, high-magnitude climate instability.publishedVersio

Diagnosis of ventilator-associated pneumonia in critically ill adult patients-a systematic review and meta-analysis.

The accuracy of the signs and tests that clinicians use to diagnose ventilator-associated pneumonia (VAP) and initiate antibiotic treatment has not been well characterized. We sought to characterize and compare the accuracy of physical examination, chest radiography, endotracheal aspirate (ETA), bronchoscopic sampling cultures (protected specimen brush [PSB] and bronchoalveolar lavage [BAL]), and CPIS > 6 to diagnose VAP. We searched six databases from inception through September 2019 and selected English-language studies investigating accuracy of any of the above tests for VAP diagnosis. Reference standard was histopathological analysis. Two reviewers independently extracted data and assessed study quality. We included 25 studies (1639 patients). The pooled sensitivity and specificity of physical examination findings for VAP were poor: fever (66.4% [95% confidence interval [CI]: 40.7–85.0], 53.9% [95% CI 34.5–72.2]) and purulent secretions (77.0% [95% CI 64.7–85.9], 39.0% [95% CI 25.8–54.0]). Any infiltrate on chest radiography had a sensitivity of 88.9% (95% CI 73.9–95.8) and specificity of 26.1% (95% CI 15.1–41.4). ETA had a sensitivity of 75.7% (95% CI 51.5–90.1) and specificity of 67.9% (95% CI 40.5–86.8). Among bronchoscopic sampling methods, PSB had a sensitivity of 61.4% [95% CI 43.7–76.5] and specificity of 76.5% [95% CI 64.2–85.6]; while BAL had a sensitivity of 71.1% [95% CI 49.9–85.9] and specificity of 79.6% [95% CI 66.2–85.9]. CPIS > 6 had a sensitivity of 73.8% (95% CI 50.6–88.5) and specificity of 66.4% (95% CI 43.9–83.3). Classic clinical indicators had poor accuracy for diagnosis of VAP. Reliance upon these indicators in isolation may result in misdiagnosis and potentially unnecessary antimicrobial use

Misfolded α-synuclein causes hyperactive respiration without functional deficit in live neuroblastoma cells

The misfolding and aggregation of the largely disordered protein, α-synuclein, is a central pathogenic event that occurs in the synucleinopathies, a group of neurodegenerative disorders that includes Parkinson's disease. While there is a clear link between protein misfolding and neuronal vulnerability, the precise pathogenic mechanisms employed by disease-associated α-synuclein are unresolved. Here, we studied the pathogenicity of misfolded α-synuclein produced using the protein misfolding cyclic amplification (PMCA) assay. To do this, previous publishedmethodswere adapted to allow PMCA-induced protein fibrillization to occur under non-toxic conditions. Insight into potential intracellular targets of misfolded α-synuclein was obtained using an unbiased lipid screen of 15 biologically relevant lipids that identified cardiolipin (CA) as a potential binding partner for PMCA-generated misfolded α-synuclein. To investigate whether such an interaction can impact the properties of α-synuclein misfolding, protein fibrillization was carried out in the presence of the lipid. We show that CA both accelerates the rate ofα-synuclein fibrillization and produces species that harbourenhanced resistance to proteolysis. Because CA is virtually exclusively expressed in the inner mitochondrial membrane, we then assessed the ability of these misfolded species to alter mitochondrial respiration in live nontransgenic SH-SY5Y neuroblastoma cells. Extensive analysis revealed that misfoldedα-synucleincauses hyperactive mitochondrial respiration without causing any functional deficit.These datagive strong support for the mitochondrion as a target for misfolded α-synuclein and reveal persistent, hyperactive respiration as a potential upstream pathogenic event associated with the synucleinopathies

Finding Our Way in the Dark Proteome

The traditional structure-function paradigm has provided significant insights for well-folded proteins in which structures can be easily and rapidly revealed by X-ray crystallography beamlines. However approximately one third of the human proteome are comprised of intrinsically disordered proteins and regions (IDPs/IDRs) that do not adopt a dominant well-folded structure, and therefore remain “unseen” by traditional structural biology methods. This Perspective article considers the challenges raised by the “Dark Proteome”, in which determining the diverse conformational substates of IDPs in their free states, in encounter complexes of bound states, and in complexes retaining significant disorder, requires an unprecedented level of integration of multiple and complementary solution-based experiments that are analyzed with state-of-the art molecular simulation, Bayesian probabilistic models, and high throughput computation. We envision how these diverse experimental and computational tools can work together through formation of a “computational beamline” that will allow key functional features to be identified in IDP structural ensembles

The North American Cordilleran Anatectic Belt

The North American Cordilleran Anatectic Belt (CAB) is a ~3,000 km long region in the hinterland of the Cordillera that comprises numerous exposures of Late Cretaceous to Eocene intrusive rocks and anatectic rocks associated with crustal melting. As such, it is comparable in size and volume to major anatectic provinces including the Himalayan leucogranite belt. The CAB rocks are chiefly peraluminous, muscovite-bearing leucogranite produced primarily by anatexis of Proterozoic to Archean metasedimentary rocks. The CAB rocks lack extrusive equivalents and were typically emplaced as thick sheets, laccoliths, and dike/sill complexes. The extent, location, and age of the CAB suggests that it is integral to understanding the tectonic evolution of North America, however, the belt is rarely considered as a whole. This paper reviews localities associated with crustal melting in the CAB and compiles geochemical, geochronologic, and isotopic data to evaluate the melt conditions and processes that generated these rocks. The geochemistry and partial melting temperatures (ca. 675–775 °C) support water-absent muscovite dehydration melting and/or water-deficient melting as the primary melt reactions and are generally inconsistent with water-excess melting and high-temperature (biotite to amphibole) dehydration melting. The CAB rocks are oldest in the central U.S. Cordillera and become younger towards both the north and south. At any single location, partial melting appears to have been a protracted process (≥10 Myr) and evidence for re-melting and remobilization of magmas is common. End-member hypotheses for the origin of the CAB include decompression, crustal thickening, fluid-flux melting, and increased heat flux from the mantle. Different parts of the CAB support different hypotheses and no single model may be able to explain the entirety of the anatectic event. Regardless, the CAB is a distinct component of the Cordilleran orogenic system

Epidemiology, prehospital care and outcomes of patients arriving by ambulance with dyspnoea: An observational study

Background: This study aimed to determine epidemiology and outcome for patients presenting to emergency departments (ED) with shortness of breath who were transported by ambulance. Methods: This was a planned sub-study of a prospective, interrupted time series cohort study conducted at three time points in 2014 and which included consecutive adult patients presenting to the ED with dyspnoea as a main symptom. For this sub-study, additional inclusion criteria were presentation to an ED in Australia or New Zealand and transport by ambulance. The primary outcomes of interest are the epidemiology and outcome of these patients. Analysis was by descriptive statistics and comparisons of proportions. Results: One thousand seven patients met inclusion criteria. Median age was 74 years (IQR 61-68) and 46.1 % were male. There was a high rate of co-morbidity and chronic medication use. The most common ED diagnoses were lower respiratory tract infection (including pneumonia, 22.7 %), cardiac failure (20.5%) and exacerbation of chronic obstructive pulmonary disease (19.7 %). ED disposition was hospital admission (including ICU) for 76.4 %, ICU admission for 5.6 % and death in ED in 0.9 %. Overall in-hospital mortality among admitted patients was 6.5 %. Discussion: Patients transported by ambulance with shortness of breath make up a significant proportion of ambulance caseload and have high comorbidity and high hospital admission rate. In this study, >60 % were accounted for by patients with heart failure, lower respiratory tract infection or COPD, but there were a wide range of diagnoses. This has implications for service planning, models of care and paramedic training. Conclusion: This study shows that patients transported to hospital by ambulance with shortness of breath are a complex and seriously ill group with a broad range of diagnoses. Understanding the characteristics of these patients, the range of diagnoses and their outcome can help inform training and planning of services

Near-Infrared photometry in the J, H and Kn bands for Polar Ring Galaxies: II. Global Properties

We discuss the properties of the host galaxy and ring light distributions in the optical and near infrared bands for a sample of Polar Ring Galaxies (PRGs), presented in Paper I (Iodice et al. 2002, Paper I). The goal of this work is to test different formation scenarios for PRGs, proposed by different authors in the last decades, by comparing their predictions with these new data. The strategy is twofold: i) the integrated colors of the main components in these systems are compared with those of standard morphological galaxy types, to investigate whether differences in colors are caused by dust absorption or difference in stellar populations. We then derived an estimate of the stellar population ages in PRGs, which can be used to set constrains on the dynamical modeling and the time evolution of these systems; ii) we analyse the structural parameters of the host galaxy in order to understand whether this component is a standard early-type system as its morphology suggests, and the light distribution in the polar ring to measure its radial extension. These observational results indicate that the global properties of PRGs are better explained by dissipative merging of disks with un-equal masses as proposed by Bekki (1998), rather than the accretion-or stripping-of gas by a pre-existing early-type galaxy.Comment: 11 pages, 7 postscript figures, accepted for publication in A&

Reciprocity and the Hyperlocal Journalist

Increased interest in hyperlocal news has led to growing evidence of its economic value, its ability to play traditional democratic roles associated with news, and its merits and deficiencies in comparison with the outputs a declining established commercial news industry. Given many hyperlocal producers cite the desire to play a role in producing better communities, this paper breaks new ground in examining the social and cultural dimensions of hyperlocal journalism’s news-making, community-building, and place-making roles. We examine this emergent cultural form’s affinity with telling stories, and enabling conversations, about civic and political concerns, but also its affinity with, and celebration of, the banal everyday. Employing the novel theoretical concept of reciprocal journalism we provide new evidence about the mutually reinforcing online, and offline, practices that underpin relationships between producers and the communities they inhabit and represent. Drawing on evidence from the most extensive multi-method study of UK hyperlocal news to date, it demonstrates the different kinds of direct and indirect reciprocal exchange practices common in community news, and shows how such work, often composed of journalistic and community-activist practices, can enable and foster relationships of sustained reciprocity which improve and strengthen both hyperlocal news and the communities it serves