800 research outputs found
British Lung Foundation/United Kingdom primary immunodeficiency network consensus statement on the definition, diagnosis, and management of granulomatous-lymphocytic interstitial lung disease in common variable immunodeficiency disorders
A proportion of people living with common variable immunodeficiency disorders develop granulomatous-lymphocytic interstitial lung disease (GLILD). We aimed to develop a consensus statement on the definition, diagnosis, and management of GLILD. All UK specialist centers were contacted and relevant physicians were invited to take part in a 3-round online Delphi process. Responses were graded as Strongly Agree, Tend to Agree, Neither Agree nor Disagree, Tend to Disagree, and Strongly Disagree, scored +1, +0.5, 0, −0.5, and −1, respectively. Agreement was defined as greater than or equal to 80% consensus. Scores are reported as mean ± SD. There was 100% agreement (score, 0.92 ± 0.19) for the following definition: “GLILD is a distinct clinico-radio-pathological ILD occurring in patients with [common variable immunodeficiency disorders], associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded.” There was consensus that the workup of suspected GLILD requires chest computed tomography (CT) (0.98 ± 0.01), lung function tests (eg, gas transfer, 0.94 ± 0.17), bronchoscopy to exclude infection (0.63 ± 0.50), and lung biopsy (0.58 ± 0.40). There was no consensus on whether expectant management following optimization of immunoglobulin therapy was acceptable: 67% agreed, 25% disagreed, score 0.38 ± 0.59; 90% agreed that when treatment was required, first-line treatment should be with corticosteroids alone (score, 0.55 ± 0.51)
Regulation of the Cardiac Na+/K+ ATPase by Phospholemman
Hansraj Dhayan, Rajender Kumar, Andreas Kukol, ‘Regulation of the Cardiac Na+/K+ ATPase by Phospholemman’, in Sajal Chakraborti, Naranjan Dhalla, eds., Regulation of Membrane Na+-K+ ATPase, (Switzerland: Springer, 2016), ISBN 978-3-319-24748-9, eISBN 978-3-319-24750-2.Peer reviewe
Comments on Systematic Effects in the NIST Beam Neutron Lifetime Experiment
We discuss issues raised by Serebrov, et al. in a recent paper regarding
systematic effects in the beam neutron lifetime experiment performed at NIST.
We show that these effects were considered in the original analyses and that
our corrections and systematic uncertainties were appropriate. We point out
some misconceptions and erroneous assumptions in the analysis of Serebrov, et
al. None of the issues raised in Serebrov, et al lead us to alter the value of
the neutron lifetime reported previously.Comment: arXiv admin note: substantial text overlap with
arXiv:nucl-ex/0411041, arXiv:2004.0116
GLP−1 Promotes Cortical and Medullary Perfusion in the Human Kidney and Maintains Renal Oxygenation During NaCl Loading
BackgroundGLP‐1 (glucagon‐like peptide‐1) receptor agonists exert beneficial long‐term effects on cardiovascular and renal outcomes. In humans, the natriuretic effect of GLP‐1 depends on GLP‐1 receptor interaction, is accompanied by suppression of angiotensin II, and is independent of changes in renal plasma flow. In rodents, angiotensin II constricts vasa recta and lowers medullary perfusion. The current randomized, controlled, crossover study was designed to test the hypothesis that GLP‐1 increases renal medullary perfusion in healthy humans.Methods and ResultsHealthy male participants (n=10, aged 27±4 years) ingested a fixed sodium intake for 4 days and were examined twice during a 1‐hour infusion of either GLP‐1 (1.5 pmol/kg per minute) or placebo together with infusion of 0.9% NaCl (750 mL/h). Interleaved measurements of renal arterial blood flow, oxygenation (R2*), and perfusion were acquired in the renal cortex and medulla during infusions, using magnetic resonance imaging. GLP‐1 infusion increased medullary perfusion (32±7%, P<0.001) and cortical perfusion (13±4%, P<0.001) compared with placebo. Here, NaCl infusion decreased medullary perfusion (−5±2%, P=0.007), whereas cortical perfusion remained unchanged. R2* values increased by 3±2% (P=0.025) in the medulla and 4±1% (P=0.008) in the cortex during placebo, indicative of decreased oxygenation, but remained unchanged during GLP‐1. Blood flow in the renal artery was not altered significantly by either intervention.ConclusionsGLP‐1 increases predominantly medullary but also cortical perfusion in the healthy human kidney and maintains renal oxygenation during NaCl loading. In perspective, suppression of angiotensin II by GLP‐1 may account for the increase in regional perfusion
Flight 20 (STS-45) polysulfide gas path investigation
This report documents the results of the investigation into causes of gas paths on the 20A and 20B case-to-nozzle joints on STS-42. The investigation was conducted by the Investigation Board appointed by the senior vice president and general manager of Space Operations, Mr. R. E. Lindstrom, on 7 Feb. 1992. The probability of gas path occurrence in the nozzle-to-case-joint polysulfide had been identified during joint redesign. However, actual flight gas path incidence has been limited to RSRM-11 and the 20A and 20B segments. The blow-by condition on the 20A segment was a first time occurrence which was a special concern. The investigation covered all technical aspects associated with the gas path and blow-by conditions: materials and processing history, design requirements and as-built compliance to the design, thermal and structural analyses, computer modeling, and laboratory experimentation with the materials involved. The investigation was coordinated with Mr. Ken Jones at NASA Marshall in bi-weekly teleconferences. The Board also supported Dr. James C. Blair's independent NASA investigation team by providing copies of collected data, conducting requested analyses, and supporting several all-day teleconferences to provide understanding and resolve issues. The Dr. Blair support requirement was successfully concluded on 4 Mar. 1992
Development and Validation of the Behavioral Tendencies Questionnaire
At a fundamental level, taxonomy of behavior and behavioral tendencies can be described
in terms of approach, avoid, or equivocate (i.e., neither approach nor avoid). While there are
numerous theories of personality, temperament, and character, few seem to take advantage
of parsimonious taxonomy. The present study sought to implement this taxonomy by
creating a questionnaire based on a categorization of behavioral temperaments/tendencies
first identified in Buddhist accounts over fifteen hundred years ago. Items were developed
using historical and contemporary texts of the behavioral temperaments, described as
“Greedy/Faithful”, “Aversive/Discerning”, and “Deluded/Speculative”. To both maintain
this categorical typology and benefit from the advantageous properties of forced-choice
response format (e.g., reduction of response biases), binary pairwise preferences for items
were modeled using Latent Class Analysis (LCA). One sample (n1 = 394) was used to estimate
the item parameters, and the second sample (n2 = 504) was used to classify the participants
using the established parameters and cross-validate the classification against
multiple other measures. The cross-validated measure exhibited good nomothetic span
(construct-consistent relationships with related measures) that seemed to corroborate the
ideas present in the original Buddhist source documents. The final 13-block questionnaire
created from the best performing items (the Behavioral Tendencies Questionnaire or BTQ)
is a psychometrically valid questionnaire that is historically consistent, based in behavioral
tendencies, and promises practical and clinical utility particularly in settings that teach and
study meditation practices such as Mindfulness Based Stress Reduction (MBSR)
Substrate Cooperativity in Marine Luciferases
Marine luciferases are increasingly used as reporters to study gene regulation. These luciferases have utility in bioluminescent assay development, although little has been reported on their catalytic properties in response to substrate concentration. Here, we report that the two marine luciferases from the copepods, Gaussia princeps (GLuc) and Metridia longa (MLuc) were found, surprisingly, to produce light in a cooperative manner with respect to their luciferin substrate concentration; as the substrate concentration was decreased 10 fold the rate of light production decreased 1000 fold. This positive cooperative effect is likely a result of allostery between the two proposed catalytic domains found in Gaussia and Metridia. In contrast, the marine luciferases from Renilla reniformis (RLuc) and Cypridina noctiluca (CLuc) demonstrate a linear relationship between the concentration of their respective luciferin and the rate of light produced. The consequences of these enzyme responses are discussed
Vasomotion and Neurovascular Coupling in the Visual Thalamus In Vivo
Spontaneous contraction and relaxation of arteries (and in some instances venules) has been termed vasomotion and has been observed in an extensive variety of tissues and species. However, its functions and underlying mechanisms are still under discussion. We demonstrate that in vivo spectrophotometry, measured simultaneously with extracellular recordings at the same locations in the visual thalamus of the cat, reveals vasomotion, measured as an oscillation (0.14hz) in the recorded oxyhemoglobin (OxyHb) signal, which appears spontaneously in the microcirculation and can last for periods of hours. During some non-oscillatory periods, maintained sensory stimulation evokes vasomotion lasting ∼30s, resembling an adaptive vascular phenomenon. This oscillation in the oxyhaemoblobin signal is sensitive to pharmacological manipulation: it is inducible by chloralose anaesthesia and it can be temporarily blocked by systemic administration of adrenaline or acetylcholine (ACh). During these oscillatory periods, neurovascular coupling (i.e. the relationship between local neural activity and the rate of blood supply to that location) appears significantly altered. This raises important questions with regard to the interpretation of results from studies currently dependent upon a linear relationship between neural activity and blood flow, such as neuroimaging
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