M giants are among the longest period pulsating stars which is why their studies were traditionally restricted to analyses of low-precision visual observations, and, more recently, accurate ...ground-based data. Here we present an overview of M giant variability on a wide range of time-scales (hours to years), based on the analysis of 13 quarters of Kepler long-cadence observations (one point per every 29.4 min), with a total time-span of over 1000 d. About two-thirds of the sample stars have been selected from the All Sky Automated Survey (ASAS)-North survey of the Kepler field, with the rest supplemented from a randomly chosen M giant control sample. We first describe the correction of the light curves from different quarters, which was found to be essential. We use Fourier analysis to calculate multiple frequencies for all stars in the sample. Over 50 stars show a relatively strong signal with a period equal to the Kepler-year and a characteristic phase dependence across the whole field of view. We interpret this as a so far unidentified systematic effect in the Kepler data. We discuss the presence of regular patterns in the distribution of multiple periodicities and amplitudes. In the period-amplitude plane we find that it is possible to distinguish between solar-like oscillations and larger amplitude pulsations which are characteristic for Mira/semiregular stars. This may indicate the region of the transition between two types of oscillations as we move upward along the giant branch.
Stem/progenitor cell niches in tissues regulate stem/progenitor cell differentiation and proliferation through local signalling.
To examine the composition and formation of stem progenitor cell ...niches.
The composition of the hepatic progenitor cell niche in independent models of liver injury and hepatic progenitor cell activation in rodents and humans was studied. To identify the origin of the progenitor and niche cells, sex-mismatched bone marrow transplants in mice, who had received the choline-ethionine-deficient-diet to induce liver injury and progenitor cell activation, were used. The matrix surrounding the progenitor cells was described by immunohistochemical staining and its functional role controlling progenitor cell behaviour was studied in cell culture experiments using different matrix layers.
The progenitor cell response in liver injury is intimately surrounded by myofibroblasts and macrophages, and to a lesser extent by endothelial cells. Hepatic progenitor cells are not of bone marrow origin; however, bone marrow-derived cells associate intimately with these cells and are macrophages. Laminin always surrounds the progenitor cells. In vitro studies showed that laminin aids maintenance of progenitor and biliary cell phenotype and promotes their gene expression (Dlk1, Aquaporin 1, gammaGT) while inhibiting hepatocyte differentiation and gene expression (CEPB/alpha).
During liver damage in rodents and humans a stereotypical cellular and laminin niche forms around hepatic progenitor cells. Laminin helps maintenance of undifferentiated progenitor cells. The niche links the intrahepatic progenitor cells with bone marrow-derived cells and links tissue damage with progenitor cell-mediated tissue repair.
As part of a broader effort to calculate effective dose rate coefficients for external exposure to photons and electrons emitted by radionuclides distributed in air, soil or water, age-specific ...stylized phantoms have been employed to determine dose coefficients relating dose rate to organs and tissues in the body. In this article, dose rate coefficients computed using the International Commission on Radiological Protection reference adult male voxel phantom are compared with values computed using the Oak Ridge National Laboratory adult male stylized phantom in an air submersion exposure geometry. Monte Carlo calculations for both phantoms were performed for monoenergetic source photons in the range of 30 keV to 5 MeV. These calculations largely result in differences under 10 % for photon energies above 50 keV, and it can be expected that both models show comparable results for the environmental sources of radionuclides.
Only a few European countries have carried out large, community-based, national surveys about psychiatric morbidity. Here is presented the first national French survey, aiming to estimate the ...prevalence of anxiety disorders and associated comorbidities according to sociodemographic characteristics.
The Mental Health in General Population (MHGP) database is derived from a representative national survey of the French adult population (n=36,105), conducted between 1999 and 2003. Data collection was done using an anonymous face-to-face interview. The presence of anxiety disorders (generalized anxiety disorder, panic disorder, agoraphobia, social phobia and post-traumatic stress disorder) was assessed using the Mini International Neuropsychiatric Interview.
The overall prevalence of anxiety disorders was estimated to be 21.6%, generalized anxiety disorder being the most prevalent one (12.8%). Women, young people, and people earning low income were identified as the more at risk. Major depressive episode, alcohol abuse and drug addiction frequently co-occur with anxiety disorders (28.3, 4.4 and 2.8% respectively).
The MHGP study showed that anxiety disorders are highly prevalent in France with a high frequency of comorbidities. Our results highlight the need for considering anxiety disorders as a public health priority in France as well as in other European countries.
This study was performed to investigate the effects of holmium:yttrium-aluminum-garnet (Ho:YAG) laser energy on articular cartilage and subchondral bone adjacent to traumatically created cartilage ...lesions in a continuous weight-bearing model. The 2.1-microns wavelength was delivered efficiently and precisely in hand-controlled contact and near-contact hard tissue arthroscopic surgery in a saline medium. Bilateral arthroscopy was performed on normal antebrachiocarpal and intercarpal joints of four adult horses. One hundred twenty traumatic lesions were created on three weight-bearing articular surfaces with a knife, curet, or motorized burr. Depths of the lesions were partial and full thickness. Configurations of the lesions were lacerations, scrapes, and craters. Left limbs were used as controls. Right limb lesions were treated with various intensities of laser energy: 0.1. 0.16, and 0.2 J. Animals were killed at intervals of 1, 3, and 8 weeks. Gross microscopic anatomy was documented, and tissue sections were subjected to blind review by a pathologist. Mankin grading for cellularity and proteoglycan content was used to qualitatively evaluate cartilage response. Cartilage adjacent to all lesions exposed to laser energy had better cellularity and proteoglycan content (p < 0.05) than did corresponding controls by Mankin grading. Mankin grades for levels of 0.16 and 0.2 J were lower (p < 0.05) than were those of controls or lesions exposed to 0.1 J. There was loss of cellularity and necrosis in subchondral bone at higher energy levels (0.16 and 0.2 J). This study examined the effects of Ho:YAG laser on articular cartilage and subchondral bone in terms of depth of damage and healing response over time in a weight-bearing model. Additional research to define dose-response curves for Ho:YAG laser treatment of cartilage and subchondral bone are indicated.
The binding of CD4 and chemokine receptors to the gp120 attachment glycoprotein of human immunodeficiency virus triggers refolding of the associated gp41 fusion glycoprotein into a trimer of hairpins ...with a 6-helix bundle (6HB) core. These events lead to membrane fusion and viral entry. Here, we examined the functions of the fusion peptide-proximal polar segment and membrane-proximal Trp-rich region (MPR), which are exterior to the 6HB. Alanine substitution of Trp666, Trp672, Phe673, and Ile675 in the MPR reduced entry by up to 120-fold without affecting gp120-gp41 association or cell-cell fusion. The L537A polar segment mutation led to the loss of gp120 from the gp120-gp41 complex, reduced entry by ∼10-fold, but did not affect cell-cell fusion. Simultaneous Ala substitution of Leu537 with Trp666, Trp672, Phe673, or Ile675 abolished entry with 50–80% reductions in cell-cell fusion. gp120-gp41 complexes of fusion-defective double mutants were resistant to soluble CD4-induced shedding of gp120, suggesting that their ability to undergo receptor-induced conformational changes was compromised. Consistent with this idea, a representative mutation, L537A/W666A, led to an ∼80% reduction in lipophilic fluorescent dye transfer between gp120-gp41-expressing cells and receptor-expressing targets, indicating a block prior to the lipid-mixing phase. The L537A/W666A double mutation increased the chymotrypsin sensitivity of the polar segment in a trimer of hairpins model, comprising the 6HB core, the polar segment, and MPR linked N-terminally to maltose-binding protein. The data indicate that the polar segment and MPR of gp41 act synergistically in forming a fusion-competent gp120-gp41 complex and in stabilizing the membrane-interactive end of the trimer of hairpins.
Abstract
Background
Seasonal influenza immunisation reduces cardiovascular events by 30% in those with atherosclerotic cardiovascular disease (ASCVD) and up to 50% in those with recent acute coronary ...syndrome. However, uptake in high-risk patients remains poor. Clinician recommendation has been shown to increase adoption of influenza immunisation in the general population; thus, cardiologists are well-placed to promote uptake in patients with cardiovascular disease.
Purpose
To describe the attitudes and behaviours of Australian cardiologists regarding seasonal influenza immunisation.
Methods
We used an exploratory sequential mixed methods design. Semi-structured interviews of 10 cardiologists were performed to identify themes for quantitative evaluation in an online survey. Multiple choice and Likert scale questions explored (a) attitudes and behaviours regarding influenza immunisation, (b) engagement with colleagues and professional bodies and (c) preventative care in cardiology. The survey was administered to 63 cardiologists between November 2020 and January 2021 and respondents received an honorarium for their time.
Results
The majority of respondents were general cardiologists (50/63) – compared with subspecialist cardiologists, and had spent an average of 21 years in practice. Less than half of the cardiologists surveyed asked patients about their vaccination status always or most of the time (46%, 29/63). Only one quarter (25.4%, 16/63) of cardiologists recommended influenza immunisation to all of their patients while higher proportions recommended it among patients with ASCVD (49.2%, 31/63), heart failure (69.8%, 44/63) and those over the age of 65 years (68.3%, 44/63). Just over half of the cardiologists (57.1%, 36/63) agreed that influenza immunisation was important/very important for prevention of cardiac events, however this was of lower priority compared with other components of preventive care including smoking cessation (100% agreed important, 63/63), anti-hypertensives (96.8%, 61/63), statins (94.3%, 60/63), exercise (80.9%, 51/63), anticoagulants (74.6%, 47/63), SGLT2 inhibitors (69.8%, 44/63) and diet (68.2%, 43/63). Three quarters of cardiologists (76.2%, 48/63) believed that the clinician predominantly responsible for ensuring that patients received the immunisation was the general practitioner, with only a minority (12.7%, 8/63) reporting that it was the role of the cardiologist.
Conclusions
Despite a relative risk reduction exceeding that of statins and antihypertensives for patients with CVD, influenza immunisation is not prioritized or recommended by many cardiologists. Efforts at increasing awareness and advocacy among cardiologists may assist in broadening uptake among high-risk patients with cardiovascular disease.
The Oak Ridge National Laboratory Center for Radiation Protection Knowledge has undertaken calculations related to various environmental exposure scenarios. A previous paper reported the results for ...submersion in radioactive air and immersion in water using age-specific mathematical phantoms. This paper presents age-specific effective dose rate coefficients derived using stylized mathematical phantoms for exposure to contaminated soils. Dose rate coefficients for photon, electron, and positrons of discrete energies were calculated and folded with emissions of 1252 radionuclides addressed in ICRP Publication 107 to determine equivalent and effective dose rate coefficients. The MCNP6 radiation transport code was used for organ dose rate calculations for photons and the contribution of electrons to skin dose rate was derived using point-kernels. Bremsstrahlung and annihilation photons of positron emission were evaluated as discrete photons. The coefficients calculated in this work compare favorably to those reported in the US Federal Guidance Report 12 as well as by other authors who employed voxel phantoms for similar exposure scenarios.
Clinical validity assessments of gene-disease associations underpin analysis and reporting in diagnostic genomics, and yet wide variability exists in practice, particularly in use of these ...assessments for virtual gene panel design and maintenance. Harmonization efforts are hampered by the lack of agreed terminology, agreed gene curation standards, and platforms that can be used to identify and resolve discrepancies at scale. We undertook a systematic comparison of the content of 80 virtual gene panels used in two healthcare systems by multiple diagnostic providers in the United Kingdom and Australia. The process was enabled by a shared curation platform, PanelApp, and resulted in the identification and review of 2,144 discordant gene ratings, demonstrating the utility of sharing structured gene-disease validity assessments and collaborative discordance resolution in establishing national and international consensus.
Clinical validity assessments of gene-disease associations underpin analysis and reporting in diagnostic genomics, and yet wide variability exists in practice, particularly in use of these assessments for virtual gene panel design and maintenance. Harmonization efforts are hampered by the lack of agreed terminology, agreed gene curation standards, and platforms that can be used to identify and resolve discrepancies at scale. We undertook a systematic comparison of the content of 80 virtual gene panels used in two healthcare systems by multiple diagnostic providers in the United Kingdom and Australia. The process was enabled by a shared curation platform, PanelApp, and resulted in the identification and review of 2,144 discordant gene ratings, demonstrating the utility of sharing structured gene-disease validity assessments and collaborative discordance resolution in establishing national and international consensus.
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