263 research outputs found
Factor relationships of metabolic syndrome and echocardiographic phenotypes in the HyperGEN Study
Extracellular ATP released by osteoblasts is a key local inhibitor of bone mineralisation
Previous studies have shown that exogenous ATP (>1µM) prevents bone formation in vitro by blocking mineralisation of the collagenous matrix. This effect is thought to be mediated via both P2 receptor-dependent pathways and a receptor-independent mechanism (hydrolysis of ATP to produce the mineralisation inhibitor pyrophosphate, PPi). Osteoblasts are also known to release ATP constitutively. To determine whether this endogenous ATP might exert significant biological effects, bone-forming primary rat osteoblasts were cultured with 0.5-2.5U/ml apyrase (which sequentially hydrolyses ATP to ADP to AMP + 2Pi). Addition of 0.5U/ml apyrase to osteoblast culture medium degraded extracellular ATP to <1% of control levels within 2 minutes; continuous exposure to apyrase maintained this inhibition for up to 14 days. Apyrase treatment for the first 72 hours of culture caused small decreases (≤25%) in osteoblast number, suggesting a role for endogenous ATP in stimulating cell proliferation. Continuous apyrase treatment for 14 days (≥0.5U/ml) increased mineralisation of bone nodules by up to 3-fold. Increases in bone mineralisation were also seen when osteoblasts were cultured with the ATP release inhibitors, NEM and brefeldin A, as well as with P2X1 and P2X7 receptor antagonists. Apyrase decreased alkaline phosphatase (TNAP) activity by up to 60%, whilst increasing the activity of the PPi-generating ecto-nucleotide pyrophosphatase/phosphodiesterases (NPPs) up to 2.7-fold. Both collagen production and adipocyte formation were unaffected. These data suggest that nucleotides released by osteoblasts in bone could act locally, via multiple mechanisms, to limit mineralisation
Hypernovae and Other Black-Hole-Forming Supernovae
During the last few years, a number of exceptional core-collapse supernovae
(SNe) have been discovered. Their kinetic energy of the explosions are larger
by more than an order of magnitude than the typical values for this type of
SNe, so that these SNe have been called `Hypernovae'. We first describe how the
basic properties of hypernovae can be derived from observations and modeling.
These hypernovae seem to come from rather massive stars, thus forming black
holes. On the other hand, there are some examples of massive SNe with only a
small kinetic energy. We suggest that stars with non-rotating black holes are
likely to collapse "quietly" ejecting a small amount of heavy elements (Faint
supernovae). In contrast, stars with rotating black holes are likely to give
rise to very energetic supernovae (Hypernovae). We present distinct
nucleosynthesis features of these two types of "black-hole-forming" supernovae.
Hypernova nucleosynthesis is characterized by larger abundance ratios
(Zn,Co,V,Ti)/Fe and smaller (Mn,Cr)/Fe. Nucleosynthesis in Faint supernovae is
characterized by a large amount of fall-back. We show that the abundance
pattern of the most Fe deficient star, HE0107-5240, and other extremely
metal-poor carbon-rich stars are in good accord with those of
black-hole-forming supernovae, but not pair-instability supernovae. This
suggests that black-hole-forming supernovae made important contributions to the
early Galactic (and cosmic) chemical evolution.Comment: 49 pages, to be published in "Stellar Collapse" (Astrophysics and
Space Science; Kluwer) ed. C. L. Fryer (2003
Theory of Star Formation
We review current understanding of star formation, outlining an overall
theoretical framework and the observations that motivate it. A conception of
star formation has emerged in which turbulence plays a dual role, both creating
overdensities to initiate gravitational contraction or collapse, and countering
the effects of gravity in these overdense regions. The key dynamical processes
involved in star formation -- turbulence, magnetic fields, and self-gravity --
are highly nonlinear and multidimensional. Physical arguments are used to
identify and explain the features and scalings involved in star formation, and
results from numerical simulations are used to quantify these effects. We
divide star formation into large-scale and small-scale regimes and review each
in turn. Large scales range from galaxies to giant molecular clouds (GMCs) and
their substructures. Important problems include how GMCs form and evolve, what
determines the star formation rate (SFR), and what determines the initial mass
function (IMF). Small scales range from dense cores to the protostellar systems
they beget. We discuss formation of both low- and high-mass stars, including
ongoing accretion. The development of winds and outflows is increasingly well
understood, as are the mechanisms governing angular momentum transport in
disks. Although outstanding questions remain, the framework is now in place to
build a comprehensive theory of star formation that will be tested by the next
generation of telescopes.Comment: 120 pages, to appear in ARAA. No changes from v1 text; permission
statement adde
Type Ia Supernovae as Stellar Endpoints and Cosmological Tools
Empirically, Type Ia supernovae are the most useful, precise, and mature
tools for determining astronomical distances. Acting as calibrated candles they
revealed the presence of dark energy and are being used to measure its
properties. However, the nature of the SN Ia explosion, and the progenitors
involved, have remained elusive, even after seven decades of research. But now
new large surveys are bringing about a paradigm shift --- we can finally
compare samples of hundreds of supernovae to isolate critical variables. As a
result of this, and advances in modeling, breakthroughs in understanding all
aspects of SNe Ia are finally starting to happen.Comment: Invited review for Nature Communications. Final published version.
Shortened, update
Interacting Supernovae: Types IIn and Ibn
Supernovae (SNe) that show evidence of strong shock interaction between their
ejecta and pre-existing, slower circumstellar material (CSM) constitute an
interesting, diverse, and still poorly understood category of explosive
transients. The chief reason that they are extremely interesting is because
they tell us that in a subset of stellar deaths, the progenitor star may become
wildly unstable in the years, decades, or centuries before explosion. This is
something that has not been included in standard stellar evolution models, but
may significantly change the end product and yield of that evolution, and
complicates our attempts to map SNe to their progenitors. Another reason they
are interesting is because CSM interaction is an efficient engine for making
bright transients, allowing super-luminous transients to arise from normal SN
explosion energies, and allowing transients of normal SN luminosities to arise
from sub-energetic explosions or low radioactivity yield. CSM interaction
shrouds the fast ejecta in bright shock emission, obscuring our normal view of
the underlying explosion, and the radiation hydrodynamics of the interaction is
challenging to model. The CSM interaction may also be highly non-spherical,
perhaps linked to binary interaction in the progenitor system. In some cases,
these complications make it difficult to definitively tell the difference
between a core-collapse or thermonuclear explosion, or to discern between a
non-terminal eruption, failed SN, or weak SN. Efforts to uncover the physical
parameters of individual events and connections to possible progenitor stars
make this a rapidly evolving topic that continues to challenge paradigms of
stellar evolution.Comment: Final draft of a chapter in the "SN Handbook". Accepted. 25 pages, 3
fig
Cutpoints for mild, moderate and severe pain in patients with osteoarthritis of the hip or knee ready for joint replacement surgery
<p>Abstract</p> <p>Background</p> <p>Cutpoints (CPs) for mild, moderate and severe pain are established and used primarily in cancer pain. In this study, we wanted to determine the optimal CPs for mild, moderate, and severe pain in joint replacement surgery candidates with osteoarthritis (OA) of the hip or knee, and to validate the different CPs.</p> <p>Methods</p> <p>Patients (n = 353) completed the Brief Pain Inventory (BPI), the WOMAC Arthritis Index, and the SF-36 health status measure. Optimal CPs for categorizing average pain with three severity levels were derived using multivariate analysis of variance, using different CP sets for average pain as the independent variable and seven interference items from the BPI as the dependent variable. To validate the CPs, we assessed if patients in the three pain severity groups differed in pain as assessed with WOMAC and SF-36, and if BPI average pain with the optimal CPs resulted in higher correlation with pain dimensions of the WOMAC and SF-36 than other CPs.</p> <p>Results</p> <p>The optimal CPs on the 0–10 point BPI scale were CP (4,6) among hip patients and CP (4,7) among knee patients. The resulting pain severity groups differed in pain, as assessed with other scales than those used to derive the CPs. The optimal CPs had the highest association of average pain with WOMAC pain scores.</p> <p>Conclusion</p> <p>CPs for pain severity differed somewhat for patients with OA of the hip and knee. The association of BPI average pain scores categorized according to the optimal CPs with WOMAC pain scores supports the validity of the derived optimal CPs.</p
Measuring quality of life in rheumatic conditions
Musculoskeletal disorders often have associated pain, functional impairment and work disability, and, not surprisingly, are the most common reasons for utilizing healthcare resources. Rheumatoid arthritis (RA) and fibromyalgia (FM) are causes of musculoskeletal pain and disability. Research indicates that there is a widespread impact of RA and FM on physical, psychological and social factors in affected individuals, and thus, outcome measures that encompass multiple aspects of quality of life are needed. Generic measures of quality of life identify associations between physical conditions and mental health and highlight the need to address psychological functioning to ultimately improve the individuals’ quality of life
QTLs of factors of the metabolic syndrome and echocardiographic phenotypes: the hypertension genetic epidemiology network study
<p>Abstract</p> <p>Background</p> <p>In a previous study of the Hypertension Genetic Epidemiology Network (HyperGEN) we have shown that metabolic syndrome (MetS) risk factors were moderately and significantly associated with echocardiographic (ECHO) left ventricular (LV) phenotypes.</p> <p>Methods</p> <p>The study included 1,393 African Americans and 1,133 whites, stratified by type 2 diabetes mellitus (DM) status. Heritabilities of seven factor scores based on the analysis of 15 traits were sufficiently high to pursue QTL discovery in this follow-up study.</p> <p>Results</p> <p>Three of the QTLs discovered relate to combined MetS-ECHO factors of "blood pressure (BP)-LV wall thickness" on chromosome 3 at 225 cM with a 2.8 LOD score, on chromosome 20 at 2.1 cM with a 2.6 LOD score; and for "LV wall thickness" factor on chromosome 16 at 113.5 with a 2.6 LOD score in whites. The remaining QTLs include one for a "body mass index-insulin (BMI-INS)" factor with a LOD score of 3.9 on chromosome 2 located at 64.8 cM; one for the same factor on chromosome 12 at 91.4 cM with a 3.3 LOD score; one for a "BP" factor on chromosome 19 located at 67.8 cM with a 3.0 LOD score. A suggestive linkage was also found for "Lipids-INS" with a 2.7 LOD score located on chromosome 11 at 113.1 cM in African Americans. Of the above QTLs, the one on chromosome 12 for "BMI-INS" is replicated in both ethnicities, (with highest LOD scores in African Americans). In addition, the QTL for "LV wall thickness" on chromosome 16q24.2-q24.3 reached its local maximum LOD score at marker D16S402, which is positioned within the 5th intron of the <it>cadherin 13 </it>gene, implicated in heart and vascular remodeling.</p> <p>Conclusion</p> <p>Our previous study and this follow-up suggest gene loci for some crucial MetS and cardiac geometry risk factors that contribute to the risk of developing heart disease.</p
QTLs of factors of the metabolic syndrome and echocardiographic phenotypes: the Hypertension Genetic Epidemiology Network Study
Abstract Background In a previous study of the Hypertension Genetic Epidemiology Network (HyperGEN) we have shown that metabolic syndrome (MetS) risk factors were moderately and significantly associated with echocardiographic (ECHO) left ventricular (LV) phenotypes. Methods The study included 1,393 African Americans and 1,133 whites, stratified by type 2 diabetes mellitus (DM) status. Heritabilities of seven factor scores based on the analysis of 15 traits were sufficiently high to pursue QTL discovery in this follow-up study. Results Three of the QTLs discovered relate to combined MetS-ECHO factors of "blood pressure (BP)-LV wall thickness" on chromosome 3 at 225 cM with a 2.8 LOD score, on chromosome 20 at 2.1 cM with a 2.6 LOD score; and for "LV wall thickness" factor on chromosome 16 at 113.5 with a 2.6 LOD score in whites. The remaining QTLs include one for a "body mass index-insulin (BMI-INS)" factor with a LOD score of 3.9 on chromosome 2 located at 64.8 cM; one for the same factor on chromosome 12 at 91.4 cM with a 3.3 LOD score; one for a "BP" factor on chromosome 19 located at 67.8 cM with a 3.0 LOD score. A suggestive linkage was also found for "Lipids-INS" with a 2.7 LOD score located on chromosome 11 at 113.1 cM in African Americans. Of the above QTLs, the one on chromosome 12 for "BMI-INS" is replicated in both ethnicities, (with highest LOD scores in African Americans). In addition, the QTL for "LV wall thickness" on chromosome 16q24.2-q24.3 reached its local maximum LOD score at marker D16S402, which is positioned within the 5th intron of the cadherin 13 gene, implicated in heart and vascular remodeling. Conclusion Our previous study and this follow-up suggest gene loci for some crucial MetS and cardiac geometry risk factors that contribute to the risk of developing heart disease
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