1,509 research outputs found
Emergence of heat extremes attributable to anthropogenic influences
Climate scientists have demonstrated that a substantial fraction of the probability of numerous recent extreme events may be attributed to human-induced climate change. However, it is likely that for temperature extremes occurring over previous decades a fraction of their probability was attributable to anthropogenic influences. We identify the first record-breaking warm summers and years for which a discernible contribution can be attributed to human influence. We find a significant human contribution to the probability of record-breaking global temperature events as early as the 1930s. Since then, all the last 16 record-breaking hot years globally had an anthropogenic contribution to their probability of occurrence. Aerosol-induced cooling delays the timing of a significant human contribution to record-breaking events in some regions. Without human-induced climate change recent hot summers and years would be very unlikely to have occurred.111411Ysciescopu
Changes in temperature and precipitation extremes in the IPCC ensemble of global coupled model simulations
Temperature and precipitation extremes and their potential future changes are evaluated in an ensemble of global coupled climate models participating in the Intergovernmental Panel on Climate Change (IPCC) diagnostic exercise for the Fourth Assessment Report (AR4). Climate extremes are expressed in terms of 20-yr return values of annual extremes of near-surface temperature and 24-h precipitation amounts. The simulated changes in extremes are documented for years 2046–65 and 2081–2100 relative to 1981–2000 in experiments with the Special Report on Emissions Scenarios (SRES) B1, A1B, and A2 emission scenarios. Overall, the climate models simulate present-day warm extremes reasonably well on the global scale, as compared to estimates from reanalyses. The model discrepancies in simulating cold extremes are generally larger than those for warm extremes, especially in sea ice–covered areas. Simulated present-day precipita-tion extremes are plausible in the extratropics, but uncertainties in extreme precipitation in the Tropics are very large, both in the models and the available observationally based datasets. Changes in warm extremes generally follow changes in the mean summertime temperature. Cold ex-tremes warm faster than warm extremes by about 30%–40%, globally averaged. The excessive warming of cold extremes is generally confined to regions where snow and sea ice retreat with global warming. With th
String theoretic QCD axions in the light of PLANCK and BICEP2
The QCD axion solving the strong CP problem may originate from antisymmetric
tensor gauge fields in compactified string theory, with a decay constant around
the GUT scale. Such possibility appears to be ruled out now by the detection of
tensor modes by BICEP2 and the PLANCK constraints on isocurvature density
perturbations. A more interesting and still viable possibility is that the
string theoretic QCD axion is charged under an anomalous U(1)_A gauge symmetry.
In such case, the axion decay constant can be much lower than the GUT scale if
moduli are stabilized near the point of vanishing Fayet-Illiopoulos term, and
U(1)_A-charged matter fields get a vacuum value far below the GUT scale due to
a tachyonic SUSY breaking scalar mass. We examine the symmetry breaking pattern
of such models during the inflationary epoch with the Hubble expansion rate
10^{14} GeV, and identify the range of the QCD axion decay constant, as well as
the corresponding relic axion abundance, consistent with known cosmological
constraints. In addition to the case that the PQ symmetry is restored during
inflation, there are other viable scenarios, including that the PQ symmetry is
broken during inflation at high scales around 10^{16}-10^{17} GeV due to a
large Hubble-induced tachyonic scalar mass from the U(1)_A D-term, while the
present axion scale is in the range 10^{9}-5\times 10^{13} GeV, where the
present value larger than 10^{12} GeV requires a fine-tuning of the axion
misalignment angle. We also discuss the implications of our results for the
size of SUSY breaking soft masses.Comment: 29 pages, 1 figure; v3: analysis updated including the full
anharmonic effects, references added, version accepted for publication in
JHE
The validity of using ICD-9 codes and pharmacy records to identify patients with chronic obstructive pulmonary disease
Background: Administrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear. We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD.
Methods: Sequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007). COPD was defined as: 1) FEV1/FVC <0.70, and 2) FEV1/FVC < lower limits of normal. Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry. Model performance was assessed using standard criteria.
Results: 4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70. The presence of ≥1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76). Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78). The best performing model included: ≥6 albuterol MDI, ≥3 ipratropium MDI, ≥1 outpatient ICD-9 code, ≥1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80).
Conclusion: Commonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD. Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD.Department of Veterans Affairs, Health Services Research and Development (DHA), American Lung Association (CI- 51755-N) awarded to DHA, the American Thoracic Society Fellow Career Development AwardPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84155/1/Cooke - ICD9 validity in COPD.pd
Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.
A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease
Inflation and dark matter in two Higgs doublet models
We consider the Higgs inflation in the extension of the Standard Model with
two Higgs doublets coupled to gravity non-minimally. In the presence of an
approximate global U(1) symmetry in the Higgs sector, both radial and angular
modes of neutral Higgs bosons drive inflation where large non-Gaussianity is
possible from appropriate initial conditions on the angular mode. We also
discuss the case with single-field inflation for which the U(1) symmetry is
broken to a Z_2 subgroup. We show that inflationary constraints, perturbativity
and stability conditions restrict the parameter space of the Higgs quartic
couplings at low energy in both multi- and single-field cases. Focusing on the
inert doublet models where Z_2 symmetry remains unbroken at low energy, we show
that the extra neutral Higgs boson can be a dark matter candidate consistent
with the inflationary constraints. The doublet dark matter is always heavy in
multi-field inflation while it can be light due to the suppression of the
co-annihilation in single-field inflation. The implication of the extra quartic
couplings on the vacuum stability bound is also discussed in the light of the
recent LHC limits on the Higgs mass.Comment: (v1) 28 pages, 8 figures; (v2) 29 pages, a new subsection 3.3 added,
references added and typos corrected, to appear in Journal of High Energy
Physic
Branch Mode Selection during Early Lung Development
Many organs of higher organisms, such as the vascular system, lung, kidney,
pancreas, liver and glands, are heavily branched structures. The branching
process during lung development has been studied in great detail and is
remarkably stereotyped. The branched tree is generated by the sequential,
non-random use of three geometrically simple modes of branching (domain
branching, planar and orthogonal bifurcation). While many regulatory components
and local interactions have been defined an integrated understanding of the
regulatory network that controls the branching process is lacking. We have
developed a deterministic, spatio-temporal differential-equation based model of
the core signaling network that governs lung branching morphogenesis. The model
focuses on the two key signaling factors that have been identified in
experiments, fibroblast growth factor (FGF10) and sonic hedgehog (SHH) as well
as the SHH receptor patched (Ptc). We show that the reported biochemical
interactions give rise to a Schnakenberg-type Turing patterning mechanisms that
allows us to reproduce experimental observations in wildtype and mutant mice.
The kinetic parameters as well as the domain shape are based on experimental
data where available. The developed model is robust to small absolute and large
relative changes in the parameter values. At the same time there is a strong
regulatory potential in that the switching between branching modes can be
achieved by targeted changes in the parameter values. We note that the sequence
of different branching events may also be the result of different growth
speeds: fast growth triggers lateral branching while slow growth favours
bifurcations in our model. We conclude that the FGF10-SHH-Ptc1 module is
sufficient to generate pattern that correspond to the observed branching modesComment: Initially published at PLoS Comput Bio
Magnetism, FeS colloids, and Origins of Life
A number of features of living systems: reversible interactions and weak
bonds underlying motor-dynamics; gel-sol transitions; cellular connected
fractal organization; asymmetry in interactions and organization; quantum
coherent phenomena; to name some, can have a natural accounting via
interactions, which we therefore seek to incorporate by expanding the horizons
of `chemistry-only' approaches to the origins of life. It is suggested that the
magnetic 'face' of the minerals from the inorganic world, recognized to have
played a pivotal role in initiating Life, may throw light on some of these
issues. A magnetic environment in the form of rocks in the Hadean Ocean could
have enabled the accretion and therefore an ordered confinement of
super-paramagnetic colloids within a structured phase. A moderate H-field can
help magnetic nano-particles to not only overcome thermal fluctuations but also
harness them. Such controlled dynamics brings in the possibility of accessing
quantum effects, which together with frustrations in magnetic ordering and
hysteresis (a natural mechanism for a primitive memory) could throw light on
the birth of biological information which, as Abel argues, requires a
combination of order and complexity. This scenario gains strength from
observations of scale-free framboidal forms of the greigite mineral, with a
magnetic basis of assembly. And greigite's metabolic potential plays a key role
in the mound scenario of Russell and coworkers-an expansion of which is
suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed
Krishnaswami Alladi, Springer 201
Daratumumab plus bortezomib, cyclophosphamide, and dexamethasone in Asian patients with newly diagnosed AL amyloidosis: subgroup analysis of ANDROMEDA
Subcutaneous daratumumab plus bortezomib/cyclophosphamide/dexamethasone (VCd; D-VCd) improved outcomes versus VCd for patients with newly diagnosed immunoglobulin light-chain (AL) amyloidosis in the phase 3 ANDROMEDA study. We report a subgroup analysis of Asian patients (Japan; Korea; China) from ANDROMEDA. Among 388 randomized patients, 60 were Asian (D-VCd, n = 29; VCd, n = 31). At a median follow-up of 11.4 months, the overall hematologic complete response rate was higher for D-VCd versus VCd (58.6% vs. 9.7%; odds ratio, 13.2; 95% confidence interval [CI], 3.3–53.7; P < 0.0001). Six-month cardiac and renal response rates were higher with D-VCd versus VCd (cardiac, 46.7% vs. 4.8%; P = 0.0036; renal, 57.1% vs. 37.5%; P = 0.4684). Major organ deterioration progression-free survival (MOD-PFS) and major organ deterioration event-free survival (MOD-EFS) were improved with D-VCd versus VCd (MOD-PFS: hazard ratio [HR], 0.21; 95% CI, 0.06–0.75; P = 0.0079; MOD-EFS: HR, 0.16; 95% CI, 0.05–0.54; P = 0.0007). Twelve deaths occurred (D-VCd, n = 3; VCd, n = 9). Twenty-two patients had baseline serologies indicating prior hepatitis B virus (HBV) exposure; no patient experienced HBV reactivation. Although grade 3/4 cytopenia rates were higher than in the global safety population, the safety profile of D-VCd in Asian patients was generally consistent with the global study population, regardless of body weight. These results support D-VCd use in Asian patients with newly diagnosed AL amyloidosis. ClinicalTrials.gov Identifier: NCT03201965
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