502 research outputs found
[Epidemiology of oral cavity cancers in France].
INTRODUCTION: We had for objective to describe the updated epidemiology of oral cancers in France. MATERIAL AND METHODS: Estimates made from data collected from various French cancer institutions. The distribution by topography, histology, regions, mean age, and specific incidence rates were calculated from the collected data. The survival data was taken from the Francim network studies. RESULTS: Approximately 7000 oral cavity cancers were diagnosed in France in 2005. In 2007, 1746 people died of that cancer. Standardized (world population) incidence rates are respectively, in men and women, 12.3 and 3.0 cases per 100,000 person-years. These cancers have significantly decreased in men: the standardized incidence rate decreased by 43.2% between 1980 and 2005. Among women, the trend is reversed with an increased incidence of 51.7% over the same period. CONCLUSION: In France, the incidence of oral cavity cancers has been strongly decreasing in men and strongly increasing in women. This trend should be compared to the frequency of the main risk factors: alcohol and tobacco
Validation of the DECAF score to predict hospital mortality in acute exacerbations of COPD
Background
Hospitalisation due to acute
exacerbations of COPD (AECOPD) is common, and
subsequent mortality high. The DECAF score was derived
for accurate prediction of mortality and risk strati
fi
cation
to inform patient care. We aimed to validate the DECAF
score, internally and externally, and to compare its
performance to other predictive tools.
Methods
The study took place in the two hospitals
within the derivation study (internal validation) and in
four additional hospitals (external validation) between
January 2012 and May 2014. Consecutive admissions
were identi
fi
ed by screening admissions and searching
coding records. Admission clinical data, including DECAF
indices, and mortality were recorded. The prognostic
value of DECAF and other scores were assessed by the
area under the receiver operator characteristic (AUROC)
curve.
Results
In the internal and external validation cohorts,
880 and 845 patients were recruited. Mean age was
73.1 (SD 10.3) years, 54.3% were female, and mean
(SD) FEV
1
45.5 (18.3) per cent predicted. Overall
mortality was 7.7%. The DECAF AUROC curve for
inhospital mortality was 0.83 (95% CI 0.78 to 0.87) in
the internal cohort and 0.82 (95% CI 0.77 to 0.87) in
the external cohort, and was superior to other
prognostic scores for inhospital or 30-day mortality.
Conclusions
DECAF is a robust predictor of mortality,
using indices routinely available on admission. Its
generalisability is supported by consistent strong
performance; it can identify low-risk patients (DECAF
0
–
1) potentially suitable for Hospital at Home or early
supported discharge services, and high-risk patients
(DECAF 3
–
6) for escalation planning or appropriate early
palliation.
Trial registration number
UKCRN ID 14214
The JCMT Legacy Survey of the Gould Belt: a first look at Orion B with HARP
‘The definitive version is available at www3.interscience.wiley.com '. Copyright Royal Astronomical Society.The Gould Belt Legacy Survey will survey nearby star-forming regions (within 500 pc), using Heterodyne Array Receiver Programme (HARP), Submillimetre Common-User Bolometer Array 2 and Polarimeter 2 on the James Clerk Maxwell Telescope. This paper describes the initial data obtained using HARP to observe 12CO, 13CO and C18O J= 3 → 2 towards two regions in Orion B, NGC 2024 and NGC 2071. We describe the physical characteristics of the two clouds, calculating temperatures and opacities utilizing all the three isotopologues. We find good agreement between temperatures calculated from CO and from dust emission in the dense, energetic regions. We determine the mass and energetics of the clouds, and of the high-velocity material seen in 12CO emission, and compare the relative energetics of the high- and low-velocity material in the two clouds. We present a clumpfind analysis of the 13CO condensations. The slope of the condensation mass functions, at the high-mass ends, is similar to the slope of the initial mass function.Peer reviewe
The Mathematical Universe
I explore physics implications of the External Reality Hypothesis (ERH) that
there exists an external physical reality completely independent of us humans.
I argue that with a sufficiently broad definition of mathematics, it implies
the Mathematical Universe Hypothesis (MUH) that our physical world is an
abstract mathematical structure. I discuss various implications of the ERH and
MUH, ranging from standard physics topics like symmetries, irreducible
representations, units, free parameters, randomness and initial conditions to
broader issues like consciousness, parallel universes and Godel incompleteness.
I hypothesize that only computable and decidable (in Godel's sense) structures
exist, which alleviates the cosmological measure problem and help explain why
our physical laws appear so simple. I also comment on the intimate relation
between mathematical structures, computations, simulations and physical
systems.Comment: Replaced to match accepted Found. Phys. version, 31 pages, 5 figs;
more details at http://space.mit.edu/home/tegmark/toe.htm
Discovering the Microbial Enzymes Driving Drug Toxicity with Activity-Based Protein Profiling
It is increasingly clear that interindividual variability in human gut microbial composition contributes to differential drug responses. For example, gastrointestinal (GI) toxicity is not observed in all patients treated with the anticancer drug irinotecan, and it has been suggested that this variability is a result of differences in the types and levels of gut bacterial β-glucuronidases (GUS). GUS enzymes promote drug toxicity by hydrolyzing the inactive drug-glucuronide conjugate back to the active drug, which damages the GI epithelium. Proteomics-based identification of the exact GUS enzymes responsible for drug reactivation from the complexity of the human microbiota has not been accomplished, however. Here, we discover the specific bacterial GUS enzymes that generate SN-38, the active and toxic metabolite of irinotecan, from human fecal samples using a unique activity-based protein profiling (ABPP) platform. We identify and quantify gut bacterial GUS enzymes from human feces with an ABPP-enabled proteomics pipeline and then integrate this information with ex vivo kinetics to pinpoint the specific GUS enzymes responsible for SN-38 reactivation. Furthermore, the same approach also reveals the molecular basis for differential gut bacterial GUS inhibition observed between human fecal samples. Taken together, this work provides an unprecedented technical and bioinformatics pipeline to discover the microbial enzymes responsible for specific reactions from the complexity of human feces. Identifying such microbial enzymes may lead to precision biomarkers and novel drug targets to advance the promise of personalized medicine.Bio-organic SynthesisMedical Biochemistr
Quantity and quality of soil organic matter as a sustainability index under different land uses in Eastern Amazon
Fast-timing measurements in neutron-rich odd-mass zirconium isotopes using LaBr3:Ce detectors coupled with Gammasphere
A fast-timing experiment was performed at the Argonne National Laboratory to measure the lifetimes of the lowest lying states of nuclei belonging to the deformed regions around mass number A 110 and A 150. These regions were populated via spontaneous fission of 252 Cf and the gamma radiation following the decay of excited states in the fission fragments was measured using 51 Gammasphere detectors coupled with 25 LaBr 3 :Ce detectors. A brief description of the acquisition system and some preliminary results from the fast-timing analysis of the fission fragment 100Zr are presented. The lifetime value of \u3c4 = 840(65) ps was found for the 2 + state in 100 Zr consistent within one standard deviation of the adopted value with 791 +26 -35 ps. This is associated with a quadrupole deformation parameter of 0.36(2) which is within one standard deviation of the literature value of 0.3556 +82 -57
Fast-timing measurements in the ground-state band of Pd114
Using a hybrid Gammasphere array coupled to 25 LaBr3(Ce) detectors, the lifetimes of the first three levels of the yrast band in Pd-114, populated via Cf-252 decay, have been measured. The measured lifetimes are tau(2+) = 103(10) ps, tau(4+) = 22(13) ps, and tau(6+) <= 10 ps for the 2(1)(+), 4(1)(+), and 6(1)(+) levels, respectively. Palladium-114 was predicted to be the most deformed isotope of its isotopic chain, and spectroscopic studies have suggested it might also be a candidate nucleus for low-spin stable triaxiality. From the lifetimes measured in this work, reduced transition probabilities B(E2; J -> J - 2) are calculated and compared with interacting boson model, projected shell model, and collective model calculations from the literature. The experimental ratio R-B(E2) = B(E2; 4(1)(+) -> 2(1)(+))/B(E2; 2(1)(+) -> 0(1)(+)) = 0.80(42) is measured for the first time in Pd-114 and compared with the known values R-B(E2) in the palladium isotopic chain: the systematics suggest that, for N = 68, a transition from gamma-unstable to a more rigid gamma-deformed nuclear shape occurs
Distinct Assemblies of Heterodimeric Cytokine Receptors Govern Stemness Programs in Leukemia
Published first May 16, 2023Leukemia stem cells (LSC) possess distinct self-renewal and arrested differentiation properties that are responsible for disease emergence, therapy failure, and recurrence in acute myeloid leukemia (AML). Despite AML displaying extensive biological and clinical heterogeneity, LSC with high interleukin-3 receptor (IL3R) levels are a constant yet puzzling feature, as this receptor lacks tyrosine kinase activity. Here, we show that the heterodimeric IL3Rα/βc receptor assembles into hexamers and dodecamers through a unique interface in the 3D structure, where high IL3Rα/βc ratios bias hexamer formation. Importantly, receptor stoichiometry is clinically relevant as it varies across the individual cells in the AML hierarchy, in which high IL3Rα/βc ratios in LSCs drive hexamer-mediated stemness programs and poor patient survival, while low ratios mediate differentiation. Our study establishes a new paradigm in which alternative cytokine receptor stoichiometries differentially regulate cell fate, a signaling mechanism that may be generalizable to other transformed cellular hierarchies and of potential therapeutic significance.Winnie L. Kan, Urmi Dhagat, Kerstin B. Kaufmann, Timothy R. Hercus, Tracy L. Nero, Andy G.X. Zeng, John Toubia, Emma F. Barry, Sophie E. Broughton, Guillermo A. Gomez, Brooks A. Benard, Mara Dottore, Karen S. Cheung Tung Shing, Héléna Boutzen, Saumya E. Samaraweera, Kaylene J. Simpson, Liqing Jin, Gregory J. Goodall, C. Glenn Begley, Daniel Thomas, Paul G. Ekert, Denis Tvorogov, Richard J. D, Andrea, John E. Dick, Michael W. Parker, and Angel F. Lope
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