Interpreting syndepositional sediment remobilization and deformation beneath submarine gravity flows; a kinematic boundary layer approach

Turbidite sandstones and related deposits commonly contain deformation structures and remobilized sediment that might have resulted from post-depositional modification such as downslope creep (e.g. slumping) or density-driven loading by overlying deposits. However, we consider that deformation can occur during the passage of turbidity currents that exerted shear stress on their substrates (whether entirely pre-existing strata, sediment deposited by earlier parts of the flow itself or some combination of these). Criteria are outlined here, to avoid confusion with products of other mechanisms (e.g. slumping or later tectonics), which establish the synchronicity between the passage of overriding flows and deformation of their substrates. This underpins a new analytical framework for tracking the relationship between deformation, deposition and the transit of the causal turbidity current, through the concept of kinematic boundary layers. Case study examples are drawn from outcrop (Miocene of New Zealand, and Apennines of Italy) and subsurface examples (Britannia Sandstone, Cretaceous, UK Continental Shelf). Example structures include asymmetric flame structures, convolute lamination, some debritic units and injection complexes, together with slurry and mixed slurry facies. These structures may provide insight into the rheology and dynamics of submarine flows and their substrates, and have implications for the development of subsurface turbidite reservoirs

Mutational signatures reveal ternary relationships between homologous recombination repair, APOBEC, and mismatch repair in gynecological cancers

Background Revealing the impacts of endogenous and exogenous mutagenesis processes is essential for understanding the etiology of somatic genomic alterations and designing precise prognostication and treatment strategies for cancer. DNA repair deficiency is one of the main sources of endogenous mutagenesis and is increasingly recognized as a target for cancer therapeutics. The role and prevalence of mechanisms that underly different forms of DNA repair deficiencies and their interactions remain to be elucidated in gynecological malignancies. Methods We analyzed 1231 exomes and 268 whole-genomes from three major gynecological malignancies including uterine corpus endometrial carcinoma (UCEC) as well as ovarian and cervical cancers. We also analyzed data from 134 related cell lines. We extracted and compared de novo and refitted mutational signature profiles using complementary and confirmatory approaches and performed interaction analysis to detect co-occurring and mutually exclusive signatures. Results We found an inverse relationship between homologous recombination deficiency (HRd) and mismatch repair deficiency (MMRd). Moreover, APOBEC co-occurred with HRd but was mutually exclusive with MMRd. UCEC tumors were dominated by MMRd, yet a subset of them manifested the HRd and APOBEC signatures. Conversely, ovarian tumors were dominated by HRd, while a subset represented MMRd and APOBEC. In contrast to both, cervical tumors were dominated by APOBEC with a small subsets showing the POLE, HRd, and MMRd signatures. Although the type, prevalence, and heterogeneity of mutational signatures varied across the tumor types, the patterns of co-occurrence and exclusivity were consistently observed in all. Notably, mutational signatures in gynecological tumor cell lines reflected those detected in primary tumors. Conclusions Taken together, these analyses indicate that application of mutation signature analysis not only advances our understanding of mutational processes and their interactions, but also it has the potential to stratify patients that could benefit from treatments available for tumors harboring distinct mutational signatures and to improve clinical decision-making for gynecological malignancies

Big Bang Nucleosynthesis with Gaussian Inhomogeneous Neutrino Degeneracy

We consider the effect of inhomogeneous neutrino degeneracy on Big Bang nucleosynthesis for the case where the distribution of neutrino chemical potentials is given by a Gaussian. The chemical potential fluctuations are taken to be isocurvature, so that only inhomogeneities in the electron chemical potential are relevant. Then the final element abundances are a function only of the baryon-photon ratio $\eta$, the effective number of additional neutrinos $\Delta N_\nu$, the mean electron neutrino degeneracy parameter $\bar \xi$, and the rms fluctuation of the degeneracy parameter, $\sigma_\xi$. We find that for fixed $\eta$, $\Delta N_\nu$, and $\bar \xi$, the abundances of helium-4, deuterium, and lithium-7 are, in general, increasing functions of $\sigma_\xi$. Hence, the effect of adding a Gaussian distribution for the electron neutrino degeneracy parameter is to decrease the allowed range for $\eta$. We show that this result can be generalized to a wide variety of distributions for $\xi$.Comment: 9 pages, 3 figures, added discussion of neutrino oscillations, altered presentation of figure

The Uncertainty in Newton's Constant and Precision Predictions of the Primordial Helium Abundance

The current uncertainty in Newton's constant, G_N, is of the order of 0.15%. For values of the baryon to photon ratio consistent with both cosmic microwave background observations and the primordial deuterium abundance, this uncertainty in G_N corresponds to an uncertainty in the primordial 4He mass fraction, Y_P, of +-1.3 x 10^{-4}. This uncertainty in Y_P is comparable to the effect from the current uncertainty in the neutron lifetime, which is often treated as the dominant uncertainty in calculations of Y_P. Recent measurements of G_N seem to be converging within a smaller range; a reduction in the estimated error on G_N by a factor of 10 would essentially eliminate it as a source of uncertainty in the calculation of the primordial 4He abundance.Comment: 3 pages, no figures, fixed typos, to appear in Phys. Rev.

Fermion Masses and Mixing in Extended Technicolor Models

We study fermion masses and mixing angles, including the generation of a seesaw mechanism for the neutrinos, in extended technicolor (ETC) theories. We formulate an approach to these problems that relies on assigning right-handed $Q=-1/3$ quarks and charged leptons to ETC representations that are conjugates of those of the corresponding left-handed fermions. This leads to a natural suppression of these masses relative to the $Q=2/3$ quarks, as well as the generation of quark mixing angles, both long-standing challenges for ETC theories. Standard-model-singlet neutrinos are assigned to ETC representations that provide a similar suppression of neutrino Dirac masses, as well as the possibility of a realistic seesaw mechanism with no mass scale above the highest ETC scale of roughly $10^3$ TeV. A simple model based on the ETC group SU(5) is constructed and analyzed. This model leads to non-trivial, but not realistic mixing angles in the quark and lepton sectors. It can also produce sufficiently light neutrinos, although not simultaneously with a realistic quark spectrum. We discuss several aspects of the phenomenology of this class of models.Comment: 74 pages, revtex with embedded figure

How Does CMB + BBN Constrain New Physics?

Recent cosmic microwave background (CMB) results from BOOMERANG, MAXIMA, and DASI provide cosmological constraints on new physics that can be competitive with those derived from Big Bang Nucleosynthesis (BBN). In particular, both CMB and BBN can be used to place limits on models involving neutrino degeneracy and additional relativistic degrees of freedom. However, for the case of the CMB, these constraints are, in general, sensitive to the assumed priors. We examine the CMB and BBN constraints on such models and study the sensitivity of ``new physics" to the assumed priors. If we add a constraint on the age of the universe (t_0 \ga 11 Gyr), then for models with a cosmological constant, the range of baryon densities and neutrino degeneracy parameters allowed by the CMB and BBN is fairly robust: $\eta_{10} = 6.0 \pm 0.6$, \deln \la 6, \xi_e \la 0.3. In the absence of new physics, models without a cosmological constant are only marginally compatible with recent CMB observations (excluded at the 93% confidence level).Comment: 6 pages, 5 figures; version to appear in Phys. Rev.

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701