Hurricanes Katrina and Rita were powerful storms that impacted southern Louisiana and Mississippi during the 2005 hurricane season. In Part I, the authors describe and validate a high-resolution ...coupled riverine flow, tide, wind, wave, and storm surge model for this region. Herein, the model is used to examine the evolution of these hurricanes in more detail. Synoptic histories show how storm tracks, winds, and waves interacted with the topography, the protruding Mississippi River delta, east-west shorelines, manmade structures, and low-lying marshes to develop and propagate storm surge. Perturbations of the model, in which the waves are not included, show the proportional importance of the wave radiation stress gradient induced setup.
Rapid adjustments are responses to forcing agents that cause a perturbation to the top of atmosphere energy budget but are uncoupled to changes in surface warming. Different mechanisms are ...responsible for these adjustments for a variety of climate drivers. These remain to be quantified in detail. It is shown that rapid adjustments reduce the effective radiative forcing (ERF) of black carbon by half of the instantaneous forcing, but for CO2 forcing, rapid adjustments increase ERF. Competing tropospheric adjustments for CO2 forcing are individually significant but sum to zero, such that the ERF equals the stratospherically adjusted radiative forcing, but this is not true for other forcing agents. Additional experiments of increase in the solar constant and increase in CH4 are used to show that a key factor of the rapid adjustment for an individual climate driver is changes in temperature in the upper troposphere and lower stratosphere.
Plain Language Summary
Long‐term global warming can be estimated with knowledge of how climate forcing agents affect the Earth's top‐of‐atmosphere energy imbalance or effective radiative forcing. Changes in climate forcers, such as greenhouse gases, the Sun's intensity, or emission of aerosol particles, typically impose a direct change in the energy budget, termed an instantaneous radiative forcing. Further to this, a climate forcer may induce changes in the atmosphere, such as a change in thermal structure, clouds, or humidity. These changes themselves, termed rapid adjustments, contribute to the top‐of‐atmosphere energy budget. Together, the instantaneous radiative forcing plus rapid adjustments equals the effective radiative forcing. We show that for different climate forcing agents, the rapid adjustments behave very differently and are driven by different atmospheric mechanisms. For example, rapid adjustments add to the instantaneous forcing for a carbon dioxide increase, due to a cooling of the stratosphere, but oppose instantaneous forcing for black carbon, driven by a warming troposphere and lowering of cloud height. Understanding rapid adjustments gives a more complete picture of the climate effects of different climate forcers.
Key Points
Rapid adjustments affect the Earth's energy balance in different ways for greenhouse gas, aerosol, and solar forcing
Radiative kernels and partial radiative perturbations are used to diagnose rapid adjustments from atmospheric and cloud changes
Noncloud adjustments agree well between models, whereas cloud adjustments exhibit more spread
Colorectal cancer (CRC) is an illness strongly influenced by sex and gender, with mortality rates in males significantly higher than females. There is still a dearth of understanding on where sex ...differences exist along the pathway from presentation to survival. The aim of this review is to identify where actions are needed to improve outcomes for both sexes, and to narrow the gap for CRC.
A cross-sectional review of national data was undertaken to identify sex differences in incidence, screening uptake, route to diagnosis, cancer stage at diagnosis and survival, and their influence in the sex differences in mortality.
Overall incidence is higher in men, with an earlier age distribution, however, important sex differences exist in anatomical site. There were relatively small differences in screening uptake, route to diagnosis, cancer staging at diagnosis and survival. Screening uptake is higher in women under 69 years. Women are more likely to present as emergency cases, with more men diagnosed through screening and two-week-wait. No sex differences are seen in diagnosis for more advanced disease. Overall, age-standardised 5-year survival is similar between the sexes.
As there are minimal sex differences in the data from routes to diagnosis to survival, the higher mortality of colorectal cancer in men appears to be a result of exogenous and/or endogenous factors pre-diagnosis that lead to higher incidence rates. There are however, sex and gender differences that suggest more targeted interventions may facilitate prevention and earlier diagnosis in both men and women.
We investigate galactic-scale outflows in the redshift range 0.71 ≤ z ≤ 1.63, using 413 K-band selected galaxies observed in the spectroscopic follow-up of the UKIDSS Ultra-Deep Survey (UDSz). The ...galaxies have an average stellar mass of ∼109.5 M and span a wide range in rest-frame colours, representing typical star-forming galaxies at this epoch. We stack the spectra by various galaxy properties, including stellar mass, O ii equivalent width, star formation rate, specific star formation rate and rest-frame spectral indices. We find that outflows are present in virtually all spectral stacks, with velocities ranging from 100 to 1000 km s−1, indicating that large-scale outflowing winds are a common property at these redshifts. The highest velocity outflows (>500 km s−1) are found in galaxies with the highest stellar masses and the youngest stellar populations. Our findings suggest that high-velocity galactic outflows are mostly driven by star-forming processes rather than active galactic nuclei, with implied mass outflow rates comparable to the rates of star formation. Such behaviour is consistent with models required to reproduce the high-redshift mass-metallicity relation.
We report the discovery of TOI 837b and its validation as a transiting planet. We characterize the system using data from the NASA Transiting Exoplanet Survey Satellite mission, the ESA Gaia mission, ...ground-based photometry from El Sauce and ASTEP400, and spectroscopy from CHIRON, FEROS, and Veloce. We find that TOI 837 is a T = 9.9 mag G0/F9 dwarf in the southern open cluster IC 2602. The star and planet are therefore million years old. Combining the transit photometry with a prior on the stellar parameters derived from the cluster color-magnitude diagram, we find that the planet has an orbital period of and is slightly smaller than Jupiter ( ). From radial velocity monitoring, we limit to less than 1.20 MJup (3 ). The transits either graze or nearly graze the stellar limb. Grazing transits are a cause for concern, as they are often indicative of astrophysical false-positive scenarios. Our follow-up data show that such scenarios are unlikely. Our combined multicolor photometry, high-resolution imaging, and radial velocities rule out hierarchical eclipsing binary scenarios. Background eclipsing binary scenarios, though limited by speckle imaging, remain a 0.2% possibility. TOI 837b is therefore a validated adolescent exoplanet. The planetary nature of the system can be confirmed or refuted through observations of the stellar obliquity and the planetary mass. Such observations may also improve our understanding of how the physical and orbital properties of exoplanets change in time.
Deregulated Notch signaling due to mutation or overexpression of ligands and/or receptors is implicated in various human malignancies. γ-Secretase inhibitors inhibit Notch signaling by preventing ...cleavage of transmembrane domain of Notch protein. LY3039478 is a novel, potent Notch inhibitor decreases Notch signaling and its downstream biologic effects. In this first-in-human study, we report the safety, pharmacokinetic (PK) profile, pharmacodynamic effects, and antitumor activity of LY3039478 in patients with advanced or metastatic cancer.
This phase I, open-label, multicenter, nonrandomized, and dose-escalation phase study determined and confirmed the recommended phase II dose of LY3039478 (oral dose: 2.5–100mg, thrice weekly (TIW) on a 28-day cycle). The primary objectives are to determine (part A) and confirm (part B) a recommended phase II dose that may be safely administered to patients with advanced or metastatic cancer, and secondary objectives include evaluation of safety, tolerability, PK parameters, and preliminary antitumor activity of LY3039478.
A total of 110 patients were treated with LY3039478 monotherapy between 31 October 2012 and 15 July 2016. Dose-limiting toxicities were thrombocytopenia, colitis, and nausea. Most adverse events were gastrointestinal. The recommended phase II dose was 50mg TIW, because of its better tolerability compared with 75mg. The PKs of LY3039478 appeared dose proportional. Pharmacodynamic data indicate an ∼80% inhibition of plasma Aβ, and >50% inhibition of Notch-regulated genes hairy and enhancer of split-1, cyclin D1, and Notch-regulated ankyrin repeat at 45–100-mg dose. Clinical activity (tumor necrosis, metabolic response, or tumor shrinkage) was observed in patients with breast cancer, leiomyosarcoma, and adenoid cystic carcinoma.
Potent inhibition of Notch signaling by LY3039478 was well tolerated at doses associated with target engagement, and demonstrated evidence of clinical activity in heavily pretreated patients. Further investigation with LY3039478 as monotherapy and in combination with targeted agent or chemotherapy is ongoing.
NCT01695005.
DTI is increasingly being used as a measure to study tissue damage in several neurologic diseases. Our aim was to investigate the comparability of DTI measures between different MR imaging magnets ...and platforms.
Two healthy volunteers underwent DTI on five 3T MR imaging scanners (3 Trios and 2 Signas) by using a matched 33 noncollinear diffusion-direction pulse sequence. Within each subject, a total of 16 white matter (corpus callosum, periventricular, and deep white matter) and gray matter (cortical and deep gray) ROIs were drawn on a single image set and then were coregistered to the other images. Mean FA, ADC, and longitudinal and transverse diffusivities were calculated within each ROI. Concordance correlations were derived by comparing ROI DTI values among each of the 5 magnets.
Mean concordance for FA was 0.96; for both longitudinal and transverse diffusivities, it was 0.93; and for ADC, it was 0.88. Mean scan-rescan concordance was 0.96-0.97 for all DTI measures. Concordance correlations within platforms were, in general, better than those between platforms for all DTI measures (mean concordance of 0.96).
We found that a 3T magnet and high-angular-resolution pulse sequence yielded comparable DTI measurements across different MR imaging magnets and platforms. Our results indicate that FA is the most comparable measure across magnets, followed by individual diffusivities. The comparability of DTI measures between different magnets supports the feasibility of multicentered clinical trials by using DTI as an outcome measure.
The Global Burden of Disease 2015 study aims to use all available data of sufficient quality to generate reliable and valid prevalence, incidence, and disability-adjusted life year (DALY) estimates ...of oral conditions for the period of 1990 to 2015. Since death as a direct result of oral diseases is rare, DALY estimates were based on years lived with disability, which are estimated only on those persons with unmet need for dental care. We used our data to assess progress toward the Federation Dental International, World Health Organization, and International Association for Dental Research’s oral health goals of reducing the level of oral diseases and minimizing their impact by 2020. Oral health has not improved in the last 25 y, and oral conditions remained a major public health challenge all over the world in 2015. Due to demographic changes, including population growth and aging, the cumulative burden of oral conditions dramatically increased between 1990 and 2015. The number of people with untreated oral conditions rose from 2.5 billion in 1990 to 3.5 billion in 2015, with a 64% increase in DALYs due to oral conditions throughout the world. Clearly, oral diseases are highly prevalent in the globe, posing a very serious public health challenge to policy makers. Greater efforts and potentially different approaches are needed if the oral health goal of reducing the level of oral diseases and minimizing their impact is to be achieved by 2020. Despite some challenges with current measurement methodologies for oral diseases, measurable specific oral health goals should be developed to advance global public health.
ABSTRACT
We present the dust mass function (DMF) of 15 750 galaxies with redshift $z$ < 0.1, drawn from the overlapping area of the GAMA and H-ATLAS surveys. The DMF is derived using the density ...corrected Vmax method, where we estimate Vmax using: (i) the normal photometric selection limit (pVmax) and (ii) a bivariate brightness distribution (BBD) technique, which accounts for two selection effects. We fit the data with a Schechter function, and find $M^{*}=(4.65 \pm 0.18)\times 10^{7}\,h^2_{70}\, \mathrm{ M}_{\odot }$, α = (−1.22 ± 0.01), $\phi ^{*}=(6.26 \pm 0.28)\times 10^{-3}\,h^3_{70}\,\rm Mpc^{-3}\,dex^{-1}$. The resulting dust mass density parameter integrated down to 104 M⊙ is Ωd = (1.11 ± 0.02) × 10−6 which implies the mass fraction of baryons in dust is $f_{m_\mathrm{ b}}=(2.40\pm 0.04)\times 10^{-5}$; cosmic variance adds an extra 7–17 per cent uncertainty to the quoted statistical errors. Our measurements have fewer galaxies with high dust mass than predicted by semi-analytic models. This is because the models include too much dust in high stellar mass galaxies. Conversely, our measurements find more galaxies with high dust mass than predicted by hydrodynamical cosmological simulations. This is likely to be from the long time-scales for grain growth assumed in the models. We calculate DMFs split by galaxy type and find dust mass densities of Ωd = (0.88 ± 0.03) × 10−6 and Ωd = (0.060 ± 0.005) × 10−6 for late types and early types, respectively. Comparing to the equivalent galaxy stellar mass functions (GSMF) we find that the DMF for late types is well matched by the GSMF scaled by (8.07 ± 0.35) × 10−4.
The Electric Fields and Waves (EFW) Instruments on the two Radiation Belt Storm Probe (RBSP) spacecraft (recently renamed the Van Allen Probes) are designed to measure three dimensional quasi-static ...and low frequency electric fields and waves associated with the major mechanisms responsible for the acceleration of energetic charged particles in the inner magnetosphere of the Earth. For this measurement, the instrument uses two pairs of spherical double probe sensors at the ends of orthogonal centripetally deployed booms in the spin plane with tip-to-tip separations of 100 meters. The third component of the electric field is measured by two spherical sensors separated by ∼15 m, deployed at the ends of two stacer booms oppositely directed along the spin axis of the spacecraft. The instrument provides a continuous stream of measurements over the entire orbit of the low frequency electric field vector at 32 samples/s in a survey mode. This survey mode also includes measurements of spacecraft potential to provide information on thermal electron plasma variations and structure. Survey mode spectral information allows the continuous evaluation of the peak value and spectral power in electric, magnetic and density fluctuations from several Hz to 6.5 kHz. On-board cross-spectral data allows the calculation of field-aligned wave Poynting flux along the magnetic field. For higher frequency waveform information, two different programmable burst memories are used with nominal sampling rates of 512 samples/s and 16 k samples/s. The EFW burst modes provide targeted measurements over brief time intervals of 3-d electric fields, 3-d wave magnetic fields (from the EMFISIS magnetic search coil sensors), and spacecraft potential. In the burst modes all six sensor-spacecraft potential measurements are telemetered enabling interferometric timing of small-scale plasma structures. In the first burst mode, the instrument stores all or a substantial fraction of the high frequency measurements in a 32 gigabyte burst memory. The sub-intervals to be downloaded are uplinked by ground command after inspection of instrument survey data and other information available on the ground. The second burst mode involves autonomous storing and playback of data controlled by flight software algorithms, which assess the “highest quality” events on the basis of instrument measurements and information from other instruments available on orbit. The EFW instrument provides 3-d wave electric field signals with a frequency response up to 400 kHz to the EMFISIS instrument for analysis and telemetry (Kletzing et al. Space Sci. Rev.
2013
).
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