Abstract Objective Lynch syndrome (LS) is an inherited tumor predisposition condition caused by mutations in the mismatch repair (MMR) genes. Mutation carriers are at increased risk of various ...malignancies, including ovarian cancer (OC). Relatively little is known about the pathological features and clinical behavior of LS associated OC. Methods We analyzed the data of 1047 proven MMR mutated individuals from a prospectively maintained database at a large referral center for genomic medicine in the North West of England. Data were crosschecked with pathology reports, the National Cancer Registry and death certificates, where appropriate. Data from gynecological surveillance and risk reducing surgery were analyzed. Results We identified 53 cases of LSAOC in proven MMR mutated individuals. The cumulative risk of LSAOC was 20% at age 80 in those who retained their ovaries. LSAOC presented at an earlier age (average 51, range 24–70 years) than sporadic OC. The predominant histological subtype was endometrioid adenocarcinoma (53%). Most cases presented early (85% at stage I/II vs. 15% at stage III/IV, p < 0.001) and overall survival was excellent (80% 5-year survival), however, patients with advanced disease had a poor prognosis (40% 5-year survival). Most women were found to have LS after their OC diagnosis, however, two were detected at Stage 1c through gynecological surveillance and a further three were detected following surgery for screen-detected synchronous endometrial pathology. Conclusion The predominance of early stage disease in LSAOC is linked to its good prognosis. We support risk-reducing surgery for women whose families are complete especially if undertaking hysterectomy for endometrial risk, and ovarian surveillance as part of gynecological screening for those who have not.
Cerebral infarctions are common in older persons but their relationship with dementia and cognitive function remains controversial.
Participants were 164 older Catholic nuns, priests, and brothers ...who underwent annual clinical evaluation and brain autopsy at death. The authors quantified number and volume of old cerebral infarctions on postmortem examination and determined the association with dementia and cognitive function proximate to death. Analyses controlled for age, sex, and education.
A total of 58 (35.4%) subjects had cerebral infarctions: 29 had one infarction and 29 had multiple infarctions. In logistic regression analyses, infarctions increased the odds of dementia twofold (OR 2.12; 95% CI 1.06 to 4.25). The odds of dementia increased by 2.67-fold for multiple infarctions (95% CI 1.08 to 6.61), whereas the odds of dementia with single infarctions increased by 69% (95% CI 0.70 to 4.09). In linear regression analyses, there was a trend for multiple infarctions to be associated with lower global cognitive scores (-0.44 standard units, p = 0.057). Multiple infarctions were related to perceptual speed, visuospatial skills, and working memory, but not to episodic or semantic memory. The authors found similar results with infarction volume. In secondary analyses, only infarctions that were clinically evident during life were associated with dementia and cognitive function.
Cerebral infarctions are associated with a twofold increase in odds of dementia. Odds are higher in persons with multiple, large, or clinically evident infarctions. In addition, cerebral infarctions do not affect all cognitive systems equally, showing the strongest association with perceptual speed and the weakest with episodic memory.
We present the first results of a survey of the CII157.7 mu m emission line in 241 luminous infrared galaxies (LIRGs) comprising the Great Observatories All-sky LIRG Survey (GOALS) sample, obtained ...with the PACS instrument on board the Herschel Space Observatory. The CII luminosities, L sub(CII), of the LIRGs in GOALS range from ~10 super(7) to 2 x 10 super(9) L sub(middot in circle). We find that LIRGs show a tight correlation of CII/FIR with far-IR (FIR) flux density ratios, with a strong negative trend spanning from ~10 super(-2) to 10 super(-4), as the average temperature of dust increases. We find correlations between the CII/FIR ratio and the strength of the 9.7 mu m silicate absorption feature as well as with the luminosity surface density of the mid-IR emitting region (summationoperator sub(MIR)), suggesting that warmer, more compact starbursts have substantially smaller CII/FIR ratios. Pure star-forming LIRGs have a mean CII/FIR ~ 4 x 10 super(-3), while galaxies with low polycyclic aromatic hydrocarbon (PAH) equivalent widths (EWs), indicative of the presence of active galactic nuclei (AGNs), span the full range in CII/FIR. However, we show that even when only pure star-forming galaxies are considered, the CII/FIR ratio still drops by an order of magnitude, from 10 super(-2) to 10 super(-3), with summationoperator sub(MIR) and summationoperator sub(IR), implying that the CII157.7 mu m luminosity is not a good indicator of the star formation rate (SFR) for most local LIRGs, for it does not scale linearly with the warm dust emission most likely associated to the youngest stars. Moreover, even in LIRGs in which we detect an AGN in the mid-IR, the majority (2/3) of galaxies show CII/FIR > or =, slanted 10 super(-3) typical of high 6.2 mu m PAH EW sources, suggesting that most AGNs do not contribute significantly to the FIR emission. We provide an empirical relation between the CII/FIR and the specific SFR for star-forming LIRGs. Finally, we present predictions for the starburst size based on the observed CII and FIR luminosities which should be useful for comparing with results from future surveys of high-redshift galaxies with ALMA and CCAT.
The spectrum of the hydrogen atom has played a central part in fundamental physics over the past 200 years. Historical examples of its importance include the wavelength measurements of absorption ...lines in the solar spectrum by Fraunhofer, the identification of transition lines by Balmer, Lyman and others, the empirical description of allowed wavelengths by Rydberg, the quantum model of Bohr, the capability of quantum electrodynamics to precisely predict transition frequencies, and modern measurements of the 1S-2S transition by Hänsch to a precision of a few parts in 10
. Recent technological advances have allowed us to focus on antihydrogen-the antimatter equivalent of hydrogen. The Standard Model predicts that there should have been equal amounts of matter and antimatter in the primordial Universe after the Big Bang, but today's Universe is observed to consist almost entirely of ordinary matter. This motivates the study of antimatter, to see if there is a small asymmetry in the laws of physics that govern the two types of matter. In particular, the CPT (charge conjugation, parity reversal and time reversal) theorem, a cornerstone of the Standard Model, requires that hydrogen and antihydrogen have the same spectrum. Here we report the observation of the 1S-2S transition in magnetically trapped atoms of antihydrogen. We determine that the frequency of the transition, which is driven by two photons from a laser at 243 nanometres, is consistent with that expected for hydrogen in the same environment. This laser excitation of a quantum state of an atom of antimatter represents the most precise measurement performed on an anti-atom. Our result is consistent with CPT invariance at a relative precision of about 2 × 10
.
The Hubble Tarantula Treasury Project (HTTP) is an ongoing panchromatic imaging survey of stellar populations in the Tarantula Nebula in the Large Magellanic Cloud that reaches into the sub-solar ...mass regime (<0.5 Modot). HTTP utilizes the capability of the Hubble Space Telescope to operate the Advanced Camera for Surveys and the Wide Field Camera 3 in parallel to study this remarkable region in the near-ultraviolet, optical, and near-infrared spectral regions, including narrow-band H alpha images. The combination of all these bands provides a unique multi-band view. The resulting maps of the stellar content of the Tarantula Nebula within its main body provide the basis for investigations of star formation in an environment resembling the extreme conditions found in starburst galaxies and in the early universe. Access to detailed properties of individual stars allows us to begin to reconstruct the temporal and spatial evolution of the stellar skeleton of the Tarantula Nebula over space and time on a sub-parsec scale. In this first paper we describe the observing strategy, the photometric techniques, and the upcoming data products from this survey and present preliminary results obtained from the analysis of the initial set of near-infrared observations.
Visual cues provide an important means for aerial creatures to ascertain their self-motion through the environment. In many insects, including flies, moths, and bees, wide-field motion-sensitive ...neurons in the third optic ganglion are thought to underlie such motion encoding; however, these neurons can only respond robustly over limited speed ranges. The task is more complicated for some species of dragonflies that switch between extended periods of hovering flight and fast-moving pursuit of prey and conspecifics, requiring motion detection over a broad range of velocities. Since little is known about motion processing in these insects, we performed intracellular recordings from hawking, emerald dragonflies (
) and identified a diverse group of motion-sensitive neurons that we named lobula tangential cells (LTCs). Following prolonged visual stimulation with drifting gratings, we observed significant differences in both temporal and spatial tuning of LTCs. Cluster analysis of these changes confirmed several groups of LTCs with distinctive spatiotemporal tuning. These differences were associated with variation in velocity tuning in response to translated, natural scenes. LTCs with differences in velocity tuning ranges and optima may underlie how a broad range of motion velocities are encoded. In the hawking dragonfly, changes in LTC tuning over time are therefore likely to support their extensive range of behaviors, from hovering to fast-speed pursuits.
Understanding how animals navigate the world is an inherently difficult and interesting problem. Insects are useful models for understanding neuronal mechanisms underlying these activities, with neurons that encode wide-field motion previously identified in insects, such as flies, hawkmoths, and butterflies. Like some Dipteran flies, dragonflies exhibit complex aerobatic behaviors, such as hovering, patrolling, and aerial combat. However, dragonflies lack halteres that support such diverse behavior in flies. To understand how dragonflies might address this problem using only visual cues, we recorded from their wide-field motion-sensitive neurons. We found these differ strongly in the ways they respond to sustained motion, allowing them collectively to encode the very broad range of velocities experienced during diverse behavior.
This work documents the first version of the U.S. Department of Energy (DOE) new Energy Exascale Earth System Model (E3SMv1). We focus on the standard resolution of the fully coupled physical model ...designed to address DOE mission‐relevant water cycle questions. Its components include atmosphere and land (110‐km grid spacing), ocean and sea ice (60 km in the midlatitudes and 30 km at the equator and poles), and river transport (55 km) models. This base configuration will also serve as a foundation for additional configurations exploring higher horizontal resolution as well as augmented capabilities in the form of biogeochemistry and cryosphere configurations. The performance of E3SMv1 is evaluated by means of a standard set of Coupled Model Intercomparison Project Phase 6 (CMIP6) Diagnosis, Evaluation, and Characterization of Klima simulations consisting of a long preindustrial control, historical simulations (ensembles of fully coupled and prescribed SSTs) as well as idealized CO2 forcing simulations. The model performs well overall with biases typical of other CMIP‐class models, although the simulated Atlantic Meridional Overturning Circulation is weaker than many CMIP‐class models. While the E3SMv1 historical ensemble captures the bulk of the observed warming between preindustrial (1850) and present day, the trajectory of the warming diverges from observations in the second half of the twentieth century with a period of delayed warming followed by an excessive warming trend. Using a two‐layer energy balance model, we attribute this divergence to the model's strong aerosol‐related effective radiative forcing (ERFari+aci = −1.65 W/m2) and high equilibrium climate sensitivity (ECS = 5.3 K).
Plain Language Summary
The U.S. Department of Energy funded the development of a new state‐of‐the‐art Earth system model for research and applications relevant to its mission. The Energy Exascale Earth System Model version 1 (E3SMv1) consists of five interacting components for the global atmosphere, land surface, ocean, sea ice, and rivers. Three of these components (ocean, sea ice, and river) are new and have not been coupled into an Earth system model previously. The atmosphere and land surface components were created by extending existing components part of the Community Earth System Model, Version 1. E3SMv1's capabilities are demonstrated by performing a set of standardized simulation experiments described by the Coupled Model Intercomparison Project Phase 6 (CMIP6) Diagnosis, Evaluation, and Characterization of Klima protocol at standard horizontal spatial resolution of approximately 1° latitude and longitude. The model reproduces global and regional climate features well compared to observations. Simulated warming between 1850 and 2015 matches observations, but the model is too cold by about 0.5 °C between 1960 and 1990 and later warms at a rate greater than observed. A thermodynamic analysis of the model's response to greenhouse gas and aerosol radiative affects may explain the reasons for the discrepancy.
Key Points
This work documents E3SMv1, the first version of the U.S. DOE Energy Exascale Earth System Model
The performance of E3SMv1 is documented with a set of standard CMIP6 DECK and historical simulations comprising nearly 3,000 years
E3SMv1 has a high equilibrium climate sensitivity (5.3 K) and strong aerosol‐related effective radiative forcing (‐1.65 W/m2)
Nuclear stellar cusps are defined as central excess light component in the stellar light profiles of galaxies and are suggested to be stellar relics of intense compact starbursts in the central ...∼100-500 pc region of gas-rich major mergers. Here, we probe the build-up of nuclear cusps during the actual starburst phase for a complete sample of luminous infrared galaxy (LIRG) systems (85 LIRGs, with 11.4 < log L
IR/L < 12.5) in the Great Observatories All-sky LIRG Survey sample. Cusp properties are derived via 2D fitting of the nuclear stellar light imaged in the near-infrared (NIR) by the Hubble Space Telescope and have been combined with mid-infrared (IR) diagnostics for active galactic nucleus (AGN)/starburst characterization. We find that nuclear stellar cusps are resolved in 76 per cent of LIRGs (merger and non-interacting galaxies). The cusp strength and luminosity increase with far-IR luminosity (excluding AGN) and merger stage, confirming theoretical models that starburst activity is associated with the build-up of nuclear stellar cusps. Evidence for ultracompact nuclear starbursts is found in ∼13 per cent of LIRGs, which have a strong unresolved central NIR light component but no significant contribution of an AGN. The nuclear NIR surface density (measured within 1 kpc radius) increases by a factor of ∼5 towards late merger stages. A careful comparison to local early-type galaxies with comparable masses reveals (a) that local (U)LIRGs have a significantly larger cusp fraction and (b) that the majority of the cusp LIRGs have host galaxy luminosities (H band) similar to core ellipticals which are roughly one order in magnitude larger than those for cusp ellipticals.
Generation-integrated energy storage (GIES) systems store energy at some point along the transformation between the primary energy form and electricity. Instances exist already in natural hydro ...power, biomass generation, wave power, and concentrated solar power. GIES systems have been proposed for wind, nuclear power and they arise naturally in photocatalysis systems that are in development. GIES systems can compare very favourably in both performance and total cost against equivalent non-integrated systems comprising both generation and storage. Despite this, they have not hitherto been recognised as a discrete class of systems. Consequently policy decisions affecting development or demonstration projects and policy approaches concerning low-carbon generation are not fully informed. This paper highlights that policy structures exist militating against the development and introduction of GIES systems-probably to the detriment of overall system good.
•Current wisdom considers that energy storage and generation must be separate.•Integrating energy storage with generation lowers capital costs.•Integrating energy storage with generation reduces total energy losses.•Existing policies militate against such integrated systems being developed.
•We introduce spline forests.•Spline forests can represent complex surfaces and volumes.•We describe adaptive h-refinement and coarsening algorithms.•We develop a Bézier extraction framework for ...splines forests.•Several transient advection–diffusion benchmark problems are solved.
In this paper we present isogeometric spline forests. An isogeometric spline forest is a hierarchical spline representation capable of representing surfaces or volumes of arbitrarily complex geometry and topological genus. Spline forests can accomodate arbitrary degree and smoothness in the underlying hierarchical basis as well as non-uniform knot interval configurations. We describe adaptive h-refinement and coarsening algorithms for isogeometric spline forests and develop a Bézier extraction framework which provides a simple and efficient single level finite element description of the complex multi-level, unstructured hierarchical spline basis. We then demonstrate the potential of spline forests as a basis for analysis in the context of transient advection–diffusion problems where fully integrated adaptivity is demonstrated for the first time in an isogeometric simulation. In all cases, the adaptive process remains local (even in the case of moving fronts) and preserves exact geometry at the coarsest level of the discretization. The accuracy and robustness of the approach is demonstrated in all cases.
PDF
![EXPLAINING THE [C II]157.7 ...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0004-637X/small "EXPLAINING THE [C II]157.7 μm DEFICIT IN LUMINOUS INFRARED GALAXIES—FIRST RESULTS FROM A HERSCHEL /PACS STUDY OF THE GOALS SAMPLE")
