Relative age of interior layered deposits in southwest Candor Chasma based on high-resolution structural mapping

High-resolution topography generated from stereo HiRISE (High-Resolution Imaging Science Experiment) imagery reveals the meter-scale structure of interior layered deposits (ILD) in southwest Candor Chasma. This study seeks to determine the age of the local ILD relative to any normal faults that can be attributed to chasma formation. The study area is located near the contact of these ILD and the wall rock and is in an area where chasma-forming normal faults have been proposed. We find that while normal faults are found in the study area, these faults are not sufficiently large nor appropriately located or oriented to accommodate the roughly northeast-southwest extension that is required for normal faults that can be attributed to chasma formation. Additionally, bedding exposed in the local ILD generally dips toward the center of Candor Chasma, consistent with sediment deposition in a preexisting basin. Further, pit craters of Tithonia Catena, presumed to predate or be contemporaneous with the formation of west Candor Chasma, do not cut into the ILD within the study area. These independent lines of evidence support a postchasma age for the ILD exposed within the study area. Chasma-related normal faults may exist within these ILD at depth but are not exposed at the surface. Approximately 2 km of conformable stratigraphy is exposed in the study area, and therefore at least several kilometers of the local ILD were deposited subsequent to any chasma-related normal faulting that may have occurred in this part of Candor Chasma

Geology and Topography of Ra Patera, Io, in the Voyager era: Prelude to Eruption

Voyager era stereo images are used to map the geology and topography of Ra Patera (a major active volcanic center and possible site of sulfur eruptions on Io). The summit of Ra Patera reaches only approx.1 km above the surrounding plains. Pre-Voyager-era lava flows occur on slopes of 0.1-0.3 deg, comparable to the lunar mare. These flows were emplaced at either low viscosities, high eruption rates, or both. A 600- km-long ridged mountain unit (rising to approx. 8 km near Carancho Patera) forms a 60 by 90 km wide plateau approx. 0.5 km high 50 km east of Ra Patera. The new lava flows observed by Galileo flowed around the southern edge of this plateau

The Role of Ejecta in the Small Crater Populations on the Mid-Sized Saturnian Satellites

We find evidence that crater ejecta play an important role in the small crater populations on the Saturnian satellites, and more broadly, on cratered surfaces throughout the Solar System. We measure crater populations in Cassini images of Enceladus, Rhea, and Mimas, focusing on image data with scales less than 500 m/pixel. We use recent updates to crater scaling laws and their constants to estimate the amount of mass ejected in three different velocity ranges: (i) greater than escape velocity, (ii) less than escape velocity and faster than the minimum velocity required to make a secondary crater (v_min), and (iii) velocities less than v_min. Although the vast majority of mass on each satellite is ejected at speeds less than v_min, our calculations demonstrate that the differences in mass available in the other two categories should lead to observable differences in the small crater populations; the predictions are borne out by the measurements we have made to date. Rhea, Tethys, and Dione have sufficient surface gravities to retain ejecta moving fast enough to make secondary crater populations. The smaller satellites, such as Enceladus but especially Mimas, are expected to have little or no traditional secondary populations because their escape velocities are near the threshold velocity necessary to make a secondary crater. Our work clarifies why the Galilean satellites have extensive secondary crater populations relative to the Saturnian satellites. The presence, extent, and sizes of sesquinary craters (craters formed by ejecta that escape into temporary orbits around Saturn before re-impacting the surface) is not yet well understood. Finally, our work provides further evidence for a "shallow" size-frequency distribution (slope index of ~2 for a differential power-law) for comets a few km diameter and smaller. [slightly abbreviated]Comment: Submitted to Icarus. 77 double-spaced pages, including 25 figures and 5 table

Development and characterization of a high-throughput in vitro cord formation model insensitive to VEGF inhibition

BACKGROUND: Anti-VEGF therapy reduces tumor blood vessels, however, some vessels always remain. These VEGF insensitive vessels may help support continued tumor growth and metastases. Many in vitro assays examining multiple steps of the angiogenic process have been described, but the majority of these assays are sensitive to VEGF inhibition. There has been little focus on the development of high-throughput, in vitro assays to model the vessels that are insensitive to VEGF inhibition. METHODS: Here, we describe a fixed end-point and kinetic, high-throughput stem cell co-culture model of cord formation. RESULTS: In this system, cords develop within 24 hours, at which point they begin to lose sensitivity to VEGF inhibitors, bevacizumab, and ramucirumab. Consistent with the hypothesis that other angiogenic factors maintain VEGF-independent vessels, pharmacologic intervention with a broad spectrum anti-angiogenic antagonist (suramin), a vascular disrupting agent (combretastatin), or a combination of VEGF and Notch pathway inhibitors reduced the established networks. In addition, we used our in vitro approach to develop an in vivo co-implant vasculogenesis model that connects with the endogenous vasculature to form functional blood vessels. Similar to the in vitro system, over time these vessels become insensitive to VEGF inhibition. CONCLUSION: Together, these models may be used to identify novel drugs targeting tumor vessels that are not sensitive to VEGF inhibition

Obesity and type 2 diabetes have additive effects on left ventricular remodelling in normotensive patients-a cross sectional study

BackgroundIt is unclear whether obesity and type 2 diabetes (T2D), either alone or in combination, induce left ventricular hypertrophy (LVH) independent of hypertension. In the current study, we provide clarity on this issue by rigorously analysing patient left ventricular (LV) structure via clinical indices and via LV geometric patterns (more commonly used in research settings). Importantly, our sample consisted of hypertensive patients that are routinely screened for LVH via echocardiography and normotensive patients that would normally be deemed low risk with no further action required.MethodsThis cross sectional study comprised a total of 353 Caucasian patients, grouped based on diagnosis of obesity, T2D and hypertension, with normotensive obese patients further separated based on metabolic health. Basic metabolic parameters were collected and LV structure and function were assessed via transthoracic echocardiography. Multivariable logistic and linear regression analyses were used to identify predictors of LVH and diastolic dysfunction.ResultsMetabolically healthy normotensive obese patients exhibited relatively low risk of LVH. However, normotensive metabolically non-healthy obese, T2D and obese/T2D patients all presented with reduced normal LV geometry that coincided with increased LV concentric remodelling. Furthermore, normotensive patients presenting with both obesity and T2D had a higher incidence of concentric hypertrophy and grade 3 diastolic dysfunction than normotensive patients with either condition alone, indicating an additive effect of obesity and T2D. Alarmingly these alterations were at a comparable prevalence to that observed in hypertensive patients. Interestingly, assessment of LVPWd, a traditional index of LVH, underestimated the presence of LV concentric remodelling. The implications for which were demonstrated by concentric remodelling and concentric hypertrophy strongly associating with grade 1 and 3 diastolic dysfunction respectively, independent of sex, age and BMI. Finally, pulse pressure was identified as a strong predictor of LV remodelling within normotensive patients.ConclusionsThese findings show that metabolically non-healthy obese, T2D and obese/T2D patients can develop LVH independent of hypertension. Furthermore, that LVPWd may underestimate LV remodelling in these patient groups and that pulse pressure can be used as convenient predictor of hypertrophy status.<br /

Reasons given by general practitioners for non-treatment decisions in younger and older patients with newly diagnosed type 2 diabetes mellitus in the United Kingdom: a survey study

<p>Abstract</p> <p>Background</p> <p>Older patients with newly diagnosed type 2 diabetes mellitus are less likely to receive antihyperglycaemic therapy compared to their younger counterparts. The purpose of this study was to assess the reasons of general practitioners (GPs) for not treating younger and older patients with newly diagnosed type 2 diabetes mellitus with antihyperglycaemic agents.</p> <p>Methods</p> <p>In a survey conducted between November 2009 and January 2010, 358 GPs from the United Kingdom selected reasons for not initiating antihyperglycaemic therapy in younger (< 65 years) and older (≥65 years) patients with newly diagnosed type 2 diabetes mellitus and untreated with any antihyperglycaemic agent for at least six months following diagnosis. Thirty-six potential reasons were classified into four major categories: <it>Mild hyperglycaemia</it>, <it>Factors related to antihyperglycaemic agents</it>, <it>Comorbidities and polypharmacy</it>, and <it>Patient-related reasons</it>. Reasons for non-treatment were compared between younger (n = 1, 023) and older (n = 1, 005) patients.</p> <p>Results</p> <p>Non-treatment reasons related to <it>Mild hyperglycaemia </it>were selected more often by GPs for both younger (88%) and older (86%) patients than those in other categories. For older patients, <it>Factors related to antihyperglycaemic agents </it>(46% vs. 38%) and <it>Comorbidities and polypharmacy </it>(33% vs. 19%), both including safety-related issues, were selected significantly (p < 0.001) more often by GPs. No between-group difference was observed for the <it>Patient-related reasons </it>category. The GP-reported HbA_1cthreshold for initiating antihyperglycaemic therapy was significantly (p < 0.001) lower for younger patients (mean ± standard deviation: 7.3% ± 0.7) compared to older patients (7.5% ± 0.9).</p> <p>Conclusions</p> <p>GPs selected reasons related to <it>Mild hyperglycaemia </it>for non-treatment of their untreated patients with newly diagnosed type 2 diabetes mellitus, despite nearly one-third of these patients having their most recent HbA_1cvalue ≥7%. The findings further suggest that safety-related issues may influence the non-treatment of older patients with type 2 diabetes mellitus.</p

A recent gibbon ape leukemia virus germline integration in a rodent from New Guinea

Germline colonization by retroviruses results in the formation of endogenous retroviruses (ERVs). Most colonization’s occurred millions of years ago. However, in the Australo-Papuan region (Australia and New Guinea), several recent germline colonization events have been discovered . The Wallace Line separates much of Southeast Asia from the Australo-Papuan region restricting faunal and pathogen dispersion. West of the Wallace Line, gibbon ape leukemia viruses (GALVs) have been isolated from captive gibbons. Two microbat species from China appear to have been infected naturally. East of Wallace’s Line, the woolly monkey virus (a GALV) and the closely related koala retrovirus (KoRV) have been detected in eutherians and marsupials in the Australo-Papuan region, often vertically transmitted. The detected vertically transmitted GALV-like viruses in Australo-Papuan fauna compared to sporadic horizontal transmission in Southeast Asia and China suggest the GALV-KoRV clade originates in the former region and further models of early-stage genome colonization may be found. We screened 278 samples, seven bat and one rodent family endemic to the Australo-Papuan region and bat and rodent species found on both sides of the Wallace Line. We identified two rodents ( Melomys ) from Australia and Papua New Guinea and no bat species harboring GALV-like retroviruses. Melomys leucogaster from New Guinea harbored a genomically complete replication-competent retrovirus with a shared integration site among individuals. The integration was only present in some individuals of the species indicating this retrovirus is at the earliest stages of germline colonization of the Melomys genome, providing a new small wild mammal model of early-stage genome colonization