The effects of tides on swash statistics on an intermediate beach

Swash hydrodynamics were investigated on an intermediate beach using runup data obtained from video images. Under mild, near-constant, offshore wave conditions, the presence of a sandbar and the tidally controlled water depth over its crest determined whether most of the incoming waves broke before reaching the shoreline. This forced a change in the pattern of wave energy dissipation across the surf zone between low and high tide, which was reflected by changes to swash on time scales of a few hours. Significant runup height (Rs, defined as 4 times the standard deviation of the waterline time series), was found to vary by a factor of 2 between low tide, when most of the waves were breaking over the sandbar (Rs/Hs ≈ 1.5, where Hs is the offshore significant wave height) and high tide, when the waves were barely breaking (Rs/Hs ≈ 2.7). The increase in wave energy dissipation during low tide was also associated with changes in swash maxima distribution, a decrease in mean swash period, and increasing energy at infragravity frequencies. Bispectral analysis suggested that this infragravity modulation might have been connected with the presence of secondary waves

Establishing storm thresholds for the spanish gulf of Cádiz coast

In this study critical thresholds are defined for storm impacts along the Spanish coast of the Gulf of Cádiz. The thresholds correspond to the minimum wave and tide conditions necessary to produce significant morphological changes on beaches and dunes and/or damage on coastal infrastructure or human occupation. Threshold definition was performed by computing theoretical sea-level variations during storms and comparing them with the topography of the study area and the location of infrastructure at a local level. Specifically, the elevations of the berm, the dune foot and the entrance of existing washovers were selected as threshold parameters. The total sea-level variation generated by a storm event was estimated as the sum of the tidal level, the wind-induced setup, the barometric setup and the wave-associated sea-level variation (wave setup and runup), assuming a minimum interaction between the different processes. These components were calculated on the basis of parameterisations for significant wave height (Hs) obtained for the oceanographic and environmental conditions of the Gulf of Cadiz. For this purpose real data and reanalysis time-series (HIPOCAS project) were used. Validation of the obtained results was performed for a range of coastal settings over the study area. The obtained thresholds for beach morphological changes in spring tide conditions range between a significant wave height of 1.5 m and 3.7 m depending on beach characteristics, while for dune foot erosion are around 3.3 to 3.7 m and for damage to infrastructure around 7.2 m. In case of neap tide conditions these values are increased on average by 50% over the areas with large tidal range. Furthermore, records of real damage in coastal infrastructure caused by storms were collected at a regional level from newspapers and other bibliographic sources and compared with the hydrodynamic conditions that caused the damage. These were extracted from the hindcast database of the HIPOCAS project, including parameters such as storm duration, mean and maximum wave height and wave direction. Results show that the duration of the storm is not critical in determining the occurrence of coastal damage in the regional study area. This way, the threshold would be defined as a duration ≥30 hours, with moderate average wave height (≥3.3 m) and high maximum wave height (≥4.1 m) approaching from the 3rd and 4th quadrants, during mean or spring tide situation. The calculated thresholds constitute snapshots of risk conditions within a certain time framework. Beach and nearshore zones are extremely dynamic, and also the characteristics of occupation on the coast change over time, so critical storm thresholds will change accordingly and therefore will need to be updated

Differential effects of glucagon-like peptide-1 receptor agonists on heart rate

Abstract While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are known to increase heart rate (HR), it is insufficiently recognized that the extent varies greatly between the various agonists and is affected by the assessment methods employed. Here we review published data from 24-h time-averaged HR monitoring in healthy individuals and subjects with type 2 diabetes mellitus (T2DM) treated with either short-acting GLP-1 RAs, lixisenatide or exenatide, or long-acting GLP-1 RAs, exenatide LAR, liraglutide, albiglutide, or dulaglutide (N\ua0=\ua01112; active-treatment arms). HR effects observed in two independent head-to-head trials of lixisenatide and liraglutide (N\ua0=\ua0202; active-treatment arms) are also reviewed. Short-acting GLP-1 RAs, exenatide and lixisenatide, are associated with a transient (1\u201312\ua0h) mean placebo- and baseline-adjusted 24-h HR increase of 1\u20133\ua0beats per minute (bpm). Conversely, long-acting GLP-1 RAs are associated with more pronounced increases in mean 24-h HR; the highest seen with liraglutide and albiglutide at 6\u201310\ua0bpm compared with dulaglutide and exenatide LAR at 3\u20134\ua0bpm. For both liraglutide and dulaglutide, HR increases were recorded during both the day and at night. In two head-to-head comparisons, a small, transient mean increase in HR from baseline was observed with lixisenatide; liraglutide induced a substantially greater increase that remained significantly elevated over 24\ua0h. The underlying mechanism for increased HR remains to be elucidated; however, it could be related to a direct effect at the sinus node and/or stimulation of the sympathetic nervous system, with this effect related to the duration of action of the respective GLP-1 RAs. In conclusion, this review indicates that the effects on HR differ within the class of GLP-1 RAs: short-acting GLP-1 RAs are associated with a modest and transient HR increase before returning to baseline levels, while some long-acting GLP-1 RAs are associated with a more pronounced and sustained increase during the day and night. Findings from recently completed trials indicate that a GLP-1 RA-induced increase in HR, regardless of magnitude, does not present an increased cardiovascular risk for subjects with T2DM, although a pronounced increase in HR may be associated with adverse clinical outcomes in those with advanced heart failure

THE APOGEE SPECTROSCOPIC SURVEY OF KEPLER PLANET HOSTS: FEASIBILITY, EFFICIENCY, AND FIRST RESULTS

The Kepler mission has yielded a large number of planet candidates from among the Kepler Objects of Interest(KOIs), but spectroscopic follow-up of these relatively faint stars is a serious bottleneck in confirming and characterizing these systems. We present motivation and survey design for an ongoing project with the Sloan Digital Sky Survey III multiplexed Apache Point Observatory Galactic Evolution Experiment (APOGEE) near-infrared spectrograph to monitor hundreds of KOI host stars. We report some of our first results using representative targets from our sample, which include current planet candidates that we find to be false positives, as well as candidates listed as false positives that we do not find to be spectroscopic binaries. With this survey, KOI hosts are observed over ∼20 epochs at a radial velocity (RV) precision of 100–200ms−1. These observations can easily identify a majority of false positives caused by physically associated stellar or substellar binaries, and in many cases, fully characterize their orbits. We demonstrate that APOGEE is capable of achieving RV precision at the 100–200ms−1 level over long time baselines, and that APOGEE’s multiplexing capability makes it substantially more efficient at identifying false positives due to binaries than other single-object spectrographs working to confirm KOIs as planets. These APOGEE RVs enable ancillary science projects, such as studies of fundamental stellar astrophysics or intrinsically rare substellar companions. The coadded APOGEE spectra can be used to derive stellar properties (Teff, log g) and chemical abundances of over a dozen elements to probe correlations of planet properties with individual elemental abundances

Chronic insulin treatment of diabetes does not fully normalize alterations in the retinal transcriptome

<p>Abstract</p> <p>Background</p> <p>Diabetic retinopathy (DR) is a leading cause of blindness in working age adults. Approximately 95% of patients with Type 1 diabetes develop some degree of retinopathy within 25 years of diagnosis despite normalization of blood glucose by insulin therapy. The goal of this study was to identify molecular changes in the rodent retina induced by diabetes that are not normalized by insulin replacement and restoration of euglycemia.</p> <p>Methods</p> <p>The retina transcriptome (22,523 genes and transcript variants) was examined after three months of streptozotocin-induced diabetes in male Sprague Dawley rats with and without insulin replacement for the later one and a half months of diabetes. Selected gene expression changes were confirmed by qPCR, and also examined in independent control and diabetic rats at a one month time-point.</p> <p>Results</p> <p>Transcriptomic alterations in response to diabetes (1376 probes) were clustered according to insulin responsiveness. More than half (57%) of diabetes-induced mRNA changes (789 probes) observed at three months were fully normalized to control levels with insulin therapy, while 37% of probes (514) were only partially normalized. A small set of genes (5%, 65 probes) was significantly dysregulated in the insulin-treated diabetic rats. qPCR confirmation of findings and examination of a one month time point allowed genes to be further categorized as prevented or rescued with insulin therapy. A subset of genes (Ccr5, Jak3, Litaf) was confirmed at the level of protein expression, with protein levels recapitulating changes in mRNA expression.</p> <p>Conclusions</p> <p>These results provide the first genome-wide examination of the effects of insulin therapy on retinal gene expression changes with diabetes. While insulin clearly normalizes the majority of genes dysregulated in response to diabetes, a number of genes related to inflammatory processes, microvascular integrity, and neuronal function are still altered in expression in euglycemic diabetic rats. Gene expression changes not rescued or prevented by insulin treatment may be critical to the pathogenesis of diabetic retinopathy, as it occurs in diabetic patients receiving insulin replacement, and are prototypical of metabolic memory.</p

Musculoskeletal pain is associated with restless legs syndrome in young adults

Background - In recent years, there is considerable evidence of a relationship between the sensorimotor disorder restless legs syndrome (RLS) and pain disorders, including migraine and fibromyalgia. An association between multi-site pain and RLS has been reported in adult women. In the current study, we explored the association between musculoskeletal (MSK) pain and RLS in a large cohort of young adults. Methods - Twenty two year olds (n = 1072), followed since birth of part of the Western Australian Pregnancy Cohort (Raine) Study, provided data on MSK pain (duration, severity, frequency, number of pain sites). RLS was considered present when 4 diagnostic criteria recommended by the International Restless Legs Syndrome Study Group were met (urge to move, dysaesthesia, relief by movement, worsening symptoms during the evening/night) and participants had these symptoms at least 5 times per month. Associations between MSK pain and RLS were analyzed by multivariable logistic regression with bias-corrected bootstrapped confidence intervals, with final models adjusted for sex, psychological distress and sleep quality. Results - The prevalence of RLS was 3.0 % and MSK pain was reported by 37.4 % of the participants. In multivariable logistic regression models, strong associations were found between RLS-diagnosis and long duration (three months or more) of MSK pain (odds ratio 3.6, 95 % confidence interval 1.4–9.2) and reporting three or more pain sites (4.9, 1.6–14.6). Conclusions - Different dimensions of MSK pain were associated with RLS in young adults, suggestive of shared pathophysiological mechanisms. Overlap between these conditions requires more clinical and research attention

O-Glycosylation Regulates Ubiquitination and Degradation of the Anti-Inflammatory Protein A20 to Accelerate Atherosclerosis in Diabetic ApoE-Null Mice

Background: Accelerated atherosclerosis is the leading cause of morbidity and mortality in diabetic patients. Hyperglycemia is a recognized independent risk factor for heightened atherogenesis in diabetes mellitus (DM). However, our understanding of the mechanisms underlying glucose damage to the vasculature remains incomplete. Methodology/Principal Findings: High glucose and hyperglycemia reduced upregulation of the NF-κB inhibitory and atheroprotective protein A20 in human coronary endothelial (EC) and smooth muscle cell (SMC) cultures challenged with Tumor Necrosis Factor alpha (TNF), aortae of diabetic mice following Lipopolysaccharide (LPS) injection used as an inflammatory insult and in failed vein-grafts of diabetic patients. Decreased vascular expression of A20 did not relate to defective transcription, as A20 mRNA levels were similar or even higher in EC/SMC cultured in high glucose, in vessels of diabetic C57BL/6 and FBV/N mice, and in failed vein grafts of diabetic patients, when compared to controls. Rather, decreased A20 expression correlated with post-translational O-Glucosamine-N-Acetylation (O-GlcNAcylation) and ubiquitination of A20, targeting it for proteasomal degradation. Restoring A20 levels by inhibiting O-GlcNAcylation, blocking proteasome activity, or overexpressing A20, blocked upregulation of the receptor for advanced glycation end-products (RAGE) and phosphorylation of PKCβII, two prime atherogenic signals triggered by high glucose in EC/SMC. A20 gene transfer to the aortic arch of diabetic ApoE null mice that develop accelerated atherosclerosis, attenuated vascular expression of RAGE and phospho-PKCβII, significantly reducing atherosclerosis. Conclusions: High glucose/hyperglycemia regulate vascular A20 expression via O-GlcNAcylation-dependent ubiquitination and proteasomal degradation. This could be key to the pathogenesis of accelerated atherosclerosis in diabetes

CfA3: 185 Type Ia Supernova Light Curves from the CfA

We present multi-band photometry of 185 type-Ia supernovae (SN Ia), with over 11500 observations. These were acquired between 2001 and 2008 at the F. L. Whipple Observatory of the Harvard-Smithsonian Center for Astrophysics (CfA). This sample contains the largest number of homogeneously-observed and reduced nearby SN Ia (z < 0.08) published to date. It more than doubles the nearby sample, bringing SN Ia cosmology to the point where systematic uncertainties dominate. Our natural system photometry has a precision of 0.02 mag or better in BVRIr'i' and roughly 0.04 mag in U for points brighter than 17.5 mag. We also estimate a systematic uncertainty of 0.03 mag in our SN Ia standard system BVRIr'i' photometry and 0.07 mag for U. Comparisons of our standard system photometry with published SN Ia light curves and comparison stars, where available for the same SN, reveal agreement at the level of a few hundredths mag in most cases. We find that 1991bg-like SN Ia are sufficiently distinct from other SN Ia in their color and light-curve-shape/luminosity relation that they should be treated separately in light-curve/distance fitter training samples. The CfA3 sample will contribute to the development of better light-curve/distance fitters, particularly in the few dozen cases where near-infrared photometry has been obtained and, together, can help disentangle host-galaxy reddening from intrinsic supernova color, reducing the systematic uncertainty in SN Ia distances due to dust.Comment: Accepted to the Astrophysical Journal. Minor changes from last version. Light curves, comparison star photometry, and passband tables are available at http://www.cfa.harvard.edu/supernova/CfA3

Sex Differences in the Brain: A Whole Body Perspective

Most writing on sexual differentiation of the mammalian brain (including our own) considers just two organs: the gonads and the brain. This perspective, which leaves out all other body parts, misleads us in several ways. First, there is accumulating evidence that all organs are sexually differentiated, and that sex differences in peripheral organs affect the brain. We demonstrate this by reviewing examples involving sex differences in muscles, adipose tissue, the liver, immune system, gut, kidneys, bladder, and placenta that affect the nervous system and behavior. The second consequence of ignoring other organs when considering neural sex differences is that we are likely to miss the fact that some brain sex differences develop to compensate for differences in the internal environment (i.e., because male and female brains operate in different bodies, sex differences are required to make output/function more similar in the two sexes). We also consider evidence that sex differences in sensory systems cause male and female brains to perceive different information about the world; the two sexes are also perceived by the world differently and therefore exposed to differences in experience via treatment by others. Although the topic of sex differences in the brain is often seen as much more emotionally charged than studies of sex differences in other organs, the dichotomy is largely false. By putting the brain firmly back in the body, sex differences in the brain are predictable and can be more completely understood