•Saltmarsh restored by managed realignment (MR) has fewer creeks than natural marsh.•MRs are topographically more like agricultural land than natural marsh.•MRs are flatter with greater potential for ...water accumulation than natural marsh.•Such differences could impact vegetation development and ecosystem functioning.
Saltmarshes can be created to compensate for lost habitat by a process known as managed realignment (MR), where sea defences are deliberately breached to flood low-lying agricultural land. However, the vegetation that develops on MR sites is not equivalent to natural habitat. In natural sites, surface topography and creek networks are drivers of vegetation diversity, but their development on restored sites has not been well studied. We investigate the topographic characteristics of 19 MR areas, and compare these to nearby natural saltmarshes (representing desired conditions) and to coastal agricultural landscapes (representing conditions prior to MR). From high-resolution LiDAR data, we extracted values of elevation, six measures of surface topography (although two were later excluded due to collinearity), and three measures of creek density. MR and natural marshes differed significantly in all surface topographic indices, with MR sites having lower rugosity and more concave features, with greater potential for water accumulation. MR sites also had significantly lower creek density. MRs and coastal agricultural landscapes were more similar, differing in only one topographic measure. Importantly, there was no relationship between age since restoration and any of the topographic variables, indicating that restored sites are not on a trajectory to become topographically similar to natural marshes. MR schemes need to consider actively constructing topographic heterogeneity; better mirroring natural sites in this way is likely to benefit the development of saltmarsh vegetation, and will also have implications for a range of ecosystem functions.
Flood early warning systems mitigate damages and loss of life and are an economically efficient way of enhancing disaster resilience. The use of continental scale flood early warning systems is ...rapidly growing. The European Flood Awareness System (EFAS) is a pan-European flood early warning system forced by a multi-model ensemble of numerical weather predictions. Responses to scientific and technical changes can be complex in these computationally expensive continental scale systems, and improvements need to be tested by evaluating runs of the whole system. It is demonstrated here that forecast skill is not correlated with the value of warnings. In order to tell if the system has been improved an evaluation strategy is required that considers both forecast skill and warning value. The combination of a multi-forcing ensemble of EFAS flood forecasts is evaluated with a new skill-value strategy. The full multi-forcing ensemble is recommended for operational forecasting, but, there are spatial variations in the optimal forecast combination. Results indicate that optimizing forecasts based on value rather than skill alters the optimal forcing combination and the forecast performance. Also indicated is that model diversity and ensemble size are both important in achieving best overall performance. The use of several evaluation measures that consider both skill and value is strongly recommended when considering improvements to early warning systems.
Self-collected specimens can expand access to SARS-CoV-2 testing. At a large inner-city hospital 1,082 participants self-collected saliva and anterior nasal swab (ANS) samples before healthcare ...workers collected nasopharyngeal swab (NPS) samples on the same day. To characterize patient preferences for self-collection, this investigation explored ability, comfort, and ease of ANS and saliva self-collection for SARS-CoV-2 testing along with associated patient characteristics, including medical history and symptoms of COVID-19. With nearly all participants successfully submitting a specimen, favorable ratings from most participants (at least >79% in ease and comfort), and equivocal preference between saliva and ANS, self-collection is a viable SARS-CoV-2 testing option.
The second meal phenomenon, which occurs in normal and diabetic individuals, refers to the improvement in glucose tolerance seen following a second identical meal. We previously showed that 4h of ...morning (AM) hyperinsulinemia, but not hyperglycemia, enhanced hepatic glucose uptake (HGU) and glycogen storage during a PM hyperinsulinemic hyperglycemic clamp (HIHG) later that day. Our aim was to determine if the duration of morning hyperinsulinemia is important for the PM response to a HIHG clamp. To determine this, we administered the same amount of insulin over 2h in the first half of the morning (Ins2h-A), over 2h in the 2nd half of the morning (Ins2h-B), or over the entire 4h (Ins4h) of the morning. We then assessed the impact of the AM insulin duration on HGU during a PM HIHG clamp in conscious dogs. The dogs underwent an AM hyperinsulinemic euglycemic clamp from 0-120 min, 120-240 min, or 0-240 min (Ins2h-A, Ins2h-B, or Ins4h; n=6/group). The insulin infusion rates used in the Ins4h were selected to mimic the rise in endogenous insulin secretion previously observed during a 4h AM duodenal glucose infusion (2.1 mU/kg/min (0-30 min), 2.4 mU/kg/min (30-60 min), and 1.5 mU/kg/min (60-240 min)). These rates were doubled in both 2h groups to match the total amount of insulin being infused in the 4h AM clamp. In the PM, all groups had 4x basal insulin, 2x basal glycemia, and portal glucose infusion to simulate a 2nd meal. During the 4h PM clamp, there were no significant differences between the two 2h groups. However, there was a marked effect on the mean HGU in the Ins4h group compared to the Ins2h-A and Ins2h-B groups (HGU of 6.3±0.9 vs 3.8±0.3 and 4.4±0.4 mg/kg/min; AUC of 1393±199 vs 822±68 and 971±93 mg/kg/4hr, P<0.05), respectively, despite matched hepatic glucose loads. The longer duration (Ins4h) of AM hyperinsulinemia allowed for a 41% and 66% greater uptake of glucose in the PM clamp (vs Ins2hA + B). Thus, the duration of AM hyperinsulinemia is an important determinant of hepatic metabolism later in the day.
Disclosure
H.L.Waterman: None. M.S.Smith: None. B.Farmer: None. G.Kraft: None. M.Scott: None. D.S.Edgerton: None. A.D.Cherrington: Advisory Panel; Metavention, vTv Therapeutics, Diakard, Sekkei Bio, Sensulin Labs, LLC, Other Relationship; Fractyl Health, Inc., Novo Nordisk, Abvance Therapeutics, Research Support; Cellular Longevity, Inc, dba Loyal, Senda Biosciences. M.C.Moore: None.
Funding
National Institutes of Health (5T32DK007563-34, 5R01DK131082-02)
Treatment for osteosarcoma (OS) has been largely unchanged for several decades, with typical therapies being a mixture of chemotherapy and surgery. Although therapeutic targets and products against ...cancer are being continually developed, only a limited number have proved therapeutically active in OS. Thus, the understanding of the OS microenvironment and its interactions are becoming more important in developing new therapies. Three-dimensional (3D) models are important tools in increasing our understanding of complex mechanisms and interactions, such as in OS. In this review, in vivo animal models, in vitro 3D models and in ovo chorioallantoic membrane (CAM) models, are evaluated and discussed as to their contribution in understanding the progressive nature of OS, and cancer research. We aim to provide insight and prospective future directions into the potential translation of 3D models in OS.
Early Voting Changes and Voter Turnout Walker, Hannah L.; Herron, Michael C.; Smith, Daniel A.
Political behavior,
12/2019, Volume:
41, Issue:
4
Journal Article
Peer reviewed
North Carolina offers its residents the opportunity to cast early in-person (EIP) ballots prior to Election Day, a practice known locally as “One-Stop” voting. Following a successful legal challenge ...to the state’s controversial 2013 Voter Information and Verification Act, North Carolina’s 100 counties were given wide discretion over the hours and locations of EIP voting for the 2016 General Election. This discretion yielded a patchwork of election practices across the state, providing us with a set of natural experiments to study the effect of changes in early voting hours on voter turnout. Drawing on individual-level voting records from the North Carolina State Board of Elections, our research design matches voters on race, party, and geography. We find little evidence that changes to early opportunities in North Carolina had uniform effects on voter turnout. Nonetheless, we do identify areas in the presidential battleground state where voters appear to have reacted to local changes in early voting availability, albeit not always in directions consistent with the existing literature. We suspect that effects of changes to early voting rules are conditional on local conditions, and future research on the effects of election law changes on turnout should explore these conditions in detail.
ABSTRACT
We present the discovery of NGTS-19b, a high-mass transiting brown dwarf discovered by the Next Generation Transit Survey. We investigate the system using follow-up photometry from the South ...African Astronomical Observatory, as well as sector 11 Transiting Exoplanet Survey Satellite data, in combination with radial velocity measurements from the CORALIE spectrograph to precisely characterize the system. We find that NGTS-19b is a brown dwarf companion to a K-star, with a mass of $69.5 ^{+5.7}_{-5.4}$ MJup and radius of $1.034 ^{+0.055}_{-0.053}$RJup. The system has a reasonably long period of 17.84 d, and a high degree of eccentricity of $0.3767 ^{+0.0061}_{-0.0061}$. The mass and radius of the brown dwarf imply an age of $0.46 ^{+0.26}_{-0.15}$ Gyr, however, this is inconsistent with the age determined from the host star spectral energy distribution, suggesting that the brown dwarf may be inflated. This is unusual given that its large mass and relatively low levels of irradiation would make it much harder to inflate. NGTS-19b adds to the small, but growing number of brown dwarfs transiting main-sequence stars, and is a valuable addition as we begin to populate the so-called brown dwarf desert.
Six PARP inhibitors (PARPi) are approved for cancer therapy as monotherapy agents in daily or twice-daily continuous dosing schedules to maintain the necessary continuous suppression of PARP ...activity. Continuous PARP inhibition is required for single-agent anticancer activity. To investigate if such intense schedules are necessary, we determined the durability of PARP inhibition up to 72 h after a 1 h pulse of 1 µM of five of the approved PARPi, rucaparib, olaparib, niraparib, talazoparib and pamiparib, in IGROV-1 and ES-2 (human ovarian cancer) cells. Rucaparib caused the most persistent inhibition of PARP activity when maintained at ≥75% at 72 h after drug withdrawal in both IGROV-1 and ES-2 cells, but inhibition was more rapidly lost with the other PARPi. PARPi are also under clinical investigation with ATR inhibitors, and thus, we evaluated the implications for scheduling with an ATR inhibitor (VE-821). Rucaparib enhanced VE-821 cytotoxicity in co-exposure, sequential and delayed (24 h drug-free) schedules in IGROV-1 and ES-2 cells. Olaparib and niraparib enhanced VE-821 cytotoxicity only in co-exposed cells and not in sequential exposures. These data have clinical implications for the scheduling of PARPi as a monotherapy and in combination with ATR inhibitors and other cytotoxic drugs.
Update on Immune Mechanisms in Hypertension Navaneethabalakrishnan, Shobana; Smith, Hannah L; Arenaz, Cristina M ...
American journal of hypertension,
10/2022, Volume:
35, Issue:
10
Journal Article
Peer reviewed
Open access
Abstract
The contribution of immune cells in the initiation and maintenance of hypertension is undeniable. Several studies have established the association between hypertension, inflammation, and ...immune cells from the innate and adaptive immune systems. Here, we provide an update to our 2017 American Journal of Hypertension review on the overview of the cellular immune responses involved in hypertension. Further, we discuss the activation of immune cells and their contribution to the pathogenesis of hypertension in different in vivo models. We also highlight existing gaps in the field of hypertension that need attention. The main goal of this review is to provide a knowledge base for translational research to develop therapeutic strategies that can improve cardiovascular health in humans.
Graphical Abstract
Graphical Abstract
Since the passage of the Farm Bill in 2018, the availability of synthetic tetrahydrocannabinols has increased, including delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and ...tetrahydrocannabinol-O acetate. The objective of this study is to investigate the characteristics of delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate exposures reported to United States poison centers from 2021 to 2022.
National Poison Data System data were analyzed, including year, individual demographics, substance category and type, reason for exposure, highest level of health care received, and medical outcome. United States Census Bureau data were used to calculate population-based rates.
There were 5,022 reported cases involving delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate as the primary substance reported to United States poison centers from 1 January 2021 to 31 December 2022. The rate of exposure per 100,000 United States population increased by 89.1 percent from 0.55 in 2021 to 1.04 in 2022. Children less than 6 years old accounted for 30.1 percent of cases, with a mode at age 2 years (representing 8.9 percent of cases). Most cases involved delta-8 tetrahydrocannabinol (98.1 percent), were single-substance exposures (94.3 percent), or occurred in a residence (95.9 percent). Ingestions accounted for 94.2 percent of cases, including 95.1 percent among children less than 6 years old. The leading reason for exposure was unintentional-general (40.2 percent), followed by abuse (33.1 percent). The most common related clinical effects were mild central nervous system depression (25.0 percent), tachycardia (23.0 percent), and agitation (15.6 percent). More than one-third (38.4 percent) of cases experienced a serious medical outcome, and 10.3 percent were admitted to a noncritical care unit and 5.3 percent to a critical care unit.
The National Poison Data System is limited by its passive surveillance design. Delta-8 tetrahydrocannabinol, delta-10 tetrahydrocannabinol, and tetrahydrocannabinol-O acetate have toxic effects, and reports to United States poison centers increased from 2021 to 2022. Unintentional ingestions by young children are of particular concern.
Opportunities exist to improve regulation, with accompanying enforcement, of these products and to educate the public about their potential toxicity.
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