Relative Sea Level Rise in the Winyah Bay-Waccamaw River Tidal System Over the Last Thirteen Years

Prediction of sea level rise (SLR) in response to climate change has been the focus of worldwide research, most focusing on the impact by human development. The research has been limited to estuaries and tidal rivers near harbors dealing with the hydrodynamics of reversing tidal flows. This article focuses on the Waccamaw River National Wildlife Refuge in coastal South Carolina where freshwater unidirectional flow is common. We examined the record of water levels in the Waccamaw and Pee Dee Rivers over the period 2007–2019 and the length of record of the United States Geographical Survey (USGS) gauge at Pawleys Island on the Waccamaw River. The Atlantic Ocean, off the southeastern coast of the US, has experienced accelerated SLR since 2000. National Oceanic and Atmosphere Administration (NOAA) tide gauges from Fort Pulaski on Cockspur Island in Georgia to Beaufort, North Carolina, show significant increase in long-term SLR since then with an average since 2007 of approximately 10 mm y-1. Since the study period was less than the 18.6-year cycle of lunar precession, tidal ranges were expanding for much of the study period resulting in the rate of rise of Mean Higher High Water (MHHW; the average of the highest tide levels during each day) being greater than the rate of increase of Mean Lower Low Water (MLLW; the average of the lowest tide levels during each day) in all ocean stations. We examined water levels at NOAA and USGS gauges from Oyster Creek, in North Inlet to Conway on the Waccamaw River and Near Bucksport on the Pee Dee River. We found mean water levels increased more rapidly with distance from the ocean with an apparent SLR \u3e 40 mm y-1 at Conway on the Waccamaw and Bucksport on the Pee Dee. In contrast to the ocean NOAA gauges, the estuary/river gauges showed more rapid increase of daily minimum water level (an approximation of MLLW) than daily maximum water level (an approximation of MHHW) with an extreme of apparent rise of minimum water levels of 58 mm y-1 at Bucksport on the Pee Dee. Nearly 50% of the increase in apparent SLR was due to an increase in the annual average freshwater flow of the Pee Dee and Waccamaw Rivers. Over the past 13 years the Waccamaw National Wildlife Refuge has experienced an apparent SLR that was more than double that observed at the edge of the ocean. The rise has been greater in the height of daily low water than in the height of daily high water. The increase was driven by both tidal hydrodynamics and an increase in the rate of flow in the Pee Dee and Waccamaw Rivers. These findings have important implications for land managers, policymakers, and homeowners in the region as people in the middle to upper estuaries need to plan for rates of relative SLR rise much greater than the frequently discussed rates in the ocean

Developing a monthly radiative kernel for surface albedo change from satellite climatologies of Earth\u27s shortwave radiation budget: CACK v1.0

Due to the potential for land-use–land-cover change (LULCC) to alter surface albedo, there is need within the LULCC science community for simple and transparent tools for predicting radiative forcings (ΔF) from surface albedo changes (Δαs). To that end, the radiative kernel technique – developed by the climate modeling community to diagnose internal feedbacks within general circulation models (GCMs) – has been adopted by the LULCC science community as a tool to perform offline ΔF calculations for Δαs. However, the codes and data behind the GCM kernels are not readily transparent, and the climatologies of the atmospheric state variables used to derive them vary widely both in time period and duration. Observation-based kernels offer an attractive alternative to GCM-based kernels and could be updated annually at relatively low costs. Here, we present a radiative kernel for surface albedo change founded on a novel, simplified parameterization of shortwave radiative transfer driven with inputs from the Clouds and the Earth\u27s Radiant Energy System (CERES) Energy Balance and Filled (EBAF) products. When constructed on a 16-year climatology (2001–2016), we find that the CERES-based albedo change kernel – or CACK – agrees remarkably well with the mean kernel of four GCMs (rRMSE = 14 %). When the novel parameterization underlying CACK is applied to emulate two of the GCM kernels using their own boundary fluxes as input, we find even greater agreement (mean rRMSE = 7.4 %), suggesting that this simple and transparent parameterization represents a credible candidate for a satellite-based alternative to GCM kernels. We document and compute the various sources of uncertainty underlying CACK and include them as part of a more extensive dataset (CACK v1.0) while providing examples showcasing its application

Hurricane Florence Flooding in Georgetown County: A Qualitative Explanation of the Interactions of Estuary and Tidal River

This paper examines data from 18 USGS gauges in the lower Pee Dee Basin in an effort to explain the behavior of the flooding following Hurricane Florence (2018) in Georgetown County, South Carolina. Despite record or near-record flooding in all the tributaries to the Winyah Bay estuary, water levels near the city of Georgetown were well below predicted heights. Floodplain storage in the lower Great Pee Dee, Lynches, and Little Pee Dee River valleys stored over 1.2 million acre-feet of floodwaters, delaying peak stage near Bucksport for five days and reducing peak flow into the Winyah Bay tidal river/estuary system by nearly 50%. An unknown amount of flow from the Winyah Bay tidal river/estuary system flowed through the Atlantic Intracoastal Water Way to Little River rather than through Winyah Bay. The resulting freshwater flow to Winyah Bay only moved the point of tidal stagnation (where upstream tidal flow balances downstream freshwater flow) to near Georgetown. Since the city of Georgetown was near the point of stagnation, water level there was driven by ocean tidal height rather than river flood stage. The lack of discharge data from the tidal rivers in Georgetown County prevents evaluation of the importance of each of these factors and will limit efforts to make quantitative predictions of future flooding in the county

Immune phenotypes that are associated with subsequent COVID-19 severity inferred from post-recovery samples

Severe COVID-19 causes profound immune perturbations, but pre-infection immune signatures contributing to severe COVID-19 remain unknown. Genome-wide association studies (GWAS) identified strong associations between severe disease and several chemokine receptors and molecules from the type I interferon pathway. Here, we define immune signatures associated with severe COVID-19 using high-dimensional flow cytometry. We measure the cells of the peripheral immune system from individuals who recovered from mild, moderate, severe or critical COVID-19 and focused only on those immune signatures returning to steady-state. Individuals that suffered from severe COVID-19 show reduced frequencies of T cell, mucosal-associated invariant T cell (MAIT) and dendritic cell (DC) subsets and altered chemokine receptor expression on several subsets, such as reduced levels of CCR1 and CCR2 on monocyte subsets. Furthermore, we find reduced frequencies of type I interferon-producing plasmacytoid DCs and altered IFNAR2 expression on several myeloid cells in individuals recovered from severe COVID-19. Thus, these data identify potential immune mechanisms contributing to severe COVID-19

Zur and zinc increase expression of E. coli ribosomal protein L31 through RNA-mediated repression of the repressor L31p

Bacteria can adapt in response to numerous stress conditions. One such stress condition is zinc depletion. The zinc-sensing transcription factor Zur regulates the way numerous bacterial species respond to severe changes in zinc availability. Under zinc sufficient conditions, Zn-loaded Zur (Zn2-Zur) is well-known to repress transcription of genes encoding zinc uptake transporters and paralogues of a few ribosomal proteins. Here, we report the discovery and mechanistic basis for the ability of Zur to up-regulate expression of the ribosomal protein L31 in response to zinc in E. coli. Through genetic mutations and reporter gene assays, we find that Zur achieves the up-regulation of L31 through a double repression cascade by which Zur first represses the transcription of L31p, a zinc-lacking paralogue of L31, which in turn represses the translation of L31. Mutational analyses show that translational repression by L31p requires an RNA hairpin structure within the l31 mRNA and involves the N-terminus of the L31p protein. This work uncovers a new genetic network that allows bacteria to respond to host-induced nutrient limiting conditions through a sophisticated ribosomal protein switching mechanism

Development and validation of Australian aphasia rehabilitation best practice statements using the RAND/UCLA appropriateness method

Objectives: To develop and validate a national set of best practice statements for use in post-stroke aphasia rehabilitation. Design: Literature review and statement validation using the RAND/UCLA Appropriateness Method (RAM). Participants: A national Community of Practice of over 250 speech pathologists, researchers, consumers and policymakers developed a framework consisting of eight areas of care in aphasia rehabilitation. This framework provided the structure for the development of a care pathway containing aphasia rehabilitation best practice statements. Nine speech pathologists with expertise in aphasia rehabilitation participated in two rounds of RAND/UCLA appropriateness ratings of the statements. Panellists consisted of researchers, service managers, clinicians and policymakers. Main outcomes measures: Statements that achieved a high level of agreement and an overall median score of 7–9 on a nine-point scale were rated as ‘appropriate’. Results: 74 best practice statements were extracted from the literature and rated across eight areas of care (eg, receiving the right referrals, providing intervention). At the end of Round 1, 71 of the 74 statements were rated as appropriate, no statements were rated as inappropriate, and three statements were rated as uncertain. All 74 statements were then rated again in the face-to-face second round. 16 statements were added through splitting existing items or adding new statements. Seven statements were deleted leaving 83 statements. Agreement was reached for 82 of the final 83 statements. Conclusions: This national set of 82 best practice statements across eight care areas for the rehabilitation of people with aphasia is the first to be validated by an expert panel. These statements form a crucial component of the Australian Aphasia Rehabilitation Pathway (AARP) (http://www.aphasiapathway.com.au) and provide the basis for more consistent implementation of evidence-based practice in stroke rehabilitation

Radiative forcing of natural forest disturbances

Forest disturbances are major sources of carbon dioxide to the atmosphere, and therefore impact global climate. Biogeophysical attributes, such as surface albedo (reflectivity), further control the climate-regulating properties of forests. Using both tower-based and remotely sensed data sets, we show that natural disturbances from wildfire, beetle outbreaks, and hurricane wind throw can significantly alter surface albedo, and the associated radiative forcing either offsets or enhances the CO2 forcing caused by reducing ecosystem carbon sequestration over multiple years. In the examined cases, the radiative forcing from albedo change is on the same order of magnitude as the CO2 forcing. The net radiative forcing resulting from these two factors leads to a local heating effect in a hurricane-damaged mangrove forest in the subtropics, and a cooling effect following wildfire and mountain pine beetle attack in boreal forests with winter snow. Although natural forest disturbances currently represent less than half of gross forest cover loss, that area will probably increase in the future under climate change, making it imperative to represent these processes accurately in global climate models

Radiation-Enhanced Therapeutic Targeting of Galectin-1 Enriched Malignant Stroma in Triple Negative Breast Cancer

Currently there are no FDA approved targeted therapies for Triple Negative Breast Cancer (TNBC). Ongoing clinical trials for TNBC have focused primarily on targeting the epithelial cancer cells. However, targeted delivery of cytotoxic payloads to the non-transformed tumor associated-endothelium can prove to be an alternate approach that is currently unexplored. The present study is supported by recent findings on elevated expression of stromal galectin-1 in clinical samples of TNBC and our ongoing findings on stromal targeting of radiation induced galectin-1 by the anginex-conjugated arsenic-cisplatin loaded liposomes using a novel murine tumor model. We demonstrate inhibition of tumor growth and metastasis in response to the multimodal nanotherapeutic strategy using a TNBC model with orthotopic tumors originating from 3D tumor tissue analogs (TTA) comprised of tumor cells, endothelial cells and fibroblasts. The ‘rigorous’ combined treatment regimen of radiation and targeted liposomes is also shown to be well tolerated. More importantly, the results presented provide a means to exploit clinically relevant radiation dose for concurrent receptor mediated enhanced delivery of chemotherapy while limiting overall toxicity. The proposed study is significant as it falls in line with developing combinatorial therapeutic approaches for stroma-directed tumor targeting using tumor models that have an appropriate representation of the TNBC microenvironment

Mechanistic interrogation of combination Bevacizumab/dual PI3K/mTOR inhibitor response in Glioblastoma implementing novel MR and PET imaging biomarkers.

Purpose: Resistance to bevacizumab (BEV) in glioblastoma (GBM) is believed to occur via activation of molecular networks including the mTOR/PI3K pathway. Implementing an MRI/PET molecular imaging biomarker approach, we sought to interrogate response to combining BEV with the mTOR/PI3K inhibitor BEZ235. Methods: Tumors were established by orthotopically implanting U87MG-luc2 in mice. Animals were treated with BEZ235 and/or BEV, and imaged using diffusion weighted-MRI, T2 weighted (T2w), and T2* weighted (T2*w) before and following delivery of superparamagnetic iron oxide (SPIO) contrast. Maps for changes in relaxation rates: ΔR2, ΔR2* and apparent diffusion coefficient (ADC) were calculated. Vessel Size Index (VSI) and micro vessel density index (MDI) were derived. 3´-deoxy-3´-[18F]fluorothymidine ([18F]FLT)- and O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) PET was further performed and tumor endothelium/proliferation markers assessed by immunohistochemistry. Results: Treatment with BEV resulted in a pronounced decrease in tumor volume (T2w MRI). No additive effect on tumour volume was observed in BEV/BEZ235 combination compared with BEV monotherapy. Ki67 proliferation index staining and [18F]FLT uptake studies were used to support observations. Using ΔR2* and ΔR2 values respectively, BEZ235 + BEV combination significantly reduced tumor microvessel volume in comparison to BEV alone. Decreased MDI was further observed in the combination group; supported by von Willebrand Factor (vWF) immunohistochemistry. We observed decreased [18F]FET uptake following BEV, but failed to observe further reduced [18F]FET uptake in the combination cohort. vWF IHC analysis showed mean tumor vessel size increased in all cohorts. Conclusions: Assessing MR imaging biomarker parameters together with [18F]FET and [18F]FLT PET, informed drug combination mechanism of action and provided clues as to potential clinical response. Translation of a BEZ35/BEV combination regimen could support reduction of peritumoral edemaobviating the requirement for steroids. Implementing hypothesis driven molecular imaging studies facilitates the interrogation of drug response in the pre-clinic. These data may more accurately predict the clinical potential of novel therapeutic approaches in oncology

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial

IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19. OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. INTERVENTIONS: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). MAIN OUTCOMES AND MEASURES: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. RESULTS: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. CONCLUSIONS AND RELEVANCE: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04593940