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Coastal Louisiana has lost about 5,000 km 2 of wetlands over the past century and concern exists whether remaining wetlands will persist while facing some of the world’s highest rates of relative sea-level rise (RSLR). Here we analyse an unprecedented data set derived from 274 rod surface-elevation table-marker horizon stations, to determine present-day surface-elevation change, vertical accretion and shallow subsidence rates. Comparison of vertical accretion rates with RSLR rates at the land surface (present-day RSLR rates are 12±8 mm per year) shows that 65% of wetlands in the Mississippi Delta (SE Louisiana) may keep pace with RSLR, whereas 58% of the sites in the Chenier Plain (SW Louisiana) do not, rendering much of this area highly vulnerable to RLSR. At least 60% of the total subsidence rate occurs within the uppermost 5–10 m, which may account for the higher vulnerability of coastal Louisiana wetlands compared to their counterparts elsewhere. Coastal Louisiana wetlands face some of the world’s highest rates of relative sea-level rise and loss. Here, the authors show that there is a strong regional component to coastal Louisiana wetland vulnerability to relative sea-level rise as well as contributing to the understanding of subsidence in the region.

Accurate high-resolution runoff predictions are essential for effective flood mitigation and water planning. In hydrology, conceptual models are preferred for their simplicity, despite their limited capacity for accurate predictions. Deep-learning applications have recently shown promise for runoff predictions; however, they usually require longer input data sequences, especially for high-temporal resolution simulations, thus leading to increased model complexity. To address these challenges, this study evaluates the robustness of two novel approaches using Long Short-Term Memory (LSTM) models. The first model integrates the outputs of a simple conceptual model with LSTM capabilities, while the second model is a stand-alone model that combines coarse and fine temporal inputs to capture both long and short dependencies. To ensure accuracy and reliability, we utilized a century-long meteorological dataset generated from a sophisticated physics-based model, eliminating any influence of measurement errors. The training phase employed multiple sub-periods ranging from 7- to 50-year, with a separate 50-year subset for validation. Our findings highlight the consistent improvement of both LSTM models with increasing training dataset lengths, while conceptual models show no notable enhancement beyond 15 years of training data. Both LSTM models demonstrate superior performance in capturing the reference flow duration curve, offering a promising pathway for more computationally efficient models for runoff predictions.

Studying the centennial or millennial timescale response of large rivers to changing patterns in precipitation, discharge, flood intensity and recurrence, and associated sediment erosion is critical for understanding long‐term fluvial geomorphic adjustment to climate. Long hydrographs, maintaining reliable Flow Duration Curves (FDCs), are a fundamental input for such simulations; however, recorded discharge series rarely span more than a few decades. The absence of robust methodologies for generating representative long‐term hydrographs, especially those incorporating coarse temporal resolution or lacking continuous simulations, is therefore a fundamental challenge for climate resilience. We present a novel approach for constructing multi‐century hydrographs that successfully conserve the statistical, especially frequency analysis, and stochastic characteristics of observed hydrographs. This approach integrates a powerful combination of a weather generator with a fine disaggregation technique and a continuous rainfall‐runoff transformation model. We tested our approach to generate a statistically representative 300‐year hydrograph on the Ninnescah River Basin in Kansas, using a satellite precipitation data set to address the considerable gaps in the available hourly observed data sets. This approach emphasizes the similarities of FDCs between the observed and generated hydrographs, exhibiting a reasonably acceptable range of average absolute deviation between 6% and 18%. We extended this methodology to create projected high‐resolution hydrographs based on a range of climate change scenarios. The projected outcomes present pronounced increases in the FDCs compared to the current condition, especially for more distant futures, which necessitates more efficient adaptation strategies. This approach represents a paradigm shift in long‐term hydrologic modeling. Plain Language Summary River hydrographs are key inputs for understanding long term Earth surface processes. Due to the limited lengths of observational streamflow records, various techniques were previously developed with limited capabilities to generate representative long hydrographs. Through a novel integrated approach, we are able to construct robust high‐resolution hydrographs on multi‐century timescales, based on developing a linkage between hydroclimatic forces and watershed characteristics within a stochastic framework. We used this methodology to generate a 300‐year high‐resolution hydrograph with satisfactory correlation with the observed FDC. Due to the stochastic background of this framework, the deviation between the observed and generated FDCs was estimated to fall within a reasonable range of 6% and 18%. This framework was extended to provide hourly runoff projections for several future climatic models. Median projections for the near‐term period 2040–2069 demonstrated less deviation from reference data set compared to those for the more distant future 2070–2099. This study represents a scientific shift for long‐term simulations through re‐constructing past, simulating present, or projecting future hydrographs. Key Points Introducing a novel framework designed to generate statistically robust hydrographs on multi‐century timescales for long‐term simulations Integrating a weather generator and a disaggregation technique within a rainfall runoff model to achieve high‐temporal resolution hydrographs Utilizing multiple climate models to evaluate the impacts of climate change on hourly runoff responses

In patients with nonobstructive HCM, mavacamten did not significantly improve peak oxygen uptake or decrease symptoms as compared with placebo, and more patients had a reduction in LVEF with mavacamten.

Background Plasmodium vivax is the second most prevalent cause of malaria yet remains challenging to study due to the lack of a continuous in vitro culture system, highlighting the need to establish a biobank of clinical isolates with multiple freezes per sample for use in functional assays. Different methods for cryopreserving parasite isolates were compared and subsequently the most promising one was validated. Enrichment of early- and late-stage parasites and parasite maturation were quantified to facilitate assay planning. Methods In order to compare cryopreservation protocols, nine clinical P. vivax isolates were frozen with four glycerolyte-based mixtures. Parasite recovery post thaw, post KCl-Percoll enrichment and in short-term in vitro culture was measured via slide microscopy. Enrichment of late-stage parasites by magnetic activated cell sorting (MACS) was measured. Short and long-term storage of parasites at either − 80 °C or liquid nitrogen were also compared. Results Of the four cryopreservation mixtures, one mixture (glycerolyte:serum:RBC at a 2.5:1.5:1 ratio) resulted in improved parasite recovery and statistically significant (P < 0.05) enhancement in parasite survival in short-term in vitro culture. A parasite biobank was subsequently generated using this protocol resulting in a collection of 106 clinical isolates, each with 8 vials. The quality of the biobank was validated by measuring several factors from 47 thaws: the average reduction in parasitaemia post-thaw (25.3%); the average fold enrichment post KCl-Percoll (6.65-fold); and the average percent recovery of parasites (22.0%, measured from 30 isolates). During short-term in vitro culture, robust maturation of ring stage parasites to later stages (> 20% trophozoites, schizonts and gametocytes) was observed in 60.0% of isolates by 48 h. Enrichment of mature parasite stages via MACS showed good reproducibility, with an average of 30.0% post-MACS parasitaemia and an average of 5.30 × 10 5 parasites/vial. Finally, the effect of storage temperature was tested, and no large impacts from short-term (7 days) or long-term (7–10 years) storage at − 80 °C on parasite recovery, enrichment or viability was observed. Conclusions Here, an optimized freezing method for P. vivax clinical isolates is demonstrated as a template for the generation and validation of a parasite biobank for use in functional assays.

Introduction: MET Exon 14 skipping alterations are drivers of non-small cell lung carcinoma (NSCLC) with responses to tyrosine kinase inhibitors. Amplicon-based DNA NGS assays (DNA NGSs) for the detection of METex14 skipping can yield false-negative results. We examined the efficacy of METex14 skipping with a DNA NGS and reflex RNA-based NGS (RNA NGS) strategy. Materials and Methods: Clinical cases with definitive or suspected lung adenocarcinoma (LungCa), lacking driver mutations with targeted DNA NGS, underwent the RNA NGS to identify oncogenic drivers. Samples with METex14 skipping identified on reflex RNA NGSs were confirmed with Sanger sequencing. Results:METex14 skipping events were detected in 22/762 (2.9%) samples by DNA NGS. RNA NGS identified 10 additional samples, for an overall frequency of 32/762 (4.1%). All 22 METex14 DNA variants affected the donor splice site. Sanger sequencing revealed that missed METex14 variants were largely deletions spanning the ~30 bp intronic region upstream of the splice acceptor site. The failure of DNA NGS to detect all METex14 mutants was due to a lack of coverage of the 3′ splice acceptor site of intron 13, branch point, and polypyrimidine tract. Conclusions: Modification of amplicon-based DNA hotspot assays, with primers that cover both donor and acceptor splice sites, can identify a larger number of METex14 skipping events. Clinical data show that patients with advanced NSCLC and METex14 variants responded to targeted therapy.

Background Malaria remains an important cause of morbidity and mortality in India. Though many comprehensive studies have been carried out in Africa and Southeast Asia to characterize and examine determinants of Plasmodium falciparum and Plasmodium vivax malaria pathogenesis, fewer have been conducted in India. Methods A prospective study of malaria-positive individuals was conducted at Goa Medical College and Hospital (GMC) from 2012 to 2015 to identify demographic, diagnostic and clinical indicators associated with P. falciparum and P. vivax infection on univariate analysis. Results Between 2012 and 2015, 74,571 febrile individuals, 6287 (8.4%) of whom were malaria positive, presented to GMC. The total number of malaria cases at GMC increased more than two-fold over four years, with both P. vivax and P. falciparum cases present year-round. Some 1116 malaria-positive individuals (mean age = 27, 91% male), 88.2% of whom were born outside of Goa and 51% of whom were construction workers, were enroled in the study. Of 1088 confirmed malaria-positive patients, 77.0% had P. vivax, 21.0% had P. falciparum and 2.0% had mixed malaria. Patients over 40 years of age and with P. falciparum infection were significantly ( p  < 0.001) more likely to be hospitalised than younger and P. vivax patients, respectively. While approximately equal percentages of hospitalised P. falciparum (76.6%) and P. vivax (78.9%) cases presented with at least one WHO severity indicator, a greater percentage of P. falciparum inpatients presented with at least two (43.9%, p  < 0.05) and at least three (29.9%, p  < 0.01) severity features. There were six deaths among the 182 hospitalised malaria positive patients, all of whom had P. falciparum. Conclusion During the four year study period at GMC, the number of malaria cases increased substantially and the greatest burden of severe disease was contributed by P. falciparum .

Plasmodium vivax is the second most prevalent cause of malaria yet remains challenging to study due to the lack of a continuous in vitro culture system, highlighting the need to establish a biobank of clinical isolates with multiple freezes per sample for use in functional assays. Different methods for cryopreserving parasite isolates were compared and subsequently the most promising one was validated. Enrichment of early- and late-stage parasites and parasite maturation were quantified to facilitate assay planning.BackgroundPlasmodium vivax is the second most prevalent cause of malaria yet remains challenging to study due to the lack of a continuous in vitro culture system, highlighting the need to establish a biobank of clinical isolates with multiple freezes per sample for use in functional assays. Different methods for cryopreserving parasite isolates were compared and subsequently the most promising one was validated. Enrichment of early- and late-stage parasites and parasite maturation were quantified to facilitate assay planning.In order to compare cryopreservation protocols, nine clinical P. vivax isolates were frozen with four glycerolyte-based mixtures. Parasite recovery post thaw, post KCl-Percoll enrichment and in short-term in vitro culture was measured via slide microscopy. Enrichment of late-stage parasites by magnetic activated cell sorting (MACS) was measured. Short and long-term storage of parasites at either -80°C or liquid nitrogen were also compared.MethodsIn order to compare cryopreservation protocols, nine clinical P. vivax isolates were frozen with four glycerolyte-based mixtures. Parasite recovery post thaw, post KCl-Percoll enrichment and in short-term in vitro culture was measured via slide microscopy. Enrichment of late-stage parasites by magnetic activated cell sorting (MACS) was measured. Short and long-term storage of parasites at either -80°C or liquid nitrogen were also compared.Of the four cryopreservation mixtures, one mixture (glycerolyte:serum:RBC at a 2.5:1.5:1 ratio) resulted in improved parasite recovery and statistically significant (P<0.05) enhancement in parasite survival in short-term in vitro culture. A parasite biobank was subsequently generated using this protocol resulting in a collection with 106 clinical isolates, each with 8 vials. The quality of the biobank was validated by measuring several factors from 47 thaws: the average reduction in parasitemia post-thaw (25.3%); the average fold enrichment post KCl-Percoll (6.65-fold); and the average percent recovery of parasites (22.0%, measured from 30 isolates). During short-term in vitro culture, robust maturation of ring stage parasites to later stages (>20% trophozoites, schizonts and gametocytes) was observed in 60.0% of isolates by 48 hours. Enrichment of mature parasite stages via MACS showed good reproducibility, with an average 30.0% post-MACS parasitemia and an average 5.30 × 10 5 parasites/vial. Finally, the effect of storage temperature was tested, and no large impacts from short-term (7 day) or long term (7 - 10 year) storage at -80°C on parasite recovery, enrichment or viability was observed.ResultsOf the four cryopreservation mixtures, one mixture (glycerolyte:serum:RBC at a 2.5:1.5:1 ratio) resulted in improved parasite recovery and statistically significant (P<0.05) enhancement in parasite survival in short-term in vitro culture. A parasite biobank was subsequently generated using this protocol resulting in a collection with 106 clinical isolates, each with 8 vials. The quality of the biobank was validated by measuring several factors from 47 thaws: the average reduction in parasitemia post-thaw (25.3%); the average fold enrichment post KCl-Percoll (6.65-fold); and the average percent recovery of parasites (22.0%, measured from 30 isolates). During short-term in vitro culture, robust maturation of ring stage parasites to later stages (>20% trophozoites, schizonts and gametocytes) was observed in 60.0% of isolates by 48 hours. Enrichment of mature parasite stages via MACS showed good reproducibility, with an average 30.0% post-MACS parasitemia and an average 5.30 × 10 5 parasites/vial. Finally, the effect of storage temperature was tested, and no large impacts from short-term (7 day) or long term (7 - 10 year) storage at -80°C on parasite recovery, enrichment or viability was observed.Here, an optimized freezing method for P. vivax clinical isolates is demonstrated as a template for the generation and validation of a parasite biobank for use in functional assays.ConclusionsHere, an optimized freezing method for P. vivax clinical isolates is demonstrated as a template for the generation and validation of a parasite biobank for use in functional assays.