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Uncertainty in hydrological modeling is of significant concern due to its effects on prediction and subsequent application in watershed management. Similar to other distributed hydrological models, model uncertainty is an issue in applying the Soil and Water Assessment Tool (SWAT). Previous research has shown how SWAT predictions are affected by uncertainty in parameter estimation and input data resolution. Nevertheless, little information is available on how parameter uncertainty and output uncertainty are affected by input data of varying complexity. In this study, SWAT-Hillslope (SWAT-HS), a modified version of SWAT capable of predicting saturation-excess runoff, was applied to assess the effects of input data with varying degrees of complexity on parameter uncertainty and output uncertainty. Four digital elevation model (DEM) resolutions (1, 3, 10 and 30 m) were tested for their ability to predict streamflow and saturated areas. In a second analysis, three soil maps and three land use maps were used to build nine SWAT-HS setups from simple to complex (fewer to more soil types/land use classes), which were then compared to study the effect of input data complexity on model prediction/output uncertainty. The case study was the Town Brook watershed in the upper reaches of the West Branch Delaware River in the Catskill region, New York, USA. Results show that DEM resolution did not impact parameter uncertainty or affect the simulation of streamflow at the watershed outlet but significantly affected the spatial pattern of saturated areas, with 10m being the most appropriate grid size to use for our application. The comparison of nine model setups revealed that input data complexity did not affect parameter uncertainty. Model setups using intermediate soil/land use specifications were slightly better than the ones using simple information, while the most complex setup did not show any improvement from the intermediate ones. We conclude that improving input resolution and complexity may not necessarily improve model performance or reduce parameter and output uncertainty, but using multiple temporal and spatial observations can aid in finding the appropriate parameter sets and in reducing prediction/output uncertainty.

Background: Disaster education for nurses at all levels is imperative to improve the ability for communities to be prepared to respond and recover from disasters and public health emergencies. A variety of educational strategies are available to deliver this vital content. Method: A variety of strategies to deliver necessary disaster nursing education are discussed. The development of online disaster response modules for nurses at all levels from nursing student through advanced practice, delivered via a learning management system is described along with standard approaches to disaster content delivery. Results: All methods of teaching disaster nursing competencies are valued. Conclusion: Through the effective online approach, nurses can receive disaster management training at the time and location that is most comfortable and convenient for them, thus increasing the potential to train more nurses in this important content area. [J Nurs Educ. 2024;63(X):XXX–XXX.]

We quantified genome-wide patterns of lysine H3K27 acetylation (H3K27ac) in entorhinal cortex samples from Alzheimer’s disease (AD) cases and matched controls using chromatin immunoprecipitation and highly parallel sequencing. We observed widespread acetylomic variation associated with AD neuropathology, identifying 4,162 differential peaks (false discovery rate < 0.05) between AD cases and controls. Differentially acetylated peaks were enriched in disease-related biological pathways and included regions annotated to genes involved in the progression of amyloid-β and tau pathology (for example, APP, PSEN1, PSEN2, and MAPT), as well as regions containing variants associated with sporadic late-onset AD. Partitioned heritability analysis highlighted a highly significant enrichment of AD risk variants in entorhinal cortex H3K27ac peak regions. AD-associated variable H3K27ac was associated with transcriptional variation at proximal genes including CR1, GPR22, KMO, PIM3, PSEN1, and RGCC. In addition to identifying molecular pathways associated with AD neuropathology, we present a framework for genome-wide studies of histone modifications in complex disease.

Background Variation in locomotor capacity among animals often reflects adaptations to different environments. Despite evidence that physical performance is heritable, the molecular basis of locomotor performance and performance trade-offs remains poorly understood. In this study we identify the genes, signaling pathways, and regulatory processes possibly responsible for the trade-off between burst performance and endurance observed in Xenopus allofraseri , using a transcriptomic approach. Results We obtained a total of about 121 million paired-end reads from Illumina RNA sequencing and analyzed 218,541 transcripts obtained from a de novo assembly. We identified 109 transcripts with a significant differential expression between endurant and burst performant individuals (FDR ≤ 0.05 and logFC ≥2), and blast searches resulted in 103 protein-coding genes. We found major differences between endurant and burst-performant individuals in the expression of genes involved in the polymerization and ATPase activity of actin filaments, cellular trafficking, proteoglycans and extracellular proteins secreted, lipid metabolism, mitochondrial activity and regulators of signaling cascades. Remarkably, we revealed transcript isoforms of key genes with functions in metabolism, apoptosis, nuclear export and as a transcriptional corepressor, expressed in either burst-performant or endurant individuals. Lastly, we find two up-regulated transcripts in burst-performant individuals that correspond to the expression of myosin-binding protein C fast-type ( mybpc2 ). This suggests the presence of mybpc2 homoeologs and may have been favored by selection to permit fast and powerful locomotion. Conclusion These results suggest that the differential expression of genes belonging to the pathways of calcium signaling, endoplasmic reticulum stress responses and striated muscle contraction, in addition to the use of alternative splicing and effectors of cellular activity underlie locomotor performance trade-offs. Ultimately, our transcriptomic analysis offers new perspectives for future analyses of the role of single nucleotide variants, homoeology and alternative splicing in the evolution of locomotor performance trade-offs.

The long-read sequencers from Pacific Bioscience (PacBio) and Oxford Nanopore Technologies (ONT) offer the opportunity to phase mutations multiple kilobases apart directly from sequencing reads. In this study, we used long-range PCR with ONT and PacBio sequencing to phase two variants 9 kb apart in the RET gene. We also re-analysed data from a recent paper which had apparently successfully used ONT to phase clinically important haplotypes at the CYP2D6 and HLA loci. From these analyses, we demonstrate PCR-chimera formation during PCR amplification and reference alignment bias are pitfalls that need to be considered when attempting to phase variants using amplicon-based long-read sequencing technologies. These methodological pitfalls need to be avoided if the opportunities provided by long-read sequencers are to be fully exploited.

Seasonal behavior is important for fitness in temperate environments but it is unclear how progeny gain their initial seasonal entrainment. Plants use temperature signals to measure time of year, and changes to life histories are therefore an important consequence of climate change. Here we show that in Arabidopsis the current and prior temperature experience of the mother plant is used to control germination of progeny seeds, via the activation of the florigen Flowering Locus T (FT) in fruit tissues. We demonstrate that maternal past and current temperature experience are transduced to the FT locus in silique phloem. In turn, FT controls seed dormancy through inhibition of proanthocyanidin synthesis in fruits, resulting in altered seed coat tannin content. Our data reveal that maternal temperature history is integrated through FT in the fruit to generate a metabolic signal that entrains the behavior of progeny seeds according to time of year. Significance Seed behavior is known to be highly dependent on the temperature during seed set, but the mechanism is poorly understood. Here we show that the mother plant plays a central role in the control of progeny seed dormancy, integrating long-term temperature memories in fruit tissues using the same pathway that controls flowering time. Regulation of seed coat properties by maternal flowering time pathways effectively passes timing information across generations, aligning progeny behavior with time of year.

Background Primary hemophagocytic lymphohistiocytosis (pHLH) is a rare and life-threatening disorder, which usually occurs during infancy or early childhood and is characterized by abnormal activation of the immune system. However, the burden of pHLH on children and their families has not been previously evaluated. This qualitative study investigated the impact of pHLH and its treatment on the physical, emotional, and social well-being of patients and caregivers in the USA and UK using interviews to provide a comprehensive insight from the perspective of the caregivers and young survivors. Results Twenty-one caregivers were enrolled (median [range] age, 41.1 [26–58] years) and represented 20 patients, four from the UK and 16 from the USA. At enrollment, 17 of the 20 patients were alive with a median [range] age of 12.75 [5–31] years at a mean [range] of 7.8 [0.6–11.6] years after diagnosis. In addition, four adult survivors (median [range] age, 23.3 [21–30] years) were also enrolled (total participants n = 25). From noticing initial symptoms to receiving a diagnosis, caregivers reported a mean (range) of 25.9 (0–258) months. pHLH and its treatment had a substantial and long-lasting impact on patients and caregivers, affecting their physical, emotional and social well-being, family relationships, friendships, and ability to work and study. Many of the experiences reported were negative, even after curative treatment, and some participants experienced long-lasting physical and emotional issues. The most noticeable impact of pHLH for patients was on their physical well-being, whereas for caregivers it was emotional well-being. Across all participants there was a sense of isolation due to the illness and its treatment, particularly regarding the patient being immunocompromised and the fear of infection. Areas having a major impact and considered in need of improvement included: delays in diagnosis, lack of patient-specific information on pHLH and a lack of support and understanding about the condition. Conclusions pHLH placed a substantial burden on patients and caregivers, which for some were long-lasting. This was compounded by the lack of awareness and understanding of pHLH by healthcare professionals, and a lack of accessible information for those affected by pHLH.