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201 result(s) for "Beck, Nicole"
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Modeling the impact of future rainfall changes on the effectiveness of urban stormwater control measures
The convergence of urban expansion, deteriorating infrastructure, and a changing climate will escalate the risks of stormwater pollution and urban flooding in the coming decades. Using outputs from an ensemble of global climate models to drive a high spatial resolution stormwater model, we analyzed climate change impacts on urban stormwater runoff and control measures for 23 cities across the United States. Runoff model outputs for two future emissions scenarios ending in 2055 were compared against a historical scenario to assess changes. All cities showed increases in average annual stormwater runoff, with changes up to 30% over the next 30 years due to a greater frequency of high intensity storm events. Runoff model outputs showed substantial variation across cities with untreated stormwater runoff increasing by as much as 48%. Patterns of future runoff impacts within cities will affect the performance of distributed treatment strategies such as Green Stormwater Infrastructure (GSI) to meet municipal water quality improvement and runoff reduction goals. Results indicate that adoption of adaptable design standards and decision support tools that readily accommodate projected precipitation changes are critical for supporting more resilient designs of stormwater control measures.
Congenital heart disease risk loci identified by genome-wide association study in European patients
Genetic factors undoubtedly affect the development of congenital heart disease (CHD) but still remain ill defined. We sought to identify genetic risk factors associated with CHD and to accomplish a functional analysis of SNP-carrying genes. We performed a genome-wide association study (GWAS) of 4034 White patients with CHD and 8486 healthy controls. One SNP on chromosome 5q22.2 reached genome-wide significance across all CHD phenotypes and was also indicative for septal defects. One region on chromosome 20p12.1 pointing to the MACROD2 locus identified 4 highly significant SNPs in patients with transposition of the great arteries (TGA). Three highly significant risk variants on chromosome 17q21.32 within the GOSR2 locus were detected in patients with anomalies of thoracic arteries and veins (ATAV). Genetic variants associated with ATAV are suggested to influence the expression of WNT3, and the variant rs870142 related to septal defects is proposed to influence the expression of MSX1. We analyzed the expression of all 4 genes during cardiac differentiation of human and murine induced pluripotent stem cells in vitro and by single-cell RNA-Seq analyses of developing murine and human hearts. Our data show that MACROD2, GOSR2, WNT3, and MSX1 play an essential functional role in heart development at the embryonic and newborn stages.
Aggrecan: a new biomarker for acute type A aortic dissection
Acute type A aortic dissection (ATAAD) constitutes a life-threatening aortic pathology with significant morbidity and mortality. Without surgical intervention the usual mortality rate averages between 1 and 2% per hour. Thus, an early diagnosis of ATAAD is of pivotal importance to direct the affected patients to the appropriate treatment. Preceding tests to find an appropriate biomarker showed among others an increased aggrecan (ACAN) mRNA expression in aortic tissue of ATAAD patients. As a consequence, we investigated whether ACAN is a potential biomarker for diagnosing ATAAD. Mean ACAN protein concentration showed a significantly higher plasma concentration in ATAAD patients (38.59 ng/mL, n = 33) compared to plasma of patients with thoracic aortic aneurysms (4.45 ng/mL, n = 13), patients with myocardial infarction (11.77 ng/mL, n = 18) and healthy volunteers (8.05 ng/mL, n = 12). Cardiac enzymes like creatine kinase MB and cardiac troponin T showed no correlation with ACAN levels in ATAAD patients. Receiver-operator characteristics (ROC) curve analysis for ATAAD patients versus control subjects an optimum discrimination limit of ACAN plasma levels at 14.3 ng/mL with a corresponding sensitivity of 97% and specificity of 81%. According to our findings ACAN is a reliable potential biomarker in plasma samples to detect ATAAD with high sensitivity and specificity.
Recruiting children and young people with vision impairment for clinical research – experience from the SeeMyLife study
Background Effective participant recruitment is crucial for the success of clinical trials, yet little is known about facilitators and barriers to recruitment in pediatric populations with visual impairment. Understanding which methods yield the highest participant engagement can help optimize recruitment efforts and improve study outcomes. Thus, we assessed factors associated with recruitment in the SeeMyLife study, a European multi-center cohort study about quality of life and participation of children and young people with visual impairment. Methods Data on the perceived effectiveness of recruitment strategies were collected from principal investigators, study coordinators, clinical and research staff using an online survey. Additional information on recruitment approaches was obtained through document analysis of study-related communications, including e-mails and meeting minutes. Descriptive statistics were used to summarize recruitment rates and perceived effectiveness scores. Open-ended responses regarding recruitment challenges were analyzed thematically to identify common barriers and facilitators. Results Seventeen clinical and research staff members from six countries participated in the survey and shared their insights and experience with participant recruitment. In total, study staff reported using twelve distinct recruitment sources to enhance participant enrolment. These sources were grouped into three broad categories: healthcare settings, community engagement and educational settings, and professional and system-level approaches. The recruitment of participants using the hospital information system was perceived as the most effective recruitment strategy, used by 71% of respondents. Other highly ranked sources included pediatric visual rehabilitation centers, patient associations, and affiliated university ophthalmology departments, where staff actively presented the study to their patients and referred eligible participants. Commonly reported recruitment challenges included restrictive inclusion criteria, limited parental responsiveness, concerns about the impact of study participation on children’s well-being, and institutional barriers. Conclusions Successful strategies for enrolling children and young people with visual impairment into clinical research include direct interactions between clinical staff and families, likely due to established trust, easier identification of eligible participants, and clearer communication about the study. In contrast, recruitment approaches outside clinical care settings were perceived as less effective. These findings highlight the importance of integrating recruitment efforts within established healthcare networks when conducting pediatric vision impairment research.
Uncovering the molecular identity of cardiosphere-derived cells (CDCs) by single-cell RNA sequencing
Cardiosphere-derived cells (CDCs) generated from human cardiac biopsies have been shown to have disease-modifying bioactivity in clinical trials. Paradoxically, CDCs’ cellular origin in the heart remains elusive. We studied the molecular identity of CDCs using single-cell RNA sequencing (sc-RNAseq) in comparison to cardiac non-myocyte and non-hematopoietic cells (cardiac fibroblasts/CFs, smooth muscle cells/SMCs and endothelial cells/ECs). We identified CDCs as a distinct and mitochondria-rich cell type that shared biological similarities with non-myocyte cells but not with cardiac progenitor cells derived from human-induced pluripotent stem cells. CXCL6 emerged as a new specific marker for CDCs. By analysis of sc-RNAseq data from human right atrial biopsies in comparison with CDCs we uncovered transcriptomic similarities between CDCs and CFs. By direct comparison of infant and adult CDC sc-RNAseq data, infant CDCs revealed GO-terms associated with cardiac development. To analyze the beneficial effects of CDCs (pro-angiogenic, anti-fibrotic, anti-apoptotic), we performed functional in vitro assays with CDC-derived extracellular vesicles (EVs). CDC EVs augmented in vitro angiogenesis and did not stimulate scarring. They also reduced the expression of pro-apoptotic Bax in NRCMs. In conclusion, CDCs were disclosed as mitochondria-rich cells with unique properties but also with similarities to right atrial CFs. CDCs displayed highly proliferative, secretory and immunomodulatory properties, characteristics that can also be found in activated or inflammatory cell types. By special culture conditions, CDCs earn some bioactivities, including angiogenic potential, which might modify disease in certain disorders.
The global reach of social media in oral and maxillofacial surgery
Purpose Social media use among oral and maxillofacial surgeons (OMSs) has grown in recent years, serving as an important resource for the dissemination of medical/surgical knowledge, research, education, diplomacy, and advocacy. However, no studies have attempted to characterize the global reach of social media in OMS. Methods This study examined the profile activity, content performance, and demographic characteristics of followers from a single OMS-related Instagram account. Variables assessed include the total number of followers since the account’s inception, profile views over the selected time period, and unique media content posts, as well as likes, comments, saves, impressions, and reach for all media content posts. The top 45 countries, cities, and languages based on each follower’s geolocation and user settings were also included. Results There were 9569 followers of which 6208 (64.9%) were listed as public accounts. Of the 6208 followers with public accounts, 2496 (40.2%) were female. The countries with the most followers included the United States (31.7%), India (12.5%), Malaysia (5.3%), Mexico (4.0%), and Pakistan (3.6%). The cities with the most followers included New York, New York (8.9%), Boston, Massachusetts (5.2%), Cairo, Egypt (4.3%), Santiago, Chile (3.7%), and Karachi, Pakistan (3.5%). Conclusion OMS-related social media is uniquely positioned to facilitate global collaboration and augment the dissemination of surgical knowledge and expertise. This information is critical in understanding the distribution and demographics of the OMS workforce, trainees, and affiliates around the world.
Assessing the Feasibility of a Cloud-Based, Spatially Distributed Modeling Approach for Tracking Green Stormwater Infrastructure Runoff Reductions
Use of green stormwater infrastructure (GSI) to mitigate urban runoff impacts has grown substantially in recent decades, but municipalities often lack an integrated approach to prioritize areas for implementation, demonstrate compelling evidence of catchment-scale improvements, and communicate stormwater program effectiveness. We present a method for quantifying runoff reduction benefits associated with distributed GSI that is designed to align with the spatial scale of information required by urban stormwater implementation. The model was driven by a probabilistic representation of rainfall events to estimate annual runoff and reductions associated with distributed GSI for various design storm levels. Raster-based calculations provide estimates on a 30-m grid, preserving unique combinations of drainage factors that drive runoff production, hydrologic storage, and infiltration benefits of GSI. The model showed strong correspondence with aggregated continuous runoff data from a set of urbanized catchments in Salinas, California, USA, over a three-year monitoring period and output sensitivity to the storm drain network inputs. Because the model runs through a web browser and the parameterization is based on readily available spatial data, it is suitable for nonmodeling experts to rapidly update GSI features, compare alternative implementation scenarios, track progress toward urban runoff reduction goals, and demonstrate regulatory compliance.
B-cell intrinsic RANK signaling cooperates with TCL1 to induce lineage-dependent B-cell transformation
B-cell malignancies, such as chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), remain incurable, with MM particularly prone to relapse. Our study introduces a novel mouse model with active RANK signaling and the TCL1 oncogene, displaying both CLL and MM phenotypes. In younger mice, TCL1 and RANK expression expands CLL-like B1-lymphocytes, while MM originates from B2-cells, becoming predominant in later stages and leading to severe disease progression and mortality. The induced MM mimics human disease, exhibiting features like clonal plasma cell expansion, paraproteinemia, anemia, and kidney and bone failure, as well as critical immunosurveillance strategies that promote a tumor-supportive microenvironment. This research elucidates the differential impacts of RANK activation in B1- and B2-cells and underscores the distinct roles of single versus combined oncogenes in B-cell malignancies. We also demonstrate that human MM cells express RANK and that inhibiting RANK signaling can reduce MM progression in a xenotransplantation model. Our study provides a rationale for further investigating the effects of RANK signaling in B-cell transformation and the shaping of a tumor-promoting microenvironment.
Diel Biogeochemical Cycling in a Hyperventilating Shallow Estuarine Environment
A diel biogeochemical study was performed to assess the influence that periods of elevated biological activity have on the biogeochemical cycling of macronutrients and redox-sensitive elements in a natural estuarine environment. High-resolution data (15 min sampling) illustrates periodic extreme variations in dissolved oxygen (DO) in the shallow waters of Azevedo Pond, Elkhorn Slough, California. During periods of low tidal flushing, DO values can range from highly oxic ($>560\\ \\mu {\\rm M}\\ {\\rm O}_{2}$: > 250% saturation) during sunny days to suboxic conditions (< 5 μM) at night. Nutrient cycling and redox-sensitive trace element biogeochemistry were evaluated in response to the extreme daily DO fluctuations. A diel sampling study was conducted over a 26-h period, where O2 concentrations ranged from 346 μM to sustained non-detectable levels in the night hours. In concert with the DO fluctuations, diel phosphate cycling was on the order of 4 μM in response to tidal flushing events and biological assimilation and regeneration. The IO3-/ I- redox couple quickly responded to suboxic conditions in the water column by a marked increase in I- concentrations and corresponding depletion of IO3-. The extreme fluctuations of the pϵ in the water column resulted in diel dissolved Mn2+ variations of nearly 5 μM, with observed dissolved Mn removal rates on the order of 1 μ M h-1. The elevated biogeochemical cycling of oxygen, nitrogen, phosphorus, iodine, manganese, and iron found in this shallow estuarine environment suggest that tidal restrictions and anthropogenic nutrient enrichments can amplify diel variations and potentially hinder the functional and ecological stability of these systems. These data suggest that accurate chemical monitoring of the health of an estuarine ecosystem must account for the diel variability inherent in these highly productive environments.
Short-Term Biogeochemical Influence of a Diatom Bloom on the Nutrient and Trace Metal Concentrations in South San Francisco Bay Microcosm Experiments
Two laboratory microcosm experiments were conducted to mimic an annual spring diatom bloom in South San Francisco Bay by isolating the phytoplankton community from the benthic grazing pressure to induce a phytoplankton bloom. The purpose of these experiments was to isolate the impact of a spring diatom bloom on the nutrient and trace metal geochemical cycling. Microcosms were created in 2.5 L incubation bottles and subjected to one of 4 treatments (control, copper [Cu] addition, manganese [Mn] addition, and both Cu and Mn addition) to investigate the toxicity of Cu on the resident plankton and the potential antagonistic effects of Mn on reducing Cu toxicity. Dissolved macronutrient (nitrate + nitrite, phosphate, and silicate), and dissolved and particulate trace metal (Cu, Ni, Mn) concentrations were monitored in the grow-out incubations on a daily basis. Chlorophyll a concentrations were also monitored over the course of the experiment and used to calculate diatom-specific growth rates. In the experiments containing ambient South San Francisco Bay surface waters, average specific growth rates were on the order of 1.1 d-1. The induced diatom blooms resulted in significant removal of macronutrients from the microcosms over the course of the experiments. Our research supports previous suggestions that dissolved Ni and Cu concentrations in South San Francisco Bay have a very low biological availability as a result of organic chelation. Ni( EDTA)2- has been found to be the dominant dissolved Ni species by other researchers and Cu speciation analyses from this study and others indicate that > 99% of the dissolved Cu in South San Francisco Bay is strongly chelated as CuL1. The free cupric ion concentration was on the order of 10-12 M. Marked removal of dissolved Mn was observed in the control treatments, well exceeding expected dissolved Mn removal by diatom uptake. Additions of 375 nM Cu resulted in the complete titration of the chelating ligand ( L1) concentrations. The elevated [ Cu2+] (≈ 10-8 M) appeared to have a toxic effect on the diatom community observed in the significant decreases in their specific growth rates (μ =0.4 d-1). The suppression of dissolved Mn removal from solution was also observed in treatments spiked with high levels of dissolved Cu, providing support that Mn precipitation was due to biologically mediated oxidation not phytoplankton assimilation. The observed geochemical behavior in the concurrent Cu and Mn addition treatments provide evidence in support of Mn alleviation of Cu toxicity. The biological role in the ambient short-term biogeochemical cycling of Cu and Ni in South San Francisco Bay appears to be minimal due to the inert character of the organic ligand-metal complexes. A significant portion of the annual macronutrient and Mn cycling occurs as a result of spring diatom blooms in South San Francisco Bay.