The 2021 summer upwelling season off the United States Pacific Northwest coast was unusually strong leading to widespread near-bottom, low-oxygen waters. During summer 2021, an unprecedented number ...of ship- and underwater glider-based measurements of dissolved oxygen were made in this region. Near-bottom hypoxia, that is dissolved oxygen less than 61 µmol kg
and harmful to marine animals, was observed over nearly half of the continental shelf inshore of the 200-m isobath, covering 15,500 square kilometers. A mid-shelf ribbon with near-bottom, dissolved oxygen less than 50 µmol kg
extended for 450 km off north-central Oregon and Washington. Spatial patterns in near-bottom oxygen are related to the continental shelf width and other features of the region. Maps of near-bottom oxygen since 1950 show a consistent trend toward lower oxygen levels over time. The fraction of near-bottom water inshore of the 200-m isobath that is hypoxic on average during the summer upwelling season increases over time from nearly absent (2%) in 1950-1980, to 24% in 2009-2018, compared with 56% during the anomalously strong upwelling conditions in 2021. Widespread and increasing near-bottom hypoxia is consistent with increased upwelling-favorable wind forcing under climate change.
Mass spectrometry (MS)-based proteomic measurements are uniquely poised to impact the development of cell and gene therapies. With the adoption of rigorous instrumental performance qualifications ...(PQs), large-scale proteomics can move from a research to a manufacturing control tool. Especially suited, data-independent acquisition (DIA) approaches have distinctive qualities to extend multiattribute method (MAM) principles to characterize the proteome of cell therapies. Here, we describe the development of a DIA method for the sensitive identification and quantification of proteins on a Q-TOF instrument. Using the improved acquisition parameters, we defined a control strategy and highlighted some metrics to improve the reproducibility of SWATH acquisition-based proteomic measurements. Finally, we applied the method to analyze the proteome of Jurkat cells that here serves as a model for human T-cells. Raw and processed data were deposited in PRIDE (PXD029780).
Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high‐resolution manometry (HRM). Fifty‐two diverse international experts ...separated into seven working subgroups utilized formal validated methodologies over two‐years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ.
Key updates in the CCv4.0 include a protocol inclusive of varying positions and provocative tests, recognitions of conclusive and inconclusive patterns, requirement of clinically relevant symptoms for a conclusive diagnosis of EGJOO, distal esophageal spasm or hypercontractile esophagus, and increasingly stringent criteria for EGJOO and IEM.The classification using CCv4.0 is based on the primary position (either supine or upright), while assessment of swallows in the secondary position and with provocation provides supportive data, particularly for inconclusive settings.
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The functional lumen imaging probe (FLIP) measures luminal dimensions using impedance planimetry, performed most often during sedated upper endoscopy. Mechanical properties of the esophageal wall and ...opening dynamics of the esophagogastric junction (EGJ) can be objectively evaluated in esophageal motor disorders, eosinophilic esophagitis, esophageal strictures, during esophageal surgery and in postsurgical symptomatic states. Distensibility index, the ratio of EGJ cross sectional area to intraballoon pressure, is the most useful FLIP metric. Secondary peristalsis from balloon distension can be displayed topographically as repetitive anterograde or retrograde contractile activity in the esophageal body, similar to high-resolution manometry. Real-time interpretation and postprocessing of FLIP metadata can complement the identification of esophageal outflow obstruction and achalasia, especially when findings are inconclusive from alternate esophageal tests in symptomatic patients. FLIP can complement the diagnosis of achalasia when manometry and barium studies are inconclusive or negative in patients with typical symptoms. FLIP can direct adequacy of disruption of the EGJ in achalasia when used during and immediately after myotomy and pneumatic dilation. Lumen diameter measured using FLIP in eosinophilic esophagitis and in complex strictures can potentially guide management. An abbreviated modification of the Grading of Recommendations Assessment, Development, and Evaluation was used to determine the quality of available evidence and recommendations regarding FLIP utilization. FLIP metrics that are diagnostic or suggestive of an abnormal motor pattern and metrics that define normal esophageal physiology were developed by consensus and are described in this review.
In the California Current Ecosystem, the California Undercurrent (CU) is the predominate subsurface current that transports nutrient-rich water from southern California poleward. In this study, we ...used a large dataset of spatially explicit in situ observations of Pacific hake ( Merluccius productus) and the CU (36.5–48.3°N) to estimate relationships between northward undercurrent velocity and hake distribution and determine whether these relationships vary across space or life-history stage. We found that both hake occurrence and density had strong spatially complex relationships with the CU. In areas north of 44°N (central Oregon), the CU effect was spatially consistent and opposite for occurrence (negative) and density (positive), indicating that hake may aggregate in areas of high northward velocity in this region. In areas south of 44°N, the CU effect showed a cross-shelf gradient for both occurrence and density, indicating a more nearshore hake distribution when northward velocity is higher in this region. Together, our results suggest that future changes in the CU due to climate change are likely to impact hake differently in northern and southern areas.
Harvesting different species as foods or raw materials calls for differing skills depending on the species being harvested and the circumstances under which they are being taken. In some situations ...and for some species, the tactics used are mainly behavioral--that is, people adjust, or adapt, their own actions to fit the behavior and circumstances of the species they are taking. Under other circumstances and for other species, the skills and tactics used may call for greater environmental preparation or manipulation. Therefore, instead of trying to distinguish people today and in the past as either "foragers" or "farmers," it makes sense to define human subsistence behavior as an interactive matrix of species and harvesting tactics, that is, as a provisions spreadsheet.
A major challenge in using spins in the solid state for quantum technologies is protecting them from sources of decoherence. This is particularly important in nanodevices where the proximity of ...material interfaces, and their associated defects, can play a limiting role. Spin decoherence can be addressed to varying degrees by improving material purity or isotopic composition, for example, or active error correction methods such as dynamic decoupling (or even combinations of the two). However, a powerful method applied to trapped ions in the context of atomic clocks is the use of particular spin transitions that are inherently robust to external perturbations. Here, we show that such 'clock transitions' can be observed for electron spins in the solid state, in particular using bismuth donors in silicon. This leads to dramatic enhancements in the electron spin coherence time, exceeding seconds. We find that electron spin qubits based on clock transitions become less sensitive to the local magnetic environment, including the presence of (29)Si nuclear spins as found in natural silicon. We expect the use of such clock transitions will be of additional significance for donor spins in nanodevices, mitigating the effects of magnetic or electric field noise arising from nearby interfaces and gates.
La Clasificación de Chicago v4.0 (CCv4.0) es el esquema actualizado para clasificar las alteraciones de la motilidad esofágica utilizando la métrica de la manometría de alta resolución (HRM). Para ...desarrollar la CCv4.0, 52 expertos internacionales diversos separados en siete subgrupos de trabajo utilizaron una metodología formalmente validada, en un periodo de dos años. Las actualizaciones claves de la CCv4.0 consisten en un protocolo de HRM más riguroso y expansivo que incorpora las posiciones en decúbito supino y sedestación, así como pruebas provocadoras; una definición refinada de la obstrucción del flujo de salida de la unión esofagogástrica (EGJOO), criterios diagnósticos más estrictos para la motilidad esofágica inefectiva, y descripción de la métrica basal de la EGJ. Adicionalmente, la CCv4.0 se propuso definir el diagnóstico de alteración de la motilidad como conclusivo o no conclusivo con base en los síntomas asociados, los hallazgos en las pruebas provocadoras, y los resultados de los exámenes de apoyo como el esofagograma con tableta de bario y/o la prueba con sonda para imagen endoluminal funcional. Estos cambios buscan minimizar la ambigüedad presente en iteraciones previas de la Clasificación de Chicago; además proveen criterios más estandarizados y rigurosos para los patrones de alteración de la peristalsis y obstrucción de la EGJ.
Detection and characterization of genomic structural variation are important for understanding the landscape of genetic variation in human populations and in complex diseases such as cancer. Recent ...studies demonstrate the feasibility of detecting structural variation using next-generation, short-insert, paired-end sequencing reads. However, the utility of these reads is not entirely clear, nor are the analysis methods with which accurate detection can be achieved. The algorithm BreakDancer predicts a wide variety of structural variants including insertion-deletions (indels), inversions and translocations. We examined BreakDancer's performance in simulation, in comparison with other methods and in analyses of a sample from an individual with acute myeloid leukemia and of samples from the 1,000 Genomes trio individuals. BreakDancer sensitively and accurately detected indels ranging from 10 base pairs to 1 megabase pair that are difficult to detect via a single conventional approach.
Current therapeutic options for treating colorectal cancer have little clinical efficacy and acquired resistance during treatment is common, even following patient stratification. Understanding the ...mechanisms that promote therapy resistance may lead to the development of novel therapeutic options that complement existing treatments and improve patient outcome. Here, we identify RAC1B as an important mediator of colorectal tumourigenesis and a potential target for enhancing the efficacy of EGFR inhibitor treatment. We find that high RAC1B expression in human colorectal cancer is associated with aggressive disease and poor prognosis and deletion of Rac1b in a mouse colorectal cancer model reduces tumourigenesis. We demonstrate that RAC1B interacts with, and is required for efficient activation of the EGFR signalling pathway. Moreover, RAC1B inhibition sensitises cetuximab resistant human tumour organoids to the effects of EGFR inhibition, outlining a potential therapeutic target for improving the clinical efficacy of EGFR inhibitors in colorectal cancer.
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