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The electrical conductivity of the ocean is a fundamental parameter in the electrodynamics of the Earth System. This parameter is involved in a number of applications ranging from the calibration of in situ ocean flow meters, through extensions of traditional induction studies, and into quite new opportunities involving the remote sensing of ocean flow and properties from space-borne magnetometers such as carried aboard the three satellites of the Swarm mission launched in 2013. Here, the first ocean conductivity data set calculated directly from observed temperature and salinity measurements is provided. These data describe the globally gridded, three-dimensional mean conductivity as well as seasonal variations, and the statistics of spatial and seasonal variations are shown. This “climatology” data set of ocean conductivity is offered as a standard reference similar to the ocean temperature and salinity climatologies that have long been available.

Climatologies, which depict mean fields of oceanographic variables on a regular geographic grid, and atlases, which provide graphical depictions of specific areas, play pivotal roles in comprehending the societal vulnerabilities linked to ocean acidification (OA). This significance is particularly pronounced in coastal regions where most economic activities, such as commercial and recreational fisheries and aquaculture industries, occur. In this paper, we unveil a comprehensive data product featuring coastal ocean acidification climatologies and atlases, encompassing the fugacity of carbon dioxide, pH on the total scale, total hydrogen ion content, free hydrogen ion content, carbonate ion content, aragonite saturation state, calcite saturation state, Revelle factor, total dissolved inorganic carbon content, and total alkalinity content. These variables are provided on 1° × 1° spatial grids at 14 standardized depth levels, ranging from the surface to a depth of 500 m, along the North American ocean margins, defined as the region between the coastline and a distance of 200 nautical miles (∼370 km) offshore. The climatologies and atlases were developed using the World Ocean Atlas (WOA) gridding methods of the NOAA National Centers for Environmental Information (NCEI) based on the recently released Coastal Ocean Data Analysis Product in North America (CODAP-NA), along with the 2021 update to the Global Ocean Data Analysis Project version 2 (GLODAPv2.2021) data product. The relevant variables were adjusted to the index year of 2010. The data product is available in NetCDF (https://doi.org/10.25921/g8pb-zy76, Jiang et al., 2022b) on the NOAA Ocean Carbon and Acidification Data System: https://www.ncei.noaa.gov/data/oceans/ncei/ocads/metadata/0270962.html (last access: 15 July 2024). It is recommended to use the objectively analyzed mean fields (with “_an” suffix) for each variable. The atlases can be accessed at https://www.ncei.noaa.gov/access/ocean-carbon-acidification-data-system/synthesis/nacoastal.html (last access: 15 July 2024).

The World Ocean Database (WOD) contains over 1.3 million oceanographic casts (where cast refers to an oceanographic profile or set of profiles collected concurrently at more than one depth between the ocean surface and ocean bottom) collected in the Arctic Ocean basin and its surrounding marginal seas. The data, collected from 1849 to the present, come from many submitters and countries, and were collected using a variety of instruments and platforms. These data, along with the derived products World Ocean Atlas (WOA) and the Arctic Regional Climatologies, are exceptionally useful – the data are presented in a standardized, easy to use format and include metadata and quality control information. Collecting data in the Arctic Ocean is challenging, and coverage in space and time ranges from excellent to nearly non-existent. WOD continues to compile a comprehensive collection of Arctic Ocean profile data, ideal for oceanographic, environmental and climatic analyses (https://doi.org/10.7289/V54Q7S16).

Using human evaluation of 100,000 words spread across 24 corpora in 10 languages diverse in origin and culture, we present evidence of a deep imprint of human sociality in language, observing that ( i ) the words of natural human language possess a universal positivity bias, ( ii ) the estimated emotional content of words is consistent between languages under translation, and ( iii ) this positivity bias is strongly independent of frequency of word use. Alongside these general regularities, we describe interlanguage variations in the emotional spectrum of languages that allow us to rank corpora. We also show how our word evaluations can be used to construct physical-like instruments for both real-time and offline measurement of the emotional content of large-scale texts. Significance The most commonly used words of 24 corpora across 10 diverse human languages exhibit a clear positive bias, a big data confirmation of the Pollyanna hypothesis. The study’s findings are based on 5 million individual human scores and pave the way for the development of powerful language-based tools for measuring emotion.

Vaccines are urgently needed to combat the global coronavirus disease 2019 (COVID-19) pandemic, and testing of candidate vaccines in an appropriate non-human primate (NHP) model is a critical step in the process. Infection of African green monkeys (AGM) with a low passage human isolate of SARS-CoV-2 by aerosol or mucosal exposure resulted in mild clinical infection with a transient decrease in lung tidal volume. Imaging with human clinical-grade 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) co-registered with computed tomography (CT) revealed pulmonary lesions at 4 days post-infection (dpi) that resolved over time. Infectious virus was shed from both respiratory and gastrointestinal (GI) tracts in all animals in a biphasic manner, first between 2-7 dpi followed by a recrudescence at 14-21 dpi. Viral RNA (vRNA) was found throughout both respiratory and gastrointestinal systems at necropsy with higher levels of vRNA found within the GI tract tissues. All animals seroconverted simultaneously for IgM and IgG, which has also been documented in human COVID-19 cases. Young AGM represent an species to study mild/subclinical COVID-19 disease and with possible insights into live virus shedding. Future vaccine evaluation can be performed in AGM with correlates of efficacy being lung lesions by PET/CT, virus shedding, and tissue viral load.

Patients with relapsed or refractory large B-cell lymphoma after first-line treatment who are not intended for haematopoietic stem-cell transplantation (HSCT) have poor outcomes and limited treatment options. We assessed the antitumour activity and safety of lisocabtagene maraleucel, an autologous, CD19-directed chimeric antigen receptor (CAR) T-cell product, as second-line treatment in adults with relapsed or refractory large B-cell lymphoma not intended for HSCT. PILOT, an open-label, phase 2 trial done at 18 clinical sites in the USA, included adults aged 18 years or older who had relapsed or refractory large B-cell lymphoma and PET-positive disease, had received first-line therapy containing an anthracycline and a CD20-targeted agent, were not intended for HSCT by their physician, and met at least one prespecified transplantation not intended criterion. Patients received lymphodepleting chemotherapy (intravenous fludarabine 30 mg/m2 and intravenous cyclophosphamide 300 mg/m2 daily for 3 days) followed 2–7 days later by two sequential lisocabtagene maraleucel infusions (equal target doses of CD8+ and CD4+ CAR+ T cells for a total target dose of 100 × 106 CAR+ T cells). The primary endpoint was the overall response rate and was assessed in all patients who received lisocabtagene maraleucel and had confirmed PET-positive disease before lisocabtagene maraleucel administration based on an independent review committee according to the Lugano 2014 criteria. Safety was assessed in all patients who received lisocabtagene maraleucel. Patient follow-up is ongoing. This study is registered with ClinicalTrials.gov, NCT03483103. Between July 26, 2018, and Sept 24, 2021 (data cutoff for the primary analysis), 74 patients underwent leukapheresis and 61 received lisocabtagene maraleucel (efficacy and safety sets); median age was 74 years (IQR 70–78), 24 (39%) patients were women versus 37 (61%) men, and 54 (89%) patients were White. 16 (26%) of 61 patients had an Eastern Cooperative Oncology Group performance status of 2, 33 (54%) had refractory disease, 13 (21%) relapsed within 1 year of first-line therapy, and 15 (25%) relapsed after 12 months of first-line therapy. Median on-study follow-up was 12·3 months (IQR 6·1–18·0). 49 (80% [95% CI 68–89]; p<0·0001) patients had an overall response. The most common grade 3 or worse treatment-emergent adverse events were neutropenia (29 [48%] patients), leukopenia (13 [21%]), and thrombocytopenia (12 [20%]). Lisocabtagene maraleucel-related serious treatment-emergent adverse events were reported in 13 (21%) patients. There were no treatment-related deaths. Cytokine release syndrome occurred in 23 (38%; grade 3 in one) patients and neurological events in 19 (31%; grade 3 in three) patients, with no grade 4 events or deaths. These results support lisocabtagene maraleucel as a potential second-line treatment in patients with large B-cell lymphoma for whom HSCT is not intended. Juno Therapeutics, a Bristol-Myers Squibb company.

Cells sense the extracellular environment and mechanical stimuli and translate these signals into intracellular responses through mechanotransduction, which alters cell maintenance, proliferation, and differentiation. Here we use a mouse model of trauma-induced heterotopic ossification (HO) to examine how cell-extrinsic forces impact mesenchymal progenitor cell (MPC) fate. After injury, single-cell (sc) RNA sequencing of the injury site reveals an early increase in MPC genes associated with pathways of cell adhesion and ECM-receptor interactions, and MPC trajectories to cartilage and bone. Immunostaining uncovers active mechanotransduction after injury with increased focal adhesion kinase signaling and nuclear translocation of transcriptional coactivator TAZ, inhibition of which mitigates HO. Similarly, joint immobilization decreases mechanotransductive signaling, and completely inhibits HO. Joint immobilization decreases collagen alignment and increases adipogenesis. Further, scRNA sequencing of the HO site after injury with or without immobilization identifies gene signatures in mobile MPCs correlating with osteogenesis, and signatures from immobile MPCs with adipogenesis. scATAC-seq in these same MPCs confirm that in mobile MPCs, chromatin regions around osteogenic genes are open, whereas in immobile MPCs, regions around adipogenic genes are open. Together these data suggest that joint immobilization after injury results in decreased ECM alignment, altered MPC mechanotransduction, and changes in genomic architecture favoring adipogenesis over osteogenesis, resulting in decreased formation of HO.

Background Rib fractures are common injuries among traumatically injured patients, and elderly patients with rib fractures are at increased risk for adverse events and death. The purpose of this study was to determine if oral Per os (PO) acetaminophen is as effective as intravenous (IV) acetaminophen in treating the pain associated with rib fractures. Methods We performed a single-center, randomized, placebo-controlled, double-blinded study. Trauma patients who were ≥65 years old and had ≥1 rib fracture were included in this study. Patients were randomized into IV acetaminophen and oral placebo (n = 63) or IV placebo and oral solution acetaminophen (n = 75) groups. The primary outcome was a mean reduction in pain score at 24 hours, and secondary outcomes included opioid use, intensive care unit (ICU) length of stay (LOS), hospital LOS, hospital mortality, the difference in incentive spirometry, and development of pneumonia. Results Among the 138 patients included, there was no statistically significant difference between the 2 study groups in a mean reduction in pain score at 24 hours after injury (PO: 3.24, IV: 2.49; P = .230). Opioid pain medication use was equivalent between groups (P = .212), and there was no significant difference in hospital mortality rate between groups (P = .827). There was no statistically significant difference in ICU LOS, hospital LOS, or development of pneumonia. Discussion In elderly trauma patients (age ≥65 years) with 1 or more rib fractures, PO acetaminophen is equivalent to IV acetaminophen for pain control, with no difference in morbidity or mortality. Oral acetaminophen should be preferentially used over IV acetaminophen when treating the elderly trauma patient with rib fractures.

The Sequencing Quality Control (SEQC) consortium shows that junction discovery and differential gene expression profiling with RNA-seq can be robust but transcript-level and absolute measurements remain challenging. We present primary results from the Sequencing Quality Control (SEQC) project, coordinated by the US Food and Drug Administration. Examining Illumina HiSeq, Life Technologies SOLiD and Roche 454 platforms at multiple laboratory sites using reference RNA samples with built-in controls, we assess RNA sequencing (RNA-seq) performance for junction discovery and differential expression profiling and compare it to microarray and quantitative PCR (qPCR) data using complementary metrics. At all sequencing depths, we discover unannotated exon-exon junctions, with >80% validated by qPCR. We find that measurements of relative expression are accurate and reproducible across sites and platforms if specific filters are used. In contrast, RNA-seq and microarrays do not provide accurate absolute measurements, and gene-specific biases are observed for all examined platforms, including qPCR. Measurement performance depends on the platform and data analysis pipeline, and variation is large for transcript-level profiling. The complete SEQC data sets, comprising >100 billion reads (10Tb), provide unique resources for evaluating RNA-seq analyses for clinical and regulatory settings.

Introduction Colorectal cancer (CRC) screening is an important strategy to reduce morbidity and mortality of cancer. However, evidence on CRC screening and outcomes among Métis people is limited and results are often conflicting. Methods This retrospective study examined CRC screening participation and retention rates, abnormal fecal test results, follow-up colonoscopy rates and wait times, and invasive CRC detection rates and distribution according to Métis status (Métis, non-Métis) and sex (male, female) from 2014 to 2022 among adults living in Alberta. Multiple administrative health databases were linked to investigate study outcomes. Adults aged 50 to 74 years who were eligible for CRC screening were included. Chi-square tests of independence and z-tests compared screening indicators between Métis and non-Métis people and between males and females within each subpopulation. Data over time and across age groups were plotted in scatter plots, and trends were assessed using Joinpoint models. Results CRC screening participation rates among Métis males and females remained slightly higher than, or similar to, their non-Métis counterparts. However, retention rates among Métis people were lower compared to non-Métis people. Comparing females and males, participation rates were higher among females while retention rates were higher among males. A higher proportion of Métis people had abnormal FIT results than their non-Métis counterparts. There were no significant differences in invasive CRC detection rates or CRC stage distribution at diagnosis between Métis and non-Métis people. Conclusion Findings from this study highlight the need for ongoing collaboration among Indigenous leaders, researchers, and healthcare services to support ongoing participation in CRC screening among Métis people. Plain language summary Why was the study done? Screening for colorectal cancer (CRC) is important to lower the chance of getting or dying from cancer. However, there is little known about CRC screening in Métis people. What did the researchers do? The research team studied CRC screening, screening results, and CRC diagnoses in Métis people from 2014 to 2022 and compared them to non-Métis people. We also compared males and females. People living in Alberta, Canada, aged 50 to 74 years were included in the study. What did the researchers find? A similar number or more Métis people had CRC screening compared to non-Métis people. However, fewer Métis people returned for repeat CRC screening. Comparing females and males, more females had CRC screening while more males returned for repeat screening. More Métis people had positive screening results than non-Métis people, so they required more follow-up tests to see if they had CRC. The severity of CRC diagnosed was similar for Métis and non-Métis.