37 research outputs found

    Immediate effect of the COVID-19 pandemic on patient health, health-care use, and behaviours : results from an international survey of people with rheumatic diseases

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    Funding Information: We would like to thank all the clinicians, health-care providers, and patient organisations who helped to develop and disseminate this survey. A full list of all the contributors can be found in the appendix (pp 44?45). Preliminary results were presented at the American College of Rheumatology 2020 conference. The views expressed here are those of the authors and participating members of the COVID-19 Global Rheumatology Alliance and do not necessarily represent the views of the American College of Rheumatology, the European League Against Rheumatism, the UK National Health Service, the National Institute for Health Research, the UK Department of Health, or any other organisation. Funding Information: JSH reports grants from Childhood Arthritis and Rheumatology Research Alliance and Rheumatology Research Alliance; and personal fees from Novartis, Pfizer, and Biogen, outside of the submitted work. JWL reports grants from Pfizer, outside of the submitted work. JAS reports grants and personal fees from Bristol-Myers Squibb; and personal fees from Gilead, Inova Diagnostics, Optum, and Pfizer, outside of the submitted work. CH reports personal fees from AstraZeneca and Aurinia Pharmaceuticals, outside of the submitted work. MJL reports grants from American College of Rheumatology during the conduct of the study and consulting fees from AbbVie, Amgen, Actelion, Boehringer Ingelheim, BMS, Celgene, Gilead, Johnson & Johnson, Mallinckrodt, Novartis, Pfizer, Roche, Sandoz, Sanofi, Sobi, and UCB, outside of the submitted work. SES is supported by the Vasculitis Clinical Research Consortium and Vasculitis Foundation outside of the submitted work. KLD reports grants from Novartis, Sobi, National Institutes of Health, and Horizon Bio, outside of the submitted work. EFM reports that the Liga Portuguesa Contra as Doenças Reumaticas received support for specific activities: grants from Abbvie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal SA, MSD, Celgene, Medac, Pharmakern, GAfPA, AMGEN, A Menarini Portugal; grants and non-financial support from Pfizer; and non-financial support from Grünenthal GmbH and Tilray, outside of the submitted work. DPR is the volunteer Vice President of the Canadian Arthritis Patient Alliance, which is primarily supported by independent grants from pharmaceutical companies. DPR reports consulting fees from NovoNordisk Canada and speaking fees and an honoraria from Eli Lilly Canada, outside of the submitted work. DPR also lives with rheumatoid arthritis. SB reports personal fees from Novartis, AbbVie, Pfizer, and Horizon Pharma, outside of the submitted work. RG reports personal fees from AbbVie New Zealand, Cornerstones, Janssen New Zealand; and personal fees and non-financial support from Pfizer New Zealand, (all <$10 000) outside of the submitted work. PMM reports personal fees from Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB; and grants and personal fees from Orphazyme, outside of the submitted work. PCR reports personal fees from Abbvie, Gilead, Lilly, and Roche; grants and personal fees from Novartis, UCB Pharma, Janssen, and Pfizer; and non-financial support from BMS, outside of the submitted work. PS reports honoraria from being a social media editor for @ACR_Journals, outside of the submitted work. ZSW reports grants from National Institutes of Health, BMS, and Sanofi; and personal fees from Viela Bio and MedPace, outside of the submitted work. JY reports personal fees from Pfizer and Eli Lilly, and grants and personal fees from Astra Zeneca, outside of the submitted work. ES is a Board Member of the Canadian Arthritis Patient Alliance, which is a patient-run, volunteer-based organisation whose activities are primarily supported by independent grants from pharmaceutical companies. All other authors declare no competing interests. Publisher Copyright: © 2021 Elsevier LtdBackground: The impact and consequences of the COVID-19 pandemic on people with rheumatic disease are unclear. We developed the COVID-19 Global Rheumatology Alliance Patient Experience Survey to assess the effects of the COVID-19 pandemic on people with rheumatic disease worldwide. Methods: Survey questions were developed by key stakeholder groups and disseminated worldwide through social media, websites, and patient support organisations. Questions included demographics, rheumatic disease diagnosis, COVID-19 diagnosis, adoption of protective behaviours to mitigate COVID-19 exposure, medication access and changes, health-care access and communication with rheumatologists, and changes in employment or schooling. Adults age 18 years and older with inflammatory or autoimmune rheumatic diseases were eligible for inclusion. We included participants with and without a COVID-19 diagnosis. We excluded participants reporting only non-inflammatory rheumatic diseases such as fibromyalgia or osteoarthritis. Findings: 12 117 responses to the survey were received between April 3 and May 8, 2020, and of these, 10 407 respondents had included appropriate age data. We included complete responses from 9300 adults with rheumatic disease (mean age 46·1 years; 8375 [90·1%] women, 893 [9·6%] men, and 32 [0·3%] participants who identified as non-binary). 6273 (67·5%) of respondents identified as White, 1565 (16·8%) as Latin American, 198 (2·1%) as Black, 190 (2·0%) as Asian, and 42 (0·5%) as Native American or Aboriginal or First Nation. The most common rheumatic disease diagnoses included rheumatoid arthritis (3636 [39·1%] of 9300), systemic lupus erythematosus (2882 [31·0%]), and Sjögren's syndrome (1290 [13·9%]). Most respondents (6921 [82·0%] of 8441) continued their antirheumatic medications as prescribed. Almost all (9266 [99·7%] of 9297) respondents adopted protective behaviours to limit SARS-CoV-2 exposure. A change in employment status occurred in 2524 (27·1%) of 9300) of respondents, with a 13·6% decrease in the number in full-time employment (from 4066 to 3514). Interpretation: People with rheumatic disease maintained therapy and followed public health advice to mitigate the risks of COVID-19. Substantial employment status changes occurred, with potential implications for health-care access, medication affordability, mental health, and rheumatic disease activity. Funding: American College of Rheumatology.publishersversionPeer reviewe

    ABCA transporter gene expression and poor outcome in epithelial ovarian cancer

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    Background ATP-binding cassette (ABC) transporters play various roles in cancer biology and drug resistance, but their association with outcomes in serous epithelial ovarian cancer (EOC) is unknown. Methods The relationship between clinical outcomes and ABC transporter gene expression in two independent cohorts of high-grade serous EOC tumors was assessed with real-time quantitative polymerase chain reaction, analysis of expression microarray data, and immunohistochemistry. Associations between clinical outcomes and ABCA transporter gene single nucleotide polymorphisms were tested in a genome-wide association study. Impact of short interfering RNA-mediated gene suppression was determined by colony forming and migration assays. Association with survival was assessed with Kaplan-Meier analysis and log-rank tests. All statistical tests were two-sided. Results Associations with outcome were observed with ABC transporters of the A subfamily, but not with multidrug transporters. High-level expression of ABCA1, ABCA6, ABCA8, and ABCA9 in primary tumors was statistically significantly associated with reduced survival in serous ovarian cancer patients. Low levels of ABCA5 and the C-allele of rs536009 were associated with shorter overall survival (hazard ratio for death = 1.50; 95% confidence interval [CI] =1.26 to 1.79; P = 6.5e-6). The combined expression pattern of ABCA1, ABCA5, and either ABCA8 or ABCA9 was associated with particularly poor outcome (mean overall survival in group with adverse ABCA1, ABCA5 and ABCA9 gene expression = 33.2 months, 95% CI = 26.4 to 40.1; vs 55.3 months in the group with favorable ABCA gene expression, 95% CI = 49.8 to 60.8; P =. 001), independently of tumor stage or surgical debulking status. Suppression of cholesterol transporter ABCA1 inhibited ovarian cancer cell growth and migration in vitro, and statin treatment reduced ovarian cancer cell migration. Conclusions Expression of ABCA transporters was associated with poor outcome in serous ovarian cancer, implicating lipid trafficking as a potentially important process in EOC. © 2014 The Author 2014. Published by Oxford University Press. All rights reserved

    The Western Channel Observatory: a century of physical, chemical and biological data compiled from pelagic and benthic habitats in the western English Channel

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    The Western Channel Observatory (WCO) comprises a series of pelagic, benthic and atmospheric sampling sites within 40 km of Plymouth, UK, that have been sampled by the Plymouth institutes on a regular basis since 1903. This longevity of recording and the high frequency of observations provide a unique combi�nation of data; for example temperature data were first collected in 1903, and the reference station L4, where nearly 400 planktonic taxa have been enumerated, has been sampled on a weekly basis since 1988. While the component datasets have been archived, here we provide the first summary database bringing together a wide suite of the observations. This provides monthly average values of some of the key pelagic and benthic measure�ments for the inshore site L4 (50◦15.000 N, 4◦13.020 W; approx. depth 55 m), the offshore site E1 (50◦02.000 N, 4 ◦22.000 W; approx. depth 75 m) and the intermediate L5 site (50◦10.800 N, 4◦18.000 W; approx. depth 58 m). In brief, these data include the following: water temperature (from 1903); macronutrients (from 1934); dissolved inorganic carbon and total alkalinity (from 2008); methane and nitrous oxide (from 2011); chlorophyll a (from 1992); high-performance liquid chromatography (HPLC)-derived pigments (from 1999); <20 µm plankton by flow cytometry, including bacteria (8 functional groups from 2007); phytoplankton by microscopy (6 functional groups from 1992); microplankton and mesozooplankton from FlowCam (6 groups from 2012); Noctiluca sp. dinoflagellate (from 1997); mesozooplankton by microscopy (8 groups from 1988); Calanus helgolandicus egg production rates (from 1992); fish larvae from the Young Fish Trawl survey (4 groups from 1924); benthic macrofauna (4 groups from 2008); demersal fish (19 families from 2008); blue shark, Prionace glauca (from 1958); and 16S alpha diversity for sediment and water column (from 2012). These data have varying coverage with respect to time and depth resolution. The metadata tables describe each dataset and provide pointers to the source data and other related Western Channel Observatory datasets and outputs not compiled here. We pro�vide summaries of the main trends in seasonality and some major climate-related shifts that have been revealed over the last century. The data are available from the Data Archive for Seabed Species and Habitats (DASSH): https://doi.org/10.17031/645110fb81749 (McEvoy and Atkinson, 2023). Making these data fully accessible and including units of both abundance and biomass will stimulate a variety of uptakes. These may include uses as an educational resource for projects, for models and budgets, for the analysis of seasonality and long-term change in a coupled benthic–pelagic system, or for supporting UK and north-eastern Atlantic policy and management

    Recent Findings Regarding Maintenance of Enzootic Variants of Yersinia pestis in Sylvatic Reservoirs and Their Significance in the Evolution of Epidemic Plague

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    Despite the widespread presence of bubonic plague in sylvatic reservoirs throughout the world, the causative agent (Yersinia pestis) evolved in its present form within the last 20,000 years from enteropathogenic Yersinia pseudotuberculosis. Comparison of the genomes from the two species revealed that Y. pestis possesses only a few unique plasmid-encoded genes that contribute to acute disease, whereas this organism has lost about 13% of the chromosomal genes that remain active in Y. pseudotuberculosis. These losses reflect readily detectable additions, deletions, transpositions, inversions, and acquisition of about 70 insertion sequence (IS) inserts, none of which are likely to promote increased virulence. In contrast, major enzymes of intermediary metabolism, including glucose 6-phosphate dehydrogenase (Zwf ) and aspartase, are present but not catalytically functional due to the presence of missense mutations. The latter are generally not detectable by the technology of bioinformatics and, in the case of Y. pestis, result in radical changes in the metabolic flow of carbon. As an important consequence, plague bacilli exhibit a stringent low-calcium response characterized by conversion of L-glutamate (and metabolically related amino acids) to L-aspartate with secretion of the latter into supernatant fluid at 37°C in culture media containing Na+ but lacking added Ca2+. This phenomenon also occurs in vivo and likely adversely affects the bioenergetics of host amino acid pools. Curiously, aspartase is functional in all tested enzootic (pestoides) strains of Y. pestis. These isolates are typically restricted to the ancient plague reservoirs of Central Asia and Africa and are fully virulent in members of the rodent Superfamily Muroidea but avirulent in guinea pigs and man. The implications of these findings for the distribution and ecology of Y. pestis could be significant
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