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  • 1
    In: JAMA Network Open, American Medical Association (AMA), Vol. 6, No. 2 ( 2023-02-14), p. e2255795-
    Abstract: Individuals who survived COVID-19 often report persistent symptoms, disabilities, and financial consequences. However, national longitudinal estimates of symptom burden remain limited. Objective To measure the incidence and changes over time in symptoms, disability, and financial status after COVID-19–related hospitalization. Design, Setting, and Participants A national US multicenter prospective cohort study with 1-, 3-, and 6-month postdischarge visits was conducted at 44 sites participating in the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network's Biology and Longitudinal Epidemiology: COVID-19 Observational (BLUE CORAL) study. Participants included hospitalized English- or Spanish-speaking adults without severe prehospitalization disabilities or cognitive impairment. Participants were enrolled between August 24, 2020, and July 20, 2021, with follow-up occurring through March 30, 2022. Exposure Hospitalization for COVID-19 as identified with a positive SARS-CoV-2 molecular test. Main Outcomes and Measures New or worsened cardiopulmonary symptoms, financial problems, functional impairments, perceived return to baseline health, and quality of life. Logistic regression was used to identify factors associated with new cardiopulmonary symptoms or financial problems at 6 months. Results A total of 825 adults (444 [54.0%] were male, and 379 [46.0%] were female) met eligibility criteria and completed at least 1 follow-up survey. Median age was 56 (IQR, 43-66) years; 253 (30.7%) participants were Hispanic, 145 (17.6%) were non-Hispanic Black, and 360 (43.6%) were non-Hispanic White. Symptoms, disabilities, and financial problems remained highly prevalent among hospitalization survivors at month 6. Rates increased between months 1 and 6 for cardiopulmonary symptoms (from 67.3% to 75.4%; P  = .001) and fatigue (from 40.7% to 50.8%; P   & amp;lt; .001). Decreases were noted over the same interval for prevalent financial problems (from 66.1% to 56.4%; P   & amp;lt; .001) and functional limitations (from 55.3% to 47.3%; P  = .004). Participants not reporting problems at month 1 often reported new symptoms (60.0%), financial problems (23.7%), disabilities (23.8%), or fatigue (41.4%) at month 6. Conclusions and Relevance The findings of this cohort study of people discharged after COVID-19 hospitalization suggest that recovery in symptoms, functional status, and fatigue was limited at 6 months, and some participants reported new problems 6 months after hospital discharge.
    Type of Medium: Online Resource
    ISSN: 2574-3805
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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  • 2
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Journal of Bone and Joint Surgery Vol. 102, No. 4 ( 2020-2-19), p. 332-339
    In: Journal of Bone and Joint Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 102, No. 4 ( 2020-2-19), p. 332-339
    Abstract: The opioid crisis is a well-known public health issue. The risk of new long-term opioid prescription-filling behavior has been investigated after certain spinal procedures and total knee and hip arthroplasty. However, this has not been examined after many other common orthopaedic procedures. The purpose of this study was to determine the rates of long-term opioid prescription-filling behavior after common orthopaedic surgical procedures in patients who were not taking opioids preoperatively. Methods: This study utilized the Virginia All-Payer Claims Database (APCD), an insurance claims database with data from 3.7 to 4 million patients per year. Patients who underwent orthopaedic procedures and who had not filled an opioid prescription in the time period from 2 weeks to 1 year preceding the surgical procedure were selected for evaluation in our study. The percentage of these patients who then filled at least 10 prescriptions or a 120-day supply of opioids in the time period from 90 to 455 days following the surgical procedure was calculated for the 50 most commonly billed orthopaedic surgical procedures. Results: The rate of long-term opioid prescription-filling behavior in patients who were not taking opioids preoperatively for the 50 most common orthopaedic procedures was 5.3% (95% confidence interval, 5.1% to 5.5%). The highest rates were observed after spinal procedures. The lowest rates were seen after anterior cruciate ligament (ACL) reconstruction. Revision surgical procedures were found to have a significantly higher rate than primary procedures (p 〈 0.05). The rate was also related to increasing case complexity. Conclusions: New long-term opioid prescription-filling behavior is common after orthopaedic surgical procedures in patients who were not taking opioids preoperatively. Risk factors include spine surgery, revision surgery, and cases with increased complexity. Orthopaedic surgeons need to be aware of this risk. Level of Evidence: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.
    Type of Medium: Online Resource
    ISSN: 0021-9355 , 1535-1386
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    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 3
    In: Bulletin of the American Meteorological Society, American Meteorological Society, Vol. 99, No. 7 ( 2018-07), p. 1449-1471
    Abstract: The Coupled Air–Sea Processes and Electromagnetic Ducting Research (CASPER) project aims to better quantify atmospheric effects on the propagation of radar and communication signals in the marine environment. Such effects are associated with vertical gradients of temperature and water vapor in the marine atmospheric surface layer (MASL) and in the capping inversion of the marine atmospheric boundary layer (MABL), as well as the horizontal variations of these vertical gradients. CASPER field measurements emphasized simultaneous characterization of electromagnetic (EM) wave propagation, the propagation environment, and the physical processes that gave rise to the measured refractivity conditions. CASPER modeling efforts utilized state-of-the-art large-eddy simulations (LESs) with a dynamically coupled MASL and phase-resolved ocean surface waves. CASPER-East was the first of two planned field campaigns, conducted in October and November 2015 offshore of Duck, North Carolina. This article highlights the scientific motivations and objectives of CASPER and provides an overview of the CASPER-East field campaign. The CASPER-East sampling strategy enabled us to obtain EM wave propagation loss as well as concurrent environmental refractive conditions along the propagation path. This article highlights the initial results from this sampling strategy showing the range-dependent propagation loss, the atmospheric and upper-oceanic variability along the propagation range, and the MASL thermodynamic profiles measured during CASPER-East.
    Type of Medium: Online Resource
    ISSN: 0003-0007 , 1520-0477
    Language: Unknown
    Publisher: American Meteorological Society
    Publication Date: 2018
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  • 4
    In: Biological Psychiatry, Elsevier BV, Vol. 41, No. 9 ( 1997-05), p. 929-938
    Type of Medium: Online Resource
    ISSN: 0006-3223
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 1997
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  • 5
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 5012-5012
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 5012-5012
    Abstract: Septins are members of a highly conserved family of 14 genes whose products are thought to act primarily as scaffolds, recruiting other proteins to particular cellular locations. This gene family shares a complexity of alternative splicing and encodes proteins involved in a number of diverse processes within the cell including cytokinesis, apoptosis and vesicle trafficking, and septins have been implicated in a number of diseases. Work in our laboratory has focussed on the SEPT9 gene and it was mapped it to a region of allelic imbalance on chromosome 17q in sporadic epithelial ovarian tumours. SEPT9 undergoes extensive alternative splicing and can form a possible 18 transcripts due to splicing at the 5’ (v1, v2, v3, v4, v4*, v5) and 3’ (a, b and c) ends, with SEPT9_v4 and SEPT9_v4* differing only in their 5’UTRs thus encoding the same protein. Previously we have shown perturbed expression of the SEPT9_v1 and SEPT9_v4* transcripts in neoplasia. In this study, we sought to determine the expression levels of all SEPT9 transcripts in ovarian tumours using samples from the Scottish Randomised Trial in Ovarian Cancer (SCOTROC) cohort, which compares two chemotherapy regimes. RNA was extracted from 100 FFPE tumour samples and qRT-PCR was performed for each SEPT9 transcript. Results were correlated with clinical data provided from the trial. Statistical significant elevated expression of SEPT9_v1 and SEPT9_v4* (p & lt;0.0001) in tumour tissue compared to normal ovarian tissue was observed, in accordance with our previous data. Furthermore, we detected elevated expression of SEPT9_v5 and SEPT9_vb (p & lt;0.0001) in tumour tissue compared to normal. Further statistical analysis shows correlations of SEPT9_v1, v4*, v5 and vb with tumour stage and SEPT9_v1, v5 and vb with tumour histology. This data suggests that the expression of the various SEPT9 transcripts is independently regulated. Of some note is the difference in 3’UTRs of the 3’ transcripts of SEPT9, with the b and c transcripts sharing the same short 3’UTR (57bases) while the a transcript has a longer 3’UTR (1.938kb). Bioinformatic analysis of the different 3’UTRs of SEPT9 identified a number of potential microRNA binding sites in the 3’UTR of SEPT9_va and only one of note in SEPT9_vb & c, with a number of these microRNAs previously shown to have altered expression in ovarian cancer. Therefore, we wished to determine if the 3’UTRs were important in the regulation of SEPT9. Luciferase assays performed from A2780 ovarian cancer cells show that the various 3’UTRs of SEPT9 drive the expression of reporter genes in a sequence dependent manner and particular microRNAs (hsa-miR-124, has-miR-494 and hsa-miR-199a) may regulate the expression of SEPT9_va. In summary, our data supports the hypothesis that the expression of the splice variants of SEPT9 and their various isoforms is tightly regulated and provides the first evidence that this regulation includes differential action of microRNAs on sites within 3′UTRs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5012. doi:10.1158/1538-7445.AM2011-5012
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
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  • 6
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 260-260
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 260-260
    Abstract: The septins are a family of 14 genes, the products of which are thought to function primarily as scaffolds which recruit other proteins to particular cellular locations. This gene family is highly conserved and encodes proteins involved in a variety of cellular functions including cytokinesis, apoptosis and vesicle trafficking. Septin colocalisation with actin and tubulin has also been reported. Previous work from this laboratory mapped the SEPT9 gene to a region of allelic imbalance on chromosome 17q in sporadic epithelial ovarian tumours. SEPT9 undergoes extensive alternate splicing at both the 5’ (v1, v2 v3, v4, v4* and v5) and 3’ (a, b and c) ends, with SEPT9_v4 and _v4* differing only in their 5’UTRs, therefore encoding the same polypeptide. We have shown perturbed expression of SEPT9 transcripts in neoplasia, specifically up-regulation of SEPT9_v1 and _v4* transcripts. In a range of normal tissues we noted three alternatively spliced 3’ transcripts (a, b & c) were expressed. However, in ovarian tumour development expression of 2 of these (b & c) is decreased. This suggests that expression of the various SEPT9 transcripts is independently regulated. We therefore sought to gain some insight into control of expression of these various splice variants and why specific patterns of deregulation might contribute to neoplasia. With respect to the cell cycle, we observed by immunofluoresence that SEPT9 protein is visible around the cell membrane during anaphase and into telophase. During cytokinesis the SEPT9 protein localises to the cleavage furrow and is part of the ‘ring’ structure of dividing cells. We also used a double thymidine block to synchronise HeLa cells but there was no alteration in levels of transcripts with specific 5’ or 3’ ends in these cells. Next we looked at expression of the SEPT9 5’ and 3’ ends in response to cellular stress, in particular DNA damage following doxorubicin treatment. We observe an up-regulation of the 5’ v4* transcript and 3’ c variant after doxorubicin treatment in a p53 wild type background but not in p53 null cells. We then used a model of ovarian surface epithelial cells immortalised with telomerase and a temperature sensitive SV40 large T antigen which proliferate at 330C but senesce when shifted to the non-permissive temperature (370C). We see that SEPT9_v2 and v4 mRNA levels increase significantly as cells undergo senescence. Finally, we note that the b and c variants share the same short 3’UTR (57 bases) while the a variant has a long 3’UTR (1.938kb). Bioinformatics of both 3’UTRs identified several putative microRNA binding sites present in the 3’UTR of the a variant but only one in that of b and c. We show that the 3’UTR of a drives a reporter gene when cloned upstream of luciferase and in a sequence dependant manner. In summary, our data supports the hypothesis that the alternatively spliced transcripts of SEPT9 play individual roles within the cell and that the 3’UTRs appear to be important in the regulation of SEPT9. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 260.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
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  • 7
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 101, No. 40 ( 2022-10-07), p. e30854-
    Abstract: MicroRNAs (miRNAs) are small non-coding RNA that are powerful regulators of gene expression and can affect the expression of hundreds of genes. miRNAs can be packed in small extracellular vesicles (SEV) and released into the extracellular space by neurons and microglia to act locally as well as pass through the blood-brain barrier and act systemically. We sought to understand the differences in neuronal SEV miRNA expression between frontotemporal dementia (FTD), Alzheimer’s disease (AD), and healthy aging. Plasma was obtained from FTD, AD, and healthy aging participants that were matched based on age, sex, and race/ethnicity. Additionally, a subset of participants also provided paired cerebrospinal fluid samples to compare neuronal SEV miRNAs in plasma and cerebrospinal fluid. Neuronal SEV were isolated using differential ultracentrifugation and antibody conjugated Dynabeads® for the neuronal surface marker, L1CAM. RNA sequencing was performed. 12 FTD, 11 with AD, and 10 healthy aging participants were enrolled in the study. In FTD, SEV miRNA-181c was downregulated compared to healthy controls. In AD, miRNA-122 and miRNA-3591 were downregulated compared to those in healthy controls and FTD. Using an FDR 〈 0.2, only miRNA-21-5p was found to have increased expression in the cerebrospinal fluid compared to plasma in a group of AD and FTD participants. SEV miRNA-181c is significantly downregulated in FTD compared to healthy controls and may mediate its effects through microglial-directed neuroinflammation and interaction with TAR DNA-binding protein 43 (TDP-43) based on pathway analysis. Additionally, the FOXO and Hippo pathways may be important mediators of FTD, based on pathway analysis. Lastly, because only one SEV miRNA was differentially expressed between the plasma and cerebrospinal fluid in paired samples, plasma represents an appropriate biofluid for studying neuronal SEV miRNA.
    Type of Medium: Online Resource
    ISSN: 1536-5964
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 8
    Online Resource
    Online Resource
    American Association for the Advancement of Science (AAAS) ; 2018
    In:  Science Vol. 360, No. 6395 ( 2018-06-22), p. 1342-1346
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 360, No. 6395 ( 2018-06-22), p. 1342-1346
    Abstract: Einstein’s theory of gravity, General Relativity, has been precisely tested on Solar System scales, but the long-range nature of gravity is still poorly constrained. The nearby strong gravitational lens ESO 325-G004 provides a laboratory to probe the weak-field regime of gravity and measure the spatial curvature generated per unit mass, γ. By reconstructing the observed light profile of the lensed arcs and the observed spatially resolved stellar kinematics with a single self-consistent model, we conclude that γ = 0.97 ± 0.09 at 68% confidence. Our result is consistent with the prediction of 1 from General Relativity and provides a strong extragalactic constraint on the weak-field metric of gravity.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2018
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  • 9
    In: The Clinical Neuropsychologist, Informa UK Limited, Vol. 17, No. 4 ( 2003-11), p. 446-459
    Type of Medium: Online Resource
    ISSN: 1385-4046 , 1744-4144
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2003
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    SSG: 5,2
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  • 10
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: We previously demonstrated that standardizing the documentation of the outpatient parenteral antimicrobial therapy (OPAT) plan led to improved post-discharge outcomes. This study investigated whether centralizing the OPAT documentation to an infectious diseases (ID) pharmacist would lead to improved documentation quality and further improvements in post-discharge outcomes. Methods We conducted a single-center, retrospective study to evaluate outcomes associated with the centralization of the OPAT plan documentation to an ID pharmacist. The study was a multiphase quality improvement study consisting of a pre-intervention period and two intervention periods on each of the General ID consult services (first on Team 1 then on Team 2). The scope of the intervention was focused on the timeliness and completeness of OPAT note documentation, while other workflow processes involving OPAT remained unchanged. The primary objective was to compare hospital length of stay (LOS) between patients with OPAT Notes documented by an ID pharmacist versus ID providers. Secondary objectives were to compare post-discharge outcomes. Results A total of 350 patients met inclusion criteria; baseline characteristics were similar between the pharmacist and provider groups (Table 1). OPAT note documentation quality improved during the pharmacist intervention phases for each General ID team (Figure 1). The median LOS was 7.9 days in the pharmacist documentation group compared to 6.8 days in the provider group [Median difference, 1.1; 95% Confidence Interval (CI), -0.4 - 3.7]. Laboratory monitoring within 10 days of discharge, 30- and 60-day death or readmission rates, and late ID visit cancellations between the two groups were comparable (Table 2). ID clinic no show appointments occurred less often in the pharmacist documentation patients. Table 1:Baseline DemographicsFigure 1:Control Chart Comparisons of OPAT Notes Without All “Perfect Care” ElementsTable 2:Post-discharge outcomes for pharmacist compared to provider documentation patientsa: Pharmacist note patients are the reference for all comparisonsb: Adjusted for discharge destination and primary payorc: Adjusted for Charlson comorbidity indexd: Adjusted for age and primary payor Conclusion Improved OPAT note documentation did not translate into shorter hospital LOS. Post-discharge outcomes were similar between pharmacist and provider patients, although no show visits occurred less often when pharmacists documented the OPAT plan. Disclosures Russell J. Benefield, PharmD, BCPS-AQ ID, Paratek Pharmaceuticals: Grant/Research Support.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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