Publications by authors named "Jason Turner"

36 Publications

Massive hemoperitoneum without peritoneal signs: An unusual presentation of omental ectopic rupture. A case report.

Case Rep Womens Health 2021 Jul 15;31:e00327. Epub 2021 May 15.

West Virginia University School of Medicine, United States of America.

Background: Extrauterine ectopic pregnancy is a rare form of ectopic pregnancy, accounting for roughly 1:10,000-30,000 of all pregnancies. Primary omental pregnancy is the least common form of abdominal ectopic pregnancies, making it extremely rare. Typical presentation includes pelvic pain, secondary amenorrhea, with or without vaginal bleeding. Atypical presentations range from nonspecific pain to asymptomatic.

Case: A 19-year-old woman presented to the emergency department after several syncopal episodes. She had a positive urine pregnancy test (serum hCG 446 IU/L). Her hemoglobin level was 10.6 g/dL. Due to lack of pain or bleeding, abdominal imaging was not indicated. A head CT scan rendered negative results. She was subsequently diagnosed with idiopathic headaches and anemia and was discharged. She returned to hospital 48 h later with vaginal bleeding and additional syncopal episodes. She was not experiencing any abdominal pain or discomfort. Her anemia worsened (hemoglobin 7.5 g/dL). For this reason, imaging was performed. It was significant for massive hemoperitoneum. Due to the imaging findings and worsening anemia, diagnostic exploratory laparoscopy was recommended to evaluate for ruptured ectopic pregnancy. Laparoscopic findings revealed large hemoperitoneum and a 10-week gestational sac attached to the greater omentum near the transverse colon. This exceedingly rare presentation of extrauterine ectopic pregnancy offered few clinical clues other than worsening anemia until imaging later revealed the abnormality. Ruptured ectopic pregnancy, a potentially fatal complication of pregnancy, should be included into the differential diagnosis of any gravid patient with syncope and anemia unexplained by extensive diagnostic workup.
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http://dx.doi.org/10.1016/j.crwh.2021.e00327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167815PMC
July 2021

Organisational support and turnover intentions: A moderated mediation approach.

Nurs Open 2021 May 12. Epub 2021 May 12.

School of Nursing and Midwifery Amol, Mazandaran University of Medical Sciences, Sari, Iran.

Aim: The current study aims to examine the moderating role of psychological ownership in the process that translates organisational support into nurses' turnover intentions through job satisfaction.

Design: A cross-sectional research design was used to test the hypotheses.

Method: Using a purposive sampling 341 self-completed survey data were collected from nurses working in two public hospitals in Iran. Structural equation modelling was used to analyse the data.

Result: The research revealed that organisational support and job satisfaction were negatively related to a healthcare professionals' turnover intention. Moreover, job satisfaction mediated the negative relationship between organisational support and turnover intention. The research also revealed that psychological ownership strengthened the positive relationship between organisational support and job satisfaction.
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http://dx.doi.org/10.1002/nop2.911DOI Listing
May 2021

Gallstone Ileus Treated by Incidental Meckel's Diverticulectomy.

Cureus 2021 Mar 24;13(3):e14078. Epub 2021 Mar 24.

Department of Surgery, West Virginia University, Martinsburg, USA.

Gallstone ileus is an uncommon cause of intestinal obstruction in the elderly. It is typically recognized on computed tomography by the presence of pneumobilia and a gallstone in the right iliac fossa. Nonetheless, it is important to consider that gallstone ileus may represent the presentation of another pathology rather than an entity on its own. Here, we report successful retrieval of a gallstone that was causing ileus. Intraoperatively, the gallstone was noted lodged in the terminal ileum distal to an incidentally noted Meckel's diverticulum. The gallstone was milked proximally into the Meckel's diverticulum and the base was transected. This case illustrates a rare, but unique, surgical technique utilizing a small bowel diverticulum as a vector for stone removal.
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http://dx.doi.org/10.7759/cureus.14078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065097PMC
March 2021

The complement system drives local inflammatory tissue priming by metabolic reprogramming of synovial fibroblasts.

Immunity 2021 May 23;54(5):1002-1021.e10. Epub 2021 Mar 23.

Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, 91054 Erlangen, Germany; Deutsches Zentrum fuer Immuntherapie, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, 91054 Erlangen, Germany.

Arthritis typically involves recurrence and progressive worsening at specific predilection sites, but the checkpoints between remission and persistence remain unknown. Here, we defined the molecular and cellular mechanisms of this inflammation-mediated tissue priming. Re-exposure to inflammatory stimuli caused aggravated arthritis in rodent models. Tissue priming developed locally and independently of adaptive immunity. Repeatedly stimulated primed synovial fibroblasts (SFs) exhibited enhanced metabolic activity inducing functional changes with intensified migration, invasiveness and osteoclastogenesis. Meanwhile, human SF from patients with established arthritis displayed a similar primed phenotype. Transcriptomic and epigenomic analyses as well as genetic and pharmacological targeting demonstrated that inflammatory tissue priming relies on intracellular complement C3- and C3a receptor-activation and downstream mammalian target of rapamycin- and hypoxia-inducible factor 1α-mediated metabolic SF invigoration that prevents activation-induced senescence, enhances NLRP3 inflammasome activity, and in consequence sensitizes tissue for inflammation. Our study suggests possibilities for therapeutic intervention abrogating tissue priming without immunosuppression.
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http://dx.doi.org/10.1016/j.immuni.2021.03.003DOI Listing
May 2021

Penetrating Thoracoabdominal Trauma With a Cryptic Diaphragmatic Injury in a 23-Year-Old Male.

Cureus 2021 Feb 3;13(2):e13102. Epub 2021 Feb 3.

Surgery, West Virginia University, Martinsburg, USA.

Traumatic diaphragmatic injuries are a rare entity and can occur in relation to penetrating thoracic and abdominal trauma. The most common clinical features of diaphragm rupture include chest or abdominal bruising, decreased breath sounds, and signs of bowel obstruction. However, the classic signs and symptoms of diaphragmatic injury are not always present and can be obscured even in the highest resolution imaging. This highlights the importance for maintaining a high index of suspicion to make the diagnosis and properly manage these patients. Here, we present a rare case of a 23-year-old male who experienced a laceration to his left thorax and was later discovered to have concurrent diaphragmatic injury despite an initially noncontributory physical exam and imaging findings. The patient subsequently underwent robotic repair of the injury and reduction of herniated contents.
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http://dx.doi.org/10.7759/cureus.13102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934803PMC
February 2021

Volatility and Persistence of Value-Based Purchasing Adjustments: A Challenge to Integrating Population Health and Community Benefit Into Business Operations.

Front Public Health 2020 9;8:165. Epub 2020 Jun 9.

Bryan Memorial Hospital, Lincoln, NE, United States.

With the passage of the Deficit Reduction Act of 2005 and the Patient Protection and Affordable Care Act in 2010, Medicare's Inpatient Prospective Payment System (IPPS) began a transition to value-based purchasing (VBP) that rewards or penalizes hospitals based on patient satisfaction, clinical processes of care, outcomes, and efficiency metrics. However, hospital-level volatility vs. persistence in value-based payments year-over-year could result in unpredictable cash flows that negatively influence investment behavior, drive underinvestment in community benefit/population health management initiatives, and make management of the factors that drive the VBP adjustment more challenging. To evaluate the volatility and persistence of hospital VBP adjustments, the sample includes VBP adjustments and the associated domain scores for the 2,547 hospitals that participated in the program from 2013 to 2016. The sample includes urban (74%), teaching (29.1%), system affiliated (46.5%), and not-for-profit (63.6%) facilities. Volatility was measured using basic descriptive statistics, relative risk ratios, and a fixed effect, autoregressive, dynamic panel model that robust-clustered the standard errors. There is substantial change in a given facility's total VBP score with an average standard deviation of 10.74 (on a 100-point scale) that is driven by significant volatility in all metrics but particularly by efficiency and outcomes metrics. Relative risk ratios have dropped substantially over the life of the program, and there is low persistence of VBP scores from one period to the next. Findings indicate that if hospitals receive a positive adjustment in 1 year, they are almost as likely to receive a negative adjustment as a positive adjustment the following year. Furthermore, using a fixed-effect dynamic panel model that controls for autocorrelation, we find that only 13.5% of a facility's prior year IPPS adjustment (positive or negative) carries forward to the next year. The low persistence makes investment in population health management and community benefit more challenging.
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http://dx.doi.org/10.3389/fpubh.2020.00165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296160PMC
May 2021

In situ bypass and extra-anatomic bypass procedures result in similar survival in patients with secondary aortoenteric fistulas.

J Vasc Surg 2021 01 21;73(1):210-221.e1. Epub 2020 May 21.

Division of Vascular Surgery, Keio University, Tokyo, Japan.

Objective: The optimal revascularization modality in secondary aortoenteric fistula (SAEF) remains unclear in the literature. The purpose of this investigation was to determine the revascularization approach associated with the lowest morbidity and mortality using real-world data in patients with SAEF.

Methods: A retrospective, multi-institutional study of SAEF from 2002 to 2014 was performed using a standardized database. Baseline demographics, comorbidities, and operative and postoperative variables were recorded. The primary outcome was long-term mortality. Descriptive statistics, Kaplan-Meier survival analysis, and univariate and multivariate analyses were performed.

Results: During the study period, 182 patients at 34 institutions from 11 countries presented with SAEF (median age, 72 years; 79% male). The initial aortic procedures that resulted in SAEF were 138 surgical grafts (76%) and 42 endografts (23%), with 2 unknown; 102 of the SAEFs (56%) underwent complete excision of infected aortic graft material, followed by in situ (in-line) bypass (ISB), including antibiotic-soaked prosthetic graft (53), autogenous femoral vein (neoaortoiliac surgery; 17), cryopreserved allograft (28), and untreated prosthetic grafts (4). There were 80 patients (44%) who underwent extra-anatomic bypass (EAB) with infected graft excision. Overall median Kaplan-Meier estimated survival was 319 days (interquartile range, 20-2410 days). Stratified by EAB vs ISB, there was no significant difference in Kaplan-Meier estimated survival (P = .82). In comparing EAB vs ISB, EAB patients were older (74 vs 70 years; P = .01), had less operative hemorrhage (1200 mL vs 2000 mL; P = .04), were more likely to initiate dialysis within 30 days postoperatively (15% vs 5%; P = .02), and were less likely to experience aorta-related hemorrhage within 30 days postoperatively (3% aortic stump dehiscence vs 11% anastomotic rupture; P = .03). There were otherwise no significant differences in presentation, comorbidities, and intraoperative or postoperative variables. Multivariable Cox regression showed that the duration of antibiotic use (hazard ratio, 0.92; 95% confidence interval, 0.86-0.98; P = .01) and rifampin use at time of discharge (hazard ratio, 0.20; 95% confidence interval, 0.05-0.86; P = .03) independently decreased mortality.

Conclusions: These data suggest that ISB does not offer a survival advantage compared with EAB and does not decrease the risk of postoperative aorta-related hemorrhage. After repair, <50% of SAEF patients survive 10 months. Each week of antibiotic use decreases mortality by 8%. Further study with risk modeling is imperative for this population.
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http://dx.doi.org/10.1016/j.jvs.2020.04.515DOI Listing
January 2021

New Developments in Transcriptomic Analysis of Synovial Tissue.

Front Med (Lausanne) 2020 31;7:21. Epub 2020 Jan 31.

Institute for Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom.

Transcriptomic technologies are constantly changing and improving, resulting in an ever increasing understanding of gene expression in health and disease. These technologies have been used to investigate the pathological changes occurring in the joints of rheumatoid arthritis patients, leading to discoveries of disease mechanisms, and novel potential therapeutic targets. Microarrays were initially used on both whole tissue and cell subsets to investigate research questions, with bulk RNA sequencing allowing for further elaboration of these findings. A key example is the classification of pathotypes in rheumatoid arthritis using RNA sequencing that had previously been discovered using microarray and histology. Single-cell sequencing has now delivered a step change in understanding of the diversity and function of subpopulations of cells, in particular synovial fibroblasts. Future technologies, such as high resolution spatial transcriptomics, will enable step changes integrating single cell transcriptomic and geographic data to provide an integrated understanding of synovial pathology.
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http://dx.doi.org/10.3389/fmed.2020.00021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005068PMC
January 2020

Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology.

Proc Natl Acad Sci U S A 2019 07 18;116(27):13490-13497. Epub 2019 Jun 18.

Rheumatoid Arthritis Pathogenesis Centre of Excellence, Institute of Inflammation and Ageing, College of Medical & Dental Sciences, University of Birmingham Research Laboratories, Queen Elizabeth Hospital, B15 2WB Birmingham, United Kingdom;

Resident fibroblasts at sites of infection, chronic inflammation, or cancer undergo phenotypic and functional changes to support leukocyte migration and, in some cases, aggregation into tertiary lymphoid structures (TLS). The molecular programming that shapes these changes and the functional requirements of this population in TLS development are unclear. Here, we demonstrate that external triggers at mucosal sites are able to induce the progressive differentiation of a population of podoplanin (pdpn)-positive stromal cells into a network of immunofibroblasts that are able to support the earliest phases of TLS establishment. This program of events, that precedes lymphocyte infiltration in the tissue, is mediated by paracrine and autocrine signals mainly regulated by IL13. This initial fibroblast network is expanded and stabilized, once lymphocytes are recruited, by the local production of the cytokines IL22 and lymphotoxin. Interfering with this regulated program of events or depleting the immunofibroblasts in vivo results in abrogation of local pathology, demonstrating the functional role of immunofibroblasts in supporting TLS maintenance in the tissue and suggesting novel therapeutic targets in TLS-associated diseases.
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http://dx.doi.org/10.1073/pnas.1905301116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613169PMC
July 2019

Distinct fibroblast subsets drive inflammation and damage in arthritis.

Nature 2019 06 29;570(7760):246-251. Epub 2019 May 29.

Rheumatology Research Group, Institute for Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK.

The identification of lymphocyte subsets with non-overlapping effector functions has been pivotal to the development of targeted therapies in immune-mediated inflammatory diseases (IMIDs). However, it remains unclear whether fibroblast subclasses with non-overlapping functions also exist and are responsible for the wide variety of tissue-driven processes observed in IMIDs, such as inflammation and damage. Here we identify and describe the biology of distinct subsets of fibroblasts responsible for mediating either inflammation or tissue damage in arthritis. We show that deletion of fibroblast activation protein-α (FAPα) fibroblasts suppressed both inflammation and bone erosions in mouse models of resolving and persistent arthritis. Single-cell transcriptional analysis identified two distinct fibroblast subsets within the FAPα population: FAPαTHY1 immune effector fibroblasts located in the synovial sub-lining, and FAPαTHY1 destructive fibroblasts restricted to the synovial lining layer. When adoptively transferred into the joint, FAPαTHY1 fibroblasts selectively mediate bone and cartilage damage with little effect on inflammation, whereas transfer of FAPα THY1 fibroblasts resulted in a more severe and persistent inflammatory arthritis, with minimal effect on bone and cartilage. Our findings describing anatomically discrete, functionally distinct fibroblast subsets with non-overlapping functions have important implications for cell-based therapies aimed at modulating inflammation and tissue damage.
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http://dx.doi.org/10.1038/s41586-019-1263-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690841PMC
June 2019

Fibroblasts and Osteoblasts in Inflammation and Bone Damage.

Adv Exp Med Biol 2018;1060:37-54

Division of Clinical Immunology & Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.

This review discusses the important role fibroblasts play in the process of inflammation and the evidence that these cells may drive the persistence of inflammation. Fibroblasts are key components of the stroma normally involved in maintenance of extracellular matrix and tissue function; however, the term 'fibroblast' is used to describe a heterogeneous population of cells that vary in phenotype both between and within anatomical sites. Fibroblasts possess Toll-like receptors allowing them to respond to pathogen and damage-related signals by producing proinflammatory mediators such as IL-6, PGE, and GM-CSF and can produce a range of chemokines such as CXCL12, CXCL13, and CXCL8 which attract B and T lymphocytes, monocytes, and neutrophils to sites of inflammation. Interactions between leukocytes and fibroblasts can facilitate increased survival of the leukocytes and modulate phenotypes leading to differential gene expression in the presence of mediators involved in inflammation. Fibroblasts also contribute to collateral tissue damage during inflammation through the production of members of the metalloproteinase family and cathepsins and also through induction of osteoclastogenesis leading to increased bone resorption rates. In persistent diseases, fibroblasts obtain an imprinted, aggressive phenotype leading to the production of higher basal levels of proinflammatory cytokines and the ability to damage tissue in the absence of continual stimuli. This aggressive phenotype offers an attractive new target for therapeutics that could help alleviate the burden of persistent inflammation.
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http://dx.doi.org/10.1007/978-3-319-78127-3_3DOI Listing
February 2019

Methods for high-dimensional analysis of cells dissociated from cryopreserved synovial tissue

Arthritis Res Ther 2018 07 11;20(1):139. Epub 2018 Jul 11.

Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.

Background: Detailed molecular analyses of cells from rheumatoid arthritis (RA) synovium hold promise in identifying cellular phenotypes that drive tissue pathology and joint damage. The Accelerating Medicines Partnership RA/SLE Network aims to deconstruct autoimmune pathology by examining cells within target tissues through multiple high-dimensional assays. Robust standardized protocols need to be developed before cellular phenotypes at a single cell level can be effectively compared across patient samples.

Methods: Multiple clinical sites collected cryopreserved synovial tissue fragments from arthroplasty and synovial biopsy in a 10% DMSO solution. Mechanical and enzymatic dissociation parameters were optimized for viable cell extraction and surface protein preservation for cell sorting and mass cytometry, as well as for reproducibility in RNA sequencing (RNA-seq). Cryopreserved synovial samples were collectively analyzed at a central processing site by a custom-designed and validated 35-marker mass cytometry panel. In parallel, each sample was flow sorted into fibroblast, T-cell, B-cell, and macrophage suspensions for bulk population RNA-seq and plate-based single-cell CEL-Seq2 RNA-seq.

Results: Upon dissociation, cryopreserved synovial tissue fragments yielded a high frequency of viable cells, comparable to samples undergoing immediate processing. Optimization of synovial tissue dissociation across six clinical collection sites with ~ 30 arthroplasty and ~ 20 biopsy samples yielded a consensus digestion protocol using 100 μg/ml of Liberase™ TL enzyme preparation. This protocol yielded immune and stromal cell lineages with preserved surface markers and minimized variability across replicate RNA-seq transcriptomes. Mass cytometry analysis of cells from cryopreserved synovium distinguished diverse fibroblast phenotypes, distinct populations of memory B cells and antibody-secreting cells, and multiple CD4 and CD8 T-cell activation states. Bulk RNA-seq of sorted cell populations demonstrated robust separation of synovial lymphocytes, fibroblasts, and macrophages. Single-cell RNA-seq produced transcriptomes of over 1000 genes/cell, including transcripts encoding characteristic lineage markers identified.

Conclusions: We have established a robust protocol to acquire viable cells from cryopreserved synovial tissue with intact transcriptomes and cell surface phenotypes. A centralized pipeline to generate multiple high-dimensional analyses of synovial tissue samples collected across a collaborative network was developed. Integrated analysis of such datasets from large patient cohorts may help define molecular heterogeneity within RA pathology and identify new therapeutic targets and biomarkers.
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http://dx.doi.org/10.1186/s13075-018-1631-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042350PMC
July 2018

Routine Papillary Muscle Realignment and Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy.

Ann Thorac Surg 2018 09 16;106(3):670-675. Epub 2018 May 16.

Division of Cardiovascular Medicine, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon.

Background: Septal myectomy has been the mainstay of the surgical treatment of obstructive hypertrophic cardiomyopathy (HCM); however, recently there is growing appreciation for associated mitral valve abnormalities that contribute to left ventricular outflow tract (LVOT) obstruction. In this study, we describe our experience with combined papillary muscle realignment (PMR) and septal myectomy for the treatment of obstructive HCM.

Methods: We identified 44 patients undergoing surgery for obstructive HCM whose anatomy was amenable to combined PMR and septal myectomy at our institution over a 20-month period. All patients underwent resting and stress echocardiography preoperatively and postoperatively. Demographic, clinical, and imaging data were prospectively collected in a cardiac surgery database.

Results: Patient age ranged broadly, with mean age of 54 (range, 18 to 76) years. Preoperatively, 70% of patients were New York Heart Association functional class III or IV, the mean stress LVOT gradient was 144 mm Hg, and severe mitral regurgitation (MR) with stress was seen in 81%. Additional procedures included division of myocardial bands (50%) and chordae (43%) and resection of accessory papillary muscles (25%). Following the procedure, mean resting and stress gradients were reduced to normal (12 and 27 mm Hg, respectively; p < 0.0001). No patient had severe MR and only 3 (6.8%) had moderate MR (p < 0.0001). Mean length of stay was 6 days and there were no mortalities.

Conclusions: Septal myectomy combined with PMR is a safe, highly effective, and reproducible procedure that reliably relieves LVOT obstruction and corrects MR without the need for mitral valve repair or replacement.
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http://dx.doi.org/10.1016/j.athoracsur.2018.04.026DOI Listing
September 2018

Post-ruminal branched-chain amino acid supplementation and intravenous lipopolysaccharide infusion alter blood metabolites, rumen fermentation, and nitrogen balance of beef steers.

J Anim Sci 2018 Jun;96(7):2886-2906

Department of Extension Animal Sciences and Natural Resources, New Mexico State University, Las Cruces, NM.

Steers exposed to an endotoxin may require additional branched-chain AA (BCAA) to support an increase in synthesis of immune proteins. This study evaluated effects of bacterial lipopolysaccharide (LPS) and BCAA supplementation on blood metabolites and N balance of 20 ruminally-cannulated steers (177 ± 4.2 kg BW). The experiment was a randomized block design, with 14-d adaptation to metabolism stalls and diet (DM fed = 1.5% BW) and 6-d collection. Treatments were a 2 × 2 factorial of LPS (0 vs. 1.0 to 1.5 μg/kg BW; -LPS vs. +LPS) and BCAA (0 vs. 35 g/d; -BCAA vs. +BCAA). The LPS in 100 mL sterile saline was infused (1 mL/min via i.v. catheter) on day 15. The BCAA in an essential AA solution were abomasally infused (900 mL/d) three times daily in equal portions beginning on day 7. Blood, rumen fluid, and rectal temperature were collected on day 15 at h 0, 2, 4, 8, 12, and 24 after LPS infusion. Feces and urine were collected from day 16 to 20. Rectal temperatures were greater for +LPS vs. -LPS steers at 4 h and lower at 8 h after LPS infusion (LPS × h, P < 0.01). Serum cortisol and plasma urea N were greater for +LPS than -LPS steers at 2 (cortisol only), 4, 8, 12, and 24 h after LPS infusion (LPS × h, P < 0.01). Serum cortisol was greater for +BCAA than -BCAA steers at 12 h after LPS infusion (BCAA × h, P < 0.05). Serum glucose was greater for +LPS than -LPS steers at 2 h after LPS infusion (LPS × h, P < 0.01). Plasma Ile, Leu, and Val were lower, and plasma His was greater in +LPS than -LPS steers (LPS, P < 0.05). Plasma Lys, Met, Thr, and Trp of +LPS steers were lower than -LPS steers at 4 (Thr only), 8 (Lys and Trp only), 12, and 24 h after infusion (LPS × h, P < 0.05). Plasma Ile, Leu, and Val were greater (BCAA, P < 0.01), and Met, His, Phe, Thr, and Trp were lower for +BCAA than -BCAA steers at 0 and 24 h after LPS infusion (BCAA × h, P ≤ 0.05). Steers receiving +LPS had lower rumen pH at 8 h, greater total VFA at 8 h, and lower rumen NH3 at 24 h after LPS infusion compared with -LPS steers (LPS × h, P ≤ 0.04). Total tract passage rates, DM, OM, NDF, ADF, and N intake, fecal N, digested N, and retained N were lower (P < 0.05) for +LPS than -LPS steers. Total N supply (dietary plus infused) and fecal N were greater (P < 0.05) for +BCAA vs. -BCAA steers. The absence of LPS × BCAA interactions (P ≥ 0.20) for N balance indicated that post-ruminal supplementation of BCAA did not alleviate the negative effects of endotoxin on N utilization by growing steers.
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http://dx.doi.org/10.1093/jas/sky168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095451PMC
June 2018

Functionally distinct disease-associated fibroblast subsets in rheumatoid arthritis.

Nat Commun 2018 02 23;9(1):789. Epub 2018 Feb 23.

Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.

Fibroblasts regulate tissue homeostasis, coordinate inflammatory responses, and mediate tissue damage. In rheumatoid arthritis (RA), synovial fibroblasts maintain chronic inflammation which leads to joint destruction. Little is known about fibroblast heterogeneity or if aberrations in fibroblast subsets relate to pathology. Here, we show functional and transcriptional differences between fibroblast subsets from human synovial tissues using bulk transcriptomics of targeted subpopulations and single-cell transcriptomics. We identify seven fibroblast subsets with distinct surface protein phenotypes, and collapse them into three subsets by integrating transcriptomic data. One fibroblast subset, characterized by the expression of proteins podoplanin, THY1 membrane glycoprotein and cadherin-11, but lacking CD34, is threefold expanded in patients with RA relative to patients with osteoarthritis. These fibroblasts localize to the perivascular zone in inflamed synovium, secrete proinflammatory cytokines, are proliferative, and have an in vitro phenotype characteristic of invasive cells. Our strategy may be used as a template to identify pathogenic stromal cellular subsets in other complex diseases.
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http://dx.doi.org/10.1038/s41467-018-02892-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824882PMC
February 2018

Stromal cell markers are differentially expressed in the synovial tissue of patients with early arthritis.

PLoS One 2017 9;12(8):e0182751. Epub 2017 Aug 9.

Rheumatology Research Group, Institute of Inflammation and Ageing, The University of Birmingham, United Kingdom.

Introduction: Previous studies have shown increased expression of stromal markers in synovial tissue (ST) of patients with established rheumatoid arthritis (RA). Here, ST expression of stromal markers in early arthritis in relationship to diagnosis and prognostic outcome was studied.

Methods: ST from 56 patients included in two different early arthritis cohorts and 7 non-inflammatory controls was analysed using immunofluorescence to detect stromal markers CD55, CD248, fibroblast activation protein (FAP) and podoplanin. Diagnostic classification (gout, psoriatic arthritis, unclassified arthritis (UA), parvovirus associated arthritis, reactive arthritis and RA), disease outcome (resolving vs persistent) and clinical variables were determined at baseline and after follow-up, and related to the expression of stromal markers.

Results: We observed expression of all stromal markers in ST of early arthritis patients, independent of diagnosis or prognostic outcome. Synovial expression of FAP was significantly higher in patients developing early RA compared to other diagnostic groups and non-inflammatory controls. In RA FAP protein was expressed in both lining and sublining layers. Podoplanin expression was higher in all early inflammatory arthritis patients than controls, but did not differentiate diagnostic outcomes. Stromal marker expression was not associated with prognostic outcomes of disease persistence or resolution. There was no association with clinical or sonographic variables.

Conclusions: Stromal cell markers CD55, CD248, FAP and podoplanin are expressed in ST in the earliest stage of arthritis. Baseline expression of FAP is higher in early synovitis patients who fulfil classification criteria for RA over time. These results suggest that significant fibroblast activation occurs in RA in the early window of disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182751PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549962PMC
October 2017

A Longitudinal Analysis of the Association Between Living Arrangements and Health Among Older Adults in China.

Res Aging 2018 01 8;40(1):72-97. Epub 2016 Dec 8.

1 State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Xiamen University, Xiamen, Fujian, China.

This article used the nationally representative Chinese Longitudinal Healthy Longevity Survey to explore the associations between living arrangements and health among older adults. Living arrangements were stratified into six categories. Health was measured by self-rated health, activities of daily living (ADL) disability, and cognitive impairment. Random-effects ordered probit regressions were applied. The results indicated that coresidence had a positive effect on self-rated health compared with living alone. After introducing psychological well-being, the health differences observed in living with a spouse and living with both spouse and children were not significant. Participants with each of the living arrangement were more likely to have a higher rate of cognitive impairment and ADL disability than those living alone. Living arrangements were associated with older adults' health. Psychological well-being was a key factor in this association, which may result from living with a spouse, and could contribute to the self-rated health of older adults.
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http://dx.doi.org/10.1177/0164027516680854DOI Listing
January 2018

Rheumatoid synovial fibroblasts differentiate into distinct subsets in the presence of cytokines and cartilage.

Arthritis Res Ther 2016 11 18;18(1):270. Epub 2016 Nov 18.

Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham Research Laboratories, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, B15 2WB, UK.

Background: We investigated two distinct synovial fibroblast populations that were located preferentially in the lining or sub-lining layers and defined by their expression of either podoplanin (PDPN) or CD248, and explored their ability to undergo self-assembly and transmigration in vivo.

Methods: Synovial fibroblasts (SF) were cultured in vitro and phenotypic changes following stimulation with interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β1 were examined. To examine the phenotype of SF in vivo, a severe combined immunodeficiency (SCID) human-mouse model of cartilage destruction was utilised.

Results: SF in the lining layer in rheumatoid arthritis (RA) expressed high levels of PDPN compared to the normal synovium, whereas CD248 expression was restricted to sub-lining layer cells. TNF-α or IL1 stimulation in vitro resulted in an increased expression of PDPN. In contrast, stimulation with TGF-β1 induced CD248 expression. In the SCID human-mouse model, rheumatoid SF recapitulated the expression of PDPN and CD248. Fibroblasts adjacent to cartilage expressed PDPN, and attached to, invaded, and degraded cartilage. PDPN CD248 SF preceded the appearance of PDPN CD248 cells in contralateral implants.

Conclusions: We have identified two distinct SF populations identified by expression of either PDPN or CD248 which are located within different anatomical compartments of the inflamed synovial membrane. These markers discriminate between SF subsets with distinct biological properties. As PDPN-expressing cells are associated with early fibroblast migration and cartilage erosion in vivo, we propose that PDPN-expressing cells may be an attractive therapeutic target in RA.
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http://dx.doi.org/10.1186/s13075-016-1156-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116193PMC
November 2016

Complementary echo and CCTA findings with superior sinus venosus atrial septal defect.

Echocardiography 2016 Oct;33(10):1600-1601

Heart Clinic of Louisiana, Marrero, LA, USA.

A young female developed progressive dyspnea on minimal exertion. Echocardiography demonstrated a large right heart with severe pulmonary hypertension. Cardiac computed tomographic angiography then demonstrated a superior sinus venosus atrial septal defect with an anomalous right upper pulmonary venous drainage. Echo and CCTA were complementary in making a proper diagnosis.
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http://dx.doi.org/10.1111/echo.13319DOI Listing
October 2016

Pediatric Pulmonary Embolism: Diagnostic and Management Challenges.

World J Pediatr Congenit Heart Surg 2018 01 12;9(1):110-113. Epub 2016 Sep 12.

4 Department of Surgery, Louisiana State University Health Sciences Center School of Medicine, New Orleans, LA, USA.

A rare case of massive pulmonary embolism is presented in an oligosymptomatic teenager with predisposing factors. Computed tomography pulmonary angiography supported by three-dimensional reconstruction was diagnostic. The embolus qualified as massive by conventional anatomical guidelines, but as low risk by more recent functional criteria. Functional assessment has complemented morphologic assessment for risk stratification in adult patients. Such evidence is scarce in pediatrics. The patient underwent surgical embolectomy, followed by prophylactic anticoagulation, without further events. Diagnostic and management challenges are discussed.
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http://dx.doi.org/10.1177/2150135116663698DOI Listing
January 2018

Teaching EHRs security with simulation for non-technical healthcare professionals.

J Healthc Prot Manage 2016 ;32(1):84-97

This paper intends to simplify challenging concepts through role-play demonstrations and serve as a foundation for understanding the basis of securing healthcare data. Disparity exists between the rising need for security of electronic healthcare information and the number of healthcare leaders who understand the concepts behind ensuring privacy and accuracy of such data. Healthcare managers with a basic understanding of data encryption and how it safeguards health information are vital to the success of Electronic Health Records. They often are responsible for proper oversight of such systems and should instill confidence in medical providers and patients that electronic medical data is safe and accurate. However, data security and privacy are complex concepts and remain foreign to many healthcare managers. This paper reviews the benefits of simulation learning and outlines a workshop and simulation game developed in response to difficulties teaching the technology of encryption. The simulation has been successfully tested with graduate health administration students, as well as members of the technical, academic, and teaching community.
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May 2016

Delineation of Criteria for Admission to Step Down in the Mild Traumatic Brain Injury Patient.

Am Surg 2016 Jan;82(1):36-40

Division of Trauma, Acute Care Surgery and Critical Care, Department of Surgery, West Virginia University, Morgantown, West Virginia, USA.

Patients that suffer a mild traumatic brain injury (TBI) with intracranial hemorrhage are commonly admitted to an intensive care unit with repeat imaging in 12 to 24 hours. This is costly to the health-care system. This study aimed to evaluate this practice and to identify criteria to triage patients to lower levels of monitored care. A retrospective review was performed at a university-based Level I trauma center. Patients with mild TBI were included. Data were collected on demographics, neurological status at 6, 12, and 24 hours, CT scan results, and medical or surgical interventions were required. A total of 389 patients were evaluated, 53 had a documented neurological decline while being admitted. Factors found to be associated with a neurological decline included Glasgow Coma Scale (GCS) < 15 (P = 0.002), age greater than 55 (P < 0.001), and warfarin use (P = 0.039). Aspirin and Plavix were not associated with neurological decline. No patient age <55 with a GCS of 15 had a documented decline. Several risk factors were found to be associated with neurological decline after mild TBI. These include age, GCS < 15, and warfarin use. Patients aged <55 with GCS 15, posed minimal risk for deterioration. Patients aged <55 and with a GCS of 15 can be admitted to a monitored step-down bed with less frequent neurological checks.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865797PMC
January 2016

Is There a Relationship Between Value-Based Purchasing and Hospital Profitability? An Exploratory Study of Missouri Hospitals.

Health Serv Res Manag Epidemiol 2015 Jan-Dec;2:2333392815606096. Epub 2015 Oct 1.

Department of Health Management & Policy, Saint Louis University, Saint Louis, MO, USA.

Recent US legislation is attempting to transition inpatient Medicare payments to a value-based purchasing (VBP) program. The VBP program is a pay-for-performance (P4P) system that incentivizes hospitals to improve patient satisfaction, health outcomes, and adherence to clinical protocols while simultaneously holding down costs. Our study evaluates (1) the impact of financial performance on the VBP adjustments and (2) whether there is a correlation between the VBP adjustment and the financial performance of Missouri hospitals that opted into the program. While upward and downward adjustments to the inpatient base rate may be related to hospital financial performance, prior financial performance may also be related to the adjustments. Financial health may allow facilities to invest and position the hospital for favorable future P4P adjustments. The results of our analysis indicate the VBP adjustment to the inpatient base rate is very small (±0.18%), clustered around zero, and is not correlated with financial performance. We also find that financial performance and improvement in the years prior to the adjustment are not related to the VBP adjustment or its respective components. This suggests that CMS is avoiding penalizing less profitable facilities, but the adjustment is also so small and tightly clustered around zero that it is failing to provide an adequate incentive to hospitals. The costs of improving patient satisfaction, clinical process adherence, health care outcomes, and efficiency above that of peers coupled with the growing number of metrics being used to calculate the VBP adjustments call into question the financial incentives of the hospital VBP program.
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http://dx.doi.org/10.1177/2333392815606096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266466PMC
October 2015

What Should We Expect? A Comparison of the Community Benefit and Projected Government Support of Maryland Hospitals.

Med Care Res Rev 2016 Apr 22;73(2):205-26. Epub 2015 Sep 22.

Saint Louis University, Saint Louis, MO, USA.

Designation as a tax-exempt, not-for-profit entity carries with it specific tax benefits. In exchange for tax exemptions, not-for-profit entities are expected to provide benefits to their communities. To evaluate whether hospitals provide community benefits (CBs) equivalent to the financial subsidies and advantages extended to them, tax liabilities and financial support were projected for all Maryland acute care hospitals between 2010 and 2012 and in the aggregate over the 3 years of this study. A comparison was then made between the provision of CBs and the financial support that governments provide to the hospitals. The results indicate that hospitals provide significantly and substantially more CBs than the material financial support they receive. Even after modeling changes in CB activities and the associated tax liabilities that may result from transitioning to taxable status, the benefits that hospitals provide to the communities they serve continue to exceed the potential government tax revenues.
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http://dx.doi.org/10.1177/1077558715604565DOI Listing
April 2016

Moans, Bones, Groans, and a Thyroid Mass.

Am Surg 2015 Aug;81(8):319-21

Department of Surgery, West Virginia University School of Medicine, Morgantown, West Virginia, USA.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700504PMC
August 2015

A Decomposition of Hospital Profitability: An Application of DuPont Analysis to the US Market.

Health Serv Res Manag Epidemiol 2015 Jan-Dec;2:2333392815590397. Epub 2015 Jul 22.

Department of Health Management and Policy, Saint Louis University, Saint Louis, MO USA 63104.

Objectives: This paper evaluates the drivers of profitability for a large sample of U.S. hospitals. Following a methodology frequently used by financial analysts, we use a DuPont analysis as a framework to evaluate the quality of earnings. By decomposing returns on equity (ROE) into profit margin, total asset turnover, and capital structure, the DuPont analysis reveals what drives overall profitability.

Methods: Profit margin, the efficiency with which services are rendered (total asset turnover), and capital structure is calculated for 3,255 U.S. hospitals between 2007 and 2012 using data from the Centers for Medicare & Medicaid Services' Healthcare Cost Report Information System (CMS Form 2552). The sample is then stratified by ownership, size, system affiliation, teaching status, critical access designation, and urban or non-urban location. Those hospital characteristics and interaction terms are then regressed (OLS) against the ROE and the respective DuPont components. Sensitivity to regression methodology is also investigated using a seemingly unrelated regression.

Results: When the sample is stratified by hospital characteristics, the results indicate investor-owned hospitals have higher profit margins, higher efficiency, and are substantially more leveraged. Hospitals in systems are found to have higher ROE, margins, and efficiency but are associated with less leverage. In addition, a number of important and significant interactions between teaching status, ownership, location, critical access designation, and inclusion in a system are documented. Many of the significant relationships, most notably not-for-profit ownership, lose significance or are predominately associated with one interaction effect when interaction terms are introduced as explanatory variables. Results are not sensitive to the alternative methodology.

Conclusion: The results of the DuPont analysis suggest that although there appears to be convergence in the behavior of NFP and IO hospitals, significant financial differences remain depending on their respective hospital characteristics. Those differences are tempered or exacerbated by location, size, teaching status, system affiliation, and critical access designation. With the exception of cost-based reimbursement for critical access hospitals, emerging payment systems are placing additional financial pressures on hospitals. The financial pressures being applied treat hospitals as a monolithic category and, given the delicate and often negative ROE for many hospitals, the long-term stability of the healthcare facility infrastructure may be negatively impacted.
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http://dx.doi.org/10.1177/2333392815590397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266468PMC
July 2015

Population, community, and public health: measuring the benefits.

Adv Health Care Manag 2014 ;16:151-69

Purpose: Population, community, and public health notions are addressed separately in the Patient Protection and Affordable Care Act (ACA), have different foci and stakeholders, build on different frameworks to achieve their aims, and apply different measures to determine the long-term impact of interventions. This paper attempts to clarify each concept and proposes a method of evaluating each of these sets of health-related activities based on the benefits that accrue to the respective stakeholders.

Approach: In addition to indicating how to affect change and improvements in health, the ecological model of health also provides insight into how the benefits from health-related activities may or may not flow back to the entities sponsoring health interventions. By clearly defining each of the concepts and examining the methods and metrics being used to select activities and measure benefits, a valuation model is developed that measures the financial impact on the targeted population as well as the sponsoring institution.

Findings: Defining, measuring, and evaluating are important to bring clarity to how individual organizations can contribute to the overall health of the population, as well as the limits of any single organization in doing so. Collective and upstream action will be required to improve the population's health, but identifying and justifying the role of each participating organization is a challenge that still lacks an overarching vision that can be explained and measured to the satisfaction of all stakeholders. VALUE: Decision makers must justify how resources are committed in an era of scarcity and limited financial means. Moreover, methods must be in place to measure the impact of potential collaborations. The proposed valuation framework lays out the natural incentives, the responses to those incentives, and how to select initiatives that maximize value from the perspective of the various stakeholders.
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http://dx.doi.org/10.1108/s1474-823120140000016007DOI Listing
March 2015

The role of the synovial fibroblast in rheumatoid arthritis pathogenesis.

Curr Opin Rheumatol 2015 Mar;27(2):175-82

aCentre for Translational Inflammation Research, The University of Birmingham bUniversity Hospitals Birmingham NHS Foundation Trust, New Queen Elizabeth Hospital, Edgbaston, Birmingham, UK.

Purpose Of Review: Synovial fibroblasts continue to grow in prominence both as the subjects of research into the pathogenesis of rheumatoid arthritis and as novel therapeutic targets. This timely review aims to integrate the most recent findings with existing paradigms of fibroblast-related mechanisms of disease.

Recent Findings: Linking the role of synovial fibroblasts as innate sentinels expressing pattern recognition receptors such as toll-like receptors to their effector roles in joint damage and interactions with leukocyte subpopulations has continued to advance. Understanding of the mechanisms underlying increased fibroblast survival in the inflamed synovium has led to therapeutic strategies such as cyclin-dependent kinase inhibition. Major advances have taken place in understanding of the interactions between epigenetic and micro-RNA regulation of transcription in synovial fibroblasts, improving our understanding of the unique pathological phenotype of these cells. Finally, the impact of new markers for fibroblast subpopulations is beginning to become apparent, offering the potential for targeting of pathological cells as the roles of different populations become clearer.

Summary: Over the past 2 years, major advances have continued to emerge in understanding of the relationship between synovial fibroblasts and the regulation of inflammatory pathways in the rheumatoid arthritis synovium.
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http://dx.doi.org/10.1097/BOR.0000000000000148DOI Listing
March 2015

Nonclassical Ly6C(-) monocytes drive the development of inflammatory arthritis in mice.

Cell Rep 2014 Oct 16;9(2):591-604. Epub 2014 Oct 16.

Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address:

Different subsets and/or polarized phenotypes of monocytes and macrophages may play distinct roles during the development and resolution of inflammation. Here, we demonstrate in a murine model of rheumatoid arthritis that nonclassical Ly6C(-) monocytes are required for the initiation and progression of sterile joint inflammation. Moreover, nonclassical Ly6C(-) monocytes differentiate into inflammatory macrophages (M1), which drive disease pathogenesis and display plasticity during the resolution phase. During the development of arthritis, these cells polarize toward an alternatively activated phenotype (M2), promoting the resolution of joint inflammation. The influx of Ly6C(-) monocytes and their subsequent classical and then alternative activation occurs without changes in synovial tissue-resident macrophages, which express markers of M2 polarization throughout the course of the arthritis and attenuate joint inflammation during the initiation phase. These data suggest that circulating Ly6C(-) monocytes recruited to the joint upon injury orchestrate the development and resolution of autoimmune joint inflammation.
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http://dx.doi.org/10.1016/j.celrep.2014.09.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223808PMC
October 2014

The tiger genome and comparative analysis with lion and snow leopard genomes.

Nat Commun 2013 ;4:2433

Personal Genomics Institute, Genome Research Foundation, Suwon 443-270, Republic of Korea.

Tigers and their close relatives (Panthera) are some of the world's most endangered species. Here we report the de novo assembly of an Amur tiger whole-genome sequence as well as the genomic sequences of a white Bengal tiger, African lion, white African lion and snow leopard. Through comparative genetic analyses of these genomes, we find genetic signatures that may reflect molecular adaptations consistent with the big cats' hypercarnivorous diet and muscle strength. We report a snow leopard-specific genetic determinant in EGLN1 (Met39>Lys39), which is likely to be associated with adaptation to high altitude. We also detect a TYR260G>A mutation likely responsible for the white lion coat colour. Tiger and cat genomes show similar repeat composition and an appreciably conserved synteny. Genomic data from the five big cats provide an invaluable resource for resolving easily identifiable phenotypes evident in very close, but distinct, species.
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http://dx.doi.org/10.1038/ncomms3433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778509PMC
April 2014
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