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Find video protocols related to scientific articles indexed in Pubmed.
Comparative effectiveness of carotid revascularization therapies: evidence from a national hospital discharge database.
Stroke
PUBLISHED: 10-09-2014
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Clinical equipoise of carotid revascularization therapies remains controversial. We sought to determine whether adverse outcomes after carotid endarterectomy (CEA) or carotid angioplasty and stenting (CAS) were similar using propensity score-matched analysis of retrospective data from a large hospital discharge database.
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Sequencing of Charcot-Marie-Tooth disease genes in a toxic polyneuropathy.
Ann. Neurol.
PUBLISHED: 09-17-2014
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Mutations in Charcot-Marie-Tooth disease (CMT) genes are the cause of rare familial forms of polyneuropathy. Whether allelic variability in CMT genes is also associated with common forms of polyneuropathy-considered "acquired" in medical parlance-is unknown. Chemotherapy-induced peripheral neuropathy (CIPN) occurs commonly in cancer patients and is individually unpredictable. We used CIPN as a clinical model to investigate the association of non-CMT polyneuropathy with CMT genes.
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Prevalence of multimorbidity in a geographically defined American population: patterns by age, sex, and race/ethnicity.
Mayo Clin. Proc.
PUBLISHED: 06-17-2014
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To describe the prevalence of multimorbidity involving 20 selected chronic conditions in a geographically defined US population, emphasizing age, sex, and racial/ethnic differences.
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A New Clinically Based Staging System for Perihilar Cholangiocarcinoma.
Am. J. Gastroenterol.
PUBLISHED: 06-01-2014
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OBJECTIVES:Current staging systems for perihilar cholangiocarcinoma (pCCA) are inadequate, as they are based on surgical pathology and therefore not relevant to unresectable patients. Clinical trials for potential targeted therapies for pCCA are hampered by the lack of an accurate, nonoperative staging system for predicting survival. We aimed at developing a clinical staging system for pCCA, which would be of prognostic relevance for all pCCA patients and help stratify patients for clinical trials.METHODS:Clinical information at the time of pCCA diagnosis of 413 patients seen at Mayo Clinic, Rochester, MN between 2002 and 2010 was retrospectively analyzed. A survival predictive model was developed using Cox proportional hazards analysis. The performance of the staging system was compared with the current AJCC/UICC (the American Joint Committee on Cancer/the Union for International Cancer Control) 7th tumor-node-metastasis (TNM) staging system.RESULTS:Eastern Cooperative Oncology Group (ECOG) status, tumor size and number, vascular encasement, lymph node and peritoneal metastasis and CA 19-9 level were grouped into a four-tier staging system. The median survivals of stages I, II, III, and IV patients were 48.6, 21.8, 8.6, and 2.8 months, with hazard ratios (95% confidence interval) of 1.0 (reference), 1.7 (1.1-2.6), 3.1 (2.0-4.7), and 8.7 (5.2-14.5), respectively (P<0.0001). This staging system had greater concordance statistics (standard error) than the TNM staging system (0.725 (0.018) vs. 0.614 (0.017)), indicating better performance in predicting survival.CONCLUSIONS:This staging system, based on nonoperative information at the time of pCCA diagnosis, has excellent discriminatory power to classify patients into four prognostic stages. It could be useful to clinicians and for the design of clinical trials.Am J Gastroenterol advance online publication, 11 November 2014; doi:10.1038/ajg.2014.327.
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Time trends in glucocorticoid use in rheumatoid arthritis: results from a population-based inception cohort, 1980-1994 versus 1995-2007.
Arthritis Care Res (Hoboken)
PUBLISHED: 04-29-2014
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To examine trends in glucocorticoid (GC) use and dosing among patients diagnosed with rheumatoid arthritis (RA) over time.
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Metformin does not improve survival in patients with hepatocellular carcinoma.
World J. Gastroenterol.
PUBLISHED: 02-28-2014
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To assess whether metformin, which has a chemopreventive effect in chronic liver disease, has any chemotherapeutic effect in hepatocellular carcinoma.
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Chronic kidney disease and associated mortality after liver transplantation--a time-dependent analysis using measured glomerular filtration rate.
J. Hepatol.
PUBLISHED: 02-25-2014
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The accuracy of creatinine-based estimated GFR (eGFR) in assessing the prevalence of chronic kidney disease (CKD) and associated mortality after liver transplantation (LTx) is unknown. Using measured GFR (mGFR) by iothalamate clearance, we determined the prevalence of the entire spectrum of renal dysfunction and the impact of CKD on mortality after LTx.
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BIMA V3: an aligner customized for mate pair library sequencing.
Bioinformatics
PUBLISHED: 02-12-2014
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Mate pair library sequencing is an effective and economical method for detecting genomic structural variants and chromosomal abnormalities. Unfortunately, the mapping and alignment of mate-pair read pairs to a reference genome is a challenging and time-consuming process for most next-generation sequencing alignment programs. Large insert sizes, introduction of library preparation protocol artifacts (biotin junction reads, paired-end read contamination, chimeras, etc.) and presence of structural variant breakpoints within reads increase mapping and alignment complexity. We describe an algorithm that is up to 20 times faster and 25% more accurate than popular next-generation sequencing alignment programs when processing mate pair sequencing.
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The kinship2 R package for pedigree data.
Hum. Hered.
PUBLISHED: 02-11-2014
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The kinship2 package is restructured from the previous kinship package. Existing features are now enhanced and new features added for handling pedigree objects.
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Effect of the pretransplant serum sodium concentration on outcomes following liver transplantation.
Liver Transpl.
PUBLISHED: 02-04-2014
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Hyponatremia is associated with an increased risk of mortality on the liver transplantation (LT) waiting list. Although the incorporation of the serum sodium (Na) level into the Model for End-Stage Liver Disease score may reduce wait-list mortality, concerns remain about a potential association between pre-LT hyponatremia and decreased post-LT survival. Furthermore, the relationship between pre-LT hypernatremia and post-LT survival remains unexplored. The purpose of this study was to investigate the impact of the entire spectrum of pre-LT serum Na levels on post-LT outcomes. We identified 19,537 patients from 2003 to 2010 for whom serum Na levels immediately before LT were available. The patients were divided into 3 groups [hyponatremic (Na ? 130 mEq/L), normonatremic (Na = 131-145 mEq/L), and hypernatremic (Na > 145 mEq/L)], and their post-LT outcomes were compared. There was no difference in in-hospital mortality or 90-day survival between patients with hyponatremia and patients with normonatremia. A fraction of the patients (2.4%) had hypernatremia, which was associated with increased in-hospital mortality (11.2% versus 4.2%, P < 0.001) and diminished 90-day survival (86.4% versus 94.0.%, P < 0.001). After adjustments for important clinical variables, the association of pre-LT hypernatremia with posttransplant mortality remained significant with a hazard ratio of 1.13 for each unit increase in the Na level > 145 mEq/L (P < 0.001). The duration of the hospitalization after LT was significantly longer for hypernatremic patients (P < 0.001). In conclusion, hyponatremia per se does not affect post-LT survival. Pre-LT hypernatremia is a highly significant risk factor for post-LT mortality.
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Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes.
Hepatology
PUBLISHED: 01-24-2014
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The risks and benefits of metformin use in patients with cirrhosis with diabetes are debated. Although data on a protective effect of metformin against liver cancer development have been reported, metformin is frequently discontinued once cirrhosis is diagnosed because of concerns about an increased risk of adverse effects of metformin in patients with liver impairment. This study investigated whether continuation of metformin after cirrhosis diagnosis improves survival of patients with diabetes. Diabetic patients diagnosed with cirrhosis between 2000 and 2010 who were on metformin at the time of cirrhosis diagnosis were identified (n = 250). Data were retrospectively abstracted from the medical record. Survival of patients who continued versus discontinued metformin after cirrhosis diagnosis was compared using the log-rank test. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox's proportional hazards analysis. Overall, 172 patients continued metformin whereas 78 discontinued metformin. Patients who continued metformin had a significantly longer median survival than those who discontinued metformin (11.8 vs. 5.6 years overall, P < 0.0001; 11.8 vs. 6.0 years for Child A patients, P = 0.006; and 7.7 vs. 3.5 years for Child B/C patients, P = 0.04, respectively). After adjusting for other variables, continuation of metformin remained an independent predictor of better survival, with an HR of 0.43 (95% CI: 0.24-0.78; P = 0.005). No patients developed metformin-associated lactic acidosis during follow-up. Conclusion: Continuation of metformin after cirrhosis diagnosis reduced the risk of death by 57%. Metformin should therefore be continued in diabetic patients with cirrhosis if there is no specific contraindication. (Hepatology 2014).
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Modeling trajectories of perceived leg exertion during maximal cycle ergometer exercise in children and adolescents.
BMC Med Res Methodol
PUBLISHED: 01-09-2014
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Borg developed scales for rating pain and perceived exertion in adults that have also been used in pediatric populations. Models describing functional relationships between perceived exertion and work capacity have not been studied in children. We compared different models and their fits to individual trajectories and assessed the variability in these trajectories.
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Predictors of excess mortality after fracture: a population-based cohort study.
J. Bone Miner. Res.
PUBLISHED: 01-07-2014
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To determine the extent to which excess mortality after fractures attributable to particular causes at specific skeletal sites can be predicted using data about all medical diagnoses, we conducted a historical cohort study among 1991 Olmsted County, Minnesota, residents aged ? 50 years who experienced any fracture in 1989 to 1991 and who were followed passively for up to 22 years for death from any cause. We used a machine learning approach, gradient boosting machine (GBM) modeling, to determine whether the comorbid conditions present at the time of fracture and those that arose subsequently could, in aggregate, identify patients at the greatest increased risk of death. During 21,867 person-years of follow-up, 1245 deaths were observed when 1061 were expected (standardized mortality ratio, 1.2; 95% confidence interval [CI] 1.1-1.2). Patients presented with a median history of 26 comorbid conditions each as assessed by the Clinical Classification Software system and 57 each over the total duration of follow-up. Using all available information, the excess deaths could be predicted with good accuracy (c-index ? 0.80) in 89% of the GBM models built for patients with different types of fracture; in one-third of the models, the c-index was ? 0.90. The conditions most prominent in the GBM prediction models were also reflected in the specific causes of death that were elevated, suggesting the influence of confounding on the relationship. However, the predominant comorbid conditions were mainly those responsible for mortality in the general population, rather than the specific diseases most closely associated with secondary osteoporosis. To reduce long-term deaths in the fracture population as a whole, a more general approach to the fracture patient is indicated.
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Serum adipokine and inflammatory markers before and after liver transplantation in recipients with major cardiovascular events.
Liver Transpl.
PUBLISHED: 01-03-2014
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In the nontransplant setting, aberrant serum adipokine levels are associated with cardiovascular (CV) disease. The effects of liver transplantation (LT) on serum adipokine levels and their association with post-LT CV disease have not been studied. A nested case-control study of 77 patients with major CV events more than 4 months after LT analyzed serum adiponectin, resistin, leptin, C-reactive protein, and apolipoprotein levels measured before transplantation and 4, 12, and 24 months after LT. Adiponectin and resistin levels decreased dramatically after LT in all patients. Recipients with CV disease had lower levels of adiponectin and higher levels of resistin, leptin, C-reactive protein, and apolipoprotein B100 than controls. The pre-LT adiponectin level was associated with a 16% increased risk for CV events for every 1 ?g/mL decrease in adiponectin [hazard ratio (HR)?=?0.84, P?=?0.046]. Pre-LT C-reactive protein levels (HR?=?1.03, P?=?0.047) and 12-month C-reactive protein levels (HR?=?1.03, P?=?0.03) were associated with CV events after LT. Pre-LT Diabetes (HR?=?2.14, P?=?0.09), and post-LT resistin (HR?=?1.07, P?=?0.07), and apolipoprotein B (HR?=?1.08, P?=?0.08) were associated with a nonsignificantly increased risk of CV events in this small sample size. In conclusion, pre- and post-LT changes in serum adipokine and inflammatory markers may be signals of an increased risk of CV events after LT, but further study is needed.
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Comparative effectiveness of telaprevir-based triple therapy in patients with chronic hepatitis C.
Mayo Clin. Proc.
PUBLISHED: 01-03-2014
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To examine the effectiveness and tolerability of triple therapy with pegylated interferon (p-IFN), ribavirin (RBV), and telaprevir in patients with chronic hepatitis C receiving treatment in an academic practice setting and in a more clinically diverse population compared with patients receiving treatment in phase 3 trials.
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Proximal femoral density distribution and structure in relation to age and hip fracture risk in women.
J. Bone Miner. Res.
PUBLISHED: 08-30-2013
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Hip fracture risk rises exponentially with age, but there is little knowledge about how fracture-related alterations in hip structure differ from those of aging. We employed computed tomography (CT) imaging to visualize the three-dimensional (3D) spatial distribution of bone mineral density (BMD) in the hip in relation to age and incident hip fracture. We used intersubject image registration to integrate 3D hip CT images into a statistical atlas comprising women aged 21 to 97 years (n?=?349) and a group of women with (n?=?74) and without (n?=?148) incident hip fracture 4 to 7 years after their imaging session. Voxel-based morphometry was used to generate Students t test statistical maps from the atlas, which indicated regions that were significantly associated with age or with incident hip fracture. Scaling factors derived from intersubject image registration were employed as measures of bone size. BMD comparisons of young, middle-aged, and older American women showed preservation of load-bearing cortical and trabecular structures with aging, whereas extensive bone loss was observed in other trabecular and cortical regions. In contrast, comparisons of older Icelandic fracture women with age-matched controls showed that hip fracture was associated with a global cortical bone deficit, including both the superior cortical margin and the load-bearing inferior cortex. Bone size comparisons showed larger dimensions in older compared to younger American women and in older Icelandic fracture women compared to controls. The results indicate that older Icelandic women who sustain incident hip fracture have a structural phenotype that cannot be described as an accelerated pattern of normal age-related loss. The fracture-related cortical deficit noted in this study may provide a biomarker of increased hip fracture risk that may be translatable to dual-energy X-ray absorptiometry (DXA) and other clinical images.
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Calculating sample size estimates for RNA sequencing data.
J. Comput. Biol.
PUBLISHED: 08-20-2013
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Abstract Background: Given the high technical reproducibility and orders of magnitude greater resolution than microarrays, next-generation sequencing of mRNA (RNA-Seq) is quickly becoming the de facto standard for measuring levels of gene expression in biological experiments. Two important questions must be taken into consideration when designing a particular experiment, namely, 1) how deep does one need to sequence? and, 2) how many biological replicates are necessary to observe a significant change in expression? Results: Based on the gene expression distributions from 127 RNA-Seq experiments, we find evidence that 91%?±?4% of all annotated genes are sequenced at a frequency of 0.1 times per million bases mapped, regardless of sample source. Based on this observation, and combining this information with other parameters such as biological variation and technical variation that we empirically estimate from our large datasets, we developed a model to estimate the statistical power needed to identify differentially expressed genes from RNA-Seq experiments. Conclusions: Our results provide a needed reference for ensuring RNA-Seq gene expression studies are conducted with the optimally sample size, power, and sequencing depth. We also make available both R code and an Excel worksheet for investigators to calculate for their own experiments.
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A new statistic for identifying batch effects in high-throughput genomic data that uses guided principal component analysis.
Bioinformatics
PUBLISHED: 08-19-2013
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Batch effects are due to probe-specific systematic variation between groups of samples (batches) resulting from experimental features that are not of biological interest. Principal component analysis (PCA) is commonly used as a visual tool to determine whether batch effects exist after applying a global normalization method. However, PCA yields linear combinations of the variables that contribute maximum variance and thus will not necessarily detect batch effects if they are not the largest source of variability in the data.
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Structural patterns of the proximal femur in relation to age and hip fracture risk in women.
Bone
PUBLISHED: 08-09-2013
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Fractures of the proximal femur are the most devastating outcome of osteoporosis. It is generally understood that age-related changes in hip structure confer increased risk, but there have been few explicit comparisons of such changes in healthy subjects to those with hip fracture. In this study, we used quantitative computed tomography and tensor-based morphometry (TBM) to identify three-dimensional internal structural patterns of the proximal femur associated with age and with incident hip fracture. A population-based cohort of 349 women representing a broad age range (21-97years) was included in this study, along with a cohort of 222 older women (mean age 79±7years) with (n=74) and without (n=148) incident hip fracture. Images were spatially normalized to a standardized space, and age- and fracture-specific morphometric features were identified based on statistical maps of shape features described as local changes of bone volume. Morphometric features were visualized as maps of local contractions and expansions, and significance was displayed as Students t-test statistical maps. Significant age-related changes included local expansions of regions low in volumetric bone mineral density (vBMD) and local contractions of regions high in vBMD. Some significant fracture-related features resembled an accentuated aging process, including local expansion of the superior aspect of the trabecular bone compartment in the femoral neck, with contraction of the adjoining cortical bone. However, other features were observed only in the comparison of hip fracture subjects with age-matched controls including focal contractions of the cortical bone at the superior aspect of the femoral neck, the lateral cortical bone just inferior to the greater trochanter, and the anterior intertrochanteric region. Results of this study support the idea that the spatial distribution of morphometric features is relevant to age-related changes in bone and independent to fracture risk. In women, the identification by TBM of fracture-specific morphometric alterations of the proximal femur, in conjunction with vBMD and clinical risk factors, may improve hip fracture prediction.
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Brief report: accelerated aging influences cardiovascular disease risk in rheumatoid arthritis.
Arthritis Rheum.
PUBLISHED: 06-20-2013
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To determine whether the impact of aging on cardiovascular disease (CVD) risk in patients with rheumatoid arthritis (RA) differs from that in the general population (as estimated by the Framingham Risk Score [FRS]).
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Impact of the center on graft failure after liver transplantation.
Liver Transpl.
PUBLISHED: 05-19-2013
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The hospital at which liver transplantation (LT) is performed has a substantial impact on post-LT outcomes. Center-specific outcome data are closely monitored not only by the centers themselves but also by patients and government regulatory agencies. However, the true magnitude of this center effect, apart from the effects of the region and donor service area (DSA) as well as recipient and donor determinants of graft survival, has not been examined. We analyzed data submitted to the Organ Procurement and Transplantation Network for all adult (age???18 years) primary LT recipients (2005-2008). Using a mixed effects, proportional hazards regression analysis, we modeled graft failure within 1 year after LT on the basis of center (de-identified), region, DSA, and donor and recipient characteristics. At 115 unique centers, 14,654 recipients underwent transplantation. Rates of graft loss within a year varied from 5.9% for the lowest quartile of centers to 20.2% for the highest quartile. Gauged by a comparison of the 75th and 25th percentiles of the data, the magnitude of the center effect on graft survival (1.49-fold change) was similar to that of the recipient Model for End-Stage Liver Disease (MELD) score (1.47) and the donor risk index (DRI; 1.45). The center effect was similar across the DRI and MELD score quartiles and was not associated with a centers annual LT volume. After stratification by region and DSA, the magnitude of the center effect, though decreased, remained significant and substantial (1.30-fold interquartile difference). In conclusion, the LT center is a significant predictor of graft failure that is independent of region and DSA as well as donor and recipient characteristics. Liver Transpl 19:957-964, 2013. © 2013 AASLD.
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Underestimation of liver-related mortality in the United States.
Gastroenterology
PUBLISHED: 03-29-2013
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According to the National Center for Health Statistics (NCHS), chronic liver disease and cirrhosis is the 12(th) leading cause of death in the United States. However, this single descriptor might not adequately enumerate all deaths from liver disease. The aim of our study was to update data on liver mortality in the United States.
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Brief report: rheumatoid arthritis is associated with left ventricular concentric remodeling: results of a population-based cross-sectional study.
Arthritis Rheum.
PUBLISHED: 03-19-2013
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To study left ventricular (LV) geometry in patients with rheumatoid arthritis (RA) and no history of heart failure compared with that in subjects with neither RA nor a history of heart failure, and to determine the impact of RA on LV remodeling.
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Immunoglobulin m monoclonal gammopathy of undetermined significance and smoldering Waldenström macroglobulinemia.
Clin Lymphoma Myeloma Leuk
PUBLISHED: 03-13-2013
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Monoclonal gammopathy of undetermined significance of the immunoglobulin M class was diagnosed in 213 patients at the Mayo Clinic, 29 (14%) of whom developed lymphoma, Waldenström macroglobulinemia, or a related disorder over 1567 person-years of follow-up. The cumulative probability of progression was 10% at 5 years, 18% at 10 years, and 24% at 15 years, or approximately 1.5% per year. The concentration of serum monoclonal protein at diagnosis and the initial serum albumin value were the only independent predictors of progression with multivariate analysis. By contrast, during 285 person-years of follow-up, 34 (71%) of 48 patients with smoldering Waldenström macroglobulinemia (SWM) progressed to Waldenström macroglobulinemia (WM), which required therapy, along with amyloid light chain (AL) amyloidosis (1) and lymphoma (1). The cumulative probability of progression was 6% at 1 year, 39% at 3 years, 59% at 5 years, and 65% at 10 years. The percentage of lymphoplasmacytic cells in the bone marrow, size of the serum monoclonal (M) spike, and hemoglobin value were significant independent risk factors for progression.
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Uncovering the biology of multiple myeloma among African Americans: a comprehensive genomics approach.
Blood
PUBLISHED: 02-19-2013
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Epidemiological data have suggested that African American (AA) persons are twice as likely to be diagnosed with multiple myeloma (MM) compared with European American (EA) persons. Here, we have analyzed a set of cytogenetic and genomic data derived from AA and EA MM patients. We have compared the frequency of IgH translocations in a series of data from 115 AA patients from 3 studies and 353 EA patients from the Eastern Cooperative Oncology Group (ECOG) studies E4A03 and E9487. We have also interrogated tumors from 45 AA and 196 EA MM patients for somatic copy number abnormalities associated with poor outcome. In addition, 35 AA and 178 EA patients were investigated for a transcriptional profile associated with high-risk disease. Overall, based on this cohort, genetic profiles were similar except for a significantly lower frequency of IgH translocations (40% vs 52%; P = .032) in AA patients. Frequency differences of somatic copy number aberrations were not significant after correction for multiple testing. There was also no significant difference in the frequency of high-risk disease based on gene expression profiling. Our study represents the first comprehensive comparisons of the frequency and distribution of molecular alterations in MM tumors between AA and EA patients. ECOG E4A03 is registered with ClinicalTrials.gov, number NCT00098475. ECOG E9487 is a companion validation set to the ECOG study E9486 and is registered with the National Institutes of Health, National Cancer Institute, Clinical Trials (PDQ), number EST-9486.
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Longterm outcomes and treatment after myocardial infarction in patients with rheumatoid arthritis.
J. Rheumatol.
PUBLISHED: 02-15-2013
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To investigate the risk profiles, treatment, and outcomes of patients with rheumatoid arthritis (RA) with myocardial infarction (MI) and matched MI patients without RA.
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Immune response profiling in early rheumatoid arthritis: discovery of a novel interaction of treatment response with viral immunity.
Arthritis Res. Ther.
PUBLISHED: 02-09-2013
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It remains challenging to predict the outcomes of therapy in patients with rheumatoid arthritis (RA). The objective of this study was to identify immune response signatures that correlate with clinical treatment outcomes in patients with RA.
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Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States.
Hepatology
PUBLISHED: 01-25-2013
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The clinical and public health significance of nonalcoholic fatty liver disease (NAFLD) is not well established. We investigated the long-term effect of NAFLD on mortality. This analysis utilized the National Health and Nutrition Examination Survey conducted in 1988-1994 and subsequent follow-up data for mortality through December 31, 2006. NAFLD was defined by ultrasonographic detection of hepatic steatosis in the absence of other known liver diseases. The presence and severity of hepatic fibrosis in subjects with NAFLD was determined by the NAFLD fibrosis score (NFS), the aspartate aminotransferase to platelet ratio index (APRI), and FIB-4 score. Of 11,154 participants, 34.0% had NAFLD--the majority (71.7%) had NFS consistent with lack of significant fibrosis (NFS <-1.455), whereas 3.2% had a score indicative of advanced fibrosis (NFS >0.676). After a median follow-up of 14.5 years, NAFLD was not associated with higher mortality (age- and sex-adjusted hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 0.93-1.19). In contrast, there was a progressive increase in mortality with advancing fibrosis scores. Compared to subjects without fibrosis, those with a high probability of advanced fibrosis had a 69% increase in mortality (for NFS: HR, 1.69, 95% CI: 1.09-2.63; for APRI: HR, 1.85, 95% CI: 1.02-3.37; for FIB-4: HR, 1.66, 95% CI: 0.98-2.82) after adjustment for other known predictors of mortality. These increases in mortality were almost entirely from cardiovascular causes (for NFS: HR, 3.46, 95% CI: 1.91-6.25; for APRI: HR, 2.53, 95% CI: 1.33-4.83; for FIB-4: HR, 2.68, 95% CI: 1.44-4.99). Conclusions: Ultrasonography-diagnosed NAFLD is not associated with increased mortality. However, advanced fibrosis, as determined by noninvasive fibrosis marker panels, is a significant predictor of mortality, mainly from cardiovascular causes, independent of other known factors.
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Quality assessment metrics for whole genome gene expression profiling of paraffin embedded samples.
BMC Res Notes
PUBLISHED: 01-18-2013
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Formalin fixed, paraffin embedded tissues are most commonly used for routine pathology analysis and for long term tissue preservation in the clinical setting. Many institutions have large archives of Formalin fixed, paraffin embedded tissues that provide a unique opportunity for understanding genomic signatures of disease. However, genome-wide expression profiling of Formalin fixed, paraffin embedded samples have been challenging due to RNA degradation. Because of the significant heterogeneity in tissue quality, normalization and analysis of these data presents particular challenges. The distribution of intensity values from archival tissues are inherently noisy and skewed due to differential sample degradation raising two primary concerns; whether a highly skewed array will unduly influence initial normalization of the data and whether outlier arrays can be reliably identified.
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Long-term biological variation of serum protein electrophoresis M-spike, urine M-spike, and monoclonal serum free light chain quantification: implications for monitoring monoclonal gammopathies.
Clin. Chem.
PUBLISHED: 10-06-2011
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We analyzed serial data in patients with clinically stable monoclonal gammopathy to determine the total variation of serum M-spikes [measured with serum protein electrophoresis (SPEP)], urine M-spikes [measured with urine protein electrophoresis (UPEP)], and monoclonal serum free light chain (FLC) concentrations measured with immunoassay.
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Estimating underreported N2 disease in rectal cancer patients with low lymph node counts.
J Surg Oncol
PUBLISHED: 08-13-2011
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The variability in the number of lymph nodes examined needs to be taken into account for adequate staging. The definition of nodal staging was refined by quantifying the likelihood of N2 disease when the patient had fewer than four positive LN.
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Relative quantification: characterization of bias, variability and fold changes in mass spectrometry data from iTRAQ-labeled peptides.
J. Proteome Res.
PUBLISHED: 08-02-2011
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Shotgun proteomics via mass spectrometry (MS) is a powerful technology for biomarker discovery that has the potential to lead to noninvasive disease screening mechanisms. Successful application of MS-based proteomics technologies for biomarker discovery requires accurate expectations of bias, reproducibility, variance, and the true detectable differences in platforms chosen for analyses. Characterization of the variability inherent in MS assays is vital and should affect interpretation of measurements of observed differences in biological samples. Here we describe observed biases, variance structure, and the ability to detect known differences in spike-in data sets for which true relative abundance among defined samples were known and were subsequently measured with the iTRAQ technology on two MS platforms. Global biases were observed within these data sets. Measured variability was a function of mean abundance. Fold changes were biased toward the null and variance of a fold change was a function of protein mass and abundance. The information presented herein will be valuable for experimental design and analysis of the resulting data.
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Batch effect correction for genome-wide methylation data with Illumina Infinium platform.
BMC Med Genomics
PUBLISHED: 07-29-2011
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Genome-wide methylation profiling has led to more comprehensive insights into gene regulation mechanisms and potential therapeutic targets. Illumina Human Methylation BeadChip is one of the most commonly used genome-wide methylation platforms. Similar to other microarray experiments, methylation data is susceptible to various technical artifacts, particularly batch effects. To date, little attention has been given to issues related to normalization and batch effect correction for this kind of data.
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Assessing immune function by profiling cytokine release from stimulated blood leukocytes and the risk of infection in rheumatoid arthritis.
Clin. Immunol.
PUBLISHED: 05-16-2011
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Persons with rheumatoid arthritis (RA) suffer a high burden of infections, but currently no biomarkers are available to identify individuals at greatest risk. A prospective longitudinal study was therefore conducted to determine the association between the responsiveness of ex vivo cytokine production and 6-month risk of infections. Infections were identified by billing codes and validated by medical record review. At baseline, the release of 17 cytokines by peripheral blood mononuclear cells in response to stimulation, or media alone, was measured using multiplexed cytokine analysis. Production of IL-2, IL-8, IL-10, IL-17, TNF-?, IFN-?, and GM-CSF, induced by various conditions, was significantly associated with the occurrence of infections. A multivariable prediction model based on these data provided new information on the risk of infection beyond standard assessments of disease activity, severity, and treatment. Future studies could utilize this information to devise new biomarkers for the prediction of infection in patients with RA.
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The influence of rheumatoid arthritis disease characteristics on heart failure.
J. Rheumatol.
PUBLISHED: 05-15-2011
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To examine the influence of rheumatoid arthritis (RA) characteristics and antirheumatic medications on the risk of heart failure (HF) in patients with RA.
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Design and rationale of the HCC BRIDGE study in China: a longitudinal, multicenter cohort trial in hepatocellular carcinoma.
BMC Gastroenterol
PUBLISHED: 05-12-2011
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More than 50% of the worldwide cases of hepatocellular carcinoma occur in China, and this malignancy currently represents the countrys second leading cause of cancer death in cities and the leading cause in rural areas. Despite recent advances in the control and management of hepatocellular carcinoma within China, this disease remains a major health care issue. The global HCC BRIDGE study, designed to assess patterns of hepatocellular carcinoma therapy use and associated outcomes across real-world clinical practice, has recently been expanded as a national study in China, allowing a detailed analysis of hepatocellular carcinoma in this important country.
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Fracture risk in men with prostate cancer: a population-based study.
J. Bone Miner. Res.
PUBLISHED: 04-27-2011
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Fractures are increased among men with prostate cancer, especially those on androgen-deprivation therapy (ADT), but few data are available on men with localized prostate cancer. The purpose of this investigation was to estimate fracture risk among unselected community men with prostate cancer and systematically assess associations with ADT and other risk factors for fracture. In a population-based retrospective cohort study, 742 Olmsted County, MN, men with prostate cancer first diagnosed in 1990-1999 (mean age 68.2?±?8.9 years) were followed for 6821 person-years. We estimated cumulative fracture incidence, assessed relative risk by standardized incidence ratios, and evaluated risk factors in time-to-fracture regression models. All together, 482 fractures were observed in 258 men (71 per 1000 person-years). Overall fracture risk was elevated 1.9-fold, with an absolute increase in risk of 9%. Relative to rates among community men generally, fracture risk was increased even among men not on ADT but was elevated a further 1.7-fold among ADT-treated compared with untreated men with prostate cancer. The increased risk following various forms of ADT was accounted for mainly by associations with pathologic fractures (14% of all fractures). Among men not on ADT (62% of the cohort), more traditional osteoporosis risk factors were implicated. In both groups, underlying clinical characteristics prompting different treatments (indication bias) may have been partially responsible for the associations seen with specific therapies. To the extent that advanced-stage disease and pathologic fractures account for the excess risk, the effectiveness of fracture prevention among men with prostate cancer may be limited.
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IgM monoclonal gammopathy of undetermined significance (MGUS) and smoldering Waldenströms macroglobulinemia (SWM).
Clin Lymphoma Myeloma Leuk
PUBLISHED: 04-02-2011
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Monoclonal gammopathy of undetermined significance of IgM class (IgM MGUS) was diagnosed in 213 Mayo Clinic patients who were residents of 11 counties in Southeastern Minnesota from 1960 to 1994. During long-term follow-up 29 (14%) developed non-Hodgkin lymphoma (n=17), Waldenströms macroglobulinemia (n=6), chronic lymphocytic leukemia (n=3), and AL amyloidosis (n=3) with relative risks of 15-, 262-, 6-, and 16-fold, respectively. The cumulative probability of progression to one of these disorders was 10% at 5 years, 18% at 10 years, and 24% at 15 years, approximately 1.5% per year.Forty-eight patients with SWM were identified at Mayo Clinic from 1974 to 1995. During 285 cumulative person-years of follow-up (median, 15.4 years) 34 (71%) progressed to Waldenströms macroglobulinemia (WM), 1 to AL amyloidosis, and 1 to lymphoma (total, 36 [75%]). The cumulative probability of progressing to WM, amyloidosis, or lymphoma was 6% at 1 year, 39% at 3 years, and 59% at 5 years (12% per year).
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Insights on the robust variance estimator under recurrent-events model.
Biometrics
PUBLISHED: 03-18-2011
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Recurrent events are common in medical research for subjects who are followed for the duration of a study. For example, cardiovascular patients with an implantable cardioverter defibrillator (ICD) experience recurrent arrhythmic events that are terminated by shocks or antitachycardia pacing delivered by the device. In a published randomized clinical trial, a recurrent-event model was used to study the effect of a drug therapy in subjects with ICDs, who were experiencing recurrent symptomatic arrhythmic events. Under this model, one expects the robust variance for the estimated treatment effect to diminish when the duration of the trial is extended, due to the additional events observed. However, as shown in this article, that is not always the case. We investigate this phenomenon using large datasets from this arrhythmia trial and from a diabetes study, with some analytical results, as well as through simulations. Some insights are also provided on existing sample size formulae using our results.
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A signature of aberrant immune responsiveness identifies myocardial dysfunction in rheumatoid arthritis.
Arthritis Rheum.
PUBLISHED: 03-09-2011
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Heart failure is an important cause of death in patients with rheumatoid arthritis (RA). Evidence suggests that immune mechanisms contribute to myocardial injury and fibrosis, leading to left ventricular diastolic dysfunction (LVDD). The purpose of this study was to identify a signature of LVDD in patients with RA by analyzing the responsiveness of the innate and adaptive immune systems to stimulation ex vivo.
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The lifetime risk of adult-onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases.
Arthritis Rheum.
PUBLISHED: 03-02-2011
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Understanding of the personal risks for rheumatoid arthritis (RA) and other rheumatic diseases remains poor, despite advances in knowledge with regard to their pathogenesis, therapeutics, and clinical impact, in part because the personal lifetime risk of developing these diseases is unknown. This study was undertaken to estimate the lifetime risk of RA, as well as other inflammatory autoimmune rheumatic diseases, including systemic lupus erythematosus, psoriatic arthritis, polymyalgia rheumatica (PMR), giant cell arteritis, ankylosing spondylitis, and Sjögrens syndrome, and to provide an overall estimate of the risk of developing inflammatory autoimmune rheumatic disease over a lifetime.
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Factors that affect risk for hepatocellular carcinoma and effects of surveillance.
Clin. Gastroenterol. Hepatol.
PUBLISHED: 02-25-2011
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The incidence of hepatocellular carcinoma (HCC) in the United States is increasing. Surveillance may affect the stage at diagnosis and consequently the treatment options available for HCC. We evaluated risk factors for HCC, the proportion of cases detected via surveillance, tumor characteristics, treatment approaches, and overall patient survival in a referral center cohort.
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Association of hip strength estimates by finite-element analysis with fractures in women and men.
J. Bone Miner. Res.
PUBLISHED: 02-10-2011
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Finite-element analysis (FEA) of quantitative computed tomography (QCT) scans can estimate site-specific whole-bone strength. However, it is uncertain whether the site-specific detail included in FEA-estimated proximal femur (hip) strength can determine fracture risk at sites with different biomechanical characteristics. To address this question, we used FEA of proximal femur QCT scans to estimate hip strength and load-to-strength ratio during a simulated sideways fall and measured total hip areal and volumetric bone mineral density (aBMD and vBMD) from QCT images in an age-stratified random sample of community-dwelling adults age 35 years or older. Among 314 women (mean age ± SD: 61 ± 15 years; 235 postmenopausal) and 266 men (62 ± 16 years), 139 women and 104 men had any prevalent fracture, whereas 55 Women and 28 men had a prevalent osteoporotic fracture that had occurred at age 35 years or older. Odds ratios by age-adjusted logistic regression analysis for prevalent overall and osteoporotic fractures each were similar for FEA hip strength and load-to-strength ratio, as well as for total hip aBMD and vBMD. C-statistics (estimated areas under ROC curves) also were similar [eg, 0.84 to 0.85 (women) and 0.75 to 0.78 (men) for osteoporotic fractures]. In women and men, the association with prevalent osteoporotic fractures increased below an estimated hip strength of approximately 3000 N. Despite its site-specific nature, FEA-estimated hip strength worked equally well at predicting prevalent overall and osteoporotic fractures. Furthermore, an estimated hip strength below 3000 N may represent a critical level of systemic skeletal fragility in both sexes that warrants further investigation.
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A revised model for end-stage liver disease optimizes prediction of mortality among patients awaiting liver transplantation.
Gastroenterology
PUBLISHED: 01-16-2011
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The Model for End Stage Liver Disease (MELD) was originally developed based on data from patients who underwent the transjugular intrahepatic portosystemic shunt procedure. An updated MELD based on data from patients awaiting liver transplantation should improve mortality prediction and allocation efficiency.
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Use of B-type natriuretic peptide as a screening tool for left ventricular diastolic dysfunction in rheumatoid arthritis patients without clinical cardiovascular disease.
Arthritis Care Res (Hoboken)
PUBLISHED: 01-13-2011
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Patients with rheumatoid arthritis (RA) are at an increased risk for heart failure and left ventricular diastolic dysfunction (LVDD). B-type natriuretic peptide (BNP) may be useful to screen for LVDD in the general population. We compared the effectiveness of BNP as a screening tool for LVDD in RA and non-RA subjects without cardiovascular disease (CVD).
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Lipid paradox in rheumatoid arthritis: the impact of serum lipid measures and systemic inflammation on the risk of cardiovascular disease.
Ann. Rheum. Dis.
PUBLISHED: 01-07-2011
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To examine the impact of systemic inflammation and serum lipids on cardiovascular disease (CVD) in rheumatoid arthritis (RA).
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Utility of serum immunoglobulin G4 in distinguishing immunoglobulin G4-associated cholangitis from cholangiocarcinoma.
Hepatology
PUBLISHED: 01-06-2011
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Elevated serum immunoglobulin G4 (sIgG4) is a feature of autoimmune pancreatitis (AIP) and IgG4-associated cholangitis (IAC); a >2-fold increase in sIgG4 is considered highly specific for these disorders. Many patients with IAC present with biliary strictures and obstructive jaundice, making cholangiocarcinoma (CCA) an important differential diagnosis. We determined the value of sIgG4 in distinguishing IAC from CCA. sIgG4 levels were measured in a test cohort of 126 CCA and 50 IAC patients. The results were confirmed in a validation cohort of 161 CCA and 47 IAC patients. Of the 126 CCA patients in the test cohort, 17 (13.5%) had elevated sIgG4 (>140 mg/dL) and four (3.2%) had a >2-fold (>280 mg/dL) increase. Primary sclerosing cholangitis (PSC) was present in 31/126 CCA patients, of whom seven (22.6%) had elevated sIgG4 and two (6.5%) had a >2-fold elevation. Of the 50 IAC patients, 39 (78.0%) had elevated sIgG4 and 25 (50.0%) had a >2-fold increase. The results in the validation cohort were consistent with those of the test cohort. Conclusion: Although elevated sIgG4 levels are characteristic of IAC, some patients with CCA, particularly with PSC, have elevated sIgG4 levels, including a small percentage with a more than a 2-fold increase in sIgG4. Therefore, sIgG4 elevation alone does not exclude the diagnosis of CCA. Depending on the prevalence of the two diagnoses, the use of a 2-fold cutoff for sIgG4 may not reliably distinguish IAC from CCA. At a cutoff of 4 times the upper limit of normal, sIgG4 is 100% specific for IAC.
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Bi-Linear Regression for O Quantification: Modeling across the Elution Profile.
J Proteomics Bioinform
PUBLISHED: 11-15-2010
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MOTIVATION: Interpreting and quantifying labeled mass-spectrometry data is complex and requires automated algorithms, particularly for large scale proteomic profiling. Here, we propose the use of bi-linear regression to quantify relative abundance across the elution profile in a unified model. The bi-linear regression model takes advantage of the fact that while peptides differ in overall abundance across the elution profile multiplicatively, the relative abundance between the mixed samples remains constant across the elution profile. We describe how to apply bi-linear regression models to (18)O stable-isotope labeled data, which allows for the direct comparison of two samples simultaneously. Interpretation of model parameters is also discussed. The incorporation rate of the labeling isotope is estimated as part of the modeling process and can be used as a measure of data quality. Application is demonstrated in a controlled experiment as well as in a complex mixture. RESULTS: Bi-linear regression models allow for more precise and accurate estimates of abundance, in comparison to methods that treat each spectrum independently, by taking into account the abundance of the molecule throughout the entire elution profile, with precision increased by one-to-two orders of magnitude.
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Increased prevalence of metabolic syndrome associated with rheumatoid arthritis in patients without clinical cardiovascular disease.
J. Rheumatol.
PUBLISHED: 10-15-2010
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to examine whether patients with rheumatoid arthritis (RA) with no overt cardiovascular disease (CVD) have a higher prevalence of metabolic syndrome (MetS) than subjects without RA or CVD. We also examined whether RA disease characteristics are associated with the presence of MetS in RA patients without CVD.
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Endothelial nitric oxide synthase gene variation associated with chronic kidney disease after liver transplant.
Mayo Clin. Proc.
PUBLISHED: 09-03-2010
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To identify single nucleotide polymorphisms (SNPs) associated with risk of developing chronic kidney disease (CKD), a prevalent comorbidity, after liver transplant (LT).
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Anxious personality predicts an increased risk of Parkinsons disease.
Mov. Disord.
PUBLISHED: 07-30-2010
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We studied the association of three personality traits related to neuroticism with the subsequent risk of Parkinsons disease (PD) using a historical cohort study. We included 7,216 subjects who resided within the 120-mile radius centered in Rochester, MN, at the time they completed the Minnesota Multiphasic Personality Inventory (MMPI) for research at the Mayo Clinic from 1962 to 1965. We considered three MMPI personality scales (pessimistic, anxious, and depressive traits). A total of 6,822 subjects (94.5%) were followed over four decades either actively or passively. During follow-up, 227 subjects developed parkinsonism (156 developed PD). An anxious personality was associated with an increased risk of PD [hazard ratio (HR), 1.63; 95% confidence interval (CI), 1.16-2.27]. A pessimistic personality trait was also associated with an increased risk of PD but only in men (HR = 1.92; 95% CI = 1.20-3.07). By contrast, a depressive trait was not associated with increased risk. Analyses combining scores from the three personality scales into a composite neuroticism score showed an association of neuroticism with PD (HR = 1.54; 95% CI = 1.10-2.16). The association with neuroticism remained significant even when the MMPI was administered early in life (ages 20-39 years). By contrast, none of the three personality traits was associated with the risk of non-PD types of parkinsonism grouped together. Our long-term historical cohort study suggests that an anxious personality trait may predict an increased risk of PD developing many years later.
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Cirrhosis is present in most patients with hepatitis B and hepatocellular carcinoma.
Clin. Gastroenterol. Hepatol.
PUBLISHED: 06-11-2010
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There are few data available about the prevalence or effects of cirrhosis in patients with hepatocellular carcinoma (HCC) from viral hepatitis. We compared patients with HCC and hepatitis B virus (HBV) or hepatitis C virus (HCV) infections to determine the proportions of cirrhosis in each group, virologic and tumor characteristics, and overall survival.
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Relation of vertebral deformities to bone density, structure, and strength.
J. Bone Miner. Res.
PUBLISHED: 06-10-2010
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Because they are not reliably discriminated by areal bone mineral density (aBMD) measurements, it is unclear whether minimal vertebral deformities represent early osteoporotic fractures. To address this, we compared 90 postmenopausal women with no deformity (controls) with 142 women with one or more semiquantitative grade 1 (mild) deformities and 51 women with any grade 2-3 (moderate/severe) deformities. aBMD was measured by dual-energy X-ray absorptiometry (DXA), lumbar spine volumetric bone mineral density (vBMD) and geometry by quantitative computed tomography (QCT), bone microstructure by high-resolution peripheral QCT at the radius (HRpQCT), and vertebral compressive strength and load-to-strength ratio by finite-element analysis (FEA) of lumbar spine QCT images. Compared with controls, women with grade 1 deformities had significantly worse values for many bone density, structure, and strength parameters, although deficits all were much worse for the women with grade 2-3 deformities. Likewise, these skeletal parameters were more strongly associated with moderate to severe than with mild deformities by age-adjusted logistic regression. Nonetheless, grade 1 vertebral deformities were significantly associated with four of the five main variable categories assessed: bone density (lumbar spine vBMD), bone geometry (vertebral apparent cortical thickness), bone strength (overall vertebral compressive strength by FEA), and load-to-strength ratio (45-degree forward bending ÷ vertebral compressive strength). Thus significantly impaired bone density, structure, and strength compared with controls indicate that many grade 1 deformities do represent early osteoporotic fractures, with corresponding implications for clinical decision making.
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Increased prevalence of diastolic dysfunction in rheumatoid arthritis.
Ann. Rheum. Dis.
PUBLISHED: 05-24-2010
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To compare the prevalence of left ventricular (LV) diastolic dysfunction in subjects with and without rheumatoid arthritis (RA), among those with no history of heart failure (HF), and to determine risk factors for diastolic dysfunction in RA.
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Impact of optimal follow-up of monoclonal gammopathy of undetermined significance on early diagnosis and prevention of myeloma-related complications.
Blood
PUBLISHED: 05-21-2010
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Monoclonal gammopathy of undetermined significance (MGUS) is associated with a long-term risk of progression to multiple myeloma (MM) or related malignancy. To prevent serious myeloma-related complications, lifelong annual follow-up has been recommended, but its value is unknown. We reviewed all patients from southeastern Minnesota seen at Mayo Clinic between 1973 and 2004 with MGUS who subsequently progressed to MM. Of 116 patients, 69% had optimal follow-up of MGUS. Among these, abnormalities on serial follow-up laboratory testing led to the diagnosis of MM in 16%, whereas MM was diagnosed only after serious MM-related complications in 45%. In the remaining, workup of less serious symptoms (25%), incidental finding during workup of unrelated medical conditions (11%), and unknown (3%) were the mechanisms leading to MM diagnosis. High-risk MGUS patients (? 1.5 g/dL and/or non-IgG MGUS) were more likely to be optimally followed (81% vs 64%), and be diagnosed with MM secondary to serial follow-up testing (21% vs 7%). This retrospective study suggests that routine annual follow-up of MGUS may not be required in low-risk MGUS. Future studies are needed to replicate and expand our findings and to determine the optimal frequency of monitoring in higher-risk MGUS patients.
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Analysis of complex biomarkers for human immune-mediated disorders based on cytokine responsiveness of peripheral blood cells.
J. Immunol.
PUBLISHED: 05-21-2010
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The advent of improved biomarkers promises to enhance the clinical care for patients with rheumatoid arthritis (RA) and other immune-mediated disorders. We have developed an innovative approach to broadly assess the cytokine responsiveness of human PBMCs using a multistimulant panel and multiplexed immunoassays. The objective of this study was to demonstrate this concept by determining whether cytokine profiles could discriminate RA patients according to disease stage (early versus late) or severity. A 10-cytokine profile, consisting of IL-12, CCL4, TNF-alpha, IL-4, and IL-10 release in response to stimulation with anti-CD3/anti-CD28, CXCL8 and IL-6 in response to CMV and EBV lysate, and IL-17A, GM-CSF, and CCL2 in response to human heat shock protein 60, easily discriminated the early RA group from controls. These data were used to create an immune response score, which performed well in distinguishing the early RA patients from controls and also correlated with several markers of disease severity among the patients with late RA. In contrast, the same 10-cytokine profile assessed in serum was far less effective in discriminating the groups. Thus, our approach lays the foundation for the development of immunologic "signatures" that could be useful in predicting disease course and monitoring the outcomes of therapy among patients with immune-mediated diseases.
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Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study.
Lancet
PUBLISHED: 05-18-2010
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Monoclonal gammopathy of undetermined significance (MGUS) is defined by expression of heavy-chain immunoglobulin (IgH) and is the precursor lesion for 80% of cases of multiple myeloma. The remaining 20% are characterised by absence of IgH expression; we aimed to assess prevalence of a corresponding precursor entity, light-chain MGUS.
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Is the incidence of rheumatoid arthritis rising?: results from Olmsted County, Minnesota, 1955-2007.
Arthritis Rheum.
PUBLISHED: 03-02-2010
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To examine trends in the incidence and prevalence of rheumatoid arthritis (RA) from 1995 to 2007.
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Spatial normalization improves the quality of genotype calling for Affymetrix SNP 6.0 arrays.
BMC Bioinformatics
PUBLISHED: 02-16-2010
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Microarray measurements are susceptible to a variety of experimental artifacts, some of which give rise to systematic biases that are spatially dependent in a unique way on each chip. It is likely that such artifacts affect many SNP arrays, but the normalization methods used in currently available genotyping algorithms make no attempt at spatial bias correction. Here, we propose an effective single-chip spatial bias removal procedure for Affymetrix 6.0 SNP arrays or platforms with similar design features. This procedure deals with both extreme and subtle biases and is intended to be applied before standard genotype calling algorithms.
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Nonalcoholic fatty liver disease increases risk of death among patients with diabetes: a community-based cohort study.
Am. J. Gastroenterol.
PUBLISHED: 02-09-2010
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The significance of nonalcoholic fatty liver disease (NAFLD) among patients with diabetes is unknown. We sought to determine whether a diagnosis of NAFLD influenced mortality among a community-based cohort of patients with type II diabetes mellitus.
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Serum sodium, renal function, and survival of patients with end-stage liver disease.
J. Hepatol.
PUBLISHED: 02-04-2010
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Serum creatinine, a component of the model for end-stage liver disease (MELD), is an important prognostic indicator in patients with end-stage liver disease (ESLD). In addition, serum sodium has recently been recognized as an important predictor of mortality in patients with ESLD. We investigate the role of serum creatinine and sodium, and glomerular filtration rate (GFR) as determinants of survival in patients with ESLD.
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Could accelerated aging explain the excess mortality in patients with seropositive rheumatoid arthritis?
Arthritis Rheum.
PUBLISHED: 01-30-2010
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To determine whether the mortality pattern in patients with seropositive rheumatoid arthritis (RA) is consistent with the concept of accelerated aging, by comparing the observed mortality rates in patients with RA with the age-accelerated mortality rates from the general population.
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Donor race does not predict graft failure after liver transplantation.
Gastroenterology
PUBLISHED: 01-26-2010
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Donor race has been proposed to predict graft failure after liver transplantation. We evaluated the extent to which the center where the transplantation surgery was performed and other potential confounding factors might account for the observed association between donor race and graft failure.
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Total cholesterol and LDL levels decrease before rheumatoid arthritis.
Ann. Rheum. Dis.
PUBLISHED: 10-23-2009
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To compare lipid profiles in patients with rheumatoid arthritis (RA) and in non-RA subjects during the 5 years before and 5 years after the RA incidence/index date.
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Autoantibodies and the risk of cardiovascular events.
J. Rheumatol.
PUBLISHED: 10-15-2009
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Inflammation and autoimmunity are associated with increased cardiovascular (CV) risk in patients with rheumatoid arthritis. This association may also be present in those without rheumatic diseases. Our purpose was to determine whether rheumatoid factor (RF), antinuclear antibody (ANA), and cyclic citrullinated peptide antibody (CCP) positivity are associated with increased risk of CV events and overall mortality in those with and without rheumatic diseases.
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Disease associations with monoclonal gammopathy of undetermined significance: a population-based study of 17,398 patients.
Mayo Clin. Proc.
PUBLISHED: 08-04-2009
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To systematically study the association of monoclonal gammopathy of undetermined significance (MGUS) with all diseases in a population-based cohort of 17,398 patients, all of whom were uniformly tested for the presence or absence of MGUS.
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Statistical metrics for quality assessment of high-density tiling array data.
Biometrics
PUBLISHED: 07-23-2009
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High-density tiling arrays are designed to blanket an entire genomic region of interest using tiled oligonucleotides at very high resolution and are widely used in various biological applications. Experiments are usually conducted in multiple stages, in which unwanted technical variations may be introduced. As tiling arrays become more popular and are adopted by many research labs, it is pressing to develop quality control tools as was done for expression microarrays. We propose a set of statistical quality metrics analogous to those in expression microarrays with application to tiling array data. We also develop a method to estimate the significance level of an observed quality measurement using randomization tests. These methods have been applied to multiple real data sets, including three independent ChIP-chip experiments and one transcriptom mapping study, and they have successfully identified good quality chips as well as outliers in each study.
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3 tag digital gene expression profiling of human brain and universal reference RNA using Illumina Genome Analyzer.
BMC Genomics
PUBLISHED: 07-06-2009
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Massive parallel sequencing has the potential to replace microarrays as the method for transcriptome profiling. Currently there are two protocols: full-length RNA sequencing (RNA-SEQ) and 3-tag digital gene expression (DGE). In this preliminary effort, we evaluated the 3 DGE approach using two reference RNA samples from the MicroArray Quality Control Consortium (MAQC).
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Hospitalizations after heart failure diagnosis a community perspective.
J. Am. Coll. Cardiol.
PUBLISHED: 05-06-2009
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The purpose of this study was to determine the lifetime burden and risk factors for hospitalization after heart failure (HF) diagnosis in the community.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.