scholarly journals False Discovery Rate Control in Cancer Biomarker Selection Using Knockoffs

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 744 ◽  
Author(s):  
Arlina Shen ◽  
Han Fu ◽  
Kevin He ◽  
Hui Jiang
Keyword(s):  
Cancer Risk Assessment ◽  
Survival Models ◽  
Vast Number ◽  
False Discovery ◽  
Human Genes ◽  
Number Of Patients ◽  
Unbiased Manner ◽  
Nonlinear Associations ◽  
Melanoma Patients ◽  
False Discoveries

The discovery of biomarkers that are informative for cancer risk assessment, diagnosis, prognosis and treatment predictions is crucial. Recent advances in high-throughput genomics make it plausible to select biomarkers from the vast number of human genes in an unbiased manner. Yet, control of false discoveries is challenging given the large number of genes versus the relatively small number of patients in a typical cancer study. To ensure that most of the discoveries are true, we employ a knockoff procedure to control false discoveries. Our method is general and flexible, accommodating arbitrary covariate distributions, linear and nonlinear associations, and survival models. In simulations, our method compares favorably to the alternatives; its utility of identifying important genes in real clinical applications is demonstrated by the identification of seven genes associated with Breslow thickness in skin cutaneous melanoma patients.

scholarly journals Prognostic Significance of Molecular Upstaging of Paraffin-Embedded Sentinel Lymph Nodes in Melanoma Patients

2004 ◽  
Vol 22 (13) ◽  
pp. 2671-2680 ◽  
Author(s):  
Hiroya Takeuchi ◽  
Donald L. Morton ◽  
Christine Kuo ◽  
Roderick R. Turner ◽  
David Elashoff ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Lymph Nodes ◽  
Risk Ratio ◽  
Disease Recurrence ◽  
Sentinel Lymph Nodes ◽  
Independent Prognostic Factor ◽  
Number Of Patients ◽  
Significant Independent Prognostic Factor ◽  
Melanoma Patients

PurposeDetection of micrometastases in sentinel lymph nodes (SLNs) is important for accurate staging and prognosis in melanoma patients. However, a significant number of patients with histopathology-negative SLNs subsequently develop recurrent disease. We hypothesized that a quantitative realtime reverse transcriptase polymerase chain reaction (qRT) assay using multiple specific mRNA markers could detect occult metastasis in paraffin-embedded (PE) SLNs to upstage and predict disease outcome.Patients and MethodsqRT was performed on retrospectively collected PE SLNs from 215 clinically node-negative patients who underwent lymphatic mapping and sentinel lymphadenectomy for melanoma and were followed up for at least 8 years. PE SLNs (n = 308) from these patients were sectioned and assessed by qRT for mRNA of four melanoma-associated genes: MART-1 (antigen recognized by T cells-1), MAGE-A3 (melanoma antigen gene-A3 family), GalNAc-T (β1→4-N-acetylgalactosaminyl-transferase), and Pax3 (paired-box homeotic gene transcription factor 3).ResultsFifty-three (25%) patients had histopathology-positive SLNs by hemotoxylin and eosin and/or immunohistochemistry. Of the 162 patients with histopathology-negative SLNs, 48 (30%) had nodes that expressed at least one of the four qRT markers, and these 48 patients also had a significantly increased risk of disease recurrence by a Cox proportional hazards model analysis (P < .0001; risk ratio, 7.48; 95% CI, 3.70 to 15.15). The presence of ≥ one marker in histopathology-negative SLNs was also a significant independent prognostic factor by multivariate analysis for overall survival (P = .0002; risk ratio, 11.42; 95% CI, 3.17 to 41.1).ConclusionMolecular upstaging of PE histopathology-negative SLNs by multiple-marker qRT assay is a significant independent prognostic factor for long-term disease recurrence and overall survival of patients with early-stage melanoma.

scholarly journals The Functional False Discovery Rate with Applications to Genomics

2017 ◽  
Author(s):  
Xiongzhi Chen ◽  
David G. Robinson ◽  
John D. Storey
Keyword(s):  
Gene Expression ◽  
False Discovery Rate ◽  
Genetic Marker ◽  
Read Depth ◽  
False Discovery Rates ◽  
Additional Information ◽  
False Discovery ◽  
Gene Expression Trait ◽  
Genetics Of Gene Expression ◽  
False Discoveries

AbstractThe false discovery rate measures the proportion of false discoveries among a set of hypothesis tests called significant. This quantity is typically estimated based on p-values or test statistics. In some scenarios, there is additional information available that may be used to more accurately estimate the false discovery rate. We develop a new framework for formulating and estimating false discovery rates and q-values when an additional piece of information, which we call an “informative variable”, is available. For a given test, the informative variable provides information about the prior probability a null hypothesis is true or the power of that particular test. The false discovery rate is then treated as a function of this informative variable. We consider two applications in genomics. Our first is a genetics of gene expression (eQTL) experiment in yeast where every genetic marker and gene expression trait pair are tested for associations. The informative variable in this case is the distance between each genetic marker and gene. Our second application is to detect differentially expressed genes in an RNA-seq study carried out in mice. The informative variable in this study is the per-gene read depth. The framework we develop is quite general, and it should be useful in a broad range of scientific applications.

scholarly journals Profile of patients undergoing palliative radiotherapy: A single-institute study from a tertiary care oncology center

2017 ◽  
Vol 06 (04) ◽  
pp. 190-193
Author(s):  
Virender Suhag ◽  
B. S. Sunita ◽  
Pankaj Vats ◽  
Nilotpal Chakravarty ◽  
Mayuri Jain ◽  
...  
Keyword(s):  
Symptomatic Relief ◽  
Tertiary Care ◽  
Palliative Radiotherapy ◽  
Study Patient ◽  
Vast Number ◽  
Common Indication ◽  
Outdoor Setting ◽  
Number Of Patients ◽  
Medical Documents ◽  
Metastatic Sites

Abstract Background: Palliative radiotherapy (PRT) plays a significant role in the palliation of symptoms in patients with cancer and constitutes nearly 50% of the workload in different settings. Aims: The aim is to study patient-, disease-, and treatment-related characteristics in locoregionally advanced and metastatic malignancies meriting palliative management. Setting and Design: This was a retrospective observational study in a tertiary care government institute with academic and research potential. Methodology: The electronic medical records, medical documents, and radiotherapy (RT) treatment charts were retrieved and studied. Observations: A total of 460 patients were included in the study over 2 years, forming 30% of the total number of patients treated during the study period. Three hundred and ninety-six patients received PRT to the metastatic sites, while 64 patients received extremely hypofractionated PRT to the primary for symptomatic relief. Totally 442 patients showed good symptomatic response to PRT. One hundred and thirty-eight patients underwent re-irradiation. Lung was the most common primary site seen in 155 cases. The most common indication for PRT was palliation of pain from painful metastases as seen in 240 cases, and the next common indication was palliative whole-brain RT for brain metastases as seen in 159 cases. Conclusion: PRT forms an integral and important aspect of palliative care to the vast number of patients harboring metastatic disease that warrants some form of treatment for symptomatic relief. Short course of PRT in outdoor setting is a preferred mode of treatment to improve the quality of life of these distressed patients.

Frequency, predictors, and outcomes of readmission to index versus non-index hospitals after mechanical thrombectomy in patients with ischemic stroke

2019 ◽  
Vol 12 (2) ◽  
pp. 136-141 ◽  
Author(s):  
Kristina Shkirkova ◽  
Michelle Connor ◽  
Krista Lamorie-Foote ◽  
Arati Patel ◽  
Qinghai Liu ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Ischemic Stroke ◽  
Mechanical Thrombectomy ◽  
Systems Of Care ◽  
Multivariable Logistic Regression Analysis ◽  
Complication Rates ◽  
Hub And Spoke ◽  
Vast Number ◽  
Number Of Patients ◽  
Index Hospital

BackgroundStroke systems of care employ a hub-and-spoke model, with fewer centers performing mechanical thrombectomy (MT) compared with stroke-receiving centers, where a higher number offer high-level, centralized treatment to a large number of patients.ObjectiveTo characterize rates and outcomes of readmission to index and non-index hospitals for patients with ischemic stroke who underwent MT.MethodsThis study leveraged a population-based, nationally representative sample of patients with stroke undergoing MT from the Nationwide Readmissions Database between 2010 and 2014. Descriptive, logistic regression analyses, and univariate and multivariate logistic regression models were carried out to determine patient- and hospital-level factors, mortality, complications, and subsequent readmissions associated with index and non-index hospitals' 90-day readmissions.ResultsIn the study, 2111 patients with a stroke were treated with MT, of whom 534 were readmitted within 90 days. The most common reasons for readmission were: septicemia (5.9%), atrial fibrillation (4.8%), and cerebral artery occlusion with infarct (4.8%). Among readmitted patients, 387 (74%) were readmitted to index and 136 (26%) to non-index hospitals. On multivariable logistic regression analysis, non-index hospital readmission was not independently associated with major complications (p=0.09), mortality (p=0.34), neurological complications (p=0.47), or second readmission (p=0.92).ConclusionOne-quarter of patients with a stroke treated with MT were readmitted within 90 days, and one quarter of these patients were readmitted to non-index hospitals. Readmission to a non-index hospital was not associated with mortality or increased complication rates. In a hub-and-spoke model it is important that follow-up care for a specialized procedure can be performed effectively at a vast number of non-index hospitals covering a large geographic area.

Clinical characteristics of melanoma patients with non-V600E/K BRAF mutations.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20036-e20036 ◽  
Author(s):  
Sasan Nowroozi ◽  
Zhuang Zuo ◽  
Keyur Patel ◽  
Sapna Pradyuman Patel ◽  
Rajyalakshmi Luthra ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Primary Melanoma ◽  
Stage Iv ◽  
Distant Metastases ◽  
Unknown Primary ◽  
Sequencing Analysis ◽  
Superficial Spreading ◽  
Braf Mutations ◽  
Number Of Patients ◽  
Melanoma Patients

e20036 Background: BRAF mutations are found in ~50% of melanoma. V600E/K substitutions are the most common and well-characterized. We analyzed the clinical characteristics of patients with non-V600E/K BRAF mutations. Methods: We identified 38 melanoma patients whose tumor contained a non-V600E/K BRAF mutation and reviewed the clinical characteristics. The sequencing analysis was performed with either pyrosequencing or next generation sequencing assay. Results: 38 patients were identified with non-V600E/K BRAF mutations. Mutations detected in more than 1 patient included V600R (n=14, 37%), K601E (5, 13%), G469E (3, 8%); L597S (3, 7%), D594G (2, 5%); 11 other mutations were identified in single patients. Median age was 57 yrs; 82% were men; 95% were white. The common primary subtypes were nodular (26%), superficial spreading (24%), unknown primary (21%); no one were acral, mucosal or uveal melanomas. Ten (26%) of 27 with known ulceration status had ulceration, and 3 (7%) of 22 with known mitosis status had < 1 mitosis /mm2. The sites of primary melanoma were located mostly in the head/neck and the trunk (63%), extremities (16%) and unknown primary (21%). The stage at diagnosis was I /II (29%), III (40%), IV (18%) and unknown (13%). Among 33 (87%) patients who ultimately developed distant metastases, 23(67%) had metastasis in the soft tissue/nodes, 21 (63%) in the lung, 9 (24%) in the brain, 7 (21%) in the liver, 6 (16%) in the bone, and 5 (15%) in the adrenal gland. Among patients (n=25) with initial stage I-III melanoma who later developed distant metastasis, the median duration between the time of initial diagnosis and distant metastases was 36 months. Among the 32 (84%) of the patients who developed stage IV melanoma, the median survival from the time of stage IV diagnosis was 18 months. Five patients received vemurafenib treatment, and 2 patients (K601E; T599_V600ins2) had stable disease and 2 patients (L597Q; G466E) had disease progression and 1 lost to follow up. Conclusions: Unexpectedly higher proportion of the patients with non-V600E/K mutant-melanoma had unknown primary melanoma and higher mitotic rate. In a small number of patients who received vemurafenib, the clinical response appears to be low.

scholarly journals (P2-78) The Unique Role of Emergency Medical Services (EMS) in an Earthquake – A Community Based Approach

2011 ◽  
Vol 26 (S1) ◽  
pp. s162-s162
Author(s):  
E. Jaffe ◽  
S. Ben-zvi
Keyword(s):  
Medical Personnel ◽  
Accurate Method ◽  
Early Response ◽  
Local Health ◽  
Community Based ◽  
Vast Number ◽  
Medical Interventions ◽  
Early Arrival ◽  
Number Of Patients ◽  
Practical Guidelines

IntroductionThe goal of most EMS is to provide treatment to those in need of urgent medical care, with the purpose of satisfactorily treating the problem, or arranging for timely removal of the patient to the next point of definitive care. Earthquakes are among the most destructive types of natural disasters, striking suddenly with no accurate method of prediction or warning, thereby taking a heavy toll on life, injury and property. The damage created affects all aspects of the community - transportation, telecommunication, and infrastructure and can easily overwhelm local health services, damage clinics, hospitals and render them useless.AimTo review the pertinent literature and to analyze the information in order to set practical guidelines for EMS work in earthquakes with a community-based approach.ResultsSurvival of casualties extricated from under the rubble depends upon early medical interventions by emergency teams on site. EMS needs to strive for: • early arrival • early qualified treatment • Earthquakes differ from other disasters, where the system is intact.: early transport and definitive care. • They present a vast number of patients • problems concerning availability of medical personnel, • accessibility to patients, means of transportation & communication.ConclusionsA routine national community-based approach will strengthen the ability to provide early response in both daily and disastrous events, improving both morbidity and mortality rates. Possibly no immediate definitive care.

scholarly journals An averaging strategy to reduce variability in target-decoy estimates of false discovery rate

2018 ◽  
Author(s):  
Uri Keich ◽  
Kaipo Tamura ◽  
William Stafford Noble
Keyword(s):  
False Discovery Rate ◽  
Statistical Power ◽  
Shotgun Proteomics ◽  
Database Search ◽  
Proteomics Data ◽  
Decoy Database ◽  
Software Toolkit ◽  
True Proportion ◽  
False Discovery ◽  
False Discoveries

AbstractDecoy database search with target-decoy competition (TDC) provides an intuitive, easy-to-implement method for estimating the false discovery rate (FDR) associated with spectrum identifications from shotgun proteomics data. However, the procedure can yield different results for a fixed dataset analyzed with different decoy databases, and this decoy-induced variability is particularly problematic for smaller FDR thresholds, datasets or databases. In such cases, the nominal FDR might be 1% but the true proportion of false discoveries might be 10%. The averaged TDC protocol combats this problem by exploiting multiple independently shuffled decoy databases to provide an FDR estimate with reduced variability. We provide a tutorial introduction to aTDC, describe an improved variant of the protocol that offers increased statistical power, and discuss how to deploy aTDC in practice using the Crux software toolkit.

scholarly journals Management of Alarming Hemangiomas with Oral Prednisolone in Infants

2017 ◽  
Vol 7 (1) ◽  
pp. 7-11
Author(s):  
Kamal M Choudhury ◽  
Shafiqul Hoque
Keyword(s):  
Oral Prednisolone ◽  
Single Mode ◽  
Duration Of Treatment ◽  
College Hospital ◽  
Vast Number ◽  
Prednisolone Therapy ◽  
Medical College ◽  
Number Of Patients ◽  
Study Population ◽  
Medical University

Background: Treatment of hemangiomas remains a contentious and difficult issue for the physicians as well as for the surgeons. The numerous modality of treatment for hemangiomas testifies that no single mode of treatment is entirely satisfactory in their management. However, for alarming hemangiomas oral prednisolone had been used for long with encouraging resultsMethods: From a vast number of patients with hemangiomas attending the out-patient departments (OPDs) of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka Shishu Hospital (DSH), Rajshahi Medical College Hospital (RMCH) and BIRDEM General Hospital between 1999 through 2014, we had selected consecutively 462 infants with alarming hemangiomas. The whole study population (462 infants with alarming hemangiomas) received oral prednisolone at a dose of 2-4 mg/kg/day, and the results were observed sequentially in serial follow-ups.Results: About 71% patients showed substantial regression of the hemangiomas with oral prednisolone therapy after a mean duration of treatment of 6 months. Few adverse effects were associated with oral prednisolone but these were mostly transient and reversible.Conclusion: The authors assert that the management of alarming hemangiomas with oral prednisolone therapy is safe and effective.Birdem Med J 2017; 7(1): 7-11

scholarly journals False discovery control for penalized variable selections with high-dimensional covariates

2018 ◽  
Vol 17 (6) ◽  
Author(s):  
Kevin He ◽  
Xiang Zhou ◽  
Hui Jiang ◽  
Xiaoquan Wen ◽  
Yi Li
Keyword(s):  
Variable Selection ◽  
Linear Models ◽  
Broad Class ◽  
High Dimensional ◽  
High Throughput Data ◽  
False Discovery ◽  
Dimensional Variable ◽  
Selection Algorithms ◽  
False Discoveries ◽  
Linear Regressions

Abstract Modern bio-technologies have produced a vast amount of high-throughput data with the number of predictors much exceeding the sample size. Penalized variable selection has emerged as a powerful and efficient dimension reduction tool. However, control of false discoveries (i.e. inclusion of irrelevant variables) for penalized high-dimensional variable selection presents serious challenges. To effectively control the fraction of false discoveries for penalized variable selections, we propose a false discovery controlling procedure. The proposed method is general and flexible, and can work with a broad class of variable selection algorithms, not only for linear regressions, but also for generalized linear models and survival analysis.

756 Homeless and Burned – A Retrospective Analysis of an Especially Challenged Patient Population

2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S212-S212
Author(s):  
Mathangi A Chandramouli ◽  
Jamie Heffernan ◽  
Angela Rabbitts ◽  
Philip Chang
Keyword(s):  
Burn Injury ◽  
Discharge Planning ◽  
Average Length ◽  
Wound Care ◽  
Length Of Hospital Stay ◽  
Cold Injury ◽  
Vast Number ◽  
Burn Center ◽  
Number Of Patients ◽  
Average Size

Abstract Introduction The undomiciled burned patient presents more challenges to the burn team with regards to safe disposition. Discharge planning is complicated by the lack of a safe, clean environment to perform requisite wound care, thus prolonging hospital stays. The purpose of our study was to analyze the homeless patients admitted to a major urban burn center. This data would then better help identify trends and characteristics that could inform development of support services for this unfortunate population. Methods Demographic and clinical data from inpatients was collected from a single urban ABA verified burn center over a 3 year period between 1/2016 and 12/2018. Simple descriptive statistical analysis was performed. Results 1985 patients were admitted over the 3 year period. 48 homeless patients were identified (2.4%). The average age of this population was 39.8±16.8 years (range 3 months to 63 years old). There were 5 children (10.4% of the homeless cohort) in this population (ranging from 3 months to 4 years of age). Only 2 homeless burn inpatients were greater than 60 years of age (2% of the homeless cohort). There were 15 females (31%) and 33 males (69%). The mean TBSA was 5.8±9.9%. The average length of hospital stay was 21.9±29 days. 27 of the 48 patients (56%) required operative treatment. The 3 most common etiologies of skin injury were flame burns (29%), scald burns (25%), and cold injury (19%). The vast number of patients (39 out of 48, 81%) were discharged back to “their previous condition” (i.e. homeless shelter or the streets). There was 1 mortality in this group. Conclusions Contrary to widespread assumptions about the homeless being overwhelmingly male and adult, a significant percentage of the homeless burn patients were female with a percentage of patients being pediatric as well. The length of stay was significantly longer for most patients given the relatively small average size of burn injury. Cold injury was more significant etiology in this population compared to the overall burn population. Applicability of Research to Practice This analysis of the undomiciled burn inpatient at a single urban burn center will help better describe this especially challenging population and help focus social support and discharge planning resources for this group.

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