scholarly journals bootComb - An R Package to Derive Confidence Intervals for Combinations of Independent Parameter Estimates

2020 ◽  
Author(s):  
Marc Y. R. Henrion
Keyword(s):  
Confidence Intervals ◽  
Negative Binomial ◽  
Parametric Bootstrap ◽  
R Package ◽  
Independent Parameter ◽  
Parameter Estimates ◽  
List Type ◽  
Bootstrap Sampling ◽  
Link Type ◽  
Best Fit

AbstractMotivationThe epidemiologist sometimes needs to combine several independent parameter estimates: e.g. (i) adjust an incidence rate for healthcare utilisation, (ii) derive a disease prevalence from the conditional prevalence on another condition and the prevalence of that condition, (iii) adjust a seroprevalence for test sensitivity and specificity. While obtaining the combined parameter estimate is usually straightforward, deriving a corresponding confidence interval often is not. bootComb is an R package using parametric bootstrap sampling to derive such confidence intervals.ImplementationbootComb is a package for the statistical computation environment R.General featuresAs well as a function that returns confidence intervals for parameters combined from several independent estimates, bootComb provides auxiliary functions for 6 common distributions (beta, normal, exponential, gamma, Poisson and negative binomial) to derive best-fit distributions (and their sampling functions) for parameters given their reported confidence intervals.AvailabilitybootComb is available from the Comprehensive R Archive Network (https://CRAN.R-project.org/package=bootComb).Key FeaturesbootComb derives confidence intervals with the required coverage for parameters that are computed from independent parameter estimates for which confidence intervals are reported.Includes auxilliary functions for 6 common distributions (beta, normal, exponential, gamma, Poisson and negative binomial) to derive best-fit distributions (and their sampling functions) for parameters given their reported confidence intervals.R package: open-source, easy-to-use, platform independent.Stable version hosted on CRAN: https://CRAN.R-project.org/package=bootCombLatest development version available from GitHub: https://github.com/gitMarcH/bootComb

scholarly journals gwasurvivr: an R package for genome wide survival analysis

2018 ◽  
Author(s):  
Abbas A Rizvi ◽  
Ezgi Karaesmen ◽  
Martin Morgan ◽  
Leah Preus ◽  
Junke Wang ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Cox Model ◽  
R Package ◽  
Supplementary Information ◽  
Parameter Estimates ◽  
Survival Analyses ◽  
Link Type ◽  
Genome Wide ◽  
Size Number ◽  
Simple Interface

ABSTRACTSummaryTo address the limited software options for performing survival analyses with millions of SNPs, we developed gwasurvivr, an R/Bioconductor package with a simple interface for conducting genome wide survival analyses using VCF (outputted from Michigan or Sanger imputation servers), IMPUTE2 or PLINK files. To decrease the number of iterations needed for convergence when optimizing the parameter estimates in the Cox model we modified the R package survival; covariates in the model are first fit without the SNP, and those parameter estimates are used as initial points. We benchmarked gwasurvivr with other software capable of conducting genome wide survival analysis (genipe, SurvivalGWAS_SV, and GWASTools). gwasurvivr is significantly faster and shows better scalability as sample size, number of SNPs and number of covariates increases.Availability and implementationgwasurvivr, including source code, documentation, and vignette are available at: http://bioconductor.org/packages/gwasurvivrContactAbbas Rizvi, [email protected]; Lara E Sucheston-Campbell, [email protected] information: Supplementary data are available at https://github.com/suchestoncampbelllab/gwasurvivr_manuscript

scholarly journals AB0210 ACREULAR: AN R PACKAGE FOR THE CALCULATION AND VISUALISATION OF ACR/EULAR RELATED RHEUMATOID ARTHRITIS MEASURES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1405.1-1406
Author(s):  
F. Morton ◽  
J. Nijjar ◽  
C. Goodyear ◽  
D. Porter
Keyword(s):  
Rheumatoid Arthritis ◽  
Functional Status ◽  
Rheumatic Diseases ◽  
Web Application ◽  
R Package ◽  
Diagnostic Classification ◽  
Microsoft Excel ◽  
Link Type ◽  
Large Joint ◽  
Programming Skills

Background:The American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) individually and collaboratively have produced/recommended diagnostic classification, response and functional status criteria for a range of different rheumatic diseases. While there are a number of different resources available for performing these calculations individually, currently there are no tools available that we are aware of to easily calculate these values for whole patient cohorts.Objectives:To develop a new software tool, which will enable both data analysts and also researchers and clinicians without programming skills to calculate ACR/EULAR related measures for a number of different rheumatic diseases.Methods:Criteria that had been developed by ACR and/or EULAR that had been approved for the diagnostic classification, measurement of treatment response and functional status in patients with rheumatoid arthritis were identified. Methods were created using the R programming language to allow the calculation of these criteria, which were incorporated into an R package. Additionally, an R/Shiny web application was developed to enable the calculations to be performed via a web browser using data presented as CSV or Microsoft Excel files.Results:acreular is a freely available, open source R package (downloadable fromhttps://github.com/fragla/acreular) that facilitates the calculation of ACR/EULAR related RA measures for whole patient cohorts. Measures, such as the ACR/EULAR (2010) RA classification criteria, can be determined using precalculated values for each component (small/large joint counts, duration in days, normal/abnormal acute-phase reactants, negative/low/high serology classification) or by providing “raw” data (small/large joint counts, onset/assessment dates, ESR/CRP and CCP/RF laboratory values). Other measures, including EULAR response and ACR20/50/70 response, can also be calculated by providing the required information. The accompanying web application is included as part of the R package but is also externally hosted athttps://fragla.shinyapps.io/shiny-acreular. This enables researchers and clinicians without any programming skills to easily calculate these measures by uploading either a Microsoft Excel or CSV file containing their data. Furthermore, the web application allows the incorporation of additional study covariates, enabling the automatic calculation of multigroup comparative statistics and the visualisation of the data through a number of different plots, both of which can be downloaded.Figure 1.The Data tab following the upload of data. Criteria are calculated by the selecting the appropriate checkbox.Figure 2.A density plot of DAS28 scores grouped by ACR/EULAR 2010 RA classification. Statistical analysis has been performed and shows a significant difference in DAS28 score between the two groups.Conclusion:The acreular R package facilitates the easy calculation of ACR/EULAR RA related disease measures for whole patient cohorts. Calculations can be performed either from within R or by using the accompanying web application, which also enables the graphical visualisation of data and the calculation of comparative statistics. We plan to further develop the package by adding additional RA related criteria and by adding ACR/EULAR related measures for other rheumatic disorders.Disclosure of Interests:Fraser Morton: None declared, Jagtar Nijjar Shareholder of: GlaxoSmithKline plc, Consultant of: Janssen Pharmaceuticals UK, Employee of: GlaxoSmithKline plc, Paid instructor for: Janssen Pharmaceuticals UK, Speakers bureau: Janssen Pharmaceuticals UK, AbbVie, Carl Goodyear: None declared, Duncan Porter: None declared

scholarly journals Homeopathy for Covid-19 in Primary Care: A structured summary of a study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ubiratan Cardinalli Adler ◽  
Maristela Schiabel Adler ◽  
Livia Mitchiguian Hotta ◽  
Ana Elisa Madureira Padula ◽  
Amarilys de Toledo Cesar ◽  
...  
Keyword(s):  
Primary Care ◽  
Alternative Hypothesis ◽  
University Hospital ◽  
List Type ◽  
Study Medication ◽  
Link Type ◽  
Care Protocol ◽  
Full Protocol ◽  
Isolation Period

Abstract Objectives To investigate the effectiveness and safety of homeopathic medicine Natrum muriaticum (LM2) for mild cases of COVID-19 in Primary Health Care. Trial design A randomized, two-armed (1:1), parallel, placebo-controlled, double-blind, clinical trial is being performed to test the following hypotheses: H0: homeopathic medicines = placebo (null hypothesis) vs. H1: homeopathic medicines ≠ placebo (alternative hypothesis) for mild cases of COVID-19 in Primary Care. Participants Setting: Primary Care of São Carlos – São Paulo – Brazil. One hundred participants aged 18 years or older, with Influenza-like symptoms and a positive RT-PCR for SARS-CoV-2. Willingness to give informed consent and to comply with the study procedures is also required. Exclusion criterium: severe acute respiratory syndrome. Intervention and comparator Homeopathy: 1 globule of Natrum muriaticum LM2 diluted in 20 mL of alcohol 30% and dispensed in a 30 ml bottle. Placebo: 20 mL of alcohol 30% dispensed in a 30 ml bottle. Posology: one drop taken orally every 4 hours (6 doses/day) while there is fever, cough, tiredness, or pain (headache, sore throat, muscle aches, chest pain, etc.) followed by one drop every 6 hours (4 doses/day) until the fourteenth day of use. The bottle of study medication should be submitted to 10 vigorous shakes (succussions) before each dose. Posology may be changed by telemedicine, with no break in blinding. Study medication should be maintained during home isolation. According to the Primary Care protocol, the home isolation period lasts until the 10th day after the appearance of the first symptom, or up to 72 hours without symptoms. Main outcomes The primary endpoint will be time to recovery, defined as the number of days elapsed before all COVID-19 Influenza-like symptoms are recorded as mild or absent during home isolation period. Secondary measures are recovery time for each COVID-19 symptom; score of the scale created for the study (COVID-Simile Scale); medicines used during follow-up; number of days of follow-up; number of visits to emergency services; number of hospitalizations; other symptoms and Adverse Events during home isolation period. Randomisation The study Statistician generated a block randomization list, using a 1:1 ratio of the two groups (denoted as A and B) and a web-based tool (http://www.random.org/lists). Blinding (masking) The clinical investigators, the statistician, the Primary Care teams, the study collaborators, and the participants will remain blinded from the identity of the two treatment groups until the end of the study. Numbers to be randomised (sample size) One hundred participants are planned to be randomized (1:1) to placebo (50) or homeopathy (50). Trial Status Protocol version/date May 21, 2020. Recruitment is ongoing. First participant was recruited/included on June 29,2020. Due to recruitment adaptations to Primary Care changes, the authors anticipate the trial will finish recruiting on April 10, 2021. Trial registration COVID-Simile Study was registered at the University Hospital Medical Information Network (UMIN - https://www.umin.ac.jp/ctr/index.htm) on June 1st, 2020, and the trial start date was June 15, 2020. Unique ID: UMIN000040602. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

scholarly journals Inter-professional agreement and collaboration between extended scope physiotherapists and orthopaedic surgeons in an orthopaedic outpatient shoulder clinic – a mixed methods study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Merete Nørgaard Madsen ◽  
Maria Lange Kirkegaard ◽  
Thomas Martin Klebe ◽  
Charlotte Lorenzen Linnebjerg ◽  
Søren Martin Riis Villumsen ◽  
...  
Keyword(s):  
Treatment Plan ◽  
Random Order ◽  
Primary Diagnosis ◽  
Diagnosis And Treatment ◽  
List Type ◽  
Professional Collaboration ◽  
Relational Coordination ◽  
Orthopaedic Surgeons ◽  
Link Type ◽  
Shoulder Disorders

Abstract Background Extended scope physiotherapists (ESP) are increasingly supplementing orthopaedic surgeons (OS) in diagnosing patients with musculoskeletal disorders. Studies have reported satisfactory diagnostic and treatment agreement between ESPs and OSs, but methodological study quality is generally low, and only few studies have evaluated inter-professional collaboration. Our aims were: 1) to evaluate agreement on diagnosis and treatment plan between ESPs and OSs examining patients with shoulder disorders, 2) to explore and evaluate their inter-professional collaboration. Methods In an orthopaedic outpatient shoulder clinic, 69 patients were examined independently twice on the same day by an ESP and an OS in random order. Primary and secondary diagnoses (nine categories) and treatment plan (five categories, combinations allowed) were registered by each professional and compared. Percentage of agreement and kappa-values were calculated. Two semi-structured focus-group interviews were performed with ESPs and OSs, respectively. Interviews were based on the theoretical concept of Relational Coordination, encompassing seven dimensions of communication and relationship among professionals. A thematic analysis was conducted. Results Agreement on primary diagnosis was 62% (95% CI: [50; 73]). ESPs and OSs agreed on the combination of diagnoses in 79% (95% CI: [70; 89]) of the cases. Partial diagnostic agreement (one professional’s primary diagnosis was also registered as either primary or secondary diagnosis by the other) was 96% (95% CI: [91; 100]). Across treatment categories, agreement varied between 68% (95% CI: [57; 79]) and 100%. In 43% (95% CI: [31; 54]) of the cases, ESP and OS had full concordance between treatment categories chosen, while they agreed on at least one recommendation in 96% (95% CI: [91; 100]). Positive statements of all dimensions of relational coordination were found. Three themes especially important in the inter-professional collaboration emerged: Close communication, equal and respectful relationship and professional skills. Conclusions In the majority of cases, the ESP and OS registered the same or partly the same diagnosis and treatment plan. Indications of a high relational coordination implying a good inter-professional collaboration were found. Our results support that ESPs and OSs can share the task of examining selected patients with shoulder disorders in an orthopaedic clinic. Trial registration ClinicalTrials.gov Identifier: NCT03343951. Registered 10 November 2017

scholarly journals Identifying Temporal Aggregation Effect on Crash-Frequency Modeling

2021 ◽  
Vol 13 (11) ◽  
pp. 6214
Author(s):  
Bumjoon Bae ◽  
Changju Lee ◽  
Tae-Young Pak ◽  
Sunghoon Lee
Keyword(s):  
Traffic Safety ◽  
Negative Binomial ◽  
Random Effect ◽  
Temporal Correlation ◽  
Negative Binomial Regression ◽  
Spatiotemporal Analysis ◽  
Parameter Estimates ◽  
Crash Frequency ◽  
Crash Frequency Modeling ◽  
Using Data

Aggregation of spatiotemporal data can encounter potential information loss or distort attributes via individual observation, which would influence modeling results and lead to an erroneous inference, named the ecological fallacy. Therefore, deciding spatial and temporal resolution is a fundamental consideration in a spatiotemporal analysis. The modifiable temporal unit problem (MTUP) occurs when using data that is temporally aggregated. While consideration of the spatial dimension has been increasingly studied, the counterpart, a temporal unit, is rarely considered, particularly in the traffic safety modeling field. The purpose of this research is to identify the MTUP effect in crash-frequency modeling using data with various temporal scales. A sensitivity analysis framework is adopted with four negative binomial regression models and four random effect negative binomial models having yearly, quarterly, monthly, and weekly temporal units. As the different temporal unit was applied, the result of the model estimation also changed in terms of the mean and significance of the parameter estimates. Increasing temporal correlation due to using the small temporal unit can be handled with the random effect models.

347 Clinical outcomes of ovarian cancer patients treated with ALKS 4230, a novel engineered cytokine, in combination with pembrolizumab: ARTISTRY-1 trial

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A372-A373
Author(s):  
Ira Winer ◽  
Lucy Gilbert ◽  
Ulka Vaishampayan ◽  
Seth Rosen ◽  
Christopher Hoimes ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Tumor Marker ◽  
Solid Tumors ◽  
Cd8 T Cells ◽  
Comprehensive Cancer Center ◽  
List Type ◽  
Link Type ◽  
Heavily Pretreated

BackgroundALKS 4230 is a novel engineered cytokine that selectively targets the intermediate-affinity interleukin-2 receptor complex to activate CD8+ T cells and natural killer cells.1 The ARTISTRY-1 trial (NCT02799095) has shown encouraging efficacy and acceptable tolerability of ALKS 4230 among patients with advanced solid tumors.2 We report a detailed analysis of ovarian cancer (OC) patients who received combination therapy in ARTISTRY-1.MethodsARTISTRY-1 is an ongoing multicohort phase 1/2 trial exploring intravenous ALKS 4230 as monotherapy and combined with pembrolizumab. OC patients were enrolled into a cohort with mixed anti PD 1/L1 unapproved tumor types who had progressed on prior chemotherapy. OC patients received ALKS 4230 (3 µg/kg) on days 1–5 and pembrolizumab (200 mg) on day 1 of a 21 day cycle. Outcomes presented include antitumor activity (RECIST v1.1) and safety as of 7/24/2020. To evaluate changes in tumor microenvironment (TME), baseline and on-treatment biopsies were collected.ResultsFourteen heavily pretreated patients with OC were enrolled. Patients received a median of 5 (range, 2 11) prior regimens and all were previously treated with platinum based therapy. Among 13 evaluable patients with ≥1 assessment, 9 experienced disease control and 4 experienced disease progression; median treatment duration was approximately 7 weeks. Three patients experienced an objective response, including 1 complete response, 1 partial response (PR), and 1 unconfirmed PR; all were platinum resistant and negative for BRCA mutations. Five patients experienced tumor burden reductions (table 1). Treatment-related adverse events at the doses tested have generally been transient and manageable, with the majority being grade 1 and 2 in severity. Overall, based on preliminary data, the combination with ALKS 4230 did not demonstrate any additive toxicity to that already established with pembrolizumab alone. Additional safety and efficacy data are being collected in ongoing cohorts. In the monotherapy dose escalation portion of the study, ALKS 4230 alone increased markers of lymphocyte infiltration in 1 paired melanoma biopsy (1 of 1; on treatment at cycle 2); CD8+ T cell density and PD-L1 tumor proportion score increased 5.2- and 11 fold, respectively, supporting evidence that ALKS 4230 has immunostimulatory impact on the TME and providing rationale for combining ALKS 4230 with pembrolizumab (figure 1).Abstract 347 Table 1Summary of response observations among patients with ovarian cancerAbstract 347 Figure 1Increased markers of lymphocyte tumor infiltrationAn increase in CD3+CD8+ T cells (A, red = CD3; blue = CD8; purple = CD3+CD8+; teal = tumor marker), GranzymeB (B, red = CD8; green = granzymeB; yellow = granzymeB+CD8+; teal = tumor marker), and PD-L1 (C, red = PD-L1; blue = tumor marker) in the tumor microenvironment of a single patient was observed after the patient received monotherapy ALKS 4230ConclusionsThe combination of ALKS 4230, an investigational agent, and pembrolizumab demonstrates an acceptable safety profile and provides some evidence of tumor shrinkage and disease stabilization in some patients with heavily pretreated OC. This regimen could represent a new therapeutic option for these patients.AcknowledgementsThe authors would like to thank all of the patients who are participating in this trial and their families. The trial is sponsored by Alkermes, Inc. Medical writing and editorial support was provided by Parexel and funded by Alkermes, Inc.Trial RegistrationClinicalTrials. gov NCT02799095Ethics ApprovalThis trial was approved by Ethics and Institutional Review Boards (IRBs) at all trial sites; IRB reference numbers 16–229 (Dana-Farber Cancer Institute), MOD00003422/PH285316 (Roswell Park Comprehensive Cancer Center), 20160175 (Western IRB), i15-01394_MOD23 (New York University School of Medicine), TRIAL20190090 (Cleveland Clinic), and 0000097 (ADVARRA).ReferencesLopes JE, Fisher JL, Flick HL, Wang C, Sun L, Ernstoff MS, et al. ALKS 4230: a novel engineered IL-2 fusion protein with an improved cellular selectivity profile for cancer immunotherapy. J Immunother Cancer 2020;8:e000673. doi: 10.1136/jitc-2020-000673.Vaishampayan UN, Muzaffar J, Velcheti V, Winer I, Hoimes CJ, Rosen SD, et al. ALKS 4230 monotherapy and in combination with pembrolizumab (pembro) in patients (pts) with refractory solid tumors (ARTISTRY-1). Oral presentation at: European Society for Medical Oncology Annual Meeting; September 2020; virtual.

395 A first-in-human study of FS118, a tetravalent bispecific antibody targeting LAG-3 and PD-L1, in patients with advanced cancer and resistance to PD-(L)1 therapy

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A420-A420
Author(s):  
Timothy Yap ◽  
Deborah Wong ◽  
Siwen Hu-Lieskovan ◽  
Kyriakos Papadopoulos ◽  
Michelle Morrow ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Advanced Cancer ◽  
Bispecific Antibody ◽  
Acquired Resistance ◽  
Human Study ◽  
Clinical Activity ◽  
List Type ◽  
Link Type ◽  
Antibody Targeting

BackgroundUpregulation of immune checkpoints, such as LAG-3, plays an important role in promoting resistance to anti-PD-(L)1 therapy. Targeting PD-L1 and LAG-3 using a bispecific antibody may overcome resistance to PD-(L)1 blockade.1 We report initial data from a first-in-human study evaluating FS118 in patients with advanced cancer and resistance to PD-(L)1 therapy.MethodsThe ongoing Phase I FIH study (NCT03440437) is being conducted to evaluate safety, tolerability, immunogenicity, PK/PD and clinical activity of FS118 administered IV weekly to heavily pre-treated patients who had previously received anti-PD-(L)1 therapy for a minimum of 12 weeks. Adverse events were assessed using CTCAEv4.03 and tumor responses assessed using RECISTv1.1 and iRECIST. Single subject dose escalation cohorts were followed by a 3+3 ascending dose design. Three cohorts (3, 10, 20 mg/kg) were expanded to evaluate PK, PD and clinical activity. Pharmacodynamic studies examined soluble LAG-3 production and peripheral T-cell expansion.ResultsForty-three patients (median 6 lines of prior therapy, including ICB) with solid tumors received FS118 at doses from 0.8 mg up to 20 mg/kg across 8 dose levels. Weekly administration of FS118 was well tolerated and did not result in dose- or treatment-limiting toxicities. An MTD was not reached. No safety signals unexpected for the drug class of immune-checkpoint inhibitors were identified in the early study population. The majority (95%) of treatment-emergent adverse events (TEAE) considered by the Safety Review Committee (SRC) to be treatment-related were Grade 1 and 2. Grade 3 TEAEs toxicities (elevated liver enzymes) were observed in 2 patients (5%). No SAEs or deaths were attributed to FS118 treatment. Anti-drug antibodies, observed in half of patients, were typically transient in nature. The pharmacokinetic profile confirmed preclinical predictions and PD parameters included a dose-dependent increase in serum soluble LAG-3 and expansion of peripheral T cells. Long-lasting disease stabilisation (>6 months) was observed in a subset of patients with acquired resistance (defined as a CR, PR or SD ≥3 months on previous PD-(L)1 treatment), but not in patients with primary resistance. Two patients remain on FS118 treatment as of 2 Jul 2020 (duration 10 and 16 months). Retrospective IHC analysis of PD-L1 and LAG-3 co-expression in the tumor was assessed as a potential biomarker associated with clinical outcome.ConclusionsWeekly treatment with FS118 was well tolerated up to 20 mg/kg and was associated with pharmacodynamic markers of FS118 activity. Encouraging signs of clinical activity were observed in highly pre-treated patients who had acquired resistance to prior PD-(L)1 therapy.Trial RegistrationRegistered at www.clinicaltrials.gov, NCT03440437ReferenceKraman M, Faroudi M, Allen N, Kmiecik K, Gliddon D, Seal C, Koers A, Wydro M, Winnewisser J, Young L, Tuna M, Doody J, Morrow M, Brewis N. FS118, a bispecific antibody targeting LAG-3 and PD-L1, Enhances T-Cell activation resulting in potent antitumor activity. Clin Cancer Res 2020; 26:3333–3344.

scholarly journals GLM-Based Flexible Monitoring Methods: An Application to Real-Time Highway Safety Surveillance

Symmetry ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 362
Author(s):  
Arshad Jamal ◽  
Tahir Mahmood ◽  
Muhamad Riaz ◽  
Hassan M. Al-Ahmadi
Keyword(s):  
Real Time ◽  
Control Charts ◽  
Negative Binomial ◽  
Highway Safety ◽  
Monitoring Methods ◽  
Count Data Models ◽  
Crash Data ◽  
Safety Surveillance ◽  
Study Results ◽  
Best Fit

Statistical modeling of historical crash data can provide essential insights to safety managers for proactive highway safety management. While numerous studies have contributed to the advancement from the statistical methodological front, minimal research efforts have been dedicated to real-time monitoring of highway safety situations. This study advocates the use of statistical monitoring methods for real-time highway safety surveillance using three years of crash data for rural highways in Saudi Arabia. First, three well-known count data models (Poisson, negative binomial, and Conway–Maxwell–Poisson) are applied to identify the best fit model for the number of crashes. Conway–Maxwell–Poisson was identified as the best fit model, which was used to find the significant explanatory variables for the number of crashes. The results revealed that the road type and road surface conditions significantly contribute to the number of crashes. From the perspective of real-time highway safety monitoring, generalized linear model (GLM)-based exponentially weighted moving average (EWMA) and cumulative sum (CUSUM) control charts are proposed using the randomized quantile residuals and deviance residuals of Conway–Maxwell (COM)–Poisson regression. A detailed simulation-based study is designed for predictive performance evaluation of the proposed control charts with existing counterparts (i.e., Shewhart charts) in terms of the run-length properties. The study results showed that the EWMA type control charts have better detection ability compared with the CUSUM type and Shewhart control charts under small and/or moderate shift sizes. Finally, the proposed monitoring methods are successfully implemented on actual traffic crash data to highlight the efficacy of the proposed methods. The outcome of this study could provide the analysts with insights to plan sound policy recommendations for achieving desired safety goals.

scholarly journals kataegis: an R package for identification and visualization of the genomic localized hypermutation regions using high-throughput sequencing

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xue Lin ◽  
Yingying Hua ◽  
Shuanglin Gu ◽  
Li Lv ◽  
Xingyu Li ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Sequencing ◽  
Somatic Mutations ◽  
R Package ◽  
Frequency Of Occurrence ◽  
Link Type ◽  
Genomic Landscape ◽  
One Step ◽  
Flanking Regions

Abstract Background Genomic localized hypermutation regions were found in cancers, which were reported to be related to the prognosis of cancers. This genomic localized hypermutation is quite different from the usual somatic mutations in the frequency of occurrence and genomic density. It is like a mutations “violent storm”, which is just what the Greek word “kataegis” means. Results There are needs for a light-weighted and simple-to-use toolkit to identify and visualize the localized hypermutation regions in genome. Thus we developed the R package “kataegis” to meet these needs. The package used only three steps to identify the genomic hypermutation regions, i.e., i) read in the variation files in standard formats; ii) calculate the inter-mutational distances; iii) identify the hypermutation regions with appropriate parameters, and finally one step to visualize the nucleotide contents and spectra of both the foci and flanking regions, and the genomic landscape of these regions. Conclusions The kataegis package is available on Bionconductor/Github (https://github.com/flosalbizziae/kataegis), which provides a light-weighted and simple-to-use toolkit for quickly identifying and visualizing the genomic hypermuation regions.

scholarly journals Parameter stability and consistency in an alongshore-current model determined with Markov chain Monte Carlo

2008 ◽  
Vol 10 (2) ◽  
pp. 153-162 ◽  
Author(s):  
B. G. Ruessink
Keyword(s):  
Monte Carlo ◽  
Markov Chain ◽  
Markov Chain Monte Carlo ◽  
Parameter Estimates ◽  
Model Parameters ◽  
Parameter Stability ◽  
Small Uncertainty ◽  
Best Fit ◽  
Stability And Consistency

When a numerical model is to be used as a practical tool, its parameters should preferably be stable and consistent, that is, possess a small uncertainty and be time-invariant. Using data and predictions of alongshore mean currents flowing on a beach as a case study, this paper illustrates how parameter stability and consistency can be assessed using Markov chain Monte Carlo. Within a single calibration run, Markov chain Monte Carlo estimates the parameter posterior probability density function, its mode being the best-fit parameter set. Parameter stability is investigated by stepwise adding new data to a calibration run, while consistency is examined by calibrating the model on different datasets of equal length. The results for the present case study indicate that various tidal cycles with strong (say, >0.5 m/s) currents are required to obtain stable parameter estimates, and that the best-fit model parameters and the underlying posterior distribution are strongly time-varying. This inconsistent parameter behavior may reflect unresolved variability of the processes represented by the parameters, or may represent compensational behavior for temporal violations in specific model assumptions.

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