scholarly journals A Generative Approach Toward Precision Antimicrobial Peptide Design

2020 ◽  
Author(s):  
Jonathon B. Ferrell ◽  
Jacob M. Remington ◽  
Colin M. Van Oort ◽  
Mona Sharafi ◽  
Reem Aboushousha ◽  
...  
Keyword(s):  
False Positive Rate ◽  
Membrane Binding ◽  
Molecular Simulations ◽  
Sampling Technique ◽  
Cost Effective ◽  
Umbrella Sampling ◽  
Generative Model ◽  
Screening Process ◽  
Knowledge Based ◽  
Positive Rate

AbstractAntimicrobial peptides (AMPs) are peptides with promising applications for healthcare, veterinary, and agriculture industries. Despite prior success in AMP design using physics- or knowledge-based approaches, there is still a critical need to create new methodologies to design peptides with a low false positive rate and high AMP activity and selectivity. Toward this goal, we invented a cost-effective approach which utilizes a generative model to produce AMP-like sequences and molecular simulations to select peptides based on their structures and interactions. For a proof of concept, we curated a dataset that comprises 500,000 non-AMP peptide sequences and 8,000 labeled AMP sequences to train the generative model, which generated novel and diverse AMP candidates to potentially target a wide variety of microbes. Following a screening process to select peptides that are cationic and likely helical, we assessed 12 candidates by simulating their membrane-binding tendency to a lipid bilayer model. With the umbrella sampling technique, we determined the free energy change during transfer from the solution to the membrane environments for each peptide. Accordingly, we selected the six peptides with the best membrane-binding tendency, synthesized them, and characterized through spectroscopies and biological assays. Three novel peptides were validated with activity to inhibit bacterial growth. In aggregate, the combination of AMP generator and molecular simulations afford an enhanced accuracy in AMP design. Towards future precision AMP design, our methodology and results demonstrate the viability to design novel AMP-like peptides to target selected pathogens and mechanisms.

Frozen Section of Thyroid and Parathyroid Specimens

2005 ◽  
Vol 129 (12) ◽  
pp. 1575-1584 ◽  
Author(s):  
Rose C. Anton ◽  
Thomas M. Wheeler
Keyword(s):  
Thyroid Nodules ◽  
Frozen Section ◽  
False Positive Rate ◽  
Cost Effective ◽  
Needle Aspiration ◽  
Thyroid Lobectomy ◽  
Parathyroid Lesions ◽  
Surgical Evaluation ◽  
Positive Rate ◽  
Accurate Procedure

Abstract Context.—Preoperative fine-needle aspiration of thyroid lesions has greatly diminished the need for surgical evaluation. However, because thyroid nodules are common lesions, many still require surgical intervention and represent a substantial number of cases that the pathologist encounters in the frozen section laboratory. Objective.—Comprehensive reviews of frozen section indications, as well as gross, cytologic, and histologic features of the most common and diagnostically important thyroid and parathyroid lesions, are presented to provide a guideline for proper triage and management of these cases in the frozen section laboratory. The most common pitfalls are discussed in an attempt to avoid discordant diagnoses. Data Sources.—Thyroid lobectomy, subtotal or total thyroidectomy, and parathyroid biopsy or parathyroidectomy cases are included in this review. Conclusions.—The frozen section evaluation of thyroid and parathyroid lesions remains a highly accurate procedure with a low false-positive rate. Gross inspection, complemented by cytologic and histologic review, provides the surgeon with the rapid, reliable, cost-effective information necessary for optimum patient care.

scholarly journals Clinical and Economic Evaluation after Adopting Contingent Cell-Free DNA Screening for Fetal Trisomies in South Spain

2020 ◽  
Vol 47 (10) ◽  
pp. 749-756
Author(s):  
José A. Sainz ◽  
María R. Torres ◽  
Ignacio Peral ◽  
Reyes Granell ◽  
Manuel Vargas ◽  
...  
Keyword(s):  
False Positive Rate ◽  
Cost Effective ◽  
First Trimester ◽  
Nuchal Translucency ◽  
University Hospitals ◽  
Combined Test ◽  
Positive Rate ◽  
Fetal Malformations ◽  
Cfdna Screening ◽  
Singleton Pregnancies

<b><i>Introduction:</i></b> Contingent cell-free (cf) DNA screening on the basis of the first-trimester combined test (FCT) results has emerged as a cost-effective strategy for screening of trisomy 21 (T21). <b><i>Objectives:</i></b> To assess performance, patients’ uptake, and cost of contingent cfDNA screening and to compare them with those of the established FCT. <b><i>Methods:</i></b> This is a prospective cohort study including all singleton pregnancies attending to their FCT for screening of T21 at 2 university hospitals in South Spain. When the FCT risk was ≥1:50, there were major fetal malformations, or the nuchal translucency was ≥3.5 mm, women were recommended invasive testing (IT); if the risk was between 1:50 and 1:270, women were recommended cfDNA testing; and for risks bellow 1:270, no further testing was recommended. Detection rate (DR), false-positive rate (FPR), patients’ uptake, and associated costs were evaluated. <b><i>Results:</i></b> We analyzed 10,541 women, including 46 T21 cases. DR of our contingent strategy was 89.1% (41/46) at 1.4% (146/10,541) FPR. Uptake of cfDNA testing was 91.2% (340/373), and overall IT rate was 2.0%. The total cost of our strategy was €1,462,895.7, similar to €1,446,525.7 had cfDNA testing not been available. <b><i>Conclusions:</i></b> Contingent cfDNA screening shows high DR, low IT rate, and high uptake at a similar cost than traditional screening.

scholarly journals Object Detection and Instance Segmentation in Chest X-rays for Tuberculosis Screening

2021 ◽  
Vol 3 (1) ◽  
pp. 1-24
Author(s):  
Terence Griffin ◽  
Yu Cao ◽  
Benyuan Liu ◽  
Maria J. Brunette ◽  
Xinzi Sun
Keyword(s):  
Object Detection ◽  
False Positive Rate ◽  
X Rays ◽  
Tuberculosis Screening ◽  
Screening Process ◽  
Middle Income ◽  
Middle Income Countries ◽  
Positive Rate ◽  
Object Level ◽  
Instance Segmentation

Tuberculosis (TB) is a highly contagious disease leading to the deaths of approximately 2 million people annually. TB primarily affects the lungs and is spread through the air when people cough, sneeze, or spit. Providing healthcare professionals with better information, at a faster pace, is essential for combating this disease, especially in Low and Middle Income Countries (LMICs) with resource-constrained health systems. In this paper we describe how using convolution neural networks (CNNs) with an object level annotated dataset of chest X-rays (CXRs) allows us to identify the location of pulmonary issues indicative of TB. We compare the performance of Faster R-nobreakdash-CNN, Mask R-nobreakdash-CNN, Cascade versions of each, and SOLOv2, demonstrating reasonable results with a small dataset. We present a method to reduce the false positive rate by comparing the location of a detected object with the known location of areas where the detected class is likely to occur in the lung. Our results show that object detection and instance segmentation of CXRs can be achieved with a dataset of high-quality, object level annotations, and could be used as part of an automated TB screening process. This work has the potential to improve the speed of TB diagnosis in LMICs, if properly integrated into the healthcare system and adapted to existing clinical workflows and local regulations.

Comparing the clinical and economic effects of clinical examination, pulse oximetry, and echocardiography in newborn screening for congenital heart defects: A probabilistic cost-effectiveness model and value of information analysis

2007 ◽  
Vol 23 (2) ◽  
pp. 192-204 ◽  
Author(s):  
Ingolf Griebsch ◽  
Rachel L. Knowles ◽  
Jacqueline Brown ◽  
Catherine Bull ◽  
Christopher Wren ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Newborn Screening ◽  
Pulse Oximetry ◽  
Clinical Examination ◽  
Heart Defects ◽  
False Positive Rate ◽  
Research Priorities ◽  
Cost Effective ◽  
Positive Rate ◽  
Clinically Significant

Objectives: Congenital heart defects (CHD) are an important cause of death and morbidity in early childhood, but the effectiveness of alternative newborn screening strategies in preventing the collapse or death—before diagnosis—of infants with treatable but life-threatening defects is uncertain. We assessed their effectiveness and efficiency to inform policy and research priorities.Methods: We compared the effectiveness of clinical examination alone and clinical examination with either pulse oximetry or screening echocardiography in making a timely diagnosis of life-threatening CHD or in diagnosing clinically significant CHD. We contrasted their cost-effectiveness, using a decision-analytic model based on 100,000 live births, and assessed future research priorities using value of information analysis.Results: Clinical examination alone, pulse oximetry, and screening echocardiography achieved 34.0, 70.6, and 71.3 timely diagnoses per 100,000 live births, respectively. This finding represents an additional cost per additional timely diagnosis of £4,894 and £4,496,666 for pulse oximetry and for screening echocardiography. The equivalent costs for clinically significant CHD are £1,489 and £36,013, respectively. Key determinants of cost-effectiveness are detection rates and screening test costs. The false-positive rate is very high with screening echocardiography (5.4 percent), but lower with pulse oximetry (1.3 percent) or clinical examination alone (.5 percent).Conclusions: Adding pulse oximetry to clinical examination is likely to be a cost-effective newborn screening strategy for CHD, but further research is required before this policy can be recommended. Screening echocardiography is unlikely to be cost-effective, unless the detection of all clinically significant CHD is considered beneficial and a 5 percent false-positive rate acceptable.

scholarly journals Handling Imbalanced Class Problem of Measles InfectionRisk Prediction Model

2019 ◽  
Vol 9 (1) ◽  
pp. 3431-3435
Keyword(s):  
Logistic Regression ◽  
False Positive Rate ◽  
False Negative ◽  
False Negative Rate ◽  
Sampling Technique ◽  
True Positive Rate ◽  
True Positive ◽  
Positive Rate ◽  
Imbalanced Class ◽  
Medical Dataset

Measles is an emerging infectious disease with increasing number of reported cases. It is a vaccine-preventable disease;thus, it is common to have imbalanced class problem in the dataset. This study aims to resolve the imbalanced class problem for the prediction of measles infection risk and to compare the predictive results on a balanced dataset based on three machine learningtechniques. The data that was utilized in this study contained 37,884 records of suspected measles casesthat were highly imbalanced towards negative measles cases. The Synthetic Minority Over-Sampling Technique (SMOTE) was performed to balance thedistribution of the target attribute. The balanced dataset was then modelled using logistic regression, decision tree and Naïve Bayes. The predicted results indicated that logistic regression executed on the balanced dataset by SMOTE has the highest and most accurateclassification with 94.5% overall accuracy, 93.9% true positive rate, 5.8% false positive rate and 5.1% false negative rate. Therefore, SMOTE and other over-sampling approaches may be applicable to overcome imbalanced class issues in the medical dataset.

scholarly journals Limitations of multidetector computed tomography angiography for the diagnosis of blunt cerebrovascular injury

2018 ◽  
Vol 128 (6) ◽  
pp. 1642-1647 ◽  
Author(s):  
Ramesh Grandhi ◽  
Gregory M. Weiner ◽  
Nitin Agarwal ◽  
David M. Panczykowski ◽  
William J. Ares ◽  
...  
Keyword(s):  
False Positive ◽  
Antithrombotic Therapy ◽  
Multidetector Ct ◽  
False Positive Rate ◽  
Cost Effective ◽  
Blunt Cerebrovascular Injury ◽  
Cerebrovascular Injury ◽  
Current Series ◽  
Positive Rate ◽  
Level I

OBJECTIVEBlunt cerebrovascular injuries (BCVIs) following trauma carry risk for morbidity and mortality. Since patients with BCVI are often asymptomatic at presentation and neurological sequelae often occur within 72 hours, timely diagnosis is essential. Multidetector CT angiography (CTA) has been shown to be a noninvasive, cost-effective, reliable means of screening; however, the false-positive rate of CTA in diagnosing patients with BCVI represents a key drawback. Therefore, the authors assessed the role of DSA in the screening of BCVI when utilizing CTA as the initial screening modality.METHODSThe authors performed a retrospective analysis of patients who experienced BCVI between 2013 and 2015 at 2 Level I trauma centers. All patients underwent CTA screening for BCVI according to the updated Denver Screening Criteria. Patients who were diagnosed with BCVI on CTA underwent confirmatory digital subtraction angiography (DSA). Patient demographics, screening indication, BCVI grade on CTA and DSA, and laboratory values were collected. Comparison of false-positive rates stratified by BCVI grade on CTA was performed using the chi-square test.RESULTSA total of 140 patients (64% males, mean age 50 years) with 156 cerebrovascular blunt injuries to the carotid and/or vertebral arteries were identified. After comparison with DSA findings, CTA findings were incorrect in 61.5% of vessels studied, and the overall CTA false-positive rates were 47.4% of vessels studied and 47.9% of patients screened. The positive predictive value (PPV) for CTA was higher among worse BCVI subtypes on initial imaging (PPV 76% and 97%, for BCVI Grades II and IV, respectively) compared with Grade I injuries (PPV 30%, p < 0.001).CONCLUSIONSIn the current series, multidetector CTA as a screening test for blunt cerebrovascular injury had a high-false positive rate, especially in patients with Grade I BCVI. Given a false-positive rate of 47.9% with an estimated average of 132 patients per year screening positive for BCVI with CTA, approximately 63 patients per year would potentially be treated unnecessarily with antithrombotic therapy at a busy United States Level I trauma center. The authors’ data support the use of DSA after positive findings on CTA in patients with suspected BCVI. DSA as an adjunctive test in patients with positive CTA findings allows for increased diagnostic accuracy in correctly diagnosing BCVI while minimizing risk from unnecessary antithrombotic therapy in polytrauma patients.

scholarly journals Optimising multi-layered security screening

2021 ◽  
Author(s):  
David Anderson
Keyword(s):  
False Positive Rate ◽  
True Positive Rate ◽  
False Positives ◽  
System Level ◽  
Screening Process ◽  
Security Screening ◽  
Software Model ◽  
Positive Rate ◽  
The Individual ◽  
The Cost

Abstract Screening for prohibited items at airports is an example of a multi-layered screening process. Multiple layers of screening – often comprising different technologies with complementary strengths and weaknesses – are combined to create a single screening process. The detection performance of the overall system depends on multiple factors, including the performance of individual layers, the complementarity of different layers, and the decision rule(s) for determining how outputs from individual layers are combined. The aim of this work is to understand and optimise the overall system performance of a multi-layered screening process. Novel aspects include the use of realistic profiles of alarm distributions based on experimental observations and a focus on the influence of correlation/orthogonality amongst the layers of screening. The results show that a cumulative screening architecture can outperform a cascading one, yielding a significant increase in system-level true positive rate for only a modest increase in false positive rate. A cumulative screening process is also more resilient to weaknesses in the individual layers. The performance of a multi-layered screening process using a cascading approach is maximised when the false positives are orthogonal across the different layers and the true positives are correlated. The system-level performance of a cumulative screening process, on the other hand, is maximised when both false positives and true positives are as orthogonal as possible. The cost of ignoring orthogonality between screening layers is explored with some numerical examples. The underlying software model is provided in a Jupyter Notebook as supplementary material.

scholarly journals SARSeq, a robust and highly multiplexed NGS assay for parallel detection of SARS-CoV2 and other respiratory infections

2020 ◽  
Author(s):  
Ramesh Yelagandula ◽  
Aleksandr Bykov ◽  
Alexander Vogt ◽  
Robert Heinen ◽  
Ezgi Özkan ◽  
...  
Keyword(s):  
Influenza A ◽  
Respiratory Infections ◽  
False Positive Rate ◽  
Cost Effective ◽  
Rt Pcr ◽  
Robust Performance ◽  
Saliva Analysis ◽  
Positive Rate ◽  
Double Blinded ◽  
Generation Sequencing

During a pandemic, mitigation as well as protection of system-critical or vulnerable institutions requires massively parallel, yet cost-effective testing to monitor the spread of agents such as the current SARS-CoV2 virus. Here we present SARSeq, saliva analysis by RNA sequencing, as an approach to monitor presence of SARS-CoV2 and other respiratory viruses performed on tens of thousands of samples in parallel. SARSeq is based on next generation sequencing of multiple amplicons generated in parallel in a multiplexed RT-PCR reaction. It relies on a two-dimensional unique dual indexing strategy using four indices in total, for unambiguous and scalable assignment of reads to individual samples. We calibrated this method using dilutions of synthetic RNA and virions to show sensitivity down to a few molecules, and applied it to hundreds of patient samples validating robust performance across various sample types. Double blinded benchmarking to gold-standard quantitative RT-PCR performed in a clinical setting and a human diagnostics laboratory showed robust performance up to a Ct of 36. The false positive rate, likely due to cross contamination during sample pipetting, was estimated at 0.04-0.1%. In addition to SARS-CoV2, SARSeq detects Influenza A and B viruses as well as human rhinovirus and can be easily expanded to include detection of other pathogens. In sum, SARSeq is an ideal platform for differential diagnostic of respiratory diseases at a scale, as is required during a pandemic.

scholarly journals Incorporation of unique molecular identifiers in TruSeq adapters improves the accuracy of quantitative sequencing

2017 ◽  
Author(s):  
Jungeui Hong ◽  
David Gresham
Keyword(s):  
Quantitative Analysis ◽  
Frequency Estimation ◽  
False Positive Rate ◽  
Cost Effective ◽  
Next Generation Sequencing Data ◽  
Sequencing Data ◽  
Pcr Duplicates ◽  
Positive Rate ◽  
Bona Fide ◽  
Multiplex Sequencing

Quantitative analysis of next-generation sequencing data requires discriminating duplicate reads generated by PCR from identical molecules that are of unique origin. Typically, PCR duplicates are defined as sequence reads that align to the same genomic coordinates using reference-based alignment. However, identical molecules can be independently generated during library preparation. The false positive rate of coordinate-based deduplication has not been well characterized and may introduce unforeseen biases during analyses. We developed a cost-effective sequencing adapter design by modifying Illumina TruSeq adapters to incorporate a unique molecular identifier (UMI) while maintaining the capacity to undertake multiplexed sequencing. Incorporation of UMIs enables identification of bona fide PCR duplicates as identically mapped reads with identical UMIs. Using TruSeq adapters containing UMIs (TrUMIseq adapters), we find that accurate removal of PCR duplicates results in enhanced data quality for quantitative analysis of allele frequencies in heterogeneous populations and gene expression.Method SummaryTrUMIseq adapters incorporate unique molecular identifiers in TruSeq adapters while maintaining the capacity to multiplex sequencing libraries using existing workflows. The use of UMIs increases the accuracy of quantitative sequencing assays, including RNAseq and allele frequency estimation, by enabling accurate detection of PCR duplicates.

scholarly journals STUDY OF OPERATIVE OUTCOME OF CORNUAL CANNULATION IN HYSTEROLAPAROSCOPY

2020 ◽  
pp. 1-3
Author(s):  
Minal Dhanvij ◽  
Kiran Dhurve ◽  
Nitin Narvekar
Keyword(s):  
Success Rate ◽  
False Positive Rate ◽  
Cost Effective ◽  
Peritoneal Disease ◽  
Operative Outcome ◽  
Positive Rate ◽  
Reproductive Techniques ◽  
Promising Treatment ◽  
Tubal Pathology ◽  
Infertile Patients

Tubo-Peritoneal disease is the cause of infertility in approximately 30% of women, and 10–25% of these are due to proximal tubal obstruction. Hysterosalpngography(HSG) can diagnose the proximal tubal block but confirmation needed by hysterolaparoscopic chromopertubation before subjecting patient to expensive reproductive techniques. In our study of 48 cases, we find out the success rate of cornual cannulation by catheter-guidewire system is almost 81.25% with false positive rate of HSG is 27.2% and sensitivity of 86.4%. We also find out that pelvic inflammatory disease and tuberculosis contributes to 43.9% cases of proximal tubal block and success rate was approximately 50% can be achived in this cases. Hysterolaparoscopic cornual cannulation is simple, cost effective and promising treatment for proximal tubal pathology than tubo-cornual anastomosis with minimal complications. So we conclude that it should be offer on priority basis to treat infertile patients.

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