Faster Turnaround Time Research Articles

Fast cortical surface reconstruction from MRI using deep learning

Reconstructing cortical surfaces from structural magnetic resonance imaging (MRI) is a prerequisite for surface-based functional and anatomical image analyses. Conventional algorithms for cortical surface reconstruction are computationally inefficient and typically take several hours for each subject, causing a bottleneck in applications when a fast turnaround time is needed. To address this challenge, we propose a fast cortical surface reconstruction (FastCSR) pipeline by leveraging deep machine learning. We trained our model to learn an implicit representation of the cortical surface in volumetric space, termed the “level set representation”. A fast volumetric topology correction method and a topology-preserving surface mesh extraction procedure were employed to reconstruct the cortical surface based on the level set representation. Using 1-mm isotropic T1-weighted images, the FastCSR pipeline was able to reconstruct a subject’s cortical surfaces within 5 min with comparable surface quality, which is approximately 47 times faster than the traditional FreeSurfer pipeline. The advantage of FastCSR becomes even more apparent when processing high-resolution images. Importantly, the model demonstrated good generalizability in previously unseen data and showed high test–retest reliability in cortical morphometrics and anatomical parcellations. Finally, FastCSR was robust to images with compromised quality or with distortions caused by lesions. This fast and robust pipeline for cortical surface reconstruction may facilitate large-scale neuroimaging studies and has potential in clinical applications wherein brain images may be compromised.

EP369: Increased automation reduces turnaround time for submissions to ClinVar

eP369: Increased automation reduces turnaround time for submissions to ClinVar

EP396: Collaborative efforts between clinical genetics, cytogenetics, and neonatology improve genetic testing practices in the NICU

Genetic disorders, taken together, are overrepresented in the neonatal intensive care unit (NICU) population. As chromosome abnormalities are frequent findings in these patients, karyotype and chromosomal microarray analysis (CMA) are commonly used first-line tests. Historically, karyotype studies were the primary test for these patients, offering a fast turnaround time (TAT) and an unbiased approach to whole genome analysis. When CMAs came into use, both tests were frequently performed concurrently to obtain results as quickly as possible as CMA testing often had a longer TAT than karyotype.

Is faster better? An economic evaluation of rapid and ultra-rapid genomic testing in critically ill infants and children

PurposeTo evaluate whether the additional cost of providing increasingly faster genomic results in pediatric critical care is outweighed by reductions in health care costs and increases in personal utility. MethodsHospital costs and medical files from a cohort of 40 children were analyzed. The health economic impact of rapid and ultra-rapid genomic testing, with and without early initiation, relative to standard genomic testing was evaluated. ResultsShortening the time to results led to substantial economic and personal benefits. Early initiation of ultra-rapid genomic testing was the most cost-beneficial strategy, leading to a cost saving of AU$26,600 per child tested relative to standard genomic testing and a welfare gain of AU$12,000 per child tested. Implementation of early ultra-rapid testing of critically ill children is expected to lead to an annual cost saving of AU$7.3 million for the Australian health system and an aggregate welfare gain of AU$3.3 million, corresponding to a total net benefit of AU$10.6 million. ConclusionEarly initiation of ultra-rapid genomic testing can offer substantial economic and personal benefits. Future implementation of rapid genomic testing programs should focus not only on optimizing the laboratory workflow to achieve a fast turnaround time but also on changing clinical practice to expedite test initiation.

A novel approach to concentrate human and animal viruses from wastewater using receptors-conjugated magnetic beads

Viruses are present at low concentrations in wastewater; therefore, an effective method for concentrating virus particles is necessary for accurate wastewater-based epidemiology (WBE). We designed a novel approach to concentrate human and animal viruses from wastewater using porcine gastric mucin-conjugated magnetic beads (PGM-MBs). We systematically evaluated the performances of the PGM-MBs method (sensitivity, specificity, and robustness to environmental inhibitors) with six viral species, including Tulane virus (a surrogate for human norovirus), rotavirus, adenovirus, porcine coronavirus (transmissible gastroenteritis virus or TGEV), and two human coronaviruses (NL63 and SARS-CoV-2) in influent wastewater and raw sewage samples. We determined the multiplication factor (the ratio of genome concentration of the final solution to that of the initial solution) for the PGM-MBs method, which ranged from 1.3 to 64.0 depending on the viral species. Because the recovery efficiency was significantly higher when calculated with virus titers than it was with genome concentration, the PGM-MBs method could be an appropriate tool for assessing the risk to humans who are inadvertently exposed to wastewater contaminated with infectious viruses. Furthermore, PCR inhibitors were not concentrated by PGM-MBs, suggesting that this tool will be successful for use with environmental samples. In addition, the PGM-MBs method is cost-effective (0.5 USD/sample) and has a fast turnaround time (3 h from virus concentration to genome quantification). Thus, this method can be implemented in high throughput facilities. Because of its strong performance, intrinsic characteristics of targeting the infectious virus, robustness to wastewater, and adaptability to high throughput systems, the PGM-MBs method can be successfully applied to WBE and ultimately provides valuable public health information.

TILDA: Tat/Rev Induced Limiting Dilution Assay.

Recently the Tat/rev Induced Limiting Dilution Assay, or TILDA, has been proposed as a possible alternative method to quantify the HIV-1 reservoir. TILDA estimates the frequency of latently infected cells by probing, in a limiting dilution format, the presence or inducibility of tat and rev multiply spliced HIV-1 RNA. In doing so, TILDA reduces overestimation of reservoir size compared to HIV-1DNA measurements because multiply spliced HIV-1 RNA is less likely to be transcribed from dysfunctional genomes with replication defects. TILDA is easy to perform, requires a very low input number of cells and has a fast turnaround time, making it ideal for use in clinical settings. Here we describe the execution of TILDA with particular emphasis on cell preparation and the limiting dilution scheme.

Plasma-first: accelerating lung cancer diagnosis and molecular profiling through liquid biopsy.

Introduction:Molecular profiling of tumor tissue is the gold standard for treatment decision-making in advanced non-small cell lung cancer (NSCLC). Results may be delayed or unavailable due to insufficient tissue, prolonged wait times for biopsy, pathology assessment and testing. We piloted the use of plasma testing in the initial diagnostic workup for patients with suspected advanced lung cancer.Methods:Patients with ⩽15 pack-year smoking history and suspected advanced lung cancer referred to the lung cancer rapid diagnostic program underwent plasma circulating-tumor DNA testing using a DNA-based mutation panel. Tissue testing was performed per standard of care, including comprehensive next-generation sequencing (NGS). The primary endpoint was time from diagnostic program referral to cancer treatment in stage IV NSCLC patients (Cohort A) compared to a contemporary cohort not enrolled in the study (Cohort B) and an historical pre-COVID cohort referred to the program between 2018 and 2019 (Cohort C).Results:From January to June 2021, 20 patients were enrolled in Cohort A; median age was 70.5 years (range 33–87), 70% were female, 55% Caucasian, 85% never smokers, and 75% were diagnosed with NSCLC. Seven had actionable alterations detected in plasma or tissue (4/7 concordant). Fusions, not tested in plasma, were identified by immunohistochemistry for three patients. Mean result turnaround time was 17.8 days for plasma NGS and 23.6 days for tissue (p = 0.10). Mean time from referral to treatment initiation was significantly shorter in cohort A at 32.6 days (SD 13.1) versus 62.2 days (SD 31.2) in cohort B and 61.5 days (SD 29.1) in cohort C, both p < 0.0001.Conclusion:Liquid biopsy in the initial diagnostic workup of patients with suspected advanced NSCLC can lead to faster molecular results and shorten time to treatment even with smaller DNA panels. An expansion study using comprehensive NGS plasma testing with faster turnaround time is ongoing (NCT04862924).

Optimizing the Illumina COVIDSeq laboratorial and bioinformatics pipeline on thousands of samples for SARS-CoV-2 Variants of Concern tracking

The SARS-CoV-2 Variants of Concern tracking via Whole Genome Sequencing represents a pillar of public health measures for the containment of the pandemic. The ability to track down the lineage distribution on a local and global scale leads to a better understanding of immune escape and to adopting interventions to contain novel outbreaks. This scenario poses a challenge for NGS laboratories worldwide that are pressed to have both a faster turnaround time and a high-throughput processing of swabs for sequencing and analysis. In this study, we present an optimization of the Illumina COVID-seq protocol carried out on thousands of SARS-CoV-2 samples at the wet and dry level. We discuss the unique challenges related to processing hundreds of swabs per week such as the tradeoff between ultra-high sensitivity and negative contamination levels, cost efficiency and bioinformatics quality metrics.

Patterns of SARS-CoV-2 Testing Preferences in a National Cohort in the United States: Latent Class Analysis of a Discrete Choice Experiment.

BackgroundInadequate screening and diagnostic testing in the United States throughout the first several months of the COVID-19 pandemic led to undetected cases transmitting disease in the community and an underestimation of cases. Though testing supply has increased, maintaining testing uptake remains a public health priority in the efforts to control community transmission considering the availability of vaccinations and threats from variants.ObjectiveThis study aimed to identify patterns of preferences for SARS-CoV-2 screening and diagnostic testing prior to widespread vaccine availability and uptake.MethodsWe conducted a discrete choice experiment (DCE) among participants in the national, prospective CHASING COVID (Communities, Households, and SARS-CoV-2 Epidemiology) Cohort Study from July 30 to September 8, 2020. The DCE elicited preferences for SARS-CoV-2 test type, specimen type, testing venue, and result turnaround time. We used latent class multinomial logit to identify distinct patterns of preferences related to testing as measured by attribute-level part-worth utilities and conducted a simulation based on the utility estimates to predict testing uptake if additional testing scenarios were offered.ResultsOf the 5098 invited cohort participants, 4793 (94.0%) completed the DCE. Five distinct patterns of SARS-CoV-2 testing emerged. Noninvasive home testers (n=920, 19.2% of participants) were most influenced by specimen type and favored less invasive specimen collection methods, with saliva being most preferred; this group was the least likely to opt out of testing. Fast-track testers (n=1235, 25.8%) were most influenced by result turnaround time and favored immediate and same-day turnaround time. Among dual testers (n=889, 18.5%), test type was the most important attribute, and preference was given to both antibody and viral tests. Noninvasive dual testers (n=1578, 32.9%) were most strongly influenced by specimen type and test type, preferring saliva and cheek swab specimens and both antibody and viral tests. Among hesitant home testers (n=171, 3.6%), the venue was the most important attribute; notably, this group was the most likely to opt out of testing. In addition to variability in preferences for testing features, heterogeneity was observed in the distribution of certain demographic characteristics (age, race/ethnicity, education, and employment), history of SARS-CoV-2 testing, COVID-19 diagnosis, and concern about the pandemic. Simulation models predicted that testing uptake would increase from 81.6% (with a status quo scenario of polymerase chain reaction by nasal swab in a provider’s office and a turnaround time of several days) to 98.1% by offering additional scenarios using less invasive specimens, both viral and antibody tests from a single specimen, faster turnaround time, and at-home testing.ConclusionsWe identified substantial differences in preferences for SARS-CoV-2 testing and found that offering additional testing options would likely increase testing uptake in line with public health goals. Additional studies may be warranted to understand if preferences for testing have changed since the availability and widespread uptake of vaccines.

Highly Sensitive and Specific SARS-CoV-2 Serological Assay Using a Magnetic Modulation Biosensing System.

Sensitive serological assays are needed to provide valuable information about acute and past viral infections. For example, detection of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibodies could serve as the basis for an “immunity passport” that would enable individuals to travel internationally. Here, utilizing a novel Magnetic Modulation Biosensing (MMB) system and the receptor-binding domain of the SARS-CoV-2 spike protein, we demonstrate a highly sensitive and specific anti-SARS-CoV-2 IgG serological assay. Using anti-SARS-CoV-2 IgG antibodies, RT-qPCR SARS-CoV-2-positive and healthy patients’ samples, and vaccinees’ samples, we compare the MMB-based SARS-CoV-2 IgG assay’s analytical and clinical sensitivities to those of the enzyme-linked immunosorbent assay (ELISA). Compared with ELISA, the MMB-based assay has an ~6-fold lower limit of detection (129 ng/L vs. 817 ng/L), and it detects an increase in the IgG concentration much earlier after vaccination. Using 85 RT-qPCR SARS-CoV-2-positive samples and 79 -negative samples, the MMB-based assay demonstrated similar clinical specificity (98% vs. 99%) and sensitivity (93% vs. 92%) to the ELISA test, but with a much faster turnaround time (45 min vs. 245 min). The high analytical and clinical sensitivity, short turnaround time, and simplicity of the MMB-based assay makes it a preferred method for antibody detection.

Numerical simulations and analysis of the turbulent flow field in a practical gas turbine engine combustor

The turbulent flow field in a practical gas turbine combustor is very complex because of the interactions between various flows resulting from components like multiple types of swirlers, dilution holes, and liner effusion cooling holes. Numerical simulations of flows in such complex combustor configurations are challenging. The challenges result from (a) the complexities of the interfaces between multiple three-dimensional shear layers, (b) the need for proper treatment of a large number of tiny effusion holes with multiple angles, and (c) the requirements for fast turnaround times in support of engineering design optimization. Both the Reynolds averaged Navier–Stokes simulation (RANS) and the large eddy simulation (LES) for the practical combustor geometry are considered. An autonomous meshing using the cut-cell Cartesian method and adaptive mesh refinement (AMR) is demonstrated for the first time to simulate the flow in a practical combustor geometry. The numerical studies include a set of computations of flows under a prescribed pressure drop across the passage of interest and another set of computations with all passages open with a specified total flow rate at the plenum inlet and the pressure at the exit. For both sets, the results of the RANS and the LES flow computations agree with each other and with the corresponding measurements. The results from the high-resolution LES simulations are utilized to gain fundamental insights into the complex turbulent flow field by examining the profiles of the velocity, the vorticity, and the turbulent kinetic energy. The dynamics of the turbulent structures are well captured in the results of the LES simulations.

671. Initial Impression of Explify Respiratory Testing: Is It an Effective Diagnostic Tool?

Abstract Background Respiratory infections are a common cause of hospital admissions resulting in significant morbidity and mortality. Isolating specific pathogens from the respiratory tract is a diagnostic challenge. Traditional testing modalities are prone to contamination, time consuming, and have low sensitivity. Next generation genetic sequencing technology has made possible the development of a number of hypothesis free, fast, and highly accurate genome-based identification tests. In this study, we aim at assessing the initial use and performance of one of these tests, the Explify Respiratory panel, at a large quaternary hospital in west Michigan. Methods We performed retrospective analysis on 16 patients with suspected lower respiratory infections. Subjects were chosen for inclusion in the analysis based on the suspicion of pulmonary infection without an identified pathogen. The patient population included 5 immunocompromised patients, 3 with hematologic malignancy, 4 with solid tumor malignancy, and 2 transplant recipients. Results The test resulted in: lack of identified organism (5 patients), identification of non-pathogenic organisms (6 patients), and identification of organisms that were either identified by other traditional testing or did not impact provider’s therapeutic plan (5 patients). The results of Explify testing in all 16 patients did not have a clinical impact on patient care or treatment plan. Conclusion Explify testing seemed to be an appealing cost-effective tool that could replace other available testing modalities such as culture, other sequencing tests, and serological testing with faster turn-around time and less cost. However, it failed to demonstrate any benefit to clinicians in identifying respiratory pathogens while resulting in added cost burden to the patient. Moreover, it resulted in clinical delays of further investigation while awaiting the results. It remains unclear if the lack of clinical impact results from the extensive interventions and treatments that patients receive prior to Explify testing or from the poor sensitivity and performance of the test.This study emphasizes the importance of continuous evaluation of new diagnostic testing before widespread implementation to improve patient care and minimize cost burden. Disclosures All Authors: No reported disclosures

Oxford Nanopore MinION Direct RNA-Seq for Systems Biology.

Simple SummaryA new technology has been recently developed by Oxford Nanopore Technologies, enabling researchers to investigate the structure and relative abundance of specific molecules, ribonucleic acids. The ribonucleic acids carry information from the genes to proteins, which are responsible for virtually every process in the human organism, including disease progression and response to therapies. Special computational methods allow identification of various activated biological processes by analyzing the changes in concentrations of ribonucleic acids. This is of particular interest for precision medicine which aims at single-patient analysis. Here we evaluated whether ribonucleic acid abundances measured by new technology are suited for robust predictions of activated biological processes in single samples. We performed simulations varying the number of experimental replicates and analysed activated biological processes’ predictions using two algorithms. In brief, we found that at least two replicates are required to obtain reproducible results. We hope that our findings may be of interest to researchers planning their nanopore experiments and may stimulate further development of clinical applications of this technology.Long-read direct RNA sequencing developed by Oxford Nanopore Technologies (ONT) is quickly gaining popularity for transcriptome studies, while fast turnaround time and low cost make it an attractive instrument for clinical applications. There is a growing interest to utilize transcriptome data to unravel activated biological processes responsible for disease progression and response to therapies. This trend is of particular interest for precision medicine which aims at single-patient analysis. Here we evaluated whether gene abundances measured by MinION direct RNA sequencing are suited to produce robust estimates of pathway activation for single sample scoring methods. We performed multiple RNA-seq analyses for a single sample that originated from the HepG2 cell line, namely five ONT replicates, and three replicates using Illumina NovaSeq. Two pathway scoring methods were employed—ssGSEA and singscore. We estimated the ONT performance in terms of detected protein-coding genes and average pairwise correlation between pathway activation scores using an exhaustive computational scheme for all combinations of replicates. In brief, we found that at least two ONT replicates are required to obtain reproducible pathway scores for both algorithms. We hope that our findings may be of interest to researchers planning their ONT direct RNA-seq experiments.

Excellence in Laboratory Practice with the Validation of Opiate Confirmation using Liquid Chromatography/Mass Spectrometry

Abstract Introduction/Objective Veterans are more susceptible to opioid addiction as they are more likely to suffer from chronic pain which leads to increased need of confirmed identification of opiates in toxicology laboratories. Gas chromatography-mass spectrometry (GC-MS) had been a long-accepted method for the quantitative analysis of opiates in urine, but requires tedious, time-consuming, and complex sample preparation steps. On the other hand, liquid chromatography-mass spectrometry (LC/MS) has comparatively simpler sample preparation steps, can handle three times the number of specimens, much faster turnaround times and produces equally valid results. However, the validation experience of this simpler detection method has not been well published, particularly in a Veterans Healthcare Clinical Laboratory setting. Methods/Case Report The quality assurance goal of the validation is to demonstrate that the Agilent 6410 Triple Quadrupole LC/MS (Wilmington DE) is able to identify the same opiate drug analytes performed by the GC-MS. Method to method correlation, within run precision, day to day precision, carryover study, matrix (ion) suppression study, and a limit of detection study were performed as part of this validation. Results (if a Case Study enter NA) For the total of 156 specimens run for the method comparison, there was 94.9% agreement, or 148/156 samples were concordant. The 8 discrepancies had drugs that were present below the cutoff limit of the LC/MS. Within run precision with 20 replicates of negative, positive, and at the cutoff were run with all results as expected. The day to day precision of a positive and negative sample run over 10 days also yielded results as expected. The carryover study demonstrated minimal carryover. The matrix (ion) suppression study showed ion suppression at 16.8%, which is below the amount needed to affect analyte concentrations. The LC/MS was highly sensitive with a limit of detection of &amp;gt;97% at 25 ng/mL. Thus, the result of comparison showed good concordance. Conclusion LC/MS is a simpler, more efficient method of opiate testing that is comparable to GC-MS for the detection of opiate drugs of abuse in urine. This is an example of excellence in laboratory practice by extending the best quality laboratory care with proper validation of instrument methods conducive to laboratory workflow.

Performance of four commercial real-time PCR assays for the detection of bacterial enteric pathogens in clinical samples

ObjectivesMany laboratories use culture-independent diagnostic tests for bacterial gastroenteritis (i.e. real-time polymerase chain reaction, RT-PCR) instead of culture because of better sensitivity, automation, and faster turnaround times. To address some gaps in initial evaluations and lack of intraassay comparisons for many commercial RT-PCRs, this study compared the ability of four commercially available RT-PCR tests (Ridagene, Fast Track Diagnostics, BD Max, and Prodesse Progastro) to detect five major bacterial enteric pathogens: Campylobacter, Salmonella, Shiga-toxin producing Escherichia coli (STEC), Shigella, and Yersinia. MethodsClinical stool specimens and contrived samples comprising commonly circulating species, serotypes, biovars, and/or toxin subtypes were used for the comparison. ResultsConcordance rates for RT-PCR and culture using culture-positive and culture-negative clinical stools were >90% for Campylobacter (97.5-100%), Salmonella (97.5-100%), Shigella (100%), and STEC (90-100%). However, the agreement between RT-PCR and culture for Y. enteroccolitica ranged from 70-90%. For the contrived sample set, stx2f was detected by one of four assays. Of note, no assay could detect Yersinia non-enterocolitica and Campylobacter upsaliensis. ConclusionsDepending on the prevalence of certain stx sub-types, Yersinia species, and Campylobacter species in a laboratory's jurisdiction, without further improvement in culture-independent tests, culture methods remain critical for the detection of these pathogens.

An Update on the Laboratory Diagnosis of Rickettsia spp. Infection.

Rickettsia species causing human illness are present globally and can cause significant disease. Diagnosis and identification of this intracellular bacteria are challenging with many available diagnostic modalities suffering from several shortcomings. Detection of antibodies directed against Rickettsia spp. via serological methods remains widely used with a broad range of sensitivity and specificity values reported depending on the assay. Molecular methods, including polymerase chain reaction (PCR) testing, enables species-specific identification with a fast turnaround time; however, due to resource requirements, use in some endemic settings is limited. Reports on the use of next-generation sequencing (NGS) and metagenomics to diagnose Rickettsia spp. infection have been increasing. Despite offering several potential advantages in the diagnosis and surveillance of disease, genomic approaches are currently only limited to reference and research laboratories. Continued development of Rickettsia spp. diagnostics is required to improve disease detection and epidemiological surveillance, and to better understand transmission dynamics.

A Real-World Application of Liquid Biopsy in Metastatic Colorectal Cancer: The Poseidon Study.

Simple SummaryThe choice of first-line regimen represents a critical step in the therapeutic road for patients with metastatic colorectal cancer (mCRC) because the response to first-line treatment is the primary determinant of outcomes. The extended characterization of RAS and BRAF mutational status is one the key points to select the optimal first-line therapy. Despite the great strides, there are still many challenges in the decision-making regarding the upfront strategy in mCRC patients. RAS testing turnaround time and the unavailability of tissue are the factors most frequently cited by physicians for treating mCRC patients with unknown RAS status, particularly in small volume centers. An accurate blood-based RAS/BRAF mutation assay with fast turnaround time would help circumvent these hurdles. Our experience suggests that genotyping RAS/BRAF to guide therapy may be the first use of liquid biopsy in the daily care with mCRC patients, particularly in the urgent situation to define the first-line regimen.Background: First-line decision making is the key to the successful care of mCRC patients and RAS/BRAF status is crucial to select the best targeted agent. In hub centers, a relevant proportion of patients referred from small volume centers may not have standard tissue-based (STB) molecular results available at the time of the first visit (T0). Liquid biopsy (LB) may help circumvent these hurdles. Methods: A monoinstitutional prospective head-to-head comparison of LB versus (vs.) STB testing was performed in a real-world setting. Selection criteria included: mCRC diagnosis with unknown RAS/BRAF status at T0, tumoral tissue archived in external centers, no previous treatment with anti-EGFR. At T0, patients underwent plasma sampling for LB testing and procedure for tissue recovery. RAS/BRAF genotyping was carried out by droplet digital PCR on circulating-tumoral (ct) DNA. The primary endpoint was the comparison of time to LB (T1) vs. STB (T2) results using the Mann–Whitney U test. Secondary endpoints were the concordance between LB and STB defined as overall percent agreement and the accuracy of LB in terms of specificity, sensitivity, positive and negative predictive value. We also performed an exploratory analysis on urinary (u) ctDNA. Results: A total of 33 mCRC patients were included. Mean T1 and T2 was 7 and 22 days (d), respectively (p < 0.00001). T2 included a mean time for archival tissue recovery of 17 d. The overall percent agreement between LB and STB analysis was 83%. Compared to STB testing, LB specificity and sensitivity were 90% and 80%, respectively, with a positive predictive value of 94% and negative one of 69%. In detail, at STB and LB testing, RAS mutation was found in 45% and 42% of patients, respectively; BRAF mutation in 15%. LB results included one false positive and four false negative. False negative cases showed a significantly lower tumor burden at basal CT scan. Concordance between STB and uctDNA testing was 89%. Conclusions: Faster turnaround time, high concordance and accuracy are three key points supporting the adoption of LB in routinary mCRC care, in particular when decision on first-line therapy is urgent and tissue recovery from external centers may require a long time. Results should be interpreted with caution in LB wild-type cases with low tumor burden.

Fan design assessment for BLI propulsion systems

Civil aviation is aiming at fuel efficient aircraft concepts. Propulsion systems using boundary layer ingestion (BLI) are promising to reach this goal. The focus of this study is on the DLR UHBR fan stage of a tube and wing aircraft with rear-integrated engines. In this integration scenario the propulsion system and especially the fan stage receives distorted inflow in steady-state flight conditions. The distortion pattern and distortion intensity are dependent on the operating conditions. Consequently, the interaction of the fan and the distortion changes over the flight envelope. The first part of the paper aims at gaining knowledge of the BLI fan performance in the operating points end of field, approach, cruise (CR) and top of climb (TOC) using high-fidelity, unsteady RANS approaches. The analysis includes fan map performance metrics and a deeper insight into the flow field at CR and TOC. The preliminary design of a fan stage requires fast turn-around times, which are not fulfilled by high-fidelity approaches. Therefore, a fast, throughflow-based methodology is developed, which enables aerodynamicists to design distortion-tolerant fans. The main characteristics of the methodology is outlined in the second part. Consequently, the methodology is taken advantage of to investigate parameter sensitivities in terms of tip speed, blade thickness, solidity, the annulus geometry and a non-axisymmetric stator. This study suggests that distortion-tolerant fans should be designed at higher tip speeds than conventional design experience recommends to limit the local operating point excursion.

Cost-benefit Analysis of Point-of-care Dental Implant Guides

Guided dental implant surgery is becoming more common and has been shown to have higher accuracy than freehand implant placement. Many surgeons outsource the fabrication of implant guides, even as the tools needed to produce a guide in-house become more ubiquitous and less expensive. The authors' institution prints the majority of its implant guides in-house. Currently, there are very few studies that evaluate the economics of point-of-care 3D printing and dental implants. This study aimed to perform a cost-benefit analysis of point-of-care dental implant guides. A retrospective review of guides made in-house at the University of Louisville Oral and Maxillofacial Surgery Department from July 2020 through July 2021 was conducted. A cost-benefit analysis was performed with the costs defined as the annualized price of acquisition for a 3D printing system, materials, and annual maintenance. This was then divided by the number of annual guides printed to obtain a cost per part. The benefit was defined as the price per outsourced guide minus the price per guide when printed in-house. This benefit per guide was then multiplied by the number of guides printed annually to calculate annual cost-savings. A total of 79 implant guides were printed in-house from July 2020 through July 2021. Total annual costs including the printing system, materials, and maintenance were $13,790. The majority of these costs were associated with the startup cost of the 3D printing system digital scanner, and implant planning software. The annual cost per part of in-house guides was $175. Outsourced guides in Louisville are $350. Subtracting the cost of the in-house guide from the dental lab guides gave a per-guide benefit of $175. The annual benefit of cost-savings for the program was $13,825. In conclusion, this cost-benefit analysis showed that cost reduction with point-of-care implant guides is substantial. This amount could easily be increased as more guides are produced. Not only are in-house guides more affordable, but they also have a faster turnaround time and are just as accurate as surgical guides commercially produced in a lab. As 3D printing and CAD-CAM technologies become more ubiquitous and affordable, more multi-surgeon practices with large implant volumes will likely produce their guides in-house. To maximize efficiency, these offices could train an employee to handle all aspects of 3D printing and processing. Point-of-care dental implant guides are becoming an increasing reality and offer significant cost-savings potential for practices with high implant volumes that outsource their guide fabrication.

Detection of malignant melanoma in H&E-stained images using deep learning techniques

Histopathological images are widely used to diagnose diseases including skin cancer. As digital histopathological images are typically of very large size, in the order of several billion pixels, automated identification of all abnormal cell nuclei and their distribution within multiple tissue sections would assist rapid comprehensive diagnostic assessment. In this paper, we propose a deep learning-based technique to segment the melanoma regions in Hematoxylin and Eosin (H&E) stained histopathological images. In this technique, the nuclei in the image are first segmented using a Convolutional Neural Network (CNN). The segmented nuclei are then used to generate melanoma region masks. Experimental results with a small melanoma dataset show that the proposed method can potentially segment the nuclei with more than 94 % accuracy and segment the melanoma regions with a Dice coefficient of around 85 %. The proposed technique also has a small execution time making it suitable for clinical diagnosis with a fast turnaround time.