Journal articles: 'Automatic fever screening'

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Perpetuini, David, Chiara Filippini, Daniela Cardone, and Arcangelo Merla. "An Overview of Thermal Infrared Imaging-Based Screenings during Pandemic Emergencies." International Journal of Environmental Research and Public Health 18, no. 6 (March 22, 2021): 3286. http://dx.doi.org/10.3390/ijerph18063286.

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Infrared thermal imaging (IRI) is a contact-less technology able to monitor human skin temperature for biomedical applications and in real-life contexts. Its capacity to detect fever was exploited for mass screening during past epidemic emergencies as well as for the current COVID-19 pandemic. However, the only assessment of fever may not be selective for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Hence, novel approaches for IRI data analysis have been investigated. The present review aims to describe how IRI have been employed during the last epidemics, highlighting the potentialities and the limitations of this technology to contain the contagions. Specifically, the methods employed for automatic face recognition and fever assessment and IRI’s performances in mass screening at airports and hospitals are reviewed. Moreover, an overview of novel machine learning methods for IRI data analysis, aimed to identify respiratory diseases, is provided. In addition, IRI-based smart technologies developed to support the healthcare during the COVID-19 pandemic are described. Finally, relevant guidelines to fully exploit IRI for COVID-19 identification are defined, to improve the effectiveness of IRI in the detection of the SARS-CoV-2 infection.

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Hakim, Muhammad Hanifuddin, Rudi Irmawanto, and Poniman Poniman. "Rancang Bangun Wastafel dan Portal Otomatis dengan Mempertimbangkan Antropometri Guna Mencegah Penularan COVID19." RESISTOR (Elektronika Kendali Telekomunikasi Tenaga Listrik Komputer) 4, no. 1 (May 22, 2021): 29. http://dx.doi.org/10.24853/resistor.4.1.29-36.

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Coronavirus yang merajalela pada tahun 2019 (Covid19) mempunyai karakteristik mudah menular, sehingga menjadikan virus ini sangat berbahaya. Meskipun Vaksin sudah ditemukan, protokol kesehatan masih harus diterapkan setidaknya selama 4 tahun kedepan. Salah satu protokol kesehatan yaitu selalu mencuci tangan dengan air mengalir dan sabun. Akan tetapi pada saat mencuci tangan, orang akan tetap menyentuh keran air dan botol sabun, padahal hal ini sangat berpotensi menjadi salah satu media penularan virus. Oleh karena itu penelitian ini bertujuan untuk menghindari sentuhan fisik saat mencuci tangan. Alat ini dilengkapi dengan portal pendeteksi suhu yang berfungi melakukan screening untuk memastikan orang yang akan masuk tidak sedang mengalami demam. Pengembangan teknologi dalam penelitian ini menggunakan metode rancang bangun (research and development). Desain yang dibuat mempertimbangkan Antropometri orang Indonesia. Sehingga Teknologi Tepat Guna (TTG) tersebut dapat memberikan rasa nyaman dan aman saat digunakan. Dari hasil pengujian alat, menunjukkan sensor MLX90614 (temperatur) memiliki tingkat kesalahan rata-rata pengukuran sebesar 0.213ºC atau sekitar 0.58%, sedangkan sensor PIR (jarak) memiliki tingkat sukses 90%. Secara keseluruhan sistem otomatis pada wastafel dan portal dapat berjalan dengan baik.The Coronavirus spread in early 2019 (Covid19) has characteristics of being easily transmitted, making this virus very dangerous. Even though the vaccines has been found, health protocols still have to be implemented for at least the next 4 years. One of the health protocols is washing hands with running water and soap. However, when washing hands, people still touch the water tap and soap bottles, even though this could potentially be a virus transmission media. Therefore, this study aims to avoid physical touch when washing hands. This tool is equipped with a temperature detector portal that functions to ensure that people who enter, do not have a fever. The technology development in this research uses research and development methods. The sink design is made considering Indonesian Anthropometry. Thus Appropriate Technology (TTG) can provide a sense of comfort and safety when used. From the test results, it shows that the MLX90614 sensor (temperature) has an average measurement error rate of 0.213ºC or about 0.58%. while the PIR (distance) sensor has a success rate of 90%. Overall the automatic system on the sink and portal can work well.

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Edwards, Timothy L. "Automated Canine Scent-Detection Apparatus: Technical Description and Training Outcomes." Chemical Senses 44, no. 7 (June 12, 2019): 449–55. http://dx.doi.org/10.1093/chemse/bjz039.

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Abstract To date, laboratory scent-detection work with dogs has been a manual process whereby some or all aspects of the procedures are mediated by researchers. Automation of this process would eliminate issues associated with cuing, subjectivity in data collection, and reinforcement delivery. Herein, I describe an automated apparatus that can accommodate almost any type of sample that can be brought into the laboratory. The apparatus consists of a 17-segment carousel that rotates behind a panel. Dogs can access a single sample at a time through a port in the panel. Infrared beams are used to detect sample observations and indications, and a dog-activated switch is used to advance the carousel to the next sample. Correct indications are reinforced with an automated feeder. After screening 12 dogs, 5 dogs were selected and trained to use the apparatus to classify samples containing amyl acetate. All dogs achieved hit rates and correct rejection rates at or near 100% in fewer than 25 half-days of training (mean: 19.6, range: 12–24). These data suggest that the apparatus can be used to obtain accurate sample classification without excessive training requirements. Future improvements to the apparatus and training protocols may reduce the training requirements further.

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Ortiz, Daniel A., and Michael J. Loeffelholz. "Evaluation of the Lumipulse G TP-N Chemiluminescent Immunoassay as a Syphilis Screening Test." Journal of Clinical Microbiology 55, no. 11 (September 6, 2017): 3236–41. http://dx.doi.org/10.1128/jcm.00966-17.

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ABSTRACTA syphilis diagnosis is often aided by the detection of treponemal and nontreponemal antibodies. Automated treponemal antibody detection systems enable high-volume clinical laboratories to perform syphilis screening at a faster pace with lower labor costs. The Lumipulse G TP-N chemiluminescent immunoassay is an automated system that qualitatively detects IgG and IgM antibodies againstTreponema pallidumantigens in human serum and plasma. To assess performance characteristics and workflow efficiency, the Lumipulse G TP-N assay was compared to the Bioplex 2200 Syphilis IgG multiplex flow immunoassay. Among the 4,134 routine and HIV samples tested by the two automated assays, the percentage of agreement was excellent at 99.0% (95% confidence interval [CI], 98.6% to 99.2%; κ, 0.89), with the Lumipulse G TP-N having a shorter time to first and subsequent results. All specimens with reactive syphilis screening results were further tested by rapid plasma reagin (RPR) andTreponema pallidumparticle agglutination (TP·PA) testing (n= 231). The results from the RPR-reactive samples (n= 82) showed complete concordance with the two automated assays, while the TP·PA assay displayed some discrepancies. The positive percent agreement (PPA) and negative percent agreement (NPA) between the TP·PA test and the Lumipulse G TP-N test were 98.9% and 77.3%, respectively. The Bioplex 2200 Syphilis IgG immunoassay displayed a similar PPA (100%) but a substantially lower NPA (15.9%). Patient chart reviews of discrepant results suggested that the Lumipulse G TP-N assay produced 27 fewer falsely reactive results and can reduce the amount of additional confirmatory RPR and TP·PA testing needed. The analogous performance characteristics of the two automated systems indicate that the Lumipulse G TP-N assay is suitable for high-throughput syphilis screening.

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Zhao, Oliver S., Nikhil Kolluri, Anagata Anand, Nicholas Chu, Ravali Bhavaraju, Aditya Ojha, Sandhya Tiku, et al. "Convolutional neural networks to automate the screening of malaria in low-resource countries." PeerJ 8 (August 4, 2020): e9674. http://dx.doi.org/10.7717/peerj.9674.

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Malaria is an infectious disease caused by Plasmodium parasites, transmitted through mosquito bites. Symptoms include fever, headache, and vomiting, and in severe cases, seizures and coma. The World Health Organization reports that there were 228 million cases and 405,000 deaths in 2018, with Africa representing 93% of total cases and 94% of total deaths. Rapid diagnosis and subsequent treatment are the most effective means to mitigate the progression into serious symptoms. However, many fatal cases have been attributed to poor access to healthcare resources for malaria screenings. In these low-resource settings, the use of light microscopy on a thin blood smear with Giemsa stain is used to examine the severity of infection, requiring tedious and manual counting by a trained technician. To address the malaria endemic in Africa and its coexisting socioeconomic constraints, we propose an automated, mobile phone-based screening process that takes advantage of already existing resources. Through the use of convolutional neural networks (CNNs), we utilize a SSD multibox object detection architecture that rapidly processes thin blood smears acquired via light microscopy to isolate images of individual red blood cells with 90.4% average precision. Then we implement a FSRCNN model that upscales 32 × 32 low-resolution images to 128 × 128 high-resolution images with a PSNR of 30.2, compared to a baseline PSNR of 24.2 through traditional bicubic interpolation. Lastly, we utilize a modified VGG16 CNN that classifies red blood cells as either infected or uninfected with an accuracy of 96.5% in a balanced class dataset. These sequential models create a streamlined screening platform, giving the healthcare provider the number of malaria-infected red blood cells in a given sample. Our deep learning platform is efficient enough to operate exclusively on low-tier smartphone hardware, eliminating the need for high-speed internet connection.

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Manuel, Kevin, Marie Moses Ambroise, Anita Ramdas, and Renu G'Boy Varghese. "Pseudobasophilia as a Screening Tool in Dengue: A Single Center Study." Journal of Laboratory Physicians 13, no. 02 (June 2021): 156–61. http://dx.doi.org/10.1055/s-0041-1730849.

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Abstract Objectives Proper serological testing for the definite diagnosis of dengue is costly and may not be easily available in a resource-limited setting. Hematological parameters can help in the early identification of dengue cases. This study aims to evaluate the occurrence and utility of pseudobasophilia in identifying dengue-affected patients. Materials and Methods This retrospective cross-sectional study included 1,304 dengue cases confirmed by serology and 1,044 dengue serology negative acute febrile illness cases as controls. Complete blood count (CBC) values of the first EDTA (ethylenediamine tetraacetic acid) blood sample from automated hematology analyzers were reviewed. The hematological parameters in the dengue and control groups were compared and the variation of these parameters with the day of fever was also analyzed. Statistical Analysis Mann-Whitney’s test, Kruskal-Wallis test, and Fisher’s exact test were used for statistical analysis. A p-value < 0.05 was considered statistically significant for all tests. Results There was a statistically significant variation between dengue cases and controls for hematocrit, platelet count, mean platelet volume, total white blood cell count, and absolute basophil count. The dengue group had a higher hematocrit from day 2 to day 10, platelet count ≤ 100,000/µL from day 4 to day 9, higher mean platelet volume from day 2 to day 7, leucopenia from day 3 to day 5, and higher absolute basophil count from day 2 to day 10. Interestingly, pseudobasophilia was seen in 533 (40.87%) of dengue cases and only 3 (0.28%) of the controls. Pseudobasophilia was also observed to have an increasing trend to the day of fever. Conclusion Pseudobasophilia along with other CBC parameters is useful and cost effective for the early identification of dengue. This can prompt early investigations and supportive treatment leading to improved clinical outcomes.

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Mardovina, Tatsiana, John G. Chromczak, and Paul W. Riley. "Comparison of Two Different ELISA Methods for Heparin-Induced Thrombocytopenia (HIT) Screening on an Automated ELISA Platform." Blood 134, Supplement_1 (November 13, 2019): 4935. http://dx.doi.org/10.1182/blood-2019-125293.

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BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an adverse complication of unfractionated and low molecular weight heparin caused by antibodies recognizing platelet factor 4-heparin (PF4/hep) complexes leading to platelet activation. The diagnosis of HIT is based on the combination of the clinical picture, using the 4T score along with screening and confirmatory methods to detect platelet activating anti‐PF4/H antibodies. OBJECTIVES: Performance was evaluated for two enzyme linked immunosorbent assays (ELISAs), 1) Asserachrom HPIA , Diagnostica Stago Inc., Parsippany, NJ, USA and 2) LIFECODES PF4 Enhanced, Immucor, Inc., Norcross, GA, USA for screening-based detection of PF4/hep antibodies. METHODS: ELISA assays were run per manufacturer recommendations and adapted for automation on a Dynex DS2 automated ELISA platform. Performance characteristics of the two immunoassays were assessed, including sensitivity, specificity, concordance with serotonin release assay (SRA), positive predictive value (PPV) and negative predictive value (NPV). 21 samples were used in the study. Results: Both assays, Asserachrom HPIA and LIFECODES PF4 Enhanced demonstrated 100% sensitivity and NPV, confirming both assays' reliability to detect and rule out HIT (see table). The diagnostic specificity was significantly higher for Asserachrom HPIA vs. LIFECODES PF4 Enhanced (77.8% vs 31.6%). Asserachrom HPIA showed fewer false positive results, with PPV of 42.9% for Asserachrom HPIA vs. 13.3% for LIFECODES PF4 Enhanced. No false negative results were found for either assay. Asserachrom HPIA demonstrated 81.0% concordance with SRA, vs. 38.1% for LIFECODES PF4 Enhanced. CONCLUSIONS: HIT is a life-threatening disorder, with diagnosis depending on clinical findings using the 4T score along with laboratory evaluation. Combining the 4T score with PF4/hep antibody screening increases the accuracy of excluding HIT. Our observations indicate Asserachrom HPIA provides results with high sensitivity and specificity, minimizing false positivess, allowing use of alternative anticoagulants more selectively in at risk patients, to potentially improve patient management while minimizing costs. Disclosures Mardovina: Diagnostica Stago, Inc.: Employment. Chromczak:Diagnostica Stago, Inc.: Employment. Riley:Diagnostica Stago, Inc.: Employment.

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Uchida, Akiko, Kenji Tanimura, Mayumi Morizane, Kazumichi Fujioka, Ichiro Morioka, Masanobu Oohashi, Toshio Minematsu, and Hideto Yamada. "Clinical Factors Associated With Congenital Cytomegalovirus Infection: A Cohort Study of Pregnant Women and Newborns." Clinical Infectious Diseases 71, no. 11 (December 2, 2019): 2833–39. http://dx.doi.org/10.1093/cid/ciz1156.

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Abstract Background The aim of this prospective cohort study was to determine clinical factors associated with the occurrence of congenital cytomegalovirus infection (cCMV) in pregnant women. Methods Between March 2009 and November 2017, newborns born at a primary maternity hospital received polymerase chain reaction (PCR) analyses for CMV DNA in their urine with informed consent of the mothers at a low risk. Clinical data, including age, gravidity, parity, body mass index, occupation, maternal fever/flulike symptoms, pregnancy complications, gestational weeks at delivery, birth weight, and automated auditory brainstem response, were collected. Logistic regression analyses were performed to determine clinical factors associated with cCMV. Results cCMV was diagnosed by positive PCR results of neonatal urine in 9 of 4125 pregnancies. Univariate and multivariable analyses revealed that the presence of fever/flulike symptoms (odds ratio [OR], 17.9; 95% confidence interval [CI], 3.7–86.7; P < .001) and threatened miscarriage/premature labor in the second trimester (OR, 6.0; 95% CI, 1.6–22.8; P < .01) were independent clinical factors associated with cCMV. Maternal fever/flulike symptoms or threatened miscarriage/premature labor in the second trimester had 100% sensitivity, 53.2% specificity, and a maximum Youden index of .85. Conclusions This cohort study for the first time demonstrated that these clinical factors of pregnant women and newborns were associated with the occurrence of cCMV. This is useful information for targeted screening to assess risks of cCMV in low-risk mothers, irrespective of primary or nonprimary CMV infection.

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Wang, Yanli, Tiejun Cheng, and Stephen H. Bryant. "PubChem BioAssay: A Decade’s Development toward Open High-Throughput Screening Data Sharing." SLAS DISCOVERY: Advancing the Science of Drug Discovery 22, no. 6 (January 13, 2017): 655–66. http://dx.doi.org/10.1177/2472555216685069.

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High-throughput screening (HTS) is now routinely conducted for drug discovery by both pharmaceutical companies and screening centers at academic institutions and universities. Rapid advance in assay development, robot automation, and computer technology has led to the generation of terabytes of data in screening laboratories. Despite the technology development toward HTS productivity, fewer efforts were devoted to HTS data integration and sharing. As a result, the huge amount of HTS data was rarely made available to the public. To fill this gap, the PubChem BioAssay database ( https://www.ncbi.nlm.nih.gov/pcassay/ ) was set up in 2004 to provide open access to the screening results tested on chemicals and RNAi reagents. With more than 10 years’ development and contributions from the community, PubChem has now become the largest public repository for chemical structures and biological data, which provides an information platform to worldwide researchers supporting drug development, medicinal chemistry study, and chemical biology research. This work presents a review of the HTS data content in the PubChem BioAssay database and the progress of data deposition to stimulate knowledge discovery and data sharing. It also provides a description of the database’s data standard and basic utilities facilitating information access and use for new users.

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Benekohal, Rahim F., Yoassry M. El-Zohairy, and Stanley Wang. "Truck Travel Time Around Weigh Stations: Effects of Weigh in Motion and Automatic Vehicle Identification Systems." Transportation Research Record: Journal of the Transportation Research Board 1716, no. 1 (January 2000): 135–43. http://dx.doi.org/10.3141/1716-16.

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Weigh in motion (WIM) technology may provide an efficient and cost-effective complement to static weighing. An evaluation of the effectiveness of an automated bypass system around a weigh station in Illinois is presented. The system combines the use of automatic vehicle identification (AVI), high-speed weigh in motion (HSWIM), and low-speed weigh in motion (LSWIM) technologies to facilitate preclearance for trucks at the weigh station. The preinstallation conditions were compared with post-installation conditions of WIM/AVI so that the effects and benefits of the system could be evaluated. During preinstallation, average delay was 4.9 min/truck, and 7 percent of trucks had delays of more than 10 min. The station was intermittently closed to prevent the truck queue from backing up onto the Interstate highway, allowing 15 to 51 percent of trucks to bypass the station without being weighed. In postinstallation, the delay for trucks equipped with transponder and allowed to bypass on the freeway was reduced by 4.17 min. The delay for trucks equipped with transponders and allowed to bypass inside the weigh station was reduced by 2.02 min. The delay for trucks that reported to the weigh station decreased by 1.25 min. On the other hand, less than 1 percent of trucks that have been observed in after-study were able to bypass on the freeway. With greater numbers of trucks being checked, fewer trucks on the road may exceed the allowable weight limits. Consequently, electronic screening minimizes road deterioration and risks to public safety and levels the playing field for illegally operating carriers and carriers who operate in compliance with the law.

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Crowell, Elizabeth Faris, Cyril Bazin, François Saunier, Romain Brixtel, Yann Caillot, Boris Lesner, Matthieu Toutain, et al. "CytoProcessorTM: A New Cervical Cancer Screening System for Remote Diagnosis." Acta Cytologica 63, no. 3 (2019): 215–23. http://dx.doi.org/10.1159/000497111.

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Background: Current automated cervical cytology screening systems still heavily depend on manipulation of glass slides. We developed a new system called CytoProcessorTM (DATEXIM, Caen, France), which increases sensitivity and takes advantage of virtual slide technology to simplify the workflow and save worker time. We used an approach based on artificial intelligence to identify abnormal cells among the tens of thousands in a cervical preparation. Objectives: We set out to compare the diagnostic sensitivity and specificity of CytoProcessorTM and the ThinPrep Imaging System (HOLOGIC, Marlborough, MA, USA). Methods: A representative population of 1,352 cases was selected from the routine workflow in a private laboratory. Diagnoses were established using the ThinPrep Imaging System and CytoProcessorTM. All discordances were resolved by a consensus committee. Results: Compared to the ThinPrep Imaging System, CytoProcessorTM significantly improves diagnostic sensitivity without compromising specificity. The sensitivity of detection of “atypical squamous cells of undetermined significance (ASC-US) and more severe” and “low-grade squamous intraepithelial lesion and more severe” was significantly higher using CytoProcessorTM. Considering that cases with a truth diagnosis of ASC-US or more severe required clinical follow-up, 1.5% of the cases (21/1,360) would have been missed if the CytoProcessorTM diagnosis had been used for clinical decision-making. In contrast, 4% of the cases (54/1,360) were missed when the ThinPrep Imaging System diagnosis was used for clinical decision-making. There were 2.6 times fewer false negatives using CytoProcessorTM. The CytoProcessorTM workflow was 1.5 times faster in terms of worker time. Conclusions: CytoProcessorTM is the first of a new generation of automated screening systems, demonstrating improved sensitivity and yielding significant gains in processing time. In addition, the fully digital nature of slide presentation in CytoProcessorTM allows the remote diagnosis of Papanicolaou tests for the first time.

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Lian, Wanmin, Li Wen, Qiru Zhou, Weijie Zhu, Wenzhou Duan, Xiongzhi Xiao, Florence Mhungu, et al. "Digital Health Technologies Respond to the COVID-19 Pandemic In a Tertiary Hospital in China: Development and Usability Study." Journal of Medical Internet Research 22, no. 11 (November 24, 2020): e24505. http://dx.doi.org/10.2196/24505.

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Background The outbreak of COVID-19 has caused a continuing global pandemic. Hospitals are integral to the control and prevention of COVID-19; however, they are facing numerous challenges during the epidemic. Objective Our study aimed to introduce the practical experience of the design and implementation of a web-based COVID-19 service platform at a tertiary hospital in China as well as the preliminary results of the implementation. Methods The web-based COVID-19 service platform was deployed within the health care system of the Guangdong Second Provincial General Hospital and Internet Hospital; the function of the platform was to provide web-based medical services for both members of the public and lay health care workers. The focal functions of this system included automated COVID-19 screening, related symptom monitoring, web-based consultation, and psychological support; it also served as a COVID-19 knowledge hub. The design and process of each function are introduced. The usage data for the platform service were collected and are represented by three periods: the pre-epidemic period (December 22, 2019, to January 22, 2020, 32 days), the controlled period (January 23 to March 31, 2020, 69 days), and the postepidemic period (April 1 to June 30, 2020, 91 days). Results By the end of June 2020, 96,642 people had used the automated COVID-19 screening and symptom monitoring systems 161,884 and 7,795,194 times, respectively. The number of general web-based consultation services per day increased from 30 visits in the pre-epidemic period to 122 visits during the controlled period, then dropped to 73 visits in the postepidemic period. The psychological counseling program served 636 clients during the epidemic period. For people who used the automated COVID-19 screening service, 160,916 (99.40%) of the total users were classified in the no risk category. 464 (0.29%) of the people were categorized as medium to high risk, and 12 people (0.01%) were recommended for further COVID-19 testing and treatment. Among the 96,642 individuals who used the COVID-19 related symptoms monitoring service, 6696 (6.93%) were symptomatic at some point during the monitoring period. Fever was the most frequently reported symptom, with 2684/6696 symptomatic people (40.1%) having had this symptom. Cough and sore throat were also relatively frequently reported by the 6696 symptomatic users (1657 people, 24.7%, and 1622 people, 24.2%, respectively). Conclusions The web-based COVID-19 service platform implemented at a tertiary hospital in China is exhibited to be a role model for using digital health technologies to respond to the COVID-19 pandemic. The digital solutions of automated COVID-19 screening, daily symptom monitoring, web-based care, and knowledge propagation have plausible acceptability and feasibility for complementing offline hospital services and facilitating disease control and prevention.

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Kwon, Jung-ah, Hyeseon Lee, Kap N. o. Lee, Kwangchun Chae, Seram Lee, Dong-ki Lee, and Soyoun Kim. "High Diagnostic Accuracy of Antigen Microarray for Sensitive Detection of Hepatitis C Virus Infection." Clinical Chemistry 54, no. 2 (February 1, 2008): 424–28. http://dx.doi.org/10.1373/clinchem.2007.090464.

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Abstract Background: Hepatitis C virus (HCV) can be transmitted through blood transfusion. Screening ELISA, the most widely used method for HCV diagnosis, sometimes yields false-positive and false-negative results, so a confirmatory test is used. This secondary testing is labor-intensive and expensive, and thus is impractical for massive blood bank screening. Therefore, a new massive screening method with high accuracy is needed for sensitive and specific detection of HCV. Methods: With sol-gel material, we designed novel antigen microarray in 96-well plates for HCV detection. Each individual well was spotted with 4 different HCV antigens. We used this new system to test 154 patient serum samples previously tested for HCV by ELISA (87 HCV positive and 67 HCV negative) (HCV EIA3.0, ABBOTT). We assessed the detection limit of our microarray system with the use of serial 10-fold dilutions of an HCV-positive sample. Results: Our microarray assay was reproducible and displayed higher diagnostic accuracy (specificity) (98.78%) than did the ELISA (81.71%). Our method yielded significantly fewer false-positive results than did the ELISA. The detection limit of our assay was 1000 times more sensitive than that of the ELISA. In addition, we found this novel assay technology to be compatible with the currently employed automated methods used for ELISA. Conclusion: We successfully applied the sol-gel–based protein microarray technology to a screening assay for HCV diagnosis with confirmatory test-level accuracy. This new, inexpensive method will improve the specificity and sensitivity of massive sample diagnosis.

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Rahman, Md Toufiq, Andrew J. Codlin, Md Mahfuzur Rahman, Ayenun Nahar, Mehdi Reja, Tariqul Islam, Zhi Zhen Qin, Md Abdus Shakur Khan, Sayera Banu, and Jacob Creswell. "An evaluation of automated chest radiography reading software for tuberculosis screening among public- and private-sector patients." European Respiratory Journal 49, no. 5 (May 2017): 1602159. http://dx.doi.org/10.1183/13993003.02159-2016.

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Computer-aided reading (CAR) of medical images is becoming increasingly common, but few studies exist for CAR in tuberculosis (TB). We designed a prospective study evaluating CAR for chest radiography (CXR) as a triage tool before Xpert MTB/RIF (Xpert).Consecutively enrolled adults in Dhaka, Bangladesh, with TB symptoms received CXR and Xpert. Each image was scored by CAR and graded by a radiologist. We compared CAR with the radiologist for sensitivity and specificity, area under the receiver operating characteristic curve (AUC), and calculated the potential Xpert tests saved.A total of 18 036 individuals were enrolled. TB prevalence by Xpert was 15%. The radiologist graded 49% of CXRs as abnormal, resulting in 91% sensitivity and 58% specificity. At a similar sensitivity, CAR had a lower specificity (41%), saving fewer (36%) Xpert tests. The AUC for CAR was 0.74 (95% CI 0.73–0.75). CAR performance declined with increasing age. The radiologist grading was superior across all sub-analyses.Using CAR can save Xpert tests, but the radiologist's specificity was superior. Differentiated CAR thresholds may be required for different populations. Access to, and costs of, human readers must be considered when deciding to use CAR software. More studies are needed to evaluate CAR using different screening approaches.

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Li Pira, Giuseppina, Federico Ivaldi, Chiara Dentone, Elda Righi, Valerio Del Bono, Claudio Viscoli, Gerrit Koopman, and Fabrizio Manca. "Evaluation of Antigen-Specific T-Cell Responses with a Miniaturized and Automated Method." Clinical and Vaccine Immunology 15, no. 12 (October 22, 2008): 1811–18. http://dx.doi.org/10.1128/cvi.00322-08.

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ABSTRACT The evaluation of antigen-specific T-cell responses is helpful for both research and clinical settings. Several techniques can enumerate antigen-responsive T cells or measure their products, but they require remarkable amounts of peripheral blood mononuclear cells (PBMCs). Since screening numerous antigens or testing samples from pediatric or lymphopenic patients is hampered in clinical practice, we refined a miniaturized, high-throughput assay for T-cell immunity. Antigens and cells in 10-μl volumes were dispensed into 1,536-well culture plates precoated with anti-gamma interferon (anti-IFN-γ) antibodies. After being cultured, the wells were developed by enzyme-linked immunosorbent assay for bound cytokine. Miniaturization and automation allowed quantitation of antigen-specific responses on 104 PBMCs. This method was applied for epitope mapping of mycobacterial antigens and was used in the clinic to evaluate T-cell immunity to relevant opportunistic pathogens by using small blood samples. A comparison with conventional methods showed similar sensitivity. Therefore, current flow cytometric methods that provide information on frequency and phenotype of specific T cells can be complemented by this assay that provides extensive information on cytokine concentrations and profiles and requires 20- to 50-fold fewer PBMCs than other analytical methods.

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Hilletofth, Per, Movin Sequeira, and Wendy Tate. "Fuzzy-logic-based support tools for initial screening of manufacturing reshoring decisions." Industrial Management & Data Systems 121, no. 5 (March 25, 2021): 965–92. http://dx.doi.org/10.1108/imds-05-2020-0290.

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PurposeThis paper investigates the suitability of fuzzy-logic-based support tools for initial screening of manufacturing reshoring decisions.Design/methodology/approachTwo fuzzy-logic-based support tools are developed together with experts from a Swedish manufacturing firm. The first uses a complete rule base and the second a reduced rule base. Sixteen inference settings are used in both of the support tools.FindingsThe findings show that fuzzy-logic-based support tools are suitable for initial screening of manufacturing reshoring decisions. The developed support tools are capable of suggesting whether a reshoring decision should be further evaluated or not, based on six primary competitiveness criteria. In contrast to existing literature this research shows that it does not matter whether a complete or reduced rule base is used when it comes to accuracy. The developed support tools perform similarly with no statistically significant differences. However, since the interpretability is much higher when a reduced rule base is used and it require fewer resources to develop, the second tool is more preferable for initial screening purposes.Research limitations/implicationsThe developed support tools are implemented at a primary-criteria level and to make them more applicable, they should also include the sub-criteria level. The support tools should also be expanded to not only consider competitiveness criteria, but also other criteria related to availability of resources and strategic orientation of the firm. This requires further research with regard to multi-stage architecture and automatic generation of fuzzy rules in the manufacturing reshoring domain.Practical implicationsThe support tools help managers to invest their scarce time on the most promising reshoring projects and to make timely and resilient decisions by taking a holistic perspective on competitiveness. Practitioners are advised to choose the type of support tool based on the available data.Originality/valueThere is a general lack of decision support tools in the manufacturing reshoring domain. This paper addresses the gap by developing fuzzy-logic-based support tools for initial screening of manufacturing reshoring decisions.

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Parshall, G. W. "Trends in processing and manufacturing that will affect implementation of the Chemical Weapons Convention." Pure and Applied Chemistry 74, no. 12 (January 1, 2002): 2259–63. http://dx.doi.org/10.1351/pac200274122259.

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Several new developments in synthesis science and manufacturing technology may affect the task of implementing the Chemical Weapons Convention (CWC) constraints on the production of toxic agents for military or terrorist purposes. The combination of automated synthesis methods and high-throughput screening protocols could potentially yield new toxic agents not specifically proscribed by the CWC, but such approaches are unlikely to seriously impact the work of the Organisation for the Prohibition of Chemical Weapons (OPCW) in the near future. On the other hand, new developments in manufacturing may have a serious impact on the work of the OPCW inspectors. The wide use of versatile, multipurpose production facilities in making fine chemicals complicates the task of discerning whether a particular facility is used only for nonprohibited purposes under the CWC. New catalytic processes and automated process control permit production of toxic chemicals with fewer emissions that contaminate the environment and might provide clues to the nature of the processes being conducted. Tiny microreactors operated continuously under computer control can produce significant quantities of toxic chemicals (including CWC scheduled compounds) with a very small “footprint”within a larger production facility. These technical developments together with the dispersal of chemical production facilities and skills may seriously complicate the tasks of the OPCW inspectors.

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IKAWA, NOBUKO. "AUTOMATED AVERAGING OF AUDITORY EVOKED RESPONSE WAVEFORMS USING WAVELET ANALYSIS." International Journal of Wavelets, Multiresolution and Information Processing 11, no. 04 (July 2013): 1360009. http://dx.doi.org/10.1142/s0219691313600096.

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The auditory brainstem response (ABR) is widely used as an index to assist hearing and brain function diagnoses. In particular, in clinical applications, the rapid detection of ABR peak characteristics is required. One approach to improving the speed of detection is to decrease the number of signal averaging procedures while denoising during the detection of ABR waveforms; another approach is to extract the characteristics of ABR waveform components. In our previous study, to represent ABR waveform components, we obtained not only the frequency characteristics of an ABR but also the frequency characteristics of each component of the ABR based on the time (latency). Using a one-dimensional discrete wavelet transform (DWT) in this latency-frequency analysis, we described an approximate method of reproducing ABR signals with a low SNR from observed values obtained with a smaller number of averaging procedures. At the same time, using this multiple-level frequency decomposition of ABR signals according to the known frequency content of the ABR, we extracted the peak latency of the fast component of the ABR using fewer averagings of the ABR data. From these decomposition and reconstruction results for ABR signals, we proposed the optimal decomposition level of the ABR and explained how we used the waveform of the ABR reconstructed by the inverse DWT (IDWT). In this paper, we propose a method of automated averaging of the ABR using the waveform reconstructed by discrete wavelet multiresolution analysis (MRA). Our proposed method will be useful for the fast detection of ABR latency characteristics in hearing screening test.

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Spangler, Danielle A., Ricardo F. Muñoz, Joyce Chu, and Yan Leykin. "Perceived Utility of the Internet-Based Safety Plan in a Sample of Internet Users Screening Positive for Suicidality." Crisis 41, no. 2 (March 2020): 146–49. http://dx.doi.org/10.1027/0227-5910/a000600.

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Abstract. Background: The Internet may offer resources for individuals who struggle with suicidality but have no access to other resources or fail to use them. Aims: To develop an automated, self-guided Internet-based safety plan (IBSP), and to evaluate its use and perceived utility among individuals who report suicidality online. Method: Participants ( N = 150) were recruited from a depression/suicide screening website. Participants developed personalized safety plans and reported their perceived utility. Results: Participants reported moderate utility of the IBSP. Participants' demographic and clinical characteristics were not related to any metrics reflecting the perceived utility of the IBSP, suggesting that the ISBP does not appeal more or less to any particular group. Similarly, participant characteristics were largely unrelated to IBSP completion rates. The sole exception was gender, with males completing fewer steps ( p < .001). Interestingly, participants were more likely to believe that IBSP could be helpful for others than for themselves ( p < .001). Limitations: Quality and use of IBSPs were not assessed; poststudy assessments were limited to those completing the study; participants uninterested in reducing suicidality are not represented. Conclusion: The IBSP may eventually be an acceptable tool for Internet users at risk for suicide.

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Leitner, Martina, Christian Büchold, Ralf Pasternack, Nikolaus B. Binder, and Gary W. Moore. "Clinical Validation of an Automated Fluorogenic Factor XIII Activity Assay Based on Isopeptidase Activity." International Journal of Molecular Sciences 22, no. 3 (January 20, 2021): 1002. http://dx.doi.org/10.3390/ijms22031002.

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Hereditary factor XIII (FXIII) deficiency is a rare autosomal bleeding disorder which can cause life-threatening bleeding. Acquired deficiency can be immune-mediated or due to increased consumption or reduced synthesis. The most commonly used screening test is insensitive, and widely used quantitative assays have analytical limitations. The present study sought to validate Technofluor FXIII Activity, the first isopeptidase-based assay available on a routine coagulation analyser, the Ceveron s100. Linearity was evidenced throughout the measuring range, with correlation coefficients of >0.99, and coefficients of variation for repeatability and reproducibility were <5% and <10%, respectively. A normally distributed reference range of 47.0–135.5 IU/dL was derived from 154 normal donors. Clinical samples with Technofluor FXIII Activity results between 0 and 167.0 IU/dL were assayed with Berichrom® FXIII Activity, a functional ammonia release assay, and the HemosIL™ FXIII antigen assay, generating correlations of 0.950 and 0.980, respectively. Experiments with a transglutaminase inhibitor showed that Technofluor FXIII Activity can detect inhibition of enzymatic activity. No interference was exhibited by high levels of haemolysis and lipaemia, and interference by bilirubin was evident at 18 mg/dL, a level commensurate with severe liver disease. Technofluor FXIII Activity is a rapid, accurate and precise assay suitable for routine diagnostic use with fewer interferents than ammonia release FXIII activity assays.

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Sanyal, Amit, James M. Heun, Jessica Sweeney, and Clemens Janssen. "Mobile-Health Tool to Improve Care of Patients with Hematological Malignancies." Blood 136, Supplement 1 (November 5, 2020): 35–36. http://dx.doi.org/10.1182/blood-2020-143405.

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INTRODUCTION Adverse effects are common during treatment of hematological malignancies. Treatment toxicities can impact quality of life [1], impose financial hardship and cause cancer related distress[2]. Symptom monitoring using electronic technology can facilitate early detection of complications[3], reduce symptom burden[4], cost of care[5] and improve survival[6]. Cancer treatment also increases risk of mortality from infections such as coronavirus disease 2019 (COVID-19) and routine screening has been recommended[7]. METHODS We developed an application that periodically delivers toxicity questionnaires to patients during treatment . Based on NCI- PRO-CTCAE™, the questions are delivered through SMS or e-mail. Patient responses crossing prespecified thresholds trigger automated alerts on a dashboard, resulting in additional interventions as needed. Nature and time to intervention is tracked. Patient experience is measured using a Likert-scale and free-text box. Centers for Disease Control recommended COVID-19 screening questions were incorporated. Finally, a distress thermometer for cancer distress screening has been recently added. The app was offered to patients with hematological cancers in a community-based cancer center. RESULTS Since introduction in April 2020, we have enrolled 37 patients. 9 patients had chronic lymphocytic leukemia, 6 diffuse large B cell, 5 mantle cell, 4 Hodgkin's and 3 follicular lymphoma. 2 each had chronic myelogenous, multiple myeloma and Richter's syndrome. 1 each had hairy cell leukemia, acute myelogenous leukemia and T Cell lymphoma. Median age was 64 years (range 24-85). Patient experience has been favorable. On a scale of 1-5, 85.5% rated the experience as 3 or higher. Median patient engagement, calculated by dividing the number of forms completions by number of days enrolled was 34.2% (0.9-66.2 %). Symptom tracker captured 536 responses. Fatigue (153), no symptoms (152), shortness of breath (57), nausea/vomiting, diarrhea (46) and numbness/tingling (28) were the most common response categories. Of 1107 completed check ins, 75 triggered flags. There were 2 hospitalizations for neutropenic fever with the remainder managed as outpatients. Average time between patient generated response and provider intervention was 90.9 minutes. 88% follow-ups were completed within 1 business day. COVID-19 screening module captured 1096 responses. 988 were no symptoms. All positive responses (44 diarrhea, 39 cough, 23 shortness of breath and 2 fever) were false positives. Distress thermometer implemented a week before data cut-off captured 2 responses, 1 in the physical and 1 in the psychological domain. CONCLUSION We demonstrate feasibility of electronic capture of treatment toxicities and offer proof of concept that a mobile app can be used for infection screening. Additionally, the quick response time by care team indicated a high adoption rate. REFERENCES Doorduijn J, B.I., Holt B, Steijaert M, Uyl-de Groot C, Sonneveld P., Self-reported quality of life in elderly patients with aggressive non-Hodgkin's lymphoma treated with CHOP chemotherapy. . European Journal of Hemtology 2005. 75(2): p. 116-123.Troy JD, L.S., Samsa GP, Feliciano J, Richhariya A, LeBlanc TW., Patient-reported distress in Hodgkin lymphoma across the survivorship continuum. Supportive Care Cancer, 2019. 27(7): p. 2453-2462.Stover A M, H.S., Deal A M, Stricker C T, Bennett A V, Carr P M, Jansen J, Kottschade L A, Dueck A C, Basch E M, Methods for alerting clinicians to concerning symptom questionnaire responses during cancer care: Approaches from two randomized trials (STAR, AFT-39 PRO-TECT). Journal of Clinical Oncology 2018. 36(30 supplement): p. 158.Mooney KH, B.S., Wong B, Whisenant M, Donaldson G, Automated home monitoring and management of patient-reported symptoms during chemotherapy: results of the symptom care at home RCT. Cancer Medicine, 2017. 6(3): p. 537-546.Barkley R, S.M.-J., Wang J, Blau S, Page RD, Reducing Cancer Costs Through Symptom Management and Triage Pathways. Journal of Oncology Practice, 2019. 15(2): p. e91-e97.Denis F, B.E., Septans AL, Urban T, Dueck AC, Letellier C., Two-Year Survival Comparing Web-Based Symptom Monitoring vs Routine Surveillance Following Treatment for Lung Cancer. JAMA, 2019. 321(3): p. 306-307.ASCO Special Report: A guide to cancer care delivery during COVID-19 pandemic. 2020, ASCO: Alexandria, VA. Disclosures Janssen: wellbe Inc.: Current Employment.

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Hughes, M. Joseph, and Robert Kennedy. "High-Quality Cloud Masking of Landsat 8 Imagery Using Convolutional Neural Networks." Remote Sensing 11, no. 21 (November 5, 2019): 2591. http://dx.doi.org/10.3390/rs11212591.

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The Landsat record represents an amazing resource for discovering land-cover changes and monitoring the Earth’s surface. However, making the most use of the available data, especially for automated applications ingesting thousands of images without human intervention, requires a robust screening of cloud and cloud-shadow, which contaminate clear views of the land surface. We constructed a deep convolutional neural network (CNN) model to semantically segment Landsat 8 images into regions labeled clear-sky, clouds, cloud-shadow, water, and snow/ice. For training, we constructed a global, hand-labeled dataset of Landsat 8 imagery; this labor-intensive process resulted in the uniquely high-quality dataset needed for the creation of a high-quality model. The CNN model achieves results on par with the ability of human interpreters, with a total accuracy of 97.1%, omitting only 3.5% of cloud pixels and 4.8% of cloud shadow pixels, which is seven to eight times fewer missed pixels than the masks distributed with the imagery. By harnessing the power of advanced tensor processing units, the classification of full images is I/O bound, making this approach a feasible method to generate masks for the entire Landsat 8 archive.

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Dorrell, Michael I., Heidi R. Kast-Woelbern, Ryan T. Botts, Stephen A. Bravo, Jacob R. Tremblay, Sarah Giles, Jessica F. Wada, et al. "A novel method of screening combinations of angiostatics identifies bevacizumab and temsirolimus as synergistic inhibitors of glioma-induced angiogenesis." PLOS ONE 16, no. 6 (June 2, 2021): e0252233. http://dx.doi.org/10.1371/journal.pone.0252233.

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Tumor angiogenesis is critical for the growth and progression of cancer. As such, angiostasis is a treatment modality for cancer with potential utility for multiple types of cancer and fewer side effects. However, clinical success of angiostatic monotherapies has been moderate, at best, causing angiostatic treatments to lose their early luster. Previous studies demonstrated compensatory mechanisms that drive tumor vascularization despite the use of angiostatic monotherapies, as well as the potential for combination angiostatic therapies to overcome these compensatory mechanisms. We screened clinically approved angiostatics to identify specific combinations that confer potent inhibition of tumor-induced angiogenesis. We used a novel modification of the ex ovo chick chorioallantoic membrane (CAM) model that combined confocal and automated analyses to quantify tumor angiogenesis induced by glioblastoma tumor onplants. This model is advantageous due to its low cost and moderate throughput capabilities, while maintaining complex in vivo cellular interactions that are difficult to replicate in vitro. After screening multiple combinations, we determined that glioblastoma-induced angiogenesis was significantly reduced using a combination of bevacizumab (Avastin®) and temsirolimus (Torisel®) at doses below those where neither monotherapy demonstrated activity. These preliminary results were verified extensively, with this combination therapy effective even at concentrations further reduced 10-fold with a CI value of 2.42E-5, demonstrating high levels of synergy. Thus, combining bevacizumab and temsirolimus has great potential to increase the efficacy of angiostatic therapy and lower required dosing for improved clinical success and reduced side effects in glioblastoma patients.

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Sejr, Michala Herskind, Ole May, Dorte Damgaard, Birgitte Forsom Sandal, and Jens Cosedis Nielsen. "External continuous ECG versus loop recording for atrial fibrillation detection in patients who had a stroke." Heart 105, no. 11 (March 21, 2019): 848–54. http://dx.doi.org/10.1136/heartjnl-2018-314186.

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BackgroundDetection of atrial fibrillation (AF) in patients who had ischaemic stroke and transient ischaemic attack (IS/TIA) is recommended. We aimed to compare external loop recording (ELR) against simultaneous continuous ECG recording for AF detection in patients who had acute IS/TIA and determine sensitivity, specificity and positive predictive value of AF detection using ELR. We hypothesised ELR to detect 15% fewer patients with AF than continuous ECG recording.MethodsIn this prospective cohort study, we included 1412 patients who had acute IS/TIA without prior AF. Monitoring was 48 hours. Primary outcome was AF >30 s. Cardiologist verified AF in continuous ECG was gold standard.ResultsIn continuous ECG, 38 (2.7%) patients had AF. ELR automatically categorised 219/1412 patients (15.5%) with AF, including 32/38 (85%) patients with AF in continuous ECG. After cardiologist adjudication of ELR recordings, AF was diagnosed in 57/219 patients, of which 32 (56%) had AF in continuous ECG. For adjudicated AF detection by ELR, sensitivity was 84%, 95% CI (69% to 94%), specificity was 98%, 95% CI (97% to 99%) and positive predictive value was 56%, 95% CI (42% to 69%).ConclusionAutomatic AF detection with ELR results in an AF diagnosis in more than five patients without AF for each patient with AF as verified in continuous ECG. For adjudicated AF detection by ELR, sensitivity was confirmed to 84% and specificity 98%. Automatic ELR as investigated in this study may be considered to rule out AF, but it is not suitable as a single monitoring device for AF screening in patients early after stroke.Trial registration numberNCT02155907.

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Achieng, Catherine, Mary Masheti, Jeanne Goodman, Kirkby Tickell, Mareme Diakhate, Jennifer Unger, Barbra Richardson, et al. "Developing Caregiver Led mHealth Solutions for Screening and Managing Childhood Wasting in the Mama Aweza Trial in Kenya." Current Developments in Nutrition 4, Supplement_2 (May 29, 2020): 797. http://dx.doi.org/10.1093/cdn/nzaa053_002.

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Abstract Objectives Globally, only 17% of children with wasting receive treatment. In Kenya, 4% of the 7 million children under-5 years of age are wasted and 26% are stunted. The Mama Aweza trial will test whether a two-way short message service (SMS) mobile health system, the Maternal Administered Malnutrition Monitoring System (MAMMS), can increase the coverage of malnutrition management programs in low-and-middle income countries. Methods Five formative focus group discussions (FGDs) were conducted with caregivers at an immunization clinic in Migori County, Kenya to inform feasibility and content of SMS messages in the MAMMS system. Caregivers were asked to explain anticipated facilitators and barriers to participation in a SMS program to facilitate home-based mid upper-arm circumference (MUAC) monitoring. FGDs also reviewed educational messages that accompany weekly SMS reminders to measure and report their child's MUAC. The feedback from these FGDs was included in the clinical trial, which begun in August 2019. Results The most anticipated challenge to responding to weekly messages was the use of a shared phone particularly that the SMS would be deleted or the caregiver would not be informed of the message. The greatest anticipated challenge for sending messages was and not knowing how to send a SMS. Overall, 52 messages were written on the following topics: developmental milestones, encouragement, fever, diarrhea, malaria, ear infections, sanitation and hygiene, vaccinations, respiratory illness, and kitchen gardening. To date, 144 mother-infant dyads have been enrolled and 77 randomly assigned to the MAMMS arm. Sixty-nine (90%) caregivers have responded to ≥1 message and 503 (68%) of 742 automated messages have received a response. At enrollment, 21 (27%) of caregivers in the MAMMS arm reported a shared phone, with no current evidence that caregivers sharing a phone respond less than those with their own phone. Conclusions Caregivers found SMS-based malnutrition screening to be acceptable and engaging. In regions with high literacy and high mobile phone ownership, such as Kenya, SMS supported home MUAC monitoring may improve malnutrition screening coverage and lead to earlier identification and treatment. Funding Sources Thrasher Research Foundation 14,656.

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Young, Lauren M., Sarah Gauci, Andrew Scholey, David J. White, Annie-Claude Lassemillante, Denny Meyer, and Andrew Pipingas. "Self-Reported Diet Quality Differentiates Nutrient Intake, Blood Nutrient Status, Mood, and Cognition: Implications for Identifying Nutritional Neurocognitive Risk Factors in Middle Age." Nutrients 12, no. 10 (September 28, 2020): 2964. http://dx.doi.org/10.3390/nu12102964.

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Evidence for diet quality representing a modifiable risk factor for age-related cognitive decline and mood disturbances has typically come from retrospective, cross-sectional analyses. Here a diet screening tool (DST) was used to categorize healthy middle-aged volunteers (n = 141, 40–65 years) into “optimal” or “sub-optimal” diet groups to investigate cross-sectional associations between diet quality, cognitive function, and mood. The DST distinguished levels of nutrient intake as assessed by Automated Self-Administered 24-h dietary recall and nutrient status, as assessed by blood biomarker measures. Compared with the “sub-optimal” group, the “optimal” diet group showed significantly higher intake of vitamin E (p = 0.007), magnesium (p = 0.001), zinc (p = 0.043) and fiber (p = 0.015), higher circulating levels of vitamin B6 (p = 0.030) and red blood cell folate (p = 0.026) and lower saturated fatty acids (p = 0.012). Regarding psychological outcomes, the “optimal” diet group had significantly better Stroop processing than those with a “sub-optimal” diet (p = 0.013). Regression analysis revealed that higher DST scores were associated with fewer mood disturbances (p = 0.002) and lower perceived stress (p = 0.031), although these differences were not significant when comparing “optimal” versus “sub-optimal” as discrete groups. This study demonstrates the potential of a 20-item diet screen to identify both nutritional and psychological status in an Australian setting.

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Jansen van Vuren, Petrus, Antoinette Grobbelaar, Nadia Storm, Ousman Conteh, Kelfala Konneh, Abdul Kamara, Ian Sanne, and Janusz T. Paweska. "Comparative Evaluation of the Diagnostic Performance of the Prototype Cepheid GeneXpert Ebola Assay." Journal of Clinical Microbiology 54, no. 2 (December 4, 2015): 359–67. http://dx.doi.org/10.1128/jcm.02724-15.

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The Ebola virus disease (EVD) outbreak in West Africa has highlighted an urgent need for point-of-care (POC) assays for the diagnosis of this devastating disease in resource-limited African countries. The diagnostic performance characteristics of a prototype Cepheid GeneXpert Ebola POC used to detect Ebola virus (EBOV) in stored serum and plasma samples collected from suspected EVD cases in Sierra Leone in 2014 and 2015 was evaluated. The GeneXpert Ebola POC is a self-contained single-cartridge automated system that targets the glycoprotein (GP) and nucleoprotein (NP) genes of EBOV and yields results within 90 min. Results from 281 patient samples were compared to the results of a TaqMan real-time reverse transcription-PCR (RT-PCR) targeting the polymerase gene and performed on two real-time PCR machines. Agreement between the three platforms was 100% at cycle threshold (CT) values of ≤34.99, but discordant results were noted betweenCTvalues of 35 and 45.The diagnostic sensitivity of the three platforms was 100% in 91 patient samples that were confirmed to be infectious by virus isolation. All three molecular platforms detected viral EBOV RNA in additional samples that did not contain viable EBOV. The analytical sensitivity of the GeneXpert Ebola POC for the detection of NP was higher, and comparable to that of polymerase gene detection, than that for the detection of GP when using a titrated laboratory stock of EBOV. There was no detectable cross-reactivity with other hemorrhagic fever viruses or arboviruses. The GeneXpert Ebola POC offers an easy to operate and sensitive diagnostic tool that can be used for the rapid screening of suspected EVD cases in treatment or in holding centers during EVD outbreaks.

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Vardy, Emma, Niamh Collins, Umang Grover, Rebecca Thompson, Alexandra Bagnall, Georgia Clarke, Shelley Heywood, et al. "Use of a digital delirium pathway and quality improvement to improve delirium detection in the emergency department and outcomes in an acute hospital." Age and Ageing 49, no. 4 (May 16, 2020): 672–78. http://dx.doi.org/10.1093/ageing/afaa069.

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Abstract Background delirium is a common condition associated with hospital admission. Detection and diagnosis is important to identify the underlying precipitating cause and implement effective management and treatment. Quality improvement (QI) methodology has been applied in limited publications. There are even fewer publications of the role of development of the electronic health record (EHR) to enhance implementation. Methods we used QI methodology to improve delirium detection in the emergency department (ED). Plan Do Study Act (PDSA) cycles could be broadly categorised into technology, training and education and leadership. As part of the technology PDSA an electronic delirium pathway was developed as part of an NHS England digital systems improvement initiative (NHS England Global Digital Exemplar). The electronic pathway incorporated the 4AT screening tool, the Confusion Assessment Method, the TIME delirium management bundle, investigation order sets and automated coding of delirium as a health issue. Results development of the EHR combined with education initiatives had benefit in terms of the number of people assessed for delirium on admission to the ED and the total number of people diagnosed with delirium across the organisation. The implementation of a delirium pathway as part of the EHR improved the use of 4AT in those 65 years and over from baseline of 3% completion in October 2017 to 43% in January 2018. Conclusion we showed that enhancement of the digital record can improve delirium assessment and diagnosis. Furthermore, the implementation of a delirium pathway is enhanced by staff education.

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Arenas, Alicia, Pilar Hernandez-Campo, Daniel Primo, Santiago Barrio, Rosa M. Ayala, Joan Ballesteros, and Joaquín Martínez-López. "High Throughput Screening, With a Flow Cytometry Automated Platform (Ex vivo Biotech), To Identify Potential Combination Partners, For The JAK 2 Inhibitor Ruxolitinib." Blood 122, no. 21 (November 15, 2013): 2534. http://dx.doi.org/10.1182/blood.v122.21.2534.2534.

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Abstract Background Identifying the most promising synergistic drugs combinations for a drug is a challenge for researchers. Identification of optimal combinations are key and should be translated in better designed clinical trials with fewer patients and ultimately more effective treatments. Ruxolitinib is a potent JAK1/JAK2 inhibitor that has demonstrated improved survival, rapid and durable improvements in splenomegaly, in patients with myelofibrosis (MF), however although improve survival in most of patients it does not change the natural history of the disease. There is however always a drive to improve outcomes and we hypothesize that treatment with a synergistic drug could enhance the activity in MF. Aim To design an ex-vivo model, based on flow cytometry, to identify the most synergistic drugs with Ruxolitinib in cell lines and primary samples from MF patients. Methods We have studied five secondary or primary MF patients (n = 5) and one cell line, BA/F3 transfected with mutated JAK2 V617F (BA/F3 JAK2V617F). We combined Ruxolitinib with a panel of 30 drugs whose mechanism of action is implicated in proliferation, differentiation and survival, cell-cycle inhibition, protein stabilisation, epigenetic, immune response. Briefly, mononuclear cells from peripheral blood, isolated, was cultured in Methocult TM GF_H4535 supplemented with 20 ng/ml interleukin (IL)-3, and 50 ng/ml stem-cell factor (SCF). After 2 weeks incubation, viable cells were plated at 15.000 per well in 96-well plates in increasing concentrations of each drug, alone or in combination with Ruxolitinib, in 8 or 5 point dose response curve. After 72 hr incubation, we performed a multiparametric flow cytometry, using Annexin V-fluorescein isothiocyanate (FITC) and CD13 to monitoring drug sensibility of myeloid lineage, in the ExviTech platform for screening by flow cytometry. Synergism will be evaluated by the Median Effect methods described by T-C Chou and P. Talalay. Regarding the cell line model, it confirms the results obtained in patients samples: Panobinostat was the most potent drugs tested in the assay with an IC50 of 86 nM and the most synergistic drugs with Ruxolitinib was Everolimus (CI = 0.613 when Ruxolitinib and Everolimus were 370 nM and 7.41 Î¼M respectively). Conclusions This Vivia Ex vivo platform is highly efficient to study multiple synergisms of drugs in myeloproliferative diseases. We can test 30 drugs, inhibitors of multiple signaling pathways, epigenetics and immune response, alone or in combination with Ruxolitinib and test its activity and its potential synergy with Ruxolitinib. Based in these results, clinical trials combination Ruxolitinib with BKM120 (ongoing), Everolimus and LDE225 (ongoing) could potentially be explored in phase I clinical trials. Disclosures: Hernandez-Campo: Vivia Biotech: Employment. Primo:Vivia Biotech: Employment. Ballesteros:Vivia Biotech: Equity Ownership. Martínez-López:Vivia Biotech: Honoraria; Novartis: Research Funding.

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DiCarlo, Jessica M., Sricharan Gopakumar, Preet K. Dhillon, and Suneeta Krishnan. "Adoption of Information and Communication Technologies for Early Detection of Breast and Cervical Cancers in Low- and Middle-Income Countries." Journal of Global Oncology 2, no. 4 (August 2016): 222–34. http://dx.doi.org/10.1200/jgo.2015.002063.

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Purpose In response to the growing burden of breast and cervical cancers, low- and middle-income countries (LMICs) are beginning to implement national cancer prevention programs. We reviewed the literature on information and communication technology (ICT) applications in the prevention of breast and cervical cancers in LMICs to examine their potential to enhance cancer prevention efforts. Methods Ten databases of peer-reviewed and gray literature were searched using an automated strategy for English-language articles on the use of mobile health (mHealth) and telemedicine in breast and cervical cancer prevention (screening and early detection) published between 2005 and 2015. Articles that described the rationale for using these ICTs and/or implementation experiences (successes, challenges, and outcomes) were reviewed. Bibliographies of articles that matched the eligibility criteria were reviewed to identify additional relevant references. Results Of the initial 285 citations identified, eight met the inclusion criteria. Of these, four used primary data, two were overviews of ICT applications, and two were commentaries. Articles described the potential for mHealth and telemedicine to address both demand- and supply-side challenges to cancer prevention, such as awareness, access, and cost, in LMICs. However, there was a dearth of evidence to support these hypotheses. Conclusion This review indicates that there are few publications that reflect specifically on the role of mHealth and telemedicine in cancer prevention and even fewer that describe or evaluate interventions. Although articles suggest that mHealth and telemedicine can enhance the implementation and use of cancer prevention interventions, more evidence is needed.

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Beavis, Lizzie, Ronan O'Malley, Bahman Mirheidari, Heidi Christensen, and Daniel Blackburn. "How can automated linguistic analysis help to discern functional cognitive disorder from healthy controls and mild cognitive impairment?" BJPsych Open 7, S1 (June 2021): S7. http://dx.doi.org/10.1192/bjo.2021.78.

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AimsThe disease burden of cognitive impairment is significant and increasing. The aetiology of cognitive impairment can be structural, such as in mild cognitive impairment (MCI) due to early Alzheimer's disease (AD), or in functional cognitive disorder (FCD), where there is no structural pathology. Many people with FCD receive a delayed diagnosis following invasive or costly investigations. Accurate, timely diagnosis improves outcomes across all patients with cognitive impairment. Research suggests that analysis of linguistic features of speech may provide a non-invasive diagnostic tool. This study aimed to investigate the linguistic differences in conversations between people with early signs of cognitive impairment with and without structural pathology, with a view to developing a screening tool using linguistic analysis of conversations.MethodIn this explorative, cross-sectional study, we recruited 25 people with MCI considered likely due to AD, (diagnosed according to Petersen's criteria and referred to as PwMCI), 25 healthy controls (HCs) and 15 people with FCD (PwFCD). Participants’ responses to a standard questionnaire asked by an interactional virtual agent (Digital Doctor) were quantified using previously identified parameters. This paper presents statistical analyses of the responses and a discussion of the results.ResultPwMCI produced fewer words than PwFCD and HCs. The ratio of pauses to speech was generally lower for PwMCI and PwFCD than for HCs. PwMCI showed a greater pause to speech ratio for recent questions (such as ‘what did you do at the weekend?’) compared with the HCs. Those with FCD showed the greatest pause to speech ratio in remote memory questions (such as ‘what was your first job?’). The average age of acquisition of answers for verbal fluency questions was lower in the MCI group than HCs.ConclusionThe results and qualitative observations support the relative preservation of remote memory compared to recent memory in MCI due to AD and decreased spontaneous elaboration in MCI compared with healthy controls and patients with FCD. Word count, age of acquisition and pause to speech ratio could form part of a diagnostic toolkit in identifying those with structural and functional causes of cognitive impairment. Further investigation is required using a large sample.

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Capling, Louise, Ryan Tam, Kathryn L. Beck, Gary J. Slater, Victoria M. Flood, Helen T. O’Connor, and Janelle A. Gifford. "Diet Quality of Elite Australian Athletes Evaluated Using the Athlete Diet Index." Nutrients 13, no. 1 (December 31, 2020): 126. http://dx.doi.org/10.3390/nu13010126.

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While athletes’ nutrient intakes have been widely reported, few studies have assessed the diet quality of athletes. This is the first study to evaluate the diet quality of athletes using the purpose-built Athlete Diet Index (ADI). A convenience sample of 165 elite athletes from Australian sporting institutions completed the ADI online, with subsequent automated results provided to their respective accredited sports dietitians (ASDs). At the completion of athlete participation, ASDs (n = 12) responded to a range of survey items using a Likert scale (i.e., 1 = strongly agree to 5 = strongly disagree) to determine the suitability of the ADI in practice. Differences in ADI scores for demographics and sport-specific variables were investigated using independent t-tests, analysis of variance (ANOVA) and Bonferroni multiple comparisons. Spearman’s rank correlation was used to assess the association between total scores and demographics. The mean total ADI score was 91.4 ± 12.2 (range 53–117, out of a possible 125). While there was no difference in total scores based on demographics or sport-specific variables; team sport athletes scored higher than individual sport athletes (92.7 vs. 88.5, p < 0.05). Athletes training fewer hours (i.e., 0–11 h/week) scored higher on Dietary Habits sub-scores compared with athletes training more hours (≥12 h/week; p < 0.05), suggesting that athletes who train longer may be at risk of a compromised dietary pattern or less than optimal nutrition practices that support training. Most (75%) ASDs surveyed strongly agreed with the perceived utility of the ADI for screening athletes and identifying areas for nutrition support, confirming its suitability for use in practice.

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Binder, Steven R., Mark C. Genovese, Joan T. Merrill, Robert I. Morris, and Allan L. Metzger. "Computer-Assisted Pattern Recognition of Autoantibody Results." Clinical Diagnostic Laboratory Immunology 12, no. 12 (December 2005): 1353–57. http://dx.doi.org/10.1128/cdli.12.12.1353-1357.2005.

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ABSTRACT Immunoassay-based anti-nuclear antibody (ANA) screens are increasingly used in the initial evaluation of autoimmune disorders, but these tests offer no “pattern information” comparable to the information from indirect fluorescence assay-based screens. Thus, there is no indication of “next steps” when a positive result is obtained. To improve the utility of immunoassay-based ANA screening, we evaluated a new method that combines a multiplex immunoassay with a k nearest neighbor (kNN) algorithm for computer-assisted pattern recognition. We assembled a training set, consisting of 1,152 sera from patients with various rheumatic diseases and nondiseased patients. The clinical sensitivity and specificity of the multiplex method and algorithm were evaluated with a test set that consisted of 173 sera collected at a rheumatology clinic from patients diagnosed by using standard criteria, as well as 152 age- and sex-matched sera from presumably healthy individuals (sera collected at a blood bank). The test set was also evaluated with a HEp-2 cell-based enzyme-linked immunosorbent assay (ELISA). Both the ELISA and multiplex immunoassay results were positive for 94% of the systemic lupus erythematosus (SLE) patients. The kNN algorithm correctly proposed an SLE pattern for 84% of the antibody-positive SLE patients. For patients with no connective tissue disease, the multiplex method found fewer positive results than the ELISA screen, and no disease was proposed by the kNN algorithm for most of these patients. In conclusion, the automated algorithm could identify SLE patterns and may be useful in the identification of patients who would benefit from early referral to a specialist, as well as patients who do not require further evaluation.

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Bennett, Teresa A., Sandra Sapia, Daniel Primo, Lilia Suarez, Santiago Lago, Maria Matoses, Ana Espinosa, et al. "Screening Thousands of Drugs in Leukemia Patient Samples to Identify Novel Uses for Approved Drugs." Blood 114, no. 22 (November 20, 2009): 4414. http://dx.doi.org/10.1182/blood.v114.22.4414.4414.

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Abstract Abstract 4414 Introduction Discovery of novel non cytotoxic drugs for cancer focuses on targets selectively expressed in malignant cells, only testing at the end if they are toxic to patients. We have developed a novel approach to discover these drugs starting at the end; we screen 2.000 approved drugs with proven safety, directly on freshly extracted (ex vivo) blood samples of patients with Chronic Lymphocytic Leukemia (CLL). These screens are enabled by a novel technology platform based on automated flow cytometry we call ExviTech for ex vivo technology. Patients and Methods All screening studies were performed directly on either peripheral blood or bone marrow samples from 44 patients diagnosed with various subtypes of B-cell malignancies, after informed consent. Patient samples were diluted and plated with each of the 2.000 drugs individually, retaining the erythrocyte population and serum proteins to enable clinically relevant concentrations. The experimental assay was setup the same or a day after sample extraction. Each sample was diluted to achieve a leukemic cell concentration of approximately 3,000 cells/μl; then 45μl of the suspension is added to each well of 96-well plates that contain the pharmacological agents (final concentration of 30μM). The compound plates were then sequentially incubated for 24 hours at 37°C with 5% CO2 for screening (sterile conditions). After incubation, the erythrocytes were lysed and the leucocytes incubated with Annexin V-FITC, anti-CD45-APC and anti-CD19-PE added to each well. The plates were then transferred to an automated flow cytometry system where the contents of each well were aspirated and analyzed by a CyAn flow cytometer. Candidates from the primary screens were validated in additional samples with dose-responses, combinations with approved drugs, multiple incubation times, etc… Results Analyzing primary screens from 24 CLL patients, three related compounds (Vivia007, Vivia008 and Vivia009) were found to consistently induce apoptosis of nearly all leukemic B-cells from most of the patient samples diagnosed with B-cell chronic lymphocytic leukemia at levels equal to or greater than known CLL active cytotoxic agents. Notably, these candidates are equally effective against samples of p53 mutated patients. These 3 drugs are pharmacologically me-too drugs sharing the same target and mechanism of action, and are non cytotoxic drugs with a known and good safety profile, administered to millions of patients over many years. Validation experiments were done on 20 additional CLL patients and Vivia009 emerged as the most effective agent with an average EC50 of 18.2μM. The mechanism of action is different than the known mechanism of Vivia009 and its class members for their approved indications. Consistent with this observation, only 3 of 15 members of the same pharmacological drug class were efficacious against CLL malignant cells. All 3 Vivia′s candidates were equally efficacious against other B-Cell Malignancies such as B-ALL (pediatric and adult), and Multiple Myeloma. These drugs are not effective in their current oral formulation and require a novel intravenous formulation. Interestingly, kinetics of induction of apoptosis were faster for Vivia009 than for fludarabine, cyclophosphamide and mitoxantrone. Vivia009 requires only 1 hour of incubation with fresh cells to induce maximal apoptosis. This timeline is less than the 3 hours in which Vivia009 was found present at high concentrations in bone marrow of rats using a single intravenous bolus. Thus, Vivia009 seems to fulfill the pharmacokinetic criteria to eliminate all leukemic cells with a single intravenous bolus, which would be a major advantage over current treatments (5-days fludarabine or 3 days FCR). Animal models are ongoing to confirm the non cytotoxic nature of the candidates in the novel IV formulation and the fewer days needed to reach remission, both compared with fludarabine monotherapy. Conclusions In summary, our results demonstrate the potential of the ExviTech technology platform as a successful model for the systematic search of new uses for already existing approved drugs directly on patient samples of hematological malignancies. A new drug candidate with excellent safety profile has been identified with similar efficacy ex vivo as the best approved cytotoxic drugs, which is a non-cytotoxic drug with fast kinetics that might enable significantly safer and shorter treatments. Disclosures: Bennett: Vivia Biotech: Employment. Sapia:Vivia Biotech SL: Employment. Primo:Vivia Biotech SL: Employment. Suarez:Vivia Biotech SL: Employment. Lago:Vivia Biotech SL: Employment. Matoses:Vivia Biotech: Employment. Espinosa:Vivia Biotech: Ana Espinosa, Employment. Tudela:Vivia Biotech SL: Employment. Arroyo:Vivia Biotech SL: Employment. Jackson:Vivia Biotech SL: Employment. Okun:Vivia Biotech SL: Research Funding. Lopez:Vivia Biotech SL: Employment. Gornemann:Vivia Biotech SL: Employment. Diez:Vivia Biotech SL: Employment. González:Vivia Biotech SL: Consultancy. Dominguez-Gil:Vivia Biotech SL: Consultancy. Troconiz:Vivia Biotech SL: Consultancy. Rodriguez de Fonseca:Vivia Biotech SL: Consultancy. Saunders:Vivia Biotech: Consultancy. Montejo:Vivia Biotech SL: Consultancy. Caveda:Vivia Biotech SL: Employment. Orfao:Vivia Biotech SL: Research Funding. Ballesteros:Vivia Biotech SL: Equity Ownership.

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Wong, Emily C., Celia P. Kaplan, Nickolas Dreher, Jimmy Hwang, Laura van’t Veer, and Michelle E. Melisko. "Integration of Health Questionnaire Systems to Facilitate Supportive Care Services for Patients at an Academic Breast Care Center." JCO Clinical Cancer Informatics, no. 2 (December 2018): 1–13. http://dx.doi.org/10.1200/cci.18.00018.

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Purpose This study evaluated the use of an electronic Health Questionnaire System (HQS) within the University of California San Francisco Breast Care Center as a screening and triage tool to proactively recognize patients’ supportive care needs during new patient consultations and identify demographic characteristics associated with referrals to three supportive care services. Patients and Methods A total of 428 patients with and without breast cancer between the ages of 18 and 84 years completed HQS intake forms before appointments at the University of California San Francisco Breast Care Center between November 2014 and May 2015 and agreed to participate in this study. Patient HQS responses triggered referrals to supportive care services, and a review of electronic health records was conducted to determine the outcomes of these referrals. Results A total of 242 patients (56.5%) met criteria for at least one supportive care referral. Women with invasive breast cancer or ductal carcinoma in situ met criteria for supportive services more frequently than women without breast cancer diagnoses (76.9% v 23.8%; P < .001) and were most likely to receive referrals for genetic counseling (67.0%), psychological services (32.2%), and social services (12.1%). Multivariable logistic regression analysis showed that being married was associated with fewer referrals to social work (OR, 0.42; 95% CI, 0.21 to 0.81) and that those between 45 and 54 years of age were less likely to receive referrals to genetic counseling than those ≥ 55 years of age (OR, 0.41; 95% CI, 0.23 to 0.73). Among all referrals (n = 369), 26.8% resulted in completed appointments. Conclusion Using an automated intake form is an efficient way to identify and triage individuals in need of supportive care services and can provide insight into the populations with supportive care needs for targeted outreach.

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Gangahar, Chiraag, Daniel Webber, and Ronald Jackups. "Reduction in False-Positive PF4/Heparin Antibody Testing Following Implementation of a Latex Immunoturbidimetric Assay." American Journal of Clinical Pathology 152, Supplement_1 (September 11, 2019): S34. http://dx.doi.org/10.1093/ajcp/aqz112.064.

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Abstract Background Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of exposure to heparin that is caused by autoantibodies against heparin-PF4 complexes. We recently changed our in-house HIT screening platform from a manual, daily batched ELISA (Stago-Asserochrom HPIA Immunoassay) to an automated, on-demand latex immunoturbidimetric assay (LIA, HemosIL HIT-Ab) and have also implemented a reflex from a positive LIA result to the confirmatory serotonin release assay (SRA). We compared the two methods in terms of utilization, test performance, and turnaround time. Methods Data were collected retrospectively from a 7-month period before (June-December 2017) and after (June-December 2018) implementation of the HemosIL LIA in the clinical laboratory at a large academic institution. This study includes consecutive test results from adults (median age: 64 years, range: 19-98 years) seen at our 1,300-bed main hospital. Test utilization, turnaround time (sample receipt to verification), and test performance characteristics were compared between the two methods. Repeat testing was excluded from the analysis. Samples with a positive result on the HemosIL LIA were reflexed to a serotonin release assay (SRA), performed at a large reference laboratory, whereas samples tested with the earlier ELISA assay were referred for SRA testing based upon clinical judgment. When performed, SRA was considered the gold standard for diagnosis of HIT. Results During the 7 months before and after switching methods, there were 109 of 594 (18.4%) positive ELISA results and 45 of 523 (8.6%) positive LIA results. Only 90 of 109 (82%) of the positive results from the ELISA HIT Ab test were sent out by clinicians for SRA testing, whereas 45 of 45 (100%) of the positive results from LIA testing were reflexed to SRA per protocol. Although fewer LIA tests were sent out for SRA testing, there were an equal number of SRA-confirmed cases of HIT with the ELISA (PPV: 16/90 [17.8%]) and LIA methods (PPV: 16/45 [35.6%]), resulting in a high positive predictive value (PPV) with the newly implemented method. Not only was the PPV higher with the LIA test, but it had a significantly shorter mean turnaround time of 96 minutes compared to the ELISA TAT of 1,234 minutes (P < .0001). Conclusions With the new testing protocol, patients received results faster (average 96-minute TAT) and had fewer false-positive results (74/594 pre vs 29/523 post), with no apparent reduction in detection of true-positive cases of HIT (16/594 pre vs 16/523 post).

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Golla, Rajasree, and Ramakrishna Seethala. "A Homogeneous Enzyme Fragment Complementation Cyclic AMP Screen for GPCR Agonists." Journal of Biomolecular Screening 7, no. 6 (December 2002): 515–25. http://dx.doi.org/10.1177/1087057102238625.

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In the new high-throughput screening (HTS) campaign, receptor functional assays, 3’,5’-cyclic adenosine mono-phosphate (cAMP), intracellular [Ca2+]i, phosphatidylinositol turnover, and reporter-based assays are being used as primary screens as they are now developed as homogeneous and automation-friendly assays. FlashPlate assay and scintillation proximity assay using radiolabeled cAMP have been used for measuring cAMP. A nonradioactive homogeneous HTS assay using HitHunter™ enzyme fragment complementation (EFC) technology was evaluated for measuring cAMP in adherent and suspension cells overexpressing a Gαs-coupled receptor. In the EFC-cAMP assay, the β-galactosidase (β-gal) donor fragment-cAMP (ED-cAMP) conjugate complements with the β-gal enzyme acceptor (EA) fragment to form an active β-gal enzyme. Binding of ED-cAMP conjugate to the anti-cAMP antibody prevents its complementation with the EA fragment to form an active enzyme. Cyclic AMP in the samples compete with ED-cAMP to bind to the anti-cAMP antibody, thus increasing the free ED-cAMP that can complement with the EA fragment to form an active enzyme that is assayed with a luminescent substrate. Thus, this assay results in a positive signal unlike other technologies, wherein the signal is completed by cAMP in the sample. Glucagon-like peptide (GLP)-1 binds to GLP-1 receptor (with a Kd of 0.2 nM) signals through Gαs to activate adenylate cyclase, which results in an increase of intracellular cAMP (EC50 of 0.3 nM). GLP-1 stimulation of cAMP levels measured by the EFC method was similar in both adherent and suspension cell formats (EC50 ~0.3 nM) at different cell numbers. The assay was further validated with forskolin, exendin, and several active GLP-1 peptide analogues. The stimulation of cAMP by GLP-1 and forskolin was effectively inhibited by the adenylate cyclase inhibitors MDL-12330A and SQ-22536, confirming that the increased cAMP is through the AC pathway. The assay tolerates dimethyl sulfoxide (DMSO) up to 10%, and tartrazine does not interfere with the assay with the adherent cells up to 1 mM and affects minimally up to 10 μM in suspension cells. The assay is very robust, with a Z value of 0.7 to 0.8. The assay was validated with several plates of low molecular weight nonpeptide compounds and peptide agonists with different potencies. The suspension cell protocol is a robust homogeneous assay that involves fewer steps than the adherent cell protocol and is suitable for HTS. The cAMP assay using EFC technology is advantageous in that it has a greater dynamic range of detection; is nonradioactive, very sensitive, robust; has minimal interference from DMSO and colored compounds; and is amenable for automation. An added advantage of this assay is that the cAMP is measured as a positive signal, thereby reducing the incidence of false positives.

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Pande, Mala, Connie Okon, Y. Nancy You, Susan K. Peterson, Banu Arun, and Patrick M. Lynch. "Adequacy of self-reported family history in electronic health record for genetic risk assessment for Lynch syndrome." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 1515. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.1515.

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1515 Background: Self-reported family cancer history (FCH) is one of the key indicators of hereditary cancer risk. Studies have shown that accurate FCH documentation by healthcare providers is suboptimal, but data regarding patient-provided FCH are limited. We evaluated the quality of FCH as entered by the patient into the electronic health record (EHR) to determine its adequacy for Lynch syndrome (LS) risk assessment. Methods: At our tertiary referral cancer center, FCH is self-reported via an online questionnaire sent prior to appointment, which is reviewed/updated by clinic nurse during initial visit and then imported into EHR review of systems. Records of all new patients from September 2016 to August 2017 were retrospectively reviewed and analyzed. FCH quality was estimated by calculating rates of reporting of 3 FCH variables required for PREMM5, a risk-prediction model for LS. Parameters required for the model were sex, age, personal history of cancer, and for FCH, degree of kinship (first/second degree), cancer site/type, and age at diagnosis. Results: Of 47,647 unique patients, 47.5% reported FCH for 1 or more relative (46.1% were first degree, 64.8% second degree, 3.0% other, and 2.4% missing). A cancer type/site was specified for 88.8% reporting FCH. Age at diagnosis was listed for 21.7% of the relatives’ cancers. Overall, only 20.9% provided all 3 FCH data elements required for running PREMM5 (9.9% of the total sample, n=4738). Fewer men (9.5%) than women (28.1%) provided all 3 FCH elements. Furthermore, 46.7% of breast cancer patients, 21.9% of gastrointestinal cancer patients, 47.2% and 23.1% of patients seen for cancer prevention screening and endoscopy respectively, reported 3 FCH elements. Lower rates were observed for other cancers. Conclusions: Patient self-reported FCH is suboptimal for estimation of LS risk and genetic counseling referral. Future steps to optimize online patient-facing FCH collection to enable routine automated risk-assessment in an essentially provider-free setting may include, patient education regarding importance of FCH, EHR prompts for FCH completion, and implementation of algorithms in EHRs using FCH to identify patients at risk for hereditary cancer predisposition syndromes.

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Spinner, Michael A., Steven A. Schaffert, Alexey Aleshin, Marianne T. Santaguida, Hiroomi Tada, and Peter L. Greenberg. "Correlating Clinical and Genomic Features with Ex Vivo Drug Sensitivity in Patients with Myelodysplastic Syndromes and Related Myeloid Neoplasms." Blood 136, Supplement 1 (November 5, 2020): 19–20. http://dx.doi.org/10.1182/blood-2020-140095.

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Background Myelodysplastic syndromes (MDS) are heterogeneous myeloid neoplasms characterized by ineffective hematopoiesis, dysplasia, cytopenias, and a variable risk of progression to acute myeloid leukemia (AML). The biologic heterogeneity of MDS and related myeloid neoplasms relates to the genomic complexity of these disorders with different combinations of cytogenetic abnormalities and mutations associated with distinct clinical phenotypes. Ex vivo drug sensitivity screening (DSS) is a promising tool that may inform personalized therapy in MDS, particularly in patients refractory to standard therapies such as hypomethylating agents (HMAs). We report our updated experience using a fully automated ex vivo DSS platform in 64 patients with MDS and related myeloid neoplasms and identify correlations between clinical and genomic features and ex vivo drug sensitivity. Methods Patients: Patients were evaluated at the Stanford MDS Center between September 2016 and May 2020 and had a diagnosis of MDS, MDS/MPN, or secondary AML. Bone marrow (BM) aspirate and peripheral blood (PB) samples were procured for mutation testing (164-gene panel) and ex vivo DSS (Notable Labs, Foster City, CA). Ex vivo DSS: Fresh BM aspirate and PB specimens were RBC-lysed and resuspended in serum-free media with cytokines as previously described (Spinner et al, Blood Adv 2020;4(12):2768-78). Samples were plated in 384-well microtiter plates and screened against a collection of up to 74 drugs and 36 drug combinations in triplicate. Specimens were treated for 72 hours and assayed using high-throughput, multi-parametic flow cytometry, gating on the blast population (expressing CD34, CD33, and/or HLA-DR) to assess for blast viability. Patient clustering & statistical analysis: The Euclidean distance metric and Ward minimum variance method were used to identify patient clusters with distinct ex vivo drug sensitivity patterns. A 1-way repeated measures ANOVA was used to identify drug classes with variable sensitivity across clusters and to identify associations between clusters and clinical variables, including blast count, mutations and cytogenetic groups, IPSS-R risk group, and prior HMA exposure. A generalized estimation equation model was used to identify associations between mutations and ex vivo drug sensitivity. Results Ex vivo DSS was performed in 64 patients with myeloid neoplasms including 43 with MDS (67%), 11 with MDS/MPNs (17%), and 10 with secondary AML (16%). The median age was 75 years (range 23-90) and 78% were male. The majority of patients had higher risk disease with IPSS-R >3.5 (66%), excess blasts (58%), and adverse cytogenetics or mutations (53%) by IPSS-R or the ELN classification. Patients had a median of 2 pathogenic mutations (range 0-7), with the most frequent including TET2, ASXL1, DNMT3A, SF3B1, RUNX1, STAG2, SRSF2, NRAS, KRAS, BCOR, TP53, and EZH2. The majority of patients (64%) had prior HMA exposure. Ex vivo DSS defined three distinct patient clusters with differential sensitivity to numerous drug classes (Figure 1). Cluster 1 (N=13) demonstrated the greatest ex vivo sensitivity to HMAs, HMA/venetoclax combinations, cytotoxic agents, kinase inhibitors, mTOR inhibitors, HDAC inhibitors, and PARP inhibitors, while cluster 3 (N=19) demonstrated the greatest ex vivo resistance (p<0.0001 for all comparisons). Correlating clinical variables with drug sensitivity clusters, only IPSS-R score differed significantly among clusters, with fewer higher risk patients in cluster 3 (p=0.02). Correlating specific mutations with ex vivo drug sensitivity, STAG2 mutations were associated with greater ex vivo sensitivity to HMAs (p=0.002), HMA/venetoclax combinations (p=0.003), kinase inhibitors (p=0.002), and PARP inhibitors (p=0.003). TP53 mutations were associated with greater ex vivo sensitivity to proteasome inhibitors (p=0.0002). Conclusions Ex vivo DSS defined distinct patient clusters with differential sensitivity to numerous drug classes. Specific mutations, such as STAG2 and TP53, were associated with greater ex vivo sensitivity to specific drug classes. A larger sample size is needed to evaluate combinations of mutations and better define associations between genotype and drug sensitivity phenotype. Ultimately, combining both genomics and functional screening may further refine personalized therapy selection for patients with MDS and related myeloid neoplasms. Figure Disclosures Spinner: Notable Labs: Honoraria. Schaffert:Notable Labs: Current Employment. Aleshin:Notable Labs: Consultancy. Santaguida:Notable Labs: Current Employment. Tada:Notable Labs: Current Employment, Current equity holder in private company. Greenberg:BMS: Research Funding; Aprea: Research Funding; H3 Biotech: Research Funding; Notable Labs: Research Funding.

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Morelle, Johann, Joanna Stachowska-Pietka, Carl Öberg, Liliana Gadola, Vincenzo La Milia, Zanzhe Yu, Mark Lambie, Rajnish Mehrotra, Javier de Arteaga, and Simon Davies. "ISPD recommendations for the evaluation of peritoneal membrane dysfunction in adults: Classification, measurement, interpretation and rationale for intervention." Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis 41, no. 4 (February 10, 2021): 352–72. http://dx.doi.org/10.1177/0896860820982218.

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Lay summary Peritoneal dialysis (PD) uses the peritoneal membrane for dialysis. The peritoneal membrane is a thin layer of tissue that lines the abdomen. The lining is used as a filter to help remove extra fluid and poisonous waste from the blood. Everybody is unique. What is normal for one person’s membrane may be very different from another person’s. The kidney care team wants to provide each person with the best dialysis prescription for them and to do this they must evaluate the person’s peritoneal lining. Sometimes dialysis treatment itself can cause the membrane to change after some years. This means more assessments (evaluations) will be needed to determine whether the person’s peritoneal membrane has changed. Changes in the membrane may require changes to the dialysis prescription. This is needed to achieve the best dialysis outcomes. A key tool for these assessments is the peritoneal equilibration test (PET). It is a simple, standardized and reproducible tool. This tool is used to measure the peritoneal function soon after the start of dialysis. The goal is to understand how well the peritoneal membrane works at the start of dialysis. Later on in treatment, the PET helps to monitor changes in peritoneal function. If there are changes between assessments causing problems, the PET data may explain the cause of the dysfunction. This may be used to change the dialysis prescription to achieve the best outcomes. The most common problem with the peritoneal membrane occurs when fluid is not removed as well as it should be. This happens when toxins (poisons) in the blood cross the membrane more quickly than they should. This is referred to as a fast peritoneal solute transfer rate (PSTR). Since more efficient fluid removal is associated with better outcomes, developing a personal PD prescription based on the person’s PSTR is critically important. A less common problem happens when the membrane fails to work properly (also called membrane dysfunction) because the peritoneal membrane is less efficient, either at the start of treatment or developing after some years. If membrane dysfunction gets worse over time, then this is associated with progressive damage, scarring and thickening of the membrane. This problem can be identified through another change of the PET. It is called reduced ‘sodium dip’. Membrane dysfunction of this type is more difficult to treat and has many implications for the individual. If the damage is major, the person may need to stop PD. They would need to begin haemodialysis treatment (also spelled hemodialysis). This is a very important and emotional decision for individuals with kidney failure. Any decision that involves stopping PD therapy or transitioning to haemodialysis therapy should be made jointly between the clinical team, the person on dialysis and a caregiver, if requested. Although evidence is lacking about how often tests should be performed to determine peritoneal function, it seems reasonable to repeat them whenever there is difficulty in removing the amount of fluid necessary for maintaining the health and well-being of the individual. Whether routine evaluation of membrane function is associated with better outcomes has not been studied. Further research is needed to answer this important question as national policies in many parts of the world and the COVID-19 has placed a greater emphasis and new incentives encouraging the greater adoption of home dialysis therapies, especially PD. For Chinese and Spanish Translation of the Lay Summary, see Online Supplement Appendix 1. Key recommendations Guideline 1: A pathophysiological taxonomy: A pathophysiological classification of membrane dysfunction, which provides mechanistic links to functional characteristics, should be used when prescribing individualized dialysis or when planning modality transfer (e.g. to automated peritoneal dialysis (PD) or haemodialysis) in the context of shared and informed decision-making with the person on PD, taking individual circumstances and treatment goals into account. (practice point) Guideline 2a: Identification of fast peritoneal solute transfer rate (PSTR): It is recommended that the PSTR is determined from a 4-h peritoneal equilibration test (PET), using either 2.5%/2.27% or 4.25%/3.86% dextrose/glucose concentration and creatinine as the index solute. (practice point) This should be done early in the course dialysis treatment (between 6 weeks and 12 weeks) (GRADE 1A) and subsequently when clinically indicated. (practice point) Guideline 2b: Clinical implications and mitigation of fast solute transfer: A faster PSTR is associated with lower survival on PD. (GRADE 1A) This risk is in part due to the lower ultrafiltration (UF) and increased net fluid reabsorption that occurs when the PSTR is above the average value. The resulting lower net UF can be avoided by shortening glucose-based exchanges, using a polyglucose solution (icodextrin), and/or prescribing higher glucose concentrations. (GRADE 1A) Compared to glucose, use of icodextrin can translate into improved fluid status and fewer episodes of fluid overload. (GRADE 1A) Use of automated PD and icodextrin may mitigate the mortality risk associated with fast PSTR. (practice point) Guideline 3: Recognizing low UF capacity: This is easy to measure and a valuable screening test. Insufficient UF should be suspected when either (a) the net UF from a 4-h PET is <400 ml (3.86% glucose/4.25% dextrose) or <100 ml (2.27% glucose /2.5% dextrose), (GRADE 1B) and/or (b) the daily UF is insufficient to maintain adequate fluid status. (practice point) Besides membrane dysfunction, low UF capacity can also result from mechanical problems, leaks or increased fluid absorption across the peritoneal membrane not explained by fast PSTR. Guideline 4a: Diagnosing intrinsic membrane dysfunction (manifesting as low osmotic conductance to glucose) as a cause of UF insufficiency: When insufficient UF is suspected, the 4-h PET should be supplemented by measurement of the sodium dip at 1 h using a 3.86% glucose/4.25% dextrose exchange for diagnostic purposes. A sodium dip ≤5 mmol/L and/or a sodium sieving ratio ≤0.03 at 1 h indicates UF insufficiency. (GRADE 2B) Guideline 4b: Clinical implications of intrinsic membrane dysfunction (de novo or acquired): in the absence of residual kidney function, this is likely to necessitate the use of hypertonic glucose exchanges and possible transfer to haemodialysis. Acquired membrane injury, especially in the context of prolonged time on treatment, should prompt discussions about the risk of encapsulating peritoneal sclerosis. (practice point) Guideline 5: Additional membrane function tests: measures of peritoneal protein loss, intraperitoneal pressure and more complex tests that estimate osmotic conductance and ‘lymphatic’ reabsorption are not recommended for routine clinical practice but remain valuable research methods. (practice point) Guideline 6: Socioeconomic considerations: When resource constraints prevent the use of routine tests, consideration of membrane function should still be part of the clinical management and may be inferred from the daily UF in response to the prescription. (practice point)

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Martins Fernandes, S., L. Badano, A. Garcia Campos, T. Erdei, G. Mehdipoor, N. Hanboly, BW Michalski, et al. "Poster session 2THE IMAGING EXAMINATIONP536Appropriate use criteria of transthoracic echocardiography and its clinical impact: a continuous challengeP537Implementation of proprietary plug-ins in the DICOM-based computerized echo reporting system fuels the use of 3D echo and deformation imaging in the clinical routine of a multivendor laboratoryP538Exercise stress echocardiography appropriate use criteria: real-life cases classification ease and agreement among cardiologistsANATOMY AND PHYSIOLOGY OF THE HEART AND GREAT VESSELSP539Functional capacity in older people with normal ejection fraction correlates with left ventricular functional reserve and carotid-femoral pulse wave velocity but not with E/e and augmentation indexP540Survey of competency of practitioners for diagnosis of acute cardiopulmonary diseases manifest on chest x-rayASSESSMENT OF DIAMETERS, VOLUMES AND MASSP541Left atrium remodeling in dialysis patients with normal ejection fractionP542The prediction of postinfarction left ventricular remodeling and the role of of leptin and MCP-1 in regard to the presence of metabolic syndromeP543Ascending aorta and common carotid artery: diameters and stiffness in a group of 584 healthy subjectsAssessments of haemodynamicsP544Alternate echo parameters in patients without estimable RVSPAssessment of systolic functionP545Reduced contractile performance in heart failure with preserved ejection fraction: determination using novel preload-adjusted maximal left ventricular ejection forceP546Left ventricular dimensions and prognosis in acute coronary syndromesP547Time course of myocardial alterations in a murine model of high fat diet: A strain rate imaging studyP548Subclinical left ventricular systolic dysfunction in patients with premature ventricular contractionsP549Global myocardial strain by CMR-based feature tracking (FT) and tagging to predict development of severe left ventricular systolic dysfunction after acute st-elevation myocardial infarctionP550Echocardiographic analysis of left and right ventricular function in patients after mitral valve reconstructionP551The role of regional longitudinal strain assessment in predicting response to cardiac resynchronization therapy in patients with left ventricular systolic dysfunction and left bundle branch blockP552Speckle tracking automatic border detection improves echocardiographic evaluation of right ventricular systolic function in repaired tetralogy of fallot patients: comparison with MRI findingsP553Echocardiography: a reproducible and relevant tool in pah? intermediate results of the multicentric efort echogardiographic substudy (evaluation of prognostic factors and therapeutic targets in pah)Assessment of diastolic functionP554Relationship between left ventricular filling pressures and myocardial fibrosis in patients with uncomplicated arterial hypertensionP555Cardiac rehabilitation improves echocardiographic parameters of diastolic function in patients with ischemic heart diseaseP556Diastolic parameters in the calcified mitral annulusP557Biomarkers and echocardiography - combined weapon to diagnose and prognose heart failure with and without preserved ejection fractionP558Diastolic function changes of the maternal heart in twin and singleton pregnancyIschemic heart diseaseP559Syntax score as predictor for the correlation between epicardial adipose tissue and the severity of coronary lesions in patients with significant coronary diseaseP560Impact of strain analysis in ergonovine stress echocardiography for diagnosis vasospastic anginaP561Cardiac magnetic resonance tissue tracking: a novel method to predict infarct transmurality in acute myocardial infarctionP562Infarct size is correlated to global longitudinal strain but not left ventricular ejection fraction in the early stage of acute myocardial infarctionP563Magnetic resonance myocardial deformation assessment with tissue tracking and risk stratification in acute myocardial infarction patientsP564Increase in regional end-diastolic wall thickness by transthoracic echocardiography as a biomarker of successful reperfusion in anterior ST elevation acute myocardial infarctionP565Mitral regurgitation is associated with worse long-term prognosis in ST-segment elevation myocardial infarction treated with primary percutaneous coronary interventionP566Statistical significance of 3D motion and deformation indexes for the analysis of LAD infarctionHeart valve DiseasesP567Paradoxical low gradient aortic stenosis: echocardiographic progression from moderate to severe diseaseP568The beneficial effects of TAVI in mitral insufficiencyP569Impact of thoracic aortic calcification on the left ventricular hypertrophy and its regression after aortic valve replacement in patients with severe aortic stenosisP570Additional value of exercise-stress echocardiography in asymptomatic patients with aortic valve stenosisP571Valvulo-arterial impedance in severe aortic stenosis: a dual imaging modalities studyP572Left ventricular mechanics: novel tools to evaluate left ventricular performance in patients with aortic stenosisP573Comparison of long-term outcome after percutaneous mitral valvuloplasty versus mitral valve replacement in moderate to severe mitral stenosis with left ventricular dysfunctionP574Incidence of de novo left ventricular dysfunction in patient treated with aortic valve replacement for severe aortic regurgitationP575Transforming growth factor-beta dependant progression of the mitral valve prolapseP576Quantification of mitral regurgitation with multiple jets: in vitro validation of three-dimensional PISA techniqueP577Impaired pre-systolic contraction and saddle-shape deepening of mitral annulus contributes to atrial functional regurgitation: a three-dimensional echocardiographic studyP578Incidence and determinants of left ventricular (lv) reverse remodeling after MitraClip implantation in patients with moderate-to severe or severe mitral regurgitation and reduced lv ejection fractionP579Severe functional tricuspid regurgitation in rheumatic heart valve disease. New insights from 3D transthoracic echocardiographyP58015 years of evolution of the etiologic profile for prosthetic heart valve replacement through an echocardiography laboratoryP581The role of echocardiography in the differential diagnosis of prolonged fever of unknown originP582Predictive value for paravalvular regurgitation of 3-dimensional anatomic aortic annulus shape assessed by multidetector computed tomography post-transcatheter aortic valve replacementP583The significance and advantages of echo and CT imaging & measurement at transcatherter aortic valve implantation through the left common carotid accessP584Comparison of the self-expandable Medtronic CoreValve versus the balloon-expandable Edwards SAPIEN bioprostheses in high-risk patients undergoing transfemoral aortic valve implantationP585The impact of transcatheter aortic valve implantation on mitral regurgitation severityP586Echocardiographic follow up of children with valvular lesions secondary to rheumatic heart disease: Data from a prospective registryP587Valvular heart disease and different circadian blood pressure profilesCardiomyopathiesP588Comparison of transthoracic echocardiography versus cardiac magnetic for implantable cardioverter defibrillator therapy in primary prevention strategy dilated cardiomyopathy patientsP589Incidence and prognostic significance of left ventricle reverse remodeling in a cohort of patients with idiopathic dilated cardiomyopathyP590Early evaluation of diastolic function in fabry diseaseP591Echocardiographic predictors of atrial fibrillation development in hypertrophic cardiomyopathyP592Altered Torsion mechanics in patients with hypertrophic cardiomyopathy: LVOT-obstruction is the topdog?P593Prevention of sudden cardiac death in hypertrophic cardiomyopathy: what has changed in the guidelines?P594Coronary microcirculatory function as determinator of longitudinal systolic left ventricular function in hypertrophic cardiomyopathyP595Detection of subclinical myocardial dysfunction by tissue Doppler ehocardiography in patients with muscular dystrophiesP596Speckle tracking myocardial deformation analysis and three dimensional echocardiography for early detection of chemotherapy induced cardiac dysfunction in bone marrow transplantation patientsP597Left ventricular non compaction or hypertrabeculation: distinguishing between physiology and pathology in top-level athletesP598Role of multi modality imaging in familiar screening of Danon diseaseP599Early impairment of global longitudinal left ventricular systolic function independently predicts incident atrial fibrillation in type 2 diabetes mellitusP600Fetal cardiovascular programming in maternal diabetes mellitus and obesity: insights from deformation imagingP601Longitudinal strain stress echo evaluation of aged marginal donor hearts: feasibility in the Adonhers project.P602Echocardiographic evaluation of left ventricular size and function following heart transplantation - Gender mattersSystemic diseases and other conditionsP603The impact of septal kinetics on adverse ventricular-ventricular interactions in pulmonary stenosis and pulmonary arterial hypertensionP604Improvement in right ventricular mechanics after inhalation of iloprost in pulmonary hypertensionP605Does the treatment of patients with metabolic syndrome correct the right ventricular diastolic dysfunction?P606Predictors of altered cardiac function in breast cancer survivors who were treated with anthracycline-based therapyP607Prevalence and factors related to left ventricular systolic dysfunction in asymptomatic patients with rheumatoid arthritis: a prospective tissue-doppler echocardiography studyP608Diastolic and systolic left ventricle dysfunction presenting different prognostic implications in cardiac amyloidosisP609Diagnostic accuracy of Bedside Lung Ultrasonography in Emergency (BLUE) protocol for the diagnosis of pulmonary embolismP610Right ventricular systolic dysfunction and its incidence in breast cancer patients submitted to anthracycline therapyP611Right ventricular dysfunction is an independent predictor of survival among cirrhotic patients undergoing liver transplantCongenital heart diseaseP612Hypoplasia or absence of posterior leaflet: a rare congenital anomaly of the mitral valveP613ECHO screening for Barlow disease in proband's relativesDiseases of the aortaP614Aortic size distribution and prognosis in an unselected population of patients referred for standard transthoracic echocardiographyP615Abdominal aorta aneurysm ultrasonographic screening in a large cohort of asympromatic volounteers in an Italian urban settingP616Thoracic aortic aneurysm and left ventricular systolic functionStress echocardiographyP617Wall motion score index, systolic mitral annulus velocity and left ventricular mass predicted global longitudinal systolic strain in 238 patients examined by stress echocardiographyP618Prognostic parameters of exercise-induced severe mitral valve regurgitation and exercise-induced systolic pulmonary hypertensionP619Risk stratification after myocardial infarction: prognostic value of dobutamine stress echocardiographyP620relationship between LV and RV myocardial contractile reserve and metabolic parameters during incremental exercise and recovery in healthy children using 2-D strain analysisP621Increased peripheral extraction as a mechanism compensatory to reduced cardiac output in high risk heart failure patients with group 2 pulmonary hypertension and exercise oscillatory ventilationP622Can exercise induced changes in cardiac synchrony predict response to CRT?Transesophageal echocardiographyP623Fully-automated software for mitral valve assessment in chronic mitral regurgitation by three-dimensional transesophageal echocardiographyP624Real-time 3D transesophageal echocardiography provides more accurate orifice measurement in percutaneous transcatheter left atrial appendage closureP625Percutaneous closure of left atrial appendage: experience of 36 casesReal-time three-dimensional TEEP626Real-time three-dimensional transesophageal echocardiography during pulmonary vein cryoballoon ablation for atrial fibrilationP627Three dimensional ultrasound anatomy of intact mitral valve and in the case of type 2 disfunctionTissue Doppler and speckle trackingP629Left ventricle wall motion tracking from echocardiographic images by a non-rigid image registrationP630The first experience with the new prototype of a robotic system for remote echocardiographyP631Non-invasive PCWP influence on a loop diuretics regimen monitoring model in ADHF patients.P632Normal range of left ventricular strain, dimensions and ejection fraction using three-dimensional speckle-tracking echocardiography in neonatesP633Circumferential ascending aortic strain: new parameter in the assessment of arterial stiffness in systemic hypertensionP634Aortic vascular properties in pediatric osteogenesis imperfecta: a two-dimensional echocardiography derived aortic strain studyP635Assessment of cardiac functions in children with sickle cell anemia: doppler tissue imaging studyP636Assessment of left ventricular function in type 1 diabetes mellitus patients by two-dimensional speckle tracking echocardiography: relation to duration and control of diabetesP637A study of left ventricular torsion in l-loop ventricles using speckle-tracking echocardiographyP638Despite No-Reflow, global and regional longitudinal strains assessed by two-dimensional speckle tracking echocardiography are predictive indexes of left ventricular remodeling in patients with STEMIP639The function of reservoir of the left atrium in patients with medicaly treated arterial hypertensionP640The usefulness of speckle tracking analysis for predicting the recovery of regional systolic function after myocardial infarctionP641Two dimensional speckle tracking echocardiography in assessment of left ventricular systolic function in patients with rheumatic severe mitral regurgitation and normal ejection fractionP642The prediction of left-main and tripple vessel coronary artery disease by tissue doppler based longitudinal strain and strain rate imagingP643Role of speckle tracking in predicting arrhythmic risk and occurrence of appropriate implantable defibrillator Intervention in patients with ischemic and non-ischemic cardiomyopathyComputed Tomography & Nuclear CardiologyP644Cardiac adrenergic activity in patients with nonischemic dilated cardiomyopathy. Correlation with echocardiographyP645Different vascular territories and myocardial ischemia, there is a gradient of association?" European Heart Journal – Cardiovascular Imaging 16, suppl 2 (December 2015): S73—S101. http://dx.doi.org/10.1093/ehjci/jev278.

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Hong, Liang, Enling Ye, Gangqiang Sun, Xiaoyang Wang, Shengguo Zhang, Yanghe Wu, Xiangao Xie, et al. "Clinical and radiographic characteristics, management and short-term outcomes of patients with COVID-19 in Wenzhou, China." BMC Infectious Diseases 20, no. 1 (November 13, 2020). http://dx.doi.org/10.1186/s12879-020-05528-z.

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Abstract Background Coronavirus disease 2019 (COVID-19) is an emerging viral disease. Here, we report the clinical features, management, and short-term outcomes of COVID-19 patients in Wenzhou, China, an area outside Wuhan. Methods Patients admitted to the Infectious Diseases Department of Ruian People’s Hospital in Wenzhou, from January 21 to February 7, 2020, were recruited. Medical data on epidemiological history, demographics, clinical characteristics, laboratory tests, chest computerized tomography (CT) examination, treatment, and short-term outcomes were retrospectively reviewed. Blood biochemistry and routine tests were examined using standard methods and automatic machines. CT examination was performed several times during hospitalization as necessary. Results A total of 67 confirmed COVID-19 cases were diagnosed; 64 (95.4%) were common cases and three (4.5%) were severe cases. The most common symptoms at admission were fever (86.6%), cough (77.6%), productive cough (52.2%), chest distress (17.9%), and sore throat (11.9%), followed by diarrhea (7.4%), headache (7.4%), shortness of breath (6.0%), dizziness (4.5%), muscular soreness (4.5%), and running nose (4.5%). Thirty patients (47.8%) had increased C-reactive protein levels. The CT radiographs at admission showed abnormal findings in 54 (80.6%) patients. The patients were treated mainly by oxygen therapy and antiviral drugs. By March 3, 2020, all 67 patients completely recovered and had negative nucleic acid tests. The patients were discharged from the hospital and transferred to a medical observation isolation center for further observation. Conclusion Cases of COVID-19 in Wenzhou are milder and have a better prognosis, compared to those in Wuhan. Timely and appropriate screening, diagnosis, and treatment are the key to achieve good outcomes.

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Li, Jieming, Leyou Zhang, Alexander Johnson-Buck, and Nils G. Walter. "Automatic classification and segmentation of single-molecule fluorescence time traces with deep learning." Nature Communications 11, no. 1 (November 17, 2020). http://dx.doi.org/10.1038/s41467-020-19673-1.

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AbstractTraces from single-molecule fluorescence microscopy (SMFM) experiments exhibit photophysical artifacts that typically necessitate human expert screening, which is time-consuming and introduces potential for user-dependent expectation bias. Here, we use deep learning to develop a rapid, automatic SMFM trace selector, termed AutoSiM, that improves the sensitivity and specificity of an assay for a DNA point mutation based on single-molecule recognition through equilibrium Poisson sampling (SiMREPS). The improved performance of AutoSiM is based on accepting both more true positives and fewer false positives than the conventional approach of hidden Markov modeling (HMM) followed by hard thresholding. As a second application, the selector is used for automated screening of single-molecule Förster resonance energy transfer (smFRET) data to identify high-quality traces for further analysis, and achieves ~90% concordance with manual selection while requiring less processing time. Finally, we show that AutoSiM can be adapted readily to novel datasets, requiring only modest Transfer Learning.

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Dharap, Parag, and Sebastien Raimbault. "Performance evaluation of machine learning-based infectious screening flags on the HORIBA Medical Yumizen H550 Haematology Analyzer for vivax malaria and dengue fever." Malaria Journal 19, no. 1 (November 23, 2020). http://dx.doi.org/10.1186/s12936-020-03502-3.

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Abstract Background Automated detection of malaria and dengue infection has been actively researched for more than two decades. Although many improvements have been achieved, these solutions remain too expensive for most laboratories and clinics in developing countries. The low range HORIBA Medical Haematology Analyzer, Yumizen H550, now provides dedicated flags ‘vivax malaria’ and ‘dengue fever’ in routine blood testing, developed through machine learning methods, to be used as a screening tool for malaria and dengue fever in endemic areas. This study sought to evaluate the effectiveness of these flags under real clinical conditions. Methods A total of 1420 samples were tested using the Yumizen H550 Haematology Analyzer, including 1339 samples from febrile patients among whom 202 were infected with malaria parasites (Plasmodium vivax only: 182, Plasmodium falciparum only: 18, both: 2), 210 were from febrile dengue infected patients, 3 were from afebrile dengue infected patients and 78 were samples from healthy controls, in an outpatient laboratory clinic in Mumbai, India. Microscopic examination was carried out as the confirmatory reference method for detection of malarial parasite, species identification and assessing parasitaemia based on different stages of parasite life cycle. Rapid diagnostic malarial antigen tests were used for additional confirmation. For dengue infection, NS1 antigen detection by ELISA was used as a diagnostic marker. Results For the automated vivax malaria flag, the original manufacturer’s cut off yielded a sensitivity and specificity of 65.2% and 98.9% respectively with the ROC AUC of 0.9. After optimization of cut-off value, flag performance improved to 72% for sensitivity and 97.9% specificity. Additionally it demonstrated a positive correlation with increasing levels of parasitaemia. For the automated dengue fever flag it yielded a ROC AUC of 0.82 with 79.3% sensitivity and 71.5% specificity. Conclusions The results demonstrate a possibility of the effective use of automated infectious flags for screening vivax malaria and dengue infection in a clinical setting.

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Gates, Michelle, Sarah A. Elliott, Allison Gates, Meghan Sebastianski, Jennifer Pillay, Liza Bialy, and Lisa Hartling. "LOCATE: a prospective evaluation of the value of Leveraging Ongoing Citation Acquisition Techniques for living Evidence syntheses." Systematic Reviews 10, no. 1 (April 19, 2021). http://dx.doi.org/10.1186/s13643-021-01665-x.

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Abstract Background Living systematic reviews (LSRs) can expedite evidence synthesis by incorporating new evidence in real time. However, the methods needed to identify new studies in a timely manner are not well established. Objectives To explore the value of complementary search approaches in terms of search performance, impact on results and conclusions, screening workload, and feasibility compared to the reference standard. Methods We developed three complementary search approaches for a systematic review on treatments for bronchiolitis: Automated Full Search, PubMed Similar Articles, and Scopus Citing References. These were automated to retrieve results monthly; pairs of reviewers screened the records and commented on feasibility. After 1 year, we conducted a full update search (reference standard). For each complementary approach, we compared search performance (proportion missed, number needed to read [NNR]) and reviewer workload (number of records screened, time required) to the reference standard. We investigated the impact of the new trials on the effect estimate and certainty of evidence for the primary outcomes. We summarized comments about feasibility. Results Via the reference standard, reviewers screened 505 titles/abstracts, 24 full texts, and identified four new trials (NNR 127; 12.4 h). Of the complementary approaches, only the Automated Full Search located all four trials; these were located 6 to 12 months sooner than via the reference standard but did not alter the results nor certainty in the evidence. The Automated Full Search was the most resource-intensive approach (816 records screened; NNR 204; 17.1 h). The PubMed Similar Articles and Scopus Citing References approaches located far fewer records (452 and 244, respectively), thereby requiring less screening time (9.4 and 5.2 h); however, each approach located only one of the four new trials. Reviewers found it feasible and convenient to conduct monthly screening for searches of this yield (median 15–65 records/month). Conclusions The Automated Full Search was the most resource-intensive approach, but also the only to locate all of the newly published trials. Although the monthly screening time for the PubMed Similar Articles and Scopus Citing Articles was far less, most relevant records were missed. These approaches were feasible to integrate into reviewer work processes. Systematic review registration Open Science Framework. 10.17605/OSF.IO/6M28H.

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N.S., Mujahid. "Evaluation of the Performance of Widal Slide Agglutination Test Compared to Blood Culture and Evaluation of Interferon Gamma Response in the Diagnosis of Typhoid Fever." UMYU Journal of Microbiology Research (UJMR), December 30, 2020, 117–22. http://dx.doi.org/10.47430/ujmr.2052.016.

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Typhoid fever remains a public health challenge in developing countries including Nigeria. Widal test is widely used for the diagnosis of typhoid fever due to its simplicity and short turnaround time. However, the specificity of this test has been debated. The aim of the study was to evaluate the performance of Widal test compared to blood culture and determine interferon gamma response among the study subjects. Blood samples were collected from 90 patients who complained of fever and other symptoms suggestive of typhoid fever. Widal slide agglutination test, automated blood culture and interferon gamma concentrations were conducted using rapid antibody detection kit, BACTEC and sandwich enzyme linked immunosorbent assay (ELISA) respectively. Of the 90 samples tested, 63 (70.0%) were positive for anti-Typhi O antigen while 42 (46.7%) were positive for anti-Typhi H antigen. Similarly, 18 (20%) of the blood samples were non- S. Typhi culture positive while 72 (80%) had no bacteria isolated. None of the cases had S. Typhi positive culture. With regards to interferon gamma, subjects with lower levels of 15pg/mL had no bacteria isolated from their blood. As the interferon gamma concentration increased, more subjects had non- S. Typhi bacteria isolated from their blood which shows the relationship between interferon gamma and bacteraemia. The study demonstrated that the use of Widal serology test in the diagnosis of typhoid fever may be erroneous as all the samples were found to be negative for S. Typhi using the gold standard culture methods while Interferon gamma concentration was statistically related to the isolation of non- S. Typhi in blood culture as such, could be a good marker for the development of an alternative screening test, possibly an interferon gamma based detection system for typhoid fever. However, further research is recommended to elucidate that. Keywords: Typhoid, Widal test, Blood culture, Interferon gamma

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Pham, Ba’, Jelena Jovanovic, Ebrahim Bagheri, Jesmin Antony, Huda Ashoor, Tam T. Nguyen, Patricia Rios, et al. "Text mining to support abstract screening for knowledge syntheses: a semi-automated workflow." Systematic Reviews 10, no. 1 (May 26, 2021). http://dx.doi.org/10.1186/s13643-021-01700-x.

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Abstract Background Current text mining tools supporting abstract screening in systematic reviews are not widely used, in part because they lack sensitivity and precision. We set out to develop an accessible, semi-automated “workflow” to conduct abstract screening for systematic reviews and other knowledge synthesis methods. Methods We adopt widely recommended text-mining and machine-learning methods to (1) process title-abstracts into numerical training data; and (2) train a classification model to predict eligible abstracts. The predicted abstracts are screened by human reviewers for (“true”) eligibility, and the newly eligible abstracts are used to identify similar abstracts, using near-neighbor methods, which are also screened. These abstracts, as well as their eligibility results, are used to update the classification model, and the above steps are iterated until no new eligible abstracts are identified. The workflow was implemented in R and evaluated using a systematic review of insulin formulations for type-1 diabetes (14,314 abstracts) and a scoping review of knowledge-synthesis methods (17,200 abstracts). Workflow performance was evaluated against the recommended practice of screening abstracts by 2 reviewers, independently. Standard measures were examined: sensitivity (inclusion of all truly eligible abstracts), specificity (exclusion of all truly ineligible abstracts), precision (inclusion of all truly eligible abstracts among all abstracts screened as eligible), F1-score (harmonic average of sensitivity and precision), and accuracy (correctly predicted eligible or ineligible abstracts). Workload reduction was measured as the hours the workflow saved, given only a subset of abstracts needed human screening. Results With respect to the systematic and scoping reviews respectively, the workflow attained 88%/89% sensitivity, 99%/99% specificity, 71%/72% precision, an F1-score of 79%/79%, 98%/97% accuracy, 63%/55% workload reduction, with 12%/11% fewer abstracts for full-text retrieval and screening, and 0%/1.5% missed studies in the completed reviews. Conclusion The workflow was a sensitive, precise, and efficient alternative to the recommended practice of screening abstracts with 2 reviewers. All eligible studies were identified in the first case, while 6 studies (1.5%) were missed in the second that would likely not impact the review’s conclusions. We have described the workflow in language accessible to reviewers with limited exposure to natural language processing and machine learning, and have made the code available to reviewers.

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Choo, Nicholas, Susanne Ramm, Jennii Luu, Jean M. Winter, Luke A. Selth, Amy R. Dwyer, Mark Frydenberg, et al. "High-Throughput Imaging Assay for Drug Screening of 3D Prostate Cancer Organoids." SLAS DISCOVERY: Advancing the Science of Drug Discovery, June 11, 2021, 247255522110206. http://dx.doi.org/10.1177/24725552211020668.

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New treatments are required for advanced prostate cancer; however, there are fewer preclinical models of prostate cancer than other common tumor types to test candidate therapeutics. One opportunity to increase the scope of preclinical studies is to grow tissue from patient-derived xenografts (PDXs) as organoid cultures. Here we report a scalable pipeline for automated seeding, treatment and an analysis of the drug responses of prostate cancer organoids. We established organoid cultures from 5 PDXs with diverse phenotypes of prostate cancer, including castrate-sensitive and castrate-resistant disease, as well as adenocarcinoma and neuroendocrine pathology. We robotically embedded organoids in Matrigel in 384-well plates and monitored growth via brightfield microscopy before treatment with poly ADP-ribose polymerase inhibitors or a compound library. Independent readouts including metabolic activity and live-cell imaging–based features provided robust measures of organoid growth and complementary ways of assessing drug efficacy. Single organoid analyses enabled in-depth assessment of morphological differences between patients and within organoid populations and revealed that larger organoids had more striking changes in morphology and composition after drug treatment. By increasing the scale and scope of organoid experiments, this automated assay complements other patient-derived models and will expedite preclinical testing of new treatments for prostate cancer.

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Francis, Rania, Maxime Mioulane, Marion Le Bideau, Marie-Charlotte Mati, Pierre-Edouard Fournier, Didier Raoult, Jacques Yaacoub Bou Khalil, and Bernard La Scola. "High-Content Screening, a Reliable System for Coxiella burnetii Isolation from Clinical Samples." Journal of Clinical Microbiology 58, no. 5 (March 4, 2020). http://dx.doi.org/10.1128/jcm.02081-19.

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ABSTRACT Q fever, caused by Coxiella burnetii, is a worldwide zoonotic disease that may cause severe forms in humans and requires a specific and prolonged antibiotic treatment. Although current serological and molecular detection tools allow a reliable diagnosis of the disease, culture of C. burnetii strains is mandatory to assess their susceptibility to antibiotics and sequence their genome in order to optimize patient management and epidemiological studies. However, cultivating this fastidious microorganism is difficult and restricted to reference centers, as it requires biosafety level 3 laboratories and relies on cell culture performed by experienced technicians. In addition, the culture yield is low, which results in a small number of isolates being available. In this work, we developed a novel high-content screening (HCS) isolation strategy based on optimized high-throughput cell culture and automated microscopic detection of infected cells with specifically designed algorithms targeting cytopathic effects. This method was more efficient than the shell vial assay, at the level of time dependency, when applied to both frozen specimens (7 isolates recovered by HCS only, sensitivity 91% versus 78% for shell vial) and fresh samples (1 additional isolate using HCS, sensitivity 7% versus 5% for shell vial), for which most strains were recovered more rapidly with the new technique. In addition, detecting positive cultures by an automated microscope reduced the need for expertise and saved 24% of technician working time. Application of HCS to antibiotic susceptibility testing of 12 strains demonstrated that it was as efficient as the standard procedure that combines shell vial culture and quantitative PCR.

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Gobbett, Anne, Jonathan Smith, and Claire Bracewel. "P01 Hydroxychloroquine retinopathy: is screening necessary?" Rheumatology 59, Supplement_2 (April 1, 2020). http://dx.doi.org/10.1093/rheumatology/keaa111.

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Abstract Background Hydroxychloroquine (HCQ) has long been associated with a low prevalence (0.5%) of retinal toxicity with possible irreversible sight loss. New retinal imaging techniques have suggested a significantly increased prevalence of HCQ retinopathy (7.5%). In light of this result, the American Academy of Ophthalmology (AAO) in 2016 and subsequently the Royal College of Ophthalmologists (RCO) in 2018 produced new screening guidelines. We report the HCQ retinopathy screening results for all patients referred to our Ophthalmology department from 1/11/2017 to date. Methods We collected prospective data from all patients referred for HCQ screening. Patients were screened according to the new RCO guidelines. We recorded each patient's dose and duration of HCQ treatment, their weight and renal function, and concurrent use of tamoxifen to determine their risk factors. Retinal images: colour fundal photos, ocular coherence tomography (OCT) and auto-fluorescence (AF), were performed on all patients (baseline tests), and visual acuity, automated central visual field testing (Humphrey 10:2) and multi focal electroretinography (mfERG) performed as indicated for those at risk, needing annual testing. Results We have diagnosed two definite cases of hydroxychloroquine retinopathy, giving us a prevalence of 2/639 (0.31%) of all screened, and 2/308 (0.64%) of those considered to be at risk according to RCO guidelines. 711 patients have been referred to our screening service so far. 639 of these have been screened with 72 failing to attend. 308 of all those screened have been categorised to be at increased risk of retinopathy: duration of treatment >5 years (224), dose > 5mg/kg/day (40), eGFR< 60ml/min/1.73m2 (111) and use of tamoxifen (0). 64 have multiple risk factors. 119 of those screened have completed their second cycle of screening, with 48 patients failing to attend for this repeat screening. Conclusion Our results for HCQ retinopathy screening suggest a prevalence more in keeping with the originally proposed figure than that in the recent literature; this may be multifactorial. We have a smaller number of patients, with fewer of those patients in the higher risk categories than in the study that prompted the change in screening guidelines. We only have baseline or two years of serial images for each patient at present, the comparison of multiple serial images may highlight more cases of retinopathy. More data is needed before we can suggest our figures are statistically different. Disclosures A. Gobbett None. J. Smith None. C. Bracewell None.

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Journal articles on the topic 'Automatic fever screening'

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