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Prognostic significance of electrical alternans versus signal averaged electrocardiography in predicting the outcome of electrophysiological testing and arrhythmia-free survival

OBJECTIVE: To investigate the accuracy of signal averaged electrocardiography (SAECG) and measurement of microvolt level T wave alternans as predictors of susceptibility to ventricular arrhythmias. DESIGN: Analysis of new data from a previously published prospective investigation. SETTING: Electrophysiology laboratory of a major referral hospital. PATIENTS AND INTERVENTIONS: 43 patients, not on class I or class III antiarrhythmic drug treatment, undergoing invasive electrophysiological testing had SAECG and T wave alternans measurements. The SAECG was considered positive in the presence of one (SAECG-I) or two (SAECG-II) of three standard criteria. T wave alternans was considered positive if the alternans ratio exceeded 3.0. MAIN OUTCOME MEASURES: Inducibility of sustained ventricular tachycardia or fibrillation during electrophysiological testing, and 20 month arrhythmia-free survival. RESULTS: The accuracy of T wave alternans in predicting the outcome of electrophysiological testing was 84% (p < 0.0001). Neither SAECG-I (accuracy 60%; p < 0.29) nor SAECG-II (accuracy 71%; p < 0.10) was a statistically significant predictor of electrophysiological testing. SAECG, T wave alternans, electrophysiological testing, and follow up data were available in 36 patients while not on class I or III antiarrhythmic agents. The accuracy of T wave alternans in predicting the outcome of arrhythmia-free survival was 86% (p < 0.030). Neither SAECG-I (accuracy 65%; p < 0.21) nor SAECG-II (accuracy 71%; p < 0.48) was a statistically significant predictor of arrhythmia-free survival. CONCLUSIONS: T wave alternans was a highly significant predictor of the outcome of electrophysiological testing and arrhythmia-free survival, while SAECG was not a statistically significant predictor. Although these results need to be confirmed in prospective clinical studies, they suggest that T wave alternans may serve as a non-invasive probe for screening high risk populations for malignant ventricular arrhythmias.

Non-NASA Center↗

Heart Rhythm Monitoring in the Constellation Lunar and Launch/Landing EVA Suit: Recommendations from an Expert Panel

Currently there are several physiological monitoring requirements for Extravehicular Activity (EVA) in the Human-Systems Interface Requirements (HSIR) document, including continuous heart rhythm monitoring. However, it is not known whether heart rhythm monitoring in the lunar surface space suit is a necessary capability for lunar surface operations or in launch/landing suit the event of a cabin depressurization enroute to or from the moon. Methods: Current US astronaut corps demographic information was provided to an expert panel of cardiovascular medicine experts, including specialists in electrophysiology, exercise physiology, interventional cardiology and arrhythmia. This information included averages for male/female age, body mass index (BMI), blood pressure, cholesterol, inflammatory markers, echocardiogram, ranges for coronary artery calcium (CAC) scores for long duration astronauts, and ranges for heart rate (HR) and metabolic (MET) rates obtained during microgravity and lunar EVA. Results: The panel determined that no uncontrolled hazard was likely to occur in the suit during lunar surface or contingency microgravity ops that would require ECG monitoring in the highly screened US astronaut population. However having the capability for rhythm monitoring inside the vehicle (IVA) was considered critical to manage an astronaut in distress. Discussion: Heart rate (HR) monitoring alone allows effective monitoring of astronaut health and function. Consequently, electrocardiographic (ECG) monitoring capability as a clinical tool is not essential in the lunar or launch/landing space suit. However, the panel considered that rhythm monitoring could be useful in certain clinical situations, it was not considered required for safe operations. Also, lunar vehicles should be required to have ECG monitoring capability with a minimum of 5-lead ECG (derived 12- lead) for IVA medical assessments.

Scheuring, Richard A.↗

Optimal Stopping Ages for Colorectal Cancer Screening

Importance Prior studies have shown that the benefits, harms, and costs of colorectal cancer (CRC) screening at older ages are associated with a patient’s sex, health, and screening history. However, these studies were hypothetical exercises and not directly informed by data on CRC risk. Objective To identify the optimal stopping ages for CRC screening by sex, comorbidity, and screening history from a cost-effectiveness perspective. Design, Setting, and Participants This economic evaluation first validated the MISCAN-Colon (Microsimulation Screening Analysis–Colon) model against community-based CRC incidence and mortality rates for 2 subcohorts of the PRECISE (Optimizing Colorectal Cancer Screening Precision and Outcomes in Community-Based Populations) cohort. Subsequently, different CRC screening scenarios were simulated in older individuals. Cohorts of US adults aged 76 to 90 years varied by sex and comorbidity status (none, low, moderate, or severe). Statistical and sensitivity analyses were performed from March 2023 to May 2024. Exposures CRC screening histories including fecal immunochemical test (FIT) or colonoscopy, such as a negative colonoscopy result from 10, 15, 20, 25, or 30 years before the index age; 1 to 5 negative FIT results within 5 years of the index age, with different patterns of recency; or a combination of negative colonoscopy and negative FIT results. Main Outcomes and Measures The main outcomes included estimated lifetime clinical outcomes, incremental costs, and quality-adjusted life-years gained (QALYG) associated with 1 additional FIT or colonoscopy. Optimal stopping age for screening, defined as the oldest age for which the incremental cost-effectiveness ratio was still below the willingness-to-pay threshold of $\$$100 000 per QALYG, was evaluated. Results The first of the 2 PRECISE subcohorts used in validating the simulation model included 25 974 adults (15 060 females [58.0%]; 54.7% aged 76 to 80 years) with a negative colonoscopy result 10 years before the index date. The second subcohort consisted of 118 269 adults (67 058 females [56.7%]; 90.5% aged 76 to 80 years) with a negative FIT result 1 year before the index date. Older age, male sex, higher comorbidity levels, and recent CRC screenings were associated with reduced incremental benefit and cost-effectiveness of additional screening. For the reference cohort of 76-year-old females without comorbidities and a negative colonoscopy result 10 years before the index age, 1 additional colonoscopy cost $\$$38 226 per QALYG. For cohorts with otherwise equivalent characteristics, associated costs increased to $\$$1 689 945 per QALYG for females at age 90 years without comorbidities and a negative colonoscopy results 10 years before the index age, $\$$51 604 per QALYG for males at age 76 years without comorbidities and a negative colonoscopy result 10 years before the index age, and $\$$108 480 per QALYG for females at age 76 years with severe comorbidities and a negative colonoscopy result 10 years before the index age and decreased to $\$$16 870 per QALYG for females without comorbidities and a negative colonoscopy result 30 years before the index age. The optimal stopping ages across different cohorts ranged from younger than 76 to 86 years for colonoscopy and younger than 76 to 88 years for FIT. Conclusions and Relevance In this economic evaluation, age, sex, screening history, comorbidity, and future screening modality were associated with the clinical outcomes, cost-effectiveness, and optimal stopping age for CRC screening. These results can inform guideline development and patient-directed informed decision-making.

Harlass, Matthias [Erasmus Erasmus University Medi↗

Pre-screening to guide coronary artery calcium scoring for early identification of high-risk individuals in the general population

Abstract Aims To evaluate the ability of Systematic COronary Risk Estimation 2 (SCORE2) and other pre-screening methods to identify individuals with high coronary artery calcium score (CACS) in the general population. Methods and results Computed tomography-based CACS quantification was performed in 6530 individuals aged 45 years or older from the general population. Various pre-screening methods to guide referral for CACS were evaluated. Miss rates for high CACS (CACS ≥300 and ≥100) were evaluated for various pre-screening methods: moderate (≥5%) and high (≥10%) SCORE2 risk, any traditional coronary artery disease (CAD) risk factor, any Risk Or Benefit IN Screening for CArdiovascular Disease (ROBINSCA) risk factor, and moderately (>3 mg/24 h) increased urine albumin excretion (UAE). Out of 6530 participants, 643 (9.8%) had CACS ≥300 and 1236 (18.9%) had CACS ≥100. For CACS ≥300 and CACS ≥100, miss rate was 32 and 41% for pre-screening by moderate (≥5%) SCORE2 risk and 81 and 87% for high (≥10%) SCORE2 risk, respectively. For CACS ≥300 and CACS ≥100, miss rate was 8 and 11% for pre-screening by at least one CAD risk factor, 24 and 25% for at least one ROBINSCA risk factor, and 67 and 67% for moderately increased UAE, respectively. Conclusion Many individuals with high CACS in the general population are left unidentified when only performing CACS in case of at least moderate (≥5%) SCORE2, which closely resembles current clinical practice. Less stringent pre-screening by presence of at least one CAD risk factor to guide CACS identifies more individuals with high CACS and could improve CAD prevention.

Ties, Daan (ORCID:0000000164729886)↗

Development and validation of a diabetes risk score among two populations

The purpose of this study was to assess the validity of a practical diabetes risk score amongst two heterogenous populations, a working population and a non-working population. Study population 1 (n = 2,089) participated in a large-scale screening program offered to retired workers to discover previously undetected/incipient chronic illness. Study population 2 (n = 3,293) was part of a Colorado worksite wellness program health risk assessment. We assessed the relationship between a continuous diabetes risk score at baseline and development of diabetes in the future using logistic regression. Receiver operating curves and sensitivity/specificity of the models were calculated. Across both study populations, we observed that participants with diabetes at follow-up had higher diabetes risk scores at baseline than participants who did not have diabetes at follow-up. On average, the odds ratio of developing diabetes in the future was 1.38 (95% CI: 1.26–1.50, p < 0.0001) for study population 1 and 1.68 (95% CI: 1.45–1.95, p-value < 0.0001) for study population 2. These findings indicate that the diabetes risk score may be generalizable to diverse individuals, and thus potentially a population level diabetes screening tool. Minimally-invasive diabetes risk scores can aid in the identification of sub-populations of individuals at risk for diabetes.

60 APPLIED LIFE SCIENCES↗

Colonoscopy Screening in the US Astronaut Corps

Historically, colonoscopy screenings for astronauts have been conducted to ensure that astronauts are in good health for space missions. This data has been identified as being useful for determining appropriate occupational surveillance targets and requirements. Colonoscopies in the astronaut corps can be used for: (a) Assessing overall colon health, (b) A point of reference for future tests in current and former astronauts, (c) Following-up and tracking rates of colorectal cancer and polyps; and (d) Comparison to military and other terrestrial populations. In 2003, medical screening requirements for the active astronaut corps changed to require less frequent colonoscopies. Polyp removal during a colonoscopy is an intervention that prevents the polyp from potentially developing into cancer and decreases the individual's risk for colon cancer.

Masterova, K.↗

Computer-aided classification of suspicious pigmented lesions using wide-field images

Early identification of melanoma is conducted through whole-body visual examinations to detect suspicious pigmented lesions, a situation that fluctuates in accuracy depending on the experience and time of the examiner. Computer-aided diagnosis tools for skin lesions are typically trained using pre-selected single-lesion images, taken under controlled conditions, which limits their use in wide-field scenes. Here, we propose a computer-aided classifier system with such input conditions to aid in the rapid identification of suspicious pigmented lesions at the primary care level. 133 patients with a multitude of skin lesions were recruited for this study. All lesions were examined by a board-certified dermatologist and classified into “suspicious” and “non-suspicious”. A new clinical database was acquired and created by taking Wide-Field images of all major body parts with a consumer-grade camera under natural illumination condition and with a consistent source of image variability. 3–8 images were acquired per patient on different sites of the body, and a total of 1759 pigmented lesions were extracted. A machine learning classifier was optimized and build into a computer aided classification system to binary classify each lesion using a suspiciousness score. In a testing set, our computer-aided classification system achieved a sensitivity of 100% for suspicious pigmented lesions that were later confirmed by dermoscopy examination (“SPL_A”) and 83.2% for suspicious pigmented lesions that were not confirmed after examination (“SPL_B”). Sensitivity for non-suspicious lesions was 72.1%, and accuracy was 75.9%. With these results we defined a suspiciousness score that is aligned with common macro-screening (naked eye) practices. This work demonstrates that wide-field photography combined with computer-aided classification systems can distinguish suspicious from non-suspicious pigmented lesions, and might be effective to assess the severity of a suspicious pigmented lesions. We believe this approach could be useful to support skin screenings at a population-level.

60 APPLIED LIFE SCIENCES↗

Results of the second Round Robin on opening-load measurement conducted by ASTM Task Group E24.04.04 on crack closure measurement and analysis

A second experimental Round Robin on the measurement of the crack opening load in fatigue crack growth tests has been completed by the ASTM Task Group E24.04.04 on Crack Closure Measurement and Analysis. Fourteen laboratories participated in the testing of aluminum alloy compact tension specimens. Opening-load measurements were made at three crack lengths during constant Delta K, constant stress ratio tests by most of the participants. Four participants made opening-load measurements during threshold tests. All opening-load measurements were based on the analysis of specimens compliance behavior, where the displacement/strain was measured either at the crack mouth or the mid-height back face location. The Round Robin data were analyzed for opening load using two non-subjective analysis methods: the compliance offset and the correlation coefficient methods. The scatter in the opening load results was significantly reduced when some of the results were excluded from the analysis population based on an accept/reject criterion for raw data quality. The compliance offset and correlation coefficient opening load analysis methods produced similar results for data populations that had been screened to eliminate poor quality data.

Phillips, E. P.↗

Improved high-throughput screening technique to rapidly isolate Chlamydomonas transformants expressing recombinant proteins

Abstract The single-celled eukaryotic green alga Chlamydomonas reinhardtii has long been a model system for developing genetic tools for algae, and is also considered a potential platform for the production of high-value recombinant proteins. Identifying transformants with high levels of recombinant protein expression has been a challenge in this organism, as random integration of transgenes into the nuclear genome leads to low frequency of cell lines with high gene expression. Here, we describe the design of an optimized vector for the expression of recombinant proteins in Chlamydomonas , that when transformed and screened using a dual antibiotic selection, followed by screening using fluorescence activated cell sorting (FACS), permits rapid identification and isolation of microalgal transformants with high expression of a recombinant protein. This process greatly reduces the time required for the screening process, and can produce large populations of recombinant algae transformants with between 60 and 100% of cells producing the recombinant protein of interest, in as little as 3 weeks, that can then be used for whole population sequencing or individual clone analysis. Utilizing this new vector and high-throughput screening (HTS) process resulted in an order of magnitude improvement over existing methods, which normally produced under 1% of algae transformants expressing the protein of interest. This process can be applied to other algal strains and recombinant proteins to enhance screening efficiency, thereby speeding up the discovery and development of algal-derived recombinant protein products. Key points • A protein expression vector using double-antibiotic resistance genes was designed • Double antibiotic selection causes fewer colonies with more positive for phenotype • Coupling the new vector with FACS improves microalgal screening efficiency > 60%

59 BASIC BIOLOGICAL SCIENCES↗

Kennedy Space Center Coronary Heart Disease Risk Screening Program

The number one cause of death in the U.S. is coronary heart disease (CHD). It is probably a major cause of death and disability in the lives of employees at Kennedy Space Center (KSC) as well. The KSC Biomedical Office used a multifactorial mathematical formula from the Framingham Heart Study to calculate CHD risk probabilities for individuals in a segment of the KSC population that required medical evaluation for job certification. Those assessed to be high-risk probabilities will be targeted for intervention. Every year, several thousand KSC employees require medical evaluations for job related certifications. Most medical information for these evaluations is gathered on-site at one of the KSC or Cape Canaveral Air Station (CCAS) medical clinics. The formula used in the Framingham Heart Study allows calculation of a person's probability of acquiring CHD within 10 years. The formula contains the following variables: Age, Diabetes, Smoking, Left Ventricular Hypertrophy, Blood Pressure (Systolic or Diastolic), Cholesterol, and HDL cholesterol. The formula is also gender specific. It was used to calculate the 10-year probabilities of CHD in KSC employees who required medical evaluations for job certifications during a one-year time frame. This KSC population was profiled and CHD risk reduction interventions could be targeted to those at high risk. Population risk could also be periodically reevaluated to determine the effectiveness of intervention. A 10-year CHD risk probability can be calculated for an individual quite easily while gathering routine medical information. An employee population's CHD risk probability can be profiled graphically revealing high risk segments of the population which can be targeted for risk reduction intervention. The small audience of NASA/contractor physicians, nurses and exercise/fitness professionals at the breakout session received the lecture very well. Approximately one third indicated by a show of hands that they would be interested in implementing a similar program at their NASA Center. Questions were asked pertaining to standardization for age, the validity of using the idealized male values also for the female population, and indications of the screening test's sensitivity and specificity.

Tipton, David A.↗

Screening EEG in Aircrew Selection: Clinical Aerospace Neurology Perspective

As clinical aerospace neurologists we do not favor using screening EEG in pilot selection on unselected and otherwise asymptomatic individuals. The role of EEG in aviation screening should be as an adjunct to diagnosis, and the decision to disqualify a pilot should never be based solely on the EEG. Although a policy of using a screening EEG in an unselected population might detect an individual with a potentially increased relative risk, it would needlessly exclude many applicants who would probably never have a seizure. A diagnostic test performed on an asymptomatic individual without clinical indications, in a population with a low prevalence of disease (seizure) may be of limited or possibly detrimental value. We feel that rather than do EEGs on all candidates, a better approach would be to perform an EEG for a specific indication, such as family history of seizure, single convulsion (seizure) , history of unexplained loss of consciousness or head injury. Routine screening EEGs in unselected aviation applications are not done without clinical indication in the U.S. Air Force, Navy, or NASA. The USAF discontinued routine screening EEGs for selection in 1978, the U.S. Navy discontinued it in 1981 , and NASA discontinued it in 1995. EEG as an aeromedical screening tool in the US Navy dates back to 1939. The US Navy routinely used EEGs to screen all aeromedical personnel from 1961 to 1981. The incidence of epileptiform activity on EEG in asymptomatic flight candidates ranges from 0.11 to 2.5%. In 3 studies of asymptomatic flight candidates with epileptiform activity on EEG followed for 2 to 15 years, 1 of 31 (3.2%), 1 of 30 (3.3%), and 0 of 14 (0%) developed a seizure, for a cumulative risk of an individual with an epileptiform EEG developing a seizure of 2.67% (2 in 75). Of 28,658 student naval aviation personnel screened 31 had spikes and/or slow waves on EEG, and only 1 later developed a seizure. Of the 28,627 who had a normal EEG, 4 later developed seizures, or .0139% (4/28627). After review of the value of the EEG as a screening tool, the US Navy now uses EEG only for certain clinical indications (head injury, unexplained loss of consciousness, family history of epilepsy, and abnormal neurological exam). Currently the US Navy does not use EEG for screening for any flight applicant without a neurologic indication. In the US Navy, an electroencephalographic pattern is determined to be epileptiform by a neurologist.

Clark, Jonathan B.↗

Measuring Image Navigation and Registration Performance at the 3-Sigma Level Using Platinum Quality Landmarks

Geostationary Operational Environmental Satellite (GOES) Image Navigation and Registration (INR) performance is specified at the 3- level, meaning that 99.7% of a collection of individual measurements must comply with specification thresholds. Landmarks are measured by the Replacement Product Monitor (RPM), part of the operational GOES ground system, to assess INR performance and to close the INR loop. The RPM automatically discriminates between valid and invalid measurements enabling it to run without human supervision. In general, this screening is reliable, but a small population of invalid measurements will be falsely identified as valid. Even a small population of invalid measurements can create problems when assessing performance at the 3-sigma level. This paper describes an additional layer of quality control whereby landmarks of the highest quality ("platinum") are identified by their self-consistency. The platinum screening criteria are not simple statistical outlier tests against sigma values in populations of INR errors. In-orbit INR performance metrics for GOES-12 and GOES-13 are presented using the platinum landmark methodology.

Carr, James L.↗

Discovery of genes that positively affect biomass and stress associated traits in poplar

Woody biomass serves as a renewable resource for various industries, including pulp and paper production, construction, biofuels, and electricity generation. However, the molecular mechanisms behind biomass traits are poorly understood, which significantly curtails the speed and efficiency of their improvement. We used activation tagging to discover genes that can positively affect tree biomass-associated traits. We generated and screened under greenhouse conditions a population of 2,700 independent activation tagging lines. A total of 761 lines, which had significantly and positively affected at least one biomass-associated trait, were discovered. The tag was positioned in the genome for forty lines which were affected in multiple traits and activation of proximal genes validated for a subset. For two lines we fully recapitulated the phenotype of the original lines through overexpression. Moreover, the overexpression led to more pronounced and additional improvements, not observed in the original lines. Importantly, the overexpression of a Fasciclin-like gene (PtaFLA10) and a Patatin-like gene (PtaPAT) was found to substantially improve biomass, with a 40% increase in dry-stem weight, and enhance drought tolerance, respectively. Additionally, PtaPAT overexpression increased cellulose content, which is crucial for biofuel production. Our work shows that the activation tagging approach applied even on a non-genome saturation scale in a poplar tree can be successfully used for the discovery of genes positively modify biomass productivity. Such dominant forward genetics approaches can aid in biotechnological manipulation of woody biomass traits and help unravel the functions and mechanisms of individual genes, gene families, and regulatory modules.

Plant Sciences↗

A Specialized Ultrasound Protocol for NASA's Renal Stone Surveillance and Clinical Practice

INTRODUCTION Ample evidence exists on the effectiveness of ultrasound in the diagnosis of kidney stones. However, terrestrial practice is mostly concerned with diagnosis of clinically significant urolithiasis. Adapting this non-irradiating, low-cost imaging modality for the asymptomatic astronaut population offers high-sensitivity screening and limits their career radiation dose. METHODS NASA developed a novel ultrasound-based detection and surveillance protocol to identify, categorize, and monitor mineralized renal material (MRM) in astronauts. The term MRM was developed to denote abnormal, presumably calcified, focal material of unknown clinical significance in the kidneys. Sonographic criteria for MRMs include measurable echogenic foci, their detectability in multiple, designated imaging plains, posterior shadowing, and “twinkle” pattern visualized in Color Doppler and/or demonstrated in Spectral Doppler modes. The mere discovery of an MRM does not trigger further imaging or intervention, unless the affected crewmember is mission-assigned, or the MRM meets actionable criteria based on size, location, and sonographic characteristics. If the threshold is met, the crew surgeon is notified, and additional diagnostic imaging and urology consultation are considered. RESULTS In total, 73 individuals have been scanned using our specialized methods, 60 have had more than one study done. As of April 2023, 282 total studies have been performed. So far, over 30 pairs of pre-and postflight studies have been obtained, and the findings are presented elsewhere in this panel. DISCUSSION A surveillance program was initiated nine years ago to screen asymptomatic members of the astronaut corps for renal calcifications, from their initial hiring, through their mission timeframes, and throughout their career. The goal is to reduce the probability that an astronaut will fly with a renal stone that may become symptomatic. This also gives NASA the information it needs to improve screening criteria for future long-duration crewed missions.

H Lyons↗

Conjunction Assessment Screening Volume Sizing and Event Filtering in Light of Natural Conjunction Event Development Behaviors

Conjunction Assessment screening volumes used in the protection of NASA satellites are constructed as geometric volumes about these satellites, of a size expected to capture a certain percentage of the serious conjunction events by a certain time before closest approach. However, the analyses that established these sizes were grounded on covariance-based projections rather than empirical screening results, did not tailor the volume sizes to ensure operational actionability of those results, and did not consider the adjunct ability to produce data that could provide prevenient assistance for maneuver planning. The present study effort seeks to reconsider these questions based on a six-month dataset of empirical screening results using an extremely large screening volume. The results, pursued here for a highly-populated orbit regime near 700 km altitude, identify theoretical limits of screening volume performance, explore volume configuration to facilitate both maneuver remediation planning as well as basic asset protection, and recommend sizing principles that maximize volume performance while minimizing the capture of "chaff" conjunctions that are unlikely ever to become serious events.

screening volume↗

Singleplex, multiplex and pooled sample real-time RT-PCR assays for detection of SARS-CoV-2 in an occupational medicine setting

Abstract For workplaces which cannot operate as telework or remotely, there is a critical need for routine occupational SARS-CoV-2 diagnostic testing. Although diagnostic tests including the CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel (CDC Diagnostic Panel) (EUA200001) were made available early in the pandemic, resource scarcity and high demand for reagents and equipment necessitated priority of symptomatic patients. There is a clearly defined need for flexible testing methodologies and strategies with rapid turnaround of results for (1) symptomatic, (2) asymptomatic with high-risk exposures and (3) asymptomatic populations without preexisting conditions for routine screening to address the needs of an on-site work force. We developed a distinct SARS-CoV-2 diagnostic assay based on the original CDC Diagnostic Panel (EUA200001), yet, with minimum overlap for currently employed reagents to eliminate direct competition for limited resources. As the pandemic progressed with testing loads increasing, we modified the assay to include 5-sample pooling and amplicon target multiplexing. Analytical sensitivity of the pooled and multiplexed assays was rigorously tested with contrived positive samples in realistic patient backgrounds. Assay performance was determined with clinical samples previously assessed with an FDA authorized assay. Throughout the pandemic we successfully tested symptomatic, known contact and travelers within our occupational population with a ~ 24–48-h turnaround time to limit the spread of COVID-19 in the workplace. Our singleplex assay had a detection limit of 31.25 copies per reaction. The three-color multiplexed assay maintained similar sensitivity to the singleplex assay, while tripling the throughput. The pooling assay further increased the throughput to five-fold the singleplex assay, albeit with a subtle loss of sensitivity. We subsequently developed a hybrid ‘multiplex-pooled’ strategy to testing to address the need for both rapid analysis of samples from personnel at high risk of COVID infection and routine screening. Herein, our SARS-CoV-2 assays specifically address the needs of occupational healthcare for both rapid analysis of personnel at high-risk of infection and routine screening that is essential for controlling COVID-19 disease transmission. In addition to SARS-CoV-2 and COVID-19, this work demonstrates successful flexible assays developments and deployments with implications for emerging highly transmissible diseases and future pandemics.

60 APPLIED LIFE SCIENCES↗

Accelerated test techniques for micro-circuits: Evaluation of high temperature (473 k - 573 K) accelerated life test techniques as effective microcircuit screening methods

The application of high temperature accelerated test techniques was shown to be an effective method of microcircuit defect screening. Comprehensive microcircuit evaluations and a series of high temperature (473 K to 573 K) life tests demonstrated that a freak or early failure population of surface contaminated devices could be completely screened in thirty two hours of test at an ambient temperature of 523 K. Equivalent screening at 398 K, as prescribed by current Military and NASA specifications, would have required in excess of 1,500 hours of test. All testing was accomplished with a Texas Instruments' 54L10, low power triple-3 input NAND gate manufactured with a titanium- tungsten (Ti-W), Gold (Au) metallization system. A number of design and/or manufacturing anomalies were also noted with the Ti-W, Au metallization system. Further study of the exact nature and cause(s) of these anomalies is recommended prior to the use of microcircuits with Ti-W, Au metallization in long life/high reliability applications. Photomicrographs of tested circuits are included.

Johnson, G. M.↗