Concurrent Testing Research Articles

Concurrent Preimplantation Genetic Testing and Competence Assessment of Human Embryos by Transcriptome Sequencing.

Preimplantation genetic testing (PGT) can minimize the risk of birth defects. However, the accuracy and applicability of routine PGT is confounded by uneven genome coverage and high allele drop-out rate from existing single-cell whole genome amplification methods. Here, a method to diagnose genetic mutations and concurrently evaluate embryo competence by leveraging the abundant mRNA transcript copies present in trophectoderm cells is developed. The feasibility of the method is confirmed with 19 donated blastocysts. Next, the method is applied to 82 embryos from 26 families with monogenic defects for simultaneous mutation detection and competence assessment. The accuracy rate of direct mutation detection is up to 95%, which is significantly higher than DNA-based method. Meanwhile, this approach correctly predicted seven out of eight (87.5%) embryos that failed to implant. Of six embryos that are predicted to implant successfully, four met such expectations (66.7%). Notably, this method is superior at conditions for mutation detection that are challenging when using DNA-based PGT, such as when detecting pathogenic genes with a high de novo rate, multiple pseudogenes, or an abnormal expansion of CAG trinucleotide repeats. Taken together, this study establishes the feasibility of an RNA-based PGT that is also informative for assessing implantation competence.

#1329 Assessing eGFR performance against measured GFR stratifying for ethnicity and albumin: development of the AIM CKD UK study

Abstract Background and Aims Accurate measurement of kidney function using estimated glomerular filtration rate (eGFR) is essential for appropriate risk stratification of cardiovascular events, kidney failure and prescribing medications. The AIM CKD UK study (IRAS 320215) will assess the accuracy of current and novel creatinine-based eGFR equations compared to exogenous filtration marker derived measured GFR (mGFR) for people of different ethnicities in large national cohort. We performed a preliminary analysis from a single centre in AIM CKD UK to inform future data collection and assessed: Method All adults (≥18-years) who had paired mGFR and eGFR tests within 30 days between 2009-2022 were included. Patients with mGFR ≥150 ml/min/1.73 m2, incomplete datasets and previous amputations were excluded. Age, reported ethnicity, biological sex, referral specialty, height, weight, exogenous filtration marker, creatinine and albumin concentration were recorded. eGFR was calculated from creatinine, age and sex using five equations (Fig. 1). Each eGFR equation was compared to mGFR using median bias, precision, 30% accuracy (P30). Agreement was demonstrated with Bland-Altman plots. Results were stratified for time between eGFR-mGFR (≤7 days vs 8-30 days) and albumin concentration; low (<35 g/L) vs normal / high (≥35 g/L). Assessment of equation performance in different ethnicity was also stratified for the three largest ethnicity groups (White, Black and South Asian ethnicity). Data were analysed using software R V4.2.2. Results There were 2623 patients who met the inclusion criteria. Mean age was 54.8 ± 13.1 years, with 57.8% male (N = 1515). The majority of patients were White ethnicity (58.7%; N = 1539). Median mGFR was 77 mL/min/1.73 m2 (IQR 62–91 mL/min/1.73 m2). Median serum creatinine concentration was 74 umol/L (IQR 61–90 umol/L). The CKD-EPI 2009 equation, compared to mGFR, demonstrated a median bias of +12.8 mL/min/1.73 m2, percentage bias of 16.9% and P30 of 68.6%. The Lund-Malmo revised equation performed best with median bias of 2.1 mL/min/1.73 m2 (percentage bias 2.9%) and a P30 of 82.7%. Agreement, with ethnicity stratification is summarised in Table 1. The majority of patients (N = 2439; 93.0%) had paired mGFR-eGFR tests within 7-days. There was no significant difference between the median bias of each group (P = .749). 2610 (99.5%) patients had concurrent albumin tests performed; 183 (7.0%) of these patients had low albumin concentrations. Median bias was significantly higher in this group compared to normal/high albumin for each equation (e.g. Low vs Normal/high albumin median bias for CKD-EPI equation = 20.3 vs 12.5 mL/min/1.73 m2; P <. 001). Conclusion The LM revised and European Kidney Function Consortium equations perform best in this cohort. Limitations include selection bias and retrospective data. Future data analysis for the AIM CKD study can include paired samples within 30 days as there is no significant difference between 0-7 and 8-30 days. The impact of serum albumin on mGFR-eGFR association in a larger cohort stratified for confounding variables, such as liver disease, malignancy and body mass index is required.

Six-minute walk test in healthy British service personnel

IntroductionThe 6 min walk test (6MWT) is a widely used, safe and effective submaximal exercise test. The primary outcome is the distance walked, but additional physiological and patient-reported metrics can...

Validation of the Mexican version of the EORTC QLQ-CR29 in patients with colorectal cancer.

The evaluation of the quality of life (QoL) of patients with colorectal cancer (CRC) is an essential measure to measure the impact of the disease and treatments on the lives of patients. However, in Latin America there is no validated and reliable instrument to assess this construct. This study aims to validate the EORTC QLQ-CR29 instrument in the Mexican population with CRC. This study aims to validate the EORTC QLQ-CR29 instrument in the Mexican population with CRC. The study used an instrumental design and a nonprobabilistic sample due to availability, made up of 251 patients with CRC, with an average age of 54.7 ± 12.28 years. Exploratory and confirmatory factor analyses were performed, as well as concurrent validity tests. The exploratory factorial analysis yielded 4 factors that explained 51.64% of the variance, with a Cronbach reliability coefficient of .766 and an Omega index of .725. The confirmatory factor analysis indicated that the proposed theoretical model fits the data almost perfectly, with an error close to 0, which shows that it is a balanced and parsimonious instrument to measure the QoL of the patients with CRC. The EORTC QLQ-CR29 instrument proved to be a valid and reliable instrument for use in clinical care and research directed at patients with CRC in Mexico. Its use is recommended by multidisciplinary health teams in oncology in Mexico, since it allows knowing the patient's perspective on the impact of CRC on their life, guiding therapeutic decision-making and being a primary outcome measure.

Concurrent validity and test–retest reliability of VALD ForceDecks' strength, balance, and movement assessment tests

ObjectivesTo evaluate the concurrent validity and test–retest reliability of common movement, strength, and balance tests using portable uniaxial dual force plates. DesignRepeated measures cross-sectional study. MethodsSixteen healthy individuals participated in two testing sessions, where they performed 12 different movement, strength, and balance tests. Vertical ground reaction force and centre of pressure data were collected using the VALD ForceDecks simultaneously with ground-embedded laboratory force plates. Concurrent validity was assessed using root mean square error for raw time-series data and Bland–Altman plots for discrete metrics. Test–retest reliability was assessed using intraclass correlation coefficients and minimal detectable changes. ResultsForceDecks recorded vertical ground reaction forces and center of pressure with high accuracy compared to laboratory force plates. The mean bias between systems was negligible (<2 N or 0.1 mm), with small limits of agreement (<5 N or 1 mm). Overall, 530/674 (79%) showed good or excellent validity (<10% difference) and 611/773 (79%) had good or excellent reliability (intraclass correlation coefficient >0.75). ForceDecks reliability was similar to laboratory force plates (<0.07 intraclass correlation coefficient median difference for all metrics). ConclusionsPortable uniaxial force plates record highly accurate vertical ground reaction forces and center of pressure during a range of movement, strength, and balance tests. The VALD ForcDecks are a valid and reliable alternative to laboratory force plates when strict standardized testing and data analysis procedures are followed. Users should be aware of the validity and reliability characteristics of the tests and metrics they choose.

Prevalence of high-risk human papillomavirus infection among women with diabetes mellitus in Accra, Ghana

BackgroundThere is increasing evidence of a higher risk and poorer prognosis of cervical cancer among women with diabetes mellitus (DM) compared to the general population. These are mediated by higher susceptibility to persistent high-risk human papillomavirus (hr-HPV) infection due to dysfunctional clearance in an immunocompromised state. We aimed to determine the prevalence of hr-HPV infection and cervical lesions in a cohort of women with DM in Ghana. We further disaggregated the prevalence according to DM type and explored factors associated with hr-HPV infection.MethodsThis retrospective descriptive cross-sectional study assessed 198 women with DM who underwent cervical screening via concurrent hr-HPV DNA testing and visual inspection with acetic acid in an outpatient department of the National Diabetes Management and Research Centre in Korle-Bu Teaching Hospital, Accra from March to May 2022. Univariate and multivariable binary logistic regression were used to explore factors associated with hr-HPV positivity.ResultsAmong 198 women with DM (mean age, 60.2 ± 12.1 years), the overall hr-HPV prevalence rate was 21.7% (95% CI, 16.1–28.1), disaggregated as 1.5% (95% CI, 0.3–4.4) each for HPV16 and HPV18 and 20.7% (95% CI, 15.3–27.0) for other HPV genotype(s). Respective hr-HPV prevalence rates were 37.5% (95% CI, 15.2–64.6) for type 1 DM, 19.8% (95% CI, 13.9–26.7) for type 2 DM, and 25.0% (95% CI, 8.7–49.1) for unspecified/other DM types. Past use of the combined contraceptive pill independently increased the risk of hr-HPV infection by approximately three times (adjusted odds ratio [aOR] = 2.98; 95% CI, 1.03 − 8.64; p-value = 0.045), whereas each unit increase in FBG level increased the odds of hr-HPV infection by about 15% (aOR = 1.15; 95% CI, 1.02 − 1.30; p-value = 0.021).ConclusionOur study points to a high prevalence of hr-HPV among women with DM and highlights a need for glycemic control among them as this could contribute to lowering their odds of hr-HPV infection. The low overall rates of HPV vaccination and prior screening also indicate a need to build capacity and expand the scope of education and services offered to women with DM as regards cervical precancer screening.

Capturing Evaluation Capacity: Findings from a Mapping of Evaluation Capacity Instruments

This article surveys the literature on organizational evaluation capacity (EC) instruments. Over the past 25 years, articles have been published in four waves covering the development of organizational evaluation capacity models, surveys of the evaluation capacity and practice landscape, the development of EC instruments, and their replication and adaptation. Altogether, the authors identified 20 studies applying 16 EC instruments. Several studies applied variants of the same instrument. We found instruments of three types: checklists, rubrics, and questionnaires. The instruments vary in terms of type, purpose, scoring, dimensions, number of items, and validation processes. In general, the validation studies demonstrated acceptable face, content, construct validity, and internal consistency. Only two studies tested for predictive validity. No studies covered concurrent validity and test–retest, or inter-rater reliability.

Peer-Assessment Academic Integrity Scale (PAAIS-24)

This study aims to develop an academic integrity scale to help lecturers evaluate the academic integrity of university students with peer-assessment learning experiences using the ADDIE research and development method. Twenty-four items were designed using the concepts of academic integrity; honesty, trust, fairness, respect, responsibility, and courage validated by six raters and tested on 520 students from various universities in Indonesia. Testing content validity using the Aiken-V formula, construct validity testing using discriminant indexes, factor analysis (Exploratory and Confirmatory Factor Analysis), and concurrent validity testing by correlating PAAIS-24 with the developed Academic Integrity Scale. While the reliability test used Cronbach's alpha formula. The study results proved that each item of content validity meets with an Aiken value &gt;0.80; on construct validity testing, the discriminant index value is &gt;0.50, and the EFA and CFA loading factor values are &gt;0.50. In addition, the model is appropriate because the theoretical model of PAAIS-24 is in accordance with empirical data. Whereas in reliability testing, Cronbach's alpha value is 0.95. Lastly, PAAIS-24 is one of the credible instruments. It contributes to developing knowledge that assists lecturers in measuring, assessing, and evaluating student academic integrity based on peer-assessment to promote increased academic performance. Doi: 10.28991/ESJ-2024-08-02-09 Full Text: PDF

Examining the Measurement Invariance and Validity of the SSIS SEL Brief + Mental Health Scales – Student Version in Austria and Germany

The SSIS SEL Brief + Mental Health Scales (SSIS SELb+MHS) are multi-informant assessments developed in the United States to assess the social and emotional learning (SEL) competencies and emotional behavior concerns (EBCs) of school-age youth. Although there are translations of the SEL items of the SSIS SELb+MHS available in other languages, a German translation has never been completed and validated, despite the growing need for SEL and mental health assessment in German-speaking countries. To address this need, this study’s primary purpose was the examination of a German translation of the assessment with a specific focus on measurement invariance and concurrent validity invariance testing with 821 3rd through 6th-grade students in Austria and Germany. Results indicated that the SELb+MHS items clustered into 2 SEL factors and 2 EBC factors. With regard to measurement invariance, the SELb+MHS functioned similarly across both Austria and Germany and full scalar invariance was achieved. Additionally, the overall pattern of concurrent validity relationships was as expected and similar across countries. Implications and future directions are discussed.

BRIDGING THEORY AND PRACTICE: COMPARATIVE INSIGHTS INTO EVALUATING USER INTERFACES

Abstract Keywords Cite This Article as User interface (UI) evaluation is an important aspect of software development, ensuring that software or systems are efficient and user satisfactory. Among the various usability testing methods available, Cognitive Walkthrough Method, Heuristic Evaluation Method and Concurrent Usability Testing Method stand out as most popular approaches. This research paper presents a comparative analysis of these testing methods, emphasizing their strengths, flaws, and applicability in different situations. Through a detailed analysis of each testing method's procedural steps, and practical concerns, we aim to provide insights into their effectiveness and suitability for evaluating User Interface (UI) designs. Additionally, we discuss potential synergies and inadequacies when combining these testing methods in practice. Our results and findings contribute to a deeper understanding of UI evaluation techniques and provide guidance for selecting the most appropriate approach for testing team’s specific needs.

Digitally improving UK police surveillance and incidence response using real-time crowd reporting app: Digipolice

Overtime, evolving technologies has made ways of monitoring and controlling crime and action in the United Kingdom (UK) become more challenging which needs optimization with the help of technologies. Also with the rate of crime across cities in the UK like mass shootings, murder and gang gun battles, the UK Police system within localities are overwhelmed or may not efficiently cope with crime alerts and incidences coming in at increasing frequencies. However looking in the area of real time crowd reporting, there is need to leverage technology to enhance public safety, improve incident response, and foster community engagement. This necessitated the aim of this study to develop a digital policing surveillance app for crowd reporting in the UK. By utilizing digital policing surveillance apps, the aim is to improve crowd management capabilities by enabling real-time reporting of incidents and observations from both the public and law enforcement personnel. This was positioned to facilitate better situational awareness, efficient resource allocation, and effective response strategies. To achieve the objectives, Python Programming Language 3.8 were deployed together with a Django Framework and a Microsoft Visual Studio Build Tools. In the DP system, the Model-View-Controller (MVC) pattern, which divides an application into three interconnected components—the model, the view, and the controller—was used for the architectural design of the system. For the database, Django's ORM makes it simple to support many databases, and in this project straightforward SQLite3 database were utilised which is ideal for small-footprint applications. Using WebSockets to establish real-time, bidirectional communication between web clients and servers, the user interface and intelligence board for the system were developed. A clean designed frontend design system with Bootstrap version 5—an open-source, reusable design framework created by Twitter—was selected for its easy user interface. The system was put through 50 concurrent load tests with actual users swarming the app since the DP app was subjected to hundreds of people complaining in real time. 2. The host computer had a Core i5 vPro CPU running at 4GHz and 4GB of RAM. The result shows that 50 users successfully generated an average of 29.7 requests per second. The system scaled up nicely to 50 users and reached its highest response time of 2600 milliseconds (2.6 seconds) in total. A dramatic rise in activity and a longer response time occurred after there were more than 50 users. The system could not operate at its peak efficiency with 100 users because response times were inconsistent and exceeded 7000 milliseconds (7 seconds) for each request. The effectiveness of the online deployment was evaluated with respectable results, and the system requirements also underwent successful testing. The appropriate investigation of ethical issues was done to meet requirements. DigiPolice has the potential to develop into a cutting-edge programme for real-time crowd surveillance and incident reporting. UK Police can employ it to as advancement to its “My Police” with as fast-track real-time and collaborative crowd reporting enhancements.

The impact of insomnia and depression on asthma control

Background Poor sleep quality is often reported by individuals with asthma, particularly by those who have poor asthma control overall. However, there is little understanding of how underlying sleep disorders such as insomnia may impact asthma control. Furthermore, given the frequent overlap of depression and insomnia, the incremental impact of mood disorders and insomnia on asthma control remains unclear. Methods We conducted a retrospective analysis of patients at a large asthma center to further elucidate connections between these disease processes. Asthma patients with and without a diagnosis of insomnia were matched by age, sex, Charlson comorbidity index, and biologic therapy. We evaluated the presence of concurrent obstructive sleep disorder, mood disorders, exacerbation frequency, and asthma control test (ACT) scores. Results From a cohort of 659 patients with an asthma diagnosis, 89 subjects with insomnia (13.5%) were matched 1:1 to patients without insomnia. Compared to those without insomnia, patients with insomnia were more likely to have a concurrent diagnosis of obstructive sleep apnea (57.3% vs. 18%, p < 0.001) and to have a diagnosis of depression or anxiety (68.5% vs. 11.4%, p < 0.001). Among insomnia patients, there was an average of 0.93 asthma exacerbations per year, compared to 0.59 exacerbations per year for those without insomnia (p = 0.039). Conclusion Our data reveal a considerable interaction between insomnia, depression, and obstructive sleep apnea in individuals with asthma. The increased exacerbation rate suggests that underlying sleep and mood disorders negatively affect asthma control.

Study on tiered storage algorithm based on heat correlation of astronomical data

With the surge in astronomical data volume, modern astronomical research faces significant challenges in data storage, processing, and access. The I/O bottleneck issue in astronomical data processing is particularly prominent, limiting the efficiency of data processing. To address this issue, this paper proposes a tiered storage algorithm based on the access characteristics of astronomical data. The C4.5 decision tree algorithm is employed as the foundation to implement an astronomical data access correlation algorithm. Additionally, a data copy migration strategy is designed based on tiered storage technology to achieve efficient data access. Preprocessing tests were conducted on 418GB NSRT (Nanshan Radio Telescope) formaldehyde spectral line data, showcasing that tiered storage can potentially reduce data processing time by up to 38.15%. Similarly, utilizing 802.2 GB data from FAST (Five-hundred-meter Aperture Spherical radio Telescope) observations for pulsar search data processing tests, the tiered storage approach demonstrated a maximum reduction of 29.00% in data processing time. In concurrent testing of data processing workflows, the proposed astronomical data heat correlation algorithm in this paper achieved an average reduction of 17.78% in data processing time compared to centralized storage. Furthermore, in comparison to traditional heat algorithms, it reduced data processing time by 5.15%. The effectiveness of the proposed algorithm is positively correlated with the associativity between the algorithm and the processed data. The tiered storage algorithm based on the characteristics of astronomical data proposed in this paper is poised to provide algorithmic references for large-scale data processing in the field of astronomy in the future.

Prevalence of high-risk human papillomavirus infection and cervical lesions among female migrant head porters (kayayei) in Accra, Ghana: a pilot cross-sectional study

BackgroundLittle attention has been given to the risk of high-risk human papillomavirus (hr-HPV) infection and cervical precancerous lesions among female migrant head porters (kayayei) in Ghana, as a vulnerable group, and to promote cervical screening in these women. This pilot study aimed to determine the prevalence of hr-HPV infection and cervical lesions among kayayei in Accra, the capital of the Greater Accra Region of Ghana and to describe our approach to triaging and treating these women.MethodsThis descriptive cross-sectional cohort study involved the screening of 63 kayayei aged ≥ 18 years at the Tema Station and Agbogbloshie markets in March 2022 and May 2022. Concurrent hr-HPV DNA testing (with the MA-6000 platform) and visual inspection with acetic acid (VIA) was performed. We present prevalence estimates for hr-HPV DNA positivity and VIA ‘positivity’ as rates, together with their 95% confidence intervals (CIs). We performed univariate and multivariable nominal logistic regression to explore factors associated with hr-HPV infection.ResultsGross vulvovaginal inspection revealed vulval warts in 3 (5.0%) and vaginal warts in 2 (3.3%) women. Overall, the rate of hr-HPV positivity was 33.3% (95% CI, 21.7–46.7), whereas the VIA ‘positivity’ rate was 8.3% (95% CI, 2.8–18.4). In the univariate logistic regression analysis, none of the sociodemographic and clinical variables assessed, including age, number of prior pregnancies, parity, past contraceptive use, or the presence of abnormal vaginal discharge showed statistically significant association with hr-HPV positivity. After controlling for age and past contraceptive use, only having fewer than two prior pregnancies (compared to having ≥ 2) was independently associated with reduced odds of hr-HPV infection (adjusted odds ratio, 0.11; 95% CI, 0.02–0.69).ConclusionIn this relatively young cohort with a high hr-HPV positivity rate of 33.3% and 8.3% of women showing cervical lesions on visual inspection, we posit that kayayei may have an increased risk of developing cervical cancer if their accessibility to cervical precancer screening services is not increased.

The combination of high-frequency QRS and ST-segment alterations during exercise stress tests enhanced the diagnostic efficacy for coronary artery disease.

High-frequency QRS (HF-QRS) manifests as a novel adjunct electrocardiographic marker with potential utility in coronary artery disease (CAD) detection. We hypothesize that HF-QRS analysis may be superior to conventional ST-segment analysis in detecting CAD, and the combination of these two analyses in the exercise stress test may enhance the diagnostic efficacy for CAD. The study incorporated a sample of 157 patients (mean age 62 9 years) referred for nonemergent angiography. Before angiography, patients underwent exercise stress testing utilizing an upright bicycle. High-resolution electrocardiogram (ECG) data were collected during the exercise test, facilitating both HF-QRS and conventional ST-segment analyses. The diagnostic efficacy of HF-QRS and ST-segment analysis were compared, utilizing angiographic outcomes as the gold standard. The study design integrated HF-QRS analysis and ST-segment analysis via sequential and concurrent testing protocols. In terms of CAD detection, HF-QRS analysis displayed superior sensitivity compared to conventional ST-segment analysis (63% vs. 37%, p = .002). The serial test significantly increased specificity from 79% to 97% (p = .002) compared to ST-deviation analysis alone. It showed a markedly low sensitivity of 26%. The parallel test significantly increased sensitivity from 37% to 77% (p < .001), while retaining a moderate level of specificity of 51%. The quantity of ECG leads exhibiting a positive HF-QRS response demonstrated a correlation with the severity of CAD (p < .001). HF-QRS analysis exhibited superior sensitivity in detecting angiographically confirmed CAD relative to conventional ST-segment analysis. Moreover, the combination of HF-QRS and ST-segment alterations during exercise stress test enhanced the diagnostic efficacy for CAD.

Lower (1,3)-beta-d-glucan sensitivity and in vitro levels in Candida auris and Candida parapsilosis strains

ObjectivesThe serum (1,3)-beta-d-glucan (BDG) assay gives quicker results and has higher sensitivity than blood cultures, therefore it is advised for early diagnosis of invasive candidemia and/or discontinuation of empirical therapy. Its sensitivity may depend on different factors. The aim of our study was to analyse the in vitro and in vivo BDG levels in clinical isolates of three species of Candida responsible for candidemia. MethodsC. albicans, C. parapsilosis, and C. auris strains were collected from blood cultures of patients who had a concurrent (–1 to +3 days) serum BDG test (Fungitell assay). Supernatants of all strains were tested in quadruplicate for BDG levels. ResultsTwenty-two C. auris, 14 C. albicans, and ten C. parapsilosis strains were included. The median BDG levels in supernatants were 463 pg/mL (interquartile range [IQR] 379–648) for C. auris, 1080 pg/mL (IQR 830–1276) for C. albicans, and 755 pg/mL (IQR 511–930) for C. parapsilosis, with the significant difference among the species (p < 0.0001). Median serum BDG levels (IQR) were significantly lower in case C. auris and C. parapsilosis vs. C. albicans (p < 0.0001), respectively, 50 pg/mL (IQR 15–161) and 57 pg/mL (IQR 18–332), vs. 372 pg/mL (IQR 102–520). Sensitivity of serum BDG was 39% (95% confidence interval [CI], 18–64) in case of C. auris, 30% (95% CI, 8–65) C. parapsilosis and 78% (95% CI, 49–94) C. albicans candidemia. DiscussionIn our centre C. auris and C. parapsilosis strains have lower BDG content as compared with C. albicans, with a potential impact on serum BDG performance for the diagnosis of candidemia.

A Bilayer Method for Measuring Toughness and Strength of Dental Ceramics

The ever-increasing usage of ceramic materials in restorative dentistry necessitates a simple and effective method to evaluate flexural strength σF and fracture toughness KC. We propose a novel method to determine these quantities using a bilayer specimen composed of a brittle plate adhesively bonded onto a transparent polycarbonate substrate. When this bilayer structure is placed under spherical indentation, tunneling radial cracks initiate and propagate in the lower surface of the brittle layer. The failure analysis is based on previous theoretical relationships, which correlate σF with the indentation force P and layer thickness d, and KC with P and mean length of radial cracks. This work examines the accuracy and limitations of this approach using a wide range of contemporary dental ceramic materials. The effect of layer thickness, indenter radius, load level, and length and number of radial cracks are carefully examined. The accuracy of the predicted σF and KC is similar to those obtained with other concurrent test methods, such as biaxial flexure and 3-point bending (σF), and bending specimens with crack-initiation flaws (KC). The benefits of the present approach include treatment for small and thin plates, elimination of the need to introduce a precrack, and avoidance of dealing with local material nonlinearity effects for the KC measurements. Finally, the bilayer configuration resembles occlusal loading of a ceramic restoration (brittle layer) bonded to a posterior tooth (compliant substrate).

Effects of a concurrent maximum performance aerobic exercise test and cognitive task on physical and cognitive performance and effort

ABSTRACT Theoretical models of the effect of aerobic activity on concurrent cognitive tasks predict both impairments and improvements depending on the specific characteristics of the cognitive task. It can be assumed that both aerobic and cognitive tasks share neural resources of limited capacity (such as self-control) or that they interact by confliction or facilitation of brain activation. Detrimental effects are thus expected for cognitive tasks requiring self-control or conflicting brain activation. Effects of cognitive tasks on simultaneous aerobic activity have rarely been investigated, but predictions can be made by adaptations of the same theoretical models. The predicted effects should be enhanced at higher intensities due to increasing drains of neural resources and stronger brain activations. The current study aimed to investigate the interaction of aerobic and cognitive tasks under increasing and maximum physical load. Fifty participants (31 men, 19 women, mean age 22.8 ± 2.6 years) performed two maximum performance cycling tests, one in combination with mental rotation tasks (dual-task condition) and one without a cognitive task (control condition). Cognitive (reaction time, accuracy) and physical (power, cadence) performance, as well as objective (heart rate) and subjective (cognitive and physical ratings of perceived exertion) effort, were measured during the respective tests. The results showed increased cognitive effort during increased physical load and a focus on speed rather than accuracy, which can be interpreted in support of the models. Physical performance, however, could be upheld without increased physiological effort. The physical results contradict the suspected impairment predicted by the adaptations of the theoretical models.

Concurrent Tissue and Circulating Tumor DNA Molecular Profiling to Detect Guideline-Based Targeted Mutations in a Multicancer Cohort

Tissue-based next-generation sequencing (NGS) of solid tumors is the criterion standard for identifying somatic mutations that can be treated with National Comprehensive Cancer Network guideline-recommended targeted therapies. Sequencing of circulating tumor DNA (ctDNA) can also identify tumor-derived mutations, and there is increasing clinical evidence supporting ctDNA testing as a diagnostic tool. The clinical value of concurrent tissue and ctDNA profiling has not been formally assessed in a large, multicancer cohort from heterogeneous clinical settings. To evaluate whether patients concurrently tested with both tissue and ctDNA NGS testing have a higher rate of detection of guideline-based targeted mutations compared with tissue testing alone. This cohort study comprised 3209 patients who underwent sequencing between May 2020, and December 2022, within the deidentified, Tempus multimodal database, consisting of linked molecular and clinical data. Included patients had stage IV disease (non-small cell lung cancer, breast cancer, prostate cancer, or colorectal cancer) with sufficient tissue and blood sample quantities for analysis. Received results from tissue and plasma ctDNA genomic profiling, with biopsies and blood draws occurring within 30 days of one another. Detection rates of guideline-based variants found uniquely by ctDNA and tissue profiling. The cohort of 3209 patients (median age at diagnosis of stage IV disease, 65.3 years [2.5%-97.5% range, 43.3-83.3 years]) who underwent concurrent tissue and ctDNA testing included 1693 women (52.8%). Overall, 1448 patients (45.1%) had a guideline-based variant detected. Of these patients, 9.3% (135 of 1448) had variants uniquely detected by ctDNA profiling, and 24.2% (351 of 1448) had variants uniquely detected by solid-tissue testing. Although largely concordant with one another, differences in the identification of actionable variants by either assay varied according to cancer type, gene, variant, and ctDNA burden. Of 352 patients with breast cancer, 20.2% (71 of 352) with actionable variants had unique findings in ctDNA profiling results. Most of these unique, actionable variants (55.0% [55 of 100]) were found in ESR1, resulting in a 24.7% increase (23 of 93) in the identification of patients harboring an ESR1 mutation relative to tissue testing alone. This study suggests that unique actionable biomarkers are detected by both concurrent tissue and ctDNA testing, with higher ctDNA identification among patients with breast cancer. Integration of concurrent NGS testing into the routine management of advanced solid cancers may expand the delivery of molecularly guided therapy and improve patient outcomes.

Rapid and reliable testing for clinically actionable EGFR mutations in non-small cell lung cancer using the IdyllaTM platform: a real-world two-center experience in Greece

ABSTRACT Background Limited information exists on epidermal growth factor receptor (EGFR) molecular epidemiology in Greece. Next-generation sequencing (NGS) is the recommended method for EGFR genotyping in NSCLC. The Idylla Biocartis platform is a fully automated system for actionable EGFR mutation detection. Research design and methods We describe the prevalence of EGFR mutations in NSCLC patients in two high-volume clinical centers in Greece and compare key methods used for their determination. Eight hundred and fifty-seven FFPE samples from NSCLC patients were tested for EGFR mutations at University of Crete (UoC; n = 324) and at Evangelismos Hospital, Athens (Evangelismos; n = 503). Results The prevalence of EGFR mutations was 11.1% in the whole cohort (11.5% in non-squamous). The detection rate was 11.0% by NGS, 9.8% by Sanger and 11.3% by Idylla for the whole cohort (12.0% in non-squamous). The agreement between Idylla and Sanger was 93.2%. A targetable EGFR mutation was detected in 10.0% using tissue NGS alone, and in 16.0% using concurrent Idylla ctEGFR testing. Conclusion The frequency of EGFR mutations was as expected for a Caucasian population. The Idylla EGFR test performance is comparable to reference methods and with a shorter TAT. Adding a concurrent plasma Idylla test to tissue NGS testing increases the detection rate of EGFR mutations in NSCLC.