Panel Size Research Articles

French-Language Adaptation of the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V)

ObjectivesThis study aimed to adapt the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) protocol for perceptual voice assessment to the French language. The primary objective was to achieve consensus among an international panel of voice experts on the content of the adapted protocol. MethodsTo ensure the relevance and robustness of the French CAPE-V protocol, this study employed a systematic Delphi method and involved an international panel primarily comprising speech therapists and lecturers from France and Belgium. The multi-stage process included an initial panel size of 15 experts. Three rounds of online questionnaires, integrating both quantitative and qualitative data collection, were conducted. Participants provided feedback and ratings on various protocol elements until consensus was reached. Adaptations targeted the choice of task stimuli (sustained vowel, sentence reading, semi-spontaneous speech), of the rating scales, and vocal quality terminology. ResultsThe Delphi process achieved consensus on all elements of the adapted CAPE-V protocol. Notably, the sustained vowel task saw consensus in favor of the vowel /a/. Sentence adaptations achieved substantial agreement, with the final set unanimously approved. The simple Visual Analog Scale (VAS) emerged as the preferred rating scale. Agreement on terms for describing vocal qualities marked a crucial step in establishing a shared vocabulary among French-speaking voice experts. ConclusionsThe study successfully adapted the CAPE-V protocol for perceptual voice assessment to the French language through a systematic Delphi process. The final protocol closely resembles the original English version, maintaining its structure and core objectives. Consensus on sustained vowel tasks, sentence adaptations, rating scales, and vocal quality terminology indicates the relevance and robustness of the adapted protocol. Ongoing validation studies in France demonstrate the potential clinical utility of the adapted CAPE-V in French-speaking contexts, representing a significant step toward standardized and validated voice assessment tools for clinicians and researchers globally.

Tumor Mutation Burden as a Cornerstone in Precision Oncology Landscapes: Effect of Panel Size and Uncertainty in Cutoffs.

Tumor mutation burden (TMB) has profound implications for personalized cancer therapy, particularly immunotherapy. However, the size of the panel and the cutoff values for an accurate determination of TMB are still controversial. In this study, a pan-cancer analysis was performed on 22 cancer types from The Cancer Genome Atlas. The efficiency of gene panels of different sizes and the effect of cutoff values in accurate TMB determination was assessed on a large cohort using Whole Exome Sequencing data (n = 9929 patients) as the gold standard. Gene panels of four different sizes (i.e., 0.44-2.54 Mb) were selected for comparative analyses. The heterogeneity of TMB within and between cancer types is observed to be very high, and it becomes possible to obtain the exact TMB value as the size of the panel increases. In panels with limited size, it is particularly difficult to recognize patients with low TMB. In addition, the use of a general TMB cutoff can be quite misleading. The optimal cutoff value varies between 5 and 20, depending on the TMB distribution of the different tumor types. The use of comprehensive gene panels and the optimization of TMB cutoff values for different cancer types can make TMB a robust biomarker in precision oncology. Moreover, optimization of TMB can help accelerate translational medicine research, and by extension, delivery of personalized cancer care in the future.

Abstract 5041: Next generation liquid biopsy reference material performance across NGS assays and platforms

Abstract Liquid biopsy testing has grown to support early disease diagnosis, therapy selection, and disease and treatment surveillance in cancer survivors. Recent advances in next generation sequencing (NGS) have enabled larger panel sizes, pan-cancer target sets, and wider ranges of genomic alterations. More inclusive analytical validation materials are needed to assess assay sensitivity, specificity, and limit of detection of all variant types to serve the expanded utility of liquid biopsy testing. Here we describe the development and multisite evaluation of expanded Seraseq® ctDNA Mutation Mix v4 reference materials. Genomic DNA from the GM24385 cell line was blended with 93 clinically relevant biosynthetic DNA variants including single nucleotide variants (SNVs), insertions and deletions (indels), structural variants (SVs), copy number variations (CNVs), and mono- and dinucleotide biomarkers for microsatellite instability (MSI). Variant allele frequency (VAF) was targeted to 0.5% and total copy number for CNVs was targeted to 2.5 and verified using the Bio-Rad QX-200 Droplet Digital PCR (ddPCR) System. The DNA mix was fragmented and purified to create ctDNA-like size profiles. Wild-type (WT) material was prepared for comparison and identification of background variants. Agilent Bioanalyzer High Sensitivity DNA and TapeStation Cell-free DNA ScreenTape analyses were used to assess fragment size. The ctDNA mixes were analyzed with the Illumina TruSight™ Oncology 500 (TSO 500) ctDNA assay, the Thermo Oncomine™ Precision assay, and additional assays. All biosynthetic SNVs, indels, SVs, and CNVs in the 0.5% ctDNA mix were detected near target values. The average fragment size was about 190 bp, similar to native ctDNA. The VAFs and CNVs observed in the TSO 500 data correlated well with those that were obtained by dPCR. Variants reported by all evaluation site assays showed good concordance of VAF values. The two sites that tested the materials with TSO 500 revealed consistency in both VAF and total copies with an average CV of 16.1% and 2.5%, respectively. The sequencing performance of the reference material was similar to patient samples and showed comparable levels of background noise. The performance of the Seraseq ctDNA v4 mutation mix across NGS assays, supported by robust digital PCR data, demonstrated that these materials will allow for assessment of complex and sensitive liquid biopsy tests. Comparing data measured at different sites highlights the variability in liquid biopsy assay performance and the importance of highly multiplexed and consistent reference materials. Remnant samples are typically not an option due to limited yields from a standard blood draw, thus contrived standards are especially needed. Expanded variant content and improvements in the methods used to produce the Seraseq ctDNA Mutation Mix v4 materials will enable advancements in the blood-based NGS clinical diagnostics space. Citation Format: Dana Ruminski Lowe, Sanchita Jamindar, Yves Konigshofer, Andrew Anfora, Krystyna Nahilk, Dianren Xia, Edward S. Davis, David Merriam, Catherine Huang, Russell Garlick, Bharathi Anekella. Next generation liquid biopsy reference material performance across NGS assays and platforms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5041.

Abstract 2522: Predictive value of tumor mutational burden (TMB) in patients with metastatic microsatellite-stable (MSS) colorectal cancer (CRC) given first-line oxaliplatin-based chemotherapy and immune checkpoint blockade (ICB)

Abstract Purpose: Most CRC patients harbor primarily non-immunogenic MSS tumor. The randomized METIMMOX trial (NCT03388190) examined if patients with previously untreated, unresectable abdominal metastases from MSS-CRC may achieve therapeutic efficacy from short-course oxaliplatin-based chemotherapy (FLOX) and sequential ICB (nivolumab) repeatedly. Half of study patients assigned to this experimental treatment had significantly extended progression-free survival (PFS) while the other half had shortened PFS, compared to the control-group patients given standard FLOX chemotherapy with median PFS 9.3 months. Here we explored if somatic mutations (mut) unveiled by next-generation sequencing might provide insights into responsiveness to the METIMMOX regimen. Procedures: Patients had MSS-CRC with infradiaphragmatic metastases deemed unresectable and were eligible for first-line oxaliplatin-based therapy. They were randomly assigned to the control group of FLOX (oxaliplatin, 5-fluorouracil, folinic acid) Q2W or the experimental group of alternating 2 cycles each of FLOX Q2W and nivolumab Q2W, with prespecified break periods. Radiologic response assessment was done every 8 weeks with PFS as the primary endpoint. Diagnostic tumor biopsies and baseline metastasis biopsies were sequenced with the TruSight Oncology 500 assay. TMB was calculated using only coding, non-synonymous single-nucleotide variants and insertions/deletions with variant allele frequency ≥5% and sequencing depth ≥50 ×, applying the effective panel size as the megabases (Mb) denominator. Results: Sequencing data were acquired from 20 experimental-group patients with median PFS 7.9 months (minimum 2.0, maximum 41.6). Median TMB was 5.1 mut/Mb (minimum 0.8, maximum 11.8), concordant in patient-paired primary tumor and metastasis specimens. The TMB was associated with treatment outcome; the higher TMB, the better PFS with hazard ratio 0.83 (95% confidence interval (CI) 0.70-0.98; p = 0.026, Cox regression) for a PFS event with increasing TMB. TMB cut-off as low as 5.0 mut/Mb distinguished between patient groups (p = 0.007, log-rank test) with median PFS 34.9 months (95% CI 10.6-59.2; TMB>5, n = 10) and median PFS 4.6 months (95% CI 2.7-6.5; TMB≤5, n = 10). In the TMB>5 group, 8/10 were KRAS- or BRAF-mutant cases. In the TMB≤5 group, 9/10 metastasis specimens were RAS/BRAF-wildtype cases. Conclusions: TMB >5 mut/Mb was associated with tumor KRAS or BRAF driver mutation and remarkably long PFS in first-line treatment of patients with abdominal metastases from MSS-CRC with alternating short-course oxaliplatin-based chemotherapy and ICB. Citation Format: Anne Hansen Ree, Paula A. Bousquet, Hilde L. Nilsen, Torben Lüders, Shixiong Wang, Tina Visnovska, Diana L. Bordin, Eirik Høye, Hanne M. Hamre, Christian Kersten, Eva Hofsli, Marianne G. Guren, Halfdan Sorbye, Kjersti Flatmark, Sebastian Meltzer. Predictive value of tumor mutational burden (TMB) in patients with metastatic microsatellite-stable (MSS) colorectal cancer (CRC) given first-line oxaliplatin-based chemotherapy and immune checkpoint blockade (ICB) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2522.

Abstract 3498: A novel combination of tissue-informed, comprehensive genomic profiling (CGP) and non-bespoke blood-based profiling for quantifying circulating tumor DNA (ctDNA)

Abstract Background: Estimating quantitative circulating tumor fraction in liquid biopsy samples is a promising area of clinical development for monitoring therapeutic molecular response and correlates with patient outcomes. Here we introduce a sensitive measure of estimating ctDNA tumor fraction (ctDNA TF) using a novel combination of tissue-informed CGP with a non-bespoke, blood-based liquid biopsy panel. Methods: Advanced pan-solid tumor samples were sequenced with both the Tempus xF/xF+ (105/523 gene, liquid biopsy) and Tempus xT (648 genes, solid-tumor with matched buffy coat) NGS assays (samples collected within 90 days). A normal distribution was fit against the somatic variants detected in solid-tissue and variants with variant allele fractions (VAF) within two standard deviations were used as selected biomarkers in the corresponding liquid biopsy to calculate a tumor-informed ctDNA TF for each sample. Results: In the initial validation set (n=79 samples also sequenced with low-pass whole genome sequencing), the linearity of tumor-informed ctDNA TF was compared to mean VAF (R2=0.26, slope=0.55), ichorCNA (R2=0.84, slope=0.84), and tumor-naive ctDNA TF (R2=0.71, slope=0.90). In a larger validation set (n=12,080), 37.5% samples had no variants detected in both xF and/or xT. Of the remaining samples, the linearity of tumor-informed ctDNA TF was compared to mean VAF (R2=0.21, slope=0.55) and tumor-naive ctDNA TF (R2=0.65, slope=0.81). In a follow-up analysis, we required 5 or more variants be detected in both xF and xT (n=1,659 samples) and compared the linearity of tumor-informed ctDNA TF to mean VAF (R2=0.37, slope=0.64) and tumor-naive ctDNA TF (R2=0.68, slope=0.98). In samples that received xF+ profiling (n=567), 24.3% had no variants detected in both xF+ and xT. The linearity of tumor-informed ctDNA TF of the remaining samples was compared to mean VAF (R2=0.01, slope=0.26) and tumor-naive ctDNA TF (R2=0.63, slope=1.02). Increasing the required number of variants to 5 or more had marginal improvement in linearity of tumor-informed ctDNA TF to mean VAF (R2=0.12, slope=0.47) and tumor-naive ctDNA TF (R2=0.67, slope=1.13).The limit-of-blank of the tumor-informed ctDNA TF approach was established to be 0% in both xF and xF+, and the limit-of-detection was ≤0.1% demonstrating that tumor informed ctDNA TF is a sensitive measure in detecting tumor fraction at low concentration levels. Conclusion: Here we introduce a novel sensitive and specific tumor-informed, non-bespoke approach for estimating ctDNA TF. Linearity improves with increased panel size and increased variant number. These results suggest that a tumor-informed ctDNA TF can be utilized to improve the sensitivity of existing methods for estimating tumor fraction to help in treatment decisions using Tempus’ tissue and liquid comprehensive NGS genomic profiling platform. Citation Format: Terri Driessen, Christine Lo, Wei Zhu, Robert Tell, Jonathan Freaney, Halla Nimeiri, Kate Sasser. A novel combination of tissue-informed, comprehensive genomic profiling (CGP) and non-bespoke blood-based profiling for quantifying circulating tumor DNA (ctDNA) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3498.

Fluorochrome-dependent specific changes in spectral profiles using different compensation beads or primary cells in full spectrum cytometry.

Full spectrum flow cytometry is a powerful tool for immune monitoring on a single-cell level and with currently available machines, panels of 40 or more markers per sample are possible. However, with an increased panel size, spectral unmixing issues arise, and appropriate single stain reference controls are required for accurate experimental results and to avoid unmixing errors. In contrast to conventional flow cytometry, full spectrum flow cytometry takes into account even minor differences in spectral signatures and requires the full spectrum of each fluorochrome to be identical in the reference control and the fully stained sample to ensure accurate and reliable results. In general, using the cells of interest is considered optimal, but certain markers may not be expressed at sufficient levels to generate a reliable positive control. In this case, compensation beads show some significant advantages as they bind a consistent amount of antibody independent of its specificity. In this study, we evaluated two types of manufactured compensation beads for use as reference controls for 30 of the most commonly used and commercially available fluorochromes in full spectrum cytometry and compared them to human and murine primary leukocytes. While most fluorochromes show the same spectral profile on beads and cells, we demonstrate that specific fluorochromes show a significantly different spectral profile depending on which type of compensation beads is used, and some fluorochromes should be used on cells exclusively. Here, we provide a list of important considerations when selecting optimal reference controls for full spectrum flow cytometry.

High Speed Transmission Characteristics on Glass Based Interposers

Interposers for system in package will became more and more important for advanced electronic systems. As the industry moves toward HPC (High Performance Computing) for huge data transmission with low power consumption. The major engineering requirements for HPC application are highdensity, high speed data transmission, low loss, precision manufacturing and low cost. On the 2.5D heterogenous package structure, key technology is fine wiring connected with CPU chip and HBM chips. The fine wires needed high speed transmission. This paper presents the demonstration of Glass-based twin type interposers, Glass interposer with fine pitch metalized through via and RDL interposer with low loss dielectrics on Glass carrier. We compare twin types of Interposes fabrication process capability with panel size format 300x400mm. Finally, we compare the transmission characteristics using eye diagram for heterogenous integration application. Glass Interposer has low loss glass via, it is effective vertical interconnection. RDL interposer has low loss dielectric layers, excellent transmission characteristics obtained on fine pitch trace area.

Few‐shot learning for satellite characterisation from synthetic inverse synthetic aperture radar images

AbstractSpace situational awareness systems primarily focus on detecting and tracking space objects, providing crucial positional data. However, understanding the complex space domain requires characterising satellites, often involving estimation of bus and solar panel sizes. While inverse synthetic aperture radar allows satellite visualisation, developing deep learning models for substructure segmentation in inverse synthetic aperture radar images is challenging due to the high costs and hardware requirements. The authors present a framework addressing the scarcity of inverse synthetic aperture radar data through synthetic training data. The authors approach utilises a few‐shot domain adaptation technique, leveraging thousands of rapidly simulated low‐fidelity inverse synthetic aperture radar images and a small set of inverse synthetic aperture radar images from the target domain. The authors validate their framework by simulating a real‐case scenario, fine‐tuning a deep learning‐based segmentation model using four inverse synthetic aperture radar images generated through the backprojection algorithm from simulated raw radar data (simulated at the analogue‐to‐digital converter level) as the target domain. The authors results demonstrate the effectiveness of the proposed framework, significantly improving inverse synthetic aperture radar image segmentation across diverse domains. This enhancement enables accurate characterisation of satellite bus and solar panel sizes as well as their orientation, even when the images are sourced from different domains.

Mapping Interindividual Variability of Toxicodynamics Using High-Throughput Transcriptomics and Primary Human Hepatocytes from Fifty Donors.

Understanding the variability across the human population with respect to toxicodynamic responses after exposure to chemicals, such as environmental toxicants or drugs, is essential to define safety factors for risk assessment to protect the entire population. Activation of cellular stress response pathways are early adverse outcome pathway (AOP) key events of chemical-induced toxicity and would elucidate the estimation of population variability of toxicodynamic responses. We aimed to map the variability in cellular stress response activation in a large panel of primary human hepatocyte (PHH) donors to aid in the quantification of toxicodynamic interindividual variability to derive safety uncertainty factors. High-throughput transcriptomics of over 8,000 samples in total was performed covering a panel of 50 individual PHH donors upon 8 to 24 h exposure to broad concentration ranges of four different toxicological relevant stimuli: tunicamycin for the unfolded protein response (UPR), diethyl maleate for the oxidative stress response (OSR), cisplatin for the DNA damage response (DDR), and tumor necrosis factor alpha () for signaling. Using a population mixed-effect framework, the distribution of benchmark concentrations (BMCs) and maximum fold change were modeled to evaluate the influence of PHH donor panel size on the correct estimation of interindividual variability for the various stimuli. Transcriptome mapping allowed the investigation of the interindividual variability in concentration-dependent stress response activation, where the average of BMCs had a maximum difference of 864-, 13-, 13-, and 259-fold between different PHHs for UPR, OSR, DDR, and signaling-related genes, respectively. Population modeling revealed that small PHH panel sizes systematically underestimated the variance and gave low probabilities in estimating the correct human population variance. Estimated toxicodynamic variability factors of stress response activation in PHHs based on this dataset ranged between 1.6 and 6.3. Overall, by combining high-throughput transcriptomics and population modeling, improved understanding of interindividual variability in chemical-induced activation of toxicity relevant stress pathways across the human population using a large panel of plated cryopreserved PHHs was established, thereby contributing toward increasing the confidence of in vitro-based prediction of adverse responses, in particular hepatotoxicity. https://doi.org/10.1289/EHP11891.

INSTITUTIONAL OWNERSHIP MEMODERASI HUBUNGAN TAX HAVEN COUNTRY, MULTINATIONALITY DAN UKURAN KOMITE AUDIT PADA PRAKTIK THIN CAPITALIZATION

The peculiarity of dainty capitalization rehearses in Indonesia uncovered by the Directorate General of Duties and the Assessment Equity Organization is firmly connected with global exercises and unfamiliar interests completed by multiple thousand unfamiliar organizations in Indonesia and is assessed to make misfortunes the condition of as much as 11 million bucks consistently. This study means to inspect and investigate institutional proprietorship directing the connection between duty sanctuary nation, multinationality and review panel size on slender capitalization. The kind of examination utilized is quantitative acquainted. The populace in this study are organizations that are individuals from IDX SMC Fluid which are recorded on the Indonesia Stock Trade in 2018-2022 upwards of 60 organizations. Saturated sampling was used to select the sample for this study, which included 60 businesses over a five-year period. This resulted in a total of 285 observations. The information examination strategy utilizes board information relapse investigation with te help of Eviews form 12 as an estimating device. The outcomes show that expense shelter nation and multinationality emphatically affected Meager Capitalization, review panel size affected Slim Capitalization, institutional proprietorship directs the connection between assessment asylum nation, multinationality and Slight Capitalization,Institutional Possession debilitates the connection between Board of trustees Size Review with Flimsy Capitalization.

ScGIST: gene panel design for spatial transcriptomics with prioritized gene sets

A critical challenge of single-cell spatial transcriptomics (sc-ST) technologies is their panel size. Being based on fluorescence in situ hybridization, they are typically limited to panels of about a thousand genes. This constrains researchers to build panels from only the marker genes of different cell types and forgo other genes of interest, e.g., genes encoding ligand-receptor complexes or those in specific pathways. We propose scGIST, a constrained feature selection tool that designs sc-ST panels prioritizing user-specified genes without compromising cell type detection accuracy. We demonstrate scGIST’s efficacy in diverse use cases, highlighting it as a valuable addition to sc-ST’s algorithmic toolbox.

The impact of nuance DAX ambient listening AI documentation: a cohort study.

To assess the impact of the use of an ambient listening/digital scribing solution (Nuance Dragon Ambient eXperience (DAX)) on caregiver engagement, time spent on Electronic Health Record (EHR) including time after hours, productivity, attributed panel size for value-based care providers, documentation timeliness, and Current Procedural Terminology (CPT) submissions. We performed a peer-matched controlled cohort study from March to September 2022 to evaluate the impact of DAX in outpatient clinics in an integrated healthcare system. Primary outcome measurements included provider engagement survey results, reported patient safety events related to DAX use, patients' Likelihood to Recommend score, number of patients opting out of ambient listening, change in work relative values units, attributed value-based primary care panel size, documentation completion and CPT code submission deficiency rates, and note turnaround time. A total of 99 providers representing 12 specialties enrolled in the study; 76 matched control group providers were included for analysis. Median utilization of DAX was 47% among active participants. We found positive trends in provider engagement, while non-participants saw worsening engagement and no practical change in productivity. There was a statistically significant worsening of after-hours EHR. There was no quantifiable effect on patient safety. Nuance DAX use showed positive trends in provider engagement at no risk to patient safety, experience, or clinical documentation. There were no significant benefits to patient experience, documentation, or measures of provider productivity. Our results highlight the potential of ambient dictation as a tool for improving the provider experience. Head-to-head comparisons of EHR documentation efficiency training are needed.

Real-world Trends, Rural-urban Differences, and Socioeconomic Disparities in Utilization of Narrow versus Broad Next-generation Sequencing Panels.

We identified socioeconomic and rurality disparities in the use of genomic tests and trial matching by panel size, which may have implications for equal access to targeted therapies. The lack of association between large panel tests and clinical trial matching by socioeconomic status, suggests a potential health equity impact, while removing barriers in access to large panels for rural patients may improve access to trials. However, further research is needed.

A Study on Predicting Installation Scale of Photovoltaic Panels and Hydrogen Fuel Storage Facilities to Achieve Net Zero Carbon Emissions Exploiting Idle Sites of Military Bases

In this study, the scale of renewable photovoltaic(PV) panels and hydrogen fuel storage facilities required to achieve “net zero carbon emissions” in military facilities were predicted based on actual electricity consumption. It was set up to expect the appropriate installation size of PV panel and hydrogen fuel storage facility for achieving carbon neutrality, limited to the electricity consumption in the public sector, including national defense and social security administration in Yeongcheon. The experimental results of this paper are largely composed of two parts. First, representative meteorological factors were considered to predict solar power generation in the Yeongcheon area, and solar power generation was estimated through a multiple regression model using deep learning techniques. Second, the size of solar power generation facilities and hydrogen storage facilities in military bases was estimated with the amount of solar power generation and electricity consumption. As a result of this analysis, it was calculated that a site of 155.76×104 m<sup>2</sup> for PV panels was needed and a facility capable of storing 27,657 kg of hydrogen gas was required. Through these results, it is meaningful to demonstrated the prospect that military units can lead the achievement of “carbon net zero 2050” by using PV panels and hydrogen fuel storage facilities on idle sites of military bases.

Financing Thresholds for Sustainability of Community Health Worker Programs for Patients Receiving Medicaid Across the United States.

States have turned to novel Medicaid financing to pay for community health worker (CHW) programs, often through fee-for-service or capitated payments. We sought toestimate Medicaid payment rates to ensure CHW program sustainability. A microsimulation model was constructed toestimate CHW salaries, equipment, transportation, space, and benefits costs across the U.S. Fee-for-service rates per 30-min CHW visit (code 98960) and capitated rates were calculated for financial sustainability. The mean CHW hourly wage was $23.51, varying from $15.90 in Puerto Rico to $31.61 in Rhode Island. Overhead per work hour averaged $43.65 nationwide, and washighest for transportation among other overhead categories(65.1% of overhead). The minimum fee-for-service rate for a 30-min visit was $53.24 (95% CI $24.80, $91.11), varying from $40.44 in South Dakota to $70.89 in Washington D.C. The minimum capitated rate was $140.18 per member per month (95% CI $105.94, $260.90), varyingfrom $113.55 in South Dakota to $176.58 in Washington D.C. Rates varied minimally by metro status but more by panel size. Higher Medicaid fee-for-service and capitated rates than currently used may be needed to support financial viability of CHW programs. A revised payment estimation approach may help state officials, health systems and plans discussing CHW program sustainability.

Development of an Electronic Decision Aid Tool to Facilitate Mainstream Genetic Testing in Ovarian Cancer Patients.

Multigene panel testing is an important component of cancer treatment plans and risk assessment, but there are many different panel options and choosing the most appropriate panel can be challenging for health care providers and patients. Electronic tools have been proposed to help patients make informed decisions about which gene panel to choose by considering their preferences and priorities. An electronic decision aid (DA) tool was developed in line with the International Patient Decision Aids Standards collaboration. The multidisciplinary project team collaborated with an external health care communications agency and the MGH Cancer Center Patient and Family Advisory Council (PFAC) to develop the DA. Surveys of genetic counselors and patients were used to scope the content, and alpha testing was used to refine the design and content. Surveys of genetic counselors (n = 12) and patients (n = 228) identified common themes in discussing panel size and strategies for helping patients decide between panels and in identifying confusing terms for patients and distribution of patients' choices. The DA, organized into 2 major sections, provides educational text, graphics, and videos to guide patients through the decision-making process. Alpha testing feedback from the PFAC (n = 4), genetic counselors (n = 3) and a group of lay people (n = 8) identified areas to improve navigation, simplify wording, and improve layout. The DA developed in this study has the potential to facilitate informed decision-making by patients regarding cancer genetic testing. The distinctive feature of this DA is that it addresses the specific question of which multigene panel may be most suitable for the patient. Its acceptability and effectiveness will be evaluated in future studies.

A design approach of panel size for the cooperative development of cropland protection and coal mining in a coal-cropland overlapping area.

Cropland is the foundation of food security. Coal is the guarantee of energy security. As China's demand for coal and grain continues to increase, so does the overlap area of their production bases. Unrestrained underground mining can cause serious damage to cropland, leading to increasing conflicts between coal mining and food production. Thus, this paper used a partial backfilling mining technology to control surface subsidence and thus protect cropland. The key to successfully implementing the technology is how to design the panel size. However, the design efficiency of the conventional enumeration method is low. Therefore, this paper proposed a design approach based on improved particle swarm optimization. The results indicated that the approach could quickly find the optimal size of the panel compared with the enumeration method and particle swarm optimization. Moreover, if the longwall panel is mined according to the size designed by the approach, the cropland will be protected, and the cost will be reduced. This study can provide technical support for the cooperative development of cropland protection and coal mining in a coal-cropland overlapping area.

Enhancing the quality of panel-based tumor mutation burden assessment: a comprehensive study of real-world and in-silico outcomes

Targeted panel-based tumor mutation burden (TMB) assays are widely employed to guide immunotherapy for patients with solid tumors. However, the accuracy and consistency of this method can be compromised due to the variability in technical details across different laboratories, particularly in terms of panel size, somatic mutation detection and TMB calculation rules. Currently, systematic evaluations of the impact of these technical factors on existing assays and best practice recommendations remain lacking. We assessed the performance of 50 participating panel-based TMB assays involving 38 unique methods using cell line samples. In silico experiments utilizing TCGA MC3 datasets were performed to further dissect the impact of technical factors. Here we show that the panel sizes beyond 1.04 Mb and 389 genes are necessary for the basic discrete accuracy, as determined by over 40,000 synthetic panels. The somatic mutation detection should maintain a reciprocal gap of recall and precision less than 0.179 for reliable psTMB calculation results. The inclusion of synonymous, nonsense and hotspot mutations could enhance the accuracy of panel-based TMB assay. A 5% variant allele frequency cut-off is suitable for TMB assays using tumor samples with at least 20% tumor purity. In conclusion, this multicenter study elucidates the major technical factors as sources of variability in panel-based TMB assays and proposed comprehensive recommendations for the enhancement of accuracy and consistency. These findings will assist clinical laboratories in optimizing the methodological details through bioinformatic experiments to enhance the reliability of panel-based methods.

Panel Sizing for Solar PV Panel Area Requirement and Performance at Various Locations

Panel Sizing for Solar PV Panel Area Requirement and Performance at Various Locations

Evaluation of ancient DNA imputation: a simulation study

Ancient genomic data is becoming increasingly available thanks to recent advances in high-throughput sequencing technologies. Yet, post-mortem degradation of endogenous ancient DNA often results in low depth of coverage and subsequently high levels of genotype missingness and uncertainty. Genotype imputation is a potential strategy for increasing the information available in ancient DNA samples and thus improving the power of downstream population genetic analyses. However, the performance of genotype imputation on ancient genomes under different conditions has not yet been fully explored, with all previous work primarily using an empirical approach of downsampling high coverage paleogenomes. While these studies have provided invaluable insights into best practices for imputation, they rely on a fairly limited number of existing high coverage samples with significant temporal and geographical biases. As an alternative, we used a coalescent simulation approach to generate genomes with characteristics of ancient DNA in order to more systematically evaluate the performance of two popular imputation software, BEAGLE and GLIMPSE, under variable divergence times between the target sample and reference haplotypes, as well as different depths of coverage and reference sample size. Our results suggest that for genomes with coverage <=0.1x imputation performance is poor regardless of the strategy employed. Beyond 0.1x coverage imputation is generally improved as the size of the reference panel increases, and imputation accuracy decreases with increasing divergence between target and reference populations. It may thus be preferable to compile a smaller set of less diverged reference samples than a larger more highly diverged dataset. In addition, the imputation accuracy may plateau beyond some level of divergence between the reference and target populations. While accuracy at common variants is similar regardless of divergence time, rarer variants are better imputed on less diverged target samples. Furthermore, both imputation software, but particularly GLIMPSE, overestimate high genotype probability calls, especially at low coverages. Our results provide insight into optimal strategies for ancient genotype imputation under a wide set of scenarios, complementing previous empirical studies based on imputing downsampled high-coverage ancient genomes.