Parallel Samples Research Articles

Automated and Continuous-Flow Platform to Analyze Semiconductor–Metal Complex Hybrid Systems for Photocatalytic CO2 Reduction

Sunlight-driven CO2 reduction is increasingly considered as a promising approach to contribute toward a carbon-neutral fuel cycle, but most photocatalyst systems are currently studied individually under batch conditions with manual, labor-intensive analytical procedures. Here, we present the advantages of a continuous-flow setup to study photocatalytic CO2 to CO reduction systems, which also benefits from aspects of automation (using programmed in-line gas quantification of multiple samples in parallel). The capabilities of the methodology are demonstrated using a state-of-the-art light absorber platform based on ZnSe quantum dots (QDs) in combination with a series of molecular co-catalysts based on Ni and Co for visible-light-driven CO2 reduction in aqueous ascorbate solution. A newly synthesized Co-tetraphenylporphyrin featuring three sulfonate groups and one amine group (Co(tppS3N1)) is identified to exhibit a benchmark photocatalytic activity (18.6 μmol of CO, 79.7 mmol of CO gZnSe–1, TONCo (CO) of 619, external quantum efficiency (EQE) >5%). The utility of our methodology is further shown by applying the setup to study the photocatalyst systems under lower light intensities, low CO2 concentration, and aerobic conditions, which impact the photocatalytic activity and selectivity. Overall, this work reports an improved methodology for studying photocatalytic CO2 reduction alongside advancing the understanding of QD molecular co-catalyst hybrids using ZnSe QDs as a versatile light absorber based on earth-abundant components that operate under fully aqueous conditions.

Men\u2019s reproductive coercion of women: prevalence, experiences, and coping strategies\u2014a mixed method study in urban health facilities in Le\xf3n, Nicaragua

BackgroundReproductive coercion (RC) is a common form of violence against women. It can take several expressions aiming at limiting women’s reproductive autonomy. Thus, the frequency and how reproductive coercion can be resisted must be investigated. There is limited research regarding RC in Latin America. Therefore, this study aimed to measure RC prevalence and associated factors and to explore the women experiences and coping strategies for RC.MethodsA convergent mixed-methods study with parallel sampling was conducted in Nicaragua. A quantitative phase was applied with 390 women 18–35 years old attending three main urban primary health care facilities. Lifetime and 12 months of exposure to RC behaviors including pregnancy promotion (PP) and contraceptive sabotage (CS) were assessed. Poisson regression with a robust variance estimator was used to obtain adjusted prevalence rate ratios and 95% Confidence Intervals (CIs). In addition, seven in-depth interviews were collected and analyzed using qualitative content analysis.ResultsEver RC prevalence was 17.4% (95% CI, 13.8–21.6) with similar proportions reporting ever experiencing PP (12.6%, 95% CI 9.4–16.3) or ever experiencing CS (11.8%, 95% CI 8.7–15.4). The prevalence of last twelve months RC was slightly lower (12.3%, 95% CI, 9.2–16.0) than above. Twelve months PP (7.4%, 95% CI 5.0–10.5) and CS (8.7%, 95% CI 6.1–12.0) were also similar. Women’s higher education was a protective factor against ever and 12 months of exposure to any RC behaviors by a current or former partner. Informants described a broad spectrum of coping strategies during and after exposure to RC. However, these rarely succeeded in preventing unintended pregnancies or regaining women’s long-term fertility autonomy.ConclusionsOur facility-based study showed that men’s RC is a continuous phenomenon that can be enacted through explicit or subtle behaviors. Women in our study used different strategies to cope with RC but rarely succeeded in preventing unintended pregnancies or regaining their long-term fertility autonomy. Population-based studies are needed assess this phenomenon in a larger sample. The Nicaraguan health system should screen for RC and develop policies to protect women’s reproductive autonomy.

Shrinkage cracking and strength deterioration of red clay under cyclic drying and wetting

Taking the red clay from Guilin, China as the object, this paper prepares red clay samples with different initial water contents, extracts the crack parameters from the images on the samples under cyclic drying and wetting through image processing, and analyzes the laws of crack development. In addition, parallel red clay samples were subject to shrinkage tests and direct shear tests under the same cyclic drying and wetting. Based on the test results, the authors discussed the laws of shrinkage deformaiton and strength change for the samples under cyclic drying and wetting, and examined the relationship between cracking, shrinkage properties, and strength detiroation of the red clay. The results show that: (1) With the growing crack rate, the volume shrinkage ratio constantly declined; the area shrinkage ratio was generally decreasing, but the decrement was not obvious in local places (in some places, the area shrinkage ratio even increased); the shrinkage coefficient generally declined, (2) Through the five dry-wet cycles, it was learned that the cohesion and internal friction angle of red clay strength can be quantified using the crack rate. This finding lays the basis for judging soil strength based on crack rate, and solving actual engineering problems with the red clay.

Evaluation of Kappa Index as a Tool in the Diagnosis of Multiple Sclerosis: Implementation in Routine Screening Procedure.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Previous studies have shown that cerebrospinal fluid (CSF) kappa free light chains (K-FLCs) may have a role in MS diagnosis. In this regard, the kappa index (K-Index) has demonstrated higher sensitivity, and slightly lower specificity than oligoclonal bands (OCBs), the gold standard for the detection of intrathecal immunoglobulin synthesis, a feature of MS. Here, we evaluated the performance of the K-Index (K-Index = CSF/serum K-FLC divided by CSF/serum albumin) for the differential diagnosis of MS in a cohort of patients with suspected MS. K-FLCs were quantitatively measured in parallel serum and CSF samples by turbidimetry (Freelite Mx reagent on an Optilite system, The Binding Site Group Ltd). From 160 (63.4%) of a total of 252 patients who had K-FLC in CSF <0.03 mg/dl, below the sensitivity limit of the technique, only one had a diagnosis of MS. However, the absence of OCB in this same patient suggested no synthesis of intrathecal immunoglobulin. Globally, MS patients presented significantly higher K-Index levels than patients without an MS diagnosis (66.96 vs. 0.025, respectively; p < 0.0001). In agreement, patients with positive OCB testing also exhibited higher K-Index levels than patients negative for OCB (65.02 vs. 0.024, respectively; p < 0.0001). An optimal K-Index cutoff of 3.045 was defined by receiver operating characteristic (ROC) analysis for screening suspected MS, achieving a higher diagnostic sensitivity and slightly lower specificity than OCB (Sens. 0.9778 and Spec. 0.8629 vs. Sens. 0.8889 and Spec. 0.9086, respectively). A previously reported K-Index cutoff of 6.6 also showed good diagnostic performance (Sens. 0.9333; Spec. 0.8731), validating its power as a diagnostic biomarker for MS. Finally, a time- and cost-effective algorithm for MS screening is proposed that would offer an initial rapid evaluation of the intrathecal immunoglobulin synthesis through the K-FLC in CSF and K-Index analysis, followed by reflexing OCB testing that may be ordered more selectively.

Confined combustion of polymeric solid materials in microgravity

Microgravity experiments are performed to study the effects of confinement on the burning behavior of polymeric solid materials. Flat, 100 × 22 × 1 mm PMMA samples are burned in concurrent air flow in a small flow duct aboard the International Space Station. Three different burning scenarios are examined, double-sided, single-sided, and parallel samples. In the first two scenarios, single samples are burned on both sides and on one side, respectively. Flat baffles are placed parallel to the sample to confine the available space for combustion. The distance between the baffle and the sample (H) is varied in different tests. In each test, imposed flow is reduced in steps and steady flame spread is achieved at each flow speed until the flame quenches. The results show that at the same confined condition, steady state flame length and spread rate are proportional to flow speed over the range tested. When confinement increases (or H decreases), the flame spread rate and flame length increase first and then decrease. In addition, the quenching flow speed decreases and then increases with decreasing H. These results suggest that the confinement can increase or decrease solid fuel flammability depending on conditions. In the third burning scenario, two PMMA samples are placed parallel to each other separated by a distance H. Twin flames are observed and combustion is confined between the two samples. Among the three tested burning scenarios, twin flames have the largest flame length and burning rate at the same confinement level (H). This is because the thermal interaction between the twin flames enhances the heat feedback to the solid fuel and reduces the relative heat loss to the surrounding flow duct. Comparing single- and double-sided flames with the same baffle-sample distance, the spread rate of a single-sided flame is slightly less than half of that of a double-sided flame. This is due to the halved pyrolysis area exposed to the flame and heat loss on the back side of the sample. Optimal transport of oxygen to the flames also plays a role.

Spatially resolved correlative microscopy and microbial identification reveal dynamic depth- and mineral-dependent anabolic activity in salt marsh sediment.

SummaryCoastal salt marshes are key sites of biogeochemical cycling and ideal systems in which to investigate the community structure of complex microbial communities. Here, we clarify structural–functional relationships among microorganisms and their mineralogical environment, revealing previously undescribed metabolic activity patterns and precise spatial arrangements within salt marsh sediment. Following 3.7‐day in situ incubations with a non‐canonical amino acid that was incorporated into new biomass, samples were resin‐embedded and analysed by correlative fluorescence and electron microscopy to map the microscale arrangements of anabolically active and inactive organisms alongside mineral grains. Parallel sediment samples were examined by fluorescence‐activated cell sorting and 16S rRNA gene sequencing to link anabolic activity to taxonomic identity. Both approaches demonstrated a rapid decline in the proportion of anabolically active cells with depth into salt marsh sediment, from ~60% in the top centimetre to 9.4%–22.4% between 2 and 10 cm. From the top to the bottom, the most prominent active community members shifted from sulfur cycling phototrophic consortia, to putative sulfate‐reducing bacteria likely oxidizing organic compounds, to fermentative lineages. Correlative microscopy revealed more abundant (and more anabolically active) organisms around non‐quartz minerals including rutile, orthoclase and plagioclase. Microbe–mineral relationships appear to be dynamic and context‐dependent arbiters of biogeochemical cycling.

Modern Methodological Approaches to Sample Preparation for the Determination of Trace Elements in Food Products and Plant Raw Materials

Introduction. Various copper compounds are most widely used as plant protection agents in agriculture. From a hygienic point of view, information on excessive accumulation of copper in plants related to the use of a specific formulation of copper-containing pesticides is of interest. Our objective was to assess feasibility of increasing statistical significance of results of determining low residue levels of a copper-containing pesticide in apple samples by flame atomic absorption spectrometry using a high-resolution spectrometer in combination with developed approaches to sample preparation of plant-based foods, including homogenization with dry ice and microwave mineralization. Materials and methods: We analyzed 30 samples of apples collected in three different agro-climatic zones by flame atomic absorption spectrometry and electrothermal atomization atomic absorption spectrometry. Both methods were validated on 10 samples with added copper at levels 1-5 of the lower limit of quantitation. A statistical calculation was performed based on a simple Student’s test to assess the significance of differences between the results of measurements by flame and electrothermal techniques. Homogeneity of variances was estimated using the Fisher test to clarify the possibility of comparing two data sets. Results: The use of a technique of cryo-grinding and microwave decomposition in a microwave reactor in combination with a high-resolution continuum source atomic absorption spectrometry demonstrated a decrease in scattering and the limit of detection and better repeatability in the analysis of parallel samples. Results of statistical calculations confirmed the homogeneity of variances in data samples obtained for electrothermal and flame techniques, and the further Student’s t-test showed insignificant differences between the results of measurements obtained by FAAS and ET-AAS. Conclusion: Our findings prove that modern methods of sample preparation in combination with highly sensitive equipment allow a significant reduction in the limit of detection and scattering of test results.

Ethical conduct-do and general well-being among university students, moderated by religious internalization: An Islamic perspective

Although topics related to well-being are being studied, those which focused on Islamic values, principles, and beliefs in this region is still sparse. The purpose of this study is to identify the correlation between (1) Islamic ethical conduct-do and the general Islamic well-being, (2) Islamic religious internalization and Islamic general well-being, and (3) Islamic ethical conduct-do and Islamic general well-being, moderated by Islamic religious internalization. Data collection was carried out in October 2019 and involved the 1st semester students of the 2019-2020 academic year in the Faculty of Psychology, Universitas Muhammadiyah Surakarta. The subjects were selected using parallel sampling by choosing students from parallel classes; as many as 74 students were selected. The research instruments met the requirements of convergent and discriminant validity, as well as reliability. Data analysis was undertaken with the help of the PLS moderation program. The results indicated the following: (1) Islamic ethical conduct-do has a positive significant relationship with university students’ Islamic general well-being; (2) Islamic religious internalization has a positive significant association with university students’ Islamic general well-being; and (3) Islamic ethical conduct-do was significantly correlated with university students’ Islamic general well-being, Islamic religious internalization as a moderator variable.Keywords: Islamic ethical conduct-do; Islamic general well-being; Islamic religious internalization; Islamic well-being; Islamic religiousness

A 10-bit 200 MS/s pipelined ADC with parallel sampling and switched op-amp sharing technique

PurposeIn parallel sampling method, the size of the sampling capacitor is reduced to improve the bandwidth of the ADC.Design/methodology/approachVarious low-power techniques for 10-bit 200MS/s pipelined analog-to-digital converter (ADC) are presented. This work comprises two techniques including parallel sampling and switched op-amp sharing technique.FindingsThis paper aims to study the effect of parallel sampling and switched op-amp sharing techniques on power consumption in pipelined ADC. In switched op-amp sharing technique, the numbers of op-amps used in the stages are reduced. Because of the reduction in the size of capacitors in parallel sampling technique and op-amps in the switched op-amp sharing technique, the power consumption of the proposed pipelined ADC is reduced to a greater extent.Originality/valueSimulated the 10-bit 200MS/s pipelined ADC with complementary metal oxide semiconductor process and the simulation results shows a maximum differential non-linearity of +0.31/−0.31 LSB and the maximum integral non-linearity (of +0.74/−0.74 LSB with 62.9 dB SFDR, 55.90 dB SNDR and ENOB of 8.99 bits, respectively, for 18mW power consumption with the supply voltage of 1.8 V.

Clinical utility of a rapid 'on-demand' laboratory-based SARS-CoV-2 diagnostic testing service in an acute hospital setting admitting COVID-19 patients.

BackgroundWith the onset of the COVID-19 pandemic in 2020, hospital clinical teams have realised that there is a need for a rapid, accurate testing facility that will allow them to move patients quickly into isolation rooms or specific COVID-19 cohort wards as soon as possible after admission.MethodsStarting from July 2020, PCR-based test platforms, which could test 4–8 samples in parallel with turnaround (sample-to-result) times of 50–80 min, were placed in a satellite laboratory. This laboratory was on the same floor and within walking distance to the acute respiratory admissions ward. It was staffed by a team of three mid-Band 4 staff that split a 0700–2200 h-work day, 7 days a week, with 2 senior supervisors. Urgent sample testing was decided upon by the clinical teams and requested by phone. The test results were entered manually in real-time as they became available, and sent electronically to the requesting ward teams.ResultsThe daily/monthly PCR positive test numbers approximately followed the local and national UK trend in COVID-19 case numbers, with the daily case numbers being reflective of the November and December 2020 surges. Test results were used to rapidly segregate positive patients into dedicated COVID-19 ward areas to minimise risk of potential nosocomial transmission in crowded waiting areas. Testing capacity was sufficient to include cases with uncertain diagnosis likely to require hospital admission. Following completion of other admission processes, based on these rapid test results, patients were allocated to dedicated COVID-19 positive or negative cohort wards.ConclusionsThis rapid testing facility reduced unnecessary ‘length-of-stay’ in a busy acute respiratory ward. In the current absence of a treatment for mild-to-moderate COVID-19, on which patients could be discharged home to complete, the rapid test facility has become a successful aid to patient flow and reduced exposure and nosocomial transmission.

Anisotropic effects of oxygen vacancy defects on the electrical properties of highly oriented bismuth titanate ferroelectric ceramics

Bismuth titanate (Bi4Ti3O12, BIT) exhibits a high Curie temperature and anisotropic electrical performance owing to its layered perovskite structure, and hence, it is an important ferroelectric material for high-temperature piezoelectric applications. It is crucial to understand the effects of the anisotropy in BIT-based ferroelectrics for developing novel high-temperature piezoelectric materials. In this study, a highly textured BIT ceramic was fabricated using the tape-casting technique from highly grain-oriented BIT platelets prepared by the molten salt method. The textured BIT ceramic showed a dense microstructure and high grain orientation along the (00l) plane with a texturing degree F00l = 0.86. It exhibited significant anisotropy in the electrical properties along the directions parallel and perpendicular to the axis of the tape-casting plane. Double ferroelectric hysteresis P–E loops and normal ferroelectric P–E loops were observed in the parallel and perpendicular samples, respectively. In addition to the layered crystal structure and domains, the anisotropy in the arrangement of the oxygen vacancy defects and their transport in the structure led to a significant anisotropy in the ferroelectric properties of the textured BIT ceramics. This work demonstrates the anisotropic arrangement of the oxygen vacancy defects and its effect on the electrical properties of high-temperature bismuth layer-structured ferroelectrics.

COVseq is a cost-effective workflow for mass-scale SARS-CoV-2 genomic surveillance

While mass-scale vaccination campaigns are ongoing worldwide, genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to monitor the emergence and global spread of viral variants of concern (VOC). Here, we present a streamlined workflow—COVseq—which can be used to generate highly multiplexed sequencing libraries compatible with Illumina platforms from hundreds of SARS-CoV-2 samples in parallel, in a rapid and cost-effective manner. We benchmark COVseq against a standard library preparation method (NEBNext) on 29 SARS-CoV-2 positive samples, reaching 95.4% of concordance between single-nucleotide variants detected by both methods. Application of COVseq to 245 additional SARS-CoV-2 positive samples demonstrates the ability of the method to reliably detect emergent VOC as well as its compatibility with downstream phylogenetic analyses. A cost analysis shows that COVseq could be used to sequence thousands of samples at less than 15 USD per sample, including library preparation and sequencing costs. We conclude that COVseq is a versatile and scalable method that is immediately applicable for SARS-CoV-2 genomic surveillance and easily adaptable to other pathogens such as influenza viruses.

Measurement of the refractive index of glass with 10−4 level accuracy based on the lateral displacement method

The measurement of the refractive index of optical glass samples is a common and fundamental activity in numerous fields of expertise. Several measurement techniques exist with relative accuracies from 10 − 2 to, at least, 10 − 7 with complexities that are inversely related to the corresponding uncertainty. We describe an implementation of a technique based on the measurement of the lateral displacement variation of a collimated beam caused by the rotation of a parallel plate glass sample. The method was aimed to achieve an uncertainty in the range from 10 − 3 to 10 − 4 without increasing the complexity normally associated with techniques with this level of accuracy. The system was designed and optimized based on a detailed analysis of the uncertainty budget. We describe the implementation, the data processing, and the results obtained with calibrated samples, showing a relative uncertainty at the level of 10 − 4.

Enhanced thermoelectric performance of BiSe by Sn doping and ball milling

BiSe has emerged as a promising Te-free high-performance thermoelectric (TE) material base owing to its ultra-low lattice thermal conductivity caused by the Bi bilayers in its lattice. Herein, the TE properties of BiSe were modified by Sn doping and ball milling to improve its performance. The ball milling process reduced the grain size of the samples and affected their anisotropy during the pressing process, leading to the random arrangement of the (00l) plane, which improved the electrical conductivity of the samples in the direction parallel to the spark plasma sintering direction and increased the Seebeck coefficient. The increased defects and smaller grain size of the samples due to Sn doping and ball milling enhanced the scattering of phonon transport, thereby decreasing the lattice thermal conductivity. The improvement in the ZT of the samples was realized through the improvement in their thermal and electrical transport. The Spark plasma-sintered bulk of the ball-milled Bi0.9Sn0.1Se sample exhibited a high-power factor of 8.4 μW · cm−1 · K−2 at 473 K and an ultra-low lattice thermal conductivity of 0.43 W · m−1 · K−1 at 673 K along with the maximum ZT value of 0.32 at 473 K, which is 31.6% higher than that of the pristine BiSe sample.

Surrogate-based optimization with adaptive parallel infill strategy enhanced by inaccurate multi-objective search

In recent decades, surrogate-based optimization (SBO) has been developed to replace costly models with cheap surrogates to improve efficiency. In this article, an adaptive parallel infill strategy is proposed to balance exploration and exploitation over the design space during the optimization process of SBO. Within this method, an inaccurate search strategy is adopted to optimize the surrogate models, thereby helping to locate the exploitation point. An elite archive is exploited to store superior sampling points for batch sampling, while a customized batch size determination strategy is introduced. The proposed SBO method with its adaptive parallel sampling strategy is tested on six unconstrained and five constrained analytical cases with the optimization results compared to state-of-the-art optimization algorithms. The optimization of a 582-bar tower truss system is also performed and utilized to verify the proposed SBO method. The proposed SBO with the adaptive parallel sampling strategy shows excellent performance and better stability.

Determination of tetracycline and fluoroquinolone residues in fish by polydopamine nanofiber mat based solid phase extraction combined with ultra performance liquid chromatography-tandem mass spectrometry

制备聚多巴胺(PDA)修饰的聚苯乙烯纳米纤维膜(PS NFsM)作为固相萃取吸附介质,可快速提取淡水鱼中3种四环素类(四环素、金霉素、土霉素)和3种氟喹诺酮类(恩诺沙星、环丙沙星、诺氟沙星)药物残留,结合超高效液相色谱-串联质谱(UPLC-MS/MS),建立了药物残留检测的新方法。利用静电纺丝法制备了聚苯乙烯纳米纤维膜,将其作为模板,通过自聚合作用,进行聚多巴胺功能化修饰,得到PDA-PS NFsM材料。对制得的PS NFsM和PDA-PS NFsM材料进行傅里叶红外光谱和场发射扫描电镜表征,证明PDA的成功修饰,修饰后的纳米纤维表面粗糙,呈现核-壳形貌,纤维内部为蜂窝状多孔结构。以空白加标样品的回收率为指标,对PDA-PS NFsM材料的用量、离子强度、样品溶液的流速、洗脱液和突破体积等影响SPE的因素进行考察及条件优化,确定了最佳的SPE条件。该方法对6种目标物的检出限为0.3~1.5 μg/kg,定量限为1.0~5.0 μg/kg,低于国家标准和行业标准;在各目标物的线性范围内均有良好的线性关系,决定系数(R2)大于0.999,方法的回收率为94.37%~102.82%,日间和日内的相对标准偏差(RSD)均小于10%,与国家标准和行业标准相当。通过固相萃取前后的基质效应对比,表明PDA-PS NFsM具有优秀的净化能力。最后,通过实际样品分析验证了方法的实际应用可行性。该文建立的基于PDA-PS NFsM材料的SPE方法是一种高效环保的方法,可为淡水鱼中药物残留的常规监测提供技术支持。

Cancer predisposition in pediatric neuro-oncology-practical approaches and ethical considerations.

A genetic predisposition to tumor development can be identified in up to 10% of pediatric patients with central nervous system (CNS) tumors. For some entities, the rate of an underlying predisposition is even considerably higher. In recent years, population-based approaches have helped to further delineate the role of cancer predisposition in pediatric oncology. Investigations for cancer predisposition syndrome (CPS) can be guided by clinical signs and family history leading to directed testing of specific genes. The increasingly adopted molecular analysis of tumor and often parallel blood samples with multi-gene panel, whole-exome, or whole-genome sequencing identifies additional patients with or without clinical signs. Diagnosis of a genetic predisposition may put an additional burden on affected families. However, information on a given cancer predisposition may be critical for the patient as potentially influences treatment decisions and may offer the patient and healthy carriers the chance to take part in intensified surveillance programs aiming at early tumor detection. In this review, we discuss some of the practical and ethical challenges resulting from the widespread use of new diagnostic techniques and the most important CPS that may manifest with brain tumors in childhood.

Multiplexed detection of SARS-CoV-2 and other respiratory infections in high throughput by SARSeq

The COVID-19 pandemic has demonstrated the need for massively-parallel, cost-effective tests monitoring viral spread. Here we present SARSeq, saliva analysis by RNA sequencing, a method to detect SARS-CoV-2 and other respiratory viruses on tens of thousands of samples in parallel. SARSeq relies on next generation sequencing of multiple amplicons generated in a multiplexed RT-PCR reaction. Two-dimensional, unique dual indexing, using four indices per sample, enables unambiguous and scalable assignment of reads to individual samples. We calibrate SARSeq on SARS-CoV-2 synthetic RNA, virions, and hundreds of human samples of various types. Robustness and sensitivity were virtually identical to quantitative RT-PCR. Double-blinded benchmarking to gold standard quantitative-RT-PCR performed by human diagnostics laboratories confirms this high sensitivity. SARSeq can be used to detect Influenza A and B viruses and human rhinovirus in parallel, and can be expanded for detection of other pathogens. Thus, SARSeq is ideally suited for differential diagnostic of infections during a pandemic.

Pharmacokinetic (PK) analyses in CSF and plasma from TBCRC049, an ongoing trial to assess the safety and efficacy of the combination of tucatinib, trastuzumab and capecitabine for the treatment of leptomeningeal metastasis (LM) in HER2 positive breast cancer.

1044 Background: Tucatinib is a potent and highly selective HER2-targeted tyrosine kinase inhibitor approved for use in combination with trastuzumab and capecitabine for patients with metastatic HER2+ breast cancer (MBC) who have received ≥1 prior HER2-based regimen in the metastatic setting, including patients with brain metastases (BM). TBCRC049 (NCT03501979) is an investigator-initiated phase 2 single-arm study currently enrolling to evaluate the safety and efficacy of tucatinib, trastuzumab and capecitabine in HER2+ BC with newly diagnosed LM. Here, we report the pre-specified pharmacokinetic (PK) analysis for the first 15 patients to determine bioavailability of tucatinib and its predominant metabolite, ONT-993, in the CSF. Methods: Eligible patients included adults with HER2+ MBC, KPS &gt; 50, and newly diagnosed, untreated LM (defined as positive CSF cytology and/or radiographic evidence of LM, plus clinical signs/symptoms). Patients with treated or concurrent/new BM were allowed. The primary endpoint is overall survival with an accrual goal of 30 pts. Parallel PK samples were collected in plasma and CSF via Ommaya reservoir on day 1 of cycles 1 and 2 at 0h (baseline), 2-3h, 5-7h and 24h (optional) following initiation of tucatinib 300 mg BID. Tucatinib and ONT-993 were quantified in plasma (n=15) and CSF (n=13) using validated liquid chromatography-mass spectrometry methods. Results: Tucatinib and ONT-993 plasma concentrations were consistent with previous studies and exhibited high interindividual variability. Tucatinib and ONT-993 were detectable in the CSF within 2 hours post tucatinib administration; concentrations ranged from 0.57 to 25 ng/mL for tucatinib (IC50 for tucatinib against HER2 is 3.3 ng/mL) and 0.28 to 4.7 ng/mL for ONT-993. Tucatinib concentrations in the CSF per timepoint were in a similar range to unbound plasma (plasmaub) tucatinib. CSF to plasmaub ratios were generally consistent over time; the steady-state (cycle 2) median tucatinib CSF to plasmaub ratio was 0.83 (0.19 to 2.1). ONT-993 CSF to plasmaub ratios were similar to tucatinib CSF to plasmaub ratios. Conclusions: In patients with LM from HER2+MBC who were treated with tucatinib, trastuzumab, and capecitabine, tucatinib and ONT-993 were detectable in the CSF of all patients at median levels similar to plasmaub tucatinib. This is the first documented evidence of tucatinib distributing into the CSF in patients with HER2+MBC. Efficacy and safety of tucatinib, trastuzumab, and capecitabine in patients with HER2+ LM will be reported upon completion of TBCRC 049 accrual. Clinical trial information: NCT03501979 .

Real-Life Head-to-Head Comparison of Performance of Two High-Throughput Automated Assays for the Detection of SARS-CoV-2 RNA in Nasopharyngeal Swabs: The Alinity m and cobas 6800 SARS-CoV-2 Assays

The Alinity m (Abbott Molecular, Des Plaines, IL) automated molecular analyzer allows continuous loading of samples and sample-to-result molecular detection of several microorganisms. The detection of SARS-CoV-2 by the Alinity m was compared with that of the cobas 6800 (Roche Molecular Systems, Branchburg, NJ; standard comparator) in a manufacturer-independent clinical evaluation on 2157 consecutive nasopharyngeal swab samples. Valid initial results on Alinity m and cobas 6800 were obtained from 2129 (98.7%) and 2157 (100%) samples, respectively. The overall percent agreement (95% CI) was 98.3% (2092/2129 [97.6%–98.7%]); positive percent agreement, 100% (961/961 [99.6%–100%]); negative percent agreement, 96.8% (1131/1168 [95.7%–97.7%]); and high κ value, 0.965 (0.954–0.976). There were 37 discordant results on Alinity m and, based on discordant analyses, including previous and/or follow-up PCR results, 22 could be considered analytically true positive with high probability. Due to a lack of additional information and an inability to perform repeated/further testing, the status of the remaining 15 discordant results remained unresolved. The throughput of the two analyzers was compared using testing on 564 samples in parallel across two 8-hour shifts in clinical practice. The turnaround times were compared using processing of 94 routine samples in parallel on each working day for 5 consecutive days. The two analyzers showed similar performance, with certain differences that have potential importance in some laboratory settings.