The ATLAS experiment will replace its existing Inner Detector with the new all-silicon Inner Tracker (ITk) to cope with the operating conditions of the forthcoming high-luminosity phase of the LHC ...(HL-LHC). The outer regions of the ITk will be instrumented with ∼18000 ATLAS18 strip sensors fabricated by Hamamatsu Photonics K.K. (HPK). With the launch of full-scale sensor production in 2021, the ITk strip sensor community has undertaken quality control (QC) testing of these sensors to ensure compliance with mechanical and electrical specifications agreed with HPK. The testing is conducted at seven QC sites on each of the monthly deliveries of ∼500 sensors.
This contribution will give an overview of the QC procedures and analysis; the tests most likely to determine pass/fail for a sensor are IV, long-term leakage current stability, full strip test and visual inspection. The contribution will then present trends in the results and properties following completion of ∼60% of production testing. It will also mention challenges overcome through collaborative efforts with HPK during the early phases of production. With less than 5% of sensors rejected by QC testing, the overall production quality has been very good.
Summary
Sensitive and accurate RT‐qPCR tests are the primary diagnostic tools to identify SARS‐CoV‐2‐infected patients. While many SARS‐CoV‐2 RT‐qPCR tests are available, there are significant ...differences in test sensitivity, workflow (e.g. hands‐on‐time), gene targets and other functionalities that users must consider. Several publicly available protocols shared by reference labs and public health authorities provide useful tools for SARS‐CoV‐2 diagnosis, but many have shortcomings related to sensitivity and laborious workflows. Here, we describe a series of SARS‐CoV‐2 RT‐qPCR tests that are originally based on the protocol targeting regions of the RNA‐dependent RNA polymerase (RdRp) and envelope (E) coding genes developed by the Charité Berlin. We redesigned the primers/probes, utilized locked nucleic acid nucleotides, incorporated dual probe technology and conducted extensive optimizations of reaction conditions to enhance the sensitivity and specificity of these tests. By incorporating an RNase P internal control and developing multiplexed assays for distinguishing SARS‐CoV‐2 and influenza A and B, we streamlined the workflow to provide quicker results and reduced consumable costs. Some of these tests use modified enzymes enabling the formulation of a room temperature‐stable master mix and lyophilized positive control, thus increasing the functionality of the test and eliminating cold chain shipping and storage. Moreover, a rapid, RNA extraction‐free version enables high sensitivity detection of SARS‐CoV‐2 in about an hour using minimally invasive, self‐collected gargle samples. These RT‐qPCR assays can easily be implemented in any diagnostic laboratory and can provide a powerful tool to detect SARS‐CoV‐2 and the most common seasonal influenzas during the vaccination phase of the pandemic.
Here, we describe a series of SARS‐CoV‐2 RT‐qPCR tests that are originally based on the protocol targeting regions of the RNA‐dependent RNA polymerase (RdRp) and envelope (E) coding genes developed by the Charité Berlin. We redesigned the primers/probes, added an RNase P internal control, utilized locked nucleic acid nucleotides and dual probe technology to enhance sensitivity and specificity, optimized an RNA‐extraction free workflow, and multiplexed the assays to detect influenza. These RT‐qPCR assays can easily be implemented in any diagnostic laboratory and can provide a powerful tool to detect SARS‐CoV‐2 and the most common seasonal influenzas.
This is an open access title available under the terms of a CC BY-NC-ND 4.0 License. It is free to read, download and share on Elgaronline.com. Centralising the role of land and landowners, Spatial ...Flood Risk Management brings together knowledge from socio-economy, public policy, hydrology, geomorphology, and engineering to establish an interdisciplinary knowledge base on spatial approaches to managing flood risks.
Distal hypoperfusion ischemic syndrome (DHIS), commonly referred to as hand ischemia or 'steal' after dialysis access placement, occurs in 5-10% of cases when the brachial artery is used, or 10 times ...that of wrist arteriovenous fistulas (AVFs) using the radial artery. It is typically seen in elderly women with diabetes, and may carry severe morbidity including tissue or limb loss if not recognized and treated. Three distinct etiologies include (1) blood flow restriction to the hand from arterial occlusive disease either proximal or distal to the AV access anastomosis, (2) excess blood flow through the AV fistula conduit (true steal), and (3) lack of vascular (arterial) adaptation or collateral flow reserve (ie atherosclerosis) to the increased flow demand from the AV conduit. These three causes of steal may occur alone or in concert. The diagnosis of steal is based on an accurate history and physical examination and confirmed with tests including an arteriogram, duplex Doppler ultrasound (DDU) evaluation with finger pressures and waveform analysis. Treatment of steal includes observation of developing symptoms in mild cases. Balloon angioplasty is the appropriate intervention for an arterial stenosis. At least three distinct surgical corrective procedures exist to counteract the pathophysiology of steal. The ultimate treatment strategy depends on severity of symptoms, the extent of patient co-morbidity, and the local dialysis access technical team support and skills available.
The production of strip sensors for the ATLAS Inner Tracker (ITk) started in 2021. Since then, a Quality Assurance (QA) program has been carried out continuously, by using specific test structures, ...in parallel to the Quality Control (QC) inspection of the sensors. The QA program consists of monitoring sensor-specific characteristics and the technological process variability, before and after the irradiation with gammas, neutrons, and protons. After two years, half of the full production volume has been reached and we present an analysis of the parameters measured as part of the QA process. The main devices used for QA purposes are miniature strip sensors, monitor diodes, and the ATLAS test chip, which contains several test structures. Such devices are tested by several sites across the collaboration depending on the type of samples (non-irradiated components or irradiated with protons, neutrons, or gammas). The parameters extracted from the tests are then uploaded to a database and analyzed by Python scripts. These parameters are mainly examined through histograms and time-evolution plots to obtain parameter distributions, production trends, and meaningful parameter-to-parameter correlations. The purpose of this analysis is to identify possible deviations in the fabrication or the sensor quality, changes in the behavior of the test equipment at different test sites, or possible variability in the irradiation processes. The conclusions extracted from the QA program have allowed test optimization, establishment of control limits for the parameters, and a better understanding of device properties and fabrication trends. In addition, any abnormal results prompt immediate feedback to a vendor.
Abstract
Background
Whether baseline cardiovascular health status significantly influences the risk of Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD) in patients receiving de-novo ...chemotherapy exposure is an important clinical question for both surveillance and management decisions. The reference standard technique for the serial monitoring of left ventricular (LV) volumes and ejection fraction (EF) is cardiovascular magnetic resonance (CMR). Using this technique, we sought to prospectively evaluate baseline clinical risk factors and CMR-based pre-exposure characteristics for their influence on the incident occurrence of CTRCD.
Methods
We prospectively enrolled 371 cancer patients referred for baseline (pre-chemotherapy) followed by surveillance CMR imaging as part of the Cardiotoxicity Prevention Research Initiative (CAPRI). We also recruited 62 healthy volunteers to evaluate for referral population differences in CMR-based markers. Study subjects and healthy volunteers underwent identical CMR imaging protocols inclusive of cine imaging, T1 and T2 mapping. CTRCD was defined according to surveillance CMR imaging with criteria established as a drop in LVEF by >5% (meaningful detectable difference for CMR technique) to a value ≤56% (lower limit of normal) at any time point during chemotherapy surveillance. A total of 1474 CMR studies were performed over a median surveillance period of 12.5 months (range 2.3 to 68.9 months).
Results
The majority of patients were female (77%), being referred for breast cancer (64%) or lymphoma (36%), with a mean age of 54.0±14 years. The baseline prevalence of hypertension, diabetes, hyperlipidemia, and current smoking were 32%, 11%, 46%, and 13%, respectively. Compared to healthy volunteers, cancer patients at baseline showed smaller indexed LV and RV volumes, higher indexed LV mass, and higher native T1 values (mean difference +33 msec; p<0.001). LV and right ventricular (RV) EF and T2 mapping values were not significantly different. CTRCD criteria were met in 22% of patients. Figure 1 shows a forest plot of univariable and multivariable predictors of CTRCD occurrence. Following multivariable adjustment, only combined anthracycline/trastuzumab regimen (OR 4.4, 95% CI 2.0–9.5) and baseline indexed LVEDV (OR 2.3, 95% CI 1.2–4.5) were found to be significant predictors of this outcome.
Conclusion
Using the reference standard of serial CMR imaging we identified that of all baseline (pre-chemotherapy) clinical and CMR-based markers of cardiovascular health, only indexed LV end-doastolic volume (EDV) was independently associated with future occurrence of CTRCD following adjustment for chemotherapy regimen. We did not observe significant associations with conventional cardiac risk factors in our study population. The observed risk for indexed LVEDV was clinically meaningful (2.3-fold risk per 10 ml/m2) and warrants further investigation as a relevant baseline marker of risk in this referral population.
Figure 1. Forest plot of predictors of CTRCD
Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): Alberta Innovates/Genome Alberta: CAPRI
Ten strains of an asexual arthroconidial yeast species were isolated from Bryndza, a traditional Slovak artisanal sheep cheese, which was manufactured from raw milk during a 4-month summer production ...period at two Slovakian sites (the northern RuZomberok and the central-southern Tisovec areas). Sequence comparison of the D1/D2 domains of the large-subunit rRNA gene revealed that this yeast represents a novel species of the genus Geotrichum, which contains anamorphs of the ascogenous genus Galactomyces, for which the name Geotrichum bryndzae sp. nov. is proposed (type culture CCY 16-2-1T=NRRL Y-48450T=CBS 11176T). The novel species is most closely related to Geotrichum silvicola NRRL Y-27641T, although yeasts with identical or very similar sequences have been found throughout the world.
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