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•Copper resinate is a mixed abietate/acetate copper salt dissolved in resin.•Its green color comes from the blue organic copper salt and the yellow resin.•Mild basic solutions convert ...copper resinate to orange-brown CuO.
Copper resinate was a green pigment used through the Renaissance when it was largely discontinued due to its tendency to discolor to brown over time. Historically, this pigment was made by grinding copper(II) acetate, or verdigris, in a tree resin rich in abietic acid. Commercial copper resinate and copper(II) abietate mixtures were analyzed by electrospray ionization mass spectrometry, infrared and visible spectroscopy. The pigment consists of mixed organic copper salts with bridged acetate (Ac) and abietate (Ab) ligands (i.e, Cu2Ab4, Cu2Ab3Ac, and Cu2Ab2Ac2) based upon sodiated ions detected in mass spectra. The lipophilic abietate groups allow the molecules to dissolve in the resin and oil binders for a transparent glaze free of pigment particles. A paddlewheel bridged-dimer structure of Cu2Ab4 modeled by density functional theory has similar bond distances to copper(II) acetate. Experimental results suggest that copper(II) abietate lacks the axial water ligands found in copper(II) acetate. The green color of copper resinate originates from a combination of the blue typical for organic copper salts and the yellow of free abietate/abietic acid. Solutions of both verdigris and copper resinate quickly discolor to brown upon the addition of a dilute basic solution. Slow conversion of organic copper salts in the paint layer to brown copper(II) oxide, possibly enhanced by environmental conditions or cleaning with alkaline materials, may be an alternate discoloration mechanism in cultural artifacts. Copper detected by portable energy dispersive X-ray fluorescence (XRF) spectroscopy and scanning electron microscopy with energy dispersive X-ray (SEM-EDX) in discolored paint layers of an Italian Renaissance painting by Tintoretto is consistent with this artist’s established use of copper resinate.
There have been significant advances in the understanding of the biology and treatment of non–small-cell lung cancer (NSCLC) during the past few years. A number of molecularly targeted agents are in ...the clinic or in development for patients with advanced NSCLC. We are beginning to understand the mechanisms of acquired resistance after exposure to tyrosine kinase inhibitors in patients with oncogene addicted NSCLC. The advent of next-generation sequencing has enabled to study comprehensively genomic alterations in lung cancer. Finally, early results from immune checkpoint inhibitors are very encouraging. This review summarizes recent advances in the area of cancer genomics, targeted therapies, and immunotherapy.
Accurate rapid diagnostic tests for SARS-CoV-2 infection could contribute to clinical and public health strategies to manage the COVID-19 pandemic. Point-of-care antigen and molecular tests to detect ...current infection could increase access to testing and early confirmation of cases, and expediate clinical and public health management decisions that may reduce transmission.
To assess the diagnostic accuracy of point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection. We consider accuracy separately in symptomatic and asymptomatic population groups.
Electronic searches of the Cochrane COVID-19 Study Register and the COVID-19 Living Evidence Database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) were undertaken on 30 Sept 2020. We checked repositories of COVID-19 publications and included independent evaluations from national reference laboratories, the Foundation for Innovative New Diagnostics and the Diagnostics Global Health website to 16 Nov 2020. We did not apply language restrictions.
We included studies of people with either suspected SARS-CoV-2 infection, known SARS-CoV-2 infection or known absence of infection, or those who were being screened for infection. We included test accuracy studies of any design that evaluated commercially produced, rapid antigen or molecular tests suitable for a point-of-care setting (minimal equipment, sample preparation, and biosafety requirements, with results within two hours of sample collection). We included all reference standards that define the presence or absence of SARS-CoV-2 (including reverse transcription polymerase chain reaction (RT-PCR) tests and established diagnostic criteria).
Studies were screened independently in duplicate with disagreements resolved by discussion with a third author. Study characteristics were extracted by one author and checked by a second; extraction of study results and assessments of risk of bias and applicability (made using the QUADAS-2 tool) were undertaken independently in duplicate. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test and pooled data using the bivariate model separately for antigen and molecular-based tests. We tabulated results by test manufacturer and compliance with manufacturer instructions for use and according to symptom status.
Seventy-eight study cohorts were included (described in 64 study reports, including 20 pre-prints), reporting results for 24,087 samples (7,415 with confirmed SARS-CoV-2). Studies were mainly from Europe (n = 39) or North America (n = 20), and evaluated 16 antigen and five molecular assays. We considered risk of bias to be high in 29 (50%) studies because of participant selection; in 66 (85%) because of weaknesses in the reference standard for absence of infection; and in 29 (45%) for participant flow and timing. Studies of antigen tests were of a higher methodological quality compared to studies of molecular tests, particularly regarding the risk of bias for participant selection and the index test. Characteristics of participants in 35 (45%) studies differed from those in whom the test was intended to be used and the delivery of the index test in 39 (50%) studies differed from the way in which the test was intended to be used. Nearly all studies (97%) defined the presence or absence of SARS-CoV-2 based on a single RT-PCR result, and none included participants meeting case definitions for probable COVID-19. Antigen tests Forty-eight studies reported 58 evaluations of antigen tests. Estimates of sensitivity varied considerably between studies. There were differences between symptomatic (72.0%, 95% CI 63.7% to 79.0%; 37 evaluations; 15530 samples, 4410 cases) and asymptomatic participants (58.1%, 95% CI 40.2% to 74.1%; 12 evaluations; 1581 samples, 295 cases). Average sensitivity was higher in the first week after symptom onset (78.3%, 95% CI 71.1% to 84.1%; 26 evaluations; 5769 samples, 2320 cases) than in the second week of symptoms (51.0%, 95% CI 40.8% to 61.0%; 22 evaluations; 935 samples, 692 cases). Sensitivity was high in those with cycle threshold (Ct) values on PCR ≤25 (94.5%, 95% CI 91.0% to 96.7%; 36 evaluations; 2613 cases) compared to those with Ct values >25 (40.7%, 95% CI 31.8% to 50.3%; 36 evaluations; 2632 cases). Sensitivity varied between brands. Using data from instructions for use (IFU) compliant evaluations in symptomatic participants, summary sensitivities ranged from 34.1% (95% CI 29.7% to 38.8%; Coris Bioconcept) to 88.1% (95% CI 84.2% to 91.1%; SD Biosensor STANDARD Q). Average specificities were high in symptomatic and asymptomatic participants, and for most brands (overall summary specificity 99.6%, 95% CI 99.0% to 99.8%). At 5% prevalence using data for the most sensitive assays in symptomatic people (SD Biosensor STANDARD Q and Abbott Panbio), positive predictive values (PPVs) of 84% to 90% mean that between 1 in 10 and 1 in 6 positive results will be a false positive, and between 1 in 4 and 1 in 8 cases will be missed. At 0.5% prevalence applying the same tests in asymptomatic people would result in PPVs of 11% to 28% meaning that between 7 in 10 and 9 in 10 positive results will be false positives, and between 1 in 2 and 1 in 3 cases will be missed. No studies assessed the accuracy of repeated lateral flow testing or self-testing. Rapid molecular assays Thirty studies reported 33 evaluations of five different rapid molecular tests. Sensitivities varied according to test brand. Most of the data relate to the ID NOW and Xpert Xpress assays. Using data from evaluations following the manufacturer's instructions for use, the average sensitivity of ID NOW was 73.0% (95% CI 66.8% to 78.4%) and average specificity 99.7% (95% CI 98.7% to 99.9%; 4 evaluations; 812 samples, 222 cases). For Xpert Xpress, the average sensitivity was 100% (95% CI 88.1% to 100%) and average specificity 97.2% (95% CI 89.4% to 99.3%; 2 evaluations; 100 samples, 29 cases). Insufficient data were available to investigate the effect of symptom status or time after symptom onset.
Antigen tests vary in sensitivity. In people with signs and symptoms of COVID-19, sensitivities are highest in the first week of illness when viral loads are higher. The assays shown to meet appropriate criteria, such as WHO's priority target product profiles for COVID-19 diagnostics ('acceptable' sensitivity ≥ 80% and specificity ≥ 97%), can be considered as a replacement for laboratory-based RT-PCR when immediate decisions about patient care must be made, or where RT-PCR cannot be delivered in a timely manner. Positive predictive values suggest that confirmatory testing of those with positive results may be considered in low prevalence settings. Due to the variable sensitivity of antigen tests, people who test negative may still be infected. Evidence for testing in asymptomatic cohorts was limited. Test accuracy studies cannot adequately assess the ability of antigen tests to differentiate those who are infectious and require isolation from those who pose no risk, as there is no reference standard for infectiousness. A small number of molecular tests showed high accuracy and may be suitable alternatives to RT-PCR. However, further evaluations of the tests in settings as they are intended to be used are required to fully establish performance in practice. Several important studies in asymptomatic individuals have been reported since the close of our search and will be incorporated at the next update of this review. Comparative studies of antigen tests in their intended use settings and according to test operator (including self-testing) are required.
Extremes in body condition reduce fertility and overall productivity in beef cattle herds, due in part to altered systemic metabolic conditions that influence the intrafollicular and uterine ...environment. Follicular fluid and serum metabolome profiles are influenced by body composition in women and dairy cattle; however, such information is lacking in beef cattle. We hypothesized that body condition score (BCS)-related alterations in the metabolome of preovulatory follicular fluid and serum may influence oocyte maturation while impacting the oviductal or uterine environment. Therefore, we performed a study with the objective to determine the relationship between BCS and the metabolome of follicular fluid and serum in lactating beef cattle. We synchronized the development of a preovulatory follicle in 130 cows of varying BCS. We collected blood and performed transvaginal follicle aspirations to collect follicular fluid from the preovulatory follicle ~18 h after gonadotropin-releasing hormone administration to stimulate the preovulatory gonadotropin surge. We then selected follicular fluid and serum samples from cows with BCS 4 (Thin; n = 14), BCS 6 (Moderate; n = 18), or BCS >8 (Obese; n = 14) for ultra-high performance liquid chromatography-high resolution mass spectrometry. We identified differences in the follicular fluid or serum of thin, moderate, and obese animals based on multiple linear regression. MetaboAnalyst 5.0 was used for enrichment analysis of significant metabolites. We identified 38 metabolites in follicular fluid and 49 metabolites in serum. There were no significant differences in follicular fluid metabolite content among BCS classifications. There were 5, 22, and 1 serum metabolites differentially abundant between thin-obese, moderate-thin, and moderate-obese classifications, respectively (false discovery rate FDR < 0.10). These metabolites were enriched in multiple processes including "arginine biosynthesis," "arginine/proline metabolism," and "D-glutamine/D-glutamate metabolism" (FDR < 0.04). Pathways enriched with serum metabolites associated with BCS indicate potentially increased reactive oxygen species (ROS) in serum of thin cows. ROS crossing the blood follicular barrier may negatively impact the oocyte during oocyte maturation and contribute to the reduced pregnancy rates observed in thin beef cows.
Implant failure has become more common as the number of primary total ankle arthroplasties (TAAs) performed has increased. Although revision arthroplasty has gained attention for functional ...preservation, the long-term results remain unclear. This study aimed to assess the long-term outcomes of revision TAA using a mobile-bearing prosthesis in a considerably large cohort; the risk factors for failure were also determined.
This single-centre retrospective cohort study included 116 patients (117 ankles) who underwent revision TAA for failed primary TAA between July 2000 and March 2010. Survival analysis and risk factor assessment were performed, and clinical performance and patient satisfaction were evaluated preoperatively and at last follow-up.
The mean duration from initial revision TAA to last follow-up was 15.0 years (SD 3.0; 11.2 to 20.5). The cumulative survival rates of the revised ankles were 81% (95% confidence interval (CI) 74% to 88%), 74% (65% to 82%), and 70% (61% to 79%) at five, ten, and 15 years, respectively. Comorbidities prior to primary TAA, aseptic loosening, instability, or grafting of cysts were found to be the most common risk factors for secondary revision. The median value for preoperative pain, as assessed using the visual analogue scale, declined from 6 (interquartile range (IQR) 5 to 8) to 2 (IQR 0 to 5) (p < 0.001) and the mean American Orthopaedic Foot and Ankle Society ankle-hindfoot score improved from 43 (SD 17) preoperatively to 70 (SD 20) (p < 0.001) at last follow-up.
Revision TAA offers acceptable survival rates after 15 years; it therefore offers a valuable option for treatment of implant failure in carefully selected cases. Although patient-reported outcomes improve substantially, the degree of improvement reported following primary TAA is not achieved.
Induced ovulation of small pre-ovulatory follicles reduced pregnancy rates, embryo survival, day seven embryo quality, and successful embryo cleavage in beef cows undergoing fixed-time artificial ...insemination. RNA-sequencing of oocytes and associated cumulus cells collected from pre-ovulatory follicles 23 h after gonadotropin-releasing hormone (GnRH) administration to induce the pre-ovulatory gonadotropin surge suggested reduced capacity for glucose metabolism in cumulus cells of follicles ≤11.7 mm. We hypothesized that the follicular fluid metabolome influences metabolic capacity of the cumulus-oocyte complex and contributes to reduced embryo cleavage and quality grade observed following induced ovulation of small follicles. Therefore, we performed a study to determine the correlation between pre-ovulatory follicle diameter and follicular fluid metabolome profiles in lactating beef cows (Angus, n = 130). We synchronized the development of a pre-ovulatory follicle and collected the follicular contents approximately 20 h after GnRH administration. We then performed ultra-high performance liquid chromatography—high resolution mass spectrometry (UHPLC-HRMS) metabolomic studies on 43 follicular fluid samples and identified 38 metabolites within pre-ovulatory follicles of increasing size. We detected 18 metabolites with a significant, positive correlation to follicle diameter. Individual and pathway enrichment analysis of significantly correlated metabolites suggest that altered glucose and amino acid metabolism likely contribute to reduced developmental competence of oocytes when small pre-ovulatory follicles undergo induced ovulation.
Fast and reliable detection of patients with severe and heterogeneous illnesses is a major goal of precision medicine.sup.1,2. Patients with leukaemia can be identified using machine learning on the ...basis of their blood transcriptomes.sup.3. However, there is an increasing divide between what is technically possible and what is allowed, because of privacy legislation.sup.4,5. Here, to facilitate the integration of any medical data from any data owner worldwide without violating privacy laws, we introduce Swarm Learning--a decentralized machine-learning approach that unites edge computing, blockchain-based peer-to-peer networking and coordination while maintaining confidentiality without the need for a central coordinator, thereby going beyond federated learning. To illustrate the feasibility of using Swarm Learning to develop disease classifiers using distributed data, we chose four use cases of heterogeneous diseases (COVID-19, tuberculosis, leukaemia and lung pathologies). With more than 16,400 blood transcriptomes derived from 127 clinical studies with non-uniform distributions of cases and controls and substantial study biases, as well as more than 95,000 chest X-ray images, we show that Swarm Learning classifiers outperform those developed at individual sites. In addition, Swarm Learning completely fulfils local confidentiality regulations by design. We believe that this approach will notably accelerate the introduction of precision medicine.
Little is known about the function of the cytoplasmic histone deacetylase HDAC6 in striated muscle. Here, we addressed the role of HDAC6 in cardiac and skeletal muscle remodeling induced by the ...peptide hormone angiotensin II (ANG II), which plays a central role in blood pressure control, heart failure, and associated skeletal muscle wasting. Comparable with wild-type (WT) mice, HDAC6 null mice developed cardiac hypertrophy and fibrosis in response to ANG II. However, whereas WT mice developed systolic dysfunction upon treatment with ANG II, cardiac function was maintained in HDAC6 null mice treated with ANG II for up to 8 wk. The cardioprotective effect of HDAC6 deletion was mimicked in WT mice treated with the small molecule HDAC6 inhibitor tubastatin A. HDAC6 null mice also exhibited improved left ventricular function in the setting of pressure overload mediated by transverse aortic constriction. HDAC6 inhibition appeared to preserve systolic function, in part, by enhancing cooperativity of myofibrillar force generation. Finally, we show that HDAC6 null mice are resistant to skeletal muscle wasting mediated by chronic ANG-II signaling. These findings define novel roles for HDAC6 in striated muscle and suggest potential for HDAC6-selective inhibitors for the treatment of cardiac dysfunction and muscle wasting in patients with heart failure.
Suprastomal collapse and granulation are common sequelae of pediatric tracheostomy. We present the first measure of suprastomal obstructive pathology, the Seattle Suprastomal Safety Score (5S), an ...instrument with 2 domains: collapse and granulation.
Cross-sectional repeated testing survey.
Electronic survey.
A library of images was assembled from still pictures of the suprastomal area in 50 patients who previously underwent trachea-bronchoscopy at a quaternary children's hospital. Five pediatric otolaryngologists and 2 pediatric pulmonologists reviewed the images in random, blinded fashion and provided 5S scores. Participants repeated this process 2 to 4 weeks later. Interrater agreement was calculated with an intraclass correlation coefficient (ICC) with a 2-way random-effects model and Fleiss's κ. Intrarater agreement was measured with an ICC using a 2-way mixed-effects model as well as with test-retest correlations using Spearman rank coefficient. All measures were performed separately on collapse and granulation domains.
ICC for interrater agreement was 0.88 (95% CI, 0.82-0.93) for collapse and 0.97 (95% CI, 0.96-0.98) for granulation, indicating almost perfect agreement. Fleiss's κ demonstrated moderate agreement for collapse and almost perfect agreement for granulation. ICC for intrarater agreement was 0.95 (95% CI, 0.93-0.97) and 0.99 (95% CI, 0.98-0.99) for collapse and granulation, respectively, indicating almost perfect agreement. Spearman rank correlation for test-retest demonstrated substantial agreement for collapse and almost perfect agreement for granulation.
The 5S demonstrates excellent interrater and intrarater agreement, making it highly reliable as a novel measure of suprastomal collapse and granulation in tracheostomy-dependent pediatric patients.
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