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[en] Breast screening specificity is improved if previous mammograms are available, which presents a challenge when converting to digital mammography. Two display options were investigated: mounting previous film mammograms on a multiviewer adjacent to the workstation, or digitising them for soft copy display. Eight qualified screen readers were videotaped undertaking routine screen reading for two 45-min sessions in each scenario. Analysis of gross eye and head movements showed that when digitised, previous mammograms were examined a greater number of times per case (p=0.03), due to a combination of being used in 19% more cases (p=0.04) and where used, looked at a greater number of times (28% increase, p=0.04). Digitising previous mammograms reduced both the average time taken per case by 18% (p=0.04) and the participants' perceptions of workload (p < 0.05). Digitising previous analogue mammograms may be advantageous, in particular in increasing their level of use. (orig.)
[en] Spontaneous activity represents an early, primitive form of motor activity within zebrafish embryos, providing a potential readout for identification of neuroactive compounds. However, despite use as an endpoint in chemical screens around the world, the predictive power and limitations of assays relying on spontaneous activity remain unclear. Using an improved high-content screening assay that increased throughput from 384 to 3072 wells per week, we screened a well-characterized library of 1280 pharmacologically active compounds (LOPAC1280) – 612 of which target neurotransmission – to identify which targets are detected using spontaneous activity as a readout. Results from this screen revealed that (1) 8% of the LOPAC1280 library was biologically active; (2) spontaneous activity was affected by compounds spanning a broad array of targets; (3) only 4% of compounds targeting neurotransmission impacted spontaneous activity; and (4) hypoactivity was observed for 100% of hits detected, including those that exhibit opposing mechanisms of action for the same target. Therefore, while this assay was able to rapidly identify potent neuroactive chemicals, these data suggest that spontaneous activity may lack the ability to discriminate modes of action for compounds interfering with neurotransmission, an issue that may be due to systemic uptake following waterborne exposure, persistent control variation, and/or interference with non-neurotransmission-related mechanisms. - Highlights: • Assay throughput was increased from 384 to 3072 wells per week. • 8% of the LOPAC1280 library was biologically active within zebrafish embryos. • Spontaneous activity was affected by compounds spanning a broad array of targets. • Only 4% of compounds targeting neurotransmission impacted spontaneous activity. • Hypoactivity was observed for 100% of hits detected.
[en] Background: The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function. Results: Here, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-Term memory. Conclusion: We conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens. © 2019 The Author(s).
[en] Droplet-based microfluidics holds enormous potential for transforming the way that many biological screens are performed by affording unprecedented increases in screening throughput and reductions in reagent usage. In this paper, we describe this maturing field and the pioneering work that has laid the foundation for its application to ultrahigh-throughput biological analysis. We begin by introducing the basic elements of the approach and describe the numerous microfluidic components that have been developed for droplet manipulation, with special emphasis on the ones most useful for ultrahigh-throughput analysis. We conclude with a discussion of the first demonstrations of this approach to perform novel, ultrahigh-throughput biological screens. (paper)
[en] Purpose: to epidemiologically evaluate the impact of digital mammography screening on incidence rates and tumor characteristics for breast cancer. Materials and methods: the first German digital screening units in the clinical routine were evaluated during the implementation period by using data from the cancer registry to compare the incidence rate of breast cancers and prognostic characteristics. 74% of women aged 50-69 within the region of Muenster/Coesfeld/Warendorf were invited between 10/2005 and 12/2007 for initial screening; 55% participated (n = 35961). Results: in 2002-2004 the average breast cancer incidence rate (per 100000) was 297.9. During the implementation of screening, the rate rose to 532.9 in 2007. Of the 349 cancers detected with screening, 76% (265/349) were invasive compared to 90% (546/608) of cases not detected with screening during the same period. 37% (97/265) of cancers detected in the screening program had a diameter of ≤ 10 mm and 75% (198/265) were node-negative compared to 15% (79/546) and 64% (322/503), respectively, in cancers detected outside the screening program. The distribution of invasive tumor size (pT categories) and the nodal status differed with statistical significance between cancers detected in and outside the program (p = 0.005 and p = 0.004, respectively). (orig.)
[en] Within the physical-technical quality assurance of the German breast cancer screening program all digital mammography systems have to perform the contrast resolution test and the determination of the average glandular dose based on the European guidelines for quality assurance in breast cancer screening and diagnosis (4th Edition). Since 1.1.2009 this applies to digital systems outside the screening program too. To accomplish uniform measurements in all federal states of Germany, the physical board of the reference centers developed together a special guideline for these test position. This Guideline describes the determination of the average glandular dose for different types of mammography systems, the CDMAM image acquisition and the CDMAM image evaluation as well. This guideline was verified by the German task group ''Roentgenverordnung''. (orig.)
[en] Active polymer materials allow the construction of cheap, flexible circuitry using simple printing techniques. A process and devices capable of performing a variety of circuit functions using electrolytic technology have been developed. The process is based on a simple screen printing system that allows the formation of multilayer circuitry with no active layer-to-layer alignment. Using this system, it has been possible to build a number of circuits utilizing transistor-like electrolytic devices and other active devices with novel topologies. Models have been developed that provide the ability to simulate arbitrary device geometries using a standard-cell approach for the basic elements required. These have allowed accurate simulation of the dynamic response of a number of device structures to be performed
[en] In spite of the fact that the German Society of Endocrinology has recommended calcitonin as screening-parameter the majority of physicians in Germany do not routinely use calcitonin in patients with thyroid nodules to exclude medullary thyroid cancer (MTC). The future revision of the recommendation should describe reference values for each commercially available assay, separately for men and women (basal and after pentagastrin-stimulation), and should define sonomorphological inclusion criteria. The epidemiological database of the prevalence of MTC is controversial and the specificity of basal elevated calcitonin levels is limited up to the 5-fold of the upper reference level. If renal insufficiency, bacterial infection, and an alcohol- or druginduced stimulation of calcitonin is excluded, hypercalcitoninaemia should be confirmed by a second measurement (if necessary using another assay). Stimulation of calcitonin by use of pentagastrin is mandatory prior to the decision on thyroidectomy. A stimulated calcitonin level < 100 pg/ml justifies 'wait and see'. If stimulated calcitonin levels range between 100 and 200 pg/ml or higher, the differentiation between C-cell hyperplasia and MTC remains uncertain, especially in men. The implementation of calcitonin- screening requires the definition of sonographic inclusion criteria and validation of each assay. Additional prerequisites are excellent logistic (short period between blood sampling and start of the laboratory test), knowledge of differential diagnoses, knowledge of the consumption of drugs and alcohol, availability of pentagastrin-testing and of moleculargenetic testing with full information to the patients and sufficient time before the decision on surgery is made. All this and the choice of a skilled surgeon, experienced in thyroidectomy and lymphadenectomy with a low rate of local complications are the rationale to recommend calcitonin-screening primarily in centers for thyroid disorders. (orig.)
[en] Thoughts on screening for lung cancer are based on the very poor prognosis of this tumor when the diagnosis is made because of symptoms (<15% 5-year survival), the markedly better prognosis if it is detected in asymptomatic early stages (up to 80% 5-year survival), the high sensitivity of unenhanced low-dose CT in the detection of small tumors, and the clear definition of persons at risk. Feasibility studies using well-defined diagnostic algorithms for management of detected pulmonary nodules have demonstrated a high proportion (>50 to >90%) of small, resectable non-small-cell lung carcinomas in the early stages, with a good prognosis for the patients affected and a low rate of unnecessary biopsies. However, biases such as overdiagnosis, length-time and lead-time could hamper potential reduction of mortality from lung cancer, and the results of large prospective randomized trials are therefore awaited. At the same time, other techniques for early diagnosis of lung cancer are under evaluation, such as sophisticated methods of sputum analysis, molecular markers in the blood and analysis of exhaled air. (orig.)
[de]Ueberlegungen zum Screening des Lungenkarzinoms werden motiviert durch die sehr schlechte Prognose des Tumors bei Diagnose aufgrund von Symptomen (<15% 5-Jahres-Ueberleben), die deutlich bessere Prognose asymptomatischer frueher Stadien (bis 80% 5-Jahres-Ueberleben), die hohe Sensitivitaet der nativen Niedrigdosis-CT fuer kleine Tumoren und die gute Identifizierbarkeit von Risikopersonen. Machbarkeitsstudien unter Verwendung genau definierter diagnostischer Algorithmen zum Umgang mit gefundenen Lungenrundherden zeigten einen grossen Anteil (>50 bis >90%) kleiner, resektabler nichtkleinzelliger Lungenkarzinome in fruehen Stadien mit guter Prognose der betroffenen Patienten bei einer geringen Rate unnoetiger Biopsien. Da allerdings Verzerrungsfaktoren wie Ueberdiagnose, length-time und lead-time Aussagen zum tatsaechlichen Nutzen der Methode hinsichtlich einer Senkung der Sterblichkeit am Lungenkarzinom nicht zulassen, werden derzeit die Ergebnisse grosser prospektiver randomisierter Studien abgewartet. Gleichzeitig sind andere Frueherkennungsmethoden wie verfeinerte Sputumdiagnostik, Analyse molekularer Marker im Blut oder Atemluftanalyse in der Evaluation. (orig.)
[en] Highlights: •We fabricated flexible anthrax sensors with a simple screen-printing method. •The sensors selectively detected B. anthracis biomarker. •The sensors provide the visible alarm against anthrax attack. -- Abstract: Since the 2001 anthrax attacks, efforts have focused on the development of an anthrax detector with rapid response and high selectivity and sensitivity. Here, we demonstrate a fluorescence sensor for detecting anthrax biomarker with high sensitivity and selectivity using a screen-printing method. A lanthanide–ethylenediamine tetraacetic acid complex was printed on a flexible polyethersulfone film. Screen-printing deposition of fluorescent detecting moieties produced fluorescent patterns that acted as a visual alarm against anthrax