Re-evaluating blood culture incubation times during SARS-CoV-2: Can we shorten incubation times without compromising results?

No abstract

Comparative Analysis of Carrier-Based Obturation and Lateral Compaction: A Retrospective Clinical Outcomes Study

The purpose of this retrospective study was to compare the outcome of primary endodontic treatment using a standardized cleaning and shaping technique and obturation with either lateral compaction or carrier-based obturation. Patients received primary endodontic treatment in the predoctoral dental clinic using a standardized cleaning and shaping protocol. All root canals were obturated using AH PlusTM sealer with lateral compaction of gutta-percha (LC) or carrier-based obturation (CBO). A total of 205 cases met the inclusion criteria. 71 teeth in 60 patients were recalled after 2 years and evaluated both clinically and radiographically by two independent examiners. Success was defined as a lack of clinical symptoms and a normal periodontal ligament space or reduction in size of a previously existing periapical radiolucency. Chi-square and logistic regression were used for statistical analysis with a significance level of P < 0.05. There was no difference in success rates between cases obturated with LC or CBO (P = 0.802); overall success rate was 83%. Molars had a significantly lower success rate (53%) than premolar and anterior teeth (89%) (P = 0.005), irrespective of the obturation technique used. When a standardized cleaning and shaping protocol was used by predoctoral dental students in a controlled university setting, there was no difference in success rates between cases obturated with LC or CBO

Magnetic Gaps related to Spin Glass Order in Fermionic Systems

We provide evidence for spin glass related magnetic gaps in the fermionic density of states below the freezing temperature. Model calculations are presented and proposed to be relevant for explaining resistivity measurements which observe a crossover from variable-range- to activated behavior. The magnetic field dependence of a hardgap and the low temperature decay of the density of states are given. In models with fermion transport a new metal-insulator transition is predicted to occur due to the spin-glass gap, anteceding the spin glass to quantum paramagnet transition at smaller spin density. Important fluctuation effects due to finite range frustrated interactions are estimated and discussed.Comment: 4 pages, 1 Postscript figure, revised version accepted for publication in Physical Review Letter

Detection of AR-V7 in liquid biopsies of castrate resistant prostate cancer patients : a comparison of AR-V7 analysis in circulating tumor cells, circulating tumor RNA and exosomes

Detection of androgen receptor (AR) variant 7 (AR-V7) is emerging as a clinically important biomarker in castrate resistant prostate cancer (CRPC). Detection is possible from tumor tissue, which is often inaccessible in the advanced disease setting. With recent progress in detecting AR-V7 in circulating tumor cells (CTCs), circulating tumor RNA (ctRNA) and exosomes from prostate cancer patients, liquid biopsies have emerged as an alternative to tumor biopsy. Therefore, it is important to clarify whether these approaches differ in sensitivity in order to achieve the best possible biomarker characterization for the patient. In this study, blood samples from 44 prostate cancer patients were processed for CTCs and ctRNA with subsequent AR-V7 testing, while exosomal RNA was isolated from 16 samples and tested. Detection of AR and AR-V7 was performed using a highly sensitive droplet digital PCR-based assay. AR and AR-V7 RNA were detectable in CTCs, ctRNA and exosome samples. AR-V7 detection from CTCs showed higher sensitivity and has proven specificity compared to detection from ctRNA and exosomes. Considering that CTCs are almost always present in the advanced prostate cancer setting, CTC samples should be considered the liquid biopsy of choice for the detection of this clinically important biomarker

Sequence-based prediction for vaccine strain selection and identification of antigenic variability in foot-and-mouth disease virus

Identifying when past exposure to an infectious disease will protect against newly emerging strains is central to understanding the spread and the severity of epidemics, but the prediction of viral cross-protection remains an important unsolved problem. For foot-and-mouth disease virus (FMDV) research in particular, improved methods for predicting this cross-protection are critical for predicting the severity of outbreaks within endemic settings where multiple serotypes and subtypes commonly co-circulate, as well as for deciding whether appropriate vaccine(s) exist and how much they could mitigate the effects of any outbreak. To identify antigenic relationships and their predictors, we used linear mixed effects models to account for variation in pairwise cross-neutralization titres using only viral sequences and structural data. We identified those substitutions in surface-exposed structural proteins that are correlates of loss of cross-reactivity. These allowed prediction of both the best vaccine match for any single virus and the breadth of coverage of new vaccine candidates from their capsid sequences as effectively as or better than serology. Sub-sequences chosen by the model-building process all contained sites that are known epitopes on other serotypes. Furthermore, for the SAT1 serotype, for which epitopes have never previously been identified, we provide strong evidence - by controlling for phylogenetic structure - for the presence of three epitopes across a panel of viruses and quantify the relative significance of some individual residues in determining cross-neutralization. Identifying and quantifying the importance of sites that predict viral strain cross-reactivity not just for single viruses but across entire serotypes can help in the design of vaccines with better targeting and broader coverage. These techniques can be generalized to any infectious agents where cross-reactivity assays have been carried out. As the parameterization uses pre-existing datasets, this approach quickly and cheaply increases both our understanding of antigenic relationships and our power to control disease

Interhemispheric comparison of GPS phase scintillation at high latitudes during the magnetic-cloud-induced geomagnetic storm of 5–7 April 2010

Arrays of GPS Ionospheric Scintillation and TEC Monitors (GISTMs) are used in a comparative scintillation study focusing on quasi-conjugate pairs of GPS receivers in the Arctic and Antarctic. Intense GPS phase scintillation and rapid variations in ionospheric total electron content (TEC) that can result in cycle slips were observed at high latitudes with dual-frequency GPS receivers during the first significant geomagnetic storm of solar cycle 24 on 5–7 April 2010. The impact of a bipolar magnetic cloud of north-south (NS) type embedded in high speed solar wind from a coronal hole caused a geomagnetic storm with maximum 3-hourly Kp = 8- and hourly ring current Dst =−73 nT. The interhemispheric comparison of phase scintillation reveals similarities but also asymmetries of the ionospheric response in the northern and southern auroral zones, cusps and polar caps. In the nightside auroral oval and in the cusp/cleft sectors the phase scintillation was observed in both hemispheres at about the same times and was correlated with geomagnetic activity. The scintillation level was very similar in approximately conjugate locations in Qiqiktarjuaq (75.4° N; 23.4° E CGM lat. and lon.) and South Pole (74.1° S; 18.9° E), in Longyearbyen (75.3° N; 111.2° E) and Zhongshan (74.7° S; 96.7° E), while it was significantly higher in Cambridge Bay (77.0° N; 310.1° E) than at Mario Zucchelli (80.0° S; 307.7° E). In the polar cap, when the interplanetary magnetic field (IMF) was strongly northward, the ionization due to energetic particle precipitation was a likely cause of scintillation that was stronger at Concordia (88.8° S; 54.4° E) in the dark ionosphere than in the sunlit ionosphere over Eureka (88.1° N; 333.4° E), due to a difference in ionospheric conductivity. When the IMF tilted southward, weak or no significant scintillation was detected in the northern polar cap, while in the southern polar cap rapidly varying TEC and strong phase scintillation persisted for many hours. This interhemispheric asymmetry is explained by the difference in the location of solar terminator relative to the cusps in the Northern and Southern Hemisphere. Solar terminator was in the immediate proximity of the cusp in the Southern Hemisphere where sunlit ionospheric plasma was readily convected into the central polar cap and a long series of patches was observed. In contrast, solar terminator was far poleward of the northern cusp thus reducing the entry of sunlit plasma and formation of dense patches. This is consistent with the observed and modeled seasonal variation in occurrence of polar cap patches. The GPS scintillation and TEC data analysis is supported by data from ground-based networks of magnetometers, riometers, ionosondes, HF radars and all-sky imagers, as well as particle flux measurements by DMSP satellites

Targeted disruption of bone marrow stromal cell-derived Gremlin1 limits multiple myeloma disease progression in vivo

In most instances, multiple myeloma (MM) plasma cells (PCs) are reliant on factors made by cells of the bone marrow (BM) stroma for their survival and growth. To date, the nature and cellular composition of the BM tumor microenvironment and the critical factors which drive tumor progression remain imprecisely defined. Our studies show that Gremlin1 (Grem1), a highly conserved protein, which is abundantly secreted by a subset of BM mesenchymal stromal cells, plays a critical role in MM disease development. Analysis of human and mouse BM stromal samples by quantitative PCR showed that GREM1/Grem1 expression was significantly higher in the MM tumor-bearing cohorts compared to healthy controls (p < 0.05, Mann-Whitney test). Additionally, BM-stromal cells cultured with 5TGM1 MM PC line expressed significantly higher levels of Grem1, compared to stromal cells alone (p < 0.01, t-test), suggesting that MM PCs promote increased Grem1 expression in stromal cells. Furthermore, the proliferation of 5TGM1 MM PCs was found to be significantly increased when co-cultured with Grem1-overexpressing stromal cells (p < 0.01, t-test). To examine the role of Grem1 in MM disease in vivo, we utilized the 5TGM1/KaLwRij mouse model of MM. Our studies showed that, compared to immunoglobulin G (IgG) control antibody-treated mice, mice treated with an anti-Grem1 neutralizing antibody had a decrease in MM tumor burden of up to 81.2% (p < 0.05, two-way ANOVA). The studies presented here demonstrate, for the first time, a novel positive feedback loop between MM PCs and BM stroma, and that inhibiting this vicious cycle with a neutralizing antibody can dramatically reduce tumor burden in a preclinical mouse model of MM.Kimberley C. Clark, Duncan R. Hewett, Vasilios Panagopoulos, Natalya Plakhova, Khatora S. Opperman, Alanah L. Bradey, Krzysztof M. Mrozik, Kate Vandyke, Siddhartha Mukherjee, Gareth C.G. Davies, Daniel L. Worthley, and Andrew C.W. Zannettin

Sequence of the hyperplastic genome of the naturally competent Thermus scotoductus SA-01

<p>Abstract</p> <p>Background</p> <p>Many strains of <it>Thermus </it>have been isolated from hot environments around the world. <it>Thermus scotoductus </it>SA-01 was isolated from fissure water collected 3.2 km below surface in a South African gold mine. The isolate is capable of dissimilatory iron reduction, growth with oxygen and nitrate as terminal electron acceptors and the ability to reduce a variety of metal ions, including gold, chromate and uranium, was demonstrated. The genomes from two different <it>Thermus thermophilus </it>strains have been completed. This paper represents the completed genome from a second <it>Thermus </it>species - <it>T. scotoductus</it>.</p> <p>Results</p> <p>The genome of <it>Thermus scotoductus </it>SA-01 consists of a chromosome of 2,346,803 bp and a small plasmid which, together are about 11% larger than the <it>Thermus thermophilus </it>genomes. The <it>T. thermophilus </it>megaplasmid genes are part of the <it>T. scotoductus </it>chromosome and extensive rearrangement, deletion of nonessential genes and acquisition of gene islands have occurred, leading to a loss of synteny between the chromosomes of <it>T. scotoductus and T. thermophilus</it>. At least nine large inserts of which seven were identified as alien, were found, the most remarkable being a denitrification cluster and two operons relating to the metabolism of phenolics which appear to have been acquired from <it>Meiothermus ruber</it>. The majority of acquired genes are from closely related species of the Deinococcus-Thermus group, and many of the remaining genes are from microorganisms with a thermophilic or hyperthermophilic lifestyle. The natural competence of <it>Thermus scotoductus </it>was confirmed experimentally as expected as most of the proteins of the natural transformation system of <it>Thermus thermophilus </it>are present. Analysis of the metabolic capabilities revealed an extensive energy metabolism with many aerobic and anaerobic respiratory options. An abundance of sensor histidine kinases, response regulators and transporters for a wide variety of compounds are indicative of an oligotrophic lifestyle.</p> <p>Conclusions</p> <p>The genome of <it>Thermus scotoductus </it>SA-01 shows remarkable plasticity with the loss, acquisition and rearrangement of large portions of its genome compared to <it>Thermus thermophilus</it>. Its ability to naturally take up foreign DNA has helped it adapt rapidly to a subsurface lifestyle in the presence of a dense and diverse population which acted as source of nutrients. The genome of <it>Thermus scotoductus </it>illustrates how rapid adaptation can be achieved by a highly dynamic and plastic genome.</p

Determination of Preferred pH for Root-knot Nematode Aggregation Using Pluronic F-127 Gel

Root-knot nematodes (Meloidogyne spp.) are obligate endoparasites of a wide range of plant species. The infective stage is attracted strongly to and enters host roots at the zone of elongation, but the compounds responsible for this attraction have not been identified. We developed a simple assay to investigate nematode response to chemical gradients that uses Pluronic F-127, a synthetic block copolymer that, as a 23% aqueous solution, forms a liquid at low temperature and a gel at room temperature. Test chemicals are put into a modified pipette tip, or ‘chemical dispenser,’ and dispensers are inserted into the gel in which nematodes have been dispersed. Meloidogyne hapla is attracted to pH gradients formed by acetic acid and several other Brønsted acids and aggregates between pH 4.5 and 5.4. While this pH range was attractive to all tested root-knot nematode strains and species, the level of aggregation depended on the species/strain assessed. For actively growing roots, the pH at the root surface is most acidic at the zone of elongation. This observation is consistent with the idea that low pH is an attractant for nematodes. Root-knot nematodes have been reported to be attracted to carbon dioxide, but our experiments suggest that the observed attraction may be due to acidification of solutions by dissolved CO2 rather than to CO2 itself. These results suggest that Pluronic F-127 gel will be broadly applicable for examining responses of a range of organisms to chemical gradients or to each other