Diagnosis of major cancer resection specimens with virtual slides: Impact of a novel digital pathology workstation

Digital pathology promises a number of benefits in efficiency in surgical pathology, yet the longer time required to review a virtual slide than a glass slide currently represents a significant barrier to the routine use of digital pathology. We aimed to create a novel workstation that enables pathologists to view a case as quickly as on the conventional microscope. The Leeds Virtual Microscope (LVM) was evaluated using a mixed factorial experimental design. Twelve consultant pathologists took part, each viewing one long cancer case (12-25 slides) on the LVM and one on a conventional microscope. Total time taken and diagnostic confidence were similar for the microscope and LVM, as was the mean slide viewing time. On the LVM, participants spent a significantly greater proportion of the total task time viewing slides and revisited slides more often. The unique design of the LVM, enabling real-time rendering of virtual slides while providing users with a quick and intuitive way to navigate within and between slides, makes use of digital pathology in routine practice a realistic possibility. With further practice with the system, diagnostic efficiency on the LVM is likely to increase yet more

Sedimentary geology of the Middle Carboniferous of the Donbas region (Dniepr-Donets basin, Ukraine)

Peer reviewedPublisher PD

Self-repair ability of evolved self-assembling systems in cellular automata

Self-repairing systems are those that are able to reconfigure themselves following disruptions to bring them back into a defined normal state. In this paper we explore the self-repair ability of some cellular automata-like systems, which differ from classical cellular automata by the introduction of a local diffusion process inspired by chemical signalling processes in biological development. The update rules in these systems are evolved using genetic programming to self-assemble towards a target pattern. In particular, we demonstrate that once the update rules have been evolved for self-assembly, many of those update rules also provide a self-repair ability without any additional evolutionary process aimed specifically at self-repair

Chamber basis of the Orlik-Solomon algebra and Aomoto complex

We introduce a basis of the Orlik-Solomon algebra labeled by chambers, so called chamber basis. We consider structure constants of the Orlik-Solomon algebra with respect to the chamber basis and prove that these structure constants recover D. Cohen's minimal complex from the Aomoto complex.Comment: 16 page

Hyperglycemia-related advanced glycation end-products is associated with the altered phosphatidylcholine metabolism in osteoarthritis patients with diabetes

To test whether type 2 diabetic patients have an elevated level of advanced glycation end-products (AGEs) and responsible for altered phosphatidylcholine metabolism, which we recently found to be associated with osteoarthritis (OA) and diabetes mellitus (DM), synovial fluid (SF) and plasma samples were collected from OA patients with and without DM. Hyperglycemia-related AGEs including methylglyoxal (MG), free methylglyoxal-derived hydroimidazolone (MG-H1), and protein bound N-(Carboxymethyl)lysine (CML) and N-(Carboxyethyl)lysine (CEL) levels were measured in both SF and plasma samples using liquid chromatography coupled tandem mass spectrometry methodology. The correlation between these AGEs and phosphatidylcholine acyl-alkyl C34:3 (PC ae C34:3) and C36:3 (PC ae C36:3) were examined. Eighty four patients with knee OA, including 46 with DM and 38 without DM, were included in the study. There was no significant difference in plasma levels of MG, MG-H1, CML, and CEL between OA patients with and without DM. However, the levels of MG and MG-H1, but not CML and CEL in SF were significantly higher in OA patients with DM than in those without (all p ≤0.04). This association strengthened after adjustment for age, body mass index (BMI), sex and hexose level (p<0.02). Moreover, the levels of MG-H1 in SF was negatively and significantly correlated with PC ae C34:3 (ρ = -0.34; p = 0.02) and PC ae C36:3 (ρ = -0.39; P = 0.03) after the adjustment of age, BMI, sex and hexose level. Our data indicated that the production of non-protein bound AGEs was increased within the OA-affected joint of DM patients. This is associated with changes in phosphatidylcholine metabolism and might be responsible for the observed epidemiological association between OA and DM

Effect of display resolution on time to diagnosis with virtual pathology slides in a systematic search task

Performing diagnoses using virtual slides can take pathologists significantly longer than with glass slides, presenting a significant barrier to the use of virtual slides in routine practice. Given the benefits in pathology workflow efficiency and safety that virtual slides promise, it is important to understand reasons for this difference and identify opportunities for improvement. The effect of display resolution on time to diagnosis with virtual slides has not previously been explored. The aim of this study was to assess the effect of display resolution on time to diagnosis with virtual slides. Nine pathologists participated in a counterbalanced crossover study, viewing axillary lymph node slides on a microscope, a 23-in 2.3-megapixel single-screen display and a three-screen 11-megapixel display consisting of three 27-in displays. Time to diagnosis and time to first target were faster on the microscope than on the single and three-screen displays. There was no significant difference between the microscope and the three-screen display in time to first target, while the time taken on the single-screen display was significantly higher than that on the microscope. The results suggest that a digital pathology workstation with an increased number of pixels may make it easier to identify where cancer is located in the initial slide overview, enabling quick location of diagnostically relevant regions of interest. However, when a comprehensive, detailed search of a slide has to be made, increased resolution may not offer any additional benefit

Restoration of R117H CFTR folding and function in human airway cells through combination treatment with VX-809 and VX-770

Cystic fibrosis (CF) is a lethal recessive genetic disease caused primarily by the F508del mutation in the CF transmembrane conductance regulator (CFTR). The potentiator VX-770 was the first CFTR modulator approved by the FDA for treatment of CF patients with the gating mutation G551D. Orkambi is a drug containing VX-770 and corrector VX809 and is approved for treatment of CF patients homozygous for F508del, which has folding and gating defects. At least 30% of CF patients are heterozygous for the F508del mutation with the other allele encoding for one of many different rare CFTR mutations. Treatment of heterozygous F508del patients with VX-809 and VX-770 has had limited success, so it is important to identify heterozygous patients that respond to CFTR modulator therapy. R117H is a more prevalent rare mutation found in over 2,000 CF patients. In this study we investigated the effectiveness of VX-809/VX-770 therapy on restoring CFTR function in human bronchial epithelial (HBE) cells from R117H/F508del CF patients. We found that VX-809 stimulated more CFTR activity in R117H/F508del HBEs than in F508del/F508del HBEs. R117H expressed exclusively in immortalized HBEs exhibited a folding defect, was retained in the ER, and degraded prematurely. VX-809 corrected the R117H folding defect and restored channel function. Because R117 is involved in ion conductance, VX-770 acted additively with VX-809 to restore CFTR function in chronically treated R117H/F508del cells. Although treatment of R117H patients with VX-770 has been approved, our studies indicate that Orkambi may be more beneficial for rescue of CFTR function in these patients

Quantized spin waves in the metallic state of magnetoresistive manganites

High resolution spin waves measurements have been carried out in ferromagnetic (F) La(1-x)(Sr,Ca)xMnO3 with x(Sr)=0.15, 0.175, 0.2, 0.3 and x(Ca)=0.3. In all q-directions, close to the zone boundary, the spin wave spectra consist of several energy levels, with the same values in the metallic and the x\approx 1/8 ranges. Mainly the intensity varies, jumping from the lower energy levels determined in the x\approx 1/8 range to the higher energy ones observed in the metallic state. On the basis of a quantitative agreement found for x(Sr)=0.15 in a model of ordered 2D clusters, the spin wave anomalies of the metallic state can be interpreted in terms of quantized spin waves within the same 2D clusters, embedded in a 3D matrix.Comment: 4 pages, 5 figure

Mereotopological Connection

The paper outlines a model-theoretic framework for investigating and comparing a variety of mereotopological theories. In the first part we consider different ways of characterizing a mereotopology with respect to (i) the intended interpretation of the connection primitive, and (ii) the composition of the admissible domains of quantification (e.g., whether or not they include boundary elements). The second part extends this study by considering two further dimensions along which different patterns of topological connection can be classified—the strength of the connection and its multiplicity

Numerical simulations of stellar SiO maser variability. Investigation of the effect of shocks

A stellar hydrodynamic pulsation model has been combined with a SiO maser model in an attempt to calculate the temporal variability of SiO maser emission in the circumstellar envelope (CE) of a model AGB star. This study investigates whether the variations in local physical conditions brought about by shocks are the predominant contributing factor to SiO maser variability because, in this work, the radiative part of the pump is constant. We find that some aspects of the variability are not consistent with a pump provided by shock-enhanced collisions alone. In these simulations, gas parcels of relatively enhanced SiO abundance are distributed in a model CE by a Monte Carlo method, at a single epoch of the stellar cycle. From this epoch on, Lagrangian motions of individual parcels are calculated according to the velocity fields encountered in the model CE during the stellar pulsation cycle. The potentially masing gas parcels therefore experience different densities and temperatures, and have varying line-of-sight velocity gradients throughout the stellar cycle, which may or may not be suitable to produce maser emission. At each epoch (separated by 16.6 days), emission lines from the parcels are combined to produce synthetic spectra and VLBI-type images. We report here the results for v=1, J=1-0 (43-GHz) and J=2-1 (86-GHz) masers.Comment: 16 pages, 8 figures, accepted by A&