A Method for Serial Tissue Processing and Parallel Analysis of Aberrant Crypt Morphology, Mucin Depletion, and Beta-Catenin Staining in an Experimental Model of Colon Carcinogenesis

The use of architectural and morphological characteristics of cells for establishing prognostic indicators by which individual pathologies are assigned grade and stage is a well-accepted practice. Advances in automated micro- and macroscopic image acquisition and digital image analysis have created new opportunities in the field of prognostic assessment; but, one area in experimental pathology, animal models for colon cancer, has not taken advantage of these opportunities. This situation is primarily due to the methods available to evaluate the colon of the rodent for the presence of premalignant and malignant pathologies. We report a new method for the excision and processing of the entire colon of the rat and illustrate how this procedure permitted the quantitative assessment of aberrant crypt foci (ACF), a premalignant colon pathology, for characteristics consistent with progression to malignancy. ACF were detected by methylene blue staining and subjected to quantitative morphometric analysis. Colons were then restained with high iron diamine–alcian blue for assessment of mucin depletion using an image overlay to associate morphometric data with mucin depletion. The subsequent evaluation of ACF for beta-catenin staining is also demonstrated. The methods described are particularly relevant to the screening of compounds for cancer chemopreventive activity

Disbond Detection and Characterization Using Horizontally Polarized Shear Waves and EMAT Probes

Horizontally polarized shear waves offer high sensitivity for inspection of adhesively bonded structures. They produce a strong shear deformation on the adherent-adhesive interface allowing a relatively direct estimation of the adhesive failure (disbonds). Compared to localized conventional point-by-point ultrasonic waves, horizontal shear guided waves can be launched over long distances and larger areas of structural parts can be covered. Guided horizontal shear waves have a multimodal character and do not exhibit mode conversion at interfaces. The first fundamental symmetric shear mode (HS0) propagates non-dispersively in isotropic materials, while higher orders modes are dispersive and behave as guided Lamb waves

The continuum limit of the static-light meson spectrum

We investigate the continuum limit of the low lying static-light meson spectrum using Wilson twisted mass lattice QCD with N_f = 2 dynamical quark flavours. We consider three values of the lattice spacing a ~ 0.051 fm, 0.064 fm, 0.080 fm and various values of the pion mass in the range 280 MeV < m_PS < 640 MeV. We present results in the continuum limit for light cloud angular momentum j = 1/2, 3/2, 5/2 and for parity P = +, -. We extrapolate our results to physical quark masses, make predictions regarding the spectrum of B and B_s mesons and compare with available experimental results.Comment: 18 pages, 3 figure

Increased expression of axogenesis-related genes and mossy fibre length in dentate granule cells from adult HuD overexpressor mice

The neuronal RNA-binding protein HuD plays a critical role in the post-transcriptional regulation of short-lived mRNAs during the initial establishment and remodelling of neural connections. We have generated transgenic mice overexpressing this protein (HuD-Tg) in adult DGCs (dentate granule cells) and shown that their mossy fibres contain high levels of GAP-43 (growth-associated protein 43) and exhibit distinct morphological and electrophysiological properties. To investigate the basis for these changes and identify other molecular targets of HuD, DGCs from HuD-Tg and control mice were collected by LCM (laser capture microscopy) and RNAs analysed using DNA microarrays. Results show that 216 known mRNAs transcripts and 63 ESTs (expressed sequence tags) are significantly up-regulated in DGCs from these transgenic mice. Analyses of the 3′-UTRs (3′-untranslated regions) of these transcripts revealed an increased number of HuD-binding sites and the presence of several known instability-conferring sequences. Among these, the mRNA for TTR (transthyretin) shows the highest level of up-regulation, as confirmed by qRT–PCR (quantitative reverse transcription–PCR) and ISH (in situ hybridization). GO (gene ontology) analyses of up-regulated transcripts revealed a large over-representation of genes associated with neural development and axogenesis. In correlation with these gene expression changes, we found an increased length of the infrapyramidal mossy fibre bundle in HuD-Tg mice. These results support the notion that HuD stabilizes a number of developmentally regulated mRNAs in DGCs, resulting in increased axonal elongation

Integration of airborne and ground observations of nitryl chloride in the Seoul metropolitan area and the implications on regional oxidation capacity during KORUS-AQ 2016

Nitryl chloride (ClNO2) is a radical reservoir species that releases chlorine radicals upon photolysis. An integrated analysis of the impact of ClNO2 on regional photochemistry in the Seoul metropolitan area (SMA) during the Korea-United States Air Quality Study (KORUS-AQ) 2016 field campaign is presented. Comprehensive multiplatform observations were conducted aboard the NASA DC-8 and at two ground sites (Olympic Park, OP; Taehwa Research Forest, TRF), representing an urbanized area and a forested suburban region, respectively. Positive correlations between daytime Cl2 and ClNO2 were observed at both sites, the slope of which was dependent on O3 levels. The possible mechanisms are explored through box model simulations constrained with observations. The overall diurnal variations in ClNO2 at both sites appeared similar but the nighttime variations were systematically different. For about half of the observation days at the OP site the level of ClNO2 increased at sunset but rapidly decreased at around midnight. On the other hand, high levels were observed throughout the night at the TRF site. Significant levels of ClNO2 were observed at both sites for 4-5 h after sunrise. Airborne observations, box model calculations, and back-trajectory analysis consistently show that these high levels of ClNO2 in the morning are likely from vertical or horizontal transport of air masses from the west. Box model results show that chlorine-radical-initiated chemistry can impact the regional photochemistry by elevating net chemical production rates of ozone by 25% in the morning

Variation in antibiotic treatment for diabetic patients with serious foot infections: A retrospective observational study

<p>Abstract</p> <p>Background</p> <p>Diabetic foot infections are common, serious, and diverse. There is uncertainty about optimal antibiotic treatment, and probably substantial variation in practice. Our aim was to document whether this is the case: A finding that would raise questions about the comparative cost-effectiveness of different regimens and also open the possibility of examining costs and outcomes to determine which should be preferred.</p> <p>Methods</p> <p>We used the Veterans Health Administration (VA) Diabetes Epidemiology Cohorts (DEpiC) database to conduct a retrospective observational study of hospitalized patients with diabetic foot infections. DEpiC contains computerized VA and Medicare patient-level data for VA patients with diabetes since 1998, including demographics, ICD-9-CM diagnostic codes, antibiotics prescribed, and VA facility. We identified all patients with ICD-9-CM codes for cellulitis/abscess of the foot and then sub-grouped them according to whether they had cellulitis/abscess plus codes for gangrene, osteomyelitis, skin ulcer, or none of these. For each facility, we determined: 1) The proportion of patients treated with an antibiotic and the initial route of administration; 2) The first antibiotic regimen prescribed for each patient, defined as treatment with the same antibiotic, or combination of antibiotics, for at least 5 continuous days; and 3) The antibacterial spectrum of the first regimen.</p> <p>Results</p> <p>We identified 3,792 patients with cellulitis/abscess of the foot either alone (16.4%), or with ulcer (32.6%), osteomyelitis (19.0%) or gangrene (32.0%). Antibiotics were prescribed for 98.9%. At least 5 continuous days of treatment with an unchanged regimen of one or more antibiotics was prescribed for 59.3%. The means and (ranges) across facilities of the three most common regimens were: 16.4%, (22.8%); 15.7%, (36.1%); and 10.8%, (50.5%). The range of variation across facilities proved substantially greater than that across the different categories of foot infection. We found similar variation in the spectrum of the antibiotic regimen.</p> <p>Conclusions</p> <p>The large variations in regimen appear to reflect differences in facility practice styles rather than case mix. It is unlikely that all regimens are equally cost-effective. Our methods make possible evaluation of many regimens across many facilities, and can be applied in further studies to determine which antibiotic regimens should be preferred.</p

Behavior and Ecology of Silky Sharks Around the Chagos Archipelago and Evidence of Indian Ocean Wide Movement

Silky sharks (Carcharhinus falciformis) represent a major component of global shark catch, both directly and as bycatch, and populations are declining as a result. An improved understanding of their movement ecology is needed to support conservation efforts. We deployed satellite and acoustic tags (2013-2018) and analysed historical fisheries records (1997-2009), to investigate the spatial ecology of silky sharks in the central Indian Ocean and a large Marine Protected Area (MPA; 640,000 km2) around the Chagos Archipelago. We observed high fidelity to the MPA, and a sustained diurnal association with a seamount complex, with individuals moving off at night and returning at sunrise. Yet, we also observed large-scale divergent movements in two satellite tagged individuals and documented the furthest recorded displacement distance for the species to date, with one individual moving from the MPA to the Kenyan coast – a displacement distance of 3,549 km (track distance ~4,782 km). Silky sharks undertook diel vertical migrations and oscillatory diving behaviour, spending >99% of their time in the top 100 m, and diving to depths of greater than 300 m, overlapping directly with typical deployments of purse seine and longline sets in the Indian Ocean. One individual was recorded to a depth of 1,112 m, the deepest recorded silky shark dive to date. Individuals spent 96% of their time at liberty within water temperatures between 24-30 °C. Historic fisheries data revealed that silky sharks were a major component of the shark community around the archipelago, representing 13.7% of all sharks caught by longlines before the fishery closed in 2010. Over half (55.9%) of all individuals caught by longlines and purse seiners were juveniles. The large proportion of juveniles, coupled with the high site fidelity and residence observed in some individuals, suggests that the MPA could provide considerable conservation benefits for silky sharks, particularly during early life-history stages. However, their high mobility potential necessitates that large MPAs need to be considered in conjunction with fisheries regulations and conservation measures in adjacent EEZs and in areas beyond national jurisdiction

Carbon monoxide production from five volatile anesthetics in dry sodalime in a patient model: halothane and sevoflurane do produce carbon monoxide; temperature is a poor predictor of carbon monoxide production

BACKGROUND: Desflurane and enflurane have been reported to produce substantial amounts of carbon monoxide (CO) in desiccated sodalime. Isoflurane is said to produce less CO and sevoflurane and halothane should produce no CO at all. The purpose of this study is to measure the maximum amounts of CO production for all modern volatile anesthetics, with completely dry sodalime. We also tried to establish a relationship between CO production and temperature increase inside the sodalime. METHODS: A patient model was simulated using a circle anesthesia system connected to an artificial lung. Completely desiccated sodalime (950 grams) was used in this system. A low flow anesthesia (500 ml/min) was maintained using nitrous oxide with desflurane, enflurane, isoflurane, halothane or sevoflurane. For immediate quantification of CO production a portable gas chromatograph was used. Temperature was measured within the sodalime container. RESULTS: Peak concentrations of CO were very high with desflurane and enflurane (14262 and 10654 ppm respectively). It was lower with isoflurane (2512 ppm). We also measured small concentrations of CO for sevoflurane and halothane. No significant temperature increases were detected with high CO productions. CONCLUSION: All modern volatile anesthetics produce CO in desiccated sodalime. Sodalime temperature increase is a poor predictor of CO production

Gate-tuned normal and superconducting transport at the surface of a topological insulator

Three-dimensional topological insulators are characterized by the presence of a bandgap in their bulk and gapless Dirac fermions at their surfaces. New physical phenomena originating from the presence of the Dirac fermions are predicted to occur, and to be experimentally accessible via transport measurements in suitably designed electronic devices. Here we study transport through superconducting junctions fabricated on thin Bi2Se3 single crystals, equipped with a gate electrode. In the presence of perpendicular magnetic field B, sweeping the gate voltage enables us to observe the filling of the Dirac fermion Landau levels, whose character evolves continuously from electron- to hole-like. When B=0, a supercurrent appears, whose magnitude can be gate tuned, and is minimum at the charge neutrality point determined from the Landau level filling. Our results demonstrate how gated nano-electronic devices give control over normal and superconducting transport of Dirac fermions at an individual surface of a three-dimensional topological insulator.Comment: 28 pages, 5 figure