Effects of freshwater sponge Ephydatia fluviatilis on conjugative transfer of antimicrobial resistance in Enterococcus faecalis strains in aquatic environments.

Filter feeding is a biotic process that brings waterborne bacteria in close contact with each other and may thus support the horizontal transfer of their antimicrobial resistance genes. This laboratory study investigated whether the freshwater sponge Ephydatia fluviatilis supported the transfer of vancomycin resistance between two Enterococcus faecalis strains that we previously demonstrated to exhibit pheromone responsive plasmid conjugation. Microcosm experiments exposed live and dead colonies of laboratory-grown sponges to a vancomycin-resistant donor strain and a rifampicin-resistant recipient strain of Ent. faecalis. Enterococci with both resistance phenotypes were detected on double selection plates. In comparison to controls, abundance of these presumed transconjugants increased significantly in water from sponge microcosms. Homogenized suspensions of sponge cells also yielded presumed transconjugants; however, there was no significant difference between samples from live or dead sponges. Fluorescent in situ hybridization analysis of the sponge cell matrix using species-specific probes revealed the presence of enterococci clusters with cells adjacent to each other. The results demonstrated that sponge colonies can support the horizontal transfer of antimicrobial resistance although the mechanism underlying this process, such as binding of the bacteria to the sponge collagen matrix, has yet to be fully elucidated.

An economic analysis of ransomware and its welfare consequences.

We present in this work an economic analysis of ransomware, a relatively new form of cyber-enabled extortion. We look at how the illegal gains of the criminals will depend on the strategies they use, examining uniform pricing and price discrimination. We also explore the welfare costs to society of such strategies. In addition, we present the results of a pilot survey which demonstrate proof of concept in evaluating the costs of ransomware attacks. We discuss at each stage whether the different strategies we analyse have been encountered already in existing malware, and the likelihood of them being implemented in the future. We hope this work will provide some useful insights for predicting how ransomware may evolve in the future.

Quantitative analysis of an enlarged area Solid State X-ray Image Intensifier (SSXII) detector based on Electron Multiplying Charge Coupled Device (EMCCD) technology.

Present day treatment for neurovascular pathological conditions involves the use of devices with very small features such as stents, coils, and balloons; hence, these interventional procedures demand high resolution x-ray imaging under fluoroscopic conditions to provide the capability to guide the deployment of these fine endovascular devices. To address this issue, a high resolution x-ray detector based on EMCCD technology is being developed. The EMCCD field-of-view is enlarged using a fiber-optic taper so that the detector features an effective pixel size of 37 µm giving it a Nyquist frequency of 13.5 lp/mm, which is significantly higher than that of the state of the art Flat Panel Detectors (FPD). Quantitative analysis of the detector, including gain calibration, instrumentation noise equivalent exposure (INEE) and modulation transfer function (MTF) determination, are presented in this work. The gain of the detector is a function of the detector temperature; with the detector cooled to 5° C, the highest relative gain that could be achieved was calculated to be 116 times. At this gain setting, the lowest INEE was measured to be 0.6 µR/frame. The MTF, measured using the edge method, was over 2% up to 7 cycles/ mm. To evaluate the performance of the detector under clinical conditions, an aneurysm model was placed over an anthropomorphic head phantom and a coil was guided into the aneurysm under fluoroscopic guidance using the detector. Image sequences from the procedure are presented demonstrating the high resolution of this SSXII.

Image acquisition, geometric correction and display of images from a 2×2 x-ray detector array based on Electron Multiplying Charge Coupled Device (EMCCD) technology.

A high resolution (up to 11.2 lp/mm) x-ray detector with larger field of view (8.5 cm × 8.5 cm) has been developed. The detector is a 2 × 2 array of individual imaging modules based on EMCCD technology. Each module outputs a frame of size 1088 × 1037 pixels, each 12 bits. The frames from the 4 modules are acquired into the processing computer using one of two techniques. The first uses 2 CameraLink communication channels with each carrying information from two modules, the second uses a application specific custom integrated circuits, the Multiple Module Multiplexer Integrated Circuit (MMMIC), 3 of which are used to multiplex the data from 4 modules into one CameraLink channel. Once the data is acquired using either of the above mentioned techniques, it is decoded in the graphics processing unit (GPU) to form one single frame of size 2176 × 2074 pixels each 16 bits. Each imaging module uses a fiber optic taper coupled to the EMCCD sensor. To correct for mechanical misalignment between the sensors and the fiber optic tapers and produce a single seamless image, the images in each module may be rotated and translated slightly in the x-y plane with respect to each other. To evaluate the detector acquisition and correction techniques, an aneurysm model was placed over an anthropomorphic head phantom and a coil was guided into the aneurysm under fluoroscopic guidance using the detector array. Image sequences before and after correction are presented which show near-seamless boundary matching and are well suited for fluoroscopic imaging.

Two dimensional extensible array configuration for EMCCD-based solid state x-ray detectors.

We have designed and developed from the discrete component level a high resolution dynamic x- ray detector to be used for fluoroscopic and angiographic medical imaging. The heart of the detector is a 1024 × 1024 pixel electron multiplying charge coupled device (EMCCD) with a pixel size of 13 × 13 µm(2) (Model CCD201-20, e2v Technologies, Inc.), bonded to a fiber optic plate (FOP), and optically coupled to a 350 µm thick micro-columnar CsI(TI) scintillator via a fiber optic taper (FOT). Our aim is to design an array of these detectors that could be extended to any arbitrary X × Y size in two dimensions to provide a larger field of view (FOV). A physical configuration for a 3×3 array is presented that includes two major sub-systems. First is an optical front end that includes (i) a phosphor to convert the x-ray photons into light photons, and (ii) a fused array of FOTs that focuses light photons from the phosphor onto an array of EMCCD's optically coupled using FOPs. Second is an electronic front end that includes (i) an FPGA board used for generating clocks and for data acquisition (ii) driver boards to drive and digitize the analog output from the EMCCDs, (iii) a power board, and (iv) headboards to hold the EMCCD's while they are connected to their respective driver board using flex cables. This configuration provides a larger FOV as well as region-of- interest (ROI) high-resolution imaging as required by modern neurovascular procedures.

Dose Reduction Technique Using a Combination of a Region of Interest (ROI) Material X-Ray Attenuator and Spatially Different Temporal Filtering for Fluoroscopic Interventions.

We demonstrate a novel approach for achieving patient dose savings during image-guided neurovascular interventions, involving a combination of a material x-ray region of interest (ROI) attenuator and a spatially different ROI temporal filtering technique. The part of the image under the attenuator is reduced in dose but noisy and less bright due to fewer x-ray quanta reaching the detector, as compared to the non-attenuating (or less attenuating) region. First the brightness is equalized throughout the image by post processing and then a temporal filter with higher weights is applied to the high attenuating region to reduce the noise, at the cost of increased lag; however, in the regions where less attenuation is present, a lower temporal weight is needed and is applied to preserve temporal resolution. A simulation of the technique is first presented on an actual image sequence obtained from an endovascular image guided interventional (EIGI) procedure. Then the actual implementation of the technique with a physical ROI attenuator is presented. Quantitative analysis including noise analysis and integral dose calculations are presented to validate the proposed technique.

Graphics Processing Unit (GPU) implementation of image processing algorithms to improve system performance of the Control, Acquisition, Processing, and Image Display System (CAPIDS) of the Micro-Angiographic Fluoroscope (MAF).

We present the image processing upgrades implemented on a Graphics Processing Unit (GPU) in the Control, Acquisition, Processing, and Image Display System (CAPIDS) for the custom Micro-Angiographic Fluoroscope (MAF) detector. Most of the image processing currently implemented in the CAPIDS system is pixel independent; that is, the operation on each pixel is the same and the operation on one does not depend upon the result from the operation on the other, allowing the entire image to be processed in parallel. GPU hardware was developed for this kind of massive parallel processing implementation. Thus for an algorithm which has a high amount of parallelism, a GPU implementation is much faster than a CPU implementation. The image processing algorithm upgrades implemented on the CAPIDS system include flat field correction, temporal filtering, image subtraction, roadmap mask generation and display window and leveling. A comparison between the previous and the upgraded version of CAPIDS has been presented, to demonstrate how the improvement is achieved. By performing the image processing on a GPU, significant improvements (with respect to timing or frame rate) have been achieved, including stable operation of the system at 30 fps during a fluoroscopy run, a DSA run, a roadmap procedure and automatic image windowing and leveling during each frame.

Implementation of digital multiplexing for high resolution X-ray detector arrays.

We describe and demonstrate for the first time the use of the novel Multiple Module Multiplexer (MMMIC) for a 2×2 array of new electron multiplying charge coupled device (EMCCD) based x-ray detectors. It is highly desirable for x-ray imaging systems to have larger fields of view (FOV) extensible in two directions yet to still be capable of doing high resolution imaging over regions-of-interest (ROI). The MMMIC achieves these goals by acquiring and multiplexing data from an array of imaging modules thereby enabling a larger FOV, and at the same time allowing high resolution ROI imaging through selection of a subset of modules in the array. MMMIC also supports different binning modes. This paper describes how a specific two stage configuration connecting three identical MMMICs is used to acquire and multiplex data from a 2×2 array of EMCCD based detectors. The first stage contains two MMMICs wherein each MMMIC is getting data from two EMCCD detectors. The multiplexed data from these MMMICs is then forwarded to the second stage MMMIC in the similar fashion. The second stage that has only one MMMIC gives the final 12 bit multiplexed data from four modules. This data is then sent over a high speed Camera Link interface to the image processing computer. X-ray images taken through the 2×2 array of EMCCD based detectors using this two stage configuration of MMMICs are shown successfully demonstrating the concept.

A 2×2 array of EMCCD-based solid state x-ray detectors.

We have designed and developed a new solid-state x-ray imaging system that consists of a 2×2 array of electron multiplying charge coupled devices (EMCCDs). This system is intended for fluoroscopic and angiographic medical imaging. The key components are the four 1024 × 1024 pixel EMCCDs with a pixel size of 13 × 13 µm(2). Each EMCCD is bonded to a fiber optic plate (FOP), and optically coupled to a 350 µm thick micro-columnar CsI(TI) scintillator via a 3.22∶1 fiber optic taper (FOT). The detector provides x-ray images of 9 line pairs/mm resolution at 15 frames/sec and real-time live video at 30 frames/sec with binning at a lower resolution, independent of the electronic gain applied to the EMCCD. The total field of view (FOV) of the array is 8.45 cm × 8.45 cm. The system is designed to also provide the ability to do region-of- interest imaging (ROI) by selectively enabling individual modules of the array.

The outcome of brittle type 1 diabetes--a 20 year study.

AIMS: To determine the long-term (20 years from presentation) outcome of brittle type 1 diabetes characterized by recurrent episodes of ketoacidosis (DKA). METHODS: The cohort studied was a group of brittle diabetic patients from various parts of UK originally identified between 1979 and 1985. Patients were traced, where possible, via their diabetic clinics and/or general practitioners. Data on survival or otherwise were obtained from hospital case notes and information from diabetes care team members. For survivors, clinical and demographic information obtained included complication status and whether they still had brittle characteristics. They were also compared with a matched case-control group of type 1 patients with no history of brittle behaviour. RESULTS: The original cohort comprised 33 patients- all female and mean ± SD, aged 18 ± 5 years and diabetes duration 8 ± 4 years. Thirteen were not traceable and 10 of the remaining 20 (50%) had died during the mean 22 years of follow-up. Deaths occurred evenly throughout the period, and causes were chronic renal failure (3), DKA (3), hypoglycaemia (2), subarachnoid haemorrhage (1) and uncertain (1). Age at death ranged from 27 to 45 years. Of the 10 survivors, none remained brittle, but they had a substantial burden of complications. Compared with the non-brittle control group, there was a significant excess of nephropathy and autonomic neuropathy. CONCLUSION: We conclude that brittle diabetes characterized by recurrent DKA has high long-term outcome mortality. These deaths were premature and almost all diabetes related. Those who survived had resolution of brittleness, but suffered a significant complication burden.

Spatially different, real-time temporal filtering and dose reduction for dynamic image guidance during neurovascular interventions.

Fluoroscopic systems have excellent temporal resolution, but are relatively noisy. In this paper we present a recursive temporal filter with different weights (lag) for different user selected regions of interest (ROI) to assist the neurointerventionalist during an image guided catheter procedure. The filter has been implemented on a Graphics Processor (GPU), enabling its usage for fast frame rates such as during fluoroscopy. We first demonstrate the use of this GPU-implemented rapid temporal filtering technique during an endovascular image guided intervention with normal fluoroscopy. Next we demonstrate its use in combination with ROI fluoroscopy where the exposure is substantially reduced in the peripheral region outside the ROI, which is then software-matched in brightness and filtered using the differential temporal filter. This enables patient dose savings along with improved image quality.

EMCCD-based high resolution dynamic x-ray detector for neurovascular interventions.

We have designed and developed from the discrete component level a high resolution dynamic detector for neurovascular interventions. The heart of the detector is a 1024 × 1024 pixel electron multiplying charge coupled device (EMCCD) with a pixel size of 13 × 13 µm(2), bonded to a fiber optic plate (FOP), and optically coupled to a 350 µm micro-columnar CsI(TI) scintillator via a 3.3:1 fiber optic taper (FOT). The detector provides x-ray images of 9 cycles/mm resolution at 15 frames/sec and real time live video at 30 frames/sec with binning at a lower resolution, both independent of gain applied to EMCCD, as needed for region-of-interest (ROI) image guidance during neurovascular interventions.

Novel Multiplexer to Enable Multiple-Module Imaging with Adjustable High Spatial Resolution and Predetermined Display Bandwidth for Array Medical Imaging Systems.

We describe a custom multiple-module multiplexer integrated circuit (MMMIC) that enables the combination of discrete Electron multiplying charge coupled devices (EMCCD) based imaging modules to improve medical imaging systems. It is highly desirable to have flexible imaging systems that provide high spatial resolution over a specific region of interest (ROI) and a field of view (FOV) large enough to encompass areas of clinical interest. Also, such systems should be dynamic, i.e. should be able to maintain a specified acquisition bandwidth irrespective of the size of the imaged FOV. The MMMIC achieves these goals by 1) multiplexing the outputs of an array of imaging modules to enable a larger FOV, 2) enabling a number of binning modes for adjustable high spatial resolution, and 3) enabling selection of a subset of modules in the array to achieve ROI imaging at a predetermined display bandwidth. The MMMIC design also allows multiple MMMICs to be connected to control larger arrays. The prototype MMMIC was designed and fabricated in the ON-SEMI 0.5µm CMOS process through MOSIS (www.mosis.org). It has three 12-bit inputs, a single 12-bit output, three input enable bits, and one output enable, so that one MMMIC can control the output from three discrete imager arrays. The modular design of the MMMIC enables four identical chips, connected in a two-stage sequential arrangement, to readout a 3×3 collection of individual imaging modules. The first stage comprises three MMMICs (each connected to three of the individual imaging module), and the second stage is a single MMMIC whose 12-bit output is then sent via a CameraLink interface to the system computer. The prototype MMMIC was successfully tested using digital outputs from two EMCCD-based detectors to be used in an x-ray imaging array detector system.Finally, we show how the MMMIC can be used to extend an imaging system to include any arbitrary (M×N) array of imaging modules enabling a large FOV along with ROI imaging and adjustable high spatial resolution.

Guar meal diets as an alternative approach to inducing molt and improving Salmonella enteritidis resistance in late-phase laying hens.

Induced molting of laying hens is a practice used by commercial egg producers to increase the productive lifetime of their flock. However, the conventional method of inducing molt, which involves removal of feed, water, or both as well as a reduction in photoperiod to less than a natural day has drawn criticism due to animal welfare and food safety concerns. The objective of this study was to explore the efficacy of diets containing high levels of guar meal (GM) in inducing molt and reducing susceptibility to Salmonella Enteritidis colonization in late-phase laying hens. Late-phase (68 wk old) Lohmann laying hens were either full-fed standard laying hen diets (nonmolted control), induced to molt by feed withdrawal, or full-fed standard laying hen diets containing 20% GM with or without 250 units/kg of mannanase Hemicell supplementation. On the fourth day of treatment, all hens were orally challenged with SE (1.65 x 10(7) cfu). Hens were killed and evaluated for Salmonella colonization and differences in organ weights 5 d postinoculation. Salmonella Enteritidis present in crop, liver, ovary, and cecal contents were significantly reduced by feeding GM with enzyme supplementation compared with feed withdrawal hens. No significant differences were observed in reproductive tract weights of molted groups, although a difference in liver weight was detected. Results indicate that feeding diets containing 20% GM are as effective as complete feed withdrawal with respect to inducing molt with the added benefit of improved resistance to Salmonella Enteritidis colonization and translocation.

Differential expression of syndecans and glypicans in chronically inflamed synovium.

BACKGROUND: Membrane-bound heparan sulphate proteoglycans (HSPGs) act as co-receptors and presenters of cytokines and are involved in cell-matrix and cell-cell adhesion. AIM: To investigate which HSPGs are expressed in knee joint synovia from patients with different forms of arthritis and normal individuals. METHODS: Synovial samples were obtained from patients with early rheumatoid arthritis (n = 8), longstanding rheumatoid arthritis (n = 13), psoriatic arthritis (n = 7), osteoarthritis (n = 6) and normal joints (n = 12). Expression of syndecan-1, -2, -3 and -4 and glypican-1, -3 and -4 was analysed by immunohistochemistry and dual label immunofluorescence. RESULTS: The expression of HSPGs in chronically inflamed synovium exhibited a differential distribution. Syndecan-1 was present in the mononuclear infiltrates of synovia from patients with rheumatoid and psoriatic arthritis where it was expressed by plasma cells. Syndecan-2 was present mainly in blood vessels where it occurred on endothelial cells, pericytes and smooth muscle cells. Syndecan-3 stained intensely in endothelial cells but also occurred in sublining macrophages and the lining layer. Glypican-4 occurred in the lining layer and blood vessels. Increased expression of these HSPGs was apparent in rheumatoid and psoriatic compared to osteoarthritic and normal synovia. Little or no staining for syndecan-4, glypican-1 and glypican-3 was seen in all samples. DISCUSSION: Selected HSPGs, such as syndecan-1, -2 and -3 and glypican-4, could play a part in the pathophysiology of arthritis, such as the migration and retention of leukocytes and angiogenesis in the chronically inflamed synovium.

Use of guar by-products in high-production laying hen diets.

A 5x5 Latin square experiment was conducted to evaluate the effect of feeding low concentrations of guar germ or a combination of guar germ and hull (guar meal) in high-production laying hen diets. A total of 125 Lohmann laying hens (21 wk old) of similar BW were randomly assigned to 5 blocks. Each block was divided into 5 experimental units, consisting of 5 hens per unit. Hens were fed either a nonguar control diet, or 1 of 4 diets containing either 2.5 or 5% guar germ, or 2.5 or 5% guar meal over a 20-wk trial period (five 4-wk periods). No significant differences were observed when feeding either 2.5 or 5% guar germ or meal (P>0.05) on hen-day egg production or feed consumption. Significant differences in egg weight, total egg mass per hen, and feed conversion ratio were detected in hens fed 2.5% guar meal, whereas they remained unchanged for diets containing either level of guar germ or 5% guar meal. Feeding either level of guar germ or guar meal did not affect shell quality (shell thickness, egg breaking force, and specific gravity), Haugh units, or egg yolk color (L*, a*, b*). The results showed that both guar germ and guar meal can be fed to high-production laying hens at up to 5% without adverse effects on laying hen performance.

Effects of guar meal by-product with and without beta-mannanase Hemicell on broiler performance.

Guar gum production yields a high protein guar meal that can be subdivided into germ and hull fractions. Feeding high concentrations of guar meal reduces body weight and feed efficiency in chickens due to the presence of a residual guar gum. Two experiments determined the upper feeding levels of guar meal and the hull and germ fractions in broiler chickens. An industrial source beta-mannanase (Hemicell) also was fed in combination with guar meals. Experiment 1 utilized a 3 x 4 factorial design to feed broiler chickens diets containing guar germ, guar hull, or guar meal at 4 levels (2.5, 5.0, 7.5, and 10.0%) compared with a negative control diet. Results indicated that any of the 3 guar meals could be fed at a 2.5% dietary inclusion rate without adversely affecting broiler chicken growth to 6 wk of age. In experiment 2, a 4 x 2 factorial design consisting of the 3 by-products meals at 5% inclusion and soybean meal control with and without enzyme tested whether Hemicell could increase inclusion rates without decreasing broiler growth or feed consumption to 6 wk of age. Addition of Hemicell to feed had no effect on measures of growth in chickens fed the control diet. Hemicell significantly improved feed:gain ratio of diets containing 5% of each fraction of guar meal versus the untreated diets. Feed:gain ratio for the Hemicell-treated 5% germ fraction diet was improved to control diet levels. Results indicated that the upper feeding level of guar meal and germ and hull fraction of guar meal is 2.5%, and addition of beta-mannanase (Hemicell) increases the upper feeding level for the germ fraction to 5%.