bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinicopathological indices to predict hepatocellular carcinoma molecular classification
Authors: Tan Poh Seng , Nakagawa Shigeki , Goossens Nicolas , Venkatesh Anu , Huang Tiangui , Ward Stephen C. , Sun Xiaochen , Song Won‐Min , Koh Anna , Canasto‐Chibuque Claudia , Deshmukh Manjeet , Nair Venugopalan , Mahajan Milind , Zhang Bin , Fiel Maria Isabel , Kobayashi Masahiro , Kumada Hiromitsu , Hoshida Yujin
Published: June 2015

Background & Aims

Hepatocellular carcinoma (HCC) is the second most lethal cancer caused by lack of effective therapies. Although promising, HCC molecular classification, which enriches potential responders to specific therapies, has not yet been assessed in clinical trials of anti‐HCC drugs. We aimed to overcome these challenges by developing clinicopathological surrogate indices of HCC molecular classification.

Methods

Hepatocellular carcinoma classification defined in our previous transcriptome meta‐analysis (S1, S2 and S3 subclasses) was implemented in an FDA‐approved diagnostic platform (Elements assay, NanoString). Ninety‐six HCC tumours (training set) were assayed to develop molecular subclass‐predictive indices based on clinicopathological features, which were independently validated in 99 HCC tumours (validation set). Molecular deregulations associated with the histopathological features were determined by pathway analysis. Sample sizes for HCC clinical trials enriched with specific molecular subclasses were determined.

Results

Hepatocellular carcinoma subclass‐predictive indices were steatohepatitic (SH)‐HCC variant and immune cell infiltrate for S1 subclass, macrotrabecular/compact pattern, lack of pseudoglandular pattern, and high serum alpha‐foetoprotein (>400 ng/ml) for S2 subclass, and microtrabecular pattern, lack of SH‐HCC and clear cell variants, and lower histological grade for S3 subclass. Macrotrabecular/compact pattern, a predictor of S2 subclass, was associated with the activation of therapeutically targetable oncogene YAP and stemness markers EPCAM/KRT19. BMP4 was associated with pseudoglandular pattern. Subclass‐predictive indices‐based patient enrichment reduced clinical trial sample sizes from 121, 184 and 53 to 30, 43 and 22 for S1, S2 and S3 subclass‐targeting therapies respectively.

Conclusions

Hepatocellular carcinoma molecular subclasses can be enriched by clinicopathological indices tightly associated with deregulation of therapeutically targetable molecular pathways.
Combined action of the major secreted exo‐ and endopolygalacturonases is required for full virulence of Fusarium oxysporum
Authors: Bravo Ruiz Gustavo , Di Pietro Antonio , Roncero M. Isabel G.
Published: June 2015

The genome of the tomato pathogen Fusarium oxysporum f. sp. lycopersici encodes eight different polygalacturonases (PGs): four endoPGs and four exoPGs. Quantitative real‐time reverse transcription‐polymerase chain reaction (RT‐PCR) revealed that endoPGs pg1 and pg5 and exoPGs pgx4 and pgx6 are expressed at significant levels during growth on citrus pectin, polygalacturonic acid or the monomer galacturonic acid, as well as during the infection of tomato plants. The remaining PG genes exhibit low expression levels under all the conditions tested. Secreted PG activity was decreased significantly during growth on pectin in the single deletion mutants lacking either pg1 or pgx6, as well as in the double mutant. Although the single deletion mutants did not display a significant virulence reduction on tomato plants, the Δpg1Δpgx6 double mutant was significantly attenuated in virulence. The combined action of exoPGs and endoPGs is thus essential for plant infection by the vascular wilt fungus F. oxysporum.
Impact of cinacalcet pre‐transplantation on mineral metabolism in renal transplant recipients
Authors: Sharma Ashish K , Masterson Rosemary , Holt Stephen G , Tan Sven‐Jean , Hughes Peter D , Chu Melissa , Jayadeva Pavithra , Toussaint Nigel D
Published: June 2015

Aim

Cinacalcet is effective in reducing parathyroid hormone (PTH) in patients on dialysis. Reports of biochemical profiles and other clinical outcomes in patients discontinuing cinacalcet at time of renal transplantation are limited.

Methods

A retrospective study assessing markers of mineral metabolism, graft and patient outcomes in renal transplant recipients to determine differences in patients discontinuing cinacalcet (C+) compared with patients not treated with cinacalcet (C−) at time of transplantation. To allow for differences between groups in pre‐transplant biochemical parameters, we also analysed a matched cohort of C− with C+ recipients (2:1), matched for age, calcium and PTH levels at transplantation.

Results

Five hundred thirty‐two recipients (460 C−, 72 C+), transplanted January 2006–December 2012, were analysed, mean age 48.0 ± 12.7 years and 64.3% were men. At a median 42.9 months follow up, there were 10 deaths (1.9%), 56 allograft loss (10.6%) and 5 parathyroidectomies post‐transplant (0.8%). Median PTH immediately pre‐transplant was higher in C+ versus C− (50.7(25.4–75.2) versus 28.3(13.9–49.7) pmol/L, P < 0.001). Twelve‐month post‐transplant PTH was reduced but higher in C+ (11.7(6.9–21.2) vs 7.2(4.6–11.2) pmol/L, P < 0.001). Mean calcium was higher for C+ versus C− at 12 months (2.50 ± 0.19 vs 2.43 ± 0.17 mmol/L, P < 0.001), with differences to 4 years post‐transplant. No difference was seen in renal function, graft loss, post‐transplant parathyroidectomy rate and mortality. In the matched cohort (144 C− vs 72 C+), similar findings were also seen.

Conclusion

Differences in mineral metabolism post‐transplant are seen with cinacalcet pre‐transplant compared with no cinacalcet. Transplant recipients discontinuing cinacalcet had higher post‐transplant PTH and calcium although the clinical significance is unclear.
Metabolic engineering of sugarcane to accumulate energy‐dense triacylglycerols in vegetative biomass
Authors: Zale Janice , Jung Je Hyeong , Kim Jae Yoon , Pathak Bhuvan , Karan Ratna , Liu Hui , Chen Xiuhua , Wu Hao , Candreva Jason , Zhai Zhiyang , Shanklin John , Altpeter Fredy
Published: June 2015

Elevating the lipid content in vegetative tissues has emerged as a new strategy for increasing energy density and biofuel yield of crops. Storage lipids in contrast to structural and signaling lipids are mainly composed of glycerol esters of fatty acids, also known as triacylglycerol (TAG). TAGs are one of the most energy‐rich and abundant forms of reduced carbon available in nature. Therefore, altering the carbon‐partitioning balance in favour of TAG in vegetative tissues of sugarcane, one of the highest yielding biomass crops, is expected to drastically increase energy yields. Here we report metabolic engineering to elevate TAG accumulation in vegetative tissues of sugarcane. Constitutive co‐expression of WRINKLED1 (WRI1), diacylglycerol acyltransferase1‐2 (DGAT1‐2) and oleosin1 (OLE1) and simultaneous cosuppression of ADP‐glucose pyrophosphorylase (AGPase) and a subunit of the peroxisomal ABC transporter1 (PXA1) in transgenic sugarcane elevated TAG accumulation in leaves or stems by 95‐ or 43‐fold to 1.9% or 0.9% of dry weight (DW), respectively, while expression or suppression of one to three of the target genes increased TAG levels by 1.5‐ to 9.5‐fold. Accumulation of TAG in vegetative progeny plants was consistent with the results from primary transgenics and contributed to a total fatty acid content of up to 4.7% or 1.7% of DW in mature leaves or stems, respectively. Lipid droplets were visible within mesophyll cells of transgenic leaves by confocal fluorescence microscopy. These results provide the basis for optimizations of TAG accumulation in sugarcane and other high yielding biomass grasses and will open new prospects for biofuel applications.
Reimagining Woland: The Shadow Archetype and the Paradox of Evil in The Master and Margarita
Authors: CARROLL ALEXANDRA NICEWICZ
Published: June 2015

Scholars suggest that, following a 1926 OGPU search and seizure of his home, Mikhail Bulgakov turned attention to his father's spiritual and academic world and, in so doing, returned to elements of his childhood. Ultimately, Bulgakov's attention to Christianity led to his composition of The Master and Margarita. Psychologically, a return to elements of childhood amidst crisis reflects a process of regression, a return to familiar and stabilizing elements on which an individual builds a foundation for dealing with life difficulties. Situated against the broader suggestion that The Master and Margarita developed as a psychological response to professional persecution, my essay argues that the devil character Woland emerged within this regression as the shadow archetype, a psychological personification often interpreted as nefarious that operates as a paradox of evil necessary for psycho‐spiritual restoration amidst personal suffering.
Higher rate of fat oxidation during rowing compared with cycling ergometer exercise across a range of exercise intensities
Authors: Egan B. , Ashley D. T. , Kennedy E. , O'Connor P. L. , O'Gorman D. J.
Published: June 2015

The relative contribution of carbohydrate and fat oxidation to energy expenditure during exercise is dependent on variables including exercise intensity, mode, and recruited muscle mass. This study investigated patterns of substrate utilization during two non‐weightbearing exercise modalities, namely cycling and rowing. Thirteen young, moderately trained males performed a continuous incremental (3‐min stages) exercise test to exhaustion on separate occasions on an electronically braked cycle (CYC) ergometer and an air‐braked rowing (ROW) ergometer, respectively. On two further occasions, participants performed a 20‐min steady‐state exercise bout at ∼50%VO2peak on the respective modalities. Despite similar oxygen consumption, rates of fat oxidation (FATox) were ∼45% higher during ROW compared with CYC (P < 0.05) across a range of power output increments. The crossover point for substrate utilization occurred at a higher relative exercise intensity for ROW than CYC (57.8 ± 2.1 vs 42.1 ± 3.6%VO2peak, P < 0.05). During steady‐state submaximal exercise, the higher FATox during ROW compared with CYC was maintained (P < 0.05), but absolute FATox were 42% (CYC) and 28% (ROW) lower than during incremental exercise. FATox is higher during ROW compared with CYC exercise across a range of exercise intensities matched for energy expenditure, and is likely as a consequence of larger muscle mass recruited during ROW.
CCR1, an enzyme required for lignin biosynthesis in Arabidopsis, mediates cell proliferation exit for leaf development
Authors: Xue Jingshi , Luo Dexian , Xu Deyang , Zeng Minhuan , Cui Xiaofeng , Li Laigeng , Huang Hai
Published: June 2015

After initiation, leaves first undergo rapid cell proliferation. During subsequent development, leaf cells gradually exit the proliferation phase and enter the expansion stage, following a basipetally ordered pattern starting at the leaf tip. The molecular mechanism directing this pattern of leaf development is as yet poorly understood. By genetic screening and characterization of Arabidopsis mutants defective in exit from cell proliferation, we show that the product of the CINNAMOYL CoA REDUCTASE (CCR1) gene, which is required for lignin biosynthesis, participates in the process of cell proliferation exit in leaves. CCR1 is expressed basipetally in the leaf, and ccr1 mutants exhibited multiple abnormalities, including increased cell proliferation. The ccr1 phenotypes are not due to the reduced lignin content, but instead are due to the dramatically increased level of ferulic acid (FeA), an intermediate in lignin biosynthesis. FeA is known to have antioxidant activity, and the levels of reactive oxygen species (ROS) in ccr1 were markedly reduced. We also characterized another double mutant in CAFFEIC ACID O‐METHYLTRANSFERASE (comt) and CAFFEOYL CoA 3‐O‐METHYLTRANSFERASE (ccoaomt), in which the FeA level was dramatically reduced. Cell proliferation in comt ccoaomt leaves was decreased, accompanied by elevated ROS levels, and the mutant phenotypes were partially rescued by treatment with FeA or another antioxidant (N‐acetyl‐l‐cysteine). Taken together, our results suggest that CCR1, FeA and ROS coordinate cell proliferation exit in normal leaf development.
Evaluation of Laboratory and Field Experimentation Characterizing Concrete Crosstie Rail Seat Load Distributions
Authors: Greve Matthew J. , Dersch Marcus S. , Edwards J. Riley , Barkan Christopher P. L.
Published: June 2015

As higher demands are placed on North American railroad infrastructure by heavy haul traffic, it is increasingly important to understand the factors affecting the magnitude and distribution of load imparted to concrete crosstie rail seats. The rail seat load distribution is critical to the analysis of failure mechanisms associated with rail seat deterioration (RSD), the degradation of the concrete surface at the crosstie rail seat. RSD can lead to wide gauge, cant deficiency, and an increased risk of rail rollover, and is therefore of primary concern to Class I Freight Railroads in North America. Researchers at the University of Illinois at Urbana-Champaign (UIUC) have successfully characterized the loading environment at the rail seat using matrix-based tactile surface sensors (MBTSS). Previous research has proven the feasibility of using MBTSS in both laboratory and field applications, and recent field experimentation has yielded several hypotheses concerning the effect of fastening system wear on the rail seat load distribution. This paper will focus on the analysis of data gathered from laboratory experimentation with MBTSS to evaluate these hypotheses, and will propose a metric for crosstie and fastening system design which considers the uniformity of the load distribution. The knowledge gained from this experimentation will be integrated with associated research conducted at UIUC to form the framework for a mechanistic design approach for concrete crossties and fastening systems.
Analysis of Instabilities in Railway Vehicles Employing Operational Modal Analysis
Authors: Calvo Lara Erviti , Castellanos Gorka Agirre , Gimenez Germán
Published: June 2015

The application of Operational Modal Analysis (OMA) in the railway sector opens a broad field of opportunities. The validation of the numerical model employed in the design phase is usually performed employing data obtained in static tests. The drawback is that some suspension parameters, such as dampers, only have an influence in the dynamic behavior and not in the static behavior. Because of that, the use of the mode shapes identified from track measurements in combination with the static tests leads to a more accurate validation of the numerical model. Apart from that, most passenger comfort and dynamic problems are associated to slightly damped modes. A correct identification of the modal parameters can be used as a continuous design improvement tool to improve the comfort and dynamic characteristics of future designs.

Another valuable application of OMA techniques is the identification of the mode shapes corresponding to instabilities, due to the safety impact that they have. In railway vehicles, instabilities are associated to mode shapes that present a damping rate which decreases with the increase of the running speed. Above a certain speed value, the excitation coming from track cannot be damped by the vehicle and it reaches an unstable condition. This unstable condition leads to high acceleration levels experienced by the passengers and high interaction forces between the wheel and the rail that may lead to safety hazards. The speed above which the vehicle is unstable is known as critical speed, and has to be greater than the maximum speed of the vehicle with a reasonable safety margin.

The use of OMA techniques allows identifying the mode shape that causes the instability. This paper presents the application of OMA techniques to measurements performed on a passenger vehicle, in which the speed was increased until the vehicle was unstable. The mode shape that caused the instability was identified as well as its corresponding natural frequency and damping rate.
Rapid Construction Technology for Railroad Concrete Infrastructure: Microwave Heat Curing Technology
Authors: Koh Taehoon , Hwang Seonkeun , Yoo Junghoon , Lee Donggeun
Published: June 2015

The cast-in-place concrete lining construction process represents about 25% of the total railroad tunnel construction period. Moreover, the construction period for lining concrete depends on the speed of the curing process of the lining concrete. Therefore, in cold weather when the air temperature in mountain railroad tunnel is consistently 10 degrees or below, equipment for heat insulation of cast-in-place concrete lining, such as a portable fossil fuel heater, must also be prepared to maintain an appropriate curing temperature in the tunnel. It generally takes about 24 to 36 hours to reach the compressive strength (3 to 5MPa) required to remove the lining form.

Recently, microwave heat curing technology has been developed as a way of substantially reducing the concrete curing time, to achieve a reduction in the total construction period. The microwave heating system developed in this technology is comprised of a microwave generator, cavity, insulator, and exothermic body (microwave irradiated pyrogen). In this system, microwaves generated from the magnetron are irregularly reflected inside the cavity, and rapidly heat up the exothermic body so that the heat is transferred to the lining form and the concrete in turn, resulting in the accelerated hydration of concrete.

Based on the field test data from the construction of the railroad tunnel cast-in-place concrete lining, it is found that this technology is able in 6 to 12 hours to complete the curing of concrete lining sufficiently to remove the form. It is hoped that this approach will substantially reduce the construction period and cost of tunnel lining, even during cold-weather.
The Development of a Roller Rig for Experimental Evaluation of Contact Mechanics for Railway Vehicles
Authors: Meymand Sajjad Z. , Hosseinipour Milad , Ahmadian Mehdi
Published: June 2015

This paper discusses the development of a state of the art single-wheel roller rig for studying contact mechanics and dynamics in railroad applications. The use of indoor-based simulation tools has become a mainstay in vehicle testing for the automotive and railroad industries. In contrast to field-testing, roller rigs offer a controlled laboratory environment that can provide a successful path for obtaining data on the mechanics and dynamics of railway systems for a variety of operating conditions. The idea to develop a laboratory test rig started from the observation that there is a need for better-developed testing fixtures capable of accurately explaining the relatively unknown physics of the wheel-rail contact mechanics and dynamics. Developing a better understanding of such physics would assist with designing faster, safer, and more efficient railroad systems. A review of the existing roller rigs indicated that many desired functional requirements for studying contact mechanics are not readily available. The Virginia Tech Railway Technologies Laboratory (RTL) has embarked on a mission to develop a state-of-the-art testing facility that will allow experimental testing for contact mechanics in a dynamic, controlled, and consistent manner. The VT roller rig is intended to allow for actively controlling all the wheel-rail interface degrees of freedom: cant angle, angle of attack, and lateral displacement. Two AC synchronous servomotors, accompanied with proper gearheads, accurately drive the rotating wheels. A novel force measurement system, suitable for steel on steel contact, is configured to precisely measure the contact forces and torques. The control architecture is developed based on the SynqNet data acquisition system offered by Kollmorgen, the drive-motor and actuator supplier. The Synqnet provides a unified communication protocol between actuators, drives, and data acquisition system; therefore eliminating any difficulty with data conversion among these units. Other auxiliary sensors and measurement systems are implemented to help with characterizing the contact mechanics and contact geometry. This paper will describe the main steps in the design process of the VT roller rig and the final design solution selected. It will also present the testing capabilities of the rig. The design analysis indicates that the rig can successfully meet the set requirements: additional accuracy in measurements, and better control on the design of experiments.
Experimental Investigation of the Influence of Surface Contaminants on the Transfer Length of Smooth and Indented Prestressing Reinforcements Used in the Manufacture of Concrete Railroad Ties
Authors: Beck B. Terry , Peterman Robert J. , Wu Chih-Hang John , Mattson Steve
Published: June 2015

It has been hypothesized that surface contaminants, such as lubricants on prestressing wires or strands, influence the resulting transfer length. However, until recently, the extent of this possible influence has only been speculation, as has been the relative influence on wire in comparison to strand. With the recent development of the ability to rapidly assess transfer length using new non-contact optical methods, it is now possible to explore hypothetical scenarios such as this with nearly real-time capability in the manufacturing plant.

This paper presents a recent attempt to determine the effect of lubricating oil on the transfer length of ties, by conducting nearly real-time in-plant transfer length measurements using a newly developed prototype multi-camera non-contact transfer length measurement system. The testing was conducted on prismatic concrete turnout ties manufactured at the Nortrak plant in Cheyenne, Wyoming. Two different types of turnout ties were investigated, one containing indented 5.32-mm-diameter wire reinforcement and the other containing 3/8-in.-diameter 7-wire strand. These ties were located near the end of the casting bed. Prior to casting, one end of the form was sprayed with a generic lubricant, literally saturating the prestressing wires or strands. The ties were then cast and de-tensioned following the normal manufacturing process. This clearly represented a highly worst-case scenario for the influence of surface contaminants.

Measurements were made using the new multi-camera system, providing a detailed profile of surface strain over several feet along each end of the last three ties in the casting beds (one for strand and one for wire) — the last tie being the one subjected to the application of oil prior to casting. Hence, the influence of oil application on adjacent ties was also revealed by these tests. For the tie end with strand reinforcement subjected to oil soaking, the maximum compressive strain only reached about 400 microstrain, far below the nominal average maximum strain level of approximately 1000 microstrain. In fact, the associated transfer length for the oil-soaked end could not be definitively measured because the strain level never achieved the plateau level of strain. In contrast, the tie end with oil-soaked indented wire exhibited a significant increase in transfer length; however, the transfer length remained well below the distance to the rail seat. From these worst-case tests, one can conclude that smooth strand is potentially highly influenced by lubricating oils, whereas the influence on indented wire is likely small by comparison.
Finite Element Bond Models for Seven-Wire Prestressing Strands in Concrete Crossties
Authors: Yu Hailing , Jeong David
Published: June 2015

Seven-wire strands are commonly used in pretensioned concrete ties, but its bonding mechanism with concrete needs further examination to provide a better understanding of some concrete tie failure modes. As a key component in the finite element (FE) analysis of concrete crossties, macro-scale or phenomenological FE bond models are developed for seven-wire strands in this paper. The strand-concrete interfaces are homogenized with a thin layer of cohesive elements applied between the strand and concrete elements. Further, the cohesive elements are assigned traction-displacement constitutive or bond relations that are defined in terms of normal and shear stresses versus interfacial dilation and slip. The bond relations are developed within an elasto-plastic framework that characterizes the adhesive, frictional and/or dilatational bonding mechanisms in the interface. The yield functions and plastic flow rules specific for the seven-wire strands are presented. The bond parameters are calibrated from untensioned pullout tests and pretensioned prism tests conducted on concrete specimens. The bond models are then verified with (1) the surface strain data measured on actual concrete crossties made at a tie manufacturing plant, and (2) the force-displacement relation obtained in a center negative moment test conducted also on concrete crossties.
Rail Tank Car Total Containment Fire Testing: Planning and Test Development
Authors: Gonzalez Francisco , Prabhakaran Anand , Robitaille Andrew , Booth Graydon , Birk A. M. , Otremba Frank
Published: June 2015

Given the frequent incidences of Non-Accident Releases (NARs) of hazardous materials from tank cars, there in an increasing interest in transporting hazardous materials in total containment conditions (i.e., no pressure relief devices). However, the ability of tank cars to meet thermal protection requirements provided in the Code of Federal Regulations under conditions of total containment has not been established. Also, the modeling tool commonly used by industry to evaluate thermal protection, AFFTAC, has not been validated under these conditions. The intent of this effort was to evaluate through a series of third-scale fire tests, the ability of tank cars to meet the thermal protection requirements under total containment conditions, and also, to validate AFFTAC for such conditions.

This paper describes the test design and planning effort associated with this research, including the design and evaluation of a fire test setup to simulate a credible, fully engulfing, pool fire that is consistent and repeatable, and the design and hydro-static testing of a third-scale tank specimen. The fire design includes controls on the spatial distribution and temperature variation of the flame temperature, the heat flux, and the radiative balance, to best reflect large liquid hydrocarbon pool fire conditions that may be experienced during derailment scenarios.
Correction of MRI‐induced geometric distortions in whole‐body small animal PET‐MRI
Authors: Frohwein Lynn J. , Hoerr Verena , Faber Cornelius , Schäfers Klaus P.
Published: June 2015

Purpose:

The fusion of positron emission tomography (PET) and magnetic resonance imaging (MRI) data can be a challenging task in whole‐body PET‐MRI. The quality of the registration between these two modalities in large field‐of‐views (FOV) is often degraded by geometric distortions of the MRI data. The distortions at the edges of large FOVs mainly originate from MRI gradient nonlinearities. This work describes a method to measure and correct for these kind of geometric distortions in small animal MRI scanners to improve the registration accuracy of PET and MRI data.

Methods:

The authors have developed a geometric phantom which allows the measurement of geometric distortions in all spatial axes via control points. These control points are detected semiautomatically in both PET and MRI data with a subpixel accuracy. The spatial transformation between PET and MRI data is determined with these control points via 3D thin‐plate splines (3D TPS). The transformation derived from the 3D TPS is finally applied to real MRI mouse data, which were acquired with the same scan parameters used in the phantom data acquisitions. Additionally, the influence of the phantom material on the homogeneity of the magnetic field is determined via field mapping.

Results:

The spatial shift according to the magnetic field homogeneity caused by the phantom material was determined to a mean of 0.1 mm. The results of the correction show that distortion with a maximum error of 4 mm could be reduced to less than 1 mm with the proposed correction method. Furthermore, the control point‐based registration of PET and MRI data showed improved congruence after correction.

Conclusions:

The developed phantom has been shown to have no considerable negative effect on the homogeneity of the magnetic field. The proposed method yields an appropriate correction of the measured MRI distortion and is able to improve the PET and MRI registration. Furthermore, the method is applicable to whole‐body small animal imaging routines including different standard MRI sequences.
A novel computer aided breast mass detection scheme based on morphological enhancement and SLIC superpixel segmentation
Authors: Chu Jinghui , Min Hang , Liu Li , Lu Wei
Published: June 2015

Purpose:

To develop a computer‐aided detection (CAD) scheme for mass detection on digitized mammograms that achieves a high sensitivity while maintaining a low false positive (FP) rate using morphological enhancement and simple linear iterative clustering (SLIC) method.

Methods:

The authors developed a multiple stage method for breast mass detection. The proposed CAD scheme consists of five major components: (1) preprocessing based on morphological enhancement, which enhances mass‐like patterns while removing unrelated background clutters, (2) segmentation of mass candidates based on the SLIC method, which groups mass and background tissue into different regions, (3) prescreening of suspicious regions using rule‐based classification that eliminates regions unlikely to represent masses, (4) potential lesion contour refinement based on distance regularized level set evolution, and (5) FP reduction based on feature extraction and an ensemble of undersampled support vector machines. Two datasets were built to design and evaluate the system: a mass dataset containing 187 cases (386 mammograms) and a nonmass dataset containing 88 mammograms. All cases were acquired from the digital database for screening mammography (DDSM). Approximately two thirds of the available masses were used for training the system, and the remaining masses and nonmass dataset were used for testing.

Results:

Testing of the proposed CAD system on the mass dataset yielded a mass‐based sensitivity of 98.55%, 97.10%, 92.75% at 0.84, 0.63, 0.55 FP mark/image, respectively. Tested on the nonmass dataset, the scheme showed a FP rate of 0.55, 0.34, 0.30 mark/image.

Conclusions:

The results indicate that the system is promising in improving the performance of current CAD systems by reducing FP rate while achieving relatively high sensitivity.
Computer‐aided pulmonary image analysis in small animal models
Authors: Xu Ziyue , Bagci Ulas , Mansoor Awais , Kramer‐Marek Gabriela , Luna Brian , Kubler Andre , Dey Bappaditya , Foster Brent , Papadakis Georgios Z. , Camp Jeremy V. , Jonsson Colleen B. , Bishai William R. , Jain Sanjay , Udupa Jayaram K. , Mollura Daniel J.
Published: June 2015

Purpose:

To develop an automated pulmonary image analysis framework for infectious lung diseases in small animal models.

Methods:

The authors describe a novel pathological lung and airway segmentation method for small animals. The proposed framework includes identification of abnormal imaging patterns pertaining to infectious lung diseases. First, the authors’ system estimates an expected lung volume by utilizing a regression function between total lung capacity and approximated rib cage volume. A significant difference between the expected lung volume and the initial lung segmentation indicates the presence of severe pathology, and invokes a machine learning based abnormal imaging pattern detection system next. The final stage of the proposed framework is the automatic extraction of airway tree for which new affinity relationships within the fuzzy connectedness image segmentation framework are proposed by combining Hessian and gray‐scale morphological reconstruction filters.

Results:

133 CT scans were collected from four different studies encompassing a wide spectrum of pulmonary abnormalities pertaining to two commonly used small animal models (ferret and rabbit). Sensitivity and specificity were greater than 90% for pathological lung segmentation (average dice similarity coefficient > 0.9). While qualitative visual assessments of airway tree extraction were performed by the participating expert radiologists, for quantitative evaluation the authors validated the proposed airway extraction method by using publicly available EXACT’09 data set.

Conclusions:

The authors developed a comprehensive computer‐aided pulmonary image analysis framework for preclinical research applications. The proposed framework consists of automatic pathological lung segmentation and accurate airway tree extraction. The framework has high sensitivity and specificity; therefore, it can contribute advances in preclinical research in pulmonary diseases.
Development and evaluation of aperture‐based complexity metrics using film and EPID measurements of static MLC openings
Authors: Götstedt Julia , Karlsson Hauer Anna , Bäck Anna
Published: June 2015

Purpose:

Complexity metrics have been suggested as a complement to measurement‐based quality assurance for intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). However, these metrics have not yet been sufficiently validated. This study develops and evaluates new aperture‐based complexity metrics in the context of static multileaf collimator (MLC) openings and compares them to previously published metrics.

Methods:

This study develops the converted aperture metric and the edge area metric. The converted aperture metric is based on small and irregular parts within the MLC opening that are quantified as measured distances between MLC leaves. The edge area metric is based on the relative size of the region around the edges defined by the MLC. Another metric suggested in this study is the circumference/area ratio. Earlier defined aperture‐based complexity metrics—the modulation complexity score, the edge metric, the ratio monitor units (MU)/Gy, the aperture area, and the aperture irregularity—are compared to the newly proposed metrics. A set of small and irregular static MLC openings are created which simulate individual IMRT/VMAT control points of various complexities. These are measured with both an amorphous silicon electronic portal imaging device and EBT3 film. The differences between calculated and measured dose distributions are evaluated using a pixel‐by‐pixel comparison with two global dose difference criteria of 3% and 5%. The extent of the dose differences, expressed in terms of pass rate, is used as a measure of the complexity of the MLC openings and used for the evaluation of the metrics compared in this study. The different complexity scores are calculated for each created static MLC opening. The correlation between the calculated complexity scores and the extent of the dose differences (pass rate) are analyzed in scatter plots and using Pearson's r‐values.

Results:

The complexity scores calculated by the edge area metric, converted aperture metric, circumference/area ratio, edge metric, and MU/Gy ratio show good linear correlation to the complexity of the MLC openings, expressed as the 5% dose difference pass rate, with Pearson's r‐values of −0.94, −0.88, −0.84, −0.89, and −0.82, respectively. The overall trends for the 3% and 5% dose difference evaluations are similar.

Conclusions:

New complexity metrics are developed. The calculated scores correlate to the complexity of the created static MLC openings. The complexity of the MLC opening is dependent on the penumbra region relative to the area of the opening. The aperture‐based complexity metrics that combined either the distances between the MLC leaves or the MLC opening circumference with the aperture area show the best correlation with the complexity of the static MLC openings.
Body-Cooling Paradigm in Sport: Maximizing Safety and Performance During Competition
Authors: Adams William M. , Hosokawa Yuri , Casa Douglas J.
Published: June 2015

Context:

Although body cooling has both performance and safety benefits, knowledge on optimizing cooling during specific sport competition is limited.

Objectives:

To identify when, during sport competition, it is optimal for body cooling and to identify optimal body-cooling modalities to enhance safety and maximize sport performance.

Evidence Acquisition:

A comprehensive literature search was conducted to identify articles with specific context regarding body cooling, sport performance, and cooling modalities used during sport competition. A search of scientific peer-reviewed literature examining the effects of body cooling on exercise performance was done to examine the influence of body cooling on exercise performance. Subsequently, a literature search was done to identify effective cooling modalities that have been shown to improve exercise performance.

Evidence Synthesis:

The cooling modalities that are most effective in cooling the body during sport competition depend on the sport, timing of cooling, and feasibility based on the constraints of the sports rules and regulations. Factoring in the length of breaks (halftime substitutions, etc), the equipment worn during competition, and the cooling modalities that offer the greatest potential to cool must be considered in each individual sport.

Conclusions:

Scientific evidence supports using body cooling as a method of improving performance during sport competition. Developing a strategy to use cooling modalities that are scientifically evidence-based to improve performance while maximizing athlete’s safety warrants further investigation.
Structural Insights into Binding of the Antifungal Drug Fluconazole to Saccharomyces cerevisiae Lanosterol 14α-Demethylase
Authors: Sagatova Alia A. , Keniya Mikhail V. , Wilson Rajni K. , Monk Brian C. , Tyndall Joel D. A.
Published: June 2015

Infections by fungal pathogens such as
Candida albicans
and
Aspergillus fumigatus
and their resistance to triazole drugs are major concerns. Fungal lanosterol 14α-demethylase belongs to the CYP51 class in the cytochrome P450 superfamily of enzymes. This monospanning bitopic membrane protein is involved in ergosterol biosynthesis and is the primary target of azole antifungal drugs, including fluconazole. The lack of high-resolution structural information for this drug target from fungal pathogens has been a limiting factor for the design of modified triazole drugs that will overcome resistance. Here we report the X-ray structure of full-length
Saccharomyces cerevisiae
lanosterol 14α-demethylase in complex with fluconazole at a resolution of 2.05 Å. This structure shows the key interactions involved in fluconazole binding and provides insight into resistance mechanisms by revealing a water-mediated hydrogen bonding network between the drug and tyrosine 140, a residue frequently found mutated to histidine or phenylalanine in resistant clinical isolates.
Genome-Wide Identification of Klebsiella pneumoniae Fitness Genes during Lung Infection
Authors: Bachman Michael A. , Breen Paul , Deornellas Valerie , Mu Qiao , Zhao Lili , Wu Weisheng , Cavalcoli James D. , Mobley Harry L. T.
Published: June 2015

Klebsiella pneumoniae
is an urgent public health threat because of resistance to carbapenems, antibiotics of last resort against Gram-negative bacterial infections. Despite the fact that
K. pneumoniae
is a leading cause of pneumonia in hospitalized patients, the bacterial factors required to cause disease are poorly understood. Insertion site sequencing combines transposon mutagenesis with high-throughput sequencing to simultaneously screen thousands of insertion mutants for fitness defects during infection. Using the recently sequenced
K. pneumoniae
strain KPPR1 in a well-established mouse model of pneumonia, insertion site sequencing was performed on a pool of >25,000 transposon mutants. The relative fitness requirement of each gene was ranked based on the ratio of lung to inoculum read counts and concordance between insertions in the same gene. This analysis revealed over 300 mutants with at least a 2-fold fitness defect and 69 with defects ranging from 10- to >2,000-fold. Construction of 6 isogenic mutants for use in competitive infections with the wild type confirmed their requirement for lung fitness. Critical fitness genes included those for the synthesis of branched-chain and aromatic amino acids that are essential in mice and humans, the transcriptional elongation factor RfaH, and the copper efflux pump CopA
.
The majority of fitness genes were conserved among reference strains representative of diverse pathotypes. These results indicate that regulation of outer membrane components and synthesis of amino acids that are essential to its host are critical for
K. pneumoniae
fitness in the lung.

IMPORTANCE
Klebsiella pneumoniae
is a bacterium that commonly causes pneumonia in patients after they are admitted to the hospital.
K. pneumoniae
is becoming resistant to all available antibiotics, and when these infections spread to the bloodstream, over half of patients die. Since currently available antibiotics are failing, we must discover new ways to treat these infections. In this study, we asked what genes the bacterium needs to cause an infection, since the proteins encoded by these genes could be targets for new antibiotics. We identified over 300 genes that
K. pneumoniae
requires to grow in a mouse model of pneumonia. Many of the genes that we identified are found in
K. pneumoniae
isolates from throughout the world, including antibiotic-resistant forms. If new antibiotics could be made against the proteins that these genes encode, they may be broadly effective against
K. pneumoniae.
Diverging prevalences and different risk factors for childhood asthma and eczema: a cross-sectional study
Authors: Barnish Maxwell S , Tagiyeva Nara , Devereux Graham , Aucott Lorna , Turner Steve
Published: June 2015

Objective

To compare the prevalences of and risk factors for asthma, wheeze, hay fever and eczema in primary schoolchildren in Aberdeen in 2014.

Design

Cross-sectional survey.

Setting

Primary schools in Aberdeen, North-East Scotland.

Participants

Children in Scottish school years primary 1–7 were handed a questionnaire by their class teacher to be completed by their parents and returned to the researchers by post or online.

Main outcome measures

Lifetime history of asthma, eczema and hay fever, and recent history of wheeze.

Results

41 schools agreed to participate (87%). 11 249 questionnaires were distributed and 3935 returned (35%). A parent-reported lifetime history of asthma, eczema and hay fever was present in 14%, 30% and 24% of children, respectively. The odds of lifetime asthma increased with age (OR 1.1 per year, 95% CI 1.1 to 1.2), male sex (OR 1.89, 95% CI 1.4 to 2.3), parental smoking (OR 1.7, 95% CI 1.2 to 2.3) and eczema (OR 6.6, 95% CI 5.2 to 8.4). Prevalence of recent wheeze was also reported to be 14% and was positively associated with male sex, parental smoking and eczema. In contrast, parental eczema was the only identified predictor of childhood eczema risk.

Conclusions

The lifetime prevalence of asthma in primary schoolchildren was 14% in this survey, approximately half the prevalence of eczema. We report diverging prevalences in relation to previous studies in our locality, and different risk factors for asthma and eczema. These findings suggest that asthma and eczema are unlikely to have a common origin.
Improving handover from intensive care to ward medical teams with simple changes to paperwork
Authors: Messing Jonathan
Published: June 2015

Medical handover has been highlighted by the General Medical Council[1] as a critical step in patient care, ensuring continuity of care, patient safety, and enabling efficient multidisciplinary functioning. Handover between doctors on the intensive care team and the ward teams in the Great Western Hospital on step down was evaluated by assessing discharge summaries and patient notes, and by following up discharged patients. Handover was found to be present only in the minority of patients and documented in none.

Simple changes were made to discharge paperwork in the form of a prompt and documentation of to whom handover was made, as well as the creation of space in the daily review sheets for patients with outstanding handover to be completed. The initial audit findings were presented at a local meeting to remind staff of the importance of handover. These simple modifications brought the handover rates up to 100% (n=12). The rates of documentation of handover also rose from 0% to 100%. This quality improvement project serves to demonstrate that carefully targeted, simple changes to practice in identified critical areas can produce dramatic as well as legally and ethically required results in a very short space of time.
Identifying Knowledge Gap to Meet Client Project Requirements in Refurbishment Projects
Authors: Lee Cynthia ChinTian
Published: June 2015

Refurbishment can be a complicated process which requires a wide variety of skills from the project team. A knowledgeable project team that is able to understand and interpret client's requirements and rely on their knowledge and experience to meet client's requirements is likely to increase the chance of delivering a project on time and within budget. Very often, a major cause of process delays is the lack of timely, correct information or knowledge, which slows down or halts the work. Until appropriate information or knowledge is acquired for the performance of tasks, there will be a delay and consequent incurrence of costs. This paper illustrates the development of a methodology for the matching of knowledge of the project team with client's project requirements during the refurbishment process. Through the matching process, knowledge gap between the existing knowledge of the project team and the required knowledge is identified and knowledge is captured to fill this gap.
Synthesis and functionalization of β-alkyl-meso-triarylcorroles
Authors: Pomarico Giuseppe , Stefanelli Manuela , Nardis Sara , Lentini Sara , Cicero Daniel O. , McCandless Gregory T. , Smith Kevin M. , Paolesse Roberto
Published: June 2015

After the definition of efficient synthetic routes for the preparation of triarylcorroles, the functionalization of these macrocycles is becoming a necessary and challenging field of research. One important synthetic step is the introduction of substituents able to influence the electronic distribution in the macrocyclic ring. A valuable target would be a corrole macrocycle with some β-pyrrole positions occupied by methyl groups, while exploiting other positions to introduce electron-withdrawing substituents. To explore the scope of this approach, we investigated the bromination and the nitration of the corrole ring and the desired products have been obtained in moderate to good yield. The successful preparation of selectively halogenated corroles is particularly interesting since they are suitable substrates for the preparation of more complex partially alkylated structures using modern cross coupling methodologies.