bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of gastrointestinal motility with MRI: Advances, challenges and opportunities
Authors: de Jonge C. S. , Smout A. J. P. M. , Nederveen A. J. , Stoker J.
Published: December 2017

Dynamic magnetic resonance imaging (MRI) of gastrointestinal motility has developed rapidly over the past few years. The non‐invasive and non‐ionizing character of MRI is an important advantage together with the fact that it is fast and can visualize the entire gastrointestinal tract. Advances in imaging and quantification techniques have facilitated assessment of gastric, small intestinal, and colonic motility in a clinical setting. Automated quantitative motility assessment using dynamic MRI meets the need for non‐invasive techniques. Recently, studies have begun to examine this technique in patients, including those with IBD, pseudo‐obstruction and functional bowel disorders. Remaining challenges for clinical implementation are processing the large amount of data, standardization and validation of the numerous MRI metrics and subsequently assessment of the potential role of dynamic MRI. This review examines the methods, advances, and remaining challenges of evaluation of gastrointestinal motility with MRI. It accompanies an article by Khalaf et al. in this journal that describes a new protocol for assessment of pan‐intestinal motility in fasted and fed state in a single MRI session.
Novel DNAJ‐related proteins in Arabidopsis thaliana
Authors: Pulido Pablo , Leister Dario
Published: December 2017

Classical DNAJ proteins are co‐chaperones that together with HSP70s control protein homeostasis. All three classical types of DNAJ proteins (DNAJA, DNAJB and DNAJC types) possess the J‐domain for interaction with HSP70. DNAJA proteins contain, in addition, both the zinc‐finger motif and the C‐terminal domain which are involved in substrate binding, while DNAJB retains only the latter and DNAJC comprises only the J‐domain. There is increasing evidence that some of the activities of DNAJ proteins do not require the J‐domain, highlighting the functional significance of the other two domains. Indeed, the so‐called DNAJ‐like proteins with a degenerate J‐domain have been previously coined as DNAJD proteins, and also proteins containing only a DNAJ‐like zinc‐finger motif appear to be involved in protein homeostasis. Therefore, we propose to extend the classification of DNAJ‐related proteins into three different groups. The DNAJD type comprises proteins with a J‐like domain only, and has 15 members in Arabidopsis thaliana, whereas proteins of the DNAJE (33 Arabidopsis members) and DNAJF (three Arabidopsis members) types contain a DNAJA‐like zinc‐finger domain and DNAJA/B‐like C‐terminal domain, respectively. Here, we provide an overview of the entire repertoire of these proteins in A. thaliana with respect to their physiological function and possible evolutionary origin.
The push and pull of plant specialized metabolism underlies a long‐standing, colorful mystery
Authors: Moghe Gaurav D. , Smith Stacey D.
Published: December 2017

This article is a Commentary on Lopez‐Nieves et al., 217: 896–908.
Current perspectives on biological approaches for osteoarthritis
Authors: Whitney Kaitlyn E. , Liebowitz Andrea , Bolia Ioanna K. , Chahla Jorge , Ravuri Sudheer , Evans Thos A. , Philippon Marc J. , Huard Johnny
Published: December 2017

Musculoskeletal injuries that disrupt the structure and function of diarthrodial joints can cause permanent biomechanical alterations and lead to a more severe, chronic condition. Despite advancements that have been made to restore tissue function and delay the need for joint replacement, there are currently no disease‐modifying therapies for osteoarthritis (OA). To reduce the risk of OA, innovative preventive medicine approaches have been developed over the last decade to treat the underlying pathology. Several biological approaches are promising treatment modalities for various stages of OA owing to their minimally invasive nature and actively dynamic physiological mechanisms that attenuate tissue degradation and inflammatory responses. Individualized growth factor and cytokine therapies, tissue‐engineered biomaterials, and cell‐based therapies have revolutionary potential for orthopedic applications; however, the paucity of standardization and categorization of biological components and their counterparts has made it difficult to determine their clinical and biological efficacy. Cell‐based therapies and tissue‐engineered biologics have become lucrative in sports medicine and orthopedics; nonetheless, there is a continued effort to produce a biological treatment modality tailored to target intra‐articular structures that recapitulates tissue function. Advanced development of these biological treatment modalities will potentially optimize tissue healing, regeneration, and joint preservation strategies. Therefore, the purpose of this paper is to review current concepts on several biological treatment approaches for OA.
Bone quality changes associated with aging and disease: a review
Authors: Boskey Adele L. , Imbert Laurianne
Published: December 2017

Bone quality encompasses all the characteristics of bone that, in addition to density, contribute to its resistance to fracture. In this review, we consider changes in architecture, porosity, and composition, including collagen structure, mineral composition, and crystal size. These factors all are known to vary with tissue and animal ages, and health status. Bone morphology and presence of microcracks, which also contribute to bone quality, will not be discussed in this review. Correlations with mechanical performance for collagen cross‐linking, crystallinity, and carbonate content are contrasted with mineral content. Age‐dependent changes in humans and rodents are discussed in relation to rodent models of disease. Examples are osteoporosis, osteomalacia, osteogenesis imperfecta (OI), and osteopetrosis in both humans and animal models. Each of these conditions, along with aging, is associated with increased fracture risk for distinct reasons.
Intraocular light scatter, reflections, fluorescence and absorption: what we see in the slit lamp
Authors: van den Berg Thomas J. T. P.
Published: December 2017

Purpose

Much knowledge has been collected over the past 20 years about light scattering in the eye‐ in particular in the eye lens‐ and its visual effect, called straylight. It is the purpose of this review to discuss how these insights can be applied to understanding the slit lamp image.

Results

The slit lamp image mainly results from back scattering, whereas the effects on vision result mainly from forward scatter. Forward scatter originates from particles of about wavelength size distributed throughout the lens. Most of the slit lamp image originates from small particle scatter (Rayleigh scatter). For a population of middle aged lenses it will be shown that both these scatter components remove around 10% of the light from the direct beam. For slit lamp observation close to the reflection angles, zones of discontinuity (Wasserspalten) at anterior and posterior parts of the lens show up as rough surface reflections. All these light scatter effects increase with age, but the correlations with age, and also between the different components, are weak. For retro‐illumination imaging it will be argued that the density or opacity seen in areas of cortical or posterior subcapsular cataract show up because of light scattering, not because of light loss.

Notes

(1) Light scatter must not be confused with aberrations. Light penetrating the eye is divided into two parts: a relatively small part is scattered, and removed from the direct beam. Most of the light is not scattered, but continues as the direct beam. This non‐scattered part is the basis for functional imaging, but its quality is under the control of aberrations. Aberrations deflect light mainly over small angles (<1°), whereas light scatter is important because of the straylight effects over large angles (>1°), causing problems like glare and hazy vision. (2) The slit lamp image in older lenses and nuclear cataract is strongly influenced by absorption. However, this effect is greatly exaggerated by the light path lengths concerned. This obviates proper judgement of the functional importance of absorption, and hinders the appreciation of the Rayleigh nature of what is seen in the slit lamp image.
Paranoia and maladaptive behaviours in homelessness: The mediating role of emotion regulation
Authors: Powell Kathryn , Maguire Nick
Published: December 2017

Objectives

Current research has implicated a role for cognitive and emotional processes in the pathways to becoming homeless. Evidence implicates three risk factors, which are often associated with an increased incidence of homelessness: paranoid thinking, emotion regulation, and engaging in maladaptive behaviours. Maladaptive behaviours include deliberate self‐harm, substance misuse, and high‐risk sexual practices. Currently, no studies have investigated the specific psychological mechanisms, such as difficulty regulating emotions, which underpin the association between paranoia and maladaptive behaviours.

Design

A mediational design was employed in a group of homeless individuals. Method: Participants (N = 40), who were homeless at the time of the study, completed a single‐session assessment of paranoia, emotion regulation, and maladaptive behaviours.

Results

Mediation analyses indicated that individuals scoring high on paranoia were more likely to engage in maladaptive behaviours, particularly substance misuse and aggression, when they had difficulty regulating their emotions. These results demonstrate a novel finding relating to the effect of emotion regulation in maintaining psychopathology and behaviours in vulnerable individuals, which may in turn sustain periods of homelessness.

Conclusions

Emotion regulation may therefore be one particular psychological mechanism through which severe mental illness affects engagement in self‐destructive behaviours in homelessness. These findings have valuable clinical implications for targeted therapeutic interventions, in this often difficult to treat homeless population.

Practitioner points

Psychosis is over‐represented in the homeless population; the cycle of homelessness may be attenuated by addressing psychotic symptomology.

Homeless individuals engage in drug abuse, self‐harm, aggression, and high‐risk sexual practices due to an inability to regulate distressing emotions effectively.

Therapeutic interventions, such as MBT and DBT, which target emotion regulation difficulties, may be useful in reducing maladaptive behaviours and preventing homelessness, by providing emotion regulation strategies to cope when homeless persons become distressed.
Acute encephalopathy with biphasic seizures and late reduced diffusion in Kawasaki disease
Authors: Shiba Takeshi , Hamahata Keigo , Yoshida Akira
Published: December 2017

Herein we describe the case of a 7‐month‐old girl with Kawasaki disease (KD) in whom status epilepticus with fever developed on day 3 and cluster of seizures on day 6 of illness, followed by severe disturbance of consciousness afterward. Diffusion‐weighted magnetic resonance imaging on day 6 of illness showed diffuse high signals in the bilateral subcortical white matter, while electroencephalogram indicated low‐voltage slow waves. This indicated acute encephalopathy with biphasic seizures and late reduced diffusion (AESD); severe neurological sequelae remained. This is the first report of AESD as a complication of KD.
Prelisting predictions of early postoperative survival in infant heart transplantation using classification and regression tree analysis
Authors: Chen Ching Kit , Manlhiot Cedric , Mital Seema , Schwartz Steven M. , Van Arsdell Glen S. , Caldarone Christopher , McCrindle Brian W. , Dipchand Anne I.
Published: December 2017

Infants listed for heart transplantation experience high waitlist and early post‐transplant mortality, and thus, optimal allocation of scarce donor organs is required. Unfortunately, the creation and validation of multivariable regression models to identify risk factors and generate individual‐level predictions are challenging. We sought to explore the use of data mining methods to generate a prediction model. CART analysis was used to create a model which, at the time of listing, would predict which infants listed for heart transplantation would survive at least 3 months post‐transplantation. A total of 48 infants were included; 13 died while waiting, and six died within 3 months of heart transplant. CART analysis identified RRT, blood urea nitrogen, and hematocrit as terminal nodes with alanine transaminase as an intermediate node predicting death. No patients listed on RRT (n = 10) survived and only three of 12 (25%) patients listed on ECLS survived >3 months post‐transplant. CART analysis overall accuracy was 83%, with sensitivity of 95% and specificity 76%. This study shows that CART analysis can be used to generate accurate prediction models in small patient populations. Model validation will be necessary before incorporation into decision‐making algorithms used to determine transplant candidacy.
Implementation Intentions, Information, and Voter Turnout: An Experimental Study
Authors: Anderson Cameron D. , Loewen Peter J. , McGregor R. Michael
Published: December 2017

Are citizens more likely to vote when they are asked to make plans about how they will cast their ballots? Such planning—typically described as “implementation intentions”—has been shown to increase many types of desirable behaviors, including exercising and healthy eating, receiving vaccinations, physical rehabilitation, and recycling. Important earlier work in political science suggests voter turnout can also be influenced by implementation intention interventions, whereby electors are prompted to “make a plan” to vote (Nickerson & Rogers, ), though this finding has gone largely unreplicated. At the same time, elections management bodies (EMBs) in many contexts regularly conduct informational campaigns in the period leading up to elections, though little is known about the effects of such efforts upon turnout. Using data from an online experiment conducted at the time of the 2015 Canadian Federal Election, we demonstrate that implementation intention interventions can improve voter turnout but that this effect is conditional upon electors being exposed to informational materials about how to vote in the election. When survey respondents were provided with information on voting requirements and methods, and then prompted with questions forcing them to contemplate the act of casting their ballots, we observe a sizable increase in turnout rates.
Hopelessness as a Predictor of Suicide Ideation in Depressed Male and Female Adolescent Youth
Authors: Wolfe Kristin L. , Nakonezny Paul A. , Owen Victoria J. , Rial Katherine V. , Moorehead Alexandra P. , Kennard Beth D. , Emslie Graham J.
Published: December 2017

We examined hopelessness as a predictor of suicide ideation in depressed youth after acute medication treatment. A total of 158 depressed adolescents were administered the Children's Depression Rating Scale‐Revised (CDRS‐R) and Columbia Suicide Severity Rating Scale (C‐SSRS) as part of a larger battery at baseline and at weekly visits across 6 weeks of acute fluoxetine treatment. The Beck Hopelessness Scale (BHS) was administered at baseline and week 6. A negative binomial regression model via a generalized estimating equation analysis of repeated measures was used to estimate suicide ideation over the 6 weeks of acute treatment from baseline measure of hopelessness. Depression severity and gender were included as covariates in the model. The negative binomial analysis was also conducted separately for the sample of males and females (in a gender‐stratified analysis). MeanCDRS‐R total scores were 60.30 ± 8.93 at baseline and 34.65 ± 10.41 at week 6. Mean baseline and week 6BHSscores were 9.57 ± 5.51 and 5.59 ± 5.38, respectively. Per the C‐SSRS, 43.04% and 83.54% reported having no suicide ideation at baseline and at week 6, respectively. The analyses revealed that baseline hopelessness was positively related to suicide ideation over treatment (p = .0027), independent of changes in depression severity. This significant finding persisted only for females (p = .0024). These results indicate the importance of early identification of hopelessness.
Basal and stress‐induced salivary testosterone variation across the menstrual cycle and linkage to motivation and muscle power
Authors: Cook C. J. , Kilduff L. P. , Crewther B. T.
Published: December 2017

This study investigated salivary testosterone (sal‐T) variation across the menstrual cycle in female athletes, at different competitive levels, and its association with motivation and neuromuscular power. Six elite and 16 non‐elite female athletes were monitored on days 7 (D7), 14 (D14), and 21 (D21) across 3 menstrual cycles for basal sal‐T concentrations and self‐appraised motivation to train and compete. Two further measures were taken on D7, D14, and D21 across 2 menstrual cycles: (1) the sal‐T response (delta change) to a physical stress test and (2) peak power (PP) response to a 6‐second cycle sprint following a post‐activation potentiation (PAP) stimulus. Basal sal‐T concentrations increased by 17 ± 27% from D7 to D14 before decreasing by −25 ± 43% on D21 (P < .05), but this result was biased by elite females with higher sal‐T (>102%) who showed larger menstrual changes. Motivation, sal‐T reactivity to stress, and the PP responses to a PAP stimulus also varied by testing day (P < .05), in parallel with basal sal‐T and in favor of the elite group. Furthermore, stronger within‐subject relationships (P < .001) between basal sal‐T and motivation emerged in the elites (r = .70‐.75) vs the non‐elite group (r = .41‐.50). In conclusion, menstrual cycle changes in sal‐T were more obvious in high‐performing female athletes with higher sal‐T concentrations. This was accompanied by greater training motivation, a more pronounced sal‐T response to a physical stressor and greater neuromuscular power in the elite group. These results support observations that female athletes with higher T are more represented at elite levels of performance.
Impact of grassland contract policy on soil organic carbon losses from alpine grassland on the Qinghai–Tibetan Plateau
Authors: Cao J. , Gong Y. , Yeh E. T. , Holden N. M. , Adamowski J. F. , Deo R. C. , Liu M. , Zhou J. , Zhang J. , Zhang W. , Zhang S. , Sheng D. , Yang S. , Xu X. , Li M. , Feng Q.
Published: December 2017

Carbon storage in the soils on the Qinghai–Tibetan Plateau plays a very important role in the global carbon budget. In the 1990s, a policy of contracting collective grasslands to smaller units was implemented, resulting in a change from the traditional collective grassland management to two new management patterns: a multi‐household management pattern (MMP: grassland shared by several households without enclosures) and a single‐household management pattern (SMP: grassland enclosed and used by only one household). In 2016, 50 MMP and 54 SMP winter pastures on the Qinghai–Tibetan Plateau were sampled to assess the differences in soil organic carbon (SOC) between the two management patterns. Results showed that average SOC was significantly greater under MMP than under SMP, with an estimated 0.41 Mg C/ha/yr lost due to SMP following the new grassland contract. Based on the government's grassland policy, four grassland utilization scenarios were developed for both summer and winter pastures. We found that if the grassland were managed under SMP, likely C losses ranged between 0.31 × 107 and 6.15 × 107 Mg C/yr across the Qinghai–Tibetan Plateau relative to MMP, which more closely resembles pre‐1990s grassland management. Previous estimates of C losses have only considered land use change (with cover change) and ignored the impacts driven by land management pattern changes (without cover change). The new data suggest that C losses from the Qinghai–Tibetan Plateau are greater than previously estimated, and therefore that the grassland contract policy should be reviewed and SMP households should be encouraged to reunite into the MMP. These findings have potential implications for land management strategies not only on the Qinghai–Tibetan Plateau but also other grazing regions globally where such practices may exist.
Psychometric Testing of the Personal Workplace Safety Instrument for Emergency Nurses
Authors: Burchill Christian N. , Bena James , Polomano Rosemary C.
Published: December 2017

Background

Patient‐visitor violence (PVV) committed against nurses is a worldwide problem. Registered nurses in emergency departments (EDs) are particularly susceptible. The frequency and severity of PVV against emergency nurses (ENs) internationally is well documented. Little is known about factors that make ENs feel safe from PVV.

Aim

Examine the psychometric properties of the Personal Workplace Safety Instrument for Emergency Nurses (PWSI‐EN), developed to measure ENs’ perceptions of safety from PVV.

Methods

Instrument development was based on a literature review, input from ENs, and expert opinion. An online version of the PWSI‐EN was distributed to a convenience sample of ENs practicing in EDs across the United States. Psychometric testing included measures of internal consistency reliability, construct validity to support subscales, and comparisons on demographic variables.

Results

Three‐hundred and five (N = 305) ENs from 16 hospitals responded to the original 31‐item PWSI‐EN. Based on item analysis and exploratory factor analysis (EFA), the instrument was reduced to 23 items with Cronbach's α = .912. EFA delineated six subscales relevant to perception of safety from PVV with factor loadings from .342 to .879. Low to moderate subscale correlations showed a degree of independence for concept domains. Known groups approach for construct validity revealed statistically significant differences (p < .05) for five subscales and the total score between community and academic or teaching hospitals. Hospital type, organizational confidence, and fear for patient safety were significant predictors of greater perceptions of safety from PVV.

Linking Evidence to Action

The PWSI‐EN is a valid and reliable survey instrument to assess EN perceptions of safety. ED and hospital leaders can use this instrument to determine specific areas to focus efforts in order to improve ENs’ perception of safety from PVV. Researchers exploring interventions aimed at improving perceptions of safety from PVV for ENs may find the PWSI‐EN useful.
Tempol augments the blunted cutaneous microvascular thermal reactivity in healthy young African Americans
Authors: Hurr Chansol , Patik Jordan C. , Kim KiYoung , Christmas Kevin M. , Brothers R. Matthew
Published: December 2017

New Findings

What is the central question of this study?

The purpose was to determine whether there is a difference between African Americans and Caucasians in cutaneous microvascular function and whether this difference is attributable to elevated oxidative stress.

What is the main finding and its importance?

The main finding is that African Americans have an attenuated cutaneous vasodilatation during local heating relative to Caucasians that is restored with local infusion of the superoxide dismutase mimetic, tempol. This suggests that superoxide mediates microvascular dysfunction and might contribute to the greater prevalence of cardiovascular disease in this population.

African Americans (AA) have elevated risk for cardiovascular disease relative to other populations. We hypothesized that the cutaneous hyperaemic response to local heating is reduced in young AA relative to Caucasian Americans (CA) and that this is attributable to elevated oxidative stress. As such, ascorbic acid (a global antioxidant) and tempol (a superoxide dismutase mimetic) would improve this response in AA. Microdialysis fibres received lactated Ringer solution (control), 10 mm ascorbic acid or 10 μm 4‐hydroxy‐2,2,6,6‐tetramethylpiperidine‐1‐oxyl (tempol) at a rate of 2.0 μl min−1. Cutaneous vascular conductance (CVC) was calculated as the red blood cell flux divided by mean arterial pressure. Data were presented as a percentage of maximal CVC (%CVCmax) induced by 44°C heating plus sodium nitroprusside. Twenty‐four (12 AA, 12 CA) young (23 ± 4 years old) subjects participated. During 39°C heating, the %CVCmax was lower in AA at the control (CA, 65 ± 20% versus AA, 47 ± 15%; P < 0.05) and ascorbic acid sites (CA, 73 ± 14% versus AA: 49 ± 17%; P < 0.01). At the tempol site, there were no differences between groups. This was followed by infusion of 10 mm l‐NAME at all sites to assess the contribution of nitric oxide to vasodilatation during local heating. The contribution of nitric oxide was lower in AA relative to CA at 39°C; however, this was restored with tempol. These data suggest that: (i) cutaneous vasodilatation in response to local heating is blunted in AA relative to CA; and (ii) elevated superoxide generation attenuates nitric oxide‐mediated cutaneous vasodilatation in AA.
Configurational Forces on Elastic Line Singularities
Authors: Seo Youjung , Jung Gyu-Jin , Kim In-Ho , Eugene Pak Y.
Published: December 2017

Configurational forces acting on two-dimensional (2D) elastic line singularities are evaluated by path-independent J-, M-, and L-integrals in the framework of plane strain linear elasticity. The elastic line singularities considered in this study are the edge dislocation, the line force, the nuclei of strain, and the concentrated couple moment that are subjected to far-field loads. The interaction forces between two similar parallel elastic singularities are also calculated. Self-similar expansion force, M, evaluated for the line force shows that it is exactly the negative of the strain energy prelogarithmic factor as in the case for the well-known edge dislocation result. It is also shown that the M-integral result for the nuclei of strain and the L-integral result for the line force yield interesting nonzero expressions under certain circumstances.
Experimental Investigation on Infrared Signatures of Axisymmetric Vectoring Exhaust Nozzle With Film Cooling and Low-Emissivity Coating
Authors: Liu Jian , Ji Honghu
Published: December 2017

Investigations on infrared (IR) radiation suppression of axisymmetric vectoring exhaust nozzle (AVEN) are meaningful, due to the requests for maneuverability and IR stealth capability of aircrafts. In this paper, the synthetic suppression scheme of film cooling and low-emissivity coating was adopted on the center body and divergent flaps of the nozzles at 0 deg, 10 deg, and 20 deg vectoring angles. The IR signatures of both the baseline AVEN and the nozzles with IR suppression were measured. Comparing the IR signatures of the nozzles with and without IR suppression measures, the IR suppression effectiveness of the film cooling and low-emissivity coating was obtained. The investigation results indicate that the IR signatures of AVEN decrease with the increase of vectoring angle. The film cooling enables a remarkable decrease of the IR signatures of AVEN. The synthetic suppression of film cooling and low-emissivity coating enables a further decrease of IR signatures. For the case studied in this paper, the integrated radiation intensities of the nozzles with film cooling and low-emissivity coating at 0 deg, 10 deg, and 20 deg vectoring angles are decreased by 52.3%, 57.9%, and 37.2% at 0 deg measurement angle, respectively.
Computational Fluid Dynamics Investigation of a Core-Mounted Target-Type Thrust Reverser—Part 2: Reverser Deployed Configuration
Authors: Mahmood Tashfeen , Jackson Anthony , Sethi Vishal , Khanal Bidur , Ali Fakhre
Published: December 2017

Core-mounted target-type thrust reverser (CMTTTR) design was proposed by NASA in the second half of the 90 s. NASA carried out several experiments at static conditions, and their acquired results suggested that the performance characteristics of the CMTTTR design fall short to comply with the mandatory thrust reverser (TR) performance criteria, and were therefore regarded as an infeasible design. However, the authors of this paper believe that the results presented by NASA for the CMTTTR design require further exploration to facilitate the complete understanding of its true performance potential. This part 2 paper is a continuation from Part 1 (reverser stowed configuration) and presents a comprehensive three-dimensional (3D) computational fluid dynamics (CFD) analyses of the CMTTTR in deployed configuration. The acquired results are extensively analyzed for aforementioned TR configuration operating under the static operating conditions at sea level, i.e., sea-level static, International Standard Atmosphere (ISA); the analyses at forward flight conditions will be covered in part 3. The key objectives of this paper are: First, to validate the acquired CFD results with the experimental data provided by NASA; this is achieved by measuring the static pressure values on various surfaces of the deployed CMTTTR model. The second objective is to estimate the performance characteristics of the CMTTTR design and corroborate the results with experimental data. The third objective is to estimate the pressure thrust (i.e., axial thrust generated due to the pressure difference across various reverser surfaces) and discuss its significance for formulating the performance of any TR design. The fourth objective is to investigate the influence of kicker plate installation on overall TR performance. The fifth and final objective is to examine and discuss the overall flow physics associated with the thrust reverse under deployed configuration.
Global Sensitivity Analysis for Vehicle–Track Interactions: Special Attention on Track Irregularities
Authors: Xu Lei , Zhai Wanming , Gao Jianmin
Published: December 2017

The dynamic vehicle–track interactions are complex processes due to the highly nonlinear terms and spatially varying excitations in vehicle design, track maintenance, dynamic prediction, etc. Therefore, it is of importance to clarify the key factors affecting the dynamic behaviors of system components. In this paper, a comprehensive model is presented, which is capable of analyzing the global sensitivity of vehicle–track interactions. In this model, the vehicle–track interactions considering the nonlinear wheel–rail contact geometries are depicted in three-dimensional (3D) space, and then the approaches for global sensitivity analysis (GSA) and time–frequency analysis are combined with the dynamic model. In comparison to the local sensitivity analysis, the proposed model has accounted for the coupling contributions of various factors. Thus, it is far more accurate and reliable to evaluate the critical factors dominating the vehicle–track interactions. Based on the methods developed in the present study, numerical examples have been conducted to draw the following marks: track irregularities possess the dominant role in guiding the dynamic performance of vehicle–track systems, besides, the vertical stiffness of primary suspension and rail pads also shows significant influence on vertical acceleration of the car body and the wheel–rail vertical force, respectively. Finally, a method is developed to precisely extract the characteristic wavelengths and amplitude limits of track irregularities.
Observation of the Mott insulator to superfluid crossover of a driven-dissipative Bose-Hubbard system
Authors: Tomita Takafumi , Nakajima Shuta , Danshita Ippei , Takasu Yosuke , Takahashi Yoshiro
Published: December 2017

We engineer the on-site dissipation to reveal its impact on the quantum phase transition from Mott insulator to superfluid.
Spatial charge inhomogeneity and defect states in topological Dirac semimetal thin films of Na
3
Bi
Authors: Edmonds Mark T. , Collins James L. , Hellerstedt Jack , Yudhistira Indra , Gomes Lídia C. , Rodrigues João N. B. , Adam Shaffique , Fuhrer Michael S.
Published: December 2017

Small potential variations in 3D semimetal Na
3
Bi enable close approach to the Dirac point, allowing exploration of new physics.
Workflow interruptions and stress atwork: a mixed-methods study among physicians and nurses of a multidisciplinary emergency department
Authors: Weigl Matthias , Beck Joana , Wehler Markus , Schneider Anna
Published: December 2017

Objectives

Dealing with multiple workflow interruptions is a major challenge in emergency department (ED) work. This study aimed to establish a taxonomy of workflow interruptions that takes into account the content and purpose of interruptive communication. It further aimed to identify associations of workflow interruptions with ED professionals’ work stress.

Design

Combined data from expert observation sessions and concomitant self-evaluations of ED providers.

Setting

ED of an academic community hospital in Germany.

Participants

Multidisciplinary sample of ED physicians and nurses. 77 matched observation sessions of interruptions and self-evaluations of work stress were obtained on 20 randomly selected days.

Outcome measures

ED professionals’ stress evaluations were based on standardised measures. ED workload data on patient load, patient acuity and staffing were included as control variables in regression analyses.

Results

Overall mean rate was 7.51 interruptions/hour. Interruptions were most frequently caused by ED colleagues of another profession (27.1%; mean interruptions/hour rate: 2.04), by ED colleagues of the same profession (24.1%; 1.81) and by telephone/beeper (21%; 1.57). Concerning the contents of interruption events, interruptions most frequently occurred referring to a parallel case under care (30.3%, 2.07), concerning the current case (19.1%; 1.28), or related to coordination activities (18.2%, 1.24). Regression analyses revealed that interruptive communication related to parallel cases significantly increased ED providers’ stress levels (β=0.24, P=0.03). This association remained significant after controlling for ED workload.

Discussion

Interruptions that refer to parallel cases under care were associated with increased stress among ED physicians and nurses. Our approach to distinguish between sources and contents of interruptions contributes to an improved understanding of potential benefits and risks of workflow interruptions in ED work environments. Despite some limitations, our findings add to future research on the implications of interruptions for effective and safe patient care and work in complex and dynamic care environments.
Wild type Kirsten rat sarcoma is a novel microRNA-622-regulated therapeutic target for hepatocellular carcinoma and contributes to sorafenib resistance
Authors: Dietrich Peter , Koch Andreas , Fritz Valerie , Hartmann Arndt , Bosserhoff Anja Katrin , Hellerbrand Claus
Published: December 2017

Objective

Sorafenib is the only effective therapy for advanced hepatocellular carcinoma (HCC). Combinatory approaches targeting mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK)- and phosphatidylinositol-4,5-bisphosphate-3-kinase (PI3K)/protein-kinase B(AKT) signalling yield major therapeutic improvements. RAS proteins regulate both RAF/MAPK and PI3K/AKT signalling. However, the most important RAS isoform in carcinogenesis, Kirsten rat sarcoma (KRAS), remains unexplored in HCC.

Design

Human HCC tissues and cell lines were used for expression and functional analysis. Sorafenib-resistant HCC cells were newly generated. RNA interference and the novel small molecule deltarasin were used for KRAS inhibition both in vitro and in a murine syngeneic orthotopic HCC model.

Results

Expression of wild type KRAS messenger RNA and protein was increased in HCC and correlated with extracellular-signal regulated kinase (ERK) activation, proliferation rate, advanced tumour size and poor patient survival. Bioinformatic analysis and reporter assays revealed that KRAS is a direct target of microRNA-622. This microRNA was downregulated in HCC, and functional analysis demonstrated that KRAS-suppression is the major mediator of its inhibitory effect on HCC proliferation. KRAS inhibition markedly suppressed RAF/ERK and PI3K/AKT signalling and proliferation and enhanced apoptosis of HCC cells in vitro and in vivo. Combinatory KRAS inhibition and sorafenib treatment revealed synergistic antitumorigenic effects in HCC. Sorafenib-resistant HCC cells showed elevated KRAS expression, and KRAS inhibition resensitised sorafenib-resistant cells to suppression of proliferation and induction of apoptosis.

Conclusions

KRAS is dysregulated in HCC by loss of tumour-suppressive microRNA-622, contributing to tumour progression, sorafenib sensitivity and resistance. KRAS inhibition alone or in combination with sorafenib appears as novel promising therapeutic strategy for HCC.
Evaluation of the relative effectiveness of the 2017 updated Manchester scoring system for predicting BRCA1/2 mutations in a Southeast Asian country
Authors: Chew Winston , Moorakonda Rajesh Babu , Courtney Eliza , Soh Hazel , Li Shao Tzu , Chen Yanni , Shaw Tarryn , Allen John Carson , Evans Dafydd Gareth R , Ngeow Joanne
Published: December 2017

Background

Germline mutations in the BRCA1 and BRCA2 genes have significant clinical implications for both risk-reducing and early surveillance management. The third and most recent revision of the Manchester scoring system (MSS3) used to distinguish patients indicated for germline BRCA1/2 testing included further adjustments for triple negative breast cancer, high-grade serous ovarian cancer and human epidermal growth factor 2 (HER2) receptor status. This study aims to evaluate the relative effectiveness of MSS3 in a Southeast Asian population.

Methods

All patients in our centre were tested using next-generation sequencing (NGS) panels that included full gene sequencing as well as coverage for large deletions/duplications in BRCA1/2. We calculated MSS1-3 scores for index patients between 2014 and 2017 who had undergone BRCA1/2 genetic testing and recorded their genetic test results. MSS1-3 outcomes were compared using receiver operating characteristic analysis, while associations with predictors were investigated using Fisher’s exact test and logistics regression. Calculations were performed using Medcalc17.

Results

Of the 330 included patients, 47 (14.2%) were found to have a germline mutation in BRCA1 or BRCA2. A positive HER2 receptor was associated with a lower likelihood of a BRCA1/2mutation (OR=0.125, 95% CI 0.016 to 0.955; P=0.007), while high-grade serous ovarian cancer was conversely associated with an increased likelihood of a BRCA1/2 mutation (OR=5.128, 95% CI 1.431 to 18.370; P=0.012). At the 10% threshold, 43.0% (142/330) of patients were indicated for testing under MSS3, compared with 35.8% (118/330) for MSS1% and 36.4% (120/330) for MSS2. At the 10% threshold, MSS3 sensitivity was 91.5% and specificity 65.0%, significantly better than the previous MSS1 (P=0.037) and MSS2 (P=0.032) models.

Conclusion

Our results indicate that the updated MSS3 outperforms previous iterations and relative to the Manchester population, is just as effective in identifying patients with BRCA1/2 mutations in a Southeast Asian population.
A two-layer model for the intrusion of two-phase debris flow into a river
Authors: Liu Wei , He Siming
Published: December 2017

The intrusion of debris flow into a river is a common phenomenon that usually occurs in mountainous areas. Debris flow, unlike a landslide, has a complex component that makes its simulation more difficult. In this paper, a two-layer, 2D model is presented for use in the preliminary study of debris flow intruding into a river. In this model, the upper layer is assumed to be a single-phase flow and the lower layer to be a solid–liquid two-phase flow. The drag force between the fluid and solid phases of the debris flow is considered in this model. The basal friction term of the debris flow is considered as the phase-averaged value of the solid shear stresses and fluid shear stresses. A numerical method based on the finite-volume method is proposed to solve the complex model equations involved. Several numerical tests were performed to confirm the feasibility of the proposed numerical method and model. The numerical results yielded a reasonable prediction of debris flow motion and tsunami wave generation and illustrate the complex interplay between the debris flow and tsunami waves. The characteristics of the river have extra effects on the distribution of subaqueous debris flow (e.g. flow velocity) and should not be neglected.
Role of histamine H1- and H2-receptors in myoelectric activity of small bowel in the dog
Authors: Konturek S. J. , Siebers R.
Published: December 2017

Studies were conducted in conscious dogs implanted with monopolar silver electrodes along the small intestine to determine whether the intestinal motility response to histamine is mediated by H1-receptors alone or whether H2-receptors are also involved in the response. Histamine infusion alone induced a marked increase in the appearance rate and the propagation velocity of the interdigestive myoelectric complexes (IMC). This effect was reproduced by the administration of the selective H1-receptor agonist, 2-methylhistamine, and abolished by the H1-receptor antagonist, tripelennamine. Tripelennamine alone decreased the frequency of occurrence of the IMC in fasted animals and reduced significantly the spike potential activity of the small bowel in fed dogs. Neither the H2-receptor agonist, dimaprit, nor the H2-receptor antagonist, metiamide, had any influence on the motility patterns in fasted or fed animals. We conclude that histamine influences the patterns of small bowel motility via stimulation of H1-receptors but its physiological role in modulating intestinal motility remains to be determined.
Nervous control of migratory myoelectric complex of the small bowel
Authors: Aeberhard P. F. , Magnenat L. D. , Zimmermann W. A.
Published: December 2017

The effects on the migratory myoelectric complex (MMC) of transplantation of small bowel loops were investigated in miniature swine with chronically implanted bipolar electrodes. Four experimental models (A--D) were studied. In groups A and B, jejunal loops were either interchanged in sequence or transplanted to the ileum with preservation of intact neurovascular pedicles. In groups C and D, bowel segments were totally isolated and replanted in situ (group C) or as modified Thiry-Vella loops (group D). Weekly records of fasting myoelectrical activity were then taken. Group A and B animals showed reintegration of the transplanted bowel segments into a normal MMC sequence after a remodeling period. The replanted bowel segments of groups C and D displayed MMCs throughout the study period. The in situ replanted segments of group C were reintegrated into the normal sequence after a delay of 3--4 wk. These results indicate that the organization of the MMC is not solely determined by the extrinsic nervous system.
Gastric glucagon release during gastric and intestinal phase of a meal in dogs
Authors: Schusdziarra V. , Rouiller D. , Unger R. H.
Published: December 2017

The intragastric instillation of a liver meal at pH 7 elicited a prompt and significant rise in gastric vein glucagon levels in anesthetized dogs. This was reduced by truncal vagotomy and by atropine. The liver meal at pH 2 elicited significantly smaller rise in gastric vein glucagon levels that was not reduced by truncal vagotomy, but was abolished by atropine. Infusion of gastrin-17 (0.1 micrograms . kg-1 . h-1) failed to increase gastric vein glucagon levels above the control group. Gastric glucagon release was significantly increased by intestinal instillation of the liver meal at pH 7. This was reduced by truncal vagotomy and atropine infusion. Gastric inhibitory peptide (GIP) (1 microgram . kg-1 . h-1), but neither CCK-octapeptide (0.5 microgram . kg-1 . h-1) nor secretin (1 CU . kg-1 . h-1), elicited a significant rise in gastric vein glucagon levels. It is concluded that 1) gastric glucagon release is stimulated during the gastric and intestinal phase of a meal, 2) gastric glucagon release is stimulated by GIP, and 3) gastric glucagon release is modified by vagal and muscarinic cholinergic mechanisms, suggesting a neuroendocrine influence on its release.
Diurnal pH changes in duodenum of conscious dogs
Authors: Itoh Z. , Honda R. , Aizawa I.
Published: December 2017

Continuous measurements of intraduodenal pH changes were made in five healthy conscious dogs by means of a miniature pH electrode inserted into the duodenum through a chronically implanted duodenal cannula. Gastric motor activity was also recorded simultaneously by means of a chronically implanted force transducer. When dogs were fed once a day with a measured volume of dog food, it was found that 24-h pH changes in the duodenal contents could be divided into three major periods: the weak acid period, the strong acid period, and alkaline period. The weak acid period lasted for 9.2 +/- 0.43 h after feeding with the duodenal pH ranging from 7.0 to 4.0. The weak acid period was gradually changed to the strong acid period in which the duodenal pH fluctuated widely from 8.0 to 1.0. This period lasted for 5.2 +/- 0.26 h. After the strong acid period, pH of the duodenum abruptly turned alkaline and remained between 7.0 and 8.3 until the next meal. These three periods of pH change are closely related to those of three different gastric motor patterns; the digestive, intermediate, and interdigestive patterns, respectively.
Demonstration of a pancreatic proelastase 2-alpha 1-protease inhibitor complex in normal human plasma
Authors: Largman C. , Brodrick J. W. , Geokas M. C. , Johnson J. H. , Fassett M.
Published: December 2017

A peak of immunoreactive pancreatic elastase 2 with a molecular weight consistent with that of a complex of elastase 2 and alpha 1-protease inhibitor (also referred to as alpha 1-antitrypsin) can be detected by radioimmunoassay in normal human serum or plasma (Geokas et al., J. Biol. Chem. 252:61-67, 1977). This material has been purified by gel filtration on Sephadex G-200 and by ion-exchange chromatography on DEAE-cellulose. The alpha 1-protease inhibitor-bound immunoreactive elastase 2 has been dissociated by incubation with hydroxylamine, and the resulting immunoreactive product isolated by gel filtration on Sephadex G-100. The dissociated immunoreactive elastase 2 was shown by affinity chromatography on turkey egg white inhibitor-bound agarose, before and after activation by bovine trypsin, to consist only of proelastase 2. A second peak of immunoreactive material associated with the high molecular weight fraction of plasma has been shown to result from a specific interaction of the 125I-labeled phenylmethanesulfonyl-elastase 2 employed as tracer in the radioimmunoassay with alpha 2-macroglobulin, resulting in apparent immunoreactivity. These results demonstrate that all of the detectable immunoreactive pancreatic elastase 2 in normal human plasma is proelastase 2 bound to alpha 1-protease inhibitor.
Role of the interstitial matrix during intestinal volume absorption
Authors: Granger D. N. , Mortillaro N. A. , Kvietys P. R. , Rutili G. , Parker J. C. , Taylor A. E.
Published: December 2017

The effects of net volume absorption rate (Jv,m) on intestinal interstitial fluid volume (VI), lymph flow (JL), and the excluded volume fraction for interstitial albumin (FE) were analyzed in an autoperfused cat ileum preparation. Tissue blood volume, extracellular space, and extracellular albumin (VA) were estimated using 51Cr-labeled red blood cells, 99mTc-labeled diethylenetriamine pentaacetic acid (DTPA), and 125I-labeled human serum albumin, respectively. Nonabsorptive values of 27.8 ml/100 g, 18.2 ml/100 g, and 0.37 were acquired for VI, VA, and FE, respectively. Net volume absorption results in an increase in intestinal interstitial volume and lymph flow and decreases the degree of albumin exclusion in the interstitial matrix. The magnitude of the changes in interstitial volume, lymph flow, and excluded volume of albumin during net volume absorption are related to the rate of absorption. The increased matrix hydration during absorption serves to enchance vascular and lymphatic removal of absorbed volume.