bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental study on punching shear behavior of hollow floor slab-column reinforced connection
Authors: Pang Rui , Dang Longji , Ni Hongmei , Liang Shuting , Li Qianqian
Published: December 2018

This article presents an experimental study on hollow floor slab-column-reinforced connections, which are enhanced by installing locally solid zone of slab around the column and hidden beam in the floor. To investigate the punching-shear behavior of hollow floor slab-column-reinforced connections, six hollow floor slab-column-reinforced connections under vertical load were conducted on three types of connections with different thickness, namely, two hollow floor slab-column-reinforced connections without punching component, two hollow floor slab-column-reinforced connections with bent-up steel bars, and two hollow floor slab-column-reinforced connections with welding section steel cross bridging. Meanwhile, the strength, stiffness, failure mode, and ductility of hollow floor slab-column-reinforced connections with punching components were obtained and compared with the hollow floor slab-column-reinforced connections without punching component. The results showed that hollow floor slab-column-reinforced connections had the double failure characteristics including punching shear and flexural failure, and flexural failure was the main failure mode as a result of installing hidden beam. The hollow floor slab-column-reinforced connections with punching components exhibited higher initial stiffness and higher loading capacity than hollow floor slab-column-reinforced connections without punching components, but welding section steel cross bridging have a better on improving the connections’ punching-shear capacity than bent-up steel bars.
Mediators of burden and depression in dementia family caregivers: Kinship differences
Authors: McAuliffe Linda , Ong Ben , Kinsella Glynda
Published: December 2018

Objectives

To investigate kinship differences in the caregiver stress process by developing multiple mediation models for two distinct caregiver subgroups (spouses and adult children of older adults living with dementia). The effect of four potential mediating variables (mastery, self-efficacy, satisfaction with social support, positive caregiving appraisals) on the relationship between perceived burden and depression was evaluated.

Method

Family caregivers of a person living with dementia were recruited through national dementia and carer organisations. Participants completed a paper-based or electronic version of the study survey. A bias-corrected, accelerated bootstrapping method was used to test the effect of the four proposed mediating variables on the relationship between perceived burden and depression in each caregiver subgroup (spouses and adult children).

Results

Perceived burden was directly and significantly related to depression for both spouse caregivers and adult child caregivers. The mediation models explained approximately 50% of the variance in the burden-to-depression pathway for both caregiver subgroups. Mastery and social support (but not self-efficacy, nor positive caregiving appraisals) were found to individually significantly influence the impact of perceived burden on depression in spouse caregivers. All four proposed mediators failed to reach statistical significance as individual mediators of the burden-to-depression pathway in adult child caregivers.

Conclusion

These findings demonstrate differences in the dementia caregiver experience according to kinship, and that certain mediating variables are more relevant for some subgroups of caregivers than others. Implications for the design of psychosocial interventions are discussed.
Theoretical investigation of alteration and radiation of large-scale structures due to jet impingement
Authors: Miller SAE , Carr Alexander N
Published: December 2018

Jet flows impinge on launch pad structures and aircraft carrier deck blast deflectors. Turbulent structures are deformed and acoustic radiation is reflected by the deflector. The coupling of reflected acoustic waves with the instability waves of the jet turbulence increases their amplitude and causes a feedback loop. Resultant far-field acoustic radiation is amplified. This amplification results in additional tones with significant spectral broadening occurring at frequencies corresponding to the constructive interference. We present a simple prediction methodology in the form of an acoustic analogy. The analogy accounts for reflected acoustic waves through a tailored Green’s function and models the large-scale structures as spatially and temporarily growing and decaying instability waves. The predictions are compared with two experimental datasets. Predictions compare favorably with measured frequencies and spectral broadening in the far-field.
Changing the heart and soul? Inequalities in Finland’s current pursuit of a narrow education policy
Authors: Tervasmäki Tuomas , Okkolin Mari-Anne , Kauppinen Ilkka
Published: December 2018

The Finnish educational system is well known for its excellent learning results, highly trained teachers and egalitarian values. However, when the political leanings of the government change, its policies are usually altered as well. In this policy report we give an account of the recent changes and current trends in Finnish education policy. We analyse the characteristics of the Sipilä Government’s current education policy since 2015 and compare it to the Nordic welfare-state ideals of universalism, equality and social justice which have traditionally been the key building blocks of the Finnish education system. The Government’s policy appears to be narrow-minded and ignorant of issues related to educational equality, stressing instead the importance of a flexible workforce and national competitiveness. We will reflect on the characteristics of Finnish education policy in light of the debate regarding academic capitalism and as part of an overarching trend of social inequality in Europe.
Toward a Critical Race Nepantlera Methodology: Embracing Liminality in Anti-Colonial Research
Authors: Acevedo-Gil Nancy
Published: December 2018

Given the inequitable opportunities and marginalizing experiences for undocumented Students of Color, this manuscript builds on the work of previous Scholars of Color to challenge the traditional roles of researchers during the data collection process. Guided by critical race theory, nepantleras, and Chicana feminist epistemology, the article proposes a critical race nepantlera methodology (CRNM). CRNM entails a reflexive and reciprocal approach that guides the research process and is rooted in anti-colonial social justice actions. Two exemplars from previous studies elaborate on CRNM and the relevance to critically conscious researchers, particularly when conducting studies with undocumented Students of Color.
Fatal Complications of New-Onset Complicated Type B Aortic Dissection After Endovascular Abdominal Aortic Aneurysm Repair: Report of 2 Cases and Literature Review
Authors: Nomura Yoshikatsu , Nagao Kanetsugu , Hasegawa Shota , Kawashima Motoharu , Tsujimoto Takanori , Izumi So , Matsumori Masamichi , Murakami Hirohisa , Honda Tasuku , Mukohara Nobuhiko
Published: December 2018

New-onset antegrade Stanford type B aortic dissection (TBAD) after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) is rare. The extension of aortic dissection leads to various symptoms and affects the stent graft. Moreover, various symptoms may arise owing to a stent graft being present. We describe 2 cases of complicated acute TBAD occurring after EVAR, which were ultimately fatal. The case in which rupture occurred could not be treated and the patient died. In another case with bilateral lower extremity malperfusion caused by collapse and occlusion of the endograft, extra-anatomical bypass was performed. Although the collapsed endograft gradually re-expanded, the patient ultimately died because of multiorgan failure. We have reviewed the literature and analyzed the treatment of complicated TBAD after EVAR.
Improving Latino Health Equity Through Spanish Language Interpreter Advocacy in Kansas
Authors: Showstack Rachel E. , Guzman Kelly , Chesser Amy K. , Woods Nikki Keene
Published: December 2018

Introduction:

Federal law requires any agency receiving federal aid to take “reasonable steps” to provide meaningful access to qualified limited English proficient (LEP) individuals. However, policies for the provision of language access services, including medical interpretation, vary substantially by state. The Latino population and the number of LEP individuals in the U.S. state of Kansas have grown substantially over the past 20 years, necessitating increased attention to the state’s language access policies.

Method:

Though a review of previous research, we present health disparities affecting Latinos in Kansas, examine the state’s language access policies for health care, and argue that health disparities could be reduced through improved language access.

Findings:

While Kansas reimburses health care entities for interpreter services associated with Medicaid, the state has no health care interpreter competency requirements. As a result, LEP persons, primarily Spanish speakers, may be left to navigate through complex hospital systems with inadequate guidance in their language and may be at an increased risk for medical errors due to language barriers.

Conclusion:

We suggest changes that could be implemented to improve access and reduce health disparities affecting Latinos in Kansas and across the United States, and we describe work that is currently underway to support these changes.
Comprehensive model of upper human body clothing ventilation in standing and walking conditions
Authors: Ismail Nagham , Ghaddar Nesreen , Ghali Kamel
Published: December 2018

The ventilation of the microclimate air of the clothed human body segment is a result of (1) the air flow from the environment through the clothing open apertures, (2) the penetration of the porous clothing, or (3) air flow originating in the microclimate of the other clothed body parts. The microclimate air flow at the connections of clothed segments is named the inter-segmental ventilation and constitutes a real physical boundary condition that leads to ventilation of connected segments. In this study, a simplified electric circuit model is developed to estimate clothing ventilation based on the analogy between the air flow in the microclimate air layer and an electric circuit composed of resistance and inductance elements. The model takes into account the inter-connection between the segments for the clothed human upper part driven by difference of pressure in the microclimate air of the trunk and the upper arms. The developed model is validated using the tracer gas method applied on a walking manikin placed in a climatic chamber under windy conditions. Good agreement was found between predicted segmental ventilation and the experimental values with a maximum error of 16%. It was found that the inter-segmental ventilation is significant at high relative velocity for permeable clothing and increased with the increase in the relative velocity constituting about 30% of the arm ventilation and 14% of the trunk ventilation.
Stretch properties of elastic knitted fabric with pillar stitch
Authors: Kyzymchuk Olena , Melnyk Liudmyla
Published: December 2018

Knitted fabrics and products are subjected to a variety of stresses and loads/deformation during their usage. The loads are different by value, by direction, and by duration. The alternations of loading and unloading or resting processes affect the knitted structure and could bring about changes in the linear dimensions of the fabric or result in the deformation of the knitted items and ultimately the loss of product appearance or its functional properties. A wide range of textile materials resistant to multiply loads was produced by using elastomeric yarn that has an elongation of more than 95% and is able to attain full recovery after relaxation due to its chemical composition. This case study examines two existing test methods for evaluating the stretch properties of textile materials produced with the elastomeric yarns with emphasis on warp knitted abdominal binder-type fabrics. It was found that the linear density of the weft in-laying threads and the preliminary tension of the ground yarn which formed pillar stitch affect stretch properties of elastic warp knitted fabric: the full deformation and its constituent parts. The change in the preliminary elongation of the bare spandex in the 210%–270% range does not have a significant effect.
Laser holography measurement and theoretical analysis of a pressure-swirl nozzle spray
Authors: Xiao Yinli , Wang Changwu , Cao Zhibo , Song Wenyan
Published: December 2018

The characteristic of the spray within combustion chamber is one of the determining factors that affect the performance and exhaust gas emissions of an aero-engine. Recently, the holography technique has been successfully applied to spray atomization measurement due to its significant advances. In this article, an atmospheric test rig of pressure-swirl nozzle is built. The kerosene spray generated at the atmospheric condition and in an aero-engine combustor is measured. The Sauter mean diameter of the spray droplets is obtained. In addition, the theoretical analysis of film formation and sheet breakup processes are conducted. Comparison of theoretical analysis and experimental results on the spray atomization of a pressure-swirl nozzle is presented.
Research on the position–pressure cooperative control strategy for full-hydraulic leveler
Authors: He Dongping , Wang Tao , Wang Jun , Ren Zhongkai , Gao Xiangyu
Published: December 2018

The characteristics of electro-hydraulic servo system of full-hydraulic leveler are high speed, large inertia, high frequency response, and multi-degree of freedom. In order to improve the degree of automation of full-hydraulic leveler and achieve the simultaneous control between position and pressure, the position–pressure cooperative control strategy is presented in the article. In the working process, the dynamic working pressure signal of the hydraulic cylinder is turned into a real-time position signal by the pressure–position conversion gain and then compensates the converted signal into the position closed loop. Meanwhile, the pressure signal of the rear cavity of the hydraulic cylinder is fed back to the input of the proportional relief valve at the pump source, and then the system work pressure changes quickly according to the different thickness. In this article, the mathematical model of position–pressure cooperative control of hydraulic straightening machine is established. The simulation results in AMESim software verify the correctness of the control strategy. Finally, the feasibility and practicability of the control strategy are verified by the field prototype of 11-roller full-hydraulic leveler. The control strategy provides the theoretical basis for designing the electro-hydraulic servo system.
Colour associations in children and adults
Authors: Kramer Robin SS , Prior Joanne Y
Published: December 2018

A growing body of research has investigated how we associate colours and social traits. Specifically, studies have explored the links between red and perceptions of qualities like attractiveness and anger. Although less is known about other colours, the prevailing framework suggests that the specific context plays a significant role in determining how a particular colour might affect our perceptions of a person or item. Importantly, this factor has yet to be considered for children’s colour associations, where researchers focused on links between colours and emotions, rather than social traits. Here, we consider whether context-specific colour associations are demonstrated by 5- to 10-year-old children and compare these associations with adult data collected on the same task. We asked participants to rank order sets of six identical images (e.g., a boy completing a test), which varied only in the colour of a single item (his T-shirt). Each question was tailored to the image set to address a specific context, for example, “Which boy do you think looks the most likely to cheat on a test?” Our findings revealed several colour associations shared by children, and many of these were also present in adults, although some had strengthened or weakened by this stage of life. Taken together, our results demonstrate the presence of both stable and changing context-specific colour associations during development, revealing a new area of study for further exploration.
What Makes a Leadership Preparation Program Exemplary?
Authors: Cosner Shelby
Published: December 2018

What makes a leadership preparation program exemplary? All three exemplary programs featured in this special issue evidence strong learning orientations and more sustained improvement work in their pursuit of exemplary preparation. I therefore examine exemplary preparation from a process perspective that emphasizes continuous improvement. To help readers make more meaning of the exemplary preparation programs featured in this special issue as well as to advance the field’s understanding of and ability to support and pursue truly exemplary forms of leadership preparation, I examine key improvement technologies, external resources, and internal capacities of importance to continuous program improvement work.
Impossible Movement Illusions
Authors: Wiseman Richard , Houstoun Will
Published: December 2018

Past research has used the phi phenomenon to create the illusion of one object moving through another. This article presents three optical illusions that are conceptually similar, yet little known within academic psychology. Two of the illusions have been developed within the magic community and involve the performer appearing to make a finger jump from one hand to another and a cup penetrate through another cup. The article explores the factors underpinning these illusions and describes how these factors were used to enhance a similar illusion developed outside of magic (the penetration of one hand through another).
Computer-assisted navigation in Birmingham hip resurfacing: A case report
Authors: Shah Ritesh , Benson Jessica R , Muir Jeffrey M
Published: December 2018

Component malpositioning during Birmingham hip resurfacing increases the risk for component wear, metallosis, component loosening, and the likelihood of dislocation and revision surgery. Computer-assisted navigation can increase the accuracy to which components are placed, and the utilization of this technology in Birmingham hip resurfacing is increasing. The present report summarizes the accuracy of acetabular component positioning in a Birmingham hip resurfacing case utilizing navigation. Intraoperative C-arm fluoroscopy following the use of the navigation tool confirmed excellent seating, positioning, and stability of the acetabular component. In addition, post-operative antero-posterior radiographs confirmed device accuracy and revealed a stable joint with no evidence of acetabular loosening or femoral fracture. Computer-assisted navigation may therefore be an effective tool to improve the accuracy of component positioning during Birmingham hip resurfacing.
Weight and social comparison: Does the weight of a stranger affect a person’s perception of their own weight?
Authors: Christensen Vibeke Tornhøj , Jæger Mads Meier
Published: December 2018

Research suggests that social context affects individuals’ perception of their own weight. Using face-to-face interviews as the social context, we analyze the effect of interviewers’ (N = 90) body mass index on respondents’ (N = 3068) self-perceived weight level. Respondents reported a higher weight level when the interviewer had a higher body mass index (absolute social comparison). Female respondents reported a lower weight level if interviewers had a higher body mass index than they did (relative social comparison). Results suggest that weight perception reflects both absolute and relative social comparison, especially among women. Future research should consider causation and self-selection when studying social context and body image.
Time course of chemotaxis and chemokinesis of neutrophils following stimulation with IL-8 or FMLP
Authors: Hattenkofer Matthias , Gruber Michael , Metz Sophia , Pfaehler Sophie-Marie , Lehle Karla , Trabold Benedikt
Published: December 2018

Polymorphonuclear cells (PMNs) attend to inflammatory sites by chemotactic movement, caused by chemoattractants (CAs) like n-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP) and interleukin-8 (IL-8). However, distinct but applicable assays for investigations of PMNs’ migration limit in vitro examination. We integrated CD15-bead-based isolation of PMNs with analysing their chemotaxis in a novel 3D-µ-Slide migration chamber. The PMNs were exposed to different concentrations of FMLP and IL-8 (1, 10 and 100 nM) and observed for 180 min in cell-physiological environment conditions. Moving PMNs’ percentage (median and interquartile range) decreased from 62% (27%) to 36% (31%) without CA, from 88% (30%) to 22% (26%) for 1 nM IL-8, from 70% (22%) to 28% (13%) for 100 nM IL-8, from 30% (23%) to 18% (46%) for 1 nM FMLP and from 76% (20%) to 28% (13%) for 100 nM FMLP. Centres of cell movement turned towards the CAs (negative values) within a single 30-min observation period: 5.37 µm (16.82 µm) without CA, −181.37 µm (132.18 µm) with 10 nM and −239.34 µm (152.19 µm) with 100 nM IL-8; −116.2 µm (69.07 µm) with 10 nM and −71.59 µm (98.58 µm) with 100 nM FMLP. FMLP and IL-8 ensure chemotaxis without increase of chemokinesis. 3D-µ-Slide chemotaxis chambers facilitate time course analyses of PMNs’ migration in stable conditions over a long time with concise distinction of chemotaxis and chemokinesis.
Developing College EFL Writers’ Critical Thinking Skills Through Online Resources: A Case Study
Authors: Zhang Xiaodong
Published: December 2018

This study reports on how the supplementation of online resources, informed by systemic functional linguistics (SFL), impacted English-as-a-foreign-language (EFL) student writers’ development of critical thinking skills. Through qualitative analyses of student-teacher interactions, interviews with students, and students’ written documents, the case study shows that through 1 semester of intensive exposure to SFL-based online resources in a college Chinese EFL writing classroom, EFL writers were able to develop critical thinking skills in regard to the construction of effective academic writing, although it was a process of encountering and overcoming challenges. Through teacher mediation and their own efforts, they could adjust to the online resources-based classroom, exemplified by their utilization of SFL-related categories offered through online resources to analyze and evaluate the interrelationship between language features and the content manifested in valued texts, and regulate the content of their own academic writing.
No Laughing Matter: Workplace Bullying, Humor Orientation, and Leadership Styles
Authors: Mills Carol Bishop , Keller Marieke , Chilcutt Alexa , Nelson Mark D.
Published: December 2018

Workplace bullying is associated with a host of negative outcomes for the worker who is the target of bullying, as well as for the organization where the bullying occurs. Moreover, we know that rates of bullying are particularly high in health care settings; however, we are less familiar with the factors that may reduce workplace bullying in hospitals. Thus, this study was conducted to determine whether the humor orientation styles of individuals, including nurses working in hospitals, as well as their managers’ leadership styles, can influence perceptions of bullying in the workplace. Using data from 459 workers employed in a large hospital in the Southern United States, we examined associations between the Multidimensional Sense of Humor Scale, which has four dimensions, as well as the Multifactor Leadership Questionnaire, with three leadership substyles, and their associations with the risk of being bullied. We observed that one of the four humor subscales, Humor Appreciation, did affect perceptions of bullying in the workplace. The other three, Humor Recognition, Humor Production, and Humor for Coping, did not. However, the leadership styles of managers did affect reports of negative acts. In fact, transformational leadership was associated with 22% of the variance in reports of decreased bullying activity. This work is consistent with previous work on the importance of leadership styles for creating positive work environments, particularly in hospital settings. Given these findings, we offer suggestions for leaders to further improve nursing communication.
Graft-Tunnel Mismatch in Endoscopic ACL Reconstruction: Reliability of Measuring Tunnel Lengths and Intra-articular Distance
Authors: Dwyer Tim , Bristow Lucas , Bayley Nicholas , Sheth Ujash , Abouali Jihad , Murnaghan M. Lucas , Wasserstein David , Ogilvie-Harris Darrell , Fine Ben , Theodoropoulos John , Chahal Jaskarndip
Published: December 2018

Background:

A continued technical challenge for surgeons performing bone–patellar tendon–bone anterior cruciate ligament (ACL) reconstruction with endoscopic techniques is graft-tunnel mismatch. If tibial tunnel and intra-articular distances could be reliably estimated, surgeons could adjust the length of the femoral tunnel to minimize graft-tunnel mismatch.

Purpose/Hypothesis:

To determine whether arthroscopic measurement of the following was reliable: femoral tunnel distance (FTD), tibial tunnel distance (TTD), intra-articular distance (IAD), and total distance (TD; sum of these 3 measurements). It was hypothesized that intraoperative measurement of these distances would be reliable.

Study Design:

Controlled laboratory study.

Methods:

Eight sports fellowship–trained orthopedic surgeons independently performed arthroscopic measurements of the FTD, TTD, IAD, and TD in 7 cadaveric knees in which femoral and tibial tunnels had been drilled. Each surgeon performed the measurements twice using an EndoButton depth gauge. Following this, each parameter was measured open with a medial parapatellar approach. Finally, a computed tomography (CT) scan of each knee was performed, with the FTD, TTD, and IAD measured by a musculoskeletal radiologist. Inter- and intrarater reliability of the arthroscopic measurements was calculated, as well as the correlation between arthroscopic measurements and open and CT measurements.

Results:

Interrater reliability for the arthroscopic measurements was 0.8 for FTD, 0.89 for TTD, 0.61 for IAD, and 0.76 (range, 0.54-0.93) for TD. Intrarater reliability was 0.94 for FTD, 0.97 for TTD, 0.83 for IAD, and 0.93 for TD. The correlation between arthroscopic and open measurements was 0.9 for FTD, 0.94 for TTD, 0.4 for IAD, and 0.84 for TD. The correlation between arthroscopic and CT measurements was 0.85 for FTD, 0.92 for TTD, and 0.71 for IAD.

Conclusion:

The results of this study show that arthroscopic measurement of FTD and TTD has a high degree of intra- and interrater reliability, while that of IAD and TD demonstrates high intrarater reliability but moderate interrater reliability.

Clinical Relevance:

Reliable measurement of the TTD and IAD can potentially allow adjustment of the FTD, minimizing graft-tunnel mismatch in endoscopic ACL reconstruction.
Cognitive consequences of regression of cerebral small vessel disease
Authors: van Leijsen Esther MC , Bergkamp Mayra I , van Uden Ingeborg WM , Cooijmans Sjacky , Ghafoorian Mohsen , van der Holst Helena M , Norris David G , Kessels Roy PC , Platel Bram , Tuladhar Anil M , de Leeuw Frank-Erik
Published: December 2018

Introduction

Recent studies have shown that neuroimaging markers of cerebral small vessel disease can also regress over time. We investigated the cognitive consequences of regression of small vessel disease markers.

Patients and methods

Two hundred and seventy-six participants of the RUNDMC study underwent neuroimaging and cognitive assessments at three time-points over 8.7 years. We semi-automatically assessed white matter hyperintensities volumes and manually rated lacunes and microbleeds. We analysed differences in cognitive decline and accompanying brain atrophy between participants with regression, progression and stable small vessel disease by analysis of variance.

Results

Fifty-six participants (20.3%) showed regression of small vessel disease markers: 31 (11.2%) white matter hyperintensities regression, 10 (3.6%) vanishing lacunes and 27 (9.8%) vanishing microbleeds. Participants with regression showed a decline in overall cognition, memory, psychomotor speed and executive function similar to stable small vessel disease. Participants with small vessel disease progression showed more cognitive decline compared with stable small vessel disease (p < 0.001 for cognitive index and memory; p < 0.01 for executive function), although significance disappeared after adjusting for age and sex. Loss of total brain, gray matter and white matter volume did not differ between participants with small vessel disease regression and stable small vessel disease, while participants with small vessel disease progression showed more volume loss of total brain and gray matter compared to those with stable small vessel disease (p < 0.05), although significance disappeared after adjustments.

Discussion

Regression of small vessel disease markers was associated with similar cognitive decline compared to stable small vessel disease and did not accompany brain atrophy, suggesting that small vessel disease regression follows a relatively benign clinical course. Future studies are required to validate these findings and to assess the role of vascular risk factor control on small vessel disease regression and possible recovery of clinical symptoms.

Conclusion

Our findings of comparable cognitive decline between participants with regression and stable small vessel disease might suggest that small vessel disease regression has a relative benign cognitive outcome.
The Rod-Shaped ATG2A-WIPI4 Complex Tethers Membranes In Vitro
Authors: Otomo Takanori , Chowdhury Saikat , Lander Gabriel C.
Published: December 2018

The autophagosome precursor membrane, termed the isolation membrane or phagophore, emerges adjacent to a phosphatidylinositol 3-phosphate (PI3P)-enriched transient subdomain of the endoplasmic reticulum called the omegasome, thereafter expanding to engulf cytoplasmic content. Uncovering the molecular events that occur in the vicinity of the omegasome during phagophore biogenesis is imperative for understanding the mechanisms involved in this critical step of the autophagy pathway. We recently characterized the ATG2A-WIPI4 complex, one of the factors that localize to the omegasome and play a critical role in mediating phagophore expansion. Our structural and biochemical studies revealed that ATG2A is a rod-shaped protein with membrane-interacting properties at each end, endowing ATG2A with membrane-tethering capability. Association of the PI3P-binding protein WIPI4 at one of the ATG2A tips enables the ATG2A-WIPI4 complex to specifically tether PI3P-containing membranes to non-PI3P-containing membranes. We proposed models for the ATG2A-WIPI4 complex-mediated membrane associations between the omegasome and surrounding membranes, including the phagophore edge, the endoplasmic reticulum, ATG9 vesicles, and COPII vesicles.
Evaluating the reliability of a tool to measure the quality of gastrointestinal multidisciplinary cancer conferences: A generalizability study
Authors: Fahim C , Ratcliffe J , McConnell M , Sonnadara R , Simunovic M
Published: December 2018

Background

Lamb et al. developed the metric for the observation of decision-making tool (MTB-MODe) to evaluate the quality of urologic multidisciplinary cancer conferences (MCCs) in the United Kingdom. We used generalizability theory to assess the reliability of a modified version of MTB-MODe in a North American context. Specifically, we wished to determine if the tool could distinguish between high- and low-quality MCC decision-making.

Methods

Two assessors independently evaluated two MCCs (MCC1, MCC2) using the modified MTB-MODe. Generalizability theory was used to assess overall tool reliability and to identify sources most likely to contribute to variance in reliability scores. A total of 60 cases were evaluated.

Results

The overall reliability scores of MCC1 and MCC2 were 0.72 and 0.74, respectively. Inter-rater reliability scores were reasonable (>0.55) and raters did not contribute significantly to variance in reliability scores. Internal consistency of the individual MTB-MODe items was low, demonstrating that items were not highly correlated.

Conclusions

The MTB-MODe reliably assessed the quality of individual MCC cases. Raters did not contribute significantly to reliability scores, suggesting that the tool can be successfully implemented using a single rater. Low internal consistency of the MTB-MODe items demonstrates that the tool can be used to provide feedback on individual tool items. Such data can be used by stakeholders to help improve MCC quality.
Genetic susceptibility to radiation-induced breast cancer after Hodgkin lymphoma
Authors: Opstal-van Winden Annemieke W. J. , de Haan Hugoline G. , Hauptmann Michael , Schmidt Marjanka K. , Broeks Annegien , Russell Nicola S. , Janus Cécile P. M. , Krol Augustinus D. G. , van der Baan Frederieke H. , De Bruin Marie L. , van Eggermond Anna M. , Dennis Joe , Anton-Culver Hoda , Haiman Christopher A. , Sawyer Elinor J. , Cox Angela , Devilee Peter , Hooning Maartje J. , Peto Julian , Couch Fergus J. , Pharoah Paul , Orr Nick , Easton Douglas F. , Aleman Berthe M. P. , Strong Louise C. , Bhatia Smita , Cooke Rosie , Robison Leslie L. , Swerdlow Anthony J. , van Leeuwen Flora E.
Published: December 2018

Female Hodgkin lymphoma (HL) patients treated with chest radiotherapy (RT) have a very high risk of breast cancer. The contribution of genetic factors to this risk is unclear. We therefore examined 211 155 germline single-nucleotide polymorphisms (SNPs) for gene-radiation interaction on breast cancer risk in a case-only analysis including 327 breast cancer patients after chest RT for HL and 4671 first primary breast cancer patients. Nine SNPs showed statistically significant interaction with RT on breast cancer risk (false discovery rate, <20%), of which 1 SNP in the PVT1 oncogene attained the Bonferroni threshold for statistical significance. A polygenic risk score (PRS) composed of these SNPs (RT-interaction-PRS) and a previously published breast cancer PRS (BC-PRS) derived in the general population were evaluated in a case-control analysis comprising the 327 chest-irradiated HL patients with breast cancer and 491 chest-irradiated HL patients without breast cancer. Patients in the highest tertile of the RT-interaction-PRS had a 1.6-fold higher breast cancer risk than those in the lowest tertile. Remarkably, we observed a fourfold increased RT-induced breast cancer risk in the highest compared with the lowest decile of the BC-PRS. On a continuous scale, breast cancer risk increased 1.4-fold per standard deviation of the BC-PRS, similar to the effect size found in the general population. This study demonstrates that genetic factors influence breast cancer risk after chest RT for HL. Given the high absolute breast cancer risk in radiation-exposed women, these results can have important implications for the management of current HL survivors and future patients.
Mechanisms of immune escape after allogeneic hematopoietic cell transplantation
Authors: Zeiser Robert , Vago Luca
Published: December 2018

Relapse of the original disease is a major cause of death after allogeneic hematopoietic cell transplantation for acute leukemias. There is growing evidence that relapses may be explained not only by resistance to chemotherapy but also by the escape of tumor cells from the control of the allogeneic immune response. Mechanisms of immune evasion can involve abrogation of leukemia cell recognition due to loss of HLA genes, immunosuppression by immune-checkpoint ligand expression, production of anti-inflammatory factors, release of metabolically active enzymes, loss of proinflammatory cytokine production, and acquisition of novel driver mutations that promote leukemia outgrowth. These mechanisms, and therapeutic targeting of immune escape, will be discussed. We divide the evidence in support of immune-escape mechanisms into animal studies, human laboratory studies, and human clinical experience. A better understanding of the molecular pathways connected to immune escape and relapse may help to improve our therapeutic armamentarium against acute myeloid leukemia relapse.
A locus on chromosome 5 shows African ancestry–limited association with alloimmunization in sickle cell disease
Authors: Williams Lesedi M. , Qi Zhihua , Batai Ken , Hooker Stanley , Hall Nancy J. , Machado Roberto F. , Chen Alice , Campbell-Lee Sally , Guan Yongtao , Kittles Rick , Hanchard Neil A.
Published: December 2018

Red blood cell (RBC) transfusion remains a critical therapeutic intervention in sickle cell disease (SCD); however, the apparent propensity of some patients to regularly develop RBC alloantibodies after transfusion presents a significant challenge to finding compatible blood for so-called alloimmunization responders. Predisposing genetic loci have long been thought to contribute to the responder phenomenon, but to date, no definitive loci have been identified. We undertook a genome-wide association study of alloimmunization responder status in 267 SCD multiple transfusion recipients, using genetic estimates of ancestral admixture to bolster our findings. Analyses revealed single nucleotide polymorphisms (SNPs) on chromosomes 2 and 5 approaching genome-wide significance (minimum P = 2.0 × 10−8 and 8.4 × 10−8, respectively), with local ancestry analysis demonstrating similar levels of admixture in responders and nonresponders at implicated loci. Association at chromosome 5 was nominally replicated in an independent cohort of 130 SCD transfusion recipients, with meta-analysis surpassing genome-wide significance (rs75853687, Pmeta = 6.6 × 10−9), and this extended to individuals forming multiple (>3) alloantibodies (Pmeta = 9.4 × 10−5). The associated variant is rare outside of African populations, and orthogonal genome-wide haplotype analyses, contingent on local ancestry, revealed genome-wide significant sharing of a ∼60-kb haplotype of African ancestry at the chromosome 5 locus (Bayes Factor = 4.95). This locus overlaps a putative cis-acting enhancer predicted to regulate transcription of ADRA1B and the lncRNA LINC01847, both members of larger ontologies associated with immune regulation. Our findings provide potential insights to the pathophysiology underlying the development of alloantibodies and implicate non-RBC ancestry-limited loci in the susceptibility to alloimmunization.
Systematic and combined endosonographic staging of lung cancer (SCORE study)
Authors: Crombag Laurence M.M. , Dooms Christophe , Stigt Jos A. , Tournoy Kurt G. , Schuurbiers Olga C.J. , Ninaber Maarten K. , Buikhuisen Wieneke A. , Hashemi Sayed M.S. , Bonta Peter I. , Korevaar Daniël A. , Annema Jouke T.
Published: December 2018

Guidelines recommend endosonography for mediastinal nodal staging in patients with resectable nonsmall cell lung cancer (NSCLC). We hypothesise that a systematic endobronchial ultrasound (EBUS) evaluation combined with an oesophageal investigation using the same EBUS bronchoscope (EUS-B) improves mediastinal nodal stagingversusthe current practice of targeted positron emission tomography (PET)-computed tomography (CT)-guided EBUS staging alone.

A prospective, multicentre, international study (NCT02014324) was conducted in consecutive patients with (suspected) resectable NSCLC. After PET-CT, patients underwent systematic EBUS and EUS-B. Node(s) suspicious on CT, PET, EBUS and/or EUS-B imaging and station 4R, 4L and 7 (short axis ≥8 mm) were sampled. For patients without N2/N3 disease determined on endosonography, surgical-pathological staging was the reference standard.

229 patients were included in this study. The prevalence of N2/N3 disease was 103 out of 229 patients (45%). A PET-CT-guided targeted approach by EBUS identified 75 patients with N2/N3 disease (sensitivity 73%, 95% CI 63–81%; negative predictive value (NPV) 81%, 95% CI 74–87%). Four additional patients with N2/N3 disease were found by systematic EBUS (sensitivity 77%, 95% CI 67–84%; NPV 84%, 95% CI 76–89%) and five more by EUS-B (84 patients total; sensitivity 82%, 95% CI 72–88%; NPV 87%, 95% CI 80–91%). Additional clinical relevant staging information was obtained in 23 out of 229 patients (10%).

Systematic EBUS followed by EUS-B increased sensitivity for the detection of N2/N3 disease by 9% compared to PET-CT-targeted EBUS alone.
Fibroblast growth factor 21 predicts outcome in community-acquired pneumonia: secondary analysis of two randomised controlled trials
Authors: Ebrahimi Fahim , Wolffenbuttel Carole , Blum Claudine A. , Baumgartner Christine , Mueller Beat , Schuetz Philipp , Meier Christian , Kraenzlin Marius , Christ-Crain Mirjam , Betz Matthias Johannes
Published: December 2018

Acute systemic inflammatory conditions are accompanied by profound alterations of metabolism. However, the role of fibroblast growth factor 21 (FGF21), a recently identified central regulator of metabolism, is largely unknown in community-acquired pneumonia (CAP). This study aims to characterise the pattern of FGF21 in pneumonia and associations with disease severity and outcome.

This is a secondary analysis of two independent multicentre randomised controlled trials in patients presenting to the emergency department with CAP. Primary and secondary efficacy parameters included 30-day mortality, length of hospital stay, time to clinical stability and duration of antibiotic treatment.

A total of 509 patients were included in the analysis. FGF21 levels at admission strongly correlated with disease severity, as measured by the Pneumonia Severity Index. Increased levels of FGF21 were associated with prolonged time to clinical stability, antibiotic treatment and hospitalisation. FGF21 levels at admission were significantly higher in nonsurvivors than in survivors, yielding a 1.61-fold increased adjusted odds ratio of 30-day mortality (95% CI 1.21–2.14; p=0.001). Moreover, FGF21 was found to identify patients for 30-day mortality with superior discriminative power compared with routine diagnostic markers.

Moderate-to-severe CAP patients with higher levels of FGF21 were at increased risk for clinical instability, prolonged hospitalisation and 30-day all-cause mortality.
Widening the landscape of heritable pulmonary hypertension mutations in paediatric and adult cases
Authors: Eyries Mélanie , Montani David , Nadaud Sophie , Girerd Barbara , Levy Marilyne , Bourdin Arnaud , Trésorier Romain , Chaouat Ari , Cottin Vincent , Sanfiorenzo Céline , Prevot Grégoire , Reynaud-Gaubert Martine , Dromer Claire , Houeijeh Ali , Nguyen Karine , Coulet Florence , Bonnet Damien , Humbert Marc , Soubrier Florent
Published: December 2018

Background

Heritable forms of pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis (PVOD/PCH) diverge by lung histopathological lesions, clinical and para-clinical presentation, their responsible genes, and mode of transmission. Since the identification of theBMPR2gene in families affected by PAH, mutations in several other genes have been discovered for both forms. The mutation landscape in these new genes is not yet well known.

Methods

We set up a next-generation sequencing-based targeted sequencing gene panel allowing known genes for PAH and PVOD/PCH to be analysed simultaneously.Genetic analysis was prospectively performed on 263 PAH and PVOD/PCH patients (adult and paediatric cases).

Results

Pathogenic mutations were identified in 19.5% of sporadic PAH patients (n=180), 54.5% of familial PAH patients and 13.3% of PVOD/PCH patients.BMPR2was the most frequently mutated gene, followed byTBX4in both paediatric and adult PAH.BMP9mutations were identified in 1.2% of adult PAH cases.EIF2AK4biallelic mutations were restricted to PVOD/PCH. A truncating mutation and a predicted loss-of-function variant were also identified inBMP10in two severely affected sporadic PAH female patients.

Conclusion

Our results confirm that mutations are found in genes beyondBMPR2in heritable PAH, emphasise the role ofTBX4andBMP9, and designateBMP10as a new PAH gene.
Role of imaging in progressive-fibrosing interstitial lung diseases
Authors: Walsh Simon L.F. , Devaraj Anand , Enghelmayer Juan Ignacio , Kishi Kazuma , Silva Rafael S. , Patel Nina , Rossman Milton D. , Valenzuela Claudia , Vancheri Carlo
Published: December 2018

Imaging techniques are an essential component of the diagnostic process for interstitial lung diseases (ILDs). Chest radiography is frequently the initial indicator of an ILD, and comparison of radiographs taken at different time points can show the rate of disease progression. However, radiography provides only limited specificity and sensitivity and is primarily used to rule out other diseases, such as left heart failure. High-resolution computed tomography (HRCT) is a more sensitive method and is considered central in the diagnosis of ILDs. Abnormalities observed on HRCT can help identify specific ILDs. HRCT also can be used to evaluate the patient's prognosis, while disease progression can be assessed through serial imaging. Other imaging techniques such as positron emission tomography-computed tomography and magnetic resonance imaging have been investigated, but they are not commonly used to assess patients with ILDs. Disease severity may potentially be estimated using quantitative methods, as well as visual analysis of images. For example, comprehensive assessment of disease staging and progression in patients with ILDs requires visual analysis of pulmonary features that can be performed in parallel with quantitative analysis of the extent of fibrosis. New approaches to image analysis, including the application of machine learning, are being developed.
Still Fighting for Breath: a patient survey of the challenges and impact of severe asthma
Authors: Katsaounou Paraskevi , Odemyr Mikaela , Spranger Otto , Hyland Michael E. , Kroegel Claus , Conde Lorena Garcia , Gore Robin , Menzella Francesco , Domingo Ribas Christian , Morais-Almeida Mario , Gasser Matthias , Kasujee Ismail
Published: December 2018

We conducted a large global survey, Still Fighting for Breath, in patients with severe persistent asthma, 10 years after the Fighting for Breath survey to assess the impact of disease on patients' lives and to determine if control and management have changed in recent years.

Data were collected from 1333 adults (aged >18 years) and caregivers of children (aged 6–17 years) with severe persistent asthma from nine countries through an online survey conducted in 2016 by GfK.

A decade after the first survey, our results showed that the impact of severe asthma has not changed significantly and a high proportion of patients with severe asthma remain inadequately controlled. A large discrepancy was observed between the proportion of patients who perceived their asthma to be well controlled (42%) and the proportion of patients who reported to be well controlled as per the Global Initiative for Asthma (GINA) assessment (6%). Although most patients perceived their asthma to be controlled, many experienced frequent symptoms that affected their daily lives.

Thus, there is a need for improved management (support and strategies) of patients with severe persistent asthma and improved coordination of efforts that would enable these patients to achieve better disease control.