bluuebunny/crossref_metadata_2025 huggingface dataset:
Using the Saphenous Artery and Great Saphenous Vein Combined with Anterolateral Thigh Flap to Treat Skin Defects after Amputation
Authors: Kong Ling , Cheng Han , Nie Tao , Dai Min
Published: October 2018

Background Aim of this study was to determine the feasibility of using the saphenous artery (SA) and great saphenous vein (GSV) as recipient vessels, combined with anterolateral thigh (ALT) flap, in the treatment of skin defects after lower limb amputation.

Methods From June 2015 to June 2017, 12 patients (average age, 33.5 years; range, 14–56 years; males, 9; female, 3) with large skin defects and symptoms of bone exposure in the proximal lower extremity were included in our study. The patients underwent emergency treatment and multiple debridement combined with vacuum sealing drainage therapy, followed by free flap surgery using the SA and GSV as recipient vessels, and ALT to cover the wound.

Results All 12 patients who underwent free flap surgery survived, but two patients had distal flap necrosis, which, however, was salvaged with conservative measures. All patients were satisfied with the postoperative outcome at the 3 and 6-month follow-up.

Conclusion The SA and GSV can be used as recipient vessels, combined with ALT, to treat skin defects after lower limb amputation.
Endoscopic Intramural Surgery Part 1: Resectional Therapies
Authors: Wadhwa Vaibhav , Gupta Kapil , Erim Tolga
Published: October 2018

Endoscopic resectional therapies for lesions of gastrointestinal tract have progressed rapidly over the past two decades. Advances in minimally invasive endoscopic approaches continue to emerge and evolve, while boundaries of resection techniques continue to be pushed. The concept of third space endoscopy with mucosal flap as a safety valve has emerged arguably as the most innovative technique among these approaches. We review several techniques for intramural endoscopic resection of lesions of the gastrointestinal tract, but to gain a full understanding of why these exist, we must first examine the background from which they emerged.
Doubling the quality factor of cantilevers in liquid through fluid coupling-based actuation
Authors: Leahy Stephane , Lai Yongjun
Published: October 2018

Dynamic-mode cantilevers are a promising tool for real-time biosensing applications due to their high sensitivity and ability to perform label-free measurements. However, operating dynamic-mode cantilevers in liquid is challenging since viscous damping greatly reduces their quality factor and thus the limit of detection. We reasoned through physical analysis that if the motion of the surrounding fluid is driven by an external force and not by the sensing cantilever itself, then the dissipative fluid force on the cantilever could be reduced and the quality factor of the cantilever could be increased. Here, we demonstrate a new fluid coupling-based actuation method, where one piezoelectric cantilever (directly excited) is used to excite another closely located cantilever (indirectly excited) through vibrations transferred through the surrounding medium. We performed the measurements in several mediums, including air, water, ethanol, and acetone, and observed that the viscosity of the medium influences the effectiveness of fluid coupling-based actuation. We also observed that fluid coupling-based actuation is more effective for the first bending mode of the cantilever, likely since fluid motion decays with distance from the tip of the directly excited cantilever. A significant result is that the indirectly excited cantilever has a quality factor that is double that of the directly excited one for the first bending mode in water. This method could improve the performance of dynamic-mode cantilevers operated in liquid.
Oxygen transfer from bubble-plumes
Authors: Niida Yasuo , Watanabe Yasunori
Published: October 2018

Air-bubble plumes produced beneath ocean breaking waves have important roles in gas transfer between atmosphere and ocean because the gas within the bubbles, convected by breaking-wave-induced turbulence, is dissolved at a deeper level. In particular, oxygen dissolution supports all biological activities in a marine ecosystem. Oxygen transfer from bubbles to bulk water depends on the dynamics of local bubble flows. As lateral bubble motion associated with vortex wakes generates turbulence in the ambient fluid, depending on the bubble size, the dissolved gas in the plume is transported via complex convection and diffusion processes. Although analytical and empirical models of gas transfer from a small, rigid bubble have been proposed previously, the effects of bubble size on gas concentrations in the turbulence field remain poorly understood. In this study, we examine the explicit effects of bubble size on bubble plume turbulence and the dissolved oxygen (DO) concentration field, and propose a new empirical gas transfer model that is applicable to large deformable bubbles on the basis of experimental imaging analysis. The gas transport process in the plume was identified using bubble turbulence coupled flow computations with the proposed gas source model, which well explained the variation in experimental DO concentration. The proposed transfer velocity model extended the applicable bubble size range and predicted the major features of the increasing oxygen concentration within the plume. We expect these findings to serve as a starting point to improve our understanding of the dynamics of practical bubble plume flows with wider bubble size ranges, as typically formed under breaking waves, and to predict oxygen concentrations in marine environments.
Magnetohydrodynamic waves and the Kelvin-Helmholtz instability at the boundary of plasma mediums
Authors: Cheremnykh O. , Cheremnykh S. , Kozak L. , Kronberg E.
Published: October 2018

It has been theoretically established that shear plasma flows at the boundary of the medium can generate eight MHD modes, of which only one can be unstable due to the development of the Kelvin-Helmholtz instability. It is shown that oblique perturbations propagating at an angle with respect to the velocity vector play a dominant role in the development of this instability. Analytic expressions are obtained for the criteria and instability increments that take into account the angle of propagation of perturbations, the effect of the magnetic field, and the compressibility of the medium and in the limiting cases coincide with the previously obtained results. It is noted that the appearance of a large number of waves can lead to a flow with a complicated structure at the boundary of the magnetotail.
Analysis of rotational Doppler effect based on radio waves carrying orbital angular momentum
Authors: Zheng Jiayu , Zheng Shilie , Shao Zhenlei , Zhang Xianmin
Published: October 2018

The electromagnetic beam carrying orbital angular momentum (OAM) has a twisted phase front, which can induce a rotational Doppler frequency shift when it is illuminating on a spinning object. In this paper, the rotational Doppler effect induced by a radio wave carrying OAM is theoretically analyzed and experimentally verified. Compared with an optical vortex beam, the divergence angle of a radio wave carrying OAM is typically larger than that of an optical vortex beam, which results in the radio OAM-based sensing system with short-range detection distance. In this case, the receiver's location and the deflection of the rotating plane are important factors that affect the radio rotational Doppler effect. For an off-axis receiver or a deflected spinning object, a series of extra Doppler frequency shifts (L ± N)Ω/2π are induced when the spinning object is illuminated by a wave carrying OAM with topological charge L, even for L = 0, the plane wave. Hence, the high order OAM wave should be used to distinguish the real rotational frequency shift and improve detection sensitivity of spinning velocity. Combining the rotational Doppler effect with the linear Doppler effect, a vector velocity detecting scheme is discussed.
Self-trapping and acceleration of ions in laser-driven relativistically transparent plasma
Authors: Liu B. , Meyer-ter-Vehn J. , Ruhl H.
Published: October 2018

Self-trapping and acceleration of ions in laser-driven relativistically transparent plasma are investigated with the help of particle-in-cell simulations. A theoretical model based on ion wave breaking is established in describing ion evolution and ion trapping. The threshold for ion trapping is identified. Near the threshold ion trapping is self-regulating and stops when the number of trapped ions is large enough. The model is applied to ion trapping in three-dimensional geometry. Longitudinal distributions of ions and the electric field near the wave breaking point are derived analytically in terms of power-law scalings. The areal density of trapped charge is obtained as a function of the strength of ion wave breaking, which scales with target density for fixed laser intensity. The results of the model are confirmed by the simulations.
Computational study of nonlinear dielectric composites with field-induced antiferroelectric-ferroelectric phase transition
Authors: Geng Liwei D. , Jin Yongmei M. , Tan Daniel Q. , Wang Yu U.
Published: October 2018

Electric field-induced antiferroelectric-ferroelectric phase transition and the associated nonlinear dielectric behavior in particulate composites are investigated for achieving a high dielectric capacity. A phenomenological thermodynamic model based on the Landau theory is first developed to discuss the generic phenomena of a temperature-electric field phase diagram, coexistence of antiferroelectric and ferroelectric phases, field-induced antiferroelectric-ferroelectric phase transition, and nonlinear dielectric behavior. The model is then used to carry out the phase field simulation of particulate nonlinear dielectric composites. It is found that the composites exhibit nonlinear dielectric behaviors, and the depolarization field in the composites helps reduce the dielectric hysteresis and enhance the reversibility of antiferroelectric-ferroelectric phase transitions, which are desired for energy storage applications. The simulations also reveal the underlying domain-level mechanisms for nucleation and growth processes of the phase transitions. It is shown that the macroscopic properties of the composites sensitively depend on the directional alignment of the antiferroelectric filler particles, and thus the filler morphology is an effective control variable in designing nonlinear dielectric composites.
Number of stems around the H.V. electrode in a 0.74-m air gap under positive impulse
Authors: Yang Yongchao , He Junjia , Zhao Xiangen , Xiao Pei
Published: October 2018

Stem is a special short bright zone for the streamer to leader transition in long air gap discharges, whose characteristics play an important role in leader initiation and development. For the purpose of observing the number of stems around the H.V. electrode at the initial corona discharge, experiments were conducted under positive switching and lightning impulses with different crest values, and the schlieren photographs of stems and the discharge current were recorded synchronously. The associated analysis of the experimental results shows that the number of stems around the electrode at the initial corona discharge is always more than one in most cases. In addition, the average number of stems increases with the radius of the electrode and the crest value of applied impulse. If we focus on the characteristic of only one stem for special study, the conditions with a lower crest value under switching impulse and the electrode with a radius as small as possible are preferable.
Caspase-8 induces cleavage of gasdermin D to elicit pyroptosis during
Yersinia
infection
Authors: Sarhan Joseph , Liu Beiyun C. , Muendlein Hayley I. , Li Peng , Nilson Rachael , Tang Amy Y. , Rongvaux Anthony , Bunnell Stephen C. , Shao Feng , Green Douglas R. , Poltorak Alexander
Published: October 2018

Significance

Here we demonstrate that
Yersinia
YopJ-induced murine macrophage death involves caspase-8–induced cleavage of both gasdermin D (GSDMD) and gasdermin E (GSDME). The ensuing cell death is rapid, morphologically is similar to pyroptosis, and induces IL-1 release. Recently, both GSDMD and GSDME were reported to be critical effectors of caspase-1/11–driven pyroptosis and caspase-3–dependent secondary necrosis, which prompted the redefinition of pyroptosis as cell death-mediated by gasdermin activation. Our work extends these studies and shows that activation of caspase-8 in the context of TAK1 inhibition results in cleavage of both GSDMD and GSDME, leading to pyroptotic-like cell death. Further study will be needed to determine whether caspase-8 cleaves GSDMD directly or via intermediate substrates.
Silencing of retrotransposon-derived imprinted gene RTL1 is the main cause for postimplantational failures in mammalian cloning
Authors: Yu Dawei , Wang Jing , Zou Huiying , Feng Tao , Chen Lei , Li Jia , Qi Xiaolan , Li Zhifang , Duan Xiaoyue , Xu Chunlong , Zhang Liang , Long Xi , Lan Jing , Chen Chao , Wang Chao , Xu Xinyu , Ren Jilong , Zhao Yiqiang , Hu Xiaoxiang , Lian Zhengxing , Men Hongsheng , Pan Dengke , Li Ning , Capecchi Mario R. , Du Xuguang , Zhao Yaofeng , Wu Sen
Published: October 2018

Significance

To investigate the epigenetic mechanism of pregnancy failure in mammals, we exploited the high rate of fetal loss in pig induced pluripotent stem cell (iPSC) nuclear transfer. We generated methylomes of pig iPSCs and associated nuclear transfer embryos from reciprocal crosses between two distinct pig breeds. Our methylome analysis revealed that misregulation of RTL1 as the principal basis of pregnancy failure using pig iPSCs. Remarkably, RTL1 has broad fertility implications across mouse, rat, pig, cattle, and human from nuclear transfer cloning, tetraploid complementation, and artificial insemination, to natural fertilization. In all of these procedures, low RTL1 expression consistently corresponds to pregnancy failures.
IFNγ-activated dermal lymphatic vessels inhibit cytotoxic T cells in melanoma and inflamed skin
Authors: Lane Ryan S. , Femel Julia , Breazeale Alec P. , Loo Christopher P. , Thibault Guillaume , Kaempf Andy , Mori Motomi , Tsujikawa Takahiro , Chang Young Hwan , Lund Amanda W.
Published: October 2018

Mechanisms of immune suppression in peripheral tissues counteract protective immunity to prevent immunopathology and are coopted by tumors for immune evasion. While lymphatic vessels facilitate T cell priming, they also exert immune suppressive effects in lymph nodes at steady-state. Therefore, we hypothesized that peripheral lymphatic vessels acquire suppressive mechanisms to limit local effector CD8+ T cell accumulation in murine skin. We demonstrate that nonhematopoietic PD-L1 is largely expressed by lymphatic and blood endothelial cells and limits CD8+ T cell accumulation in tumor microenvironments. IFNγ produced by tissue-infiltrating, antigen-specific CD8+ T cells, which are in close proximity to tumor-associated lymphatic vessels, is sufficient to induce lymphatic vessel PD-L1 expression. Disruption of IFNγ-dependent crosstalk through lymphatic-specific loss of IFNγR boosts T cell accumulation in infected and malignant skin leading to increased viral pathology and tumor control, respectively. Consequently, we identify IFNγR as an immunological switch in lymphatic vessels that balances protective immunity and immunopathology leading to adaptive immune resistance in melanoma.
ACVR1R206HFOP mutation alters mechanosensing and tissue stiffness during heterotopic ossification
Authors: Haupt Julia , Stanley Alexandra , McLeod Claire M. , Cosgrove Brian D. , Culbert Andria L. , Wang Linda , Mourkioti Foteini , Mauck Robert L. , Shore Eileen M.
Published: October 2018

An activating bone morphogenetic proteins (BMP) type I receptor ACVR1 (ACVR1R206H) mutation enhances BMP pathway signaling and causes the rare genetic disorder of heterotopic (extraskeletal) bone formation fibrodysplasia ossificans progressiva. Heterotopic ossification frequently occurs following injury as cells aberrantly differentiate during tissue repair. Biomechanical signals from the tissue microenvironment and cellular responses to these physical cues, such as stiffness and rigidity, are important determinants of cell differentiation and are modulated by BMP signaling. We used an Acvr1R206H/+mouse model of injury-induced heterotopic ossification to examine the fibroproliferative tissue preceding heterotopic bone and identified pathologic stiffening at this stage of repair. In response to microenvironment stiffness, in vitro assays showed that Acvr1R206H/+cells inappropriately sense their environment, responding to soft substrates with a spread morphology similar to wild-type cells on stiff substrates and to cells undergoing osteoblastogenesis. Increased activation of RhoA and its downstream effectors demonstrated increased mechanosignaling. Nuclear localization of the pro-osteoblastic factor RUNX2 on soft and stiff substrates suggests a predisposition to this cell fate. Our data support that increased BMP signaling in Acvr1R206H/+cells alters the tissue microenvironment and results in misinterpretation of the tissue microenvironment through altered sensitivity to mechanical stimuli that lowers the threshold for commitment to chondro/osteogenic lineages.
Robust and stable transcriptional repression inGiardiausing CRISPRi
Authors: McInally S. G. , Hagen K. D. , Nosala C. , Williams J. , Nguyen K. , Booker J. , Jones K. , Dawson Scott C.
Published: October 2018

Giardia lamblia is a binucleate protistan parasite causing significant diarrheal disease worldwide. An inability to target Cas9 to both nuclei, combined with the lack of nonhomologous end joining and markers for positive selection, has stalled the adaptation of CRISPR/Cas9-mediated genetic tools for this widespread parasite. CRISPR interference (CRISPRi) is a modification of the CRISPR/Cas9 system that directs catalytically inactive Cas9 (dCas9) to target loci for stable transcriptional repression. Using a Giardia nuclear localization signal to target dCas9 to both nuclei, we developed efficient and stable CRISPRi-mediated transcriptional repression of exogenous and endogenous genes in Giardia. Specifically, CRISPRi knockdown of kinesin-2a and kinesin-13 causes severe flagellar length defects that mirror defects with morpholino knockdown. Knockdown of the ventral disk MBP protein also causes severe structural defects that are highly prevalent and persist in the population more than 5 d longer than defects associated with transient morpholino-based knockdown. By expressing two guide RNAs in tandem to simultaneously knock down kinesin-13 and MBP, we created a stable dual knockdown strain with both flagellar length and disk defects. The efficiency and simplicity of CRISPRi in polyploid Giardia allows rapid evaluation of knockdown phenotypes and highlights the utility of CRISPRi for emerging model systems.
Environmental stresses induce karyotypic instability in colorectal cancer cells
Authors: Tan Zhihao , Chan Yong Jie Andrew , Chua Ying Jie Karen , Rutledge Samuel D. , Pavelka Norman , Cimini Daniela , Rancati Giulia
Published: October 2018

Understanding how cells acquire genetic mutations is a fundamental biological question with implications for many different areas of biomedical research, ranging from tumor evolution to drug resistance. While karyotypic heterogeneity is a hallmark of cancer cells, few mutations causing chromosome instability have been identified in cancer genomes, suggesting a nongenetic origin of this phenomenon. We found that in vitro exposure of karyotypically stable human colorectal cancer cell lines to environmental stress conditions triggered a wide variety of chromosomal changes and karyotypic heterogeneity. At the molecular level, hyperthermia induced polyploidization by perturbing centrosome function, preventing chromosome segregation, and attenuating the spindle assembly checkpoint. The combination of these effects resulted in mitotic exit without chromosome segregation. Finally, heat-induced tetraploid cells were on the average more resistant to chemotherapeutic agents. Our studies suggest that environmental perturbations promote karyotypic heterogeneity and could contribute to the emergence of drug resistance.
Beyond the L-Strut: Redefining the Biomechanics of Rhinoplasty Using Topographic Optimization Modeling
Authors: Glass Graeme Ewan , Staruch Robert M T , Ruston Julia , East Charles A , Tan P J
Published: October 2018

Rhinoplasty utilizes cartilage harvested from the nasal septum as autologous graft material. Traditional dogma espouses preservation of the “L-strut” of dorsal and caudal septum, which is less resistant to axial loading than virgin septum. Considering the 90° angle between dorsal and caudal limbs, the traditional L-strut also suffers from localized increases in internal stresses leading to premature septal “cracking,” structural-scale deformation, or both. Deformation and failure of the L-strut leads to nasal deviation, saddle deformity, loss of tip support, or restriction of the nasal valve. The balance between cartilage yield and structural integrity is a topographical optimization problem. Guided by finite element (FE) modelling, recent efforts have yielded important modifications including the chamfering of right-angled corners to reduce stress concentrations and the preservation of a minimum width along the inferior portion of the caudal strut. However, all existing FE studies offer simplified assumptions to make the construct easier to model. This review article highlights advances in our understanding of septal engineering and identifies areas that require more work to further refine the balance between the competing interests of graft acquisition and the maintenance of nasal structural integrity.
Discovering network phenotype between genetic risk factors and disease status via diagnosis-aligned multi-modality regression method in Alzheimer’s disease
Authors: Wang Meiling , Hao Xiaoke , Huang Jiashuang , Shao Wei , Zhang Daoqiang
Published: October 2018

Motivation

Neuroimaging genetics is an emerging field to identify the associations between genetic variants [e.g. single-nucleotide polymorphisms (SNPs)] and quantitative traits (QTs) such as brain imaging phenotypes. However, most of the current studies focus only on the associations between brain structure imaging and genetic variants, while neglecting the connectivity information between brain regions. In addition, the brain itself is a complex network, and the higher-order interaction may contain useful information for the mechanistic understanding of diseases [i.e. Alzheimer’s disease (AD)].

Results

A general framework is proposed to exploit network voxel information and network connectivity information as intermediate traits that bridge genetic risk factors and disease status. Specifically, we first use the sparse representation (SR) model to build hyper-network to express the connectivity features of the brain. The network voxel node features and network connectivity edge features are extracted from the structural magnetic resonance imaging (sMRI) and resting-state functional magnetic resonance imaging (fMRI), respectively. Second, a diagnosis-aligned multi-modality regression method is adopted to fully explore the relationships among modalities of different subjects, which can help further mine the relation between the risk genetics and brain network features. In experiments, all methods are tested on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The experimental results not only verify the effectiveness of our proposed framework but also discover some brain regions and connectivity features that are highly related to diseases.

Availability and implementation

The Matlab code is available at http://ibrain.nuaa.edu.cn/2018/list.htm.
The Value of Mixing It Up: Student Experiences of a Multi-Modal Approach to Supervision on Placement
Authors: Vassos Sevi , Harms Louise , Rose David
Published: October 2018

One-to-one supervision has been widely acknowledged in the social work literature as the gold-standard approach in field education. However, the sustainability of this approach has been challenged in recent decades amidst the managerial mandates permeating both education and health/human service sectors. Universities and placement organisations have experimented with alternative supervision approaches in response to these contextual pressures, although the research on these alternatives is limited at this point. In an attempt to contribute to the emerging research base, this article reports on a three-year trial of a multi-modal supervision approach involving the systematic application of individual and collective supervision modes within each student placement. The study explored the supervision experiences of 128 Master of Social Work students participating in the multi-modal supervision trial across five health networks in Melbourne, Australia. The study adopted a mixed-methods research design involving surveys followed by interviews. The findings suggest that, although one-to-one supervision is integral, students value the combination of one-to-one and collective supervision, provided that supervision content is student-centred; and that inter-personal trust and mutual engagement imbue the supervisory process. Ultimately, the study points to the importance of both content and relationships in the supervisory process, irrespective of the supervision mode employed.
Enhanced Population Coding for Rewarded Choices in the Medial Frontal Cortex of the Mouse
Authors: Siniscalchi Michael J , Wang Hongli , Kwan Alex C
Published: October 2018

Instrumental behavior is characterized by the selection of actions based on the degree to which they lead to a desired outcome. However, we lack a detailed understanding of how rewarded actions are reinforced and preferentially implemented. In rodents, the medial frontal cortex is hypothesized to play an important role in this process, based in part on its capacity to encode chosen actions and their outcomes. We therefore asked how neural representations of choice and outcome might interact to facilitate instrumental behavior. To investigate this question, we imaged neural ensemble activity in layer 2/3 of the secondary motor region (M2) while mice engaged in a two-choice auditory discrimination task with probabilistic outcomes. Correct choices could result in one of three reward amounts (single, double or omitted reward), which allowed us to measure neural and behavioral effects of reward magnitude, as well as its categorical presence or absence. Single-unit and population decoding analyses revealed a consistent influence of outcome on choice signals in M2. Specifically, rewarded choices were more robustly encoded relative to unrewarded choices, with little dependence on the exact magnitude of reinforcement. Our results provide insight into the integration of past choices and outcomes in the rodent brain during instrumental behavior.
The prothrombotic state in atrial fibrillation: pathophysiological and management implications
Authors: Khan Ahsan A , Lip Gregory Y H
Published: October 2018

Atrial fibrillation (AF) is the commonest sustained cardiac arrhythmia and is associated with significant morbidity and mortality. There is plenty of evidence available to support the presence of a prothrombotic or hypercoagulable state in AF, but the contributory factors are multifactorial and cannot simply be explained by blood stasis. Abnormal changes in atrial wall (anatomical and structural, as ‘vessel wall abnormalities’), the presence of spontaneous echo contrast to signify abnormal changes in flow and stasis (‘flow abnormalities’), and abnormal changes in coagulation, platelet, and other pathophysiologic pathways (‘abnormalities of blood constituents’) are well documented in AF. The presence of these components therefore fulfils Virchow’s triad for thrombogenesis. In this review, we present an overview of the established and professed pathophysiological mechanisms for thrombogenesis in AF and its management implications.
Distances and Intersections of Curves
Authors: Watanabe Yohsuke
Published: October 2018

We obtain a coarse relationship between geometric intersection numbers of curves and the sum of their subsurface projection distances with explicit quasi-constants. By using this relationship, we study intersection numbers of curves contained in geodesics in the curve graph. Furthermore, we generalize a well-known result on intersection number growth of curves under iteration of Dehn twists and multitwists for all kinds of pure mapping classes.
Performance of ceftazidime/avibactam susceptibility testing methods against clinically relevant Gram-negative organisms
Authors: Wenzler E , Lee M , Wu T J , Meyer K A , Shields R K , Nguyen M H , Clancy C J , Humphries R M , Harrington A T
Published: October 2018

Objectives

To ensure the accuracy of susceptibility testing methods for ceftazidime/avibactam.

Methods

The performances of the Etest (bioMérieux), 30/20 μg disc (Hardy diagnostics) and 10/4 μg disc (Mast Group) were evaluated against the reference broth microdilution (BMD) method for 102 clinically relevant Gram-negative organisms: 69 ceftazidime- and meropenem-resistant Klebsiella pneumoniae and 33 MDR non-K. pneumoniae. Essential and categorical agreement along with major and very major error rates were determined according to CLSI guidelines.

Results

A total of 78% of isolates were susceptible to ceftazidime/avibactam. None of the three methods met the defined equivalency threshold against all 102 organisms. The Etest performed the best, with categorical agreement of 95% and major errors of 6.3%. Against the 69 ceftazidime- and meropenem-resistant K. pneumoniae, only the Etest and the 10/4 μg disc met the equivalency threshold. None of the three methods met equivalency for the 33 MDR isolates. There were no very major errors observed in any analysis. These results were pooled with those from a previous study of 74 carbapenem-resistant Enterobacteriaceae and data from the ceftazidime/avibactam new drug application to define optimal 30/20 μg disc thresholds using the error-rate bound model-based approaches of the diffusion breakpoint estimation testing software. This analysis identified a susceptibility threshold of ≤19 mm as optimal.

Conclusions

Our data indicate that the Etest is a suitable alternative to BMD for testing ceftazidime/avibactam against ceftazidime- and meropenem-resistant K. pneumoniae. The 30/20 μg discs overestimate resistance and may lead to the use of treatment regimens that are more toxic and less effective.
Comprehensive Assessment of Didactic Curriculum and Career Interest in Infectious Diseases Among Graduating United States Pharmacy Students
Authors: Jeffres Meghan N , Biehle Lauren R , MacDougall Conan
Published: October 2018

Background

The growing need for clinicians with antimicrobial stewardship (AS) skills has resulted in an examination of educational methods for pharmacy and medical learners. This study explores characteristics associated with student assessment of didactic infectious diseases (ID) education quality and variables associated with a career interest in ID and/or AS.

Methods

Infectious diseases faculty from US pharmacy schools were sent a 15-question survey in September 2017. Faculty members e-mailed the survey link to graduating pharmacy students.

Results

Participants from 29 pharmacy schools, representing 21 states, resulted in 537 student responses. Quality of ID didactic education was rated as Very Good by 41%, Good by 40%, Acceptable by 14%, and Poor by 4% of participants. The mean number of faculty-provided learning resources differed by quality rating and was significantly associated with perceived educational needs. Infectious diseases was identified as a career interest by 29% of students. These students more frequently rated their ID didactic education as Very Good (52% vs 37%, P < .01) and were more likely to become interested in ID during or after it was taught in pharmacy school (39% vs 21%, P < .01).

Conclusions

In this cohort of graduating pharmacy students, the perceived quality of didactic ID education was associated with a career interest in ID and/or AS. Factors associated with quality of education were quantity and quality of faculty-provided resources. Increasing the quality of the didactic ID curriculum has potential to increase interest in ID/AS careers among pharmacy students.
Association between physical activity and alcohol consumption: sociodemographic and behavioral patterns in Brazilian adults
Authors: Werneck André O , Oyeyemi Adewale L , Szwarcwald Célia L , Silva Danilo R
Published: October 2018

Background

Our aim was to investigate the association between physical activity and alcohol consumption, as well as the sociodemographic and behavioral patterns of this association in a representative sample of Brazilian adults.

Methods

Data from the Brazilian Health Survey (PNS), a nationally representative survey conducted in 2013 (n = 60 202; age≥18 years), were used. Time spent in leisure physical activity, alcohol consumption as well as sociodemographic (chronological age, educational status and skin color) and associated behavioral factors (TV viewing and tobacco smoking) were collected via interview. Logistic regression models were used for the main analyses.

Results

Prevalence of weekly and almost daily alcohol consumption were 29.5% and 6.7% for men and 12.0% and 1.0% for women respectively. Adults with weekly alcohol consumption were more likely to be classified as physically active [young: men=OR:1.20 (CI 95%:1.02–1.39), women= OR:2.33 (CI 95%:1.92–2.82); middle-aged: men= OR:1.46 (CI 95%: 1.17–1.82), women= OR:1.75 (CI 95%:1.38–2.22); older: men= OR:1.83 (CI 95%:1.27–2.66), women= OR:2.11 (CI 95%: s1.26–3.52)], when compared to adults with no alcohol consumption. Almost daily alcohol consumption was associated with lower physical activity among young and middle-aged adults but with higher physical activity among older adults of both sexes and young women.

Conclusions

Weekly alcohol consumption was associated with a higher level of physical activity among young, middle aged and older adults.
Reassessment of the Accuracy of Cardiac Doppler Pulmonary Artery Pressure Measurements in Ventilated ICU Patients: A Simultaneous Doppler-Catheterization Study*
Authors: Mercado Pablo , Maizel Julien , Beyls Christophe , Kontar Loay , Orde Sam , Huang Stephen , McLean Anthony , Tribouilloy Christophe , Slama Michel
Published: October 2018

Objectives:

Doppler echocardiography is a well-recognized technique for the noninvasive evaluation of pulmonary artery pressure; however, little information is available concerning patients receiving mechanical ventilation. Furthermore, recent studies have debatable results regarding the relevance of this technique to assess pulmonary artery pressure. The aim of our study was to reassess the accuracy of Doppler echocardiography to evaluate pulmonary artery pressure and to predict pulmonary hypertension.

Design:

Prospective observational study.

Setting:

Amiens ICU, France.

Patients.

ICU patients receiving mechanical ventilation.

Interventions:

In 40 patients, we simultaneously recorded Doppler echocardiography variables (including tricuspid regurgitation and pulmonary regurgitation) and invasive central venous pressure, systolic pulmonary artery pressure, diastolic pulmonary artery pressure, and mean pulmonary artery pressure.

Measurements and Main Results:

Systolic pulmonary artery pressure assessed from the tricuspid regurgitation derived maximal pressure gradient added to the central venous pressure demonstrated the best correlation with the invasive systolic pulmonary artery pressure (r = 0.87) with a small bias (–3 mm Hg) and a precision of 9 mm Hg. A Doppler echocardiography systolic pulmonary artery pressure greater than 39 mm Hg predicted pulmonary hypertension (mean pulmonary artery pressure ≥ 25 mm Hg) with 100% sensitivity and specificity. Tricuspid regurgitation maximal velocity greater than 2.82 m/s as well as tricuspid regurgitation pressure gradient greater than 32 mm Hg predicted the presence of pulmonary hypertension. Pulmonary regurgitation was recorded in 10 patients (25%). No correlation was found between pulmonary regurgitation velocities and either mean pulmonary artery pressure or diastolic pulmonary artery pressure. Pulmonary acceleration time less than 57 ms and isovolumic relaxation time less than 40 ms respectively predicted pulmonary hypertension 100% of the time and had a 100% negative predictive value.

Conclusions:

Tricuspid regurgitation maximal velocity pressure gradient added to invasive central venous pressure accurately estimates systolic pulmonary artery pressure and mean pulmonary artery pressure in ICU patients receiving mechanical ventilation and may predict pulmonary hypertension.
Increased Plasma Acetylcarnitine in Sepsis Is Associated With Multiple Organ Dysfunction and Mortality: A Multicenter Cohort Study
Authors: Chung Kuei-Pin , Chen Guan-Yuan , Chuang Tzu-Yi , Huang Yen-Tsung , Chang Hou-Tai , Chen Yen-Fu , Liu Wei-Lun , Chen Yi-Jung , Hsu Chia-Lin , Huang Miao-Tzu , Kuo Ching-Hua , Yu Chong-Jen
Published: October 2018

Objectives:

Recent metabolomic studies of sepsis showed that increased circulatory acylcarnitines were associated with worse survival. However, it is unknown whether plasma carnitine and acylcarnitines can reflect the severity of sepsis, and the role of specific acylcarnitines in prognostic assessment need further confirmation. This study aimed to clarify these questions.

Design:

Prospective multicenter cohort studies with derivation and validation cohort design.

Setting:

ICUs at two medical centers and three regional hospitals in Taiwan.

Patients:

Patients with sepsis and acute organ dysfunction were enrolled. Recruitment of the derivation (n = 90) and validation cohorts (n = 120) occurred from October 2010 through March 2012 and January 2013 through November 2014, respectively.

Interventions:

Plasma samples were collected immediately after admission, and the levels of carnitine and acylcarnitines were measured by ultra-high performance liquid chromatography-mass spectrometry.

Measurements and Main Results:

In the derivation cohort, increased plasma levels of short- and medium-chain acylcarnitines were significantly associated with hepatobiliary dysfunction, renal dysfunction, thrombocytopenia, and hyperlactatemia. However, acetylcarnitine is the only acylcarnitine significantly correlating with various plasma cytokine concentrations and also associated with blood culture positivity and 28-day mortality risk. The association between plasma acetylcarnitine and multiple organ dysfunction severity, blood culture positivity, and 28-day mortality, was confirmed in the validation cohort. Patients with high plasma acetylcarnitine (≥ 6,000 ng/mL) had significantly increased 28-day mortality compared with those with plasma acetylcarnitine less than 6,000 ng/mL (52.6% vs 13.9%; hazard ratio, 5.293; 95% CI, 2.340–11.975; p < 0.001 by Cox proportional hazard model).

Conclusions:

We confirm that plasma acetylcarnitine can reflect the severity of organ dysfunction, inflammation, and infection in sepsis and can serve as a prognostic biomarker for mortality prediction.
ANATOMICAL AND VISUAL OUTCOMES OF INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE VERSUS INTERNAL LIMITING MEMBRANE PEELING IN MYOPIC MACULAR HOLE WITHOUT RETINAL DETACHMENT
Authors: Bové Álvarez María , Sabaté Sergi , Gómez-Resa María , García-Arumí José
Published: October 2018

Purpose:

To compare the results of vitrectomy with internal limiting membrane (ILM) peeling and inverted ILM flap for treating myopic macular hole without retinal detachment.

Methods:

Twenty-eight eyes of 28 patients undergoing vitrectomy with either ILM peeling (n = 16) or inverted ILM flap technique (n = 12) were included. Outcomes were myopic macular hole closure by optical coherence tomography and visual acuity at 6 months and at the end of follow-up.

Results:

Closure of myopic macular hole was achieved in 13 eyes (81.2%) of the ILM peeling group and in 11 eyes (91.7%) of the inverted ILM flap group. The median length of follow-up was 18 months in the peeling group and 10.3 in the inverted group. There were not statistically significant differences between restoration of the external limiting membrane, external limiting membrane and ellipsoid zone, and none of both layers between the two groups. The median best-corrected visual acuity (logarithm of minimal angle of resolution) at the end of follow-up was 0.25 (20/35 Snellen) in the peeling group and 0.4 (20/50) in the inverted group (P = 0.027).

Conclusion:

Both techniques were associated with high closure rates of myopic macular hole but the small sample size and the retrospective design prevents any claims of superiority of one technique over the other.
SEQUENTIAL PNEUMATIC RETINOPEXIES FOR THE TREATMENT OF PRIMARY INFERIOR RHEGMATOGENOUS RETINAL DETACHMENTS WITH INFERIOR BREAKS
Authors: Alali Alaa , Bourgault Serge , Hillier Roxane J. , Muni Rajeev H. , Kertes Peter J.
Published: October 2018

Purpose:

To evaluate a new approach of sequential pneumatic retinopexies for the management of inferior rhegmatogenous retinal detachments (RD) with inferior breaks.

Methods:

Multicenter retrospective consecutive case series of inferior RDs caused by retinal breaks located within the inferior 4 clock hours treated with sequential pneumatic retinopexies, 24 to 48 hours apart. A total of 26 patients with inferior RDs secondary to one or more breaks between the 4 o'clock and 8 o'clock meridians were included from September 2007 to February 2012.

Results:

The mean follow-up duration was 35.3 weeks. Anatomical success at 8 weeks was achieved in 65.4% of all patients (including those with giant retinal tear and patients with previous RD in the study eye). When excluding patients with giant retinal tear and previous RD in the study eye, the anatomical success rate increased to 70%. Overall, the mean visual acuity improved from 1.00 logMAR (Snellen equivalent 20/200) at baseline to 0.38 logMAR (Snellen equivalent 20/50) at last follow-up.

Conclusion:

Sequential pneumatic retinopexy offers a new viable surgical option for the treatment of RDs secondary to inferior breaks.
Impact of Cytomegalovirus Infection on the Outcome of Patients With Cirrhosis
Authors: Faivre Morgan , Cottet Vanessa , Bour Jean-Baptiste , Richou Carine , Valmary-Degano Séverine , Thiefin Gerard , Andreoletti Laurent , Geist Claire , Schvoerer Evelyne , Malvé Brice , Habersetzer François , Fafi-Kremer Samira , Binquet Christine , Jouve Jean-Louis , Bronowicki Jean-Pierre , Doffoel Michel , Hillon Patrick , Herbein Georges , Monnet Elisabeth , Di Martino Vincent
Published: October 2018

Goals:

The aims of this study were to evaluate whether cytomegalovirus (CMV) infection is associated with hepatocellular carcinoma (HCC) and liver-related mortality in cirrhotic patients.

Background:

In cirrhotic patients, the determinants of HCC and liver-related death are imperfectly known. CMV infection, by its prooncogenic and proinflammatory properties, may favor both the development of HCC and deleterious systemic inflammation.

Study:

In the 1178 patients included between June 2008 and December 2012 in the CIrrhose et Risque de Carcinome Hépatocellulaire dans le grand-Est (CIRCE) study, a French multicenter case-control study designed to identify risk factors of HCC among cirrhotic patients, we identified 432 patients with interpretable CMV serological status at baseline. They included 159 cases with HCC and 273 controls. We measured factors associated with HCC at baseline and subsequent HCC in controls, and predictors of overall and liver-related death in the whole study population.

Results:

During a median follow-up of 31 months, 25 cases of HCC developed in controls, and 209 deaths (163 liver-related) were recorded. There were 247 (57.2%) CMV-seropositive patients. CMV seropositivity was not associated with more frequent HCC at baseline or during follow-up, but among CMV-positive patients with HCC, the proportion of multinodular, infiltrative, or metastatic tumors at diagnosis was higher (73.8% vs. 57.3%; P=0.029), inducing higher mortality (74% vs. 52% at 3 years; P=0.004). By Cox-regression adjusted for age, gender, Model for End-stage Liver Disease (MELD) score, HCC at baseline, and diabetes, CMV seropositivity independently predicted all-cause (hazard ratio=1.45; 95% confidence interval, 1.08-1.94; P=0.013) and liver-related mortality (hazard ratio=1.56; 95% confidence interval, 1.04-2.30; P=0.031).

Conclusions:

In this preliminary study, CMV-seropositive cirrhotic patients were at higher risk of liver-related death caused by more aggressive HCCs or severe cirrhosis complications. These findings warrant confirmation.
Comprehensive assessment gene signatures for clear cell renal cell carcinoma prognosis
Authors: Chang Peng , Bing Zhitong , Tian Jinhui , Zhang Jingyun , Li Xiuxia , Ge Long , Ling Juan , Yang Kehu , Li Yumin
Published: October 2018

There are many prognostic gene signature models in clear cell renal cell carcinoma (ccRCC). However, different results from various methods and samples are hard to contribute to clinical practice. It is necessary to develop a robust gene signature for improving clinical practice in ccRCC.

A method was proposed to integrate least absolute shrinkage and selection operator and multiple Cox regression to obtain mRNA and microRNA signature from the cancer genomic atlas database for predicting prognosis of ccRCC. The gene signature model consisted by 5 mRNAs and 1 microRNA was identified. Prognosis index (PI) model was constructed from RNA expression and median value of PI is used to classified patients into high- and low-risk groups.

The results showed that high-risk patients showed significantly decrease survival comparison with low-risk groups [hazard ratio (HR) =7.13, 95% confidence interval = 3.71–13.70, P < .001]. As the gene signature was mainly consisted by mRNA, the validation data can use transcriptomic data to verify. For comparison of the performance with previous works, other gene signature models and 4 datasets of ccRCC were retrieved from publications and public database. For estimating PI in each model, 3 indicators including HR, concordance index , and the area under the curve of receiver operating characteristic for 3 years were calculated across 4 independent datasets.

The comparison results showed that the integrative model from our study was more robust than other models via comprehensive analysis. These findings provide some genes for further study their functions and mechanisms in ccRCC tumorigenesis and malignance, and may be useful for effective clinical decision making of ccRCC patients.