bluuebunny/crossref_metadata_2025 huggingface dataset:
FRCS first pass variance: deanery and specialty contrariety
Authors: Brown Chris , Abdelrahman Tarig , Pollitt John , Holt Mark , Lewis Wyn G
Published: August 2017

Background

FRCS exit examination success may be interpreted as a surrogate marker for UK Deanery-related training quality. The aim of this study was to evaluate relative FRCS examination pass rates related to Deanery and Surgical Specialty.

Methods

Joint Committee on Surgical Training-published examination first attempt pass rates were scrutinised for type I higher surgical trainees and outcomes compared related to Deanery and Surgical Specialty.

Results

Of 9363 FRCS first attempts, 3974 were successful (42.4%). Median and mean pass rates related to Deanery were 42.1% and 30.7%, respectively, and ranged from 26.7% to 45.6%. Median (range) pass rates by specialty were urology 76.3% (60%–100%), trauma and orthopaedic surgery 74.7% (58.2%–100%), general surgery 70.0% (63.1%–86%), ENT 62.5% (50%–100%), cardiothoracic surgery 50.0% (25%–100%), oral and maxillofacial surgery 50% (40.0%–100%), neurosurgery 50% (22.7%–100%), plastic surgery 47.6% (30.0%–100%) and paediatric surgery 25% (16.7%–100%). Significant variance was observed across all specialties and deaneries (p=0.001).

Conclusion

As much as threefold variance exists related to FRCS examination first attempt success, trainees should be aware of this spectrum when preferencing deaneries during national selection.
Glycosylation with O-linked β-N-acetylglucosamine induces vascular dysfunction via production of superoxide anion/reactive oxygen species
Authors: Souza-Silva Leonardo , Alves-Lopes Rheure , Silva Miguez Jéssica , Dela Justina Vanessa , Neves Karla Bianca , Mestriner Fabíola Leslie , Tostes Rita de Cassia , Giachini Fernanda Regina , Lima Victor Vitorino
Published: August 2017

Overproduction of superoxide anion (•O2−) and O-linked β-N-acetylglucosamine (O-GlcNAc) modification in the vascular system are contributors to endothelial dysfunction. This study tested the hypothesis that increased levels of O-GlcNAc-modified proteins contribute to •O2− production via activation of NADPH oxidase, resulting in impaired vasodilation. Rat aortic segments and vascular smooth muscle cells (VSMCs) were incubated with vehicle (methanol) or O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N-phenylcarbamate (PUGNAc) (100 μM). PUGNAc produced a time-dependent increase in O-GlcNAc levels in VSMC and decreased endothelium-dependent relaxation, which was prevented by apocynin and tiron, suggesting that •O2− contributes to endothelial dysfunction under augmented O-GlcNAc levels. Aortic segments incubated with PUGNAc also exhibited increased levels of reactive oxygen species, assessed by dihydroethidium fluorescence, and augmented •O2− production, determined by lucigenin-enhanced chemiluminescence. Additionally, PUGNAc treatment increased Nox-1 and Nox-4 protein expression in aortas and VSMCs. Translocation of the p47phox subunit from the cytosol to the membrane was greater in aortas incubated with PUGNAc. VSMCs displayed increased p22phox protein expression after PUGNAc incubation, suggesting that NADPH oxidase is activated in conditions where O-GlcNAc protein levels are increased. In conclusion, O-GlcNAc levels reduce endothelium-dependent relaxation by overproduction of •O2− via activation of NADPH oxidase. This may represent an additional mechanism by which augmented O-GlcNAc levels impair vascular function.
Wavelet Multiresolution Complex Network for Analyzing Multivariate Nonlinear Time Series
Authors: Gao Zhong-Ke , Li Shan , Dang Wei-Dong , Yang Yu-Xuan , Do Younghae , Grebogi Celso
Published: August 2017

Characterizing complicated behavior from time series constitutes a fundamental problem of continuing interest and it has attracted a great deal of attention from a wide variety of fields on account of its significant importance. We in this paper propose a novel wavelet multiresolution complex network (WMCN) for analyzing multivariate nonlinear time series. In particular, we first employ wavelet multiresolution decomposition to obtain the wavelet coefficients series at different resolutions for each time series. We then infer the complex network by regarding each time series as a node and determining the connections in terms of the distance among the feature vectors extracted from wavelet coefficients series. We apply our method to analyze the multivariate nonlinear time series from our oil–water two-phase flow experiment. We construct various wavelet multiresolution complex networks and use the weighted average clustering coefficient and the weighted average shortest path length to characterize the nonlinear dynamical behavior underlying the derived networks. In addition, we calculate the permutation entropy to support the findings from our network analysis. Our results suggest that our method allows characterizing the nonlinear flow behavior underlying the transitions of oil–water flows.
Flow-mediated dilation and peripheral arterial tonometry are disturbed in preeclampsia and reflect different aspects of endothelial function
Authors: Mannaerts Dominique , Faes Ellen , Goovaerts Inge , Stoop Tibor , Cornette Jerome , Gyselaers Wilfried , Spaanderman Marc , Van Craenenbroeck Emeline M. , Jacquemyn Yves
Published: August 2017

Endothelial function and arterial stiffness are known to be altered in preeclamptic pregnancies. Previous studies have shown conflicting results regarding the best technique for assessing vascular function in pregnancy. In this study, we made a comprehensive evaluation of in vivo vascular function [including flow-mediated dilatation (FMD), peripheral arterial tonometry (PAT), and arterial stiffness] in preeclamptic patients and compared them with normal pregnancies. In addition, we assessed the relation between vascular function and systemic inflammation. Fourteen patients with preeclampsia (PE) and 14 healthy pregnant controls were included. Endothelial function was determined by FMD and PAT and arterial stiffness by carotid-femoral pulse-wave velocity and augmentation index. Systemic inflammation was assessed using mean platelet volume (MPV) and neutrophil-lymphocyte ratio (NLR). The reactive hyperemia index, assessed using PAT, is decreased at the third trimester compared with the first trimester in a normal, uncomplicated pregnancy ( P = 0.001). Arterial stiffness is significantly higher in PE versus normal pregnancy ( P < 0.001). Endothelial function, obtained by FMD, is deteriorated in PE versus normal pregnancy ( P = 0.015), whereas endothelial function assessment by PAT is improved in PE versus normal pregnancy ( P = 0.001). Systemic inflammation (MPV and NLR) increases during normal pregnancy. FMD and PAT are disturbed in PE. Endothelial function, assessed by FMD and PAT, shows distinct results. This may indicate that measurements with FMD and PAT reflect different aspects of endothelial function and that PAT should not be used as a substitute for FMD as a measure of endothelial function in pregnancy.
Characterization of decision commitment rule alterations during an auditory change detection task
Authors: Johnson Bridgette , Verma Rebeka , Sun Manying , Hanks Timothy D.
Published: August 2017

A critical component of decision making is determining when to commit to a choice. This involves stopping rules that specify the requirements for decision commitment. Flexibility of decision stopping rules provides an important means of control over decision-making processes. In many situations, these stopping rules establish a balance between premature decisions and late decisions. In this study we use a novel change detection paradigm to examine how subjects control this balance when invoking different decision stopping rules. The task design allows us to estimate the temporal weighting of sensory information for the decisions, and we find that different stopping rules did not result in systematic differences in that weighting. We also find bidirectional post-error alterations of decision strategy that depend on the type of error and effectively reduce the probability of making consecutive mistakes of the same type. This is a generalization to change detection tasks of the widespread observation of unidirectional post-error slowing in forced-choice tasks. On the basis of these results, we suggest change detection tasks as a promising paradigm to study the neural mechanisms that support flexible control of decision rules.

NEW & NOTEWORTHY Flexible decision stopping rules confer control over decision processes. Using an auditory change detection task, we found that alterations of decision stopping rules did not result in systematic changes in the temporal weighting of sensory information. We also found that post-error alterations of decision stopping rules depended on the type of mistake subjects make. These results provide guidance for understanding the neural mechanisms that control decision stopping rules, one of the critical components of decision making and behavioral flexibility.
Object comparison in the lateral intraparietal area
Authors: Ong Wei Song , Mirpour Koorosh , Bisley James W.
Published: August 2017

We can search for and locate specific objects in our environment by looking for objects with similar features. Object recognition involves stimulus similarity responses in ventral visual areas and task-related responses in prefrontal cortex. We tested whether neurons in the lateral intraparietal area (LIP) of posterior parietal cortex could form an intermediary representation, collating information from object-specific similarity map representations to allow general decisions about whether a stimulus matches the object being looked for. We hypothesized that responses to stimuli would correlate with how similar they are to a sample stimulus. When animals compared two peripheral stimuli to a sample at their fovea, the response to the matching stimulus was similar, independent of the sample identity, but the response to the nonmatch depended on how similar it was to the sample: the more similar, the greater the response to the nonmatch stimulus. These results could not be explained by task difficulty or confidence. We propose that LIP uses its known mechanistic properties to integrate incoming visual information, including that from the ventral stream about object identity, to create a dynamic representation that is concise, low dimensional, and task relevant and that signifies the choice priorities in mental matching behavior.

NEW & NOTEWORTHY Studies in object recognition have focused on the ventral stream, in which neurons respond as a function of how similar a stimulus is to their preferred stimulus, and on prefrontal cortex, where neurons indicate which stimulus is being looked for. We found that parietal area LIP uses its known mechanistic properties to form an intermediary representation in this process. This creates a perceptual similarity map that can be used to guide decisions in prefrontal areas.
Exploring Cultural Competence amongst OT Students
Authors: Govender Pragashnie , Mpanza December M. , Carey Tarryn , Jiyane Kwenzile , Andrews Bicolé , Mashele Sam
Published: August 2017

Occupational therapy relies primarily on communication between the therapist and client for effective intervention. Adequate communication may be influenced by language and cultural differences between the therapist and client. Cultural competence in relation to language and culture is thus a vital part in practice. Limited research exists on cultural competence in occupational therapy students. This study thus aimed to explore the cultural competence of final year students and their perceptions of their own cultural competence, with respect to language and culture in their practice as students. An explorative qualitative study design was utilised with a nonprobability purposeful sample of 21 final year undergraduate students at a tertiary institute in South Africa. Three focus groups were conducted, comprising between 6 and 8 students in each group. Thematic analysis using inductive reasoning was undertaken in order to analyse the students’ experiences and understanding of cultural competence. Findings of the study suggest that cultural competence, in relation to language and culture, influences the occupational therapy intervention process. It was shown to both positively and negatively influence intervention through supporting or hindering rapport building, client centeredness, and effective intervention.
Identification of Anisomerous Motor Imagery EEG Signals Based on Complex Algorithms
Authors: Liu Rensong , Zhang Zhiwen , Duan Feng , Zhou Xin , Meng Zixuan
Published: August 2017

Motor imagery (MI) electroencephalograph (EEG) signals are widely applied in brain-computer interface (BCI). However, classified MI states are limited, and their classification accuracy rates are low because of the characteristics of nonlinearity and nonstationarity. This study proposes a novel MI pattern recognition system that is based on complex algorithms for classifying MI EEG signals. In electrooculogram (EOG) artifact preprocessing, band-pass filtering is performed to obtain the frequency band of MI-related signals, and then, canonical correlation analysis (CCA) combined with wavelet threshold denoising (WTD) is used for EOG artifact preprocessing. We propose a regularized common spatial pattern (R-CSP) algorithm for EEG feature extraction by incorporating the principle of generic learning. A new classifier combining the K-nearest neighbor (KNN) and support vector machine (SVM) approaches is used to classify four anisomerous states, namely, imaginary movements with the left hand, right foot, and right shoulder and the resting state. The highest classification accuracy rate is 92.5%, and the average classification accuracy rate is 87%. The proposed complex algorithm identification method can significantly improve the identification rate of the minority samples and the overall classification performance.
Dynamic Output Feedback Compensation Control for Discrete Closed‐Loop Nonlinear System with Multiple Time‐Delays
Authors: Zheng Wei , Wang Hong-bin , Zhang Zhi-ming
Published: August 2017

This paper addresses the dynamic output feedback control problem for a class of discrete system with uncertainties and multiple time‐delays. First, the system is decomposed into two subsystems based on the output matrix and input control matrix. Secondly, a dynamic compensator is employed for the first subsystem, and then, given the multiple uncertainties, the output feedback controller is designed based on the second subsystem and the dynamic compensator. Thirdly, by choosing the Lyapunov‐Krasovskii function, it can be seen that the developed controller makes the closed‐loop system convergent to an adjustable region, which can be rendered arbitrary small by adjusting design parameters. Compared with the previous researches, the proposed controller is not only smooth and memoryless, but also only dependent on the system output. Furthermore, with the given dynamic compensator, the controller design conditions are relaxed, while the approach is extended to the conventional nonlinear system. Finally, numerical example is given to illustrate the effectiveness of the theoretical results.
Recent Advances in Hydrogel-Based Drug Delivery for Melanoma Cancer Therapy: A Mini Review
Authors: Vishnubhakthula Sowmya , Elupula Ravinder , Durán-Lara Esteban F.
Published: August 2017

The purpose of this study is to describe some of the latest advances in using hydrogels for cancer melanoma therapy. Hydrogel formulations of polymeric material from natural or synthetic sources combined with therapeutic agents have gained great attention in the recent years for treating various maladies. These formulations can be categorized according to the strategies that induce cancer cell death in melanoma. First of all, we should note that these formulations can only play a supporting role that releases bioactive agents against cancer cells rather than the main role. This strategy involves delivering the drug via transdermal pathways, resulting in the death of cancerous cells. Another strategy utilizes magnetic gel composites to combat melanoma via hyperthermia therapy. This review discusses both transdermal and hyperthermia therapies and the recent advances that have occurred in the field.
Aging: Molecular Pathways and Implications on the Cardiovascular System
Authors: Almeida Arthur José Pontes Oliveira de , Ribeiro Thaís Porto , Medeiros Isac Almeida de
Published: August 2017

The world’s population over 60 years is growing rapidly, reaching 22% of the global population in the next decades. Despite the increase in global longevity, individual healthspan needs to follow this growth. Several diseases have their prevalence increased by age, such as cardiovascular diseases, the leading cause of morbidity and mortality worldwide. Understanding the aging biology mechanisms is fundamental to the pursuit of cardiovascular health. In this way, aging is characterized by a gradual decline in physiological functions, involving the increased number in senescent cells into the body. Several pathways lead to senescence, including oxidative stress and persistent inflammation, as well as energy failure such as mitochondrial dysfunction and deregulated autophagy, being ROS, AMPK, SIRTs, mTOR, IGF‐1, and p53 key regulators of the metabolic control, connecting aging to the pathways which drive towards diseases. In addition, senescence can be induced by cellular replication, which resulted from telomere shortening. Taken together, it is possible to draw a common pathway unifying aging to cardiovascular diseases, and the central point of this process, senescence, can be the target for new therapies, which may result in the healthspan matching the lifespan.
Using Deep Learning for Classification of Lung Nodules on Computed Tomography Images
Authors: Song QingZeng , Zhao Lei , Luo XingKe , Dou XueChen
Published: August 2017

Lung cancer is the most common cancer that cannot be ignored and cause death with late health care. Currently, CT can be used to help doctors detect the lung cancer in the early stages. In many cases, the diagnosis of identifying the lung cancer depends on the experience of doctors, which may ignore some patients and cause some problems. Deep learning has been proved as a popular and powerful method in many medical imaging diagnosis areas. In this paper, three types of deep neural networks (e.g., CNN, DNN, and SAE) are designed for lung cancer calcification. Those networks are applied to the CT image classification task with some modification for the benign and malignant lung nodules. Those networks were evaluated on the LIDC-IDRI database. The experimental results show that the CNN network archived the best performance with an accuracy of 84.15%, sensitivity of 83.96%, and specificity of 84.32%, which has the best result among the three networks.
A Multiscale Simulation Method and Its Application to Determine the Mechanical Behavior of Heterogeneous Geomaterials
Authors: Li Shengwei , Xie Heping , Zhang Ru , Gao Mingzhong , Zhang Zetian , Li Guo , Xie Jing
Published: August 2017

To study the micro/mesomechanical behaviors of heterogeneous geomaterials, a multiscale simulation method that combines molecular simulation at the microscale, a mesoscale analysis of polished slices, and finite element numerical simulation is proposed. By processing the mesostructure images obtained from analyzing the polished slices of heterogeneous geomaterials and mapping them onto finite element meshes, a numerical model that more accurately reflects the mesostructures of heterogeneous geomaterials was established by combining the results with the microscale mechanical properties of geomaterials obtained from the molecular simulation. This model was then used to analyze the mechanical behaviors of heterogeneous materials. Because kernstone is a typical heterogeneous material that comprises many types of mineral crystals, it was used for the micro/mesoscale mechanical behavior analysis in this paper using the proposed method. The results suggest that the proposed method can be used to accurately and effectively study the mechanical behaviors of heterogeneous geomaterials at the micro/mesoscales.
ATM Deficiency Generating Genomic Instability Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Therapy-Induced DNA Damage
Authors: Perkhofer Lukas , Schmitt Anna , Romero Carrasco Maria Carolina , Ihle Michaela , Hampp Stephanie , Ruess Dietrich Alexander , Hessmann Elisabeth , Russell Ronan , Lechel André , Azoitei Ninel , Lin Qiong , Liebau Stefan , Hohwieler Meike , Bohnenberger Hanibal , Lesina Marina , Algül Hana , Gieldon Laura , Schröck Evelin , Gaedcke Jochen , Wagner Martin , Wiesmüller Lisa , Sipos Bence , Seufferlein Thomas , Reinhardt Hans Christian , Frappart Pierre-Olivier , Kleger Alexander
Published: August 2017

Pancreatic ductal adenocarcinomas (PDAC) harbor recurrent functional mutations of the master DNA damage response kinase ATM, which has been shown to accelerate tumorigenesis and epithelial–mesenchymal transition. To study how ATM deficiency affects genome integrity in this setting, we evaluated the molecular and functional effects of conditional Atm deletion in a mouse model of PDAC. ATM deficiency was associated with increased mitotic defects, recurrent genomic rearrangements, and deregulated DNA integrity checkpoints, reminiscent of human PDAC. We hypothesized that altered genome integrity might allow synthetic lethality-based options for targeted therapeutic intervention. Supporting this possibility, we found that the PARP inhibitor olaparib or ATR inhibitors reduced the viability of PDAC cells in vitro and in vivo associated with a genotype-selective increase in apoptosis. Overall, our results offered a preclinical mechanistic rationale for the use of PARP and ATR inhibitors to improve treatment of ATM-mutant PDAC. Cancer Res; 77(20); 5576–90. ©2017 AACR.
GSK3 Inhibition Drives Maturation of NK Cells and Enhances Their Antitumor Activity
Authors: Cichocki Frank , Valamehr Bahram , Bjordahl Ryan , Zhang Bin , Rezner Betsy , Rogers Paul , Gaidarova Svetlana , Moreno Stacey , Tuininga Katie , Dougherty Phillip , McCullar Valarie , Howard Peter , Sarhan Dhifaf , Taras Emily , Schlums Heinrich , Abbot Stewart , Shoemaker Daniel , Bryceson Yenan T. , Blazar Bruce R. , Wolchko Scott , Cooley Sarah , Miller Jeffrey S.
Published: August 2017

Maturation of human natural killer (NK) cells as defined by accumulation of cell-surface expression of CD57 is associated with increased cytotoxic character and TNF and IFNγ production upon target-cell recognition. Notably, multiple studies point to a unique role for CD57+ NK cells in cancer immunosurveillance, yet there is scant information about how they mature. In this study, we show that pharmacologic inhibition of GSK3 kinase in peripheral blood NK cells expanded ex vivo with IL15 greatly enhances CD57 upregulation and late-stage maturation. GSK3 inhibition elevated the expression of several transcription factors associated with late-stage NK-cell maturation including T-BET, ZEB2, and BLIMP-1 without affecting viability or proliferation. When exposed to human cancer cells, NK cell expanded ex vivo in the presence of a GSK3 inhibitor exhibited significantly higher production of TNF and IFNγ, elevated natural cytotoxicity, and increased antibody-dependent cellular cytotoxicity. In an established mouse xenograft model of ovarian cancer, adoptive transfer of NK cells conditioned in the same way also displayed more robust and durable tumor control. Our findings show how GSK3 kinase inhibition can greatly enhance the mature character of NK cells most desired for effective cancer immunotherapy. Cancer Res; 77(20); 5664–75. ©2017 AACR.
Cyclophilin A Maintains Glioma-Initiating Cell Stemness by Regulating Wnt/β-Catenin Signaling
Authors: Wang Guangzhi , Shen Jia , Sun Jiahang , Jiang Zhenfeng , Fan Jiabing , Wang Hongjun , Yu Shan , Long Yu , Liu Yi , Bao Hongbo , Zhang Kelvin Xi , Han Ke , Zhu Minwei , Zheng Yongri , Lin Zhiguo , Jiang Chuanlu , Guo Mian
Published: August 2017

Purpose: Glioma-initiating cells (GIC) are glioma stem–like cells that contribute to glioblastoma (GBM) development, recurrence, and resistance to chemotherapy and radiotherapy. They have recently become the focus of novel treatment strategies. Cyclophilin A (CypA) is a cytosolic protein that belongs to the peptidyl–prolyl isomerase (PPIase) family and the major intracellular target of the immunosuppressive drug cyclosporin A (CsA). In this study, we investigate the functions of CypA and its mechanism of action in GICs' development.

Experimental Design: We analyzed differences in CypA expression between primary tumors and neurospheres from the GDS database, both before and after GIC differentiation. A series of experiments was conducted to investigate the role of CypA in GIC stemness, self-renewal, proliferation, radiotherapy resistance, and mechanism. We then designed glutathione S-transferase (GST) pulldown and coimmunoprecipitation assays to detect signaling activity.

Results: In this study, we demonstrated that CypA promotes GIC stemness, self-renewal, proliferation, and radiotherapy resistance. Mechanistically, we found that CypA binds β-catenin and is recruited to Wnt target gene promoters. By increasing the interaction between β-catenin and TCF4, CypA enhances transcriptional activity.

Conclusions: Our results demonstrate that CypA enhances GIC stemness, self-renewal, and radioresistance through Wnt/β-catenin signaling. Due to its promotive effects on GICs, CypA is a potential target for future glioma therapy. Clin Cancer Res; 23(21); 6640–9. ©2017 AACR.
Prospective Validation of Molecular Prognostic Markers in Cutaneous Melanoma: A Correlative Analysis of E1690
Authors: Kashani-Sabet Mohammed , Nosrati Mehdi , Miller James R. , Sagebiel Richard W. , Leong Stanley P.L. , Lesniak Andrew , Tong Schuyler , Lee Sandra J. , Kirkwood John M.
Published: August 2017

Purpose: To validate the prognostic impact of combined expression levels of three markers (SPP1, RGS1, and NCOA3) in melanoma specimens from patients enrolled in the E1690 clinical trial of high-dose or low-dose IFNα-2b versus observation.

Experimental Design: Tissue was available from 248 patients. Marker expression was determined by digital imaging of immunohistochemically stained slides. The prognostic impact of each marker was first assessed by recording its expression value relative to the median. A multimarker index was then developed to combine marker expression levels by counting for each patient the number of markers with high expression. The impact of the multimarker index on relapse-free survival (RFS) and overall survival (OS) was assessed using Kaplan–Meier analysis, and both univariate and multivariate Cox regression analyses.

Results: By Kaplan–Meier analysis, high multimarker expression scores were significantly predictive of RFS (P < 0.001) and OS (P < 0.001). Stepwise multivariate Cox regression analysis with backward elimination that included routine clinical and histologic prognostic factors revealed high multimarker expression scores and tumor thickness as the only factors significantly and independently predicting RFS and OS. Stepwise multivariate Cox regression analyses that also included treatment type and number of positive lymph nodes generated identical results for both RFS and OS. In the molecularly defined low-risk subgroup, patients treated with high-dose IFN had a significantly improved RFS compared with patients in the other two subgroups (P < 0.05).

Conclusions: These results validate the independent impact of combined expression levels of SPP1, RGS1, and NCOA3 on survival of melanoma in a prospectively collected cohort. Clin Cancer Res; 23(22); 6888–92. ©2017 AACR.
Huangqi Decoction Ameliorates Streptozotocin-Induced Rat Diabetic Nephropathy through Antioxidant and Regulation of the TGF-β/MAPK/PPAR-γ Signaling
Authors: Han Haiyan , Cao Aili , Wang Li , Guo Hengjiang , Zang Yingjun , Li Zezheng , Zhang Xuemei , Peng Wen
Published: August 2017

Background/Aims: Huangqi Decoction (HQD) has been traditionally used to treat diabetes mellitus in China. The present study was carried out to assess the protective effect of HQD on diabetic nephropathy (DN) using the streptozotocin-induced (STZ) diabetic rats. Methods: Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg) in male Wistar rats. 40 diabetic rats were divided into 5 groups: vehicle-treated (DN group), 0.45, 0.15, 0.05 g/kg HQD-treated diabetic group (HQD group) and 1 mg/kg rosiglitazone-treated diabetic group (RGZ group). 16 normal rats were randomly divided into 2 groups: vehicle-treated normal control group (NC) and 0.45 g/kg HQD-treated normal control group (NC+0.45 g/kg HQD). At the end of 8-week experiment, we measured changes of renal pathological morphology, function, antioxidant enzyme levels and the activation of TGF-β/PPAR-γ/MAPK signaling pathway. Results: After HQD treatment, renal function, including blood urea nitrogen (BUN), 24-h albuminuria and blood glucose level were improved significantly; meanwhile, impaired kidney redox balance was diminished in diabetic rats. The activation of TGF-β, phospho-JNK, phospho-p44/42, p47 and p42 phox was blocked and the decrease in PPAR-γ in diabetic rats was attenuated by treatment with HQD in a dose-dependent manner. Conclusion: These results suggest that HQD shows therapeutic efficacy in DN characterized by renal dysfunction and pathological changes through hypoglycemic and antioxidant effects.
IL-33 Attenuates Sepsis by Inhibiting IL-17 Receptor Signaling through Upregulation of SOCS3
Authors: Lv Ran , Zhao Jinning , Lei Min , Xiao Dongju , Yu Yijin , Xie Junran
Published: August 2017

Background/Aims: Sepsis is a systemic inflammatory response during infection. There are limited therapeutic options for sepsis patients. Interleukin (IL)-33 has been reported recently with a beneficial effect in mouse sepsis. Methods: In this study, we initiated a clinical study to measure serum levels of pro-inflammatory cytokines including IL-33 in sepsis patients. Next, we employed cecal ligation and puncture (CLP) to study the role of IL-33 during sepsis. To further dissect the molecular mechanism, we used in vivo knockout models and in vitro knockdown murine embryonic fibroblasts (MEFs) to investigate the cross-talk between IL-33 and IL-17 signaling, and to identify the potential downstream mediators. Results: IL-33 and IL-17 were upregulated in both clinical and experimental sepsis. In CLP, IL-33 (-/-) mice showed higher mortality rate, and IL-33 treatment improved the survival rate. Elevated proinflammatory cytokines in sepsis were related to IL-17 from γδT cells. IL-33 treatment suppressed production of these cytokines by targeting IL-17 signaling both in vivo and in vitro. Finally, IL-33 was shown to inhibit the IL-17 pathway via activating suppressor of cytokine signaling (SOCS)-3. Conclusion: Collectively, the results suggest that IL-33 plays a negative regulatory role in sepsis progression by inhibiting IL-17 pathway through activating SOCS3. This finding would inspire a new therapeutic strategy for treating sepsis.
First-in-Man Analysis of the Relationship Between Electrical Rotors From Noninvasive Panoramic Mapping and Atrial Fibrosis From Magnetic Resonance Imaging in Patients With Persistent Atrial Fibrillation
Authors: Sohns Christian , Lemes Christine , Metzner Andreas , Fink Thomas , Chmelevsky Mikhail , Maurer Tilman , Budanova Margarita , Solntsev Vladislav , Schulze Walther H.W. , Staab Wieland , Mathew Shibu , Heeger Christian , Reißmann Bruno , Kholmovski Eugene , Kivelitz Dietmar , Ouyang Feifan , Kuck Karl-Heinz
Published: August 2017

Background—

Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging can be used to evaluate characteristics of atrial fibrosis. The novel noninvasive epicardial and endocardial electrophysiology system (NEEES) allows for the identification of sources with rotor activity. This study describes a new technique to examine the relationship between rotors and LGE signal intensity in patients with persistent atrial fibrillation (PERS) scheduled for ablation.

Methods and Results—

Ten consecutive patients underwent pulmonary vein isolation for persistent atrial fibrillation. LGE CMR of both atria was performed, and NEEES-based analysis was conducted to identify rotors. For each mapping point, the intracardiac locations were transferred onto an individual CMR-derived 3-dimensional shell. This allowed the LGE signal intensity to be projected onto the anatomy from the NEEES analysis. NEEES analysis identified a total number of 410 electric rotors, 47.8% were located in the left atrium and 52.2% in the right atrium. Magnetic resonance imaging analysis was performed from 10 right atria and 10 left atria data sets, including 86 axial LGE CMR planes per atrium. The mean LGE burden for left atrium and right atrium was 23.9±1.6% and 15.9±1.8%, respectively. Statistical analysis demonstrated a lack of regional association between the extent of LGE signal intensity and the presence of rotors.

Conclusions—

This is the first study demonstrating that the presence of rotors based on NEEES analysis is not directly associated with the extent and anatomic location of LGE signal intensity from CMR. Further studies evaluating the relationship between rotors and fibrosis in patients with persistent atrial fibrillation are mandatory and may inform strategies to improve ablation outcome.
Multiple Gene Variants in Hypertrophic Cardiomyopathy in the Era of Next-Generation Sequencing
Authors: Burns Charlotte , Bagnall Richard D. , Lam Lien , Semsarian Christopher , Ingles Jodie
Published: August 2017

Background—

Multiple likely pathogenic/pathogenic (LP/P; ≥2) variants in patients with hypertrophic cardiomyopathy were described 10 years ago with a prevalence of 5%. We sought to re-examine the significance of multiple rare variants in patients with hypertrophic cardiomyopathy in the setting of comprehensive and targeted panels.

Methods and Results—

Of 758 hypertrophic cardiomyopathy probands, we included 382 with ≥45 cardiomyopathy genes screened. There were 224 (59%) with ≥1 rare variant (allele frequency ≤0.02%). Variants were analyzed using varying sized gene panels to represent comprehensive or targeted testing. Based on a 45-gene panel, 127 (33%) had a LP/P variant, 139 (36%) had variants of uncertain significance, and 66 (17%) had multiple rare variants. A targeted 8-gene panel yielded 125 (32%) LP/P variants, 52 (14%) variants of uncertain significance, and 14 (4%) had multiple rare variants. No proband had 2 LP/P variants. Including affected family members (total n=412), cluster-adjusted analyses identified a phenotype effect, with younger age (odds ratio, 0.95; 95% confidence interval, 0.92–0.98;
P
=0.004) and family history of sudden cardiac death (odds ratio, 3.5; 95% confidence interval, 1.3–9.9;
P
=0.02) significantly more likely in multiple versus single variant patients when considering an 8-gene panel but not larger panels. Those with multiple variants had worse event-free survival from all-cause death, cardiac transplantation, and cardiac arrest (log-rank
P
=0.008).

Conclusions—

No proband had multiple LP/P variants in contrast to previous reports. However, multiple rare variants regardless of classification were seen in 4% and contributed to earlier disease onset and cardiac events. Our findings support a cumulative variant hypothesis in hypertrophic cardiomyopathy.
Prognostic Value of Fractional Flow Reserve Measured Immediately After Drug-Eluting Stent Implantation
Authors: Piroth Zsolt , Toth Gabor G. , Tonino Pim A.L. , Barbato Emanuele , Aghlmandi Soheila , Curzen Nick , Rioufol Gilles , Pijls Nico H.J. , Fearon William F. , Jüni Peter , De Bruyne Bernard
Published: August 2017

Background—

The predictive value of fractional flow reserve (FFR) measured immediately after percutaneous coronary intervention (PCI) with drug-eluting stent placement has not been prospectively investigated. We investigated the potential of post-PCI FFR measurements to predict clinical outcome in patients from FAME 1 and 2 trials (Fractional Flow Reserve or Angiography for Multivessel Evaluation).

Methods and Results—

All patients of FAME 1 and FAME 2 who had post-PCI FFR measurement were included. The primary outcome was vessel-oriented composite end point at 2 years, defined as vessel-related cardiovascular death, vessel-related spontaneous myocardial infarction, and ischemia-driven target vessel revascularization. Eight hundred thirty-eight vessels in 639 patients were analyzed. Baseline FFR values did not differ between vessels with versus without vessel-oriented composite end point (0.66±0.11 versus 0.63±0.14, respectively;
P
=0.207). Post-PCI FFR was significantly lower in vessels with vessel-oriented composite end point (0.88±0.06 versus 0.90±0.06, respectively;
P
=0.019). Comparing the 2-year outcome of lower and upper tertiles of post-PCI FFR significant difference was found favoring upper tertile in terms of overall vessel-oriented composite end point (9.2% versus 3.8%, respectively; hazard ratio, 1.46; 95% confidence interval, 1.02–2.08;
P
=0.037) and target vessel revascularization (7.0% versus 2.4%, respectively; hazard ratio, 1.59; 95% confidence interval, 1.03–2.46;
P
=0.037). When adjusted to sex, hypertension, diabetes mellitus, target vessel, serial stenosis, and baseline percentage diameter stenosis, a strong trend was preserved in terms of target vessel revascularization (harzard ratio, 1.55; 95% confidence interval, 0.97–2.46;
P
=0.066), favoring the upper tertile. Post-PCI FFR of 0.92 was found to have the highest diagnostic accuracy; however, the positive likelihood ratio remained low (<1.4).

Conclusions—

A higher post-PCI FFR value is associated with a better vessel-related outcome. However, its predictive value is too low to advocate its use as a surrogate clinical end point.
Explaining Global Norms: The Case of Negotiations on Restraining Conventional Arms
Authors: Garcia Denise
Published: August 2017

International norms are central to world politics and they set boundaries for what is deemed commonly accepted behavior. The literature has not effectively explained the rise of new norms through negotiation and how actors from the Global South have played active roles, especially in the complex areas of developing security norms. This article argues that norm-making is not a unidirectional movement or phenomenon, but rather a highly circuitous process. The circuitous norm building model accounts for an increasing connectedness among domestic and regional/international levels in norm building in Global South and North countries.
New records of Palaeocorystoidea from the Iberian Peninsula and remarks on the taxonomic significance of the posterior margin of Cenomanocarcinus Van Straelen, 1936 and Hasaracancer Jux, 1971 (Decapoda; Brachyura; Cenomanocarcinidae)
Authors: OSSÓ ÀLEX
Published: August 2017

Two species of Cenomanocarcinus (Cenomanocarcinidae) from the late Albian and Turonian of Spain are reported herein, increasing the number of Iberian Cenomanocarcinus species. Likewise, Necrocarcinus woodwardii (Necrocarcinidae) is reported for the first time in the Iberian Peninsula and constitutes the southernmost record for the species. As well, the features of the posterior margin of the cenomanocarcinids Cenomanocarcinus and Hasaracancer, are reviewed and clarified.
A 1D Theoretical Analysis of Northerly Low-Level Jets over the Great Plains
Authors: Gebauer Joshua G. , Fedorovich Evgeni , Shapiro Alan
Published: August 2017

The forcing of northerly low-level jets over the eastward-sloped terrain of the U.S. Great Plains was studied using a one-dimensional (1D) nonstationary analytical model based on the Boussinesq-approximated equations of motion and thermal energy. For northerly low-level jets, the forcing from diurnal changes in surface heating of the sloped terrain (Holton mechanism) is out of phase with the nocturnal inertial oscillation resulting from the cessation of turbulent mixing at sunset (Blackadar mechanism), which results in weaker northerly nocturnal low-level jets when compared to southerly nocturnal low-levels jets with the same-magnitude background pressure gradient forcing. Because of the Blackadar and Holton mechanisms acting out of phase, nocturnal northerly low-level jets cannot solely explain the northerly low-level jet maximum over the Great Plains found in climatological studies. It is shown that negative buoyancy values over the eastward-sloped terrain enhance the low-level northerly geostrophic wind, which can cause low-level jetlike wind profiles that do not necessarily depend on the diurnal cycle. However, nocturnal northerly low-level jets primarily caused by an inertial oscillation still occur when daytime mixing is strong and buoyancy is small at sunset. These conditions are possible when strong capping inversions are present in the daytime convective boundary layer. The occurrence of both types of northerly low-level jets, those caused by negative buoyancy values over the sloped terrain and those driven by an inertial oscillation, better explains the findings of previous low-level jet climatologies.
A Grid-Refinement-Based Approach for Modeling the Convective Boundary Layer in the Gray Zone: A Pilot Study
Authors: Zhou Bowen , Xue Ming , Zhu Kefeng
Published: August 2017

The model gray zone refers to the range of grid spacings comparable to the dominant length scale of the flow. In the gray zone, the flow is partially resolved and partially subgrid scale (SGS). Neither ensemble-averaging-based parameterizations nor turbulence closures are appropriate for parameterizing the effects of SGS motions on the resolved flow. The gray zone of the convective boundary layer (CBL) is in the range of CBL depth, typically O(1) km. A new approach that seeks explicit resolution of the unstable surface layer through a nest layer of fine grid spacing is proposed to improve CBL parameterization in the gray zone. To provide the theoretical basis for the approach, a linear analytic model is presented, and one-way nested simulations are performed to investigate the dynamical coupling between the surface layer and the mixed layer. The analytic model shows that at the onset of thermal instability, the vertical and horizontal structures of the mixed layer are set by surface-layer forcings. The nested 3D simulations extend the findings from the analytic model and further reveal potential improvements in high-order statistics and resolved convective structures both including and extending above the nest region compared to the stand-alone gray-zone simulations. This study suggests that when the most energetic scales of CBL convection are resolved in the surface layer, the overall simulation of the CBL improves at gray-zone resolutions.
Reshaping the Antarctic Circumpolar Current via Antarctic Bottom Water Export
Authors: Stewart Andrew L. , Hogg Andrew McC.
Published: August 2017

Zonal momentum input into the Antarctic Circumpolar Current (ACC) by westerly winds is ultimately removed via topographic form stress induced by large bathymetric features that obstruct the path of the current. These bathymetric features also support the export of Antarctic Bottom Water (AABW) across the ACC via deep, geostrophically balanced, northward flows. These deep geostrophic currents modify the topographic form stress, implying that changes in AABW export will alter the ocean bottom pressure and require a rearrangement of the ACC in order to preserve its zonal momentum balance. A conceptual model of the ACC momentum balance is used to derive a relationship between the volume export of AABW and the shape of the sea surface across the ACC’s standing meanders. This prediction is tested using an idealized eddy-resolving ACC/Antarctic shelf channel model that includes both the upper and lower cells of the Southern Ocean meridional overturning circulation, using two different topographic configurations to obstruct the flow of the ACC. Eliminating AABW production leads to a shallowing of the sea surface elevation within the standing meander. To quantify this response, the authors introduce the “surface-induced topographic form stress,” the topographic form stress that would result from the shape of the sea surface if the ocean were barotropic. Eliminating AABW production also reduces the magnitude of the eddy kinetic energy generated downstream of the meander and the surface speed of the ACC within the meander. These findings raise the possibility that ongoing changes in AABW export may be detectable via satellite altimetry.
Daily Report Card Intervention and Attention Deficit Hyperactivity Disorder: A Meta-Analysis of Single-Case Studies
Authors: Pyle Kellina , Fabiano Gregory A.
Published: August 2017

The daily report card (DRC) is a commonly employed behavioral intervention for treating attention deficit hyperactivity disorder (ADHD) in schools. Much of the support for the DRC comes from single-case studies, which have traditionally received less attention than group studies. This lack of attention to single-case studies results in an incomplete review of the literature for this intervention. The present study utilized meta-analytic techniques to examine the DRC as used in single-case studies, with moderating variables explored through hierarchical linear modeling. Fourteen articles, including data on 40 single-subject cases, were included in the analyses. Effect sizes generally illustrated improvement with use of the DRC, with some differences across methods of effect size estimation. Study quality and class type moderated outcomes. Overall, the present study supports the use of the DRC with students who have ADHD, and it provides guidance for using single-case studies in meta-analyses of intervention effects.
Why Permit Telework? Exploring the Determinants of California City Governments’ Decisions to Permit Telework
Authors: Kwon Myungjung , Jeon So Hee
Published: August 2017

This study examines what factors influence a local government’s decision to permit its employees to telework. Drawing on insights from contingency theory, this study investigates how external forces influence California local governments’ decisions regarding whether or not to permit telework for their employees. To examine this question, this article uses the 2010 International City/County Management Association survey data and the 2009 American Communities Survey by the U.S. Census Bureau as its primary data sources. The findings show that various contextual factors such as municipal climate protection efforts, citizen participation, population diversity, political institutions, and support from state legislators play a significant role in a city government’s decision to permit telework for city employees.
The opioid epidemic
Authors: Chopra Nitin , Marasa Lauren H
Published: August 2017

Opioid use disorder is a growing epidemic, with an alarming number of associated deaths. In 2014, in the United States, 18,893 lethal overdoses were related to prescription opioids and 10,574 due to heroin. Despite the growing number of treatment options for substance use disorders, which are chronic, relapsing-remitting conditions, relapse rates remain as high as 91%. In the United States, 7.5 million children reside with at least one patient who abuses drugs or alcohol. Mothers are twice as likely to lose custody of their children. They have higher rates of comorbid abuse and psychopathology and limited social supports. Child service agencies, commonly involved in these scenarios, are often pressured to find permanent placement for children, within an expedited timeframe, inconsistent with the need for sufficient time for recovery and goals of family inclusion and unity. We present the complicated case of a 25-year-old woman with a history of opioid use disorder and depression, who, after being in and out of treatment programs for years, had a lethal overdose. She had a significant family history of addiction and had lost custody of her children. This challenging, but common presentation draws attention to challenges in providing treatment during this opioid epidemic.