bluuebunny/crossref_metadata_2025 huggingface dataset:
Run‐time calibration scheme for the implementation of a robust field‐programmable gate array–based time‐to‐digital converter
Authors: Chen Yuan‐Ho
Published: September 2018

In this study, we propose a robust field‐programmable gate array (FPGA)–based time‐to‐digital converter (TDC) with run‐time calibration. A code density test was used for differential nonlinearity (DNL) calibration to deal with nonuniformity in delay cells. The proposed calibration scheme is implemented as a four‐step finite state machine (FSM) for run‐time calibration. We implemented the TDC with the proposed run‐time calibration circuit on the Xilinx 65‐nm FPGA platform. This improved the DNL and integral nonlinearity (INL) values over those obtained using a TDC without run‐time calibration circuit. The DNL and INL values at a time resolution of 46.875 picoseconds were [−0.68, 1.04] and [−4.27, 2.27] least significant bits, respectively. More than 30% DNL and INL improvements are achieved for the TDC with calibration circuit. The results obtained at temperatures of 27°C to approximately 70°C indicated that the proposed run‐time calibration circuit enhanced the capability of the FPGA‐based TDC against temperature effects. The FPGA‐based TDC with the proposed run‐time calibration FSM provides robust high‐resolution performance suited for a range of scientific applications.
Novel in situ Bi−Sb‐Film Electrodes for Trace Heavy Metal Analysis
Authors: Finšgar Matjaž , Petovar Barbara
Published: September 2018

This work reports on new in situ formed Bi−Sb‐film glassy carbon electrodes (Bi−SbFEs) with different Bi(III):Sb(III) mass concentration ratios (1 : 9, 2 : 8, 3 : 7, 4 : 6, 5 : 5, 6 : 4, 7 : 3, 8 : 2, 9 : 1) and at two different total mass concentrations of Bi(III) and Sb(III), i. e. 0.5 and 1.0 mg/L. The analytical performance of these Bi−SbFEs was compared with Bi‐film (BiFE) and Sb‐film (SbFE) electrodes in 0.1 M acetate buffer solution. All combinations of Bi−SbFEs were selective for Zn(II), Cd(II), and Pb(II) detection. Bi−SbFEs showed linear concentration ranges for Zn(II), Cd(II), and Pb(II) substantially wider than that for BiFE. Moreover, the method's sensitivities can be substantially improved by using different Bi−SbFEs compared with BiFE and SbFE. Most of the Bi−SbFE methods provided satisfactory recovery for Cd(II) determination, many of them also for Pb(II), whereas for Zn(II) only a few methods provided recovery values within the 80.0–120.0 % recovery range. The precision of different Bi−SbFEs were satisfactory for Pb(II) and Cd(II) with an RSD lower than 20.0 %. Accumulation time optimisation resulted in lower LOD and LOQ, higher sensitivity. Finally, electrochemical impedance spectroscopy was employed for the first time to characterise the electroanalytical behaviour of an SbFE. The latter analysis was employed to compare the electrode's properties with pure BiFE and pure GCE, and to show when the system is under a kinetic‐ and/or diffusion‐controlled process.
Development of a multi‐layered skin simulant for burn injury evaluation of protective fabrics exposed to low radiant heat
Authors: Zhai Lina , Spano Fabrizio , Li Jun , Rossi René M.
Published: September 2018

To simulate temperature rise of human skin and to predict burn injury during radiant heat exposure, the traditional method is to use a sensor to simulate skin surface and use a numerical model to simulate heat transfer in inner skin. However, the numerical models of skin burns are based on few experimental data of nude skin and some simplifications of human skin characteristics. In this study, a new multi‐layered skin simulant is presented for low radiant heat exposures up to 15 kW/m2. The skin simulant has implanted thermocouples into layered polydimethylsiloxane (PDMS) materials with controlled thermal properties and thicknesses of the skin layers. The multi‐layered skin simulant developed in this study has a good reproducibility for temperature measurements with similar temperature rise profiles compared with human skin except at skin surface. For burn injury prediction, the results of our PDMS skin model can be linearly corrected using ASTM model as a reference. Our developed skin simulant provides an advanced method to directly simulate the heat transfer inside human skin in a multi‐layered structure rather than using the combined physical sensor‐numerical model in the traditional way.
Seasonality study of essential oil from leaves of Cymbopogon densiflorus and nanoemulsion development with antioxidant activity
Authors: Seibert Janaína Brandão , Rodrigues Ivanildes Vasconcelos , Carneiro Simone Pinto , Amparo Tatiane Roquete , Lanza Juliane Sousa , Frézard Frédéric Jean G. , de Souza Gustavo Henrique Bianco , Santos Orlando David Henrique dos
Published: September 2018

The development of formulations that maintain the biological and physical chemistry properties of essential oils is an important choice when they are used as an active ingredient. This study aimed to characterize the essential oil from leaves of Cymbopogon densiflorus and evaluate the antioxidant activity of the oil, and to produce a nanoemulsion formulation containing it. The essential oil was obtained by hydrodistillation, and seasonality was analysed every 2 months by gas chromatography–mass spectrometry, showing that more than 90% of the composition was maintained for the whole period and that the major compounds were trans‐p‐menta‐2,8‐dien‐1‐ol, cis‐p‐menta‐2,8‐dien‐1‐ol, trans‐p‐menta‐1(7),8‐dien‐2‐ol, cis‐piperitol, and cis‐p‐menta‐1(7),8‐dien‐2‐ol. Stable nanoemulsions were prepared by phase inversion method encapsulating the essential oil. The antioxidant activity was evaluated by 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) free radical scavenging and 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulphonic acid (ABTS) methods. In the first test, free and nanoemulsified essential oil showed half‐maximal inhibitory concentration (IC50) values equivalent to 14.689 and 3.692 mg mL−1, respectively. In the second test, these values were 0.567 and 0.43 mg mL−1. The development of nanoemulsion‐based essential oil from leaves of C. densiflorus was viable, and the formulated oil was able to reproduce the antioxidant activity at a concentration four times lower than that of the pure essential oil.
Ventral prefrontal cortex and emotion regulation in aging: A case for utilizing transcranial magnetic stimulation
Authors: Kim Joseph U. , Weisenbach Sara L. , Zald David H.
Published: September 2018

Objectives

The ventrolateral prefrontal cortex (vlPFC) has been speculated to play an important role in complex processes that allow emotional factors to influence human cognition. Accumulating evidence from human neuroimaging studies, in conjunction with studies of patients with lesions and animal models, shed light on the role of the vlPFC in emotion regulation (ER). This review aims to discuss and integrate recent findings related to vlPFC's role in ER in the context of aging, drawing from diverse sources, and suggest future directions for research utilizing transcranial magnetic stimulation (TMS).

Methods/Design

We summarize findings from the existing literature investigating the neural basis of frontal‐lobe mediated ER and then highlight major findings from recent studies directly comparing healthy younger and older adult groups. We conclude by pointing to unaddressed questions worth pursuing in future research.

Results and Discussion

We propose future research directions utilizing TMS to answer key unaddressed questions. Moreover, we discuss the potential advantages, challenges, and limitations of using TMS as a complement to the existing neuroimaging methods in ER.
A tail of two sides: Artificially doubled false positive rates in neuroimaging due to the sidedness choice with t‐tests
Authors: Chen Gang , Cox Robert W. , Glen Daniel R. , Rajendra Justin K. , Reynolds Richard C. , Taylor Paul A.
Published: September 2018

One‐sided t‐tests are widely used in neuroimaging data analysis. While such a test may be applicable when investigating specific regions and prior information about directionality is present, we argue here that it is often mis‐applied, with severe consequences for false positive rate (FPR) control. Conceptually, a pair of one‐sided t‐tests conducted in tandem (e.g., to test separately for both positive and negative effects), effectively amounts to a two‐sided t‐test. However, replacing the two‐sided test with a pair of one‐sided tests without multiple comparisons correction essentially doubles the intended FPR of statements made about the same study; that is, the actual family‐wise error (FWE) of results at the whole brain level would be 10% instead of the 5% intended by the researcher. Therefore, we strongly recommend that, unless otherwise explicitly justified, two‐sided t‐tests be applied instead of two simultaneous one‐sided t‐tests.
Angiopoietin‐2 Promotes Pathological Angiogenesis and Is a Therapeutic Target in Murine Nonalcoholic Fatty Liver Disease
Authors: Lefere Sander , Van de Velde Frederique , Hoorens Anne , Raevens Sarah , Van Campenhout Sanne , Vandierendonck Astrid , Neyt Sara , Vandeghinste Bert , Vanhove Christian , Debbaut Charlotte , Verhelst Xavier , Van Dorpe Jo , Van Steenkiste Christophe , Casteleyn Christophe , Lapauw Bruno , Van Vlierberghe Hans , Geerts Anja , Devisscher Lindsey
Published: September 2018

Angiogenesis contributes to the development of nonalcoholic steatohepatitis (NASH) and promotes inflammation, fibrosis, and progression to hepatocellular carcinoma (HCC). Angiopoietin‐2 (Ang‐2) is a key regulator of angiogenesis. We aimed to investigate the role of Ang‐2 and its potential as a therapeutic target in NASH using human samples, in vivo mouse models, and in vitro assays. Serum Ang‐2 levels were determined in 104 obese patients undergoing bariatric surgery and concomitant liver biopsy. The effect of the Ang‐2/Tie2 receptor inhibiting peptibody L1‐10 was evaluated in the methionine‐choline deficient (MCD) and streptozotocin‐western diet nonalcoholic fatty liver disease mouse models, and in vitro on endothelial cells and bone marrow–derived macrophages. The hepatic vasculature was visualized with µCT scans and scanning electron microscopy of vascular casts. Serum Ang‐2 levels were increased in patients with histological NASH compared with patients with simple steatosis and correlated with hepatic CD34 immunoreactivity as a marker of hepatic angiogenesis. Serum and hepatic Ang‐2 levels were similarly increased in mice with steatohepatitis. Both preventive and therapeutic L1‐10 treatment reduced hepatocyte ballooning and fibrosis in MCD diet‐fed mice and was associated with reduced hepatic angiogenesis and normalization of the vascular micro‐architecture. Liver‐isolated endothelial cells and monocytes from MCD‐fed L1‐10–treated mice showed reduced expression of leukocyte adhesion and inflammatory markers, respectively, compared with cells from untreated MCD diet‐fed mice. In the streptozotocin‐western diet model, therapeutic Ang‐2 inhibition was able to reverse NASH and attenuate HCC progression. In vitro, L1‐10 treatment mitigated increased cytokine production in lipopolysaccharide‐stimulated endothelial cells but not in macrophages. Conclusion: Our findings provide evidence for Ang‐2 inhibition as a therapeutic strategy to target pathological angiogenesis in NASH.
Prohibitin 1 Acts As a Negative Regulator of Wingless/Integrated‐Beta‐Catenin Signaling in Murine Liver and Human Liver Cancer Cells
Authors: Mavila Nirmala , Tang Yuanyuan , Berlind Joshua , Ramani Komal , Wang Jiaohong , Mato José M. , Lu Shelly C.
Published: September 2018

Prohibitin1 (PHB1) is a mitochondrial chaperone with diverse functions that include cell proliferation, apoptosis, and mitochondrial homoeostasis. Liver‐specific Phb1 knockout (KO) mice develop spontaneous injury and hepatocellular carcinoma (HCC). Our previous work demonstrated that PHB1 negatively regulates the H19‐insulin‐like growth factor 2 (IGF2)‐H19‐IGF2 axis signaling pathway and E‐box activity in hepatocytes and HCC cells. Phb1 KO livers exhibited increased expression of multiple wingless/integrated (WNT) target genes compared to control littermates. Therefore, we hypothesized that PHB1 is a negative regulator of WNT‐beta‐catenin signaling in the liver. Analysis of livers from Phb1 KO mice demonstrated an activation of the WNT‐beta‐catenin pathway as determined by phosphorylation of glycogen synthase kinase 3 (GSK3)betaserine [Ser]9 and protein kinase B (AKT)Ser473. Phb1 KO livers showed increased messenger RNA (mRNA) levels of multiple WNT ligands, with Wnt7a (79‐fold), Wnt10a (12‐fold), and Wnt16 (48‐fold) being most highly overexpressed compared to control littermates. Subcellular fractionation of liver cells from Phb1 KO mice indicated that hepatocytes are the main source of WNT ligands. Immunostaining and cellular colocalization analysis of Phb1 KO livers demonstrated expression of WNT7a, WNT10a, and WNT16 in hepatocytes. Chromatin immunoprecipitation revealed increased binding of transcription factor E2F1 (E2F1) to the Wnt10a promoter in Phb1 KO livers and WNT9A in HepG2 cells. PHB1 silencing in HepG2 cells activated WNT signaling, whereas its overexpression caused inactivation of this pathway. PHB1 silencing in HepG2 cells induced the expression of multiple WNT ligands of which WNT9A induction was partly regulated through E2F1. Conclusion: PHB1 acts as a negative regulator of WNT signaling, and its down‐regulation causes the induction of multiple WNT ligands and downstream activation of canonical WNT‐beta‐catenin signaling in murine liver and human HCC cells, in part through E2F1.
Patient satisfaction with primary healthcare services in Lebanon
Authors: Hemadeh Randa , Hammoud Rawan , Kdouh Ola , Jaber Tarek , Ammar Lea
Published: September 2018

Background

Reorienting the model of care towards preventive services is integral to successfully move towards a people‐centered healthcare system. Patient satisfaction is an essential component of people‐centered care and an important quality of care indicator. In its efforts to strengthen primary healthcare, the Ministry of Public Health in Lebanon assessed patient satisfaction with services offered at primary healthcare centers (PHCCs) and explored the relationship between patient satisfaction and patient characteristics and accreditation.

Methodology

The study followed a cross‐sectional design. A survey was administered through phone calls with 1313 patients receiving services as part of a benefits package provided by 59 PHCCs. The survey collected data on patients' sociodemographic characteristics, perceptions, and satisfaction.

Results

Overall, 96.66% of surveyed patients reported being either satisfied (60.23%) or very satisfied (36.43%) with the services provided at the PHCCs. Patients' perceptions of patient‐provider communication, healthcare provider competency, and health education quality constituted strong predictors for satisfaction. However, facilities' accreditation status was not associated with satisfaction with PHC services.

Conclusion

Patient satisfaction with primary healthcare services in Lebanon was remarkably high. Findings highlighted the need for quality improvement particularly in health education and the alignment of accreditation standards with patient needs and expectations.
FcγR interaction is not required for effective anti‐PD‐L1 immunotherapy but can add additional benefit depending on the tumor model
Authors: Sow Heng Sheng , Benonisson Hreinn , Breukel Cor , Visser Remco , Verhagen Onno J.H.M. , Bentlage Arthur E.H. , Brouwers Conny , Claassens Jill W.C. , Linssen Margot M. , Camps Marcel , van Hall Thorbald , Ossendorp Ferry , Fransen Marieke F. , Vidarsson Gestur , Verbeek J. Sjef
Published: September 2018

Immunomodulatory antibodies blocking interactions of coinhibitory receptors to their ligands such as CTLA‐4, PD1 and PD‐L1 on immune cells have shown impressive therapeutic efficacy in clinical studies. The therapeutic effect of these antibodies is mainly mediated by reactivating antitumor T cell immune responses. Detailed analysis of anti‐CTLA4 antibody therapy revealed that an optimal therapeutic efficacy also requires binding to Fc receptors for IgG, FcγR, mediating depletion of intratumoral regulatory T cells. Here, we investigated the role of Fc binding in anti‐PD‐L1 antibody therapy in the MC38 C57BL/6 and CT26 BALB/c colon adenocarcinoma tumor models. In the MC38 tumor model, all IgG subclasses anti‐PD‐L1 showed similar therapeutic efficacy when compared to each other in either wild‐type mice or in mice deficient for all FcγR. In contrast, in the CT26 tumor model, anti‐PD‐L1 mIgG2a, the IgG subclass with the highest affinity for activating FcγR, showed stronger therapeutic efficacy than other IgG subclasses. This was associated with a reduction of a myeloid cell subset with high expression of PD‐L1 in the tumor microenvironment. This subclass preference for mIgG2a was lost in C57BL/6 × BALB/c F1 mice, indicating that the genetic background of the host may determine the additional clinical benefit of the high affinity antibody subclasses. Based on these data, we conclude that FcγR are not crucial for anti‐PD‐L1 antibody therapy but might play a role in some tumor models.
The flexibility of association between temporal concepts and physical space in the Japanese language
Authors: Mochizuki Masaya
Published: September 2018

Previous studies have indicated that temporal concepts such as the past and future are associated with horizontal (left–right) space. This association has been interpreted as reflecting left‐to‐right writing systems. The Japanese language, however, is written both horizontally and vertically and, when texts are presented vertically, the sequence of columns runs from right to left. This study examines whether the associations between time and space are changed by the direction of the character strings using a word categorization task. Consistent with previous studies, response times and error rates indicated left‐past and right‐future associations when participants read words presented horizontally. On the other hand, response times indicated the opposite (i.e., left‐future and right‐past associations) when participants read words presented vertically. These results suggest that temporal concepts are not associated with one's body or physical space in an inflexible manner, but rather the associations can flexibly change through experience.
Molecular analysis of HIF activation as a potential biomarker for adverse reaction to metal debris (ARMD) in tissue and blood samples
Authors: Nyga Agata , Hart Alister , Tetley Teresa D.
Published: September 2018

We aimed to find a biomarker for patients with adverse reaction to metal debris (ARMD) due to a metal‐on‐metal (MoM) hip implant. First, we compared molecular markers of hypoxia‐inducible factor (HIF) pathway activation (BNIP3, GLUT1, HO1, VEGF, and HIF1A) and inflammatory response (IL1B and COX2) in tissue from patients undergoing revision of MoM hip implant with tissue from patients undergoing primary hip replacement (PHR). Second, we compared blood levels of the above molecular markers and additional inflammatory markers: TNFA, IL18, CASPASE1, NFKB or IKB, and TLR1–4 mRNA in patients with non‐failed MoM hips. We report the presence of increased expression of HIF‐target genes in the periprosthetic tissue in MoM patients when compared to the PHR group. This suggests HIF pathway activation due to MoM debris and the potential of using HIF targets as a predictor of failure. Analysis of blood samples from nonoverlapping, nonfailed, MoM group showed significantly higher expression of COX2 mRNA and significant correlations between HIF1A and GLUT1 mRNA expressions, and between HIF1A mRNA and selection of inflammatory genes, including IL18, IKB, TLR1, and TLR4. HIF pathway activation in the periprosthetic tissue biopsies of patients with hip replacements may represent the first biomarker to identify early ARMD. Further studies investigating blood biomarkers could also prove beneficial in detecting ARMD that could lead to an early intervention and improved patient outcome after hip revision surgery. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1352–1362, 2019.
A dissecting aneurysm of interventricular septum resulting from congenital coronary artery fistula
Authors: Wu Qing , Jin Yanping , Zhou Lin , Liu Yongfang , Wu Daozhu
Published: September 2018

Rationale

Ventricular septal dissecting aneurysms are rarely caused by congenital coronary artery fistulas.

Patient concerns

We present a rare case of ventricular septal dissecting aneurysm that resulted from a congenital coronary artery fistula in a 41‐year‐old female patient with the complaint of chest pain.

Diagnosis

Ventricular septal dissecting aneurysm resulting from a right coronary artery fistula.

Interventions

The patient was advised to receive transcatheter interventional therapy in the department of cardiology.

Outcomes

It was difficult for the cardiac catheter to reach the orifice of fistula due to the long and circuitous nature of the right coronary artery, which ultimately resulted in abandoning interventional fistula occlusion therapy. The patient finally decided to undergo surgical treatment in Shanghai and the symptoms have been markedly improved after hemodynamic correction.

Lessons

The right coronary artery was the dominant vessel and the fistula was located in the distal part of the posterior descending branch of right coronary artery. Hence, transcatheter closure was appropriate; however, due to the fact that right coronary artery was too long and circuitous, the length of cardiac catheter was relatively insufficient. For this reason, a comprehensive and careful assessment before the operation is necessary.
Moth flame optimization based design of linear and circular antenna array for side lobe reduction
Authors: Das Avishek , Mandal D. , Ghoshal S.P. , Kar R.
Published: September 2018

This paper presents an accurate approach to design a symmetrical linear antenna array (LAA) and a non‐uniformly excited single ring circular antenna array (CAA) to improve the far‐field radiation characteristics. The far‐field radiation pattern is improved with lower side lobe level (SLL) which is essential for the reduction of interference in the entire side lobe regions. A recently proposed meta‐heuristic based optimization algorithm called moth flame optimization (MFO) is applied to determine the optimal sets of current excitation weights and the inter‐element spacing among the array elements to reduce the SLL. In this context, 10‐element and 16‐element LAA and 8‐element, 10‐element, and 12‐element CAA design examples are presented by optimizing the array parameters. The simulation results obtained by using MFO algorithm based approach yield a considerable improvement in SLL and some marked improvement of half power beam width with respect to the uniform array pattern and those of the recently reported literature.
Cover Image, Volume 98, Issue 14
Authors: Zhang Xiumin , Wang Min , Wang Rong , Ma Zhiyuan , Long Donglei , Mao Hongxiang , Wen Jiangnan , Bernard Lukuyu A , Beauchemin Karen A , Tan Zhiliang
Published: September 2018

The cover image, by Xiumin Zhang et al., is based on the Research Article Urea plus nitrate pretreatment of rice and wheat straws enhances degradation and reduces methane production in in vitro ruminal culture, DOI: 10.1002/jsfa.9056.

image
FOLFIRINOX and radiotherapy for locally advanced pancreatic cancer: A cohort study
Authors: Suker Mustafa , Nuyttens Joost J. , Groot Koerkamp Bas , Eskens Ferry A. L. M. , van Eijck Casper H. J.
Published: September 2018

Introduction

One‐third of the patients with pancreatic cancer present with locally advanced unresectable pancreatic cancer (LAPC). Our aim was to determine survival outcomes and toxicity after FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) followed by radiotherapy (RT) in biopsy‐proven patients with LAPC.

Methods

We analysed a cohort of biopsy‐proven patients with LAPC, who were eligible for induction FOLFIRINOX (eight cycles) and subsequent RT (30 fractions, 60 Gy). Eligible patients underwent a staging laparoscopy to detect occult metastasis before the treatment. The primary outcome was overall survival (OS), and secondary outcomes were progression‐free survival (PFS), treatment‐related toxicity, and resection rate.

Results

Forty‐four patients were diagnosed with biopsy‐proven LAPC. Twenty‐five patients were eligible and all underwent staging laparoscopy before the treatment. In three (12%) patients occult metastases were found. Twenty‐two patients started induction FOLFIRINOX, 17 (77%) completed all cycles. Seventeen (77%) patients were treated with subsequent RT, with 16 (94%) receiving the full dosage. Three (14%) patients underwent a radical resection after the treatment. Median OS was 15.4 months (95% confidence interval [CI], 10.0‐20.7), median PFS was 11 months (95% CI, 7.7‐14.4).

Conclusions

Median OS after FOLFIRINOX and RT was 15 months in patients with LAPC. Toxicity remains severe, however, most patients completed all eight scheduled cycles of FOLFIRINOX and RT.
Bone tumor resection guide using three‐dimensional printing for limb salvage surgery
Authors: Park Jong Woong , Kang Hyun Guy , Lim Kwun Mook , Park Dae Woo , Kim June Hyuk , Kim Han Soo
Published: September 2018

Background and Objectives

The three‐dimensional (3D)‐printed bone tumor resection guide can be personalized for a specific patient and utilized for bone tumor surgery. It is noninvasive, eidetic, and easy to use. We aimed to categorize the use of the 3D‐printed guide and establish in vivo accuracy data.

Methods

We retrospectively reviewed 12 patients, who underwent limb salvage surgery using the 3D‐printed guide at a single institution. To confirm the achievement of a safe bone margin, we compared the actual and planned distances between the cutting surface and tumor, which were reported in the final pathological report and measured from the same virtual cutting plane using graphical data of the cutting guide design, respectively.

Results

The use of the 3D‐printed guide was categorized as follows: (a) wide excision only, (b) wide excision and biological reconstruction with a structural bone allograft shaped in accordance with the 3D‐printed guide, and (c) wide excision and reconstruction with a 3D‐printed personalized implant. The maximal cutting error was 3 mm.

Conclusions

The 3D‐printed resection guide is easy to use and shows promise in the field of orthopedic oncology, with its application in bone tumor resection and reconstruction with a structural bone allograft or 3D‐printed implant.
Supermicrosurgery: Principles and applications
Authors: Hong Joon Pio (Jp) , Song Sinyoung , Suh Hyun Suk Peter
Published: September 2018

Supermicrosurgery is defined as microsurgery in less than 0.8 mm vessels. It is an evolved form of microsurgery but with the same principle: (1) enhanced working environment including microscopes and finer instruments; (2) detailed preoperative evaluation and planning; (3) supermicrosurgical technique; and (4) postoperative care. Supermicrosurgery now provides reconstructive solutions to address lymphedema, distal finger amputations, allows minimal invasive reconstruction using a perforator to perforator approach, and will eventually allow targeted customized reconstruction.
Early recurrence of well‐differentiated (G1) neuroendocrine liver metastasis after curative‐intent surgery: Risk factors and outcome
Authors: Xiang Jun‐Xi , Zhang Xu‐Feng , Weiss Matthew , Aldrighetti Luca , Poultsides George A. , Bauer Todd W. , Fields Ryan C. , Maithel Shishir Kumar , Marques Hugo P. , Pawlik Timothy M.
Published: September 2018

Background

The objective of the current study was to identify the risk of early vs late recurrence of well‐differentiated (G1) neuroendocrine liver metastasis (NELM) after curative‐intent resection.

Methods

Patients who underwent curative‐intent resection for well‐differentiated NELM were identified from a multi‐institutional database. Clinicopathological details, as well as the long‐term overall (OS) and recurrence free survival (RFS) were obtained and compared. The optimal cutoff value to differentiate early and late recurrence was determined to be 1 year based on trend curve analysis.

Results

Among the 548 patients undergoing curative resection for NELM, 162 patients had a well‐differentiated NELM. After a median follow‐up of 69 months, 59 (36.4%) patients had tumor recurrence; 23 (39.0%) patients recurred within 1 year (early recurrence) after surgery, while 36 (61.0%) recurred after 1 year (late recurrence). Early recurrence was associated with worse outcome vs late recurrence (5‐year OS, 72.4% vs 92.0%; P = 0.020) and no recurrence (5‐year OS, 72.4% vs 100.0%;
P < 0.001). In addition, postrecurrence survival was worse within 36 months after recurrence among patients who recurred early compared with patients who recurred late (survival after recurrence at 36 months: early recurrence, 71.6% vs late recurrence, 91.4%;
P = 0.047), although survival was comparable at 60 months (early recurrence, 71.6% vs late recurrence, 70.0%;
P = 0.304). On multivariable analysis, nonfunctional neuroendocrine tumors (hazard ratio [HR], 4.4; 95% confidence interval [CI], 1.2‐16.7;
P = 0.029) and lymph node metastasis (HR, 3.6; 95% CI, 1.1‐11.1;
P = 0.028) were independent risk factors for early recurrence, whereas lymph node metastasis (HR, 3.0; 95% CI, 1.2‐7.8;
P = 0.020) and R1 resection (HR, 3.9; 95% CI, 1.4‐10.5;
P = 0.008) were independently associated with late recurrence.

Conclusions

Roughly, one‐third of patients with well‐differentiated NELM experienced a recurrence following curative‐intent surgery. Among patients who recurred, two out of five patients recurred within 1 year after surgery. Early recurrence of well‐differentiated NELM was associated with the hormone functional status and lymph node metastasis.
Impact of specific modes of circumferential resection margin involvement in rectal cancer local recurrence: A retrospective study
Authors: Suárez Javier , Goicoetxea Andrea , Gómez M.L. , Jiménez G. , Llanos M.C. , Jiménez J. , Montes B. , de Miguel M.
Published: September 2018

Purpose

To compare the local recurrence rate and overall survival between patients with circumferential resection margin (CRM) involvement by direct tumor spread and by a tumor within a lymph node.

Methods

A total of 776 patients diagnosed with rectal cancer underwent rectal resection. Patients with CRM involvement by direct tumor spread were named group A. CRM involvement by tumor within a lymph node formed group B. Patient data, including sex, age, pT, pN, stage I‐III versus IV, neoadjuvant radiotherapy, adjuvant chemotherapy, carcinoembryonic antigen, primary tumor location, lymph node retrieval, and need for abdominoperineal resection, were compared between both groups.

Results

In total, 10.5% of the patients had CRM involvement. Of these, in 57 cases (7.3%), it was by direct tumor spread and in 19 cases (2.4%) by tumor within a lymph node. Other types of CRM involvement were found in six patients. With a mean follow‐up of 32.9 months, 18 patients from group A (31.5%) and one patient from group B (5.2%) suffered a local recurrence. Local recurrence‐free survival was significantly higher in patients from group B (P = 0.049).

Patients in stage I‐III (P = 0.037) and from group B (
P = 0.049) had better overall survival.

Conclusion

Patients with CRM involvement by tumor within a lymph node have a low risk of local recurrence and better overall survival than patients with CRM involvement by direct tumor spread.
High nuclear Survivin expression as a poor prognostic marker in pancreatic ductal adenocarcinoma
Authors: Zhou Li , Lu Jun , Liang Zhi‐Yong , Zhou Wei‐Xun , Yuan Da , Li Bing‐Qi , You Lei , Guo Jun‐Chao , Zhao Yu‐Pei
Published: September 2018

Background

Survivin, one of the key regulators of mitosis and apoptosis, has long been well recognized to play important biological roles in many neoplasms, including pancreatic ductal adenocarcinoma (PDAC). However, its prognostic value in PDAC remains controversial.

Patients and Methods

Nuclear expression of Survivin was detected, using tissue microarray‐based immunohistochemistry, in paired‐tumor and nontumor samples from 306 patients with radically resected PDAC. The staining H scores were further correlated with clinicopathologic features and disease‐specific survival (DSS).

Results

Nuclear Survivin expression was much higher in tumor than in nontumor tissues (P < 0.001). No significant association between tumoral Survivin expression and clinicopathologic variables was found. For prognosis, high Survivin expression was associated with shortened DSS in all eligible patients and four subgroups, that is, male and nondiabetic patients as well as those with head‐located and G1‐2 tumors, shown by univariate analyses. In addition, a statistically marginal significance was revealed in eight subgroups. For the entire cohort and two subgroups, nuclear Survivin expression was also multivariate identified as an independent predictor for DSS. For patients with G1‐2 tumors, it was the single prognostic marker.

Conclusion

Our data suggest an association between high nuclear Survivin expression and poor prognosis in PDAC. However, further confirmation might be necessary.
Equipping an underwater glider with a new echosounder to explore ocean ecosystems
Authors: Benoit‐Bird K. J. , Patrick Welch T. , Waluk C. M. , Barth J. A. , Wangen I. , McGill P. , Okuda C. , Hollinger G. A. , Sato M. , McCammon S.
Published: September 2018

Mobile autonomous platforms are revolutionizing our understanding of ocean systems by providing a solution for the four‐dimensional observation problem faced in the ocean. The sensors commonly used in autonomous platforms, however, leave a large gap in our observations of the food chain between primary producers and large predators. Echosounders have the potential to fill this gap. Here, we present details of a new, commercially available quantitative scientific echosounder specifically designed to meet the challenges of deployment in autonomous platforms, including those of relatively low power and small size, while providing data comparable to systems deployed from ships. We detail the integration into a Slocum glider of this echosounder and both upward‐ and downward‐looking transducers to provide guidance for those considering similar efforts. We also identify key features of the system and the challenges that must be overcome to ensure collection of high‐quality data. The most important feature of the integrated glider is that it carries instruments capable of providing depth profiles of bio‐optical and environmental variables that are synoptic with the echosounder data. On a dive‐by‐dive basis, we can use these co‐located data to quantify relationships between the acoustic, bio‐optical, and environmental data. A field deployment of the echosounder‐equipped glider elucidated the processes driving diel migration in zooplankton and nekton in Monterey Bay, emphasizing the novel science questions that can be addressed using contemporary means of accessing the sea and new, integrated tools for describing the habitat and its inhabitants.
Living Donor Liver Transplantation Using Selected Grafts With 2 Bile Ducts Compared With 1 Bile Duct Does Not Impact Patient Outcome
Authors: Kollmann Dagmar , Goldaracena Nicolas , Sapisochin Gonzalo , Linares Ivan , Selzner Nazia , Hansen Bettina E. , Bhat Mamatha , Cattral Mark S. , Greig Paul D. , Lilly Les , McGilvray Ian D. , Ghanekar Anand , Grant David R. , Selzner Markus
Published: September 2018

The outcome after living donor liver transplantation (LDLT) using grafts with multiple bile ducts (BDs) remains unclear. We analyzed 510 patients who received an adult‐to‐adult right lobe LDLT between 2000 and 2015 and compared outcome parameters of those receiving grafts with 2 BDs (n = 169) with patients receiving grafts with 1 BD (n = 320). Additionally, patients receiving a graft with 3 BDs (n = 21) were analyzed. Demographic variables and disease severity were similar between the groups. Roux‐en‐Y reconstruction was significantly more common in the 2 BD group (77% versus 38%; P < 0.001) compared with the 1 BD group. No difference was found in biliary complication rates within 1 year after LDLT (1 BD versus 2 BD groups, 18% versus 21%, respectively; P = 0.46). In the 2 BD group, 82/169 (48.5%) patients were reconstructed with 2 anastomoses. The number of anastomoses did not negatively impact biliary complication rates. Recipients’ major complication rate (Clavien ≥ 3b) was similar between both groups (1 BD versus 2 BD groups, 21% versus 24%, respectively; P = 0.36). Furthermore, no difference could be found between the 1 BD, the 2 BD, and the 3 BD groups in the frequency of developing biliary complications within 1 year (18%, 21%, 14%, respectively; P = 0.64), BD strictures (15%, 15%, 5%, respectively; P = 0.42), or BD leaks (10%, 11%, 10%, respectively; P = 0.98). In addition, the 1‐year (90% versus 91%), 5‐year (82% versus 77%), and 10‐year (70% versus 66%) graft survival rates as well as the 1‐year (92% versus 93%), 5‐year (84% versus 80%), and 10‐year (75% versus 76%) patient survival rates were comparable between the 1 BD and the 2 BD groups (P = 0.41 and P = 0.54, respectively). In conclusion, this study demonstrates that selected living donor grafts with 2 BDs can be used safely without negatively impacting biliary complication rates and graft or patient survival rates.
A longitudinal investigation of customer cooperation in services: The role of appraisal of cooperation behaviors
Authors: Zhang Junzhou , Tang Chuanyi , Guo Lin , Xu Hangjun
Published: September 2018

The customer cooperation level in behavior change programs (e.g., weight‐loss programs, alcohol‐quitting programs, and debt management programs) is low, which leads to a low program success rate. To address this problem, this study draws on the goal‐driven behavior theory and develops a theoretical framework to explain how goal intention, and behavioral appraisal processes influence the subsequent cooperation behaviors, which, in turn, influence customers’ goal attainment. A two‐wave longitudinal survey was used to test the theoretical model. Results show that customers’ appraisals of the cooperation behaviors play a vital role in influencing customers’ cooperation behaviors. Three appraisal factors (self‐efficacy, instrumental belief, and affect toward cooperation behaviors) fully mediate the relationship between goal intention and cooperation. Customer cooperation contributes directly to goal attainment. Both theoretical and managerial implications are provided.
The underdog trap: The moderating role of transgression type in forgiving underdog brands
Authors: Kim Yaeri , Park Kiwan , Stacey Lee Seojin
Published: September 2018

This study aims to investigate the interactive effects of brand biography and brand transgression type on consumers’ forgiveness intention. Brand transgression is categorized as relational or nonrelational, with the former (compared to the latter) seriously undermining consumers’ high identification with underdog brands. Across four experimental studies in which transgression type is manipulated in three different ways, it is confirmed that when facing nonrelational transgressions, participants show greater forgiveness intention for underdog than for top‐dog brands. However, when facing relational transgressions, they do not show increased forgiveness intention for underdog brands compared to top‐dog brands. Moreover, perceived anger mediates the interaction effect between brand biography and brand transgression type on forgiveness intention. The theoretical and managerial implications of the findings are discussed.
The role of institutional and regulatory adjustments on Foreign Direct Investment in the European Union area
Authors: Desli Evangelia
Published: September 2018

The paper examines the impact on Foreign Direct Investment inflows of a series of institutional and regulatory adjustments that were implemented by or imposed upon countries in the European Union (EU) following the start of the financial crisis. The study of 28 EU members over a period that includes the economic crisis era (1995–2015) provides evidence that these adjustments (government efficiency, quality of regulation, cost competitiveness, and reduction of corruption) matter only for the countries that are more financially robust but have no influence for the countries that received aid, and macroeconomic factors such as market size and trade openness are important.
Fatigue in Parkinson's disease: A systematic review and meta‐analysis
Authors: Siciliano Mattia , Trojano Luigi , Santangelo Gabriella , De Micco Rosa , Tedeschi Gioacchino , Tessitore Alessandro
Published: September 2018

We conducted a systematic review and meta‐analysis aimed at establishing robust prevalence estimates and identifying clinical correlates of fatigue in PD. From 2,459 titles and abstracts, we selected 44 relevant studies (n = 7427 patients). Overall, the meta‐analysis showed a prevalence of fatigue of 50% in PD. This prevalence estimate, however, was significantly moderated by study heterogeneity in measurement scales and cut‐off thresholds. In contrast, demographic features, disease severity, cognitive impairment, and depression did not moderate prevalence estimates. Moreover, fatigue prevalence did not differ between de novo and treated PD patients. Compared to nonfatigued patients, fatigued patients had sligthly higher age (1.44 years), disease duration (0.93 years), l‐dopa equivalent daily dose (50.89 units), UPDRS‐III (4.99 points), and H & Y (0.33 points), as well as risk of comorbid depression (risk ratio = 1.89) and had a little lower MMSE score (–0.66 points). Fatigue was moderately associated with apathy (Hedges' g = 0.55), anxiety (Hedges' g = 0.67), daytime somnolence (Hedges' g = 0.43), sleep disturbances (Hedges' g = 0.66), and poorer quality of life (Hedges' g = 1.23). Our analyses suggest that fatigue is a frequent, independent nonmotor symptom in PD appearing early and persisting throughout the disease course, and that establishing uniform diagnostic criteria for PD‐related fatigue is critical. In addition, several nonmotor symptoms appear to be associated with fatigue and negatively impact quality of life. Pharmacological and nonpharmacological interventions targeting fatigue and associated symptoms may improve quality of life in patients with PD. © 2018 International Parkinson and Movement Disorder Society
Opicapone for the treatment of Parkinson's disease: A review of a new licensed medicine
Authors: Fabbri Margherita , Ferreira Joaquim J. , Lees Andrew , Stocchi Fabrizio , Poewe Werner , Tolosa Eduardo , Rascol Olivier
Published: September 2018

Catechol‐O‐methyl transferase inhibitors are currently used as first‐line add‐on therapy to levodopa for the treatment of end‐of‐dose motor fluctuations in Parkinson's disease patients, as they increase levodopa bioavailability. Several factors hamper the use of current available catechol‐O‐methyl transferase inhibitors, that is, the moderate efficacy and multiple dosing for entacapone and the risk of liver toxicity with tolcapone. Opicapone, a new long‐acting, peripherally selective, once‐daily catechol‐O‐methyl transferase inhibitor, was recently licensed in Europe. Two phase 3 double‐blind clinical trials demonstrated opicapone efficacy in reducing OFF time by an average of about 60 minutes daily compared with placebo, without increasing ON time with troublesome dyskinesias. These effects were also maintained during a subsequent open‐label extension consisting of 1‐year follow‐up. Opicapone showed a good safety profile. From June 2016, Opicapone received the approval for marketing authorization from the European Commission as adjunctive therapy to levodopa/DOPA decarboxylase inhibitors in patients with PD and end‐of‐dose motor fluctuations. We aimed to review the clinical pharmacological data of opicapone, summarize its clinical efficacy and safety issues, and discuss its potential role in the management of Parkinson's disease. © 2018 International Parkinson and Movement Disorder Society
Calculating and communicating ensemble‐based volcanic ash dosage and concentration risk for aviation
Authors: Prata Andrew T. , Dacre Helen F. , Irvine Emma A. , Mathieu Eric , Shine Keith P. , Clarkson Rory J.
Published: September 2018

During volcanic eruptions, aviation stakeholders require an assessment of the volcanic ash hazard. Operators and regulators are required to make fast decisions based on deterministic forecasts, which are subject to various sources of uncertainty. For a robust decision to be made, a measure of the uncertainty of the hazard should be considered, but this can lead to added complexity preventing fast decision‐making. A proof‐of‐concept risk‐matrix approach is presented that combines uncertainty estimation and volcanic ash hazard forecasting into a simple warning system for aviation. To demonstrate the methodology, an ensemble of 600 dispersion model simulations is used to characterize uncertainty (due to eruption source parameters, meteorology and internal model parameters) in ash dosages and concentrations for a hypothetical Icelandic eruption. To simulate aircraft encounters with volcanic ash, trans‐Atlantic air routes between New York (JFK) and London (LHR) are generated using time‐optimal routing software. This approach was developed in collaboration with operators, regulators and engine manufacturers; it demonstrates how an assessment of ash dosage and concentration risk can be used to make fast and robust flight‐planning decisions, even when the model uncertainty spans several orders of magnitude. The results highlight the benefit of using an ensemble over a deterministic forecast and a new method for visualizing dosage risk along flight paths. The risk‐matrix approach is applicable to other aviation hazards such as sulphur dioxide (SO2) dosages, desert dust, aircraft icing and clear‐air turbulence, and is expected to aid flight‐planning decisions by improving the communication of ensemble‐based forecasts to aviation.
Controllability of hybrid PDE‐ODE systems with structural instability and applications to mathematical models on intermittent hormonal therapy for prostate cancer
Authors: Hiruko Kurumi , Okabe Shinya
Published: September 2018

Several mathematical models on intermittent androgen suppression (IAS) therapy for prostate cancer are classified into hybrid PDE‐ODE system with structural instability. The purpose of this paper is to give a unified strategy to prove the controllability of the mathematical models on the IAS therapy. For this aim, we prove that (1) a generalized hybrid PDE‐ODE system is controllable for any initial data and (2) the result given by (1) is applicable to the mathematical models on the IAS therapy. Finally, we conclude that the mathematical models on the IAS therapy for prostate cancer are controllable for any initial data.
Time‐dependent photon statistics in variable media
Authors: Kryuchkov Sergey I. , Suazo Erwin , Suslov Sergei K.
Published: September 2018

We find explicit solutions of the Heisenberg equations of motion for a quadratic Hamiltonian, which describes a generic model of variable media in the case of multiparameter squeezed input photon configuration. The corresponding probability amplitudes and photon statistics are also derived in the Schrödinger picture in an abstract operator setting of the quantum electrodynamics; a comparison discussion is made in Heisenberg's picture as well. The unitary transformation and an extension of the squeeze/evolution operator are introduced formally. The time‐dependent photon probability amplitudes with respect to the Fock basis are indeed derived in an operator form. Further, explicit expressions for the matrix elements of the displacement and squeeze operators are derived in terms of hypergeometric functions and solutions of a certain Ermakov‐type system. In the Supporting Information, we provide a computer algebra verification of the derivation of the Ermakov‐system and of the solutions of the Heisenberg equations.