bluuebunny/crossref_metadata_2025 huggingface dataset:
Ataluren Pharmacokinetics in Healthy Japanese and Caucasian Subjects
Authors: Kong Ronald , Laskin Oscar L. , Kaushik Diksha , Jin Fengbin , Ma Jiyuan , McIntosh Joseph , Souza Marcio , Almstead Neil
Published: January 2019

To evaluate the potential for ethnicity‐related differences in ataluren pharmacokinetics (PK) and safety, a phase 1 single‐dose study was conducted in 48 healthy (24 Japanese and 24 Caucasian subjects), nonsmoking male volunteers who were equally divided into 3 cohorts of oral doses at 5, 10, and 20 mg/kg. Blood samples were collected until 48 hours postdose. PK results demonstrated rapid absorption of ataluren, with peak plasma levels (Cmax) being attained between 0.875 and 2.5 hours after dosing. The mean Cmax and area under the concentration‐time curve (AUC(0‐last)) increased with each increasing dose level in both Japanese and Caucasian subjects. Although the Cmax was similar across all subjects at each dose regardless of ethnicity, Japanese subjects had a mean AUC(0‐last) approximately 14% to 34% lower than that of Caucasian subjects across the 3 dose levels. This difference was likely due to the higher variability of AUC values in Caucasian subjects and the relatively small study population. In conclusion, similar ataluren PK profiles were observed in healthy Japanese and Caucasian subjects following single oral administration of ataluren at all dose levels.
Accelerating white blood cells image segmentation using GPUs
Authors: Bani Baker Qanita , Alsmirat Mohammad A. , Balhaf Khaled , Shehab Mohammed A.
Published: January 2019

White Blood Cell (WBC) segmentation is one of the important topics in the medical image processing field. Many researchers proposed several clustering approaches to segment WBC from blood smear microscopic images. However, a fast and robust segmentation of WBCs is still a challenging task. In this work, we propose parallel algorithms that utilize the parallelism capabilities of the Graphics Processing Units (GPUs) to accelerate the segmentation of WBC from microscopic images. In this research, we implement the main image segmentation clustering algorithms using one thread that we run on a single CPU (sequential implementation) and using multiple threads that we run on both the CPU and the GPU (hybrid CPU‐GPU). We focus our work on the most common four segmentation algorithms: Standard K‐means (SKM), Adaptive K‐means (AKM), Fuzzy C‐means (FCM), and Fuzzy Possibilistic C‐means (FPCM). We implement these algorithms and the pre‐processing steps for WBC image segmentation in CUDA programming to take the advantages of the large number of cores in GPUs. In this work, our hybrid implementation accelerated the four studied sequential algorithms by 4X, 3.8X, 3.4X, and 3.4X, respectively, without affecting WBC segmentation quality.
Tunable Supramolecular Nanoarchitectures Constructed by the Complexation of Diphenanthro‐24‐Crown‐8/Cesium(I) with Nickel(II) and Silver(I) Ions
Authors: Zhang Zhi‐Yuan , Chen Yong , Zhou Yan , Liu Yu
Published: January 2019

Tunable supramolecular nanoarchitectures have received enormous attention because of their potential in materials fabrication. Herein, a variety of morphologically intriguing nanoarchitectures have been constructed from diphenanthro‐24‐crown‐8 ether (DPC) and metal ions. SEM and TEM showed that the self‐assembled nanofibers undergo a CsI‐induced transformation into regular nanoribbons, and further into nanospheres and nanoparticles by the complexation of NiII and AgI ions because of the strong ion‐dipole interaction. Moreover, the X‐ray crystal structure determination and powder X‐diffraction data further confirmed that these morphological transformations resulted from the different complexation between DPC and metal ions. This result provides a new strategy for the subtle manipulation of supramolecular assemblies.
Using CRISPR/Cas9 engineering to generate a mouse with a conditional knockout allele for the promyelocytic leukemia zinc finger transcription factor
Authors: Hai Lan , Szwarc Maria M. , Lanza Denise G. , Heaney Jason D. , Lydon John P.
Published: January 2019

The promyelocytic leukemia zinc finger (PLZF) transcription factor mediates a wide‐range of biological processes. Accordingly, perturbation of PLZF function results in a myriad of physiologic defects, the most conspicuous of which is abnormal skeletal patterning. Although whole body knockout of Plzf in the mouse (Plzf
KO) has significantly expanded our understanding of Plzf function in vivo, a conditional knockout mouse model that enables tissue or cell‐type specific ablation of Plzf has not been developed. Therefore, we used CRISPR/Cas 9 gene editing to generate a mouse model in which exon 2 of the murine Plzf gene is specifically flanked (or floxed) by LoxP sites (Plzf
f/f). Crossing our Plzf
f/f mouse with a global cre‐driver mouse to generate the Plzf
d/d bigenic mouse, we demonstrate that exon 2 of the Plzf gene is ablated in the Plzf
d/d bigenic. Similar to the previously reported Plzf
KO mouse, the Plzf
d/d mouse exhibits a severe defect in skeletal patterning of the hindlimb, indicating that the Plzf
f/f mouse functions as designed. Therefore, studies in this short technical report demonstrate that the Plzf
f/f mouse will be useful to investigators who wish to explore the role of the Plzf transcription factor in a specific tissue or cell‐type.
Capacitor current imbalance and its suppression method between phase legs for three‐phase inverter
Authors: Hirao Takashi , Wada Keiji , Shimizu Toshihisa
Published: January 2019

This paper proposes a method to suppress the capacitor current imbalance between the phase legs of a three‐phase inverter circuit. This circuit consists of half‐bridge modules and DC‐link capacitors closely connected to each module. It can be designed for low stray inductance between power semiconductor devices and DC‐link capacitors in each module. However, in the conventional structure, the stray inductance between the phase legs may lead to an imbalance in the capacitor current due to the DC‐side resonance phenomenon under a higher switching frequency condition by using a SiC MOSFET. This paper presents the analyses of the equivalent circuit considering the circuit configuration, which suggests that capacitor current imbalance occurs depending on the stray inductance between phase legs. To suppress the capacitor current imbalance, a delta‐type bus bar connecting phase legs is proposed. The experiment results at 300 V and 4.6 A demonstrate the suppression effectiveness of the proposed method.
Serum potassium and clinical outcomes in heart failure patients: results of risk calculations in 21 334 patients in the UK
Authors: Linde Cecilia , Qin Lei , Bakhai Ameet , Furuland Hans , Evans Marc , Ayoubkhani Daniel , Palaka Eirini , Bennett Hayley , McEwan Phil
Published: January 2019

Aims

At present, the clinical burden of hypokalaemia and hyperkalaemia among European heart failure patients, and relationships between serum potassium and adverse clinical outcomes in this population, is not well characterized. The aim of this study was to investigate associations between mortality, major adverse cardiac events, and renin–angiotensin–aldosterone system inhibitor (RAASi) discontinuation across serum potassium levels, in a UK cohort of incident heart failure patients.

Methods and results

This was a retrospective observational cohort study of newly diagnosed heart failure patients listed in the Clinical Practice Research Datalink, with a first record of heart failure (index date) between 2006 and 2015. Hypokalaemia and hyperkalaemia episodes were defined as the number of serum potassium measurements exceeding each threshold (<3.5, ≥5.0, ≥5.5, and ≥6.0 mmol/L), without such a measurement in the preceding 7 days. Risk equations developed using Poisson generalized estimating equations were utilized to estimate adjusted incident rate ratios (IRRs) relating serum potassium and clinical outcomes (death, major adverse cardiac event, and RAASi discontinuation). Among 21,334 eligible heart failure patients, 1969 (9.2%), 7648 (35.9%), 2725 (12.8%), and 763 (3.6%) experienced episodes of serum potassium <3.5, ≥5.0, ≥5.5, and ≥6.0 mmol/L, respectively. The adjusted IRRs for mortality exhibited a U‐shaped association pattern with serum potassium. Relative to the reference category (4.5 to <5.0 mmol/L), adjusted IRRs for mortality were estimated as 1.98 (95% confidence interval: 1.69–2.33), 1.23 (1.12–1.36), 1.35 (1.14–1.60), and 3.02 (2.28–4.02), for patients with serum potassium <3.5, ≥5.0 to <5.5, ≥5.5 to <6.0, and ≥6.0 mmol/L, respectively. The adjusted IRRs for major adverse cardiac events demonstrated a non‐statistically significant relationship with serum potassium. Discontinuation of RAASi therapy exhibited a J‐shaped trend in association with serum potassium. Compared with the reference category (4.5 to <5.0 mmol/L), adjusted IRRs were estimated as 1.07 (0.89–1.28) in patients with serum potassium <3.5 mmol/L, increasing to 1.32 (1.14–1.53) and 2.19 (1.63–2.95) among those with serum potassium ≥5.5 to <6.0 and ≥6.0 mmol/L, respectively.

Conclusions

In UK patients with new onset heart failure, both hypokalaemia and hyperkalaemia were associated with increased mortality risk, and hyperkalaemia was associated with increased likelihood of RAASi discontinuation. Our results demonstrate the potential importance of serum potassium monitoring for heart failure outcomes and management.
Cyclic Voltammetry in Lithium–Sulfur Batteries—Challenges and Opportunities
Authors: Huang Xia , Wang Zhiliang , Knibbe Ruth , Luo Bin , Ahad Syed Abdul , Sun Dan , Wang Lianzhou
Published: January 2019

Lithium–sulfur batteries (LSBs) have attracted tremendous interest due to their high theoretical energy density and the earth‐abundant sulfur feedstock. Multifarious characterization techniques have been applied to investigate the electrochemical mechanisms and the structure–property relationships in LSBs. Among them, cyclic voltammetry (CV), a basic electrochemical tool, can provide indispensable thermodynamic and kinetics information of the redox processes. However, the CV analysis in most LSB studies is sketchy—providing some well‐known information while ignoring some specific features. To fulfill the versatile role of CV and thus spur further breakthroughs on LSBs, the electrochemical reactions and challenges are first described, followed by the work principles and experimental setup of LSBs for the CV technique. Then, various protocols for specific research purposes in LSBs are summarized, particularly on the performance evaluation of sulfur cathodes. Ending with challenges and the outlook of the CV technique in the LSB study, the Review provides a timely summary and thus can be a guidance for future studies on batteries.
High‐Temperature One‐Step Synthesis of Efficient Nanostructured Bismuth Vanadate Photoanodes for Water Oxidation
Authors: Tran‐Phu Thanh , Chen Hongjun , Bo Renheng , Di Bernardo Iolanda , Fusco Zelio , Simonov Alexandr N. , Tricoli Antonio
Published: January 2019

Bismuth vanadate (BiVO4) is a promising photoanode material for photoelectrochemical water splitting due to its well‐suited valence band edge and comparatively narrow band gap. First insights on the high‐temperature and scalable synthesis of efficient nanostructured BiVO4 photoanodes for water oxidation are provided. Nanostructured BiVO4 films with a tunable optical density and porosity ranging from 12% to 80% are synthesized in few seconds by direct deposition of flame‐made BiVO4 nanoparticle aerosols. The impact of the BiVO4 film structural properties on the photooxidation performance has been systematically investigated by a set of electrochemical and physical characterizations indicating key directions for its morphological optimization. It is found that the BiVO4 water oxidization performance is mainly determined by two competitive factors, viz., accessible surface area and carrier conductivity through the grain boundaries. Optimization of these two factors increases the photocurrent densities by more than three times resulting in ≈1.5 mA cm−2 for sulfite oxidation and ≈1 mA cm−2 for water oxidation with a FeOOH/NiOOH co‐catalyst at 1.0 V vs the reversible hydrogen electrode (RHE) under simulated 1 sun illumination. These findings provide novel insights into the structure–activity relationships of high‐temperature synthesized BiVO4 photoanodes for solar‐powered water splitting and introduce a scalable and low‐cost approach for their rapid nanofabrication.
Effect of treatment modality on chronic opioid use in patients with T1/T2 oropharyngeal cancer
Authors: Bollig Craig A. , Jorgensen Jeffrey B.
Published: January 2019

Background

The effect of treatment modality on long‐term opioid dependence in patients with oropharyngeal cancer has not been reported.

Methods

A retrospective cohort of 122 patients with T1/T2 oropharyngeal cancer undergoing treatment was generated. Risk factors associated with chronic opioid use were investigated by univariate and multivariate analyses.

Results

The prevalence of chronic opioid use was 45.9%. On multivariate analysis, primary nonsurgical treatment (odds ratio [OR] 4.5, 95% confidence interval [CI]: 1.7‐11.4), pretreatment opioid use (OR 14.9, 95% CI: 3.5‐62.5), psychiatric disorder (OR 4.3, 95% CI: 1.03‐18.5), alcohol use (OR 2.6, 95% CI: 1.03‐6.5), and younger age (OR 1.1, 95% CI: 1.02‐1.11) were significantly associated with chronic opioid use.

Conclusion

Primary nonsurgical treatment, younger age, pretreatment opioid use, alcohol use, and psychiatric disorder were independently associated with an increased risk of chronic opioid use. Preventative strategies should be especially focused toward these patients to reduce their risk of long‐term opioid use.
Clinical management and outcomes of lacrimal sac squamous cell carcinoma
Authors: Song Xinmao , Wang Shengzi , Wang Jie , Wang Weifang , Wang Shuyi , Yang Gang , Li Ji , Zhu Yi , Chen Fu , Zhu Wenjia
Published: January 2019

Background

To investigate the management and outcomes of patients with lacrimal sac squamous cell carcinoma (SCC).

Methods

This retrospective study examined 69 lacrimal sac SCC cases treated at our hospital between 1992 and 2017. The potential risk factors for prognosis, a new staging method, treatment outcomes, and complications were investigated.

Results

The 5‐year overall survival (OS) and progression‐free survival (PFS) were 87.6 ± 4.8% and 76.3 ± 6.4%, respectively. Positive lymph node was associated with worse OS and PFS. We divided lacrimal sac SCC into four clinical stages, with significant differences in OS (P = .026) and PFS (P = .042) among each stage. Definitive radiotherapy was equivalent to surgery plus radiotherapy in 26.1% (18/69) of cases, and the incidence of complications was not higher.

Conclusions

Lymph node status was a key factor in determining outcomes. Our staging method could effectively classify tumor stage and predict prognosis, which can contribute to optimizing treatment regimes. Radiotherapy played an important role in treatment.
The histone demethylase UTX/KDM6A in cancer: Progress and puzzles
Authors: Schulz Wolfgang A. , Lang Alexander , Koch Julian , Greife Annemarie
Published: January 2019

The lysine‐specific demethylase 6A/UTX (gene name KDM6A) acts as a component of the COMPASS complex to control gene activation. UTX demethylates H3K27me2/3 at genes and enhancers. Deleterious mutations in KDM6A are found in many cancer types, prominently urothelial carcinoma and certain T‐cell leukemias. In certain cancers, however, UTX supports oncogenic transcription factors, e.g. steroid hormone receptors in breast and prostate cancer. In fetal development, UTX regulates lineage choice and cell differentiation. Analogously, loss of UTX function in cancer may lead to metaplasia or impede differentiation. Likely because its function is contingent on its interacting transcription factors, the effects of UTX inactivation are not uniform and require detailed investigation in each cancer type. In urothelial carcinoma, in particular, the functional consequences of the frequent mutations in KDM6A and other COMPASS component genes are poorly understood. Nevertheless, UTX inactivation appears to sensitize many cancers to inhibitors of the H3K27 methyltransferase EZH2. Conversely, inhibitors of UTX enzymatic activity may be applicable in cancers with an oncogenic UTX function. Intriguingly, the fact that KDM6A is localized on the X‐chromosome, but both copies are expressed, may account for gender‐specific differences in cancer susceptibility. In conclusion, despite recent progress, many open questions need to be addressed, most importantly, the detailed mechanisms by which KDM6A inactivation promotes various cancers, but also with which proteins UTX interacts in and apart from the COMPASS complex, and to which extent its catalytic function is required for its tumor‐suppressive function.
A benzoxazole compound as a novel MEK inhibitor for the treatment of RAS/RAF mutant cancer
Authors: Cheng Ying , Wang Xingkai , Xia Xiangying , Zhang Wei , Tian Hongqi
Published: January 2019

Mutations in RAS/RAF occur in large portion of malignancies and are associated with aggressive clinical behaviors and poor prognosis. Therefore, we developed a novel benzoxazole compound (KZ‐001) as a highly potent and selective MEK 1/2 inhibitor. Our efforts were focused on enhancing the activity of the known MEK inhibitor AZD6244 and overcoming the shortcomings existing in current MEK inhibitors. Here we show that compound KZ‐001 exhibits approximately 30‐fold greater inhibition against BRAF‐ and KRAS‐mutant tumor cells than that of AZD6244. These results were also demonstrated using in vivo xenograft models. Furthermore, pharmacokinetics (PK) analysis was performed for KZ‐001, and this compound showed good orally bioavailability (28%) and exposure (AUC0–∞ = 337 ± 169 ng h/mL). To determine its potential clinical application, the synergistic effect of KZ‐001 with other agents was investigated both in vitro and in vivo (xenograft models). KZ‐001 exhibited synergistic anti‐cancer effect in combination with BRAF inhibitor vemurafenib and a microtubule‐stabilizing chemotherapeutic agent docetaxel. In addition, KZ‐001 inhibited the MAPK pathway like known MEK inhibitors. In summary, KZ‐001, a structurally novel benzoxazole compound, was developed as a MEK inhibitor that has potential for cancer treatment.
Genetic counselor workflow study: The times are they a‐changin’?
Authors: Attard Courtney A. , Carmany Erin P. , Trepanier Angela M.
Published: January 2019

Genetic services have historically been time and labor intensive. Little information is known about the proportion of time genetic counselors (GCs) spend face‐to‐face with patients in comparison to the time spent on patient‐related activities (PRA). We aimed to perform a real‐time workflow study of GCs representing multiple clinics and specialties. We developed an electronic collection tool formatted in 15‐min increments for real‐time documentation of how the GC spent his/her time throughout the workday for one full week, based on a defined task list. Participants were Michigan GCs recruited via email solicitation. Sixteen of an estimated 70 patient‐facing GCs (23%) representing prenatal, cancer, adult, and pediatric genetics took part by completing a demographic survey and the workflow study. The GCs reported spending approximately 20% of their time face‐to‐face with patients, 64% on PRA including case preparation, follow‐up, and administrative tasks, and 16% on tasks unrelated to direct patient care. They saw a mean of 10 patients/week with a mean session length of 47 min. Approximately 3 hr of PRA were performed for the 0.78 hr (47 min) of face‐to‐face time with a patient. The most time‐consuming task in the PRA category was letter writing. Identifying strategies to reduce the amount of time spent on PRA could increase the amount of available time GCs have to spend on providing face‐to‐face services and subsequently, the number of patients seen. Such efforts are critical to help meet the growing demand for genetic counseling services.
Fast optimization of sparse antenna array using numerical Green's function and genetic algorithm
Authors: Raji Mordecai F. , Zhao Huapeng , Monday Happy N.
Published: January 2019

A single‐element antenna is unfit for application in most wireless systems and an alternative is an array of antenna. The desire to reduce weight and cost of antenna arrays gave rise to sparse arrays. The design of a sparse antenna array requires an optimization process, which is time‐consuming for large arrays. In order to accelerate the optimization process, a method combining the numerical Green's function (NGF) and genetic algorithm (GA) is presented in this paper. In the proposed method, binary coding is applied to describe the status of antenna elements, and GA optimization is performed to sparsify the array subject to constraint on the peak side lobe level (PSLL). The PSLL is calculated efficiently by the NGF. Simulation results are presented to illustrate the advantage of the proposed method. It is shown that the proposed method significantly reduces the optimization time.
Improvement and optimization of an autonomous photovoltaic pumping system
Authors: Ksentini Abdelhamid , Azzag El Bahi
Published: January 2019

The climate in Algeria can be considered semiarid in most areas. The water demand is expected to increase because of population growth in the coming years. Water supply is always a great concern for the populations in the landlocked regions. Pumping water using the solar photovoltaic energy is a well‐suited solution where the traditional electricity grid is absent. Indeed, the majority of these regions are very sunny, and water is available in underground aquifers. Our system consists on a photovoltaic generator (PVG), a direct current (DC)‐DC converters, a multilevel inverter with five levels, and an asynchronous motor coupled to a centrifugal pump. The objective of this process is to ensure the operation at maximum power of the PVG system under various conditions by the maximum power point tracking (MPPT) method based on fuzzy logic control (FLC). The modeling and simulation of this system were carried out and based on our experimental work in the site meteorological database of city Adrar in Algeria. This system avoids the use of a motor pump (diesel) and eliminates costs and operating constraints in an environment friendly manner according to the COP21 recommendation.
Unique abdominal twiddler syndrome
Authors: Higuchi Satoshi , Shoda Morio , Satomi Natsuko , Iwanami Yuji , Yagishita Daigo , Ejima Koichiro , Hagiwara Nobuhisa
Published: January 2019

Twiddler syndrome is an uncommon complication that occurs by twisting of the generator and may cause torsion, dislodgement, and injury of the leads. We report a rare case of a twiddler syndrome associated with an abdominal permanent pacemaker. Abdominal twiddler syndrome may possess a unique mechanism, which may not be seen in chest twiddler syndrome.
Two‐step stem cell therapy improves bone regeneration compared to concentrated bone marrow therapy
Authors: Bolte Julia , Vater Corina , Culla Anna Carla , Ahlfeld Tilman , Nowotny Jörg , Kasten Philip , Disch Alexander C. , Goodman Stuart B. , Gelinsky Michael , Stiehler Maik , Zwingenberger Stefan
Published: January 2019

Adult stem cells are a promising tool to positively influence bone regeneration. Concentrated bone marrow therapy entails isolating osteoprogenitor cells during surgery with, however, only low cells yield. Two step stem cell therapy requires an additional harvesting procedure but generates high numbers of progenitor cells that facilitate osteogenic pre‐differentiation. To further improve bone regeneration, stem cell therapy can be combined with growth factors from platelet rich plasma (PRP) or its lysate (PL) to potentially fostering vascularization. The aim of this study was to investigate the effects of bone marrow concentrate (BMC), osteogenic pre‐differentiation of mesenchymal stromal cells (MSCs), and PL on bone regeneration and vascularization. Bone marrow from four different healthy human donors was used for either generation of BMC or for isolation of MSCs. Seventy‐two mice were randomized to six groups (Control, PL, BMC, BMC + PL, pre‐differentiated MSCs, pre‐differentiated MSCs + PL). The influence of PL, BMC, and pre‐differentiated MSCs was investigated systematically in a 2 mm femoral bone defect model. After a 6‐week follow‐up, the pre‐differentiated MSCs + PL group showed the highest bone volume, highest grade of histological defect healing and highest number of bridged defects with measurable biomechanical stiffness. Using expanded and osteogenically pre‐differentiated MSCs for treatment of a critical‐size bone defect was favorable with regards to bone regeneration compared to treatment with cells from BMC. The addition of PL alone had no significant influence; therefore the role of PL for bone regeneration remains unclear. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1318–1328, 2019.
Effect of pH and mobile phase additives on the chromatographic behaviour of an amide‐embedded stationary phase: Cyanocobalamin and its diaminemonochloro‐platinum(II) conjugate as a case study
Authors: Ventura Giovanni , Calvano Cosima Damiana , Losito Ilario , Bianco Giuliana , Pascale Raffaella , Palmisano Francesco , Cataldi Tommaso R.I.
Published: January 2019

Several mobile phase additives (i.e., organic acids and their ammonium salts) were used to modulate the chromatographic retention of cyanocobalamin and its cis‐diaminemonochloroplatinum(II) conjugate, depending on the specific nature of the stationary phase. Regardless of the mobile phase additive, the positively charged cyanocobalamin‐cis‐diaminemonochloroplatinum(II) conjugate was systematically less retained than cyanocobalamin on a conventional octadecyl‐silica column. In contrast, the amide‐embedded C18 column exhibited a progressive increase in the conjugate retention time upon changing the mobile phase additive from organic (acetic, formic and trifluoroacetic) acids to ammonium salts, ultimately leading to an inversion of the elution order. This change of retention was interpreted by invoking the interplay between hydrophobic interactions, hydrogen bonding between the conjugate and the polar amide groups and the ion‐pairing ability of the lyophilic counterions, whereby the acetate anion was found to be the most suitable to control the solute retention.
Optimal sequencing of chemoradiotherapy for locally advanced laryngeal cancer
Authors: Shah Nishant K. , Qureshi Muhammad M. , Dyer Michael A. , Patel Sagar A. , Kim Kristine , Everett Peter C. , Grillone Gregory A. , Jalisi Scharukh M. , Truong Minh Tam
Published: January 2019

Objective

To determine the optimal sequencing of chemoradiotherapy for locally advanced laryngeal cancer. The hypothesis was that concurrent chemoradiotherapy (CCRT) would be associated with improved overall survival (OS) compared to induction chemotherapy followed by radiotherapy (RT)/surgery (IC).

Methods

The National Cancer Database identified 8,154 patients with American Joint Commission on Cancer stage III/IV (excluding T1) laryngeal cancer between 2004 and 2013 treated with one of the established organ preservation techniques: CCRT or IC. The association between OS and total radiation dose (< 66 gray [Gy] or ≥ 66 Gy) was analyzed using the Kaplan‐Meier method, as was the association between OS and timing of IC (21–42, 43–100, or 101–120 days before RT). Hazard ratios (HR) adjusted for patient and clinical characteristics were computed using Cox regression modeling.

Results

The median follow‐up was 32.7 months. The estimated 5‐year OS for CCRT and IC was 49.9% and 50.6%, respectively (P = 0.653). On multivariate analysis, no difference was observed between the two regimens (IC, adjusted HR 0.96, 95% confidence interval [CI] 0.88–1.04, P = 0.268). Radiation dose ≥66 Gy had improved OS overall in CCRT group but not in IC patients. When comparing CCRT and IC in patients receiving ≥66 Gy, there was no difference in OS (adjusted HR 0.97, 95% CI 0.89–1.06, P = 0.552). Patients starting chemotherapy 21 to 42 or 101 to 120 days prior to RT had inferior OS compared to patients starting between 43 to 100 days.

Conclusion

For locally advanced laryngeal cancer, there is no difference in OS between CCRT and IC. Factors associated with survival included radiation dose and timing of induction chemotherapy before RT.

Level of Evidence

3b

Laryngoscope, 129:2313–2320, 2019
Three‐dimensional endoscopy: The future of nasoendoscopic training
Authors: Bickerton Robert , Nassimizadeh Abdul‐Karim , Ahmed Shahzada
Published: January 2019

Objectives/Hypothesis

Three‐dimensional (3D) endoscopy is an emerging tool in surgery that provides real‐time depth perception. Its benefits have been investigated in surgical training, but the current literature lacks significant objective outcome data. We aimed to objectively compare the efficacy of two‐dimensional (2D) versus 3D high‐definition endoscopes in novice users.

Study Design

Prospective, randomized crossover study.

Methods

Ninety‐two novice medical students who used both 2D and 3D endoscopes to complete two validated tasks in a box trainer participated in the study. Time taken and error rates were measured, and subjective data were collected.

Results

Wilcoxon tests showed 3D technology was significantly faster than 2D (78 vs. 95 seconds, P = .004), and errors per task were significantly lower (3 vs. 5, P < .001). Sixty‐nine percent of participants preferred the 3D endoscope.

Conclusions

3D high‐definition endoscopy could be instrumental in training the next generation of endoscopic surgeons. Further research is required in a clinical setting.

Level of Evidence

2b

Laryngoscope, 129:1280–1285, 2019
A comprehensive study of immunology repertoires in both preoperative stage and postoperative stage in patients with colorectal cancer
Authors: Liu Xicheng , Cui Yuanyuan , Zhang Yaoxian , Liu Zhanli , Zhang Qiuli , Wu Wenyan , Zheng Zihao , Li Shien , Zhang Zhongjun , Li Yali
Published: January 2019

Background

Colorectal cancer (CRC) is the 3rd most common cancer type in the world. The correlation between immune repertoire and prognosis of CRC has been well studied in the last decades. The diversity and stability of the immune cells can be measured by hypervariable complementarity‐determining region 3 (CDR3) segments of the T‐cell receptor (TCR).

Methods

In this study, we collected five healthy controls and 19 CRC patients’ peripheral blood mononuclear cells (PBMCs) in three stages, namely 1 day preoperative, 3 days’ postoperative, and 7 days’ postoperative, respectively. Simultaneously, we have also done the comparative analysis of these two different anesthesia methods, namely TIVA and CEGA. Sequencing of the TCR segments has been performed by multiplex PCR and high‐throughput next‐generation sequencing. We also analyzed the distribution of CDR3 length, highly expansion clones (HECs), TRBV, and TRBJ gene usage.

Results

Our result showed a significant difference between TCR CDR3 length distribution and HEC distribution between CRC patients and healthy controls. We also found that TRBV11‐2, TRBV12‐1, TRBV16, TRBV3‐2, TRBV4‐2, TRBV4‐3, TRBV5‐4, TRBV6‐8, TRBV7‐8, TRBV7‐9 and RBV11‐2, TRBV12‐1, TRBV16, TRBV3‐2, TRBV4‐2, TRBV4‐3, TRBV5‐4, TRBV6‐8, TRBV7‐8, and TRBV7‐9 usages are different between CRC patients and healthy controls.

Conclusion

In conclusion, CRC patients were presented with different immune repertoire in comparison with healthy controls. In this study, significant difference in TRBV and TRBJ gene usage in between case and control group could provide some potential biomarker for the diagnosis and the treatment of the patients with CRC.
Multicenter CT phantoms public dataset for radiomics reproducibility tests
Authors: Kalendralis Petros , Traverso Alberto , Shi Zhenwei , Zhovannik Ivan , Monshouwer René , Starmans Martijn P. A. , Klein Stefan , Pfaehler Elisabeth , Boellaard Ronald , Dekker Andre , Wee Leonard
Published: January 2019

Purpose

The aim of this paper is to describe a public, open‐access, computed tomography (CT) phantom image set acquired at three centers and collected especially for radiomics reproducibility research. The dataset is useful to test radiomic features reproducibility with respect to various parameters, such as acquisition settings, scanners, and reconstruction algorithms.

Acquisition and validation methods

Three phantoms were scanned in three independent institutions. Images of the following phantoms were acquired: Catphan 700 and COPDGene Phantom II (Phantom Laboratory, Greenwich, NY, USA), and the Triple modality 3D Abdominal Phantom (CIRS, Norfolk, VA, USA). Data were collected at three Dutch medical centers: MAASTRO Clinic (Maastricht, NL), Radboud University Medical Center (Nijmegen, NL), and University Medical Center Groningen (Groningen, NL) with scanners from two different manufacturers Siemens Healthcare and Philips Healthcare. The following acquisition parameter were varied in the phantom scans: slice thickness, reconstruction kernels, and tube current.

Data format and usage notes

We made the dataset publically available on the Dutch instance of “Extensible Neuroimaging Archive Toolkit‐XNAT” (https://xnat.bmia.nl). The dataset is freely available and reusable with attribution (Creative Commons 3.0 license).

Potential applications

Our goal was to provide a findable, open‐access, annotated, and reusable CT phantom dataset for radiomics reproducibility studies. Reproducibility testing and harmonization are fundamental requirements for wide generalizability of radiomics‐based clinical prediction models. It is highly desirable to include only reproducible features into models, to be more assured of external validity across hitherto unseen contexts. In this view, phantom data from different centers represent a valuable source of information to exclude CT radiomic features that may already be unstable with respect to simplified structures and tightly controlled scan settings. The intended extension of our shared dataset is to include other modalities and phantoms with more realistic lesion simulations.
Pharmacologically pertinent period of effect (PPPE)
Authors: Suissa Melanie , LeLorier Jacques
Published: January 2019

Background

The period of time during which a patient is exposed to a drug does not necessarily correspond to the period during which the drug produces the adverse effect under consideration. We propose the term Pharmacologically pertinent period of effect (PPPE) to address this time window. We explored the PPPE in light of the rofecoxib saga.

Methods

We identified the observational database studies of rofecoxib at doses 25 and 50 mg daily and thromboembolic events. We also obtained the Kaplan‐Meier curves of Vioxx Gastrointestinal Outcomes Research trial (VIGOR) and Adenomatous Polyp Prevention on Vioxx (APPROVE) trials.

Results

We found seven observational studies with nine analyses. All the studies only looked at current exposure. At the dose of 25 mg, only three of nine analyses were barely statistically significant. At the dose of 50 mg, the risk ratios were much higher. The visual inspection of the Kaplan‐Meier curves shows that in the APPROVE trial (25 mg), the placebo and rofecoxib curves start separating to become statistically significantly different only after 36 months. In contrast the VIGOR (50 mg), curves start separating very early and the divergence increases after 8 months.

Discussion

The 50 mg observational studies, looking at current exposure, correctively identified the almost immediate increase in risk evident in the VIGOR Kaplan‐Meier curves. The absence of an immediate increase in risk shown by the APPROVE trial was also correctively identified by most observational 25 mg studies. To our knowledge no observational study was done on the long‐term cardiac toxicity of the 25‐mg dose. It would thus appear that the two doses of rofecoxib have different PPPEs.
Assessment of Neighbor‐Initiated Risks in an Integrated Air Separation Unit‐Gasification Facility
Authors: Cialkowski Edward J , Li Yuqiang
Published: January 2019

Gasification facility operators increasingly find it cost effective to outsource the supply of industrial gases, such as oxygen and nitrogen, to companies with a proven track record for designing and operating safe and reliable air separation unit (ASU) equipment. Air Products have built & operated many such ASU facilities in recent years and supplied industrial gases to customers directly by pipeline, with long term supply partnerships. Most of these ASU facilities are located within the customer boundary and are effectively integrated with customer gasification facilities. In addition to any risks that the ASU may pose to the customer's operations or personnel, there may be significant hazards originating with the customer's equipment or processes that pose a risk to the ASU personnel.

Air Products developed an approach to assessing risks from neighboring facilities to the ASU equipment and personnel. The focus of this article is on the work process and sequence of steps used to develop a risk assessment and mitigation plan. Overall safety and risk management is improved by sharing hazard information between the industrial gas supplier and the customer, as well as developing a joint emergency response program. © 2019 American Institute of Chemical Engineers Process Saf Prog 38: e12032, 2019
Transverse function control with prescribed performance guarantees for underactuated marine surface vehicles
Authors: Dai Shi‐Lu , He Shude , Lin Hai
Published: January 2019

This paper studies the problem of stabilizing reference trajectories (also called as the trajectory tracking problem) for underactuated marine vehicles under predefined tracking error constraints. The boundary functions of the predefined constraints are asymmetric and time‐varying. The time‐varying boundary functions allow us to quantify prescribed performance of tracking errors on both transient and steady‐state stages. To overcome difficulties raised by underactuation and nonzero off‐diagonal terms in the system matrices, we develop a novel transverse function control approach to introduce an additional control input in backstepping procedure. This approach provides practical stabilization of any smooth reference trajectory, whether this trajectory is  feasible or not. By practical stabilization, we mean that the tracking errors of vehicle position and orientation converge to a small neighborhood of zero. With the introduction of an error transformation function, we construct an inverse‐hyperbolic‐tangent‐like barrier Lyapunov function to show practical stability of the closed‐loop systems with prescribed transient and steady‐state performances. To deal with unmodeled dynamic uncertainties and external disturbances, we employ neural network (NN) approximators to estimate uncertain dynamics and present disturbance observers to estimate unknown disturbances. Subsequently, we develop adaptive control, based on NN approximators and disturbance estimates, that guarantees the prescribed performance of tracking errors during the transient stage of on‐line NN weight adaptations and disturbance estimates. Simulation results show the performance of the proposed tracking control.
Biofilm modeling in evolving porous media with Beavers‐Joseph condition
Authors: Schulz Raphael
Published: January 2019

In this article, we derive an effective model for biofilm growth in a saturated porous medium. Several experimental investigations found out that biomass is in general very heterogeneous and contains in particular channels filled with fluid. These channels facilitate the transport of nutritive substances within the biofilm by advection. Referring to this, we model the biofilm itself at the pore‐scale as a porous medium. Hence the starting point at the pore‐scale is a Darcy‐Stokes system, where the Beavers‐Joseph boundary condition at the corresponding interface is proposed. By formal periodic homogenization we derive an averaged model describing the process via Darcy's law and upscaled transport equations with effective coefficients given by the evolving microstructure. Based on the assumption of uniform evolve of the underlying pore geometry, solvability in a weak sense global in time or at least up to a possible clogging phenomenon is stated.
Note on the space group selection rule for closed strings on orbifolds
Authors: Ramos-Sánchez Saúl , Vaudrevange Patrick K. S.
Published: January 2019

Abstract

It is well-known that the space group selection rule constrains the interactions of closed strings on orbifolds. For some examples, this rule has been described by an effective Abelian symmetry that combines with a permutation symmetry to a non-Abelian flavor symmetry like D
4 or Δ(54). However, the general case of the effective Abelian symmetries was not yet fully understood. In this work, we formalize the computation of the Abelian symmetry that results from the space group selection rule by imposing two conditions only: (i) well-defined discrete charges and (ii) their conservation. The resulting symmetry, which we call the space group flavor symmetry D

S
, is uniquely specified by the Abelianization of the space group. For all Abelian orbifolds with

$$ \mathcal{N}=1 $$

N
=
1

supersymmetry we compute D

S
and identify new cases, for example, where D

S
contains a ℤ
2 dark matter-parity with charges 0 and 1 for massless and massive strings, respectively.
Exact half-BPS black hole entropies in CHL models from Rademacher series
Authors: Nally Richard
Published: January 2019

Abstract

The microscopic spectrum of half-BPS excitations in toroidally compactified heterotic string theory has been computed exactly through the use of results from analytic number theory. Recently, similar quantities have been understood macroscopically by evaluating the gravitational path integral on the M-theory lift of the AdS2 near-horizon geometry of the corresponding black hole. In this paper, we generalize these results to a subset of the CHL models, which include the standard compactification of IIA on K3 × T
2 as a special case. We begin by developing a Rademacher-like expansion for the Fourier coefficients of the partition functions for these theories, which are modular forms for congruence subgroups. We then describe a possible macroscopic interpretation of these results, emphasizing the role of twisted boundary conditions.
The complex sinh-Gordon model: form factors of descendant operators and current-current perturbations
Authors: Lashkevich Michael , Pugai Yaroslav
Published: January 2019

Abstract

We study quasilocal operators in the quantum complex sinh-Gordon theory in the form factor approach. The free field procedure for descendant operators is developed by introducing the algebra of screening currents and related algebraic objects. We work out null vector equations in the space of operators. Further we apply the proposed algebraic structures to constructing form factors of the conserved currents T

k
and Θ
k
. We propose also form factors of current-current operators of the form T

k

T
−l
. Explicit computations of the four-particle form factors allow us to verify the recent conjecture of Smirnov and Zamolodchikov about the structure of the exact scattering matrix of an integrable theory perturbed by a combination of irrelevant operators. Our calculations confirm that such perturbations of the complex sinh-Gordon model and of the ℤ

N
symmetric Ising models result in extra CDD factors in the S matrix.
The Place of the Holy Man in the Later Roman Empire
Authors: MacMullen Ramsay
Published: January 2019

The early centuries in the history of Christian asceticism, and of monasticism to which it gave rise, invite a short and accessible overview. The present article aims to supply this. It relies on a very large sampling of texts, mostly hagiographic. As ascetics are there to be seen described by contemporaries and near-contemporaries, they share many traits which can be grouped under principal headings and frequency of mention. A statistical profile emerges, presented under numerous headings and totals which in turn indicates the ascetics’ most salient aims and acts, and helps to explain the course of development of their institutions. The findings challenge a still-famous and almost universally accepted overview offered by Peter Brown (1971). This the present article seeks to replace at the outset, through calling in question Brown’s methodological assumptions, and second, in its closing pages, through challenging Brown’s picture of the holy man in other, more factual points.
Parasites in Antarctic krill guts inferred from DNA sequences
Authors: Cleary Alison C. , Casas Maria C. , Durbin Edward G. , Gómez-Gutiérrez Jaime
Published: January 2019

The keystone role of Antarctic krill,Euphausia superbaDana, in Southern Ocean ecosystems, means it is essential to understand the factors controlling their abundance and secondary production. One such factor that remains poorly known is the role of parasites. A recent study of krill diet using DNA analysis of gut contents provided a snapshot of the parasites present within 170E. superbaguts in a small area along the West Antarctic Peninsula. These parasites includedMetschnikowiaspp. fungi,Haptoglossasp. peronosporomycetes,LankesteriaandParalecudinaspp. apicomplexa,Stegophorussp. nematodes, andPseudocolliniaspp. ciliates. Of these parasites,Metschnikowiaspp. fungi andPseudocolliniaspp. ciliates had previously been observed inE. superba, as had other genera of apicomplexans, though notLankesteriaandParalecudina.In contrast, nematodes had previously only been observed in eggs ofE. superba, and there are no literature reports of peronosporomycetes in euphausiids.Pseudocolliniaspp., parasitoids which obligately kill their host, were the most frequently observed infection, with a prevalence of 12%. The wide range of observed parasites and the relatively high frequency of infections suggest parasites may play a more important role than previously acknowledged inE. superbaecology and population dynamics.
Longitudinal effects of maternal love withdrawal and guilt induction on Chinese American preschoolers’ bullying aggressive behavior
Authors: Yu Jing , Cheah Charissa S. L. , Hart Craig H. , Yang Chongming , Olsen Joseph A.
Published: January 2019

Bullying has been understudied among preschool children, especially those from Chinese American families. Previous research has also neglected the dimensional effects of psychological control on child bullying development. This study examined two psychological control dimensions, love withdrawal and guilt induction, and their effects on children's bullying aggressive behavior using a longitudinal design. Participants were first-generation Chinese American mothers (N= 133; mean age [Mage] = 37.82) and their preschool children (Mage= 4.48). Chinese immigrant mothers reported their psychologically controlling parenting and teachers rated children's bullying aggressive behaviors in the school setting. Confirmatory factor analyses were conducted to establish the psychometric properties and cross-wave measurement equivalence of the study constructs. Cross-lagged structural equation modeling analysis indicated that maternal love withdrawal prospectively predicted more bullying aggressive behavior, whereas guilt induction predicted less bullying aggressive behavior in children 6 months later. These results held after controlling for the initial level of children's problem behaviors and demographic variables (child age, gender, and maternal education). For child effects, child bullying aggressive behavior predicted more maternal guilt induction over time but not love withdrawal. Our findings highlight the importance of construct specificity and cultural context in understanding associations between parenting and child development.