bluuebunny/crossref_metadata_2025 huggingface dataset:
Brzi razvoj hibridne aplikacije za ugostiteljstvo primjenom jQuery i Apache Cordova frejmvorka
Authors: Milovanović Slađan
Published: February 2017

U ovom radu je prezentovana funkcionalna aplikacija namijenjena primjeni u ugostiteljstvu. Aplikacija je razvijena upotrebom savremenih web i mobilnih tehnologija uz minimalno korišćenje resursa. Primjena ove aplikacije ima za cilj da se podigne efikasnost poslovanja u ugostiteljskim objektima, te ubrza i poboljša kvalitet usluga uz minimalna ulaganja. Jednu od prednosti čini i jednostavno i brzo prilagođavanje aplikacije potrebama korisnika. Aplikacija je dizajnirana tako da njena upotreba ne zavisi od operativnog sistema na kojoj se koristi (cross-platform), a njena struktura omogućava lako proširivanje funkcionalnosti.
Effect of Insecurity of School Environment on the Academic Performance of Secondary School Students in Imo State
Authors: M.O. Ojukwu
Published: February 2017

The major aim of this study was to investigate the effect of insecurity of school environment on the academic performance of secondary school students in Imo state, Nigeria. A total of 1000 made up of 500 each of male and female students responded to a self-structured validated questionnaire designed for the study. Two research questions and two hypotheses were formulated to guide the study. Means and standard deviations were calculated to answer the research questions and independent samples t-tests were used for testing the hypotheses. Major findings revealed that insecurity of school environment significantly affects the academic performance of secondary school students while students’ gangsterism, smoking of Indian hemp, abusing other hard drugs, cult and related violent activities were some of the factors that constituted insecurity of the school environment which eventually cause boys to leave school and join trading while leading girls to drop out and settle for marriage. Based on the findings, it was recommended that owners of schools and other stakeholders in education should take bold steps to fence and protect school environments from intruders to ensure safety of the students.
Agentes em rede e inovações em pequenas empresas tradicionais: Direito, tradição e carisma de empreender
Authors: Barboza Ricardo Augusto Bonotto , Oliveira Edmundo Alves , Passos Fernando , Ramalheiro Geralda Cristina de Freitas
Published: February 2017

O universo das micro e pequenas empresas (MPEs) que operam em setores tradicionais da economia apresentam características peculiares, que se materializam em barreiras à inovação, sendo necessárias políticas e intervenções públicas para minimizar as dificuldades. Este estudo teve como objetivo relatar as virtudes, as limitações e as dificuldades de operacionalização de dois instrumentos como potenciais ou efetivos indutores de inovações em micro e pequenas empresas (MPEs) de base tradicional. A estratégia metodológica utilizada compreendeu uma pesquisa qualitativa, de caráter exploratório, delineada como estudo de casos simples, com dados coletados por meio de entrevistas e observação participante. Apurou-se que as micro e pequenas empresas de base tradicional, mesmo aquelas que são alvos de programas e políticas públicas, apresentam muitas dificuldades para operacionalizar inovações. Notou-se também que a junção dos dois instrumentos potencializou as atividades inovativas.
Solar cycle variations of thermospheric O/N2 longitudinal pattern from TIMED/GUVI
Authors: Luan Xiaoli , Wang Wenbin , Burns Alan , Dou Xiankang
Published: February 2017

Thermospheric composition (O/N2 ratio) is well known to have a great impact on the variation of daytime ionospheric electron density. This study aims to investigate the local time, seasonal, and solar cycle variations of the O/N2 longitudinal pattern in both hemispheres during daytime in solstices. The O/N2 data used are from TIMED/Global Ultraviolet Imager observations made over a solar cycle for geomagnetically quiet conditions. The main findings are as follows: (1) The O/N2 longitudinal patterns are generally similar during 10:00–14:00 LT and between solar minimum and maximum, although the O/N2 values change with local time and solar cycle. (2) The winter O/N2 subauroral enhancement is unexpectedly smaller in the longitudes where the magnetic pole is (near‐pole longitudes), rather than in the longitudes far from the magnetic pole, especially during solar maximum, and consequently, the longitudinal pattern of O/N2 depends on latitude in local winter. (3) The winter O/N2 subauroral enhancement generally moves to more poleward latitudes during solar maximum, as compared to solar minimum. (4) At higher midlatitudes (~45°–60°N and ~40°–50°S in geographic latitudes) in solar minimum, the winter‐to‐summer ratio of O/N2 in each hemisphere has an obvious minimum in near‐pole longitudes. This minimum becomes more evident during solar maximum. The National Center for Atmospheric Research Thermosphere‐Ionosphere‐Electrodynamics General Circulation Model simulations indicate that in the winter hemisphere, the unexpected O/N2 longitudinal pattern in higher midlatitudes is mainly associated with high‐latitude Joule heating under the impact from ion convection and auroral precipitation.
Aligned Nanofibrous Cell‐Derived Extracellular Matrix for Anisotropic Vascular Graft Construction
Authors: Xing Qi , Qian Zichen , Tahtinen Mitchell , Yap Ai Hui , Yates Keegan , Zhao Feng
Published: February 2017

There is a large demand for tissue engineered vascular grafts for the application of vascular reconstruction surgery or in vitro drug screening tissue model. The extracellular matrix (ECM) composition along with the structural and mechanical anisotropy of native blood vessels is critical to their functional performance. The objective of this study is to develop a biomimetic vascular graft recapitulating the anisotropic features of native blood vessels by employing nanofibrous aligned fibroblast‐derived ECM and human mesenchymal stem cells (hMSCs). The nanotopographic cues of aligned ECM direct the initial cell orientation. The subsequent maturation under circumferential stress generated by a rotating wall vessel (RWV) bioreactor further promotes anisotropic structural and mechanical properties in the graft. The circumferential tensile strength is significantly higher than longitudinal strength in bioreactor samples. Expression of smooth muscle cell specific genes, α‐smooth muscle actin and calponin, in hMSCs is greatly enhanced in bioreactor samples without any biochemical stimulation. In addition, employment of premade ECM and RWV bioreactor significantly reduces the graft fabrication time to three weeks. Mimicking the ECM composition, cell phenotype, structural and mechanical anisotropy, the vascular graft presented in this study is promising for vascular reconstruction surgery or in vitro tissue model applications.
Interfacial Charge Transfer in Photoelectrochemical Processes
Authors: Kumar Sandeep , Ojha Kasinath , Ganguli Ashok K.
Published: February 2017

Solar light harvesting and conversion to useful energy are the most important tasks for overcoming the world energy crisis. The design of advanced materials for solar light conversion requires focused research to obtain efficient photocatalytic systems. Photogenerated charge carrier separation is a crucial prerequisite in applications such as photo‐electrochemical water splitting, photovoltaics, and photocatalytic dye degradation. Interfacial charge‐transfer (IFCT) plays a significant role in electron–hole separation considering the energy barriers of the energy levels at semiconductor–semiconductor, semiconductor–metal, semiconductor–molecule, and semiconductor–electrolyte interfaces. Both electron and hole transport across the interface via IFCT, with comparable rates, are important for maintaining enhanced photocatalytic efficiency and stability of the catalysts. The key focus of this article is to understand the charge transfer processes at the interface and the relationship between photogenerated charge separation and photocatalytic activity. The interfacial charge transfer in different interfaces is discussed, along with the fundamentals of IFCT in photo‐electrochemical processes; semiconductor heterojunctions with materials having proper band alignment and offer new ways to design multifunctional photocatalysts are also disucssed. The charge transfer process from semiconductor to catalyst molecules and dye molecules to semiconductor is explained in detail.
Light Scattering Enhancement at the Absorption Edge in Dewetting Droplets of Cyanine Dyes
Authors: Leclaire Nicolas A. , Boudoire Florent , Hack Erwin , Brönnimann Rolf , Nüesch Frank A. , Heier Jakob
Published: February 2017

Diffraction properties of thin films of dewetted cyanine dye droplets are investigated and related to the complex refractive index. Strong changes in the index of refraction are often found near the absorption edge of organic dyes. Within a small window of droplet morphologies, scattering efficiency is maximized and becomes wavelength‐selective. The origin of the high scattering efficiency is found to be in the enhancement of scattering at the absorption edge of the dye, where anomalous refractive index dispersion occurs. For a comprehensive understanding of the scattering effect, an analytical solution for the diffraction of an array of scatterers is presented. Finite‐difference time‐domain simulations of the extinction properties are performed and good agreements to the experiments are found. These results pave the way to an easy fabrication of new organic‐based optical devices such as refractive index‐based sensors or color selective diffraction gratings.
Establishing utility values for the 22‐item Sino‐Nasal Outcome Test (SNOT‐22) using a crosswalk to the EuroQol–five‐dimensional questionnaire–three‐level version (EQ‐5D‐3L)
Authors: Crump R. Trafford , Lai Ernest , Liu Guiping , Janjua Arif , Sutherland Jason M.
Published: February 2017

Background

Chronic rhinosinusitis (CRS) is a common condition for which there are numerous medical and surgical treatments. The 22‐item Sino‐Nasal Outcome Test (SNOT‐22) is a patient‐reported outcome measure often used with patients diagnosed with CRS. However, there are no utility values associated with the SNOT‐22, limiting its use in comparative effectiveness research. The purpose of this study was to establish utilities for the SNOT‐22 by mapping responses to utility values associated with the EuroQol–5‐dimensional questionnaire–3‐level version (EQ‐5D‐3L).

Methods

This study used data collected from patients diagnosed with CRS awaiting bilateral endoscopic sinus surgery in Vancouver, Canada. Study participants completed both the SNOT‐22 and the EQ‐5D‐3L. Ordinary least squares was used for 3 models that estimated the EQ‐5D‐3L utility values as a function of the SNOT‐22 items.

Results

A total of 232 participants completed both the SNOT‐22 and the EQ‐5D‐3L. As expected, there was a negative relationship between the SNOT‐22 global scores and EQ‐5D‐3L utility values. Adjusted R2 for the 3 models ranged from 0.28 to 0.33, and root mean squared errors between 0.23 and 0.24. A nonparametric bootstrap analysis demonstrated robustness of the findings.

Conclusion

This study successfully developed a mapping model to associate utility values with responses to the SNOT‐22. This model could be used to conduct comparative effectiveness research in CRS to evaluate the various interventions available for treating this condition.
Enolonium Species—Umpoled Enolates
Authors: Arava Shlomy , Kumar Jayprakash N. , Maksymenko Shimon , Iron Mark A. , Parida Keshaba N. , Fristrup Peter , Szpilman Alex M.
Published: February 2017

Enolonium species/iodo(III)enolates of carbonyl compounds have been suggested to be intermediates in a wide variety of hypervalent iodine induced chemical transformations of ketones, including α‐C−O, α‐C−N, α‐C−C, and α‐carbon–halide bond formation, but they have never been characterized. We report that these elusive umpoled enolates may be made as discrete species that are stable for several minutes at −78 °C, and report the first spectroscopic identification of such species. It is shown that enolonium species are direct intermediates in C−O, C−N, C−Cl, and C−C bond forming reactions. Our results open up chemical space for designing a variety of new transformations. We showcase the ability of enolonium species to react with prenyl, crotyl, cinnamyl, and allyl silanes with absolute regioselectivity in up to 92 % yield.
B(C6F5)3‐katalysierte chemoselektive Defunktionalisierung von etherhaltigen primären Alkyltosylaten mit Hydrosilanen
Authors: Chatterjee Indranil , Porwal Digvijay , Oestreich Martin
Published: February 2017

Eine durch B(C6F5)3/Et3SiH vermittelte C(sp3)‐O‐Bindungsspaltung verläuft in Gegenwart von primären und sekundären Silylethern und Arylethern bevorzugt mit primären Tosylaten. Dieser Reaktivitätsunterschied ermöglicht die chemoselektive Defunktionalisierung etlicher 1,n‐Diole, und die selektive Desoxygenierung einer Hydroxymethylgruppe eines orthogonal geschützten Kohlenhydrats veranschaulicht das Potenzial der neuen Reaktionsvorschrift. Tosylate mit einer benachbarten Phenylgruppe werden mit anchimerer Unterstützung gespalten.
Train rescheduling model with train delay and passenger impatience time in urban subway network
Authors: Zhen Qu , Jing Shi
Published: February 2017

This paper considers the train rescheduling problem with train delay in urban subway network. With the objective of minimizing the negative effect of train delay to passengers, which is quantified with a weighted combination of travel time cost and the cost of giving up the planned trips, train rescheduling model is proposed to jointly synchronize both train delay operation constraints and passenger behavior choices. Space–time network is proposed to describe passenger schedule‐based path choices and obtain the shortest travel times. Impatience time is defined to describe the intolerance of passengers to train delay. By comparing the increased travel time due to train delay with the passenger impatience time, a binary variable is defined to represent whether the passenger will give up their planned trips or not. The proposed train rescheduling model is implemented using genetic algorithm, and the model effectiveness is further examined through numerical experiments of real‐world urban subway train timetabling test. Duration effects of the train delay to the optimization results are analyzed. Copyright © 2017 John Wiley & Sons, Ltd.
Development and validation of a reversed‐phase HPLC method for licarbazepine monitoring in serum of patients under oxcarbazepine treatment
Authors: Begas Elias , Tsakalof Andreas , Dardiotis Efthimios , Vatidis Georgios Emmanouil , Kouvaras Evangelos , Asprodini Eftihia Konstadinos
Published: February 2017

Licarbazepine is the pharmacologically active metabolite of oxcarbazepine, a drug indicated for the treatment of partial seizures and bipolar disorders. Several HPLC methods have been developed thus far but there is lack of control for interferences from antipsychotic drugs. The aim of the present study was to develop a simple, low‐cost and reliable HPLC‐UV method for the determination of licarbazepine in human serum in the presence of co‐administered antiepileptic, antipsychotic and commonly prescribed drugs. Sample preparation consisted of a single protein precipitation step with methanol. Separation lasted ~9 min on a reversed‐phase C18 column using a mobile phase composed of 50 mm sodium‐dihydrogen‐phosphate‐monohydrate/acetonitrile (70:30, v/v) delivered isocratically at 0.9 mL/min and 30°C. Wavelength was 210 nm and calibration curve was linear with r2 0.998 over the range 0.2–50.0 μg/mL. Coefficient of variation was <5.03% and bias <−4.92%. Recovery ranged from 99.49 to 104.52% and the limit of detection was 0.0182 μg/mL. No interferences from the matrix or from antiepileptic, antipsychotic and commonly prescribed drugs were observed. The method was applied to serum samples of patients under oxcarbazepine treatment and proved to be a useful tool for the therapeutic drug monitoring of licarbazepine during monotherapy or adjunctive treatment of seizures or affective disorders.
Simultaneous determination of eight B‐vitamins in rat intestinal perfusate to identify effects of osmotic pressures on absorptions
Authors: Wang Xiaobo , Xiao Jian , Zhou Hui , Qiu Ying , Peng Hui , Sun Yangyang , Zhang Jiwen , Qian Wei , Sun Lixin
Published: February 2017

A rapid and accurate HPLC‐DAD method was developed and validated to simultaneously determine eight B‐vitamins (VBs, namely thiamine, riboflavin, niacinamide, calcium pantothenic, pyridoxine, biotin, folic acid and cyanocobalamin) and phenolsulfonphthalein in rat intestinal perfusate. Chromatographic separation was achieved using an Inertsil ODS‐3 column (250 × 4.6 mm i.d., 5 μm) at a temperature of 40°C. Gradient elution mode was applied at the flow rate of 1.0 mL/min with the mobile phase of acetonitrile–30 mm K2HPO4 (pH 5.80). The method was successfully applied to identify the effects of osmotic pressures on the absorption of the VBs. The absorption profiles of single and mixed VBs were also compared. Histological section technology was applied to observe the microstructure of small bowel mucosa after perfusion. The results indicated that each compound possessed a better absorption profile under isotonic conditions than under hypotonic or hypertonic conditions for single or mixed solutions. Compared with single VBs, better absorptions in mixed VBs were observed. Pathological tissue slice test suggested that hypotonic and hypertonic solutions changed or damaged the microstructure of mucosa to varying degrees. Taken together, the investigations indicated that multi‐VBs administered orally under isotonic condition could generate fast and complete absorption profiles for VBs.
Preparation of a Nanobiocatalyst by Efficiently ImmobilizingAspergillus nigerLipase onto Magnetic Metal–Biomolecule Frameworks (BioMOF)
Authors: Xia Gao‐Hui , Cao Shi‐Lin , Xu Pei , Li Xue‐Hui , Zhou Jian , Zong Min‐Hua , Lou Wen‐Yong
Published: February 2017

A biocompatible support made of ZnGlu‐coated magnetic iron oxide nanoparticles (ZnGlu–MNPs) was prepared by a simple electrostatic self‐assembly technique and structurally characterized.Aspergillus nigerlipase (ANL) was immobilized onto the ZnGlu–MNPs with high protein loading (118.0 mg g−1) and high enzyme‐activity recovery (more than 82.0 %). The as‐prepared immobilized ANL exhibits high catalytic performance and a wide pH and temperature adaptability. Moreover, the stabilities and the solvent tolerance of ANL@ZnGlu‐MNPs were clearly superior to those of the free counterpart. The novel ANL@ZnGlu‐MNPs was easily recycled from the reaction medium by magnetic forces. Therefore, the as‐prepared ZnGlu‐MNPs is a promising novel carrier for immobilized enzymes.
Transition‐Metal‐Free Oxidative C(sp2)−H Hydroxylation of Terpyridines: A HOMO‐Raising Strategy for the Construction of a New Super‐Stable Terpyridine Chromophores
Authors: Huang Jiang‐Bo , Bai Xing‐Feng , Li Li , Zheng Zhan‐Jiang , Xu Zheng , Cui Yu‐Ming , Cao Jian , Xu Li‐Wen
Published: February 2017

Direct functionalization of terpyridines is an increasingly important topic in the field of dyes and catalysis as well as supramolecular chemistry, but its synthesis and transformation is usually challenging. Herein, a HOMO‐raising strategy is reported for the construction of a super‐stable novel terpyridine chromophores, in which the selective oxidation of terpyridines at its 3‐position was determined successfully to the synthesis of phenol‐functionalization of terpyridines (TPyOHs) bearing a hydrogen bonding group. The corresponding TPyOHs displayed strong aggregation‐induced emission and exhibited highly selective and visual detection of ZnII cation with a record green terpyridine‐based luminophore with nanomolar sensitivity (125 nm).
The Influence of Supporting Ions on the Electrochemical Detection of Individual Silver Nanoparticles: Understanding the Shape and Frequency of Current Transients in Nano‐impacts
Authors: Krause Kay J. , Brings Fabian , Schnitker Jan , Kätelhön Enno , Rinklin Philipp , Mayer Dirk , Compton Richard G. , Lemay Serge G. , Offenhäusser Andreas , Wolfrum Bernhard
Published: February 2017

We report the influence of electrolyte composition and concentration on the stochastic amperometric detection of individual silver nanoparticles at microelectrode arrays and show that the sensor response at certain electrode potentials is dependent on both the conductivity of the electrolyte and the concentration of chloride ions. We further demonstrate that the chloride concentration in solution heavily influences the characteristic current spike shape of recorded nanoparticle impacts: While typically too short to be resolved in the measured current, the spike widths are significantly broadened at low chloride concentrations below 10 mm and range into the millisecond regime. The analysis of more than 25 000 spikes reveals that this effect can be explained by the diffusive mass transport of chloride ions to the nanoparticle, which limits the oxidation rate of individual silver nanoparticles to silver chloride at the chosen electrode potential.
CFD as a Design Tool for Fixed‐Bed Reactors with Small Tube‐to‐Pellet Diameter Ratio: Now or in the Future?
Authors: Wehinger Gregor D. , Kraume Matthias
Published: February 2017

Festbettreaktoren mit kleinem Rohr‐zu‐Pelletdurchmesser‐Verhältnis (D/dp = N) finden vor allem bei stark exo‐ oder endothermen Reaktionen Anwendung. In diesem Beitrag werden Aspekte eines Algorithmus‐basierten Ansatzes untersucht, der Festbetten mit kleinem N ortsaufgelöst modelliert. Dabei wird das Modell hinsichtlich Bettmorphologie und den daraus resultierenden Geschwindigkeiten, Wärmetransport sowie heterogener Katalyse mit experimentellen Daten verglichen. Schlussendlich wird der Frage nachgegangen, in wie weit CFD als Designtool für Festbettreaktoren mit kleinem N verwendet werden kann.
Medicinal Chemistry Profiling of Monocyclic 1,2‐Azaborines
Authors: Zhao Peng , Nettleton David O. , Karki Rajeshri G. , Zécri Frédéric J. , Liu Shih‐Yuan
Published: February 2017

The first examples of biologically active monocyclic 1,2‐azaborines have been synthesized and demonstrated to exhibit not only improved in vitro aqueous solubility in comparison with their corresponding carbonaceous analogues, but in the context of a CDK2 inhibitor, also improved biological activity and better in vivo oral bioavailability. This proof‐of‐concept study establishes the viability of monocyclic 1,2‐azaborines as a novel pharmacophore with distinct pharmacological profiles that can help address challenges associated with solubility in drug development research.
Effect of postoperative radiotherapy on survival for surgically managed pT3N0 and pT4aN0 laryngeal cancer: Analysis of the National Cancer Data Base
Authors: Graboyes Evan M. , Zhan Kevin Y. , Garrett‐Mayer Elizabeth , Lentsch Eric J. , Sharma Anand K. , Day Terry A.
Published: February 2017

BACKGROUND

The current study was conducted to determine the effect of postoperative radiotherapy (PORT) on overall survival in patients with surgically managed pT3‐T4aN0 laryngeal squamous cell carcinoma (SCC).

METHODS

A review of the National Cancer Data Base from 2004 through 2013 was performed. Patients with surgically managed pT3‐4aN0 laryngeal SCC with negative surgical margins were included. Univariable and multivariable Cox regression analyses were used to determine factors associated with survival.

RESULTS

A total of 1460 patients were included, 46.2% of whom had pT3N0 disease (674 patients) and 53.8% of whom had pT4aN0 disease (786 patients). Approximately 72.0% of the patients with pT3N0 disease (485 patients) and 50.1% of the patients with pT4aN0 disease (394 patients) received PORT. PORT was not found to be associated with improved overall survival on univariable analysis for patients with pT3N0 disease (hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62‐1.14), but was for patients with pT4aN0 disease (HR, 0.57; 95% CI, 0.45‐0.71). For patients with pT3N0 SCC of the larynx, in a multivariable Cox regression analysis adjusting for age >65 years, severity of comorbidities, larynx subsite, extent of laryngectomy, and number of lymph nodes removed, PORT was not found to be associated with improved survival (adjusted HR, 0.88; 95% CI, 0.64‐1.21). For patients with pT4aN0 disease, the administration of PORT was associated with improved survival on multivariable analysis adjusting for age >65 years, severity of comorbidities, larynx subsite, number of lymph nodes removed, and type of hospital (adjusted HR, 0.58; 95% CI, 0.46‐0.73).

CONCLUSIONS

For patients with surgically managed pT3N0 laryngeal SCC with negative margins, PORT does not appear to be associated with improved survival. Despite a survival benefit, nearly 50% of patients with pT4aN0 laryngeal SCC and negative surgical margins do not receive standard‐of‐care PORT. Cancer 2017;123:2248–2257. © 2017 American Cancer Society.
Racial disparities in BRCA testing and cancer risk management across a population‐based sample of young breast cancer survivors
Authors: Cragun Deborah , Weidner Anne , Lewis Courtney , Bonner Devon , Kim Jongphil , Vadaparampil Susan T. , Pal Tuya
Published: February 2017

BACKGROUND

Breast cancer (BC) disparities may widen with genomic advances. The authors compared non‐Hispanic white (NHW), black, and Hispanic BC survivors for 1) cancer risk‐management practices among BRCA carriers and 2) provider discussion and receipt of genetic testing.

METHODS

A population‐based sample of NHW, black, and Hispanic women who had been diagnosed with invasive BC at age 50 years or younger from 2009 to 2012 were recruited through the state cancer registry. Multiple logistic regression was used to compare cancer risk‐management practices in BRCA carriers and associations of demographic and clinical variables with provider discussion and receipt of testing.

RESULTS

Of 1622 participants, 159 of 440 (36.1%) black women, 579 of 897 (64.5%) NHW women, 58 of 117 (49.6%) Spanish‐speaking Hispanic women, and 116 of 168 (69%) English‐speaking Hispanic women underwent BRCA testing, of whom 90 had a pathogenic BRCA mutation identified. Among BRCA carriers, the rates of risk‐reducing mastectomy and risk‐reducing salpingo‐oophorectomy were significantly lower among black women compared with Hispanic and NHW women after controlling for clinical and demographic variables (P = .025 and P = .008, respectively). Compared with NHW women, discussion of genetic testing with a provider was 16 times less likely among black women (P < .0001) and nearly 2 times less likely among Spanish‐speaking Hispanic women (P = .04) after controlling for clinical and sociodemographic factors.

CONCLUSIONS

The current results suggest that the rates of risk‐reducing salpingo‐oophorectomy are lower among black BRCA carriers compared with their Hispanic and NHW counterparts, which is concerning because benefits from genetic testing arise from cancer risk‐management practice options. Furthermore, lower BRCA testing rates among blacks may partially be because of a lower likelihood of provider discussion. Future studies are needed to improve cancer risk identification and management practices across all populations to prevent the widening of disparities. Cancer 2017;123:2497–05. © 2017 American Cancer Society.
Psychometric properties of the Dutch version of the Treatment Support Measure (TSM) parent and youth form
Authors: van Sonsbeek Maartje A. M. S. , Holtmaat Catharina J. M. , Tiemens Bea G. , Hutschemaekers Giel J. M. , de Jong Kim
Published: February 2017

The Treatment Support Measure (TSM) Parent and Youth were created to help clinicians with actionable feedback when youths are not making sufficient progress in treatment. This study examined the psychometric properties of the Dutch TSM Parent and TSM Youth. Parents (n = 172) and youth (n = 122) were recruited at 2 outpatient mental health care institutions. Children of participating parents (50.6% boys) had a mean age of 11.9 years (SD = 3.46; range 4–18). Participating youth (30.3% boys) had a mean age of 15.68 years (SD = 1.75; range 12–18). Participants were asked to complete the TSM and questionnaires measuring related constructs once during treatment. Responses to the TSM Parent items were explained by 9 instead of 5 subscales, and responses to the TSM Youth items were explained by 8 instead of 4 subscales. The internal consistency reliability of both the TSM Parent and the TSM Youth scales was generally good. The convergent validity of the TSM Parent and the TSM Youth was also good, although the divergent validity was less convincing. The criterion validity was inconclusive; the TSM Parent was not able to differentiate between problematic and nonproblematic treatments, but multiple scales of the TSM Youth were able to differentiate between these groups. The TSM Parent and TSM Youth have potential to be helpful tools in clinical practice. They could signal potential barriers to youth progress and direct the conversation between the clinician and youth and parents about adaptation of treatment.

Key practitioner message

This is the first study to investigate the psychometric properties of the Treatment Support Measure (TSM) Parent and Youth versions, which are created to help clinicians with actionable feedback when youths are not making sufficient progress in treatment.

The Dutch TSM Parent and TSM Youth have moderate to good psychometric properties.

The Dutch TSM Parent and TSM Youth might be helpful tools for use in clinical practice: they contain variables that are related to youth outcome, can signal potential barriers to youth progress, and can direct the conversation between the clinician and the youth and parents about adaptation of treatment.

The Dutch TSM Parent and TSM Youth could be added to the regular ROM to facilitate both routine monitoring of outcome and direct and concrete aid to the here‐and‐now relational processes in treatment.
Use of External Controls in Regulatory Decision‐Making
Authors: Jarow JP
Published: February 2017

The expanded use of electronic data retrieval systems has greatly expanded the potential sources of real‐world data and presents new opportunities for evidence generation outside of the traditional research trial. These data may be used to inform trial design and interpretation as well. Externally controlled trials, such as single‐arm and noninferiority designs, have long been used in regulatory decision‐making despite the potential flaws based on assumptions of assay sensitivity and constancy.
Association of Time‐Varying Clearance of Nivolumab With Disease Dynamics and Its Implications on Exposure Response Analysis
Authors: Liu C , Yu J , Li H , Liu J , Xu Y , Song P , Liu Q , Zhao H , Xu J , Maher VE , Booth BP , Kim G , Rahman A , Wang Y
Published: February 2017

Nivolumab is a human monoclonal antibody that blocks the interaction between PD‐1 programmed death‐1 (PD‐1) and its ligands, PD‐L1 and PD‐L2. Nivolumab demonstrated efficacy in clinical trials for various types of cancer. A time‐varying clearance was identified for nivolumab. We show that the change of clearance over time is associated with the post‐treatment effects: clearance decreases when disease status improves. This interaction between posttreatment effects and drug exposure may lead to a biased steep estimate of the exposure–response (E‐R) relationship for efficacy. Under this scenario, simulations were performed to develop a proposed methodology to assess the causal effect of drug exposure upon clinical response. Data from nivolumab trials were subsequently used to verify the proposed methodology for E‐R analysis. The results showed that E‐R analysis results based on pharmacokinetic (PK) metrics derived from the first dose are more consistent with the true E‐R or dose–response relationship than the steady‐state PK metrics.
Cancer Moonshot Connecting International Liquid Biopsy Efforts Through Academic Partnership
Authors: Dive C , Shishido SN , Kuhn P
Published: February 2017

The Kuhn Laboratory at the University of Southern California and the Dive Laboratory at the Cancer Research UK's Manchester Institute are teaming up to apply new cancer cell detection technology to identify patients who will progress after initial treatment. Researchers will take a simple blood sample to identify early those patients whose cancer has returned, while analyzing circulating tumor cells (CTCs) in great detail, providing new clues on the most effective therapy for the patient's cancer.
Why Has Model‐Informed Precision Dosing Not Yet Become Common Clinical Reality? Lessons From the Past and a Roadmap for the Future
Authors: Darwich A S , Ogungbenro K , Vinks A A , Powell J R , Reny J‐L , Marsousi N , Daali Y , Fairman D , Cook J , Lesko L J , McCune J S , Knibbe C A J , de Wildt S N , Leeder J S , Neely M , Zuppa A F , Vicini P , Aarons L , Johnson T N , Boiani J , Rostami‐Hodjegan A
Published: February 2017

Patient groups prone to polypharmacy and special subpopulations are susceptible to suboptimal treatment. Refined dosing in special populations is imperative to improve therapeutic response and/or lowering the risk of toxicity. Model‐informed precision dosing (MIPD) may improve treatment outcomes by achieving the optimal dose for an individual patient. There is, however, relatively little published evidence of large‐scale utility and impact of MIPD, where it is often implemented as local collaborative efforts between academia and healthcare. This article highlights some successful applications of bringing MIPD to clinical care and proposes strategies for wider integration in healthcare. Considerations are brought up herein that will need addressing to see MIPD become “widespread clinical practice,” among those, wider interdisciplinary collaborations and the necessity for further evidence‐based efficacy and cost–benefit analysis of MIPD in healthcare. The implications of MIPD on regulatory policies and pharmaceutical development are also discussed as part of the roadmap.
Data Sharing, Clinical Trials, and Biomarkers in Precision Oncology: Challenges, Opportunities, and Programs at the Department of Veterans Affairs
Authors: Fiore LD , Brophy MT , Ferguson RE , Shannon C , Turek SJ , Pierce‐Murray K , Ajjarapu S , Huang GD , Lee CSE , Lavori PW
Published: February 2017

Cancer genomic research reveals that a similar cancer clinical phenotype (e.g., non‐small cell lung cancer) can arise from various mutations in tumor DNA. Thus, organ of origin is not a definitive classification. Further, targeted therapy for cancer patients (precision oncology) capitalizes on knowledge of individual patient mutational status to deliver treatment directed against the protein products of these mutations with the goal of reducing toxicity and enhancing efficacy relative to traditional nontargeted chemotherapy.
Versatile Bulky N,N′,N′‐Substituted 1,2‐Ethanediamine Ligands and Their Lithium, Aluminium, and Gallium Derivatives
Authors: Kretschmer Robert , Dehmel Maximilian , Bodensteiner Michael
Published: February 2017

Sterically demanding N,N′,N′‐substituted 1,2‐ethanediamine ligands have been prepared from commercially available starting materials by applying a facile one‐step procedure. These ligands offer advantages compared to known systems: a suppressed delocalization due to the saturated backbone inhibits a noninnocent behaviour and the low symmetry of the related metal complexes makes them potential candidates for asymmetric catalysis. The ligands are readily transformed into the corresponding lithium derivatives 4, which in turn act as starting materials to access the corresponding aluminium and gallium dichlorides 5 and 6, respectively. In addition, deprotonation by Al(CH3)3 gives rise to the related dimethylalane 7. All main‐group element compounds have been studied by means of single X‐ray crystallography and spectroscopic methods.
Synthesis, Structure, and First Reactivity Studies of Functional (Phosphinoamino)boranes
Authors: Majhi Paresh Kumar , Franco José Manuel Villalba , Schnakenburg Gregor , Sasamori Takahiro , Streubel Rainer
Published: February 2017

Functional phosphanes having a P–N–B motif were obtained by treatment of chloro(organo)phosphanes with boryl amides. Compounds 4a–e are stable up to 100 °C and show no association in solution, even at low temperature (–70 °C). The functional phosphanes were characterized by NMR and IR spectroscopy, MS, and microanalysis, and phosphanes 4a, 4c, and 4e were additionally scrutinized by single‐crystal X‐ray crystallography. Preliminary studies on chlorine/lithium exchange of 4a led to anionic azaphosphaboriridine 5a′.
CdX2 Coordination Polymers with 2‐Chloropyrazine and 2‐Methylpyrazine: Similar Ligands – Similar Structures – Different Reactivity
Authors: Näther Christian , Jess Inke , Germann Luzia S. , Dinnebier Robert E. , Braun Michael , Terraschke Huayna
Published: February 2017

Several coordination compounds, based on Cd halides and 2‐methylpyrazine (Mepyz) or 2‐chloropyrazine (Clpyz) as N‐donor coligands, are synthesized and their crystal structures determined by either single‐crystal or X‐ray powder diffraction (XRPD). In [CdX2(2‐Clpyz)2]n (X = Cl: 1‐Cl‐Clpyz; X = Br: 1‐Br‐Clpyz; and X = I: 1‐I‐Clpyz) and [CdX2(2‐Mepyz)2]n (X = Cl: 1‐Cl‐Mepyz; X = Br: 1‐Br‐Mepyz; and X = I: 1‐I‐Mepyz), the Cd cations are octahedrally coordinated by two N‐donor ligands and are linked into chains by the halide anions that share common edges. In the ligand‐deficient compounds [CdX2(2‐methylpyrazine)]n (X = Cl: 2‐Cl‐Mepyz; X = Br: 2‐Br‐Mepyz; and X = I: 2‐I‐Mepyz), similar CdX2 chains, which are connected into layers by the N‐donor ligands, are observed. Thermal analysis of all 1‐Mepyz compounds shows a transformation into 2‐Mepyz, which is not observed for the 2‐chloropyrazine compounds. On further heating, compounds of composition [(CdX2)2(2‐Mepyz)]n (X = Cl: 3‐Cl‐Mepyz; X = Br: 3‐Br‐Mepyz) and [(CdI2)3(2‐Mepyz)2] (4‐I‐Mepyz) are observed. A discrete complex, with the composition CdI2(2‐Mepyz)2 monohydrate (1‐I‐Mepyz‐H2O), and a hydrate with the composition [(CdI2)(2‐Mepyz)]·1.5H2O (2‐I‐Mepyz‐H2O) with an unknown structure, were also synthesized. Both lose the water molecules upon heating. Luminescence measurements show blue to orange emissions in the range of ca. 22530–16276 cm–1, depending on the halide or pyrazine substituent, as well as the metal halide/ligand ratio.
Catalytic Intramolecular Wittig Reaction Based on a Phosphine/Phosphine Oxide Catalytic Cycle for the Synthesis of Heterocycles
Authors: Wang Long , Sun Mei , Ding Ming‐Wu
Published: February 2017

The catalytic intramolecular Wittig reactions of carbonyl‐containing bromides are reported. The R3PO byproducts participate in the catalytic cycle; therefore, the Wittig reaction can be accomplished with only a catalytic amount of organophosphorus reagent. The reaction has also been applied to the efficient and selective synthesis of isoquinolin‐1(2H)‐ones, indoles, 2,3‐dihydro‐1H‐2‐benzazepin‐1‐ones, benzofurans, and 1,2‐dihydroquinolines with a catalytic amount of phosphine oxide (0.1 equiv.) and a tetramethyldisiloxane/titanium isopropoxide [TMDS/Ti(OiPr)4] reductant system (yields: 35–88 %).
Tissue mechanics during temporal summation of sequentially cuff pressure‐induced pain in healthy volunteers and patients with painful osteoarthritis
Authors: Manafi‐Khanian B. , Kjær Petersen K. , Arendt‐Nielsen L.
Published: February 2017

Background

The phenomenon of temporal summation to repetitive pressure pain stimuli is an important central neural mechanism for pain intensity encoding. This study evaluated the time‐dependent behaviour of mechanical characteristics of soft tissue during repeated cuff stimulation used for eliciting temporal summation of cuff pressure‐evoked pain. Such information of tissue mechanics is important for the interpretation of the pain response evoked during sequential stimulations.

Methods

Temporal summation was assessed in 16 subjects separated into two groups (healthy controls and severe knee osteoarthritis patients) using a visual analogue scale during 10 repetitive painful cuff stimuli (1‐s duration, 1‐s break) of the lower leg. The geometry of the lower leg was constructed based on magnetic resonance image (MRI) data. The loading boundary condition of the finite element model was defined according to the parabolic pattern of the interface pressure around the limb and the time‐dependent profile of the cuff pressure during repetitive stimuli.

Results

The pain intensity significantly increased with an increasing number of stimuli (p < 0.001), and facilitated temporal summation of pain was observed in patients compared with healthy controls (p < 0.001). The maximal deep tissue stress and strain during stimuli 1–4 varied 43% and 9%, respectively. No variation was observed for stimuli 5–10.

Conclusions

The study concludes that the temporal summation of pain response during sequential cuff pressure is not explicable by a specific time‐dependent behaviour of stress and strain in the activated deep tissue and hence not due to changes in tissue biomechanics.

Significance

The temporal summation of pain during sequential cuff stimulation is inexplicable by the time‐dependent response of mechanical stress and strain in soft tissue.
Electrochemical Characterizations of four Main Redox–metabolites of Pseudomonas Aeruginosa
Authors: Oziat Julie , Gougis Maxime , Malliaras George G. , Mailley Pascal
Published: February 2017

Bacterial identification is of first importance in clinic nowadays. For few years, electrochemistry appears as a reliable route for characterizations outside of laboratories. Nowadays, researchers mainly focus on the opportunistic pathogen Pseudomonas aeruginosa because of its production of the Pyocyanin toxin which has an electrochemical case study behavior. Other P. aeruginosa secreted molecules are also studied in a lesser extent. This work deals with the systematic electrochemical characterizations in aprotic and protic solvents of 4 main metabolites of this bacterium in the view of multispecies detection of P. aeruginosa. We report here the behavior of the 2‐Heptyl‐4(1H)‐quinolone (HHQ), Pseudomonas Quinolone Signal (PQS), Pyocyanin (PYO) and the 2′aminoacetophenone (2‐AA). All the mentioned species are clearly visible by using electrochemical techniques (cyclic and square wave voltammetries). The 2 most suitable species for electrochemical detection appear to be PQS and PYO because of their detection at low potential.
Electrochemical Detection of FAM134B Mutations in Oesophageal Cancer Based on DNA‐Gold Affinity Interactions
Authors: Haque Md. Hakimul , Islam Md. Nazmul , Islam Farhadul , Gopalan Vinod , Nguyen Nam‐Trung , Lam Alfred K. , Shiddiky Muhammad J. A.
Published: February 2017

Inexpensive, simple and rapid DNA sensors capable of accurate and sensitive detection of cancer specific point mutations in DNA biomarkers are crucial for the routine screening of genetic mutations in cancer. Conventional approaches based on sequencing, mass spectroscopy, and fluorescence are highly effective, but they are tedious, slow and require labels and expensive equipment. Recent electrochemistry based approaches mostly rely on conventional DNA biosensing using recognition and transduction layers, and hence limited by the complicated steps of sensor fabrication associated with surface cleaning, self‐assembled monolayer formation, and target hybridization. Herein we report a relatively simple and inexpensive method for detecting point mutation in cancer by using the direct adsorption of purified DNA sequences onto an unmodified gold surface. The method relies on the base dependent affinity interaction of DNA with gold. Since the affinity interaction (adsorption) trend of DNA bases follows as adenine (A) > cytosine (C) > guanine (G)> thymine (T), two DNA sequences with different DNA base compositions (i. e., amplified mutated sequences will be distinctly different than its original sequence) will have different adsorption affinity towards gold. The amount of mutation sites on a DNA sequence is quantified by monitoring the electrochemical current as a function of the relative adsorption level of DNA samples onto a bare gold electrode. This method can successfully distinguish single point mutation in DNA from oesophageal cancer. We demonstrated the clinical utility of this approach by detecting different levels of mutations in tissue samples (n=9) taken from oesophageal cancer patients. Finally, the method was validated with High Resolution Melt (HRM) curve analysis and Sanger Sequencing.
Induction of oxidative stress by bisphenol A and its pleiotropic effects
Authors: Gassman Natalie R.
Published: February 2017

Bisphenol A (BPA) has become a target of intense public scrutiny since concerns about its association with human diseases such as obesity, diabetes, reproductive disorders, and cancer have emerged. BPA is a highly prevalent chemical in consumer products, and human exposure is thought to be ubiquitous. Numerous studies have demonstrated its endocrine disrupting properties and attributed exposure with cytotoxic, genotoxic, and carcinogenic effects; however, the results of these studies are still highly debated and a consensus about BPA's safety and its role in human disease has not been reached. One of the contributing factors is a lack of molecular mechanisms or modes of action that explain the diverse and pleiotropic effects observed after BPA exposure. The increase in BPA research seen over the last ten years has resulted in more studies that examine molecular mechanisms and revealed links between BPA‐induced oxidative stress and human disease. Here, a review of the current literature examining BPA exposure and the induction of reactive oxygen species (ROS) or oxidative stress will be provided to examine the landscape of the current BPA literature and provide a framework for understanding how induction of oxidative stress by BPA may contribute to the pleiotropic effects observed after exposure. Environ. Mol. Mutagen. 58:60–71, 2017. © 2017 Wiley Periodicals, Inc.
Optimization of the extraction of the p‐menthadienol isomers and aristolone contained in the essential oil from Elyonurus hensii using a 23 full factorial design
Authors: Loumouamou Aubin Nestor , Bikindou Kévin , Bitemou Ernest , Chalard Pierre , Silou Thomas , Figueredo Gilles
Published: February 2017

The aim of this study was to optimize the extraction of p‐menthadienol isomers and aristolone from the essential oil of Elyonurus hensii by hydrodistillation. The study of the seasonal variation in the chemical composition has shown that the plant material has been subject to a natural selection regarding the biosynthesis of the p‐menthadienol isomers: during periods of water stress, the extracts are rich in cis and trans‐p‐mentha‐1(7),8‐dien‐2‐ol and poor in cis and trans‐p‐mentha‐2,8‐dien‐1‐ol. Regarding the modeling, eight experiments were carried out by considering three easily interpretable factors (the extraction duration, the residual water content and the state of the division of the plant material). The average yield was 1.33% for the aerial part and 0.74% for the roots. The residual water content is the most important factor, which significantly influences the average yield of the essential oil and the content of the major constituents. Regarding the aerial part, a low residual water content of the plant material varies the essential oil yield (from 0.40% to 2.11%) and the content of cis and trans‐p‐mentha‐2.8‐dien‐1‐ol (from 15.87% to 23.24%). At the root level, the samples that have a very low residual water content provide extracts richer in aristolone. The combined effects of the extraction duration, the state of division, and the residual water content influence greatly the extraction of aristolone (from 36.68% to 54.55%). However, these interactions are more complex and difficult to assess.