bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous removal of SO2 and NO by CO reduction over prevulcanized Fe2O3/AC catalysts
Authors: Song Yongji , Wang Ting , Cheng Liang , Li Cuiqing , Wang Hong , Wang Xincheng
Published: December 2018

Low‐cost Fe2O3 modified activated carbon catalysts have been prepared by a facile incipient‐wetness impregnation method and used for the low‐temperature simultaneous catalytic reduction of SO2 and NO by CO. The effect of CO, NO, and SO2 was studied experimentally by transient response method. Removal efficiencies of 95 % for NO and 100 % for SO2 were obtained, respectively, for the optimum catalyst, in which the amount of Fe2O3 was 10 wt%. It was found that the catalyst was robust enough under SO2 and NO circumstances; moreover, the prevulcanization of Fe atoms was found to be essential for high efficiency. The reaction mechanism of the simultaneous desulphurization and denitrification reactions of Fe2O3/AC was proposed to follow both redox and COS mechanisms. These results make activated carbon supported Fe2O3 highly promising for the simultaneous abatement of SO2 and NO emissions generated during the combustion processes.
Mocetinostat for patients with previously treated, locally advanced/metastatic urothelial carcinoma and inactivating alterations of acetyltransferase genes
Authors: Grivas Petros , Mortazavi Amir , Picus Joel , Hahn Noah M. , Milowsky Matthew I. , Hart Lowell L. , Alva Ajjai , Bellmunt Joaquim , Pal Sumanta K. , Bambury Richard M. , O’Donnell Peter H. , Gupta Sumati , Guancial Elizabeth A. , Sonpavde Guru P. , Faltaos Demiana , Potvin Diane , Christensen James G. , Chao Richard C. , Rosenberg Jonathan E.
Published: December 2018

Background

The authors evaluated mocetinostat (a class I/IV histone deacetylase inhibitor) in patients with urothelial carcinoma harboring inactivating mutations or deletions in CREB binding protein [CREBBP] and/or E1A binding protein p300 [EP300] histone acetyltransferase genes in a single‐arm, open‐label phase 2 study.

Methods

Eligible patients with platinum‐treated, advanced/metastatic disease received oral mocetinostat (at a dose of 70 mg 3 times per week [TIW] escalating to 90 mg TIW) in 28‐day cycles in a 3‐stage study (ClinicalTrials.gov identifier NCT02236195). The primary endpoint was the objective response rate.

Results

Genomic testing was feasible in 155 of 175 patients (89%). Qualifying tumor mutations were CREBBP (15%), EP300 (8%), and both CREBBP and EP300 (1%). A total of 17 patients were enrolled into stage 1 (the intent‐to‐treat population); no patients were enrolled in subsequent stages. One partial response was observed (11% [1 of 9 patients; the population that was evaluable for efficacy comprised 9 of the 15 planned patients]); activity was deemed insufficient to progress to stage 2 (null hypothesis: objective response rate of ≤15%). All patients experienced ≥1 adverse event, most commonly nausea (13 of 17 patients; 77%) and fatigue (12 of 17 patients; 71%). The median duration of treatment was 46 days; treatment interruptions (14 of 17 patients; 82%) and dose reductions (5 of 17 patients; 29%) were common. Mocetinostat exposure was lower than anticipated (dose‐normalized maximum serum concentration [Cmax] after TIW dosing of 0.2 ng/mL/mg).

Conclusions

To the authors’ knowledge, the current study represents the first clinical trial using genomic‐based selection to identify patients with urothelial cancer who are likely to benefit from selective histone deacetylase inhibition. Mocetinostat was associated with significant toxicities that impacted drug exposure and may have contributed to modest clinical activity in these pretreated patients. The efficacy observed was considered insufficient to warrant further investigation of mocetinostat as a single agent in this setting.
The role of menopausal hormone therapy in women with or at risk of ovarian and breast cancers: Misconceptions and current directions
Authors: Temkin Sarah M. , Mallen Adrianne , Bellavance Emily , Rubinsak Lisa , Wenham Robert M.
Published: December 2018

For women who are candidates for menopausal hormone therapy (MHT), estrogen can provide relief from symptomatic menopause, decrease rates of chronic illnesses, and improve health‐related quality of life. However, confusion surrounds the evidence regarding the impact of exogenous estrogen and progesterone on the breast and ovary. Available data regarding the risks of MHT (estrogen and/or progestin) related to the development of breast and ovarian cancer are often inconsistent or incomplete. Modern molecular and genetic techniques have improved our understanding of the heterogeneity of breast and ovarian cancer. This enhanced understanding of the disease has impacted our understanding of carcinogenesis. Treatment options have evolved to be more targeted toward hormonal therapy for certain subtypes of disease, whereas cytotoxic chemotherapy remains the standard for other histological and molecular subtypes. The role of MHT in the breast and ovarian cancer survivor, as well as women who are at high risk for the development of hereditary breast and ovarian cancer, remains controversial despite evidence that this treatment can improve quality of life and survival outcomes. Through this article, we examine the evidence for and against the use of MHT with a focus on women who have or are at high risk for breast and ovarian cancer.
Effect of Rifampicin on the Pharmacokinetics of a Single Dose of Vemurafenib in Patients With BRAFV600 Mutation–Positive Metastatic Malignancy
Authors: Zhang Weijiang , McIntyre Christine , Forbes Harper , Gaafar Rabab , Kohail Hanaa , Beck J. Thaddeus , Plestina Stjepko , Bertran Enric , Riehl Todd
Published: December 2018

Vemurafenib prolongs survival in patients with BRAFV600‐mutated advanced melanoma. In vitro studies show cytochrome P450 (CYP) 3A4 is involved in vemurafenib metabolism, but the effect of strong inducers or inhibitors of CYP3A4 on vemurafenib exposure in vivo is unknown. This phase 1, open‐label, multicenter study evaluated the effect of rifampicin, a CYP3A4 inducer, on the pharmacokinetics of single‐dose vemurafenib in 27 patients with BRAFV600 mutation–positive metastatic malignancy. Patients received a single oral dose of vemurafenib 960 mg on day 1, oral rifampicin 600 mg daily on days 8–16 (period B), and a single oral dose of vemurafenib 960 mg on day 17 and rifampicin 600 mg daily for days 17–23 (period C), with plasma samples obtained up to 168 hours after vemurafenib dosing. The geometric mean ratio (period C/period A) of area under the concentration‐time curve from time zero to last measurable concentration time point and area under the concentration‐time curve from time zero to infinity for vemurafenib (n = 23 for the pharmacokinetic analysis) was 0.61 (90% confidence interval, 0.48–0.78) and 0.60 (90% confidence interval, 0.47–0.76), respectively, indicating rifampicin significantly decreased vemurafenib plasma exposure by approximately 40%. The geometric mean ratio of the maximum concentration for vemurafenib was 1.1; this slight increase is likely owing to one outlier in period C. Adverse events were consistent with those previously seen for rifampicin and for vemurafenib monotherapy. Caution is advised when dosing vemurafenib concurrently with CYP3A4 inducers.
Utility of intraoperative squash cytology in diagnosis of paediatric central nervous system lesions
Authors: Maity Priyanka , Sengupta Moumita , Jain Kavita , Chaudhuri Shubhamitra , Chatterjee Uttara , Datta Chhanda , Chatterjee Sandip
Published: December 2018

Background

Role of squash cytology in intraoperative diagnosis of central nervous system lesions has been well established. Intraoperative diagnosis is especially important in paediatric CNS lesions as decision regarding gross total resection or near total resection or subtotal resection is crucial and radiotherapy and chemotherapy are best avoided in this age group. The aim of this study was to evaluate the utility of squash cytology of CNS lesions in paediatric age group and to assess its diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value.

Materials and methods

A prospective study was conducted on 42 paediatric patients with clinico‐radiologically diagnosed CNS lesions. Intraoperative squash smears were stained with haematoxylin and eosin (H&E) stain. Diagnosis made subsequently on paraffin sections was taken as gold standard.

Results

The overall diagnostic accuracy of intraoperative squash cytology of CNS lesions in paediatric age group was 73.80%. The sensitivity, specificity, positive predictive value and negative predictive value of this modality were 92.31%, 87.50%, 96.00% and 77.78%, respectively.

Conclusions

The spectrum of CNS lesions in paediatric age group is different from that in adults. Though the sensitivity and specificity of squash cytology in paediatric tumours are less than that of adults, it is an important tool for intraoperative diagnosis that guides regarding the extent of resection.
Flexible communication within bird families—The consequences of behavioral plasticity for parent–offspring coadaptation
Authors: Fresneau Nolwenn , Müller Wendt
Published: December 2018

Offspring are selected to demand more resources than what is optimal for their parents to provide, which results in a complex and dynamic interplay during parental care. Parent–offspring communication often involves conspicuous begging by the offspring which triggers a parental response, typically the transfer of food. So begging and parental provisioning reciprocally influence each other and are therefore expected to coevolve. There is indeed empirical evidence for covariation of offspring begging and parental provisioning at the phenotypic level. However, whether this reflects genetic correlations of mean levels of behaviors or a covariation of the slopes of offspring demand and parental supply functions (= behavioral plasticity) is not known. The latter has gone rather unnoticed—despite the obvious dynamics of parent–offspring communication. In this study, we measured parental provisioning and begging behavior at two different hunger levels using canaries (Serinus canaria) as a model species. This enabled us to simultaneously study the plastic responses of the parents and the offspring to changes in offspring need. We first tested whether parent and offspring behaviors covary phenotypically. Then, using a covariance partitioning approach, we estimated whether the covariance predominantly occurred at a between‐nest level (i.e., indicating a fixed strategy) or at a within‐nest level (i.e., reflecting a flexible strategy). We found positive phenotypic covariation of offspring begging and parental provisioning, confirming previous evidence. Yet, this phenotypic covariation was mainly driven by a covariance at the within‐nest level. That is parental and offspring behaviors covary because of a plastic behavioral coadjustment, indicating that behavioral plasticity could be a main driver of parent–offspring coadaptation.
Treatment patterns of patients with acute heart failure who develop acute kidney injury
Authors: Boulos Jubran , Darawsha Wisam , Abassi Zaid A. , Azzam Zaher S. , Aronson Doron
Published: December 2018

Aims

In the present study, we aimed to determine the relationship between therapeutic decisions during the treatment of acute heart failure (AHF) patients who develop acute kidney injury (AKI) and subsequent renal and clinical outcomes.

Methods and results

We studied 277 patients with AHF and AKI, defined as an increase of >0.3 mg/dL in serum creatinine. The physician response to AKI was determined through a treatment composite score that captured changes in medical management in response to AKI, including a reduction (≥50%) or discontinuation of selected medication classes [angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers (ACE‐Is/ARBs), beta‐blockers, and diuretics] and fluids administration. ACE‐Is/ARBs, beta‐blockers, and diuretics were reduced or discontinued in 103 (55.4%), 84 (38.9%), and 166 (61.5%), respectively. Fluids were administered to 130 (46.9%) patients. Discontinuation rates of ACE‐Is/ARBs, beta‐blockers, diuretics, and fluids administration were higher in patients with hypotension (systolic blood pressure < 90 mm Hg; P = 0.001). In a logistic regression model, a composite score > 1 was associated with greater likelihood of renal function recovery (odds ratio 3.47, 95% confidence interval 2.06–5.83; P < 0.0001) but with a smaller reduction in congestion index (P = 0.021). Unadjusted 6 months mortality was higher in patients with a composite treatment score > 1 (hazard ratio 1.71, 95% confidence interval 1.12–2.61; P = 0.01). After adjustments, the treatment composite score was no longer associated with mortality.

Conclusions

Discontinuation or dose reduction of diuretics or neurohormonal blockers may improve renal outcome at the price of less efficient decongestion. Our results emphasize the need for randomized clinical trials that address the treatment of AHF patients with AKI.
Modern‐day cardio‐oncology: a report from the ‘Heart Failure and World Congress on Acute Heart Failure 2018’
Authors: Anker Markus S. , Lena Alessia , Hadzibegovic Sara , Belenkov Yury , Bergler‐Klein Jutta , de Boer Rudolf A. , Cohen‐Solal Alain , Farmakis Dimitrios , von Haehling Stephan , López‐Fernández Teresa , Pudil Radek , Suter Thomas , Tocchetti Carlo G. , Lyon Alexander R. ,   for the Heart Failure Association Cardio‐Oncology Study Group of the European Society of Cardiology
Published: December 2018

During the ‘Heart Failure and World Congress on Acute Heart Failure 2018’, many sessions and lectures focused on cardio‐oncology. This important field of research is constantly growing, and therefore, a great amount of time during the congress focused on it. Prevention and early recognition of side effects is very important in cancer patients. One of the most common and potentially severe problems during antineoplastic therapy is cardiotoxicity. Hence, cardio‐oncology is vital in managing cancer patients. This paper will summarize the topics discussed in three main sessions and many additional lectures throughout the ‘Heart Failure and World Congress on Acute Heart Failure 2018’. The covered topics included pathophysiological mechanisms in the development of heart failure, risk factors, and early signs of cardiotoxicity detectable with different circulating and imaging biomarkers, as well as cardioprotective treatments recommended by different guidelines and position papers.
Cobalt(II) and (I) Complexes of Diphosphine‐Ketone Ligands: Catalytic Activity in Hydrosilylation Reactions
Authors: Verhoeven Dide G. A. , Kwakernaak Joost , van Wiggen Maxime A. C. , Lutz Martin , Moret Marc‐Etienne
Published: December 2018

The hydrosilylation of unsaturated compounds homogeneously catalyzed by cobalt complexes has gained considerable attention in the last years, aiming at substituting precious metal‐based catalysts. In this study, the catalytic activity of well‐characterized CoII and CoI complexes of the pToldpbp ligand is demonstrated in the hydrosilylation of 1‐octene with phenylsilane. The CoI complex is the better precatalyst for the mentioned reaction under mild conditions, at 1 mol‐% catalyst, 1 h, room temperature, and without solvent, yielding 84 % of octylphenylsilane. Investigation of the substrate scope shows lower performance of the catalyst in styrene hydrosilylation, but excellent results with allylbenzene (84 %) and acetophenone (> 99 %). This catalytic study contributes to the field of cobalt‐catalyzed hydrosilylation reactions and shows the first example of catalysis employing the dpbp ligand in combination with a base metal.
Dehydrogenation of Formic Acid Catalyzed by Water‐Soluble Ruthenium Complexes: X‐ray Crystal Structure of a Diruthenium Complex
Authors: Patra Soumyadip , Awasthi Mahendra K. , Rai Rohit K. , Deka Hemanta , Mobin Shaikh M. , Singh Sanjay K.
Published: December 2018

Dehydrogenation of formic acid over various Ru‐arene complexes containing N‐donor chelating ligands was investigated in H2O and isolated and characterized several important catalytic intermediate species to elucidate the reaction pathway for formic acid dehydrogenation. Among the studied complexes, Ru‐arene complexes, namely [(η6‐C6H6)Ru(κ2‐NpyNH2‐AmQ)Cl]+ (C‐2), [(η6‐C10H14)Ru(κ2‐NpyNH2‐AmQ)Cl]+ (C‐3) and [(η6‐C6H6)Ru(κ2‐NpyNHMe‐MAmQ)Cl]+ (C‐4) [AmQ = 8‐aminoquinoline and MAmQ = 8‐(N‐methylamino)quinoline] were proved to be the efficient catalysts for formic acid dehydrogenation at 90 °C, even in the absence of base. With an initial TOF of 940 h–1, complex C‐4 displayed the highest catalytic activity for formic acid dehydrogenation in H2O and it can be recycled up to 5 times with a TON of 2248. Effect of temperature, pH, formic acid and catalyst concentration on the reaction kinetics were also investigated in detail. Extensive mechanistic investigations using mass spectrometry and NMR evidenced the formation of a coordinatively unsaturated species [(η6‐C6H6)Ru(κ2‐NpyNH‐AmQ)]+ (C‐2A)/[(η6‐C6H6)Ru(κ2‐NpyNMe‐MAmQ)]+ (C‐4A) as the active component during the catalytic dehydrogenation of formic acid. We further characterized the dimer‐form of C‐2A, possibly the catalyst resting state, by single‐crystal X‐ray crystallography.
A Micellar Catalysis Strategy for Amidation of Alkynyl Bromides: Synthesis of Ynamides in Water
Authors: Yang Yunqin , Meng Xiangtai , Zhu Baolong , Jia Ying , Cao Xiaoji , Huang Shenlin
Published: December 2018

Copper‐catalyzed amidation of alkynyl bromides can be carried out in water for the first time, which is made possible by a micellar catalysis strategy using rosin‐based surfactant APGS‐550‐M. The surfactant can be easily prepared from natural abundant biomass, resin acids. Studies as to substrate scope and reaction aqueous medium recycling showcase the ease and sustainability of this technology.
Boost customer service for students with a seasonal one‐stop
Authors: Hope Joan
Published: December 2018

Going from office to office seeking answers to their questions can be frustrating for students. A one‐stop shop is one way to make taking care of business easier for them, but reorganizing to create one can be expensive, and finding space for one can be a challenge.
NACAC finds increased political engagement among Generation Z students
Authors: Sutton Halley
Published: December 2018

More than half of secondary institutions reported a rise in student activism in students bound for college, according to data from two surveys conducted by the National Association for College Admission Counseling. One survey studied trends in high school students as reported by secondary school counselors. A complementary survey was administered to university admissions officers and institutional researchers to determine trends in admission.
High-throughput screening and environmental risk assessment: State of the science and emerging applications
Authors: Villeneuve Daniel L. , Coady Katie , Escher Beate I. , Mihaich Ellen , Murphy Cheryl A. , Schlekat Tamar , Garcia-Reyero Natàlia
Published: December 2018

In 2007 the United States National Research Council (NRC) published a vision for toxicity testing in the 21st century that emphasized the use of in vitro high-throughput screening (HTS) methods and predictive models as an alternative to in vivo animal testing. In the present study we examine the state of the science of HTS and the progress that has been made in implementing and expanding on the NRC vision, as well as challenges to implementation that remain. Overall, significant progress has been made with regard to the availability of HTS data, aggregation of chemical property and toxicity information into online databases, and the development of various models and frameworks to support extrapolation of HTS data. However, HTS data and associated predictive models have not yet been widely applied in risk assessment. Major barriers include the disconnect between the endpoints measured in HTS assays and the assessment endpoints considered in risk assessments as well as the rapid pace at which new tools and models are evolving in contrast with the slow pace at which regulatory structures change. Nonetheless, there are opportunities for environmental scientists and policymakers alike to take an impactful role in the ongoing development and implementation of the NRC vision. Six specific areas for scientific coordination and/or policy engagement are identified. Environ Toxicol Chem 2019;38:12–26. Published 2018 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.
Internalization choices under competition: A game theoretic approach
Authors: Hashai Niron , Adler Nicole
Published: December 2018

Research Summary

A long‐standing void in international business literature is understanding whether and how the internalization choices of competing multinational enterprises (MNEs) affect each other. This paper presents a game‐theoretic, location‐allocation mathematical model that predicts the organizational boundaries of competing MNEs. Given multiple players in the market, the game analyzes the competition between MNEs with respect to market share, yielding Nash equilibria that determine how many MNEs will be left in the market, and whether their production and marketing sites are internalized or outsourced. Results of computational experiments suggest that the internalization choices of profit maximizing MNEs that compete with each other, sharply deviate from the internalization choices ignoring such competition.

Managerial Summary

We present a game theory model of the effect of competition between multinational enterprises (MNEs) on their decisions whether to outsource or internalize production and marketing activities. Our model predicts that, at the presence of even modest knowledge transfer costs, such competition likely results in a monopoly outcome. The monopolistic MNE outsources production and builds on the resources that are freed due to this outsourcing to establish more research and development units and internalize marketing units. In addition, our model shows that when knowledge transfer costs are negligible, entry barrier reduce and more competitors arises. These competing MNEs will split markets between them in order to avoid direct competition, will have a greater propensity to outsource their marketing sites, and will need fewer marketing sites to control worldwide sales.
Human Immunodeficiency Virus/Hepatitis C Virus (HCV) Co‐infected Patients With Cirrhosis Are No Longer at Higher Risk for Hepatocellular Carcinoma or End‐Stage Liver Disease as Compared to HCV Mono‐infected Patients
Authors: Salmon‐Ceron Dominique , Nahon Pierre , Layese Richard , Bourcier Valérie , Sogni Philippe , Bani‐Sadr Firouze , Audureau Etienne , Merchadou Laurence , Dabis François , Wittkop Linda , Roudot‐Thoraval Françoise ,   for the ANRS CO12 CirVir and ANRS CO13 HEPAVIH study groups
Published: December 2018

It is widely accepted that human immunodeficiency virus (HIV) infection is a risk factor for increased severity of hepatitis C virus (HCV) liver disease. However, owing to better efficacy and safety of combination antiretroviral therapy (cART), and increased access to HCV therapy, whether this condition remains true is still unknown. Overall, 1,253 HCV mono‐infected patients and 175 HIV/HCV co‐infected patients with cirrhosis, included in two prospective French national cohorts (ANRS CO12 CirVir and CO13 HEPAVIH), were studied. Cirrhosis was compensated (Child‐Pugh A), without past history of complication, and assessed on liver biopsy. Incidences of liver decompensation (LD), hepatocellular carcinoma (HCC), and death according to HIV status were calculated by a Fine‐Gray model adjusted for age. Propensity score matching was also performed to minimize confounding by baseline characteristics. At baseline, HIV/HCV patients were younger (47.5 vs. 56.0 years; P < 0.001), more frequently males (77.1% vs. 62.3%; P < 0.001), and had at baseline and at end of follow‐up similar rates of HCV eradication than HCV mono‐infected patients. A total of 80.4% of HIV/HCV patients had an undetectable HIV viral load. After adjustment for age, 5‐year cumulative incidences of HCC and decompensation were similar in HIV/HCV and HCV patients (8.5% vs. 13.2%, P = 0.12 and 12.8% vs. 15.6%, P = 0.40, respectively). Overall mortality adjusted for age was higher in HIV/HCV co‐infected patients (subhazard ratio [SHR] = 1.88; 95% confidence interval [CI], 1.15‐3.06; P = 0.011). Factors associated with LD and HCC were age, absence of sustained virological response, and severity of cirrhosis, but not HIV status. Using a propensity score matching 95 patients of each group according to baseline features, similar results were observed. Conclusion: In HCV‐infected patients with cirrhosis, HIV co‐infection was no longer associated with higher risks of HCC and hepatic decompensation. Increased mortality, however, persisted, attributed to extrahepatic conditions.
An increase in intracellular p62/NBR1 and persistence of Burkholderia mallei and B. pseudomallei in infected mice linked to autophagy deficiency
Authors: Saikh Kamal U. , Dankmeyer Jennifer L. , Zeng Xiankun , Ulrich Robert G. , Amemiya Kei
Published: December 2018

Introduction

Burkholderia mallei (B. mallei) and Burkholderia pseudomallei (B. pseudomallei), causative agents of glanders and melioidosis, respectively, are invasive intracellular pathogens that actively multiply in phagocytic and non‐phagocytic cells. Activation of cell‐autonomous autophagy mechanism eliminate intracellular pathogens in which p62 a cytosolic cargo protein is selectively degraded, and an accumulation of this marker occurs if autophagy is deficient. Recurrent, relapsed and reinfection of B. pseudomallei in melioidosis patients in endemic area indicative of lack of complete of clearance and persistence of the pathogen. Reasoning that abundance in the levels of p62 may provide an indication of the intracellular infection, we sought to examine whether increase in intracellular p62 and bacterial burden with Burkholderia infection are linked to autophagy deficiency.

Methods

In this study, we investigated cell culture and mouse models of disease to identify an association between autophagy biomarkers (p62/NBR1) accumulation and intracellular persistence of B. mallei and B. pseudomallei.

Results

We demonstrate, that elevated levels of intracellular p62/NBR1 correlated with bacterial persistence, while pre‐treatment with a pharmacological inducer of autophagy, rapamycin, reduced both intracellular p62, and bacterial survival. Our results showed an elevated p62 levels (2‐5 fold) in spleen and liver cells of Burkholderia‐infected BALB/c mice, as well as in spleen cells of Burkholderia‐infected C57BL/6 mice, suggesting that an increase in p62/NBR1 was due to an autophagy deficiency. Similar to p62, cytosolic LC3‐I levels were also elevated, while the characteristic conversion to the autophagosome‐associated membrane bound form LC3‐II was low in spleens of the infected mice further supporting the conclusion that autophagy was deficient.

Conclusion

Taken together, our results suggest that an increase in intracellular p62/NBR1 may be a potential host cell biomarker of B. mallei or B. pseudomallei infections, and identifying autophagy manipulation may potentially aid to therapeutic approach for complete clearance of the pathogen.
The longitudinal associations between personal belief in a just world and teacher justice among advantaged and disadvantaged school students
Authors: Kiral Ucar Gözde , Dalbert Claudia
Published: December 2018

The Just World Hypothesis states that people need to believe in a just world in which they get what they deserve and deserve what they get. This study examines the longitudinal associations between personal belief in a just world (BJW), the belief that events in one's own life are just and teacher justice in different status groups. It is posited that the more individuals believe in a personal just world, the more they feel they are treated justly by others, and this should be particularly true for students with a low‐status background. Longitudinal questionnaire data were obtained from students with German and Turkish/Muslim backgrounds over a period of 3–4 months. The pattern of results revealed that personal BJW was important for the Turkish/Muslim students in evaluating teachers as more just over a given period of time, but not for the German students. That is, the buffering effect of personal BJW was crucial for the disadvantaged students.
Optical positioning technology of an assisted puncture robot based on binocular vision
Authors: Jiang Guanwu , Luo Minzhou , Bai Keqiang
Published: December 2018

Percutaneous image‐guided interventions are increasing in number in clinical practice because they are minimally invasive. Needle positioning placement is crucial and highly dependent on the physician's skills and experience, it is often the longest part of the intervention. Medical robotics and computer‐assisted surgery are hotspots in the field of robotics and medicine, changing the essence of traditional surgery using a combination of robotic, image processing, and computer technologies. The present paper aimed to study the auxiliary puncture procedure using a robot based on optical positioning technology that can be used to mark points in puncturing operation. Binocular camera is used for image acquisition, and Zhang's calibration method is used to establish the binocular camera model. In addition, the circular markers are identified by the least square method detection circle, and the coordinate information of the markers in three‐dimensional space is solved by using the visual depth information of binocular phases. This paper studies the verification of the three‐dimensional bone model of the human body, which lays a foundation for the application of the assistant puncture robot.
Equilibrium and Kinetic Studies of Adsorption of Boron on Activated Alumina
Authors: Bouguerra W. , Marzouk I. , Hamrouni B.
Published: December 2018

Boron is widely distributed in the environment, mainly in the form of boric acid or borate salts, and its contamination of waters is a concern around the world. This study focuses on boron removal by means of adsorption onto activated alumina. Optimum adsorption was achieved in the pH range 8.0 to 8.5. Approximately 60% (by mass) boron removal was achieved using an adsorbent dose of 5 g at an initial boron concentration of 50 mg/L. Adsorption isotherms at 10, 20, and 30°C were investigated. The results fitted with the Langmuir and Freundlich equations showed a monolayer adsorption onto a surface, with a finite number of identical sites. To study the rate‐limiting step, the adsorption kinetic data of boron were analyzed using first‐order (Lagergren) and second‐order kinetic models. The experimental results obtained showed that the adsorption process followed a second‐order kinetic model.
Healthcare Facility Effluents as Point Sources of Select Pharmaceuticals to Municipal Wastewater
Authors: Nagarnaik Pranav M. , Batt Angela L. , Boulanger Bryan
Published: December 2018

Effluents from four healthcare facilities were characterized for the concentration of 16 common active pharmaceutical ingredients. The sampled facilities included a hospital, nursing care, assisted living, and independent living facility located within a single municipal wastewater system in Texas. Eleven of the 16 monitored pharmaceuticals were detected in at least 1 healthcare facility effluent and 2 measured antibiotics (sulfamethoxazole and trimethoprim) were detected in all 4 facility effluents. Active pharmaceutical ingredient concentrations ranged from non‐detectable levels for several corticosteroids in all facility effluents to 180 µg/L sulfamethoxazole in the nursing care wastewater effluent. The mass of active pharmaceutical ingredients discharged to the municipality's wastewater conveyance system was determined by combining individual facility concentration data and daily wastewater flow. The estimated daily mass loading of all 16 pharmaceuticals ranged from 0.16 g/day to 23 g/day in the assisted living facility and nursing wastewater effluents, respectively. The combined active pharmaceutical ingredient mass loading for all four facilities was 42.6 g/day. These findings provide source characterization data for 16 common pharmaceuticals in healthcare facility wastewater and provide a basis for risk assessment of pharmaceuticals present in healthcare facility wastewaters.
Development of a Subcutaneous Fixed‐Dose Combination of Pertuzumab and Trastuzumab: Results From the Phase Ib Dose‐Finding Study
Authors: Kirschbrown Whitney P. , Wynne Chris , Kågedal Matts , Wada Russ , Li Hanbin , Wang Bei , Nijem Ihsan , Badovinac Crnjevic Tanja , Gasser Helena , Heeson Sarah , Eng‐Wong Jennifer , Garg Amit
Published: December 2018

Adding pertuzumab to trastuzumab (both monoclonal antibodies targeting human epidermal growth factor receptor 2 [HER2]) has proven survival benefits when combined with chemotherapy for patients with HER2‐positive breast cancer. The combination of pertuzumab and trastuzumab together in 1 vial for subcutaneous (SC) administration is being developed as a ready‐to‐use formulation to reduce the treatment burden on patients while improving healthcare efficiency. An open‐label, 2‐part, phase Ib dose‐finding study (NCT02738970) was undertaken in healthy male volunteers (part 1) and female patients with HER2‐postive early breast cancer who had completed standard (neo)adjuvant treatment (part 2). This study aimed to identify an SC pertuzumab dose given with recombinant human hyaluronidase that results in comparable exposure to that of the intravenous (IV) pertuzumab dose, based on pertuzumab serum trough concentration and area under the serum concentration–time curve. Pharmacokinetics (PK), safety, and tolerability of a single dose of SC pertuzumab given alone or in a fixed‐dose combination (comixed or coformulated) with trastuzumab were also assessed. A maintenance dose of 600 mg for SC pertuzumab resulted in an equivalent exposure to that of IV pertuzumab, and no new safety signals were identified for SC pertuzumab or trastuzumab. A loading dose of 1200 mg for SC pertuzumab was selected based on approximate dose proportionality. The PK and safety results support further development of a fixed‐dose coformulation combination of pertuzumab and trastuzumab for SC administration, which will be investigated in an upcoming phase III trial in patients with HER2‐positive early breast cancer.
Significance of repeat magnetic resonance imaging in diagnosing vertebral osteomyelitis
Authors: Kamiya Naoko , Hatakeyama Shuji , Kanda Naoki , Yonaha Sho , Akine Dai , Yamamoto Yu , Matsumura Masami
Published: December 2018

Vertebral osteomyelitis can result in serious complications if diagnosis is delayed. Magnetic resonance imaging (MRI) is considered the most useful modality for the early diagnosis of vertebral osteomyelitis. We examined three patients with vertebral osteomyelitis whose initial MRI (obtained <2 weeks after the onset of symptoms) did not reveal obvious findings of pyogenic vertebral osteomyelitis. However, follow‐up MRI clearly demonstrated typical findings of the disease. This case series illustrates that a repeat MRI must be performed 2‐4 weeks after the onset of symptoms in patients presenting with clinical manifestations and microbiological findings suggestive of vertebral osteomyelitis.
T2‐based MRI Delta‐radiomics improve response prediction in soft‐tissue sarcomas treated by neoadjuvant chemotherapy.
Authors: Crombé Amandine , Périer Cynthia , Kind Michèle , De Senneville Baudouin Denis , Le Loarer François , Italiano Antoine , Buy Xavier , Saut Olivier
Published: December 2018

Background

Standard of care for patients with high‐grade soft‐tissue sarcoma (STS) are being redefined since neoadjuvant chemotherapy (NAC) has demonstrated a positive effect on patients' outcome. Yet response evaluation in clinical trials still relies on RECIST criteria.

Purpose

To investigate the added value of a Delta‐radiomics approach for early response prediction in patients with STS undergoing NAC.

Study Type

Retrospective.

Population

Sixty‐five adult patients with newly‐diagnosed, locally‐advanced, histologically proven high‐grade STS of trunk and extremities. All were treated by anthracycline‐based NAC followed by surgery and had available MRI at baseline and after two chemotherapy cycles.

Field Strength/Sequence

Pre‐ and postcontrast enhanced T1‐weighted imaging (T1‐WI), turbo spin echo T2‐WI at 1.5 T.

Assessment

A threshold of <10% viable cells on surgical specimens defined good response (Good‐HR). Two senior radiologists performed a semantic analysis of the MRI. After 3D manual segmentation of tumors at baseline and early evaluation, and standardization of voxel‐sizes and intensities, absolute changes in 33 texture and shape features were calculated.

Statistical Tests

Classification models based on logistic regression, support vector machine, k‐nearest neighbors, and random forests were elaborated using crossvalidation (training and validation) on 50 patients ("training cohort") and was validated on 15 other patients ("test cohort").

Results

Sixteen patients were good‐HR. Neither RECIST status (P = 0.112) nor semantic radiological variables were associated with response (range of P‐values: 0.134–0.490) except an edema decrease (P = 0.003), although 14 shape and texture features were (range of P‐values: 0.002–0.037). On the training cohort, the highest diagnostic performances were obtained with random forests built on three features: Δ_Histogram_Entropy, Δ_Elongation, Δ_Surrounding_Edema, which provided: area under the curve the receiver operating characteristic = 0.86, accuracy = 88.1%, sensitivity = 94.1%, and specificity = 66.3%. On the test cohort, this model provided an accuracy of 74.6% but 3/5 good‐HR were systematically ill‐classified.

Data Conclusion

A T2‐based Delta‐radiomics approach might improve early response assessment in STS patients with a limited number of features.

Level of Evidence: 3

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;50:497–510.
Reaching across the aisle: Cross‐disciplinary collaboration in otolaryngology research
Authors: Kim Sun Joo , Choi Won Kyu , Lee Andrew H. , Yi Paul H. , Boss Emily
Published: December 2018

Objectives

Collaboration and diversity of expertise are increasingly emphasized in the production of successful research. However, the degree of cross‐disciplinary collaboration in otolaryngology research is unknown. In this study, we quantify cross‐disciplinary collaboration in otolaryngology publications.

Methods

We retrospectively analyzed authorship and study characteristics for all original articles published from January 2014 to December 2016 in three key peer‐reviewed otolaryngology journals: Laryngoscope, Otolaryngology–Head & Neck Surgery, and JAMA Otolaryngology–Head & Neck Surgery. Author affiliations and online searches were used to determine author's primary discipline. Subspecialty topic of article, study design, and funding sources were also recorded. Fisher exact test was used to compare characteristics of articles with and without cross‐disciplinary authorship.

Results

A total of 2,378 articles were reviewed, of which 1,312 (55%) articles had one or more cross‐disciplinary collaborators. Among articles with cross‐disciplinary collaboration, the greatest representation of disciplines was from other medical specialties (1,109, 50.9%), epidemiology/biostatistics (266, 12.2%), pathology/histology (175, 8.0%), biologic sciences (168, 7.7%), and radiology/imaging (144, 6.6%). Cross‐disciplinary studies had a significantly greater proportion of articles on the topic of head and neck compared to studies without collaboration (P < 0.0001). The proportion of funded studies was significantly greater among articles with collaboration compared to articles without collaboration (P < 0.0001).

Conclusion

The majority of articles published during a 3‐year period in three influential otolaryngology journals had cross‐disciplinary collaboration. There is potential opportunity for further leveraging expertise, funding opportunities, and dissemination of key findings through collaborative research.

Level of Evidence

NA

Laryngoscope, 129:1800–1805, 2019
Hybrid supracricoid partial laryngectomy with cricohyoidoepiglottopexy via transoral robotic surgery
Authors: Nakayama Meijin , Holsinger F. Christopher , Orosco Ryan K.
Published: December 2018

Objectives/Hypothesis

To describe a hybrid supracricoid partial laryngectomy with cricohyoidoepiglottopexy (hybrid SCPL‐CHEP) combining limited transcervical and transoral robotic approaches.

Study Design

Preclinical cadaveric study.

Methods

Using six human cadavers in a series of three preclinical laboratories (July 2016–February 2018), we developed a novel hybrid technique for SCPL‐CHEP. A flexible single‐port robotic surgical system was utilized for the transoral aspects of the procedure.

Results

Detailed procedural steps are defined: 1) transoral: mucosal incisions under direct visualization of the laryngopharynx (tumor resection); 2) transcervical: incision and mobilization of the larynx and pexis; and 3) transoral: mucosal closure. Hybrid SCPL‐CHEP was technically feasible and allowed for complete transoral mucosal reconstruction. We discuss potential clinical significance of adding this TORS approach to conventional open SCPL‐CHEP.

Conclusions

This hybrid technique for SCPL‐CHEP provides two main advantages over the standard technique: direct visualization during tumor resection prior to laryngotomy and full closure of the laryngopharynx defect. These technical refinements might facilitate postoperative recovery and in turn make this larynx preservation procedure more accessible to patients and surgeons. A clinical trial evaluating the efficacy of hybrid SCPL‐CHEP appears warranted to validate these observations.

Level of Evidence

NA

Laryngoscope, 129:2065–2070, 2019
Supraclavicular flap practice patterns and outcomes: A survey of 221 AHNS surgeons
Authors: Day Andrew T. , Tang Liyang , Emerick Kevin , Patel Urjeet A. , Deschler Daniel G. , Richmon Jeremy D.
Published: December 2018

Objectives

To describe American Head and Neck Society (AHNS) surgeon supraclavicular flap (SCF) practice patterns and to identify variables associated with SCF complications.

Methods

The design is a cross‐sectional study. An online survey was distributed to 782 AHNS surgeons between November 11, 2016, and December 31, 2016. The primary outcome was frequency of SCF complications. Independent variables included demographics, training, practice patterns, and SCF techniques.

Results

Adequate survey responses were obtained from 221 AHNS surgeons. Among these, 54.3% (n = 120) performed supraclavicular flaps (SCFs). Most surgeons used the SCF for cutaneous (n = 85; 78.7%) or parotid–temporal bone (n = 59; 54.6%) defects. Nearly one‐third (n = 31; 29.8%) of surgeons experienced more than a “few” SCF complications. Surgeons experienced fewer pectoralis major flap (P < 0.001) and radial forearm free flap (P < 0.001) complications compared to SCF complications. Univariate analysis demonstrated no association between surgeons with “few” SCF complications and Doppler use in SCF design (P = 0.90), harvest location (P = 0.51), and pedicle skeletonization (P = 0.25). Multivariable logistic regression revealed that surgeons performing more than 30 SCFs compared to less than or equal to 30 SCFs had a greater odds of having “few” SCF complications (odds ratio 7.1, 95% confidence interval [1.1–43.9], P = 0.04).

Conclusion

A majority of surgeons performing SCFs use the flap to reconstruct cutaneous and parotid–temporal bone defects. The significance of relatively higher SCF complications compared to other routine flaps should be explored further. Surgeon experience with the SCF appears to be significantly associated with SCF success, whereas training characteristics, practice patterns, and technical variations may not be associated with SCF outcomes.

Level of Evidence

NA

Laryngoscope, 129:2012–2019, 2019
Nationwide estimations of tracheal stenosis due to tracheostomies
Authors: Johnson Romaine F. , Saadeh Charles
Published: December 2018

Objectives

Tracheal stenosis is a recognized complication of tracheostomy. Yet, the incidence and demographics of tracheal stenosis due to tracheostomies have infrequently been studied.

Methods

We performed a cross‐sectional analysis of U.S. emergency department (ED) visits, hospital discharges, and readmissions using the 2013 National Emergency Department Sample, 2013 National Inpatient Sample, and 2013 Nationwide Readmission Database for patients with tracheal stenosis due to tracheostomies. Also, we queried the readmission database for new tracheostomy patients who were readmitted within the same calendar year with tracheal stenosis due to the tracheostomy tube.

Results

There were an estimated 6,156 ED visits; 4,920 hospital discharges; and 2,316 readmissions for tracheal stenosis due to tracheostomies in 2013. These cases represented 28% of all tracheostomy‐related complications. Of the 103,484 patients who underwent tracheostomy in 2013, 739 (1.05%) patients were readmitted within the calendar year with tracheal stenosis due to the tracheostomy tube. These stenosis patients’ average age was 55 years old. Forty‐five percent of the patients were female and 60% were white. The mortality rate was 7.9%. The demographic risk of stenosis mirrored the risk of tracheostomy: increasing age, male gender, and black ethnicity.

Conclusion

Tracheal stenosis due to tracheostomy was uncommon, accounting for 1% of readmissions after tracheostomies, although it represented 28% of tracheostomy‐related complications and had a high mortality rate. The risk of stenosis reflected the overall tracheostomy population without apparent age, gender, or racial predilections.

Level of Evidence

NA

Laryngoscope, 129:1623–1626, 2019
Reliability of grading of facial palsy using a video tutorial with synchronous video recording
Authors: Volk Gerd Fabian , Schaede Rebecca Anna , Thielker Jovanna , Modersohn Luise , Mothes Oliver , Nduka Charles C. , Barth Jodi Maron , Denzler Joachim , Guntinas‐Lichius Orlando
Published: December 2018

Objective

To determine the intrarater, interrater, and retest reliability of facial nerve grading of patients with facial palsy (FP) using standardized videos recorded synchronously during a self‐explanatory patient video tutorial.

Study Design

Prospective, observational study.

Methods

The automated videos from 10 patients with varying degrees of FP (5 acute, 5 chronic FP) and videos without tutorial from eight patients (all chronic FP) were rated by five novices and five experts according to the House‐Brackmann grading system (HB), the Sunnybrook Grading System (SB), and the Facial Nerve Grading System 2.0 (FNGS 2.0).

Results

Intrarater reliability for the three grading systems was very high using the automated videos (intraclass correlation coefficient [ICC]; SB: ICC = 0.967; FNGS 2.0: ICC = 0.931; HB: ICC = 0.931). Interrater reliability was also high (SB: ICC = 0.921; FNGS 2.0: ICC = 0.837; HB: ICC = 0.736), but for HB Fleiss kappa (0.214) and Kendell W (0.231) was low. The interrater reliability was not different between novices and experts. Retest reliability was very high (SB: novices ICC = 0.979; experts ICC = 0.964; FNGS 2.0: novices ICC = 0.979; experts ICC = 0.969). The reliability of grading of chronic FP with SB was higher using automated videos with tutorial (ICC = 0.845) than without tutorial (ICC = 0.538).

Conclusion

The reliability of the grading using the automated videos is excellent, especially for the SB grading. We recommend using this automated video tool regularly in clinical routine and for clinical studies.

Level of Evidence

4

xsLaryngoscope, 129:2274–2279, 2019