bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrochemotherapy as a New Modality in Interventional Oncology: A Review
Authors: Probst Ute , Fuhrmann Irene , Beyer Lukas , Wiggermann Philipp
Published: July 2018

Electroporation is a well-known phenomenon that occurs at the cell membrane when cells are exposed to high-intensity electric pulses. Depending on electric pulse amplitude and number of pulses, applied electroporation can be reversible with membrane permeability recovery or irreversible. Reversible electroporation is used to introduce drugs or genetic material into the cell without affecting cell viability. Electrochemotherapy refers to a combined treatment: electroporation and drug injection to enhance its cytotoxic effect up to 1000-fold for bleomycin. Since several years, electrochemotherapy is gaining popularity as minimally invasive oncologic treatment. The adoption of electrochemotherapy procedure in interventional oncology poses several unsolved questions, since suitable tumor histology and size as well as therapeutic efficacy still needs to be deepen. Electrochemotherapy is usually applied in palliative settings for the treatment of patients with unresectable tumors to relieve pain and ameliorate quality of life. In most cases, it is used in the treatment of advanced stages of neoplasia when radical surgical treatment is not possible (eg, due to lesion location, size, and/or number). Further, electrochemotherapy allows treating tumor nodules in the proximity of important structures like vessels and nerves as the treatment does not involve tissue heating. Overall, the safety profile of electrochemotherapy is favorable. Most of the observed adverse events are local and transient, moderate local pain, erythema, edema, and muscle contractions during electroporation. The aim of this article is to review the recent published clinical experiences of electrochemotherapy use in deep-seated tumors with particular focus on liver cases. The principle of electrochemotherapy as well as the application to cutaneous metastases is briefly described. A short insight in the treatment of bone metastases, unresectable pancreas cancer, and soft tissue sarcoma will be given. Preclinical and clinical studies on treatment efficacy with electrochemotherapy of hepatic lesions and safety of the procedure adopted are discussed.
Therapeutic Effect of Camel Milk and Its Exosomes on MCF7 Cells In Vitro and In Vivo
Authors: Badawy Abdelnaser A. , El-Magd Mohammed A. , AlSadrah Sana A.
Published: July 2018

Background/Objectives: In the Middle East, people consume camel milk regularly as it is believed to improve immunity against diseases and decrease the risk for cancer. Recently, it was noted that most of the beneficial effects of milk come from their nanoparticles, especially exosomes. Herein, we evaluated the anticancer potential of camel milk and its exosomes on MCF7 breast cancer cells (in vitro and in vivo) and investigated the possible underlying molecular mechanism of action. Methods/Results: Administration of camel milk (orally) and its exosomes (orally and by local injection) decreased breast tumor progression as evident by ( a) higher apoptosis (indicated by higher DNA fragmentation, caspase-3 activity, Bax gene expression, and lower Bcl2 gene expression), ( b) remarkable inhibition of oxidative stress (decrease in MDA levels and iNOS gene expression); ( c) induction of antioxidant status (increased activities of SOD, CAT, and GPX), ( d) notable reduction in expression of inflammation-( IL1b, NFκB), angiogenesis-( VEGF) and metastasis-( MMP9, ICAM1) related genes; and ( e) higher immune response (high number of CD+4, CD+8, NK1.1 T cells in spleen). Conclusions: Overall, administration of camel milk–derived exosomes showed better anticancer effect, but less immune response, than treatment by camel milk. Moreover, local injection of exosomes led to better improvement than oral administration. These findings suggest that camel milk and its exosomes have anticancer effect possibly through induction of apoptosis and inhibition of oxidative stress, inflammation, angiogenesis and metastasis in the tumor microenvironment. Thus, camel milk and its exosomes could be used as an anticancer agent for cancer treatment.
A machine learning–based framework for analyzing car brand styling
Authors: Li Baojun , Dong Ying , Wen Zhijie , Liu Mingzeng , Yang Lei , Song Mingliang
Published: July 2018

To avoid the requirement of expert knowledge in conventional methods for car styling analysis, this article proposes a machine learning–based method which requires no expert-engineered features for car frontal styling analysis. In this article, we aim to identify the group behaviors in car styling such as the degree of brand styling consistency among different automakers and car styling patterns. The brand styling consistency is considered as a group behavior in this article and is formulated as a brand classification problem. This classification problem is then solved by a machine learning method based on the PCANet for automatic feature encoding and the support vector machine for feature-based classification. The brand styling consistency can thus be measured based on the classification accuracy. To perform the analysis, a car frontal styling database with 23 brands is first built. To present discovered brand styling patterns in classification, a decoding method is proposed to map salient features for brand classification to original images for revelation of salient styling regions. To provide a direct perception in brand styling characteristics, frontal styling representatives of several brands are present as well. This study contributes to efficient identification of brand styling consistency and visualization of brand styling patterns without relying on expert experience.
A General Aesthetics of American Animation Sound Design
Authors: Taberham Paul
Published: July 2018

From the inception of sync sound in the late 1920s to the modern day, sound in animation has assumed a variety of forms. This article proposes four principal modes that have developed in the commercial realm of American animation according to changing contingencies of convention, technology and funding. The various modes are termed syncretic, zip-crash, functional and poetic authentication. Each one is utilized to different aesthetic effect, with changing relationships to the image. The use of voice, music, sound effects and atmos are considered as well as the ways in which they are recorded, manipulated and mixed. Additionally, the ways in which conventions bleed from one period to the next are also illustrated. Collectively, these proposed categories aid in understanding the history and creative range of options available to animators beyond the visual realm.
‘Diagrams of Motion’: Stop-Motion Animation as a Form of Kinetic Sculpture in the Short Films of Jan Švankmajer and the Brothers Quay
Authors: Wilson Ewan
Published: July 2018

Jean-Luc Godard wrote that ‘The cinema is not an art which films life; the cinema is something between art and life’ (cited in Roud’s, 2010, biography of Godard), an observation particularly true of stop-motion animation. The filmmakers discussed in this essay, Jan Švankmajer and the Brothers Quay, share a fascination with the latent content of found objects; they believe that forgotten toys, discarded tools and other such objects contain echoes of past experiences. Extrapolating Švankmajer’s belief that memories are imparted to the objects we touch, the manipulation of his found objects as puppets in his films becomes a means of evoking and repurposing their latent content, just as the Quays develop their dreamlike films from the psychic content they perceive in their armatures. Making a case study of a selection of these animators’ short films, this article examines the practice of stop-motion animation against that of kinetic sculpture, unpicking the complexities of the relationship between the inherently static mediums of sculpture and photography – symbolic of a fixed moment in time – and that of stop-motion animation, a temporal pocket in which these fossilized moments are revived once more.
How Animation Won Over the Lightning Sketch: Re-Evaluating Humorous Phases of Funny Faces
Authors: Greenberg Raz
Published: July 2018

The short film Humorous Phases of Funny Faces, released in 1906 and directed by J Stuart Blackton (1875–1941), is considered to be one of the earliest examples of cinematic animation. This article aims at examining the film’s influence from another perspective, beyond its pioneering use of film camera: the author argues that Blackton’s film has also laid the foundation for common design principles in subsequent animated productions, particularly in the design of animated characters. The analysis of Blackton’s film aimed at supporting this argument is based on Scott McCloud’s seminal book Understanding Comics: The Invisible Art (1993) and this article offers a modified method of McCloud’s ‘Vocabulary of Comics’ to demonstrate how Blackton has introduced the basic building-blocks of animated characters’ design that are common to this day: designs that rely on an emotional, universal core upon which culture-specific items are overlaid. Moreover, through appearance and performance of his animated characters, Blackton broke the design process of animated characters into such building blocks, emphasizing their importance.
Abiraterone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: a systematic review of ‘real-life’ studies
Authors: Marchioni Michele , Sountoulides Petros , Bada Maida , Rapisarda Sebastiano , De Nunzio Cosimo , Tamburro Fabiola Raffaella , Schips Luigi , Cindolo Luca
Published: July 2018

Background:

To assess the efficacy and safety of treatment with abiraterone acetate (AA) in chemotherapy-naïve men with metastatic castration-resistant prostate cancer (mCRPC) in the ‘real-life’ setting.

Methods:

Data acquisition on the outcomes of the use of AA in chemotherapy-naive patients with mCRPC was performed by a MEDLINE comprehensive systematic literature search using combinations of the following key words: ‘prostate cancer’, ‘metastatic’, ‘castration resistant’, ‘abiraterone’, ‘real life’, and excluding controlled clinical trials (phase II and III studies). Identification and selection of the studies was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria. Outcomes of interest were overall survival (OS), progression-free survival (PFS), 12-week 50% reduction in prostate-specific antigen (PSA), and grade 3 and higher adverse events. Data were narratively synthesized in light of methodological and clinical heterogeneity.

Results:

Within the eight identified studies that fulfilled the criteria, a total of 801 patients were included in the meta-analysis. Baseline PSA ranged between 9.5 and 212.0 ng/ml. Most of the patients had bone metastases. Duration of treatment with AA was longer in the studies with lower baseline PSA levels. The median OS ranged between 14 and 36.4 months. The PFS, assessed according to different definitions, ranged from 3.9 to 18.5 months. A 50% PSA reduction at 12 weeks was reached by a variable percentage of patients ranging from 36.0% to 62.1%. Finally, the rate of grade 3 and higher adverse events was reported in three studies and ranged from 4.4% to 15.5%.

Conclusions:

Despite the high grade of heterogeneity among studies, treatment with AA seems to ensure good survival outcomes in the ‘real-life’ setting. However, prospective studies based on patients’ characteristics being more similar to ‘real-life’ patients are necessary.
A study on the relationship between HCV NS3 and endogenous IRF-3
Authors: Liang Hong-Ping , Hak Hotta , Ji Jian-Min
Published: July 2018

This study aims to investigate the relationship between hepatitis C virus (HCV) NS3/4A and endogenous interferon regulatory factor-3 (IRF-3). The localization of endogenous IRF-3 protein before and after virus infection was analyzed by immunofluorescence assay (IFA). IFA results revealed that the synergistic action of transfection and HCV virus infection could more effectively reduce the nuclear translocation of endogenous IRF-3 in HeLa cells, compared to the activation of Sendai virus infection alone. The highest nuclear translocation of endogenous IRF-3 in transfected HeLa cells occurred at 24 h after Sendai virus infection. Our study was consistent with a published paper, which revealed that HCV NS3/4A protease could suppress the activation of IRF-3 and was indispensable in the transcription of interferon (IFN)-α/β.
The ASCAP/CBDNA Frederick Fennell Prize: Interviews With the Eight Winning Composers
Authors: Cornett Patricia
Published: July 2018

Initiated in 2002, the ASCAP/CBDNA Frederick Fennell Young Composers Award is a biennial recognition of an outstanding new work for winds by an American composer between the ages of 18 and 30. The winning work is selected through a juried competition that attracts submissions from eligible composers from across the United States. The award has been given eight times to the following composers and pieces: Michael Djupstrom for Homages, Yotam Haber for Espresso, Matthew Tommasini for Three Spanish Songs, Kathryn Salfelder for Cathedrals, Joshua Hummel for Haiku Symphony no. 4, Takuma Itoh for Daydreams, Shuying Li for Slippery Slope, and Nathan Stang for Undertow. The eight winning composers were interviewed via telephone by the author in January 2017.
Treatment of First-Time Traumatic Anterior Dislocation of the Sternoclavicular Joint With Surgical Repair of the Anterior Capsule Augmented With Internal Bracing
Authors: Tytherleigh-Strong Graham , Pecheva Mira , Titchener Andrew
Published: July 2018

Background:

Traumatic anterior dislocations of the sternoclavicular joint (SCJ) are rare. Although they can usually be treated by a closed reduction, the reported subsequent recurrence rate is 50%.

Purpose:

To determine whether further instability after first-time traumatic anterior dislocation would be prevented by a minimally invasive open repair of the anterior SCJ capsule, augmented with internal bracing.

Study Design:

Case series; Level of evidence, 4.

Methods:

Open repair of the anterior SCJ capsule was completed on a series of patients who had sustained a first-time traumatic anterior dislocation of the SCJ. Patients with preexisting SCJ instability and recurrent dislocations were excluded. Through a transverse incision, the anterior SCJ capsule was repaired and plicated by use of sutures. The repair was then protected by use of an internal brace, bridging between the sternum and the medial end of the clavicle.

Results:

Six patients (4 males, 2 females) with a mean age of 28.3 years were included. Four patients underwent surgery within 4 weeks of their dislocation, and 2 patients had ongoing symptoms of instability but had not had a further dislocation. The median follow-up was 28.2 months (range, 24-35 months). At the most recent follow-up, none of the patients had sustained further dislocation or episode of instability, and their SCJs appeared stable. The mean abbreviated Disabilities of the Arm, Shoulder and Hand (QuickDASH) score was 2.3 (range, 0-4.5).

Conclusion:

The medium-term results of this case series suggest that after first-time dislocation, surgical repair of the anterior SCJ capsule augmented with internal bracing can prevent recurrent instability. This may be an attractive option for individuals involved in higher risk activities, as the operative management of recurrent anterior SCJ instability usually requires a figure-of-8 tendon reconstruction, which carries a significantly higher morbidity.
Headache in an Obese Adolescent Male: A Nonclassical Presentation of an Uncommon Disease
Authors: Zhou Bill , Yim Catherine , Chawla Soni
Published: July 2018

Background. Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is a diagnosis of exclusion in the clinical scenario of increased intracranial pressure without an identifiable cause. This case report provides a brief review of current literature on IIH, important differential considerations to rule out prior to diagnosis, and relevant imaging findings of IIH. Case Presentation. An 18-year-old male presenting with headache and blurry vision was found to have signs of increased intracranial pressure on imaging without other abnormalities to explain the cause, suggesting IIH as a diagnosis. Conclusion. IIH is classically seen in overweight females of childbearing age but should be considered in all obese patients, including the pediatric population given the increasing rate of childhood obesity.
Economic Nationalism in South Korea and Taiwan: Examining Identity Discourse and Threat Perceptions towards Japan after the Second World War (1960s–1970s)
Authors: Lai Christina
Published: July 2018

South Korea and Taiwan provide fruitful comparisons in political economy. During the Cold War era, they deepened their trade with Japan. However, the top political leaders in those places exhibited different levels of threat perceptions towards Japan. Why did the leaders formulate their discourse towards Japan so differently in the post-Cold War era? The role of nationalism is salient during their economic take-off periods. The motivations behind these developmental strategies and the discourse used to justify such national growth cannot be excluded from the studies of comparative politics and political economy. This article examines the political discourses of two dictators—Park Chung-hee in South Korea and Chiang Kai-shek in Taiwan—and shows how they justified their policies towards Japan while establishing economic nationalism at the same time. It concludes with findings that are relevant to recent development in comparative studies, and it offers policy implications for East Asian security.
Single-cell approaches identify the molecular network driving malignant hematopoietic stem cell self-renewal
Authors: Shepherd Mairi S. , Li Juan , Wilson Nicola K. , Oedekoven Caroline A. , Li Jiangbing , Belmonte Miriam , Fink Juergen , Prick Janine C. M. , Pask Dean C. , Hamilton Tina L. , Loeffler Dirk , Rao Anjana , Schröder Timm , Göttgens Berthold , Green Anthony R. , Kent David G.
Published: July 2018

Key Points

Single-cell approaches identify regulators of malignant HSC self-renewal. Identification of novel roles for Bmi1, Pbx1, and Meis1 in myeloproliferative neoplasms.
Glutamine via α-ketoglutarate dehydrogenase provides succinyl-CoA for heme synthesis during erythropoiesis
Authors: Burch Joseph S. , Marcero Jason R. , Maschek John Alan , Cox James E. , Jackson Laurie K. , Medlock Amy E. , Phillips John D. , Dailey Harry A.
Published: July 2018

Key Points

During late erythropoiesis, exogenous glutamine, rather than TCA cycle intermediates, provides carbons for succinyl-CoA for heme synthesis. Itaconate, a compound manufactured as part of the inflammatory response, inhibits heme synthesis in cells undergoing erythropoiesis.
Potential mechanisms responsible for cardioprotective effects of sodium–glucose co-transporter 2 inhibitors
Authors: Lahnwong Charshawn , Chattipakorn Siriporn C. , Chattipakorn Nipon
Published: July 2018

Diabetes mellitus currently affects over 350 million patients worldwide and is associated with many deaths from cardiovascular complications. Sodium–glucose co-transporter 2 (SGLT-2) inhibitors are a novel class of antidiabetic drugs with cardiovascular benefits beyond other antidiabetic drugs. In the EMPA-REG OUTCOME trial, empagliflozin significantly decreases the mortality rate from cardiovascular causes [38% relative risk reduction (RRR)], the mortality rate from all-causes (32% RRR) and the rate of heart failure hospitalization (35% RRR) in diabetic patients with established cardiovascular diseases. The possible mechanisms of SGLT-2 inhibitors are proposed to be systemic effects by hemodynamic and metabolic actions. However, the direct mechanisms are not fully understood. In this review, reports concerning the effects of SGLT-2 inhibitors in models of diabetic cardiomyopathy, heart failure and myocardial ischemia from in vitro, in vivo as well as clinical reports are comprehensively summarized and discussed. By current evidences, it may be concluded that the direct effects of SGLT-2 inhibitors are potentially mediated through their ability to reduce cardiac inflammation, oxidative stress, apoptosis, mitochondrial dysfunction and ionic dyshomeostasis.
Quality assessment of systematic reviews of vitamin D, cognition and dementia
Authors: Aghajafari Fariba , Pond Dimity , Catzikiris Nigel , Cameron Ian
Published: July 2018

Background

There is conflicting evidence regarding the association of vitamin D with cognition performance and dementia.

Aims

We aimed to summarise the evidence on the association of vitamin D with cognitive performance, dementia and Alzheimer disease through a qualitative assessment of available systematic reviews and meta-analyses.

Method

We conducted an overview of the systematic reviews of all study types with or without meta-analyses on vitamin D and either Alzheimer disease, dementia or cognitive performance up to June 2017.

Results

Eleven systematic reviews were identified, nine of which were meta-analyses with substantial heterogeneity, differing statistical methods, variable methodological quality and quality of data abstraction. A Measurement Tool to Assess Systematic Reviews checklist scores ranged from 4 to 10 out of 11, with seven reviews of ‘moderate’ and four of ‘high’ methodological quality. Out of six meta-analyses on the association between low serum concentration of 25-hydroxyvitamin D and risk of dementia, five showed a positive association. Results of meta-analyses on the association between low serum concentration of 25-hydroxyvitamin D and memory function tests showed conflicting results.

Conclusions

This systematic evaluation of available systematic reviews provided a clearer understanding of the potential link between low serum vitamin D concentrations and dementia. This evaluation also showed that the quality of the available evidence is not optimal because of both the low methodological quality of the reviews and low quality of the original studies. Interpretation of these systematic reviews should therefore be made with care.

Declaration of interest

None.
Association Between Inflammatory Biomarker C-Reactive Protein and Radiotherapy-Induced Early Adverse Skin Reactions in a Multiracial/Ethnic Breast Cancer Population
Authors: Hu Jennifer J. , Urbanic James J. , Case L. Doug , Takita Cristiane , Wright Jean L. , Brown Doris R. , Langefeld Carl D. , Lively Mark O. , Mitchell Sandra E. , Thakrar Anu , Bryant David , Baglan Kathy , Strasser Jon , Baez-Diaz Luis , Lesser Glenn J. , Shaw Edward G.
Published: July 2018

Purpose

This study examined an inflammatory biomarker, high-sensitivity C-reactive protein (hsCRP), in radiotherapy (RT)-induced early adverse skin reactions or toxicities in breast cancer.

Patients and Methods

Between 2011 and 2013, 1,000 patients with breast cancer who underwent RT were evaluated prospectively for skin toxicities through the National Cancer Institute–funded Wake Forest University Community Clinical Oncology Program Research Base. Pre- and post-RT plasma hsCRP levels and Oncology Nursing Society skin toxicity criteria (0 to 6) were used to assess RT-induced skin toxicities. Multivariable logistic regression analyses were applied to ascertain the associations between hsCRP and RT-induced skin toxicities after adjusting for potential confounders.

Results

The study comprised 623 white, 280 African American, 64 Asian/Pacific Islander, and 33 other race patients; 24% of the patients were Hispanic, and 47% were obese. Approximately 42% and 15% of patients developed RT-induced grade 3+ and 4+ skin toxicities, respectively. The hsCRP levels differed significantly by race and body mass index but not by ethnicity. In multivariable analysis, grade 4+ skin toxicity was significantly associated with obesity (odds ratio [OR], 2.17; 95% CI, 1.41 to 3.34], post-RT hsCRP ≥ 4.11 mg/L (OR, 1.61; 95% CI, 1.07 to 2.44), and both factors combined (OR, 3.65; 95% CI, 2.18 to 6.14). Above-median post-RT hsCRP (OR, 1.93; 95% CI, 1.03 to 3.63), and change in hsCRP (OR, 2.80; 95% CI, 1.42 to 5.54) were significantly associated with grade 4+ skin toxicity in nonobese patients.

Conclusion

This large prospective study is the first to our knowledge of hsCRP as an inflammatory biomarker in RT-induced skin toxicities in breast cancer. We demonstrate that nonobese patients with elevated RT-related change in hsCRP levels have a significantly increased risk of grade 4+ skin toxicity. The outcomes may help to predict RT responses and guide decision making.
Analysis of Plasma Epstein-Barr Virus DNA in Nasopharyngeal Cancer After Chemoradiation to Identify High-Risk Patients for Adjuvant Chemotherapy: A Randomized Controlled Trial
Authors: Chan Anthony T.C. , Hui Edwin P. , Ngan Roger K.C. , Tung Stewart Y. , Cheng Ashley C.K. , Ng Wai T. , Lee Victor H.F. , Ma Brigette B.Y. , Cheng Hoi C. , Wong Frank C.S. , Loong Herbert H.F. , Tong Macy , Poon Darren M.C. , Ahuja Anil T. , King Ann D. , Wang Ki , Mo Frankie , Zee Benny C.Y. , Chan K.C. Allen , Lo Y.M. Dennis
Published: July 2018

Purpose

The contribution of adjuvant chemotherapy after chemoradiation therapy (CRT) in nasopharyngeal cancer (NPC) remains controversial. Plasma Epstein-Barr virus (EBV) DNA is a potential biomarker of subclinical residual disease in NPC. In this prospective, multicenter, randomized controlled trial, we used plasma EBV DNA to identify patients with NPC at a higher risk of relapse for adjuvant chemotherapy.

Patients and Methods

Eligible patients with histologically confirmed NPC of Union for International Cancer Control stage IIB to IVB, adequate organ function, and no locoregional disease or distant metastasis were screened by plasma EBV DNA at 6 to 8 weeks after radiotherapy (RT). Patients with undetectable plasma EBV DNA underwent standard surveillance. Patients with detectable plasma EBV DNA were randomly assigned to either adjuvant chemotherapy with cisplatin and gemcitabine for six cycles (arm 1) or observation (arm 2). Patients were stratified for primary treatment (RT v CRT) and stage (II/III v IV). The primary end point was relapse-free survival (RFS).

Results

Seven hundred eighty-nine patients underwent EBV DNA screening. Plasma EBV DNA was undetectable in 573 (72.6%) and detectable in 216 (27.4%); 104 (13.2%) with detectable EBV DNA were randomly assigned to arms 1 (n = 52) and 2 (n = 52). After a median follow-up of 6.6 years, no significant difference was found in 5-year RFS rate between arms 1 and 2 (49.3% v 54.7%; P = .75; hazard ratio for relapse or death, 1.09; 95% CI, 0.63 to 1.89). The level of post-RT plasma EBV DNA correlated significantly with the hazards of locoregional failure, distant metastasis, and death.

Conclusion

In patients with NPC with detectable post-RT plasma EBV DNA, adjuvant chemotherapy with cisplatin and gemcitabine did not improve RFS. Post-RT plasma EBV DNA level should be incorporated as the selection factor in future clinical trials of adjuvant therapy in NPC.
Benefits of Ultrasound Imaging for Placement of Caudal Epidural Blockade in 3 Pediatric Patients: A Case Report
Authors: Sinskey Jina L. , Vecchione Tricia M. , Ekstrom Benjamin G. , Boretsky Karen
Published: July 2018

Pediatric caudal epidural blockade, the most common pediatric regional anesthetic, is classically placed using surface landmark technique with infrequent use of ultrasound guidance. We present 3 cases where ultrasound guidance facilitated successful placement and helped prevent complications. One infant had an unanticipated S5 dural sac necessitating needle redirection to avoid subarachnoid injection. A 5-year old had proper needle position with inability to inject secondary to needle blockage confirmed with ultrasound. An expremature infant had initial needle placement anterior to the sacrum with subsequent proper placement using real-time ultrasound imaging. Ultrasound guidance for pediatric caudal placement confers advantages and increased routine use should be considered.
Thromboelastography Before Epidural Placement in a Thrombocytopenic Parturient With Gaucher Disease Treated With Imiglucerase: A Case Report
Authors: Tharp William G. , Farhang Borzoo
Published: July 2018

Gaucher disease is a common inborn error of metabolism leading to widespread chronic inflammation and often thrombocytopenia. Here we discuss assessment of coagulation in a parturient with Gaucher disease treated with imiglucerase, who presented with thrombocytopenia and requested epidural analgesia for planned vaginal delivery. We used thromboelastography to determine the safety of placing an epidural catheter and to plan for potential peripartum bleeding. The patient had a normal coagulation profile by thromboelastography and had uncomplicated epidural analgesia for a successful spontaneous vaginal delivery.
Perioperative Management of a Child With Glucose Transporter Type 1 Deficiency Syndrome: A Case Report
Authors: Yoshida Tsubasa , Shimizu Kazuyoshi , Suzuki Satoshi , Matsuoka Yoshikazu , Morimatsu Hiroshi
Published: July 2018

Glucose transporter type 1 deficiency syndrome (GLUT1DS) causes central nervous system dysfunction including intractable epilepsy caused by impaired glucose transport to the brain. To prevent convulsions and maintain an energy source for the brain in patients with GLUT1DS, the maintenance of adequate ketone body concentrations, compensation of metabolic acidosis, and reduction of surgical stress are essential. We here report the perioperative management of a child with GLUT1DS.
Anesthetic Management for Concomitant Correction of Congenital Cardiac Defects and Long “O” Ring Tracheal Stenosis: A Role for Heliox?: Report of 2 Cases
Authors: Mauron Sylvain , Longchamp David , Perez Marie-Hélène , Prêtre René , Sandu Kishore , Di Bernardo Stefano , Boegli Yann , Dolci Mirko
Published: July 2018

We present 2 infants with the rare association of long congenital tracheal stenosis, ventricular septal defect, and pulmonary hypertension. We describe a step-by-step assessment of the patients and the necessary procedures for a successful concomitant repair of both cardiac and tracheal malformations. The use of a helium–oxygen mixture (heliox) for the induction of anesthesia and pre-cardiopulmonary bypass is discussed.
Fluctuating Pulse Oximetry Readings in an Adolescent With Hemoglobin Bibba: A Case Report
Authors: Cirenei Cedric , Veyckemans Francis , Barbati Melissa , Bert Dina , Laffargue-Vetter Anne , Richart Pierre
Published: July 2018

Hemoglobinopathies caused by unstable hemoglobins represent a wide group of diseases that include hemoglobin Bibba. Hemoglobin instability may cause chronic hemolytic anemia and conformational changes in hemoglobin that affect affinity for oxygen and absorption of wavelengths of light used in pulse oximetry devices. We report the case of an adolescent with hemoglobin Bibba and α-thalassemia. Spo
2 was unexpectedly low despite stable vital signs when his hemoglobin was closer to 10 g/dL and normal when his hemoglobin was lower, presumably when there was less unstable hemoglobin because of hemolysis.
Teresa de Jesús
Authors: McGinn Bernard
Published: July 2018

Teresa of Ávila has long been noted as one of the most influential Christian mystical teachers for her doctrine on contemplative prayer, mystical graces, and union with God. Her writings, especially the Life and The Interior Castle, have been widely read from the later sixteenth century to the present. Nevertheless, Teresa was far more than an enclosed contemplative totally separated from the world. Rather her biography reveals her as one of the most active and influential women of her time, especially because of her efforts to found seventeen houses of the reform of the Carmelite Order that she initiated in 1562. To understand how Teresa was able to combine contemplation and action it is necessary to investigate her main mystical writings in light of the major stages of her career as a reformer.
Kenosis, Charity, Love
Authors: Pessin Sarah
Published: July 2018

Thinking with the Christian mystery of kenosis (the self-emptying of God) in relation to divine motions of charity and love, this article sets out to recover a kenotic-mystical element in Greco-Judeo-Islamic Neoplatonisms. After rehearsing the postmetaphysical parameters of the term mystical (and ultimately of the term kenotic-mystical), and after identifying a “deep kenosis” (or “kenosis without kenosis”) in the postmetaphysical kenotics of Vattimo and Marion, the article identifies a ground of “kenosis-charity-love” in the Greco-Islamic Theology of Aristotle, a text whose unique lineage gives insights into Islamic, Greek, and Jewish Neoplatonic encounters with an irruptive and charitable Goodness-without-Being in the shadow of whose outpouring Being pales.
Getting leaves into shape: a molecular, cellular, environmental and evolutionary view
Authors: Maugarny-Calès Aude , Laufs Patrick
Published: July 2018

Leaves arise from groups of undifferentiated cells as small primordia that go through overlapping phases of morphogenesis, growth and differentiation. These phases are genetically controlled and modulated by environmental cues to generate a stereotyped, yet plastic, mature organ. Over the past couple of decades, studies have revealed that hormonal signals, transcription factors and miRNAs play major roles during leaf development, and more recent findings have highlighted the contribution of mechanical signals to leaf growth. In this Review, we discuss how modulating the activity of some of these regulators can generate diverse leaf shapes during development, in response to a varying environment, or between species during evolution.
GRWD1 regulates ribosomal protein L23 levels via the ubiquitin-proteasome system
Authors: Watanabe Shinya , Fujiyama Hiroki , Takafuji Takuya , Kayama Kota , Matsumoto Masaki , Nakayama Keiichi I. , Yoshida Kazumasa , Sugimoto Nozomi , Fujita Masatoshi
Published: July 2018

Glutamate-rich WD40 repeat-containing 1 (GRWD1) is a Cdt1-binding protein that promotes mini-chromosome maintenance (MCM) loading through its histone chaperone activity. GRWD1 acts as a tumor-promoting factor by downregulating p53 (also known as TP53) via the RPL11–MDM2–p53 axis. Here, we identified GRWD1-interacting proteins using a proteomics approach and showed that GRWD1 interacts with various proteins involved in transcription, translation, DNA replication and repair, chromatin organization, and ubiquitin-mediated proteolysis. We focused on the ribosomal protein ribosomal protein L23 (RPL23), which positively regulates nucleolar stress responses through MDM2 binding and inhibition, thereby functioning as a tumor suppressor. Overexpression of GRWD1 decreased RPL23 protein levels and stability; this effect was restored upon treatment with the proteasome inhibitor MG132. EDD (also known as UBR5), an E3 ubiquitin ligase that interacts with GRWD1, also downregulated RPL23, and the decrease was further enhanced by co-expression of GRWD1. Conversely, siRNA-mediated GRWD1 knockdown upregulated RPL23. Co-expression of GRWD1 and EDD promoted RPL23 ubiquitylation. These data suggest that GRWD1 acts together with EDD to negatively regulate RPL23 via the ubiquitin-proteasome system. GRWD1 expression reversed the RPL23-mediated inhibition of anchorage-independent growth in cancer cells. Our data suggest that GRWD1-induced RPL23 proteolysis plays a role in downregulation of p53 and tumorigenesis.
Persistent actin depolarization caused by ethanol induces the formation of multiple small cortical septin rings in yeast
Authors: Homoto Sena , Izawa Shingo
Published: July 2018

Short-term exposure to severe ethanol stress has adverse effects on yeast cells. However, limited information is available on the effects of long-term exposure to severe ethanol stress. In this study, we examined the effects of a long-term treatment with a high ethanol concentration [10% (v/v)] on yeast morphology. We found that long-term severe ethanol stress induced the continuous depolarization of the actin cytoskeleton and hypertrophy in yeast cells, accompanied by the aberrant localization of septins, which formed multiple small cortical rings (MSCRs). The formation of MSCRs was also induced by the continuous depolarization of the actin cytoskeleton caused by a treatment with latrunculin-A, an effective inhibitor of actin polymerization. Unlike the formation of conventional septin rings, the formation of MSCRs did not require Cdc42 and its effectors, Gic1, Gic2 and Cla4. These results provide novel insights into the effects of persistent actin depolarization caused by long-term exposure to severe ethanol stress on yeast cytomorphology.
GSK-3β, a double-edged sword in Nrf2 regulation: Implications for neurological dysfunction and disease
Authors: Culbreth Megan , Aschner Michael
Published: July 2018

In the past decade, it has become evident that glycogen synthase kinase 3β (GSK-3β) modulates the nuclear factor erythroid 2-related factor 2 (Nrf2) oxidative stress response. GSK-3β functions as an inhibitor, both directly in the activation and indirectly in the post-induction of Nrf2. The incidence of oxidative stress in neurological dysfunction and disease has made this signaling pathway an attractive therapeutic target. There is minimal evidence, however, to support a distinctive function for GSK-3β mediated Nrf2 inhibition in nervous system decline, apart from the typical oxidative stress response. In both Alzheimer’s disease and brain ischemia, this pathway has been explored for potential benefits on disease etiology and advancement. Presently, it is unclear whether GSK-3β mediated Nrf2 inhibition markedly influences these disease states. Furthermore, the potential that each has unique function in neurodegenerative decline is unsubstantiated.
DataPackageR: Reproducible data preprocessing, standardization and sharing using R/Bioconductor for collaborative data analysis
Authors: Finak Greg , Mayer Bryan , Fulp William , Obrecht Paul , Sato Alicia , Chung Eva , Holman Drienna , Gottardo Raphael
Published: July 2018

A central tenet of reproducible research is that scientific results are published along with the underlying data and software code necessary to reproduce and verify the findings. A host of tools and software have been released that facilitate such work-flows and scientific journals have increasingly demanded that code and primary data be made available with publications. There has been little practical advice on implementing reproducible research work-flows for large ’omics’ or systems biology data sets used by teams of analysts working in collaboration. In such instances it is important to ensure all analysts use the same version of a data set for their analyses. Yet, instantiating relational databases and standard operating procedures can be unwieldy, with high "startup" costs and poor adherence to procedures when they deviate substantially from an analyst’s usual work-flow. Ideally a reproducible research work-flow should fit naturally into an individual’s existing work-flow, with minimal disruption. Here, we provide an overview of how we have leveraged popular open source tools, including Bioconductor, Rmarkdown, git version control, R, and specifically R’s package system combined with a new tool DataPackageR, to implement a lightweight reproducible research work-flow for preprocessing large data sets, suitable for sharing among small-to-medium sized teams of computational scientists. Our primary contribution is the DataPackageR tool, which decouples time-consuming data processing from data analysis while leaving a traceable record of how raw data is processed into analysis-ready data sets. The software ensures packaged data objects are properly documented and performs checksum verification of these along with basic package version management, and importantly, leaves a record of data processing code in the form of package vignettes. Our group has implemented this work-flow to manage, analyze and report on pre-clinical immunological trial data from multi-center, multi-assay studies for the past three years.
High dose oral and intravenous rifampicin for improved survival from adult tuberculous meningitis: a phase II open-label randomised controlled trial (the RifT study)
Authors: Cresswell Fiona V. , Ssebambulidde Kenneth , Grint Daniel , te Brake Lindsey , Musabire Abdul , Atherton Rachel R. , Tugume Lillian , Muzoora Conrad , Lukande Robert , Lamorde Mohammed , Aarnoutse Rob , Meya David B. , Boulware David R. , Elliott Alison M.
Published: July 2018

Background: Tuberculous meningitis (TBM) has 44% (95%CI 35-52%) in-hospital mortality with standard therapy in Uganda. Rifampicin, the cornerstone of TB therapy, has 70% oral bioavailability and ~10-20% cerebrospinal fluid (CSF) penetration.  With current WHO-recommended TB treatment containing 8-12mg/kg rifampicin, CSF rifampicin exposures frequently fall below the minimal inhibitory concentration for M. tuberculosis. Two Indonesian phase II studies, the first investigating intravenous rifampicin 600mg and the second oral rifampicin ~30mg/kg, found the interventions were safe and resulted in significantly increased CSF rifampicin exposures and a reduction in 6-month mortality in the investigational arms. Whether such improvements can be replicated in an HIV-positive population remains to be determined.

Protocol: We will perform a phase II, open-label randomised controlled trial, comparing higher-dose oral and intravenous rifampicin with current standard of care in a predominantly HIV-positive population. Participants will be allocated to one of three parallel arms (I:I:I): (i) intravenous rifampicin 20mg/kg for 2-weeks followed by oral rifampicin 35mg/kg for 6-weeks; (ii) oral rifampicin 35mg/kg for 8-weeks; (iii) standard of care, oral rifampicin 10mg/kg/day for 8-weeks. Primary endpoints will be: (i) pharmacokinetic parameters in plasma and CSF; (ii) safety. We will also examine the effect of higher-dose rifampicin on survival time, neurological outcomes and incidence of immune reconstitution inflammatory syndrome. We will enrol 60 adults with suspected TBM, from two hospitals in Uganda, with follow-up to 6 months post-enrolment.

Discussion: HIV co-infection affects the bioavailability of rifampicin in the initial days of therapy, risk of drug toxicity and drug interactions, and ultimately mortality from TBM. Our study aims to demonstrate, in a predominantly HIV-positive population, the safety and pharmacokinetic superiority of one or both investigational arms compared to current standard of care. The most favourable dose may ultimately be taken forward into an adequately powered phase III trial.

Trial registration: ISRCTN42218549 (24th April 2018)
Channels of Impact: User Reviews When Quality Is Dynamic and Managers Respond
Authors: Chevalier Judith A. , Dover Yaniv , Mayzlin Dina
Published: July 2018

We examine the effect of managerial response on consumer voice in a dynamic quality environment. We argue that the consumer is motivated to write reviews not only because reviews may impact other consumers, but because reviews may impact the management and the quality of the service. We examine this empirically in a scenario in which reviewers receive a credible signal that the service provider is listening. Specifically, we examine the “managerial response” feature allowed by many review platforms. We hypothesize that managerial responses will stimulate reviewing activity and, in particular, will stimulate negative reviews that are seen as more impactful. This effect is further heightened because managers respond more and in more detail to negative reviews. Using a multiple-differences specification, we show that reviewing activity and particularly negative reviewing is indeed stimulated by managerial response. Our specification exploits comparison of the same hotel immediately before and after response initiation and compares a given hotel’s reviewing activity on sites with review response initiation to that on sites that do not allow managerial response. We also explore the mechanism behind the effect using an online experiment.

Data and the online appendix are available at https://doi.org/10.1287/mksc.2018.1090 .
Dynamic Agency and Endogenous Risk-Taking
Authors: Wong Tak-Yuen
Published: July 2018

I study a continuous-time principal–agent model in which a multitasking agent engages in unobserved risk-taking. Risk-taking creates short-term profits but also increases the chance of large losses. The optimal contract incentivizes excessive risk-taking when the agent has insufficient skin in the game. Moreover, if the low effort is not too value-destroying and the private benefit of shirking is low enough, the principal can eliminate risk-taking by implementing the low effort. However, with variable project scale, addressing the risk-taking incentives by downsizing projects is not optimal. The implementation of the optimal contract shows that risk management should take agency problems into account. Complete hedging against downside risks provides incentives for the agent to gamble.

This paper was accepted by Gustavo Manso, finance.
Winners, Losers, and Facebook: The Role of Social Logins in the Online Advertising Ecosystem
Authors: Krämer Jan , Schnurr Daniel , Wohlfarth Michael
Published: July 2018

Social logins, such as “Log in with Facebook,” improve a website’s user experience and therefore enjoy great popularity among content providers (CPs) and users alike. Moreover, they also enable the social network and the CPs to share data, which individually improves their ability to place targeted advertising. On the basis of a game-theoretic model that offers a microfoundation for CPs’ competition for advertisements, on the one hand, and CPs’ competition for users, on the other hand, we demonstrate the strategic effects of social logins in the online advertising ecosystem. We fully characterize the market conditions under which social logins are offered and adopted, and when the adoption is actually profitable for the CPs. In particular, we show across several model extensions that the voluntary adoption of the social login may yield a prisoner’s dilemma outcome for the CPs.

The online appendix is available at https://doi.org/10.1287/mnsc.2017.3012 .

This paper was accepted by Chris Forman, information systems.
It Is Time to Get Some Rest
Authors: Baucells Manel , Zhao Lin
Published: July 2018

We introduce the fatigue disutility model. Set in continuous time, the model formalizes the notion that fatigue accumulates with effort, decays with rest, and produces an increase in marginal instant disutility. The model is meant to be prescriptive, although it rationalizes several anomalies observed in time preference. Under very general conditions, the most efficient temporal profile of effort exhibits a high-low-high pattern. We consider a variant whereby marginal productivity decreases with fatigue, and we examine the optimal management of fatigue and productivity under various scenarios. We also reexamine the beneficial role of breaks in reducing fatigue. We bring the model to the data and provide a calibration that favorably predicts the speed profiles observed in swimming competitions.

Data are available at https://doi.org/10.1287/mnsc.2017.3018 .

This paper was accepted by Han Bleichrodt, decision analysis.
Inventário do significado do trabalho: explorando evidências de validade no setor de edificações
Authors: Pinheiro Rafaele De Araújo , Bendassolli Pedro Fernando , Borges Livia De Oliveira
Published: July 2018

Este artigo teve como objetivo explorar características de validade do Inventário do Significado do Trabalho (IST), bem como explorar a relação dos tipos de significados e as variáveis sócio-ocupacionais. Para tanto, aplicamos o IST a 402 trabalhadores do setor de edificações em duas capitais do Nordeste brasileiro. Analisamos as respostas dos participantes com a técnica Smallest Space Analisys (SSA). Obtivemos cinco tipos de atributos valorativos e sete de atributos descritivos do trabalho, que se revelaram associados à idade, ao tempo de trabalho em edificações e ao tempo de trabalho no emprego atual.