bluuebunny/crossref_metadata_2025 huggingface dataset:
Perfect Deterrence Theory
Authors: Zagare Frank C.
Published: January 2017

Perfect deterrence theory and classical deterrence theory are two theoretical frameworks that have divergent empirical implications and dissimilar policy recommendations. In perfect deterrence theory, threat credibility plays a central role in the operation of both direct and extended deterrence relationships. But credible threats are neither necessary nor sufficient for deterrence to prevail, and under certain conditions, the presence of a credible threat may actually undermine deterrence. In perfect deterrence theory, the cost of conflict and status quo evaluations are also important strategic variables. Classical deterrence theorists tend to fixate on the former and ignore the latter. This theoretical oversight precludes a nuanced understanding of the dynamics of deterrence.
Performance Psychology with Performing Artists
Authors: Hays Kate F.
Published: January 2017

Performance psychology addresses issues of optimal performance across a wide range of fields. Optimal performance can be enhanced via psychological methods; psychology also addresses the mental barriers and detriments to performance.

One major performance arena is the performing arts. The performing arts include music, dance, and theatre arts. In some instances, people are performing live in front of an audience; in other situations, their performance is prepared for a future audience (e.g., movie, TV, or video).

A number of psychological aspects need to be addressed to produce optimal performance: flawless performance, optimal arousal, focus maintenance, competition and perfectionism, and artistic expression.

Much of the knowledge concerning the enhancement of performance is derived from the field of sport psychology. Some common concerns include the management of performance arousal, developmental issues in relation to early training, injury recovery, and transitions within or out of the performance arena. Although many concerns and expectations are similar with regard to the end “product” of excellent performance, there are also vast differences in such aspects as the culture of the performing arts, historical roots, purpose of the activity, resources and supports, and the place of the particular performance arena within the larger culture. Both research and practice opportunities are increasingly of interest to academicians, practitioners, and performing artists themselves.
Archaeology of Buddhism in Asia
Authors: Ray Himanshu Prabha
Published: January 2017

The eightfold path shown by the Buddha in the middle of the first millennium bce was founded on wisdom, morality, and concentration. Like other contemporary Indic religions, Buddha dhamma had no central organization, nor did it follow a single text as its guiding principle. Its core principle was refuge in the Buddha, the Dhamma, and the Sangha, though as it expanded across Asia, it absorbed local traditions, responded to historical factors, and evolved philosophically. The physical manifestations of the dhamma appeared in the archaeological record at least two hundred to three hundred years later, in the form of inscriptions, stūpas, images, and other objects of veneration. Relic and image worship were important factors in the expansion of Buddhism across the subcontinent and into other parts of Asia.

This essay is framed. Four themes are significant in the archaeology of Buddhism: the history of archaeology in Asia with reference to Buddhism; defining a chronology for the historical Buddha and sites associated with Buddhism; identifying regional specificities and contexts for Buddhist sites as they emerged across Asia; and finally addressing the issue of interconnectedness and interlinkages between the various sites within the Buddhist sāsana. The active participation of learned monks and nuns in the stūpa cult and their mobility across Asia is a factor that is underscored in this paper.
Chinese Ceramic Production and Trade
Authors: Miksic John
Published: January 2017

Ceramics are the most abundant types of artifacts made by human beings in the last 12,000 years. Chinese potters discern two types of products: earthenware (tao), which is porous and does not resonate when struck, and wares with vitreous bodies (ci), which ring like a bell. Western potters and scholars differentiate stoneware, which is semi-porous, from porcelain, which is completely vitrified.

The earliest ceramics in the world are thought to have been made in China around 15,000 years ago. By the Shang dynasty, potters in China began to decorate the surfaces of their pottery with ash glaze, in which wood ash mixed with feldspar in clay to impart a shiny surface to the pottery. The first ash-glazed wares were probably made south of the Yangzi in Jiangnan.

In the 9th century, China began to export pottery, which quickly became sought after in maritime Asia and Africa. Pottery making for export became a major industry in China, employing hundreds of thousands of people, and stimulating the development of the first mass-production techniques in the world. Much of the ceramic industry was located along China’s south and southeast coasts, conveniently located near ports that connected China with international markets. Chinese merchants had to adapt their wares to suit different consumers. For the last 1,000 years, Chinese ceramics provided an enormous amount of archaeological information on trade and society in the lands bordering the South China Sea and the Indian Ocean, contributing a major source of data to the study of early long-distance commerce, art, technology, urbanization, and many other topics. Statistics are presented from important sites outside China where Chinese ceramics have been found.
The Uyghur Empire (744–840)
Authors: Drompp Michael R.
Published: January 2017

The Uyghurs (Chinese Huihe迴 紇, Huihu回鶻) were a pastoral nomadic people living in the region of the Selenga and Orkhon river valleys in modern Mongolia; they spoke a Turkic language. The empire that they created on the steppe lasted for nearly a century (744–840) and played an important role, both politically and culturally, in East Asia. Centered on the Mongolian Plateau, the Uyghur Empire at its height controlled numerous other peoples within a territory that included lands to the north in the modern regions of Tuva and Buryatia, as well as some parts of the northern Tarim Basin and eastern Inner Mongolia.1 During its eventful history, the Uyghur Empire sent cavalry to help the Tang Dynasty put down the An Lushan rebellion, maintained strong political and economic ties with China, fought with the Tibetan Empire for control of important international trade routes, built cities on the steppe, celebrated its rulers’ achievements in stone stelae, and—uniquely in the world—adopted Manichaeism as its state religion. After their empire collapsed, the Uyghurs developed new polities in Gansu and the Tarim Basin that continued to exercise influence in Inner Asia.
Madhyamaka
Authors: Donnelly Paul B.
Published: January 2017

Along with Yogācāra, Madhyamaka (Middle Way) is one of the two foundational doctrinal systems of Indian Mahāyāna Buddhism, which flourished from the 3rd century ce to the final disappearance of Buddhism from the subcontinent in the 12th–13th centuries. Beginning in the 4th century, it spread to East Asia, where it became the foundation of an independent school of thought and influenced the other major Chinese Buddhist schools. It took root in Tibet beginning in the 7th century, where it served as the cornerstone of all the scholastically inclined Buddhist sects. Throughout the Mahāyāna Buddhist world, Madhyamaka has occupied a foundational position in doctrinal formulations and practices. Madhyamaka has tended to be regarded as either the supreme formulation of Mahāyāna thought, as was often the case in Tibet, or as complementary to Yogācāra, which was more commonly held in China and Japan.

The name “Middle Way” references a fundamental assumption in Buddhism that stakes a middle position between the idea that the self is an irreducible, enduring entity and one in which it is wholly reducible to the physical body and perishes after death. Though central Madhyamaka ideas, such as the doctrine of the Two Truths, Dependent Origination, and Emptiness, can be found in Nikāya Buddhism and in Mahāyāna sutras, it is in the treatises of Nāgārjuna (2nd–3rd centuries ce) that we have a fully formed and distinct system of thought that can be called Madhyamaka. In earlier canonical works, and more explicitly in the Abhidharma, this notion of middle way applied exclusively to the self (Skt ātman/Pali atta) and conceptually constructed phenomena. In Mahāyāna sutras and in Nāgārjuna works, the assertion is extended to the fundamental component parts of all existents, which are declared to be empty of intrinsic nature. In Abhidharma works, the self and other composite phenomena are said to be reducible to their fundamental parts, the dharmas (Pali dhamma), which, being irreducible, must have their own identifiable intrinsic mode of existence even if they exist dependently. According to Madhyamaka, a dharma cannot possess an intrinsic nature precisely because it exists dependently. Denying any intrinsic nature, Madhyamaka asserts that things exist only dependently, and this only in terms of conventional truth, and that ultimately, emptiness of intrinsic nature is the truth and reality of all things. Not surprisingly, such a position was contentious, and numerous interpreters attempted to elucidate this rather radical position. The question of which commentator or commentators are definitive has occupied many generations of Indian, East Asian, and Tibetan Buddhists, and the issue remains very much alive in modern scholarship on Madhyamaka. Though much of this scholarship has come from a philosophical perspective, the intent of Madhyamaka, like all Buddhist thought, is primarily soteriological in nature.
Folk Festivals, Community Development, and the Sugar Industry Crisis in Tucumán, Argentina, 1966–1973
Authors: Chamosa Oscar
Published: January 2017

In the late 1960s, the sugar-growing province of Tucumán, Argentina, was undergoing the deepest economic crisis of its history. In 1966, eleven large sugar mills closed by order of the national government, then ruled by military dictator Juan Carlos Onganía. The mills closure left a quarter of the province’s labor force unemployed, which, in turns, prompted a massive rural exodus and a permanent state of social unrest. Paradoxically, at the same time, the suddenly impoverished region was experiencing a boom of folk music festivals organized by small cities and rural towns, including those severely hit by the sugar industry crisis. This essay explores the context of the folk festival phenomenon, analyzing the role of town notables and local civic organizations in responding to the crisis brought about by the closure of the mills. The festivals were, in fact, part of a wider effort of local towns to develop their infrastructure and social services. By organizing festivals and fostering community development, local notables acted as a counterweight to the activism of the working class, generating spaces of consent that aided the military government’s plans to reorder the provincial economy.
Japanese Linguistics
Authors: Tsujimura Natsuko
Published: January 2017

The rigor and intensity of investigation on Japanese in modern linguistics has been particularly noteworthy over the past 50 years. Not only has the elucidation of the similarities to and differences from other languages properly placed Japanese on the typological map, but Japanese has served as a critical testing area for a wide variety of theoretical approaches.

Within the sub-fields of Japanese phonetics and phonology, there has been much focus on the role of mora. The mora constitutes an important timing unit that has broad implications for analysis of the phonetic and phonological system of Japanese. Relatedly, Japanese possesses a pitch-accent system, which places Japanese in a typologically distinct group arguably different from stress languages, like English, and tone languages, like Chinese. A further area of intense investigation is that of loanword phonology, illuminating the way in which segmental and suprasegmental adaptations are processed and at the same time revealing the fundamental nature of the sound system intrinsic to Japanese.

In morphology, a major focus has been on compounds, which are ubiquitously found in Japanese. Their detailed description has spurred in-depth discussion regarding morphophonological (e.g., Rendaku—sequential voicing) and morphosyntactic (e.g., argument structure) phenomena that have crucial consequences for morphological theory. Rendaku is governed by layers of constraints that range from segmental and prosodic phonology to structural properties of compounds, and serves as a representative example in demonstrating the intricate interaction of the different grammatical aspects of the language. In syntax, the scrambling phenomenon, allowing for the relatively flexible permutation of constituents, has been argued to instantiate a movement operation and has been instrumental in arguing for a configurational approach to Japanese. Japanese passives and causatives, which are formed through agglutinative morphology, each exhibit different types: direct vs. indirect passives and lexical vs. syntactic causatives. Their syntactic and semantic properties have posed challenges to and motivations for a variety of approaches to these well-studied constructions in the world’s languages.

Taken together, the empirical analyses of Japanese and their theoretical and conceptual implications have made a tremendous contribution to linguistic research.
Connectionism in Linguistic Theory
Authors: Zhao Xiaowei
Published: January 2017

Connectionism is an important theoretical framework for the study of human cognition and behavior. Also known as Parallel Distributed Processing (PDP) or Artificial Neural Networks (ANN), connectionism advocates that learning, representation, and processing of information in mind are parallel, distributed, and interactive in nature. It argues for the emergence of human cognition as the outcome of large networks of interactive processing units operating simultaneously. Inspired by findings from neural science and artificial intelligence, connectionism is a powerful computational tool, and it has had profound impact on many areas of research, including linguistics. Since the beginning of connectionism, many connectionist models have been developed to account for a wide range of important linguistic phenomena observed in monolingual research, such as speech perception, speech production, semantic representation, and early lexical development in children. Recently, the application of connectionism to bilingual research has also gathered momentum. Connectionist models are often precise in the specification of modeling parameters and flexible in the manipulation of relevant variables in the model to address relevant theoretical questions, therefore they can provide significant advantages in testing mechanisms underlying language processes.
The lowdown on Down syndrome
Authors: Perkins Amanda
Published: January 2017

Due to advances in healthcare and the older age of individuals with Down syndrome, it's becoming increasingly important for nurses to understand how to care for patients with this disorder.
Borrow or Serve? An Economic Analysis of Options for Financing a Medical School Education
Authors: Marcu Mircea I. , Kellermann Arthur L. , Hunter Christine , Curtis Jerri , Rice Charles , Wilensky Gail R.
Published: January 2017

Purpose

To understand the long-term economic implications of key pathways for financing a medical school education.

Method

The authors calculated the net present value (NPV) of cash flow over a 30-year career for a 2013 matriculant associated with (1) self-financing, (2) federally guaranteed loans, (3) the Public Service Loan Forgiveness program, (4) the National Health Service Corps, (5) the Armed Forces Health Professions Scholarship Program, and (6) matriculation at the Uniformed Services University of the Health Sciences. They calculated the NPV for students pursuing one of four specialties in two cities with divergent tax policies. Borrowers were assumed to have a median level of debt ($180,000), and conservative projections of inflation, discount rates, and income growth were employed. Sensitivity analyses examined different discount and income growth rates, alternative repayment strategies, and various lengths of public-sector service by scholarship recipients.

Results

For those wealthy enough to pay cash or fortunate enough to secure a no-strings scholarship, self-financing produced the highest NPV in almost every scenario. Borrowers start practice $300,000 to $400,000 behind their peers who secure a national service scholarship, but those who enter a highly paid specialty, such as orthopedic surgery, overtake their national service counterparts 4 to 11 years after residency. Those in lower-paid specialties take much longer. Borrowers who enter primary care never close the gap.

Conclusions

Over time, the value of a medical degree offsets the high up-front cost. Debt avoidance confers substantial economic benefits, particularly for students interested in primary care.
The Good Investment
Authors: Prescott John E. , Fresne Julie A. , Youngclaus James A.
Published: January 2017

The authors reflect on the article in this issue entitled “Borrow or Serve? An Economic Analysis of Options for Financing a Medical School Education” by Marcu and colleagues, which makes a compelling case that a medical school education is a good investment, no matter what financing option students use, from federal service programs to federal loans. The lead author of this Commentary shares lessons learned from his own medical school education, which was funded by an Armed Forces Health Professions Scholarship, and from his current position interacting with medical students across the United States.

Regardless of the financing path they choose, all students should understand basic financial concepts and the details of the various pathways that are available to pay for their medical school education, as well as how each could potentially impact their own future and that of their families. One underappreciated aspect of financing a medical school education is that federal repayment scenarios can link loan payments to income, rather than debt levels, which means that all physicians are able to afford their loan payments no matter what specialty they practice, what they are paid, or where they live.

Medical education, while expensive, remains the good investment. An MD degree can lead to a lifetime of personal fulfillment and societal contributions. Everyone, with rare exceptions, accepted to a U.S. medical school will be able to finance their medical education via a path that aligns with their personal values and priorities.
Comparative Analysis of Combined (First Anterior, Then Posterior) Versus Only Posterior Approach for Treating Severe Scoliosis
Authors: Hero Nikša , Vengust Rok , Topolovec Matevž
Published: January 2017

Study Design.

A retrospective, one center, institutional review board approved study.

Objective.

Two methods of operative treatments were compared in order to evaluate whether a two-stage approach is justified for correction of bigger idiopathic scoliosis curves. Two stage surgery, combined anterior approach in first operation and posterior instrumentation and correction in the second operation. One stage surgery included only posterior instrumentation and correction.

Summary of Background Data.

Studies comparing two-stage approach and only posterior approach are rather scarce, with shorter follow up and lack of clinical data.

Methods.

Three hundred forty eight patients with idiopathic scoliosis were operated using Cotrel–Dubousset (CD) hybrid instrumentation with pedicle screw and hooks. Only patients with curvatures more than or equal to 61° were analyzed and divided in two groups: two stage surgery (N = 30) and one stage surgery (N = 46). The radiographic parameters as well as duration of operation, hospitalization time, and number of segments included in fusion and clinical outcome were analyzed.

Results.

No statistically significant difference was observed in correction between two-stage group (average correction 69%) and only posterior approach group (average correction 66%). However, there were statistically significant differences regarding hospitalization time, duration of the surgery, and the number of instrumented segments.

Conclusion.

Two-stage surgery has only a limited advantage in terms of postoperative correction angle compared with the posterior approach. Posterior instrumentation and correction is satisfactory, especially taking into account that the patient is subjected to only one surgery.

Level of Evidence: 3
Post-traumatic Spinal Hygroma Causing Cord Compression in Type III Odontoid Fracture With Vertical Atlantoaxial Instability
Authors: Russo Salvatore , Belli Antonio , Eynon Andy , Nader-Sepahi Ali
Published: January 2017

Study Design.

Case report.

Objective.

To report the first case in the literature of a traumatic cervical spine subdural cerebrospinal fluid (CSF) collection (hygroma) under tension causing cord compression. We suggest etiopathogenesis and modality of treatment.

Summary of Background Data.

Hygromas are subdural cranial CSF collection. A literature review showed no previous published case of post-traumatic spinal hygroma. This was a potential life-threatening sequelae of a high cervical injury that warranted early diagnosis and emergency treatment.

Methods.

We present a case of a young adult who sustained a traumatic vertical atlantoaxial dislocation associated with a type III odontoid fracture. He was initially scored C6 ASIA D. Magnetic resonance imaging (MRI) demonstrated cord contusion at the craniocervical junction and a small fluid collection anterior to the cervical cord. On day 5 after his injury he developed complete paraplegia and priapism. An urgent MRI of his spine revealed expansion of the intraspinal fluid collection with distortion of the cord. He was treated with an emergency surgical decompression. The cervical fluid collection was found to be subdural extra-arachnoidal CSF. A subdural-pleural shunt was inserted. The atlantoaxial injury was reduced and fixed with posterior instrumentation.

Results.

At 1 year from the injury the patient was independent and fully ambulant. MRI and computed tomography images of his spine demonstrated complete resolution of the cervical hygroma, appropriate placement of the cervical-pleural shunt, and stability of the atlantoaxial injury.

Conclusion.

We describe a unique case of post-traumatic spinal hygroma causing cord compression in a patient with an unstable craniocervical injury. The early recognition and correction of this dangerous complication is of paramount importance to savage cord function.

Level of Evidence: 5
Superior Suppression of ErbB2-positive Tumor Cells by a Novel Human Triparatopic Tribody
Authors: Riccio Gennaro , Da Fonseca-Ricardo Ana R. , Passariello Margherita , Cunnah Philip , Mertens Nico , De Lorenzo Claudia
Published: January 2017

Downregulation of the epidermal growth factor receptor family of receptors is improved by combining different antibodies to noncompetitive epitopes. For ErbB2/HER2 this has already been translated into clinical practice by using a combination of trastuzumab and pertuzumab. Moreover, cocktails of 2 or 3 anti-epidermal growth factor receptor antibodies show an enhanced downregulation of the receptor due to the induction of matrix formation. A more efficient method for inducing matrix formation and receptor downregulation might include the use of trispecific reagents. A triparatopic Tribody consisting of 3 noncompeting ErbB2 binders was compared with equivalent trivalent monoparatopic counterparts, as well as to a cocktail of 3 monoclonal antibodies for its effects on downregulation of the ErbB2 receptor’s kinase activity and survival of several ErbB2-expressing cancer cell lines. The triparatopic Tribody was significantly more efficient in downregulating ErbB2 and inhibiting tumor cell growth than either the control monoparatope tribodies or the combinatorial treatment with the 3 different parental antibodies on all the tested tumor cells, including trastuzumab-resistant cell lines. The enhancement of effectivity was dependent on all 3 binding moieties. Because the novel Tribody allows reduction of the costs of production (as only 1 construct provides the antitumor effects of 3 antibodies) and has an intermediate molecular size (∼100 kDa) well suited for both tumor penetration and acceptable half-life, it has the potential to become a precious tool for therapeutic use particularly in trastuzumab-resistant cancer patients.
A Dendritic Cell Vaccine Combined With Radiotherapy Activates the Specific Immune Response in Patients With Esophageal Cancer
Authors: Wang Chengshi , Pu Juan , Yu Hanxu , Liu Yanyan , Yan Honghuan , He Zhongxiang , Feng Xin
Published: January 2017

Dendritic cells (DC) are highly efficient antigen-presenting cells. DC may be used to create DC vaccines against cancer, but the optimal strategies remain to be elucidated. This study aimed to examine the benefits and adverse effects of using esophageal cancer cell antigens to stimulate DC to trigger the specific immune response in patients with esophageal cancer undergoing radiotherapy. This was an observational cohort study performed at Lianshui County People’s Hospital between September 2010 and June 2012. Forty patients with esophageal cancer planned to receive radiotherapy were selected, and 28 received the DC vaccine. DC were isolated, loaded with antigens, and intradermally injected after being cultured for 1 week. One week after injection, the patients underwent a delayed-type hypersensitivity test. Serum Th1 cytokines [interleukin (IL)-2, IL-12, and interferon (IFN)-γ] and antigen-specific IFN-γ+CD8+ T cells were tested before and after vaccination. Patients were followed up for 2 years. Adverse events were monitored. Patients in the vaccine group tolerated the DC vaccine. Levels of serum IL-2 (+92.4%), IL-12 (+70.9%), and IFN-γ (+214.3%) as well as the proportion of IFN-γ+CD8+ T cells (3.0–16.4-fold) were significantly increased compared with baseline and the control group (all P<0.05). The 1- (82.1% vs. 50.0%, P=0.04) and 2-year survival (67.8% vs. 33.3%, P=0.04) was improved by vaccination. Only 2 patients showed mild fever. In conclusion, the DC vaccine triggered the specific immune response and induced the secretion of Th1 cytokines. The vaccine may lead to better survival, but this have to be confirmed. Adverse events were rare and mild.
Basal neutrophil-to-lymphocyte ratio is associated with overall survival in melanoma
Authors: Lino-Silva Leonardo S. , Salcedo-Hernández Rosa A. , García-Pérez Leticia , Meneses-García Abelardo , Zepeda-Najar César
Published: January 2017

Several studies have reported that a high neutrophil-to-lymphocyte ratio (NLR) is associated with poor clinical outcomes in several cancers, but this ratio has not been thoroughly studied in melanoma except in stage IV. This is the first study on NLR in melanoma stages I–III. This was a retrospective study of 742 melanoma patients. The NLR was classified into NLR<2 and a NLR≥2 on the basis of a receiver operating characteristic curve. Associations of NLR with clinicopathological characteristics and survival were examined. The median patient age was 57 years (range: 15–91; Q1=46, Q3=70), and the median Breslow’s thickness was 3.0 mm (range: 0.5–60; Q1=1.0, Q3=7). Clinical stage at presentation was as follows: (i) stage I in 27%; (ii) stage II in 33.2%; (iii) stage III in 36.5%; and (iv) stage IV in 3.3%. NLR≥2 was associated with lymph node metastasis (36.6 vs. 18.1%) and recurrence (28.2 vs. 22.1%). The 5-year overall survival (OS) was 63% for the NLR<2 group and 53% for the NLR≥2 group. Stage-by-stage analysis showed that the 5-year OS in the NLR≥2 group for stages I, II, III, and IV were 91, 60, 28, and 0%, respectively, whereas for the NLR<2 group the 5-year OS were 98, 68, 31, and 0%, respectively. Significant differences between NLR<2 and ≥2 occurred only in stage II (P=0.014). Univariate analysis showed that factors associated with decreased OS clinical stage were Breslow’s thickness, ulceration, male sex, and NLR≥2. In the multivariate analysis, all of these factors were predictors of decreased survival. The NLR appears to be an accurate prognostic marker for decreased OS in patients with melanoma, especially in clinical stage II. NLR≥2 correlated with lymph node metastasis and recurrence.
KCNQ2/3 channel agonist flupirtine reduces cocaine place preference in rats
Authors: Mooney James , Rawls Scott M.
Published: January 2017

The efficacy of KCNQ2/3 channel agonists against drug reward has not been defined despite their ability to reduce locomotor-stimulant and dopamine-activating effects of psychostimulants. We tested the hypothesis that flupirtine (FLU) (2.5, 10, 20 mg/kg), a KCNQ2/3 agonist, reduces cocaine (15 mg/kg) conditioned place preference. FLU (20 mg/kg), injected concurrently with cocaine during conditioning, reduced the development of cocaine conditioned place preference. FLU (20 mg/kg) also reduced cocaine locomotor activation without affecting baseline activity. The disruption of cocaine place preference by FLU suggests that KCNQ2/3 channels influence cocaine’s rewarding effects.
Oral modafinil facilitates intracranial self-stimulation in rats: comparison with methylphenidate
Authors: Lazenka Matthew F. , Negus S. Stevens
Published: January 2017

Modafinil is a low-potency inhibitor of dopamine transporters (DAT) approved clinically to promote wakefulness. In most procedures used for abuse-liability assessment, modafinil produces effects similar to those of abused DAT inhibitors such as cocaine and methylphenidate, although modafinil often shows lower effectiveness. However, modafinil has failed to maintain drug self-administration or produce conditioned place preferences in rats. The low potency and poor solubility of modafinil complicate its delivery by parenteral routes of administration commonly used in rats, and this may contribute toward negative results. This study evaluated the effects of orally administered modafinil in rats using an assay of intracranial self-stimulation (ICSS) that has been used to examine the effects of other DAT inhibitors. Adult male Sprague-Dawley rats equipped with electrodes in the medial forebrain bundle responded for pulses of brain stimulation that varied across a range of frequencies (158–56 Hz) during daily behavioral sessions. Modafinil (20–600 mg/kg, orally) and methylphenidate (1.0–10 mg/kg, intraperitoneally; 3.2–32 mg/kg, orally) produced dose-dependent and time-dependent facilitation of ICSS, an effect produced by abused DAT inhibitors and other classes of abused drugs. These results are in agreement with other evidence for stimulant-like abuse liability of modafinil and show the sensitivity of ICSS to orally administered drug.
Measurement of Clozapine, Norclozapine, and Amisulpride in Plasma and in Oral Fluid Obtained Using 2 Different Sampling Systems
Authors: Fisher Danielle S. , Beyer Chad , van Schalkwyk Gerrit , Seedat Soraya , Flanagan Robert J.
Published: January 2017

Background:

There is a poor correlation between total concentrations of proton-accepting compounds (most basic drugs) in unstimulated oral fluid and in plasma. The aim of this study was to compare clozapine, norclozapine, and amisulpride concentrations in plasma and in oral fluid collected using commercially available collection devices [Thermo Fisher Scientific Oral-Eze and Greiner Bio-One (GBO)].

Methods:

Oral-Eze and GBO samples and plasma were collected in that order from patients prescribed clozapine. Analyte concentrations were measured by liquid chromatography–tandem mass spectrometry.

Results:

There were 112 participants [96 men, aged (median, range) 47 (21–65) years and 16 women, aged 44 (21–65) years]: 74 participants provided 2 sets of samples and 7 provided 3 sets (overall 2 GBO samples not collected). Twenty-three patients were co-prescribed amisulpride, of whom 17 provided 2 sets of samples and 1 provided 3 sets. The median (range) oral fluid within the GBO samples was 52 (13%–86%). Nonadherence to clozapine was identified in all 3 samples in one instance. After correction for oral fluid content, analyte concentrations in the GBO and Oral-Eze samples were poorly correlated with plasma clozapine and norclozapine (R2= 0.57–0.63) and plasma amisulpride (R2= 0.65–0.72). Analyte concentrations in the 2 sets of oral fluid samples were likewise poorly correlated (R2= 0.68–0.84). Mean (SD) plasma clozapine and norclozapine were 0.60 (0.46) and 0.25 (0.21) mg/L, respectively. Mean clozapine and norclozapine concentrations in the 2 sets of oral fluid samples were similar to those in plasma (0.9–1.8 times higher), that is, approximately 2- to 3-fold higher than those in unstimulated oral fluid. The mean (±SD) amisulpride concentrations (microgram per liter) in plasma (446 ± 297) and in the Oral-Eze samples (501 ± 461) were comparable and much higher than those in the GBO samples (233 ± 318).

Conclusions:

Oral fluid collected using either the GBO system or the Oral-Eze system cannot be used for quantitative clozapine and/or amisulpride therapeutic drug monitoring.
Coping with interdependencies related to patient choice: Boundary-spanning at four accountable care organizations
Authors: Hilligoss Brian , McAlearney Ann Scheck , Song Paula H.
Published: January 2017

Background:

Accountable care organizations (ACOs) are responsible for outcomes that are only partially under their control because patients may choose to self-refer outside the ACO, overuse resource-intensive services, or underuse evidence-based care. ACOs must devise boundary-spanning practices to manage these interdependencies related to patient choice.

Purpose:

The aim of this study was to identify, conceptualize, and categorize ACO efforts to cope with interdependencies related to patient choice.

Approach:

We conducted qualitative organizational case studies of four ACOs. We interviewed 89 executives, mid-level managers, and physicians and analyzed the data through multiple rounds of inductive coding.

Results:

We identified 15 boundary-spanning practices, in which two or more ACOs engaged in efforts to understand, cope with, or alter interdependencies related to patient choice. Analysis of these practices revealed five categories of factors that appeared to shape patient choices in ways that may impact ACO performance: the availability of services, interactions with patients, system complexities, care provided to ACO patients by non-ACO providers, and uncertainties related to the environment. Our findings provide a process theory of ACO boundary-spanning: Each individual boundary-spanning practice contributes to a broader strategic goal, through which it may impact a particular aspect of interdependence and thereby reduce underuse, overuse, or leakage (i.e., provision of services outside the ACO).

Practice Implications:

In identifying ACO boundary-spanning practices and proposing how they may impact interdependence, our theory highlights conceptual relationships that researchers can study and test. Similarly, in identifying key aspects of interdependencies related to patient choice and a broad assortment of ACO boundary-spanning practices, our findings provide managers with a tool for evaluating and developing their own boundary-spanning efforts.
Eyelid Eccrine Cyst: An Exceptional Lesion Among Dominant Apocrine Cysts
Authors: Jakobiec Frederick A. , Qureshi Sana , Zakka Fouad R. , Tu Yufei , Lee Nhayoung Grace
Published: January 2017

A 71-year-old woman developed a small bluish lesion beneath the cilia of the left lower eyelid. Excision and microscopic examination disclosed a cyst with an intimately associated eccrine sweat gland. Immunohistochemistry demonstrated that the cyst’s epithelium was strongly CK5/6+, CK14+, CK7 weakly positive, and gross cystic disease fluid protein-15 and smooth muscle actin negative. This is the first immunohistochemically proven eccrine cyst of the eyelid skin. Apocrine cysts develop only at the eyelid margin where the glands of Moll are located. They immunostain positively for cytoplasmic gross cystic disease fluid protein-15 in the adlumenal cells and smooth muscle actin in an outer myoepithelial (abluminal) layer.
Age-Related Change in Vestibular Ganglion Cell Populations in Individuals With Presbycusis and Normal Hearing
Authors: Gluth Michael B. , Nelson Erik G.
Published: January 2017

Hypothesis:

We sought to establish that the decline of vestibular ganglion cell counts uniquely correlates with spiral ganglion cell counts, cochlear hair cell counts, and hearing phenotype in individuals with presbycusis.

Background:

The relationship between aging in the vestibular system and aging in the cochlea is a topic of ongoing investigation. Histopathologic age-related changes the vestibular system may mirror what is seen in the cochlea, but correlations with hearing phenotype and the impact of presbycusis are not well understood.

Methods:

Vestibular ganglion cells, spiral ganglion cells, and cochlear hair cells were counted in specimens from individuals with presbycusis and normal hearing. These were taken from within a large collection of processed human temporal bones. Correlations between histopathology and hearing phenotype were investigated.

Results:

Vestibular ganglion cell counts were positively correlated with spiral ganglion cell counts and cochlear hair cell counts and were negatively correlated with hearing phenotype. There was no statistical evidence on linear regression to suggest that the relationship between age and cell populations differed significantly according to whether presbycusis was present or not. Superior vestibular ganglion cells were more negatively correlated with age than inferior ganglion cells. No difference in vestibular ganglion cells was noted based on sex.

Conclusion:

Vestibular ganglion cell counts progressively deteriorate with age, and this loss correlates closely with changes in the cochlea, as well as hearing phenotype. However, these correlations do not appear to be unique in individuals with presbycusis as compared with those with normal hearing.
Pao 2/Fio 2 Ratio Derived From the Spo 2/Fio 2 Ratio to Improve Mortality Prediction Using the Pediatric Index of Mortality-3 Score in Transported Intensive Care Admissions*
Authors: Ray Samiran , Rogers Libby , Pagel Christina , Raman Sainath , Peters Mark J. , Ramnarayan Padmanabhan
Published: January 2017

Objectives:

To derive a relationship between the Spo
2/Fio
2 ratio and Pao
2/Fio
2 ratio across the entire range of Spo
2 values (0–100%) and to evaluate whether mortality prediction using the Pediatric Index of Mortality-3 can be improved by the use of Pao
2/Fio
2 values derived from Spo
2/Fio
2.

Design:

Retrospective analysis of prospectively collected data.

Setting:

A regional PICU transport service.

Patients:

Children transported to a PICU.

Interventions:

None.

Measurements and Main Results:

The relationship between Spo
2/Fio
2 and Pao
2/Fio
2 across the entire range of Spo
2 values was first studied using several mathematical models in a derivation cohort (n = 1,235) and then validated in a separate cohort (n = 306). The best Spo
2/Fio
2-Pao
2/Fio
2 relationship was chosen according to the ability to detect respiratory failure (Pao
2/Fio
2 ≤ 200). The discrimination of the original Pediatric Index of Mortality-3 score and a derived Pediatric Index of Mortality-3 score (where Spo
2/Fio
2-derived Pao
2/Fio
2 values were used in place of missing Pao
2/Fio
2 values) were compared in a different cohort (n = 1,205). The best Spo
2/Fio
2-Pao
2/Fio
2 relationship in 1,703 Spo
2/Fio
2-to-Pao
2/Fio
2 data pairs was a linear regression equation of ln[PF] regressed on ln[SF]. This equation identified children with a Pao
2/Fio
2 less than or equal to 200 with a specificity of 73% and sensitivity of 61% in children with Spo
2 less than 97% (92% and 33%, respectively, when Spo
2 ≥ 97%) in the validation cohort. Pao
2/Fio
2 derived from Spo
2/Fio
2 (derived Pao
2/Fio
2) was better at predicting PICU mortality (area under receiver operating characteristic curve, 0.64; 95% CI, 0.55–0.73) compared with the original Pao
2/Fio
2 (area under receiver operating characteristic curve, 0.54; 95% CI, 0.49–0.59; p = 0.02). However, there was no difference in the original and derived Pediatric Index of Mortality-3 scores and their discriminatory ability for mortality.

Conclusions:

Spo
2-based metrics perform no worse than arterial blood gas–based metrics in mortality prediction models. Future Pediatric Index of Mortality score versions may be improved by the inclusion of risk factors based on oxygen saturation values, especially in settings where Pao
2 values are missing in a significant proportion of cases.
Epidemiology of Pediatric Critical Illness in a Population-Based Birth Cohort in Olmsted County, MN
Authors: Crow Sheri S. , Undavalli Chaitanya , Warner David O. , Katusic Slavica K. , Kandel Pujan , Murphy Sinead L. , Schroeder Darrell R. , Watson R. Scott
Published: January 2017

Objectives:

Investigations of pediatric critical illness typically focus on inpatient cohorts drawn from wide referral areas and diverse healthcare systems. Cohorts amenable to investigating the full spectrum of critical illness as it develops within a community have yet to be studied in the United States. Our objective was to provide the first epidemiologic report of the incidence and presentation of pediatric critical illness within a U.S. population-based birth cohort.

Design:

Retrospective cohort study.

Setting:

A geographically defined community (Olmsted, MN) with medical record linkage across all health systems. All ICU services are provided within a single children’s hospital.

Patients:

A birth cohort of children (n =9,441) born 2003–2007 in Olmsted County, MN.

Measurements and Main Results:

During the study period, there were a total of 15,277 ICU admissions to Mayo Clinic Children’s Hospital. A total of 577 birth cohort children accounted for 824 of these admissions during the 61,770 person-years of follow-up accumulated. Incidence of first-time ICU admission was 9.3 admits per 1,000 person-years. Admission rates were highest in the first year of life and then declined steadily. Respiratory problems were among the most common reasons for admission at any age and diagnoses reflect changes in health risk factors as children grow and develop over time. After 1 year old, a majority of children admitted have preexisting chronic comorbidities and/or prior ICU stays. In-hospital mortality occurred exclusively in children admitted prior to 5 days of age (n = 4). Seven children died after hospital discharge.

Conclusions:

This is the first report characterizing critical illness within a population-based birth cohort of U.S. children. The results demonstrate the changing incidence, presentation, and healthcare requirements associated with critical illness across the developmental spectrum as a population of children ages.
Central Venous to Arterial Co 2 Difference After Cardiac Surgery in Infants and Neonates*
Authors: Rhodes Leslie A. , Erwin W. Clinton , Borasino Santiago , Cleveland David C. , Alten Jeffrey A.
Published: January 2017

Objectives:

Venous to arterial Co2difference correlates with cardiac output in critically ill adults, but its utility in pediatric patients is unclear. We sought to correlate venous to arterial Co2difference with other cardiac output surrogates (arteriovenous oxygen saturation difference, central venous oxygen saturation, and lactate) and investigate its capacity to predict poor outcomes associated with low cardiac output (low cardiac output syndrome) in infants after cardiac surgery with cardiopulmonary bypass.

Design:

Retrospective chart review. Poor outcome was defined as any inotrope score greater than 15; death, cardiac arrest, extracorporeal membrane oxygenation; and unplanned surgical reintervention.

Setting:

Pediatric cardiovascular ICU.

Patients:

One hundred thirty-nine infants less than 90 days who underwent cardiopulmonary bypass, from October 2012 to May 2015.

Intervention:

None.

Measurements and Main Results:

Two hundred ninety-six arterial and venous blood gas pairs from admission (n= 139), 6 (n= 62), 12 (n= 73), and 24 hours (n= 22) were included in analysis. For all pairs, venous to arterial Co2difference was moderately correlated with arteriovenous oxygen saturation difference (R2= 0.53;p< 0.01) and central venous oxygen saturation (R2= –0.43;p< 0.01), but not lactate. At admission, venous to arterial Co2difference was also moderately correlated with central venous oxygen saturation (R2= –0.40;p< 0.01) and arteriovenous oxygen saturation difference (R2= 0.55;p< 0.01), but not lactate. Thirty-four of 139 neonates (24.5%) had poor outcome. Median admission venous to arterial Co2difference was 5.9 mm Hg (3.8–9.2 mm Hg). Patients with poor outcome had median admission venous to arterial Co2difference 8.3 (5.6–14.9) versus 5.4 mm Hg (3.0–8.4 mm Hg) in those without poor outcome. Venous to arterial Co2difference (area under the curve = 0.69;p< 0.01), serum lactate (area under the curve = 0.64;p= 0.02), and central venous oxygen saturation (area under the curve = 0.74;p< 0.01) were predictive of poor outcome. After controlling for covariates, admission venous to arterial Co2difference remained significantly associated with poor outcome (odds ratio, 1.3; 95% CI, 1.1–1.45), including independent association with mortality (odds ratio, 1.2; 95% CI, 1.07–1.31).

Conclusions:

Venous to arterial Co2difference is correlated with important surrogates of cardiac output, and is associated with poor outcome and mortality related to low cardiac output syndrome after cardiac surgery in infants. Prospective validation of these findings, including confirmation that venous to arterial Co2difference can identify low cardiac output syndrome in real time, is warranted.
International Epidemiological Differences in Acute Poisonings in Pediatric Emergency Departments
Authors: Mintegi Santiago , Azkunaga Beatriz , Prego Javier , Qureshi Nadeem , Dalziel Stuart R. , Arana-Arri Eunate , Acedo Yordana , Martinez-Indart Lorea , Urkaregi Arantza , Salmon Nerea , Benito Javier , Kuppermann Nathan
Published: January 2017

Background and Objective

Identifying international differences in the epidemiology of acute poisonings in children may help in improving prevention. We sought to evaluate the international epidemiological differences in acute poisonings in children presenting to emergency departments (EDs) from 8 different global regions.

Methods

This was an international multicenter cross-sectional prospective study including children younger than 18 years with acute poisonings presenting to 105 EDs in 20 countries was conducted. Data collection started at each ED between January and September 2013, and continued for 1 year.

Results

During the study period, we registered 363,245 pediatric ED presentations, of which 1727 were for poisoning (0.47%; 95% confidence interval, 0.45%–0.50%), with a significant variation in incidence between the regions. Full data were obtained for 1688 presentations. Most poisonings (1361 [80.6%]) occurred at home with either ingestion (1504 [89.0%]) or inhalation of the toxin (126 [7.6%]). Nonintentional exposures accounted for 1157 poisonings (68.5%; mainly in South America and Eastern Mediterranean region), with therapeutic drugs (494 [42.7%]), household products (310 [26.8%]), and pesticides (59 [5.1%]) being the most common toxins. Suicide attempts accounted for 233 exposures (13.8%; mainly in the Western Pacific region and North America), with therapeutic drugs (214 [91.8%], mainly psychotropics and acetaminophen) being the most common toxins. Significant differences between regions were found in both types of poisonings. Recreational poisonings were more common in Europe and Western Pacific region. No patient died.

Conclusions

There are substantial epidemiological differences in acute poisonings among children in different countries and regions of the globe. International best practices need to be identified for prevention of acute poisonings in childhood.