bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral Traditions as Sources
Authors: Belcher Stephen
Published: February 2018

The use of oral tradition is a distinctive and essential element in many fields of African studies. History must acknowledge it; literature sees it as the medium for much of the indigenous creative endeavor across African cultures; anthropology and its cousin disciplines rely upon oral information for their understanding of traditional societies. An appreciation of the value of the oral tradition as a source across disciplines involves two efforts: first, a survey of the reported oral tradition as available and documented in past periods, and second, a review of the principles and practices involved in the collection, analysis, and presentation of the oral tradition.

The paucity of written records has been grounds for dismissal of the notion of African history—most notoriously in the case of Hegel, who in ignorance wrote off the home of the human species—and more recently a cause of pride among African intellectuals who have asserted the value of the oral tradition in the face of skepticism rooted in prejudice and too often in overt racism. An appreciation of the value of the oral tradition threads its path between extremes and occasional controversy. The era of the smartphone has made the documentation (and creation) of oral tradition almost too easy. Past generations made do in different ways. Their reports should not be dismissed, but studied; they are the available background to information collected in the modern era. Accurate collection and critical analysis are the essential tools for the understanding of oral tradition.
Latino Urbanism
Authors: Sandoval-Strausz A. K.
Published: February 2018

“Latino urbanism” describes a culturally specific set of spatial forms and practices created by people of Hispanic origin. It includes many different aspects of those forms and practices, including town planning; domestic, religious, and civic architecture; the adaptation of existing residential, commercial, and other structures; and the everyday use of spaces such as yards, sidewalks, storefronts, streets, and parks.

Latino urbanism has developed over both time and space. It is the evolving product of half a millennium of colonization, settlement, international and domestic migration, and globalization. It has spanned a wide geographic range, beginning in the southern half of North America and gradually expanding to much of the hemisphere.

There have been many variations on Latino urbanism, but most include certain key features: shared central places where people show their sense of community, a walking culture that encourages face-to-face interaction with neighbors, and a sense that sociability should take place as much in the public realm as in the privacy of the home. More recently, planners and architects have realized that Latino urbanism offers solutions to problems such as sprawl, social isolation, and environmental unsustainability.

The term “urbanism” connotes city spaces, and Latino urbanism is most concentrated and most apparent at the center of metropolitan areas. At the same time, it has also been manifested in a wide variety of places and at different scales, from small religious altars in private homes; to Spanish-dominant commercial streetscapes in Latino neighborhoods; and ultimately to settlement patterns that reach from the densely packed centers of cities to the diversifying suburbs that surround them, out to the agricultural hinterlands at their far peripheries—and across borders to big cities and small pueblos elsewhere in the Americas.
Southern Africa and the United States
Authors: Parrott R. Joseph
Published: February 2018

The United States never sought to build an empire in Africa in the 19th and 20th centuries, as did European nations from Britain to Portugal. However, economic, ideological, and cultural affinities gradually encouraged the development of relations with the southern third of the continent (the modern Anglophone nations of South Africa, Zimbabwe, Zambia, Namibia, the former Portuguese colonies of Mozambique and Angola, and a number of smaller states). With official ties limited for decades, missionaries and business concerns built a small but influential American presence mostly in the growing European settler states. This state of affairs made the United State an important trading partner during the 20th century, but it also reinforced the idea of a white Christian civilizing mission as justification for the domination of black peoples. The United States served as a comparison point for the construction of legal systems of racial segregation in southern Africa, even as it became more politically involved in the region as part of its ideological competition with the Soviet Union.

As Europe’s empires dissolved after World War II, official ties to white settler states such as South Africa, Angola, and Rhodesia (modern Zimbabwe) brought the United States into conflict with mounting demands for decolonization, self-determination, and racial equality—both international and domestic. Southern Africa illustrated the gap between a Cold War strategy predicated on Euro-American preponderance and national traditions of liberty and democracy, eliciting protests from civil and human rights groups that culminated in the successful anti-apartheid movement of the 1980s. Though still a region of low priority at the beginning of the 21st century, American involvement in southern Africa evolved to emphasize the pursuit of social and economic improvement through democracy promotion, emergency relief, and health aid—albeit with mixed results. The history of U.S. relations with southern Africa therefore illustrates the transformation of trans-Atlantic racial ideologies and politics over the last 150 years, first in the construction of white supremacist governance and later in the eventual rejection of this model.
Settler Colonialism and U.S. Home Missions
Authors: Smith Matthew J.
Published: February 2018

Home Missions in the United States was a white Protestant missionary movement within the geopolitical borders of the U.S. empire—both its contiguous states as well as its colonial territories—as they developed and shifted through a long history of U.S. imperial expansion, settlement, and conquest. From the beginning of the 19th century, Anglo-Protestants in the United States became invested in the home missionary movement to secure Christian supremacy on the land that made up their newly forming white settler nation. Home Missions was occupied with both the formation of a sacred homeland and the homes within that homeland. As a dual-homemaking endeavor, home missionary projects functioned as settler colonial technologies of space-making and race-making. They not only sought to transform the land into an Anglo-Protestant possession but also racialized people as foreign to maintain Anglo-Protestant sovereignty over the spaces mapped as a home through colonial conquest. Centering settler colonialism within an analysis of Home Missions denaturalizes home and foreign as taken-for-granted spatial categories by considering them colonial significations. Home Missions sought to remake conquered territory habitable for Anglo-Protestant settlement, using the concepts home and foreign to govern people differently within that conquered territory.

Gaining prominence in the postbellum United States, women’s societies for Home Missions cooperated across multiple Protestant denominations and between multiple missionary sites across the U.S. empire in forming a transcolonial network aimed at uplifting the homes of the nation. These colonial sites included missions to “Indians,” “Negroes,” “City Immigrants,” “Orientals,” “Mountaineers,” “Loggers,” “Porto Rico,” “Alaska,” and more. White women entered new public spheres by making the racial uplift of homes across the nation a practice of imperial domesticity. Women in Home Missions sought to create subject citizens of the U.S. nation by shaping the habits, tendencies, and racial constitution of people through the cultivation and management of Christian homes. Homes were spaces of both racial uplift and the maintenance of racial purity. Thus, missionaries were not only preoccupied with making Christian citizens for the nation but were also concerned with maintaining racial distinctions characteristic of the anxieties of U.S. colonial governance at the turn of the 20th century.

Through Home Missions, Anglo-Protestants participated in an imperial process that sought to transform the land and its inhabitants while also forming racializations, gender systems, and political economies that mapped onto an imaginary in which a particular vision of settled homes/homeland occupied a central analytic. By treating “home” in Home Missions as a critical category, one is able to reconsider the maneuverings of religion, empire, nation, race and gender/sexuality within the context of settler colonial conquest, possession, and settlement.
Nature and Religion in America
Authors: Grainger Brett
Published: February 2018

One of the most complex words in the English language, “nature” (sometimes personified as “Nature” or “Mother Nature”) has been central to developments in American religions. Despite their different origins, the three cosmologies present on the North American continent during the early modern “age of contact”—Native American, African American, and Euro-American—shared a number of similarities, including the belief in an enchanted or animate cosmos, the ambivalence of sacred presences manifested in nature, and the use of myth and ritual to manage these ambivalent presences in ways that secured material and spiritual benefits for individuals or communities. Through encounters on colonial borderlands and through developments in society and culture (in science, economics, politics, etc.), these cosmologies have been adapted, developed, and combined in creative ways to produce new forms of religious life. These developments have been characterized by a series of recurrent tensions, including the notion of divine or spiritual realities as being transcendent or immanent, organicism or mechanism, and of the natural world as including or excluding human beings. Organicist and animist cosmologies, severely challenged by the early modern scientific revolution, were resurgent in the antebellum period, fueling a series of new religious developments, from Transcendentalism and revivalism to Mormonism and the early environmentalist movement. These generative tensions continue to reverberate into the modern day, in part as an outworking of the environmental crisis of the 1960s, which saw a purported “greening” of established religions as well as the rise of new forms of nature spirituality.
Women in Mexican Politics since 1953
Authors: Hernández Sonia
Published: February 2018

Since the founding of the Mexican republic, women have been politically engaged in their respective communities. The creation of a modern nation-state during the last decades of the 19th century and first half of the 20th century marked an increase in women’s formal and informal political participation in the country. During the Mexican Revolution of 1910 and particularly in the post-revolutionary period, Mexican women took a much more active role in engaging the state, formed political alliances and organizations, pressed for labor and political rights, and worked collectively and individually to secure suffrage. Women have been part of an array of political parties and have played a key role in the slow and uneven process of democratization in Mexico. In and outside the bounds of formal political parties, and in the greater sphere of electoral politics, women participated in multiple ways in the post-1953 period. Even during the years when women lacked the right to vote, they were engaged politically in the local, regional, national, and international spheres. They did so by participating in all political parties, and participated in voting drives, actively promoted issues that concerned them, and pushed for gender equity in the greater electoral process. Despite lacking suffrage, women in Mexico were engaged citizens in the broadest sense of the word.

By the eve of the 21st century, women had served in almost all municipal, state, and government positions and had also competed for the highest office in the land. Yet the limits in electoral reform legislation, unequal and uneven economic development, gender and sexual violence, and continued distrust of the nation’s political system, as well as widespread insecurity caused by a violent drug war that was being strengthened by the influx of US weapons, remained major challenges to women’s continued participation on the country’s long road to democratization.
The Cuban Embassy in Uruguay, 1959–1964
Authors: García Roberto
Published: February 2018

The 1959 Cuban Revolution, the revolution’s subsequent strengthening, and the radical change that the process underwent beginning in 1961 marked a turning point in the history of Latin America. It implied the largest and most consistent regional challenge faced by the United States in an area where its influence had often been decisive. From then on, the Latin American Cold War intensified at every level. It was no longer about the “reactive” actions that took place among the conservative Latin American elite via the communism inspired by distant Moscow.

In Cuba, the culture of the “revolution” was established, and the consequences were far from mere symbolism: Cubans also launched actions of “alternative diplomacy” to lend institutional support to the Latin American guerrilla movements. However, there is no documented study on Cuba’s role in Latin America. This is explicable in large part by the secrecy with which the Caribbean isle has made archival research in the country impossible.

Although this secrecy is understandable in view of its nature as a heavily beleaguered revolution from abroad, this culture of secrecy contributed to expanding a production of journalistic and essay-based denunciation that habitually lacked rigor and interpretive frameworks. Since 2010, a certain spirit of openness has existed in the matter, an example of which is purported to be linked to the Cuban Ministry of Foreign Affairs, whose historical repository has slowly begun to receive researchers, principally from abroad.

Drawing upon the anxiety and curiosity of the international historiographic community about the images originating from Havana, an initial approach and investigation was carried out in the aforementioned tradition, with the aim of shedding light on several of the actions deployed by the Cuban Embassy in Uruguay during the initial and intense years of the Caribbean revolution.
gifts and giving, Roman
Authors: Coffee Neil
Published: February 2018

Romans not only gave gifts to express emotion and build relationships; a long-standing tradition of mutual aid gave rise to more intensive exchange of gifts and services (or reciprocity), among relatives, friends, and business associates; from the wealthy to the public in the form of public benefactions; and in legally sanctioned relationships between patrons and clients. Roman gift culture, distinctive among its contemporary Mediterranean societies, became increasingly transactional from the middle Republic to early Empire.
Scrambling in Korean Syntax
Authors: Ko Heejeong
Published: February 2018

Scrambling is one of the most widely discussed and prominent factors affecting word order variation in Korean. Scrambling in Korean exhibits various syntactic and semantic properties that cannot be subsumed under the standard A/A'-movement. Clause-external scrambling as well as clause-internal scrambling in Korean show mixed A/A'-effects in a range of tests such as anaphor binding, weak crossover, Condition C, negative polarity item licensing, wh-licensing, and scopal interpretation. VP-internal scrambling, by contrast, is known to be lack of reconstruction effects conforming to the claim that short scrambling is A-movement. Clausal scrambling, on the other hand, shows total reconstructions effects, unlike phrasal scrambling. The diverse properties of Korean scrambling have received extensive attention in the literature. Some studies argue that scrambling is a type of feature-driven A-movement with special reconstruction effects. Others argue that scrambling can be A-movement or A'-movement depending on the landing site. Yet others claim that scrambling is not standard A/A'-movement, but must be treated as cost-free movement with optional reconstruction effects. Each approach, however, faces non-trivial empirical and theoretical challenges, and further study is needed to understand the complex nature of scrambling. As the theory develops in the Minimalist Program, a variety of proposals have also been advanced to capture properties of scrambling without resorting to A/A'-distinctions.

Scrambling in Korean applies optionally but not randomly. It may be blocked due to various factors in syntax and its interfaces in the grammar. At the syntax proper, scrambling obeys general constraints on movement (e.g., island conditions, left branch condition, coordinate structure condition, proper binding condition, ban on string vacuous movement). Various semantic and pragmatic factors (e.g., specificity, presuppositionality, topic, focus) also play a crucial role in acceptability of sentences with scrambling. Moreover, current studies show that certain instances of scrambling are filtered out at the interface due to cyclic Spell-out and linearization, which strengthens the claim that scrambling is not a free option. Data from Korean pose important challenges against base-generation approaches to scrambling, and lend further credence to the view that scrambling is an instance of movement. The exact nature of scrambling in Korean—whether it is cost-free or feature-driven—must be further investigated in future research, however. The research on Korean scrambling leads us to the pursuit of a general theory, which covers obligatory A/A'-movement as well as optional displacement with mixed semantic effects in languages with free word order.
Penutian Languages
Authors: Grant Anthony P.
Published: February 2018

The Penutian language family, Penutian phylum, or better still, Penutian hypothesis is one of the largest genealogical linguistic groupings to have been proposed for western North America. It involves 16 families or isolates. Only a few of these families are demonstrably relatable to one another according to current knowledge and diachronic techniques. Sometimes Penutian is split by observers into groups of languages assumed to be interrelated, and this is done without assumptions that the groups themselves are interrelated.

This article focuses on the Canadian and US languages in “Sapir’s Penutian,” the most commonly accepted version; the most southerly family within Penutian is thus held as Yokutsan of California’s Sierra Nevada. It discusses the subclassification of the so-called Penutian languages into families and smaller units; aspects of their phonology, morphosyntax, and contact histories; and issues in their revitalization and the potential reconstruction of Proto-Penutian.
Variation in Phonology
Authors: Anttila Arto
Published: February 2018

Language is a system that maps meanings to forms, but the mapping is not always one-to-one. Variation means that one meaning corresponds to multiple forms, for example faster ~ more fast. The choice is not uniquely determined by the rules of the language, but is made by the individual at the time of performance (speaking, writing). Such choices abound in human language. They are usually not just a matter of free will, but involve preferences that depend on the context, including the phonological context. Phonological variation is a situation where the choice among expressions is phonologically conditioned, sometimes statistically, sometimes categorically. In this overview, we take a look at three studies of variable vowel harmony in three languages (Finnish, Hungarian, and Tommo So) formulated in three frameworks (Partial Order Optimality Theory, Stochastic Optimality Theory, and Maximum Entropy Grammar). For example, both Finnish and Hungarian have Backness Harmony: vowels must be all [+back] or all [−back] within a single word, with the exception of neutral vowels that are compatible with either. Surprisingly, some stems allow both [+back] and [−back] suffixes in free variation, for example, analyysi-na ~ analyysi-nä ‘analysis-ess’ (Finnish) and arzén-nak ~ arzén-nek ‘arsenic-dat’ (Hungarian). Several questions arise. Is the variation random or in some way systematic? Where is the variation possible? Is it limited to specific lexical items? Is the choice predictable to some extent? Are the observed statistical patterns dictated by universal constraints or learned from the ambient data? The analyses illustrate the usefulness of recent advances in the technological infrastructure of linguistics, in particular the constantly improving computational tools.
Agenda Setting and Natural Hazards
Authors: DeLeo Rob A.
Published: February 2018

Agenda setting describes the process through which issues are selected for consideration by a decision-making body. Among the myriad of issues policymakers can consider, few are more vexing than natural hazards. By aggregating (or threatening to aggregate) death, destruction, and economic loss, natural hazards represent a serious and persistent threat to public safety. While citizens rightfully expect policymakers to protect them, many of the policy challenges associated natural hazards fail to reach the crowded government agenda. This article reviews the literature on agenda setting and natural hazards, including the strain between preparing for emerging hazards, on the one hand, and responding to existing disasters, on the other hand. It considers the extent to which natural hazards pose distinctive difficulties during the agenda-setting process, focusing specifically on the dynamics of issue identification, problem definition, venue shopping, and interest group mobilization in natural hazard domains. It closes by suggesting a number of future avenues of agenda-setting research.
International Council on Social Welfare
Authors: Zelenev Sergei
Published: February 2018

The International Council on Social Welfare (ICSW) is a nongovernmental organization (NGO) focused on advocacy, knowledge-building, and technical assistance projects in various areas of social development carried out at the country level and internationally. Created in 1928 in Paris to address the complexities and challenges of social work, the ICSW has evolved through the years to embrace the major issues of social development, becoming a global organization committed to improving human well-being. Establishing common ground on issues of international significance and acting with partners through its nine regional networks, ICSW represents national and local organizations in more than 70 countries throughout the world. Membership also includes major international organizations. By virtue of its constitution, it operates as a democratic and accountable organization.
Parallelization of MAFFT for large-scale multiple sequence alignments
Authors: Nakamura Tsukasa , Yamada Kazunori D , Tomii Kentaro , Katoh Kazutaka
Published: February 2018

We report an update for the MAFFT multiple sequence alignment program to enable parallel calculation of large numbers of sequences. The G-INS-1 option of MAFFT was recently reported to have higher accuracy than other methods for large data, but this method has been impractical for most large-scale analyses, due to the requirement of large computational resources. We introduce a scalable variant, G-large-INS-1, which has equivalent accuracy to G-INS-1 and is applicable to 50 000 or more sequences.

Availability and implementation

This feature is available in MAFFT versions 7.355 or later at https://mafft.cbrc.jp/alignment/software/mpi.html.

Supplementary information

Supplementary data are available at Bioinformatics online.
Open science initiatives: challenges for public health promotion
Authors: Holzmeyer Cheryl
Published: February 2018

While academic open access, open data and open science initiatives have proliferated in recent years, facilitating new research resources for health promotion, open initiatives are not one-size-fits-all. Health research particularly illustrates how open initiatives may serve various interests and ends. Open initiatives not only foster new pathways of research access; they also discipline research in new ways, especially when associated with new regimes of research use and peer review, while participating in innovation ecosystems that often perpetuate existing systemic biases toward commercial biomedicine. Currently, many open initiatives are more oriented toward biomedical research paradigms than paradigms associated with public health promotion, such as social determinants of health research. Moreover, open initiatives too often dovetail with, rather than challenge, neoliberal policy paradigms. Such initiatives are unlikely to transform existing health research landscapes and redress health inequities. In this context, attunement to social determinants of health research and community-based local knowledge is vital to orient open initiatives toward public health promotion and health equity. Such an approach calls for discourses, norms and innovation ecosystems that contest neoliberal policy frameworks and foster upstream interventions to promote health, beyond biomedical paradigms. This analysis highlights challenges and possibilities for leveraging open initiatives on behalf of a wider range of health research stakeholders, while emphasizing public health promotion, health equity and social justice as benchmarks of transformation.
Development of a LAMP Method for Detecting SDHI Fungicide Resistance in Botrytis cinerea
Authors: Fan F. , Yin W. X. , Li G. Q. , Lin Y. , Luo C. X.
Published: February 2018

Resistance to succinate dehydrogenase inhibitors (SDHI) in Botrytis cinerea is associated with point mutations in the target gene succinate dehydrogenase subunit B (SdhB). The substitution from histidine to arginine at codon 272 (H272R) is currently the predominant mutation in SDHI-resistant populations in B. cinerea worldwide. In order to monitor the development of resistance to SDHI, a rapid, simple, and efficient method with high specificity to the H272R point mutation was developed based on loop-mediated isothermal amplification (LAMP). To specifically detect the H272R mutation, a set of four primers was designed based on the sequence of SdhB, and the LAMP reaction was optimized. When SYBR Green I was added after reaction, only samples with the H272R mutation showed the color change (from brown to fluorescent yellow), indicating that this set of primers could successfully discriminate the H272R genotype from other genotypes. Specificity and accuracy tests showed that this LAMP assay had high specificity and accuracy. Moreover, the LAMP method was further simplified with fungal mycelia and conidia as the amplification template which could be prepared within 5 min. Due to the low cost, simplicity, high efficiency, and specificity, the developed LAMP assay may contribute to the monitoring of resistance development to SDHI in B. cinerea, especially in field and high-throughput experiments.
Describing the Journey and Lessons Learned Implementing a Competency-Based, Time-Variable Undergraduate Medical Education Curriculum
Authors: Mejicano George C. , Bumsted Tracy N.
Published: February 2018

Oregon Health & Science University School of Medicine launched a completely new undergraduate medical education curriculum in 2014. This initiative dramatically transformed the MD degree program, changing the instructional content taught, the pedagogical methods used by the faculty, and the methods of assessment, and it added new elements such as academic coaching and programmatic entrustment to the program. One of the most exciting and impactful aspects to date of this curricular transformation has been the deliberate implementation of a competency-based framework that incorporates frequent assessment, tracking of student progression using an electronic portfolio, and academic coaching to optimize learning and customize curricular elements for each student. The next major step in this process—the implementation of time-variable progression—is currently ongoing as a planning group at the school works through the conceptual, logistical, legal, and regulatory issues related to implementing such a system. When implementation is complete, MD students will graduate only once they have earned entrustment for all 13 Core Entrustable Professional Activities for Entering Residency. This article describes the school’s progress to date in its curricular transformation and articulates lessons learned thus far in driving substantive and dramatic institutional changes that profoundly impact students, faculty, and administrators in one academic health center.
The History of Medical Education in Europe and the United States, With Respect to Time and Proficiency
Authors: Custers Eugène J.F.M. , Cate Olle ten
Published: February 2018

In this article, the authors present a historic overview of the development of medical education in the United States and Europe (in particular the Netherlands), as it relates to the issues of time (duration of the course) and proficiency (performance requirements and examinations). This overview is necessarily limited and based largely on post hoc interpretation, as historic data on time frames are not well documented and the issue of competence has only recently been addressed.

During times when there were few, if any, formal regulations, physicians were primarily “learned gentlemen” in command of few effective practical skills, and the duration of education and the competencies acquired by the end of a course simply did not appear to be issues of any interest to universities or state authorities. Though uniform criteria gradually developed for undergraduate medical education, postgraduate specialty training remained, before accreditation organizations set regulations, at the discretion of individual institutions and medical societies. This resulted in large variability in training time and acquired competencies between residency programs, which were often judged on the basis of opaque or questionable criteria. Considering the high costs of health care today and the increasing demand for patient safety and educational efficiency, continuing historic models of nonstandardized practices will no longer be feasible. Efforts to constrain, restructure, and individualize training time and licensing tracks to optimize training for safe care, both in the United States and Europe, are needed.
Biologic Impact of Mechanical Power at High and Low Tidal Volumes in Experimental Mild Acute Respiratory Distress Syndrome
Authors: Santos Raquel S. , Maia Ligia de A. , Oliveira Milena V. , Santos Cíntia L. , Moraes Lillian , Pinto Eliete F. , Samary Cynthia dos S. , Machado Joana A. , Carvalho Anna Carolinna , Fernandes Marcos Vinícius de S. , Martins Vanessa , Capelozzi Vera L. , Morales Marcelo M. , Koch Thea , Gama de Abreu Marcelo , Pelosi Paolo , Silva Pedro L. , Rocco Patricia R. M.
Published: February 2018

Background

The authors hypothesized that low tidal volume (VT) would minimize ventilator-induced lung injury regardless of the degree of mechanical power. The authors investigated the impact of power, obtained by different combinations of VT and respiratory rate (RR), on ventilator-induced lung injury in experimental mild acute respiratory distress syndrome (ARDS).

Methods

Forty Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 h, 32 rats were randomly assigned to be mechanically ventilated (2 h) with a combination of different VT (6 ml/kg and 11 ml/kg) and RR that resulted in low and high power. Power was calculated as energy (ΔP,L
2/E,L) × RR (ΔP,L = transpulmonary driving pressure; E,L = lung elastance), and was threefold higher in high than in low power groups. Eight rats were not mechanically ventilated and used for molecular biology analysis.

Results

Diffuse alveolar damage score, which represents the severity of edema, atelectasis, and overdistension, was increased in high VT compared to low VT, in both low (low VT: 11 [9 to 14], high VT: 18 [15 to 20]) and high (low VT: 19 [16 to 25], high VT: 29 [27 to 30]) power groups. At high VT, interleukin-6 and amphiregulin expressions were higher in high-power than in low-power groups. At high power, amphiregulin and club cell protein 16 expressions were higher in high VT than in low VT. Mechanical energy and power correlated well with diffuse alveolar damage score and interleukin-6, amphiregulin, and club cell protein 16 expression.

Conclusions

In experimental mild ARDS, even at low VT, high mechanical power promoted ventilator-induced lung injury. To minimize ventilator-induced lung injury, low VT should be combined with low power.
Pharmacokinetic/Pharmacodynamic Model of CW002, an Investigational Intermediate Neuromuscular Blocking Agent, in Healthy Volunteers
Authors: Kaullen Josh D. , Owen Joel S. , Brouwer Kim L. R. , Heerdt Paul M. , Lien Cynthia A. , Savarese John J. , Schmith Virginia D.
Published: February 2018

Background

CW002 is an investigational nondepolarizing, neuromuscular blocking agent with a rapid onset and intermediate duration of action in animals. This is a single ascending dose, healthy subject study exploring tolerability, pharmacokinetics, and potency.

Methods

Population pharmacokinetic and pharmacokinetic/pharmacodynamic models were developed using plasma drug concentration data from a previously published dose–response study in 28 healthy subjects receiving single doses of CW002 during sevoflurane anesthesia. Subjects included in the models were from five different dose cohorts (cohorts 3, 4, 5, 6, and 8 receiving 0.04, 0.06, 0.08, 0.10, and 0.14 mg/kg, respectively). Serial arterial plasma concentrations and muscle twitch heights were monitored.

Results

A four-compartment model was fit to the concentration–time data, whereas a transit compartment with a sigmoid Emax model was fit to the pharmacokinetic/pharmacodynamic data. The population pharmacokinetics of CW002 was linear with very low interindividual variability in clearance (10.8%). Simulations were conducted to predict the onset and offset of effect at 2×, 3×, and 4× ED95. The time to 80% block was predicted to be 1.5, 0.8, and 0.7 min for 2×, 3×, and 4× ED95 doses, respectively. The simulated 25 to 75% recovery index was independent of dose.

Conclusions

CW002 has predictable pharmacokinetics and is likely to have a rapid onset with an intermediate duration of action at 3× ED95. This model provides information to inform critical decisions (e.g., dose, study design) for continued development of CW002.
Inflammatory Markers in Serum and Cerebrospinal Fluid for Early Detection of External Ventricular Drain–associated Ventriculitis in Patients With Subarachnoid Hemorrhage
Authors: Lenski Markus , Huge Volker , Schmutzer Michael , Ueberschaer Moritz , Briegel Josef , Tonn Jörg-Christian , Schichor Christian , Thon Niklas
Published: February 2018

Background:

External ventricular drain (EVD)-associated ventriculitis is a serious complication. Early diagnosis can be difficult particularly in critically ill patients with aneurysmal subarachnoid hemorrhage (aSAH). We examined the diagnostic potential of standard serum and cerebrospinal fluid (CSF) biomarkers to differentiate between EVD-associated infections and aseptic courses in patients with aSAH.

Materials and Methods:

We retrospectively evaluated the levels of inflammatory markers in serum (white blood cell count, percentage of neutrophils [sN%], and procalcitonin) and CSF (total leukocyte count [CSFTLC], CSFglucose, CSF/serumglucose ratio, CSF total protein [CSFTP]) of 63 consecutive patients with aSAH. Receiver operating characteristic curves and the area-under-the-curve (AUC) were calculated to detect the diagnostic potential, optimized threshold, sensitivity (SE), specificity (SP), + likelihood ratio (LR), and −LR of each biomarker.

Results:

Of all patients, 17 (27%) developed an EVD-associated ventriculitis within a mean of 7.8±2.3 days after implantation. sN% had a very good diagnostic potential (AUC=0.900, SE=70.0%, SP=100%), followed by the CSFTLC with good diagnostic potential (AUC=0.841, SE=75.0%, SP=88.5%), and the CSFTP with moderate diagnostic potential (AUC=0.772, SE=73.3%, SP=76.0%). sN% higher than 70% and a CSFTLC higher than 635/µL were highly associated with the diagnosis of ventriculitis (+LR=∞ and 6.5), sN%<70% or a CSFTLC<635 made a diagnosis of ventriculitis unlikely (−LR=0.3 and 0.28).

Conclusions:

Routine determination of N% and CSFTLC are useful to distinguish ventriculitis from aseptic courses in the acute phase after aSAH and regardless of the bacteriological test result.
The Period 2 Enhancer Nobiletin as Novel Therapy in Murine Models of Circadian Disruption Resembling Delirium*
Authors: Gile Jennifer , Scott Benjamin , Eckle Tobias
Published: February 2018

Objectives:

Delirium occurs in approximately 30% of critically ill patients, and the risk of dying during admission doubles in those patients. Molecular mechanisms causing delirium are largely unknown. However, critical illness and the ICU environment consistently disrupt circadian rhythms, and circadian disruptions are strongly associated with delirium. Exposure to benzodiazepines and constant light are suspected risk factors for the development of delirium. Thus, we tested the functional role of the circadian rhythm protein Period 2 (PER2) in different mouse models resembling delirium.

Design:

Animal study.

Setting:

University experimental laboratory.

Subjects:

Wildtype, Per2
–/– mice.

Interventions:

Midazolam, lipopolysaccharide (lipopolysaccharide), constant light, nobiletin, or sham-treated animals.

Measurements and Main Results:

Midazolam significantly reduced the expression of PER2 in the suprachiasmatic nucleus and the hippocampus of wild-type mice. Behavioral tests following midazolam exposure revealed a robust phenotype including executive dysfunction and memory impairment suggestive of delirium. These findings indicated a critical role of hippocampal expressed PER2. Similar results were obtained in mice exposed to lipopolysaccharide or constant light. Subsequent studies in Per2
–/– mice confirmed a functional role of PER2 in a midazolam-induced delirium-like phenotype. Using the small molecule nobiletin to enhance PER2 function, the cognitive deficits induced by midazolam or constant light were attenuated in wild-type mice.

Conclusions:

These experiments identify a novel role for PER2 during a midazolam- or constant light–induced delirium-like state, highlight the importance of hippocampal PER2 expression for cognitive function, and suggest the PER2 enhancer nobiletin as potential therapy in delirium-like conditions associated with circadian disruption.
Stress Reduction in Postcardiac Surgery Family Members
Authors: Breisinger Lauren , Macci Bires Angela , Cline Thomas W.
Published: February 2018

The intensive care unit (ICU) can be a place of stress, anxiety, and emotional instability for both patients and families. Medical and nursing care during this acute time is patient focused, and family members are often left in the dark. Unintentional exclusion from information results in high levels of stress, anxiety, and uncertainty for families. Due to the acuity of illness, family members of cardiac surgery patients experience the highest levels of stress. Spouses may experience intense psychosomatic symptoms such as depression, anxiety, and fear for several months after the surgery. The purpose of this study was aimed at decreasing those feelings of anxiety in family members with postcardiac surgery through the use of a cardiac surgery tool kit. The study was a quality improvement project utilizing a convenience sample of 83 participants 18 years and older. Participants were asked to use the State Trait Anxiety Inventory (STAI) Form Y-1 (state anxiety) to rate their anxiety level preintervention and then again postintervention. Data were collected over a 6-month period. Descriptive data including age, education level, ethnicity, relationship, experience in the ICU, and active diagnoses of mental disorders did not affect the changes in the pre- and posttest data. A paired t test was conducted on the sample to assess changes in state anxiety, using the STAI Form Y-1. The results were statistically significant (t = 11.97, df = 81, P < .001). Respondents' scores decreased significantly from pre intervention (mean = 53.01, standard deviation = 12.19) to postintervention (mean = 37.38, standard deviation = 10.94). The data suggest that the use of a postcardiac surgery tool kit is a low-risk measure that can decrease the anxiety in family members of postcardiac surgery patients.
The Stay S.A.F.E. Strategy for Managing Interruptions Reduces Distraction Time in the Simulated Clinical Setting
Authors: Henneman Elizabeth A. , Marquard Jenna L. , Nicholas Cheryl , Martinez Vanessa , DeSotto Kristine , Scott Susan S. , Soares William E. , Henneman Philip L.
Published: February 2018

Interruptions occurring during the delivery of health care are frequent and create a serious threat to patient safety. It is important to test strategies directed at decreasing the negative effects of interruptions. The purpose of this pilot study was to test the Stay S.A.F.E. strategy for managing interruptions. A pretest, posttest quasi-experimental design was used to test the primary hypothesis that the Stay S.A.F.E. interruption management strategy would significantly (P < .05) reduce distraction time away from a primary task following an interruption. Twenty nurses with a median of 12 years of experience (range: 1-45 years) participated in the study. There was a significant decrease in the amount of time that participants were distracted away from the primary task between the pretest (134.47 seconds, SD = 6.87) and posttest (6.08 seconds, SD = 1.27) periods; P = .0004. The results of this study suggest that the Stay S.A.F.E. interruption management strategy was effective in reducing the length of time participants were distracted from the primary task in a simulated clinical setting. In addition, nurses confirmed the reports of others that interruptions are frequent, dangerous, and result in errors.
Vancomycin Area Under the Curve Simplified
Authors: Lewis Paul
Published: February 2018

Background:

Serum trough concentrations as the sole means of monitoring safety and efficacy of vancomycin are insufficient. The daily area under the curve (AUC24) of serum concentration versus time to minimum inhibitory concentration (MIC) ratio of greater than 400 mg × h/L has emerged as a more robust dosing target. A simple and practical method to extrapolate AUC24 from troughs is needed.

Methods:

This mathematical model computes the median and range AUC24 using the dose in mg/kg and the observed serum trough concentration. AUC24 is calculated using dose in mg/kg divided by the volume of distribution (Vd) and elimination constant (Ke). Vd is provided using the population median (range) of 0.7 (0.4–1) L/kg. Ke is calculated using the trough and population Vd.

Results:

For doses of 15–20 mg/kg, troughs of at least 11 mg/L will achieve AUC24 of greater than 400 mg × h/L, even with a Vd of 1 L/kg. Using the median Vd and lower, AUC24 greater than 400 mg × h/L can be achieved with troughs as little as 9 mg/L using doses of 15 mg/kg and greater. The AUC24:MIC goal of greater than 400 can still be attained with an MIC of 1.5 mg/L by using doses of at least 15 mg/kg and targeting troughs of at least 16 mg/L for a patient with a Vd of 0.7 L/kg or less.

Conclusions:

Troughs of 15–20 mg/L are rarely needed for organisms with an MIC of 1 mg/L or less. AUC24:MIC goals of greater than 400 can best be achieved with higher doses in mg/kg while targeting lower troughs.
EFFECT OF OPTIC DISK—FOVEA DISTANCE ON MEASUREMENTS OF INDIVIDUAL MACULAR INTRARETINAL LAYERS IN NORMAL SUBJECTS
Authors: Qiu Kunliang , Chen Binyao , Chen Haoyu , Gao Enting , Yang Jianling , Chen Xinjian , Zhang Mingzhi
Published: February 2018

Purpose:

To investigate the effect of optic disk—fovea distance (DFD) on measurements of macular intraretinal layers using spectral domain optical coherence tomography in normal subjects.

Methods:

One hundred and eighty-two eyes from 182 normal subjects were imaged using spectral domain optical coherence tomography. The average thicknesses of eight macular intraretinal layers were measured using an automatic segmentation algorithm. Partial correlation test and multiple regression analysis were used to determine the effect of DFD on thicknesses of intraretinal layers.

Results:

Disk—fovea distance correlated negatively with the overall average thickness in all the intraretinal layers (r ≤ −0.17, all P ≤ 0.025) except the ganglion cell layer and photoreceptor. In multiple regression analysis, greater DFD was associated with thinner nerve fiber layer (6.78 μm decrease per each millimeter increase in DFD, P < 0.001), thinner ganglion cell—inner plexiform layer (2.16 μm decrease per each millimeter increase in DFD, P = 0.039), thinner ganglion cell complex (8.94 μm decrease per each millimeter increase in DFD, P < 0.001), thinner central macular thickness (18.16 μm decrease per each millimeter increase in DFD, P < 0.001), and thinner total macular thickness (15.94 μm decrease per each millimeter increase in DFD, P < 0.001).

Conclusion:

Thinner measurements of macular intraretinal layers were significantly associated with greater DFD. A clinical assessment of macular intraretinal layers in the evaluation of various macular diseases should always be interpreted in the context of DFD.
“Off-the-Shelf” K2-EDTA for Calcific Band Keratopathy
Authors: Lee Marco E. , Ouano Dean P. , Shapiro Brett , Fong Andrew , Coroneo Minas T.
Published: February 2018

Purpose:

To explore the effectiveness of “off-the-shelf” dipotassium-ethylenediaminetetraacetic acid (K2-EDTA) as an alternative to sodium EDTA as chelation therapy in removal of calcific band keratopathy (CBK).

Methods:

This study was a retrospective case series involving 4 patients with CBK who underwent superficial keratectomy and subsequent chelation therapy with K2-EDTA in a single center (Coastal Eye Clinic) by the same surgeon. Visual acuity and symptomatic relief were the main outcomes measured in our study.

Results:

All 4 participants in this study were female with an average age of 80.3 years. Three of the patients with reasonable baseline visual acuity experienced improved visual acuity at 1 month. The other patient with multiple ocular comorbidities and severely reduced visual potential reported symptomatic pain relief at 1-month follow-up after the intervention.

Conclusions:

K2-EDTA seems to be an effective alternative to disodium EDTA in its ability to clear calcific plaques and restore visual function. Because of the logistical difficulties associated with acquiring disodium EDTA, and the relative abundance of K2-EDTA in health-care facilities, we believe that our findings warrant further investigation into its use as a more accessible and cost-effective chelating agent in CBK.