bluuebunny/crossref_metadata_2025 huggingface dataset:
From International Law and International Relations to Law and World Politics
Authors: Whytock Christopher A.
Published: February 2018

Political scientists—primarily in the discipline’s international relations subfield—have long studied international law. After considering how political scientists and legal scholars define international law, this article identifies five stages of political science research on international law, including the current interdisciplinary international law and international relations (IL/IR) stage, and it reviews three trends in political science research that constitute an emerging sixth stage of interdisciplinary scholarship: a law and world politics (L/WP) stage. First, moving beyond the “IL” in IL/IR scholarship, international relations scholars are increasingly studying domestic law and domestic courts—not only their foundational role in supporting international law and international courts but also their direct role in core areas of international relations, including international conflict and foreign policy. Second, moving beyond the “IR” in IL/IR scholarship, political scientists are adapting their research on international law to the broader world politics trend in political science by studying types of law—including extraterritoriality, conflict of laws, private international law, and the law of transnational commercial arbitration—that govern the transnational activity of private actors and can either support or hinder private global governance. Third, moving beyond the domestic-international divide, political scientists are increasingly rejecting “international law exceptionalism,” and beginning to take advantage of theoretical convergence across the domestic, comparative, and international politics subfields to develop a better general understanding law and politics.
A Review of the Validity of Juvenile Risk Assessment Across Race/Ethnicity
Authors: Campbell Christina , Miller William
Published: February 2018

Juvenile risk assessment instruments have provided juvenile courts with the opportunity to make standardized decisions concerning sentences and intervention needs. Risk assessments have replaced the reliance on professional decision-making practices in which court officials relied on their hunches or previous experience to determine what to do with youth once they became involved in corrections. A primary goal of juvenile risk assessment is to improve case management and help courts focus resources on juveniles who exhibit the greatest intervention needs. Further, juvenile risk assessments play a critical role in estimating which juveniles will likely reoffend by identifying factors that increase the propensity of future offending. Although some researchers believe that the implementation of standardized juvenile risk assessments is a good strategy for reducing biased decision-making for racial/ethnic minorities, other researchers have called into question the extent to which risk assessments overestimate risk for certain juveniles, especially those in minority groups who have a history of being marginalized due to their race, culture, or ethnicity. This article provides an overview of how well juvenile risk assessment instruments predict future delinquency across race and ethnicity. The review suggests that in general, risk assessments do a good job in predicting recidivism across racial/ethnic groups for diverse populations inside and outside the United States. However, there is still some room for improvement concerning the assessment of risk and needs for ethnic minorities. In addition, while there are some studies that do not report the predictive validity of risk assessment scores across race/ethnicity, risk assessments overall seem to be a promising effort to correctly classify and/or identify juveniles who are at greatest risk for future recidivism.
European Border and Coast Guard (Frontex): Security, Democracy, and Rights at the EU Border
Authors: Campesi Giuseppe
Published: February 2018

The European Border and Coast Guard (EBCG) was officially launched in October 2016. In the European Commission’s view, it marks a milestone in the history of the integrated management of European Union (EU) borders. This article describes the main features of the new agency, focusing on two key issues. First, it analyzes the powers that the new agency is entrusted with in an attempt to understand whether it will be able to articulate a “European space of control” where an authentically postnational border police will take the lead over national border agencies. Second, it explores whether, and to what extent, the reform of the EU border agency has been accompanied by the development of mechanisms to exercise effective democratic and judicial control over its activities. The discussion concludes by arguing that the views of those who believe that the evolution of EU justice and home affairs policies does not raise particular challenges for the exercise of democratic control over EU security agencies and the protection of fundamental rights during their operations are fundamentally flawed, and that new ways to ensure proper scrutiny over security policies that take account of the peculiarities of EU institutional structure need to be devised.
Ethnography and the Study of Gangs
Authors: Durán Robert J.
Published: February 2018

The study of gangs has emerged alongside the use of a research methodology known as ethnography. Ethnography is based on participant observation and interviews to provide a detailed description of a wide variety of social groups and settings. The researcher is trained to immerse himself or herself into the setting and group of interest and to learn the way participants think and feel. The origins of ethnography date back to W. E. B. Du Bois and the Atlanta School along with the University of Chicago, known as the Chicago School. Gang research began in the 1920s in the city of Chicago with additional studies emerging in Boston, New York City, and Los Angeles. Ethnographic researchers learned to rely on key participants to provide access to social settings and social groups, often very different from those of the researcher. The social work orientation of reaching out to gang members through the use of gang workers allowed researchers the opportunity to obtain additional forms of access. Nevertheless, the principal investigator remained the source for interpretation of the data and results. In the 1970s and 1980s greater awareness developed regarding the role of insiders and outsiders to particular groups and settings. In response, researchers moved ethnography into one of three strands of discovery: (1) cultivating an outsider role to present a non-threatening presence; (2) working in collaboration with gang members; and (3) attempting to nurture an insider status through enhanced membership roles. Contemporary gang ethnographies have moved toward utilizing mixed methodological designs as highlighted by the Eurogang program and more critically approached strategies emerging in the United States. In addition, research in Latin America has provided a greater form of reflexivity as primarily white researchers have outlined their initial standing in the community and how they have worked to develop rapport. Ethnography continues to be of importance for the study of gangs but has increasingly become more conscious as toward how personal biographies and backgrounds shape the data collection process. In so doing, ethnography has become more focused on reducing bias and increasing ethical forms of justice.
Control Balance Theory
Authors: Tittle Charles R.
Published: February 2018

Control balance theory (CBT) was developed in the mid-1990s, primarily to illustrate a particular method for building integrated theory and to show how general theories are useful in addressing various issues in studies of crime and deviance. A major theme on which the theory has been built is the idea that deficient control, a well-established classic notion, and excessive control all can have deviogenic consequences. In addition, the theory rests on expectations that sufficient explanation will necessarily involve complex arguments. Thus, CBT not only attempts to explain the phenomena within its domain, but it also challenges simplistic theories, contentions that theoretical integration is both impossible and undesirable, and neglect of contingencies in theorizing.
Martian Ionospheric Observation and Modelling
Authors: González-Galindo Francisco
Published: February 2018

The Martian ionosphere is a plasma embedded within the neutral upper atmosphere of the planet. Its main source is the ionization of the CO2-dominated Martian mesosphere and thermosphere by energetic EUV solar radiation. The ionosphere of Mars is subject to an important variability induced by changes in its forcing mechanisms (e.g., the UV solar flux) and by variations in the neutral atmosphere (e.g., the presence of global dust storms, atmospheric waves and tides, changes in atmospheric composition, etc.). Its vertical structure is dominated by a maximum in electron concentration at altitude about 120–140 km, coincident with the peak of the ionization rate. Below, there is a secondary peak produced by solar X-rays and photoelectron-impact ionization. A sporadic third layer, possibly of meteoric origin, has been also detected below.

The most abundant ion in the Martian ionosphere is O2
+, although O+ can become more abundant in the upper ionospheric layers. While below about 180–200 km the Martian ionosphere is dominated by photochemical processes, above those altitudes the dynamics of the plasma becomes more important. The ionosphere is also an important source of escaping particles via processes such as dissociative recombination of ions or ion pickup. So, characterization of the ionosphere provides or can provide information about such disparate systems and processes as solar radiation reaching the planet, the neutral atmosphere, meteoric influx, atmospheric escape to space, or the interaction of the planet with the solar wind.

It is thus not surprising that the interest about this region dates from the beginning of the space era. From the first measurements provided by the Mariner 4 mission in the 1960s to observations by the Mars Express and MAVEN orbiters in the 2010s, our knowledge of this atmospheric region is the consequence of the accumulation of more than 50 years of discontinuous measurements by different space missions. Numerical simulations by computational models able to simulate the processes that shape the ionosphere have also been commonly employed to obtain information about this region, to provide an interpretation of the observations and to fill their gaps. As a result, at the end of the 2010s the Martian ionosphere was the best known one after that of the Earth. However, there are still areas for which our knowledge is far from being complete. Examples are the details and balance of the mechanisms populating the nightside ionosphere, the origin and variability of the lower ionospheric peak, and the precise mechanisms shaping the topside ionosphere.
The United States at the End of the Cold War, 1989–1993
Authors: Wilson James Graham
Published: February 2018

The Cold War may have ended on the evening of November 9, 1989, when East German border guards opened up checkpoints and allowed their fellow citizens to stream into West Berlin; it certainly was over by January 28, 1992, when U.S. president George H. W. Bush delivered his annual State of the Union Address one month after President Mikhail Gorbachev had announced his resignation and the end of the Soviet Union. After the Berlin Wall came down, Bush and Gorbachev spoke of the Cold War in the past tense in person and on the telephone. The reunification of Germany and U.S. military campaign in the Persian Gulf confirmed that reality. In January 1991, polls indicated that, for the first time, a majority of Americans believed that the Cold War was over. However, the poll results obscured the substantial foreign and domestic crises, challenges, and opportunities created by the end of the Cold War that occupied President Bush and his national-security team between November 1989 and Bush’s defeat in the 1992 presidential inauguration and the inauguration of William Jefferson Clinton as America’s first post–Cold War president in January 1993.
Chin Chun Chan : The Zarzuela as an Ethnic and Technological Farce
Authors: Avila Jacqueline
Published: February 2018

Chin Chun Chan premiered at the Teatro Principal in Mexico City on April 9, 1904, to an enthusiastic audience. The first Mexican zarzuela written by José F. Elizondo and Rafael Medina with music by Luis G. Jordá initiated a new current in Mexican lyric theater that moved away from the Spanish zarzuelas and the operas popular during the Porfiriato: the teatro de revistas, or revistas. With the subtitle of “A Chinese Conflict in One Act and Three Scenes,” Chin Chun Chan is a story about mistaken identity in which a fed-up man attempts to escape his jealous partner by disguising himself as a Chinese dignitary at a grand hotel in Mexico City. Chin Chun Chan was a significant move away from Spanish productions, attempting to create a local entertainment that could be defined as Mexican through popular characters, dialogues, music, and colloquialisms. This formula set the stage for later revistas particularly during the armed struggle of the Revolution (1910–1920). Through a closer examination of the music numbers and the dialogue, Chin Chun Chan offers new readings on the position of ethnicity, nationalism, and sexuality during this contemporary period of political and social instability and initiates an important period in Mexican theatrical history.
polychromy, sculptural, Greek and Roman
Authors: Østergaard Jan Stubbe
Published: February 2018

The term “polychromy” has been in use since the early 19th century to denote the presence of any element of colour in Greek and Roman sculpture. The evidence for such polychromy is literary, epigraphical, archaeological, and archeometric; research on the subject therefore requires collaboration between the humanities, conservation science, and natural science. Such research should go hand in hand with the investigation of the polychromy of Greek and Roman architecture, since it is symbiotically related to sculpture, technically as well as visually.

Knowledge of Greek and Roman sculptural polychromy is still very uneven. Scholars have focused on stone sculpture, and most research has been directed towards the Archaic, Early Classical, Hellenistic, and Imperial Roman periods. For terracottas, the Hellenistic period has enjoyed the most research, while investigation of the polychromy of bronze sculpture has only recently begun.

The scientific research methodology applied concerns the materials and techniques employed. The main colouring agents are paints, metals, and coloured marbles. Pigments are based on inorganic and organic materials applied with proteins, wax, or plant gums as binding media. Metals used are bronze, copper, silver, and gold. A range of coloured marbles came into use in the Roman Imperial period, but in all periods, assorted materials such as semi-precious stones and metals were used for inlaid details and attached objects like jewelry and weapons.

The element of colour in Greek and Roman sculpture is of varied character and is found on works in all formats and materials, in a wide spectrum of contexts and functions covering the chronological and geographical history of sculpture in Classical Antiquity. No matter the period, sculptures had an element of colour; this element was not just a decorative addition but integral to the meaning and message of the sculpture. A logical relationship existed between the sculptural forms and their polychromy. A major division in the history of sculptural polychromy is therefore congruent with that found between the highly stylized forms of Archaic sculpture, on the one hand, and the naturalism dominant from the Classical period to the onset of Late Antiquity, on the other hand.

The list of sculptures on which remains of colour have been observed, but not analyzed, is long. Many are included in Reuterswärd’s 1960 monograph, which constitutes the point of departure for studies since then. This article is, however, based on the results of interdisciplinary investigation, an activity still in its infancy.
The Phonetics of Babbling
Authors: Rvachew Susan , Alhaidary Abdulsalam
Published: February 2018

Babbling is made up of meaningless speechlike syllables called canonical syllables. Canonical syllables are characterized by the coordination of consonantal and vocalic elements in syllables that have speechlike timing, phonation, and resonance characteristics. Infants begin to babble on average at approximately seven months of age. Babbling continues in parallel with less mature noncanonical vocalizations that make up the majority of utterances through the first year. Babbling also continues in parallel with the emergence of meaningful speech during the second year. Regardless of the language that the infant is learning, most canonical syllables have a CV shape with the consonant being a labial or alveolar stop or nasal and the vowel most likely to be central or low- to mid-front in place (e.g., [bʌ], [da], [mæ]). Approximately 15% of canonical utterances consist of multisyllable strings; in other words, most babbled utterances contain only a single CV syllable. The onset of the canonical babbling stage is crucially dependent upon normal hearing, permitting access to language input and feedback of self-produced speech. Many studies have reported differences in the phonetic and acoustic characteristics of babble produced by infants learning different languages. These differences include the frequency with which certain consonants are produced, the location, size, and shape of the vowel space, and the rhythmic and intonation qualities of multisyllable babbles, in each case reflecting specificities of the input language. However, replications of these findings are rare and further research is required to better understand the learning mechanisms that underlie language specific acquisition of articulatory representations during the prelinguistic stage of vocal development.
Agricultural Practices and Environmental Impacts of Aztec and Pre-Aztec Central Mexico
Authors: Nichols Deborah L.
Published: February 2018

The Basin of Mexico is a key world region for understanding agricultural intensification and the development of ancient and historic cities and states. Archaeologists working in the region have had a long-standing interest in understanding the dynamics of interactions between society and environment and their research has been at the forefront of advances in both method and theory. The Basin of Mexico was the geopolitical core of the Aztec empire, the largest state in the history of Mesoamerica. Its growth was sustained by a complex economy that has been the subject of much research.

Two themes underlie a broad interest in the pre-Hispanic agriculture of the Basin of Mexico. First, how with a Neolithic technology did the Aztecs and their predecessors sustain the growth of large cites, dense rural populations, and the largest state system in the history of pre-Hispanic Mesoamerica? Second, what is the relationship of agricultural intensification and urbanization and state formation? Mesoamerica is the only world region where primary civilizations developed that lacked domestic herbivores for either food or transportation. Their farming depended entirely on human labor and hand tools but sustained large cities, dense populations, and complex social institutions. Intensive agriculture began early and was promoted by risk, ecological diversity, and social differentiation, and included irrigation, terracing, and drained fields (chinampas). Most farming was managed by smallholder households and local communities, which encouraged corporate forms of governance and collective action. Environmental impacts included erosion and deposition, but were limited compared with the degradation that took place in the colonial period.
The Role of Cover Crops in Agriculture and Their Environmental Significance
Authors: Aronsson Helena
Published: February 2018

Growing a cover crop between main crops imitates natural ecosystems where the soil is continuously covered with vegetation. This is an important management practice in preserving soil nutrient resources and reducing nitrogen (N) losses to waters. Cover crops also provide other functions that are important for the resilience and long-term stability of cropping systems, such as reduced erosion, increased soil fertility, carbon sequestration, increased soil phosphorus (P) availability, and suppression of weeds and pathogens.

Much is known about how to use cover crops to reduce N leaching, for climates where there is a water surplus outside the growing season. Non-legume cover crops reduce N leaching by 20%–80% and legumes reduce it by, on average, 23%. There are both synergies and possible conflicts between different environmental and production aspects that should be considered when developing efficient and multifunctional cover crop systems, but contradictions about different functions provided by cover crops can sometimes be overcome with site-specific adaptation of measures. One example is cover crop effects on P losses. Cover crops reduce losses of total P, but extract soil P to available forms and may increase losses of dissolved P. How to use this effect to increase soil P availability on subtropical soils needs further studies. Knowledge and examples of how to maximize the positive effects of cover crops on cropping systems are improving, thereby increasing the sustainability of agriculture. One example is combined weed suppression in order to reduce dependence on herbicides or intensive mechanical treatment.
Preexposure Prophylaxis Initiation and Retention in Care Over 5 Years, 2012–2017: Are Quarterly Visits Too Much?
Authors: Rusie Laura K , Orengo Carlos , Burrell Diane , Ramachandran Arthi , Houlberg Magda , Keglovitz Kristin , Munar David , Schneider John A
Published: February 2018

Retention in preexposure prophylaxis (PrEP) care is critical to elimination of human immunodeficiency virus. We reviewed all Howard Brown Health patients receiving PrEP (n = 5583) from 2012 to 2017. Among those with 12 months of follow-up, 43% remained in care, yet only 15% had all 4 quarters with a PrEP visit. Insurance status and comorbid conditions were drivers of retention in care.
Major Impact of Sampling Methodology on Gene Expression in Estrogen Receptor–Positive Breast Cancer
Authors: Gao Qiong , López-Knowles Elena , U Cheang Maggie Chon , Morden James , Ribas Ricardo , Sidhu Kally , Evans David , Martins Vera , Dodson Andrew , Skene Anthony , Holcombe Chris , Mallon Elizabeth , Evans Abigail , Bliss Judith M , Robertson John , Smith Ian , Martin Lesley-Ann , Dowsett Mitch ,   POETIC Trial Management Group and Trialists
Published: February 2018

To investigate the impact of sampling methodology on gene expression data from primary estrogen receptor–positive (ER+) breast cancer biopsies, global gene expression was measured in core-cut biopsies at baseline and surgery from patients randomly assigned to receive either two weeks of presurgical aromatase inhibitor (AI; n = 157) or no presurgical treatment (n = 56). Those genes most markedly altered in the AI group (eg, FOS, DUSP1, RGS1, FOSB) were similarly altered in the no treatment group; some widely investigated genes that were apparently unaffected in the AI group (eg, MYC) were counter-altered in the control group, masking actual AI-dependent changes. In the absence of a control group, these artefactual changes would likely lead to the most affected genes being the erroneous focus of research. The findings are likely relevant to all archival collections of ER+ breast cancer.
Chromatin assembly factor-1 (CAF-1) chaperone regulates Cse4 deposition into chromatin in budding yeast
Authors: Hewawasam Geetha S , Dhatchinamoorthy Karthik , Mattingly Mark , Seidel Chris , Gerton Jennifer L
Published: February 2018

Correct localization of the centromeric histone variant CenH3/CENP-A/Cse4 is an important part of faithful chromosome segregation. Mislocalization of CenH3 could affect chromosome segregation, DNA replication and transcription. CENP-A is often overexpressed and mislocalized in cancer genomes, but the underlying mechanisms are not understood. One major regulator of Cse4 deposition is Psh1, an E3 ubiquitin ligase that controls levels of Cse4 to prevent deposition into non-centromeric regions. We present evidence that Chromatin assembly factor-1 (CAF-1), an evolutionarily conserved histone H3/H4 chaperone with subunits shown previously to interact with CenH3 in flies and human cells, regulates Cse4 deposition in budding yeast. yCAF-1 interacts with Cse4 and can assemble Cse4 nucleosomes in vitro. Loss of yCAF-1 dramatically reduces the amount of Cse4 deposited into chromatin genome-wide when Cse4 is overexpressed. The incorporation of Cse4 genome-wide may have multifactorial effects on growth and gene expression. Loss of yCAF-1 can rescue growth defects and some changes in gene expression associated with Cse4 deposition that occur in the absence of Psh1-mediated proteolysis. Incorporation of Cse4 into promoter nucleosomes at transcriptionally active genes depends on yCAF-1. Overall our findings suggest CAF-1 can act as a CenH3 chaperone, regulating levels and incorporation of CenH3 in chromatin.
Biological and Genetic Characterization of New and Known Necroviruses Causing an Emerging Systemic Necrosis Disease of Corn Salad (Valerianella locusta) in France
Authors: Verdin E. , Marais A. , Wipf-Scheibel C. , Faure C. , Pelletier B. , David P. , Svanella-Dumas L. , Poisblaud C. , Lecoq H. , Candresse T.
Published: February 2018

An emerging systemic necrosis disease of corn salad was first observed in the Nantes region of France in the late 2000s. Classical virology and high-throughput sequencing approaches demonstrated that the disease is associated with four different necroviruses: tobacco necrosis virus A (TNVA), tobacco necrosis virus D (TNVD), olive mild mosaic virus (OMMV), and a novel recombinant Alphanecrovirus for which the name corn salad necrosis virus (CSNV) is proposed. Satellite tobacco necrosis virus was also frequently observed. Koch’s postulates were completed for all four agents, each one alone being able to cause systemic necrosis of varying severity in corn salad. OMMV was the most frequently observed virus and causes the most severe symptoms. TNVA was the second, both in terms of prevalence and symptom severity while TNVD and CSNV were only rarely observed and caused the less severe symptoms. The emergence of this systemic disease may have been favored by the short and repeated cropping cycles used for corn salad, possibly allowing the selection of necrovirus isolates with an improved ability to systemically invade this specialty crop.
Career development for nurse managers
Authors: Goodyear Caryl , Goodyear Marilu
Published: February 2018

In this first installment of a two-part series on mentoring, we discuss organizing a mentor program for nurse managers who want to develop their careers.
Time-Variable Training in Medicine: Theoretical Considerations
Authors: ten Cate Olle , Gruppen Larry D. , Kogan Jennifer R. , Lingard Lorelei A. , Teunissen Pim W.
Published: February 2018

The introduction of competency-based medical education has shifted thinking from a fixed-time model to one stressing attained competencies, independent of the time needed to arrive at those competencies. In this article, the authors explore theoretical and conceptual issues related to time variability in medical training, starting with the Carroll model from the 1960s that put time in the equation of learning. They discuss mastery learning, deliberate practice, and learning curves.

While such behaviorist theories apply well to structured courses and highly structured training settings, learning in the clinical workplace is not well captured in such theories or in the model that Carroll proposed. Important in clinical training are self-regulation and motivation; neurocognitive perspectives of time and learning; professional identity formation; and entrustment as an objective of training—all of which may be viewed from the perspective of the time needed to complete training. The authors conclude that, in approaching time variability, the Carroll equation is too simplistic in its application to the breadth of medical training. The equation may be expanded to include variables that determine effective workplace learning, but future work will need to examine the validity of these additional factors.
Using Unsupervised Machine Learning to Identify Subgroups Among Home Health Patients With Heart Failure Using Telehealth
Authors: Bose Eliezer , Radhakrishnan Kavita
Published: February 2018

This study explored the use of unsupervised machine learning to identify subgroups of patients with heart failure who used telehealth services in the home health setting, and examined intercluster differences for patient characteristics related to medical history, symptoms, medications, psychosocial assessments, and healthcare utilization. Using a feature selection algorithm, we selected seven variables from 557 patients for clustering. We tested three clustering techniques: hierarchical, k-means, and partitioning around medoids. Hierarchical clustering was identified as the best technique using internal validation methods. Intercluster differences among patient characteristics and outcomes were assessed with either χ2 test or one-way analysis of variance. Ranging in size from 153 to 233 patients, three clusters displayed patterns that differed significantly (P < .05) in patient characteristics of age, sex, medical history of comorbid conditions, use of beta blockers, and quality of life assessment. Significant (P < .001) intercluster differences in number of medications, comorbidities, and healthcare utilization were also revealed. The study identified patterns of association between (1) mental health status, pulmonary disorders, and obesity, and (2) healthcare utilization for patients with heart failure who used telehealth in the home health setting. Study results also revealed a lack of prescription guideline-recommended heart failure medications for the subgroup with the highest proportion of older female adults.
Incorporation of Daily Goals in Daily Care Planning Does Not Shorten Length of Stay in the Intensive Care Unit
Authors: Binnekade Jan M. , Brunsveld-Reinders Anja H. , Arbous M. Sesmu , Dijkgraaf Marcel G. W. , Horn Janneke , van der Sloot Jos A. P. , Balzereit Anja , Schultz Marcus J. , Brinkman Sylvia , Vroom Margreeth B.
Published: February 2018

A strategy of defining and checking explicitly formulated patient-specific treatments targets or “daily goals” in the intensive care unit has been associated with improved communication. We investigated the effect of incorporation of daily goals into daily care planning on length of stay in the intensive care unit. Furthermore, the type of daily goals and deviations from daily goals in daily care with or without documented reason were evaluated. Four university hospitals in the Netherlands, of which 2 study “daily goal” hospitals and 2 control hospitals, participated in a prospective before-after study. During the before phase of the study, daily goals were formulated by the attending physician but kept blinded from doctors and nurses caring for the patient. During the after phase of the study, daily goals were integrated in the care plan for patients admitted to the 2 study hospitals but not for patients admitted to the control hospitals. The implementation of daily goals was, after case-mix correction, not associated with a change in intensive care unit length of stay. However, this study showed that an improved administrative discipline, that is, the recording of the reason why a daily goal or standard protocol was not accomplished, is in favor of the daily goal implementation.
Measurement of Teicoplanin Concentration With Liquid Chromatography-Tandem Mass Spectrometry Method Demonstrates the Usefulness of Therapeutic Drug Monitoring in Hematologic Patient Populations
Authors: Chae Hyojin , Lee Jeong Joong , Cha Kyoungho , Her Su Hyun , Kim Hyo-Young , Han Eunhee , Kim Myungshin , Kim Yonggoo , Cho Sung-Yeon , Lee Dong-Gun
Published: February 2018

Background:

Teicoplanin is a glycopeptide antibiotic that has become increasingly popular with the spread of methicillin-resistantStaphylococcus aureus. The aim of the study was to develop and validate an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for teicoplanin, and analyze trough teicoplanin concentrations achieved in patients with hematological diseases.

Methods:

The UHPLC-MS/MS method for teicoplanin was developed, validated, and applied in a retrospective analysis of trough plasma teicoplanin concentrations from 305 patients receiving standard dose, and 17 patients receiving therapeutic drug monitoring (TDM)-guided individualized dose.

Results:

The linear range was 3.9–52.9 mg/L. The imprecision was less than 12%, the limits of detection and quantification were less than 0.13 and 0.72 mg/L, respectively. The sample carry-over and ion suppression were insignificant. In the standard dose group, the median teicoplanin concentrations were 7.5 mg/L (days 3–5) and 8.9 mg/L (on days 6–8); and the proportion of trough levels achieving ≥10 mg/L was 20% (days 3–5) and 38% (days 6–8), respectively. In the TDM-guided individualized dose group, median teicoplanin concentration was higher (16.9 mg/L), and the proportion of trough levels ≥10 mg/L was also higher (77%) when compared with the standard dose group.

Conclusions:

Based on these results, the present UHPLC-MS/MS method can be considered suitable for routine TDM of teicoplanin. Also, based on the insufficient trough teicoplanin concentrations achieved with standard dose regimen, and the higher trough teicoplanin concentrations achieved with TDM-guided individualized dose regimen, this study highlights the importance of TDM of teicoplanin, especially in high-risk patient groups.
Phase II Clinical Trial of Lenalidomide and Dexamethasone Therapy in Japanese Elderly Patients With Newly Diagnosed Multiple Myeloma to Determine Optimal Plasma Concentration of Lenalidomide
Authors: Kobayashi Takahiro , Miura Masatomo , Niioka Takenori , Abumiya Maiko , Ito Fumiko , Kobayashi Isuzu , Ikeda Sho , Yoshioka Tomoko , Kameoka Yoshihiro , Takahashi Naoto
Published: February 2018

Background:

The authors conducted a phase II clinical trial of lenalidomide and dexamethasone combination therapy in Japanese elderly patients with newly diagnosed multiple myeloma to evaluate its safety and efficacy and to determine whether safety and efficacy correlate with the plasma concentration of lenalidomide.

Methods:

Forty patients received oral lenalidomide on days 1–21 of a 28-day cycle in addition to weekly doses of dexamethasone. Plasma concentrations of lenalidomide were measured, and the area under the concentration–time curve from 0 to 24 hours (AUC0–24) of lenalidomide was predicted using a formula the authors previously reported in this journal.

Results:

The median age was 75.5 years. Twenty-one patients had renal impairment severe enough to require dose adjustment of lenalidomide. The median initial doses of lenalidomide and dexamethasone were 12.5 and 20 mg, respectively. The overall response rate was 68.6%, and the 2-year overall survival rate was 88.5%. There was no correlation between the response rate and plasma concentration of lenalidomide. Grade 3–4 adverse events (AEs) were observed in 57.5% of patients. The AUC0–24 of lenalidomide was significantly higher in patients with grade 3–4 AEs than in those who did not suffer from AEs (median = 4852.0 versus 2464.9 ng·h−1·mL−1, P = 0.027). Receiver-operating characteristic curve analysis showed that the AUC0–24 of lenalidomide was a good predictor of grade 3–4 AEs, with an area under the receiver-operating characteristic curve of 0.758 (95% confidence interval, 0.572–0.943, P = 0.027). The cutoff value for best prediction of grade 3–4 AEs was 2613.5 ng·h−1·mL−1 (sensitivity 86.7%, specificity 54.5%). Multivariate logistic analysis confirmed the significance of this cutoff value.

Conclusions:

These data suggest that overexposure to lenalidomide could contribute to toxicity. Furthermore, the predicted cutoff value of AUC0–24 can be clinically used to prevent severe AEs.
SILDENAFIL CITRATE INDUCED RETINAL TOXICITY—ELECTRORETINOGRAM, OPTICAL COHERENCE TOMOGRAPHY, AND ADAPTIVE OPTICS FINDINGS
Authors: Yanoga Fatoumata , Gentile Ronald C. , Chui Toco Y. P. , Freund K. Bailey , Fell Millie , Dolz-Marco Rosa , Rosen Richard B.
Published: February 2018

Background/Purpose:

To report a case of persistent retinal toxicity associated with a high dose of sildenafil citrate intake.

Methods:

Single retrospective case report.

Results:

A 31-year-old white man with no medical history presented with complaints of bilateral multicolored photopsias and erythropsia (red-tinted vision), shortly after taking sildenafil citrate—purchased through the internet. Patient was found to have cone photoreceptor damage, demonstrated using electroretinogram, optical coherence tomography, and adaptive optics imaging. The patient's symptoms and the photoreceptor structural changes persisted for several months.

Conclusion:

Sildenafil citrate is a widely used erectile dysfunction medication that is typically associated with transient visual symptoms in normal dosage. At high dosage, sildenafil citrate can lead to persistent retinal toxicity in certain individuals.
Association of Axial Length Growth and Topographic Change in Orthokeratology
Authors: Lee Eun Jung , Lim Dong Hui , Chung Tae-Young , Hyun Joo , Han Jisang
Published: February 2018

Objectives:

To investigate the topographic factors related to axial length (AL) growth rate in orthokeratology.

Methods:

Clinical data of myopic children with orthokeratology lenses from 2010 to 2016 were investigated. Corneal topography (Orbscan II) and IOLMaster-measured AL at baseline and every posttreatment visit were analyzed. Optical map topographies from baseline- and posttreatment-stabilized corneas were analyzed to calculate the refractive power difference between the apex and the periphery (apex-periphery refractive power difference [ARPD]), which estimates the change of peripheral refraction. A generalized estimating equation (GEE) was used to assess the associations between AL growth and topographic changes in both eyes.

Results:

The mean baseline spherical equivalent (SE) was −2.40±1.12 diopters (D) and the mean AL was 24.38±0.77 mm. Over a mean follow-up period of 41.9 months, the mean AL growth rate was 0.22±0.15 mm/year. In a univariable GEE analysis, age at initial lens wear, baseline AL, baseline SE, central corneal thickness (CCT), baseline apex power, and posttreatment ARPD on optical topography maps were all significantly correlated with AL growth rate (P<0.001, 0.009, 0.024, 0.011, 0.010, and 0.006, respectively). In a multivariable GEE, CCT and posttreatment ARPD were identified as significant factors (P=0.014 and 0.016, respectively).

Conclusions:

The AL growth rate was significantly associated with CCT and posttreatment relative peripheral refractive power, in addition to age at initial lens wear. These associations might possibly demonstrate an effect of treatment-induced peripheral refraction changes on retardation of myopic progression, whereas younger age might significantly influence both AL growth rate and corneal deformation.
Orbital Hobnail Hemangioma
Authors: Thangamathesvaran Loka , Mirani Neena , Langer Paul D.
Published: February 2018

A 64-year-old woman presented with a 1 year history of progressive left proptosis and “blurry vision.” Imaging studies revealed a left superior orbital mass distorting the optic nerve and superior rectus muscle. Excisional biopsy established the diagnosis of hobnail hemangioma. This report describes the first case of an orbital hobnail hemangioma, a lesion that more commonly presents in the dermis.
Comparison Study of Percutaneous Osseointegrated Bone Conduction Device Complications When Using the 9 mm Abutment Versus 6 mm Abutment at Initial Implantation
Authors: Wise Sean R. , LaRouere Jacqueline S. , Bojrab Dennis I. , LaRouere Michael J.
Published: February 2018

Objectives:

To assess differences in the incidence, type, and management of complications encountered with implantation of percutaneous osseointegrated bone conduction devices when using a 9 mm abutment versus 6 mm abutment at initial implantation.

Study Design:

Retrospective cohort study.

Methods:

One hundred thirty consecutive patients between January 2010 and December 2011 underwent single-stage percutaneous osseointegrated bone conduction device implantation using a 9 or 6 mm abutment. Clinical outcomes assessed for the two groups included the incidence, type, and management of postoperative complications. Abutment size, age, sex, indication for surgery, implant device type, duration of follow-up, and patient comorbidities were evaluated as potential factors affecting outcomes.

Results:

Average duration of follow-up was 16 months (range 6–29 mo). Postoperative complications occurred in 38 (29.2%) patients. Twenty-four (18.4%) patients experienced minor complications requiring simple, local care; eight (6.1%) patients required in-office procedural intervention; and six (4.6%) patients required revision surgery in the operating room. Implant extrusion occurred in three (2.3%) patients. Eleven (8.5%) patients required placement of a longer abutment. Patients receiving the 6 mm abutment at initial surgery were significantly more likely to encounter a complication requiring in-office procedural intervention or revision surgery (p = 0.001).

Conclusion:

Minor complications after implantation of percutaneous osseointegrated bone conduction devices are common. The vast majority of these complications are due to localized skin reactions, most of which are readily addressed through local care. Patients receiving the 9 mm abutment during initial implantation are significantly less likely to require in-office procedural intervention or revision surgery postoperatively as compared with those receiving the shorter, 6 mm abutment.
Association of Pulsatility with Gastrointestinal Bleeding in a Cohort of HeartMate II Recipients
Authors: Edwards Adam L. , Fitzmorris Paul , Pamboukian Salpy V. , George James F. , Wilcox C. Mel , Peter Shajan
Published: February 2018

Gastrointestinal bleeding (GIB) is common in patients with continuous-flow left ventricular assist devices (CF-LVADs) possibly because of changes in blood flow. We aimed to test the hypothesis that a low pulsatility index (PI) is associated with an increased hazard of overt GIB in patients with CF-LVADs. We conducted a retrospective cohort study of patients who had a HeartMate II (HMII) CF-LVAD implanted at our center. The study end-point was the first overt GIB causing or occurring during a hospitalization between 6 days and 6 months after HMII implantation. HMII PI was recorded at 48 hours and at 1, 3, and 6 month intervals after implantation. We analyzed the associations of PI and clinical variables with the hazard of overt GIB. Ninety-five patients met eligibility criteria. PI ranged from 2.5 to 5.9 (low PI < 4.15 and high PI ≥ 4.15 on the basis of receiver operating characteristic curve analysis). Seventeen (18%) patients experienced overt GIB. In a multivariable model, only lower baseline hemoglobin was a significant predictor of an increased hazard of overt GIB. After adjusting for the baseline hemoglobin, low PI was independently associated with an increased hazard of overt GIB in our cohort of HMII recipients.
Simultaneous Venoarterial Extracorporeal Membrane Oxygenation and Percutaneous Left Ventricular Decompression Therapy with Impella Is Associated with Improved Outcomes in Refractory Cardiogenic Shock
Authors: Patel Sandeep M. , Lipinski Jerry , Al-Kindi Sadeer G. , Patel Toral , Saric Petar , Li Jun , Nadeem Fahd , Ladas Thomas , Alaiti Amer , Phillips Ann , Medalion Benjamin , Deo Salil , Elgudin Yakov , Costa Marco A. , Osman Mohammed Najeeb , Attizzani Guilherme F. , Oliveira Guilherme H. , Sareyyupoglu Basar , Bezerra Hiram G.
Published: February 2018

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been used for refractory cardiogenic shock; however, it is associated with increased left ventricular afterload. Outcomes associated with the combination of a percutaneous left ventricular assist device (Impella) and VA-ECMO remains largely unknown. We retrospectively reviewed patients treated for refractory cardiogenic shock with VA-ECMO (2014–2016). The primary outcome was all-cause mortality within 30 days of VA-ECMO implantation. Secondary outcomes included duration of support, stroke, major bleeding, hemolysis, inotropic score, and cardiac recovery. Outcomes were compared between the VA-ECMO cohort and VA-ECMO + Impella (ECPELLA cohort). Sixty-six patients were identified: 36 VA-ECMO and 30 ECPELLA. Fifty-eight percent of VA-ECMO patients (n = 21) had surgical venting, as compared to 100% of the ECPELLA cohort (n = 30) which had Impella (±surgical vent). Both cohorts demonstrated relatively similar baseline characteristics except for higher incidence of ST-elevation myocardial infarction (STEMI) and percutaneous coronary intervention (PCI) in the ECPELLA cohort. Thirty-day all-cause mortality was significantly lower in the ECPELLA cohort (57% vs. 78%; hazard ratio [HR] 0.51 [0.28–0.94], log rank p = 0.02), and this difference remained intact after correcting for STEMI and PCI. No difference between secondary outcomes was observed, except for the inotrope score which was greater in VA-ECMO group by day 2 (11 vs. 0; p = 0.001). In the largest US-based retrospective study, the addition of Impella to VA-ECMO for patients with refractory cardiogenic shock was associated with lower all-cause 30 day mortality, lower inotrope use, and comparable safety profiles as compared with VA-ECMO alone.
Left Ventricular Structural and Functional Changes in Children With β-Thalassemia and Sickle Cell Disease: Relationship to Sleep-disordered Breathing
Authors: Elalfy Mohsen S. , Youssef Omneya Ibrahim , Deghedy Marwa M.R. , Abdel Naby Mariam M.
Published: February 2018

Cardiovascular complications are well recognized in β-thalassemia and sickle cell disease (SCD). The objective of this study was to evaluate left ventricular (LV) structural and functional changes and their relationship to sleep-disordered breathing (SDB) in children with β-thalassemia and SCD. One hundred patients recruited from the hematology clinic were subjected to Pittsburgh Sleep Quality Index score; 26 patients had positive score (Pittsburgh Sleep Quality Index ≥5) (15 β-thalassemia major and 11 SCD) and were compared with 25 age-matched and sex-matched controls. All underwent polysomnography and tissue Doppler echocardiography. SDB was detected in 73% of thalassemia patients (all had increased LV mass index [LVMI], diastolic dysfunction [increased E/Em], and 53% had pulmonary hypertension [tricuspid valve resurgence (TR) velocity ≥2.5 m/s]) and in 46% of SCD patients ( all had increased LVMI, 81.8% had pulmonary hypertension, and 76% had diastolic dysfunction). Sleep O2 saturation of β-thalassemia patients negatively correlated with TR velocity and LVMI (P=0.027, 0.015), and lower asleep O2 saturation was associated with increased E/Em. In SCD patients, sleep and awake O2 saturation negatively correlated with TR velocity and E/Em (P=0.024 and 0.041), and lower sleep O2 saturation was associated with increased LV diameter (P=0.021). SDB is common and associated with LV structural and functional changes in β-thalassemia and SCD.