bluuebunny/crossref_metadata_2025 huggingface dataset:
On the energy spectrum of rapidly rotating forced turbulence
Authors: Sharma Manohar K. , Verma Mahendra K. , Chakraborty Sagar
Published: November 2018

In this paper, we investigate the statistical features of a fully developed, forced, rapidly rotating, turbulent system using numerical simulations and model the energy spectrum that fits well with the numerical data. Among the wavenumbers (k) larger than the Kolmogorov dissipation wavenumber, the energy is distributed such that the suitably non-dimensionalized energy spectrum is Ē(k¯)≈exp(−0.05k¯), where the overbar denotes appropriate non-dimensionalization. For the wavenumbers smaller than that of forcing, the energy in a horizontal plane is much more than that along the vertical rotation-axis. For such wavenumbers, we find that the anisotropic energy spectrum, E(k⊥, k∥), follows the power law scaling, k⊥−5/2k∥−1/2, where “⊥” and “∥,” respectively, refer to the directions perpendicular and parallel to the rotation axis; this result is in line with the Kuznetsov–Zakharov–Kolmogorov spectrum predicted by the weak inertial-wave turbulence theory for the rotating fluids.
Effect of long-term irrigation and tillage practices on X-ray CT and gas transport derived pore-network characteristics
Authors: Müller Karin , Dal Ferro Nicola , Katuwal Sheela , Tregurtha Craig , Zanini Filippo , Carmignato Simone , Wollesen de Jonge Lis , Moldrup Per , Morari Francesco
Published: November 2018

The gas transport parameters, diffusivity and air-filled porosity are crucial for soil aeration, microbial activity and greenhouse gas emission, and directly depend on soil structure. In this study, we analysed the effect of long-term tillage and irrigation practices on the surface structure of an arable soil in New Zealand. Our hypothesis was that topsoil structure would change under intensification of arable production, affecting gas exchange. Intact soil cores were collected from plots under intensive tillage (IT) and direct drill (DD), irrigated or rainfed. In total, 32 cores were scanned by X-ray computed tomography (CT) to derive the pore network >30µm. The cores were then used to measure soil-gas diffusivity, air-permeability and air-filled porosity of pores close to the resolution of the X-ray CT scans, namely ≥30µm. The gas measurements allow the calculation of pore-network connectivity and tortuosity parameters, which were compared with the CT-derived structural characteristics. Long-term irrigation had little effect on any of the parameters analysed. Total porosity tended to be lower under IT than DD, whereas the CT-derived porosity was comparable. Both the CT-derived mean pore diameter (MPD) and other morphological parameters, as well as gas measurement-derived parameters, highlighted a less developed structure under IT. The differences in the functional pore-network structure were attributed to SOC depletion and the mechanical disturbance through IT. Significant correlations between CT-derived parameters and functional gas transport parameters such as tortuosity and MPD were found, which suggest that X-ray CT could be useful in the prediction of gas transport.
Temperature-dependent vitamin D signaling regulates developmental trajectory associated with diapause in an annual killifish
Authors: Romney Amie L. T. , Davis Erin M. , Corona Meranda M. , Wagner Josiah T. , Podrabsky Jason E.
Published: November 2018

The mechanisms that integrate environmental signals into developmental programs remain largely uncharacterized. Nuclear receptors (NRs) are ligand-regulated transcription factors that orchestrate the expression of complex phenotypes. The vitamin D receptor (VDR) is an NR activated by 1α,25-dihydroxyvitamin D
3
[1,25(OH)
2
D
3
], a hormone derived from 7-dehydrocholesterol (7-DHC). VDR signaling is best known for regulating calcium homeostasis in mammals, but recent evidence suggests a diversity of uncharacterized roles. In response to incubation temperature, embryos of the annual killifish
Austrofundulus limnaeus
can develop along two alternative trajectories: active development and diapause. These trajectories diverge early in development, from a biochemical, morphological, and physiological perspective. We manipulated incubation temperature to induce the two trajectories and profiled changes in gene expression using RNA sequencing and weighted gene coexpression network analysis. We report that transcripts involved in 1,25(OH)
2
D
3
synthesis and signaling are expressed in a trajectory-specific manner. Furthermore, exposure of embryos to vitamin D
3
analogs and Δ4-dafachronic acid directs continuous development under diapause-inducing conditions. Conversely, blocking synthesis of 1,25(OH)
2
D
3
induces diapause in
A. limnaeus
and a diapause-like state in zebrafish, suggesting vitamin D signaling is critical for normal vertebrate development. These data support vitamin D signaling as a molecular pathway that can regulate developmental trajectory and metabolic dormancy in a vertebrate. Interestingly, the VDR is homologous to the daf-12 and ecdysone NRs that regulate dormancy in
Caenorhabditis elegans
and
Drosophila
. We suggest that 7-DHC−derived hormones and their associated NRs represent a conserved pathway for the integration of environmental information into developmental programs associated with life history transitions in animals.
Resistance protein Pit interacts with the GEF OsSPK1 to activate OsRac1 and trigger rice immunity
Authors: Wang Qiong , Li Yuying , Ishikawa Kazuya , Kosami Ken-ichi , Uno Kazumi , Nagawa Shingo , Tan Li , Du Jiamu , Shimamoto Ko , Kawano Yoji
Published: November 2018

Significance

The plant genome encodes
resistance
(
R
) genes that are one of the major genomic resources to enhance disease resistance in various crops.
R
gene products, R proteins, serve as intracellular receptors for pathogen effectors, leading to activation of effector-triggered immunity. Due to the importance of R proteins, elucidation of their signaling pathways is an important research goal. We revealed that OsSPK1, a GDP/GTP exchange factor for the small GTPase OsRac1, is a direct binding protein of the rice R protein Pit, which is a resistance protein to rice blast fungus. OsSPK1 is a key signaling molecule in Pit signaling. Our results provide a critical new insight into molecular mechanisms underlying R protein activation and new knowledge for crop improvement.
Replacement of antibiotics in poultry diets.
Authors: Denlİ M. , Demİrel R.
Published: November 2018

Poultry growth performance and feed efficiency are closely related to the intestinal microbiota quantity, wall structure and the activity of the immune system. Several antibiotics was used in poultry feeds as growth promoters to enhance growth and improve feed efficiency and to reduce mortality in the poultry industry. All commonly used feed antibiotic-growth promoters have been banned and not used in feeds in certain countries due to increased concerns about the potential for antibiotic resistant strains of bacteria and residues of antibiotics in animal tissues. After this decision many scientists have searched for alternatives to antibiotics. Many approaches or alternative natural replacements include probiotics, prebiotics, organic acids, plant extracts, etheric oils and immune stimulants have been applied to maximize performance, maintain animal productivity, preventing and controlling enteric pathogens and reducing antibiotic use in the animal production in recent years. The use of a single replacement or ideal combinations of various alternatives with good management and livestock practices may play a key role in maximizing performance and preserving animal productivity. The purpose of this review is to provide an overview of the recent knowledge on the use of the natural replacements in poultry feeds as feed additives and their effects on the poultry performance.
Upton Sinclair and the Muckrakers
Authors: Kongshaug Erik
Published: November 2018

The forerunners of modern investigative journalism emerged during the US Progressive Era Presidency of Theodore Roosevelt and became known as the muckrakers, a badge of shame they often wore with honor. Finding venues in the popular mass magazines of the early 20th century—such as Collier’s, Cosmopolitan, and McClure’s—and in more overtly populist, socialist publications, such as the Appeal to Reason, that also had considerable readerships, these writers railed against corporate greed, political corruption, and to a lesser degree race discrimination (their race investigations seldom challenged Jim Crow or Mexican- and Chinese-Exclusion). Muckrakers’ value-driven investigations often clashed with the purported professional objectivity of the day’s more politically beholden mainstream journalists. Ironically, Upton Sinclair—who began as a romantic-minded novelist and never quite worked as a journalist, properly speaking—became the most famous among them. Sinclair’s investigation into the meatpacking industry, which brought him to fame as their exemplar, began as an assignment for the Appeal, before it developed into a novel, The Jungle. He had narrated it to move readers to socialism. Instead, it provoked Roosevelt to pass the Pure Food and Drug Act. Ignoring the disdain of high literary circles, Sinclair went on to self-publish a staggering number of reform-driven novels, book-length essays, and pamphlets grounded in evidence-based critiques of every conceivable injustice. He sold them directly, democratically, and cheaply to huge and growing audiences throughout his lifetime and became, arguably, the world’s first mass-market author. Sinclair also remains representative of the white, culturally Protestant narrative privilege that historical muckrakers tended to assume. He would rise to world prominence and would carry the muckrakers’ historical moment and movement beyond their own times, into its final connection with the more racially inclusive New Left that arose at the time of his death.
Garland, Hamlin
Authors: Hirt Jen
Published: November 2018

A prolific author whose early writings established him as a promising realist in American literature, Hannibal Hamlin Garland, who went by his middle name, was born on a farm in West Salem, Wisconsin, on September 4, 1860. His family moved around the Middle Border, now known as the Midwest, before settling in Mitchell County, Iowa, in 1876. By 1882, Garland was living in Illinois, but after just two years, he relocated to Boston, Massachusetts, where in 1885, he was hired at the Boston School of Oratory. This move would define the rest of his lifelong struggle, both to identify as a Midwestern writer and to hold that identity at a distance. While he had some publishing exposure prior to 1889, that year was when he began publishing in earnest. He would go on to publish over fifty books, the last of which appeared in 1939. Most notable was his Pulitzer Prize in biography for A Daughter of the Middle Border, a 1921 book that was second in a series of family histories. The award-winning book took a hard and realistic look at Garland’s family life. Some of his later work went on to serve as a call for reform toward the treatment of Native Americans and the riparian land of the Midwest and West. However, he framed the call to action within formulaic romances and thus suffered criticism for abandoning his talents in literary realism. More recently, scholars have argued that Garland’s shifting between genres should be not be criticized; they argue he was only doing what any talented writer seeking an income in the early 20th-century publishing market would do. A 2008 memoir by his daughter, Isabel Garland Lord, also stands in support of Garland’s artistic decisions, which earned him financial stability and a steady circuit of lectures and publishing. He never returned to the Midwest, and lived out his final years in Los Angeles, California, where he was drawn to Hollywood. There, he maintained strong relationships with influential writers at home and abroad, earning him the informal title of The Dean of American Letters. His final writing projects departed even further from literary realism; he delved into the paranormal, such as the purported power of buried objects. This attempt at making a name for himself in the realm of the paranormal did not pay off (even 21st-century scholars do not make much of these later books), and for many years he remained in the shadow of more eminent American writers. He can be credited, however, as a prolific writer and lecturer who succeeded in three areas—validating American realism at a time when the fad was to romanticize the rural life, showcasing the Midwest as a place of profound struggle and beauty, and documenting the American way of life as seen by a conscientious critic. He died in Hollywood of a cerebral hemorrhage on March 4, 1940, at the age of 79. He was buried with his parents in Neshonoc Cemetery in his hometown of West Salem, Wisconsin.
Proletarian Literature
Authors: Niemi Robert
Published: November 2018

Proletarian literature (from the Latin proletarius, referring to the lowest class of free Roman citizens) is writing in all literary genres by, about, and primarily for working-class people, describing their experiences and often featuring anti-capitalist, pro-socialist, or revolutionary themes.
South Korea’s Economic Development, 1948–1996
Authors: Seth Michael J.
Published: November 2018

At its independence in 1948, South Korea was an impoverished, predominately agricultural state, and most of the industry and electrical power was in North Korea. It faced a devastating war from 1950 to 1953, and an unpromising and slow recovery in the years that followed. Then, from 1961 to 1996, South Korea underwent a period of rapid economic development, during which it was transformed into a prosperous, industrial society. During these years, its economic growth rates were among the highest in the world. Under the military government of Park Chung Hee (Pak Chǒng-hǔi), which came to power in 1961, the state gave priority to economic development, focusing on a combination of state planning and private entrepreneurship. Possessing few natural resources, it depended on a low wage, educated, and disciplined labor force to produce goods for exports. As wages rose, economic development shifted from labor to capital-intensive industries. Focusing initially on textiles and footwear, South Korean manufacturing moved into steel, heavy equipment, ships, and petrochemicals in the 1970s, and electronics and automobiles in the 1980s. Two major reforms under the administration of Syngman Rhee (Yi Sǔng-man, 1948–1961) helped prepare the way: land reform and educational development. However, it was the commitment to rapid industrialization by the military governments of Park Chung Hee and his successor, Chun Doo Hwan (Chǒn Tu-hwan), that brought about the takeoff. Industrialization was characterized by a close pattern of cooperation between the state and large family-owned conglomerates known as chaebǒls. This close relationship continued after the transition to democracy, in the late 1980s and 1990s, but after 1987, labor emerged as a major political force, and rising wages gave further impetus to the development of more capital-intensive industry. In 1996, South Korea joined the Organization for Economic Cooperation and Development, being internationally recognized as a “developed state.” Although living standards still lagged behind those of North America, Western Europe, and Japan, the gap was significantly narrowed. After 1996, its economic development slowed but was still high enough to achieve a per capita income comparable to the countries of Western Europe and to shift from a borrower of to an innovator in technology.
Civic Engagement
Authors: Kuzma Lynn M.
Published: November 2018

There is a body of evidence that suggests that young Americans are disengaged from communal life. Since the late 1980s, college students have been described as materialistic, self-absorbed, and self-interested, acting without regard for community interests. Scholars consider the “me generation” as symptomatic of an eroding democratic civic culture characterized by growing apathy, resentment, even anger. This trend continues today. In order to address this, proponents of higher education have made their attempts to develop civic engagement in young minds. Civic engagement refers to activities within a community, though in the academic setting, the definition becomes much more complex. There is a belief that through participation in a community, students will develop capacities that ultimately lead them to become more active citizens, which in turn benefits not only themselves but also the community. However, higher education’s recommitment to developing students’ civic engagement should be informed by a clear notion of what civic engagement entails. In addition, a certain amount of factual knowledge is a prerequisite for becoming an engaged citizen, as civic learning involves students coming to understand the democratic processes of a community, its history, the problems it faces, and the richness of its diversity. And civic learning opportunities can be taught both in and outside of the classroom, as co-curricular learning opportunities, projects embedded in a class, or as a requirement of a general education curriculum.
International Law and the Responsibility to Protect
Authors: Hall B. Welling , Khudayberdieva Nadira
Published: November 2018

The notion of responsibility to protect (R2P) emerged as a legal challenge to what F. R. Teson called “the moral and legal enclosure of states.” The development of the R2P doctrine coincided with the surge in popularity of the democratic peace thesis, according to which the creation of a security community rests not on the existence of a common enemy, but on the “positive shared foundation of democracy and cooperation.” The R2P doctrine was developed by international lawyers in response to the failure of the international community to prevent or react effectively enough to the commission of genocide, war crimes, crimes against humanity, and ethnic cleansing in Rwanda, Bosnia, Haiti, and elsewhere during the last decade of the 20th century and the first of the 21st century. Some scholars of international law argue that R2P reconceptualizes sovereignty as a legal construct and expands the international toolkit for the peaceful prevention of deadly conflict. The International Commission on Intervention and State Sovereignty (ICISS) report, The Responsibility to Protect, lays emphasis on military intervention as a key component of R2P. Others, however, claim that R2P simply provides new, legal justifications for the use of force. International law scholarship on R2P is overwhelmingly dedicated to the question of when and how R2P might be invoked to support military intervention (jus ad bellum) and the relationship between R2P and international criminal tribunals (jus post bellum). One area that deserves attention from scholars is a “law instead of war,” or jus non bello.
U.S. Foreign Policy and Religion
Authors: Magee Malcolm
Published: November 2018

The United States has been uniquely God-centered among Western nations, and that includes its foreign policy. From George Washington to the present, all presidents and policymakers have had to consider God in varying degrees either for their domestic audience or because they believed in a version of Providential mission in the world. In the beginning, the new United States was filled with religious people whom the founders had to consider in crafting the founding documents. In time, the very idea of the United States became so entwined with the sense of the Divine that American civil religion dominated even the most secular acts of policymakers.
Mormonism and Deseret
Authors: Turner John G.
Published: November 2018

The Mormon exodus marked a new phase for a religious movement that from its inception had always set peoples in motion. The political creation of Deseret and the settlement of the Great Basin were acts of political and religious territoriality, claiming a vast swath of land for the members of the Church of Jesus Christ of Latter-day Saints. In turn, the process of settling and defending that territory transformed the spatial dimensions of Mormonism. As the Latter-day Saints gathered to a Rocky Mountain Zion, they reshaped the environment of the Great Basin, clashed with non-Mormon Americans over matters of theocracy and polygamy, and conquered native peoples. Rather than gathering to a particular city as Mormons in the eastern United States had done, the Saints now built up what they understood to be the Kingdom of God on earth. Between 1847 and the 1869 completion of the Transcontinental Railroad, thousands of Mormon emigrants crossed the plains and mountains and settled in colonies that stretched from present-day Idaho to San Bernardino. After losing a series of struggles for political and judicial control of the Utah Territory, and after publicly abandoning the principal of plural marriage, the church stopped encouraging its members to emigrate. The Mormons came to think of Zion in figurative, non-geographic terms. By abandoning the principal of gathering, moreover, the Church of Jesus Christ—especially outside of its Great Basin heartland—functioned more like the Protestant denominations against which it had long defined itself.
Islam and the Middle East in the American Imagination
Authors: Sherrard Brooke
Published: November 2018

Americans have utilized Islam as a rhetorical device for articulating various understandings of American identity from the time of the earliest Anglo-American settlers. In every period, many rejected Islam and Muslims as oppositional to American identity, accusing Islam of inherent despotism that conflicted with American liberty. Others, though, used perceived traits of Islam to critique American behaviors or focused on similarities between Islam and Christianity. Many citizens of the early American republic assumed their country was essentially Protestant, but founding figures such as Thomas Jefferson, George Washington, and James Madison indicated their support for a more inclusive polity by listing Muslims among the varieties of people they believed could be good citizens. These men meant this abstractly, as they believed there were no Muslims in the United States at the time and did not know some African slaves were Muslim.

American Protestant organizations sent missionaries around the world starting in the early 19th century, including to areas of the Middle East where the Muslim majority was legally protected from proselytization. Therefore, missionaries tended to work with native Christian populations. American missionaries, travelers, and explorers had a great interest in the Holy Land. A frequent theme in their writings was a desire to see this area reclaimed from Islamic rule. They believed the Holy Land could be regenerated through Protestant influence and often suggested Jews could be relocated there. Over time, liberal Protestants moved away from seeking conversions and became more interested in educational and medical aspects of missions. American discussions about Islam intensified again after September 11, 2001. Samuel Huntington’s “clash of civilizations” thesis argued that Western civilization and Islamic civilization were inherently incompatible. Others, like John L. Esposito and Feisal Abdul Rauf, focused on the historical and theological similarities between Christianity and Islam to suggest common ground.
Socio-Hydrology of Floods
Authors: Di Baldassarre Giuliano
Published: November 2018

Fatalities and economic losses caused by floods are dramatically increasing in many regions of the world, and there is serious concern about future flood risk given the potentially negative effects of climatic and socio-economic changes. Over the past decades, numerous socio-economic studies have explored human responses to floods—demographic, policy and institutional changes following the occurrence of extreme events. Meanwhile, many hydrological studies have investigated human influences on floods, such as changes in frequency, magnitude, and spatial distribution of floods caused by urbanization or by implementation of risk reduction measures. Research in socio-hydrology is providing initial insights into the complex dynamics of risk resulting from the interplay (both responses and influences) between floods and people. Empirical research in this field has recently shown that traditional methods for flood risk assessment cannot capture the complex dynamics of risk emerging from mutual interactions and continuous feedback mechanisms between hydrological and social processes. It has also been shown that, while risk reduction strategies built on these traditional methods often work in the short term, they might lead to unintended consequences in the longer term. Besides empirical studies, a number of socio-hydrological models have been recently proposed to conceptualize human/flood interactions, to explain the dynamics emerging from this interplay, and to explore possible future trajectories of flood risk. Understanding the interplay between floods and societies can improve our ability to interpret flood risk changes over time and contribute to developing better policies and measures that will reduce the negative impacts of floods while maintaining the benefits of hydrological variability.
Enrichment sampling for a multi-site patient survey using electronic health records and census data
Authors: Mercaldo Nathaniel D , Brothers Kyle B , Carrell David S , Clayton Ellen W , Connolly John J , Holm Ingrid A , Horowitz Carol R , Jarvik Gail P , Kitchner Terrie E , Li Rongling , McCarty Catherine A , McCormick Jennifer B , McManus Valerie D , Myers Melanie F , Pankratz Joshua J , Shrubsole Martha J , Smith Maureen E , Stallings Sarah C , Williams Janet L , Schildcrout Jonathan S
Published: November 2018

Objective

We describe a stratified sampling design that combines electronic health records (EHRs) and United States Census (USC) data to construct the sampling frame and an algorithm to enrich the sample with individuals belonging to rarer strata.

Materials and Methods

This design was developed for a multi-site survey that sought to examine patient concerns about and barriers to participating in research studies, especially among under-studied populations (eg, minorities, low educational attainment). We defined sampling strata by cross-tabulating several socio-demographic variables obtained from EHR and augmented with census-block-level USC data. We oversampled rarer and historically underrepresented subpopulations.

Results

The sampling strategy, which included USC-supplemented EHR data, led to a far more diverse sample than would have been expected under random sampling (eg, 3-, 8-, 7-, and 12-fold increase in African Americans, Asians, Hispanics and those with less than a high school degree, respectively). We observed that our EHR data tended to misclassify minority races more often than majority races, and that non-majority races, Latino ethnicity, younger adult age, lower education, and urban/suburban living were each associated with lower response rates to the mailed surveys.

Discussion

We observed substantial enrichment from rarer subpopulations. The magnitude of the enrichment depends on the accuracy of the variables that define the sampling strata and the overall response rate.

Conclusion

EHR and USC data may be used to define sampling strata that in turn may be used to enrich the final study sample. This design may be of particular interest for studies of rarer and understudied populations.
What is in the Neuromuscular Junction Literature?
Authors: Lacomis David , Puwanant Araya
Published: November 2018

This update begins with myasthenia gravis and the roles of anti-agrin and cortactin antibodies. Regarding diagnosis, a report on repeated ice pack testing is highlighted as are several reports on the close correlation of electrodiagnostic testing with clinical features and the response to treatment. The incidence of head drop and associated clinical and ventilatory features are gleaned from a retrospective study. We also discuss a study that assessed the predominantly symmetric and conjugate ocular findings in MuSK-myasthenia gravis. Other topics that are covered include quality of life and preoperative risk. We then summarize the positive treatment trials of subcutaneous immunoglobulin and eculizumab. Turning to Lambert–Eaton Myasthenic Syndrome, we report on an epidemiologic study performed on the veteran affairs population, the results of the DAPPER study of 3, 4 diaminopyridine, and look to the future for other treatment options involving calcium gating modifiers.
Cardiotoxicity of Cancer Therapies
Authors: Mondal Pratik , Jain Diwakar , Aronow Wilbert S. , Frishman William H.
Published: November 2018

Cardiotoxicity is a known complication of many cancer therapies. While the cardiotoxicity of established agents such as anthracyclines, antimetabolites, and alkylating agents is well known, it is important to realize that newer anticancer therapies such as tyrosine kinase inhibitors, angiogenesis inhibitors, and checkpoint inhibitors are also associated with significant adverse cardiovascular effects. Echocardiography, magnetic resonance imaging, and radionuclide imaging have been used to identify these complications early and prevent further consequences. We will discuss the different classes of cancer therapeutic agents that cause cardiotoxicity, the mechanisms that lead to these effects, and strategies that can be used to prevent the cardiac morbidity and mortality associated with their use.
Fatal Carbapenem Resistance Development in Pseudomonas Aeruginosa Under Meropenem Monotherapy, Caused by Mutations in the OprD Outer Membrane Porin
Authors: Fluit Ad C. , Rentenaar Rob J. , Ekkelenkamp Miquel B. , Severs Tim T. , Mavinkurve-Groothuis Annelies M. C. , Rogers Malbert R. C. , Bruin Marrie C. A. , Wolfs Tom F. W.
Published: November 2018

A 13-year old neutropenic boy succumbed to bacteremia and sepsis with a Pseudomonas aeruginosa strain that rapidly developed resistance to carbapenems during meropenem monotherapy. Whole genome sequencing of the susceptible and resistant blood culture isolates revealed the meropenem-resistant phenotype to be caused by truncation of the OprD gene, which added to a preexisting inactivated mexR gene.
Persistence of High Neutralizing Antibody Titers After Neonatal and Early Infantile Infection with Parechovirus-A3
Authors: Izumita Ryohei , Aizawa Yuta , Watanabe Kanako , Saitoh Akihiko
Published: November 2018

This 3-year follow-up study evaluated neutralizing antibody titers (NATs) against parechovirus-A3 (PeV-A3) in neonates and young infants who developed PeV-A3 infection. All children had low NATs at disease onset and high NATs after infection during infancy. At age 3 years, all 16 patients tested had high NATs (≥1:512) against PeV-A3 indicating that specific PeV-A3 NATs persist into childhood.
Epidemiology of Meningitis in Canadian Neonatal Intensive Care Units
Authors: El-Naggar Walid , Afifi Jehier , McMillan Douglas , Toye Jennifer , Ting Joseph , Yoon Eugene W. , Shah Prakesh S.
Published: November 2018

Background:

Meningitis is a serious disease that occurs more commonly in the neonatal period than in any other age group. Recent data from large national cohorts are needed to determine if the epidemiology of neonatal meningitis (NM) has changed.

Aim:

To assess the rates, causative organisms, risk factors, temporal trends and short-term outcomes of NM in Canadian Neonatal Intensive Care Units (NICUs).

Methods:

A retrospective review of newborn infants admitted to NICUs participating in the Canadian Neonatal Network between January 2010 and December 2016. Patients with meningitis were reviewed. Outcomes of patients with meningitis were compared with 1:2 matched (for gestation, sex and birth weight) neonates without meningitis.

Results:

Rates of NM ranged between 2.2 and 3.5/1000 NICU admissions during the 7-year study period with the majority of patients (87%) having late-onset meningitis (at >3 days after birth). The most common bacterial organism for both early- and late-onset meningitis was Escherichia coli followed by group B streptococci. Only 31% [95% confidence interval (CI): 24.06–38.63) of neonates with meningitis had simultaneous bacteremia. NM was associated with increased seizures [odds ratio (OR): 8.63; 95% CI: 4.73–15.7], retinopathy of prematurity (OR: 3.23; 95% CI: 1.30–8.02), bronchopulmonary dysplasia (OR: 1.93; 95% CI: 1.11–3.35), days of mechanical ventilation (OR: 1.03; 95% CI: 1.02–1.04) and length of hospital stay (OR: 1.02; 95% CI: 1.01–1.02), but not with mortality before discharge (OR: 1.29; 95% CI: 0.74–2.23).

Conclusions:

The rate of NM remains largely unchanged in Canadian NICUs. NM was associated with increased major morbidities and longer hospital stay but not with mortality before discharge.
Lithium Carbonate in a Poststroke Population
Authors: Sun Yue Ran , Herrmann Nathan , Scott Christopher J.M. , Black Sandra E. , Swartz Richard H. , Hopyan Julia , Lanctôt Krista L.
Published: November 2018

Purpose/Background

Loss of gray matter after stroke has been associated with cognitive impairment. This pilot study aimed to investigate the therapeutic potential of lithium, a putative neurotrophic agent, in the stroke recovery process within a year of stroke occurrence.

Methods

Twelve stroke patients (mean ± SD age, 71.1 ± 11.9 years) were recruited to the study, and eligible participants were prescribed open-label lithium for 60 days. Magnetic resonance imaging was used to assess global gray matter at baseline and end of treatment; global cognition was assessed using the standardized Mini-Mental State Examination and Montreal Cognitive Assessment, and verbal memory was evaluated using the Hopkins Verbal Learning Test—Revised.

Findings/Results

There was no difference in global gray matter volume between baseline and follow-up (t = 1.977, P = 0.074). There was a significant interaction between higher lithium dose and increased global gray matter volume (F = 14.25, P = 0.004) and a correlation between higher lithium dose and improved verbal memory (r = 0.576, P = 0.05).

Implications/Conclusions

Lithium pharmacotherapy may be associated with gray matter volume change and verbal memory improvement in stroke patients, providing a rationale for future trials assessing therapeutic potential of lithium in a poststroke population.
Trajectories of Depressed Mood and Anxiety During Chemotherapy for Breast Cancer
Authors: Whisenant Meagan , Wong Bob , Mitchell Sandra A. , Beck Susan L. , Mooney Kathi
Published: November 2018

Background

Women are at risk of mood disturbance during treatment for breast cancer.

Objective

The aims of this study were to identify classes of women experiencing similar trajectories of depressed mood and anxiety while receiving chemotherapy for breast cancer and to determine associated antecedents and outcomes. The specific aims were to (1) determine the distinct trajectory classes associated with severity of depressed mood and anxiety reported by women undergoing cycles 2 and 3 of chemotherapy for breast cancer, (2) determine if class membership is associated with various antecedent variables, and (3) determine if class membership is associated with days of missed work and hours spent lying down.

Methods

In a secondary analysis, classes were identified using Latent Growth Mixture Modeling. Antecedents and outcomes related to class membership were explored.

Results

Participants (n = 166; mean age, 53 [SD, 10.8] years) were mostly white (91.46%); half had early-stage disease. Two trajectories of depressed mood and anxiety were identified. Receipt of doxorubicin was associated with the higher severity class for depressed mood (P < .01) and anxiety (P = .04). No college education (P = .03) or spending more hours lying down (P = .03) was associated with the higher severity class for anxiety.

Conclusions

Distinct trajectories of mood disturbance are distinguished by baseline severity. Further study is needed to determine if biologic or genomic factors are associated with class membership.

Implications for Practice

Identification of women at risk of mood disturbance may allow clinicians to intensify symptom management. Mood disturbance early in the treatment trajectory warrants management to improve outcomes.
Correlation Between Postoperative Health-Related Quality of Life and Care Needs of Oral Cancer Patients
Authors: Wang Tze-Fang , Li Yu-Jie , Chen Lee-Chen , Chou Chyuan , Yang Su-Chen
Published: November 2018

Background

Oral cancer is the fifth most common form of cancer in Taiwan in terms of incidence and death rate and results in at least 2700 deaths each year.

Objective

The aims of this study were to assess the postoperative health-related quality of life (QOL) and care needs of oral cancer patients comprehensively and to evaluate the correlation between health-related QOL and care needs.

Interventions/Methods

This cross-sectional study enrolled 126 oral cancer patients who had received surgical treatment within the previous 2 years and were without cognitive impairment. Each patient completed a demographic questionnaire, the European Organisation for Research and Treatment of Cancer Head and Neck Cancer Quality of Life Scale, and the Short-Form Cancer Needs Questionnaire.

Results

Female patients and patients receiving 3 or more chemotherapy treatments were significantly associated with increased Short-Form Cancer Needs Questionnaire scores (higher level of care needs) (β= 0.177 and 28.49, bothP< .05) and patients receiving 3 or more chemotherapy treatments were significantly associated with increased Head and Neck Cancer Quality of Life Scale scores (higher level of symptoms and problems) (β= 27.77,P= .007). Results of stepwise multiple linear regression analysis indicated that 4 oral cancer–related symptoms and problems, “trouble with social contacts,” “swallowing problems,” “teeth problems,” and “feeling ill,” were significantly associated with higher care needs in oral cancer patients (allP≤ .05).

Conclusion

A significant correlation exists between health-related QOL and care needs.

Implications for Practice

Using a valid health-related QOL scale may help nurses determine their perceived physical and psychological care needs.
A Population Pharmacokinetic Analysis to Study the Effect of Extracorporeal Membrane Oxygenation on Cefepime Disposition in Children
Authors: Zuppa Athena F. , Zane Nicole R. , Moorthy Ganesh , Dalton Heidi J. , Abraham Alan , Reeder Ron W. , Carcillo Joseph A. , Yates Andrew R. , Meert Kathleen L. , Berg Robert A. , Sapru Anil , Mourani Peter , Notterman Daniel A. , Dean J. Michael , Gastonguay Marc R. ,   for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN)
Published: November 2018

Objectives:

Limited data exist on the effects of extracorporeal membrane oxygenation on pharmacokinetics of cefepime in critically ill pediatric patients. The objective was to describe cefepime disposition in children treated with extracorporeal membrane oxygenation using population pharmacokinetic modeling.

Design:

Multicenter, prospective observational study.

Setting:

The pediatric and cardiac ICUs of six sites of the Collaborative Pediatric Critical Care Research Network.

Patients:

Seventeen critically ill children (30 d to < 2 yr old) on extracorporeal membrane oxygenation who received cefepime as standard of care between January 4, 2014, and August 24, 2015, were enrolled.

Interventions:

None.

Measurements and Main Results:

A pharmacokinetic model was developed to evaluate cefepime disposition differences due to extracorporeal membrane oxygenation. A two-compartment model with linear elimination, weight effects on clearance, intercompartmental clearance (Q), central volume of distribution (V1), and peripheral volume of distribution (V2) adequately described the data. The typical value of clearance in this study was 7.1 mL/min (1.9 mL/min/kg0.75) for a patient weighing 5.8 kg. This value decreased by approximately 40% with the addition of renal replacement therapy. The typical value for V1 was 1,170 mL. In the setting of blood transfusions, V1 increased by over two-fold but was reduced with increasing age of the extracorporeal membrane oxygenation circuit oxygenator.

Conclusions:

Cefepime clearance was reduced in pediatric patients treated with extracorporeal membrane oxygenation compared with previously reported values in children not receiving extracorporeal membrane oxygenation. The model demonstrated that the age of the extracorporeal membrane oxygenation circuit oxygenator is inversely correlated to V1. For free cefepime, only 14 of the 19 doses (74%) demonstrated a fT_minimum inhibitory concentration of 16 mg/L, an appropriate target for the treatment of pseudomonal infections, for greater than 70% of the dosing interval. Pediatric patients on extracorporeal membrane oxygenation might benefit from the addition of therapeutic drug monitoring of cefepime to assure appropriate dosing.
Evaluating the Need for Pediatric Procedural Sedation Training in Pediatric Critical Care Medicine Fellowship*
Authors: Hooper Michael C. , Kamat Pradip P. , Couloures Kevin G.
Published: November 2018

Objectives:

Pediatric procedural sedation has been increasingly performed by pediatric intensivists over the past decade. Pediatric Critical Care Medicine fellowship guidelines do not specify how fellows obtain proficiency in pediatric procedural sedation. We sought to survey the state of pediatric procedural sedation training during fellowship and whether fellows thought it was sufficient.

Design:

A 21-question survey gathered data on pediatric procedural sedation training provided to Pediatric Critical Care Medicine fellows. Surveys were sent to fellowship directors with instructions to distribute to second- and third-year fellows or recent graduates. Over 2 months, up to three e-mail reminders were sent to fellowship directors whose program had not completed at least one survey.

Subjects:

Senior fellows and graduates of 65 active Accreditation Council for Graduate Medical Education Pediatric Critical Care Medicine fellowship programs.

Interventions:

None.

Measurements and Main Results:

Sixty-five percent of fellowship programs (42/65) returned at least one response. Ninety senior fellows and 27 recent graduates responded. Of respondents, 38% received pediatric procedural sedation training during the fellowship, and 32% reported mandatory training. Nine percent of programs used simulation. Although 61% who received training felt adequately prepared to perform pediatric procedural sedation, 25% needed additional preceptorship to sedate independently. Nearly one third (31%) reported that completion of a predetermined number of cases was required to sedate independently. Forty-eight percent reported a minimum number of cases was required for hospital credentialing. Nearly 45% were allowed to perform pediatric procedural sedation off the unit after receiving credentials. When asked if inadequate pediatric procedural sedation training would be a deterrent to applying for a position that included pediatric procedural sedation, 8.6% replied yes, 52.6% replied no, and 38.8% replied they were unsure.

Conclusions:

Pediatric procedural sedation lacks a clearly defined training pathway. Most fellows find pediatric procedural sedation a valuable skill set. We propose that all Pediatric Critical Care Medicine fellows receive training that includes pediatric procedural sedation critical incident simulation and cases performed outside the PICU to establish proficiency.
Serum Interleukin 35 Levels in Systemic Sclerosis and Relationship With Clinical Features
Authors: Yayla Müçteba Enes , Torgutalp Murat , Okatan İlyas Ercan , Yurteri Emine Uslu , Küçükşahin Orhan , Dinçer Ayşe Bahar Keleşoğlu , Gülöksüz Emine Gözde Aydemir , Sezer Serdar , Us Ebru , Turgay Tahsin Murat , Kinikli Gülay , Ateş Aşkin
Published: November 2018

Background/Objective

Interleukin (IL) 35 is a member of the IL-12 family. Studies show that IL-35 is an important anti-inflammatory cytokine and suppresses effector T-cell activity. In this study, we aimed to evaluate serum IL-35 levels in systemic sclerosis (SSc) patients and its potential relation with clinical findings.

Methods

We conducted a cross-sectional analysis of 70 SSc patients and 29 healthy volunteers in a single center in 5 months' period. Extension of skin fibrosis was evaluated by using modified Rodnan skin score. Disease severity was assessed by Medsger disease severity scores. Serum IL-35 was measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit (Cloud-Clone Corp, Wuhan, China). The relationship between IL-35 levels and clinical and laboratory parameters was investigated. Mann-Whitney U test was used to compare parameters among the groups. Correlation was tested by Spearsman correlation coefficient.

Results

Serum IL-35 levels was significantly higher in SSc patients (8.69 [interquartile range, 29.33] pg/mL) than in healthy controls (7.11 [interquartile range 7.53] pg/mL; p < 0.001). There was no significant relationship between serum IL-35 levels and organ involvement. There was a negative correlation between serum IL-35 levels and Medsger disease severity score (Rho, −0.333; p = 0.006), modified Rodnan skin score (Rho, −0.307; p = 0.010), and C-reactive protein (Rho, −0.294; p = 0.015). There was no relationship between IL-35 and disease duration and erythrocyte sedimentation rate.

Conclusions

Our study revealed that IL-35 levels were higher in SSc patients, and in contrast to previous studies, it was the first study that showed that IL-35 levels did not increase in SSc patients with pulmonary fibrosis.
CD36himonocytes play immunoregulatory roles in human umbilical cord blood
Authors: Lee Jessica G. , Jaeger Kathleen E. , Seki Yoichi , Nelson Alexander J. , Vuchkovska Alexandra , Nishimura Michael I. , White Paula , Knight Katherine L. , Iwashima Makio
Published: November 2018

The fetal and neonatal immune systems are uniquely poised to generate tolerance to self, maternal, and environmental antigens encountered in the womb and shortly after birth. The tolerogenic nature of fetal and neonatal immunity is a rising health concern with the spread of vertically transmitted viruses, such as the Zika virus. A variety of mechanisms contribute to fetal and neonatal tolerance, including a propensity to generate Foxp3+regulatory T cells (Tregs). Here, we demonstrate that a subset of CD14+monocytes expressing the scavenger molecule, CD36, is able to generate CD4+and CD8+T cells that express Foxp3 from umbilical cord blood (UCB). Monocyte-induced Foxp3+T cells have potent suppressive functions on T cell proliferation and maintain Foxp3 expression over six weeksin vitro. Importantly, UCB-derived Foxp3+T cells are distinguishable from adult peripheral blood (APB) CD4+CD25+Tregs by surface antigen expression. While UCB-derived Foxp3+T cells express prototypic Treg-associated surface antigens, such as CD25 and glucocorticoid-induced tumor necrosis factor-related receptor (GITR), only UCB-derived Foxp3+T cells express CD26. In addition, most UCB-derived CD8+Foxp3+T cells express CD31. Mechanistically, both APB and UCB-derived monocytes support the development of Foxp3+T cells from naïve T cells, but APB naïve T cells are less efficient in expressing Foxp3 than UCB naïve T cells. These data suggest that antigen presentation by CD36himonocytes in the fetus leads to the development of a group of T cells that share some but not all phenotypes of adult thymus-derived Tregs.