bluuebunny/crossref_metadata_2025 huggingface dataset:
Transnational Movements
Authors: Wilson Janet
Published: June 2018

The post-World War II period saw the increased migration of non-anglophone Europeans and Asians to Canada, Australia, and New Zealand, resulting in the formation of hybridized diasporic communities that by the 1990s necessitated a revised rhetoric of nationhood. The chapter also examines the development of a Pacific literature and the concept of a ‘new Oceania’ founded on transformation of the past and ‘free from the taint of colonialism’, and transcending colonial patterns of regional and local identity. It discusses fiction writing in Australia, Canada, New Zealand, and the South Pacific by immigrant writers after World War II and the Vietnam War, followed by immigrants fleeing from violence in Sri Lanka, Cambodia, the Philippines, and Malaysia. Finally, it looks at the emergence of a new generation of ethnically hybridized, culturally mobile writers who attempt to move beyond diasporic binaries to tackle issues of race, language, and belonging from transnational perspectives in an era marked by changes in publishing practices in a global literary marketplace.
Modernist Fiction/Alternative Modernisms
Authors: Lang Anouk
Published: June 2018

This chapter examines the history of modernist fiction in Australia, New Zealand, and Canada within the larger context of geomodernist scholarship. It first considers how modernism relates to modernity and modernization before discussing cultural nationalism and the debate between the ‘native’ and the ‘cosmopolitan’. It then analyses boundary-troubling between realism and modernism, James Joyce's influence on fiction writers, and the works of Indigenous writers that force a reconsideration of modernism. It also explores the publishing infrastructure of modernist fiction production as well as the dialectical move between imitation and subversion as seen in Australian, New Zealand, and Canadian literatures. Finally, it provides additional contexts through which to understand how material conditions such as the availability of publication outlets shape the ways in which literary movements develop and gather momentum.
Postmodernist and Literary Experiments
Authors: Kuttainen Victoria , Manning Greg
Published: June 2018

This chapter examines postmodernist and literary experiments in Australia, Canada, New Zealand, and the South Pacific. It first considers Australia's brand of postmodernism, noting that it was much less a reaction to modernism than an effect of American influences that developed mid-century and a reflection on its late emergence from the colonial condition. It shows that Australian literature and its institutions since the 1930s had maintained a distant and uncomfortable relationship with literary modernism. Key writers discussed include Peter Carey, Gerald Murnane, and Elizabeth Jolley. The chapter goes on to discuss how Canada's scholars and writers, such as Robert Kroetsch, George Bowering and Daphne Marlatt have been interwoven in the genealogy of postmodern fiction in the Americas before concluding with an analysis of the postmodern novel in New Zealand and the South Pacific. Important writers here include Ian Wedde, Albert Wendt, and Sia Figiel.
Major Authors: Christina Stead, Patrick White, David Malouf
Authors: Harris Margaret
Published: June 2018

This chapter examines the work of three Australian novelists who are read in the context of modernism, introducing a new dimension for the exploration of individual and national identity. David Malouf defines his Old and New World cultural heritage in a significant body of non-fiction prose, encompassing memoir and cultural commentary, along with reviews and interviews, that runs in tandem with his fiction. His intense literary self-consciousness is manifest in an extended mythology of place and history that emerges in his writing, such as Johnno (1975) and Remembering Babylon (1993). Patrick White's spiritual evocation of Australian landscape is evident from his first novel Happy Valley (1934) through The Tree of Man (1956) and Voss (1957), while issues of the construction of gender and identity are explicit in his memoir Flaws in the Glass: A Self-Portrait (1981) and the posthumously published The Hanging Garden (2012). Christina Stead's later international career, initiated by the republication in 1965 of The Man Who Loved Children (1940) followed by For Love Alone (1944), reveals her radical modernist techniques, her radical politics, and her focus on gender issues, particularly her concern with women artists, ending with the posthumous publication of I'm Dying Laughing: the Humourist (1986).
The Indigenous Australian Novel
Authors: Minter Peter , Wheeler Belinda
Published: June 2018

The history of the Indigenous Australian novel begins in the second half of the twentieth century and can be traced to the traditions of the Aboriginal and Torres Strait Islander peoples of Australia. The Indigenous novel combines elements of the oral and performance traditions of classical Indigenous cultures with one of Western modernity's central narrative forms. The traditions of storytelling and poetic narration that underpin the Indigenous novel have always occupied a central place in the cultural expression of Indigenous peoples. The chapter considers Indigenous Australian novels published in four different periods: before and during the mid-1970s, 1978–1987, 1988–2000, and 2000 to the present. These include David Unaipon's (Ngarrindjeri) My Life Story (1954), Shirley Perry Smith's (Wiradjuri) Mum Shirl: An Autobiography (1981), Ruby Langford Ginibi's Don't Take Your Love to Town (1988), Kim Scott's Benang (2000), and Alexis Wright's Carpentaria (2006).
Multicultural and Transnational Novels
Authors: Morris Robyn
Published: June 2018

In Australia, the issue of multiculturalism has been the subject of considerable debate. This tension has been captured by and reflected in the reception of the strong but constantly evolving tradition of Australian multicultural writing. The controversy centres on who can speak for whom, claims of the appropriation and commodification of multicultural writing by publishers and academia, and the multicultural novel's relationship to — and place within — Australian literature. The chapter considers the rise of Australian multicultural and contemporary transnational literature since the 1950s and its connection to political and cultural ideologies. In particular, it examines how autobiographical reflections or fictional accounts of the experience of migration have influenced public discourse on issues of citizenship and belonging. A number of such works are cited, including Antigone Kefala's The Island (1984), Christos Tsiolkas's Loaded (1995), and Adib Khan's Spiral Road (2007).
Indigenous Pacific Fiction in English
Authors: Winduo Steven
Published: June 2018

This chapter examines the first wave of Indigenous Pacific novels written in English, which dates back to around 1955 and culminates in 1980 with the publication of Albert Wendt's edition, Lali: A Pacific Anthology. The period's ideals are summed up in Wendt's 1976 essay, ‘Towards A New Oceania’: ‘The new Pacific literature examines (and laments), often angrily, the effects of colonialism...’. Representing the social and cultural experiences of Islanders from the inside was the project, with the aim ‘to liberate and understand themselves in the rapidly changing world of decolonization’. The chapter first considers examples of early Indigenous writing before discussing the work of Indigenous Pacific fiction writers such as Wendt, Tom Davis and his wife Lydia Anderson Davis, Vincent Eri, and Patricia Grace. It also explores the role of the South Pacific Creative Arts Society in promoting the first generation work by Indigenous Pacific writers.
Indigenous Pacific Fiction in English
Authors: Prasad Mohit
Published: June 2018

This chapter examines the ‘niu wave’ of Indigenous Pacific novels written in English. The ‘new wave’ of South Pacific fiction was marked by the appearance of Albert Wendt's second anthology, Nuanua (1995), by new theorizing such as Epeli Hauʻofa's essay ‘Our Sea of Islands’ in A New Oceania (1993), and by the academic recognition of Pacific writing in collections of critical commentary such as Paul Sharrad's Reading Pacific Literature (1993). Two works by Regis Stella, Imagining the Other: The Representation of the Papua New Guinean Subject (2006) and Unfolding Petals: Readings in Modern PNG Literature (2012), have returned writing from the western Pacific to a more visible place in the region's culture. The chapter considers examples of the ‘niu wave’ and an expanded pan-Pacific awareness, including Rexford T. Orotaloa's Two Times Resurrection (1985), Sam Lidimani Alasia's Fata'abu: the voice of God (2003), Russell Soaba's Maiba (1985), and Celestine Hitiura Vaite's Breadfruit and Frangipani (2004).
Global Health Problems
Authors: Prah Ruger Jennifer
Published: June 2018

Serious health threats confront humankind. Unconscionable inequalities consign many millions to inadequate health care or no care at all, to a life of destitution and early death. Globalization has accelerated the spread of dangerous contagions at an unprecedented pace. Cross-border issues raise questions about who can receive medical treatment and where, at what cost. These health failures are morally arbitrary, dependent on accidents of birth or nationality, or simply the misfortune of sitting near an infected air traveler. They prod our collective conscience and present compelling moral imperatives. This chapter introduces global health challenges and asserts the need for a normative theoretical framework to undergird effective solutions.
An Alternative Account
Authors: Prah Ruger Jennifer
Published: June 2018

The world community clearly needs a moral orientation to assess and reshape the global health architecture; it needs a moral compass to determine the best way forward. It needs a comprehensive theory of global health and a governance structure to effectuate it. Such a theory would enable analysis and evaluation of the current global health system; it would ground proposals, ethically and empirically, to reform global health and align the global system more closely with moral values. This chapter sets out the foundational components of a global health justice theory, arguing for universal ethical norms with shared global and domestic responsibility for health. It offers a global minimalist view, provincial globalism, as a mean between nationalism and cosmopolitanism, in which a provincial consensus accompanies a global consensus on health morality.
WHO and Other United Nations Agencies
Authors: Prah Ruger Jennifer
Published: June 2018

WHO’s establishment in 1948 marked a new era, and “Health for All” became the hope. For decades, WHO was prominent in GHG, coordinating worldwide efforts against smallpox, handling international reporting, and managing disease outbreaks through the IHR. Still today, the world community expects WHO to solve global health governance problems, and maintain its unique coordinating function. It is the only agency with authority to develop and implement international health law. But today’s WHO is a weakened institution, riddled with budgetary problems, power politics, and diminished reputation. WHO’s failings in the 2014 West African Ebola outbreak demonstrated that it lacks the capacity to prevent and contain pandemics. Nor does it have coordination capacity, accountability, a master global health plan, or reliable compliance mechanisms. WHO’s vision of “Health for All” remains unfulfilled. Other UN agencies have important health functions but present vexing issues of their own.
The World Bank and Other Organizations
Authors: Prah Ruger Jennifer
Published: June 2018

Since its founding in 1944, the World Bank’s development priorities and approach—along with its global role—have changed from rebuilding Europe to relieving poverty in the developing world. New thinking and evidence have reshaped both development views and the Bank’s practices and decisions. The Bank has been the largest financier of health, nutrition, and population (HNP) programs in developing countries. It has expanded operational research and analysis, including its Special Programme of Research, Development and Research Training in Human Reproduction, WHO/United Nations Development Program (UNDP)/UNICEF/World Bank Special Programme for Research and Training in Tropical Diseases, and the Micronutrient Initiative. But the Bank’s main advantage in global health is its power to mobilize financial resources. Its broad expansion of HNP funding through loans and credits is striking and has the potential to be a powerful force for health governance. The G8, G20, and other economic organizations also have roles to play.
Models of Personality Development in Emerging Adulthood
Authors: Pratt Michael W. , Matsuba M. Kyle
Published: June 2018

Chapter 2 reviews research and theory on the life story and its development and relations to other aspects of personality. The authors introduce the integrative framework of McAdams and Pals, who described three levels in a broad model of personality: personality traits; personal goals, values, and projects; and the unique life story, which provides a degree of unity and purpose to the individual’s life. This narrative, which develops in late adolescence and emerging adulthood, as individuals become able to author their own stories, includes key scenes of emotional and personal importance to provide a sense of continuity, while remaining flexible and dynamic in incorporating changes in the self over time. The chapter ends with a description of Alison, an emerging adult from our Canadian Futures Study, who illustrates these levels and what they tell about personality development during this period.
Religious and Spiritual Development in Emerging Adulthood
Authors: Pratt Michael W. , Matsuba M. Kyle
Published: June 2018

Chapter 4 is the first of a series of seven chapters on particular topics/domains of everyday life. It focuses on the development of religion and spirituality, and explores the complex similarities and differences between these two related but distinct topics. The authors briefly overview these questions and then trace the literature on the relations between the three levels of personality development in the McAdams and Pals model and both religion and spirituality in emerging adulthood. Both quantitative and narrative analyses on these topics in the Futures Study are then presented, drawing on illustrative cases from the study. As a way of illustrating the key concepts from this religion chapter, the authors end with a case study of a contemporary religious icon, Pope Francis, focusing on personality development in his emerging adulthood.
Parent and Grandparent Relationships in Emerging Adulthood
Authors: Pratt Michael W. , Matsuba M. Kyle
Published: June 2018

Chapter 7 begins with an overview of Erikson’s ideas about intimacy and its place in the life cycle, followed by a summary of Bowlby and Ainsworth’s attachment theory framework and its relation to family development. The authors review existing longitudinal research on the development of family relationships in adolescence and emerging adulthood, focusing on evidence with regard to links to McAdams and Pals’ personality model. They discuss the evidence, both questionnaire and narrative, from the Futures Study data set on family relationships, including emerging adults’ relations with parents and, separately, with grandparents, as well as their anticipations of their own parenthood. As a way of illustrating the key personality concepts from this family chapter, the authors end with a case study of Jane Fonda in youth and her father, Henry Fonda, to illustrate these issues through the lives of a 20th-century Hollywood dynasty of actors.
Advancing Nursing Education: BSN Completion Messaging Materials for Associate Degree Program Nursing Faculty
Authors: Moody Linda , Teel Cynthia , Peltzer Jill
Published: June 2018

AIM

This project developed a comprehensive set of bachelor of science in nursing (BSN) completion messaging materials that associate degree in nursing (ADN) faculty can use to advise and encourage students to complete the BSN.

BACKGROUND

The Future of Nursing report calls for increasing the proportion of baccalaureate-prepared nurses to 80 percent by 2020. Faculty who teach in ADN programs have opportunities to advise students in advancing their nursing education yet often lack information to guide these conversations.

METHOD

After development of BSN completion messaging materials, the products were evaluated by faculty from two Kansas ADN programs.

RESULTS

ADN faculty positively evaluated the format and content of the messaging materials. They appreciated having a variety of customizable resources to share with students in group and individual sessions.

CONCLUSION

Next steps include disseminating the messaging materials to ADN programs and practice-based nursing leaders to guide education conversations about academic progression of ADN-prepared nurses.
Baccalaureate Nursing Students’ Perceptions of the Use of a Facebook Case Study as a Teaching Strategy
Authors: Ross Jennifer Gunberg , Beckmann Brittany , Goumas Christina
Published: June 2018

The millennial generation shows a strong preference for informatics and technology-rich educational environments. The purpose of this descriptive, qualitative study was to understand baccalaureate nursing students’ perceptions of the use of Facebook as a platform to present patient case study data. After following a simulated patient on Facebook and developing a teaching plan based on data collected from the patient’s Facebook page, undergraduate nursing students completed a survey to determine their perceptions of this teaching strategy. Five categories that emerged from the qualitative data were realism, relatability, engagement, uniqueness, and desire for expansion.
The human papilloma vaccine
Authors: Hardwicke Robin L. , Benjamins Laura J. , Grimes Richard M.
Published: June 2018

The human papilloma virus (HPV) causes approximately 30,700 annual cancer cases of the cervix, vulva, vagina, penis, oral cavity, and anus. Nurse practitioners can use their unique relationships with patients to advocate for the HPV vaccine. The purpose of this article is to update NPs on current knowledge regarding the HPV vaccine while providing appropriate information necessary for counseling patients and parents.
Mothers' Emotional Experiences Providing Care for Their Infants Within the Culture of an Iranian Neonatal Unit
Authors: Jabraeili Mahnaz , Hassankhani Hadi , Negarandeh Reza , Abbaszadeh Mohammad , Cleveland Lisa M.
Published: June 2018

Background:

Each year, 5% to 8% of Iranian newborns require care in a neonatal unit (NU). Reasons for admission include prematurity, infection, and congenital anomalies. Little research has been conducted on the culture of Iranian NUs and the impact this has on mothers' emotional caregiving experiences.

Purpose:

To explore the emotional caregiving experiences of mothers in an Iranian NU.

Methods:

Focused ethnography was used for this study. Mothers (n = 19) of term and preterm infants participated. Data were collected using observations and interviews. Roper and Shapira's 5-step framework was used to analyze the data.

Findings:

Four major themes emerged: (a) fear, (b) loneliness, (c) competence, and (d) pleasure. Fear occurred when mothers felt unprepared to care for their infants. They were afraid of harming their infant or repeating previous mistakes. Loneliness consisted of bearing the burden of care while feeling alone. Competence occurred when the mothers experienced an increasing ability to provide care for their infants and a growing self-confidence. Finally, the mothers described pleasure as they began to feel worthiness as mothers and intense love for their infants.

Implications for Practice:

The sense of fear and loneliness shared by these mothers has significant implications for practice. While it may be a challenge for nurses to provide adequate support for mothers due to the heavy workload of Iranian NUs, close relatives and other support persons may play a key role.

Implications for Research:

Future research should be conducted on the impact of maternal support on mothers' NU experiences in Iran.
ALK Rearrangements Are Infrequent in Cellular Blue Nevus and Deep Penetrating Nevus
Authors: Dunn Andrew L. J. , Gardner Jerad M. , Kaley Jennifer R. , Bellamy William , Shalin Sara C.
Published: June 2018

Recent studies have identified kinase fusions in Spitzoid melanocytic neoplasms, and approximately 10% of Spitzoid neoplasms harbor anaplastic lymphoma kinase (ALK) rearrangements and corresponding ALK immunoreactivity. Deep penetrating nevi (DPN), a subset of melanocytic neoplasms, have histologic and immunohistochemical overlap that have historically supported classification of DPN with blue/cellular blue nevi (CBN). However, HRAS mutations have rarely been detected in DPN, thereby also linking them to Spitz nevi. The purpose of this study was to see if DPN or CBN possess ALK rearrangements, thereby providing more evidence that these melanocytic lesions may be pathogenetically related to Spitzoid neoplasms. Using ALK immunohistochemistry as a surrogate for ALK rearrangement, the authors examined 26 DPN, 30 CBN, and 4 conventional blue nevi. ALK immunoreactive cases underwent fluorescent in situ hybridization to investigate for the presence of ALK gene rearrangement. Patchy and focal ALK immunostaining was found in only 1 case of DPN (1/26, 3.8%). Seven cases of CBN (7/30; 23%) showed ALK immunostaining (6 focal/patchy, 1 strong and diffuse). Fluorescent in situ hybridization using ALK break-apart probes showed various degrees of gain of 2p23 and rare ALK break-apart signals. Four CBN showed ALK rearrangement in 2%–4% of cells. Two cases of CBN showed gain of 2p23 in 10%–20% of cells. In our study, ALK rearrangements are uncommon in both CBN and DPN, making ALK an unlikely driver in tumorigenesis and classification of these melanocytic variants. However, our study did identify ALK molecular changes and immunohistochemical staining patterns that have not been previously described in CBN or DPN.
Spatial variations in the estimated production of reactive oxygen species in the epithelial lung lining fluid by iron and copper in fine particulate air pollution
Authors: Weichenthal Scott , Shekarrizfard Maryam , Kulka Ryan , Lakey Pascale S. J. , Al-Rijleh Kenan , Anowar Sabreena , Shiraiwa Manabu , Hatzopoulou Marianne
Published: June 2018

Background:

Certain metals may play an important role in the adverse health effects of fine particulate air pollution (PM2.5), but few models are available to predict spatial variations in these pollutants.

Methods:

We conducted large-scale air monitoring campaigns during summer 2016 and winter 2017 in Toronto, Canada, to characterize spatial variations in iron (Fe) and copper (Cu) concentrations in PM2.5. Information on Fe and Cu concentrations at each site was paired with a kinetic multilayer model of surface and bulk chemistry in the lung epithelial lining fluid to estimate the possible impact of these metals on the production of reactive oxygen species (ROS) in exposed populations. Land use data around each monitoring site were used to develop predictive models for Fe, Cu, and their estimated combined impact on ROS generation.

Results:

Spatial variations in Fe, Cu, and ROS greatly exceeded that of PM2.5 mass concentrations. In addition, Fe, Cu, and estimated ROS concentrations were 15, 18, and 9 times higher during summer compared with winter with little difference observed for PM2.5. In leave-one-out cross-validation procedures, final multivariable models explained the majority of spatial variations in annual mean Fe (R
2 = 0.68), Cu (R
2 =0.79), and ROS (R
2 = 0.65).

Conclusions:

The combined use of PM2.5 metals data with a kinetic multilayer model of surface and bulk chemistry in the human lung epithelial lining fluid may offer a novel means of estimating PM2.5 health impacts beyond simple mass concentrations.
Microglial P2X4R-evoked pain hypersensitivity is sexually dimorphic in rats
Authors: Mapplebeck Josiane C.S. , Dalgarno Rebecca , Tu YuShan , Moriarty Orla , Beggs Simon , Kwok Charlie H.T. , Halievski Katherine , Assi Sofia , Mogil Jeffrey S. , Trang Tuan , Salter Michael W.
Published: June 2018

Microglia–neuron signalling in the spinal cord is a key mediator of mechanical allodynia caused by peripheral nerve injury. We recently reported sex differences in microglia in pain signalling in mice: spinal mechanisms underlying nerve injury–induced allodynia are microglial dependent in male but not female mice. Whether this sex difference in pain hypersensitivity mechanisms is conserved in other species is unknown. Here, we show that in rats, the spinal mechanisms of nerve injury–induced hypersensitivity in males differ from those in females, with microglial P2X4 receptors (P2X4Rs) being a key point of divergence. In rats, nerve injury produced comparable allodynia and reactive microgliosis in both sexes. However, inhibiting microglia in the spinal cord reversed allodynia in male rats but not female rats. In addition, pharmacological blockade of P2X4Rs, by an intrathecally administered antagonist, attenuated pain hypersensitivity in male rats only. Consistent with the behavioural findings, nerve injury increased cell surface expression and function of P2X4Rs in acutely isolated spinal microglia from male rats but not from female rats. Moreover, in microglia cultured from male rats, but not in those from female rats, stimulating P2X4Rs drove intracellular signalling through p38 mitogen-activated protein kinase. Furthermore, chromatin immunoprecipitation–qPCR revealed that the transcription factor IRF5 differentially binds to the P2rx4 promoter region in female rats vs male rats. Finally, mechanical allodynia was produced in otherwise naive rats by intrathecally administering P2X4R-stimulated microglia from male rats but not those from female rats. Together, our findings demonstrate the existence of sexually dimorphic pain signalling in rats, suggesting that this sex difference is evolutionarily conserved, at least across rodent species.
Short article: Hepatitis delta in patients with resolved hepatitis B virus infection
Authors: Aguilera Antonio , Rodríguez-Calviño Javier , de Mendoza Carmen , Soriano Vincent
Published: June 2018

Background

The hepatitis delta virus (HDV) causes the most aggressive form of chronic viral hepatitis. As HDV replication requires hepatitis B virus (HBV), HDV screening is limited to HBsAg+ carriers. To date, individuals with HDV-antibodies and markers of resolved hepatitis B are considered cured. However, a subset shows elevated liver enzymes and hepatic fibrosis. Could they represent HBsAg-seronegative occult HDV infections?

Methods

We tested for HDV-antibodies 406 individuals with markers of past HBV exposure.

Results

Overall, 20 (4.9%) were reactive for HDV-antibodies. All were negative for serum HDV-RNA, including four with elevated liver enzymes.

Conclusion

These results support the current policy of screening for hepatitis delta only in HBsAg+ individuals.
Secondary Surgery following Initial Replantation/Revascularization or Completion Amputation in the Hand or Digits
Authors: Chinta Malini S. , Wilkens Suzanne C. , Vlot Margot A. , Chen Neal C. , Eberlin Kyle R.
Published: June 2018

Background:

The authors studied the rate of secondary surgery following replantation/revascularization or completion amputation in patients with traumatic upper extremity injuries. The authors hypothesized that there are no factors associated with secondary surgery after initial treatment and that travel distance to the authors’ hospital does not influence the number of secondary operations.

Methods:

A multi-institutional retrospective study was performed including patients presenting from 2006 to 2014. The authors included 1254 patients and calculated the incidence of secondary surgery following initial operative management. The authors performed multivariable regression analysis to determine factors associated with secondary surgery and ordinal logistic regression tested the association of living at a further distance (>50 miles) and having zero, one, or multiple secondary operations.

Results:

The rate of secondary surgery was 25 percent for all patients: 51 percent following replantation/revascularization and 22 percent following completion amputation. The authors observed a trend for lower rate of secondary surgery over time among patients who underwent completion amputation. The mean number of secondary operations was 1.2 after replantation/revascularization versus 0.45 operations after completion amputation. Avulsion and multiple-digit injuries were associated with higher odds and Hispanic race was associated with lower odds of secondary surgery. Patients living more than 50 miles from the hospital had a higher likelihood of undergoing one or multiple secondary operations.

Conclusions:

Twenty-five percent of patients with traumatic, dysvascular digital injuries underwent secondary surgery following initial revascularization or completion amputation. Patients undergoing initial revascularization or replantation were more than twice as likely to undergo secondary surgery compared with those undergoing completion amputation.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Living Donation of Vascularized Composite Allografts
Authors: Pomahac Bohdan , Alhefzi Muayyad , Bueno Ericka M. , McDiarmid Sue V. , Levin L. Scott
Published: June 2018

Living donation has become a medically and ethically accepted practice in solid organ transplantation. Published proceedings from the international kidney transplant community and from the Ethics Committee of The Transplantation Society articulated the general principles and specific recommendations for living donation, which remain the backbone of Centers for Medicare and Medicaid Services and Organ Procurement and Transplantation Network requirements and policies. Meanwhile, there have been major advancements in another revolutionary field of transplant medicine: vascularized composite allotransplantation. Recent interventions have demonstrated potential for superior functional and aesthetic outcomes in a single operation when compared to staged conventional reconstructions. In view of these successes, the indications for vascularized composite allotransplantation are expected to broaden to include less extensive types of transplants, which would introduce the possibility of using living vascularized composite allotransplantation donors. In this article, the authors discuss the feasibility and ethics associated with living donation of vascularized composite allografts. The authors explore the current guidelines and policies set by the Organ Procurement and Transplantation Network regarding living organ donation. In addition, the authors provide several clinical scenarios in which living donation of vascularized composite allotransplantation could be used to augment the reconstructive ladder currently used by reconstructive surgeons to guide their reconstructive strategies.
The Mitochondria-Targeted H2S-Donor AP39 in a Murine Model of Combined Hemorrhagic Shock and Blunt Chest Trauma
Authors: Wepler Martin , Merz Tamara , Wachter Ulrich , Vogt Josef , Calzia Enrico , Scheuerle Angelika , Möller Peter , Gröger Michael , Kress Sandra , Fink Marina , Lukaschewski Britta , Rumm Grégoire , Stahl Bettina , Georgieff Michael , Huber-Lang Markus , Torregrossa Roberta , Whiteman Matthew , McCook Oscar , Radermacher Peter , Hartmann Clair
Published: June 2018

Hemorrhagic shock (HS) accounts for 30% to 40% of trauma-induced mortality, which is due to multi-organ-failure subsequent to systemic hyper-inflammation, triggered by hypoxemia and tissue ischemia. The slow-releasing, mitochondria-targeted H2S donor AP39 exerted beneficial effects in several models of ischemia-reperfusion injury and acute inflammation. Therefore, we tested the effects of AP39-treatment in a murine model of combined blunt chest trauma (TxT) and HS with subsequent resuscitation.

Methods:

After blast wave-induced TxT or sham procedure, anesthetized and instrumented mice underwent 1 h of hemorrhage followed by 4 h of resuscitation comprising an i.v. bolus injection of 100 or 10 nmol kg−1 AP39 or vehicle, retransfusion of shed blood, fluid resuscitation, and norepinephrine. Lung mechanics and gas exchange were assessed together with hemodynamics, metabolism, and acid-base status. Blood and tissue samples were analyzed for cytokine and chemokine levels, western blot, immunohistochemistry, mitochondrial oxygen consumption (JO2), and histological changes.

Results:

High dose AP39 attenuated systemic inflammation and reduced the expression of inducible nitric oxide synthase (iNOS) and IκBα expression in lung tissue. In the combined trauma group (TxT + HS), animals treated with high dose AP39 presented with the lowest mean arterial pressure and thus highest norepinephrine requirements and higher mortality. Low dose AP39 had no effects on hemodynamics, leading to unchanged norepinephrine requirements and mortality rates.

Conclusion:

AP39 is a systemic anti-inflammatory agent. In our model of trauma with HS, there may be a narrow dosing and timing window due to its potent vasodilatory properties, which might result in or contribute to aggravation of circulatory shock-related hypotension.
Safety and Effectiveness of Fingolimod in Real-World Multiple Sclerosis Portuguese Patients
Authors: Ribeiro de Barros Ariana Helena , Fiadeiro Sequeira João Paulo , Lopes de Sousa Ary Severino , Cheganças Capela Carlos Miguel , Gomes Pedrosa Rui Manuel , dos Santos Manita Manuel Alexandre
Published: June 2018

Objectives

The aim of this study was to evaluate postmarketing fingolimod safety and effectiveness in a real-world clinical population.

Methods

This was a retrospective, single-center study with active multiple sclerosis patients treated with fingolimod with at least 12 months of follow-up. Demographic and clinical and imaging characteristics, including annualized relapse rate (ARR), Expanded Disability Status Score, previous treatment, adverse events, treatment duration, and reason for discontinuation, were analyzed.

Results

Sixty-three patients were included; 61.9% were females. Mean age and mean disease duration were 30.9 ± 9.3 years and 11.4 ± 6.9 years, respectively. Fifty-one patients received prior first-line disease-modifying therapies, 11 patients were previously treated with natalizumab, and 1 was treatment naive. The ARR decreased by 75.3% for the total population at the end of the first year of treatment (P < 0.0001). The proportion of relapse-free patients improved significantly. All patients previously treated with natalizumab switched because of safety concerns, although the ARR kept low after treatment initiation. Only 3 patients (4.8%) discontinued treatment because of adverse drug reactions, and 2 (3.2%) because of lack of effectiveness.

Conclusions

In this real-world audit, fingolimod appeared to be effective after first-line treatment failure in reducing disease activity and progression of disability throughout the observational period and may be an effective option after natalizumab. Fingolimod was well tolerated with low rates of discontinuation and adverse events.
Defining Inflammatory Cell States in Rheumatoid Arthritis Joint Synovial Tissues by Integrating Single-cell Transcriptomics and Mass Cytometry
Authors: Zhang Fan , Wei Kevin , Slowikowski Kamil , Fonseka Chamith Y. , Rao Deepak A. , Kelly Stephen , Goodman Susan M. , Tabechian Darren , Hughes Laura B. , Salomon-Escoto Karen , Watts Gerald F. M. , Apruzzese William , Lieb David J. , Boyle David L. , Mandelin Arthur M. ,   Accelerating Medicines Partnership: RA Phase 1, AMP RA/SLE, Boyce Brendan F. , DiCarlo Edward , Gravallese Ellen M. , Gregersen Peter K. , Moreland Larry , Firestein Gary S. , Hacohen Nir , Nusbaum Chad , Lederer James A. , Perlman Harris , Pitzalis Costantino , Filer Andrew , Holers V. Michael , Bykerk Vivian P. , Donlin Laura T. , Anolik Jennifer H. , Brenner Michael B. , Raychaudhuri Soumya
Published: June 2018

To define the cell populations in rheumatoid arthritis (RA) driving joint inflammation, we applied single-cell RNA-seq (scRNA-seq), mass cytometry, bulk RNA-seq, and flow cytometry to sorted T cells, B cells, monocytes, and fibroblasts from 51 synovial tissue RA and osteoarthritis (OA) patient samples. Utilizing an integrated computational strategy based on canonical correlation analysis to 5,452 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics together revealed cell states expanded in RA synovia: THY1+HLAhigh sublining fibroblasts (OR=33.8), IL1B+ pro-inflammatory monocytes (OR=7.8), CD11c+T-bet+ autoimmune-associated B cells (OR=5.7), and PD-1+Tph/Tfh (OR=3.0). We also defined CD8+ T cell subsets characterized by GZMK+, GZMB+, and GNLY+ expression. Using bulk and single-cell data, we mapped inflammatory mediators to source cell populations, for example attributing IL6 production to THY1+HLAhigh fibroblasts and naïve B cells, and IL1B to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.
Automatic vegetation identification in Google Earth images using a convolutional neural network: A case study for Japanese bamboo forests
Authors: Watanabe Shuntaro , Sumi Kazuaki , Ise Takeshi
Published: June 2018

Classifying and mapping vegetation are very important tasks in environmental science and natural resource management. However, these tasks are not easy because conventional methods such as field surveys are highly labor intensive. Automatic identification of target objects from visual data is one of the most promising ways to reduce the costs for vegetation mapping. Although deep learning has become a new solution for image recognition and classification recently, in general, detection of ambiguous objects such as vegetation still is considered difficult. In this paper, we investigated the potential for adapting the chopped picture method, a recently described protocol for deep learning, to detect plant communities in Google Earth images. We selected bamboo forests as the target. We obtained Google Earth images from three regions in Japan. By applying the deep convolutional neural network, the model successfully learned the features of bamboo forests in Google Earth images, and the best trained model correctly detected 97% of the targets. Our results show that identification accuracy strongly depends on the image resolution and the quality of training data. Our results also highlight that deep learning and the chopped picture method can potentially become a powerful tool for high accuracy automated detection and mapping of vegetation.
Potential impacts of transport infrastructure and traffic on bird conservation in Swedish Special Protection Areas
Authors: Helldin Jan Olof
Published: June 2018

The ecological impacts of roads and railways extend into the surrounding landscape, leading to habitat degradation and reduced animal densities within an area that is considerably larger than the actual road or railway corridor. For birds, an extensive meta-analysis has pointed at an average of 20% density reduction within 1 km from the infrastructure. I investigated to what extent this density reduction could potentially compromise the habitat quality and conservation value of Swedish Natura 2000 areas designated for the protection of birds (Special Protection Areas; SPAs). A majority (63%) of Swedish SPAs are at least to some extent found within this 1 km potential effect zone. The total overlap between SPA and effect zone is 126,000 ha, or 4.2% of the country’s SPA area. There are however large differences among biogeographical regions. In the southern (continental) and coastal regions combined, 25.8% of the total SPA area fall within the effect zone, representing an estimated 4-7% reduction in bird abundance within SPAs. The probability of overlap with effect zone is higher for larger SPAs. However, the proportion of overlap is higher for smaller SPAs, and accordingly smaller sites can be assumed to experience a greater impact from transport infrastructure and traffic. The impacts on Natura 2000 sites are particularly concerning as this network of protected areas is a cornerstone to maintain and restore biodiversity within EU. I recommend putting a stronger emphasis in the management of Natura 2000 sites on the potential threats to wildlife conservation caused by transport infrastructure and traffic. Special attention should be paid in sites with a large overlap with the effect zone, and in sites hosting particularly vulnerable taxa or habitats. Infrastructure owners and managers should do their best to minimize and compensate for the negative impacts of roads and railways and related traffic in SPAs and other protected areas.
Epigenetic analysis identifies factors driving racial disparity in prostate cancer
Authors: Rai Richa , Yadav Shalini S , Pan Heng , O’Connor James , Alshalalfa Mohamed , Davicioni Elai , Taioli Emanuela , Elemento Olivier , Tewari Ashutosh K , Yadav Kamlesh K
Published: June 2018

Prostate cancer (PCa) is the second most leading cause of death in men worldwide. African American men (AA) represent more aggressive form of PCa as compared to Caucasian (CA) counterparts. Evidence suggests that genetic and other biological factors could account for the observed racial disparity. We analyzed the cancer genome atlas (TCGA) dataset (2015) for existing epigenetic variation in AA and CA prostate cancer patients, and carried out Reduced Representation Bisulphite Sequencing (RRBS) analysis to identify global methylation changes in AA and CA prostate cancer patients. The TCGA dataset analysis revealed that the epigenetic heterogeneity could be categorized into 4 classes, where AA associated primarily to methylation cluster 1 (p value 0.048), and CA associated to methylation cluster 3 (p value 0.000146). We identified enrichment of Wnt signaling genes in both AA and CA, however they were differentially activated in terms of canonical and non-canonical Wnt signaling pathway activation. This was further validated using the GenomeDx expression data. Our RRBS data also suggested distinct methylation patterns in AA compared to CA, and in part validated our TCGA findings. Survival analysis using the RRBS data suggested hypomethylated genes to be significantly associated with recurrence of prostate cancer in CA (p=6.07×10−6) as well as in AA (p=0.0077). Overall, the observed racial disparity in the molecular mechanism involved in the pathogenesis of prostate cancer suggests diverse heterogeneity that potentially could affect survival and should be considered during prognosis and treatment.
Brain Connectivity Tracks Effects of Chemotherapy Separately from Behavioral Measures
Authors: Kardan Omid , Askren Mary K. , Jung Misook , Peltier Scott , Misic Bratislav , Churchill Nathan W. , Reuter-Lorenz Patricia A. , Cimprich Bernadine , Berman Marc G.
Published: June 2018

Several studies in cancer research have suggested that cognitive dysfunction following chemotherapy, referred to in lay terms as “chemobrain”, is a serious problem. At present, the changes in integrative brain function that underlie such dysfunction remains poorly understood. Recent developments in neuroimaging suggest that patterns of functional connectivity can provide a broadly applicable neuromarker of cognitive performance and other psychometric measures. The current study used multivariate analysis methods to identify patterns of disruption in resting state functional connectivity of the brain due to chemotherapy and the degree to which the disruptions can be linked to behavioral measures of distress and cognitive performance. Sixty two women (22 healthy control, 18 patients treated with adjuvant chemotherapy, and 22 treated without chemotherapy) were evaluated with neurocognitive measures followed by self-report questionnaires and open eyes resting-state fMRI scanning at three time points: diagnosis (M0, pre-adjuvant treatment), at least 1 month (M1), and 7 months (M7) after treatment. The results indicated deficits in cognitive health of breast cancer patients immediately after chemotherapy that improved over time. This psychological trajectory was paralleled by a disruption and later recovery of resting-state functional connectivity, mostly in the parietal and frontal brain regions. The functional connectivity alteration pattern seems to be a separable treatment symptom from the decreased cognitive health. More targeted support for patients should be developed to ameliorate these multi-faceted side effects of chemotherapy treatment on neural functioning and cognitive health.
Fbxo2VHCmouse and embryonic stem cell reporter lines delineatein vitro-generated inner ear sensory epithelia cells and enable otic lineage selection and Cre-recombination
Authors: Hartman Byron H. , Böscke Robert , Ellwanger Daniel C. , Keymeulen Sawa , Scheibinger Mirko , Heller Stefan
Published: June 2018

While the mouse has been a productive model for inner ear studies, the lack of highly specific genes and tools have presented challenges, specifically forin vitrostudies of otic development, where innate cellular heterogeneity and disorganization increase the reliance on lineage-specific markers. To address this challenge in mice and embryonic stem (ES) cells, we targeted the lineage-specific otic geneFbxo2with a multicistronic reporter cassette (Venus/Hygro/CreER = VHC). In otic organoids derived from ES cells,Fbxo2VHCspecifically delineates otic progenitors and inner ear sensory epithelia. In mice, Venus expression and CreER activity reveal a cochlear developmental gradient, label the prosensory lineage, show enrichment in a subset of type I vestibular hair cells, and expose strong expression in adult cerebellar granule cells. We provide a toolbox of multiple spectrally distinct reporter combinations to the community for studies that require use of fluorescent reporters, hygromycin selection, and conditional Cre-mediated recombination.

SUMMARY STATEMENT

A multifunctionalFbxo2-targeted reporter in mice and stem cells was developed and characterized as a resource for inner ear studies, along with a toolbox of plasmids to facilitate the use of this technique for other users.
Endolysosomal degradation of Tau and its role in glucocorticoid-driven hippocampal malfunction
Authors: Vaz-Silva João , Zhu Mei , Jin Qi , Zhuravleva Viktoriya , Gomes Patrícia , Quintremil Sebastian , Meira Torcato , Silva Joana , Dioli Chrysoula , Soares-Cunha Carina , Daskalakis Nikolaos P. , Sousa Nuno , Sotiropoulos Ioannis , Waites Clarissa L
Published: June 2018

Emerging studies implicate Tau as an essential mediator of neuronal atrophy and cognitive impairment in Alzheimer’s disease (AD), yet the factors that precipitate Tau dysfunction in AD are poorly understood. Chronic environmental stress and elevated glucocorticoids (GC), the major stress hormones, are associated with increased risk of AD, and have been shown to trigger intracellular Tau accumulation and downstream Tau-dependent neuronal dysfunction. However, the mechanisms through which stress and GC disrupt Tau clearance and degradation in neurons remain unclear. Here, we demonstrate that Tau undergoes degradation via endolysosomal sorting in a pathway requiring the small GTPase Rab35 and the endosomal sorting complex required for transport (ESCRT) machinery. Furthermore, we find that GC impair Tau degradation by decreasing Rab35 levels, and that AAV-mediated expression of Rab35 in the hippocampus rescues GC-induced Tau accumulation and related neurostructural deficits. These studies indicate that the Rab35/ESCRT pathway is essential for Tau clearance and part of the mechanism through which GC precipitate brain pathology.