Peripheral Role Research Articles

Renal transplantation in urology.

It is my pleasure to introduce the current issue of Translational Andrology and Urology with a special focus on Renal Transplantation in Urology. The role of the Urologist in transplantation is variable. In some centers such as ours, Urologists perform the surgery, manage the immunosuppression and care for post-operative complications. In other centers, Urologists have only a peripheral role, consulting for the medical and surgical complications that can follow the procedure and immunosuppression. The articles in this issue address a variety of preoperative, perioperative and postoperative issues for Urologists at every level of involvement.

Commentary: 'Ready or not here I come': developmental immaturity as a driver of impairment and referral in young-for-school-grade ADHD children. A reformulation inspired by Whitely etal. (2019).

The search for objective biological tests, sufficiently reliable, and predictive enough to be diagnostic of psychiatric disorders, continues apace - yet their discovery remains a distant dream. It seems increasingly unlikely that current diagnostic structures and concepts map biologically in a straight forward way - with heterogeneity within, and sharing across, existing diagnostic boundaries being the biological rule rather than the exception. Indeed, it now appears that the science of biological psychiatry is more likely to redraw those boundaries than it is to confirm and mark them (Sonuga-Barke, Journal of Child Psychology and Psychiatry, 2016, 57, 1). Clinical identification of childhood psychiatric disorders therefore remains, for the foreseeable future at least, an exercise in regulated social perception - reliant on the fallible and subjective judgements of parents, teachers and clinicians. Social perception of this sort is an active and motivated process and therefore prone, like all social perception, to bias and distortions - both systematic and idiosyncratic. Progress has certainly been made over the last 50years in reducing such judgement bias by, for instance filtering perceptions through the lens of standardised instruments (questionnaires and interviews) with carefully operationalised items and a degree of reliability and validity. However, such instruments often play only a peripheral role in actual diagnostic encounters and when they are used, there is still sufficient ambiguity to leave open plenty of room for interpretation. When we acknowledge that psychiatric diagnoses are social constructions - we are not saying that symptoms of inattention, impulsivity and hyperactivity are not real or do not cluster together in meaningful ways or that they do not cause real distress and disability but that their interpretation and meaning are often informed by social constructs such as ethnic or gender norms and stereotypes (Meyer, Stevenson, & Sonuga-Barke, Journal of Attention Disorders, 2019).

Abstract P5-13-16: Exploring the role of social support and adjuvant endocrine therapy use among breast cancer survivors

Abstract Background: The side-effects of adjuvant endocrine therapy treatment (AET) are one of the main reasons why women discontinue therapy. Helping women manage the side-effects may improve adherence since only half are adherent for 5-years. Generally, patients experience a decline in social support from family/friends and medical providers when beginning AET because the severity of the side effects are not as physically apparent as those associated with other cancer treatments. Therefore, the objective of this study is to explore the role of social support and identify how it is delivered during the on-going management of AET. Methods: We conducted semi-structured in-depth interviews with breast cancer patients (n=19) who had filled a prescription for AET in the previous 12 months. Women were recruited from Los Angeles, California and Houston, Texas between 2014-2015. Interviews were audio recorded and professionally transcribed. Interview questions were designed to prompt discussion about experiences with AET and examine how sources of support affect the management of AET drugs. We used an integrated approach to develop a code structure, which was applied to interview transcripts using qualitative inductive reasoning to identify major themes and subthemes. The study team met regularly, in an iterative process, to redefine the codebook by adding, removing, and revising codes to capture emerging themes. We grouped social support into four major categories to identify the sources and delivery of support: emotional, informational, instrumental, and appraisal. Results: Patients most commonly described informational support from their medical providers via consultations or phone, during which providers would explain the purpose, benefits, and side-effects of AET in a manner that they could understand. Many patients confided in their health providers when struggling with the side-effects of AET, and those who were well-received expressed trust and confidence in their physician's recommendations. Women also discussed other noteworthy sources of informational support through technology, survivorship groups, family/friends, and religious groups. Emotional support was an equally important type of social support as patients discussed the need for ongoing reassurance, communication, and empathy to help them deal with the stressors of managing their side effects, which they received from family, survivorship groups, and different forms of spirituality and religiosity but could also be delivered by medical providers. Instrumental and appraisal support played a more peripheral role as patients identified different types of organizations and exercise classes that provided them with physical and emotional benefits and that was provided by family/friends and medical providers. Conclusion: We identified all four forms of social support delivered to a group of breast cancer survivors on active AET in formal and informal settings by family/friends, medical providers, and support groups. The social support provided women with educational, physical, and emotional benefits that may play an important role in their continuation of AET. Citation Format: Toledo G, Ochoa CY, Farias AJ. Exploring the role of social support and adjuvant endocrine therapy use among breast cancer survivors [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-13-16.

Rapid Relationality: How Peripheral Experts Build a Foundation for Influence with Line Managers

This paper develops grounded theory to understand how and when experts in lower-power peripheral roles can develop influential relationships with higher-power line managers in core functions to regularly elicit their cooperation. I use data from an ethnographic study of experts in peripheral roles—mental health professionals hired by the U.S. Army to provide rehabilitative services to active-duty soldiers suffering from conditions such as post-traumatic stress disorder (PTSD)—and the line managers in core functions they depended on for their soldier-care recommendations to be followed—their soldiers’ direct commanders. I analyze relational histories of 56 commander–provider dyads and detail a three-phase process model I refer to as “rapid relationality.” Through the process of rapid relationality, mental health professionals capitalized on short windows of opportunity to quickly develop influential relationships with commanders, despite lacking formal authority over them, before a series of minor conflicts or a major conflict threatened their burgeoning influence. My analysis suggests it is not only what peripheral experts do that allows them to elicit cooperation from line managers but also when and how quickly they do it that matters. Speed and taking early action are important because experts cannot predict when conflict will occur and hence may have short initial windows of opportunity for establishing an influential relationship. I further find that some experts have fewer tactics available to them or must use more time-consuming and energy-intensive tactics than others to achieve the same relational influence based on their personal characteristics (e.g., gender). As a result, it may be harder for some experts to achieve relational influence before their window of opportunity closes.

Decreased Serum Level of Gamma-amino Butyric Acid in Egyptian Infertile Females with Polycystic Ovary Syndrome is Correlated with Dyslipidemia, Total Testosterone and 25(OH) Vitamin D Levels.

SummaryBackgroundPolycystic ovary syndrome (PCOS) is one of the most common female endocrine disorders around the world. Increasing evidence suggests that neurotransmitter Gamma-aminobutyric acid (GABA) is involved in the pathogenesis of PCOS through its central role in the hypothalamus. However, the peripheral role of GABA in PCOS has not been sufficiently investigated in spite of its existence in peripheral organs. First, the aim of this study is to, investigate serum GABA level in Egyptian PCOS patients. Second, to explore the correlation between serum GABA level with Body Mass Index (BMI), dyslipidemia, totaltestosterone and 25 (OH) vitamin D.MethodsEighty PCOS patients and eighty age-matched healthy females were included in this study. All parameters were assessed colourimetrically or with ELISA.ResultsPCOS patients exhibited significantly decreased serum GABA level compared to controls (p < 0.001). There was a significant positive correlation between serum GABA and 25(OH) vitamin D levels (r = 0.26, p = 0.018), and a significant negative correlation with total testosterone (r = - 0.3, p = 0.02), total cholesterol (TC) (r = - 0.31, p = 0.01) and LDL-Cholesterol (LDL-C) (r = - 0.23, p = 0.045), respectively.ConclusionsThe findings of this study suggest that disrupted GABA level in the peripheral circulation is an additional contributing factor to PCOS manifestations. GABA deficiency was correlated with 25 (OH) vitamin D deficiency, dyslipidemia, and total testosterone. Further investigations for GABA adjustment might provide a promising means for better management of PCOS symptoms.

The Profile of Professional Standards for Secondary School Principals in Vietnam

Gathering information on the performance of school principals and acting on the information about their effectiveness as leaders is an essential part of improving school performance. This paper reports part of the findings from an initiative conducted to sustain and improve management quality at secondary schools in Vietnam. An evaluation tool was developed based on Vietnam’s professional standards for school leaders and was used by school principals and teachers to provide more insight into their professional practices and training needs. 593 principals and 1647 teachers from 16 provinces across the eight regions of the country participated in the survey and 110 follow-up interviews were conducted. The results indicated that there were certain socio-cultural factors that conditioned the practices of Vietnamese school leaders, including demanding them to be politically, ethically and professionally fit, and to assume many peripheral roles. School principals in Vietnam generally met state standards in terms of qualifications and management expertise, and were perceived to have adequate competencies in handling school management, especially in promoting teachers’ teaching capacity and ensuring educational quality. However, Vietnamese school principals found it challenging to manage school resources and assets and to instruct teachers on leadership; areas that they have hitherto received little training in.

Andrew Jackson Donelson: Jacksonian and Unionist by Richard Douglas Spence

Reviewed by: Andrew Jackson Donelson: Jacksonian and Unionist by Richard Douglas Spence Anthony A. Repucci Andrew Jackson Donelson: Jacksonian and Unionist. Richard Douglas Spence. Nashville, TN: Vanderbilt University Press, 2017. ISBN 978-0-8265-2163-7, 448 pp., cloth, $39.95. Occasionally, individuals working in the shadows are the unsung drivers of history. Andrew Jackson Donelson is a fine biography of one of the unsung figures of the Jackson era. Richard Douglas Spence, a plant physiologist, has written a thoroughly researched, and updated biography of Andrew Jackson Donelson, the nephew and ward of President Andrew Jackson. Donelson's diverse career as a presidential advisor, diplomat, and politician placed him in the center of the critical events of the Jackson era. Spence argues that Donelson worked tirelessly to promote Jackson's vision of democracy and Union, while seeking to bridge the divisions of partisan and regional tensions that threatened to divide the country. Donelson's career "intersected many of the great events and personalities of the period … one of those [End Page 306] obscure but central figures who always seem to be at the background of history, often as a valued contributor or assistant to people in more prominent positions" (281). The book traces the major events chronologically and thematically. The first half covers the Andrew Jackson and Martin Van Buren presidencies, while the second half focuses on Donelson's career as a diplomat and politician. Early in Jackson's first term, Secretary of War John Henry Eaton's marriage to Margaret O'Neale Timberlake, the widow of a naval officer, created a perfect storm of controversy that tested the limits of Donelson's loyalty to his uncle. Washing-ton society suspected Margaret Timberlake of infidelity to her late husband. The controversy spilled over into Jackson's cabinet and family as the wives of cabinet officials and Donelson's wife, Emily, refused to receive Mrs. Eaton socially. Spence argues that Jackson's tendency to personalize political disputes fractured his cabinet and strained his relationship with Donelson. Jackson internalized the attacks on Mrs. Eaton's virtue, believing the "petticoat war" was part of a conspiracy John C. Calhoun orchestrated to undermine his presidency. Spence contends that the Eaton controversy consumed a great deal of presidential energy during Jackson's first term; altered the political dynamic of the era; marked the rise to prominence of Van Buren, who supported Eaton; and destroyed the presidential aspirations of Calhoun. Spence asserts that the petticoat war became "entangled with several major issues of Jackson's first term, and after that to a greater or lesser degree, influenced the course of contemporary national politics" (62). Following the consequent cabinet purge that resolved the controversy, Jackson relied on a network of informal advisors, his "kitchen cabinet," and Donelson performed the more mundane duties of presidential secretary, drafting letters and documents. Consequently, Donelson played a peripheral role in the major events of the Jackson presidency acting as a confidant and loyal supporter but "did little to shape Jacksonian philosophy" (65). His role as Jackson's secretary won him the respect of the period's significant political figures. His skills of discretion and tact were well suited to working behind the scenes with members of the administration and Congress. He played an active role in the disputes that split the democratic coalition in Tennessee and elevated John Bell and James K. Polk to prominence. Donelson successfully parried efforts to discredit the administration while at the same time engineering support for James K. Polk as speaker of the House, ensuring the continuation of Jacksonian policies. In 1844, President John Tyler appointed Donelson chargé d'affaires to the Republic of Texas, where he successfully superintended the treaty of annexation. Recognizing his diplomatic accomplishments, President James K. Polk named Donelson minister plenipotentiary of the United States to Prussia. The climax of Donelson's political career was his ill-fated candidacy as Millard Fillmore's American [End Page 307] Party vice presidential running mate in the election of 1856. Donelson's devotion to the Union and Jackson's legacy as its champion faced its severest test during the secession crisis of 1860–61. Torn by his devotion to the Union and loyalty to his...

Women’s Reactions to Men’s Patriarchal Oppressions in Selected Ghanaian Male and Female Novels

Social imbalances between men and women are the bedrock of injustices women encounter in the world, particularly in African societies. Patriarchy is identified by womanist and feminist scholars as one of the social practices that give men more privilege and maintain women in peripheral roles. This article examines how female characters in African patriarchal settings of two Ghanaian male and female novels, Asare Adei’s A Beautiful Daughter (2012) and Amma Darko’s The Housemaid (1998) have been able to face/cope with men’s oppressions through womanist and radical feminist theories. The findings have revealed that majority of the female characters are empowered economically and socially in the male and female fictional texts, and this has enabled them to combat men’s patriarchal oppressions. The female characters’ reactions vary from one another. Some of them made use of pacific ways such as dialogue, feminine solidarity or sisterhood in their attempts to address men’s patriarchal oppressions, while others have made use of violence against men and children in their quest for justice and equality.

Fractalkine/CX3CR1 Contributes to Endometriosis-Induced Neuropathic Pain and Mechanical Hypersensitivity in Rats.

Pain is the most severe and common symptom of endometriosis. Its underlying pathogenetic mechanism is poorly understood. Nerve sensitization is a particular research challenge, due to the limitations of general endometriosis models and sampling nerve tissue from patients. The chemokine fractalkine (FKN) has been demonstrated to play a key role in various forms of neuropathic pain, while its role in endometriotic pain is unknown. Our study was designed to explore the function of FKN in the development and maintenance of peripheral hyperalgesia and central sensitization in endometriosis using a novel endometriosis animal model developed in our laboratory. After modeling, behavioral tests were carried out and the optimal time for molecular changes was obtained. We extracted ectopic tissues and L4–6 spinal cords to detect peripheral and central roles for FKN, respectively. To assess morphologic characteristics of endometriosis-like lesions—as well as expression and location of FKN/CX3CR1—we performed H&E staining, immunostaining, and western blotting analyses. Furthermore, inhibition of FKN expression in the spinal cord was achieved by intrathecal administration of an FKN-neutralizing antibody to demonstrate its function. Our results showed that implanted autologous uterine tissue around the sciatic nerve induced endometriosis-like lesions and produced mechanical hyperalgesia and allodynia. FKN was highly expressed on macrophages, whereas its receptor CX3CR1 was overexpressed in the myelin sheath of sciatic nerve fibers. Overexpressed FKN was also observed in neurons. CX3CR1/pp38-MAPK was upregulated in activated microglia in the spinal dorsal horn. Intrathecal administration of FKN-neutralizing antibody not only reversed the established mechanical hyperalgesia and allodynia, but also inhibited the expression of CX3CR1/pp38-MAPK in activated microglia, which was essential for the persistence of central sensitization. We concluded that the FKN/CX3CR1 signaling pathway might be one of the mechanisms of peripheral hyperalgesia in endometriosis, which requires further studies. Spinal FKN is important for the development and maintenance of central sensitization in endometriosis, and it may further serve as a novel therapeutic target to relieve persistent pain associated with endometriosis.

Mitra-Mithra-Mithras: The Roman Mithras and His Indo-Iranian Background

Summary One of the key questions in the studies of the Roman cult of Mithras has been, since the works of F. Cumont, the question about the religious historical origin of the cult – regarding which there is no consensus to this day. Theories about the origin of the cult can be divided into three groups: (1) the so-called “strong” Iranian thesis, according to which the cult was imported from Iran; (2) the so-called “weak” Iranian thesis, claiming that just a few, mostly irrelevant elements of the cult originated in Iran; (3) a radical stance that there is no consistency between the Roman cult of Mithras and the Iranian cult of Mithra and what the two have in common is simply the similar name of a god. The author of this presentation has studied comparatively the character of Mitra in Indian religious literature, that of Mithra in Iranian religious and mythological texts as well as in Iranian religious iconography, and Mithras in the cult devoted to him in Rome, and has concluded that the radical belief common in current Mithras studies, according to which Mithras is connected with Mitra and Mithra only by them having similar names, is just as erroneous as the “strong” Iranian thesis defended by F. Cumont and G. Widengren. Although it is certain that the Roman cult of Mithras is not a cult imported from Iran, but a new cult that originated in the Roman Empire, the author of this presentation maintains that the Roman cult of Mithras contains a series of motifs that can be found both in the Vedas and in Iranian mythological texts: connection of Mitra/Mithras with friendship and a contract of friendship; certain military traits; connection with cosmogony and the cosmic order; connection with light, the Sun and the chariot of Sol; the role of the god as a giver of water and fertility; the idea of a sacrifice that stimulates fertility. Based on the sources linked to the Roman Mithras, in particular the iconography, it may be claimed that a large part of these motifs did not have a peripheral role in the mythology connected with the cult, but they carried an important, maybe even a central role. As the previously mentioned motifs were already interrelated in India and Iran, the author of this presentation believes that their coexistence in the mythology of the Roman cult of Mithras cannot be a coincidence but testifies to the wider Indo-Iranian background of the central figure of the cult, the god Mithras, which should not be ignored even if the Roman cult of Mithras is viewed as a new cult that evolved in the Roman Empire and within the context of the Greco-Roman religion.

Taking Divination Seriously: From Mumbo Jumbo to Worldviews and Ways of Life

The peripheral role of divination in religious studies reflects centuries of misrepresentation and depreciation in the textual record. This long history dates back to the travel literature of early modern times, particularly in West Africa, where two stereotypical themes took form: divination as mumbo jumbo, and the diviners as charlatans who shamelessly deceive their credulous clients. These two stereotypical themes persisted through the anthropological discourse about African divination until the 1970s. To undo this long history of misrepresentation and depreciation, a change of analytical focus from reified differences to similar engagement with broad ideas and big questions is in order. By considering a particular case study—basket divination in northwest Zambia—through the theoretical lens of worldviews and ways of life, it becomes possible to take divination seriously and grant it a more central place in religious studies. Four broad, inclusive ideas or big questions emerge from the ethnography of basket divination in northwest Zambia: ontology, epistemology, praxeology, and the place of suffering in human existence.

Touristische Verkehrssprachen in Dänemark

Abstract There would appear to be a significant in-balance in favour of English in tourism related areas, as is the case with most social interactions in Denmark which require the use of foreign languages. Even German only plays a peripheral role, which is somewhat surprising considering that German speakers make up the largest percentage of foreign tourists by far. However, the frequency of use of common tourism related languages in general, as well as English, would appear to vary considerably according to Danish region; hence it is worthwhile examining each region individually. Tourism degrees that include a foreign language are briefly addressed.

Involvement of central opioid receptors in protective effects of methadone on experimental colitis in rats.

There are several lines of evidence on the protective roles of opioids in gastrointestinal inflammatory conditions. This study aims to distinguish the central and peripheral roles of methadone, a non-selective opioid receptor agonist, in an acute model of ulcerative colitis in male rats. Ulcerative colitis was induced by intrarectal administration of acetic acid 4%. Methadone was injected subcutaneously (s.c.), 5 and 10mg/kg, and intracerebroventricular (i.c.v.), 50 and 300ng/rat. Opioid antagonists were employed. Methylnaltrexone (MNTX; 5mg/kg, i.p.), a peripherally acting opioid receptor antagonist, and naltrexone (NTX; 5mg/kg, i.p. and 10ng/rat, i.c.v.), a peripherally and centrally acting opioid receptor antagonist were injected before methadone (10mg/kg, s.c. and or 300ng/rat, i.c.v.) administration. NTX (5mg/kg, i.p. and 10ng/rat, i.c.v.) were administered 30min prior to administration of methadone (10mg/kg, s.c. and 300ng/rat, i.c.v.), respectively. MNTX (5mg/kg, i.p.) was injected 30min prior to methadone (10mg/kg, s.c.). Seventy-two hours following colitis induction, macroscopic and microscopic mucosal lesions, and the colonic levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) were determined. Methadone (300ng/rat, i.c.v.) and Methadone (5 and 10mg/kg, s.c.) improved the macroscopic and microscopic scores through opioid receptors. Also, a significant reduction in TNF-α and IL-1β was observed. Peripherally and centrally injected NTX significantly reversed methadone 10mg/kg s.c. anti-inflammatory effects while MNTX could not completely reverse this effect. Moreover, centrally administered methadone (300ng/rat) showed the anti-inflammatory effect which was reversed by central administration of NTX (10ng/rat). Theopioid receptors mainly the central opioid receptors maymediate the protective actions of methadone on the experimental model of inflammatory bowel disease in rat.

Becoming Parent Mediator for Performing Successful Education Integrated Model

이 연구는 교육통합모델 수행을 위한 학부모 매개자 교육과 현장에서의 실천의 과정에서 학부모들이 어떻게 진정한‘학부모 매개자’가 되어가는 가를 밝히는 데 목적이 있다. 이 연구목적을 달성하기 위해 첫째, 교육통합 모델을 실행하기 위한 학부모 매개자 교육은 어떻게 이루어지는가, 둘째, 학부모 매개자 교육 참여자들은 학교현장에서 교육통합 프로젝트를 어떻게 실천하며, 그러한 실천과정을 통해 어떻게 학부모 매개자가 되어 가는가를 밝히고자 하였다. 학부모 매개자를 위한 교육과정은 이론과정, 실습과정(타운홀 미팅, 초등학교 프로그램 참여, 참여관찰)으로 구성되어 있고, 교육과정 이수 후 교육통합모델 프로젝트에 참여하게 된다.‘학부모 매개자 되어가기’는 자신에 대해 이해하는 프로젝트 기획전사전과정(MBTI), 학생에 대해 알아가는 사전 인터뷰와 선호유형검사(MMTIC), 자신과 학생 이해를 기반으로 프로젝트 기획, 그러한 분석과 준비를 통한 교사협의회, 사전 준비과정에서 매개자들이 함께 논의하면서 실행해 보는 회차별 프로젝트 실행 사전 피드백, 회차별 실행 사후 피드백, 사후 시사회 그리고 모든 프로젝트를 마치고 아이들과 매개자가 만나는 마지막 과정인 사후인터뷰 단계를 통해 이루어진다. ‘학부모 매개자 되기’는 보살피기 어려운 아이에 대한 보살핌을 채워가는 자기 준 비이다. 다른 한편으로는 학교 현장에서 아이들을 만나기 위해 어떤 준비를 해야 하는지 묻는‘자기 물음이고, 자기 돌봄’이다. 또한 학부모 매개자 되기는 교실현장의 문제에 공동대응하여 교육의 핵심 주체로 바로 서는 것임이 확인되었다. 학부모가 교사와 공동대응 할 수 있다면 학부모의 공적역할은 교육의 변방에서 교육의 핵심주체로거듭날 수 있을 것으로 생각된다.The main purpose of this study is to explore how parents become ‘parent mediator that can implement education integration model in the process of parent mediator education and practice in the school field. Specifically, the purposes of the study are to investigate how parent mediator education for implementing the integrated model of education, and to investigate how the participants in parent mediator education practice the project of education integration model in the school field and how to become parent mediator through such a practice course. The curriculum for parental mediator is composed of theoretical course and practice course(meeting in town hall, participation in elementary school program and observation in participation) and is participated in education integrated model project after completing this curriculum.‘Becoming parental mediator’is fulfilled through pre-course before project to understand on himself(MBTI), pre-interview and preference-type check to be known on student(MMTIC), project-planning based on understanding himself and children, teacher-council through such a analysis and readiness, pre-feedback for practice by time to be discussed and practiced jointly among mediators participated in pre-readiness course, post-feedback for practicing a project by time and post-interview step as a final course to meet with children and mediator after finishing all the courses. The results show that becoming a parent mediator is self-readiness to fill care for a child who is difficult to care for. On the other hand, it is ‘self-questioning,’ and ‘self-care process that the participants asks themselves what to prepare for meeting children. Also, becoming a parent mediator means he or she is positioned as a subject that respond jointly with the teachers to the problems in the classroom. If the parents can cooperate with the teachers, the public role of the parents can be changed from a peripheral role to a core role in education.

Developers’ Progression from Periphery to Core in the Linux Kernel Development Project

To coordinate activities between developers, open source software (OSS) communities assign roles of lateral authority to some developers. Prior research has mainly described the characteristics of and functional roles within these virtual organizations, but few have examined which community members take on roles of lateral authority, or investigated what drives the progression of developers from peripheral roles to core roles. We develop and test a theoretical framework, which explains developers’ pace of progression from periphery to core through technical contributions and communication activity. Our approach differs from prior research by highlighting the moderating role of developers’ focus regarding their community engagement. Using unique longitudinal data from the Linux kernel development project, our results suggest that the positive influence of technical contributions is negatively moderated when developers make broad, rather than focused, contributions to different subsystems. Conversely, the positive effect of communication activity is amplified the more developers engage in conversations on different topics and the more they respond to the queries of other community members. Our findings contribute to research on lateral governance in OSS communities, and to the more general debate on the benefits of specialization.

Cachexia-associated adipose loss induced by tumor-secreted leukemia inhibitory factor is counterbalanced by decreased leptin.

Cachexia syndrome consists of adipose and muscle loss, often despite normal food intake. We hypothesized that cachexia-associated adipose wasting is driven in part by tumor humoral factors that induce adipocyte lipolysis. We developed an assay to purify secreted factors from a cachexia-inducing colon cancer line that increases lipolysis in adipocytes and identified leukemia inhibitory factor (LIF) by mass spectrometry. Recombinant LIF induced lipolysis in vitro. Peripheral LIF administered to mice caused >50% loss of adipose tissue and >10% reduction in body weight despite only transient hypophagia due to decreasing leptin. LIF-injected mice lacking leptin (ob/ob) resulted in persistent hypophagia and loss of adipose tissue and body weight. LIF's peripheral role of initiating lipolysis in adipose loss was confirmed in pair-fed ob/ob mouse studies. Our studies demonstrate that (a) LIF is a tumor-secreted factor that promotes cachexia-like adipose loss when administered peripherally, (b) LIF directly induces adipocyte lipolysis, (c) LIF has the ability to sustain adipose and body weight loss through an equal combination of peripheral and central contributions, and (d) LIF's central effect is counterbalanced by decreased leptin signaling, providing insight into cachexia's wasting, despite normophagia.

Adipose Tissue Expression of PACAP, VIP, and Their Receptors in Response to Cold Stress

Obesity arises from disrupted energy balance and is caused by chronically higher energy intake compared to expenditure via basal metabolic rate, exercise, and thermogenesis. The brown adipose tissue (BAT), the primary thermogenic organ, has received considerable attention as a potential therapeutic target due to its ability to burn lipids in the production of heat. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been identified as a key regulator of the physiological stress response both centrally and peripherally. While PACAP has been shown to increase thermogenesis by acting at the hypothalamus to increase sympathetic output to BAT, a peripheral role for PACAP-activated thermogenesis has not been studied. We identified PACAP receptor (PAC1, VPAC1/2) expression for the first time in murine BAT and confirmed their expression in white adipose tissues. PAC1 receptor expression was significantly altered in all three adipose tissues studied in response to 3.5-week cold acclimation, with expression patterns differing by depot type. In primary cell culture, VPAC1 was increased in differentiated compared to non-differentiated brown adipocytes, and the same trend was observed for the PACAP-specific receptor PAC1 in gonadal white fat primary cultures. The primary PAC1R mRNA splice variant in interscapular BAT was determined as isoform 2 by RNA-Seq. These results show that PACAP receptors are present in adipose tissues and may have important functional roles in adipocyte differentiation, lipid metabolism, or adipose sensitization to sympathetic signaling in response to thermogenic stimuli.

Trace Amines and Their Receptors.

Trace amines are endogenous compounds classically regarded as comprising β-phenylethyalmine, p-tyramine, tryptamine, p-octopamine, and some of their metabolites. They are also abundant in common foodstuffs and can be produced and degraded by the constitutive microbiota. The ability to use trace amines has arisen at least twice during evolution, with distinct receptor families present in invertebrates and vertebrates. The term "trace amine" was coined to reflect the low tissue levels in mammals; however, invertebrates have relatively high levels where they function like mammalian adrenergic systems, involved in "fight-or-flight" responses. Vertebrates express a family of receptors termed trace amine-associated receptors (TAARs). Humans possess six functional isoforms (TAAR1, TAAR2, TAAR5, TAAR6, TAAR8, and TAAR9), whereas some fish species express over 100. With the exception of TAAR1, TAARs are expressed in olfactory epithelium neurons, where they detect diverse ethological signals including predators, spoiled food, migratory cues, and pheromones. Outside the olfactory system, TAAR1 is the most thoroughly studied and has both central and peripheral roles. In the brain, TAAR1 acts as a rheostat of dopaminergic, glutamatergic, and serotonergic neurotransmission and has been identified as a novel therapeutic target for schizophrenia, depression, and addiction. In the periphery, TAAR1 regulates nutrient-induced hormone secretion, suggesting its potential as a novel therapeutic target for diabetes and obesity. TAAR1 may also regulate immune responses by regulating leukocyte differentiation and activation. This article provides a comprehensive review of the current state of knowledge of the evolution, physiologic functions, pharmacology, molecular mechanisms, and therapeutic potential of trace amines and their receptors in vertebrates and invertebrates.

Peripheral Melanocortin 3 Receptor (MC3R) Regulates Hepatic Autophagy in Obesity

We have previously reported homozygosity for two MC3R SNPs (C17A+G241A) that partially inactive MC3R increases adiposity in humans and mouse models. However, the precise mechanisms by which hypoactive MC3R alters metabolic homeostasis remain unclear. Given the essential role of hepatic autophagy in cellular mechanisms of obesity, we hypothesized that diminished peripheral MC3R activity leads to hepatic lipid accumulation by interfering with autophagy, leading to steatosis. We used knock-in mouse models that carry either homozygous human “wild type” (MC3RhWT/hWT) or “double mutant” MC3R (C17A+G241A, MC3RhDM/hDM). We studied hepatic autophagic pathways with biochemical/imaging analysis in wild type Mc3r (C57/BL6) and MC3RhWT/hWT as controls (WT mice), and in MC3RhDM/hDM, and mice lacking Mc3r (Mc3r-/-) which each have greater fat mass and hepatic triglycerides. We first demonstrated the MC3R specific agonist D-trp-γ-MSH induced LC3II (a marker of autophagosome formation) in hepatocytes from WT, but not Mc3r-/- or MC3RhDM/hDM mice. Interestingly D-trp-γ-MSH also induced TFEB (a master regulator of lysosomal biogenesis) translocation from cytosol to nucleus in TFEB-overexpressed NIH-3T3 cells, indicating MC3R may regulate autophagy by affecting TFEB signaling. Overnight fasting induced liver LC3II expression in WT mice, but not in MC3RhDM/hDM or Mc3r-/-; rather, basal LC3II was upregulated even in the fed state for the latter two genotypes. Hepatocytes from MC3RhDM/hDM or Mc3r-/- failed to increase autophagic flux with starvation or with the presence of chloroquine, suggesting MC3R may play a role in the regulation of autolysosomal degradation under the control of TFEB. Electron microscopy analysis of liver sections further demonstrated MC3RhDM/hDM mice exhibited fewer lipid droplet-associated autophagosomes compared to MC3RhWT/hWT mice. These data suggest MC3R plays an important peripheral role for the regulation of hepatic autophagy that is targeted to lipids. Disclosure J. Jun: None. A.Y. Seo: None. T.P. Patel: None. A.J. Uhlman: None. N.J. Levi: None. R. Roberson: None. J.A. Yanovski: Research Support; Self; Rhythm Pharmaceuticals Inc., Zafgen.

Parental experiences of family-centred care from admission to discharge in the neonatal intensive care unit.

It has been increasingly recognised that family-centred care (FCC) is associated with enhanced well-being for both parents and infants in paediatric settings, including the neonatal intensive care unit (NICU). Over the past 4 years, our NICU has increasingly adopted a collaborative philosophy of care. The purpose of the study was to examine parental experiences of FCC during both the admission and discharge time points in order to examine differences in parents' experiences and identify areas for improvement. We conducted interviews at two time points (admission and discharge) with 83 parents (mothers and fathers) of premature and medically fragile infants and analysed the data using thematic analysis. Three key themes (and sub-themes) were identified: disempowerment, hierarchy between parents and staff and the father's peripheral role. The themes were equally prevalent across admission and discharge. The challenges relating to FCC reported by parents at both admission and discharge represent some of the key barriers that parents still face in terms of being truly involved in the care of their infant in the NICU. Similar themes at both time points suggest that parents need equal amounts of support during their stay in NICU, irrespective of the level of care the infant is receiving and whether they are approaching discharge. Implications for improving FCC more generally are discussed.