bluuebunny/crossref_metadata_2025 huggingface dataset:
Y a-t-il une logique à l'addiction ?
Authors: Combaz Linda
Published: March 2014

L’article s’intéresse à la notion de dépendance en tant qu’elle désigne le rapport pathologique qu’un sujet entretient avec un objet. Il livre du matériel clinique issu d’interactions entre patients et intervenants d’un groupe en addictologie. La production de ces groupes thérapeutiques offre à la réflexion un matériel verbal et graphique d’intérêt. Leur étude permet d’aborder le comportement addict sous l’angle de l’économie pulsionnelle.
Les entrepreneurs de coalition d'ONG à Bruxelles
Authors: Berny Nathalie
Published: March 2014

La fin des années 1990 a vu la multiplication d’alliances européennes entre ONG dans la capitale des institutions de l’Union européenne. Parce qu’encouragée par les institutions européennes, cette évolution reflèterait le caractère artificiel de nombre de coalitions et ONG européennes. L’objectif de cet article est de contribuer à ce débat en éclairant les ressorts en interne de l’action collective au sein de deux coalitions, composées d’ONG respectivement nationales et européennes. L’analyse fait du concept d’entrepreneur une entrée analytique pour rendre compte des conditions d’émergence et de l’évolution de ces coalitions. Il s’agit ainsi de comparer leurs logiques de mobilisation des ressources afin de cerner la marge d’action dont des ONG parviennent à jouer dans l’arène européenne.
Competence Development and Assessment Using a Game-based Strategy
Authors: Menchaca Iratxe , Rayón Alex , García-Zubía Javier , Bardinet Bénédicte , Guenaga Mariluz
Published: March 2014

This paper presents a serious game that aims to develop and assess oral and interpersonal communication competences. Based on the University of Deustoâ??s Learning model we implement a multiplayer adventure environment using HTML5 and Javascript technologies. It includes several activities; each of them covers usually more than one of the three levels of mastery described for each competence, and provides data that match indicators to evaluate studentsâ?? performance. The main challenge, assessment, is achieved integrating automatic data collected by the system and peer and self-review using standard criteria and standards described in a rubric.
Use of Long-Term Opportunistic Surveys to Estimate Trends in Abundance of Hibernating Townsend's Big-Eared Bats
Authors: Weller Theodore J. , Thomas Shawn C. , Baldwin James A.
Published: March 2014

The advent of broad-scale threats to bats such as white-nose syndrome and climate change highlights the need for reliable baseline assessment of their populations. However, few long-term, rigorously designed assessments of bat populations exist, particularly in western North America. Consequently, results of informal monitoring efforts are often the only data available upon which to base population assessments. We evaluated whether an opportunistic collection of surveys recorded over a 22-y period could be used to assess population trend of Townsend's big-eared bats (Corynorhinus townsendii) at Lava Beds National Monument in northern California. We used records of counts of hibernating bats conducted during 1991–2012 to estimate the number of bats in 52 individual caves as well as cumulatively. Seventeen of 22 caves surveyed in four or more years had an increasing trend in the number of hibernating bats. We estimated the cumulative annual growth rate over the period to be 1.79%. Stable or increasing number of hibernating Townsend's big-eared bats may be a result of management actions taken to limit disturbance of bats during maternity and hibernation seasons. We found no evidence that annual counts depressed the number of hibernating bats, thereby broadening monitoring options and the ability to link population trends to extrinsic factors. Our results demonstrate that opportunistically collected, long-term data sets may be useful for establishing first approximations of population trends for bats.
Avaliação da gestão da fauna silvestre na comunidade de São João do Tupé (Manaus, Amazonas) pelo meio de um sistema de indicadores
Authors: Marchand Guillaume Antoine
Published: March 2014

A gestão da fauna silvestre na Amazônia brasileira foi durante muito tempo uma questão esquecida. Desde o final dos anos de 1990, alguns pesquisadores e membros de ONGs ambientalistas tentam reduzir as numerosas incertezas que ainda existem em torno deste assunto. De fato, informações concretas e confiáveis ainda são raras para aspectos fundamentais como o estado dos recursos animais, a sustentabilidade da caça/pesca praticada pelas populações tradicionais ou, ainda, a eficiência das medidas de proteção das espécies ameaçadas. O presente trabalho propõe avaliar a qualidade da gestão da fauna silvestre na comunidade São João do Tupé (RDS Tupé, município de Manaus, Amazonas) pelo meio de um sistema de indicadores. Esse sistema articula-se entre quatro temas principais: o estado do habitat, o uso da fauna silvestre pelas populações locais, os fatores sociais, econômicos e culturais que podem influenciar a gestão, assim como a organização social a respeito dela. Esses quatro temas são subdivididos em 13 indicadores e 31 subindicadores simples para serem manipulados e entendidos por um público amplo. Aplicados ao campo de estudo, esses indicadores mostram que apesar dos progressos registrados na proteção do habitat, a gestão da fauna silvestre ainda continua perfectível em vários pontos, notadamente a respeito das práticas cinegéticas e pesqueiras, da sensibilização das populações locais às medidas de proteção assim como a implementação de meios de controle (plano de manejo oficial, fiscalização).
La maritimité sous les Tropiques : les contributions d’une étude réalisée à Fortaleza (Ceará)
Authors: Dantas Eustogio Wanderley Correia
Published: March 2014

À la fin du xxe siècle tout ce qui touche à la mer est devenu un véritable phénomène de société. Les images de la mer et du maritime, véhiculées dans les pays développés, associées à de changements socio-économique et technologique, suscitent la génération d’un flux qui met en évidence les espaces littoraux des pays en voie de développement. Ce genre de valorisation, fréquemment perçue d’après la notion de tropisme, apparait dans une bibliographie fort marquée par une maritimité dichotomique. D’un côté, une maritimité externe ou moderne, concernant les occidentaux. De l’autre, une maritimité interne ou traditionnelle, concernant les populations tropicales. La prise en compte de la valorisation des espaces littoraux à Fortaleza (Ceará) permet relativiser cette approche. Dans cette ville littorale, une élite locale fascinée par les nouvelles pratiques maritimes produit les mêmes territoires et entretient les mêmes désirs qu’en Occident. Principalement dans les pays peu touchés par les flux touristiques internationaux, ce phénomène de société suscite un mouvement de caractère culturel nfluencé par les mœurs occidentales, et l’on assiste à un changement de mentalité des groupes locaux face à la mer.
Periodontal Pathogens Directly Promote Autoimmune Experimental Arthritis by Inducing a TLR2- and IL-1–Driven Th17 Response
Authors: de Aquino Sabrina G. , Abdollahi-Roodsaz Shahla , Koenders Marije I. , van de Loo Fons A. J. , Pruijn Ger J. M. , Marijnissen Renoud J. , Walgreen Birgitte , Helsen Monique M. , van den Bersselaar Liduine A. , de Molon Rafael S. , Campos Mario J. Avila , Cunha Fernando Q. , Cirelli Joni A. , van den Berg Wim B.
Published: March 2014

Increasing epidemiologic evidence supports a link between periodontitis and rheumatoid arthritis. The actual involvement of periodontitis in the pathogenesis of rheumatoid arthritis and the underlying mechanisms remain, however, poorly understood. We investigated the influence of concomitant periodontitis on clinical and histopathologic characteristics of T cell–mediated experimental arthritis and evaluated modulation of type II collagen (CII)–reactive Th cell phenotype as a potential mechanism. Repeated oral inoculations of periodontal pathogens Porphyromonas gingivalis and Prevotella nigrescens induced periodontitis in mice, as evidenced by alveolar bone resorption. Interestingly, concurrent periodontitis induced by both bacteria significantly aggravated the severity of collagen-induced arthritis. Exacerbation of arthritis was characterized by increased arthritic bone erosion, whereas cartilage damage remained unaffected. Both P. gingivalis and P. nigrescens skewed the CII-specific T cell response in lymph nodes draining arthritic joints toward the Th17 phenotype without affecting Th1. Importantly, the levels of IL-17 induced by periodontal pathogens in CII-specific T cells directly correlated with the intensity of arthritic bone erosion, suggesting relevance in pathology. Furthermore, IL-17 production was significantly correlated with periodontal disease–induced IL-6 in lymph node cell cultures. The effects of the two bacteria diverged in that P. nigrescens, in contrast to P. gingivalis, suppressed the joint-protective type 2 cytokines, including IL-4. Further in vitro studies showed that the Th17 induction strongly depended on TLR2 expression on APCs and was highly promoted by IL-1. Our data provide evidence of the involvement of periodontitis in the pathogenesis of T cell–driven arthritis through induction of Ag-specific Th17 response.
Contrasted Innate Responses to Two Viruses in Zebrafish: Insights into the Ancestral Repertoire of Vertebrate IFN-Stimulated Genes
Authors: Briolat Valérie , Jouneau Luc , Carvalho Ralph , Palha Nuno , Langevin Christelle , Herbomel Philippe , Schwartz Olivier , Spaink Herman P. , Levraud Jean-Pierre , Boudinot Pierre
Published: March 2014

Ease of imaging and abundance of genetic tools make the zebrafish an attractive model host to understand host–pathogen interactions. However, basic knowledge regarding the identity of genes involved in antiviral immune responses is still lagging in this species. We conducted a microarray analysis of the larval zebrafish response to two models of RNA virus infections with very different outcomes. Chikungunya virus (CHIKV) induces a rapid and protective IFN response. Infection with infectious hematopoietic necrosis virus is lethal and is associated with a delayed and inefficient IFN response. A typical signature of IFN-stimulated genes (ISGs) was observed with both viruses, but was stronger for CHIKV. We further compared the zebrafish and human ISG repertoires and made a genomic and phylogenic characterization of the main gene families. We describe a core set of well-induced ISGs conserved across vertebrates, as well as multigenic families diversified independently in each taxon. The conservation of ISGs involved in antiviral signaling indicates conservation of the main feedback loops in these pathways. Whole-mount in situ hybridization of selected transcripts in infected larvae revealed a typical pattern of expression for ISGs in the liver, gut, and blood vessels with both viruses. We further show that some inflammatory genes were additionally induced through IFN-independent pathways by infectious hematopoietic necrosis virus and not by CHIKV. This study provides a useful reference set for the analysis of host–virus interactions in zebrafish and highlights the differences between protective and nonprotective antiviral innate responses.
HLA-DRα1 Constructs Block CD74 Expression and MIF Effects in Experimental Autoimmune Encephalomyelitis
Authors: Meza-Romero Roberto , Benedek Gil , Yu Xiaolin , Mooney Jeffery L. , Dahan Rony , Duvshani Nerri , Bucala Richard , Offner Halina , Reiter Yoram , Burrows Gregory G. , Vandenbark Arthur A.
Published: March 2014

CD74, the cell-surface form of the MHC class II invariant chain, is a key inflammatory factor that is involved in various immune-mediated diseases as part of the macrophage migration inhibitory factor (MIF) binding complex. However, little is known about the natural regulators of CD74 in this context. In order to study the role of the HLA-DR molecule in regulating CD74, we used the HLA-DRα1 domain, which was shown to bind to and downregulate CD74 on CD11b+ monocytes. We found that DRα1 directly inhibited binding of MIF to CD74 and blocked its downstream inflammatory effects in the spinal cord of mice with experimental autoimmune encephalomyelitis (EAE). Potency of the DRα1 domain could be destroyed by trypsin digestion but enhanced by addition of a peptide extension (myelin oligodendrocyte glycoprotein [MOG]-35–55 peptide) that provided secondary structure not present in DRα1. These data suggest a conformationally sensitive determinant on DRα1-MOG that is responsible for optimal binding to CD74 and antagonism of MIF effects, resulting in reduced axonal damage and reversal of ongoing clinical and histological signs of EAE. These results demonstrate natural antagonist activity of DRα1 for MIF that was strongly potentiated by the MOG peptide extension, resulting in a novel therapeutic, DRα1–MOG-35–55, that within the limitations of the EAE model may have the potential to treat autoimmune diseases such as multiple sclerosis.
Cell Depletion in Mice That Express Diphtheria Toxin Receptor under the Control of SiglecH Encompasses More Than Plasmacytoid Dendritic Cells
Authors: Swiecki Melissa , Wang Yaming , Riboldi Elena , Kim Alfred H. J. , Dzutsev Amiran , Gilfillan Susan , Vermi William , Ruedl Christiane , Trinchieri Giorgio , Colonna Marco
Published: March 2014

Plasmacytoid dendritic cells (pDC) produce IFN-I in response to viruses and are routinely identified in mice by SiglecH expression. SiglecH is a sialic acid–binding Ig-like lectin that has an immunomodulatory role during viral infections. In this study, we evaluated the impact of SiglecH deficiency on cytokine responses in the presence and absence of pDC. We found that lack of SiglecH enhanced IFN-I responses to viral infection, regardless of whether pDC were depleted. We also examined the expression pattern of SiglecH and observed that it was expressed by specialized macrophages and progenitors of classical dendritic cells and pDC. Accordingly, marginal zone macrophages and pDC precursors were eliminated in newly generated SiglecH–diphtheria toxin receptor (DTR)–transgenic (Tg) mice but not in CLEC4C-DTR–Tg mice after diphtheria toxin (DT) treatment. Using two bacterial models, we found that SiglecH-DTR–Tg mice injected with DT had altered bacterial uptake and were more susceptible to lethal Listeria monocytogenes infection than were DT-treated CLEC4C-DTR–Tg mice. Taken together, our findings suggest that lack of SiglecH may affect cytokine responses by cell types other than pDC during viral infections, perhaps by altering viral distribution or burden, and that cell depletion in SiglecH-DTR–Tg mice encompasses more than pDC.
TCR Bias and Affinity Define Two Compartments of the CD1b–Glycolipid-Specific T Cell Repertoire
Authors: Van Rhijn Ildiko , Gherardin Nicholas A. , Kasmar Anne , de Jager Wilco , Pellicci Daniel G. , Kostenko Lyudmila , Tan Li Lynn , Bhati Mugdha , Gras Stephanie , Godfrey Dale I. , Rossjohn Jamie , Moody D. Branch
Published: March 2014

Current views emphasize TCR diversity as a key feature that differentiates the group 1 (CD1a, CD1b, CD1c) and group 2 (CD1d) CD1 systems. Whereas TCR sequence motifs define CD1d-reactive NKT cells, the available data do not allow a TCR-based organization of the group 1 CD1 repertoire. The observed TCR diversity might result from donor-to-donor differences in TCR repertoire, as seen for MHC-restricted T cells. Alternatively, diversity might result from differing CD1 isoforms, Ags, and methods used to identify TCRs. Using CD1b tetramers to isolate clones recognizing the same glycolipid, we identified a previously unknown pattern of V gene usage (TRAV17, TRBV4-1) among unrelated human subjects. These TCRs are distinct from those present on NKT cells and germline-encoded mycolyl lipid–reactive T cells. Instead, they resemble the TCR of LDN5, one of the first known CD1b-reactive clones that was previously thought to illustrate the diversity of the TCR repertoire. Interdonor TCR conservation was observed in vitro and ex vivo, identifying LDN5-like T cells as a distinct T cell type. These data support TCR-based organization of the CD1b repertoire, which consists of at least two compartments that differ in TCR sequence motifs, affinity, and coreceptor expression.
Prevalence and cost of diagnosed opioid abuse in a privately insured population in the United States
Authors: Roland, PharmD Carl L. , Joshi, PhD Ashish V. , Mardekian, PhD Jack , Walden, PharmD, MBA Steven C. , Harnett, PharmD, MS James
Published: March 2014

Objective: To evaluate the prevalence, characteristics, associated healthcare resource utilization (HRU), and costs of diagnosed prescription opioid abusers (abusers) in a managed care population.Methods: Patients aged ≥12 years with a claim for opioid abuse were identified in the Thomson MarketScan Commercial and Medicare Supplemental research databases between January 1, 2005 and September 30, 2010. HRU and costs (per patient per month) were calculated for all patients with an index date (date of opioid abuse diagnosis) from October 1, 2008 to September 30, 2009 and continuous eligibility through 6 months prior to (preindex) and 12 months after (postindex) date. Abusers were matched 1:3 on demographics to nonabusers.Results: The overall prevalence of diagnosed opioid abuse was 0.195 percent during 2005-2010, with a twofold increase from 2005 to 2010. Diagnosed abuse was more prevalent in males (0.220 percent), those aged 18-25 years (0.271 percent), those from the Northeast region (0.231 percent), those with a comorbidity of pain (0.462 percent), and those with an opioid prescription (0.924 percent). A total of 15,398 abusers were matched to 46,194 nonabusers. Medical comorbidities were significantly higher (all p < 0.0001) in abusers versus nonabusers in the preindex and postindex periods. Each healthcare resource measured was significantly higher for abusers than nonabusers in the preindex and postindex periods (p < 0.0001). Total all-cause costs were higher for abusers than nonabusers in the preindex ($1,856 vs $372, respectively) and postindex ($2,138 vs $408) periods (p < 0.0001).Conclusions: Opioid abuse increased over time and abusers were associated with significantly greater HRU and costs compared with nonabusers before and after the diagnosis of abuse.Keywords: opioid abuse, prevalence, healthcare resource utilization, costDOI:10.5055/jom.2013.0158
Gastrointestinal events after opioid treatment in nonmalignant pain: Correlates of occurrence and impact on health-related quality of life
Authors: Lapane, PhD Kate L. , Quilliam, PhD Brian J. , Benson, MS Carmela , Chow, PharmD, MPH Wing , Kim, PhD, MBA Myoung S.
Published: March 2014

Background: Gastrointestinal (GI) adverse effects are common with oral opioid treatments; their impact on health-related quality of life (HRQoL) is poorly understood. Objectives: To estimate the extent to which GI adverse effects impact HRQoL.Design: 28-day prospective, multicenter, observational registry.Setting: Outpatient settings.Participants: Six hundred thirty-nine patients with acute pain (AP; n = 243) and acute episodes of chronic pain (CP; pain ≥3 months; n = 396) requiring treatment with a prescription medication containing oxycodone immediaterelease on an as-needed basis for ≥5 days.Measurements: Modified Memorial Symptom Assessment Scale; 12-item Short Form Health Survey (SF-12) Physical (PCS); and Mental Component Scales (MCS) on days 3, 7, 14, 21, and 28. Repeated measures mixed models provided estimatesof impact of GI events on HRQoL.Results: Forty-seven percent of AP patients and 24 percent of CP patients developed constipation. More AP patients than CP developed nausea (31 percent vs 19 percent). After adjustment for confounders, constipation was associated with a 3.9-point reduction in PCS and a 2.3-point reduction in MCS among AP patients (p < 0.0001). Among AP patients, nausea/vomiting was associated with a reduction in PCS (PCS = 3.2; p < 0.0001) and MCS (MCS = 2.2; p = 0.0042). Among CP patients, constipation was not associated with reductions in HRQoL, and nausea/ vomiting was associated with a reduction in MCS but not PCS (MCS = 2.4; p ≤ 0.0001).Conclusion: GI symptoms accompanying oral opioid treatment are common and negatively affect HRQoL differentially for those with AP and CP. Effective approaches for managing opioid-induced GI symptoms are warranted.Keywords: pain, gastrointestinal adverse events, ambulatory care, opioids, registryDOI:10.5055/jom.2013.0161
Undetected Ultracet™ dependence in an adolescent with nonmalignant back pain
Authors: Khan, BA Nabil A. , Sullivan, MD, PhD Maria A. , Vitale, MD, MPH Michael G. , Tresgallo, DNP, MPH, MS Mary Ellen , Saroyan, MD John M.
Published: March 2014

Addiction to painkillers or other substances in pediatric and adolescent cases of noncancer chronic pain is an understudied phenomenon, even amidst documented increases in rates of prescription opioid use and misuse. Case studies can inform the training of clinicians in ethically negotiating a balance between optimizing analgesia and mitigating risk of aberrant drug-taking behaviors. This report discusses an 18-year-old woman with idiopathic scoliosis and clinical depression secondary to undertreated refractory chronic back pain who underwent surgery to correct pseudoarthrosis after a prior spinal instrumentation operation. This intervention in conjunction with a course of patient-controlled analgesia, hydromorphone, and outpatient tramadol, naproxen, methadone, and gabapentin was successful in addressing her long-standing lumbar pain. The patient, however, continued to complain to her pain management team of postsurgical discomfort and insisted on being prescribed Ultracet™ (acetaminophentramadol) rather than generic tramadol. The patient’s eventual disclosure of severe withdrawal discomfort and history of covert abuse of Ultracet ™ is discussed with respect to key warning signs, gaps, and contingencies in the screening, surgical, and pain management processes.Keywords: adolescent, chronic pain, prescription opioid abuse, tramadolDOI:10.5055/jom.2013.0163
AUER/SEMINOLE ROCK DEFERENCE IN THE TAX COURT
Authors: Johnson Steve R.
Published: March 2014

Deference doctrines involve the extent to which courts, in their interpretation of statutes and regulations, should be influenced by how the agencies charged with administering these authorities construe them. Deference doctrine has received enormous attention in case law and commentary during the past three decades, both in tax and in administrative law.
“LET'S GET TOGETHER”: COLLABORATIVE TAX REGULATION
Authors: Cords Danshera
Published: March 2014

High school civics classes and Schoolhouse Rock! create an image of democracy and lawmaking as resting on a foundation of voter participation in the law-making process, either through the election of representatives or the casting of votes on a ballot issue. However, over time Congress has delegated to administrative agencies substantial authority to make law. As the government and society have become more complex, Congress has had to delegate much of its legislative authority to administrative agencies just to keep up with the growing need for federal regulation. Indeed, administrative agencies create many times more laws than Congress each year. These agencies are part of the Executive Branch of government. Each agency is usually created to address a single area, i.e., the Environmental Protection Area and the Federal Election Commission. Their Congressional mandate usually allows an agency to operate largely independently and allows an agency to develop specialized knowledge and technical expertise with respect to the assigned subject matter; expertise that Congress would be unable to develop in light of the very broad areas in which Federal legislation operates. To protect against agency overreaching and ensure that the lawmaking function remain democratic, administrative rulemaking procedures must be open, transparent, and accessible.
“The Confidence Placed in You Is of the Greatest Magnitude”:
Authors: Hoberman Michael
Published: March 2014

This essay examines letters from eighteenth and early nineteenth-century Jewish American fathers to their sons for insight into a nascent Jewish American literary patrimony. Father-son letters, whose subject matter clustered around four basic themes—family, business, civic affairs, and Jewish life—enable extended consideration of how the men of one generation sought, through a range of highly stylized and mostly derivative rhetorical performances, to influence their successors against the backdrop of historical change and adaptation to the changing conditions of North American life in the aftermath of the Revolutionary War. Notwithstanding their occasional use or invocation of a Hebrew word or phrase, these letters spoke in the language of and bore witness to the Anglo-American milieu from which they emerged. In other words, I don't claim them as direct markers of Jewish “difference.” Nonetheless, the eagerness with which these letters relayed the writers' strong wishes for their sons' moral development as autonomous individuals and, at the same time, imparted firm guidance for their pursuit of familial business interests prefigures a pattern that will be familiar to readers of twentieth-century Jewish American texts. The letters offer insight into how Jewish men in the early American republic attempted to uphold familial and communal interests while negotiating the larger culture's embrace of an individualistic ethos.
The First Reform Liturgy:
Authors: Wolosky Shira
Published: March 2014

Penina Moise, when discussed at all, has been placed in the context of a nineteenth-century women's domestic sphere. Her main body of work, however, is in fact specifically public and was vital and central to the development of the first Reform Jewish movement in America, in Charleston during the 1840s. Moise wrote close to two hundred hymns for this movement, the first Reform liturgy in America, shaping community worship for the next hundred years. Her hymns combine many different contemporary discourses—Jewish, republican, evangelical, and liberal theological—in ways that reflect, enact, and generate the complex identities of Jewish Americans.
Endometrial Intraepithelial Neoplasia
Authors: Owings Richard A. , Quick Charles M.
Published: March 2014

Context.—Developed in conjunction with molecular and progression data, the sequence classification schema for endometrial intraepithelial neoplasia (EIN)/benign hyperplasia (BH) provides an easy to adopt and reproducible method for classification of endometrial biopsies.

Objective.—To review current data supporting the use of BH/EIN to classify endometrial biopsies, and to discuss the hormone-driven endometrial sequence from anovulation/disordered proliferative endometrium through BH and EIN and their diagnostic difficulty.

Data Sources.—A comprehensive review of EIN literature based on literature indexed by PubMed (National Library of Medicine) and Google Scholar.

Conclusions.—The BH/EIN schema is gaining wider acceptance among pathologist and clinicians. The research leading to the EIN criteria is based on molecular and progression data. The BH/EIN schema has better reproducibility among pathologists, is intuitively easy to use, and requires understanding of endometrial physiology and neoplasia.
Genomic Alterations in Pulmonary Adenocarcinoma In Situ in an Adolescent Patient
Authors: Salomao Marcela , Levy Brynn , Nahum Odelia , Chen Jinli , Mansukhani Mahesh , Borczuk Alain C.
Published: March 2014

Lung cancer is a rare event in the pediatric and adolescent population. To date, only a few case reports and small case series have been published, and little is known about the risk factors associated with this entity in children and adolescents. We describe a case of adenocarcinoma in situ in a 15-year-old adolescent girl with previous surgical treatment for malignant melanoma. We provide a detailed genomic characterization of this neoplasm by comparative genomic hybridization, genome-wide single-nucleotide polymorphism array, and fluorescence in situ hybridization analyses. We identify chromosomal regions with copy number changes and correlate the corresponding genes within these regions with the available literature in the area.
Progress Toward Improved Leadership and Management Training in Pathology
Authors: Weiss Ronald L. , Hassell Lewis A. , Parks Eric R.
Published: March 2014

Context.—Competency gaps in leadership and laboratory management skills continue to exist between what training programs deliver and what recent graduates and future employers expect. A number of recent surveys substantiate this. Interest in delivering content in these areas is challenged by time constraints, the presence of knowledgeable faculty role models, and the necessary importance placed on diagnostic skills development, which overshadows any priority trainees have toward developing these skills.

Objective.—To describe the problem, the near-future horizon, the current solutions, and the recommendations for improving resident training in laboratory management.

Data Sources.—The demands of new health care delivery models and the value being placed on these skills by the Pathology Milestones and Next Accreditation System initiative of the Accreditation Council for Graduate Medical Education for training programs emphasizes their importance. This initiative includes 6 milestone competencies in laboratory management. Organizations like the American Society for Clinical Pathology, the American Pathology Foundation, the College of American Pathologists, and the Association of Pathology Chairs Program Directors Section recognize these competencies and are working to create new tools for training programs to deploy.

Conclusions.—It is our recommendation that (1) every training program develop a formal educational strategy for management training, (2) greater opportunity and visibility be afforded for peer-reviewed publications on management topics in mainstream pathology literature, and (3) pathology milestones–oriented tools be developed to assist program directors and their trainees in developing this necessary knowledge and skills.
The American Board of Pathology's Maintenance of Certification Program Update
Authors: Johnson Rebecca L.
Published: March 2014

Context.—The American Board of Pathology (ABP) began issuing time-limited certificates in 2006. New diplomates of the ABP are required to participate in the ABP's Maintenance of Certification (MOC) program to maintain certification. Voluntary participation in the MOC program is also available to diplomates with non–time-limited certificates.

Objective.—To update the pathology community on the requirements of the ABP's MOC program and some current MOC policies and to demonstrate the value of MOC participation for both time-limited and non–time-limited certificate holders.

Data Sources.—This review uses ABP-archived minutes of the MOC Committee, the ABP MOC Booklet of Information, the ABP Pathway system reports, and the collective experiences of the ABP trustees and staff.

Conclusions.—The ABP's MOC program has active participation by almost 5000 diplomates of the ABP. The ABP, in conjunction with the American Board of Medical Specialties, continually strives to enhance the relevance and value of MOC to our diplomates and to the public.
Selective Pathology Fellowships: Diverse, Innovative, and Valuable Subspecialty Training
Authors: Iezzoni Julia C. , Ewton April , Chévez-Barrios Patricia , Moore Stephen , Thorsen Linda M. , Naritoku Wesley Y.
Published: March 2014

Context.—Although selective pathology fellowships have a long-standing history of developing trainees with advanced expertise in specific areas of pathology other than those of the American Board of Pathology–certified subspecialties, the widespread interest in this training continues to grow.

Objective.—To describe the historical background and current status of selective pathology fellowships, and to provide examples of 3 programs. In addition, Accreditation Council for Graduate Medical Education (ACGME)–accredited programs and nonaccredited programs in Selective Pathology are compared.

Data Sources.—ACGME data banks and publicly available online materials were used. Program directors of the fellowships examples in this paper provided program-specific information. Additionally, an online survey of the program directors and program coordinators of ACGME-accredited programs and nonaccredited programs in selective pathology was performed.

Conclusions.—There are currently 76 ACGME-accredited selective pathology programs. The programs are distributed between 3 major categories: surgical pathology, focused anatomic pathology, and focused clinical pathology. Although the vast majority of programs are concerned that their funding source may be cut in the next 3 years, most programs will not change the number of fellowship positions in their programs. Program requirements devoted specifically and solely to selective pathology have been developed and are in effect. The value of this training is recognized not only by pathologists, but by clinicians as well, in both academia and private practice. Importantly, the diversity and innovation inherent in selective pathology allow these programs to adeptly address new subspecialty areas and technologic advances in the current and evolving practice of pathology.
Progressive Approval: A Proposal for a New Regulatory Pathway for Regenerative Medicine
Authors: Caplan Arnold I. , West Michael D.
Published: March 2014

To stimulate a broad discussion between academics, practicing physicians, corporate managers, and members of the regulatory community, we describe a proposal for a new regulatory pathway for human cell- and tissue-based products. The new components of the pathway are intended to accelerate patient access to a wide array of novel therapeutics, strengthen R&D infrastructure, and expand patient numbers and timelines for efficacy testing through a transparent and publicly accessible website for real-time reporting of outcome data and 5- to 10-year, long-term follow-up
Concise Review: Optimizing Expansion of Bone Marrow Mesenchymal Stem/Stromal Cells for Clinical Applications
Authors: Hoch Allison I. , Leach J. Kent
Published: March 2014

Bone marrow-derived mesenchymal stem/stromal cells (MSCs) have demonstrated success in the clinical treatment of hematopoietic pathologies and cardiovascular disease and are the focus of treating other diseases of the musculoskeletal, digestive, integumentary, and nervous systems. However, during the requisite two-dimensional (2D) expansion to achieve a clinically relevant number of cells, MSCs exhibit profound degeneration in progenitor potency. Proliferation, multilineage potential, and colony-forming efficiency are fundamental progenitor properties that are abrogated by extensive monolayer culture. To harness the robust therapeutic potential of MSCs, a consistent, rapid, and minimally detrimental expansion method is necessary. Alternative expansion efforts have exhibited promise in the ability to preserve MSC progenitor potency better than the 2D paradigm by mimicking features of the native bone marrow niche. MSCs have been successfully expanded when stimulated by growth factors, under reduced oxygen tension, and in three-dimensional bioreactors. MSC therapeutic value can be optimized for clinical applications by combining system inputs to tailor culture parameters for recapitulating the niche with probes that nondestructively monitor progenitor potency. The purpose of this review is to explore how modulations in the 2D paradigm affect MSC progenitor properties and to highlight recent efforts in alternative expansion techniques.
Concise Review: Lessons Learned From Clinical Trials of Gene Therapy in Monogenic Immunodeficiency Diseases
Authors: Williams David A. , Thrasher Adrian J.
Published: March 2014

Thirty years ago, retroviral transfer of genetic material into hematopoietic stem and progenitor cells (HSC/Ps) led to predictions that this technology would transform modern medicine [Nature 1983;305:556–558; Nature 1984;310:476–480]. Studies in several immunodeficiency diseases in the past 15 years have demonstrated clear proof of principle that gene therapy can have long-lasting, potentially curative effects without the need to search for allogeneic donors and without risk of graft-versus-host disease. Improvement in gene transfer efficiency for target HSC/Ps brought to light issues of insertional mutagenesis caused by transfer vectors, resulting in oncogene transactivation and leukemias. Lessons from these adverse events have now led to a new generation of vectors, refinements in conditioning regimens, and manufacturing, which are paving the way for expanded applications of the current technology and recent emphasis on gene targeting/genome editing as the next advancements in the field.
Cost-effectiveness of tenofovir in the treatment of patients with chronic hepatitis B: data from literature
Authors: Fasano Massimo , Colombo Giorgio L. , Di Matteo Sergio , Randazzo Claudia , Angarano Gioacchino , Santantonio Teresa Antonia
Published: March 2014

Chronic hepatitis B (CHB) is a complex disease with significant social impact both on the patients’ quality of life of and the economic resources involved. Its chronicity affects considerably not only the clinical management of the disease (for the need for drugs with proven long-term safety and low rate of resistance), but also the economic impact (for the high costs of treatment, the management of complications, and the constant monitoring of therapy).Since, as is well known, the main problem of modern health care systems is the general scarcity of available resources in the face of growing demand for health, the issue of economic evaluation of therapies for the treatment of chronic hepatitis B has been addressed in numerous national and international studies. In fact, clinicians find a strong support for the choice of the most suitable therapeutic pathway in the major scientific societies’ guidelines (European Association for the Study of The Liver – EASL, American Association for the Study of Liver Diseases – AASLD, Associazione Italiana per lo Studio del Fegato – AISF), while the analysis of the economic implications is rather more difficult, even for the methodological differences and peculiarities of the different countries.The aim of this paper is to present a brief summary of some of the recently conducted cost-effectiveness analyses and extrapolate some data to support the economic evidence related to the treatment of CHB with nucleos(t)ide analogs. In particular, the article focuses on the comparison between entecavir (ETV) and tenofovir (TDF), the two oral antiviral therapies recommended for first-line treatment. In the selected studies, the comparison between the different treatment options was conducted in order to assess the incremental cost-effectiveness ratio (ICER) and the results were expressed in terms of QALYs (Quality Adjusted Life Years) gained.Despite the methodological differences among the selected studies, tenofovir is found to be, in the context of first-line oral antiviral therapies, the most cost-effective treatment for patients with chronic hepatitis B.
Pediatric Cranio-spinal Axis Irradiation
Authors: Myers P. A. , Mavroidis P. , Komisopoulos G. , Papanikolaou N. , Stathakis S.
Published: March 2014

Pediatric cranio-spinal axis irradiation (CSI) is a valuable treatment for many central nervous system (CNS) diseases, but due to the life expectancies and quality of life expectations for children, the minimization of the risk for radiation-induced secondary malignancies must be a high priority. This study compared the estimated CSI-induced secondary malignancy risks of three radiation therapy modalities using three different models. Twenty-four ( n = 24) pediatric patients previously treated with CSI for tumors of the CNS were planned using three different treatment modalities: three-dimensional conformal radiation therapy (3D-CRT), volume modulated arc therapy (VMAT), and Tomotherapy. Each plan was designed to deliver 23.4 Gy (1.8 Gy/fraction) to the target which was defined as the entire brain and spinal column with a 0.7 cm expansion. The mean doses as well as the dose volume histograms (DVH) of specific organs were analyzed for secondary malignancy risk according to three different methods: the effective dose equivalent (EDE), the excess relative risk (ERR), and the linear quadratic (LQ) models. Using the EDE model, the average secondary risk was highest for the 3D-CRT plans (37.60%), compared to VMAT (28.05%) and Tomotherapy (27.90%). The ERR model showed similarly that the 3D-CRT plans had considerably higher risk (10.84%) than VMAT and Tomotherapy, which showed almost equal risks (7.05 and 7.07%, respectively). The LQ model requires organ-specific cell survival parameters, which for the lungs, heart, and breast relevant values were found and applied. The lung risk for secondary malignancy was found to be 1.00, 1.96, and 2.07% for 3D-CRT, VMAT, and Tomotherapy, respectively. The secondary cancer risk for breast was estimated to be 0.09, 0.21, and 0.27% and for heart it was 9.75, 6.02 and 6.29% for 3D-CRT, VMAT, and Tomotherapy, respectively. Based on three methods of secondary malignancy estimation, the 3D-CRT plans produced highest radiation-induced secondary malignancy risk, and the VMAT and Tomotherapy plans had nearly equal risk. Pediatric patients must be treated with reducing long term sequelae as a priority.
Seletividade dos herbicidas Kapina® e Kapina Plus® aplicados em fairway de grama bermuda Tifway 419
Authors: Maciel Cleber Daniel de Goes , Sapia Juliano Guilherme , Kondo Philipp Naoki Yokoyama , Benites Welinton Lucas S. , Pereira Jhonny Anderson Antunes , Birck Vanice Ester Wesz. , Silva Alexon Ferreira da
Published: March 2014

A espécie Cynodon spp. é a principal grama predominante utilizada em fairways, greens, tees e roughs de campos de golfe, mas que necessariamente requer intensa manutenção preventiva. Com objetivo de avaliar a seletividade das formulações herbicidas Kapina® e Kapina Plus® para grama Bermuda Tifway 419, em fairway de campo de golfe, um experimento foi conduzido no gramado do Maringá Golf Club. O delineamento experimental utilizado foi o de blocos casualizados, com sete tratamentos e quatro repetições, constituídos pelos herbicidas Kapina® (750, 1500 e 2250 mL ha-1), Kapina Plus® (750, 1500 e 2250 mL ha-1) e uma testemunha sem aplicação. Os herbicidas Kapina® e Kapina Plus®, a partir de 750,0 mL ha-1, apresentaram seletividade satisfatória para a grama Bermuda Tifway 419, podendo ser recomendados em fairways de campos de golfe e de outros esportes.
Curvas de dose-resposta e eficácia de herbicidas inibidores da enzima ALS aplicados em pré-emergência sobre espécies de Amaranthus
Authors: Francischini Alessandra Constantin , Oliveira Junior Rubem Silverio , Constantin Jamil , Santos Gizelly , Takano Hudson Kagueyama , Franchini Luiz Henrique Morais , Braz Guilherme Braga Pereira
Published: March 2014

Plantas daninhas do gênero Amaranthus podem causar grandes perdas de produtividade nas culturas de interesse econômico se não controladas corretamente, entre elas do algodoeiro. Para que isso não aconteça é necessário a correta identificação das espécies, além da adequação de herbicidas e doses a serem utilizadas. Assim, o objetivo deste trabalho foi desenvolver as curvas de dose-resposta de herbicidas inibidores da enzima ALS (trifloxysulfuron-sodium e pyrithiobac-sodium) aplicados em pré-emergência, afim de verificar a eficácia de controle sobre espécies de Amaranthus (A. hybridus, A. viridis, A. lividus e A. deflexus) e a diferença de suscetibilidade entre elas. Para cada herbicida foram conduzidos experimentos isolados, onde as doses utilizadas em g ha-1 foram: 0,0; 1,8; 3,7; 7,5; 15,0 e 30,0 para trifloxysulfuron-sodium e 0; 35; 70; 140; 280 e 560 para pyrithiobac-sodium, equivalentes a 0, ¼, ½, 1, 2 e 4 vezes a dose comercial recomendada para solos de textura franco-argilosa. Os resultados indicaram que as doses utilizadas nas curvas de dose-respostas de trifloxysulfuron-sodium e pyrithiobac-sodium proporcionaram controles acima de 80% para todas as espécies de Amaranthus, caracterizando a possibilidade de utilização dos herbicidas em aplicações em pré-emergência. Houve diferença de suscetibilidade entre as espécies de Amaranthus, sendo A. hybridus e A. lividus as mais suscetíveis a ambos herbicidas.
Seletividade e eficácia de herbicidas para cultura do feijão-caupi
Authors: Fontes José Roberto Antoniol , Oliveira Inocencio Junior , Gonçalves José Ricardo Pupo
Published: March 2014

O feijão-caupi é cultivado principalmente por agricultores familiares, com adoção de baixo nível tecnológico, onde o manejo de plantas daninhas é realizado com capinas, sendo cansativa e com baixo rendimento operacional. O objetivo deste trabalho foi avaliar a seletividade de herbicidas e a eficácia de controle de plantas daninhas na cultura do feijão-caupi, variedade BRS Guariba. O experimento foi conduzido à campo com aplicação dos herbicidas (g i.a. ha-1) sulfentrazone (500) e oxadiazon (600), em pré-emergência, e bentazon (600), bentazon + paraquat (39 + 62), fomesafen (225), fluazifop-p-butyl (250) e fomesafen + fluazifop-p-butyl (125 + 125), em pós-emegência, um tratamento com capina aos 20 e 34 dias após a emergência da cultura, e uma testemunha sem capina durante todo o ciclo da cultura. A aplicação do bentazon + paraquat provocou elevada fitotoxicidade no feijão-caupi, e o oxadiazon, sulfentrazone, bentazon e fluazifop-p-butyl garantiram de bom a excelente o controle das plantas daninhas, com produtividades semelhantes à obtida quando o controle foi realizado com duas capinas. O fomesafen associado ou não ao fluazifop-p-butyl provocou fitointoxicação moderada, atrasos no florescimento e colheita e redução de produtividade da cultura. A interferência de plantas daninhas durante todo o ciclo da cultura reduziu a produtividade de grãos em 42%.
Estratégias para o controle de capim-amargoso (Digitaria insularis) resistente ao glyphosate na cultura milho safrinha
Authors: Gemelli Alexandre , Oliveira Junior Rubem Silvério de , Constantin Jamil , Braz Guilherme Braga Pereira , Jumes Talita Mayara de Campos , Gheno Eliezer Antonio , Rios Fabiano Aparecido , Franchini Luiz Henrique Morais
Published: March 2014

As características de agressividade do capim-amargoso (Digitaria insularis) e a existência de biótipos resistentes ao glyphosate colocam esta planta daninha em evidência no cenário agrícola brasileiro. Neste sentido, o trabalho teve como objetivo a avaliação de estratégias para o manejo de capim-amargoso (Digitaria insularis) resistente ao glyphosate na cultura do milho safrinha. A utilização paraquat na dessecação pré-colheita da soja seguida da aplicação de clethodim dois dias após a colheita da proporcionou a maior flexibilidade para a escolha dos herbicidas utilizados em pós-emergência do milho.