bluuebunny/crossref_metadata_2025 huggingface dataset:
RPE65 has an additional function as the lutein to
meso
-zeaxanthin isomerase in the vertebrate eye
Authors: Shyam Rajalekshmy , Gorusupudi Aruna , Nelson Kelly , Horvath Martin P. , Bernstein Paul S.
Published: September 2017

Significance

Carotenoids are plant-derived pigment molecules that cannot be synthesized de novo by higher organisms. These physiologically relevant compounds function as potent antioxidants and light screening compounds, and their supplementation has been shown to ameliorate the progression of such diseases as age-related macular degeneration. Hundreds of carotenoids are present in the plant world, but the primate macula contains only three: lutein, zeaxanthin, and
meso
-zeaxanthin. The presence of
meso
-zeaxanthin in the foveal region of primates is an unexplained phenomenon, given its lack of dietary sources. We show that RPE65 is responsible for the conversion of lutein to
meso
-zeaxanthin in vertebrates, a unique role for RPE65 in carotenoid metabolism beyond its well-known retinoid isomerohydrolase function in the vertebrate visual cycle.
Investigation of the mechanism of the SpnF-catalyzed [4+2]-cycloaddition reaction in the biosynthesis of spinosyn A
Authors: Jeon Byung-sun , Ruszczycky Mark W. , Russell William K. , Lin Geng-Min , Kim Namho , Choi Sei-hyun , Wang Shao-An , Liu Yung-nan , Patrick John W. , Russell David H. , Liu Hung-wen
Published: September 2017

Significance

Computational and structural studies of putative Diels–Alderases and the reactions that they catalyze have provided testable models of the reaction coordinates and mechanisms of catalysis; however, there has yet to be a direct experimental interrogation of these hypotheses. Herein, theα-secondary deuterium kinetic isotope effects at all sites of rehybridization on the nonenzymatic and SpnF-catalyzed [4+2]-cycloaddition during biosynthesis of spinosyn A are reported. Results implicate an intermediary state between formation of the first and second carbon–carbon bonds and provide evidence that conformational restriction of the substrate may play a role in catalysis.
A chloroplast thylakoid lumen protein is required for proper photosynthetic acclimation of plants under fluctuating light environments
Authors: Liu Jun , Last Robert L.
Published: September 2017

Significance

Photosynthesis harnesses sunlight to assimilate carbon dioxide and produce biomass essential for life on earth. Photosystem integrity and activity are negatively impacted by fluctuations in incident light from the sun. How plants regulate photosynthetic dynamics under natural fluctuating growth light is relatively poorly understood. Loss of the
Arabidopsis thaliana
chloroplast lumenal protein MPH2 causes photosystem II (PSII) repair deficiency under changing light. PSII repair mutants are impaired in growth under greenhouse fluctuating light environments, while photoprotection mutants grow normally. These findings inform strategies for engineering plant photosynthetic performance under field conditions, to sustainably address increasing needs for food, fiber, and fuel at a time of changing climate and rapid population growth.
Cadherin complexes recruit mRNAs and RISC to regulate epithelial cell signaling
Authors: Kourtidis Antonis , Necela Brian , Lin Wan-Hsin , Lu Ruifeng , Feathers Ryan W. , Asmann Yan W. , Thompson E. Aubrey , Anastasiadis Panos Z.
Published: September 2017

Cumulative evidence demonstrates that most RNAs exhibit specific subcellular distribution. However, the mechanisms regulating this phenomenon and its functional consequences are still under investigation. Here, we reveal that cadherin complexes at the apical zonula adherens (ZA) of epithelial adherens junctions recruit the core components of the RNA-induced silencing complex (RISC) Ago2, GW182, and PABPC1, as well as a set of 522 messenger RNAs (mRNAs) and 28 mature microRNAs (miRNAs or miRs), via PLEKHA7. Top canonical pathways represented by these mRNAs include Wnt/β-catenin, TGF-β, and stem cell signaling. We specifically demonstrate the presence and silencing of MYC, JUN, and SOX2 mRNAs by miR-24 and miR-200c at the ZA. PLEKHA7 knockdown dissociates RISC from the ZA, decreases loading of the ZA-associated mRNAs and miRNAs to Ago2, and results in a corresponding increase of MYC, JUN, and SOX2 protein expression. The present work reveals a mechanism that directly links junction integrity to the silencing of a set of mRNAs that critically affect epithelial homeostasis.
Electoral Systems and Constituency Service
Authors: Crisp Brian F. , Simoneau William M.
Published: September 2017

Constituency service, addressing the nonpolicy grievances of constituents or looking out for their nonpolicy interests, provides legislators an opportunity to enhance their personal reputations. Electoral incentives are the primary explanation suggested for the amount of constituency service carried out by representatives. Variation in electoral rules, such as ballot type and district magnitude, can increase personal vote-seeking incentives, increasing the utility of constituency service as a means of winning re-election. In our opinion, measures of constituency service remain underdeveloped, and while there is widespread agreement on electoral incentives as the key determinant of constituency service, the consequences of constituency service remain elusive.
Electoral Systems and Roles in the Legislative Arena
Authors: André Audrey , Depauw Sam
Published: September 2017

Do electoral systems impact the roles that elected representatives play in the legislative arena? Despite the concept’s long pedigree in legislative studies, evidence of an association between the electoral institutions and the role orientations adopted by legislators is hard to come by. After detailing what are roles in the legislative arena and reviewing the state of the literature, we explore three possible reasons—critically re-examining the utility of the role concept. After approaching representational roles from the common perspective of the representatives, we turn to the perspective of their principals in the chain of delegation. Only very recently has a literature on citizens’ expectations regarding the representative relationship started to develop, albeit in isolation.
Latent Variable Modeling of Person-Situation Data
Authors: Geiser Christian , Hintz Fred A. , Burns G. Leonard , Servera Mateu
Published: September 2017

The chapter provides a comprehensive overview of classical approaches and recent advances in the latent variable modeling of person-situation data. It begins by reviewing the key concepts of latent state-trait (LST) theory (Steyer, Ferring & Schmitt, 1992; Steyer, Mayer, Geiser, & Cole, 2015), which is a measurement theory for measuring persons in situations. Subsequently, it discusses basic LST models for measuring (1) variability processes, (2) trait changes, and (3) method effects. The chapter presents a real data application of these basic models and subsequently discusses extensions of LST models to more complex designs for studying interaction effects between persons, situations, and methods, as well as models for categorical data and latent classes. The goal is to provide researchers with a systematic review of available models that can be applied to address substantive questions in single- and multimethod person-situation research.
Language, Subjectivity, Culture, Comprehensiveness, and Structure
Authors: Saucier Gerard
Published: September 2017

We know that (besides dispositions) situations affect behavior. To understand the situational contributions to prediction, we need frameworks for cataloging the different types of situations. To this end, useful situation-classifications have emerged recently. This chapter considers several puzzles in arriving at an optimal classification of situations. Can we learn something from how language is used? Should subjective states count as a kind of situation? Is culture a situation? What else should we consider in endeavoring to make the situation-classification comprehensive? At the other extreme of parsimony, to what minimal underlying structure can situations be reduced? How might the respective structures of situations and personality be related? It is concluded that each personality dimension may have particularly diagnostic situations integral to the relevant trait variation. And there are empirical indications for two situation-dimensions apparently closely allied with two dimensions in affect and motivation.
Functional Approaches to Representing the Interplay of Situations, Persons, and Behavior
Authors: Wood Dustin , Spain Seth M. , Harms P.D.
Published: September 2017

The understanding that behaviors are shaped by their usefulness toward attaining valued ends underlies many theories of how personality traits interact with aspects of a situation. This chapter suggests how functional explanations of behavior can be more rigorously formalized through the use of functional fields, which can be regarded as a marriage of ideas within Lewin’s (1943) field theory with modern causal modeling techniques (e.g., Pearl, 2009). We illustrate how functional or process variables can be understood as forces which concern real and perceived causal relationships between features or objects within a situation, and detail how such forces can be understood as functionally mediating the effects of other situational influences on behavior. We discuss how functional fields can reveal how individuals characterize actions, objects, people, and situations in abstract terms (e.g., cooperative, assertive) and actively structure their situation to aid in the attainment of their goals.
The Study of Trust
Authors: Uslaner Eric M.
Published: September 2017

In this introductory chapter, I survey approaches to the study of social and political trust, including a focus on my own contributions. The issues I consider include: (1) what we mean by trust; (2) whether social and political trust are part of the same syndrome or rest on different foundations; (3) how we measure trust; (4) approaches to the study of trust, from analyzing surveys to conducting experiments; (5) social-psychological versus economic (rational choice) and biological explanations for trust; (6) the consequences of both social and political trust; (7) which groups have the highest/lowest levels of trust and how/where people live shapes their social trust; (8) how interpersonal trust leads to more cooperation in the international arena; and (9) how polarization has led to reduced trust and reshaped both social and political life in the West.
Associative Learning in Invertebrates
Authors: Nargeot Romuald , Bédécarrats Alexis
Published: September 2017

Behaviors of invertebrates can be modified by associative learning in a similar manner to those of vertebrates. Two simple forms of associative learning, Pavlovian and operant conditioning, allow animals to establish a predictive relationship between two events. Here we summarize five decades of studies of behavioral, cellular, and subcellular changes that are induced by these two learning paradigms in different invertebrate animal models. A comparative description of circuitry, neuronal elements, and properties that contribute to these conditioning procedures will be drawn to decipher common and distinguishing features of the learning processes. We will illustrate that similar circuits, synaptic and neuronal membrane plasticity, and similar molecular sites of detection of association are implicated in both forms of conditioning. However, evidence will also suggest that passively responding and endogenous dynamic properties of central networks and/or their constituent neurons might differentially contribute to Pavlovian and operant learning.
Rock Art and Ethnography in Australia
Authors: Brady Liam M. , Gunn Robert G. , Smith Claire , David Bruno
Published: September 2017

This chapter discusses the contribution of ethnography to the study of Australian rock art. With more than 100 years of ethnographic enquiry into rock art from across the country, valuable insights into the meaning, motives, function, and symbolism of images have been identified. However, with this information comes challenges with its use (and abuse), as well as the necessity to understand the cultural contexts of interpretation and meaning-making. This chapter explores the various ways Indigenous Australians (Aboriginal peoples and Torres Strait Islanders) engage with and describe their understandings of rock art in a variety of contexts. This review also highlights the complex nature of the interpretative process and the ethnographic gaze in which it is embedded. At its core, ethnographic approaches to Australian rock art reveal the multidimensional referential qualities of images found across the landscape.
Antarctic Climate History and Global Climate Changes
Authors: Lurcock Pontus , Florindo Fabio
Published: September 2017

Antarctic climate changes have been reconstructed from ice and sediment cores and numerical models (which also predict future changes). Major ice sheets first appeared 34 million years ago (Ma) and fluctuated throughout the Oligocene, with an overall cooling trend. Ice volume more than doubled at the Oligocene-Miocene boundary. Fluctuating Miocene temperatures peaked at 17–14 Ma, followed by dramatic cooling. Cooling continued through the Pliocene and Pleistocene, with another major glacial expansion at 3–2 Ma. Several interacting drivers control Antarctic climate. On timescales of 10,000–100,000 years, insolation varies with orbital cycles, causing periodic climate variations. Opening of Southern Ocean gateways produced a circumpolar current that thermally isolated Antarctica. Declining atmospheric CO2 triggered Cenozoic glaciation. Antarctic glaciations affect global climate by lowering sea level, intensifying atmospheric circulation, and increasing planetary albedo. Ice sheets interact with ocean water, forming water masses that play a key role in global ocean circulation.
Assessing Volcanic Hazard
Authors: Martí Molist Joan
Published: September 2017

Volcanoes represent complex geological systems capable of generating many dangerous phenomena. To evaluate and manage volcanic risk, we need first to assess volcanic hazard (i.e., identify past volcanic system behavior to infer future behavior. This requires acquisition of all relevant geological and geophysical information, such as stratigraphic studies, geological mapping, sedimentological studies, petrologic studies, and structural studies. All this information is then used to elaborate eruption scenarios and hazard maps. Stratigraphic studies represent the main tool for the reconstruction of past activity of volcanoes over time periods exceeding their historical record. This review presents a systematic approach to volcanic hazard assessment, paying special attention to reconstruction of past eruptive history. It reviews concepts and methods most commonly used in long- and short-term hazard assessment and analyzes how they help address the various serious consequences derived from the occurrence (and nonoccurrence in some crisis alerts) of volcanic eruptions and related phenomena.
Self-Determination and Decolonization
Authors: Simpson Brad
Published: September 2017

Human rights historians have made two erroneous arguments concerning self-determination: first, that anticolonial movements used the discourse of self-determination primarily for instrumental goals, and to achieve broader goals, eg, economic development, racial equality. Second, that, by the 1960s, self-determination’s fiercest advocates in the Global South had reduced the principle cum-right ‘to the receipt of statehood and perpetual non-intervention thereafter,’ diluting its liberal, democratic implications. Both arguments, this chapter argues, oversimplify the myriad ways in which a variety of state and non-state actors deployed self-determination claims to envision sovereignty and human rights in the era of decolonization, where self-determination was a form of claim making about the nature and scope of post-colonial rights and sovereignty, an open-ended, rather than a fixed, concept. This essay focuses on UN debates, over the status of self-determination as a human right, among colonial powers and anti-colonial activists concerning the proper ‘form’ that self-determination could/should take.
The Good Megadam
Authors: Scudder Thayer
Published: September 2017

Megadams are a key component of a destructive yet still dominant global political economy that continues to receive national and international support, but they are not cost effective from either an economic or financial point of view. They are also environmentally destructive—not just of free-flowing rivers, but also of the world as a global ecosystem. For more than half a billion project-affected people, megadams also create development-induced new poverty.
Megaproject Decision Making and Management
Authors: Priemus Hugo , van Wee Bert
Published: September 2017

This chapter focuses on ethical and political aspects of megaproject decision making and management. More specifically, it focuses on ethical aspects of the impacts of megaprojects on society, the ethics of doing research into the pros and cons of megaprojects, the quality of estimates of the costs and benefits of megaprojects, and the democratic quality of the decision-making process. Avenues for future research are then suggested. An overall conclusion is that ethical aspects of megaprojects are very important for society, but the topic has not received a great deal of attention from researchers yet.
Looking at Creativity through a Paradox Lens
Authors: Miron-Spektor Ella , Erez Miriam
Published: September 2017

This chapter contributes to the research and practice of creativity by increasing awareness of the inherently paradoxical nature of creativity, and offering strategies for managing the paradox. The authors’ framework delineates contradictory yet interrelated creativity outcomes, processes and identities of individuals, leaders, and groups. They highlight the paradox of creativity from multiple perspectives and suggest that when engaging in creativity, people experience paradoxical thoughts, processes, goals, identities, and perspectives. Creative people need to be generative and evaluative, flexible and persistent, passionate and disciplined, and learning and performance orientated. Drawing from related research on innovation management, attention control, and goal setting, we discuss strategies for achieving both novelty and usefulness including using paradoxical frames, task switching, pursuing contradictory goals, and gaining experience in different cultural contexts that stress different aspects of the creative process.
“I Am … I Said”
Authors: Sheep Mathew L. , Kreiner Glen E. , Fairhurst Gail T.
Published: September 2017

In reviewing identity and identity work literature, two overarching themes emerge that highlight the theoretical potency of viewing individual identity through the lens of paradox. First, while paradox is variously implicit/explicit in extant work, four primary paradoxes of identity usefully emerge that conceptually map the tensional processes of identity work: (1) paradoxes of entity, (2) paradoxes of conformity, (3) paradoxes of temporality, and (4) paradoxes of elasticity. Second, a poststructuralist understanding of the self (in which language, communication, and discourse are more fully brought to bear on identity and identity work) reveals the interplay and knottedness of these four paradoxes. The authors thus propose a research agenda that advances understanding not only of four identity paradoxes but also of their dynamic interplay. They suggest that a paradox lens can be used both to reexamine past identity and identity work research in a new light and to inspire future research efforts.
Generalization Modalities
Authors: Rizvi Shireen L. , Roman Kristen M.
Published: September 2017

Dialectical Behavior Therapy (DBT) is a complex and multifaceted treatment programme designed to treat a complex and multifaceted population. While much attention has been paid to some of the key functions of the comprehensive treatment (i.e., enhancing behavioural capabilities, improving motivation), there has been little written about the function of ensuring that skillful behaviour generalizes outside the therapy session. This chapter discusses the importance of skills generalization as a function of comprehensive treatment, ways in which generalization can be promoted in DBT treatment, and practical considerations in employing various generalization techniques. Specifically, it discusses how traditional phone coaching has evolved to include coaching in multiple formats (phone, text, and email). Guidelines for how to optimally engage in skills-focused phone coaching are provided.
Mechanisms of Change in Dialectical Behaviour Therapy
Authors: Boritz Tali , Zeifman Richard J. , McMain Shelley F.
Published: September 2017

Research on processes and mechanisms of change aim to explain how and why an intervention leads to change. Despite some theoretical and empirical progress in understanding processes and mechanisms of change in Dialectical Behaviour Therapy (DBT), this remains an understudied area in the DBT literature. This chapter considers how DBT conceptualizes the etiology and maintenance of dysfunction, and how active ingredients in DBT treatment produce client change. It proposes four key mechanisms of change that have been a focus of scientific efforts in DBT research: (1) increased awareness and acceptance of emotion; (2) increased attentional control; (3) increased ability to modulate emotion; and (4) increased use of adaptive coping skills. Next, it reviews the research evidence to support these putative mechanisms of change. Finally, it discusses clinical implications of this research, and propose recommendations for future research on mechanisms of change in DBT.
The Handling of Light
Authors: Potamianos Iakovos
Published: September 2017

This chapter explores the handling of natural light in the classical Greek temple and the Byzantine church. It discusses concepts of orientation as related to their respective functions and aims and the planning of lighting. It addresses light’s influence on the shaping of formal components in the Greek temple, such as the peristyle, fluting, and echinus of the Doric column. It attempts to establish relationships between the temple and the church layout in both plan and section, on the basis of light considerations connecting these observations to the widespread scientific interest of the period in the nature and behaviour of light. It discusses Byzantine church lighting planning, focusing on the church of Hagia Sophia of Istanbul, in an attempt to provide a perspective of relevant concepts in philosophy and theology, and to understand the development of the aesthetics of light and space within it.
Comparing Citizenship Regimes
Authors: Vink Maarten
Published: September 2017

This chapter discusses comparative research on the regulation of the acquisition and loss of citizenship status and of the implications of having this status or not. Citizenship regimes are understood here as institutionalized systems of formal and informal norms that define access to membership, as well as rights and duties associated with membership, within a polity. Comparing citizenship regimes thus implies the study of how political membership is regulated in different contexts. The chapter focuses on how the state of the art developed with regard to its key research questions. This discussion will follow the comparative literature on citizenship regimes, which is organized around three sets of questions: along which dimensions can citizenship regimes be differentiated; which factors structure variation in citizenship regimes; and how do citizenship regimes impact on social, economic and political outcomes? The concluding section reflects on theoretical and methodological challenges faced by scholars analyzing these questions.
Citizenship and State Transition
Authors: Shevel Oxana
Published: September 2017

This chapter analyzes the national citizenship regimes adopted by newly independent states and factors that influence the content of these regimes. The chapter examines how the goal of attaining state sovereignty, different visions of and debates over the boundaries of the national community in whose name the new state is constituted, perceived implications of citizenship rules for political and economic power of different groups, and external actors, including other states in the region and international organizations, inform the content of citizenship regimes in new states.
Indigenous Citizenship in Settler States
Authors: Gover Kirsty
Published: September 2017

Like most liberal democracies, the western settler states supplement jus sanguinis rules with jus soli principles that accord birthright citizenship to most people born in their territory. Indigenous tribal nations in those states, on the other hand, do not include birthplace criteria in their allocation of birthright citizenship. Thus while settler states and tribal nations both permit naturalization, tribal nations continue to use ‘jus sanguinis’ descent rules as the exclusive determinant of tribal birthright citizenship. This chapter examines the tensions that arise in settler and tribal law as a result of this divergence, and argues that the tribal preference for unlimited jus sanguinis rules is a legitimate one.
Sacred Geographies
Authors: Van Dyke Ruth
Published: September 2017

For indigenous peoples in the Southwest, sacred geographies are bound up with histories, religious practices, and cosmologies. Axis mundi and memory anchors create connections across spatial and temporal realities. High places (peaks, mesas) are the home of mythic beings or entry points into a world above. Openings in the earth (canyons, springs) lead to a world below. Special places demarcate cosmologies on current (Tewa) and ancient (Chaco Canyon) landscapes. Sacred geographies are marked by shrines, rock art, votive deposits, trails, alignments, and archaeological sites. Pilgrimages are undertaken to natural and archaeological memory anchors and axis mundi. Sacred places are increasingly threatened by groups with divergent interests.
GOLDRUSH. III. A systematic search for protoclusters at z ∼ 4 based on the >100 deg2 area
Authors: Toshikawa Jun , Uchiyama Hisakazu , Kashikawa Nobunari , Ouchi Masami , Overzier Roderik , Ono Yoshiaki , Harikane Yuichi , Ishikawa Shogo , Kodama Tadayuki , Matsuda Yuichi , Lin Yen-Ting , Onoue Masafusa , Tanaka Masayuki , Nagao Tohru , Akiyama Masayuki , Komiyama Yutaka , Goto Tomotsugu , Lee Chien-Hsiu
Published: September 2017

We conduct a systematic search for galaxy protoclusters at z ∼ 3.8 based on the latest internal data release (S16A) of the Hyper Suprime-Cam Subaru strategic program (HSC-SSP). In the Wide layer of the HSC-SSP, we investigate the large-scale projected sky distribution of g-dropout galaxies over an area of 121 deg2, and identify 216 large-scale overdense regions (>4 σ overdensity significance) that are likely protocluster candidates. Of these, 37 are located within 8΄ (3.4 physical Mpc) of other protocluster candidates of higher overdensity, and are expected to merge into a single massive structure by z = 0. Therefore, we find 179 unique protocluster candidates in our survey. A cosmological simulation that includes projection effects predicts that more than 76% of these candidates will evolve into galaxy clusters with halo masses of at least 1014 M⊙ by z = 0. The unprecedented size of our protocluster candidate catalog allows us to perform, for the first time, an angular clustering analysis of the systematic sample of protocluster candidates. We find a correlation length of 35.0 h−1 Mpc. The relation between correlation length and number density of z ∼ 3.8 protocluster candidates is consistent with the prediction of the ΛCDM model, and the correlation length is similar to that of rich clusters in the local universe. This result suggests that our protocluster candidates are tracing similar spatial structures to those expected from the progenitors of rich clusters, and enhances the confidence that our method for identifying protoclusters at high redshifts is robust. In years to come, our protocluster search will be extended to the entire HSC-SSP Wide sky coverage of ∼ 1400 deg2 to probe cluster formation over a wide redshift range of z ∼ 2–6.
The Bacterial Effector AvrPto Targets the Regulatory Coreceptor SOBIR1 and Suppresses Defense Signaling Mediated by the Receptor-Like Protein Cf-4
Authors: Wu Jinbin , van der Burgh Aranka M. , Bi Guozhi , Zhang Lisha , Alfano James R. , Martin Gregory B. , Joosten Matthieu H. A. J.
Published: September 2017

Receptor-like proteins (RLPs) and receptor-like kinases (RLKs) are cell-surface receptors that are essential for detecting invading pathogens and subsequent activation of plant defense responses. RLPs lack a cytoplasmic kinase domain to trigger downstream signaling leading to host resistance. The RLK SOBIR1 constitutively interacts with the tomato RLP Cf-4, thereby providing Cf-4 with a kinase domain. SOBIR1 is required for Cf-4–mediated resistance to strains of the fungal tomato pathogen Cladosporium fulvum that secrete the effector Avr4. Upon perception of this effector by the Cf-4/SOBIR1 complex, the central regulatory RLK SOMATIC EMBRYOGENESIS RECEPTOR KINASE 3a (SERK3a) is recruited to the complex and defense signaling is triggered. SOBIR1 is also required for RLP-mediated resistance to bacterial, fungal ,and oomycete pathogens, and we hypothesized that SOBIR1 is targeted by effectors of such pathogens to suppress host defense responses. In this study, we show that Pseudomonas syringae pv. tomato DC3000 effector AvrPto interacts with Arabidopsis SOBIR1 and its orthologs of tomato and Nicotiana benthamiana, independent of SOBIR1 kinase activity. Interestingly, AvrPto suppresses Arabidopsis SOBIR1-induced cell death in N. benthamiana. Furthermore, AvrPto compromises Avr4-triggered cell death in Cf-4-transgenic N. benthamiana, without affecting Cf-4/SOBIR1/SERK3a complex formation. Our study shows that the RLP coreceptor SOBIR1 is targeted by a bacterial effector, which results in compromised defense responses.
Presenting features of extremity necrotizing fasciitis in the pediatric patient: a case–control analysis
Authors: Sullivan Thomas B. , Bastrom Tracey P. , Marino Nikolas , Edmonds Eric W.
Published: September 2017

This analysis sought to develop a tool for early differentiation between pediatric necrotizing fasciitis (NF) of the extremity and more benign infection. All diagnoses of extremity NF, cellulitis, and abscess from a single institution from 2009 to 2015 were included. Vitals and laboratory values were compared between cohorts using analysis of variance and decision tree analysis. NF was associated with thrombocytopenia, hyperthermia, tachycardia, and tachypnea. Decision tree analysis identified C-reactive protein more than 7.0 to be 100% sensitive and 95.7% specific for differentiating NF from cellulitis or abscess. The results offer quantitative support for clinical suspicion of NF in the evaluation of pediatric extremity infection.
Metformin: oxidative and proliferative parameters in-vitro and in-vivo models of murine melanoma
Authors: de Souza Neto Fernando P. , Bernardes Sara S. , Marinello Poliana C. , Melo Gabriella P. , Luiz Rodrigo C. , Cecchini Rubens , Cecchini Alessandra L.
Published: September 2017

Cutaneous melanoma is one of the most lethal cancers because of its increased rate of metastasis and resistance to available therapeutic options. Early studies indicate that metformin has beneficial effects on some types of cancer, including melanoma. To clarify knowledge of the mechanism of action of metformin on this disease, two treatment-based approaches are presented using metformin on melanoma progression: an in-vitro and an in-vivo model. The in-vitro assay was performed for two experimental treatment periods (24 and 48 h) at different metformin concentrations. The results showed that metformin decreased cell viability, reduced proliferation, and apoptosis was a major event 48 h after treating B16F10 cells. Oxidative stress was characterized by the decrease in total thiol antioxidants immediately following 24 h of metformin treatment and showed an increase in lipid peroxidation. The in-vivo model was performed by injecting B16F10 cells into the subcutaneous of C57/BL6 mice. Treatment with metformin began on day 3 and on day 14, the mice were killed. Treatment of mice with metformin reduced tumor growth by 54% of its original volume compared with nontreatment. The decrease in systemic vascular endothelial growth factor, restoration of antioxidants glutathione and catalase, and normal levels of lipid peroxidation indicate an improved outcome for melanoma following metformin treatment, meeting a need for new strategies in the treatment of melanoma.
Performance of the QuantiFERON-TB Gold Assay Among HIV-infected Children With Active Tuberculosis in France
Authors: Hormi Myriam , Guérin-El Khourouj Valérie , Pommelet Virginie , Jeljeli Mohamed , Pédron Béatrice , Diana Jean-Sébastien , Faye Albert , Sterkers Ghislaine
Published: September 2017

Background:

Data regarding the use of QuantiFERON to assist the diagnosis of active tuberculosis (TB) in HIV-infected children are limited, especially in countries with low incidence of TB/HIV coinfection.

Methods:

QuantiFERON results were analyzed in 63 HIV-infected children who presented to our hospital in Paris, France. Seventeen HIV-uninfected children with active TB (4 culture-confirmed) were included for comparison.

Results:

The 63 HIV-infected children (median age: 11 yr) had 113 QuantiFERON tests. Thirty-four (54%) were born in sub-Saharan Africa. Vertical HIV transmission was documented for 50 of 52 (96%) and stage III HIV-infection for 30 of 50 children (60%). Over the study period, active TB was diagnosed in 7 of 63 HIV-infected children (3 culture-confirmed). Additional ongoing or previous opportunistic infections were present in 4 of 7. QuantiFERON results were positive in 2 of 7 HIV-infected children with active TB (sensitivity: 29%) and 16 of 17 HIV-uninfected children with active TB (sensitivity: 94%). At initial QuantiFERON testing of the 63 HIV-infected children, 8 (13%) had positive results (1, active TB; 5, latent TB; 2, previous TB) and 51 (81%) had negative results. Of 33 children with repeat testing after an initially positive or negative result, the only change was one conversion from a negative to a positive result at the onset of active TB. The 4 children (6%) with indeterminate quantiFERON results had a concomitant opportunistic infection. Results of repeat testing after clinical stabilization were negative in all 4.

Conclusions:

QuantiFERON testing performed poorly for active TB diagnosis in this series of children with advanced HIV infection.
Tumor necrosis factor alpha secreted from oral squamous cell carcinoma contributes to cancer pain and associated inflammation
Authors: Scheff Nicole N. , Ye Yi , Bhattacharya Aditi , MacRae Justin , Hickman Dustin N. , Sharma Atul K. , Dolan John C. , Schmidt Brian L.
Published: September 2017

Patients with oral cancer report severe pain during function. Inflammation plays a role in the oral cancer microenvironment; however, the role of immune cells and associated secretion of inflammatory mediators in oral cancer pain has not been well defined. In this study, we used 2 oral cancer mouse models: a cell line supernatant injection model and the 4-nitroquinoline-1-oxide (4NQO) chemical carcinogenesis model. We used the 2 models to study changes in immune cell infiltrate and orofacial nociception associated with oral squamous cell carcinoma (oSCC). Oral cancer cell line supernatant inoculation and 4NQO-induced oSCC resulted in functional allodynia and neuronal sensitization of trigeminal tongue afferent neurons. Although the infiltration of immune cells is a prominent component of both oral cancer models, our use of immune-deficient mice demonstrated that oral cancer–induced nociception was not dependent on the inflammatory component. Furthermore, the inflammatory cytokine, tumor necrosis factor alpha (TNFα), was identified in high concentration in oral cancer cell line supernatant and in the tongue tissue of 4NQO-treated mice with oSCC. Inhibition of TNFα signaling abolished oral cancer cell line supernatant-evoked functional allodynia and disrupted T-cell infiltration. With these data, we identified TNFα as a prominent mediator in oral cancer–induced nociception and inflammation, highlighting the need for further investigation in neural–immune communication in cancer pain.
Improving the Implementation of Lung Cancer Screening Guidelines at an Academic Primary Care Practice
Authors: Brenner Alison T. , Cubillos Laura , Birchard Katherine , Doyle-Burr Caleb , Eick John , Henderson Louise , Jones Laura , Massaro Michael , Minish Bailey , Molina Paul , Pignone Michael , Ratner Shana , Rivera Maria Patricia , Reuland Daniel S.
Published: September 2017

Expert groups recommend annual chest computed tomography for lung cancer screening (LCS) in high-risk patients. Lung cancer screening in primary care is a complex process that includes identification of the at-risk population, comorbidity assessment, and shared decision making. We identified three key processes required for high-quality screening implementation in our academic primary care practice: (1) systematic collection of lifetime cumulative smoking history to identify potentially eligible patients; (2) visit-based clinical reminders and order sets embedded in the electronic health record (EHR); and (3) tools to facilitate shared decision making and appropriate test ordering. We applied quality improvement techniques to address gaps in these processes. Over 12 months, we developed and implemented a nurse protocol for collecting complete smoking history and entering that data into discrete EHR fields. We obtained histories on over 50% of the clinic's more than 2,300 known current and former smokers, aged 55–80 years. We then built and pilot tested an automated visit-based reminder (VBR) system, driven by the discrete smoking history data. The VBR included an order set and template for documentation of shared decision making. Physicians interacted with the VBR in approximately 30% of opportunities for use. Further work is needed to better understand how to systematically provide appropriate LCS in primary care environments.
Treating Acute Pain in the Opiate-Dependent Patient
Authors: Dever Coleen
Published: September 2017

Opioid drugs, including prescription as well as heroin, have come to the national spotlight due to the unprecedented rate of overdose and addiction. The Centers for Disease Control and Prevention (CDC) has termed this problem as an “epidemic” that has reached record numbers of deaths in 2014. Approximately half of these deaths are the result from prescribed opioids. Also on the rise are the numbers of individuals who are diagnosed with chronic pain and are treated with opioids, methadone and buprenorphine. Individuals currently taking opioids for chronic pain confound the treatment of acute pain after traumatic injury. Goals of treatment include effective pain relief, prevention of opioid withdrawal, and managing the associated behavioral and psychological factors with drug addiction and dependence. The CDC has put forth guidelines on how to treat chronic pain but has yet to provide recommendations on how to treat acute pain in this unique population. The purpose of this literature review is to provide resources to treat pain, given a tolerant opioid-dependent patient.
Iliac Vascular Injury in the Absence of a Pelvic Fracture
Authors: Helton Nancy , McNeill Cathy , Witham William
Published: September 2017

This case study presents a rare iliac vascular injury in the absence of a pelvic fracture. A 36-year-old man sustained a blunt injury after being stuck by a motor vehicle. The only positive computed tomographic finding was in the pelvis that showed a 4 × 2-cm left retroperitoneal soft-tissue collection, appearing to encompass the left common and left external iliac veins. A pelvic venogram was obtained on Day 2 revealing a focal injury to the left external iliac vein with 60% narrowing. The patient was treated with clopidogrel and acetylsalicylic acid and discharged from the hospital to his home 3 days later. A follow-up pelvic venogram in 6 weeks later showed complete healing of previously visualized left external iliac venous injury without any residual stenosis.
Fetal Intra-abdominal Umbilical Vein Aneurysm
Authors: Giannubilo Stefano Raffaele , Pasculli Angela , Cecchi Alessandro , Biagini Alessandra , Ciavattini Andrea
Published: September 2017

Importance

Fetal umbilical vein aneurysm is an uncommon anomaly that accounts for approximately 4% of umbilical cord abnormalities. The rate of intrauterine fetal death is reported to be approximately 4% to 5%, higher than the background rate of 0.7% that is generally reported during pregnancy.

Objective

The aim of this study was to review the pathophysiology, diagnosis, and clinical management of fetal umbilical vein aneurysm.

Evidence Acquisition

Advances in high-resolution ultrasound combined with color Doppler and 3-dimensional rendering have contributed to an increased understanding of the fetal venous circulation in recent years.

Results

When the diagnosis of umbilical vein aneurysm is made, the patient should undergo a detailed ultrasound evaluation of the fetal anatomy, including fetal echocardiography, to exclude associated anomalies. Amniocentesis should be offered when other anomalies are found. Patients should be informed about the potential for an unfavorable outcome of pregnancy and should undergo close ultrasound surveillance to assess the size of the aneurysm, as well as any evidence of thrombosis or signs of hydrops.

Conclusions

The main prognostic feature associated with a poor outcome of umbilical vein aneurysm seems to be the presence of other anomalies. Early diagnosis is associated with a somewhat worse prognosis, and most fetal deaths have been observed between 27 and 30 weeks of gestation. In the third trimester, it is reasonable to perform serial ultrasound examinations to assess fetal growth, the size of the aneurysm, and the blood flow pattern within the aneurysm.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After completing this activity, the learner should be better able to describe the overall pathophysiology of fetal umbilical vein aneurysm, recall the diagnosis and classification of fetal umbilical aneurysm, identify the ultrasound markers in a prognostic view, and explain the obstetrics management of fetuses with umbilical vein aneurysm.
Periprocedural Outcomes Comparing Fibroid Embolization and Focused Ultrasound: A Randomized Controlled Trial and Comprehensive Cohort Analysis
Authors: Barnard Emily P. , AbdElmagied Ahmed M. , Vaughan Lisa E. , Weaver Amy L. , Laughlin-Tommaso Shannon K. , Hesley Gina K. , Woodrum David A. , Jacoby Vanessa L. , Kohi Maureen P. , Price Thomas M. , Nieves Angel , Miller Michael J. , Borah Bijan J. , Gorny Krzysztof R. , Leppert Phyllis C. , Peterson Lisa G. , Stewart Elizabeth A.
Published: September 2017

(Abstracted from Am J Obstet Gynecol 2017;216:500.e1–500.e11)

Although uterine fibroids are a common problem among reproductive-aged women, few comparative effectiveness studies are available to guide treatment decisions. Two minimally invasive treatments—uterine artery embolization (UAE) and magnetic resonance imaging–guided focused ultrasound surgery (MRgFUS)—have been approved by the US Food and Drug Administration for treatment of symptomatic uterine fibroids.
Nonuniform Distribution of High-risk Human Papillomavirus in Squamous Cell Carcinomas of the Oropharynx
Authors: Gelwan Elise , Malm Ian-James , Khararjian Armen , Fakhry Carol , Bishop Justin A. , Westra William H.
Published: September 2017

The oral cavity and oropharynx have historically been viewed as a single anatomic compartment of the head and neck. The practice of combining the oral cavity and oropharynx has recently been revised, largely owing to the observation that human papillomavirus (HPV)-related carcinogenesis has a strong predilection for the oropharynx but not the oral cavity. The purpose of this study was to determine whether HPV is evenly distributed across squamous cell carcinomas of the oropharynx including those sites that do not harbor tonsillar tissues such as the soft palate. A search of the medical records of the Johns Hopkins Hospital identified 32 primary squamous cell carcinomas of the soft palate (n=31) and posterior pharyngeal wall (n=1). All were evaluated with p16 immunohistochemistry and high-risk HPV in situ hybridization (ISH) (29 by RNA ISH and 3 by DNA ISH). For comparison, we also reviewed the medical records to obtain the HPV status of patients who had undergone HPV testing of primary tonsillar carcinomas over the same time interval as part of their clinical care. High-risk HPV as detected by ISH was present in just 1 (3.1%) of the 32 oropharyngeal squamous cell carcinomas, including 1 of 2 p16-positive carcinomas. The difference in HPV detection rates between tonsillar and nontonsillar sites was significant (1/32, 3.1% vs. 917/997, 92%;P<0.0001). HPV is not frequently detected in squamous cell carcinomas arising from nontonsillar regions of the oropharynx. Indeed, squamous cell carcinomas of the soft palate more closely resemble those arising in the oral cavity than those arising in areas of the oropharynx harboring tonsillar tissue. This finding not only further sharpens our understanding of site-specific targeting by HPV, but may have practical implications regarding HPV testing and even the way the oral vault is oncologically compartmentalized to partition HPV-positive from HPV-negative cancers.