bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term dopamine neurochemical monitoring in primates
Authors: Schwerdt Helen N. , Shimazu Hideki , Amemori Ken-ichi , Amemori Satoko , Tierney Patrick L. , Gibson Daniel J. , Hong Simon , Yoshida Tomoko , Langer Robert , Cima Michael J. , Graybiel Ann M.
Published: November 2017

Significance

Dopamine is an important neurotransmitter governing behavior and heavily implicated in a large range of neural disorders, including Parkinson’s disease, depression, and related mood and movement disorders. Methods allowing accurate monitoring of dopamine over long timescales have not been previously reported yet are crucial to enable improved diagnostics and therapeutics. We report a technical advance that allowed recording of dopamine from sensors implanted into the brains of nonhuman primates for over 100 days. Our integrated platform enabled monitoring fast changes in dopamine release in response to rewarding stimuli and the administration of dopamine-related drugs. These findings demonstrate the long-term feasibility and reproducibility of neurochemical measurements and strengthen their potential translation to human use.
Drosophila
protein phosphatases 2A B′ Wdb and Wrd regulate meiotic centromere localization and function of the MEI-S332 Shugoshin
Authors: Pinto Belinda S. , Orr-Weaver Terry L.
Published: November 2017

Significance

Meiosis is the specialized cell division that generates haploid sperm and eggs. Proper segregation of chromosomes in meiosis is required to prevent pregnancy loss and birth defects. This requires that the replicated copies of each chromosome remain attached as the homologous copies of each chromosome segregate in the first meiotic division. The replicated copies of each chromosome then segregate in the second meiotic division. The Shugoshin proteins protect attachments between the replicated chromosome copies in meiosis I. This paper shows that, in
Drosophila
meiosis, a phosphatase and the Shugoshin MEI-S332 reciprocally regulate each other’s localization to centromeres and together they thus function to ensure accurate segregation.
Globalization, translation and soft power
Authors: Wu You
Published: November 2017

Scholars have extensively explored translation as product and as process, but relatively little attention has been paid to translation as a power of defence and construction. This paper proposes a modest step in this direction by conceptualizing the power of translation in the modern world of globalization in terms of the soft power theory, with particular reference to the Chinese context. With this in mind, the author argues that globalization presents both opportunities and challenges for translation as a soft power. In the face of rising fears regarding a crisis of identities and a cultural deficit intensified by globalization, the roles of translation as a “cultural filter” and a bridge for intercultural communication give it a defensive soft power. Under soft-power-oriented policies, translation not only serves as a “charm” tool for public diplomacy and nation-branding, but also contributes to an understanding of China’s ideals and helps export Chinese cultural values, thereby highlighting its role as a constructive soft power.
Translation and contact languages
Authors: Rottet Kevin J.
Published: November 2017

In this study we use a translation corpus of English novels translated into two closely related Celtic languages, Welsh and Breton, as one way of shedding light on the extent to which languages can influence each other over time: Welsh has a long history of contact with English, and Breton with French. Ever since the work of Leonard Talmy (1991, 2000 etc.), linguists have recognized that languages fall into a small number of types with respect to how they prefer to talk about motion events. English is a good exemplar of the satellite-framed type, whereas French exemplifies the verb-framed type. Translation scholars have observed that translating between languages of two different types raises interesting questions (Slobin 2005; Cappelle 2012), and the topic is also of interest from the perspective of language contact: is it possible for a language of one type, in a situation of prolonged and intense bilingualism with a language of another type, to be influenced or perhaps even to change its own rhetorical preferences? The translation corpus provides a body of data which holds constant the starting point – the cue in each case was an English motion event in the source text. We do indeed find that Welsh and Breton have diverged in important ways in terms of their preferences for encoding motion events: Breton is revealed to have moved significantly in the direction of French with respect to these preferences.
Political participation on Facebook during Brexit
Authors: Bossetta Michael , Dutceac Segesten Anamaria , Trenz Hans-Jörg
Published: November 2017

This study investigates, over an 18-month period surrounding the 2016 Brexit referendum, the commenting activity of nearly 2 million Facebook users engaging with political news from British media or with the posts of referendum campaigns. We ask whether citizens’ engagement with political news on Facebook motivates their participation with political campaign posts, and we examine whether users commenting on campaign pages trend towards ideologically reinforcing media. Overall, we find comparatively low levels of commenting activity on the official referendum campaigns vis-à-vis the media, and the majority of users (70%) commented only once. Looking at the subset of users commenting on both page types (“cross-posters”), we identify a general spillover effect from media to campaign pages, suggesting a positive correlation between political interest and online participation on Facebook. Reverse spillover occurs immediately around and after the vote, with Remain cross-posters active on the Guardian while Leave cross-posters’ media engagement registers as more diffuse.
El grado de pluricentrismo de la lengua española
Authors: Amorós-Negre Carla , Prieto de los Mozos Emilio
Published: November 2017

El proceso globalizador ha traído consigo una reestructuración en todos los niveles, un cambio profundo en la manera en la que se distribuyen los recursos y el poder (político, económico, cultural, comunicativo, etc.). En este sentido, en el ámbito lingüístico, la difusión y hegemonía internacional de unas pocas lenguas e identidades hipercentrales se ha visto muy auxiliada por el surgimiento de organismos y agentes transnacionales y supraestatales, así como por la producción de industrias culturales globales. No obstante, frente a estas tendencias homogeneizadoras de la mundialización, las sociedades han respondido al impacto globalizador con una intensificación de flujos locales y contactos interregionales. De esta manera, las distintas comunidades lingüísticas han buscado relocalizar su identidad y han emergido nuevos sistemas de estratificación normativa en las tradicionales ‘periferias lingüísticas’. En consecuencia, la política y la planificación lingüísticas en torno al español y, en especial, los principales organismos de regulación idiomática en el mundo hispánico (las Academias de la lengua) se han visto en la necesidad de reorientar, no sin dificultades, sus líneas y estrategias de actuación. Tal y como se explica en este trabajo, el pluricentrismo lingüístico se ha presentado como un modelo de estandarización más adecuado para atender a las nuevas demandas y reivindicaciones identitarias en estos tiempos de interacción entre lo global y lo local.
Multilingual educational language policies in Switzerland and Sweden
Authors: Lundberg Adrian
Published: November 2017

Multilingualism represents a global challenge and a goal of education in European states. This meta-analysis examines how research studies on multilingual educational policy documents on a macro-level (national/regional) in Sweden and Switzerland differ in terms of foci and how the discourses in the articles represent different treatments of multilingual educational language policies. These countries were selected because of their similarities regarding the societal context, but they are different in regard to language policy issues and political formation. The articles were systematically identified via two databases, ERIC and LLBA, and in order to examine the latest developments after the introduction of a new language act in Sweden and the harmonization of public education in Switzerland in 2009, only research articles published between 2009 and 2016 were included. The results of the study suggest that a monolingual habitus exists in the Swedish nation state context compared to a more pluralistic approach in Switzerland. The most noteworthy result is the diverging definitions ofmultilingualismandplurilingual studentsand how this understanding influences the treatment of educational policies in these two linguistically and culturally superdiverse European countries.
NSD3 keeps IRF3 active
Authors: Mino Takashi , Takeuchi Osamu
Published: November 2017

In this issue of JEM, Wang et al. (https://doi.org/10.1084/jem.20170856) show a novel antiviral innate mechanism by which methyltransferase NSD3 directly monomethylates a transcription factor IRF3 and maintains IRF3 phosphorylation to enhance its transcriptional activity, consequently promoting antiviral innate immune responses.
A Health Profile of Senior-Aged Women Veterans: A Latent Class Analysis of Condition Clusters
Authors: Gonsoulin Margaret E , Durazo-Arvizu Ramon A , Goldstein Karen M , Cao Guichan , Zhang Qiuying , Ramanathan Dharani , Hynes Denise M
Published: November 2017

Background and Objectives

This study characterizes the multiple morbidities experienced by senior-aged women Veterans so that the Veterans Health Administration (VHA) and other health care systems may be better prepared to meet the health care needs of this growing cohort.

Research Design and Methods

Using the VHA’s Corporate Data Warehouse, we conducted a retrospective observational study of the 38,597 female veteran patients who were at least 65 years old and received care in the VHA during 2013 and 2014. We use a latent class analysis model to cluster diagnoses associated with inpatient and outpatient events over the years.

Results

The senior-aged women Veterans are characterized by six major classes of disease clusters. We defined these classes as: Healthy (16.24% of the cohort); Ophthalmological Disorders (13.84%); Musculoskeletal Disorders (14.22%); At Risk for Cardiovascular Disease (37.53%); Diabetic with Comorbidities (9.05%); and Multimorbid (9.12%). The patterns and prevalence of these condition classes vary by race, age, and marital status.

Discussion and Implications

Each of the six clusters can be used to develop clinical practice guidelines that are appropriate for senior-aged women Veterans. Consistent with past literature, the most common conditions in this cohort are hypertension and hyperlipidemia; together they form the most common class, “At Risk of Cardiovascular Disease (CVD)”. Results also show evidence of race-related disparities, with Blacks being more likely to be in the highest risk classes. Also, members of the cohort who are currently married having improved chances of being in the healthy class. And finally, we see a “healthy survivor” effect with the oldest women in our cohort having low overall rates of disease.
Quantifying the known unknowns: estimating maximum intrinsic rate of population increase in the face of uncertainty
Authors: Pardo Sebastián A , Cooper Andrew B , Reynolds John D , Dulvy Nicholas K
Published: November 2017

Sensitivity to overfishing is often estimated using simple models that depend upon life history parameters, especially for species lacking detailed biological information. Yet, there has been little exploration of how uncertainty in life history parameters can influence demographic parameter estimates and therefore fisheries management options. We estimate the maximum intrinsic rate of population increase (rmax) for ten coastal carcharhiniform shark populations using an unstructured life history model that explicitly accounts for uncertainty in life history parameters. We evaluate how the two directly estimated parameters, age at maturity αmat and annual reproductive output b, most influenced rmax estimates. Uncertainty in age at maturity values was low, but resulted in moderate uncertainty in rmax estimates. The model was sensitive to uncertainty in annual reproductive output for the least fecund species with fewer than 5 female offspring per year, which is not unusual for large elasmobranchs, marine mammals, and seabirds. Managers and policy makers should be careful to restrict mortality on species with very low annual reproductive output <2 females per year. We recommend elasmobranch biologists to measure frequency distributions of litter sizes (rather than just a range) as well as improving estimates of natural mortality of data-poor elasmobranchs.
Contribution of Calanus species to the mesozooplankton biomass in the Barents Sea
Authors: Aarflot Johanna Myrseth , Skjoldal Hein Rune , Dalpadado Padmini , Skern-Mauritzen Mette
Published: November 2017

Copepods from the genus Calanus are crucial prey for fish, seabirds and mammals in the Nordic and Barents Sea ecosystems. The objective of this study is to determine the contribution of Calanus species to the mesozooplankton biomass in the Barents Sea. We analyse an extensive dataset of Calanus finmarchicus, Calanus glacialis, and Calanus hyperboreus, collected at various research surveys over a 30-year period. Our results show that the Calanus species are a main driver of variation in the mesozooplankton biomass in the Barents Sea, and constitutes around 80% of the total. The proportion of Calanus decreases at low zooplankton biomass, possibly due to a combination of advective processes (low C. finmarchicus in winter) and size selective foraging. Though the Calanus species co-occur in most regions, C. glacialis dominates in the Arctic water masses, while C. finmarchicus dominates in Atlantic waters. The larger C. hyperboreus has considerably lower biomass in the Barents Sea than the other Calanus species. Stages CIV and CV have the largest contribution to Calanus species biomass, whereas stages CI-CIII have an overall low impact on the biomass. In the western area of the Barents Sea, we observe indications of an ongoing borealization of the zooplankton community, with a decreasing proportion of the Arctic C. glacialis over the past 20 years. Atlantic C. finmarchicus have increased during the same period.
Salmon lice evasion, susceptibility, retention, and development differ amongst host salmonid species
Authors: Bui Samantha , Halttunen Elina , Mohn Agnes M , Vågseth Tone , Oppedal Frode
Published: November 2017

With different ecological characteristics amongst salmonid species, their response to parasitic infestation is likely to vary according to their spatial and temporal overlap with the parasite. This study investigated the host–parasite interactions amongst three species of salmonids and the ectoparasitic salmon louse, Lepeophtheirus salmonis. To determine any variation in infestation parameters amongst salmonids, single population groups of Atlantic salmon (Salmo salar), chinook salmon (Onchorhynchus tshawytscha), and previously-infested and naïve sea trout (Salmo trutta) were exposed to a controlled infestation challenge. We found that chinook salmon and both sea trout groups were more susceptible to acquiring lice than Atlantic salmon. Behavioural responses during infestation were more pronounced in Atlantic and chinook salmon. Parasite development was similar in lice attached to Atlantic salmon and sea trout, but hindered on chinook salmon. At 16 days post-infestation, chinook salmon had reduced lice loads to the same level as Atlantic salmon, whilst sea trout retained their lice. These results demonstrate differences in interactions with L. salmonis amongst these species, and highlight the vulnerability of sea trout to infestation.
Resonances and Scattering Poles in Symmetric Spaces of Rank One
Authors: Hansen Sönke , Hilgert Joachim , Parthasarathy Aprameyan
Published: November 2017

We relate resolvent and scattering kernels for the Laplace operator on Riemannian symmetric spaces of rank one via boundary values in the sense of Kashiwara–Ōshima. From this, we derive that the poles of the corresponding meromorphic continuations agree in a half-plane, and the residues correspond to each other under the boundary value map, so in particular the multiplicities agree as well. In the opposite half-plane, which is the square root of the resolvent set, the resolvent has no poles, whereas the scattering poles agree with the poles of the standard Knapp–Stein intertwiner. As a by-product of the underlying ideas, we obtain a new and self-contained proof of Helgason’s conjecture for distributions in the case of rank one symmetric spaces.
Introduction
Authors: Hechtman Lily
Published: November 2017

The introduction stresses that well-controlled long-term prospective follow-up studies helped establish the validity of ADHD in adulthood. No other publication brings together all these highly respected and well-established studies. The studies provide a comprehensive view of the impact of this condition in educational, occupational, social, emotional, and legal domains. The book also outlines factors that can influence long-term outcome and prognosis. These include treatment, IQ, socioeconomic status, and family functioning among others. This has current treatment implications for seeking more positive outcomes. Professionals can access these relevant factors in one place and use them in treatment planning.
The Milwaukee Longitudinal Study of Hyperactive (ADHD) Children
Authors: Barkley Russell A. , Fischer Mariellen
Published: November 2017

The Milwaukee Longitudinal Study of Hyperactive (ADHD) Children followed a large group of children with hyperactive child syndrome (now ADHD Combined Presentation) along with a control group of typically developing children into young adulthood (mean age 27 years) assessing them at four points in development: childhood, adolescence (mean age 15 years), emerging adulthood (mean age 20 years), and young adulthood. A wide variety of measures were used to evaluate numerous domains of cognitive, adaptive, family, peer, educational, occupational, financial, sexual, driving, and health-related variables. Results revealed numerous differences between the groups at each follow-up point, culminating in the conclusion that ADHD is an impairing disorder across many if not all of these domains, persisting into young adulthood in at least two thirds or more of affected childhood cases, depending on the definitions of recovery and persistence.
The Berkeley Girls with ADHD Longitudinal Study
Authors: Owens Elizabeth B. , Zalecki Christine A. , Hinshaw Stephen P.
Published: November 2017

We describe the initiation and evolution of the Berkeley Girls with ADHD Longitudinal Study, an ongoing prospective, longitudinal study of 140 girls diagnosed with ADHD when they were children during the late 1990s, as well as 88 matched comparison girls. Study rationale, design, procedures, recruitment strategy, and measures are described in detail. Primary psychosocial and neuropsychological findings during childhood, adolescence, and adulthood are summarized. Our initial findings regarding predictors of outcome are presented. Results are discussed in light of the existing literature regarding long-term outcome among children with ADHD. Overall, during childhood, adolescence, and young adulthood, in almost every psychosocial and neuropsychological domain we investigated, females with ADHD show sizable disadvantages and deficits relative to females without ADHD. Our findings affirm the public health significance of ADHD in girls, given the likelihood of persisting symptoms and (especially) impairment in crucial domains over the long-term.
Influences of Treatment on Long-term Outcome
Authors: Hechtman Lily
Published: November 2017

Medication and/or psychosocial treatment in childhood do not appear to have an impact on adult outcomes of individuals with ADHD. There is, however, a marked decline in medication adherence in adolescence, which continues into adulthood, with less than 10% of adults with ADHD continuing to use medication. Moreover, psychosocial treatments too often do not continue to be used or adapted to new challenges. Thus, it is difficult to conclude what impact medication and/or psychosocial treatments would have on adult outcomes should these treatments be adhered to and applied continuously. As it stands, the lack of impact from treatments in childhood suggests that ADHD is a chronic condition, and that ongoing regular follow-up may be needed to offer patients interventions (medication and psychosocial treatment) that they require both to improve their symptoms in the short-term and promote more positive long-term outcome.
Behavioral Neuroscience of Circuits Involved in Fear Processing
Authors: Bauer Elizabeth P. , Paré Denis
Published: November 2017

Normal fear regulation includes the ability to learn by experience that some circumstances predict danger. This process, which can be modeled in the laboratory using Pavlovian fear conditioning, appears to be disrupted in individuals with post-traumatic stress disorder (PTSD). Understanding of the mechanisms underlying fear learning has progressed tremendously in the last 25 years, and constitutes a promising paradigm to study the neural bases of PTSD. This chapter first reviews current knowledge of the brain structures involved in fear learning, expression and extinction, including the contributions of the amygdala and prefrontal cortex. It then addresses how these circuits are affected by PTSD and how fear processing is altered in PTSD. Understanding PTSD within a fear-conditioning and extinction framework provides insight into why certain individuals are susceptible to developing PTSD and suggests potential therapies.
Cellular Physiology of the Basolateral Complex of the Amygdala and Its Modulation by Stress
Authors: O’Flaherty Brendan M. , Hsu Chia-Chun , Abbas M. Anzar , Rainnie Donald G.
Published: November 2017

Fear is a critical emotional response that allows an organism to safely navigate through dangerous environments. The neural systems underlying the fear response have been well characterized, and include the amygdala, hippocampus, prefrontal cortex, bed nucleus of stria terminalis, nucleus accumbens, and others. While normally these brain regions coordinate to produce an appropriate fear response, the fear network in humans can become dysregulated after a traumatic event. The resulting phenotype of hyperarousal, avoidance, and re-experiencing of fear known as post-traumatic stress disorder (PTSD) is a growing problem in the United States. This chapter focuses on the role of the basolateral complex (BLC) of the amygdala, which has been implicated in the neuropathology of PTSD, particularly the hyperarousal, fear generalization, and fear extinction deficits characteristic of the disorder, as well as aspects of the microcircuitry, network connectivity, and neuromodulation of the BLC that may be involved in the pathophysiology of PTSD.
Generalization of Learned Fear
Authors: Dunsmoor Joseph E. , Paz Rony
Published: November 2017

Autonomic hyperarousal and avoidance in post-traumatic stress disorder (PTSD) can be triggered by a host of stimuli or situations that bear some similarity or association to the trauma event. As these triggers are often encountered in safe environments removed from the original trauma, this overgeneralization of fear and anxiety is a burden that can interfere with daily life. Recent efforts to understand the neurobiology of PTSD have relied on laboratory models of Pavlovian fear conditioning and extinction. This chapter reviews studies of fear generalization in animals and humans, which provide a valuable model to conceptualize the excessive fear generalization characteristic of PTSD.
Behavioral Neuroscience of Circuits Involved in Arousal Regulation
Authors: Javanbakht Arash , Poe Gina R.
Published: November 2017

This chapter evaluates the evidence that hyper-reactive noradrenergic responses during trauma contribute to hyperarousal symptoms in PTSD, including disturbances in sleep. Some genetic vulnerability for PTSD involves the adrenergic system, and a hyperactive central noradrenergic system might serve to over-consolidate and sustain the affective component of fear memories. Reduced moderation of noradrenergic reactions during low hormone phases of the menstrual cycle could also lead to increased susceptibility to PTSD. This chapter considers a mechanism by which hyperactivity in the noradrenergic system during sleep would impair REM sleep theta and non-REM sleep spindles in the limbic system, both of which are implicated in the consolidation of new safety memories, thereby compromising extinction recall and setting into motion a positive feedback loop in PTSD pathophysiology, involving hyperarousal, failure to integrate contextual information, and biased attention to threat. If so, novel pharmacotherapeutic interventions inhibiting the noradrenergic system during sensitive periods in sleep should be considered.
Prefrontal-Limbic Brain Circuitry and the Regulation of Emotion
Authors: MacNamara Annmarie , Phan K. Luan
Published: November 2017

The ability to regulate emotion promotes mental well-being in health and is disrupted in psychopathologies such as post-traumatic stress disorder (PTSD). The prefrontal cortex (PFC)—a region of the brain involved in executive function, behavioral coordination, and cognitive control—is particularly important in implementing the regulation of emotional response. This chapter reviews a decade and a half of neuroscientific research that has made considerable progress in advancing understanding of the neural basis of emotion regulation. This work, conducted in healthy individuals, provides a platform from which to understand the neural basis of emotion dysregulation that characterizes disorders like PTSD. Therefore, the proposed model could serve as a basis for explaining the etiology and/or maintenance of PTSD. The chapter concludes by summarizing the main findings and highlighting areas that need more work, including translation into the clinical domain.
Neurobiological Pathways Involved in Fear, Stress, and PTSD
Authors: Heim Christine , Nemeroff Charles B.
Published: November 2017

The symptoms of post-traumatic stress disorder (PTSD) are believed to reflect an inadequate adaptation of neurobiological systems to exposure to severe stressors. A vast number of studies have revealed multiple alterations in neuroendocrine and neurochemical systems in patients with PTSD. It is now evident that certain neurobiological changes in PTSD actually reflect preexisting vulnerability factors that contribute to maladaptive physiological and behavioral responses to traumatic exposure, as well as altered learning and extinction of fear memories. These results suggest the development of novel pathophysiology-driven strategies for intervention that directly target the neurobiological mechanisms that lead to stress sensitization, increased fear memories, and arousal.
Translational Research from Animals to Humans
Authors: Morinobu Shigeru , Yamamoto Shigeto , Fuchikami Manabu
Published: November 2017

To elucidate the pathophysiology of post-traumatic stress disorder (PTSD), the establishment of an appropriate animal model is necessary. In a series of studies, the authors validated single prolonged stress (SPS) as a model for PTSD. SPS-treated rats mimic the pathophysiological abnormalities and behavioral characteristics of PTSD, such as enhanced anxiety-like behavior, glucocorticoid negative feedback, and analgesia. In addition, the authors demonstrated enhanced freezing in response to contextual fear conditioning, and impaired extinction of fear memory, which was alleviated by D-cycloserine (DCS). In parallel, there was a decrease in extracellular glycine mediated by an increase in glycine transporter 1 in the hippocampus of SPS-treated rats after fear conditioning, which suggested that activation of N-methyl-D-asparate receptor by DCS during fear extinction training might alleviate the impaired fear extinction. This chapter summarizes PTSD-like symptoms in SPS and evaluates the validity of SPS as an animal model of PTSD.
Novel Prevention and Treatment Approaches to PTSD
Authors: Howlett Jonathon R. , Stein Murray B.
Published: November 2017

Current therapeutic and preventive interventions for post-traumatic stress disorder (PTSD) have important limitations in terms of efficacy and tolerability. Translational research based on animal models of fear extinction and the stress response has yielded a number of new targets for investigation in clinical studies. Novel treatment approaches include new medications, psychotherapies, and the combination of exposure-based therapies with medications to enhance fear extinction. PTSD prevention represents a major opportunity, and preventive interventions can also be informed by basic neurobiology. Despite potentially useful new therapeutic and prevention approaches, the pace of clinical studies has been slow, and the evidence for most novel interventions is sparse. Given the urgent clinical need, more resources should be directed to clinical trials to fulfill the promise of translational research for this disorder.
50 Imaging Studies Every Doctor Should Know
Authors: Hochman Michael E.
Published: November 2017

This book, 50 Imaging Studies Every Doctor Should Know, provides succinct synopses of the 50 most important medical imaging studies that every doctor should know. For almost every physician specialty, imaging examinations play a central role in the screening, diagnosis, and treatment management of diseases. The appropriate use of medical imaging requires a baseline understanding of the literature we use to decide whether or not a specific imaging study would be helpful in a specific clinical scenario. These summaries therefore cover the evidence-based practice of radiology by outlining the vital clinical questions, study designs and methods, results, and clinical implications that every physician ordering and interpreting imaging examinations should be able to reference. Each chapter summarizes the most salient features of key studies, provides a clinical scenario to provide relevant context, and a relevant imaging example. Topics covered include imaging examinations for headache, back pain, chest pain, musculoskeletal and joint pain, abdominal and pelvic pain, and cancer screening and management, as well as issues of patient radiation exposure.
Neurodegenerative Diseases as Protein Misfolding Disorders
Authors: Nakamura Tomohiro , Lipton Stuart A.
Published: November 2017

Neurodegenerative diseases (NDDs) often represent disorders of protein folding. Rather than large aggregates, recent evidence suggests that soluble oligomers of misfolded proteins are the most neurotoxic species. Emerging evidence points to small, soluble oligomers of misfolded proteins as the cause of synaptic dysfunction and loss, the major pathological correlate to disease progression in many NDDs including Alzheimer’s disease. The protein quality control machinery of the cell, which includes molecular chaperones as found in the endoplasmic reticulum (ER), the ubiquitin-proteasome system (UPS), and various forms of autophagy, can counterbalance the accumulation of misfolded proteins to some extent. Their ability to eliminate the neurotoxic effects of misfolded proteins, however, declines with age. A plausible explanation for the age-dependent deterioration of the quality control machinery involves compromise of these systems by excessive generation of reactive oxygen species (ROS), such as superoxide anion (O2-), and reactive nitrogen species (RNS), such as nitric oxide (NO). The resulting redox stress contributes to the accumulation of misfolded proteins. Here, we focus on aberrantly increased generation of NO-related species since this process appears to accelerate the manifestation of key neuropathological features, including protein misfolding. We review the chemical mechanisms of posttranslational modification by RNS such as protein S-nitrosylation of critical cysteine thiol groups and nitration of tyrosine residues, showing how they contribute to the pathogenesis of NDDs.
Immunotherapy for Neurodegenerative Disorders
Authors: Morgan David
Published: November 2017

Neurodegenerative diseases are a growing health concern through the world as gains in longevity result in an increased population at risk of these age-related disorders. Unfortunately no disease modifying treatments exist for these disorders. Over the last three decades enormous insights have been gained into the causes of these disorders. One approach to treating these diseases is to direct immunotherapy against the misfolded proteins that accumulate within the brains of those with neurodegenerative disease in an attempt to clear the accumulating proteins and slow or prevent expression of the disease. This chapter summarizes the recent (and frustrating) experience with anti-Aβ‎ immunotherapy to treat mild to moderate Alzheimer’s disease, and holds hope that newer generation antibodies and treating presymptomatic disease will have greater impact. In addition, it reviews the preclinical data regarding approaches to treating tau, synuclein, and prion disorders, all of which demonstrate consistent effects in mice and cultured neurons.
Conclusions on Neurodegenerative Disorders
Authors: Pillai Jagan A. , Cummings Jeffrey L.
Published: November 2017

Neurodegenerative diseases strip an individual of his or her cognitive powers, functional capacity, and autonomy while increasing dependence on others. They are an existential threat to an aging society in its ability to provide a meaningful and high quality of life to all its citizens. The classical view of neurodegenerative disorders (NDDs) emphasized the distinctness of each NDD ,with a definable clinical syndrome of neurological deficits, behavioral changes, and progressive functional decline, underpinned by inexorable neuronal loss that is pathological for the age of the subject. Neurodegenerative Disorders: Unifying Principles has covered each of these themes from multiple expert domains to basic science to clinical therapeutics. This detailed overview emphasizes the work recently accomplished to uncover shared themes across NDDs and further posits questions for the future.
Colgate-Palmolive Company
Authors: Quelch John A. , Rodriguez Margaret L.
Published: November 2017

Every company has a public health footprint and should strive to insure that this is as positive as possible. The public health footprint stems from (a) the benefits and costs associated with using the company’s products and service, (b) the wellness of the company’s direct employees and those workers engaged in the company’s supply chain, and (c) the environmental impact of the company’s activities.
Royal Caribbean Cruises Ltd.
Authors: Quelch John A. , Rodriguez Margaret L.
Published: November 2017

Every company has a public health footprint and should strive to insure that this is as positive as possible. The public health footprint stems from (a) the benefits and costs associated with using the company’s products and service, (b) the wellness of the company’s direct employees and those workers engaged in the company’s supply chain, and (c) the environmental impact of the company’s activities.
The Slingshot
Authors: Quelch John A. , Rodriguez Margaret L. , Knoop Carin-Isabel
Published: November 2017

Not only must consumers receive and respond to motivating messages, they must then be able to afford to take the actions required of them and be able to access the solutions. Barriers to adoption of innovations include the compatibility of the innovation with existing ways of doing things, the innovation’s complexity, communicability, relative advantage and the ease with which it can be tried.
Vaxess Technologies, Inc.
Authors: Quelch John A. , Rodriguez Margaret L.
Published: November 2017

Not only must consumers receive and respond to motivating messages, they must then be able to afford to take the actions required of them and be able to access the solutions. Barriers to adoption of innovations include the compatibility of the innovation with existing ways of doing things, the innovation’s complexity, communicability, relative advantage and the ease with which it can be tried.
Demarketing Soda in New York City
Authors: Quelch John A. , Rodriguez Margaret L. , Knoop Carin-Isabel , Snively Christine
Published: November 2017

As more emphasis is placed on consumer engagement and empowerment in the health care arena there are some who wish to control or nudge consumer behavior in the “right” direction, especially if they perceive consumers to be insufficiently educated to handle the new information available to them.
Fresno’s Social Impact Bond for Asthma
Authors: Quelch John A. , Rodriguez Margaret L.
Published: November 2017

Public health officials are constantly challenged by pressure to accept new product markets that may benefit some consumers but may harm others. How are these trade-offs to be evaluated? Both E-cigarettes and the marketing of recreational marijuana are cases in point. Other innovations, such as social impact bonds, may help in stretching public health dollars and improving overall impact.
E-Cigarettes
Authors: Quelch John A. , Rodriguez Margaret L.
Published: November 2017

Public health officials are constantly challenged by pressure to accept new product markets that may benefit some consumers but may harm others. How are these trade-offs to be evaluated? Both E-cigarettes and the marketing of recreational marijuana are cases in point. Other innovations, such as social impact bonds, may help in stretching public health dollars and improving overall impact.
Principles of Electricity and Electronics
Authors: Montgomery Erwin B.
Published: November 2017

The nervous system basically is an electrical device. Thus, the clinical effects of DBS result from affecting the nervous system electronically by depositing electrical charges in brain tissue. How the electrical charge is deposited depends on the electronics of the DBS IPGs, which is what you manipulate to deliver the electrical charge. Consequently, you need to know how controlling the electronics controls the deposition of the electrical charge into the brain. The physics of the electron is fundamental to the effects of DBS, as it is fundamental of the operations of the nervous system, so the chapter begins with a discussion of electrical forces. Electronics relates to the purposeful control of the flow of electrical charges, as in deep brain stimulation: the chapter explains exactly how DBS’s effects are achieved.
Controlling the Flow of Electrical Charges
Authors: Montgomery Erwin B.
Published: November 2017

In depolarization to effect neuronal activations,, electrical charges are delivered to the neuron to affect the electrical potential across the neuronal membrane to subsequently affect voltage-gated ionic conductance channels. The orientation of the field of electrical charges to the neuronal membrane is critical. Electrical charges flow from the negative contact to the positive contact. The negative electrostatic charge “pushes” negative charges onto the outer surface of the neuron, which results in depolarization of the neuronal membrane. Neurons near the positive contact will not have negative electrical charges deposited on the outer surface, will not be depolarized, and thus, are not activated. Likewise, neurons whose membranes are oriented parallel to the lines of electrical forces that move electrical charges will not receive the electrical charges and, consequently, will not be activated. The electronics of the DBS systems are designed to control the electrostatic forces so as to control the activations of the nervous system to generate benefit and avoid adverse effects.
Nervous System Responses to DBS
Authors: Montgomery Erwin B.
Published: November 2017

The technology related to DBS has advanced considerably. DBS implanted pulse generators (IPGs) have greatly increased their capabilities, providing opportunities for different combinations of DBS pulses and stimulation trains. Yet therein lies a dilemma. An increase in technical capabilities could lead to a bewildering and potentially befuddling number of possibilities to consider. Understanding how the nervous system responses to DBS could provide a more rational and hence, more effective approach to DBS programming. Unfortunately, the increasing catalogue of known responses has not translated into an understanding of how DBS works but it is a start and is review in this chapter.
DBS Effects on Motor Control
Authors: Montgomery Erwin B.
Published: November 2017

Use of DBS extends beyond what are typically referred to as “movement disorders,” for which issues of motor control are paramount; currently approved for treatment of refractory obsessive-compulsive disorder (OCD) disorder, DBS is expected to gain approval as a treatment for epilepsy as well. Indeed, no neurological or psychiatric disorder ought to be excluded a priori from consideration as a potential indication for DBS. Post-operative management of DBS for these other disorders will benefit from a better understanding of the mechanisms of action. An understanding of the ways in which the brain responds to DBS (see Chapter 6—Nervous System Responses to DBS) related to motor control may therefore serve as an important metaphor for understanding the use of DBS for other conditions.
Approaches to Programming
Authors: Montgomery Erwin B.
Published: November 2017

Persistence and patience are the keys to successful DBS programming. Several studies show that one of the most common causes of unsuccessful DBS therapy is an inadequately programmed IPG. Note that with the rapid increase in the types and manufacturers of DBS systems now and anticipated, it is difficult to make precise statements about stimulation parameters. The responsibility for choice of stimulation parameters, electrode configurations, and pulse trains lies solely with the programmer. Specific examples of stimulation parameters, electrode configurations, and pulse trains provided in this text are for informational and educational purposes only. Covered in this chapter are issues of battery life, the optimal time to program DBS, monopolar surveys, and programming to prevent adverse effects.
Clinical Assessments
Authors: Montgomery Erwin B.
Published: November 2017

The primary endpoints of DBS adjustments are functional and as such, are related to the symptoms and signs due to the disease and consequent to stimulation. Thus, effective programming requires the programmer to be an astute clinician in the assessing symptoms and signs. This is not always a straight forward or intuitive process. For example, stimulation of the corticospinal tract can reduce tremor but interfere with other motor functions. Assesments often are complicated by the time required for changes to manifest rendering some assessments impractical in the confines of a clinic visit. A systematic approach is based on a knowledge of the disorder being treated and the regional anatomy around the DBS lead that allows anticipation of possible adverse effects. Effective assessments benefit from use of rating scales and adequate documentation.
Approach to DBS in the Vicinity of the Ventral Intermediate Nucleus of the Thalamus DBS
Authors: Montgomery Erwin B.
Published: November 2017

The regional anatomy around the DBS lead in the ventral intermediate nucleus of the thalamus (Vim) determines efficacy and adverse effects. Understanding the regional anatomy allows the programmer to adjust the stimulation to provide optimal benefit and the absence of adverse effects. Vim is the target of therapeutic DBS. The ventrocaudal nucleus of the thalamus (Vc) lies posterior to the Vim. Electrical stimulation of Vc can cause treatment-limiting paresthesias. The corticospinal and cortical bulbar tracts in the internal capsule lie lateral and ventral to the Vim. Electrical stimulation of the internal capsule can cause tonic muscle contractions. There are multiple nomenclatures of the subnuclei of the thalamus. Although the term ventrolateral thalamus (VL) is commonly used in the physiology literature, ventral intermediate thalamus (Vim), is used in the DBS literature. Technically, the VL refers to both regions of the thalamus that receive inputs from GPi and cerebellum, whereas Vim refers to the cerebellar-receiving area of the thalamus and is thus a subdivision of the VL and is the target of DBS for tremor-related disorders.
Terminally Ill Patients and the “Right to Try” Experimental Drugs
Authors: Dresser Rebecca
Published: November 2017

This chapter addresses access to unapproved drugs. Some terminally ill patients enroll in research as a way to gain access to experimental drugs. Other patients want to try the drugs without enrolling in research. The US Food and Drug Administration permits patients to do so under certain circumstances, but critics say the government rules are too restrictive. “Right to try” advocates campaign for laws permitting more liberal access, telling heart-wrenching stories about patients desperate to obtain experimental drugs. But the picture they present is one-sided. It disregards the negative impact that more liberal access policies may have on the drug trials that benefit society at large, and it ignores stories conveying the harm that can come from access to experimental drugs. These factors belong in the debate too.
Research Subjects as Literary Subjects
Authors: Dresser Rebecca
Published: November 2017

This chapter turns to literature for insights on what it is like to be a research subject. Many creative writers look at research through the eyes of research subjects. They apply imagination and literary skills to bring the research world to life. Fictional accounts like White Noise and The Normals (novels about healthy volunteers in phase 1 drug studies), “Escape from Spiderhead” (a short story about research at a prison), and We Are Not Ourselves (a novel describing participation in an Alzheimer’s drug study) illuminate ethical dimensions of the human subject experience. Stories often portray researchers as untrustworthy individuals who manipulate subjects in pursuit of their research agendas, although some also include subjects who misbehave for their own ends. In some stories, flawed researchers become better people through their encounters with research subjects. Research professionals can learn from the fresh and vivid ways in which creative writers portray research experiences.
How to Hear Subjects
Authors: Dresser Rebecca
Published: November 2017

This chapter makes the case for including experienced subjects in a variety of activities related to research ethics and policy. People with personal experience as research subjects should be involved in research review as well as in community-engaged and patient-centered research efforts. Experienced subjects should also be included in advisory groups considering ethical and policy topics like informed consent and comparative-effectiveness research. Achieving subject inclusion will require attention to matters such as selection criteria and training subjects for participation in ethics and policy activities. The inclusion challenges should not be exaggerated, however. Adding subjects to research ethics activities is a manageable step toward an improved research enterprise.
Conscripted in the Pursuit of Perfection
Authors: de Melo-Martín Inmaculada
Published: November 2017

Harris and Savulescu have argued that the use of reprogenetic technologies to select and enhance people’s offspring is not only morally permissible but morally required. This chapter shows that there are no reasons to accept that such obligations exist. Savulescu and Harris fail to offer plausible grounds for a moral obligation to select or to enhance future children. Even if the existence of these obligations were granted, their usefulness in guiding the decisions and actions of prospective parents leaves much to be desired. Finally, serious negative consequences are likely to follow from endorsing and fulfilling these putative moral obligations.