bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Accountable Care Organizations on Oncology Practice
Authors: Shulman Lawrence N.
Published: May 2014

Cancer care accounts for a significant portion of the rise in health care costs, and therefore, as national efforts escalate to control cost, cancer care will be a focus of concern. Cost increases in cancer care are related to many factors, including increasing cancer incidence in an aging population, the introduction of new high-cost therapeutics, and the high cost of end-of-life care. Accountable care organizations (ACOs) have been one of the major efforts directed at controlling health care costs. How cancer care will fit into the rubric of ACOs is not entirely clear but will certainly evolve over the coming years. The oncology profession has the opportunity to play a role in this evolution or could leave the evolution to others driving the process, such as the Centers for Medicare and Medicaid Services (CMS), private payers, and ACOs. Ideally all parties will work together to provide a construct for high-value, high-quality care for patients with cancer while contributing to cost control in overall health care.
Achieving a Deeper Understanding of the Implemented Provisions of the Affordable Care Act
Authors: Zhang Shuang Qin , Polite Blase N.
Published: May 2014

The Patient Protection and Affordable Care Act (ACA) was signed into law by President Barack Obama on March 23, 2010. Since that time, numerous regulations have been promulgated, legal battles continue to be fought and the major provisions of the law are being implemented. In the following article, we outline components of the ACA that are relevant to cancer health care, review current implementation of the new health care reform law, and identify challenges that may lie ahead in the post-ACA era. Specifically, among the things we explore are Medicaid expansion, health insurance exchanges, essential health benefits and preventive services, subsidies, access to clinical trials, the Medicare Part D donut hole, and physician quality payment reform.
Is Current Technology Improving Outcomes with Radiation Therapy for Gliomas?
Authors: Brada Michael , Haylock Brian
Published: May 2014

Radiotherapy (RT) remains the principal component of glioma treatment, and three-dimensional conformal RT (3DCRT) is the current standard of RT delivery. Advances in imaging and in RT technology have enabled more precise treatment to defined targets combined with better means of avoiding critical normal structures, and this is complemented by intensive quality assurance, which includes on-treatment imaging. The refinements of 3DCRT include intensity modulated RT (IMRT), arcing IMRT, and high-precision conformal RT, formerly described as “stereotactic,” which can be delivered using a linear accelerator or other specialized equipment. Although proton therapy uses heavy charged particles, the principal application can also be considered as refinement of 3DCRT. The technologies generally improve the dose differential between the tumor and normal tissue and enable more dose-intensive treatments. However, these have not translated into improved survival outcome in patients with low- and high-grade gliomas. More intensive altered fractionation regimens have also failed to show survival benefit. Nevertheless, novel technologies enable better sparing of normal tissue and selective avoidance of critical structures, and these need to be explored further to improve the quality of life of patients with gliomas. Principal clinical advance in RT has been the recognition that less intensive treatments are beneficial for patients with adverse prognosis high-grade gliomas. We conclude that the principal gain of modern RT technology is more likely to emerge as a reduction in treatment related toxicity rather than as an improvement in overall survival; the optimal avoidance strategies remain to be defined.
Scholastic Probability as Rational Assertability: The Rise of Theories of Reasonable Disagreement
Authors: Schüssler Rudolf
Published: May 2014

The scholastics used
On Minimum Phase
Authors: Ilchmann Achim , Wirth Fabian
Published: May 2014

We discuss the concept of `minimum phase' for scalar semi Hurwitz
transfer functions. The latter are rational functions where the
denominator polynomial has its roots in the closed left half complex
plane. In the present note, minimum phase is defined in terms of the
derivative of the argument function of the transfer function. The
main tool to characterize minimum phase is the Hurwitz reflection.
The factorization of a weakly stable transfer function into an
all-pass and a minimum phase system leads to the result that any semi
Hurwitz transfer function is minimum phase if, and only if, its
numerator polynomial is semi Hurwitz. To characterize the zero
dynamics, we use the Byrnes-Isidori form in the time domain and the
internal loop form in the frequency domain. The uniqueness of both
forms is shown. This is used to show in particular that asymptotic
stable zero dynamics of a minimal realization of a transfer function
yields minimum phase, but not vice versa.
Mathematische Modellierung des thermischen Verdampfungsverhaltens organischer
Halbleiter
Authors: Steinberger Martin , Horn Martin , Jakopič Georg
Published: May 2014

Organische elektronische Bauelemente wie z. B. Dünnfilmtransistoren
werden üblicherweise durch thermische Verdampfung organischer
Halbleitermaterialien aus einer Effusionszelle im Hochvakuum
hergestellt. In der vorliegenden Arbeit wird ein mathematisches Modell
einer Beschichtungsanlage entwickelt, welches das instationäre
Verdampfungsverhalten der Halbleiter, das thermische Verhalten der
Effusionszelle sowie das Wachstum dünner Schichten beschreibt. Das
Modell soll als Grundlage für modellbasierte Reglerentwürfe dienen.
Effect of selective cyclooxygenase-2 inhibitor lumiracoxib on phenolsulfonphthalein disposition in rats
Authors: Honjo Hiroaki , Uwai Yuichi , Nabekura Tomohiro
Published: May 2014

Selective cyclooxygenase-2 inhibitor lumiracoxib was shown to have the strong inhibitory potencies on the renal organic anion transporter (OAT)1 and also on OAT3 from drug transport experiments. The purpose of this study was to examine the effect of lumiracoxib on disposition of phenolsulfonphthalein (PSP) – which is mainly excreted into urine via OATs – from in vivo experiments. After the intravenous injection of PSP and lumiracoxib into rats, pharmacokinetic analysis was performed. After the intravenous injection of PSP as a bolus, its plasma concentration decreased time-dependently. Until 60 min after the injection, 51.1% of the dose was recovered into urine. The simultaneous administration of lumiracoxib increased the plasma levels of PSP and reduced its urinary recovery to 23.6% of the dose. The pharmacokinetic analysis using a two-compartment model exhibited that lumiracoxib affected the parameters implying the elimination of PSP. The present study demonstrates that lumiracoxib interfered with urinary excretion of PSP in rats.
Ein großes Werk zum Abschluss bringen
Authors: Gerhardt Volker , Karl Jacqueline , Esser Andrea Marlen
Published: May 2014

After a short history of the Akademie-Ausgabe der Werke Immanuel Kants, it is shown that the edition is incomplete in some essential parts: The central topic of the first part of the article is the Opus postumum. Here we have a new critical transcription which differs not only in the composition but even in many details. The second project is focused on Nachschriften of Kant’s lectures on Physische Geographie. The three volumes will show that Kant continually actualized the material for this complex area of problems, for which he presented the outlines of a new academic discipline (as he did too in his Anthropology). The other central topic is the new edition of the three Critiques. The second part of the article demonstrates principle steps of critical editing using the example of Kant’s third Critique, the Critique of Judgment.
Georg Wilhelm Friedrich Hegel: Das Editionsprojekt der Gesammelten Werke
Authors: Jaeschke Walter , Bauer Christoph J.
Published: May 2014

The edition of the Corpus Hegelianum by disciples and friends of Hegel (1832 ff.) was an enormous achievement. It nevertheless shows grave shortcomings due to its instrumental usage in the disputes of that time. Thus since 1968 the Corpus is being replaced by the new edition “Hegel: Gesammelte Werke”. This edition contains Hegel’s published and posthumous works (vols. 1-22) as well as the transcripts of his lectures (vols. 23-30, in several fascicles). Taking Hegel’s “Lecture on the Philosophy of Subjective Spirit” as an example, part II of this paper presents the transcripts as conveying an abundance of novel texts, which, furnished with explicative annotations, can give us new insights into the ‘Berliner Hegel’.
Leben Herstellen
Authors: Rödl Sebastian
Published: May 2014

It is widely believed that we might be able produce life out of nonliving substances if we possessed the relevant knowledge. Thus synthetic biology is said to be on the way towards artificial life. But this is nonsense: “artificial life” cannot be thought. The idea that biological organisms could be produced reflects a misunderstandig of the concept “life”. Life is formally characterized by the fact that that which in the case of artifacts is three distinct activities - being something, producing it, and using it - is one. For a living being, to be is to be the source of its own activity through its own activity. Hence, if there is an activity of producing distinct from being what is produced - as would have to be the case in artificial life - what is thus produced is not life.
Lebewesen verstehen
Authors: Gutmann Mathias
Published: May 2014

Artefacts are made whereas living entities generate themselves: the extent to which this distinction seems obvious is the extent to which it tends to transform the relation between living entities on the one hand and artefacts on the other into a contradiction, a tendency which in consequence conceals the intricate dialectics between φύσις and τέχνη.

The aim of this paper is to develop the dialectical relations between life - in terms of living entities - and artefacts from a constructivist point of view. The explication of the functionalistic structure of an Aristotelian concept leads to a constructivist reconstruction of the epistemic relation between living entities and artefacts on the one hand and living entities and organisms on the other hand. The resulting argumentation avoids some restrictions of Aristotelian approaches as well as of their modern counterpart (i. e. synthetic biology).
Brief aus Ungarn
Authors: Boros Gábor
Published: May 2014

My “Letter” collects some facts concerning the 20th century history of Hungarian Philosophy as a basis for understanding its situation now. Progressive and conservative systems of thought dominated the first half of the century alternately, until the post-war communist regime refused to tolerate independent thinking. The new regime after 1956 was unpredictably hostile or tolerant towards philosophical dissenters. All this resulted in a multifaceted philosophical life in the period after 1989. Its basic tendency has been a historical approach issuing in various disciplines like phenomenology and hermeneutics, analytical philosophy, postmodern thought, philosophy of religion, while ethics and aesthetics became disciplines in their own right. The “Letter” maps out some of the institutional bases of philosophizing as well as some of the dangers threatening independent philosophy.
Beobachtungen zum „Schicksalsfutur“ mit sollte. Ein Beitrag zu ‘Tempus und Textualität’
Authors: Abraham Werner
Published: May 2014

The present paper deals with the so-called ‘fate future’, a use of the German modal verb
Three ways of terminological linearisation
Authors: Roelcke Thorsten
Published: May 2014

In this article
Short and efficient synthesis of 5-aminothiazole-4-carboxamide
Authors: Wang Jin , Guo Jianyu , Tang Yihong , Zhang Suxia , Tao Jianwei , Lu Yan
Published: May 2014

5-Aminothiazole-4-carboxamide is a precursor for the synthesis of thiazole [4,5-d] pyrimidines. In this work, a new synthesis method with a high total yield (79%) of 5-aminothiazole-4-carboxamide was reported. The starting material is aminocyanacetamide. This synthesis method is environment-friendly and is suitable for industrial production.
Intergenerational Communities
Authors: Alexander Gregory S.
Published: May 2014

Under the human flourishing theory of property, owners have obligations, positive as well as negative, that they owe to members of the various communities to which they belong. But are the members of those communities limited to living persons, or do they include non-living persons as well, i.e., future persons and the dead? This Article argues that owners owe two sorts of obligation to non-living members of our generational communities, one general, the other specific. The general obligation is to provide future generations with the basic material background conditions that are necessary for them to be able to carry out what I call life-transcending projects that their forebears have transmitted to them. The specific obligation is project-specific; that is, its purpose is to enable successive generational community members to whom particular life-transcending projects have been forwarded to be carried out in their way. The future generational members to whom the project is transferred must also be given whatever resources or goods are necessary to carry the project forward in its intended way. I argue further that each generational community owes its predecessors the obligation to accept life-transcending projects transmitted to them by their forebears and make reasonable efforts to carry those projects forward into the future. The obligation is based on the past generational community members’ dependency on their successors for the projects to continue into the future, a matter that is constitutive of the project creators’ flourishing. This obligation is defeasible, rather than absolute, however.
Intergenerational Justice for Children: Restructuring Adoption, Reproduction and Child Welfare Policy
Authors: Bartholet Elizabeth
Published: May 2014

An intergenerational justice perspective requires that we look at the condition of the existing generation of children and those to be born in the future. Many millions of the existing generation of children are now in trouble and at high risk of never fulfilling their human potential. These children are in turn unlikely, if they live to produce children, to be capable of providing the nurturing parenting that the next generation will need.

The article’s starting premises are that we should count child interests as of equivalent value to adult interests and that we do owe justice not just to the existing generation of children but to the next generations as well. Justice to the next generations means encouraging the creation of children who will have a good chance to enjoy the pleasures of life, children who will be born healthy and will be brought up by nurturing parents. Given these premises, there is much wrong with current reality and related policy.

We now encourage the reproduction of more children than we can care for, provide limited child welfare enabling poor parents to better care for their children, and discourage adoption both domestic and international. We should reverse these policies. We should change the pronatalist and anti-contraception policies that encourage the reproduction of children who won’t likely be born healthy or receive nurturing care. We should provide child welfare so that poor parents who want to keep and raise their children can do so. We should encourage adoption, both domestic and international.
Parfit on the Non-identity Problem, Again
Authors: Heyd David
Published: May 2014

In his recent work, Parfit returns to the examination of the non-identity problem, but this time not in the context of a theory of value but as part of a Scanlonian theory of reasons for action. His project is to find a middle ground between pure impersonalism and the narrow person-affecting view so as to do justice to some of our fundamental intuitions regarding procreative choices. The aim of this article is to show that despite the sophisticated and challenging thought experiments and conceptual suggestions (mainly that of a “general person”), Parfit’s project fails and that we are left with the stark choice between personalism and impersonalism.
A note on nonparametric estimation of bivariate tail dependence
Authors: Bücher Axel
Published: May 2014

Nonparametric estimation of tail dependence can be based on a standardization of the marginals if their cumulative distribution functions are known.
In this paper it is shown to be asymptotically more efficient if the additional knowledge of the marginals is ignored and estimators are based on ranks. The
discrepancy between the two estimators is shown to be substantial for the popular Clayton and Gumbel–Hougaard models. A brief simulation study indicates that the asymptotic conclusions transfer to finite samples.
Entwicklung des Strömungszustandes an einer
gravimetrischen Kalt- und Warmwasser-Normalmessanlage für große
Volumenströme
Authors: Eichler Thomas , Lederer Thomas
Published: May 2014

Die Ausbildung der Strömung fließenden Wassers einer
gravimetrischen Kalt- und Warmwasser-Normalmessanlage für große
Volumenströme wird anhand von Stereoscopic Particle Image
Velocimetry (SPIV)-Messungen an verschiedenen Positionen
gezeigt. Dabei wird nachgewiesen, dass an dieser Prüfanlage nahezu
optimale Strömungszustände zur Kalibrierung von Durchflusssensoren
gewährleistet werden. SPIV eignet sich als schnelles und präzises
Messverfahren zur zeitlich und räumlich hochaufgelösten Ermittlung
von 3D-Geschwindigkeitsverteilungen in Rohrleitungen.
Rauheitsmessung an pharmazeutischen Tabletten mittels Angularer
Speckle-Korrelation
Authors: Salazar Bloise Félix , Aulbach Laura , Jakobi Martin , Koch Alexander W.
Published: May 2014

Eine vollständige Charakterisierung von pharmazeutischen Tabletten
besteht nicht nur in der Analyse der chemischen Zusammensetzung, sondern
auch in der Untersuchung der Fertigung der inneren Struktur und der
Oberflächenstruktur. Ziel dieser Arbeit ist es, die
Oberflächenrauheit von Tabletten an Originalpräparaten und Generika
mittels Angularer Speckle Korrelation (ASK) zu bestimmen. Die Ergebnisse
zeigen unterschiedliche Rauheitswerte bei Tabletten mit gleichem Wirkstoff
bei verschiedenen Trägerstoffen. Berührungslose
Speckle-Rauheitsmessung könnte eingesetzt werden, um die Regelung des
Produktionsprozesses zu verbessern, z. B. während die Tabletten aus
Pulver gepresst werden.
Tiefenscannende Weißlichtinterferometrie in maschinennaher Umgebung
Authors: Tereschenko Stanislav , Kühnhold Peter , Lehmann Peter , Zellmer Lisa , Brückner-Foit Angelika
Published: May 2014

Weißlichtinterferometer sind hochauflösende optische Messgeräte zum
dreidimensionalen Messen von Mikrostrukturen. Der Einsatz solcher
Messgeräte in maschinennaher Umgebung abseits schwingungsgedämpfter
Labore wird durch Umgebungsschwingungen erschwert oder sogar unmöglich
gemacht. Daher wird nach Algorithmen oder modifizierten Anordnungen
gesucht, um den Einfluss der Störschwingungen zu kompensieren bzw. aus
den Ergebnissen herauszurechnen. In diesem Beitrag wird ein passives
Kompensationsverfahren vorgestellt, mit dem der Einfluss einer
monofrequenten Störschwingung kompensiert werden kann. Dazu wird ein
punktförmig messendes Laserinterferometer verwendet, das in das
Weißlichtinterferometer (WLI) integriert ist und parallel zur
Weißlichtmessung mit höherer zeitlicher Auflösung das
Interferenzsignal des Lasers aufzeichnet. Die Bestimmung des
jeweiligen Abstands zwischen WLI und Messobjekt erfolgt nachträglich
durch Fourieranalyse, wobei die erforderlichen Parameter wie Frequenz,
Amplitude und Phasenlage der Störschwingung aus dem Amplituden-
bzw. Phasenspektrum des Interferenzsignals ermittelt werden. Diese
Information wird genutzt, um die gestörten WLI-Korrelogramme zu
korrigieren. Anschließend kann die Oberflächentopographie auf
konventionelle Weise mit Hilfe der Hüllkurven- und der
Phasenauswertung bestimmt werden.
Temporal Signatures of Taste Quality Driven by Active Sensing
Authors: Graham Dustin M. , Sun Chengsan , Hill David L.
Published: May 2014

Animals actively acquire sensory information from the outside world, with rodents sniffing to smell and whisking to feel. Licking, a rapid motor sequence used for gustation, serves as the primary means of controlling stimulus access to taste receptors in the mouth. Using a novel taste-quality discrimination task in head-restrained mice, we measured and compared reaction times to four basic taste qualities (salt, sour, sweet, and bitter) and found that certain taste qualities are perceived inherently faster than others, driven by the precise biomechanics of licking and functional organization of the peripheral gustatory system. The minimum time required for accurate perception was strongly dependent on taste quality, ranging from the sensory-motor limits of a single lick (salt, ∼100 ms) to several sampling cycles (bitter, >500 ms). Further, disruption of sensory input from the anterior tongue significantly impaired the speed of perception of some taste qualities, with little effect on others. Overall, our results show that active sensing may play an important role in shaping the timing of taste-quality representations and perception in the gustatory system.
Role of Nucleus Accumbens Shell Neuronal Ensembles in Context-Induced Reinstatement of Cocaine-Seeking
Authors: Cruz Fabio C. , Babin Klil R. , Leao Rodrigo M. , Goldart Evan M. , Bossert Jennifer M. , Shaham Yavin , Hope Bruce T.
Published: May 2014

Environmental contexts previously associated with drug use provoke relapse to drug use in humans and reinstatement of drug seeking in animal models of drug relapse. We examined whether context-induced reinstatement of cocaine seeking is mediated by activation of context-selected nucleus accumbens neurons. We trained rats to self-administer cocaine in Context A and extinguished their lever-pressing in a distinct Context B. On test day, reexposure to the cocaine-associated Context A reinstated cocaine seeking and increased expression of the neural activity marker Fos in 3.3% of accumbens shell and 1.6% of accumbens core neurons. To assess a causal role for these activated neurons, we used the Daun02 inactivation procedure to selectively inactivate these neurons. We trained c-fos-lacZ transgenic rats to self-administer cocaine in Context A and extinguished their lever-pressing in Context B. On induction day, we exposed rats to either Context A or a novel Context C for 30 min and injected Daun02 or vehicle into accumbens shell or core 60 min later. On test day, 3 d after induction day, the ability of Context A to reinstate cocaine seeking and increase neuronal activity in accumbens shell was attenuated when Daun02 was previously injected after exposure to Context A. Daun02 injections after exposure to the novel Context C had no effect on context-induced reinstatement of cocaine seeking despite much greater numbers of Fos-expressing neurons induced by Context C. Daun02 injections in accumbens core had no effect. Our data suggest that context-induced reinstatement of cocaine seeking is mediated by activation of context-selected accumbens shell but not core neuronal ensembles.
A Critical Role of Lateral Hypothalamus in Context-Induced Relapse to Alcohol Seeking after Punishment-Imposed Abstinence
Authors: Marchant Nathan J. , Rabei Rana , Kaganovsky Konstantin , Caprioli Daniele , Bossert Jennifer M. , Bonci Antonello , Shaham Yavin
Published: May 2014

In human alcoholics, abstinence is often self-imposed, despite alcohol availability, because of the negative consequences of excessive use. During abstinence, relapse is often triggered by exposure to contexts associated with alcohol use. We recently developed a rat model that captures some features of this human condition: exposure to the alcohol self-administration environment (context A), after punishment-imposed suppression of alcohol self-administration in a different environment (context B), provoked renewal of alcohol seeking in alcohol-preferring P rats. The mechanisms underlying context-induced renewal of alcohol seeking after punishment-imposed abstinence are unknown. Here, we studied the role of the lateral hypothalamus (LH) and its forebrain projections in this effect. We first determined the effect of context-induced renewal of alcohol seeking on Fos (a neuronal activity marker) expression in LH. We next determined the effect of LH reversible inactivation by GABAA+ GABABreceptor agonists (muscimol + baclofen) on this effect. Finally, we determined neuronal activation in brain areas projecting to LH during context-induced renewal tests by measuring double labeling of the retrograde tracer cholera toxin subunit B (CTb; injected in LH) with Fos. Context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with increased Fos expression in LH. Additionally, renewal was blocked by muscimol + baclofen injections into LH. Finally, double-labeling analysis of CTb + Fos showed that context-induced renewal of alcohol seeking after punishment-imposed abstinence was associated with selective activation of accumbens shell neurons projecting to LH. The results demonstrate an important role of LH in renewal of alcohol seeking after punishment-imposed abstinence and suggest a role of accumbens shell projections to LH in this form of relapse.
Distributed Value Representation in the Medial Prefrontal Cortex during Intertemporal Choices
Authors: Wang Qiang , Luo Shan , Monterosso John , Zhang Jintao , Fang Xiaoyi , Dong Qi , Xue Gui
Published: May 2014

The ability to resist current temptations in favor of long-term benefits is a critical human capacity. Despite the extensive studies on the neural mechanisms of intertemporal choices, how the subjective value of immediate and delayed rewards is represented and compared in the brain remains to be elucidated. The present fMRI study addressed this question by simultaneously and independently manipulating the magnitude of immediate and delayed rewards in an intertemporal decision task, combined with univariate analysis and multiple voxel pattern analysis. We found that activities in the posterior portion of the dorsal medial prefrontal cortex (DmPFC) were modulated by the value of immediate options, whereas activities in the adjacent anterior DmPFC were modulated by the subjective value of delayed options. Brain signal change in the ventral mPFC was positively correlated with the “relative value” (the absolute difference of subjective value between two intertemporal alternatives). In contrast, the dorsal anterior cingulate cortex activity was negatively correlated with the relative value. These results suggest that immediate and delayed rewards are separately represented in the dorsal mPFC and compared in the ventral mPFC to guide decisions. The functional dissociation of posterior and anterior DmPFC in representing immediate and delayed reward is consistent with the general structural and functional architecture of the prefrontal cortex and may provide a neural basis for human's unique capacity to delayed gratification.
Orbitofrontal Dopamine Depletion Upregulates Caudate Dopamine and Alters Behavior via Changes in Reinforcement Sensitivity
Authors: Clarke H. F. , Cardinal R. N. , Rygula R. , Hong Y. T. , Fryer T. D. , Sawiak S. J. , Ferrari V. , Cockcroft G. , Aigbirhio F. I. , Robbins T. W. , Roberts A. C.
Published: May 2014

Schizophrenia is associated with upregulation of dopamine (DA) release in the caudate nucleus. The caudate has dense connections with the orbitofrontal cortex (OFC) via the frontostriatal loops, and both areas exhibit pathophysiological change in schizophrenia. Despite evidence that abnormalities in dopaminergic neurotransmission and prefrontal cortex function co-occur in schizophrenia, the influence of OFC DA on caudate DA and reinforcement processing is poorly understood. To test the hypothesis that OFC dopaminergic dysfunction disrupts caudate dopamine function, we selectively depleted dopamine from the OFC of marmoset monkeys and measured striatal extracellular dopamine levels (using microdialysis) and dopamine D2/D3 receptor binding (using positron emission tomography), while modeling reinforcement-related behavior in a discrimination learning paradigm. OFC dopamine depletion caused an increase in tonic dopamine levels in the caudate nucleus and a corresponding reduction in D2/D3 receptor binding. Computational modeling of behavior showed that the lesion increased response exploration, reducing the tendency to persist with a recently chosen response side. This effect is akin to increased response switching previously seen in schizophrenia and was correlated with striatal but not OFC D2/D3 receptor binding. These results demonstrate that OFC dopamine depletion is sufficient to induce striatal hyperdopaminergia and changes in reinforcement learning relevant to schizophrenia.
Violation of the Craniocentricity Principle for Vestibularly Evoked Balance Responses under Conditions of Anisotropic Stability
Authors: Mian Omar S. , Day Brian L.
Published: May 2014

The balance response direction to electrically evoked vestibular perturbation is closely tied to head orientation. Such craniocentric response organization is expected of a simple error correction process. Here we ask whether this is maintained when the body is made more stable, but with the stability being greater in one direction than another. Since it is known that vestibularly evoked balance responses become smaller as body stability increases, the following two outcomes are possible: (1) response magnitude is attenuated, but with craniocentricity maintained; and (2) anisotropy of stability is considered such that components of the response are differentially attenuated, which would violate a craniocentric organizing principle. We tested these alternatives by measuring the direction of balance responses to electrical vestibular stimulation across a range of head orientations and stance widths in healthy humans. With feet together, the response was highly craniocentric. However, when stance width was increased so that the body was more stable in the frontal plane, response direction became biased toward the sagittal direction. This resulted in a nonlinear relationship between head orientation and response direction. While stance width changes the mechanical state of the body, the effect was also present when lateral light touch was used to produce anisotropy in stability, demonstrating that a significantly altered mechanical state was not crucial. We conclude that the balance system does not simply act according to the direction of vestibular input. Instead, it appears to assign greater relevance to components of vestibular input acting in the plane of lesser body stability than the plane of greater body stability, and acts accordingly.
Overexpression of the Astrocyte Glutamate Transporter GLT1 Exacerbates Phrenic Motor Neuron Degeneration, Diaphragm Compromise, and Forelimb Motor Dysfunction following Cervical Contusion Spinal Cord Injury
Authors: Li Ke , Nicaise Charles , Sannie Daniel , Hala Tamara J. , Javed Elham , Parker Jessica L. , Putatunda Rajarshi , Regan Kathleen A. , Suain Valérie , Brion Jean-Pierre , Rhoderick Fred , Wright Megan C. , Poulsen David J. , Lepore Angelo C.
Published: May 2014

A major portion of spinal cord injury (SCI) cases affect midcervical levels, the location of the phrenic motor neuron (PhMN) pool that innervates the diaphragm. While initial trauma is uncontrollable, a valuable opportunity exists in the hours to days following SCI for preventing PhMN loss and consequent respiratory dysfunction that occurs during secondary degeneration. One of the primary causes of secondary injury is excitotoxic cell death due to dysregulation of extracellular glutamate homeostasis. GLT1, mainly expressed by astrocytes, is responsible for the vast majority of functional uptake of extracellular glutamate in the CNS, particularly in spinal cord. We found that, in bacterial artificial chromosome-GLT1-enhanced green fluorescent protein reporter mice following unilateral midcervical (C4) contusion SCI, numbers of GLT1-expressing astrocytes in ventral horn and total intraspinal GLT1 protein expression were reduced soon after injury and the decrease persisted for ≥6 weeks. We used intraspinal delivery of adeno-associated virus type 8 (AAV8)-Gfa2 vector to rat cervical spinal cord ventral horn for targeting focal astrocyte GLT1 overexpression in areas of PhMN loss. Intraspinal delivery of AAV8-Gfa2-GLT1 resulted in transduction primarily of GFAP+astrocytes that persisted for ≥6 weeks postinjury, as well as increased intraspinal GLT1 protein expression. Surprisingly, we found that astrocyte-targeted GLT1 overexpression increased lesion size, PhMN loss, phrenic nerve axonal degeneration, and diaphragm neuromuscular junction denervation, and resulted in reduced functional diaphragm innervation as assessed by phrenic nerve-diaphragm compound muscle action potential recordings. These results demonstrate that GLT1 overexpression via intraspinal AAV-Gfa2-GLT1 delivery exacerbates neuronal damage and increases respiratory impairment following cervical SCI.
Achieving High-Frequency Optical Control of Synaptic Transmission
Authors: Jackman Skyler L. , Beneduce Brandon M. , Drew Iain R. , Regehr Wade G.
Published: May 2014

The optogenetic tool channelrhodopsin-2 (ChR2) is widely used to excite neurons to study neural circuits. Previous optogenetic studies of synapses suggest that light-evoked synaptic responses often exhibit artificial synaptic depression, which has been attributed to either the inability of ChR2 to reliably fire presynaptic axons or to ChR2 elevating the probability of release by depolarizing presynaptic boutons. Here, we compare light-evoked and electrically evoked synaptic responses for high-frequency stimulation at three synapses in the mouse brain. At synapses from Purkinje cells to deep cerebellar nuclei neurons (PC→DCN), light- and electrically evoked synaptic currents were remarkably similar for ChR2 expressed transgenically or with adeno-associated virus (AAV) expression vectors. For hippocampal CA3→CA1 synapses, AAV expression vectors of serotype 1, 5, and 8 led to light-evoked synaptic currents that depressed much more than electrically evoked currents, even though ChR2 could fire axons reliably at up to 50 Hz. The disparity between optical and electrical stimulation was eliminated when ChR2 was expressed transgenically or with AAV9. For cerebellar granule cell to stellate cell (grc→SC) synapses, AAV1 also led to artificial synaptic depression and AAV9 provided superior performance. Artificial synaptic depression also occurred when stimulating over presynaptic boutons, rather than axons, at CA3→CA1 synapses, but not at PC→DCN synapses. These findings indicate that ChR2 expression methods and light stimulation techniques influence synaptic responses in a neuron-specific manner. They also identify pitfalls associated with using ChR2 to study synapses and suggest an approach that allows optogenetics to be applied in a manner that helps to avoid potential complications.
Kainate Receptors Mediate Synaptic Input to Transient and Sustained OFF Visual Pathways in Primate Retina
Authors: Puthussery Theresa , Percival Kumiko A. , Venkataramani Sowmya , Gayet-Primo Jacqueline , Grünert Ulrike , Taylor W. Rowland
Published: May 2014

Visual signals are segregated into parallel pathways at the first synapse in the retina between cones and bipolar cells. Within the OFF pathways of mammals, the selective expression of AMPA or kainate-type glutamate receptors in the dendrites of different OFF-bipolar cell types is thought to contribute to formation of distinct temporal channels. AMPA receptors, with rapid recovery from desensitization, are proposed to transmit high temporal frequency signals, whereas kainate receptors (KARs) are presumed to encode lower temporal frequencies. Here we studied the glutamate receptors expressed by OFF-bipolar cells in slice preparations of macaque monkey retina, where the low (midget/parvocellular) and high-frequency (parasol/magnocellular) temporal channels are well characterized. We found that all OFF-bipolar types receive input primarily through KARs and that KAR antagonists block light-evoked input to both OFF-midget and OFF-parasol ganglion cells. KAR subunits were differentially expressed in OFF-bipolar types; the diffuse bipolar (DB) cells, DB2 and DB3b, expressed GluK1 and showed transient responses to glutamate and the KAR agonist, ATPA. In contrast, flat midget bipolar, DB1, and DB3a cells lacked GluK1 and showed relatively sustained responses. Finally, we found that the KAR accessory protein, Neto1, is expressed at the base of cone pedicles but is not colocalized with the GluK1 subunit. In summary, the results indicate that transient signaling in the OFF pathway of macaques is not dependent on AMPA receptors and that heterogeneity of KARs and accessory proteins may contribute to the formation of parallel temporal channels.
Modeling Inheritance of Phase Precession in the Hippocampal Formation
Authors: Jaramillo Jorge , Schmidt Robert , Kempter Richard
Published: May 2014

Spatial information about the environment is encoded by the activity of place and grid cells in the hippocampal formation. As an animal traverses a cell's firing field, action potentials progressively shift to earlier phases of the theta oscillation (6–10 Hz). This “phase precession” is observed also in the prefrontal cortex and the ventral striatum, but mechanisms for its generation are unknown. However, once phase precession exists in one region, it might also propagate to downstream regions. Using a computational model, we analyze such inheritance of phase precession, for example, from the entorhinal cortex to CA1 and from CA3 to CA1. We find that distinctive subthreshold and suprathreshold features of the membrane potential of CA1 pyramidal cells (Harvey et al., 2009; Mizuseki et al., 2012; Royer et al., 2012) can be explained by inheritance and that excitatory input is essential. The model explains how inhibition modulates the slope and range of phase precession and provides two main testable predictions. First, theta-modulated inhibitory input to a CA1 pyramidal cell is not necessary for phase precession. Second, theta-modulated inhibitory input on its own generates membrane potential peaks that are in phase with peaks of the extracellular field. Furthermore, we suggest that the spatial distribution of field centers of a population of phase-precessing input cells determines, not only the place selectivity, but also the characteristics of phase precession of the targeted output cell. The inheritance model thus can explain why phase precession is observed throughout the hippocampal formation and other areas of the brain.
miRNAs at the interface of cellular stress and disease
Authors: Emde Anna , Hornstein Eran
Published: May 2014

microRNAs (miRNAs) are a family of small, non‐coding RNAs, which provides broad silencing activity of mRNA targets in a sequence‐dependent fashion. This review explores the hypothesis that the miRNA machinery is intimately linked with the cellular stress pathway and apparatus. Stress signaling potentially alters the function of the miRNA‐bioprocessing core components and decompensates regulation. In addition, dysregulation of miRNA activity renders the cell more prone to stress and emerges as a new pathway for age‐related insults and diseases, such as neurodegeneration.
War and the Austrian School: Modern Austrian economists take on aggressive wars
Authors: Anderson William L. , Kjar Scott A. , Yohe James D.
Published: May 2014

The Austrian school of economics increasingly has become identified with antiwar groups. This is not due to religious or political views. Rather, the antiwar viewpoints of the Austrians come from the fundamental tenets of economics as expressed by the school's founders and refined for 140 years. This article applies post-world war II Austrian thought to the subject of war.
The onset of peace
Authors: Smith Ron , Tasiran Ali
Published: May 2014

Using the Uppsala Conflict Data Program's Conflict Termination Dataset, 1946-2007, we investigate determinants of war duration: How long does war last before the onset of peace? We provide an exposition of the nature of the data and of the transformations statistical issues involved in quantifying the dynamics of conflict, in particular the onset of peace. Various duration models are used to analyze the length of wars that ended with victory and peace or cease fires or show low activity. Multispell Cox proportional hazards models and single-spell log-logistic hazard models suggest that major wars are of shorter duration than minor wars, internal wars last longer than wars between states, and peace comes quicker in Europe than in other regions. We find only small differences in the determinants of terminated wars and wars with low activities or no activities.
Intimate partner violence, female employment, and male backlash in Rwanda
Authors: Finnoff Kade
Published: May 2014

Patterns of gendered violence during civil conflict are among the least well-understood aspects of civil war, and even greater gaps in our understanding exist regarding the long-term patterns of gendered power and violence in countries affected by war. This article examines the prevalence and correlates of intimate partner violence, based on household-level data from the Demographic and Health Survey conducted in Rwanda in 2005. Three results stand out. First, there are significant differences in the prevalence of three different types of gendered violence: physical, emotional and sexual violence. Second, women who are employed but whose husbands are not experience more sexual violence, not less, as would be expected in conventional household bargaining models. This can be interpreted as reflecting 'male backlash' as gender norms are destabilized. Finally, there is a strong inter-district correlation between the post-conflict prevalence of sexual violence and the intensity of political violence during the genocide.
Designing institutions for global security
Authors: Gupta Rupayan
Published: May 2014

The article merges aspects of alliance theory with bargaining theory and mechanism design. Illustrated with a numeric example, it models a within-alliance neutral agency whose purpose it is to propose an efficient level of public good provision for the alliance as a whole and suggests a mechanism by which to overcome incentives for inefficient provision. The article concludes with an extensive discussion for future research needs on alliance mechanism design, e.g., suggesting that a review of the literatures on central bank design and similar institutions might be helpful.
The defense industry in an age of austerity
Authors: Smith Ron
Published: May 2014

Reductions in military expenditure will generate pressures to restructure the defense industry. This article explores the implications of a more peaceful evolution of military expenditure for the economic structure of this industry. For example, since military expenditure and defense industry concentration have moved in opposite directions in the past, future cuts in such spending might be expected to lead to a more concentrated industry. Although eventually thwarted in 2012, the proposed merger of defense industry giants BAE and EADS – which would have created the world's largest defense firm – is discussed in some detail as a potential harbinger of defense consolidation to come.
An Evaluation of the Participatory Action‐oriented Training (PAOT) Program in Small Enterprises in Vietnam
Authors: Nguyen Toai Phuong , Khai Ton That
Published: May 2014

An Evaluation of the Participatory Action-oriented Training (PAOT) Program in Small Enterprises in Vietnam: Toai Phuong NGUYEN, et al. The Institute of Occupational and Environmental Medicine, University of Birmingham, UK—

Objectives

Participatory Action‐Oriented Training (PAOT) has been known as a practical training methodology for improving health and safety at work, particularly for small‐ and medium‐sized enterprises (SMEs). Our hypothesis is that PAOT is a better approach than a traditional local method, and the objective of this study was to evaluate the efficacy of PAOT and to make suggestions for improvement.

Methods

An intervention was performed for one year at 20 volunteer SMEs. PAOT was applied in 10 factories, and a traditional local method was applied in the other 10 SMEs as a control. Two cross‐sectional studies were performed consisting of a questionnaire and environmental measurements. Data were also collected on the number of factory improvements, productivity, worker income, accidents, and health costs.

Results

There were significant improvements among the intervention factories in terms of work environment, number of improvements and health costs between the pre‐ and post‐intervention phases. In terms of productivity, significant increases were seen in the civil engineering, metal, garment, and rice mill industries in the intervention group, while the metal casting and, garment industries in the control group also showed significant increase in productivity.

Conclusions

The findings support the idea that a PAOT program produces better outcomes in SMEs. It is recommended that a PAOT program be widely applied to SMEs to improve health and safety. A fuller examination could be obtained with more environmental measurements taken over a much longer period of time, together with data on sickness absence and accidents that have been independently validated.
High‐altitude Pulmonary Edema: Review
Authors: Bhagi Shuchi , Srivastava Swati , Singh Shashi Bala
Published: May 2014

High‐altitude Pulmonary Edema: Review: Shuchi BHAGI, et al. Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organization (DRDO), India—

Objective

At High altitude (HA) (elevation >2,500 m), hypobaric hypoxia may lead to the development of symptoms associated with low oxygen pressure in many sojourners. High‐altitude pulmonary edema (HAPE) is a potentially fatal condition, occurring at altitudes greater than 3,000 m and affecting rapidly ascending, non‐acclimatized healthy individuals. It is a multifactorial disease involving both environmental and genetic risk factors. Since thousands of lowlanders travel to high altitude areas for various reasons every year, we thought it would be interesting to review pathological aspects related to hypobaric hypoxia, particularly HAPE.

Method

Since the pathogenesis of HAPE is still a subject of study, we systematically identified and categorized a broad range of facets of HAPE such as its incidence, symptoms, physiological effects, pathophysiology including physiological and genetic factors, prevention and treatment.

Results

This review focuses on HA‐related health problems in general with special reference to HAPE, which is one of the primary causes of deaths at extreme altitudes. Hence, it is extremely important, as it summarizes the literature in this area and provides an overview of this severe HA malady for evaluation of physiological, biochemical and genetic responses during early induction and acclimatization to HA. This article could be of broad scientific interest for researchers working in the field of high altitude medicine.