bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms controlling the guidance of thalamocortical axons through the embryonic forebrain
Authors: Molnár Zoltán , Garel Sonia , López‐Bendito Guillermina , Maness Patricia , Price David J.
Published: May 2012

Thalamocortical axons must cross a complex cellular terrain through the developing forebrain, and this terrain has to be understood for us to learn how thalamocortical axons reach their destinations. Selective fasciculation, guidepost cells and various diencephalic and telencephalic gradients have been implicated in thalamocortical guidance. As our understanding of the relevant forebrain patterns has increased, so has our knowledge of the guidance mechanisms. Our aim here is to review recent observations of cellular and molecular mechanisms related to: the growth of thalamofugal projections to the ventral telencephalon, thalamic axon avoidance of the hypothalamus and extension into the telencephalon to form the internal capsule, the crossing of the pallial–subpallial boundary, and the growth towards the cerebral cortex. We shall review current theories for the explanation of the maintenance and alteration of topographic order in the thalamocortical projections to the cortex. It is now increasingly clear that several mechanisms are involved at different stages of thalamocortical development, and each contributes substantially to the eventual outcome. Revealing the molecular and cellular mechanisms can help to link specific genes to details of actual developmental mechanisms.
How Important Is Private Higher Education in Europe? A Regional Analysis in Global Context1
Authors: Levy Daniel C.
Published: May 2012

The importance of private higher education (PHE) is increasingly clear globally. But does Europe fit the global generalisation? This question can be assessed with reference to two major considerations: the size of PHE and the degree of private‐public difference. The growth of PHE in Europe has been delayed and limited compared to that in most of the world, though still significant. For the 27‐member European Union, the PHE share is best put at 12%, with a modestly higher share for Europe more broadly defined. Europe's PHE share is thus less than half that of the global share. The regional share is considerably higher in Eastern than in Western Europe. In terms of distinctiveness, European PHE differs from public higher education in important respects that reflect world patterns. Inter‐sectoral differences are decisive in finance. Though less quantifiable, they appear fundamental albeit blurred in some but not all aspects of governance and activities. Blurring in activities, governance, and even finance occurs through changes within both sectors, especially through partial privatisation within the public sector. Still, Europe's private sector is far from simply isomorphic to the public sector. Considering together size and distinctiveness, a reasonable assessment is that PHE has moderate and increased importance in Europe.
Private Higher Education and Economic Development
Authors: Reisz Robert D. , Stock Manfred
Published: May 2012

In Western Europe, especially in Germany, private higher education is generally perceived as an alternative to public higher education for students from relatively affluent families; more broadly, there is a general perception that attending a private higher education institution is correlated to wealth. This perception is influenced by private higher education in the US, which is the world's most visible private system, but also probably the most atypical. In this article, we will analyse the relationship between private higher education attainment and the wealth of nations as reflected by their per capita GDP. We will try to relate the indicators in models that use cross‐sectional transnational data as well as time series analysis for four contrasting countries (Chile, Germany, Romania, and the US). We will address two questions: (1) do wealthier nations have a higher percentage of enrolment in private higher education? and (2) does enrolment in private higher education grow with economic growth? Our analysis shows that a simple general relationship between enrolment in private higher education and the wealth of nations does not exist.
Bringing the State Back In: restoring the role of the State in Chinese higher education
Authors: Mok Ka Ho
Published: May 2012

In the last few decades, in the wake of three major crises in political faith and the overall instability that followed the end of the Cultural Revolution, the post‐Mao Chinese government has sought to improve the lives of its citizens and to restore political legitimacy through rapid economic growth that has focused almost exclusively on GDP. This strong focus has brought about rapid, widespread economic growth to China, and has, by classical market standards, been a success. At the same time, issues of social development and human well‐being have received less attention. Before the Hu‐Wen leadership's formal accession to power, the Jiang‐Zhu administration sought to adopt neo‐liberal ideas and practices to reform the delivery of social services and the implementation and funding of social policy. In this context, major fields of social policy such as health, education, and housing have been going through the processes of marketisation and privatisation, which have placed much of the financial burden of meeting these social welfare needs on China's citizens. After several decades of privatisation and marketisation in the educational system, the Chinese government has been the subject of repeated criticism for failing to tackle what is popularly known as the ‘new three mountains phenomenon’, namely, the rising cost of health, education, and housing in recent years. Against the wider policy context described above, this article examines the social and political consequences of the privatisation and marketisation of education. It also discusses the major policies and strategies recently adopted by the Chinese government to restore the role of the State in the education system in order to address the negative consequences of the privatisation of education. Finally, it critically examines the main implications of major reforms undertaken in higher education in Mainland China.
Private Sector Consultants and Public Universities: the challenges of cross‐sectoral knowledge transfers
Authors: Serrano‐Velarde Kathia , Krücken Georg
Published: May 2012

Since the early 1990s, European higher education has been undergoing drastic changes with regard to the organisation and governance of academic work. The political emphasis on higher education autonomy and accountability went hand in hand with the introduction of market type steering devices and a new discourse regarding the universities' responsibilities to society. This article is about both carriers of diffusion processes that are crucial in disseminating private sector logics and the limits to such processes. By taking into account contradictory societal pressures towards isomorphism and differentiation; we will draw on neo‐institutionalism and the sociological systems theory to provide a definition of privatisation in higher education. Especially, we are interested in detecting systematic limits to the privatisation of higher education. We therefore examine a relatively recent phenomenon in higher education governance: the increasing reliance of institutions on management consulting services. First findings show that the more market‐centred a higher education system is, the more readily it accepts the economic rationale of the consulting business. Nevertheless, our study also stresses that management consultancy for higher education institutions is of limited scope. Systemic differences remain unbroken as the adherence to different value systems, communication patterns and resources limit the scope of external, private consulting activities in higher education.
‘Being young’: a qualitative study of younger nurses' experiences in the workplace
Authors: Clendon J. , Walker L.
Published: May 2012

CLENDON J. & WALKER L. (2012) ‘Being young’: a qualitative study of younger nurses' experiences in the workplace. International Nursing Review

Aim:  The overall goal of this study was to obtain a greater understanding of the experiences of nurses aged under 30 in the New Zealand workforce with a view to developing age‐appropriate retention strategies.

Background:  Nurses aged under 30 constitute around 10% of the world's nursing workforce yet little is known about their experiences in the workplace. Poor retention of younger nurses is a cause for concern. The implications of the perceptions and needs of this generation of nurses must be considered in order to ensure effective succession planning.

Methods:  An explorative descriptive design framed within a broad qualitative methodology was utilized to explore experiences of younger nurses in the New Zealand workforce. Data were analysed thematically.

Findings and discussion:  Findings are reported under five themes: challenges of nursing, rewards of nursing, being young, coping and addressing generational differences. The study provides new knowledge about the experiences of younger nurses in the workforce and in particular the challenges facing younger Asian nurses.

Conclusions:  Managers and nurse leaders must address broader workforce issues as well as improving support for younger nurses to help improve younger nurse retention. Strategies designed to extend and challenge younger nurses in the workplace such as professional development and project work will also help, but will only be effective if nurses are given sufficient paid time to undertake this work. Being Asian provides added challenges for younger nurses in New Zealand and further research into the experiences of this subgroup is highly recommended.
The Moral Foundation of Law and the Ethos of Liberal Democracies
Authors: MINEUR DIDIER
Published: May 2012

This paper deals with the connection between law and morality. Such a connection is relevant for political theory, since demonstrating that law necessarily implies a claim to justice would require fundamental rights to be considered the horizon of any legal system, instead of being considered as dependent on the axiological context of liberal democracies. The paper approaches the controversy starting from an overview of the work of the German philosopher Robert Alexy, in particular his attempt to establish an analytical link between law and morality, and to this end considers law as a speech act with a claim to correctness. It then examines the critique put forward by Joseph Raz, that points out the lack of objectivity of this claim to correctness. In order to establish a moral foundation for law, the paper argues that it is necessary to take account of Karl‐Otto Apel's attempt to establish the transcendental foundation of language, as well as of Habermas' critique of that attempt. In conclusion, it is argued that the debate about a possible link between law and morality sheds new light on contemporary debates on liberal justification in political theory.
The Embedded Epistemologist: Dispatches from the Legal Front*
Authors: HAACK SUSAN
Published: May 2012

In ordinary circumstances, we can assess the worth of evidence well enough without benefit of any theory; but when evidence is especially complex, ambiguous, or emotionally disturbing—as it often is in legal contexts—epistemological theory may be helpful. A legal fact‐finder is asked to determine whether the proposition that the defendant is guilty, or is liable, is established to the required degree of proof by the [admissible] evidence presented; i.e., to make an epistemological appraisal. The foundherentist theory developed inEvidence and Inquirycan help us understand what this means; and reveals that degrees of proof cannot be construed as mathematical probabilities: a point illustrated by comparing the advantages of a foundherentist analysis with the disadvantages of probabilistic analyses of the evidence in the Sacco and Vanzetti case (1921), and of the role of the statistical evidence inCollins(1968).
Testing the Equality of Covariance Operators in Functional Samples
Authors: FREMDT STEFAN , STEINEBACH JOSEF G. , HORVÁTH LAJOS , KOKOSZKA PIOTR
Published: May 2012

Abstract.  We propose a non‐parametric test for the equality of the covariance structures in two functional samples. The test statistic has a chi‐square asymptotic distribution with a known number of degrees of freedom, which depends on the level of dimension reduction needed to represent the data. Detailed analysis of the asymptotic properties is developed. Finite sample perfo‐rmance is examined by a simulation study and an application to egg‐laying curves of fruit flies.
Multiple Spell‐Out and Contraction at the Syntax–Phonology Interface
Authors: Sato Yosuke
Published: May 2012

Abstract. The Multiple Spell‐Out model of Chomsky (2000, 2001, 2004) and Uriagereka (1999) provides a straightforward characterization of the syntactic environments for contraction. It is well known thatwannacontraction is possible in the subject‐control case (Who do you wanna marry?) but blocked in the DP+infinitival case (*Who do you wanna marry you?). This asymmetry receives a straightforward account if the CP‐phase boundary demarcates the domain for contraction. More complex cases of contraction discussed by Postal & Pullum (1978, 1982) fall into place if left‐branching structures form a self‐contained Spelled‐Out domain as in Uriagereka’s model. The analysis can also derive a number of well‐known generalizations regarding auxiliary reduction such as (a) the invisibility of a Case‐marked trace for reduction and (b) the inhibitory effect of the gap on reduction. Generalization (a) is a natural consequence of the TP analysis forthat‐less finite complements whereas (b) is the result of the tight interaction between the syntactic system and the fine‐grained prosodic classification of function words developed by Selkirk (1995). Particular details of the analysis support various principles of syntax such as the Economy of Projection and the notion of CP phase. This paper, therefore, achieves the minimalist desideratum of explaining linguistic phenomena solely in terms of interface conditions and computational efficiency.
Lardil “Case Stacking” and the Timing of Case Assignment
Authors: Richards Norvin
Published: May 2012

Abstract. Lardil (Tangkic, Australia) allows nominals to surface with multiple case affixes. One condition on this so‐called case stacking is that when new morphology is added to a nominal with a semantically uninterpretable Case (such as accusative), the Case is dropped; a nominal with a semantically interpretable Case (such as instrumental), by contrast, can stack more morphology outside the Case morpheme. I argue that uninterpretable Cases in these examples are in fact assigned and later eliminated, and develop an approach to Spell‐out that allows such derivations to take place, in which PF Spell‐out and LF Spell‐out are dissociated. I offer two arguments that processes like Case assignment and concord take place in the narrow syntax: one has to do with the distinction drawn between meaningful and meaningless Cases, and the other with the interaction between Lardil Tense concord and various types of movement operations.
From Latin to Romance: Configurationality, Functional Categories and Head‐Marking
Authors: Ledgeway Adam
Published: May 2012

Traditionally, the principal typological difference between Latin and Romance is taken to involve a distinction between morphology and syntax: while Latin predominantly has recourse to synthetic structures, the morphologically poorer Romance varieties make greater use of analytic structures. In this paper I reconsider this traditional theme of Romance linguistics and its repercussions on argument realisation and positional licensing, showing that the predominant analytic patterns of Romance are nothing more than the partial reflex of a more deep‐rooted structural change.A priori, this change can be interpreted in terms of at least two competing theoretical explanations, on the one hand the emergence of full configurationality and concomitant projection of functional structure, and a change in the head‐directionality parameter with a concomitant shift from specifier‐ to head‐oriented syntax in the domain of functional structure on the other. Following a critical review of the former, it is argued that the relevant changes in the passage from Latin to Romance are best characterised in relation to the latter theory, which also offers a highly natural way of capturing claims about a move from dependent‐ to head‐marking.
Ontogeny of the cranial system in Laonastes aenigmamus
Authors: Herrel Anthony , Fabre Anne‐Claire , Hugot Jean‐Pierre , Keovichit Kham , Adriaens Dominique , Brabant Loes , Van Hoorebeke Luc , Cornette Raphael
Published: May 2012

Rodents, together with bats, are among the ecologically most diverse and most speciose groups of mammals. Moreover, rodents show elaborate specializations of the feeding apparatus in response to the predominantly fore‐aft movements of the lower jaw. The Laotian rock rat Laonastes aenigmamus was recently discovered and originally thought to belong to a new family. The difficulties in classifying L. aenigmamus based on morphological characters stem from the fact that it presents a mixture of sciurognathous and hystricognathous characteristics, including the morphology of the jaw adductors. The origin of the unusual muscular organization in this species remains, however, unclear. Here, we investigate the development of the masticatory system in Laonastes to better understand the origin of its derived morphology relative to other rodents. Our analyses show that skull and mandible development is characterized by an overall elongation of the snout region. Muscle mass increases with positive allometry during development and growth, and so does the force‐generating capacity of the jaw adductor muscles (i.e. physiological cross‐sectional area). Whereas fetal crania and musculature are more similar to those of typical rodents, adults diverge in the elongation of the rostral part of the skull and the disproportionate development of the zygomaticomandibularis. Our data suggest a functional signal in the development of the unusual cranial morphology, possibly associated with the folivorous trophic ecology of the species.
Environmental factors fail to explain oviposition site use in the European common frog
Authors: Grözinger F. , Wertz A. , Thein J. , Feldhaar H. , Rödel M.‐O.
Published: May 2012

A 7‐year monitoring of potential oviposition ponds of the European common frog Rana temporaria, in northern Bavaria, Germany, indicated that breeding ponds were not randomly used. Site fidelity could not consistently explain this pattern. Because amphibians are known to select oviposition sites according to certain habitat characteristics, we investigated pond parameters that may drive breeding site selection in that area. We recorded 44 abiotic and biotic parameters, including variables within‐ponds, predator presence, as well as habitat characteristics of the terrestrial area surrounding the ponds. However, multifactorial statistics such as non‐metric multidimensional scaling, hierarchical clustering and random forest algorithm as well as single‐factor comparisons could not highlight common habitat features of chosen ponds. The results of this study indicate that breeding site choice is more than a pure function of habitat characteristics, and that understanding the reproductive biology, even of such a widespread species as R. temporaria, needs more research effort.
Comparative study between atorvastatin and losartan on high fat diet‐induced type 2 diabetes mellitus in rats
Authors: Mourad Ahmed A. , Heeba Gehan H. , Taye Ashraf , El‐Moselhy Mohamed A.
Published: May 2012

Obesity is often associated with chronic inflammatory state which contributes to the development of insulin resistance (IR) and type 2 diabetes mellitus (T2DM). This study investigated the effects of single and combined administration of atorvastatin (ATOR, lipid‐lowering drug) and losartan (LOS, angiotensin receptor antagonist) on metabolic disorders and inflammatory status that are implicated in the development of T2DM with the use of pioglitazone (PIO) as a standard antidiabetic drug. T2DM was induced in male rats by high‐fat diet (HFD) feeding for 16 weeks. Oral administrations of ATOR (10 mg/kg), LOS (20 mg/kg), PIO (3 mg/kg), their binary combinations, or vehicle were started in the last 4 weeks. Fasting serum glucose, oral glucose tolerance, fasting serum insulin, IR, serum lipid profile, serum TNF‐α and body composition index were determined. Results showed that all drugs and their combinations had positive impact effect on all measured parameters, and better results were achieved from binary drug combinations than administration of each drug alone. Combination of PIO with either ATOR or LOS provided better improvements on T2DM‐associated metabolic abnormalities and inflammatory status with respect to each drug alone. However, the most pronounced effects of drugs and their combinations regarding the above parameters were attributed to LOS + PIO combination. In conclusion, this study indicates that combination of ATOR + PIO and, in particular, LOS + PIO can be used as promising effective therapies in the management of HFD‐induced T2DM. This concept may be attributed to the combined effects of the respective monotherapies to improve lipid profile, insulin sensitivity, and TNF‐α level.
Psychological Constructs Underlying Farmers’ Decisions to Diversify or Specialise their Businesses – An Application of Theory of Planned Behaviour
Authors: Hansson Helena , Ferguson Richard , Olofsson Christer
Published: May 2012

We use the theory of planned behaviour (TPB) to explain how underlying psychological constructs influence farmers’ decisions to extend their farm businesses to income‐generating ventures outside conventional agricultural production. The analysis contrasts the influence of psychological constructs on this decision with those on decisions to specialise in a single farm enterprise or to have multiple farm enterprises. This is one of the first studies to introduce psychological constructs into the study of farm diversification. It is based on a sample of 929 Swedish farms participating in the official Swedish Farm Economic Survey. These data are supplemented with a detailed postal questionnaire to the participating farmers, generating a response rate of 73% and an effective sample size of 679 farmers and their businesses. Data are analysed with factor and multinomial logistic regression analyses. Results show that psychological constructs in TPB (attitude, subjective norm and perceived behavioural control) influence farmers’ decisions regarding the strategy they adopt. Attitude and subjective norm are found to be especially influential in these decisions. Given the prominent role agriculture still has in rural development policy, where the development of new ventures in farm businesses is perceived as the engine for rural economic growth and employment, these findings have clear policy implications.
Distal Extremity Necrosis as a Manifestation of Cutaneous Polyarteritis Nodosa: Case Report and Review of the Acute Management of a Pediatric Patient
Authors: Williams Victoria L. , Guirola Ricardo , Flemming Kristy , Modi Gunjan M. , Rosales Cecilia , DeGuzman Marietta M.
Published: May 2012

Abstract:  We present the case of an 8‐year‐old girl who presented with distal extremity necrosis of the hands, feet, nose, and ears as an acute manifestation of cutaneous polyarteritis nodosa (CPAN). She was emergently managed with intravenous steroids, nifedipine, sildenafil, pentoxifylline, nitroglycerin paste, aspirin, low‐molecular‐weight heparin, and intravenous gamma globulin. The necrosis was controlled, and reperfusion was attained to salvage the extremities. It is important for clinicians to be aware that acute distal extremity necrosis can be a manifestation of CPAN in children. Etiology is often not clear on presentation, but once infection is excluded, acute management with systemic steroids and systemic vasodilators is indicated regardless of the cause. Iloprost and bosentan may represent options for adjunctive vasodilators. More studies are needed to create guidelines for the acute and long‐term management of these children. Close follow‐up of children with CPAN, especially with a history of vaso‐occlusive symptoms, is important to allow prompt intervention in the event of distal extremity infarction.
Treatment of Hypergranulation Tissue with High Potency Topical Corticosteroids in Children
Authors: McShane Diana B. , Bellet Jane S.
Published: May 2012

Abstract:  Hypergranulation is having more granulation tissue than needed to fill a wound defect. Some pediatric dermatologists and most dermatologic surgeons will encounter this complication during their careers. Associated factors include wound site, prolonged inflammation, an imbalance in matrix metalloproteinases, and excessive angiogenesis. Reported treatments have included silver nitrate, excision, laser ablation, and topical corticosteroids. Our case series supports the use of medium‐ to high‐potency topical corticosteroids in the treatment of hypergranulation tissue.
Superficial Epidermolytic Ichthyosis: A Report of Two Families
Authors: Cervantes Tessa , Pham Catherine , Browning John C.
Published: May 2012

Abstract:  Superficial epidermolytic ichthyosis (SEI), previously known as ichthyosis bullosa of Siemens, is a rare genetic skin condition, characterized by blisters and hyperkeratosis. It can be easily confused with epidermolytic hyperkeratosis, known now as epidermolytic ichthyosis, and genetic testing can be helpful in differentiating between the two conditions. We describe two children with SEI confirmed by genetic testing, including one with a novel mutation. We also describe other affected family members with SEI.
Localized Secondary Erythromelalgia in an 11‐Year‐Old Boy
Authors: Wu Hui‐Hui , Wang Ming‐Jun , Luo Di‐Qing , Lin Qing
Published: May 2012

Abstract:  We report an 11‐year‐old boy with localized secondary erythromelalgia on his left medial thigh. The episodes responded well to indomethacin and prednisone but recurred after the medications were stopped. The disease was stable after being treated for 5 months.
Salivary Cortisol Response to Stress in Young Children with Atopic Dermatitis
Authors: Kojima Reiji , Matsuda Akio , Nomura Ichiro , Matsubara Osamu , Nonoyama Shigeaki , Ohya Yukihiro , Saito Hirohisa , Matsumoto Kenji
Published: May 2012

Abstract:  Poor responsiveness of the hypothalamic–pituitary–adrenal (HPA) axis under stress may be one explanation for stress‐induced exacerbation of atopic dermatitis (AD) symptoms. In previous studies, children and adults with AD showed attenuated salivary cortisol responses to psychosocial stress, suggesting hyporesponsiveness of the HPA axis, but few studies have been conducted in young children, who are vulnerable to systemic side effects of topical corticosteroid (TCS) therapy. We evaluated whether salivary cortisol responses to the stress of venipuncture in young children with AD were related to the severity of AD or performance of TCS therapy. We studied 38 young children with AD (median age 16.5 mos, range 3–66 mos) being treated at our outpatient unit. Patients were divided into three groups according to the scoring of atopic dermatitis index: mild (n = 12), moderate (n = 14), and severe (n = 12). To evaluate the responsiveness of the HPA axis to stress, salivary cortisol was determined before and after venipuncture. Salivary cortisol responsiveness to stress correlated negatively with severity of AD (p = 0.048) but not with previous use of TCS (p = 0.43) in young children with AD. Our findings suggest that the disease activity of AD, rather than TCS use, is responsible for HPA axis dysfunction in children with AD.
Psoriasiform Eruption and Oral Ulcerations as Adverse Effects of Topical 5% Imiquimod Treatment in Children: A Report of Four Cases
Authors: Smith Wallace A. , Siegel Dawn , Lyon Valerie B. , Holland Kristen E.
Published: May 2012

Abstract:  Imiquimod 5% cream is a topical immune‐response modifier indicated in the treatment of multiple cutaneous conditions including actinic keratoses, superficial basal cell carcinoma, and condylomata acuminata. In children, it has been approved only for ages 12 and older in the treatment of external genital and perianal warts. It has also been used off label for a variety of pediatric skin disorders, including molluscum contagiosum (MC), trichoepitheliomas, verrucae plana, and verrucae vulgaris. Local and systemic adverse reactions have been reported, with the most frequently reported events being application site reactions including itching, burning, erythema, and erosion. Although these local reactions are well known, other rare local and systemic reactions can occur. There have been multiple case reports in adults of rare adverse cutaneous reactions occurring with imiquimod, but few have been reported in children. We present four cases of rare adverse cutaneous reactions. In all cases, the children were being treated with imiquimod 5% cream for verrucae or MC. Two of these patients developed a localized psoriasiform eruption, and two developed mucosal ulcerations.
Intra‐Aortic Balloon Counterpulsation in the Treatment of Infarction‐Related Cardiogenic Shock—Review of the Current Evidence
Authors: Buerke Michael , Prondzinsky Roland , Lemm Henning , Dietz Sebastian , Buerke Ute , Ebelt Henning , Bushnaq Hasan , Silber Rolf‐Edgar , Werdan Karl
Published: May 2012

The European ST‐elevated myocardial infarction (STEMI) guideline suggested the intra‐aortic balloon pump (IABP) with a recommendation level I and a level of evidence C as an effective measure in combination with balloon angioplasty in patients with cardiogenic shock (CS), stent implantation, and inotropic and vasopressor support. Similarly, upon mechanical complication due to myocardial infarction (MI), the guideline suggests that in patients with a ventricular septal defect or in most patients with acute mitral regurgitation, preoperative IABP implantation is indicated for circulatory support. The American College of Cardiology/American Heart Association STEMI guideline recommends the use of the IABP with a recommendation level I and a level of evidence B if CS does not respond rapidly to pharmacological treatment. The guideline notes that the IABP is a stabilizing measure for angiography and early revascularization. Even in MI complications, the use of preoperative IABP is recommended before surgery. Within this overview, we summarize the current evidence on IABP use in patients with CS complicated by MI. From our Cochrane data analysis, we conclude that in CS due to acute MI (AMI) treated with adjuvant systemic fibrinolysis, the IABP should be implanted. In patients with CS following AMI, treated with primary percutaneous coronary intervention (PCI), the IABP can be implanted, although data are not distinctive (i.e., indicating positive and negative effects). In the future, randomized controlled trials are needed to determine the use of IABP in CS patients treated with PCI. When patients with CS are transferred to a PCI center with or without thrombolysis, patients should receive mechanical support with an IABP. To treat mechanical MI complications—in particular ventricular septal defect—patients should be treated with an IABP to stabilize their hemodynamic situation prior to cardiac surgery. Similar recommendations are given in the German Austrian guidelines on treatment of infarction‐related CS patients (http://www.awmf.org/leitlinien/detail/ll/019‐013.html)
Five Days of No Anticoagulation or Antiplatelet Therapy and NovoSeven Administration in a HeartWare HVAD Patient
Authors: Saeed Diyar , Albert Alexander , Kamiya Hiroyuki , Maxhera Bujar , Westenfeld Ralf , Lichtenberg Artur
Published: May 2012

Postoperative bleeding is the most common complication following the implantation of ventricular assist devices. This is a case report of a HeartWare HVAD patient with intractable bleeding following chest tube insertion necessitating massive blood transfusion and multiple thoracotomies. Anticoagulation and antiplatelet therapy were discontinued and intravenous NovoSeven was administered as last resort. Bleeding ceased immediately and no pump‐related issues were observed. However, thrombus formation in the right atrium and superior vena cava was detected.
Dihydroergotamine (DHE) Use During Gestation and the Risk of Adverse Pregnancy Outcomes
Authors: Bérard Anick , Kori Shashidhar
Published: May 2012

Background.— Dihydroergotamine (DHE) is perceived to be associated with a higher risk of adverse pregnancy events, but it has significantly less vasoconstrictive and uterotonic effects compared with ergotamine, and has demonstrated no teratogenic effect in animals. The objectives of this study were to quantify the risk of major congenital malformations (MCMs), prematurity, low birth weight (LBW), and spontaneous abortions (SAs) associated with gestational use of DHE, triptans, and nonsteroidal anti‐inflammatory drugs (NSAIDs).

Methods.— Four independent case–control analyses were conducted within the Quebec Pregnancy Registry: (1) MCM; (2) prematurity (<37 weeks of gestation); (3) LBW (birth weight <2500 g); (4) clinically detected SA. Exposure was defined dichotomously as use of DHE, triptan, and NSAIDs during pregnancy.

Results.— Overall, 59,707 pregnant women met the eligibility criteria and were considered (53 [0.08%] used DHE, 139 [0.23%] triptans, and 2990 [5.01%] NSAIDs). Adjusting for potential confounders, gestational use of DHE was not significantly associated with the risk of MCM (odds ratio [OR]: 0.97; 95% confidence interval [CI]: 0.22‐4.28), LBW (OR: 1.41; 95%CI: 0.25‐7.80), or SA (OR: 1.97; 95% CI: 0.21‐18.57). DHE use was, however, increasing the risk of prematurity (OR: 4.18; 95% CI: 1.34‐12.99). In users of triptans, the OR for MCM was 1.49 (95% CI: 0.89‐2.52), prematurity 0.76 (95% CI: 0.34‐1.66), LBW 0.83 (95% CI: 0.31‐2.25), and SA 2.65 (95% CI: 1.57‐4.48). In users of NSAIDs, the OR for MCM was 1.20 (95% CI: 1.06‐1.36), prematurity 1.10 (95% CI: 0.95‐1.26), LBW 1.29 (95% CI: 1.08‐1.54), and SA 2.97 (95% CI: 2.63‐3.36).

Conclusions.— This study showed that other than for prematurity, DHE use during pregnancy was similar to that of triptan use and was smaller than the risk associated with NSAID use.
Are you in or out? Leukocyte, ion, and neurotransmitter permeability across the epileptic blood–brain barrier
Authors: Janigro Damir
Published: May 2012

The credo that epileptic seizures can be initiated only by “epileptic” neurons has been recently challenged. The recognition of key astrocytic‐neuronal communication, and the close interaction and crosstalk between astrocytes and brain endothelial cells, has shifted attention to the blood–brain barrier (BBB) and the “neurovascular unit.” Therefore, the pursuit of mechanisms of seizure generation and epileptogenesis now includes investigations of cerebral blood flow and permeability of cerebral microvessels. For example, leukocyte adhesion molecules at the BBB have been proposed to play a role as an initiating factor for pilocarpine‐induced status epilepticus, and a viral infection model with a strong BBB etiology has been used to study epileptogenesis. Finally, the fact that in nonepileptic subjects seizures can be triggered by BBB disruption, together with the antiseizure effects obtained by administration of potent antiinflammatory “BBB repair” drugs, has increased the interest in neuroinflammation; both circulating leukocytes and resident microglia have been studied in this context. The dual scope of this review is the following: (1) outline the proposed role of BBB damage and immune cell activation in seizure disorders; and (2) explain how increased cerebrovascular permeability causes neuronal misfiring. The temporal sequence linking seizures to peripheral inflammation and BBB dysfunction remains to be clarified. For example, it is still debated whether seizures cause systemic inflammation or vice versa. The topographic localization of fundamental triggers of epileptic seizures also remains controversial: Are immunologic mechanisms required for seizure generation brain‐specific or is systemic activation of immunity sufficient to alter neuronal excitability? Finally, the causative role of “BBB leakage” remains a largely unresolved issue.
Are developmental dysplastic lesions epileptogenic?
Authors: Schwartzkroin Philip A. , Wenzel H. Jürgen
Published: May 2012

Cortical dysplasia of various types, reflecting abnormalities of brain development, have been closely associated with epileptic activities. Yet, there remains considerable discussion about if/how these structural lesions give rise to seizure phenomenology. Animal models have been used to investigate the cause–effect relationships between aberrant cortical structure and epilepsy. In this article, we discuss three such models: (1) the Eker rat model of tuberous sclerosis, in which a gene mutation gives rise to cortical disorganization and cytologically abnormal cellular elements; (2) the p35 knockout mouse, in which the genetic dysfunction gives rise to compromised cortical organization and lamination, but in which the cellular elements appear normal; and (3) the methylazoxymethanol‐exposed rat, in which time‐specific chemical DNA disruption leads to abnormal patterns of cell formation and migration, resulting in heterotopic neuronal clusters. Integrating data from studies of these animal models with related clinical observations, we propose that the neuropathologic features of these cortical dysplastic lesions are insufficient to determine the seizure‐initiating process. Rather, it is their interaction with a more subtly disrupted cortical “surround” that constitutes the circuitry underlying epileptiform activities as well as seizure propensity and ictogenesis.
Neuronal excitability and calcium/calmodulin‐dependent protein kinase type II: Location, location, location
Authors: Liu Xiao‐Bo , Murray Karl D.
Published: May 2012

Calcium/calmodulin‐dependent protein kinase type II (CaMKII) is a highly abundant serine/threonine kinase comprising a significant fraction of total protein in mammalian forebrain and forming a major component of the postsynaptic density. CaMKII is essential for certain forms of synaptic plasticity and memory consolidation and this is mediated through substrate binding and intramolecular phosphorylation of holoenzyme subunits. CaMKII is multifunctional; it targets a variety of cellular substrates, and this diversity depends on holoenzyme subunit composition. CaMKII comprises homooligomeric and heterooligomeric complexes generated from four subunits (α, β, δ, and γ) encoded by separate genes that are further expanded by extensive alternative splicing to more than 30 different isoforms. Much attention has been paid to understanding the regulation of CaMKII function through its structural diversity and/or substrate specificity. However, given the importance of subunit composition to holoenzyme activity, it is likely that specificity of cellular expression of CaMKII isoforms also plays a major role in regulation of enzyme function. Herein we review the cellular colocalization of CaMKII isoforms with special regard to the cell‐type specificity of isoform expression in brain. In addition, we highlight the remarkable specificity of subcellular localization by the CaMKIIα isoform. In addition, we discuss the role that this cellular specificity of expression might play in propagating the type of recurrent neuronal activity associated with disorders such as temporal lobe epilepsy.
Common factors among Alzheimer’s disease, Parkinson’s disease, and epilepsy: Possible role of the noradrenergic nervous system
Authors: Szot Patricia
Published: May 2012

The neurodegenerative disorders Alzheimer’s disease (AD) and Parkinson’s disease (PD) share in common the neuropathologic loss of locus coeruleus (LC) noradrenergic neurons. In addition, these two neurodegenerative disorders share two symptoms that define these disorders: cognitive impairment and depression. The hippocampus is a region that is known to play a role in cognition and depression, and the hippocampus receives sole noradrenergic innervation from LC neurons. However, it is unclear how the loss of LC noradrenergic neurons contributes to these common symptoms in these two disorders. Epilepsy is not considered a neurodegenerative disorder, but the hippocampus is severely affected in temporal lobe epilepsy. Of interest, cognitive impairment and depression are also common comorbid disorders in temporal lobe epilepsy. This article describes common symptoms among these three neurologic disorders and a possible role of the noradrenergic nervous system.
Neuroanatomical clues to altered neuronal activity in epilepsy: From ultrastructure to signaling pathways of dentate granule cells
Authors: Houser Carolyn R. , Zhang Nianhui , Peng Zechun , Huang Christine S. , Cetina Yliana
Published: May 2012

The dynamic aspects of epilepsy, in which seizures occur sporadically and are interspersed with periods of relatively normal brain function, present special challenges for neuroanatomical studies. Although numerous morphologic changes can be identified during the chronic period, the relationship of many of these changes to seizure generation and propagation remains unclear. Mossy fiber sprouting is an example of a frequently observed morphologic change for which a functional role in epilepsy continues to be debated. This review focuses on neuroanatomically identified changes that would support high levels of activity in reorganized mossy fibers and potentially associated granule cell activation. Early ultrastructural studies of reorganized mossy fiber terminals in human temporal lobe epilepsy tissue have identified morphologic substrates for highly efficacious excitatory connections among granule cells. If similar connections in animal models contribute to seizure activity, activation of granule cells would be expected. Increased labeling with two activity‐related markers, Fos and phosphorylated extracellular signal–regulated kinase, has suggested increased activity of dentate granule cells at the time of spontaneous seizures in a mouse model of epilepsy. However, neuroanatomical support for a direct link between activation of reorganized mossy fiber terminals and increased granule cell activity remains elusive. As novel activity‐related markers are developed, it may yet be possible to demonstrate such functional links and allow mapping of seizure activity throughout the brain. Relating patterns of neuronal activity during seizures to the underlying morphologic changes could provide important new insights into the basic mechanisms of epilepsy and seizure generation.
Synaptic connections of hilar basal dendrites of dentate granule cells in a neonatal hypoxia model of epilepsy
Authors: Sanchez Russell M. , Ribak Charles E. , Shapiro Lee A.
Published: May 2012

Numerous animal models of epileptogenesis demonstrate neuroplastic changes in the hippocampus. These changes occur not only for the mature neurons and glia, but also for the newly generated granule cells in the dentate gyrus. One of these changes, the sprouting of mossy fiber axons, is derived predominantly from newborn granule cells in adult rats with pilocarpine‐induced temporal lobe epilepsy. Newborn granule cells also mainly contribute to another neuroplastic change, hilar basal dendrites (HBDs), which are synaptically targeted by mossy fibers in the hilus. Both sprouted mossy fibers and HBDs contribute to recurrent excitatory circuitry that is hypothesized to be involved in increased seizure susceptibility and the development of spontaneous recurrent seizures (SRS) that occur following the initial pilocarpine‐induced status epilepticus. Considering the putative role of these neuroplastic changes in epileptogenesis, a critical question is whether similar anatomic phenomena occur after epileptogenic insults to the immature brain, where the proportion of recently born granule cells is higher due to ongoing maturation. The current study aimed to determine if such neuroplastic changes could be observed in a standardized model of neonatal seizure‐inducing hypoxia that results in development of SRS. We used immunoelectron microscopy for the immature neuronal marker doublecortin to label newborn neurons and their HBDs following neonatal hypoxia. Our goal was to determine whether synapses form on HBDs from neurons born after neonatal hypoxia. Our results show a robust synapse formation on HBDs from animals that experienced neonatal hypoxia, regardless of whether the animals experienced tonic–clonic seizures during the hypoxic event. In both cases, the axon terminals that synapse onto HBDs were identified as mossy fiber terminals, based on the appearance of dense core vesicles. No such synapses were observed on HBDs from newborn granule cells obtained from sham animals analyzed at the same time points. This aberrant circuit formation may provide an anatomic substrate for increased seizure susceptibility and the development of epilepsy.
Kv1.1 and Kv1.2: Similar channels, different seizure models
Authors: Robbins Carol A. , Tempel Bruce L.
Published: May 2012

Voltage‐gated K+ channels (Kv) represent the largest family of genes in the K+ channel family. The Kv1 subfamily plays an essential role in the initiation and shaping of action potentials, influencing action potential firing patterns and controlling neuronal excitability. Overlapping patterns with differential expression and precise localization of Kv1.1 and Kv1.2 channels targeted to specialized subcellular compartments contribute to distinctive patterns of neuronal excitability. Dynamic regulation of the components in these subcellular domains help to finely tune the cellular and regional networks. Disruption of the expression, distribution, and density of these channels through deletion or mutation of the genes encoding these channels, Kcna1 and Kcna2, is associated with neurologic pathologies including epilepsy and ataxia in humans and in rodent models. Kv1.1 and Kv1.2 knockout mice both have seizures beginning early in development; however, each express a different seizure type (pathway), although the channels are from the same subfamily and are abundantly coexpressed. Voltage‐gated ion channels clustered in specific locations may present a novel therapeutic target for influencing excitability in neurologic disorders associated with some channelopathies.
Inhibition and interneuron distribution in the dentate gyrus of p35 knockout mice
Authors: Knight Leena S. , Wenzel H. Jürgen , Schwartzkroin Philip A.
Published: May 2012

The p35 knockout (p35−/−) mouse is an animal model of temporal lobe epilepsy that recapitulates key neuroanatomic abnormalities—granule cell dispersion and mossy fiber sprouting—observed in the hippocampal formation of humans, as well as spontaneous seizure activity. It is a useful model in which to study the relationship between the abnormal neuronal structure and seizure activity to further our understanding of cortical dysplasia in epileptogenesis. Our previous work using this mouse model characterized the anatomic features of the dentate granule cells and the functional implications of these abnormalities on increased recurrent excitation. These data also suggested that there might be compromised inhibition in this animal model. We pursued this possibility, focusing our investigation on inhibitory circuitry. In preliminary investigations using neuroanatomic tools (immunocytochemistry, camera lucida reconstructions of individually labeled interneurons, and electron microscopy) combined with intracellular electrophysiology, we observed no significant reduction in the number of symmetric versus asymmetric synaptic contacts on dentate granule cell somata, and no statistically significant changes in evoked early or late inhibition. Although there were some abnormalities in the morphology/distribution of inhibitory interneurons (as well as a larger population of dentate granule cells) of the dentate gyrus, overall inhibition in the p35 knockout mouse appeared to be largely intact.