55 research outputs found
Data management in the upcoming national biobank
No full textPå baggrund af modsatrettede holdninger mellem SSI og SST angående datahåndteringen i den kommende nationale biobank vil identificeres i dette projekt et kompromis for datahåndteringen og en systemarkitektur skitseres, der benytter sig af standardmetoder. Med inspiration fra UP og ER-modellering udvikles et konceptuelt system til datahåndteringen ved at analysere systemets indhold og metoder, designe systemet ved identificering af specifikke standardmetoder samt evaluere systemkonceptet. Ved et prædefineret tidsinterval håndterer en Javaapplikation kopiering af relevante sundhedsdata fra SST's registre, tildeling af et ID til hvert CPR-nummer og lagring af relevante sundhedsdata i SSI's Biobankregister således dataanonymisering kan foretages. Evaluering af systemet illustrerede at det er muligt at identificere et kompromis samt skitsere en systemarkitektur, der benytter sig af standardmetoder, som kan imødekomme de modsatrettede holdninger til datahåndteringen i den nationale biobank
Physiological roles of CNS muscarinic receptors gained from knockout mice
No full textBecause the five muscarinic acetylcholine receptor subtypes have overlapping distributions in many CNS tissues, and because ligands with a high degree of selectivity for a given subtype long remained elusive, it has been difficult to determine the physiological functions of each receptor. Genetically engineered knockout mice, in which one or more muscarinic acetylcholine receptor subtype has been inactivated, have been instrumental in identifying muscarinic receptor functions in the CNS, at the neuronal, circuit, and behavioral level. These studies revealed important functions of muscarinic receptors modulating neuronal activity and neurotransmitter release in many brain regions, shaping neuronal plasticity, and affecting functions ranging from motor and sensory function to cognitive processes. As gene targeting technology evolves including the use of conditional, cell type specific strains, knockout mice are likely to continue to provide valuable insights into brain physiology and pathophysiology, and advance the development of new medications for a range of conditions such as Alzheimer's disease, Parkinson's disease, schizophrenia, and addictions, as well as non-opioid analgesics.This article is part of the special issue entitled 'Muscarinic Receptors in the Central Nervous System'.</p
Stanzbiopsie eines kleinen retroperitonealen Lymphoms gestützt durch Bildfusion und elektromagnetischem Nadel-Tracking
No full textAntimanic efficacy of retigabine in a proposed mouse model of bipolar disorder
No full textRetigabine is a novel compound with anticonvulsant efficacy. Preclinical studies have indicated that the compound, like other anticonvulsants may also have antimanic efficacy. Bipolar disorder is characterized by episodes of depression and mania, which show a progressively faster recurrence and an increase in severity with time. Recurrence of episodes in bipolar disorders is suggested to reflect a process of sensitization. Repeated intermittent administration of amphetamine in rodents gives rise to a behavioral sensitization phenomena argued to have similarities to the sensitization found in humans. The aims were therefore to explore the predictive validity of the amphetamine sensitization model as a behavioral model of mania by testing the effect of a range of antimanic drugs and to evaluate the effect of retigabine on the sensitized amphetamine response. Furthermore, since withdrawal from prolonged use of amphetamine in humans can result in depression symptoms it was explored if a state of anhedonia could be assessed by testing saccharine preference before and during the withdrawal period of the model. The tested antimanic drugs (lithium, valproate, carbamazepine and lamotrigine) all attenuated the sensitized locomotor activity induced and with the exception of valproate the found effects seemed not to be due to sedation. Interestingly, retigabine also attenuated the induced locomotor activity with a lowest effective dose at 1.0mg/kg, whereas basal locomotor activity was only reduced at 8.0mg/kg, suggesting a genuine calming and antimanic-like efficacy of the compound. In addition, saccharine preference data suggest that withdrawal from the d-amphetamine pre-treatment regimen may induce depression-like behavior indicating that both manic and depression-like behavior is expressed in this mouse model
Sufficient Conditions for Solvability of Operators of Subprincipal Type
No full textIn this paper we show that condition on the
subprincipal symbol is sufficient for local solvability of pseudodifferential
operators of real subprincipal type. These are the operators having real
principal symbol which vanish on an involutive manifold where the subprincipal
symbol is of principal type. This condition has previously been shown by the
author to be necessary for local solvability of pseudodifferential operators of
real subprincipal type.Comment: 67 pages. Some typos and minor errors have been corrected. Revised
the argument in the proof of Theorem A.1 in the appendix, the result is
unchange
Effect of the new antiepileptic drug retigabine in a rodent model of mania
No full textBipolar spectrum disorders are severe chronic mood disorders that are characterized by episodes of mania or hypomania and depression. Because patients with manic symptoms often experience clinical benefit from treatment with anticonvulsant drugs, it was hypothesized that retigabine, a novel compound with anticonvulsant efficacy, may also possess antimanic activity. The amphetamine (AMPH)+chlordiazepoxide (CDP)-induced hyperactivity model has been proposed as a suitable model for studying antimanic-like activity of novel compounds in mice and rats. The aims of the present study in rats were therefore (1) to confirm previous findings with lithium and lamotrigine, and (2) to evaluate the effect of the novel compound retigabine on AMPH+CDP-induced hyperactivity in rats. In all experiments, co-administration of AMPH and CDP induced a significant increase (191-295%) in locomotor activity. Lithium chloride (0.9 mg/kg) and lamotrigine (20 mg/kg), which are known to effectively stabilize mood in humans, both significantly decreased AMPH+CDP-induced locomotor activity without affecting basal locomotor activity. The results furthermore indicate that retigabine, like lithium and lamotrigine, significantly and dose-dependently attenuates the induced hyperactivity at a lowest effective dose of 1.0 mg/kg, whereas basal locomotor activity is reduced only at doses 4.0 mg/kg. In conclusion, retigabine was found to have an antimanic-like effect in the AMPH+CDP-induced hyperactivity model, suggesting a potential role for retigabine in the treatment of mania and possibly in the management of bipolar disorder
G protein-coupled receptor signaling in VTA dopaminergic neurons bidirectionally regulates the acute locomotor response to amphetamine but does not affect behavioral sensitization
No full textSubjective perception of cocaine reward in mice assessed by a single exposure place preference (sePP) paradigm
No full textBackground The potential of abused drugs to induce addiction and compulsive drug-related behavior is associated with their ability to alter dopamine signaling. Dopamine plays a key role in reward signaling and it has been of great interest to investigate how various drugs of abuse alter reward-related behavior. Comparison with existing methods In rodents, the rewarding effects of drugs have often been assessed in self-administration or place preference paradigms; both involving repeated drug exposure and weeks of training and testing. New method Our investigation describes a valid approach to assess the initial rewarding effects of cocaine in mice with a single exposure place preference (sePP) paradigm, avoiding repeated drug injections. Results We present the sePP paradigm with a 3-day protocol to assess the initial rewarding effects of cocaine. Interestingly, only male mice exhibit sePP to cocaine. To assess subsequent drug-related behavior, the protocol was extended by 3 days of extinction followed by reinstatement on day 10. Conclusion The sePP paradigm provides a reliable and convenient approach to assess the initial rewarding effects of cocaine, circumventing the need for repeated drug injections. The sePP protocol allows further dissection of the mechanism and influence of initial cocaine exposure on subsequent drug-related behaviors by including extinction and reinstatement. The lack of sePP in female mice may reflect a biologically relevant sex difference in the initial subjective perception of cocaine-induced reward. This could relate to and explain why males and females have been reported to respond differently to cocaine and cocaine-associated cues.</p
Entrepreneurial capacity and culture of innovation in the context of opportunity exploitation
No full textCurrent research posits that, with the passage of time, organizations tend to lose their ability to innovate. This process takes place as maturing entities become a guardian of the dominant social paradigms. As an integral element of the prevalent “logic of appropriateness,” maturing firms become complacent, make safer choices, and thus slowly become less responsive to external stimuli. This evolution of an organization’s logic may lead to their demise.
The research question of how some firms succeed over time while others fail to do so has long captured the interest of scholars. This dissertation aims to address this question by proposing that a firm can remain successful as long as it correctly understands and capitalizes on the implications of a changing world. The existing literature associates variation in organizational success across firms with heterogeneity of their internal resources. In turn, sustainability of a firm’s competitive advantage is explained as a function of the ongoing evolution of a firm’s heterogeneous capabilities. Building on this theoretical framework, but strongly influenced by the contingency approach, this study aims to expand existing theory by introducing the concept of entrepreneurial capacity. The dissertation proposes that entrepreneurial capacity allows a firm to capitalize on a broad scope of fresh, alternative perspectives that may fundamentally challenge embedded assumptions and path-dependent cognitive schemas that a firm uses. Due to entrepreneurial capacity, a firm becomes exposed to many alternative viewpoints that represent heterogeneity of its external environment. Exposure to a broad array of alternative perspectives prompts a firm to reconsider the effectiveness of its internal operations. As a result, a firm reallocates its internal resources, which leads to improved performance. Given this assumption, the dissertation theorizes and empirically tests the notion that higher heterogeneity among external sources of information coupled with a stronger cognitive ability to comprehend and capitalize on a broader scope of new heterogeneous information will increase the likelihood of successful opportunity exploitation resulting in superior firm performance. Consequently, this dissertation suggests that a firm will be able to succeed over time, as long as it can maintain its strong entrepreneurial capacity.
In addition to the introduction of the concept of entrepreneurial capacity, the second part of this dissertation focuses on the role of contextual factors during the process of opportunity exploitation. The existing literature indicates that sets of collective values and norms accepted and supported by employees can determine how individuals view the world, how they think, and consequently, how they act. Consistent with this tenant, this study aims to explore the impact of the culture of innovation on the relationship between entrepreneurial capacity and firm performance. The dissertation proposes that when a firm establishes shared cultural norms supporting the process of opportunity exploitation, a firm culture should increase employee motivation to become engaged in behaviors positively reinforcing the effect of entrepreneurial capacity on firm performance.
Empirical tests of the proposed model are based on data collected in the healthcare industry. Research on health care strongly suggests that this very dynamic and complex setting, characterized by a high degree of external volatility provides a valid empirical setting to test the associations between a firm’s entrepreneurial capacity, culture of innovation and firm performance. Results of empirical analyses confirm a positive relationship between entrepreneurial capacity and firm performance. Furthermore, results of the study confirm a significant role played by a culture of innovation. Findings and the study’s implications for research and practitioners are discussed.Item withdrawn by Mark Zulauf ([email protected]) on 2014-04-22T13:42:13Z
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SUBCHRONIC LOW DOSE EXENDIN-4 PRETREATMENT INHIBITS RELAPSE TO ALCOHOL DRINKING IN HIGH ALCOHOL PREFERING C57BL6 MICE
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