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Selected AbstractsMeeting risk with resilience: high daily life reward experience preserves mental healthACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2010N. Geschwind Geschwind N, Peeters F, Jacobs N, Delespaul P, Derom C, Thiery E, van Os J, Wichers M. Meeting risk with resilience: high daily life reward experience preserves mental health. Objective:, To examine prospectively whether high reward experience (the ability to generate positive affect boosts from pleasurable daily events) protects against affective symptoms and whether environmental or genetic risk factors moderate protective effects. Method:, At baseline, 498 female twins participated in an experience sampling study measuring reward experience in daily life. They also completed questionnaires on childhood adversity and recent stressful life events (SLE). Affective symptoms were measured at baseline and at four follow-ups using SCL-90 anxiety and depression subscales. Co-twin affective symptoms were used as indicators of genetic risk. Results:, Baseline reward experience did not predict follow-up affective symptoms, regardless of level of genetic risk. However, high reward experience was associated with reduced future affective symptoms after previous exposure to childhood adversity or recent SLE. Conclusion:, High daily life reward experience increases resilience after environmental adversity; modification of reward experience may constitute a novel area of therapeutic intervention. [source] The detection and quantification of lorazepam and its 3- O -glucuronide in fingerprint deposits by LC-MS/MSJOURNAL OF SEPARATION SCIENCE, JSS, Issue 13 2009Edward Goucher Abstract The use of fingerprints as an alternative biological matrix to test for the presence of drugs and/or their metabolites is a novel area of research in analytical toxicology. This investigation describes quantitative analysis for the benzodiazepine lorazepam and its 3- O -glucuronide conjugate in fingerprints following the oral administration of a single 2 mg dose of lorazepam to five volunteers. Creatinine was also measured to investigate whether the amount of drug relative to that of creatinine would help to account for the variable amount of secretory material deposited. Fingerprints were deposited on glass cover slips and extracted by dissolving them in a solution of dichloromethane/methanol, containing tetradeuterated lorazepam as an internal standard. The samples were evaporated, reconstituted with mobile phase and analysed by LC-MS/MS. Chromatography was achieved using an RP (C18) column for the analysis of lorazapem and its glucuronide, and a hydrophilic interaction column (HILIC) for the analysis of creatinine. Lorazepam and its glucuronide were only detected where ten prints had been combined, up to 12 h following drug administration. In every case, the amount of lorazepam glucuronide exceeded that of lorazepam, the peak amounts being 210 and 11 pg, respectively. Adjusting for creatinine smoothed the elimination profile. To our knowledge, this represents the first time a drug glucuronide has been detected in deposited fingerprints. [source] Gene transfer for hemophilia: can therapeutic efficacy in large animals be safely translated to patients?JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2005K. HIGH Summary., Gene transfer is a novel area of therapeutics in which the active agent is a nucleic acid rather than a protein or small molecule. As early as 1997, investigators reported long-term expression of therapeutic levels of factor IX using gene transfer techniques in hemophilia B mice, and similar data were thereafter reported in mice with hemophilia A. Efforts to translate these results to hemophilic dog models at first yielded only marginally therapeutic levels (1%,2% normal circulating levels), but within the past few years have achieved levels in the range of 10%,20% through multiple different gene transfer strategies. Early phase clinical testing has revealed that many aspects of gene transfer in humans were accurately predicted by studies in hemophilic dogs, but that other aspects were not, and were only appreciated as a result of clinical testing. Studies in the next few years will determine whether the problems identified in preclinical and early phase clinical testing can be solved to develop a therapeutic gene transfer approach to hemophilia. [source] Microbial exposure, interferon gamma gene demethylation in naïve T-cells, and the risk of allergic diseaseALLERGY, Issue 3 2009P. J. Vuillermin The period of immune programming during early life presents a critical window of opportunity for the prevention of allergic diseases. There is mounting evidence that inappropriate immune programming may involve disruption of specific epigenetic modifications (switches) at immune-related genes. This novel area of research has great potential, as epigenetic changes are known to be sensitive to environmental factors and may therefore provide a mechanistic link for the observed association between specific environmental cues, faulty immune development, and the risk of allergic disease. In addition, the dynamic and potentially reversible nature of epigenetic modifications offers potentially novel targets for therapeutic and/or preventative interventions. We review the evidence that (1) failure to up-regulate the interferon gamma (IFN,) response during infancy is an important determinant of the risk of allergic disease, (2) expression of the IFN, gene in naïve T-cells is regulated by epigenetic mechanisms, and (3) failure to up-regulate IFN, gene expression of naïve T-cells associated with low early life microbial exposure. Taken together, these lines of evidence suggest that low microbial exposure during early life increases the risk of allergic disease by reducing demethylation (activation) of the IFN, gene of naive T-cells. [source] Variations in the structure of the prelunate gyrus in Old World monkeysTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 7 2006Estel Van Der Gucht Abstract Anatomical and electrophysiological studies have revealed a complex organization in the macaque prelunate gyrus. We investigated the morphology and architecture of the prelunate gyrus in Old World monkeys. In Macaca nemestrina, we observed a sulcus crossing the prelunate gyrus within 2 mm of the vertical meridian representation. In other macaque species and other cercopithecines, we observed substantial variations in sulcal morphology across the prelunate gyrus. We did not find a sulcus in all species, and the location and depth of that indentation on the gyrus varied among species. A deep sulcus was observed in all species that emerged earlier in evolution than macaques, such as guenons, baboons, and colobines. We analyzed the regional and parcellation features of the prelunate gyrus in three macaque species, M. maura, M. mulatta, and M. radiata, and in Erythrocebus patas, with emphasis on the relation of structure to the distribution of prelunate visual areas. Nonphosphorylated neurofilament protein immunoreactivity permitted the delineation of a novel area in the prelunate gyrus of Old World monkeys, located around the prelunate sulcus. Species-specific patterns were also observed in the prelunate gyrus of the patas monkey compared to macaques. These observations, as well as a cladistic analysis of the data, suggest an expanded and diversified organization of the prelunate gyrus in some cercopithecoids that may reflect adaptation to specific ecological environments. It was, however, progressively lost in most macaques, being retained only in species that diverged early in the evolution of the genus Macaca, such as M. nemestrina and M. maura. Anat Rec Part A, 288A:753,775, 2006. © 2006 Wiley-Liss, Inc. [source] Sustained Monopolistic Business Relationships: An Interdisciplinarity CaseBRITISH JOURNAL OF MANAGEMENT, Issue 4 2003Andrew Humphries Business-to-business relationships within sustained monopolies, such as those within UK defence procurement, have received scant attention by management researchers. This is unusual because under these market circumstances there appear to be few incentives to achieve mutually beneficial outcomes despite their strategic policy importance. This paper argues that an understanding of the monopolistic environment using a transaction cost economics theoretical framework and supply-chain management, relationship marketing and transaction cost economics concepts provides an innovative, interdisciplinarity approach to solving this problem as well as testing aspects of these disciplines empirically in a novel area. This paper describes the results from a substantial research project to test this hypothesis in the UK defence procurement situation. It reveals a number of key dynamics within the sustained monopolistic relationships surveyed and suggests considerable potential for further research. [source] Do psychotherapies produce neurobiological effects?ACTA NEUROPSYCHIATRICA, Issue 2 2006Veena Kumari Background:, An area of recent interest in psychiatric research is the application of neuroimaging techniques to investigate neural events associated with the development and the treatment of symptoms in a number of psychiatric disorders. Objective:, To examine whether psychological therapies modulate brain activity and, if so, to examine whether these changes similar to those found with relevant pharmacotherapy in various mental disorders. Methods:, Relevant data were identified from Pubmed and PsycInfo searches up to July 2005 using combinations of keywords including ,psychological therapy', ,behaviour therapy', ,depression', ,panic disorder', ,phobia', ,obsessive compulsive disorder', ,schizophrenia', ,psychosis', ,brain activity', ,brain metabolism', ,PET', ,SPECT' and ,fMRI'. Results:, There was ample evidence to demonstrate that psychological therapies produce changes at the neural level. The data, for example in depression, panic disorder, phobia and obsessive compulsive disorder (OCD), clearly suggested that a change in patients' symptoms and maladaptive behaviour at the mind level with psychological techniques is accompanied with functional brain changes in relevant brain circuits. In many studies, cognitive therapies and drug therapies achieved therapeutic gains through the same neural pathways although the two forms of treatment may still have different mechanisms of action. Conclusions:, Empirical research indicates a close association between the ,mind' and the ,brain' in showing that changes made at the mind level in a psychotherapeutic context produce changes at the brain level. The investigation of changes in neural activity with psychological therapies is a novel area which is likely to enhance our understanding of the mechanisms for therapeutic changes across a range of disorders. [source] Preferences of the Ponto-Caspian amphipod Dikerogammarus haemobaphes for living zebra musselsJOURNAL OF ZOOLOGY, Issue 3 2009J. Kobak Abstract A Ponto-Caspian amphipod Dikerogammarus haemobaphes has recently invaded European waters. In the recipient area, it encountered Dreissena polymorpha, a habitat-forming bivalve, co-occurring with the gammarids in their native range. We assumed that interspecific interactions between these two species, which could develop during their long-term co-evolution, may affect the gammarid behaviour in novel areas. We examined the gammarid ability to select a habitat containing living mussels and searched for cues used in that selection. We hypothesized that they may respond to such traits of a living mussel as byssal threads, activity (e.g. valve movements, filtration) and/or shell surface properties. We conducted the pairwise habitat-choice experiments in which we offered various objects to single gammarids in the following combinations: (1) living mussels versus empty shells (the general effect of living Dreissena); (2) living mussels versus shells with added byssal threads and shells with byssus versus shells without it (the effect of byssus); (3) living mussels versus shells, both coated with nail varnish to neutralize the shell surface (the effect of mussel activity); (4) varnished versus clean living mussels (the effect of shell surface); (5) varnished versus clean stones (the effect of varnish). We checked the gammarid positions in the experimental tanks after 24 h. The gammarids preferred clean living mussels over clean shells, regardless of the presence of byssal threads under the latter. They responded to the shell surface, exhibiting preferences for clean mussels over varnished individuals. They were neither affected by the presence of byssus nor by mussel activity. The ability to detect and actively select zebra mussel habitats may be beneficial for D. haemobaphes and help it establish stable populations in newly invaded areas. [source] |