Studies on the luminance-related characteristics of the transient pattern reversal electroretinogram

The electroretinogram evoked by reversal pattern stimulation (rPERG) is known to contain both pattern contrast and luminance related components. The retinal mechanisms of the transient rPERGs subserving these functional characteristics are the main concern in the present studies. Considerable attention has been paid to the luminance-related characteristics of the response. The transient PERGs were found to consist of two subsequent processes using low frequency attenuation analysis. The processes overlapped and the individual difference in each process timings formed the major cause for the variations of the negative potential waveform of the transient rPERGs. Attention has been paid to those having ‘notch’ type of variation. Under different contrast levels, the amplitudes of the positive and negative potentials were linearly increased with higher contrast level and the negative potential showed a higher sensitivity to contrast changes and higher contrast gain. Under lower contrast levels, the decreased amplitudes made the difference in the timing course of the positive and negative processes evident, interpreting the appearance of the notch in some cases. Visual adaptation conditions for recording the transient rPERG were discussed. Another effort was to study the large variation of the transient rPERGs (especially the positive potential, P50) in the elderly who’s distant and near visual acuity were normal. It was found that reduction of retinal illumination contributed mostly to the P50 amplitude loss and contrast loss mostly to the negative potential (N95) amplitude loss. Senile miosis was thought to have little effect on the reduction of the retinal illumination, while the changes in the optics of the eye was probably the major cause for it, which interpreted the larger individual variation of the P50 amplitude of the elderly PERGs. Convex defocus affected the transient rPERGs more effectively than concave lenses, especially the N95 amplitude in the elderly. The disability of accommodation and the type and the degree of subjects’ ametropia should be taken into consideration when the elderly rPERGs were analysed.

Impact of senescence and disease on the structural and functional performance of the visual pathway

The diagnosis and monitoring of ocular disease presents considerable clinical difficulties for two main reasons i) the substantial physiological variation of anatomical structure of the visual pathway and ii) constraints due to technical limitations of diagnostic hardware. These are further confounded by difficulties in detecting early loss or change in visual function due to the masking of disease effects, for example, due to a high degree of redundancy in terms of nerve fibre number along the visual pathway. This thesis addresses these issues across three areas of study: 1. Factors influencing retinal thickness measures and their clinical interpretation As the retina is the principal anatomical site for damage associated with visual loss, objective measures of retinal thickness and retinal nerve fibre layer thickness are key to the detection of pathology. In this thesis the ability of optical coherence tomography (OCT) to provide repeatable and reproducible measures of retinal structure at the macula and optic nerve head is investigated. In addition, the normal physiological variations in retinal thickness and retinal nerve fibre layer thickness are explored. Principal findings were: • Macular retinal thickness and optic nerve head measurements are repeatable and reproducible for normal subjects and diseased eyes • Macular and retinal nerve fibre layer thickness around the optic nerve correlate negatively with axial length, suggesting that larger eyes have thinner retinae, potentially making them more susceptible to damage or disease • Foveola retinal thickness increases with age while retinal nerve fibre layer thickness around the optic nerve head decreases with age. Such findings should be considered during examination of the eye with suspect pathology or in long-term disease monitoring 2. Impact of glucose control on retinal anatomy and function in diabetes Diabetes is a major health concern in the UK and worldwide and diabetic retinopathy is a major cause of blindness in the working population. Objective, quantitative measurements of retinal thickness. particularly at the macula provide essential information regarding disease progression and the efficacy of treatment. Functional vision loss in diabetic patients is commonly observed in clinical and experimental studies and is thought to be affected by blood glucose levels. In the first study of its kind, the short term impact of fluctuations in blood glucose levels on retinal structure and function over a 12 hour period in patients with diabetes are investigated. Principal findings were: • Acute fluctuations in blood glucose levels are greater in diabetic patients than normal subjects • The fluctuations in blood glucose levels impact contrast sensitivity scores. SWAP visual fields, intraocular pressure and diastolic pressure. This effect is similar for type 1 and type 2 diabetic patients despite the differences in their physiological status. • Long-term metabolic control in the diabetic patient is a useful predictor in the fluctuation of contrast sensitivity scores. • Large fluctuations in blood glucose levels and/or visual function and structure may be indicative of an increased risk of development or progression of retinopathy 3. Structural and functional damage of the visual pathway in glaucomatous optic neuropathy The glaucomatous eye undergoes a number of well documented pathological changes including retinal nerve fibre loss and optic nerve head damage which is correlated with loss of functional vision. In experimental glaucoma there is evidence that glaucomatous damage extends from retinal ganglion cells in the eye, along the visual pathway, to vision centres in the brain. This thesis explores the effects of glaucoma on retinal nerve fibre layer thickness, ocular anterior anatomy and cortical structure, and its correlates with visual function in humans. Principal findings were: • In the retina, glaucomatous retinal nerve fibre layer loss is less marked with increasing distance from the optic nerve head, suggesting that RNFL examination at a greater distance than traditionally employed may provide invaluable early indicators of glaucomatous damage • Neuroretinal rim area and retrobulbar optic nerve diameter are strong indicators of visual field loss • Grey matter density decreases at a rate of 3.85% per decade. There was no clear evidence of a disease effect • Cortical activation as measured by fMRI was a strong indicator of functional damage in patients with significant neuroretinal rim loss despite relatively modest visual field defects These investigations have shown that the effects of senescence are evident in both the anterior and posterior visual pathway. A variety of anatomical and functional diagnostic protocols for the investigation of damage to the visual pathway in ocular disease are required to maximise understanding of the disease processes and thereby optimising patient care.

The future of the public library:reimagining the moral economy of the 'people's university'

New media technologies, the digitisation of information, learning archives and heritage resources are changing the nature of the public library and museums services across the globe, and, in so doing, changing the way present and future users of these services interact with these institutions in real and virtual spaces. New digital technologies are rewriting the nature of participation, learning and engagement with the public library, and fashioning a new paradigm where virtual and physical spaces and educative and temporal environments operate symbiotically. It is with such a creatively disruptive paradigm that the £193 million Library of Birmingham project in the United Kingdom is being developed. New and old media forms and platforms are helping to fashion new public places and spaces that reaffirm the importance of public libraries as conceived in the nineteenth century. As people’s universities, the public library service offers a web of connective learning opportunities and affordances. This article considers the importance of community libraries as sites of intercultural understanding and practical social democracy. Their significance is reaffirmed through the initial findings in the first of a series of community interventions forming part of a long-term project, ‘Connecting Spaces and Places’, funded by the Royal Society of Arts.

The impact of the Val158Met catechol-O-methyltransferase genotype on neural correlates of sad facial affect processing in patients with bipolar disorder and their relatives

Background - The Met allele of the catechol-O-methyltransferase (COMT) valine-to-methionine (Val158Met) polymorphism is known to affect dopamine-dependent affective regulation within amygdala-prefrontal cortical (PFC) networks. It is also thought to increase the risk of a number of disorders characterized by affective morbidity including bipolar disorder (BD), major depressive disorder (MDD) and anxiety disorders. The disease risk conferred is small, suggesting that this polymorphism represents a modifier locus. Therefore our aim was to investigate how the COMT Val158Met may contribute to phenotypic variation in clinical diagnosis using sad facial affect processing as a probe for its neural action. Method - We employed functional magnetic resonance imaging to measure activation in the amygdala, ventromedial PFC (vmPFC) and ventrolateral PFC (vlPFC) during sad facial affect processing in family members with BD (n=40), MDD and anxiety disorders (n=22) or no psychiatric diagnosis (n=25) and 50 healthy controls. Results - Irrespective of clinical phenotype, the Val158 allele was associated with greater amygdala activation and the Met allele with greater signal change in the vmPFC and vlPFC. Signal changes in the amygdala and vmPFC were not associated with disease expression. However, in the right vlPFC the Met158 allele was associated with greater activation in all family members with affective morbidity compared with relatives without a psychiatric diagnosis and healthy controls. Conclusions - Our results suggest that the COMT Val158Met polymorphism has a pleiotropic effect within the neural networks subserving emotional processing. Furthermore the Met158 allele further reduces cortical efficiency in the vlPFC in individuals with affective morbidity. © 2010 Cambridge University Press.

Frontline agents of globalisation:the German merchant community in Glasgow, 1840s to 1914

During the second half of the nineteenth century, a German business community of about one hundred merchants and commercial clerks developed in Glasgow. Their trade networks extended not only to Germany but also to other world markets. The main arguments and findings of the microhistorical analysis include: numbers were significantly higher than previously assumed; endogenous recruitment based on ethnic and family ties was prevalent; migrants benefited from their migration-induced social capital (training, languages, intercultural competence) to fill a skills-gap in Britain; labour market competition at the junior career level was less pronounced than contemporaneous assessments suggested; naturalisation was taken out for purely pragmatic reasons; there was a sense of community at intra-ethnic level, but also with the local business elite. The case study is embedded into the larger context of Anglo-German economic relations and globalisation. A purely local perspective does not suffice to do justice to the wider significance of expatriate business communities in an age of economic globalisation.

The morphology of the labour party's one nation narrative:story, plot and authorship

By applying narrative theory to the party political texts emerging within the UK Labour Party after 2010, which make up the corpus of One Nation discourse, we can grasp the underlying significance of this ideational revision of Labour Party and leftist thought. Through an identification and analysis of the sequence of texts and their constitution as a "story" that interpolates an underlying "plot," we can see how a revision of Labour's "tale" offers to leadership a new party discourse appropriate to it, mediating-if not reconciling-the problematic duality of narrative authorship by both party and leader. © The Political Quarterly Publishing Co. Ltd. 2013.

The prevalence and phenotype of activated microglia/macrophages within the spinal cord of the hyperostotic mouse (twy/twy) changes in response to chronic progressive spinalcord compression:implications for human cervical compressive myelopathy

Background:Cervical compressive myelopathy, e.g. due to spondylosis or ossification of the posterior longitudinal ligament is a common cause of spinal cord dysfunction. Although human pathological studies have reported neuronal loss and demyelination in the chronically compressed spinal cord, little is known about the mechanisms involved. In particular, the neuroinflammatory processes that are thought to underlie the condition are poorly understood. The present study assessed the localized prevalence of activated M1 and M2 microglia/macrophages in twy/twy mice that develop spontaneous cervical spinal cord compression, as a model of human disease.Methods:Inflammatory cells and cytokines were assessed in compressed lesions of the spinal cords in 12-, 18- and 24-weeks old twy/twy mice by immunohistochemical, immunoblot and flow cytometric analysis. Computed tomography and standard histology confirmed a progressive spinal cord compression through the spontaneously development of an impinging calcified mass.Results:The prevalence of CD11b-positive cells, in the compressed spinal cord increased over time with a concurrent decrease in neurons. The CD11b-positive cell population was initially formed of arginase-1- and CD206-positive M2 microglia/macrophages, which later shifted towards iNOS- and CD16/32-positive M1 microglia/macrophages. There was a transient increase in levels of T helper 2 (Th2) cytokines at 18 weeks, whereas levels of Th1 cytokines as well as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and macrophage antigen (Mac) -2 progressively increased.Conclusions:Spinal cord compression was associated with a temporal M2 microglia/macrophage response, which may act as a possible repair or neuroprotective mechanism. However, the persistence of the neural insult also associated with persistent expression of Th1 cytokines and increased prevalence of activated M1 microglia/macrophages, which may lead to neuronal loss and demyelination despite the presence of neurotrophic factors. This understanding of the aetiopathology of chronic spinal cord compression is of importance in the development of new treatment targets in human disease. © 2013 Hirai et al.

Clonal composition of human adamantinomatous craniopharyngiomas and somatic mutation analyses of the patched (PTCH), Gsα and Gi2α genes

Craniopharyngioma is the most common childhood tumor and thought to arise from embryonic remnants of Rathke's pouch. The paucity of published data on the molecular basis of these tumors prompted us to examine 22 adamantinomatous craniopharyngiomas looking for genetic abnormalities. Using the X-linked polymorphic androgen receptor gene as a tool for X-chromosome inactivating analysis, we found that a subset of craniopharyngiomas are monoclonal and therefore are probably due to acquired somatic genetic defects. Thus, we investigated these tumours for mutations within three candidate genes, Gsα, Gi2α and patched (PTCH). Using single stranded conformational polymorphism (SSCP), denaturing gradient gel electrophoresis and direct sequencing, the presence of somatic mutations in these genes could not be demonstrated in any tumor. Our data indicate that a subset of craniopharyngiomas are monoclonal and the mutations in the PTCH, Gsα, and Gi2α contribute little if any to cranipharyngioma development.

Community pharmacist perceptions of the loss of resale price maintenance

Focal points: This study was designed to elicit the views of community pharmacists on any perceived business and professional changes following the loss of resale price maintenance (RPM)A piloted, 22-point self-completion questionnaire containing open, closed and scaled response questions was distributed to 35 independent (<10 stores), 13 multiple group and three supermarket-based pharmacies, and 40 responses were obtained (29 independent, eight multiple and three supermarket)Theme analysis indicated that 20 respondents felt that an increased range of services was now provided, 27 reported a decreased sales potential and 25 thought that patients now purchased more medicinesThe average price at which eight common over-the-counter medicines were offered was found to be £4.34 in independents, £4.37 in multiples and £4.22 in the supermarket pharmacies, compared with an average standard list price of £4.32There are indications that removal of RPM may have instigated changes in community pharmacy

Improving brain drug targeting through exploitation of the nose-to-brain route:a physiological and pharmacokinetic perspective

With an ageing population and increasing prevalence of central-nervous system (CNS) disorders new approaches are required to sustain the development and successful delivery of therapeutics into the brain and CNS. CNS drug delivery is challenging due to the impermeable nature of the brain microvascular endothelial cells that form the blood-brain barrier (BBB) and which prevent the entry of a wide range of therapeutics into the brain. This review examines the role intranasal delivery may play in achieving direct brain delivery, for small molecular weight drugs, macromolecular therapeutics and cell-based therapeutics, by exploitation of the olfactory and trigeminal nerve pathways. This approach is thought to deliver drugs into the brain and CNS through bypassing the BBB. Details of the mechanism of transfer of administrated therapeutics, the pathways that lead to brain deposition, with a specific focus on therapeutic pharmacokinetics, and examples of successful CNS delivery will be explored. © 2014 Bentham Science Publishers.

A study of the regulatory role of retinoic acid receptor gamma in Zebrafish development

Retinoic acid (RA) is thought to signal through retinoic acid receptors (RARs), i.e. RARα, β, and γ to play important roles in embryonic development and tissue regeneration. In this thesis, the zebrafish (Danio rario) was used as a vertebrate model organism to examine the role of RARγ. Treatment of zebrafish embryos with a RARγ specific agonist reduced the axial length of developing embryos, associated with reduced somite number and loss of hoxb13a expression. There were no clear alterations in hoxc11a or myoD expression. Treatment with the RARγ agonist disrupted the formation of anterior structures of the head, the cranial bones and the anterior lateral line ganglia, associated with a loss of sox9 immunopositive cells in the same regions. Pectoral fin outgrowth was blocked by treatment with the RARγ agonist; however, this was not associated with loss of tbx5a immunopositive lateral plate cells and was reversed by wash out of the RARγ agonist or co-treatment with a RARγ antagonist. Regeneration of the transected caudal fin was also blocked by RARγ agonist treatment and restored by agonist washout or antagonist co-treatment; this phenotype was associated with a localised reduction in canonical Wnt signalling. Conversely, elevated canonical Wnt signalling after RARγ treatment was seen in other tissues, including ectopically in the notochord. Furthermore, some phenotypes seen in the RARγ treated embryos were present in mutant zebrafish embryos in which canonical Wnt signalling was constitutively increased. These data suggest that RARγ plays an essential role in maintaining neural crest and mesodermal stem/progenitor cells during normal embryonic development and tissue regeneration when the receptor is in its non-ligated state. In addition, this work has provided evidence that the activation status of RARγ may regulate hoxb13a gene expression and canonical Wnt signalling. Further research is required to confirm such novel regulatory roles.

The mission and culture of the corporation

The economic crisis has brought a new situation also for the Hungarian economic policy, as neoliberalism as the main trend in economic thought is no longer valid. This phenomenon cannot be reduced to be a mere macroeconomic course shift, as an entire economic philosophy and approach has lost its relevance. One consequence of this is the need for a thorough revision of the theory and practice of business management, along with the re-evaluation of the notion and position of the corporation. Our study aims to contribute to this theoretical reformation, presenting that social values derived from psychological and sociological findings such as human motivational theories or trust are fundamental elements of the 21st century corporate model. To point to this, we use the ideological correspondences, while proving that our national research on corporate theory and even rather its application are far behind the 21st century requirements and lack even the Western view of the 20th century.

Visszatérhet-e a "nagy elmélet" a közgazdaságtanban? Megjegyzések a rendszerparadigma elmélettörténetéhez (Can the "grand theory" return to economics? Notes on the theoretical history of the system paradigm)

Kornai János rendszerparadigma-fogalmából és az ott felsorolt közgazdászok névsorából kiindulva, a tanulmány kiemel néhány mozzanatot ennek eszmetörténeti előzményeiből. A hatvanas évek szociológiai irodalmában időszerűtlennek tartották a nagy elmélet létrehozását, a nyolcvanas évek társadalomtudományában viszont már a hagyományos nagy rendszeralkotás és elbeszélésmód visszatérését méltatták. Adam Smith közgazdaságtanát a társadalmi érintkezés átfogó elmélete részének szánta, amely tartalmazza a jog, politika és erkölcs elveit és történetét. Ezt szemlélteti a kereskedelmi társadalom paradoxonának elemzése és annak bemutatása, hogyan vezetett a fényűzés a szabadság helyreállításához és a rendszeres kormányzat létrejöttéhez. Marx és a német történeti iskola egyaránt törekedett a társadalom történeti fejlődéstörvényeinek feltárására, noha kölcsönösen elutasították egymás felfogásának többi elemét. Schumpeter életművét az a törekvés határozta meg, hogy összekapcsolja az elméleti analízist és a történeti leírást, hogy a gazdasági fejlődés elemzéséből kiindulva megalkossa a társadalmi élet különböző területeinek interdependenciáját bemutató elméletet. / === / The study starts from János Kornai's concept of a system paradigm and the list of economists there to lift certain elements from its antecedents in intellectual history. The sociological writers of the 1960s thought it was inopportune to create a grand theory, while the social scientists of the 1980s were busy celebrating the return of the great traditional system-creating process and its mode of narration. Adam Smith presented his economics as part of a comprehensive theory of social organization that would cover the principles and history of law, politics and morality. This is illustrated by his analysis of the paradox of commercial society and his demonstration of how wealth led to the restoration of liberty and the establishment of regular governance. Marx and the German historical school both strove to identify laws of the historical development of society, although they each rejected the other elements of the other's concept. Schumpeter's oeuvre was marked by an effort to combine theoretical analysis with historical description, so that from an analysis of economic development he could arrive at a theory presenting the interdependence of the various areas of social activity.

Az ajánlati könyv statisztikai tulajdonságai (Statistical properties of the limit order book)

A pénzügyi modellek jelentős része feltételezi a piacok hatékony működését. Ennek következtében számos tudományos kutatás központi témája volt a piacok hatékonyságának tesztelése és ennek igazolása, esetleg cáfolata. Ezen próbálkozások azonban mind a mai napig eredménytelenül zárultak. A tesztelések nyomán a kutatások a termékek áralakulásából indultak ki, és a hozamokat ezen keresztül elemezték. Az elmúlt években azonban a fókusz átterelődött az árak alakulásáról egy elemibb tényezőre, az ajánlati könyvre. Ugyanis végső soron az ajánlatvezérelt piacokon az árakat az ajánlati könyvbe benyújtott megbízások alakulása fogja meghatározni. Mivel a tőzsdék jelentős része ajánlatvezérelt piacként működik, ezért érdemesnek tartották a kutatók, hogy inkább az ajánlati könyv alakulásának statisztikai jellemzőit elemezzék, hátha az eredményre vezet, és sikerül közelebb jutni a hatékony piacok elméletének igazolásához vagy cáfolatához. Jelen tanulmány célja az, hogy az eddig megjelent tudományos kutatások alapján ismertesse az ajánlati könyv alapvető statisztikai tulajdonságait, és rávilágítson arra: mindez valójában hozzájárult-e a hatékony piacok elméletének igazolásához? ______ Most of the fi nancial models assume that markets are effi cient. As a result, numerous scientifi c researchers were focused on testing the effi cient market hypothesis, and tried to prove, or deny it. However, all these attempts are still unsuccessful. During these researches, the analyses of the effi cient market hypothesis were based on the price evolution of a certain asset, and through this the returns were examined. In the recent years the research interest has changed, and instead of analyzing the returns, a more primary factor got into focus, namely the limit order book. The reason is that on order driven markets the prices and the order sizes in the limit order book infl uence the price evolution on the market. Since a notable number of stock markets operate as an order driven market, the researchers thought that it worth analyzing the statistical properties of the limit order book, because maybe it will get us closer to the proof of the effi cient market hypothesis. The purpose of this study is to summarize the statistical properties of the limit order book, based on the scientifi c works published so far. The study would like to highlight whether these studies contributed to the proof or disproof of the effi cient market hypothesis.

Úton egy fenntartható gazdasági paradigma felé – A komplexitás befogadása a hálózati elméleteken keresztül (Towards a sustainable economic paradigm – Acceptance of the complexity through network theories)

Mára elkerülhetetlennek tűnik a gondolati váltás a gazdaságtudományok területén annak érdekében, hogy közelebb kerüljünk a hármas (gazdasági, társadalmi, környezeti) válságot előidéző problémák megoldásaihoz. A szerzők cikkükben amellett érvelnek, hogy a komplexitás befogadása kezdeti törekvésként értelmezhető azon az úton, amely a mindennapokban érzékelhető társadalmi és ökológiai problémák megoldásához vezet. Már léteznek olyan gazdaság- és vállalatelméletek, amelyek kezdik megkérdőjelezni az eddigi főáramú koncepciókat, és készek arra, hogy elveiket, elméleteiket a működési környezet bonyolultságát elfogadva alakítsák ki, és így találjanak mindennapos megoldásokat a gazdasági működésben. Ilyen például – a cikkben szereplő – IMP (Industrial Marketing and Purchasing) csoport hálózatelmélete. A szerzők azt kívánják bemutatni, hogy az ilyen hálózatelméletek alkalmasak arra, hogy a vállalatközi szférán túl is befolyásolják azt, ahogyan a vállalatok döntéseiket meghozzák és kapcsolataikat kezelik. ______ Today, it seems inevitable change of thought in the field of economics in order to get closer to solutions of problems which induced the triple (economic, social, environmental) crisis. In their article, the authors argue that the reception of complexity can be interpreted as an initial effort on the path that leads to the solutions of the everyday perceived social and ecological problems. The authors aim to present that the IMP (Industrial Marketing and Purchasing) group network theory is able to influence beyond the sphere of inter-company, that companies take their decisions and their relationships are treated.