Reduced transferrin binding in Down syndrome:a route to senile plaque formation and dementia

Plasma transferrin binding in Down syndrome and Alzheimer's disease is significantly reduced compared with age matched controls and it was thought this may help elucidate a pathological time sequence for the onset of dementia in Down syndrome. In Down syndrome, there was a reduction in gallium and aluminium transferrin binding both with age and the onset of dementia. Non-transferrin bound gallium species were identified as non-transportable phosphate or silicate. Thus, the route of entry of metals into the brain must be via a transferrin mediated complex only. A clear sequence of pathological events has been demonstrated in Down syndrome which shows the pathway to development of plaques and dementia and this is believed to have an immunological origin.

Service innovation, embeddedness and business performance:UK regional evidence

This paper asks to question. First, what types of linkages make firms in the service sector innovate? And second, what is the link between innovation and the firms’ productivity and export performance? Using survey data from Northern Ireland we find that links intra-regional links (i.e. within Northern Ireland) to customers, suppliers and universities have little effect on innovation, but external links (i.e. outside Northern Ireland) help to boost innovation. Relationships between innovation, exporting and productivity prove complex but suggest that innovation itself is not sufficient to generate productivity improvements. Only when innovation is combined with increased export activity are productivity gains produced. This suggests that regional innovation policy should be oriented towards helping firms to innovate only where it helps firms to enter export markets or to expand their existing export market presence.

The stratigraphy of the Fishguard volcanic complex and associated sediments, SW Dyfed, Wales

This thesis describes the geology of a Lower Palaeozoic terrain, situated west of the town of Fishguard, SW Dyfed, Wales. The area is dominated by the Fishguard Volcanic Complex (Upper Llanvirn), and sediments that range in age from the Middle Cambrian to the Lower Llandeilo. The successions represent an insight into sedimentation and volcanism for c. 100 Ma. along the south-western margin of the Lower Palaeozoic Welsh Basin. The stratigraphy of the sedimentary sequence has been completely revised and the existing volcanostratigraphy modified. The observed complexity of the stratigraphy is primarily the consequence of Caldedonide deformation which resulted in large scale repetition. Fold-thrust tectonics dominates the structural style of the area. Caledonide trending (NE-SW) cross-faults complicate preexisting structures. Middle Cambrian (?) sedimentation is documented by shallow marine clastics and red shales deposited within tidal - subtidal environments. Upper Cambrian sedimentation was dominated by shallow marine `storm' and `fair weather' sedimentation within a muddy shelf environment. Shallow marine conglomerates and heterolithic intertidal siliciclastics mark the onset of Ordovician sedimentation during the lower Arenig transgression. Mid-Arenig sediments reflect deposits influenced by storm, fair-weather and wave related processes in various shallow marine environments, including; shoreface, inner shelf, shoaling bar, and deltaic. Graptolitic marine shales were deposited from the upper mid-Arenig through to the lower Llandeilo; during which time sediments accumulated by pelagic processes and fine grained turbidites. The varied nature of sedimentation reflects both localised change within the depositional system and the influence of larger regional eustatic events. Ordovician subaqueous volcanic activity produced thick accumulations of lavas, pyroclastics, hydroclastics, and hyaloclastics. The majority of volcanism was effusive in nature, erupted below the Pressure Compensation Level. Basaltic volcanism was characterised by pillowed lavas and tube networks, whilst sheet-flow lavas, pillow breccias and minor hyaloclastites developed locally. Silicic volcanism was dominated by rhyolitic clastics of various affinities, although coherent silicic obsidian lavas, sheet-flow lavas and pyroclastics developed. Hypabyssal intrusives of variable composition and habit occur throughout the volcanic successions. Low-grade regional metamorphism has variably affected the area, conditions of the prehnite-pumpellyite and greenschist facies having been attained. Numerous secondary phases developed in response to the conditions imposed, which collectively indicate that P-T conditions were of low-pressure facies series in the range P= 1.2-2.0 kbars and T= 230-350oC, under an elevated geothermal gradient of 40-45oC km-1. Polymineralic cataclastites associated with Caledonide deformation indicate that tectonism and metamorphism were in part contemporaneous.

Targeting the glycoprotein 130 receptor subunit to control pain and inflammation

The glycoprotein 130 (gp130) is a shared signal-transducing-membrane-associated receptor for several hematopoietic cytokines. Its activation is implicated in pain and in a variety of diseases via signaling of proinflammatory cytokines. These include interleukin-6 (IL-6) subfamily cytokines, many of which play important roles in the pathogenesis of diseases such as rheumatoid arthritis, Castleman's disease, and Kaposi's sarcoma. Several strategies have been developed to block gp130-receptor-mediated signaling. These include the application of monoclonal antibodies, the creation of mutant form(s) of the gp130 with increased binding affinity for such ligands as IL-6/sIL-6R complex, and the generation of antagonists by selective mutagenesis of the specific cytokine/gp130 receptor binding site(s). Other strategies include targeting gp130-mediated signaling pathways such as that involving signal transducer and activator of transcription-3. This review provides a summary of the latest research pertaining to the role of gp130 in the pathogenesis of inflammatory and other diseases in which the gp130 receptor is implicated. An overview of antagonists targeting the gp130 receptor is included with particular emphasis on their mechanism of action and their limitations and potential for therapeutic application.

Pain response and follow-up of patients undergoing panretinal laser photocoagulation with reduced exposure times

Purpose - We performed a study of laser panretinal photocoagulation in 20 patients with proliferative retinopathy. We compared short exposure, high-energy laser settings with conventional settings, using a 532?nm, frequency doubled, Neodymium–Yag laser and assessed the patients in terms of pain experienced and effectiveness of treatment. Methods - Twenty patients having panretinal photocoagulation for the first time underwent random allocation to treatment of the superior and inferior hemi-retina. Treatment A used ‘conventional’ parameters: exposure time 0.1?s, power sufficient to produce a visible grey-white burns, spot size 300?µm. The other hemi- retina was treated with treatment B using exposure 0.02?s, 300?µm and sufficient power to have similar endpoint. All patients were asked to evaluate severity of pain on a visual analogue scale. (0=no pain, 10=most severe pain). All patients were masked as to the type of treatment and the order of carrying out the treatment on each patient was randomised. Patients underwent fundus photography and were followed up for 6–45 months. Results - Seventeen patients had proliferative diabetic retinopathy, two had ischaemic central retinal vein occlusion and one had ocular ischaemic syndrome. The mean response to treatment A was 5.11, compared to 1.40 treatment B, on the visual analogue scale, which was statistically significant (P=0.001). All patients preferred treatment B. Further treatments, if required, were performed with treatment B parameters and long-term follow-up has shown no evidence of undertreatment. Conclusions - Shortening exposure time of retinal laser is significantly less painful but equally effective as conventional parameters.

Comparing regional organizations in global multilateral institutions:ASEAN, the EU and the UN

Structural change brought about by the end of the Cold War and accelerated globalisation have transformed the global environment. A global governance complex is emerging, characterised by an ever-greater functional and regulatory role for multilateral organisations such as the United Nations (UN) and its associated agencies. The evolving global governance framework has created opportunities for regional organisations to participate as actors within the UN (and other multilateral institutions). This article compares the European Union (EU) and Association of Southeast Asian Nations (ASEAN) as actors within the UN network. It begins by extrapolating framework conditions for the emergence of EU and ASEAN actorness from the literature. The core argument of this article is that EU and ASEAN actorness is evolving in two succinct stages: Changes in the global environment create opportunities for the participation of regional organisations in global governance institutions, exposing representation and cohesion problems at the regional level. In response, ASEAN and the EU have initiated processes of institutional adaptation.

Psychological traits influence autonomic nervous system recovery following esophageal intubation in health and functional chest pain

Background: Esophageal intubation is a widely utilized technique for a diverse array of physiological studies, activating a complex physiological response mediated, in part, by the autonomic nervous system (ANS). In order to determine the optimal time period after intubation when physiological observations should be recorded, it is important to know the duration of, and factors that influence, this ANS response, in both health and disease. Methods: Fifty healthy subjects (27 males, median age 31.9 years, range 20-53 years) and 20 patients with Rome III defined functional chest pain (nine male, median age of 38.7 years, range 28-59 years) had personality traits and anxiety measured. Subjects had heart rate (HR), blood pressure (BP), sympathetic (cardiac sympathetic index, CSI), and parasympathetic nervous system (cardiac vagal tone, CVT) parameters measured at baseline and in response to per nasum intubation with an esophageal catheter. CSI/CVT recovery was measured following esophageal intubation. Key Results: In all subjects, esophageal intubation caused an elevation in HR, BP, CSI, and skin conductance response (SCR; all p < 0.0001) but concomitant CVT and cardiac sensitivity to the baroreflex (CSB) withdrawal (all p < 0.04). Multiple linear regression analysis demonstrated that longer CVT recovery times were independently associated with higher neuroticism (p < 0.001). Patients had prolonged CSI and CVT recovery times in comparison to healthy subjects (112.5 s vs 46.5 s, p = 0.0001 and 549 s vs 223.5 s, p = 0.0001, respectively). Conclusions & Inferences: Esophageal intubation activates a flight/flight ANS response. Future studies should allow for at least 10 min of recovery time. Consideration should be given to psychological traits and disease status as these can influence recovery. The psychological trait of neuroticism retards autonomic recovery following esophageal intubation in health and functional chest pain. © 2013 John Wiley & Sons Ltd.

Pain response in patients undergoing panretinal photocoagulation by continuos wave Nd-YAG laser

Purpose: Current panretinal laser photocoagulative parameters are based on the Diabetic Retinopathy Study, which used exposures of 0.1 - 0.5 second to achieve moderate intensity retinal burns. Unfortunately, many patients find these settings painful. We wanted to investigate whether reducing exposure time and increasing power to give the same endpoint, is more comfortable and effective. Methods: 20 patients having panretinal photocoagulation for the first time underwent random allocation to two forms of laser treatment: half of the retinal area scheduled for treatment was treated with Green Yag laser with conventional parameters {exposure time 0.1 second (treatment A), power density sufficient to produce a visible grey - white burns}. The other half treated with shorter exposure 0.02 second (treatment B). All patient were asked to evaluate severity of pain on a visual analogue scale ranging from 0 - 10 (0 = no pain, 10 = most severe pain). All patients were masked as to the type of treatment. The order of carrying out the treatment on each patient was randomised. Fundus photographs were taken of each hemifundus to confirm treatment. Results: Of the 20 patients, 17 had proliferative diabetic retinopathy, 2 had ischaemic central retinal vein occlusion and one had ocular ischaemic syndrome. The average pain response to treatment A was 5.11 on a visual analogue scale with a mean power of 0.178 Watt; the average pain response to treatment B was 1.40 with a mean power of 0.489 Watt. Short exposure laser burns were significantly less painful (P < 0.001). Conclusion: Shortening exposure time with increased power is more comfortable for patients undergoing panretinal photocoagulation than conventional parameters.

Neurophysiological evaluation of convergent afferents innervating the human esophagus and area of referred pain on the anterior chest wall

Noxious stimuli in the esophagus cause pain that is referred to the anterior chest wall because of convergence of visceral and somatic afferents within the spinal cord. We sought to characterize the neurophysiological responses of these convergent spinal pain pathways in humans by studying 12 healthy subjects over three visits (V1, V2, and V3). Esophageal pain thresholds (Eso-PT) were assessed by electrical stimulation and anterior chest wall pain thresholds (ACW-PT) by use of a contact heat thermode. Esophageal evoked potentials (EEP) were recorded from the vertex following 200 electrical stimuli, and anterior chest wall evoked potentials (ACWEP) were recorded following 40 heat pulses. The fear of pain questionnaire (FPQ) was administered on V1. Statistical data are shown as point estimates of difference +/- 95% confidence interval. Pain thresholds increased between V1 and V3 [Eso-PT: V1-V3 = -17.9 mA (-27.9, -7.9) P < 0.001; ACW-PT: V1-V3 = -3.38 degrees C (-5.33, -1.42) P = 0.001]. The morphology of cortical responses from both sites was consistent and equivalent [P1, N1, P2, N2 complex, where P1 and P2 are is the first and second positive (downward) components of the CEP waveform, respectively, and N1 and N2 are the first and second negative (upward) components, respectively], indicating activation of similar cortical networks. For EEP, N1 and P2 latencies decreased between V1 and V3 [N1: V1-V3 = 13.7 (1.8, 25.4) P = 0.02; P2: V1-V3 = 32.5 (11.7, 53.2) P = 0.003], whereas amplitudes did not differ. For ACWEP, P2 latency increased between V1 and V3 [-35.9 (-60, -11.8) P = 0.005] and amplitudes decreased [P1-N1: V1-V3 = 5.4 (2.4, 8.4) P = 0.01; P2-N2: 6.8 (3.4, 10.3) P < 0.001]. The mean P1 latency of EEP over three visits was 126.6 ms and that of ACWEP was 101.6 ms, reflecting afferent transmission via Adelta fibers. There was a significant negative correlation between FPQ scores and Eso-PT on V1 (r = -0.57, P = 0.05). These data provide the first neurophysiological evidence of convergent esophageal and somatic pain pathways in humans.

Regional variation in written American English

The first study of its kind, Regional Variation in Written American English takes a corpus-based approach to map over a hundred grammatical alternation variables across the United States. A multivariate spatial analysis of these maps shows that grammatical alternation variables follow a relatively small number of common regional patterns in American English, which can be explained based on both linguistic and extra-linguistic factors. Based on this rigorous analysis of extensive data, Grieve identifies five primary modern American dialect regions, demonstrating that regional variation is far more pervasive and complex in natural language than is generally assumed. The wealth of maps and data and the groundbreaking implications of this volume make it essential reading for students and researchers in linguistics, English language, geography, computer science, sociology and communication studies.

The Closed Loop Model by Regional Economics or How Big is the Ants’ Footprint?

The economy is communication between Man and Nature. It is an interaction-network between our outside and inside Nature, that is, the external Nature surrounding us and the internal nature expressing our human essence. Money is an institution of the society, an infrastructure that ensures division of labour, enables the flow of information and material between the participants. The concept of regional material and financial circular flow will be more important with the oncoming peak-oil and post-carbon era. We should describe in time the outlines of closed or semi-closed loops economy. The fundamentals of Input-Output will flourish once again; it could help us formulate the link between the efficiency and resiliency of a regional complex system.

Az európai uniós támogatások hatékonysága és hatásossága közötti különbség a ROP 1.2 intézkedésnél (The difference between the efficiency and effectiveness of using the EU-subsidies at Regional Operational Program)

A szerző cikkében megpróbál rávilágítani annak fontosságára, hogy az Európai Unióból érkező fejlesztési támogatások hasznosulása és a támogatási rendszer hatékonysága között jelentős különbség van. Ha nem tudjuk hatékonyan és hatásosan felhasználni az Unióból érkező pénzügyi eszközöket, akkor a cél: a kohézió, a konvergencia az Európai Unió régi tagállamainak fejlettségi szintjéhez, jólétéhez még nehezebben és lassabban érhető el. Az uniós támogatások hatékonysága alapvetően a rendelkezésre álló pénz lekötésének, lehívásának arányából, illetve a lekötött, lehívott és esetleg visszafizetett összeg arányából állapítható meg (kvantitatív megközelítés). A támogatások felhasználásának hatékonyságánál bonyolultabb, jóval összetettebb megközelítést igényel a hatásosság fogalma. A felhasználás hatásosságát a projektszinten a támogatás hatására megtermelt hozzáadott értékkel, programszinten a GDP hozzáadott növekedéssel lehet kifejezni. A cikk alapvetően a ROP 1.2 "Turisztikai fogadóképesség javítása" pályázati kiírás nyertes projektjeinél végzett kutatás eredményein keresztül kívánja szemléltetni a projektszintű vagy mikro hatásosság fontosságára (kvalitatív megközelítés). _________ The author tries to highlight the importance the difference between the efficiency and effectiveness of using the EU-subsidies. If Hungary cannot use the financial means of the EU efficiently and effectively, than the goal: cohesion and convergence to the level of the old, developed countries of the EU will be much harder and slowly. The efficiency of the EU-subsidies can be measured by the ratio of the amount of money obliged and the amount of money spent, and by the amount of money withdrawn by the Commission, which is actually lost (quantitative approach). The effectiveness of EU-subsidies needs a much more complicated and complex approach, than the efficiency. The effectiveness of usage on project level can be measured by the "added value" of the project, on program level by the added GDP growth or employment. The article is analysing basically the results of a survey made among the winner project of the application ROP 1.2 (Regional Operational Program 1.2) Improving the capacity for tourism (project level or micro effectiveness – qualitative approach).

A hazai védekezőtől a regionális „támadóig” – az OTP nemzetköziesedésének időbeni alakulása (From the domestic defender to the regional striker – a timebased process of the OTP Bank’s internationalization)

A vállalatok nemzetköziesedése egy széles körben vizsgált szakterület, különösképpen olyan vállalatok esetében (az ún. tradicionális multik), amelyek hagyományosan nemzetközi orientációjú országokból (Triád) származnak. A nemzetközi piacokon viszonylag újnak számító közép-kelet-európai cégek terjeszkedése az üzleti kontextus változásával párhuzamosan zajlott. Következésképpen ahhoz, hogy megértsük a nemzetköziesedés időben zajló folyamatát, a vállalatok nemzetközi evolúcióját a kontextussal összefüggésben kell vizsgálni. A vállalatok nemzetköziesedésének legelterjedtebb kutatási módszerei a nagymintás keresztmetszeti vizsgálatok, amelyek nem adnak lehetőséget a nemzetközi fejlődés időbeni alakulásának megfigyelésére és a mintázat mögött rejlő valós okok feltárására. A jelen tanulmány egy longitudinális kutatási modell mentén vizsgálja egy nem tradicionális multi, a hazai OTP nemzetköziesedésének időbeni alakulását, feltárva a nemzetközivé válás folyamata során kialakuló komplex kapcsolatrendszert. _______ The purpose of the present paper is to describe the internationalisation process of a non-traditional multinational, the Hungarian OTP Bank and to understand the dynamic linkages between the spatial and temporal context and the content of firm internationalization using a phenomenon oriented longitudinal research design. The paper contributes to the time-based processual view of firm internationalization arguing that in order to understand firm internationalization along time one should observe organizations and their contextual environments as complex interacting processes. By analysing the interaction between the multi-level processes that shape internationalization, one can explore the reasons behind the dynamic profile of firm internationalization. The paper applies an interpretative approach focusing on local causality.

Acute Posterior Ankle Pain in a Female Recreational Soccer Player

Os trigonum syndrome, a musculoskeletal disorder causing posterior ankle pain, occurs in approximately one in every 13 people. This condition can be challenging for the athletic trainer when evaluating an acute ankle injury. We present a unique case of an os trigonum successfully treated with conservative rehabilitation without a definitive diagnosis.