Truth in sentential structure: a critical analysis of standard semantic accounts of context sensitivity

The principal aim of this thesis is to assess the view that the formal properties of sentences of natural languages encode truth-conditions. The question I pursue is whether truth-conditional semantic theories are capable of accounting for the various ways in which contextual factors contribute to the determination of the truth-conditional content of sentences. The thesis will assess and evaluate three different approaches standard contemporary truth-conditional semanticists have set forth in response to what I shall refer to as the challenge from pervasive context sensitivity, which is essentially the claim that context plays a more extensive role in the determination of content than that of fixing the semantic values of standard indexical expressions. I shall aim to show that each of the approaches mentioned fails to provide an adequate account of how the phenomenon of context sensitivity can be explained on the basis of our linguistic competence alone, and shall then explore some of the consequences of this

Time for a Change? Technological Persistence in the British Watchmaking Industry

In this article the author identifies factors that led to the decline of the once-mighty British watch industry. From a dominant position in the late eighteenth century when English watchmakers supplied half of the world's demand, to a low point in the pre-World War I period, foreign producers at first challenged domestic British manufacturers in foreign markets, then virtually drove them out of their home market. The persistence of old technologies in the English watchmaking centres of London, Prescot, Birmingham and Coventry led to this terminal decline. Resistance to change was fuelled by economic, social and cultural factors. By failing both to adopt technological innovations developed in Switzerland and the United States and to adapt to changing market conditions, the sophisticated but outdated technology of Great Britain doomed itself to extinction. Résumé Dans cet article, l'auteur identifie les facteurs qui ont mené au déclin de l'industrie horlogère, autrefois puissante, en Grande-Bretagne. D'une position dominante à la fin du XVIIIe siècle, alors que les horlogers anglais satisfaisaient à la moitié de la demande mondiale, l'industrie britannique est tombée à un modeste niveau dans la période qui a précédé la Première Guerre mondiale. Les producteurs étrangers ont d'abord concurrencé les fabricants britanniques dans les marchés étrangers puis les ont pratiquement chassés de leur propre marché. C'est la persistance de vieilles technologies dans les centres d'horlogerie anglais de Londres, Prescot, Birmingham et Coventry qui a mené à ce déclin fatal. La résistance au changement s'est alimentée à des facteurs économiques, sociaux et culturels. En négligeant d'adopter les innovations techniques mises au point en Suisse et aux États-Unis, et de s'adapter aux conditions changeantes du marché, la technologie raffinée mais périmée de Grande-Bretagne s'est condamnée elle-même à disparaître

Expectations, Experiences and Impact of Engagement Between Health Researchers and Schools in Kenya

Community engagement is increasingly recognized as essential for the ethical conduct of health research, particularly in international settings where wealth, educational and cultural differences between host communities and researchers are often stark. Engagement approaches are diverse, addressing a wide range of goals. The School Engagement Programme (SEP) forms part of a wider platform of community engagement activities at the KEMRI-Wellcome Trust Research Programme (KWTRP) in Kilifi, Kenya. Key SEP goals include raising mutual understanding between researchers and community members, nurturing secondary school students’ interest in science, and raising educational aspirations. In this thesis, I address the paucity of careful evaluations of community engagement in low and middle-income countries (LMICs), and of school engagement specifically. I consider the potential contribution of school engagement to the ethical goals of research, and contribute to the identification of key elements to use in the evaluation of school engagement programmes in the region. Drawing on a novel combination of methods including participatory video, baseline and post-intervention surveys, interviews and group discussions I found that the SEP benefitted students through nurturing an interest in science and promoting confidence in speaking to researchers, laying a foundation for future interactions. Researchers benefitted through strengthened ties with the community which gave them a better understanding of the context of their work and more of a sense of being part of the community. There were also unintended outcomes and mismatches between programme goals and community expectations however, which highlight the need for broad inclusion in planning and implementing school engagement programmes, and the monitoring of perverse outcomes. The thesis draws from the SEP evaluation findings to synthesise a theory of change and a framework to guide the evaluation of school engagement programmes

How CD40L reverse signaling regulates axon and dendrite growth

CD40-activated CD40L reverse signaling is a major physiological regulator of axon and dendrite growth from developing hippocampal pyramidal neurons. Here we have studied how CD40L-mediated reverse signaling promotes the growth of these processes. Cultures of hippocampal pyramidal neurons were established from Cd40−/− mouse embryos to eliminate endogenous CD40/CD40L signaling, and CD40L reverse signaling was stimulated by a CD40-Fc chimera. CD40L reverse signaling increased phosphorylation and hence activation of proteins in the PKC, ERK, and JNK signaling pathways. Pharmacological activators and inhibitors of these pathways revealed that whereas activation of JNK inhibited growth, activation of PKC and ERK1/ERK2 enhanced growth. Experiments using combinations of pharmacological reagents revealed that these signaling pathways regulate growth by functioning as an interconnected and interdependent network rather than acting in a simple linear sequence. Immunoprecipitation studies suggested that stimulation of CD40L reverse signaling generated a receptor complex comprising CD40L, PKCβ, and the Syk tyrosine kinase. Our studies have begun to elucidate the molecular network and interactions that promote axon and dendrite growth from developing hippocampal neurons following activation of CD40L reverse signaling

An essential role for neuregulin-4 in the growth and elaboration of developing neocortical pyramidal dendrites

Neuregulins, with the exception of neuregulin-4 (NRG4), have been shown to be extensively involved in many aspects of neural development and function and are implicated in several neurological disorders, including schizophrenia, depression and bipolar disorder. Here we provide the first evidence that NRG4 has a crucial function in the developing brain. We show that both the apical and basal dendrites of neocortical pyramidal neurons are markedly stunted in Nrg4−/− neonates in vivo compared with Nrg4+/+ littermates. Neocortical pyramidal neurons cultured from Nrg4−/− embryos had significantly shorter and less branched neurites than those cultured from Nrg4+/+ littermates. Recombinant NRG4 rescued the stunted phenotype of embryonic neocortical pyramidal neurons cultured from Nrg4−/− mice. The majority of cultured wild type embryonic cortical pyramidal neurons co-expressed NRG4 and its receptor ErbB4. The difference between neocortical pyramidal dendrites of Nrg4−/− and Nrg4+/+ mice was less pronounced, though still significant, in juvenile mice. However, by adult stages, the pyramidal dendrite arbors of Nrg4−/− and Nrg4+/+ mice were similar, suggesting that compensatory changes in Nrg4−/− mice occur with age. Our findings show that NRG4 is a major novel regulator of dendritic arborisation in the developing cerebral cortex and suggest that it exerts its effects by an autocrine/paracrine mechanism

CD40L Reverse signaling influences dendrite spine morphology and expression of PSD-95 and Rho small GTPases

CD40-activated CD40L reverse signaling is a major physiological regulator of neural process growth from many kinds of developing neurons. Here we have investigated whether CD40L-reverse signaling also influences dendrite spine number and morphology in striatal medium spiny neurons (MSNs). Golgi preparations revealed no differences in the spine density, but because the dendrite arbors of MSNs were larger and branched in Cd40–/– mice, the total number of spines was greater in Cd40–/– mice. We also detected more mature spines compared with wild-type littermates. Western blot revealed that MSN cultures from Cd40–/– mice had significantly less PSD-95 and there were changes in RhoA/B/C and Cdc42. Immunocytochemistry revealed that PSD-95 was clustered in spines in Cd40–/– neurons compared with more diffuse labeling in Cd40+/+ neurons. Activation of CD40L-reverse signaling with CD40-Fc prevented the changes observed in Cd40–/– cultures. Our findings suggest that CD40L-reverse signaling influences dendrite spine morphology and related protein expression and distribution

CD40L reverse signaling suppresses prevertebral sympathetic axon growth and tissue innervation

CD40‐activated CD40L reverse signaling is a major physiological regulator of the growth of neural processes in the developing nervous system. Previous work on superior cervical ganglion (SCG) neurons of the paravertebral sympathetic chain has shown that CD40L reverse signaling enhances NGF‐promoted axon growth and tissue innervation. Here we show that CD40L reverse signaling has the opposite function in prevertebral ganglion (PVG) sympathetic neurons. During a circumscribed perinatal window of development, PVG neurons cultured from Cd40–/– mice had substantially larger, more exuberant axon arbors in the presence of NGF than PVG neurons cultured from wild‐type mice. Tissues that receive their sympathetic innervation from PVG neurons were markedly hyperinnervated in Cd40–/– mice compared with wild‐type mice. The exuberant axonal growth phenotype of cultured CD40‐deficient perinatal PVG neurons was pared back to wild‐type levels by activating CD40L reverse signaling with a CD40‐Fc chimeric protein, but not by activating CD40 forward signaling with CD40L. The co‐expression of CD40 and CD40L in PVG neurons suggests that these proteins engage in an autocrine signaling loop in these neurons. Our work shows that CD40L reverse signaling is a physiological regulator of NGF‐promoted sympathetic axon growth and tissue innervation with opposite effects in paravertebral and prevertebral neurons

Polish version of the Intermittent Claudication Questionnaire

Introduction. The assessment of health-related quality of life includes the assessment of physical condition and motor skills, mental condition, social and economic situation, and somatic experiences. The specific ques-tionnaires used in patients with intermittent claudication include i.a. Peripheral Artery Questionnaire, Vascular Quality of Life Questionnaire, PAD Quality of Life Questionnaire, and Walking Impairment Questionnaire, which is the only one of the aforementioned questionnaires that is available in Polish. The Intermittent Claudication Questionnaire (ICQ) available in English is a specific instrument for assessing the quality of life of patients with intermittent claudication. This paper attempts at evaluating the reliability of the Polish version of ICQ. Material and methods. The process of validation of the Polish version of the questionnaire involved translating the questionnaire and evaluating the newly translated tool in order to compare the results on international level for the possibility of its practical use for assessment of health-related quality of life in patients with intermittent claudication in Poland. In order to evaluate the reliability and coherence of the questionnaire, the methods of internal consistency in Cronbach’s a, as well as the intraclass correlation coefficient were applied for specific questions and for the final result of the questionnaire. Results. The Cronbach’s a as the questionnaire’s reliability index was 0.915. Intraclass correlation calculated for the total score of the questionnaire’s answers was 0.97. Conclusions. The Polish version of the Intermittent Claudication Questionnaire is a repeatable and reliable research tool for assessing the health-related quality of life in patients with intermittent claudication

Risk of intracerebral aneurysm rupture during carotid revascularization

ObjectiveRobust guidelines exist for the treatment of carotid stenosis and intracranial aneurysms independently, however, the management of tandem carotid stenosis and intracranial aneurysms remains uncertain. Although the prevalence of tandem pathologies is small (1.9%-3.2%), treating carotid stenosis can alter intracranial hemodynamics potentially predisposing to aneurysm rupture. In this review, our aim was to assess the safety of intervention in this cohort, by analyzing outcomes from the published literature.MethodsThe preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used to conduct the review. Articles from 1947 to 2012 were searched using EMBASE Classic and EMBASE (November, 1947 -March, 2012) and Ovid MEDLINE(R) In-Process and other NonIndexed Citations and Ovid MEDLINE(R) on Ovid SP, http://ClinicalTrials.gov, http://controlled-trials.com and the Cochrane review database using a predefined search strategy.ResultsOne hundred forty-one patients from 27 articles were included. Interventions ranged from single (n = 104, 74%), staged (n = 26, 18%) to simultaneous procedures (n = 11, 8%). The largest cohort of patients was treated by carotid endarterectomy alone (n = 92, 66%). The majority of patients presented with a symptomatic carotid stenosis and an asymptomatic ipsilateral intracranial aneurysm (n = 70, 50%). Five subarachnoid hemorrhages occurred (4% [5/140], three within 30 days of the procedure and two thereafter) of which two were fatal. All five occurred in patients who underwent carotid endarterectomy as a single procedure (5%). Two of the five patients presented with ruptured posterior communicating artery aneurysms.ConclusionsPublished reports of perioperative aneurysm rupture are rare in individuals with tandem carotid stenosis and intracranial aneurysms. This is the first analysis of all published cases. However, it is limited by the small number of studies and the possible underreporting due to publication bias and underdiagnosis where angiography was not performed. Although we report a low incidence of subarachnoid hemorrhage, analysis of registry data with a larger cohort is warranted to confirm these findings