Genetic mouse models of migraine

Mouse models of rare monogenic forms of migraine provide a unique experimental system to study the cellular and circuit mechanisms of the primary brain dysfunctions causing a migraine disorder. Here, we discuss the migraine-relevant phenotypes and the migraine-relevant functional alterations in the brain of five genetic mouse models of migraine, four of which carry mutations derived from patients with familial hemiplegic migraine (FHM) and the fifth carry a mutation from patients with both phenotypically normal MA and familial advanced sleep phase syndrome (FASPS). We focus on the latter mouse model, in which a ubiquitous serine-threonine kinase is mutated, and on two mouse models of pure FHM, in which a voltage-gated calcium channel controlling neurotransmitter release at most brain synapses and a Na/K ATPase that is expressed mainly in astrocytes in the adult brain are mutated, respectively. First, we describe the behavioral phenotypes of the genetic animal models and review the evidence that an increased susceptibility to experimentally induced cortical spreading depression (CSD) is a key migraine-relevant phenotype common to the five models. Second, we review the synaptic alterations in the cerebral cortex of the genetic models of migraine and discuss the mechanisms underlying their increased susceptibility to CSD. Third, we review the alterations in the trigeminovascular pain pathway and discuss possible implications for migraine pain mechanisms. Finally, we discuss the insights into migraine pathophysiology obtained from the genetic models of migraine, in particular regarding the mechanisms that make the brain of migraineurs susceptible to the ignition of "spontaneous" CSDs. Although the reviewed functional studies support the view of migraine as a disorder of the brain characterized by dysfunctional regulation of the excitatory/inhibitory balance in specific neuronal circuits, much work remains to be done in the genetic mouse models e.g. to identfy the relevant dysfunctional circuits and to establish whether and how the alterations in the function of specific circuits (in the cerebral cortex and/or other brain areas) are state-dependent and may, in certain conditions, favor CSD ignition and the migraine attack

Evaluating air traffic flow management in a collaborative decision-making environment

The collaborative decision-making (CDM) framework introduced into ground delay programs in the late 1990s is an integral component of FAA's traffic flow management (TFM) procedures. CDM allows FAA to act as a mediator when managing TFM programs, transferring as much decision making as possible to the individual airlines. Although this approach has been highly successful in practice, it creates a new question for the research community: How should proposed enhancements to TFM be evaluated in a CDM environment? A sequential evaluation procedure, developed in this paper, addresses this question. The procedure includes airline disruption responses and a quasi-compression operation, attempting to mimic the three-stage CDM process. To model airline disruption responses, an integer optimization model was developed to balance operational and passenger considerations in determining which flights to cancel, swap, or delay. The value of this procedure is demonstrated by analyzing an optimization-based TFM approach in the CDM environment

Do (and say) as I say: Linguistic adaptation in human-computer dialogs

© Theodora Koulouri, Stanislao Lauria, and Robert D. Macredie. This article has been made available through the Brunel Open Access Publishing Fund.There is strong research evidence showing that people naturally align to each other’s vocabulary, sentence structure, and acoustic features in dialog, yet little is known about how the alignment mechanism operates in the interaction between users and computer systems let alone how it may be exploited to improve the efficiency of the interaction. This article provides an account of lexical alignment in human–computer dialogs, based on empirical data collected in a simulated human–computer interaction scenario. The results indicate that alignment is present, resulting in the gradual reduction and stabilization of the vocabulary-in-use, and that it is also reciprocal. Further, the results suggest that when system and user errors occur, the development of alignment is temporarily disrupted and users tend to introduce novel words to the dialog. The results also indicate that alignment in human–computer interaction may have a strong strategic component and is used as a resource to compensate for less optimal (visually impoverished) interaction conditions. Moreover, lower alignment is associated with less successful interaction, as measured by user perceptions. The article distills the results of the study into design recommendations for human–computer dialog systems and uses them to outline a model of dialog management that supports and exploits alignment through mechanisms for in-use adaptation of the system’s grammar and lexicon

An Integrated Circuit for Signal Processing of the AMS RICH Photmultipliers Tubes

An analog integrated circuit has been designed, in a BiCMOS 0.8 micron technology, for the feasability study of the signal processing of the AMS RICH photomultiplier tubes. This low power, three channel gated integrator includes its own gate and no external analog delay is requiered. It processes PMT pulses over a dynamic range of more than 100. A logic output that indicates whether the analog charge has to be considered is provided. This gated integrator is used with a compact DSP based acquisition system in a 132 channels RICH prototype. The charge calibration of each channel is carried out using a LED. The pedestal measurement is performed on activation of a dedicated input. The noise contribution study of the input RC network and amplifiers is presented.Comment: IEEE symp. on Nucl. Sci. and Med. Imaging, Toront

Hyperglycemia and Death in Cystic Fibrosis–Related Diabetes

OBJECTIVE Diabetes is common in cystic fibrosis and increases the risk of death, yet the role of hyperglycemia remains unproven. An association between glycemia and mortality would provide compelling evidence to support glucose lowering in cystic fibrosis–related diabetes (CFRD). RESEARCH DESIGN AND METHODS Using the U.K. Cystic Fibrosis Registry, we analyzed longitudinal data from 2006 to 2009 in 520 individuals with diabetes. We tested the association between HbA1c and mortality. RESULTS During a median follow-up of 2 years, 36 patients died. The median value of HbA1c was higher in those who died (7.3%) than in those who did not (6.7%). An HbA1c value of ≥6.5% was associated with a threefold increased risk of death (hazard ratio 3.2 [95% CI 1.4–7.3]; P = 0.005) independent of potential confounders. CONCLUSIONS Hyperglycemia trebles the risk of death in patients with CFRD. These findings provide epidemiologic support for continued efforts to improve glycemic control. Diabetes frequently complicates cystic fibrosis. Cystic fibrosis–related diabetes (CFRD) has an incidence in teenagers of up to 6% per year and a prevalence in adults of >30% (1,2). Diabetes further elevates the already high mortality rates in cystic fibrosis (3–5). In individuals without cystic fibrosis, diabetes increases the risk of death, and in individuals with diabetes, hyperglycemia increases the risk of death (6,7). However, no study of CFRD using national data has investigated whether hyperglycemia, per se, increases the risk of death; likewise, no trial has tested whether controlling blood glucose prolongs survival. Proving an association between glycemia and mortality in cystic fibrosis would provide compelling observational evidence to inform clinical practice. Using the U.K. Cystic Fibrosis Registry, we performed longitudinal analyses to test the association between glycemia, as measured by HbA1c, and mortality in individuals with CFRD

Developing a quality assurance metric: a panoptic view

This article is a post-print of the published article that may be accessed at the link below. Copyright @ 2006 Sage Publications.There are a variety of techniques that lecturers can use to get feedback on their teaching - for example, module feedback and coursework results. However, a question arises about how reliable and valid are the content that goes into these quality assurance metrics. The aim of this article is to present a new approach for collecting and analysing qualitative feedback from students that could be used as the first stage in developing more reliable quality assurance metrics. The approach, known as the multi-dimensional crystal view, is based on the belief that individuals have different views on the benefits that the embedded process in a system can have on the behaviour of the system. The results of this study indicate that in the context of evaluation and feedback methods, the multi-dimensional approach appears to provide the opportunity for developing more effective student feedback mechanisms

A discursive psychology analysis of emotional support for men with colorectal cancer

Recent research into both masculinity and health, and the provision of social support for people with cancer has focussed upon the variations that may underlie broad assumptions about masculine health behaviour. The research reported here pursues this interest in variation by addressing the discursive properties of talk about emotional support, by men with colorectal cancer - an understudied group in the social support and cancer literature. Semi-structured interviews were conducted with eight men with colorectal cancer, and the transcripts analysed using an intensive discursive psychology approach. From this analysis two contrasting approaches to this group of men’s framing of emotional support in the context of cancer are described. First, talk about cancer was positioned as incompatible with preferred masculine identities. Second, social contact that affirms personal relationships was given value, subject to constraints arising from discourses concerning appropriate emotional expression. These results are discussed with reference to both the extant research literature on masculinity and health, and their clinical implications, particularly the advice on social support given to older male cancer patients, their families and friends

Voting and the Cardinal Aggregation of Judgments

The paper elaborates the idea that voting is an instance of the aggregation of judgments, this being a more general concept than the aggregation of preferences. To aggregate judgments one must first measure them. I show that such aggregation has been unproblematic whenever it has been based on an independent and unrestricted scale. The scales analyzed in voting theory are either context dependent or subject to unreasonable restrictions. This is the real source of the diverse 'paradoxes of voting' that would better be termed 'voting pathologies'. The theory leads me to advocate what I term evaluative voting. It can also be called utilitarian voting as it is based on having voters express their cardinal preferences. The alternative that maximizes the sum wins. This proposal operationalizes, in an election context, the abstract cardinal theories of collective choice due to Fleming and Harsanyi. On pragmatic grounds, I argue for a three valued scale for general elections

An acoustic charge transport imager for high definition television applications

The primary goal of this research is to develop a solid-state television (HDTV) imager chip operating at a frame rate of about 170 frames/sec at 2 Megapixels/frame. This imager will offer an order of magnitude improvements in speed over CCD designs and will allow for monolithic imagers operating from the IR to UV. The technical approach of the project focuses on the development of the three basic components of the imager and their subsequent integration. The camera chip can be divided into three distinct functions: (1) image capture via an array of avalanche photodiodes (APD's); (2) charge collection, storage, and overflow control via a charge transfer transistor device (CTD); and (3) charge readout via an array of acoustic charge transport (ACT) channels. The use of APD's allows for front end gain at low noise and low operating voltages while the ACT readout enables concomitant high speed and high charge transfer efficiency. Currently work is progressing towards the optimization of each of these component devices. In addition to the development of each of the three distinct components, work towards their integration and manufacturability is also progressing. The component designs are considered not only to meet individual specifications but to provide overall system level performance suitable for HDTV operation upon integration. The ultimate manufacturability and reliability of the chip constrains the design as well. The progress made during this period is described in detail