Chronic cough as a neuropathic disorder

Chronic cough is a common symptom that can be a daunting challenge for clinicians since treatment of the underlying cause does not always provide adequate relief, an obvious cause can remain elusive, and current antitussives have fairly poor efficacy and undesirable side-effects. Patients with chronic cough typically describe a range of sensory symptoms suggestive of upper-airway and laryngeal neural dysfunction. Additionally, patients often report cough triggered by low-level physical and chemical stimuli, which is suggestive of cough-reflex hyperresponsiveness. Pathophysiological mechanisms underlying peripheral and central augmentation of the afferent cough pathways have been identified, and compelling evidence exists for a neuropathy of vagal sensory nerves after upper-respiratory viral infections or exposure to allergic and non-allergic irritants. In this Personal View, we argue that chronic cough is a neuropathic disorder that arises from neural damage caused by a range of inflammatory, infective, and allergic factors. In support of this idea, we discuss evidence of successful treatment of chronic cough with agents used for treatment of neuropathic pain, such as gabapentin and amitriptyline. Regarding cough as a neuropathic disorder could lead to new, more effective antitussives.

The Millennium child with autism: Early childhood trajectories for health, education and economic wellbeing

Objective: Most of what we know about children with autism spectrum disorder (ASD) is based on post-diagnostic, retrospective, self-select studies. Oftentimes, there is no direct comparison between trajectories of children with ASD and children without ASD.

Methods: To circumvent both of these problems, the present secondary data analysis utilised a large-scale longitudinal general population survey of children born in the year 2000 (i.e. the Millennium Cohort Study; MCS; n=18522). Bi-annual MCS data were available from five data sweeps (children aged 9 months to 11 years of age).

Results: Pre-diagnostic data showed early health problems differentiated children later diagnosed with autism from non-diagnosed peers. Prevalence was much higher than previously estimated (3.5% for 11-year olds). Post-diagnosis, trajectories deteriorated significantly for the children with ASD and their families in relation to education, health and economic wellbeing.

Conclusion: These findings raise many issues for service delivery and the rights of persons with disabilities and their families.

Three Types of Temporal Perspective: Characterizing Developmental Changes in Temporal Thought

This paper provides an outline of the development of temporal thinking that is underpinned by the idea that temporal cognition shifts from being event dependent to event independent over the preschool period. I distinguish between three different ways in which it may be possible to have a perspective on time: (1) a perspective that is grounded in script-like representations of repeated events; (2) a more sophisticated perspective that brings in an fundamental categorical distinction between events that have already happened and events that are yet to come; and (3) a mature temporal perspective that involves orienting oneself in time using a linear temporal framework, with a grasp of the distinctions between past, present, and future. I propose that, with development, children possess each of these types of perspective in turn, and that only the last of these involves being able to represent time in an event-independent way.

Autism and ABA: The gulf between North America and Europe

Prevalence estimations for Autism Spectrum Disorder have been increasing over the past few years with rates now reported to be at 1:68. Interventions that are based on Applied Behaviour Analysis are significantly related to best outcomes and are widely considered ‘treatment as usual’ in North America. In Europe, this is not the case, instead a rather ill-defined ‘eclectic’ approach is widely promoted and in this paper we discuss some of the roots of this gulf between Europe and North America and correct some of the misconceptions that prevail about Applied Behaviour Analysis in Europe.

Development tools for opportunistic pervasive computing

The goal of the POBICOS project is a platform that facilitates the development and deployment of pervasive computing applications destined for networked, cooperating objects. POBICOS object communities are heterogeneous in terms of the sensing, actuating, and computing resources contributed by each object. Moreover, it is assumed that an object community is formed without any master plan; for example, it may emerge as a by-product of acquiring everyday, POBICOS-enabled objects by a household. As a result, the target object community is, at least partially, unknown to the application programmer, and so a POBICOS application should be able to deliver its functionality on top of diverse object communities (we call this opportunistic computing). The POBICOS platform includes a middleware offering a programming model for opportunistic computing, as well as development and monitoring tools. This paper briefly describes the tools produced in the first phase of the project. Also, the stakeholders using these tools are identified, and a development process for both the middleware and applications is presented. © 2009 IEEE.

Tangible applications for regular objects:An end-user model for pervasive computing at home

This paper describes an end-user model for a domestic pervasive computing platform formed by regular home objects. The platform does not rely on pre-planned infrastructure; instead, it exploits objects that are already available in the home and exposes their joint sensing, actuating and computing capabilities to home automation applications. We advocate an incremental process of the platform formation and introduce tangible, object-like artifacts for representing important platform functions. One of those artifacts, the application pill, is a tiny object with a minimal user interface, used to carry the application, as well as to start and stop its execution and provide hints about its operational status. We also emphasize streamlining the user's interaction with the platform. The user engages any UI-capable object of his choice to configure applications, while applications issue notifications and alerts exploiting whichever available objects can be used for that purpose. Finally, the paper briefly describes an actual implementation of the presented end-user model. © (2010) by International Academy, Research, and Industry Association (IARIA).

Challenges of a Developmental Idea towards Sustainability

This paper attempts to situate and deconstruct the meanings associated with the term development in the context of the developing world. The arguments made highlights the deeply contested and fragmented terrain of development. The paper provides a historical overview of the changing nature of discourses on development, how the imageries of development have shifted since the postwar period. It deploys diverse meanings associated with development as a concept and as a theory. Thus development without dignity means little for those living in the margins of the society. At the same time the language of development has undergone revolutions and convulsions and the role of buzzwords and catch phrases have only helped to prolong misery in a neoliberal world. Development has become a 'one size fits all' concept shorn of cultural and regional specificities. It has been decontextualised and dehumanised to relate to targets
resulting in greater dissonance than resolution of aim and outcomes. The way forward is a better appreciation of the cultural capacity of the social groups for whom development is critical for survival. The conclusion highlights the endemic contradictions inherent in the meaning and delivery of development as a goal, especially when we seek to achieve resilient and sustainable development.

Keywords: Development, Neoliberalism, growth, participation, empowerment,
efficiency, market, state, societies, entitlements and capabilities, stakeholder, rights, structural adjustments, globalisation, self-help, doing development, freedom and
unfreedom.

FKBPL Is a Critical Antiangiogenic Regulator of Developmental and Pathological Angiogenesis

OBJECTIVE: The antitumor effects of FK506-binding protein like (FKBPL) and its extracellular role in angiogenesis are well characterized; however, its role in physiological/developmental angiogenesis and the effect of FKBPL ablation has not been evaluated. This is important as effects of some angiogenic proteins are dosage dependent. Here we evaluate the regulation of FKBPL secretion under angiogenic stimuli, as well as the effect of FKBPL ablation in angiogenesis using mouse and zebrafish models.

APPROACH AND RESULTS: FKBPL is secreted maximally by human microvascular endothelial cells and fibroblasts, and this was specifically downregulated by proangiogenic hypoxic signals, but not by the angiogenic cytokines, VEGF or IL8. FKBPL's critical role in angiogenesis was supported by our inability to generate an Fkbpl knockout mouse, with embryonic lethality occurring before E8.5. However, whilst Fkbpl heterozygotic embryos showed some vasculature irregularities, the mice developed normally. In murine angiogenesis models, including the ex vivo aortic ring assay, in vivo sponge assay, and tumor growth assay, Fkbpl(+/-) mice exhibited increased sprouting, enhanced vessel recruitment, and faster tumor growth, respectively, supporting the antiangiogenic function of FKBPL. In zebrafish, knockdown of zFkbpl using morpholinos disrupted the vasculature, and the phenotype was rescued with hFKBPL. Interestingly, this vessel disruption was ineffective when zcd44 was knocked-down, supporting the dependency of zFkbpl on zCd44 in zebrafish.

CONCLUSIONS: FKBPL is an important regulator of angiogenesis, having an essential role in murine and zebrafish blood vessel development. Mouse models of angiogenesis demonstrated a proangiogenic phenotype in Fkbpl heterozygotes.

An Informant Report Behavior Diary for Measuring Temper Outbursts in an Intervention Setting

Temper outbursts are associated with several psychological disorders and comprise a high priority for intervention. However, the low frequency of outbursts presents a challenge for valid measurement. In the present study an informant report behavior diary for measuring temper outbursts was developed and its validity assessed in a case series. Caregivers of 12 individuals with the neurodevelopmental disorder Prader-Willi syndrome (PWS, in which temper outbursts are common) completed a behavior diary over 4 weeks, and a structured interview. Heart rate and movement data were recorded during a sample of the days subject to diary reporting. Individuals with PWS completed self-report ratings of negative emotion experience. Behavior diaries showed high concordance with the component behaviors and duration of temper outbursts reported in structured interviews; but tended to report a lower frequency. For outbursts reported in diaries during physiological recording, heart rate was consistently elevated above a resting state baseline; and was comparable to that recorded during high physical activity. Available self-report data demonstrated correspondence with the diaries but few self-report data were produced. The present results provide critical proof of principle data supporting the concurrent validity of the ecologically valid, resource efficient diaries, which can be exploited in future research.