Crowd sourcing of public transport problems

Social sites on the World Wide Web allow increased sharing of ideas and problems. Such online networking includes the ability to report public transport problems and get support for campaigns to improve specific aspects of public transport. One site that offers such a facility provided access to its data on problems that were reported over a 13 month period. These were assessed and comparisons were made to see if those campaigns that got the most support were inherently different to the campaigns that received little support, and to investigate the types of problems that were reported online. Whilst definitive answers cannot be given, there are some suggestions that come out of the analysis and the overall impact on improving public transport accessibility and usability is discussed

Astrocytes modulate thalamic sensory processing via mGlu2 receptor activation.

Astrocytes possess many of the same signalling molecules as neurons. However, the role of astrocytes in information processing, if any, is unknown. Using electrophysiological and imaging methods, we report the first evidence that astrocytes modulate neuronal sensory inhibition in the rodent thalamus. We found that mGlu2 receptor activity reduces inhibitory transmission from the thalamic reticular nucleus to the somatosensory ventrobasal thalamus (VB): mIPSC frequencies in VB slices were reduced by the Group II mGlu receptor agonist LY354740, an effect potentiated by mGlu2 positive allosteric modulator (PAM) LY487379 co-application (30 nM LY354740: 10.0 ± 1.6% reduction; 30 nM LY354740 & 30 μM LY487379: 34.6 ± 5.2% reduction). We then showed activation of mGlu2 receptors on astrocytes: astrocytic intracellular calcium levels were elevated by the Group II agonist, which were further potentiated upon mGlu2 PAM co-application (300 nM LY354740: ratio amplitude 0.016 ± 0.002; 300 nM LY354740 & 30 μM LY487379: ratio amplitude 0.035 ± 0.003). We then demonstrated mGlu2-dependent astrocytic disinhibition of VB neurons in vivo: VB neuronal responses to vibrissae stimulation trains were disinhibited by the Group II agonist and the mGlu2 PAM (LY354740: 156 ± 12% of control; LY487379: 144 ± 10% of control). Presence of the glial inhibitor fluorocitrate abolished the mGlu2 PAM effect (91 ± 5% of control), suggesting the mGlu2 component to the Group II effect can be attributed to activation of mGlu2 receptors localised on astrocytic processes within the VB. Gating of thalamocortical function via astrocyte activation represents a novel sensory processing mechanism. As this thalamocortical circuitry is important in discriminative processes, this demonstrates the importance of astrocytes in synaptic processes underlying attention and cognition

Seasonality of primary care utilization for respiratory diseases in Ontario: A time-series analysis

<p>Abstract</p> <p>Background</p> <p>Respiratory diseases represent a significant burden in primary care. Determining the temporal variation of the overall burden of respiratory diseases on the health care system and their potential causes are keys to understanding disease dynamics in populations and can contribute to the rational management of health care resources.</p> <p>Methods</p> <p>A retrospective, cross-sectional time series analysis was used to assess the presence and strength of seasonal and temporal patterns in primary care visits for respiratory diseases in Ontario, Canada, for a 10-year period from January 1, 1992 to December 31, 2002. Data were extracted from the Ontario Health Insurance Plan database for people who had diagnosis codes for chronic obstructive pulmonary disease, asthma, pneumonia, or upper respiratory tract infections.</p> <p>Results</p> <p>The results illustrate a clear seasonal pattern in visits to primary care physicians for all respiratory conditions, with a threefold increase in visits during the winter. Age and sex-specific rates show marked increases in visits of young children and in female adults. Multivariate time series methods quantified the interactions among primary care visits, and Granger causality criterion test showed that the respiratory syncytial virus (RSV) and influenza virus influenced asthma (p = 0.0060), COPD (p = 0.0038), pneumonia (p = 0.0001), and respiratory diseases (p = 0.0001).</p> <p>Conclusion</p> <p>Primary care visits for respiratory diseases have clear predictable seasonal patterns, driven primarily by viral circulations. Winter visits are threefold higher than summer troughs, indicating a short-term surge on primary health service demands. These findings can aid in effective allocation of resources and services based on seasonal and specific population demands.</p

Sustainability, Peak oil

none4openDe leo Federica, Pier paolo Miglietta, Stefania Massari, Marcello RubertiDE LEO, Federica; Miglietta, PIER PAOLO; Massari, Stefania; Ruberti, Marcell

Understanding innovators' experiences of barriers and facilitators in implementation and diffusion of healthcare service innovations: A qualitative study

This article is made available through the Brunel Open Access Publishing Fund - Copyright @ 2011 Barnett et al.Background: Healthcare service innovations are considered to play a pivotal role in improving organisational efficiency and responding effectively to healthcare needs. Nevertheless, healthcare organisations encounter major difficulties in sustaining and diffusing innovations, especially those which concern the organisation and delivery of healthcare services. The purpose of the present study was to explore how healthcare innovators of process-based initiatives perceived and made sense of factors that either facilitated or obstructed the innovation implementation and diffusion. Methods: A qualitative study was designed. Fifteen primary and secondary healthcare organisations in the UK, which had received health service awards for successfully generating and implementing service innovations, were studied. In-depth, semi structured interviews were conducted with the organisational representatives who conceived and led the development process. The data were recorded, transcribed and thematically analysed. Results: Four main themes were identified in the analysis of the data: the role of evidence, the function of inter-organisational partnerships, the influence of human-based resources, and the impact of contextual factors. "Hard" evidence operated as a proof of effectiveness, a means of dissemination and a pre-requisite for the initiation of innovation. Inter-organisational partnerships and people-based resources, such as champions, were considered an integral part of the process of developing, establishing and diffusing the innovations. Finally, contextual influences, both intra-organisational and extra-organisational were seen as critical in either impeding or facilitating innovators' efforts. Conclusions: A range of factors of different combinations and co-occurrence were pointed out by the innovators as they were reflecting on their experiences of implementing, stabilising and diffusing novel service initiatives. Even though the innovations studied were of various contents and originated from diverse organisational contexts, innovators' accounts converged to the significant role of the evidential base of success, the inter-personal and inter-organisational networks, and the inner and outer context. The innovators, operating themselves as important champions and being often willing to lead constructive efforts of implementation to different contexts, can contribute to the promulgation and spread of the novelties significantly.This research was supported financially by the Multidisciplinary Assessment of Technology Centre for Healthcare (MATCH)

Dendritic Spike Saturation of Endogenous Calcium Buffer and Induction of Postsynaptic Cerebellar LTP

The architecture of parallel fiber axons contacting cerebellar Purkinje neurons retains spatial information over long distances. Parallel fiber synapses can trigger local dendritic calcium spikes, but whether and how this calcium signal leads to plastic changes that decode the parallel fiber input organization is unknown. By combining voltage and calcium imaging, we show that calcium signals, elicited by parallel fiber stimulation and mediated by voltage-gated calcium channels, increase non-linearly during high-frequency bursts of electrically constant calcium spikes, because they locally and transiently saturate the endogenous buffer. We demonstrate that these non-linear calcium signals, independently of NMDA or metabotropic glutamate receptor activation, can induce parallel fiber long-term potentiation. Two-photon imaging in coronal slices revealed that calcium signals inducing long-term potentiation can be observed by stimulating either the parallel fiber or the ascending fiber pathway. We propose that local dendritic calcium spikes, evoked by synaptic potentials, provide a unique mechanism to spatially decode parallel fiber signals into cerebellar circuitry changes

A requirement for astrocyte IP3R2 signaling for whisker experience-dependent depression and homeostatic upregulation in the mouse barrel cortex.

Changes to sensory experience result in plasticity of synapses in the cortex. This experience-dependent plasticity (EDP) is a fundamental property of the brain. Yet, while much is known about neuronal roles in EDP, very little is known about the role of astrocytes. To address this issue, we used the well-described mouse whiskers-to-barrel cortex system, which expresses a number of forms of EDP. We found that all-whisker deprivation induced characteristic experience-dependent Hebbian depression (EDHD) followed by homeostatic upregulation in L2/3 barrel cortex of wild type mice. However, these changes were not seen in mutant animals (IP3R2-/-) that lack the astrocyte-expressed IP3 receptor subtype. A separate paradigm, the single-whisker experience, induced potentiation of whisker-induced response in both wild-type (WT) mice and IP3R2-/- mice. Recordings in ex vivo barrel cortex slices reflected the in vivo results so that long-term depression (LTD) could not be elicited in slices from IP3R2-/- mice, but long-term potentiation (LTP) could. Interestingly, 1 Hz stimulation inducing LTD in WT paradoxically resulted in NMDAR-dependent LTP in slices from IP3R2-/- animals. The LTD to LTP switch was mimicked by acute buffering astrocytic [Ca2+] i in WT slices. Both WT LTD and IP3R2-/- 1 Hz LTP were mediated by non-ionotropic NMDAR signaling, but only WT LTD was P38 MAPK dependent, indicating an underlying mechanistic switch. These results demonstrate a critical role for astrocytic [Ca2+] i in several EDP mechanisms in neocortex

Glucanocellulosic ethanol: The undiscovered biofuel potential in energy crops and marine biomass

Converting biomass to biofuels is a key strategy in substituting fossil fuels to mitigate climate change. Conventional strategies to convert lignocellulosic biomass to ethanol address the fermentation of cellulose-derived glucose. Here we used super-resolution fluorescence microscopy to uncover the nanoscale structure of cell walls in the energy crops maize and Miscanthus where the typical polymer cellulose forms an unconventional layered architecture with the atypical (1, 3)-β-glucan polymer callose. This raised the question about an unused potential of (1, 3)-β-glucan in the fermentation of lignocellulosic biomass. Engineering biomass conversion for optimized (1, 3)-β-glucan utilization, we increased the ethanol yield from both energy crops. The generation of transgenic Miscanthus lines with an elevated (1, 3)-β-glucan content further increased ethanol yield providing a new strategy in energy crop breeding. Applying the (1, 3)-β-glucan-optimized conversion method on marine biomass from brown macroalgae with a naturally high (1, 3)-β-glucan content, we not only substantially increased ethanol yield but also demonstrated an effective co-fermentation of plant and marine biomass. This opens new perspectives in combining different kinds of feedstock for sustainable and efficient biofuel production, especially in coastal regions

GAD1 mRNA Expression and DNA Methylation in Prefrontal Cortex of Subjects with Schizophrenia

Dysfunction of prefrontal cortex in schizophrenia includes changes in GABAergic mRNAs, including decreased expression of GAD1, encoding the 67 kDa glutamate decarboxylase (GAD67) GABA synthesis enzyme. The underlying molecular mechanisms remain unclear. Alterations in DNA methylation as an epigenetic regulator of gene expression are thought to play a role but this hypothesis is difficult to test because no techniques are available to extract DNA from GAD1 expressing neurons efficiently from human postmortem brain. Here, we present an alternative approach that is based on immunoprecipitation of mononucleosomes with anti-methyl-histone antibodies differentiating between sites of potential gene expression as opposed to repressive or silenced chromatin. Methylation patterns of CpG dinucleotides at the GAD1 proximal promoter and intron 2 were determined for each of the two chromatin fractions separately, using a case-control design for 14 schizophrenia subjects affected by a decrease in prefrontal GAD1 mRNA levels. In controls, the methylation frequencies at CpG dinucleotides, while overall higher in repressive as compared to open chromatin, did not exceed 5% at the proximal GAD1 promoter and 30% within intron 2. Subjects with schizophrenia showed a significant, on average 8-fold deficit in repressive chromatin-associated DNA methylation at the promoter. These results suggest that chromatin remodeling mechanisms are involved in dysregulated GABAergic gene expression in schizophrenia

Visualizing the Distribution of Synapses from Individual Neurons in the Mouse Brain

BACKGROUND:Proper function of the mammalian brain relies on the establishment of highly specific synaptic connections among billions of neurons. To understand how complex neural circuits function, it is crucial to precisely describe neuronal connectivity and the distributions of synapses to and from individual neurons. METHODS AND FINDINGS:In this study, we present a new genetic synaptic labeling method that relies on expression of a presynaptic marker, synaptophysin-GFP (Syp-GFP) in individual neurons in vivo. We assess the reliability of this method and use it to analyze the spatial patterning of synapses in developing and mature cerebellar granule cells (GCs). In immature GCs, Syp-GFP is distributed in both axonal and dendritic regions. Upon maturation, it becomes strongly enriched in axons. In mature GCs, we analyzed synapses along their ascending segments and parallel fibers. We observe no differences in presynaptic distribution between GCs born at different developmental time points and thus having varied depths of projections in the molecular layer. We found that the mean densities of synapses along the parallel fiber and the ascending segment above the Purkinje cell (PC) layer are statistically indistinguishable, and higher than previous estimates. Interestingly, presynaptic terminals were also found in the ascending segments of GCs below and within the PC layer, with the mean densities two-fold lower than that above the PC layer. The difference in the density of synapses in these parts of the ascending segment likely reflects the regional differences in postsynaptic target cells of GCs. CONCLUSIONS:The ability to visualize synapses of single neurons in vivo is valuable for studying synaptogenesis and synaptic plasticity within individual neurons as well as information flow in neural circuits