Mental healthcare utilisation by patients before and after receiving paliperidone palmitate treatment: mirror image analyses.

Objectives: To compare mental healthcare use and healthcare professional (HCP) contacts for patients before and after initiation of paliperidone palmitate.

Setting: The South London and Maudsley NHS Foundation Trust (SLAM) Biomedical Research Centre Clinical Record Interactive Search.

Participants: We identified all adults with a diagnosis of schizophrenia (International Classification of Diseases 10th Revision: F20.

A general principle of dendritic constancy: A neuron's size- and shape-invariant excitability.

Reducing neuronal size results in less membrane and therefore lower input conductance. Smaller neurons are thus more excitable, as seen in their responses to somatic current injections. However, the impact of a neuron's size and shape on its voltage responses to dendritic synaptic activation is much less understood.

Dendritic normalisation improves learning in sparsely connected artificial neural networks.

Artificial neural networks, taking inspiration from biological neurons, have become an invaluable tool for machine learning applications. Recent studies have developed techniques to effectively tune the connectivity of sparsely-connected artificial neural networks, which have the potential to be more computationally efficient than their fully-connected counterparts and more closely resemble the architectures of biological systems. We here present a normalisation, based on the biophysical behaviour of neuronal dendrites receiving distributed synaptic inputs, that divides the weight of an artificial neuron's afferent contacts by their number.

Risk of Recurrent Bleeding Events in Nonvalvular Atrial Fibrillation Treated with Vitamin K Antagonists: A Clinical Practice Research Datalink Study.

 There is little evidence on how the occurrence of a bleed in individuals on vitamin K antagonists (VKAs) impacts the risk of subsequent bleeds, and thromboembolic and ischemic events. Such information would help to inform treatment decisions following bleeds.  To estimate the impact of bleeding events on the risk of subsequent bleeds, venous thromboembolism (VTE), stroke, and myocardial infarction (MI) among patients initiating VKA treatment for new-onset nonvalvular atrial fibrillation (NVAF).

Model-Based Inference of Synaptic Transmission.

Synaptic computation is believed to underlie many forms of animal behavior. A correct identification of synaptic transmission properties is thus crucial for a better understanding of how the brain processes information, stores memories and learns. Recently, a number of new statistical methods for inferring synaptic transmission parameters have been introduced.

Dissecting Sholl Analysis into Its Functional Components.

Sholl analysis has been an important technique in dendritic anatomy for more than 60 years. The Sholl intersection profile is obtained by counting the number of dendritic branches at a given distance from the soma and is a key measure of dendritic complexity; it has applications from evaluating the changes in structure induced by pathologies to estimating the expected number of anatomical synaptic contacts. We find that the Sholl intersection profiles of most neurons can be reproduced from three basic, functional measures: the domain spanned by the dendritic arbor, the total length of the dendrite, and the angular distribution of how far dendritic segments deviate from a direct path to the soma (i.

Transmission of temporally correlated spike trains through synapses with short-term depression.

Short-term synaptic depression, caused by depletion of releasable neurotransmitter, modulates the strength of neuronal connections in a history-dependent manner. Quantifying the statistics of synaptic transmission requires stochastic models that link probabilistic neurotransmitter release with presynaptic spike-train statistics. Common approaches are to model the presynaptic spike train as either regular or a memory-less Poisson process: few analytical results are available that describe depressing synapses when the afferent spike train has more complex, temporally correlated statistics such as bursts.

Bayesian Inference of Synaptic Quantal Parameters from Correlated Vesicle Release.

Synaptic transmission is both history-dependent and stochastic, resulting in varying responses to presentations of the same presynaptic stimulus. This complicates attempts to infer synaptic parameters and has led to the proposal of a number of different strategies for their quantification. Recently Bayesian approaches have been applied to make more efficient use of the data collected in paired intracellular recordings.

Optimal Current Transfer in Dendrites.

Integration of synaptic currents across an extensive dendritic tree is a prerequisite for computation in the brain. Dendritic tapering away from the soma has been suggested to both equalise contributions from synapses at different locations and maximise the current transfer to the soma. To find out how this is achieved precisely, an analytical solution for the current transfer in dendrites with arbitrary taper is required.

Long-term plasticity determines the postsynaptic response to correlated afferents with multivesicular short-term synaptic depression.

Synchrony in a presynaptic population leads to correlations in vesicle occupancy at the active sites for neurotransmitter release. The number of independent release sites per presynaptic neuron, a synaptic parameter recently shown to be modified during long-term plasticity, will modulate these correlations and therefore have a significant effect on the firing rate of the postsynaptic neuron. To understand how correlations from synaptic dynamics and from presynaptic synchrony shape the postsynaptic response, we study a model of multiple release site short-term plasticity and derive exact results for the crosscorrelation function of vesicle occupancy and neurotransmitter release, as well as the postsynaptic voltage variance.

Systematic review, network meta-analysis and economic evaluation of biological therapy for the management of active psoriatic arthritis.

Background: An updated economic evaluation was conducted to compare the cost-effectiveness of the four tumour necrosis factor (TNF)-α inhibitors adalimumab, etanercept, golimumab and infliximab in active, progressive psoriatic arthritis (PsA) where response to standard treatment has been inadequate.

Methods: A systematic review was conducted to identify relevant, recently published studies and the new trial data were synthesised, via a Bayesian network meta-analysis (NMA), to estimate the relative efficacy of the TNF-α inhibitors in terms of Psoriatic Arthritis Response Criteria (PsARC) response, Health Assessment Questionnaire (HAQ) scores and Psoriasis Area and Severity Index (PASI). A previously developed economic model was updated with the new meta-analysis results and current cost data.

Systematic review and network meta-analysis of combination and monotherapy treatments in disease-modifying antirheumatic drug-experienced patients with rheumatoid arthritis: analysis of American College of Rheumatology criteria scores 20, 50, and 70.

Background: Biologic disease-modifying antirheumatic drugs (bDMARDs) extend the treatment choices for rheumatoid arthritis patients with suboptimal response or intolerance to conventional DMARDs. The objective of this systematic review and meta-analysis was to compare the relative efficacy of EU-licensed bDMARD combination therapy or monotherapy for patients intolerant of or contraindicated to continued methotrexate.

Methods: Comprehensive, structured literature searches were conducted in Medline, Embase, and the Cochrane Library, as well as hand-searching of conference proceedings and reference lists.

Topotecan for relapsed small cell lung cancer: a systematic review and economic evaluation.

Background: Topotecan is a relatively new drug for use as a second-line treatment in patients with relapsed small cell lung cancer (SCLC). We performed a systematic review and economic evaluation of topotecan, and consider it here in relation to the NICE end of life criteria.

Methods: Seventeen bibliographic databases (including Cochrane library, Medline and Embase) were searched from 1990 to February 2009, and experts and manufacturers were consulted, to identify relevant randomised controlled trials (RCTs) which were selected according to prospectively defined criteria.

The mammalian SPD-2 ortholog Cep192 regulates centrosome biogenesis.

Centrosomes are the major microtubule-organizing centers of mammalian cells. They are composed of a centriole pair and surrounding microtubule-nucleating material termed pericentriolar material (PCM). Bipolar mitotic spindle assembly relies on two intertwined processes: centriole duplication and centrosome maturation.