3,484 research outputs found
Inferring the perturbation time from biological time course data.
MOTIVATION: Time course data are often used to study the changes to a biological process after perturbation. Statistical methods have been developed to determine whether such a perturbation induces changes over time, e.g. comparing a perturbed and unperturbed time course dataset to uncover differences. However, existing methods do not provide a principled statistical approach to identify the specific time when the two time course datasets first begin to diverge after a perturbation; we call this the perturbation time. Estimation of the perturbation time for different variables in a biological process allows us to identify the sequence of events following a perturbation and therefore provides valuable insights into likely causal relationships. RESULTS: We propose a Bayesian method to infer the perturbation time given time course data from a wild-type and perturbed system. We use a non-parametric approach based on Gaussian Process regression. We derive a probabilistic model of noise-corrupted and replicated time course data coming from the same profile before the perturbation time and diverging after the perturbation time. The likelihood function can be worked out exactly for this model and the posterior distribution of the perturbation time is obtained by a simple histogram approach, without recourse to complex approximate inference algorithms. We validate the method on simulated data and apply it to study the transcriptional change occurring in Arabidopsis following inoculation with Pseudomonas syringae pv. tomato DC3000 versus the disarmed strain DC3000hrpA AVAILABILITY AND IMPLEMENTATION: : An R package, DEtime, implementing the method is available at https://github.com/ManchesterBioinference/DEtime along with the data and code required to reproduce all the results. CONTACT: [email protected] or [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online
Multivariate analysis of morphological variation in enset (Ensete ventricosum (Welw.) Cheesman) reveals regional and clinal variation in germplasm from south and south western Ethiopia
Enset (Ensete ventricosum (Welw.) Cheesman) is cultivated by millions of people across Ethiopia in diverse agro-ecological and cultural settings, selecting for various agronomic traits. However, as for other underutilized crops, our understanding of the diversity and utilization of enset remains limited. This work sought to redress this limitation by estimating morphological diversity among enset accessions collected from major enset growing regions, including across altitudinal gradients. In total, landraces comprising 387 accessions originating from nine regions of Ethiopia were characterized using multivariate analysis of 15 quantitative traits. Cluster analysis grouped accessions in to five distinct classes with maximum number of accessions 338 in cluster (I) and minimum 1 in cluster (V). The clustering of accessions did not show grouping on the basis of region of origin. The first four principal components accounted for ~74% of the total variance. Linear discriminant analysis indicated that around 40.8% (160 accessions) and 45.2% (175 accession) of the studied accessions were correctly classified to their respective regions of origin altitude groups, respectively. The breadth of phenotypic differences in these 15 traits suggests significant degrees of genetic variation. These traits will be exploited to identify potential donors for future enset improvement efforts
An olfactory \u27stress test\u27 may detect preclinical Alzheimer\u27s disease
Background: The olfactory bulb (OB) receives extensive cholinergic input from the basal forebrain and is affected very early in Alzheimer’s disease (AD). We speculated that an olfactory ‘stress test’ (OST), targeting the OB, might be used to unmask incipient AD. We investigated if change in olfactory performance following intranasal atropine was associated with several known antecedents or biomarkers of AD. Methods: We measured change in performance on the University of Pennsylvania Smell Identification Test (UPSIT) in the left nostril before (20-items) and after (remaining 20-items) intranasal administration of 1 mg of atropine. We administered cognitive tests, measured hippocampal volume from MRI scans and recorded Apolipoprotein E genotype as indices relevant to underlying AD. Results: In a convenience sample of 56 elderly individuals (14 probable AD, 13 cognitive impairment no dementia, 29 cognitively intact) the change in UPSIT score after atropine (‘atropine effect’ = AE) correlated significantly with demographically scaled episodic memory score (r = 0.57,
Palliative care making a difference in rural Uganda, Kenya and Malawi: three rapid evaluation field studies
<p>Abstract</p> <p>Background</p> <p>Many people live and die in pain in Africa. We set out to describe patient, family and local community perspectives on the impact of three community based palliative care interventions in sub-Saharan Africa.</p> <p>Methods</p> <p>Three palliative care programmes in Uganda, Kenya and Malawi were studied using rapid evaluation field techniques in each country, triangulating data from three sources: <b><it>interviews </it></b>with key informants, <b><it>observations </it></b>of clinical encounters and the local health and social care context, and routine data from local <b><it>reports and statistics</it></b>.</p> <p>Results</p> <p>We interviewed 33 patients with advanced illness, 27 family carers, 36 staff, 25 volunteers, and 29 community leaders and observed clinical care of 12 patients. In each site, oral morphine was being used effectively. Patients valued being treated with dignity and respect. Being supported at home reduced physical, emotional and financial burden of travel to, and care at health facilities. Practical support and instruction in feeding and bathing patients facilitated good deaths at home.</p> <p>In each country mobile phones enabled rapid access to clinical and social support networks. Staff and volunteers generally reported that caring for the dying in the face of poverty was stressful, but also rewarding, with resilience fostered by having effective analgesia, and community support networks.</p> <p>Conclusions</p> <p>Programmes were reported to be successful because they integrated symptom control with practical and emotional care, education, and spiritual care. Holistic palliative care can be delivered effectively in the face of poverty, but a public health approach is needed to ensure equitable provision.</p
Draft genome sequences of seven isolates of Phytophthora ramorum EU2 from Northern Ireland
Here we present draft-quality genome sequence assemblies for the oomycete Phytophthora ramorum genetic lineage EU2. We sequenced genomes of seven isolates collected in Northern Ireland between 2010 and 2012. Multiple genome sequences from P. ramorum EU2 will be valuable for identifying genetic variation within the clonal lineage that can be useful for tracking its spread
BSA Practice guidance: an overview of current management of auditory processing disorder (APD)
The Knee Arthroplasty Trial (KAT) : design features, baseline characteristics and two-year functional outcomes after alternative approaches to knee replacement
Background: The aim of continued development of total knee replacement systems has been the further improvement of the quality of life and increasing the duration of prosthetic survival. Our goal was to evaluate the effects of several design features, including metal backing of the tibial component, patellar resurfacing, and a mobile bearing between the tibial and femoral components, on the function and survival of the implant. Methods: A pragmatic, multicenter, randomized, controlled trial involving 116 surgeons in thirty-four centers in the United Kingdom was performed; 2352 participants were randomly allocated to be treated with or without a metal backing of the tibial component (409), with or without patellar resurfacing (1715), and/or with or without a mobile bearing (539). Randomization to more than one comparison was allowed. The primary outcome measures were the Oxford Knee Score (OKS), Short Form-12, EuroQol-5D, and the need for additional surgery. The results up to two years postoperatively are reported. Results: Functional status and quality-of-life scores were low at baseline but improved markedly across all trial groups following knee replacement (mean overall OKS, 17.98 points at baseline and 34.82 points at two years). Most of the change was observed at three months after the surgery. Six percent of the patients had additional knee surgery within two years. There was no evidence of differences in clinical, functional, or quality-of-life measures between the randomized groups at two years. Conclusions: Patients have substantial improvement following total knee replacement. This is the first adequately powered randomized controlled trial, of which we are aware, in which the effects of metal backing, patellar resurfacing, and a mobile bearing were investigated. We found no evidence of an effect of these variants on the rate of early complications or on functional recovery up to two years after total knee replacement. Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.NIHR Health Technology Assessment Programme (Project Number 95/10/01); Howmedica Osteonics; Zimmer; DePuy, a Johnson and Johnson company; Corin Medical; Smith and Nephew Healthcare. Biomet Merck; and Wright CremascoliPeer reviewe
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