The shape of human gene family phylogenies

BACKGROUND: The shape of phylogenetic trees has been used to make inferences about the evolutionary process by comparing the shapes of actual phylogenies with those expected under simple models of the speciation process. Previous studies have focused on speciation events, but gene duplication is another lineage splitting event, analogous to speciation, and gene loss or deletion is analogous to extinction. Measures of the shape of gene family phylogenies can thus be used to investigate the processes of gene duplication and loss. We make the first systematic attempt to use tree shape to study gene duplication using human gene phylogenies. RESULTS: We find that gene duplication has produced gene family trees significantly less balanced than expected from a simple model of the process, and less balanced than species phylogenies: the opposite to what might be expected under the 2R hypothesis. CONCLUSION: While other explanations are plausible, we suggest that the greater imbalance of gene family trees than species trees is due to the prevalence of tandem duplications over regional duplications during the evolution of the human genome

An error-tuned model for sensorimotor learning

Current models of sensorimotor control posit that motor commands are generated by combining multiple modules which may consist of internal models, motor primitives or motor synergies. The mechanisms which select modules based on task requirements and modify their output during learning are therefore critical to our understanding of sensorimotor control. Here we develop a novel modular architecture for multi-dimensional tasks in which a set of fixed primitives are each able to compensate for errors in a single direction in the task space. The contribution of the primitives to the motor output is determined by both top-down contextual information and bottom- up error information. We implement this model for a task in which subjects learn to manipulate a dynamic object whose orientation can vary. In the model, visual information regarding the context (the orientation of the object) allows the appropriate primitives to be engaged. This top-down module selection is implemented by a Gaussian function tuned for the visual orientation of the object. Second, each module's contribution adapts across trials in proportion to its ability to decrease the current kinematic error. Specifically, adaptation is implemented by cosine tuning of primitives to the current direction of the error, which we show to be theoretically optimal for reducing error. This error-tuned model makes two novel predictions. First, interference should occur between alternating dynamics only when the kinematic errors associated with each oppose one another. In contrast, dynamics which lead to orthogonal errors should not interfere. Second, kinematic errors alone should be sufficient to engage the appropriate modules, even in the absence of contextual information normally provided by vision. We confirm both these predictions experimentally and show that the model can also account for data from previous experiments. Our results suggest that two interacting processes account for module selection during sensorimotor control and learning.This work was financially supported by the Wellcome Trust (to DMW; WT097803MA, http://www.wellcome.ac.uk), the Royal Society Noreen Murray Professorship in Neurobiology (to DMW; https://royalsociety.org), Natural Sciences and Engineering Research Council of Canada (to JRF; RGPIN/04837, http://www.nserc.ca), the Canadian Institutes of Health Research (to JRF; 82837, http://www.cihr.ca). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The impact of cochlear implantation on phonological awareness in deaf children.

In recent years, it has been reported that cochlear implantation (CI) benefits deaf children's speech perception, language development and speech production. Early fitting of an implant results in improved outcomes. This thesis explores the development and determinants of phonological awareness (PA) in paediatric Cl users. Phonological awareness is important for literacy acquisition in hearing children. In hearing children phonological awareness develops first at the syllable level then at the intra-syllabic level of onset-rime and finally at the phoneme level. It is expected that paediatric Cl users will follow the same developmental trajectory. The impact of the timing of cochlear implant fitting on phonological awareness and the relationship between phonological awareness and word reading are also investigated. Three new tests of phonological awareness were developed for the thesis. Nineteen children with implants were seen twice over a 12 month period. Nine of these children were fitted with their implant early (below 3.6 years) and ten were fitted later (between 5 and 7 years). Several comparison groups were included; a group of profoundly deaf children with hearing aids, a group of severely deaf children, a group of hearing children with specific language impairment and two groups of typically developing hearing children. One hearing group was matched for reading level and the other group was matched for chronological age to the Cl group. Phonological awareness in Cl users developed along a similar trajectory to hearing children. Syllable awareness was equivalent in the Cl group to both groups of hearing children, awareness of rhyme and phonemes was significantly delayed, but was equivalent to the profoundly deaf children using hearing aids. The difference between the early and late Cl groups on PA performance was small. There was some evidence of a link between PA and word reading, but overall, receptive vocabulary emerged as the most robust longitudinal predictor of reading ability in deaf children

The Real Combination Problem : Panpsychism, Micro-Subjects, and Emergence

Panpsychism harbors an unresolved tension, the seriousness of which has yet to be fully appreciated. I capture this tension as a dilemma, and offer panpsychists advice on how to resolve it. The dilemma, briefly, is as follows. Panpsychists are committed to the perspicuous explanation of macro-mentality in terms of micro-mentality. But panpsychists take the micro-material realm to feature not just mental properties, but also micro-subjects to whom these properties belong. Yet it is impossible to explain the constitution of a macro-subject (like one of us) in terms of the assembly of micro-subjects, for, I show, subjects cannot combine. Therefore the panpsychist explanatory project is derailed by the insistence that the world’s ultimate material constituents (ultimates) are subjects of experience. The panpsychist faces a choice of abandoning her explanatory project, or recanting the claim that the ultimates are subjects. This is the dilemma. I argue that the latter option is to be preferred. This needn’t constitute a wholesale abandonment of panpsychism, however, since panpsychists can maintain that the ultimates possess phenomenal qualities, despite not being subjects of those qualities. This proposal requires us to make sense of phenomenal qualities existing independently of experiencing subjects, a challenge I tackle in the penultimate section. The position eventually reached is a form of neutral monism, so another way to express the overall argument is to say that, keeping true to their philosophical motivations, panpsychists should really be neutral monists.Peer reviewedFinal Accepted Versio

Quality determination and the repair of poor quality spots in array experiments.

BACKGROUND: A common feature of microarray experiments is the occurrence of missing gene expression data. These missing values occur for a variety of reasons, in particular, because of the filtering of poor quality spots and the removal of undefined values when a logarithmic transformation is applied to negative background-corrected intensities. The efficiency and power of an analysis performed can be substantially reduced by having an incomplete matrix of gene intensities. Additionally, most statistical methods require a complete intensity matrix. Furthermore, biases may be introduced into analyses through missing information on some genes. Thus methods for appropriately replacing (imputing) missing data and/or weighting poor quality spots are required. RESULTS: We present a likelihood-based method for imputing missing data or weighting poor quality spots that requires a number of biological or technical replicates. This likelihood-based approach assumes that the data for a given spot arising from each channel of a two-dye (two-channel) cDNA microarray comparison experiment independently come from a three-component mixture distribution--the parameters of which are estimated through use of a constrained E-M algorithm. Posterior probabilities of belonging to each component of the mixture distributions are calculated and used to decide whether imputation is required. These posterior probabilities may also be used to construct quality weights that can down-weight poor quality spots in any analysis performed afterwards. The approach is illustrated using data obtained from an experiment to observe gene expression changes with 24 hr paclitaxel (Taxol) treatment on a human cervical cancer derived cell line (HeLa). CONCLUSION: As the quality of microarray experiments affect downstream processes, it is important to have a reliable and automatic method of identifying poor quality spots and arrays. We propose a method of identifying poor quality spots, and suggest a method of repairing the arrays by either imputation or assigning quality weights to the spots. This repaired data set would be less biased and can be analysed using any of the appropriate statistical methods found in the microarray literature.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Personhood, consciousness, and god : how to be a proper pantheist

© Springer Nature B.V. 2018In this paper I develop a theory of personhood which leaves open the possibility of construing the universe as a person. If successful, it removes one bar to endorsing pantheism. I do this by examining a rising school of thought on personhood, on which persons, or selves, are understood as identical to episodes of consciousness. Through a critique of this experiential approach to personhood, I develop a theory of self as constituted of qualitative mental contents, but where these contents are also capable of unconscious existence. On this theory, though we can be conscious of our selves, consciousness turns out to be inessential to personhood. This move, I then argue, provides resources for responding to the pantheist’s problem of God’s person.Peer reviewedFinal Accepted Versio

The Brighton declaration: the value of non-communicable disease modelling in population health sciences.

The Brighton declaration arose out of a one day workshop held in Brighton in September 2013 as part of the Society for Social Medicine annual conference. The workshop convened UK based non-communicable disease modellers to discuss the challenges and opportunities for non-communicable disease modelling in the UK. The declaration describes the value and importance of non-communicable disease modelling, both for research and for informing health policy. The declaration also describes challenges and issues for non-communicable disease modelling. The declaration has been endorsed by many non-communicable disease modellers in the UK.The following academics collaborated with the authors to finalise this article are and acknowledged as co-signatories on its content. The authors are extremely grateful for their input. University of Cambridge: Ali Abbas, Marko Tanio; University of Edinburgh: Dr Susannah McLean; UK Health Forum: Martin Brown, Tim Marsh, Marco Mesa-Frias, Lise Retat; Imperial College London: Anthony Laverty; The London School of Hygiene and Tropical Medicine: Zaid Chalabi; University College London: Luz Sanchez Romero; University of Oxford: Anja Mizdrak, Mike Rayner, Marco Springmann; University of Sheffield: Alan Brennan, James Chilcott, John Holmes, Petra Meier, John Mooney; University of Southampton: Grant Aitken. ADMB and OTM are funded by the Wellcome Trust. PS is funded by the British Heart Foundation. JW is funded by an MRC Population Health Scientist Fellowship.This is the final published version. The article was originally published in the European Journal of Epidemiology (2014) 29, 867–870, DOI 10.1007/s10654-014-9978-0

Challenging behaviour around challenging behaviour

Introduction: The United Kingdom's Department for Education's advice on behaviour focuses on the power of staff and the strength of the policy in challenging behaviour, via rules, sanctions and rewards. We designed a video-feedback intervention for staff teams in a special educational setting who were working with children with intellectual disability and challenging behaviour. The intervention aimed to raise reflective capacity on relational mechanisms that offer new response possibilities in everyday practices within trans-disciplinary teams. Method: We conducted research with three teams (between five and seven participants in each). We report findings from two teams who were working with children (aged between 10 and 14) who staff identified as having behaviour that challenged. The intervention consisted of two video-feedback intervention sessions, using clips of good interactions between themselves and the child and a review. These sessions took place over three or four months. Qualitative analysis was conducted to analyse changes to the language and depictions of the children. Changes to the participants’ goals during the intervention were also analysed. Results: The staff's focus on the child's challenging behaviour reduced. Children who were originally depicted as isolated became depicted in relationship with peers and staff. Participants became more curious about the child and his interactions in the school and home environment. The participant's personal goals emerged through their understandings of what it meant to be good. Conclusions: Working with staff teams using video feedback can change the interactions around the child and the relational conceptualisation of the child and family. Further adaptations to the intervention are needed to raise critical reflection on the concepts that circulate around ‘behaviour’ that structure policy and shape everyday practices

Resource use data by patient report or hospital records: Do they agree?

Background: Economic evaluations alongside clinical trials are becoming increasingly common. Cost data are often collected through the use of postal questionnaires; however, the accuracy of this method is uncertain. We compared postal questionnaires with hospital records for collecting data on physiotherapy service use. Methods: As part of a randomised trial of orthopaedic medicine compared with orthopaedic surgery we collected physiotherapy use data on a group of patients from retrospective postal questionnaires and from hospital records. Results: 315 patients were referred for physiotherapy. Hospital data on attendances was available for 30% (n = 96), compared with 48% (n = 150) of patients completing questionnaire data (95% Cl for difference = 10% to 24%); 19% (n = 59) had data available from both sources. The two methods produced an intraclass correlation coefficient of 0.54 (95% Cl 0.31 to 0.70). However, the two methods produced significantly different estimates of resource use with patient self report recalling a mean of 1.3 extra visits (95% Cl 0.4 to 2.2) compared with hospital records. Conclusions: Using questionnaires in this study produced data on a greater number of patients compared with examination of hospital records. However, the two data sources did differ in the quantity of physiotherapy used and this should be taken into account in any analysi