Associative memory in gene regulation networks

The pattern of gene expression in the phenotype of an organism is determined in part by the dynamical attractors of the organism’s gene regulation network. Changes to the connections in this network over evolutionary time alter the adult gene expression pattern and hence the fitness of the organism. However, the evolution of structure in gene expression networks (potentially reflecting past selective environments) and its affordances and limitations with respect to enhancing evolvability is poorly understood in general. In this paper we model the evolution of a gene regulation network in a controlled scenario. We show that selected changes to connections in the regulation network make the currently selected gene expression pattern more robust to environmental variation. Moreover, such changes to connections are necessarily ‘Hebbian’ – ‘genes that fire together wire together’ – i.e. genes whose expression is selected for in the same selective environments become co-regulated. Accordingly, in a manner formally equivalent to well-understood learning behaviour in artificial neural networks, a gene expression network will therefore develop a generalised associative memory of past selected phenotypes. This theoretical framework helps us to better understand the relationship between homeostasis and evolvability (i.e. selection to reduce variability facilitates structured variability), and shows that, in principle, a gene regulation network has the potential to develop ‘recall’ capabilities normally reserved for cognitive systems

Effect Sizes for Single Word Recognition Across Adults and Children:A Meta-Analysis

Theories explaining skilled and disordered reading are based on observations about the effects of psycholinguistic variables on word naming and lexical decision performance. My interest is in reading processes in adolescents and adults who, in the absence of diagnosed organic difficulties, still struggle to attain skilled reading. In thinking about these learners, knowledge of which predictors inhibit or facilitate strong performance, and their relative importance with each other, may shape teaching practices or resources, so it's important that we have robust estimates upon which to base teaching decisions. As a baseline from which to measure this group's performance in future studies, I embarked upon a meta-analysis of the psycholinguistic research literature that studies contrasting groups and their performance in word naming and lexical decision task

Adaptation without natural selection

Document is itself an extended abstract

Treatment Outcomes of Treatment-Naïve Hepatitis C Patients co-infected with HIV: a systematic review and meta-analysis of observational cohorts

Co-infection with Hepatitis C (HCV) and HIV is common and HIV accelerates hepatic disease progression due to HCV. However, access to HCV treatment is limited and success rates are generally poor

If you can't be with the one you love, love the one you're with: How individual habituation of agent interactions improves global utility

Simple distributed strategies that modify the behaviour of selfish individuals in a manner that enhances cooperation or global efficiency have proved difficult to identify. We consider a network of selfish agents who each optimise their individual utilities by coordinating (or anti-coordinating) with their neighbours, to maximise the pay-offs from randomly weighted pair-wise games. In general, agents will opt for the behaviour that is the best compromise (for them) of the many conflicting constraints created by their neighbours, but the attractors of the system as a whole will not maximise total utility. We then consider agents that act as 'creatures of habit' by increasing their preference to coordinate (anti-coordinate) with whichever neighbours they are coordinated (anti-coordinated) with at the present moment. These preferences change slowly while the system is repeatedly perturbed such that it settles to many different local attractors. We find that under these conditions, with each perturbation there is a progressively higher chance of the system settling to a configuration with high total utility. Eventually, only one attractor remains, and that attractor is very likely to maximise (or almost maximise) global utility. This counterintutitve result can be understood using theory from computational neuroscience; we show that this simple form of habituation is equivalent to Hebbian learning, and the improved optimisation of global utility that is observed results from wellknown generalisation capabilities of associative memory acting at the network scale. This causes the system of selfish agents, each acting individually but habitually, to collectively identify configurations that maximise total utility

Perceived barriers to randomised controlled trials in breast reconstruction:obstacle to trial initiation or opportunity to resolve? A qualitative study

Background: Implant-based breast reconstruction (IBBR) is the most commonly performed breast reconstruction technique worldwide but the technique is evolving rapidly. High-quality evidence is needed to support practice. Randomised controlled trials (RCTs) provide the best evidence but can be challenging to conduct. iBRA is a four-phased study which aimed to inform the feasibility, design and conduct of an RCT in IBBR. In phase 3, the randomisation acceptability study, an electronic survey and qualitative interviews were conducted to explore professionals’ perceptions of future trials in IBBR. Findings from the interviews are presented here. Methods: Semi-structured qualitative interviews were undertaken with a purposive sample of 31 health professionals (HPs) who completed the survey to explore their attitudes to the feasibility of potential RCTs in more detail. All interviews were transcribed verbatim and data were analysed thematically using constant comparative techniques. Sampling, data collection and analysis were undertaken iteratively and concurrently until data saturation was achieved. Results: Almost all HPs acknowledged the need for better evidence to support the practice of IBBR and most identified RCTs as generating the highest-quality evidence. Despite highlighting potential challenges, most participants supported the need for an RCT in IBBR. A minority, however, were strongly opposed to a future trial. The opposition and challenges identified centred around three key themes; (i) limited understanding of pragmatic study design and the value of randomisation in minimising bias; (ii) clinician and patient equipoise and (iii) aspects of surgical culture and training that were not supportive of RCTs. Conclusion: There is a need for well-designed, large-scale RCTs to support the current practice of IBBR but barriers to their acceptability are evident. The perceived barriers to RCTs in breast reconstruction identified in this study are not insurmountable and have previously been overcome in other similar surgical trials. This may represent an opportunity, not only to establish the evidence base for IBBR, but also to improve engagement in RCTs in breast surgery in general to ultimately improve outcomes for patients. Trial Registration: International Standard Randomised Controlled Trial Number ISRCTN37664281.</p

Atypically-reading adults: a profile : an exploratory, longitudinal study of single word recognition processes

Approximately 16% of school leavers cannot read to a sufficient skill level so as to be called “functionally literate” (Castles et al., 2018; Leitch, 2006). This exploratory study explores the single word recognition processes of a group of atypically-reading adults in comparison with groups of younger and older readers. In the main study, we assessed orthographic, phonological and semantic skills longitudinally. We estimated their influence plus that of psycholinguistic properties such as word-frequency, consistency and neighbourhood-size on single word recognition processes by way of reaction time and accuracy data from four experimental tasks (letter search, lexical decision, single word naming and sentence reading). To support the estimation of our statistical models for the main study, we conducted a wide ranging meta-analysis of psycholinguistic predictor effects. We report the findings here and introduce the study as an accessible resource for use by the research community. Linear-mixed-effects-models estimated that the rate of change in reading-related skills was either too small or too slow to detect within the time-frame or data. Adult-learners perform similarly to all comparison groups in response latencies across all tasks. They perform similarly to 11-12- and 16-17-year-old readers in the lexical decision and sentence reading accuracy measures. They are more accurate in letter search and less accurate in word naming accuracy measures. Nonword reading skill, rather than word reading skill, is a reliable predictor in this sample. Word-frequency, age-of-acquisition, consistency and neighbourhood size show influence across tasks. We interpret the results through the lexical quality hypothesis. The predictors that are influential across the models, and the similarity of adult-learners’ performance to younger readers suggests that their orthographic, phonological and semantic knowledge is weakly correlated. Further, adult-learners may be using a dominant reading strategy that reflects sublexical processing, thereby impeding development of orthographic learning and knowledge over the longer term

Association between older age and adverse outcomes on antiretroviral therapy: a cohort analysis of programme data from nine countries.

Recent studies have highlighted the increased risk of adverse outcomes among older patients on antiretroviral therapy (ART). We report on the associations between older age and adverse outcomes in HIV/AIDS antiretroviral programmes across 17 programmes in sub-Saharan Africa

N-fixation in legumes – an assessment of the potential threat posed by ozone pollution

The growth, development and functioning of legumes are often significantly affected by exposure to tropospheric ozone (O3) pollution. However, surprisingly little is known about how leguminous Nitrogen (N) fixation responds to ozone, with a scarcity of studies addressing this question in detail. In the last decade, ozone impacts on N-fixation in soybean, cowpea, mung bean, peanut and clover have been shown for concentrations which are now commonly recorded in ambient air or are likely to occur in the near future. We provide a synthesis of the existing literature addressing this issue, and also explore the effects that may occur on an agroecosystem scale by predicting reductions in Trifolium (clovers) root nodule biomass in United Kingdom (UK) pasture based on ozone concentration data for a “high” (2006) and “average” ozone year (2008). Median 8% and 5% reductions in clover root nodule biomass in pasture across the UK were predicted for 2006 and 2008 respectively. Seasonal exposure to elevated ozone, or short-term acute concentrations >100 ppb, are sufficient to reduce N-fixation and/or impact nodulation, in a range of globally-important legumes. However, an increasing global burden of CO2, the use of artificial fertiliser, and reactive N-pollution may partially mitigate impacts of ozone on N-fixation