Reducing energy use in housing: insulation and retrofit problems in Wales and the UK

There is general agreement that existing and new build houses should achieve higher standards of energy efficiency. Research into different forms of insulation and methods of installation has been carried out for a new book on insulation materials. (ICE Publications later in 2019). There has been an assumption that all insulation materials are much the same and that, providing that thermal performance figures are satisfactory, any material can be used in any form of construction. The evidence shows, however, that inappropriate insulation and installation measures can lead to many unintended consequences and a gap between predicted and actual performance. Far from reducing fuel poverty and carbon emissions, mould and damp can occur, aggravating health problems, which has been confirmed by academic research. Sealing up increasingly airtight buildings with non-breathable, flammable and even hazardous synthetic materials can cause damage to building fabric and occupant health. Furthermore the embodied energy and pollution involved in the production of many commonly produced insulation materials can be bad for the environment. The importance of indoor air quality and ventilation is often overlooked, though recent work by NICE and the Environmental Audit Committee in Westminster has drawn attention to the problems. The paper will review the range of insulation materials available and their differences. It will be illustrated with case study examples of so-called retrofit disasters where cavity wall, external wall and internal insulation have been wrongly applied. Some of these case study examples are in Wales and the assistance of CIVALLI (based in Newport) will be acknowledged

Estimating and modelling rates of evolution with applications to phylogenetics and codon selection

This thesis addresses two problems that have applications in evolution and phylogenetics: (i) estimating and accounting for evolutionary rate heterogeneity in a phylogenetic context (Chapters 2 and 3); (ii) detecting synonymous selection upon a set of codons (Chapter 4).Chapter 2 presents a fast algorithm (DistR) to estimate gene/protein evolutionary rates based on pairwise distances between pairs of taxa derived from gene/protein sequence data. Simulation studies indicate that this algorithm accurately estimates rates and is robust to missing data. Moreover, by including evolutionary rates estimated by the DistR algorithm as additional parameters into a phylogenetic model, a significantly improved fit over the concatenated model is obtained as measured by the Akaike Information Criterion (AIC).However, allowing every gene/protein to have its own evolutionary rate - termed the n-parameter approach - is only one method of accounting for gene rate heterogeneity in phylogenetic inference. Under the alpha-parameter approach, a Gamma distribution is fit to the gene rates in order to account for rate heterogeneity, a method that is much slower than the n-parameter approach. Comparison of the n-parameter to the alpha-parameter approaches (Chapter 3) indicates that the n-parameter method provides a better fit over the concatenated model than the alpha-parameter approach. Interestingly, improved model fit over the concatenated model is highly correlated with the presence of a gene that has a slow relative rate.Chapter 4 addresses the question of detecting synonymous selection on sets of codons using parametric codon models. Parametric codon models are used to simulate data under the null hypothesis that there is no synonymous selection on a particular codon; codons that have unexpected synonymous usage in empirical data, compared to the null distribution, are classified as Highly Selected Codons (HSCs). Two different data sets are analyzed to identify HSCs: nuclear genes of various Saccharomyces species that are well-known to undergo translational selection; mitochondrial genes of several Reclinomonas species that are highly A+T biased. Eleven Saccharomyces codons are determined to be under synonymous selection (HSCs). Nine of these codons were previously identified as undergoing translational selection. Similarly, 10 Reclinomonas codons are identified as undergoing synonymous selection. Comparison to traditional nonparametric approaches shows that these methods do not identify any Reclinomonas codons as under synonymous selection due to the high A+T bias of the genes

Cervical radiofrequency Neurotomy reduces psychological features in individuals with chronic whiplash symptoms

Background: Individuals with chronic whiplash associated disorder (WAD) demonstrate various psychological features. It has previously been demonstrated that cervical radiofrequency neurotomy (cRFN) resolves psychological distress and anxiety. It is unknown if cRFN also improves or reduces a broader spectrum of psychological substrates now commonly identified in chronic whiplash, such as post-traumatic stress disorder (PTSD) and pain catastrophizing

Ubiquitylation activates a peptidase that promotes cleavage and destabilization of its activating E3 ligases and diverse growth regulatory proteins to limit cell proliferation in Arabidopsis

The characteristic shapes and sizes of organs are established by cell proliferation patterns and final cell sizes, but the underlying molecular mechanisms coordinating these are poorly understood. Here we characterize a ubiquitin-activated peptidase called DA1 that limits the duration of cell proliferation during organ growth in Arabidopsis thaliana. The peptidase is activated by two RING E3 ligases, Big Brother (BB) and DA2, which are subsequently cleaved by the activated peptidase and destabilized. In the case of BB, cleavage leads to destabilization by the RING E3 ligase PROTEOLYSIS 1 (PRT1) of the N-end rule pathway. DA1 peptidase activity also cleaves the deubiquitylase UBP15, which promotes cell proliferation, and the transcription factors TEOSINTE BRANCED 1/ CYCLOIDEA/PCF 15 (TCP15) and TCP22, which promote cell proliferation and repress endoreduplication. We propose that DA1 peptidase activity regulates the duration of cell proliferation and the transition to endoreduplication and differentiation during organ formation in plants by coordinating the destabilization of regulatory proteins

In vivo vitamin C supplementation increases phosphoinositol transfer protein expression in peripheral blood mononuclear cells from healthy individuals

Ascorbate can act as both a reducing and oxidising agent in vitro depending on its environment. It can modulate the intracellular redox environment of cells and therefore is predicted to modulate thiol-dependent cell signalling and gene expression pathways. Using proteomic analysis of vitamin C-treated T cells in vitro, we have previously reported changes in expression of five functional protein groups associated with signalling, carbohydrate metabolism, apoptosis, transcription and immune function. The increased expression of the signalling molecule phosphatidylinositol transfer protein (PITP) was also confirmed using Western blotting. Herein, we have compared protein changes elicited by ascorbate in vitro, with the effect of ascorbate on plasma potassium levels, on peripheral blood mononuclear cell (PBMC) apoptosis and PITP expression, in patients supplemented with vitamin C (0-2 g/d) for up to 10 weeks to investigate whether in vitro model systems are predictive of in vivo effects. PITP varied in expression widely between subjects at all time-points analysed but was increased by supplementation with 2 g ascorbate/d after 5 and 10 weeks. No effects on plasma potassium levels were observed in supplemented subjects despite a reduction of K+ channel proteins in ascorbate-treated T cells in vitro. Similarly, no effect of vitamin C supplementation on PBMC apoptosis was observed, whilst ascorbate decreased expression of caspase 3 recruitment domain protein in vitro. These data provide one of the first demonstrations that proteomics may be valuable in developing predictive markers of nutrient effects in vivo and may identify novel pathways for studying mechanisms of action in vivo

Crowd-sourced archaeological research. The MicroPasts project. Open Access: http://www.ai-journal.com/article/view/ai.1705

This paper offers a brief introduction to MicroPasts, a web-enabled crowd-sourcing and crowd-funding project whose overall goal is to promote the collection and use of high quality research data via institutional and community collaborations, both on- and off-line. In addition to introducing this initiative, the discussion below is a reflection of its lead author’s core contribution to the project and will dwell in more detail on one particular aspect of MicroPasts: its relevance to research and practice in public archaeology, cultural policy and heritage studies

Collecting genetic samples and linked mental health data from adolescents in schools:Protocol co-production and a mixed-methods pilot of feasibility and acceptability

OBJECTIVES: To coproduce a school-based protocol and examine acceptability and feasibility of collecting saliva samples for genetic studies from secondary/high school students for the purpose of mental health research. DESIGN: Protocol coproduction and mixed-methods feasibility pilot. SETTING: Secondary schools in Wales, UK. PARTICIPANTS: Students aged 11–13 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Coproduced research protocol including an interactive science workshop delivered in schools; school, parental and student recruitment rates; adherence to protocol and adverse events; ability to extract and genotype saliva samples; student enjoyment of the science workshop and qualitative analysis of teacher focus groups on acceptability and feasibility. RESULTS: Five secondary schools participated in the coproduction phase, and three of these took part in the research study (eligible sample n=868 students). Four further schools were subsequently approached, but none participated. Parental opt-in consent was received from 98 parents (11.3% eligible sample), three parents (0.3%) actively refused and responses were not received for 767 (88.4%) parents. We obtained saliva samples plus consent for data linkage for 79 students. Only one sample was of insufficient quality to be genotyped. The science workshop received positive feedback from students. Feedback from teachers showed that undertaking research like this in schools is viewed as acceptable in principle, potentially feasible, but that there are important procedural barriers to be overcome. Key recommendations include establishing close working relationships between the research team and school classroom staff, together with improved methods for communicating with and engaging parents. CONCLUSIONS: There are major challenges to undertaking large-scale genetic mental health research in secondary schools. Such research may be acceptable in principle, and in practice DNA collected from saliva in classrooms is of sufficient quality. However, key challenges that must be overcome include ensuring representative recruitment of schools and sufficient parental engagement where opt-in parental consent is required

Open science in archaeology

No abstract available

Effect of treatment of clinical seizures vs electrographic seizures in full-term and near-term neonates : a randomized clinical trial

Importance: Seizures in the neonatal period are associated with increased mortality and morbidity. Bedside amplitude-integrated electroencephalography (aEEG) has facilitated the detection of electrographic seizures; however, whether these seizures should be treated remains uncertain. Objective: To determine if the active management of electrographic and clinical seizures in encephalopathic term or near-term neonates improves survival free of severe disability at 2 years of age compared with only treating clinically detected seizures. Design, Setting, and Participants: This randomized clinical trial was conducted in tertiary newborn intensive care units recruited from 2012 to 2016 and followed up until 2 years of age. Participants included neonates with encephalopathy at 35 weeks’ gestation or more and younger than 48 hours old. Data analysis was completed in April 2021. Interventions: Randomization was to an electrographic seizure group (ESG) in which seizures detected on aEEG were treated in addition to clinical seizures or a clinical seizure group (CSG) in which only seizures detected clinically were treated. Main Outcomes and Measures: Primary outcome was death or severe disability at 2 years, defined as scores in any developmental domain more than 2 SD below the Australian mean assessed with Bayley Scales of Neonate and Toddler Development, 3rd ed (BSID-III), or the presence of cerebral palsy, blindness, or deafness. Secondary outcomes included magnetic resonance imaging brain injury score at 5 to 14 days, time to full suck feeds, and individual domain scores on BSID-III at 2 years. Results: Of 212 randomized neonates, the mean (SD) gestational age was 39.2 (1.7) weeks and 122 (58%) were male; 152 (72%) had moderate to severe hypoxic-ischemic encephalopathy (HIE) and 147 (84%) had electrographic seizures. A total of 86 neonates were included in the ESG group and 86 were included in the CSG group. Ten of 86 (9%) neonates in the ESG and 4 of 86 (4%) in the CSG died before the 2-year assessment. The odds of the primary outcome were not significantly different in the ESG group compared with the CSG group (ESG, 38 of 86 [44%] vs CSG, 27 of 86 [31%]; odds ratio [OR], 1.83; 95% CI, 0.96 to 3.49; P = .14). There was also no significant difference in those with HIE (OR, 1.77; 95% CI, 0.84 to 3.73; P = .26). There was evidence that cognitive outcomes were worse in the ESG (mean [SD] scores, ESG: 97.4 [17.7] vs CSG: 103.8 [17.3]; mean difference, −6.5 [95% CI, −1.2 to −11.8]; P = .01). There was little evidence of a difference in secondary outcomes, including time to suck feeds, seizure burden, or brain injury score. Conclusions and Relevance: Treating electrographic and clinical seizures with currently used anticonvulsants did not significantly reduce the rate of death or disability at 2 years in a heterogeneous group of neonates with seizures