Using visualization for visualization : an ecological interface design approach to inputting data

Visualization is experiencing growing use by a diverse community, with continuing improvements in the availability and usability of systems. In spite of these developments the problem of how first to get the data in has received scant attention: the established approach of pre-defined readers and programming aids has changed little in the last two decades. This paper proposes a novel way of inputting data for scientific visualization that employs rapid interaction and visual feedback in order to understand how the data is stored. The approach draws on ideas from the discipline of ecological interface design to extract and control important parameters describing the data, at the same time harnessing our innate human ability to recognize patterns. Crucially, the emphasis is on file format discovery rather than file format description, so the method can therefore still work when nothing is known initially of how the file was originally written, as is often the case with legacy binary data. © 2013 Elsevier Ltd

The genetics and evolutionary dynamics of sexual system evolution in tadpole shrimps

Sexual reproduction is found throughout the eukaryote tree of life and fundamentally affects the organisms that practice it. In particular, the sexual system of an organism can influence genetic diversity, population structure, genome structure, the evolutionary potential of species and even cause speciation. Understanding the effects of sexual reproduction, and the effects of transitions between its various forms, is therefore a central theme in biology and essential to understanding how populations and species evolve.In this thesis I investigate the genetics and evolutionary dynamics of sexual system evolution in tadpole shrimps (Notostraca), a group of branchiopod crustaceans with diverse sexual systems. Gonochorism (dioecy), hermaphroditism and androdioecy – the presence of self-­‐fertile hermaphrodites and males within a population – are all found, with this variation occurring both within and between species. In contrast to their variable sexual system, tadpole shrimps exhibit high levels of morphological conservatism, appearing to have changed little since the Early Devonian.I establish the first resolved phylogeny of Notostraca and find that tadpole shrimps have undergone at least two bouts of diversification in their evolutionary history, with extant species being younger than the fossil record would suggest. Analysis of sexual system across the phylogeny reveals the labile nature of sexual systems within Notostraca with multiple transitions having occurred between separate and combined sexes, driven by selection for reproductive assurance. Finally I use restriction site associated DNA sequencing (RAD-­‐seq) to identify over 1000 high coverage, novel genomic markers for Triops cancriformis, a mixed mating tadpole shrimp. I confirm a Z W chromosomal sex determination system for T. cancriformis, conserved in gonochoric and androdioecious populations and identify significant alterations in the structure of the W and Z chromosomes associated with the transition in sexual system. The results presented within this thesis establish tadpole shrimps as an ideal model to study the evolution of sexual systems and the genomic effects of repeated transitions between sexual systems

Effects of exercise modalities on arterial stiffness and wave reflection: a systematic review and meta-analysis of randomized controlled trials

Background and Objectives: Physical activity is associated with lower cardiovascular and all-cause mortality. However, the effects of different exercise modalities on arterial stiffness are currently unclear. Our objectives were to investigate the effects of exercise modalities (aerobic, resistance or combined) on pulse wave velocity (PWV) and augmentation index (AIx), and to determine whether the effects on these indices differed according to the participants' or exercise characteristics. Methods: We searched the Medline, Embase and Cochrane Library databases from inception until April 2014 for randomized controlled trials lasting ≥4 weeks investigating the effects of exercise modalities on PWV and AIx in adults aged ≥18 years. Results: Forty-two studies (1627 participants) were included in this analysis. Aerobic exercise improved both PWV (WMD: −0.63 m/s, 95% CI: −0.90, −0.35) and AIx (WMD:−2.63%, 95% CI: −5.25 to −0.02) significantly. Aerobic exercise training showed significantly greater reduction in brachial-ankle (WMD: −1.01 m/s, 95% CI: −1.57, −0.44) than in carotid-femoral (WMD: -0.39 m/s, 95% CI: −0.52, −0.27) PWV. Higher aerobic exercise intensity was associated with larger reductions in AIx (β: −1.55%, CI −3.09, 0.0001). In addition, aerobic exercise had a significantly larger effect in reducing PWV (WMD:−1.0 m/s, 95% CI: −1.43, −0.57) in participants with stiffer arteries (PWV ≥8 m/s). Resistance exercise had no effect on PWV and AIx. There was no significant effect of combined exercise on PWV and AIx. Conclusions: We conclude that aerobic exercise improved arterial stiffness significantly and that the effect was enhanced with higher aerobic exercise intensity and in participants with greater arterial stiffness at baseline. Trial Registration PROSPERO: Database registration: CRD42014009744,

Aged disability and community care in Australia: issues for southern Africa

Disability among the aged is an issue of growing importance to southern Africa as it is throughout the world. New methods and debates about disability and ageing are illustrated by a discussion of the Australian situation. First, trends in mortality and life expectancy are outlined, and the debate about the compression of mortality critically examined. Second, the same techniques of analysis are applied to disability and handicap rates derived from national surveys. The hypothesis of compression of morbidity or illness is also critically examined. Third, the impact on the community of disability is discussed, and expectations of life "free of community services" and ''free of institutionalization" are calculated. Finally, trends in health-risk factors and the contributions of various diseases to health expectations are outlined. Southern African countries are also part of the movement to measure quality-of-life years-not only quantity - and need to develop their population monitoring of disability and demands for community care. The development will facilitate policy planning to improve the management of community services provided for the elderly by families, the community and formal providers

Metabolic effects of a high-fat diet post-weaning after low maternal dietary folate during pregnancy and lactation

Scope Investigate the influence of low-folate supply during pregnancy and lactation on obesity and markers of the metabolic syndrome in offspring, and how provision of a high-fat diet post weaning may exacerbate the resultant phenotype. Methods and results Female C57Bl/6 mice were randomized to low or normal folate diets (0.4 or 2 mg folic acid/kg diet) prior to and during pregnancy and lactation. At 4 wk of age, offspring were randomized to high- or low-fat diets, weighed weekly and food intake assessed at 9 and 18 wk old. Adiposity was measured at 3 and 6 months. Plasma glucose and triacylglycerol (TAG) concentrations were measured at 6 months. Maternal folate supply did not influence adult offspring body weight or adiposity. High-fat feeding post weaning increased body weight and adiposity at 3 and 6 months (p > 0.001). Maternal low folate lowered plasma glucose (p = 0.010) but increased plasma TAG (p = 0.048). High-fat feeding post weaning increased plasma glucose and TAG (p = 0.023, p = 0.049 respectively). Offspring from folate-depleted (but not folate-adequate) dams had 30% higher TAG concentration when fed the high-fat diet from weaning (p = 0.005 for interaction). Conclusion Inadequate maternal folate intake has long-term effects on offspring metabolism, manifested as increased circulating TAG, particularly in offspring with high-fat intake post weaning

The long-term dynamics of invasive signal crayfish forcing of fluvial sediment supply via riverbank burrowing

Animals are important drivers of sediment dynamics. Invasive signal crayfish (Pacifastacus leniusculus) have been shown to supply sediment to rivers by burrowing into riverbanks. Burrowing directly transfers excavated sediment into the river and also has an additional indirect affect by promoting riverbank failure. While previous research has isolated burrow densities at a point in time, rates of burrow construction and of burrow loss due to erosion are unknown, which introduces uncertainty into estimates of how much sediment burrows contribute to rivers. Here we report results from a 5-year study that evaluated the temporal dynamics of crayfish populations, rates of burrow loss due to erosion, and the mass of sediment directly supplied to rivers by burrow excavation. At ten reaches across five lowland streams in England, we estimated the mass of sediment displaced by 1861 new and previously constructed burrows. Both crayfish and burrow densities were variable over time, suggesting that burrows contribute temporally variable amounts of fine sediment to riverine systems. 42 % of observed burrows were constructed within the previous 365 days, and individual burrows lasted on average 461 days. Applying this to comparable historical data, an average of 2.0 t km−1 a−1 of sediment was excavated to construct burrows in the study reaches, which is eight times more than estimated in previous studies. Whilst total burrow densities in each year were not consistently correlated with contemporary crayfish densities, the mass of sediment excavated over the prior year was strongly correlated with contemporary crayfish densities. Current fine sediment management practices are largely aimed at controlling fine sediment delivery, predominately from agricultural activities, but biotic burrowing into riverbanks may represent an important and overlooked source of fine sediment supply. Incorporation of biotic processes in sediment dynamics would improve the accuracy of fluvial sediment budgets and enhance the knowledge base underpinning effective fine-sediment management practices

DNA methylation of ESR-1 and N-33 in colorectal mucosa of patients with Ulcerative Colitis (UC)

Introduction: Epigenetic marking such as DNA methylation influence gene transcription and chromosomal stability and may also be affected by environmental exposures. Few studies exist on alteration in DNA methylation profiles (genomic and gene specific methylation) in patients with Ulcerative Colitis (UC) and none assessing its relationship with lifestyle exposures. Aims & Methods: To assess genomic methylation and promoter methylation of the ESR-1 (oestrogen receptor - 1) and N-33 (tumour suppressor candidate-3) genes in the macroscopically normal mucosa of UC patients as well as to investigate effects of anthropometric and lifestyle exposures on DNA methylation. Sixty eight subjects were recruited (24 UC and 44 age and sex matched controls). Colorectal mucosal biopsies were obtained and DNA was extracted. Genomic DNA methylation was quantified using the tritium-labelled cytosine extension assay (3[H] dCTP) whilst gene specific methylation was quantified using the COBRA method. Results: The methylation level of both ESR-1 and N-33 genes were significantly higher in UC subjects compared with controls (7.9% vs 5.9%; p = 0.015 and 66% vs 9.3%; p < 0.001 respectively). There was no detectable difference in global DNA methylation between patients with UC and age and sex matched controls. No associations between indices of DNA methylation and anthropometric measures or smoking patterns were detected. Conclusions: For the first time, we have shown increased methylation in the promoter regions of the putative tumour suppressor gene N-33 in macroscopically normal mucosa of patients with UC. In addition, we have confirmed that methylation of ESR-1 promoter is higher in UC patients compared with age and sex matched controls. These findings suggests that, inactivation through methylation of the putative tumour suppressor genes N-33 and ESR-1, may not be associated with colorectal carcinogenesis in UC

Sources of total, non-milk extrinsic, and intrinsic and milk sugars in the diets of older adults living in sheltered accommodation

The WHO recommends limiting non-milk extrinsic sugars (NMES) consumption to ≤ 10 % energy to reduce the risk of unhealthy weight gain and dental caries, and to restrict frequency of intake to ≤ 4 times/d to reduce risk of dental caries. Older adults, especially those from low-income backgrounds, are at increased risk of dental caries, yet there is little information on sugars intake (frequency of intake and food sources) in this age group. The aim of this report is to present baseline data from a community-based dietary intervention study of older adults from socially deprived areas of North East England, on the quantity and sources of total sugars, NMES, and intrinsic and milk sugars, and on frequency of NMES intake. Dietary intake was assessed using two 3-d estimated food diaries, completed by 201 participants (170 female, thirty-one male) aged 65–85 years (mean 76·7 (sd 5·5) years) recruited from sheltered housing schemes. Total sugars represented 19·6 %, NMES 9·3 %, and intrinsic and milk sugars 10·3 % of daily energy intake. Eighty-one (40·3 %) exceeded the NMES intake recommendation. Mean frequency of NMES intake was 3·4 times/d. The fifty-three participants (26·4 %) who exceeded the frequency recommendation ( ≤ 4 times/d) obtained a significantly greater percentage of energy from NMES compared with those participants who met the recommendation. The food groups ‘biscuits and cakes’ (18·9 %), ‘soft drinks’ (13·1 %) and ‘table sugar’ (11·1 %) made the greatest contributions to intakes of NMES. Interventions to reduce NMES intake should focus on limiting quantity and frequency of intake of these food groups

Effect of Maternal and Post-Weaning Folate Supply on Gene-Specific DNA Methylation in the Small Intestine of Weaning and Adult Apc+/Min and Wild Type Mice

Increasing evidence supports the developmental origins of adult health and disease hypothesis which argues for a causal relationship between adverse early life nutrition and increased disease risk in adulthood. Modulation of epigenetic marks, e.g., DNA methylation and consequential altered gene expression, has been proposed as a mechanism mediating these effects. Via its role as a methyl donor, dietary folate supply may influence DNA methylation. As aberrant methylation is an early event in colorectal cancer (CRC) pathogenesis, we hypothesized low maternal and/or post-weaning folate intake may influence methylation of genes involved in CRC development. We investigated the effects of maternal folate depletion during pregnancy and lactation on selected gene methylation in the small intestine of wild type (WT) and Apc+/Min mice at weaning and as adults. We also investigated the effects of folate depletion post-weaning on gene methylation in adult mice. Female C57BI6/J mice were fed low or normal folate diets from mating with Apc+/Min males to the end of lactation. A sub-set of offspring were killed at weaning. Remaining offspring were weaned on to low or normal folate diets, resulting in four treatment groups of Apc+/Min and WT mice. p53 was more methylated in weaning and adult WT compared with Apc+/Min mice (p > 0.001). Igf2 and Ape were hypermethylated in adult Apc+/Min compared with WT mice (p = 0.004 and 0.012 respectively). Low maternal folate reduced p53 methylation in adults (p=0.04). Low post-weaning folate increased Ape methylation in Apc+/Min mice only (p = 0.008 for interaction). These observations demonstrate that folate depletion in early life can alter epigenetic marks in a gene-specific manner. Also, the differential effects of altered folate supply on DNA methylation in WT and Apc+/Min mice suggest that genotype may modulate epigenetic responses to environmental cues and may have implications for the development of personalized nutrition

Inter-individual variation in nucleotide excision repair in young adults: effects of age, adiposity, micronutrient supplementation and genotype

Nucleotide excision repair (NER) is responsible for repairing bulky helix-distorting DNA lesions and is essential for the maintenance of genomic integrity. Severe hereditary impairment of NER leads to cancers such as those in xeroderma pigmentosum, and more moderate reductions in NER capacity have been associated with an increased cancer risk. Diet is a proven modifier of cancer risk but few studies have investigated the potential relationships between diet and NER. In the present study, the plasmid-based host cell reactivation assay was used to measure the NER capacity in peripheral blood mononuclear cells from fifty-seven volunteers aged 18–30 years before and after 6 weeks of supplementation with micronutrients (selenium and vitamins A, C and E). As a control, nine individuals remained unsupplemented over the same period. Volunteers were genotyped for the following polymorphisms in NER genes: ERCC5 Asp1104His (rs17655); XPC Lys939Gln (rs2228001); ERCC2 Lys751Gnl (rs13181); XPC PAT (an 83 bp poly A/T insertion–deletion polymorphism in the XPC gene). NER capacity varied 11-fold between individuals and was inversely associated with age and endogenous DNA strand breaks. For the first time, we observed an inverse association between adiposity and NER. No single polymorphism was associated with the NER capacity, although significant gene–gene interactions were observed between XPC Lys939Gln and ERCC5 Asp1104His and XPC Lys939Gln and ERCC2 Lys751Gnl. While there was no detectable effect of micronutrient supplementation on NER capacity, there was evidence that the effect of fruit intake on the NER capacity may be modulated by the ERCC2 Lys751Gnl single nucleotide polymorphism