Consistent approximation of epidemic dynamics on degree-heterogeneous clustered networks

Realistic human contact networks capable of spreading infectious disease, for example studied in social contact surveys, exhibit both significant degree heterogeneity and clustering, both of which greatly affect epidemic dynamics. To understand the joint effects of these two network properties on epidemic dynamics, the effective degree model of Lindquist et al. [28] is reformulated with a new moment closure to apply to highly clustered networks. A simulation study comparing alternative ODE models and stochastic simulations is performed for SIR (Susceptible–Infected–Removed) epidemic dynamics, including a test for the conjectured error behaviour in [40], providing evidence that this novel model can be a more accurate approximation to epidemic dynamics on complex networks than existing approaches

A comparison of ultrasound measurements to assess carotid atherosclerosis development in subjects with and without type 2 diabetes

BACKGROUND: Subjects with type 2 diabetes are at an increased risk of vascular complications. The use of carotid ultrasound remains an attractive, non-invasive method to monitor atherosclerotic disease progression and/or response to treatment in patients with type 2 diabetes, with intima-media thickness routinely used as the gold standard to detect pathology. However, alternative measurements, such as plaque area or volume, may represent a potentially more powerful approach. Thus, the objective of this study was to compare the traditional intima-media thickness measurement against the novel total plaque volume measurement in analyzing carotid atherosclerosis development in individuals with type 2 diabetes. METHODS: The case-control study included 49 Oji-Cree adults with diabetes or impaired glucose tolerance, aged 21–69, and 49 sex- and age-matched normoglycemic subjects. At baseline, metabolic variables were measured, including body mass index, waist circumference, total cholesterol:high density lipoprotein ratio, plasma triglycerides, plasma glucose, and serum insulin. Carotid ultrasound measurements, 7 years later, assessed carotid arterial intima-media thickness and total plaque volume. RESULTS: At baseline, the two groups were well matched for smoking habits, hypertension, body mass index, and waist circumference. Differences were noted in baseline measurements of total cholesterol:high density lipoprotein (P = 0.0006), plasma triglycerides (P < 0.0001) and fasting glucose (P < 0.0001). After seven years, carotid ultrasound scans revealed that total plaque volume measurements (P = 0.037), but not intima-media thickness measurements, were higher in subjects with diabetes/impaired glucose tolerance compared to the normoglycemic controls. Correlation between intima-media thickness and total plaque volume was moderate. Based on our study findings, to achieve power levels >0.70 when comparing intima-media thickness measurements for diabetics versus non-diabetics, thousands of study subjects are required. For comparing total plaque volume measurements, only hundreds of study subjects are required. CONCLUSION: The development of atherosclerotic plaque is greater in subjects with diabetes/impaired glucose tolerance. Total plaque volume appears to capture the atherosclerotic disease burden more effectively in subjects with type 2 diabetes, and would be an appropriate outcome measure for studies aimed at changing the diabetic milieu

Variation in pre- and post-copulatory sexual selection on male genital size in two species of lygaeid bug

This study was funded by the Natural Environmental Research Council (DTG studentship 1109354 to LRD).Sexual selection has been shown to be the driving force behind the evolution of the sometimes extreme and elaborate genitalia of many species. Sexual selection may arise before and/or after mating, or vary according to other factors such as the social environment. However, bouts of selection are typically considered in isolation. We measured the strength and pattern of selection acting on the length of the male intromittent organ (or processus) in two closely related species of lygaeid seed bug: Lygaeus equestris and Lygaeus simulans. In both species, we measured both pre- and post-copulatory selection. For L. equestris, we also varied the experimental choice design used in mating trials. We found contrasting pre- and post-copulatory selection on processus length in L. equestris. Furthermore, significant pre-copulatory selection was only seen in mating trials in which two males were present. This selection likely arises indirectly due to selection on a correlated trait, as the processus does not interact with the female prior to copulation. In contrast, we were unable to detect significant pre- or post-copulatory selection on processus length in L. simulans. However, a formal meta-analysis of previous estimates of post-copulatory selection on processus length in L. simulans suggests that there is significant stabilising selection across studies, but the strength of selection varies between experiments. Our results emphasise that the strength and direction of sexual selection on genital traits may be multifaceted and can vary across studies, social contexts and different stages of reproduction.Publisher PDFPeer reviewe

Deconstructing the outsider puzzle: The legitimation journey of novelty

The proposition that outsiders often are crucial carriers of novelty into an established institutional field has received wide empirical support. But an equally compelling proposition points to the following puzzle: the very same conditions that enhance outsiders' ability to make novel contributions also hinder their ability to carry them out. We seek to address this puzzle by examining the contextual circumstances that affect the legitimation of novelty originating from a noncertified outsider that challenged the status quo in an established institutional field. Our research case material is John Harrison's introduction of a new mechanical method for measuring longitude at sea-the marine chronometer- which challenged the dominant astronomical approach.We find that whether an outsider's new offer gains or is denied legitimacy is influenced by (1) the outsider's agency to further a new offer, (2) the existence of multiple audiences with different dispositions toward this offer, and (3) the occurrence of an exogenous jolt that helps create a more receptive social space. We organize these insights into a multilevel conceptual framework that builds on previouswork but attributes a more decisive role to the interplay between endogenous and exogenous variables in shaping a field's shifting receptiveness to novelty. The framework exposes the interdependencies between the micro-, meso-, and macro-level processes that jointly affect an outsider's efforts to introduce novelty into an existing field

Polymorphisms in the Tlr4 and Tlr5 Gene Are Significantly Associated with Inflammatory Bowel Disease in German Shepherd Dogs

Inflammatory bowel disease (IBD) is considered to be the most common cause of vomiting and diarrhoea in dogs, and the German shepherd dog (GSD) is particularly susceptible. The exact aetiology of IBD is unknown, however associations have been identified between specific single-nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) and human IBD. However, to date, no genetic studies have been undertaken in canine IBD. The aim of this study was to investigate whether polymorphisms in canine TLR 2, 4 and 5 genes are associated with IBD in GSDs. Mutational analysis of TLR2, TLR4 and TLR5 was performed in 10 unrelated GSDs with IBD. Four non-synonymous SNPs (T23C, G1039A, A1571T and G1807A) were identified in the TLR4 gene, and three non-synonymous SNPs (G22A, C100T and T1844C) were identified in the TLR5 gene. The non-synonymous SNPs identified in TLR4 and TLR5 were evaluated further in a case-control study using a SNaPSHOT multiplex reaction. Sequencing information from 55 unrelated GSDs with IBD were compared to a control group consisting of 61 unrelated GSDs. The G22A SNP in TLR5 was significantly associated with IBD in GSDs, whereas the remaining two SNPs were found to be significantly protective for IBD. Furthermore, the two SNPs in TLR4 (A1571T and G1807A) were in complete linkage disequilibrium, and were also significantly associated with IBD. The TLR5 risk haplotype (ACC) without the two associated TLR4 SNP alleles was significantly associated with IBD, however the presence of the two TLR4 SNP risk alleles without the TLR5 risk haplotype was not statistically associated with IBD. Our study suggests that the three TLR5 SNPs and two TLR4 SNPs; A1571T and G1807A could play a role in the pathogenesis of IBD in GSDs. Further studies are required to confirm the functional importance of these polymorphisms in the pathogenesis of this disease

Carbon sequestration via wood burial

To mitigate global climate change, a portfolio of strategies will be needed to keep the atmospheric CO2 concentration below a dangerous level. Here a carbon sequestration strategy is proposed in which certain dead or live trees are harvested via collection or selective cutting, then buried in trenches or stowed away in above-ground shelters. The largely anaerobic condition under a sufficiently thick layer of soil will prevent the decomposition of the buried wood. Because a large flux of CO2 is constantly being assimilated into the world's forests via photosynthesis, cutting off its return pathway to the atmosphere forms an effective carbon sink

A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects

BACKGROUND: Periconceptional use of vitamin supplements containing folic acid reduces the risk of a neural tube defect (NTD). In November 1998, food fortification with folic acid was mandated in Canada, as a public health strategy to increase the folic acid intake of all women of childbearing age. We undertook a comprehensive population based study in Newfoundland to assess the benefits and possible adverse effects of this intervention. METHODS: This study was carried out in women aged 19–44 years and in seniors from November 1997 to March 1998, and from November 2000 to March 2001. The evaluation was comprised of four components: I) Determination of rates of NTDs; II) Dietary assessment; III) Blood analysis; IV) Assessment of knowledge and use of folic acid supplements. RESULTS: The annual rates of NTDs in Newfoundland varied greatly between 1976 and 1997, with a mean rate of 3.40 per 1,000 births. There was no significant change in the average rates between 1991–93 and 1994–97 (relative risk [RR] 1.01, 95% confidence interval [CI] 0.76–1.34). The rates of NTDs fell by 78% (95% CI 65%–86%) after the implementation of folic acid fortification, from an average of 4.36 per 1,000 births during 1991–1997 to 0.96 per 1,000 births during 1998–2001 (RR 0.22, 95% CI 0.14–0.35). The average dietary intake of folic acid due to fortification was 70 μg/day in women aged 19–44 years and 74 μg/day in seniors. There were significant increases in serum and RBC folate levels for women and seniors after mandatory fortification. Among seniors, there were no significant changes in indices typical of vitamin B(12 )deficiencies, and no evidence of improved folate status masking haematological manifestations of vitamin B(12 )deficiency. The proportion of women aged 19–44 years taking a vitamin supplement containing folic acid increased from 17% to 28%. CONCLUSIONS: Based on these findings, mandatory food fortification in Canada should continue at the current levels. Public education regarding folic acid supplement use by women of childbearing age should also continue

Minimising barriers to dental care in older people

<p>Abstract</p> <p>Background</p> <p>Older people are increasingly retaining their natural teeth but at higher risk of oral disease with resultant impact on their quality of life. Socially deprived people are more at risk of oral disease and yet less likely to take up care. Health organisations in England and Wales are exploring new ways to commission and provide dental care services in general and for vulnerable groups in particular. This study was undertaken to investigate barriers to dental care perceived by older people in socially deprived inner city area where uptake of care was low and identify methods for minimising barriers in older people in support of oral health.</p> <p>Methods</p> <p>A qualitative dual-methodological approach, utilising both focus groups and individual interviews, was used in this research. Participants, older people and carers of older people, were recruited using purposive sampling through day centres and community groups in the inner city boroughs of Lambeth, Southwark and Lewisham in South London. A topic guide was utilised to guide qualitative data collection. Informants' views were recorded on tape and in field notes. The data were transcribed and analysed using Framework Methodology.</p> <p>Results</p> <p>Thirty-nine older people and/or their carers participated in focus groups. Active barriers to dental care in older people fell into five main categories: cost, fear, availability, accessibility and characteristics of the dentist. Lack of perception of a need for dental care was a common 'passive barrier' amongst denture wearers in particular. The cost of dental treatment, fear of care and perceived availability of dental services emerged to influence significantly dental attendance. Minimising barriers involves three levels of action to be taken: individual actions (such as persistence in finding available care following identification of need), system changes (including reducing costs, improving information, ensuring appropriate timing and location of care, and good patient management) and societal issues (such as reducing isolation and loneliness). Older people appeared to place greater significance on system and societal change than personal action.</p> <p>Conclusion</p> <p>Older people living within the community in an inner city area where NHS dental care is available face barriers to dental care. Improving access to care involves actions at individual, societal and system level. The latter includes appropriate management of older people by clinicians, policy change to address NHS charges; consideration of when, where and how dental care is provided; and clear information for older people and their carers on available local dental services, dental charges and care pathways.</p

Methylation-associated down-regulation of RASSF1A and up-regulation of RASSF1C in pancreatic endocrine tumors

<p>Abstract</p> <p>Background</p> <p><it>RASSF1A </it>gene silencing by DNA methylation has been suggested as a major event in pancreatic endocrine tumor (PET) but <it>RASSF1A </it>expression has never been studied. The <it>RASSF1 </it>locus contains two CpG islands (<it>A </it>and <it>C</it>) and generates seven transcripts (<it>RASSF1A</it>-<it>RASSF1G</it>) by differential promoter usage and alternative splicing.</p> <p>Methods</p> <p>We studied 20 primary PETs, their matched normal pancreas and three PET cell lines for the (i) methylation status of the <it>RASSF1 </it>CpG islands using methylation-specific PCR and pyrosequencing and (ii) expression of <it>RASSF1 </it>isoforms by quantitative RT-PCR in 13 cases. CpG island A methylation was evaluated by methylation-specific PCR (MSP) and by quantitative methylation-specific PCR (qMSP); pyrosequencing was applied to quantify the methylation of 51 CpGs also encompassing those explored by MSP and qMSP approaches.</p> <p>Results</p> <p>MSP detected methylation in 16/20 (80%) PETs and 13/20 (65%) normal pancreas. At qMSP, 11/20 PETs (55%) and 9/20 (45%) normals were methylated in at least 20% of <it>RASSF1A </it>alleles.</p> <p>Pyrosequencing showed variable distribution and levels of methylation within and among samples, with PETs having average methylation higher than normals in 15/20 (75%) cases (<it>P </it>= 0.01). The evaluation of mRNA expression of <it>RASSF1 </it>variants showed that: i) <it>RASSF1A </it>was always expressed in PET and normal tissues, but it was, on average, expressed 6.8 times less in PET (<it>P </it>= 0.003); ii) <it>RASSF1A </it>methylation inversely correlated with its expression; iii) <it>RASSF1 </it>isoforms were rarely found, except for <it>RASSF1B </it>that was always expressed and <it>RASSF1C </it>whose expression was 11.4 times higher in PET than in normal tissue (<it>P </it>= 0.001). A correlation between <it>RASSF1A </it>expression and gene methylation was found in two of the three PET cell lines, which also showed a significant increase in <it>RASSF1A </it>expression upon demethylating treatment.</p> <p>Conclusions</p> <p><it>RASSF1A </it>gene methylation in PET is higher than normal pancreas in no more than 75% of cases and as such it cannot be considered a marker for this neoplasm. <it>RASSF1A </it>is always expressed in PET and normal pancreas and its levels are inversely correlated with gene methylation. Isoform <it>RASSF1C </it>is overexpressed in PET and the recent demonstration of its involvement in the regulation of the Wnt pathway points to a potential pathogenetic role in tumor development.</p