Simultaneous sequencing of genetic and epigenetic bases in DNA.

DNA comprises molecular information stored in genetic and epigenetic bases, both of which are vital to our understanding of biology. Most DNA sequencing approaches address either genetics or epigenetics and thus capture incomplete information. Methods widely used to detect epigenetic DNA bases fail to capture common C-to-T mutations or distinguish 5-methylcytosine from 5-hydroxymethylcytosine. We present a single base-resolution sequencing methodology that sequences complete genetics and the two most common cytosine modifications in a single workflow. DNA is copied and bases are enzymatically converted. Coupled decoding of bases across the original and copy strand provides a phased digital readout. Methods are demonstrated on human genomic DNA and cell-free DNA from a blood sample of a patient with cancer. The approach is accurate, requires low DNA input and has a simple workflow and analysis pipeline. Simultaneous, phased reading of genetic and epigenetic bases provides a more complete picture of the information stored in genomes and has applications throughout biomedicine.

Hydroxymethylation profile of cell-free DNA is a biomarker for early colorectal cancer.

Early detection of cancer will improve survival rates. The blood biomarker 5-hydroxymethylcytosine has been shown to discriminate cancer. In a large covariate-controlled study of over two thousand individual blood samples, we created, tested and explored the properties of a 5-hydroxymethylcytosine-based classifier to detect colorectal cancer (CRC). In an independent validation sample set, the classifier discriminated CRC samples from controls with an area under the receiver operating characteristic curve (AUC) of 90% (95% CI [87, 93]). Sensitivity was 55% at 95% specificity. Performance was similar for early stage 1 (AUC 89%; 95% CI [83, 94]) and late stage 4 CRC (AUC 94%; 95% CI [89, 98]). The classifier could detect CRC even when the proportion of tumor DNA in blood was undetectable by other methods. Expanding the classifier to include information about cell-free DNA fragment size and abundance across the genome led to gains in sensitivity (63% at 95% specificity), with similar overall performance (AUC 91%; 95% CI [89, 94]). We confirm that 5-hydroxymethylcytosine can be used to detect CRC, even in early-stage disease. Therefore, the inclusion of 5-hydroxymethylcytosine in multianalyte testing could improve sensitivity for the detection of early-stage cancer.

Test-retest reliability of the PDQ-Carer.

INTRODUCTION: The PDQ-Carer is a 29-item measure of health-related quality of life (QoL) for use with carers of people with Parkinson's (PwP). The measure produces a profile of scores across four domains. Previous validation data indicates that the measure possesses sound psychometric properties in terms of validity and internal consistency. An additional important attribute of any measure is test-retest reliability, i.e. the ability to provide stable results over time, presuming that there has been no change in the status of the construct being measured. To date, no assessment of the test-retest reliability of the PDQ-Carer has been undertaken. METHODS: Carers of PwP were recruited via Parkinson's UK. Participants completed the PDQ-Carer online on two occasions, two weeks apart. On second administration participants answered an additional question asking how much, if at all, their QoL had changed over the two week period. Subsequent analyses focused on those carers who reported no change in their QoL. RESULTS: At first administration 142 carers fully completed the PDQ-Carer and at second administration 104 participants with no missing data responded. Seventy four of these participants (71.2%) reported no change in QoL and thus went forward to the final analysis. Intraclass correlation coefficients for each domain were calculated as follows: Social and Personal Activities .97; Anxiety and Depression .95; Self-Care .96; Stress .95 CONCLUSION: Results indicate that the PDQ-Carer demonstrates sound test-retest reliability and can be confidently used by researchers who wish to incorporate it in studies of carers of PwP.

Rationale and study protocol for the Movement Oriented Games Based Assessment (MOGBA) cluster randomized controlled trial: A complex movement skill intervention for 8-12 year old children within 'Made to Play'.

There is a positive relationship between children's movement competence and physical activity, with a further relationship established between physical activity and childhood obesity. The Movement Oriented Games Based Assessment (MOGBA) is a delivery and assessment intervention designed to improve children's complex movement skills, based on principles of motor development and assessment theories. MOGBA aims to improve children's movement competence, physical fitness and self-perceptions (physical and game) and increase children's moderate-to-vigorous physical activity (MVPA). MOGBA is to be used in the 'Made to Play' initiative, involving 105 sports and activity programs across 21 countries, involving over 25 million children. A multi-site cluster randomized controlled trial will take place across three global sites (UK, Ireland and Australia). Each site will recruit eight primary schools (four experiment, four control) with each school providing two separate classes of children from age ranges 8-12 years (Site n = ~300, total n = 904). After baseline assessments, schools will be randomly allocated to an experimental or wait-list control group. Following two half-day workshops, trained facilitators will deliver the MOGBA intervention for 9 weeks. The main intervention components include delivery of 14 games-based activities with associated assessments of children's movement and differentiation to meet children's needs by manipulating space, effort and relationships. The primary outcome of the trial is to improve children's' movement competence (The Dragon Challenge), with secondary outcomes of improving children's' in-activity and leisure-time MVPA (5-day accelerometer), physical fitness (standing long jump and push ups) and self-perceptions (physical and game). Data will be analysed using multilevel modelling approaches. The MOGBA intervention has been designed to improve children's movement competence and scalable interventions based on MOGBA could be applied across programs within the Made to Play initiative, globally. The trial is registered at the Australia New Zealand Clinical Trial Registry (ACTRN12619001320145p, 27 Sep 2019).

Development of an Exercise-Specific Parkinson's Disease Questionnaire: The PDQ-Exercise.

BACKGROUND: Exercise is now a significant and key component in the management of Parkinson's disease. However, no self-report, Parkinson's-specific measure of exercise currently exists. OBJECTIVE: To develop a patient-reported outcome measure (PROM) for use in studies and clinical trials that aim to assess the efficacy of exercise therapy for people with Parkinson's (PwP). METHODS: Participants were recruited via Parkinson's UK. To generate meaningful items, PwP participated in exploratory cognitive interviews. To pretest the items generated, PwP took part in two rounds of cognitive debrief interviews. Items were subsequently tested through an online survey that also included the eight-item Parkinson's Disease Questionnaire (PDQ-8) and Oxford Participation and Activities Questionnaire (Ox-PAQ). RESULTS: Twenty PwP were interviewed for item generation. Analyses identified issues related to adopting and maintaining exercise, resulting in the generation of 10 items. Fourteen PwP took part in subsequent cognitive debrief interviews. Following the first 10 interviews, one item was removed, and minor adjustments were made to the wording of two items. Four final interviews verified that no further adjustments were required. Consequently, nine items were included in the validation survey, which was fully completed by 398 PwP. Inspection of floor and ceiling effects resulted in the removal of two further items. A principal component analysis identified a single seven-item factor explaining 61.6% of variance. Further analyses indicated that the measure demonstrates sound reliability and validity. CONCLUSIONS: Results indicate that the PDQ-Exercise is an acceptable, reliable, and valid PROM. Further assessment of its psychometric properties is in progress. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Mortality among Hospitalized Dengue Patients with Comorbidities in Mexico, Brazil, and Colombia.

Dengue patients with comorbidities may be at higher risk of death. In this cross-sectional study, healthcare databases from Mexico (2008-2014), Brazil (2008-2015), and Colombia (2009-2017) were used to identify hospitalized dengue cases and their comorbidities. Case fatality rates (CFRs), relative risk, and odds ratios (OR) for in-hospital mortality were determined. Overall, 678,836 hospitalized dengue cases were identified: 68,194 from Mexico, 532,821 from Brazil, and 77,821 from Colombia. Of these, 35%, 5%, and 18% were severe dengue, respectively. Severe dengue and age ≥ 46 years were associated with increased risk of in-hospital mortality. Comorbidities were identified in 8%, 1%, and 4% of cases in Mexico, Brazil, and Colombia, respectively. Comorbidities increased hospitalized dengue CFRs 3- to 17-fold; CFRs were higher with comorbidities regardless of dengue severity or age. The odds of in-hospital mortality were significantly higher in those with pulmonary disorders (11.6 [95% CI 7.4-18.2], 12.7 [95% CI 9.3-17.5], and 8.0 [95% CI 4.9-13.1] in Mexico, Brazil, and Colombia, respectively), ischemic heart disease (23.0 [95% CI 6.6-79.6], 5.9 [95% CI 1.4-24.6], and 7.0 [95% CI 1.9-25.5]), and renal disease/failure (8.3 [95% CI 4.8-14.2], 8.0 [95% CI 4.5-14.4], and 9.3 [95% CI 3.1-28.0]) across the three countries; the odds of in-hospital mortality from dengue with comorbidities was at least equivalent or higher than severe dengue alone (4.5 [95% CI 3.4-6.1], 9.6 [95% CI 8.6-10.6], and 9.0 [95% CI 6.8-12.0). In conclusion, the risk of death because of dengue increases with comorbidities independently of age and/or disease severity.

Persistent homology in two-dimensional atomic networks.

The topology of two-dimensional network materials is investigated by persistent homology analysis. The constraint of two dimensions allows for a direct comparison of key persistent homology metrics (persistence diagrams, cycles, and Betti numbers) with more traditional metrics such as the ring-size distributions. Two different types of networks are employed in which the topology is manipulated systematically. In the first, comparatively rigid networks are generated for a triangle-raft model, which are representative of materials such as silica bilayers. In the second, more flexible networks are generated using a bond-switching algorithm, which are representative of materials such as graphene. Bands are identified in the persistence diagrams by reference to the length scales associated with distorted polygons. The triangle-raft models with the largest ordering allow specific bands Bn (n = 1, 2, 3, …) to be allocated to configurations of atoms separated by n bonds. The persistence diagrams for the more disordered network models also display bands albeit less pronounced. The persistent homology method thereby provides information on n-body correlations that is not accessible from structure factors or radial distribution functions. An analysis of the persistent cycles gives the primitive ring statistics, provided the level of disorder is not too large. The method also gives information on the regularity of rings that is unavailable from a ring-statistics analysis. The utility of the persistent homology method is demonstrated by its application to experimentally-obtained configurations of silica bilayers and graphene.

Web-Based and mHealth Technologies to Support Self-Management in People Living With Type 2 Diabetes: Validation of the Diabetes Self-Management and Technology Questionnaire (DSMT-Q).

BACKGROUND: A growing number of web-based and mobile health (mHealth) technologies have been developed to support type 2 diabetes self-management. Little is known about individuals' experiences with these technologies and how they support self-management. Appropriate tools are needed to understand how web-based and mHealth interventions may impact self-management. OBJECTIVE: This study aimed to develop an instrument, the Diabetes Self-Management and Technology Questionnaire (DSMT-Q), to assess self-management among people living with type 2 diabetes who use web-based and mHealth technologies. METHODS: A total of 36 candidate questionnaire items, drafted previously, were refined using cognitive debriefing interviews (n=8), expert consultation, and public patient involvement feedback. Item reduction steps were performed on survey data (n=250), and tests of validity and reliability were subsequently performed. RESULTS: Following amendments, patients and experts found 21 items relevant and acceptable for inclusion in the instrument. Survey participants included 104 (41.6%) women and 146 (58.4%) men. Two subscales with high construct validity, internal consistency, and test-retest reliability were identified: "Understanding individual health and making informed decisions" and "Confidence to reach and sustain goals." CONCLUSIONS: Analyses confirmed good psychometric properties in the DSMT-Q scales. This tool will facilitate the measurement of self-management in people living with type 2 diabetes who use web-based or mHealth technologies.

The effects of the iPlayClean education programme on doping attitudes and susceptibility to use banned substances among high-level adolescent athletes from the UK: A cluster-randomised controlled trial.

Background This study examined the effects of the iPlayClean anti-doping intervention on attitudes towards doping and susceptibility, and whether delivery mode affected the results. Methods A total of 1081 high-level UK athletes (14-18 years old, 904 males, 177 females) were cluster-randomised to the control (11 teams/organisations/schools, 314 athletes), face-to-face group presentation (8 teams/organisations/schools, 254 athletes), online (11 teams/organisations/schools, 251 athletes), or face-to-face presentation with online access (5 teams/organisations/schools, 262 athletes). Results Compared to the control group, all modes of the iPlayClean anti-doping education programme reduced favourable attitudes towards doping immediately after the intervention, which was sustained across all intervention groups 8 weeks later. All delivery modes impacted doping susceptibility immediately after the intervention, in comparison to the control group, but the effects were only sustained for the face-to-face presentation group. Conclusion Contrary to findings within previous anti-doping interventions, we have shown that doping attitudes can be changed and that the results can be sustained across all modes of delivery, 8 weeks later. Research is required to assess for how long these changes are sustained, and how often anti-doping education should be delivered to high-level athletes to reinforce clean play values.

Generalized network theory of physical two-dimensional systems.

The properties of a wide range of two-dimensional network materials are investigated by developing a generalized network theory. The methods developed are shown to be applicable to a wide range of systems generated from both computation and experiment; incorporating atomistic materials, foams, fullerenes, colloidal monolayers, and geopolitical regions. The ring structure in physical networks is described in terms of the node degree distribution and the assortativity. These quantities are linked to previous empirical measures such as Lemaître's law and the Aboav-Weaire law. The effect on these network properties is explored by systematically changing the coordination environments, topologies, and underlying potential model of the physical system.

Young People's Response to Parental Neurological Disorder: A Structured Review.

INTRODUCTION: A significant paucity of literature exists relating to the impact on children of parental neurological disorder, with the exception of multiple sclerosis. The wider literature in this field (parental cancer, depression, alcoholism, HIV/AIDS) exhibits the many potential challenges young people might experience during serious parental illness. Given this, a literature review of parental neurological disorder is long overdue. METHODS: This review is structured around the World Health Organisation (WHO) classification of neurological disorders. The WHO identifies 10 common neurological disorders; dementia, epilepsy, headache, multiple sclerosis, neuroinfections, neurological disorders associated with malnutrition, pain associated with neurological disorders, Parkinson's disease, stroke, and traumatic brain injury. A comprehensive search of the MEDLINE database was performed using key terms for each of the 10 conditions. Results for each condition were divided in to "negative", "positive and/or neutral" and "other" child responses. RESULTS: The search yielded a total of 6247 titles, of which 184 underwent a full-text assessment. Sixty-five met all eligibility criteria and were thus included in the review. A number of negative issues emerged across parental conditions including the prevalence of child mood disorders, parent-child role reversal, children's need for information on the parental condition, the importance of family cohesion, the negative effect of parental psychopathology and differences between male and female children. A limited number of positive outcomes were evident in a minority of parental conditions. Outcomes measured and methodologies employed were highly heterogeneous. CONCLUSION: Children generally respond negatively to parental neurological disorder. Responses varied between neurological disorders, suggesting the need for parental disease-specific guidance and clinical management where required.

Simplified computational model for generating biological networks.

A method to generate and simulate biological networks is discussed. An expanded Wooten-Winer-Weaire bond switching methods is proposed which allows for a distribution of node degrees in the network while conserving the mean average node degree. The networks are characterised in terms of their polygon structure and assortativities (a measure of local ordering). A wide range of experimental images are analysed and the underlying networks quantified in an analogous manner. Limitations in obtaining the network structure are discussed. A "network landscape" of the experimentally observed and simulated networks is constructed from the underlying metrics. The enhanced bond switching algorithm is able to generate networks spanning the full range of experimental observations.

Ring structure of selected two-dimensional procrystalline lattices.

Recent work has introduced the term "procrystalline" to define systems which lack translational symmetry but have an underlying high-symmetry lattice. The properties of five such two-dimensional (2D) lattices are considered in terms of the topologies of rings which may be formed from three-coordinate sites only. Parent lattices with full coordination numbers of four, five, and six are considered, with configurations generated using a Monte Carlo algorithm. The different lattices are shown to generate configurations with varied ring distributions. The different constraints imposed by the underlying lattices are discussed. Ring size distributions are obtained analytically for two of the simpler lattices considered (the square and trihexagonal nets). In all cases, the ring size distributions are compared to those obtained via a maximum entropy method. The configurations are analyzed with respect to the near-universal Lemaître curve (which connects the fraction of six-membered rings with the width of the ring size distribution) and three lattices are highlighted as rare examples of systems which generate configurations which do not map onto this curve. The assortativities are considered, which contain information on the degree of ordering of different sized rings within a given distribution. All of the systems studied show systematically greater assortativities when compared to those generated using a standard bond-switching method. Comparison is also made to two series of crystalline motifs which shown distinctive behavior in terms of both the ring size distributions and the assortativities. Procrystalline lattices are therefore shown to have fundamentally different behavior to traditional disordered and crystalline systems, indicative of the partial ordering of the underlying lattices.

The Oxford Participation and Activities Questionnaire (Ox-PAQ): development of a short form and index measure.

BACKGROUND: The Oxford Participation and Activities Questionnaire (Ox-PAQ) is a 23-item patient-reported outcome measure (PROM) theoretically grounded in the World Health Organisation International Classification of Functioning, Disability and Health. Initial validation of the Ox-PAQ identified three domains; routine activities (14 items), emotional well-being (5 items) and social engagement (4 items). The purpose of the analyses reported here were to determine whether an overall index score can be calculated from the measure, and then to determine whether a shorter form measure can replicate results on the index score. METHODS: Two surveys of people with long term conditions were undertaken. In the first study, higher order factor analysis is used to determine that a single index score can be calculated for the Ox-PAQ. Regression analyses are used to determine a sub-set of items selected for the Short Form Ox-PAQ (SF-Ox-PAQ). In the second study, results on the Ox-PAQ Single Index and SF-Ox-PAQ Single Index are compared with results from another generic measure, the EuroQol EQ-5D-5l. RESULTS: Higher order factor analysis confirmed that a single index score can be created from the Ox-PAQ. Further, linear regression indicated 14 items could reliably and accurately produce this index. The two methods of creating the index were highly correlated (ICC =0.99). The two indices were found to provide almost identical levels of correlation with EQ-5D-5L scores. CONCLUSION: Results indicate that the Ox-PAQ can be summed to provide an index score, and, furthermore, a sub set of fourteen items can very closely replicate the results gained from the original parent form.

REAL-WORLD EVIDENCE OF DENGUE BURDEN ON HOSPITALS IN MEXICO: INSIGHTS FROM THE AUTOMATED SUBSYSTEM OF HOSPITAL DISCHARGES (SAEH) DATABASE.

BACKGROUND: The incidence of dengue in Mexico has increased in recent decades. It has been suggested that dengue outbreaks may compromise treatment quality in hospitals. OBJECTIVE: The objective of the study was to quantify the burden imposed by dengue on hospital services in Mexico. METHODS: We analyzed 19.2 million records contained in the database of hospital services of the Mexican Ministry of Health between 2008 and 2014. The number of admissions due to dengue was compared to other potentially preventable hospitalizations. Hospital departments were categorized to reflect dengue-related activity as high dengue activity (HDA), low dengue activity (LDA), or zero dengue activity departments, and the impact of dengue activity on general in-hospital mortality in HDA departments was assessed. RESULTS: Dengue was the cause of more hospital admissions than most of the potentially preventable prevalent acute and chronic conditions and other infectious diseases. In HDA departments, dengue patient load was found to be a significant risk factor for overall in-hospital mortality. There was an approximately two-fold higher dengue case-fatality rate in LDA versus HDA departments, irrespective of dengue severity. CONCLUSIONS: This study confirms that dengue is an important cause of hospitalization in Mexico and highlights the impact of dengue activity not only on dengue case-fatality rate but also on the overall in-hospital mortality.

Measuring improvement in health-status with the Oxford Participation and Activities Questionnaire (Ox-PAQ).

Background: The Oxford Participation and Activities Questionnaire (Ox-PAQ) is a recently validated 23-item generic patient reported outcome measure that is theoretically grounded in the World Health Organisation International Classification of Functioning, Disability and Health (ICF), as well as fully FDA compliant. The measure comprises three domains, Routine Activities (14 items), Emotional Well-Being (5 items) and Social Engagement (4 items), and has been shown to be both valid and reliable. The aim of this study was to make a preliminary assessment of the sensitivity to the change of the Ox-PAQ. Methods: Three hundred and seventy three people with either chronic pulmonary obstructive disease, motor neurone disease, multiple sclerosis or Parkinson's disease completed the Ox-PAQ electronically on two occasions, six months apart. Participants completed an additional four questions during the second administration of the Ox-PAQ in order to assess any relevant changes since baseline. For each of the three Ox-PAQ domains, the minimally important difference (MID) and effect size (ES) was calculated from those participants indicating small, but meaningful positive improvement. Results: Two hundred and ninety respondents were entered into the final analysis, 77.74% of the original sample. For those indicating "slight improvement" in Routine Activities (n=19), an MID of 7.51 and an ES of 0.32 was calculated. For Emotional Well-Being (n=26), the MID was 10.77 and the ES 0.44. For Social Engagement (n=16), the MID was 5.47 and the ES 0.28. Conclusion: Data presented provides MID improvement and effect sizes for Ox-PAQ domains that will act as preliminary guidance for those powering clinical trials assessing activity and participation. Future research with larger samples will provide further sensitivity to change data for the Ox-PAQ.

Real-world evidence of dengue burden on hospitals in mexico: insights from the automated subsystem of hospital discharges (saeh) database

Abstract Background The incidence of dengue in Mexico has increased in recent decades. It has been suggested that dengue outbreaks may compromise treatment quality in hospitals. Objective The objective of the study was to quantify the burden imposed by dengue on hospital services in Mexico. Methods We analyzed 19.2 million records contained in the database of hospital services of the Mexican Ministry of Health between 2008 and 2014. The number of admissions due to dengue was compared to other potentially preventable hospitalizations. Hospital departments were categorized to reflect dengue-related activity as high dengue activity (HDA), low dengue activity (LDA), or zero dengue activity departments, and the impact of dengue activity on general in-hospital mortality in HDA departments was assessed. Results Dengue was the cause of more hospital admissions than most of the potentially preventable prevalent acute and chronic conditions and other infectious diseases. In HDA departments, dengue patient load was found to be a significant risk factor for overall in-hospital mortality. There was an approximately two-fold higher dengue case-fatality rate in LDA versus HDA departments, irrespective of dengue severity. Conclusions This study confirms that dengue is an important cause of hospitalization in Mexico and highlights the impact of dengue activity not only on dengue case-fatality rate but also on the overall in-hospital mortality.

Comparison of model estimates from an intra-city land use regression model with a national satellite-LUR and a regional Bayesian Maximum Entropy model, in estimating NO2 for a birth cohort in Sydney, Australia.

BACKGROUND: Methods for estimating air pollutant exposures for epidemiological studies are becoming more complex in an effort to minimise exposure error and its associated bias. While land use regression (LUR) modelling is now an established method, there has been little comparison between LUR and other recent, more complex estimation methods. Our aim was to develop a LUR model to estimate intra-city exposures to nitrogen dioxide (NO2) for a Sydney cohort, and to compare those with estimates from a national satellite-based LUR model (Sat-LUR) and a regional Bayesian Maximum Entropy (BME) model. METHODS: Satellite-based LUR and BME estimates were obtained using existing models. We used methods consistent with the European Study of Cohorts for Air Pollution Effects (ESCAPE) methodology to develop LUR models for NO2 and NOx. We deployed 46 Ogawa passive samplers across western Sydney during 2013/2014 and acquired data on land use, population density, and traffic volumes for the study area. Annual average NO2 concentrations for 2013 were estimated for 947 addresses in the study area using the three models: standard LUR, Sat-LUR and a BME model. Agreement between the estimates from the three models was assessed using interclass correlation coefficient (ICC), Bland-Altman methods and correlation analysis (CC). RESULTS: The NO2 LUR model predicted 84% of spatial variability in annual mean NO2 (RMSE: 1.2 ppb; cross-validated R2: 0.82) with predictors of major roads, population and dwelling density, heavy traffic and commercial land use. A separate model was developed that captured 92% of variability in NOx (RMSE 2.3 ppb; cross-validated R2: 0.90). The annual average NO2 concentrations were 7.31 ppb (SD: 1.91), 7.01 ppb (SD: 1.92) and 7.90 ppb (SD: 1.85), for the LUR, Sat-LUR and BME models respectively. Comparing the standard LUR with Sat-LUR NO2 cohort estimates, the mean estimates from the LUR were 4% higher than the Sat-LUR estimates, and the ICC was 0.73. The Pearson's correlation coefficients (CC) for the LUR vs Sat-LUR values were r = 0.73 (log-transformed data) and r = 0.69 (untransformed data). Comparison of the NO2 cohort estimates from the LUR model with the BME blended model indicated that the LUR mean estimates were 8% lower than the BME estimates. The ICC for the LUR vs BME estimates was 0.73. The CC for the logged LUR vs BME estimates was r = 0.73 and for the unlogged estimates was r = 0.69. CONCLUSIONS: Our LUR models explained a high degree of spatial variability in annual mean NO2 and NOx in western Sydney. The results indicate very good agreement between the intra-city LUR, national-scale sat-LUR, and regional BME models for estimating NO2 for a cohort of children residing in Sydney, despite the different data inputs and differences in spatial scales of the models, providing confidence in their use in epidemiological studies.

Controlling disorder in two-dimensional networks.

Two-dimensional networks are constructed by reference to a distribution of ring sizes and a parameter (α) which controls the preferred nearest-neighbour spatial correlations, and allows network topologies to be varied in a systematic manner. Our method efficiently utilizes the dual lattice and allows the range of physically-realisable configurations to be established and compared to networks observed for a wide range of real and model systems. Three different ring distributions are considered; a system containing five-, six- and seven-membered rings only (a proxy for amorphous graphene), the configuration proposed by Zachariasen in 1932, and a configuration observed experimentally for thin (near-2D) films of SiO2. The system energies are investigated as a function of the network topologies and the range of physically-realisable structures established and compared to known experimental results. The limits on the parameter α are discussed and compared to previous results. The evolution of the network structure as a function of topology is discussed in terms of the ring-ring pair distribution functions.