Distinct methylation patterns in genes that affect mitochondrial function are associated with kidney disease in blood-derived DNA from individuals with Type 1 diabetes

AIMS: Epigenetic modifications, such as DNA methylation, can influence the risk of developing kidney disease. We studied methylation profiles in genes related to mitochondrial function to assess whether differences in these epigenetic features were associated with diabetic kidney disease in people with Type 1 diabetes.

METHODS: A case-control association study was undertaken (n = 196 individuals with diabetic kidney disease vs. n = 246 individuals without renal disease). Participants were White and diagnosed with Type 1 diabetes before 31 years of age. Genes that encode mitochondrial proteins (n = 780) were downloaded from mitoproteome. org. DNA methylation profiles from blood-derived DNA were generated using the Illumina Infinium HumanMethylation450 (262 samples) and Illumina Infinium HumanMethylation27 (192 samples) arrays. Beta values (β) were calculated and quality control was conducted, including evaluating blind duplicate DNA samples.

RESULTS: Fifty-four Cytosine-phosphate-Guanine probes across 51 unique genes were significantly associated (P ≤ 10(-8) ) with diabetic kidney disease across both the 450K and the 27K methylation arrays. A subanalysis, employing the 450K array, identified 755 Cytosine-phosphate-Guanine probes in 374 genes that were significantly associated (P ≤ 10(-8) ) with end-stage renal disease. Forty-six of the top-ranked variants for diabetic kidney disease were also identified as being differentially methylated in individuals with end-stage renal disease. The largest change in methylation (Δβ = 0.2) was observed for cg03169527 in the TAMM41 gene, chromosome 3p25.2. Three genes, PMPCB, TSFM and AUH, were observed with differential methylation at multiple Cytosine-phosphate-Guanine sites each (P < 10(-12) ).

CONCLUSIONS: Differential methylation in genes that influence mitochondrial function are associated with kidney disease in individuals with Type 1 diabetes. 

Psychotropic prescribing patterns among adolescents in Northern Ireland presenting with psychotic symptoms during a 5-year period

Objective: To report new prescriptions of psychotropic medications among adolescents presenting with new onset psychotic symptoms during a 5-year period.
Methods: The Northern Ireland Early Onset Psychosis Study is a naturalistic longitudinal observational study of patients with an early onset first psychotic episode. All patients aged <18 years presenting to specialist mental health services across Northern Ireland with new onset psychotic symptoms between 2001 and 2006 were recruited (n = 113). Clinical case notes were analysed retrospectively for details of subsequent treatment with psychotropic medications.
Results: A total of 100 patients (88.5%) were prescribed some form of psychotropic medication. Over three-quarters of patients received an antipsychotic as their first medication. Risperidone (45.8%), olanzapine (24.0%) and chlorpromazine (12.5%) were the most commonly prescribed first-line antipsychotic medications. Of a total of 160 antipsychotic prescriptions,81 (50.6%) were off-label. Prescriptions were most likely to have been deemed off-label owing to medications not being licensed in under-18s (71.6% of off-label prescriptions) but other reasons were medications being used outsidelicensed age ranges (23.5%) and outside licensed indications (4.9%).
Conclusions: This is the first study examining psychotropic prescribing patterns in a complete sample of all children and adolescents presenting with early onset psychotic episodes in a single geographical area. The observation of risperidoneas the most commonly prescribed antipsychotic was in keeping with previous studies in child and adolescent populations. Rates of off-label prescribing were lower than previously observed although our study was the first to investigateoff-label prescribing solely in children and adolescents presenting with psychotic symptoms.

Control Patterns in Contracting-Out Relationships: It Matters What You Do, Not Who You Are

The contracting-out of public services has often been accompanied by a strong academic focus on the emergence of new governance forms, and a general neglect of the processes and practices through which contracted-out services are controlled and monitored. To fill this gap, we draw on contracting-out and inter-organizational control literatures to explore the adoption of control mechanisms for public service provision at the municipal level and the variables that can explain their choice. Our results, based on a survey of Italian municipalities, show that in the presence of contracting-out, market-, hierarchy- and trust-based controls display different intensities, can co-exist and are explained by different variables. Service characteristics are more effective in explaining market- and hierarchy-based controls than relationship characteristics. Trust-based controls are the most widespread, but cannot be explained by the variables traditionally identified in contracting-out and inter-organizational control studies.

Contribution of rarity and commonness to patterns of species richness

There is little understanding in ecology as to how biodiversity patterns emerge from the distribution patterns of individual species. Here we consider the question of the contributions of rare (restricted range) and common (widespread) species to richness patterns. Considering a species richness pattern, is most of the spatial structure, in terms of where the peaks and troughs of diversity lie, caused by the common species or the rare species (or neither)? Using southern African and British bird richness patterns, we show here that commoner species are most responsible for richness patterns. While rare and common species show markedly different species richness patterns, most spatial patterning in richness is caused by relatively few, more common, species. The level of redundancy we found suggests that a broad understanding of what determines the majority of spatial variation in biodiversity may be had by considering only a minority of species.

Coherence and discontinuity in the scaling of species' distribution patterns

The spatial distribution of a species can be characterized at many different spatial scales, from fine-scale measures of local population density to coarse-scale geographical-range structure. Previous studies have shown a degree of correlation in species' distribution patterns across narrow ranges of scales, making it possible to predict fine-scale properties from coarser-scale distributions. To test the limits of such extrapolation, we have compiled distributional information on 16 species of British plants, at scales ranging across six orders of magnitude in linear resolution (1 in to 100 km). As expected, the correlation between patterns at different spatial scales tends to degrade as the scales become more widely separated. There is, however, an abrupt breakdown in cross-scale correlations across intermediate (ca. 0.5 km) scales, suggesting that local and regional patterns are influenced by essentially non-overlapping sets of processes. The scaling discontinuity may also reflect characteristic scales of human land use in Britain, suggesting a novel method for analysing the 'footprint' of humanity on a landscape.

VIEWING LEED PATTERNS AS ELECTRON HOLOGRAMS

It is shown theoretically that LEED patterns from ordered overlayer systems bear a strong relationship to electron holograms, and that phase information is recorded in the diffraction intensities. It is, therefore, possible to obtain structural information by direct holographic inversion from conventional LEED I-V spectra.

HOLOGRAPHIC IMAGES OF IODINE ATOMS ON A SILVER SURFACE FROM ELECTRON-EMISSION PATTERNS

BARTON 1 has suggested that photoelectron interference patterns may be used directly as holograms to obtain atomic-resolution images of surface structures. Bulk structures have been obtained previously by this means from experimental patterns of high-energy Kikuchi(quasi-elastically scattered) and Auger electrons 2,3. Here we test the feasibility of this technique for determination of surface structures using Auger intensity patterns obtained 4,5 from iodine chemisorbed on a pseudomorphic silver monolayer on Pt{111}. By direct numerical holographic inversion, we obtain three-dimensional images which show that iodine adatoms are located in hollows of 3-fold symmetry on the surface. The images yield the site symmetry with good atomic resolution in the surface plane, but suffer from poor resolution along the Ag-I axis. We anticipate that data with better angular resolution obtained at low temperatures would improve the spatial resolution of such images.

A study exploring disordered eating patterns in first-year university students: student and service needs

This qualitative study explored disordered eating in a small group of first-year undergraduate students and addresses a gap in the literature by exploring their lived experience.

Aims: To better understand student’s needs in those experiencing or at risk of developing disordered eating during their first year at university and to illustrate what support mechanisms and services are required to better support students experiencing or at risk during their first year at university.

Conclusion: The University could further develop its outreach to new students with a more consistently supportive programme providing better facilities and training for stress appraisal and coping and more support via student buddying. The University could also extend its programme on positive mental health in an attempt to better inform on disordered eating and to reduce a sense of stigma within the student population. Personal tutors and student health care facilities need to be consistently trained in the understanding and person centred approach to students experiencing disordered eating, particularly the sub-clinical group. In addition the University could consider some small changes and adaptations to the refectory eating areas to better facilitate students who may be at risk from disordered eating. Finally the University could perhaps better use the potentially liminal period within the first few months of student's arrival at university (a new beginning) to help embed a program to develop a stronger sense of coherence and well-being.

Temporal and spatial patterns in α- and γ-hexachlorocyclohexane concentrations in industrially contaminated rivers

Fluxes of HCH isomers α- and γ-HCH dynamics were determined in four industrial U.K. rivers feeding the North Sea. Sampling was conducted weekly basis over a 2-year period. This was complemented by discrete studies of events where two hourly sampling periods were used to investigate the fine time scale dynamics of fluxes. Two intensively industrialized rivers had average isomer concentrations of ~20 ng L^-1 for both isomers, while average concentrations in the two less industrialized rivers ranged between 1.5 and 5.0 ng L^-1. α-HCH concentrations showed no strong temporal patterns on any river, which contrasts with γ-HCH levels that increased considerably during late summer/early autumn following sustained periods of low river flow. Sampling during high river flow events on rivers with differing HCH pollution histories both showed the same dynamics in HCH isomer concentrations. γ-HCH concentrations decreased 4-fold during events while α-HCH-concentrations stayed constant. The increases in γ-HCH concentrations under low flow conditions and the rapid dilution of this isomer during events indicate that γ-HCH has current inputs to these river systems. It was calculated that these four rivers export 30.8 kg yr^-1 of γ-HCH and 14.8 kg yr^-1 of α-HCH to the North Sea.