Differences in onset and abuse/dependence episodes between prescription opioids and heroin: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

OBJECTIVES: To examine patterns of onset and abuse/dependence episodes of prescription opioid (PO) and heroin use disorders in a national sample of adults, and to explore differences by gender and substance abuse treatment status. METHODS: Analyses of data from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093). RESULTS: Of all respondents, 5% (n = 1815) reported a history of nonmedical PO use (NMPOU) and 0.3% (n = 150) a history of heroin use. Abuse was more prevalent than dependence among NMPOUs (PO abuse, 29%; dependence, 7%) and heroin users (heroin abuse, 63%; dependence, 28%). Heroin users reported a short mean interval from first use to onset of abuse (1.5 years) or dependence (2.0 years), and a lengthy mean duration for the longest episode of abuse (66 months) or dependence (59 months); the corresponding mean estimates for PO abuse and dependence among NMPOUs were 2.6 and 2.9 years, respectively, and 31 and 49 months, respectively. The mean number of years from first use to remission from the most recent episode was 6.9 years for PO abuse and 8.1 years for dependence; the mean number of years from first heroin use to remission from the most recent episode was 8.5 years for heroin abuse and 9.7 years for dependence. Most individuals with PO or heroin use disorders were remitted from the most recent episode. Treated individuals, whether their problem was heroin or POs, tended to have a longer mean duration of an episode than untreated individuals. CONCLUSION: Periodic remissions from opioid or heroin abuse or dependence episodes occur commonly but take a long time. Timely and effective use of treatment services are needed to mitigate the many adverse consequences from opioid/heroin abuse and dependence.

A finite volume unstructured mesh approach to dynamic fluid–structure interaction: an assessment of the challenge of predicting the onset of flutter

Computational modelling of dynamic fluid–structure interaction (DFSI) is a considerable challenge. Our approach to this class of problems involves the use of a single software framework for all the phenomena involved, employing finite volume methods on unstructured meshes in three dimensions. This method enables time and space accurate calculations in a consistent manner. One key application of DFSI simulation is the analysis of the onset of flutter in aircraft wings, where the work of Yates et al. [Measured and Calculated Subsonic and Transonic Flutter Characteristics of a 45° degree Sweptback Wing Planform in Air and Freon-12 in the Langley Transonic Dynamic Tunnel. NASA Technical Note D-1616, 1963] on the AGARD 445.6 wing planform still provides the most comprehensive benchmark data available. This paper presents the results of a significant effort to model the onset of flutter for the AGARD 445.6 wing planform geometry. A series of key issues needs to be addressed for this computational approach. • The advantage of using a single mesh, in order to eliminate numerical problems when applying boundary conditions at the fluid-structure interface, is counteracted by the challenge of generating a suitably high quality mesh in both the fluid and structural domains. • The computational effort for this DFSI procedure, in terms of run time and memory requirements, is very significant. Practical simulations require even finer meshes and shorter time steps, requiring parallel implementation for operation on large, high performance parallel systems. • The consistency and completeness of the AGARD data in the public domain is inadequate for use in the validation of DFSI codes when predicting the onset of flutter.

Multiscale modeling of the onset of freckle formation during vacuum arc remelting

A multiscale model for the Vacuum Arc Remelting process (VAR) was developed to simulate dendritic microstructures during solidification and investigate the onset of freckle formation. On the macroscale, a 3D multi-physics model of VAR was used to study complex physical phenomena, including liquid metal flow with turbulence, heat transfer, and magnetohydrodynamics. The results showed that unsteady fluid flow in the liquid pool caused significant thermal perturbation at the solidification front. These results were coupled into a micromodel to simulate dendritic growth controlled by solute diffusion, including local remelting. The changes in Rayleigh number as the microstructure remelts was quantified to provide an indicator of when fluid flow channels (i.e. freckles) will initiate in the mushy zone. By examining the simulated microstructures, it was found that the Rayleigh number increased more than 300 times during remelting, which suggests that thermal perturbation could be responsible for the onset of freckle formation.

Art and Social Work: an intervention programme for transforming society’s vision to include people with early-onset dementia and Alzheimer’s

This paper presents a program centred on arts and education as tools in social work for the inclusion of people with earlyonset dementia and Alzheimer’s. The objective of the programme is to eradicate the stigma and myths associated with the disease.The program is part of the Junta de Castilla y León and the European Social Fund’s ARS Project (Arte y Salud Alzheimer; Alzheimer’s Art & Health). The programme presents a series of evaluated artistic and educational activities that can be undertaken by people in the early stages of Alzheimer’s disease and that can also be used by caregivers and family when working with this group of people, with the aim of improving their wellbeing, self-esteem and quality of life.

Sequence variation in the CHAT locus shows no association with late-onset Alzheimer's disease

There is substantial evidence for a susceptibility gene for late-onset Alzheimer's disease (AD) on chromosome 10. One of the characteristic features of AD is the degeneration and dysfunction of the cholinergic system. The genes encoding choline acetyltransferase (ChAT) and its vesicular transporter (VAChT), CHAT and SLC18A3 respectively, map to the linked region of chromosome 10 and are therefore both positional and obvious functional candidate genes for late-onset AD. We have screened both genes for sequence variants and investigated each for association with late-onset AD in up to 500 late-onset AD cases and 500 control DNAs collected in the UK. We detected a total of 17 sequence variants. Of these, 14 were in CHAT, comprising three non-synonymous variants (D7N in the S exon, A120T in exon 5 and L243F in exon 8), one synonymous change (H547H), nine single-nucleotide polymorphisms in intronic, untranslated or promoter regions, and a variable number of tandem repeats in intron 7. Three non-coding SNPs were detected in SLC18A3. None demonstrated any reproducible association with late-onset AD in our samples. Levels of linkage disequilibrium were generally low across the CHAT locus but two of the coding variants, D7N and A120T, proved to be in complete linkage disequilibrium.

SOCS3 regulates onset and maintenance of TH2- mediated allergic responses

Members of the suppressor of cytokine signaling (SOCS) family are involved in the pathogenesis of many inflammatory diseases. SOCS-3 is predominantly expressed in T-helper type 2 (TH2) cells, but its role in TH2-related allergic diseases remains to be investigated. In this study we provide a strong correlation between SOCS-3 expression and the pathology of asthma and atopic dermatitis, as well as serum IgE levels in allergic human patients. SOCS-3 transgenic mice showed increased TH2 responses and multiple pathological features characteristic of asthma in an airway hypersensitivity model system. In contrast, dominant-negative mutant SOCS-3 transgenic mice, as well as mice with a heterozygous deletion of Socs3, had decreased TH2 development. These data indicate that SOCS-3 has an important role in regulating the onset and maintenance of TH2-mediated allergic immune disease, and suggest that SOCS-3 may be a new therapeutic target for the development of antiallergic drugs.

Lack of MEF2A Δ7aa mutation in Irish families with early onset ischaemic heart disease, a family based study

Background: Ischaemic heart disease (IHD) is a complex disease due to the combination of environmental and genetic factors. Mutations in the MEF2A gene have recently been reported in patients with IHD. In particular, a 21 base pair deletion (Δ7aa) in the MEF2A gene was identified in a family with an autosomal dominant pattern of inheritance of IHD. We investigated this region of the MEF2A gene using an Irish family-based study, where affected individuals had early-onset IHD. Methods: A total of 1494 individuals from 580 families were included (800 discordant sib-pairs and 64 parent-child trios). The Δ7aa region of the MEF2A gene was investigated based on amplicon size. Results: The Δ7aa mutation was not detected in any individual. Variation in the number of CAG (glutamate) and CCG (proline) residues was detected in a nearby region. However, this was not found to be associated with IHD. Conclusion: The Δ7aa mutation was not detected in any individual within the study population and is unlikely to play a significant role in the development of IHD in Ireland. Using family-based tests of association the number of tri-nucleotide repeats in a nearby region of the MEF2A gene was not associated with IHD in our study group. © 2006 Horan et al; licensee BioMed Central Ltd.

Higher incidence of childhood-onset type 1 diabetes mellitus in remote areas: a UK regional small-area analysis

Aims/hypothesis: We investigated the association between the incidence of type 1 diabetes mellitus and remoteness (a proxy measure for exposure to infections) using recently developed techniques for statistical analysis of small-area data.

Subjects, materials and methods: New cases in children aged 0 to 14 years in Northern Ireland were prospectively registered from 1989 to 2003. Ecological analysis was conducted using small geographical units (582 electoral wards) and area characteristics including remoteness, deprivation and child population density. Analysis was conducted using Poisson regression models and Bayesian
hierarchical models to allow for spatially correlated risks that were potentially caused by unmeasured explanatory variables.

Results: In Northern Ireland between 1989 and 2003, there were 1,433 new cases of type 1 diabetes, giving a directly standardised incidence rate of 24.7 per 100,000 personyears. Areas in the most remote fifth of all areas had a significantly (p=0.0006) higher incidence of type 1 diabetes mellitus (incidence rate ratio=1.27 [95% CI 1.07, 1.50]) than those in the most accessible fifth of all areas. There was also a higher incidence rate in areas that were less deprived (p<0.0001) and less densely populated (p=0.002). After adjustment for deprivation and additional adjustment for child population density the association between diabetes and remoteness remained significant (p=0.01 and p=0.03, respectively).

Conclusions/interpretation: In Northern Ireland, there is evidence that remote areas experience higher rates of type 1 diabetes mellitus. This could reflect a reduced or delayed exposure to infections, particularly early in life, in these areas.