The hidden burden of adult allergic rhinitis : UK healthcare resource utilisation survey

Funding Funding for this survey was provided by Meda Pharma.Peer reviewedPublisher PD

Risk factors for vulnerable youth in urban townships in South Africa: the potential contribution of reactive attachment disorder

Reactive attachment disorder (RAD) is a psychiatric disorder developing in early or middle childhood as a consequence of significant failures in the caregiving environment. RAD results in children failing to relate socially, either by exhibiting markedly inhibited behaviour or by indiscriminate social behaviour and is associated with significant socio-behavioural problems in the longer term. This study examined RAD in South Africa, a setting with high environmental risks. We recruited a sub-sample of 40 10-year-old children from a cohort enrolled during pregnancy for whom early attachment status was known. Children were purposefully selected to represent the four attachment categories using the data available on the strange situation procedure (SSP) at 18 months. The Manchester Child Attachment Story Task (MCAST) assessed current attachment and RAD was diagnosed using a standardised assessment package. A high proportion of the children (5/40% or 12.5%) fulfilled diagnostic criteria for RAD; all were boys and were displaying the disinhibited type. SSP classification at 18 months was not significantly associated with RAD symptoms at age of 10 years, while current MCAST classifications were. This suggests that children in this sample are at much higher risk of RAD than in high-income populations, and despite a fairly typical attachment distribution in this population at 18 months, RAD was evidenced in later childhood and associated with current attachment disorganisation. The strengths of this research include its longitudinal nature and use of diagnostic assessments. Given increasing evidence that RAD is relatively stable over time and introduces longer term socio-behavioural risks; the high rate of RAD in this sample (12.5%) highlights potential developmental threats to children in low- and middle-income countries (LMICs). Our results should be interpreted with caution given sample size and risk of selection bias. Further research is needed to confirm these findings

Adult neurogenesis, mental health, and mental illness: hope or hype?

Psychiatric and neurologic disorders take an enormous toll on society. Alleviating the devastating symptoms and consequences of neuropsychiatric disorders such as addiction, depression, epilepsy, and schizophrenia is a main force driving clinical and basic researchers alike. By elucidating these disease neuromechanisms, researchers hope to better define treatments and preventive therapies. Research suggests that regulation of adult hippocampal neurogenesis represents a promising approach to treating and perhaps preventing mental illness. Here we appraise the role of adult hippocampal neurogenesis in major psychiatric and neurologic disorders within the essential framework of recent progress made in understanding "normal" adult neurogenesis. Topics addressed include the following: the life cycle of an adult hippocampal stem cell and the implications for aging; links between learning and hippocampal neurogenesis; the reciprocal relationship between cocaine self-administration and adult hippocampal neurogenesis; the role of adult neurogenesis in an animal model of depression and response to antidepressant exposure; the impact of neonatal seizures on dentate gyrus neurogenesis; and the contribution of a schizophrenia-susceptibility gene to adult hippocampal neurogenesis. These topics are discussed in light of the regulation of adult neurogenesis, the relationship to normal neurogenesis in adulthood and aging, and, importantly, the manipulation of neurogenesis to promote mental health and treat mental illness

Association between cognitive performance and cortical glucose metabolism in patients with mild Alzheimer's disease

Background: Neuronal and synaptic function in Alzheimer's disease (AD) is measured in vivo by glucose metabolism using positron emission tomography (PET). Objective: We hypothesized that neuronal activation as measured by PET is a more sensitive index of neuronal dysfunction than activity during rest. We investigated if the correlations between dementia severity as measured with the Mini Mental State Examination (MMSE) and glucose metabolism are an artifact of brain atrophy. Method: Glucose metabolism was measured using {[}F-18]fluorodeoxyglucose PET during rest and activation due to audiovisual stimulation in 13 mild to moderate AD patients (MMSE score >= 17). PET data were corrected for brain atrophy. Results: In the rest condition, glucose metabolism was correlated with the MMSE score primarily within the posterior cingulate and parietal lobes. For the activation condition, additional correlations were within the primary and association audiovisual areas. Most local maxima remained significant after correcting for brain atrophy. Conclusion: PET activity measured during audiovisual stimulation was more sensitive to functional alterations in glucose metabolism in AD patients compared to the resting PET. The association between glucose metabolism and MMSE score was not dependent on brain atrophy. Copyright (C) 2005 S. Karger AG, Basel

The Radio Afterglow and the Host Galaxy of the X-Ray Rich GRB 981226

We report the discovery of a radio transient VLA 232937.2-235553, coincident with the proposed X-ray afterglow for the gamma-ray burst GRB 981226. This GRB has the highest ratio of X-ray to gamma-ray fluence of all the GRBs detected by BeppoSAX so far and yet no corresponding optical transient was detected. The radio light curve of VLA 232937.2-235553 is qualitatively similar to that of several other radio afterglows. At the sub-arcsecond position provided by the radio detection, optical imaging reveals an extended R=24.9 mag object, which we identify as the host galaxy of GRB 981226. Afterglow models which invoke a jet-like geometry for the outflow or require an ambient medium with a radial density dependence, such as that produced by a wind from a massive star, are both consistent with the radio data. Furthermore, we show that the observed properties of the radio afterglow can explain the absence of an optical transient without the need for large extinction local to the GRB.Comment: Accepted for publication in the Astrophysical Journal Letters. Thirteen pages. Three Postscript figure

Calculating partial expected value of perfect information via Monte Carlo sampling algorithms

Partial expected value of perfect information (EVPI) calculations can quantify the value of learning about particular subsets of uncertain parameters in decision models. Published case studies have used different computational approaches. This article examines the computation of partial EVPI estimates via Monte Carlo sampling algorithms. The mathematical definition shows 2 nested expectations, which must be evaluated separately because of the need to compute a maximum between them. A generalized Monte Carlo sampling algorithm uses nested simulation with an outer loop to sample parameters of interest and, conditional upon these, an inner loop to sample remaining uncertain parameters. Alternative computation methods and shortcut algorithms are discussed and mathematical conditions for their use considered. Maxima of Monte Carlo estimates of expectations are biased upward, and the authors show that the use of small samples results in biased EVPI estimates. Three case studies illustrate 1) the bias due to maximization and also the inaccuracy of shortcut algorithms 2) when correlated variables are present and 3) when there is nonlinearity in net benefit functions. If relatively small correlation or nonlinearity is present, then the shortcut algorithm can be substantially inaccurate. Empirical investigation of the numbers of Monte Carlo samples suggests that fewer samples on the outer level and more on the inner level could be efficient and that relatively small numbers of samples can sometimes be used. Several remaining areas for methodological development are set out. A wider application of partial EVPI is recommended both for greater understanding of decision uncertainty and for analyzing research priorities

Post-Transcriptional Dysregulation by miRNAs Is Implicated in the Pathogenesis of Gastrointestinal Stromal Tumor [GIST]

peer-reviewedIn contrast to adult mutant gastrointestinal stromal tumors [GISTs], pediatric/wild-type GISTs remain poorly understood overall, given their lack of oncogenic activating tyrosine kinase mutations. These GISTs, with a predilection for gastric origin in female patients, show limited response to therapy with tyrosine kinase inhibitors and generally pursue a more indolent course, but still may prove fatal. Defective cellular respiration appears to underpin tumor development in these wild-type cases, which as a group lack expression of succinate dehydrogenase [SDH] B, a surrogate marker for respiratory chain metabolism. Yet, only a small subset of the wild-type tumors show mutations in the genes coding for the SDH subunits [SDHx]. To explore additional pathogenetic mechanisms in these wild-type GISTs, we elected to investigate posttranscriptional regulation of these tumors by conducting microRNA (miRNA) profiling of a mixed cohort of 73 cases including 18 gastric pediatric wild-type, 25 (20 gastric, 4 small bowel and 1 retroperitoneal) adult wild-type GISTs and 30 gastric adult mutant GISTs. By this approach we have identified distinct signatures for GIST subtypes which correlate tightly with clinico-pathological parameters. A cluster of miRNAs on 14q32 show strikingly different expression patterns amongst GISTs, a finding which appears to be explained at least in part by differential allelic methylation of this imprinted region. Small bowel and retroperitoneal wild-type GISTs segregate with adult mutant GISTs and express SDHB, while adult wildtype gastric GISTs are dispersed amongst adult mutant and pediatric wild-type cases, clustering in this situation on the basis of SDHB expression. Interestingly, global methylation analysis has recently similarly demonstrated that these wild-type, SDHB-immunonegative tumors show a distinct pattern compared with KIT and PDGFRA mutant tumors, which as a rule do express SDHB. All cases with Carney triad within our cohort cluster together tightly.Funding was obtained from the Medical Research Charities Group (http://www.mrcg.ie/) and Health Research Board of Ireland (http://www.hrb.ie) (MO’S), The Children’s Medical and Research Foundation (http://www.cmrf.org) (MO’S), the GIST Cancer Awareness Foundation [GCAF] (http://www. gistawareness.org/)(MO’S), and research grants from the Life Raft Group (http://www.liferaftgroup.org/)(MD-R) and from the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (http://www.fwo.be/)(grant # G.0286.05 MD-R)