A Prospective Longitudinal Assessment of Medical Records for Diagnostic Substitution among Subjects Diagnosed with a Pervasive Developmental Disorder in the United States

Background: Previously, investigators suggested that diagnostic substitution from other diagnoses, e.g., mental retardation (MR) and/or cerebral palsy (CP) to pervasive developmental disorder (PDD) is a driving factor behind increases in PDD. This study evaluated potential diagnostic substitution among subjects diagnosed with PDD vs MR or CP by examining birth characteristic overlap.Methods: SAS® and StatsDirect software examined medical records for subjects within the Vaccine Safety Datalink (VSD) database who were Health Maintenance Organization (HMO)-enrolled from birth until diagnosed with an International Classification of Disease, 9th revision (ICD-9) outcome of PDD (299.xx, n=84), CP (343.xx, n=300), or MR (317.xx, 318.xx, or 319.xx, n=51).Results: Subjects with PDD had significantly (p<0.01) increased: male/female ratio (PDD=5.5 vs CP=1.5 or MR=1.3), mean age of initial diagnosis in years (PDD=3.13 vs CP=1.09 or MR=1.62), mean gestational age in weeks at birth (PDD=38.73 vs CP=36.20 or MR=34.84), mean birth weight in grams (PDD=3,368 vs CP=2,767 or MR=2,406), and mean Appearance-Pulse-Grimace-Activity-Respiration (APGAR) scores at 1 minute (PDD=7.82 vs CP=6.37 or MR=6.76) and 5 minutes (PDD=8.77 vs CP=7.92 or MR=8.04), as compared to subjects diagnosed with CP or MR.Conclusion: This study suggests diagnostic substitution cannot fully explain increased PDD prevalence during the 1990s within the United States

A longitudinal cohort study of the relationship between Thimerosal-containing hepatitis B vaccination and specific delays in development in the United States: Assessment of attributable risk and lifetime care costs

AbstractEpidemiological evidence suggests a link between mercury (Hg) exposure from Thimerosal-containing vaccines and specific delays in development. A hypothesis-testing longitudinal cohort study (n=49,835) using medical records in the Vaccine Safety Datalink (VSD) was undertaken to evaluate the relationship between exposure to Hg from Thimerosal-containing hepatitis B vaccines (T-HBVs) administered at specific intervals in the first 6months of life and specific delays in development [International Classification of Disease, 9th revision (ICD-9): 315.xx] among children born between 1991 and 1994 and continuously enrolled from birth for at least 5.81years. Infants receiving increased Hg doses from T-HBVs administered within the first month, the first 2months, and the first 6months of life were significantly more likely to be diagnosed with specific delays in development than infants receiving no Hg doses from T-HBVs. During the decade in which T-HBVs were routinely recommended and administered to US infants (1991–2001), an estimated 0.5–1million additional US children were diagnosed with specific delays in development as a consequence of 25μg or 37.5μg organic Hg from T-HBVs administered within the first 6months of life. The resulting lifetime costs to the United States may exceed $1 trillion

Seizure prediction : ready for a new era

Acknowledgements: The authors acknowledge colleagues in the international seizure prediction group for valuable discussions. L.K. acknowledges funding support from the National Health and Medical Research Council (APP1130468) and the James S. McDonnell Foundation (220020419) and acknowledges the contribution of Dean R. Freestone at the University of Melbourne, Australia, to the creation of Fig. 3.Peer reviewedPostprin

Risk-taking, delay discounting, and time perspective in adolescent gamblers: an experimental study

Previous research has demonstrated that adult pathological gamblers (compared to controls) show risk-proneness, foreshortened time horizon, and preference for immediate rewards. No study has ever examined the interplay of these factors in adolescent gambling. A total of 104 adolescents took part in the research. Two equal-number groups of adolescent non-problem and problem gamblers, defined using the South Oaks Gambling Screen-Revised for Adolescents (SOGS-RA), were administered the Balloon Analogue Risk Task (BART), the Consideration of Future Consequences (CFC-14) Scale, and the Monetary Choice Questionnaire (MCQ). Adolescent problem gamblers were found to be more risk-prone, more oriented to the present, and to discount delay rewards more steeply than adolescent non-problem gamblers. Results of logistic regression analysis revealed that BART, MCQ, and CFC scores predicted gambling severity. These novel finding provides the first evidence of an association among problematic gambling, high risk-taking proneness, steep delay discounting, and foreshortened time horizon among adolescents. It may be that excessive gambling induces shortsighted behaviors that, in turn, facilitate gambling involvement

Extensive Gene-Specific Translational Reprogramming in a Model of B Cell Differentiation and Abl-Dependent Transformation

To what extent might the regulation of translation contribute to differentiation programs, or to the molecular pathogenesis of cancer? Pre-B cells transformed with the viral oncogene v-Abl are suspended in an immortalized, cycling state that mimics leukemias with a BCR-ABL1 translocation, such as Chronic Myelogenous Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL). Inhibition of the oncogenic Abl kinase with imatinib reverses transformation, allowing progression to the next stage of B cell development. We employed a genome-wide polysome profiling assay called Gradient Encoding to investigate the extent and potential contribution of translational regulation to transformation and differentiation in v-Abl-transformed pre-B cells. Over half of the significantly translationally regulated genes did not change significantly at the level of mRNA abundance, revealing biology that might have been missed by measuring changes in transcript abundance alone. We found extensive, gene-specific changes in translation affecting genes with known roles in B cell signaling and differentiation, cancerous transformation, and cytoskeletal reorganization potentially affecting adhesion. These results highlight a major role for gene-specific translational regulation in remodeling the gene expression program in differentiation and malignant transformation

Highly variable microbiota development in the chicken gastrointestinal tract

Studies investigating the role that complex microbiotas associated with animals and humans play in health and wellbeing have been greatly facilitated by advances in DNA sequencing technology. Due to the still relatively high sequencing costs and the expense of establishing and running animal trials and collecting clinical samples, most of the studies reported in the literature are limited to a single trial and relatively small numbers of samples. Results from different laboratories, investigating similar trials and samples, have often produced quite different pictures of microbiota composition. This study investigated batch to batch variations in chicken cecal microbiota across three similar trials, represented by individually analysed samples from 207 birds. Very different microbiota profiles were found across the three flocks. The flocks also differed in the efficiency of nutrient use as indicated by feed conversion ratios. In addition, large variations in the microbiota of birds within a single trial were noted. It is postulated that the large variability in microbiota composition is due, at least in part, to the lack of colonisation of the chicks by maternally derived bacteria. The high hygiene levels maintained in modern commercial hatcheries, although effective in reducing the burden of specific diseases, may have the undesirable effect of causing highly variable bacterial colonization of the gut. Studies in humans and other animals have previously demonstrated large variations in microbiota composition when comparing individuals from different populations and from different environments but this study shows that even under carefully controlled conditions large variations in microbiota composition still occur.Dragana Stanley, Mark S. Geier, Robert J. Hughes, Stuart E. Denman and Robert J. Moor

Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis

A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (∼0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD

A global research priority agenda to advance public health responses to fatty liver disease

Background & aims An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community. Methods Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a three-day in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy. Results The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of ‘agree’ responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement (‘agree’ + ‘somewhat agree’); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a super-majority of agreement (>66.7% ‘agree’), 13 priorities had 90% combined agreement. Conclusions Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community’s efforts to advance and accelerate responses to this widespread and fast-growing public health threat. Impact and implications An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease, making it the most prevalent liver disease in history. Despite substantial scientific progress in the past three decades, the burden continues to grow, with an urgent need to advance understanding of how to prevent, manage, and treat the disease. Through a global consensus process, a multidisciplinary group agreed on 28 research priorities covering a broad range of themes, from disease burden, treatment, and health system responses to awareness and policy. The findings have relevance for clinical and non-clinical researchers as well as funders working on fatty liver disease and non-communicable diseases more broadly, setting out a prioritised, ranked research agenda for turning the tide on this fast-growing public health threat