Health Status and Health Care Use Among Adolescents Identified With and Without Autism in Early Childhood — Four U.S. Sites, 2018–2020

Persons identified in early childhood as having autism spectrum disorder (autism) often have co-occurring health problems that extend into adolescence (1–3). Although only limited data exist on their health and use of health care services as they transition to adolescence, emerging data suggest that a minority of these persons receive recommended guidance* from their primary care providers (PCPs) starting at age 12 years to ensure a planned transition from pediatric to adult health care (4,5). To address this gap in data, researchers analyzed preliminary data from a follow-up survey of parents and guardians of adolescents aged 12–16 years who previously participated in the Study to Explore Early Development (https://www.cdc.gov/ncbddd/autism/seed.html). The adolescents were originally studied at ages 2–5 years and identified at that age as having autism (autism group) or as general population controls (control group). Adjusted prevalence ratios (aPRs) that accounted for differences in demographic characteristics were used to compare outcomes between groups. Adolescents in the autism group were more likely than were those in the control group to have physical difficulties (21.2% versus 1.6%;aPR = 11.6;95% confidence interval [CI] = 4.2–31.9), and to have additional mental health or other condition

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Evaluation of vaccination to support control of H5N1 avian influenza in Hong Kong

In 1997, 2002 and 2003 highly pathogenic avian influenza (HPAI) was diagnosed on chicken farms in Hong Kong. Following the February-April 2002 outbreak, vaccination using a killed oil-adjuvanted H5N2 avian influenza vaccine was evaluated as an additional control measure on 22 farms within a 2-km radius of the four farms that were depopulated following infection with HPAI H5N1 virus. Vaccination produced satisfactory flock antibody responses. The serological response was improved following a second dose of vaccine and the response to vaccination was poorer when delivered to older birds compared to birds first vaccinated at 8 days of age. Infection with field virus was not detected in any of these vaccinated flocks so the protective effect of the vaccine was tested under secure laboratory conditions on vaccinated and unvaccinated chickens challenged with HPAI H5N1 virus. Vaccinated birds were protected from disease, virus excretion was not detected in eight of ten vaccinated birds and the two birds that did excrete virus excreted much less virus than unvaccinated controls (> 1000 fold reduction). In December 2002 HPAI H5N1 outbreaks in 2 waterfowl parks and deaths in wild water birds in Hong Kong were followed by outbreaks on five previously unvaccinated chicken farms. Vaccination used in the face of outbreaks on three of these farms, coupled with selective culling, resulted in elimination of H5N1 virus infection from these farms. These investigations showed that the killed H5N2 vaccine, used in conjunction with enhanced biosecurity measures on chicken farms and in poultry markets, reduced the risk of H5N1 avianinfluenza outbreaks in Hong Kong and consequently the risk of spread to humans

The cystic fibrosis gut as a potential source of multidrug resistant pathogens

Background: The emergence of multidrug resistant (MDR) pathogens represents a profound threat to global health. Individuals with CF have amongst the highest cumulative antibiotic exposure of any pa- tient group, including to critically-important last-line agents. While there is little evidence that antibiotic resistance in airway pathogens results in worse clinical outcomes for CF patients, the potential emergence of MDR pathogens in non-respiratory systems, as a consequence of CF care, represents a potential health threat to the wider population, including family and carers. Methods: Stool from 19 adults with CF and 16 healthy adult controls was subjected to metagenomic sequencing, to assess faecal resistome, and culture-based analysis. Resistant isolates were identified phe- notypically, and genetic determinants of resistance characterised by whole genome sequencing. Results: CF and control faecal resistomes differed significantly ( P = 0.0 0 03). The proportion of reads that mapped to mobile genetic elements was significantly higher in CF ( P = 0.014) and the composition was significantly different ( P = 0.0 0 01). Notably, CF patients displayed higher carriage of plasmid-mediated aminoglycoside-modifying genes ant (6)-Ib, aac (6 ′ )-Ip, and aph (3 ′ )-IIIa ( P < 0.01). Culture-based analy- sis supported higher aminoglycoside resistance, with a higher proportion of aminoglycoside-resistant, Gram-negative bacteria ( P < 0.0 0 01). Isolated extended spectrum beta lactamase (ESBL)-positive Es- cherichia coli from CF stool exhibited phenotypic resistance to tobramycin and gentamicin. Genomic anal- ysis showed co-localisation of both aminoglycoside resistance and ESBL genes, consistent with MDR emer- gence through horizontal gene transfer. Conclusions: The carriage of potentially transmissible resistance within the adult CF gut microbiome is considerably greater than in healthy individuals and could contribute to the emergence and dissemination of MDR pathogens.Steven L. Taylor, Lex E.X. Leong, Sarah K. Sims, Rebecca L. Keating, Lito E. Papanicolas, Alyson Richard, Fredrick M. Mobegi, Steve Wesselingh, Lucy D. Burr, Geraint B. Roger

Building consensus in strategic decision-making : system dynamics as a group support system

Contains fulltext : 28724.pdf (publisher's version ) (Open Access)System dynamics was originally founded as a method for modeling and simulating the behavior of industrial systems. In recent years it is increasingly employed as a Group Support System for strategic decision-making groups. The model is constructed in direct interaction with a management team, and the procedure is generally referred to as group model-building. The model can be conceptual (qualitative) or a full-blown (quantitative) computer simulation model. In this article, a case is described in which a qualitative system dynamics model was built to support strategic decision making in a Dutch government agency. Since people from different departments held strongly opposite viewpoints on the strategy, the agency had discussed its strategic problem for more than a year, but was obviously not able to reach consensus. The application of group model-building was successful in integrating opposite points of view, as well as in fostering consensus and creating commitment. The purpose of the article is twofold: first, to illustrate the process of group model-building with system dynamics; second, to evaluate why it was successful. Evaluation results reveal the importance of both systemic thinking through model-building and the role of the facilitator in catalyzing the strategic decision-making process