Caregiver opinions about fragile X population screening

To determine caregiver perceptions about population screening for fragile X and examine factors potentially associated with support for screening

Where Do We Go From Here? The Need for Genetic Referrals in Patients who are Deaf or Hard of Hearing: Findings from a Regional Survey

Purpose: The purpose of this study was to assess primary health care providers’ knowledge and use of genetic services for children whose hearing screening indicates they may be deaf/hard of hearing (D/HH) and identify areas in which health care providers can be supported to increase family education and referral of families for genetic consultation. Methodology: A survey was developed on current practices, knowledge, and perceived beliefs regarding genetic education and referrals for deafness. The surveys were distributed to pediatricians, family medicine physicians, nurse practitioners, and physician assistants in DC, DE, MD, NJ, NY, PA, VA, and WV. Results: Among 266 respondents, 80% were uninformed about Early Hearing Detection Intervention (EHDI) 1-3-6 guidelines prior to taking the survey. Approximately 55% were not confident about the genetic causes of deafness, 44% rarely consulted genetics professionals, 41% had not referred families to genetics, and 37% were not confident about the importance of genetic referrals. Conclusions: Integrated, targeted, and user-friendly genetics education strategies in the existing EHDI framework are needed to ensure adequate awareness and delivery of genetics services for D/HH children

Parent Ratings of Ability to Consent for Clinical Trials in Fragile X Syndrome

Advances in understanding neurobiology and intellectual disabilities have led to clinical trials testing new medications. This study assessed parents’ perceptions of the ability of their son or daughter with fragile X syndrome (FXS), an inherited form of intellectual disability, to participate in the consent process for clinical trials. Four hundred and twenty-two families participated in a survey that included six items assessing various aspects of the ability to provide consent. A rank ordering of decisional tasks was found. The easiest task was to understand that the medication was different from his or her medical treatment; the most difficult was the ability to understand and weigh the potential benefits and risks of study participation. Factor analysis suggested that despite the range in difficulty, the six items were best summarized by a single decisional ability score. Parents of 29% of males reported that their son was not at all capable of participating, but the remainder exhibited a range of decisional skills. Factors associated with this variability include age, and parents’ willingness to enroll their child in clinical trials. We conclude that many individuals with FXS appear to be able to participate at some level in the consent or assent process, but will likely need individualized support to maximize effective participation

Implications of the FMR1 Premutation for Children, Adolescents, Adults, and Their Families

Background and objectivesGiven the nature of FMR1 gene expansions, most biological mothers, and often multiple other family members of children with fragile X syndrome (FXS), will have a premutation, which may increase individual and family vulnerabilities. This article summarizes important gaps in knowledge and notes potential implications for pediatric providers with regard to developmental and medical risks for children and adolescents with an FMR1 premutation, including possible implications into adulthood.MethodsA structured electronic literature search was conducted on FMR1 pre- and full mutations, yielding a total of 306 articles examined. Of these, 116 focused primarily on the premutation and are included in this review.ResultsBased on the literature review, 5 topic areas are discussed: genetics and epidemiology; phenotypic characteristics of individuals with the premutation; implications for carrier parents of children with FXS; implications for the extended family; and implications for pediatricians.ConclusionsAlthough the premutation phenotype is typically less severe in clinical presentation than in FXS, premutation carriers are much more common and are therefore more likely to be seen in a typical pediatric practice. In addition, there is a wide range of medical, cognitive/developmental, and psychiatric associated features that individuals with a premutation are at increased risk for having, which underscores the importance of awareness on the part of pediatricians in identifying and monitoring premutation carriers and recognizing the impact this identification may have on family members

Integration of an atmospheric dispersion model with a dynamic multimedia fate model: development and illustration

Growing attention is devoted to understand the influence of the short-term variations in air concentrations on the environmental fate of semivolatile organic compounds (SVOCs) such as polycyclic aromatic hydrocarbons (PAHs). These variations are ascribable to factors such as temperature-mediated air-surface exchange and variability of planetary boundary layer (PBL) height and structure. But when investigating the fate of SVOCs at a local scale, further variability can derive from specific point source contributions. In this context, a new modeling approach (AirPlus) which integrates a previously developed model (AirFug) with an air dispersion model (AERMOD) is presented. The integrated model is illustrated for two PAHs in a Northern Italy scenario. Results show how chemical contributions deriving from background advective inflows, local emissions and a point source interact in an hourly-varying meteorological scenario to determine air concentration rapid changes and the consequent response of the soil compartment. © 2012 Elsevier Ltd. All rights reserved

Improving the SoilPlusVeg model to evaluate rhizoremediation and PCB fate in contaminated soils

Tools to predict environmental fate processes during remediation of persistent organic pollutants (POPs) in soil are desperately needed since they can elucidate the overall behavior of the chemical and help to improve the remediation process. A dynamic multimedia fate model (SoilPlusVeg) was further developed and improved to account for rhizoremediation processes. The resulting model was used to predict Polychlorinated Biphenyl (PCB) fate in a highly contaminated agricultural field (1089 ng/g d.w.) treated with tall fescue (Festuca arundinacea), a promising plant species for the remediation of contaminated soils. The model simulations allowed to calculate the rhizoremediation time (about 90 years), given the available rhizoremediation half-lives and the levels and fingerprints of the PCB congeners, to reach the legal threshold, to show the relevance of the loss processes from soil (in order of importance: degradation, infiltration, volatilization, etc.) and their dependence on meteorological and environmental dynamics (temperature, rainfall, DOC concentrations). The simulations showed that the effective persistence of PCBs in soil is deeply influenced by the seasonal variability. The model also allowed to evaluate the role of DOC as a possible enhancer of PCB degradation as a microorganism \u201cspoon feeder\u201d of PCBs in the soil solution. Additionally, we preliminary predicted how the contribution of PCB metabolites could modify the PCB fingerprint and their final total concentrations. This shows that the SoilPlusVeg model could be used in selecting the best choices for a sustainable rhizoremediation of a POP contaminated site

Early Identification of Fragile X Syndrome through Expanded Newborn Screening

Over the past 20 years, research on fragile X syndrome (FXS) has provided foundational understanding of the complex experiences of affected individuals and their families. Despite this intensive focus, there has been little progress on earlier identification, with the average age of diagnosis being 3 years. For intervention and treatment approaches to have the greatest impact, they need to begin shortly after birth. To access this critical timespan, differential methods of earlier identification need to be considered, with an emerging focus on newborn screening practices. Currently, barriers exist that prevent the inclusion of FXS on standard newborn screening panels. To address these barriers, an innovative program is being implemented in North Carolina to offer voluntary screening for FXS under a research protocol, called Early Check. This program addresses the difficulties observed in prior pilot studies, such as recruitment, enrollment, lab testing, and follow-up. Early Check provides an opportunity for stakeholders and the research community to continue to gain valuable information about the feasibility and greater impact of newborn screening on the FXS population

Parent Ratings of Ability to Consent for Clinical Trials in Fragile X Syndrome

Advances in understanding neurobiology and intellectual disabilities have led to clinical trials testing new medications. This study assessed parents’ perceptions of the ability of their son or daughter with fragile X syndrome (FXS), an inherited form of intellectual disability, to participate in the consent process for clinical trials. Four hundred and twenty-two families participated in a survey that included six items assessing various aspects of the ability to provide consent. A rank ordering of decisional tasks was found. The easiest task was to understand that the medication was different from his or her medical treatment; the most difficult was the ability to understand and weigh the potential benefits and risks of study participation. Factor analysis suggested that despite the range in difficulty, the six items were best summarized by a single decisional ability score. Parents of 29% of males reported that their son was not at all capable of participating, but the remainder exhibited a range of decisional skills. Factors associated with this variability include age, and parents’ willingness to enroll their child in clinical trials. We conclude that many individuals with FXS appear to be able to participate at some level in the consent or assent process, but will likely need individualized support to maximize effective participation

Supporting informed clinical trial decisions: Results from a randomized controlled trial evaluating a digital decision support tool for those with intellectual disability.

BACKGROUND:Informed consent requires that individuals understand the nature of the study, risks and benefits of participation. Individuals with intellectual disabilities (ID) have cognitive and adaptive impairments that may affect their ability to provide informed consent. New treatments and clinical trials for fragile X syndrome, the most commonly known inherited cause of ID, necessitate the development of methods to improve the informed consent process. The goal of this study was to compare the efficacy of a digital decision support tool with that of standard practice for informed consent and to examine whether the tool can improve decisional capacity for higher functioning individuals. METHODS:Participants (N = 89; mean age = 21.2 years) were allocated to the experimental group (consenting information provided via the digital decision support tool), or the comparison group (information provided via standard practice). Participants were assessed on four aspects of decisional capacity (Understanding, Appreciating, Reasoning, and Expressing a choice). We used regression analyses to test the impact of the tool on each outcome, repeating the analyses on the higher functioning subsample. RESULTS:No differences existed in any domain of decisional capacity for the sample in full. However, participants in the higher IQ subsample who used the tool scored better on Understanding after adjustment (β = 0.25, p = 0.04), but not on Appreciating or Reasoning. No differences by experimental group existed in the decision to join the hypothetical trial for the full sample or higher functioning subsample. CONCLUSIONS:A decision support tool shows promise for individuals with fragile X syndrome with higher cognitive abilities. Future studies should examine the level of cognitive ability needed for sufficient understanding, whether these findings can be translated to other clinical populations, and the impact of the tool in larger trials and on trial retention

Sensory Difficulties in Children With an FMR1 Premutation

Abnormal sensory processing is one of the core characteristics of the fragile X phenotype. Studies of young children with fragile X syndrome (FXS) and the FMR1 premutation have shown sensory challenges as early as infancy and into early childhood. This study sought to examine differences in sensory difficulties in children with an FMR1 premutation compared with children with FXS and typically developing children. We conducted an online survey of 176 parents of affected children (FXS or FMR1 premutation). Most respondents were mothers who are Caucasian (86%), have a 4-year college or graduate degree (68%), and are married (92%). Children ranged in age from 5 to 18, with a mean age of 13.0 years (3.3 SD). Participants completed the BBC Sensory Scales, a 50-item Likert-type scale (1 = Almost Always, 4 = Almost Never) comprised of 8 subscales that assessed auditory processing, visual processing, tactile processing, and eating and feeding behaviors. Mean scores were calculated for the items and each of the subscales. Non-parametric tests examined differences in child and family-level variables. Across all BBCSS subscales, children with an FMR1 premutation displayed more sensory challenges than typically developing children. For six out of the eight subscales, children with the full mutation had the lowest scores indicating more sensory challenges, but this was closely followed by children with an FMR1 premutation. Fragile X status was associated with seven of the eight subscales; children with an FMR1 premutation did not differ from children with FXS on any of the subscales but had more digestive problems than children with no fragile X. Gender, autism status, and family income were also related to sensory sensitivities. In conclusion, these data provide further evidence that some children with an FMR1 premutation experience sensory difficulties that are similar to children with FXS but different than typically developing children