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Meeting recruitment targets for clinical trials and health research studies is a notable challenge. Unsuccessful efforts to recruit participants from traditionally underserved populations can limit who benefits from scientific discovery, thus perpetuating inequities in health outcomes and access to care. In this study, we evaluated direct mail and email outreach campaigns designed to recruit women who gave birth in North Carolina for a statewide research study offering expanded newborn screening for a panel of rare health conditions. Of the 54,887 women who gave birth in North Carolina from September 28, 2018, through March 19, 2019, and were eligible to be included on the study’s contact lists, we had access to a mailing address for 97.9% and an email address for 6.3%. Rural women were less likely to have sufficient contact information available, but this amounted to less than a one percentage point difference by urbanicity. Native American women were less likely to have an email address on record; however, we did not find a similar disparity when recruitment using direct‐mail letters and postcards was concerned. Although we sent letters and emails in roughly equal proportion by urbanicity and race/ethnicity, we found significant differences in enrollment across demographic subgroups. Controlling for race/ethnicity and urbanicity, we found that direct‐mail letters and emails were effective recruitment methods. The enrollment rate among women who were sent a recruitment letter was 4.1%, and this rate increased to 5.0% among women who were also sent an email invitation. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Under‐representation by traditionally underserved populations in clinical trials and health research is a challenge that may in part reflect inequitable opportunities to participate. WHAT QUESTION DID THIS STUDY ADDRESS? Are direct‐mail and email outreach strategies effective for reaching and recruiting women from traditionally underserved and rural populations to participate in large‐scale, population‐based research? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Despite sending recruitment letters and email invitations in roughly equal proportion by urbanicity and race/ethnicity, women living in rural areas were less likely to enroll (2.8%) than women from urban areas (4.2%). Additionally, enrollment rates decreased as the probability that women were members of a racial or ethnic minority group increased. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? Results from this study might encourage researchers to take a holistic and participant‐centered view of barriers to study enrollment that may disproportionately affect underserved communities, including differences in willingness to participate, trust, and access to resources needed for uptake.

Background Data from electronic health records (EHRs) are increasingly used in the field of genetic research to further precision medicine initiatives. However, many of these efforts exclude individuals with intellectual disabilities, which often stem from genetic conditions. To include this important subpopulation in EHR research, important ethical, legal, and social issues should be considered. Objective The goal of this study was to review prior research to better understand what ethical, legal, and social issues may need further investigation when considering the research use of EHRs for individuals with genetic conditions that may result in intellectual disability. This information will be valuable in developing methods and best practices for involving this group in research given they are considered a vulnerable population that may need special research protections. Methods We conducted a scoping review to examine issues related to the use of EHRs for research purposes and those more broadly associated with genetic research. The initial search yielded a total of 460 unique citations. We used an evaluative coding process to determine relevancy for inclusion. Results This approach resulted in 59 articles in the following areas: informed consent, privacy and security, return of results, and vulnerable populations. The review included several models of garnering informed consent in EHR or genetic research, including tiered or categorical, blanket or general, open, and opt-out models. Second, studies reported on patients’ concerns regarding the privacy and security of EHR or genetic data, such as who has access, type of data use in research, identifiability, and risks associated with privacy breach. The literature on return of research results using biospecimens examined the dissension in the field, particularly when sharing individualized genetic results. Finally, work involving vulnerable populations highlighted special considerations when conducting EHR or genetic research. Conclusions The results frame important questions for researchers to consider when designing EHR studies, which include individuals with intellectual disabilities, including appropriate safeguards and protections.

Background Angelman syndrome (AS) is a rare disorder with a relatively well-defined phenotype. Despite this, very little is known regarding the unmet clinical needs and burden of this condition, especially with regard to some of the most prevalent clinical features—movement disorders, communication impairments, behavior, and sleep. Main text A targeted literature review using electronic medical databases (e.g., PubMed) was conducted to identify recent studies focused on specific areas of the AS phenotype (motor, communication, behavior, sleep) as well as epidemiology, diagnostic processes, treatment, and burden. 142 articles were reviewed and summarized. Findings suggest significant impairment across the life span in all areas of function. While some issues may resolve as individuals get older (e.g., hyperactivity), others become worse (e.g., movement disorders, aggression, anxiety). There are no treatments focused on the underlying etiology, and the symptom-based therapies currently prescribed do not have much, if any, empirical support. Conclusions The lack of standardized treatment protocols or approved therapies, combined with the severity of the condition, results in high unmet clinical needs in the areas of motor functioning, communication, behavior, and sleep for individuals with AS and their families.

This study sought to describe food- and non-food-related behaviors of children aged 3 to 18 years with Prader&ndash, Willi syndrome (PWS) in home and school settings, as assessed by 86 parents and 63 teachers using 7 subscales of the Global Assessment of Individual&rsquo, s Behavior (GAIB). General Behavior Problem, Non-Food-Related Behavior Problem, and Non-Food-Related Obsessive Speech and Compulsive Behavior (OS/CB) scores did not differ significantly between parent and teacher reports. Food-Related Behavior Problem scores were higher in parent versus teacher reports when the mother had less than a college education (difference of 13.6 points, 95% Confidence Interval (CI) 5.1 to 22). Parents assigned higher Food-Related OS/CB scores than teachers (difference of 5.7 points, 95% CI 2.4 to 9.0). Although teachers reported fewer Food-Related OS/CB, they scored overall OS/CB higher for interfering with daily activities compared with parents (difference of 0.9 points, 95% CI 0.4 to 1.4). Understanding how behaviors manifest in home and school settings, and how they vary with socio-demographic and patient characteristics can help inform strategies to reduce behavior problems and improve outcomes.

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.

The recent Zika outbreak and its link to microcephaly and other birth defects in infants exposed in utero have garnered widespread international attention. Based on the severity of birth defects the extent of impairment in these infants is expected to be profound; however, virtually nothing is known regarding the developmental and behavioral sequela of congenital Zika syndrome. This pilot study collected parent-reported patterns of development and sleep in 47 infants with confirmed congenital Zika syndrome who are being followed for clinical services at the Altino Ventura Foundation (FAV) in Recife, Brazil. With assistance from clinicians at FAV, caregivers completed Brazilian Portuguese versions of the Ages and Stages Questionnaire, 3rd edition (ASQ-3) and the Brief Infant Sleep Questionnaire (BISQ). All infants were between 13–22 months of age at the time of the assessment. At 16 months of age, none of the children displayed age appropriate developmental skills. Most (~ 75%) mastered some communication and gross motor skills at around a 6–8-month level. Communication and gross motor skills were relative strengths for the sample, while problem-solving and fine motor skills were relative weaknesses. Sleep was noted to be a problem for around 18% of the sample. In utero exposure to the Zika virus will have lifelong consequences for affected children and their families. Understanding the developmental and behavioral trajectories of affected infants will help identify appropriate family supports to improve quality of life.

The sustainable management of natural resources can make human survival possible. Sustainable management is based on a deep understanding of the complex mechanisms of the Earth’s natural ecosystems and of how those resources can be managed without compromising future benefits and availability. The sustainable management of natural resources becomes much more complicated when there is severe and constant anthropogenic impact, and therefore, an interdisciplinary approach has to be undertaken to improve the understanding, assessment, and maintenance of the natural capital, and the related ecosystem services, in urban-industrial areas. In ecological restoration, the biggest challenge is to find a general consensus of suitable biodiversity indicators and economically viable measures, which will produce multiple socially and ecologically guided environmental benefits. There is difficulty in reaching such consensus because of the complexity, and differing understanding, of the biodiversity concept. In an effort to restore sites disturbed by industrial (mining) activities, restoration projects should involve ecologically based methods and approaches, which will be able to fulfill many stakeholders’ expectations for sustainable development and human well-being. The integrated natural and human models for sustainable management can used to understand the dynamics of ecosystems, including biodiversity and trophic levels (including midtrophic consumer influences), in order to simulate and evaluate different management scenarios in relation to biodiversity and ecosystem services. There is still a need for the increasing understanding of the role of biodiversity and ecosystem service identification as important factors influencing the dynamics of ecosystem and sustainable management scenarios.

Objective A higher rate of depressive symptoms is found among mothers of children with disabilities compared to other parents. However, there is a lack of study of mothers with children

BACKGROUND: Delays in the diagnosis of children with fragile X syndrome (FXS) suggest the possibility of newborn screening as a way to identify children earlier. However, FXS does not have a proven treatment that must be provided early, and ethical concerns have been raised about the detection of infants who are carriers. This article summarizes major findings from a multisite, prospective, longitudinal pilot screening study. METHODS: Investigators in North Carolina, California, and Illinois collaborated on a study in which voluntary screening for FXS was offered to parents in 3 birthing hospitals. FXS newborn screening was offered to >28 000 families to assess public acceptance and determine whether identification of babies resulted in any measurable harms or adverse events. Secondary goals were to determine the prevalence of FMR1 carrier gene expansions, study the consent process, and describe early development and behavior of identified children. RESULTS: A number of publications have resulted from the project. This article summarizes 10 “lessons learned” about the consent process, reasons for accepting and declining screening, development and evaluation of a decision aid, prevalence of carriers, father participation in consent, family follow-up, and maternal reactions to screening. CONCLUSIONS: The project documented public acceptance of screening as well as the challenges inherent in obtaining consent in the hospital shortly after birth. Collectively, the study provides answers to a number of questions that now set the stage for a next generation of research to determine the benefits of earlier identification for children and families.

A cross-sectional analysis was used to examine age-related differences in ASD symptoms and corresponding differences in disruptive behavior and social skills in 281 adult men with Fragile X syndrome (FXS). Four age groups were created: 18–21 years, 22–29 years, 30–39 years, and 40–49 years. The 18–21 year-old group was reported to have more impairments in verbal communication than the 22–29 year-old group and more restricted and repetitive behaviors than the 40–49 year-old group. There was not an age-group difference in the percentage of men who met criteria for an ASD diagnosis based on respondent-reported, current symptoms. There was a trend for an age-related difference in disruptive behavior. Findings add to understanding of the developmental trajectory of ASD symptoms in adulthood.

OBJECTIVES: The possibility of newborn screening for fragile X syndrome is complicated by the potential for identifying premutation carriers. Although knowing the child’s carrier status has potential benefits, the possibility of late-onset disorders in carrier children and their parents raises concerns about whether such information would be distressing to parents and potentially more harmful than helpful. This study sought to answer this question by offering voluntary fragile X screening to new parents and returning results for both the full mutation and premutation FMR1 gene expansions. We tested the assumption that such information could lead to adverse mental health outcomes or decision regret. We also wanted to know if child age and spousal support were associated with the outcomes of interest. METHODS: Eighteen mothers of screen-positive infants with the premutation and 15 comparison mothers completed a battery of assessments of maternal anxiety, postpartum depression, stress, family quality of life, decision regret, and spousal support. The study was longitudinal, with an average of 3 assessments per mother. RESULTS: The premutation group was not statistically different from the comparison group on measures of anxiety, depression, stress, or quality of life. A subset of mothers experienced clinically significant anxiety and decision regret, but factors associated with these outcomes could not be identified. Greater spousal support was generally associated with more positive outcomes. CONCLUSIONS: Although we did not find evidence of significant adverse events, disclosure of newborn carrier status remains an important consideration in newborn screening policy.

A phase II randomized, placebo-controlled, double-blind study and subsequent open-label extension study evaluated the efficacy, safety, and tolerability of mavoglurant (AFQ056), a selective metabotropic glutamate receptor subtype-5 antagonist, in treating behavioral symptoms in adolescent patients with fragile X syndrome (FXS). A novel method was applied to analyze changes in symptom domains in patients with FXS using the narratives associated with the clinician-rated Clinical Global Impression-Improvement (CGI-I) scale. In the core study, patients were randomized to receive mavoglurant (25, 50, or 100 mg BID) or placebo over 12 weeks. In the extension, patients received 100 mg BID mavoglurant (or the highest tolerated dose) for up to 32 months. Global improvement, as a measure of treatment response, was assessed using the CGI-I scale. Investigators assigning CGI-I scores of 1 (very much improved), 2 (much improved), 6 (much worse), or 7 (very much worse) were provided a standard narrative template to collect further information about the changes observed in patients. Investigator feedback was coded and clustered into categories of improvement or worsening to identify potential areas of improvement with mavoglurant. Treatment effect in each category was characterized using the Cochran–Mantel–Haenszel test. A total of 134 and 103 patients had reached 2 weeks or more of core and extension study treatment, respectively, by the pre-assigned cutoff date for investigator feedback. In the core study, 34 CGI-I scores of 1 or 2 were reported in 28 patients; one patient scored 6. Analysis of the CGI-I narratives did not indicate greater treatment response in patients receiving mavoglurant compared with placebo in any specific improvement domain. There were 54 CGI-I scores of 1 or 2 in 47 patients in the extension study. The most frequently reported categories of improvement were behavior and mood (79.3 and 76.6 % in core and extension studies, respectively), engagement (75.9 and 78.7 %), and communication (69.0 and 61.7 %). A method was established to capture and categorize FXS symptoms using CGI-I narratives. Although this method did not show benefit of drug over placebo, narratives from investigators were mostly based on parental report and thus do not represent a completely objective alternative assessment. The studies described are registered at ClinicalTrials.gov with clinical trial identifier numbers NCT01357239 and NCT01433354 .

Background Emerging evidence suggests that a subset of FMR1 premutation carriers is at an increased risk for cognitive, emotional, and medical conditions. However, because the premutation is rarely diagnosed at birth, the early developmental trajectories of children with a premutation are not known. Methods This exploratory study examined the cognitive, communication, and social-behavioral profiles of 26 infants with a premutation who were identified through participation in a newborn screening for fragile X syndrome pilot study. In this study, families whose newborn screened positive for an FMR1 premutation were invited to participate in a longitudinal study of early development. Twenty-six infants with the premutation and 21 matched, screen-negative comparison babies were assessed using validated standardized measures at 6-month intervals starting as young as 3 months of age. The babies were assessed up to seven times over a 4-year period. Results The premutation group was not statistically different from the comparison group on measures of cognitive development, adaptive behavior, temperament, or overall communication. However, the babies with the premutation had a significantly different developmental trajectory on measures of nonverbal communication and hyperresponsivity to sensory experiences. They also were significantly more hyporesponsive at all ages than the comparison group. Cytosine-guanine-guanine repeat length was linearly associated with overall cognitive development. Conclusions These results suggest that infants with a premutation may present with subtle developmental differences as young as 12 months of age that may be early markers of later anxiety, social deficits, or other challenges thought to be experienced by a subset of carriers.