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Abstract Fragile X Syndrome (FXS) is an X-linked disorder leading to the loss of expression of FMR1-protein product, FMRP. The absence or deficiency of FMRP is thought to result in the characteristic FXS phenotypes, including intellectual disability. Identifying the relationship between FMRP levels and IQ may be critical to better understand underlying mechanisms and advance treatment development and planning. A sample of 143 individuals with FXS (69% male), aged 8–50 years, completed IQ testing and blood draw via venipuncture to determine the relationship between Deviation IQ scores and FMRP levels as well as the distribution of Deviation IQ scores. In both males and females with FXS, higher FMRP levels were associated with higher Deviation IQ. However, this relationship was no longer significant when only examining full mutation, fully-methylated males. Yet, both the full and restricted male samples showed a downward shifted but otherwise normal distribution of Deviation IQ scores. Our findings support and extend previous studies establishing molecular markers of disease severity in FXS as well as provide novel evidence of a “FXS IQ standard curve”. This latter finding suggests inter-individual variation in Deviation IQ in FXS, especially among males, may be driven by similar factors known to impact cognitive outcomes in typically-developing individuals. Thus, future work aimed at understanding the mechanisms by which FMRP loss leads to intellectual disability should revisit the biological/genetic, socio-environmental, and epigenetic factors contributing to inter-individual variation in IQ in FXS.

Abstract Autistic youth experience several behavioral and emotional characteristics that can predispose them to emotion dysregulation (ED). Current literature examining ED in autism spectrum disorder (ASD) is limited to parent- and self-reported measures, indicating a need for biological or physiological methods to better assess emotion regulation in ASD. Utilizing the autonomic nervous system, specifically heart rate variability (HRV), may be a promising method to objectively measure ED in ASD, given it is one of the body’s primary means of regulating physiological arousal. Our pilot study is one of the first to examine the feasibility, utility, and construct validity of HRV along with clinical measures within an intervention targeting ED-specific symptoms in ASD. Participants included 30 autistic youth ages 8–17 years who participated in the pilot study of Regulating Together, a group-based intervention targeting emotion regulation. We demonstrate HRV is feasible, demonstrates adequate test–retest reliability, and is complimentary to clinician- and parent-reported measures. Our preliminary findings also point to certain HRV profiles being indicative of long-term outcomes after receiving treatment. HRV may be a useful, objective tool in determining differential needs of long-term follow-up care for treatment maintenance at screening or baseline stages.

IntroductionAutistic children and adolescents frequently experience emotion dysregulation, or difficulties with appropriately modifying their emotional reactions. Caregivers of autistic teens frequently seek psychotherapy support for navigating challenges associated with emotion dysregulation. During the COVID-19 pandemic, access to clinical services became limited, with interventions halted or transitioned into a telehealth format.MethodsThis study evaluates the feasibility, acceptability, and initial efficacy of a telehealth adaptation to an existing intervention for emotion dysregulation for children and teens with autism, Regulating Together. A within-subjects trial was conducted for Child (ages 8-12) and Teen groups (ages 13-18). The trial consisted of a 5-week-control lead-in period, a 5-week-intervention, and 5-and 10-weeks-post-intervention follow-ups.ResultsTwenty-eight youth with ASD + ED (n=13 Child and n=15 Teens, 71% male) participated. We observed a 93% retention rate across both groups. Improvements were found in reactivity, irritability, emotion and behavioral regulation, and flexibility immediately post-intervention and 10-weeks post-intervention in both groups. Additional improvements in dysphoria, cognitive regulation, and emotional control were observed in teens.DiscussionOur results suggest promising improvements in ED through telehealth delivery of an emotion regulation intervention in autistic children and adolescents, along with possible improvements in accessibility of this intervention.

The Mount Meager Volcanic Complex (Q̓welq̓welústen) is an active glacier-capped volcanic massif in the Garibaldi Volcanic Belt (British Columbia) and the only known glaciovolcanic cave system in North America steadily releasing sulfur-rich gases. In September 2022, leveraging specialized cave explorer expertise, the fumarole-carved ice cave at the Job Glacier on Mt. Meager was surveyed. Direct measurements of fumarolic gas concentrations were taken at the source, with H2S >200 ppm, SO2 >100 ppm, CO2 ∼5,200 ppm, and CO ∼230 ppm. Snowpack and fumarole-associated sediments were characterized for microbial diversity, functional potential, and biogeochemistry including measurements of nutrients, major ions, dissolved organic and inorganic carbon concentrations as well as the stable isotope compositions of carbon, sulfur, hydrogen and oxygen. Green algae (Chlorophyta) dominated the snowpack, consistent with other Pacific Northwest glaciers. Representatives of Firmicutes were the most abundant bacterial sequences detected in our samples, contrasting with other glacier and snowpack samples which harbor abundant Sphingobacteria, Betaproteobacteria, and Alphaproteobacteria. Sediments and water collected inside the cave were mostly high in SO42- (5.3–185.2 mg/L) and acidic (pH = 3.6–6.0), while most other major anions and cations were below detection of the method used. Snow at the cave entrance had more SO42- (0.08 mg/L) and lower pH (5.9) than snow collected at a distance (SO42- undetectable, pH 7.6), suggesting influence by fumarole exhalations. Negative δ13C values of organic matter (−29.0‰ to −26.1‰, respectively) in sediments suggest in-situ microbial carbon transformations, findings that are supported by the presence of genes encoding complete heterotrophic and autotrophic carbon transformation pathways. The δ34S value of H2S was ∼0‰, suggesting a deep magmatic origin; however, both sulfur-oxidizing and sulfate-reducing microbial phyla were present in the sediment samples as were genes encoding both dissimilatory sulfur-oxidizing and sulfate-reducing pathways. Metagenomic data suggest diverse chemosynthetic lifestyles in the cave microbial community. This study provides insight on the microbiomes associated with a sulfidic glaciovolcanic system and identifies unique analog features for icy celestial bodies like Saturn’s moon Enceladus, where cryovolcanic activity may carry biomarkers from the subsurface and deposit them on surface ice.

OBJECTIVE To improve patient outcomes and promote health equity, medical students must be taught not only biomedicine, but also the social sciences to understand the larger contexts in which patients live and health care operates. Yet, most undergraduate medical education does not explicitly cover these topics in a required, longitudinal curriculum. METHODS In January 2015 at Harvard Medical School, we created a two-part sequence (pre- and post-clerkship) of required, 4-week multidisciplinary courses—“Essentials of the Profession I and II”—to fill this gap. “Essentials of the Profession II (EOP2)” is an advanced social sciences course anchored in patient narratives and the lived experiences of students and includes clinical epidemiology and population health, healthcare delivery and leadership, health policy, medical ethics and professionalism, and social medicine that engages students to conduct structural analyses to be effective healers, advocates, and leaders. RESULTS Per student course evaluations, the overall course rating was 1.7 (SD 0.9, 1 = excellent and 5 = poor); its overall rating has improved over time; and it has scored well even when run virtually. It was rated highly in application of critical thinking, integration of the disciplines, and relevance for clinical work. Qualitative analyses of student responses revealed the following key course strengths: breadth of topics, teaching faculty and guest speakers, and small group discussions. The weaknesses included workload, lack of diversity of opinions, repetition, and time spent in lectures. CONCLUSIONS We argue that EOP2 is “essential” for post-clerkship medical education. It offers an opportunity to re-ignite and enhance humanism and activism; remind students why they chose the medical profession; equip them with frameworks and toolkits to help them to overcome challenges; and devise solutions to improve health care and patient outcomes that are applicable to their future training and ongoing practice of medicine.

Objective: Fragile X Syndrome (FXS) is the leading monogenic cause of intellectual disability and autism spectrum disorder. Currently, there are no established biomarkers for predicting and monitoring drug effects in FXS, and no approved therapies are available. Previous studies have shown electrophysiological changes in the brain using electroencephalography (EEG) in individuals with FXS and animal models. These changes may be influenced by drug therapies. In this study, we aimed to assess the reliability of resting-state EEG measures in individuals with FXS, which could potentially serve as a biomarker for drug discovery. Methods: We collected resting-state EEG data from 35 individuals with FXS participating in placebo-controlled clinical trials (23 males, 12 females; visit age mean+/-std 25.6 +/−8.3). The data were analyzed for various spectral features using intraclass correlation analysis to evaluate test-retest reliability. The intervals between EEG recordings ranged from same-day measurements to up to six weeks apart. Results: Our results showed high reliability for most spectral features, with same-day reliability exceeding 0.8. Features of interest demonstrated ICC values of 0.60 or above at longer intervals. Among the features, alpha band relative power exhibited the highest reliability. Conclusion: These findings indicate that resting-state EEG can provide consistent and reproducible measures of brain activity in individuals with FXS. This supports the potential use of EEG as an objective biomarker for evaluating the effects of new drugs in FXS. Significance: The reliable measurements obtained from power spectrum-based resting-state EEG make it a promising tool for assessing the impact of small molecule drugs in FXS.

Stellar occultation observations from space can probe the stratosphere and mesosphere at a fine vertical scale around the globe. Unlike other measurement techniques like radiosondes and aircraft, stellar occultation has the potential to observe the atmosphere above 30 km, and unlike radio occultation, stellar occultation probes fine-scale phenomena with potential to observe atmospheric turbulence. We imaged the refractive bending angle of a star centroid for a series of occultations by the atmosphere. Atmospheric refractivity, density, and then temperature are retrieved from the bending observations with the Abel transformation and Edlén's law, the hydrostatic equation, and the ideal gas law. The retrieval technique is applied to data collected by two nanosatellites operated by Terran Orbital. Measurements were primarily taken by the GEOStare SV2 mission, with a dedicated imaging telescope, supplemented with images captured by spacecraft bus sensors, namely the star trackers on other Terran Orbital missions. The bending angle noise floor is 10 and 30 arcsec for the star tracker and GEOStare SV2 data, respectively. The most significant sources of uncertainty are due to centroiding errors due to the fairly low-resolution stellar images and telescope pointing knowledge derived from noisy satellite attitude sensors. The former mainly affects the star tracker data, while the latter limits the GEOStare SV2 accuracy, with both providing low vertical resolution. This translates to a temperature profile retrieval up to roughly 20 km for both star tracker and GEOStare SV2 datasets. In preparation of an upcoming 2023 mission designed to correct these deficiencies, SOHIP, we simulated bending angle measurements with varying magnitudes of error. The expected maximum altitude of retrieved temperature is 41 km on average for these simulated measurements with a noise floor of 0.39 arcsec. Our work highlights the capabilities of stellar occultation observations from nanosatellites for atmospheric sounding. Future work will investigate high-frequency observations of atmospheric gravity waves and turbulence, mitigating the major uncertainties observed in these datasets.

The McMurdo Dry Valleys of Antarctica experience a range of selective pressures, including extreme seasonal variation in temperature, water and nutrient availability, and UV radiation. Microbial mats in this ecosystem harbor dense concentrations of biomass in an otherwise desolate environment. Microbial inhabitants must mitigate these selective pressures via specialized enzymes, changes to the cellular envelope, and the production of secondary metabolites, such as pigments and osmoprotectants. Here, we describe the isolation and characterization of a Gram-negative, rod-shaped, motile, red-pigmented bacterium, strain DJPM01, from a microbial mat within the Don Juan Pond Basin of Wright Valley. Analysis of strain DJMP01’s genome indicates it can be classified as a member of the Massilia frigida species. The genome contains several genes associated with cold and salt tolerance, including multiple RNA helicases, protein chaperones, and cation/proton antiporters. In addition, we identified 17 putative secondary metabolite gene clusters, including a number of nonribosomal peptides and ribosomally synthesized and post-translationally modified peptides (RiPPs), among others, and the biosynthesis pathway for the antimicrobial pigment prodigiosin. When cultivated on complex agar, multiple prodiginines, including the antibiotic prodigiosin, 2-methyl-3-propyl-prodiginine, 2-methyl-3-butyl-prodiginine, 2-methyl-3-heptyl-prodiginine, and cycloprodigiosin, were detected by LC–MS. Genome analyses of sequenced members of the Massilia genus indicates prodigiosin production is unique to Antarctic strains. UV-A radiation, an ecological stressor in the Antarctic, was found to significantly decrease the abundance of prodiginines produced by strain DJPM01. Genomic and phenotypic evidence indicates strain DJPM01 can respond to the ecological conditions of the DJP microbial mat, with prodiginines produced under a range of conditions, including extreme UV radiation.

A large EEG dataset from 70 patients with Fragile X syndrome reveals unique changes in neural activity and highlight the role for disrupted thalamocortical modulation in local hyperexcitability.

IntroductionBehavioral difficulties in individuals with fragile X Syndrome (FXS) are one of the primary reasons families seek medical and psychological support. Among these, behavioral inflexibility is very common, and when left untreated, can negatively impact quality of life for the individuals with FXS and their families. Behavioral inflexibility refers to the difficulty in changing one’s behaviors based on environmental demands or social contexts, thus impeding daily functioning, opportunities for learning, and social interactions. In addition to the individual and family impact, behavioral inflexibility is often recognized as a defining phenotype of FXS and appears to be specific to FXS when compared to other genetic forms of intellectual disability. Despite the pervasiveness and severity of behavioral inflexibility in FXS, there are limited measures that adequately assess behavioral inflexibility in FXS.MethodsWe conducted semi-structured virtual focus groups with 22 caregivers, 3 self-advocates, and 1 professional to gather key stakeholders’ perspectives on and experiences of inflexible behavior observed in FXS. Audio-recordings from focus groups were transcribed using NVivo, then verified and coded. Two trained professionals reviewed codes to extract primary themes.ResultsSix themes were extracted: (1) Intolerance of change, (2) Intolerance to uncertainty, (3) Repetitive interests and behaviors, (4) Family impact, (5) Change in behavior across the lifespan, and (6) Impact of the COVID pandemic. Our findings show common examples of these themes included intolerance to disruption to routine, perseverative questioning, watching the same things over and over, and caregivers having to extensively pre-plan for events.DiscussionThe purpose of the current study was to gain key stakeholders’ perspectives via focus groups to elicit information and understand patterns of inflexible behaviors in FXS, with the goal of developing a disorder-specific measure to accurately assess behavioral inflexibility across the lifespan and in response to treatment. We were able to capture several phenotypic examples of behavioral inflexibility in FXS as well as their impact on individuals with FXS and their families. The wealth of information gained through our study will aid in our next steps of item generation for measure development of Ratings of Inflexibility in Genetic Disorders associated with Intellectual Disability – Fragile X Syndrome (RIGID-FX).

In a systemic effort to survive environmental stress, organ systems fluctuate and adapt to overcome external pressures. The evolutionary drive back toward homeostasis makes it difficult to determine if an organism experienced a toxic exposure to stress, especially in early prenatal and neonatal periods of development. Previous studies indicate that primary human teeth may provide historical records of experiences related to stressors during that early time window. To assess the molecular effects of early-life adversity on enamel formation, we used a limited bedding and nesting (LBN) mouse model of early-life adversity (ELA) to assess changes in the enamel organ gene expression and enamel matrix mineralization. On average, postnatal day 12 (P12) ELA mice weighed significantly less than the controls. When adjusted for animal weight, ELA molar enamel volume was reduced as compared with the controls, and the relative mineral density of molar enamel was significantly increased. There were no obvious changes in enamel matrix crystal morphology or structure in ELA as compared with the control mouse enamel. RNAseq showed extracellular matrix organization to be the most significantly affected GO and reactome pathways, whereas butanote metabolism was the most significantly altered KEGG pathway. Transcripts expressing the enamel matrix proteins amelogenin (Amelx) and enamelin (Enam) were among the top 4 most differentially expressed genes. When evaluating molecular mechanisms for the changes in gene expression in ELA enamel organs, we found significantly increased expression of Dlx3, while transcripts for clock genes Per1 and Nrd1 were downregulated. These findings support the possibility that the developing enamel organ is sensitive to the pressures of early-life adversity and produces molecular and structural biomarkers reflecting these challenges.

Abstract Multimodal exploration of objects during toy play is important for a child’s development and is suggested to be abnormal in children with autism spectrum disorder (ASD) due to either atypical attention or atypical action. However, little is known about how children with ASD coordinate their visual attention and manual actions during toy play. The current study aims to understand if and in what ways children with ASD generate exploratory behaviors to toys in natural, unconstrained contexts by utilizing head-mounted eye tracking to quantify moment-by-moment attention. We found no differences in how 24- to 48-mo children with and without ASD distribute their visual attention, generate manual action, or coordinate their visual and manual behaviors during toy play with a parent. Our findings suggest an intact ability and willingness of children with ASD to explore toys and suggest that context is important when studying child behavior.

Gastrointestinal (GI) disorders are common in children with neurodevelopmental disorders such as autism spectrum disorder (ASD). A limited understanding of the biologic factors that predispose this population to GI disorders has prevented development of individualized therapies to address this important medical issue. The goal of the current study was to determine if elements of the salivary micro-transcriptome could provide insight into the biologic perturbations unique to children with ASD-related GI disturbance. This cohort study included 898 children (ages 18–73 months) with ASD, non-ASD developmental delay (DD), or typical development (TD). The saliva micro-transcriptome of each child was assessed with RNA-seq. Outputs were aligned to microbial and human databases. A Kruskal Wallis analysis of variance (ANOVA) was used to compare levels of 1821 micro-transcriptome features across neurodevelopmental status (ASD, DD, or TD) and GI presence or absence. An ANOVA was also used to compare micro-transcriptome levels among GI sub-groups (constipation, reflux, food intolerance, other GI condition, no GI condition), and to identify RNAs that differed among children taking three common GI medications (probiotics, reflux medication, or laxatives). Relationships between features identified in ANOVA testing were examined for associations with scores on the Autism Diagnostic Observation Schedule, 2nd Edition (ADOS-2) and the Vineland Adaptive Behavior Scales. GI disturbance rates were higher among children with ASD than peers with TD but were similar to those with DD. Five piwi-interacting RNAs and three microbial RNAs displayed an interaction between developmental status and GI disturbance. Fifty-seven salivary RNAs differed between GI sub-groups–with microRNA differences between food intolerance and reflux groups being most common. Twelve microRNAs displayed an effect of GI disturbance and showed association with GI medication uses and measures of behavior. These 12 microRNAs displayed enrichment for 13 physiologic pathways, including metabolism/digestion long-term depression, and neurobiology of addiction. This study identifies salivary micro-transcriptome features with differential expression among children with ASD-related GI disturbance. A subset of the RNAs displays relationships with treatment modality and are associated with autistic behaviors. The pathobiologic targets of the micro-transcriptome markers may serve as targets for individualized therapeutic interventions aimed at easing pain and behavioral difficulties seen in ASD-related GI disturbance.

Abstract Background Fragile X syndrome (FXS) is the leading inherited cause of autism spectrum disorder, but there remains debate regarding the clinical presentation of social deficits in FXS. The aim of this study was to compare individuals with FXS to typically developing controls (TDC) and individuals with idiopathic autism spectrum disorder (ASD) across two social eye tracking paradigms. Methods Individuals with FXS and age- and gender-matched TDC and individuals with idiopathic ASD completed emotional face and social preference eye tracking tasks to evaluate gaze aversion and social interest, respectively. Participants completed a battery of cognitive testing and caregiver-reported measures for neurobehavioral characterization. Results Individuals with FXS exhibited reduced eye and increased mouth gaze to emotional faces compared to TDC. Gaze aversive findings were found to correlate with measures of anxiety, social communication deficits, and behavioral problems. In the social interest task, while individuals with idiopathic ASD showed significantly less social preference, individuals with FXS displayed social preference similar to TDC. Conclusions These findings suggest fragile X syndrome social deficits center on social anxiety without the prominent reduction in social interest associated with autism spectrum disorder. Specifically designed eye tracking techniques clarify the nature of social deficits in fragile X syndrome and may have applications to improve phenotyping and evaluate interventions targeting social functioning impairments.

Social attention deficits are a hallmark characteristic within autism spectrum disorder (ASD) and have been hypothesized to have cascading effects on emotion recognition. Eye-tracking methodology has emerged as a potentially reliable, feasible, and sensitive biomarker for examining core phenotypic features of ASD; however, these findings are mixed with regards to measuring treatment change in clinical trials. The present study aimed to assess the utility of an eye-tracking paradigm to discriminate between clinical groups in social attention and emotion recognition through face scanning and pupillometry. The present study also assessed the reliability of this paradigm within the ASD sample to further our understanding of the utility of eye-tracking for future clinical trials. Participants included 42 individuals with ASD, 29 developmental disability (DD) controls, and 62 typically developing (TD) controls between 3 and 25 years of age. An emotional faces eye-tracking paradigm was administered to all participants, with the ASD group completing the paradigm a second time approximately 2 months later. Participants’ average proportion of looking and number of fixations to specific areas of interest (AOI) were examined along with changes in pupil reactivity while viewing different emotional faces. Results suggest atypical face-scanning through a reduced proportion of looking and the number of fixations toward the eyes in the ASD group regardless of the emotion that was presented. Further, pupillometry measures were able to detect increases in pupil dilation to happy faces in the ASD group. Lastly, test-retest reliability coefficients varied between the poor and excellent range based on the mechanism assessed, with the proportion of looking demonstrating the highest reliability coefficients. These findings build on the promise of eye-tracking as a feasible and reliable biomarker for identifying social attention and emotion recognition deficits in ASD. Detecting differences in emotion recognition explicitly through facial scanning was not as clear. Specific mechanisms within the eye-tracking paradigm may be viable options for assessing treatment-specific outcomes.

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and is associated with increased risk for autism spectrum disorder (ASD), anxiety, ADHD, and epilepsy. While our understanding of FXS pathophysiology has improved, a lack of validated blood-based biomarkers of disease continues to impede bench-to-bedside efforts. To meet this demand, there is a growing effort to discover a reliable biomarker to inform treatment discovery and evaluate treatment target engagement. Such a marker, amyloid-beta precursor protein (APP), has shown potential dysregulation in the absence of fragile X mental retardation protein (FMRP) and may therefore be associated with FXS pathophysiology. While APP is best understood in the context of Alzheimer disease, there is a growing body of evidence suggesting the molecule and its derivatives play a broader role in regulating neuronal hyperexcitability, a well-characterized phenotype in FXS. To evaluate the viability of APP as a peripheral biological marker in FXS, we conducted an exploratory ELISA-based evaluation of plasma APP-related species involving 27 persons with FXS (mean age: 22.0 ± 11.5) and 25 age- and sex-matched persons with neurotypical development (mean age: 21.1 ± 10.7). Peripheral levels of both Aβ(1–40) and Aβ(1–42) were increased, while sAPPα was significantly decreased in persons with FXS as compared to control participants. These results suggest that dysregulated APP processing, with potential preferential β-secretase processing, may be a readily accessible marker of FXS pathophysiology.

Restricted repetitive behaviors (RRBs) are a core area of impairment in autism spectrum disorder (ASD), but also affect several other neurodevelopmental disorders including fragile X syndrome (FXS). Current literature has begun to describe the RRB profile in FXS up through adolescence; however, little is known about the subtypes of RRBs in adolescents and adults. Further, literature on the RRB profile of females with FXS is limited. The present study examines the RRB profile across subtypes and specific items in both males and females with FXS while assessing for differences based on age, ASD diagnosis and the impact of IQ. Participants included 154 individuals with FXS (ages 2 to 50 years old). Results revealed a peak in RRB severity in FXS between 7–12 years for the majority of RRB subscales with the exception of Sensory-Motor behaviors peaking between 2 and 12 years before declining. Distinct RRB profiles in males and females with FXS emerged in addition to significant overlap among the item and subscale levels of RRBs across gender. Further, an added diagnosis of ASD significantly increased rates of RRBs across all subscale levels, but not necessarily across all items. Lastly, IQ did not solely account for the presence of RRBs in FXS, with Sensory-Motor behaviors being driven by comorbid ASD in males with FXS, and Restricted Interest behaviors being driven by comorbid ASD regardless of gender. These findings build on the current understanding of RRBs in FXS based on gender and comorbid ASD and lay important groundwork for the development of targeted behavioral and pharmacological treatments.

Health-related quality of life (HRQoL) is a multidimensional concept involving physical, psychological, social, and cognitive aspects of life. Individuals with Fragile X syndrome (FXS) experience a life-long disorder that impacts the HRQoL of the affected individual and their family. Thus, HRQoL may be an important outcome measure following intervention. However, it is yet not known whether HRQoL concerns relate to observed impairments in FXS. In the present study, we examined the nature and degree of association between HRQoL and established measures of functioning in FXS using the Parent Report for Children version of the PedsQL 4.0 Generic Core Scales and Cognitive Functioning Scale. We observed significant relationships between HRQoL a nd measures of adaptive behavior, maladaptive behaviors, and social functioning. The present study has implications for treatment outcomes for clinical trials in FXS.

Language impairment is a core difficulty in fragile X syndrome (FXS), and yet standardized measures lack the sensitivity to assess developmental changes in the nature of these impairments. Expressive Language Sampling Narrative (ELS-N) has emerged as a promising new measure with research demonstrating its usefulness in a wide range of ages in developmental disabilities and typical development. We examined ELS-N results in FXS and age-matched typically developing (TD) controls along with cognitive, adaptive, and clinical measures. We found the groups differed significantly on all ELS-N variables. Cognitive abilities were related to lexical diversity, syntactic complexity, and unintelligibility for the FXS group, but only verbal abilities were related to syntactic complexity in TD. Autism spectrum disorder (ASD) symptomatology was related to less intelligibility in speech. Measures of hyperactivity were related to increased talkativeness and unintelligibility. In addition, FXS males in comparison to FXS females were more impaired in cognitive ability, ASD symptoms, hyperactivity, and anxiety. This study extends the previous ELS research, supporting its use in FXS research as a measure to characterize language abilities. It also demonstrates the relationships between ELS-N variables and measures of cognitive, adaptive, ASD symptoms, and clinical symptoms.

A paired course model for under-prepared college students incorporates a dual instructional approach, academic skill building and lifelong learning development, to help students do more academically and become stronger lifelong learners. In a reading support course, students improved their reading skills and applied them directly to the paired content course. They also developed lifelong learning attributes through increased self-knowledge (using the Effective Lifelong Learning Inventory), reflection, and coaching. Students showed significant gains in lifelong learning, and 85% success rate in the paired content course, and a higher retention rate than students outside the project with similar SAT critical reading scores.

Lifelong learning skills have been shown to benefit students during and after college. This paper discusses the use of the Effective Lifelong Learning Inventory (ELLI) in a first-year composition course. Reflective writing assignments and pre- and post-semester ELLI data were used to assess student growth as lifelong learners over the course of a semester. Statistically significant gains in lifelong learning dimensions were made by students in the study as compared to those in a control group who received no direct instruction. The authors reflect on the outcomes of the project for students and instructors and question the general assumptions often made about the outcomes of a college education, namely, whether students gain lifelong learning skills simply by virtue of attending college, or is more instruction on these “intangible” qualities needed?

Executive function (EF) supports goal-directed behavior and includes key aspects such as working memory, inhibitory control, cognitive flexibility, attention, processing speed, and planning. Fragile X syndrome (FXS) is the leading inherited monogenic cause of intellectual disability and is phenotypically characterized by EF deficits beyond what is expected given general cognitive impairments. Yet, a systematic review of behavioral studies using performance-based measures is needed to provide a summary of EF deficits across domains in males and females with FXS, discuss clinical and biological correlates of these EF deficits, identify critical limitations in available research, and offer suggestions for future studies in this area. Ultimately, this review aims to advance our understanding of the underlying pathophysiological mechanisms contributing to EF in FXS and to inform the development of outcome measures of EF and identification of new treatment targets in FXS.

Language delay and communication deficits are a core characteristic of the fragile X syndrome (FXS) phenotype. To date, the literature examining early language development in FXS is limited potentially due to barriers in language assessment in very young children. The present study is one of the first to examine early language development through vocal production and the language learning environment in infants and toddlers with FXS utilizing an automated vocal analysis system. Child vocalizations, conversational turns, and adult word counts in the home environment were collected and analyzed in a group of nine infants and toddlers with FXS and compared to a typically developing (TD) normative sample. Results suggest infants and toddlers with FXS are exhibiting deficits in their early language skills when compared to their chronological expectations. Despite this, when accounting for overall developmental level, their early language skills appear to be on track. Additionally, FXS caregivers utilize less vocalizations around infants and toddlers with FXS; however, additional research is needed to understand the true gap between FXS caregivers and TD caregivers. These findings provide preliminary information about the early language learning environment and support for the feasibility of utilizing an automated vocal analysis system within the FXS population that could ease data collection and further our understanding of the emergence of language development.