Childhood unpredictability and the development of exploration.

Early in development, the process of exploration helps children gather new information that fosters learning about the world. Yet, it is unclear how childhood experiences may influence the way humans approach new learning. What influences decisions to exploit known, familiar options versus trying a novel alternative? We found that childhood unpredictability, characterized by unpredictable caregiving and unstable living environments, was associated with reduced exploratory behavior. This effect holds while controlling for individual differences, including anxiety and stress. Individuals who perceived their childhoods as unpredictable explored less and were instead more likely to repeat previous choices (habitual responding). They were also more sensitive to uncertainty than to potential rewards, even when the familiar options yielded lower rewards. We examined these effects across multiple task contexts and via both in-person (N = 78) and online replication (N = 84) studies among 10- to 13-y-olds. Results are discussed in terms of the potential cascading effects of unpredictable environments on the development of decision-making and the effects of early experience on subsequent learning.

Expectation effects in working memory training.

There is a growing body of research focused on developing and evaluating behavioral training paradigms meant to induce enhancements in cognitive function. It has recently been proposed that one mechanism through which such performance gains could be induced involves participants' expectations of improvement. However, no work to date has evaluated whether it is possible to cause changes in cognitive function in a long-term behavioral training study by manipulating expectations. In this study, positive or negative expectations about cognitive training were both explicitly and associatively induced before either a working memory training intervention or a control intervention. Consistent with previous work, a main effect of the training condition was found, with individuals trained on the working memory task showing larger gains in cognitive function than those trained on the control task. Interestingly, a main effect of expectation was also found, with individuals given positive expectations showing larger cognitive gains than those who were given negative expectations (regardless of training condition). No interaction effect between training and expectations was found. Exploratory analyses suggest that certain individual characteristics (e.g., personality, motivation) moderate the size of the expectation effect. These results highlight aspects of methodology that can inform future behavioral interventions and suggest that participant expectations could be capitalized on to maximize training outcomes.

The structure and development of explore-exploit decision making.

A critical component of human learning reflects the balance people must achieve between focusing on the utility of what they know versus openness to what they have yet to experience. How individuals decide whether to explore new options versus exploit known options has garnered growing interest in recent years. Yet, the component processes underlying decisions to explore and whether these processes change across development remain poorly understood. By contrasting a variety of tasks that measure exploration in slightly different ways, we found that decisions about whether to explore reflect (a) random exploration that is not explicitly goal-directed and (b) directed exploration to purposefully reduce uncertainty. While these components similarly characterized the decision-making of both youth and adults, younger participants made decisions that were less strategic, but more exploratory and flexible, than those of adults. These findings are discussed in terms of how people adapt to and learn from changing environments over time.Data has been made available in the Open Science Foundation platform (osf.io).

Going beyond video game consumption when considering Internet Gaming Disorder.

BACKGROUND: Recognizing the crucial importance of understanding the impact of video games on health in today's gaming-dominated world, our study aimed to investigate the relationship between gaming time and Internet Gaming Disorder (IGD). Despite the widespread assumption that a connection exists between both, previous studies have revealed highly variable associations, highlighting significant weaknesses in establishing a robust link. METHODS: To unravel this complex relationship, we recruited two independent samples of League of Legends players. We combined the collection of self-reported and actual gameplay data, together with assessments of mental health, personality traits, and cognitive abilities. RESULTS: Surprisingly, none of the gaming variables demonstrated a robust and stable association with IGD, regardless of whether players spent less than or more than 30 hours per week gaming-a threshold suggested by the American Psychiatric Association as a potential indicator of disordered gaming. Notably, mental health factors, such as anxiety, depression and ADHD, emerged as the most influential predictors of IGD. CONCLUSION: These findings, replicated across two independent samples, challenge the prevailing belief that limiting screen time alone effectively combats IGD. Instead, mental health factors play a crucial role in mitigating risks associated with gaming. Policies focusing solely on restricting screen time are insufficient in reducing the prevalence or symptoms of IGD. Rather, a comprehensive approach that considers mental health and key personality traits must be adopted to safeguard the well-being of individuals engaged in gaming.

Occupational effects in patients with post-COVID-19 syndrome.

BACKGROUND: It is well recognized that some individuals experience persistent symptoms following an initial SARS-CoV-2 infection. Symptoms affect physical, cognitive and mental well-being and can adversely impact activities of daily living, including the ability to work. AIMS: To examine the impact of post-COVID-19 syndrome with respect to effects on quality of life and impact on work in a cohort of people referred to a 'Long COVID' service. METHODS: All triaged patients (over 18 years with symptoms more than 12 weeks since the initial infection) completed a symptom assessment questionnaire. Occupation and working status (at work, at work struggling with symptoms and off work) were also recorded. Impact on function and quality of life was assessed using the EQ5D5L questionnaire. RESULTS: A total of 214 patients (median age 51.0 years, 135 females) were seen from January to September 2021. Analysis of occupational status showed: 18% were working, 40% were working but struggling and 35% had stopped working due to symptoms. Those unable to work reported significantly more fatigue, a greater perception of the need for support and lower quality-of-life scores. CONCLUSIONS: This study shows the extensive impact of post-COVID-19 syndrome on the ability to return to work. Specific return-to-work guidance is needed to support a large proportion of those struggling with the condition. The involvement of the Occupational Health team should form part of the multidisciplinary, collaborative approach to support rehabilitation and improve long-term outcomes for this condition.

The cold chain delivery of organs for transplantation: from research laboratories and individual enthusiasts to pan- global networks in 50 years.

It is some 50 years since the first published reports appeared of ex vivo preservation of organs for transplantation. Over the intervening decades, organ preservation strategies have become one essential component of world-wide clinical transplant services. In the formative years, translational research in organ hypothermic preservation was grappling with the questions about whether static or dynamic storage was preferable, and the practical implications of those choices. Those studies were also informing the newly expanding clinical transplant services. During the middle years, both preservation modalities were practiced by individual group choices. By the 2000s, the shift in donor demographics demanded a re-evaluation of organ preservation strategies, and now a new era of research and development is promoting adoption of new technologies. In this review we outline many important academic studies which have contributed to this successful history, and give profile to the increasing innovative approaches which are being evaluated for the future. Doi.org/10.54680/fr24310110112.

Transcriptomic response and immunological responses to chimpanzee adenovirus- and MVA viral-vectored vaccines for RSV in healthy adults.

Cohorts of healthy younger adults (18-50yrs) and healthy older adults (60-75yrs) were immunized intramuscularly or intranasally with an adenovirus-vectored RSV vaccine (PanAd3-RSV) as a prime dose and boosted with PanAd3-RSV or a poxvirus-vectored vaccine (MVA-RSV) encoding the same insert. Whole blood gene expression was measured at baseline, 3- and 7-days post vaccination. Intramuscular prime vaccination with PanAd3-RSV induced differential expression of 643 genes (DEGs, FDR < 0.05). Intranasal prime vaccination with PanAd3-RSV did not induce any differentially expressed genes (DEGs) in blood samples at 3 days post vaccination. Intranasally primed participants showed greater numbers of DEGS on boosting than intramuscularly primed participants. The most highly enriched biological processes related to DEGs after both prime and boost vaccination were type-1 interferon related pathways, lymphocytic and humoral immune responses.

Frequency and prediction of persistent urinary tract dilation in third trimester and postnatal urinary tract dilation in infants following diagnosis in second trimester.

OBJECTIVE: To determine the frequency, associated characteristics and prognostic value of the current risk stratification system for prenatal urinary tract dilation (UTD) for predicting persistent UTD in the third trimester and subsequent postnatal UTD in the infant, following diagnosis in the second trimester. METHODS: This was a single-institution retrospective cohort study of singleton pregnancies diagnosed with unilateral or bilateral UTD in the second trimester (before 28 weeks' gestation) with follow-up in the third trimester (at or after 28 weeks) between January 2017 and May 2019. In all cases, the prenatal diagnosis and stratification to low-risk (Grade A1) or increased-risk (Grade A2-3) UTD was made using the 2014 UTD consensus classification system. The primary outcomes included persistent prenatal UTD in the third trimester and postnatal UTD up to 6 months of age. We performed multivariable analysis to assess whether patient and second- and third-trimester sonographic characteristics (such as UTD laterality, other renal abnormality (calyceal dilation, abnormal parenchymal appearance, abnormal ureter or bladder) and anteroposterior renal pelvic diameter (AP-RPD)) were associated with the study outcomes. We assessed the predictive value of the current risk stratification system (Grade A1 vs Grade A2-3) in the second and third trimesters for persistent prenatal UTD and postnatal UTD using the area under the receiver-operating-characteristics curve (AUC). RESULTS: Of 26 620 second-trimester ultrasound assessments in the study period, 347 patients were diagnosed with UTD in the second trimester and had third-trimester follow-up, of whom 150/347 (43% (95% CI, 38-49%)) had persistent UTD in the third trimester. Among the 282/347 (81%) patients with postnatal follow-up available, the frequency of postnatal UTD was 49/282 (17% (95% CI, 13-22%)), and among the subset with persistent UTD in the third trimester, the frequency of postnatal UTD was 46/102 (45% (95% CI, 35-55%)). The most frequent postnatal diagnosis was transient UTD (76%), followed by duplicated collecting system (10%). Of infants originally diagnosed with UTD in the second trimester, 2% (7/347) required surgery; stated differently, of the 49 infants with postnatal UTD, 14% (7/49) required surgery. At second-trimester diagnosis, sonographic predictors of both persistent prenatal UTD and postnatal UTD included the presence of other renal abnormality and UTD Grade A2-3. At third-trimester follow-up, predictors of postnatal UTD were larger mean AP-RPD and UTD Grade A2-3, while all cases had other renal abnormality. Second-trimester diagnosis of UTD Grade A2-3 had satisfactory discrimination for predicting persistent prenatal UTD (AUC, 0.64 (95% CI, 0.58-0.70)) and postnatal UTD (AUC, 0.72 (95% CI, 0.63-0.81)), as did third-trimester UTD Grade A2-3 for predicting postnatal UTD (AUC, 0.66 (95% CI, 0.56-0.76)). CONCLUSIONS: The majority of cases of prenatal UTD did not result in postnatal UTD, and of those that did, very few required surgery. Follow-up third-trimester assessment after a second-trimester diagnosis of UTD is warranted. The current risk stratification system by UTD grade, based on the 2014 UTD consensus classification, can be used to predict postnatal UTD with fair accuracy. Further research is needed to determine whether the predictive performance of this system can be improved by incorporating additional risk factors. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

What is in? What is out? Updating the British Society for Cutaneous Allergy facial series.

BACKGROUND: Allergic contact dermatitis (ACD) to cosmetics is widely reported. To ensure we are accurately diagnosing ACD, patch test series should be continually reviewed to identify relevant and emerging allergens and highlight those that are outdated. The current British Society for Cutaneous Allergy (BSCA) facial series recommends 26 allergens and was last modified in 2012. OBJECTIVES: To review and update the BSCA facial series. METHODS: We retrospectively reviewed the results from 12 UK and Ireland patch test centres' facial series from January 2016 to December 2017. We recorded the number of allergens tested in each centre and the detection rate for each allergen. Using a 0·3% positive rate as the inclusion threshold, we established which allergens in the BSCA facial series had positive patch test rates < 0·3% and > 0·3%. Allergens not in the BSCA facial series that had a positive patch test rate > 0·3% were identified. RESULTS: Overall, 4224 patients were patch tested to the facial series. The number of allergens included in individual centres' facial series ranged from 24 to 66, with a total of 103 allergens tested across all centres. Twelve of the 26 allergens in the BSCA facial series had a positive patch test rate < 0·3% and 14 had a rate > 0·3%. Twenty-five allergens not recommended in the BSCA facial series had a positive patch test rate > 0·3%. CONCLUSIONS: This audit has highlighted the significant variation in practice that exists among patch test centres, despite a recommended facial series. The BSCA facial series has been updated and now contains 24 allergens. Fifteen allergens remain, 11 allergens have been dropped and nine new allergens have been added.

The implementation of routine procedural transvaginal sonography to decrease retained products of conception: a quality improvement initiative.

BACKGROUND: Retained products of conception (POC) following uterine evacuation can lead to adverse sequelae, including hemorrhage, endometritis, intrauterine adhesions, and reoperation. Use of procedural transvaginal sonography (TVUS) in the operating room has been proposed to help decrease retained POC. METHODS: A retrospective review of all first trimester uterine evacuation procedures from 1/2015 to 2/2017 was performed, noting use of transabdominal ultrasonography, retained products of conception, and complications. A practice change was implemented in May 2018, in which routine intra-procedural TVUS use was initiated. A second retrospective chart review was conducted to assess for post-implementation incidence of retained POC, re-operation, and associated complications. RESULTS: Prior to intra-procedural TVUS implementation, 130 eligible procedures were performed during the specified timeframe, with 9/130 (6.9%) incidence of retained products of conception. TAUS was performed in 59/130 (45.4%) of procedures, and 4/9 (44.4%) of those with retained products. There were eight re-operative procedures in seven patients, and two patients were treated with misoprostol. Complications included hemorrhage, Asherman's syndrome and endometritis. Following implementation, 95 first trimester procedures were performed with transvaginal sonography, with 0 (0%) cases of retained POC (p = 0.01), no incidences of re-operation (p = 0.02), and one case of Asherman's syndrome. TVUS findings led to additional focused suction curettage in 20/95 (21.0%) of procedures. The endometrium was measured on procedure completion in 64 procedures, with a mean thickness of 5.5 mm (1-12 mm). CONCLUSION: Implementation of routine TVUS during uterine evacuation may reduce the incidence of retained POC and associated reoperation rates. Further multi-center trials are needed to confirm this finding.

Assessing the functions underlying learning using by-trial and by-participant models: Evidence from two visual perceptual learning paradigms.

Inferred mechanisms of learning, such as those involved in improvements resulting from perceptual training, are reliant on (and reflect) the functional forms that models of learning take. However, previous investigations of the functional forms of perceptual learning have been limited in ways that are incompatible with the known mechanisms of learning. For instance, previous work has overwhelmingly aggregated learning data across learning participants, learning trials, or both. Here we approach the study of the functional form of perceptual learning on the by-person and by-trial levels at which the mechanisms of learning are expected to act. Each participant completed one of two visual perceptual learning tasks over the course of two days, with the first 75% of task performance using a single reference stimulus (i.e., "training") and the last 25% using an orthogonal reference stimulus (to test generalization). Five learning functions, coming from either the exponential or the power family, were fit to each participant's data. The exponential family was uniformly supported by Bayesian Information Criteria (BIC) model comparisons. The simplest exponential function was the best fit to learning on a texture oddball detection task, while a Weibull (augmented exponential) function tended to be the best fit to learning on a dot-motion discrimination task. The support for the exponential family corroborated previous by-person investigations of the functional form of learning, while the novel evidence supporting the Weibull learning model has implications for both the analysis and the mechanistic bases of the learning.

Brain plasticity through the life span: learning to learn and action video games.

The ability of the human brain to learn is exceptional. Yet, learning is typically quite specific to the exact task used during training, a limiting factor for practical applications such as rehabilitation, workforce training, or education. The possibility of identifying training regimens that have a broad enough impact to transfer to a variety of tasks is thus highly appealing. This work reviews how complex training environments such as action video game play may actually foster brain plasticity and learning. This enhanced learning capacity, termed learning to learn, is considered in light of its computational requirements and putative neural mechanisms.

Short pulse intense pulsed light versus pulsed dye laser for the treatment of facial redness.

Treating diffuse facial redness with an intense pulsed light (IPL) source usually requires multiple sessions and may not achieve complete clearance. The 595 nm pulsed dye laser (PDL) enjoys a good reputation for reducing facial redness with non-purpuric settings. The objective of this study was to compare facial redness reduction using these two devices. After establishing the lowest light dose able to achieve transient purpura for the same pulse width of 1,5 ms with each technology, right and left sides of the face were randomly assigned for each type of treatment. There were two treatment sessions 4 weeks apart and the final evaluation was performed 8 weeks after thesecond treatment. Four blinded experienced dermatologists analyzed pre and post-treatment photographs, which demonstrated an average of 60% improvement on the segment treated with the IPL as opposed to 45% on the other segment. Pain level was described as mild and the procedure was well tolerated for both types of treatment. In this study we showed that short-pulsed intense pulsed light and PDL are similar in decreasing facial redness when non-purpuric low fluence settings are used. The IPL was faster and did not have consumables.

Perceptual Learning of Appendicitis Diagnosis in Radiological Images.

A sizeable body of work has demonstrated that participants have the capacity to show substantial increases in performance on perceptual tasks given appropriate practice. This has resulted in significant interest in the use of such perceptual learning techniques to positively impact performance in real-world domains where the extraction of perceptual information in the service of guiding decisions is at a premium. Radiological training is one clear example of such a domain. Here we examine a number of basic science questions related to the use of perceptual learning techniques in the context of a radiology-inspired task. On each trial of this task, participants were presented with a single axial slice from a CT image of the abdomen. They were then asked to indicate whether or not the image was consistent with appendicitis. We first demonstrate that, although the task differs in many ways from standard radiological practice, it nonetheless makes use of expert knowledge, as trained radiologists who underwent the task showed high (near ceiling) levels of performance. Then, in a series of four studies we show that (1) performance on this task does improve significantly over a reasonably short period of training (on the scale of a few hours); (2) the learning transfers to previously unseen images and to untrained image orientations; (3) purely correct/incorrect feedback produces weak learning compared to more informative feedback where the spatial position of the appendix is indicated in each image; and (4) there was little benefit seen from purposefully structuring the learning experience by starting with easier images and then moving on to more difficulty images (as compared to simply presenting all images in a random order). The implications for these various findings with respect to the use of perceptual learning techniques as part of radiological training are then discussed.

Recommendation to include hydroxyethyl (meth)acrylate in the British baseline patch test series.

BACKGROUND: (Meth)acrylates are potent sensitizers and a common cause of allergic contact dermatitis (ACD). The frequency of (meth)acrylate ACD has increased with soaring demand for acrylic nails. A preliminary audit has suggested a significant rate of positive patch tests to (meth)acrylates using aimed testing in patients providing a clear history of exposure. To date, (meth)acrylates have not been routinely tested in the baseline patch test series in the U.K. and Europe. OBJECTIVES: To determine whether inclusion of 2-hydroxyethyl methacrylate (2-HEMA) 2% in petrolatum (pet.) in the baseline series detects cases of treatable (meth)acrylate ACD. METHODS: During 2016-2017, 15 U.K. dermatology centres included 2-HEMA in the extended baseline patch test series. Patients with a history of (meth)acrylate exposure, or who tested positive to 2-HEMA, were selectively tested with a short series of eight (meth)acrylate allergens. RESULTS: In total 5920 patients were consecutively patch tested with the baseline series, of whom 669 were also tested with the (meth)acrylate series. Overall, 102 of 5920 (1·7%) tested positive to 2-HEMA and 140 (2·4%) to at least one (meth)acrylate. Had 2-HEMA been excluded from the baseline series, (meth)acrylate allergy would have been missed in 36 of 5920 (0·6% of all patients). The top (meth)acrylates eliciting a positive reaction were 2-HEMA (n = 102, 1·7%), 2-hydroxypropyl methacrylate (n = 61, 1·0%) and 2-hydroxyethyl acrylate (n = 57, 1·0%). CONCLUSIONS: We recommend that 2-HEMA 2% pet. be added to the British baseline patch test series. We also suggest a standardized short (meth)acrylate series, which is likely to detect most cases of (meth)acrylate allergy.

Using the Fatigue Severity Scale to inform healthcare decision-making in multiple sclerosis: mapping to three quality-adjusted life-year measures (EQ-5D-3L, SF-6D, MSIS-8D).

BACKGROUND: Fatigue has a major influence on the quality of life of people with multiple sclerosis. The Fatigue Severity Scale is a frequently used patient-reported measure of fatigue impact, but does not generate the health state utility values required to inform cost-effectiveness analysis, limiting its applicability within decision-making contexts. The objective of this study was to use statistical mapping methods to convert Fatigue Severity Scale scores to health state utility values from three preference-based measures: the EQ-5D-3L, SF-6D and Multiple Sclerosis Impact Scale-8D. METHODS: The relationships between the measures were estimated through regression analysis using cohort data from 1056 people with multiple sclerosis in South West England. Estimation errors were assessed and predictive performance of the best models as tested in a separate sample (n = 352). RESULTS: For the EQ-5D and the Multiple Sclerosis Impact Scale-8D, the best performing models used a censored least absolute deviation specification, with Fatigue Severity Scale total score, age and gender as predictors. For the SF-6D, the best performing model used an ordinary least squares specification, with Fatigue Severity Scale total score as the only predictor. CONCLUSIONS: Here we present algorithms to convert Fatigue Severity Scales scores to health state utility values based on three preference-based measures. These values may be used to estimate quality-adjusted life-years for use in cost-effectiveness analyses and to consider the health-related quality of life of people with multiple sclerosis, thereby informing health policy decisions.

Probability Learning: Changes in Behavior Across Time and Development.

Individuals track probabilities, such as associations between events in their environments, but less is known about the degree to which experience-within a learning session and over development-influences people's use of incoming probabilistic information to guide behavior in real time. In two experiments, children (4-11 years) and adults searched for rewards hidden in locations with predetermined probabilities. In Experiment 1, children (n = 42) and adults (n = 32) changed strategies to maximize reward receipt over time. However, adults demonstrated greater strategy change efficiency. Making the predetermined probabilities more difficult to learn (Experiment 2) delayed effective strategy change for children (n = 39) and adults (n = 33). Taken together, these data characterize how children and adults alike react flexibly and change behavior according to incoming information.

The 'Practice Entrepreneur' - An Australian case study of a systems thinking inspired health promotion initiative.

The potential of systems science concepts to inform approaches for addressing complex public health problems, such as obesity prevention, has been attracting significant attention over the last decade. Despite its recent popularity, there are very few studies examining the application of systems science concepts, termed systems thinking, in practice and whether (if at all) it influences the implementation of health promotion in real world settings and in what ways. Healthy Together Victoria (HTV) was based on a systems thinking approach to address obesity prevention alongside other chronic health problems and was implemented across 14 local government areas. This paper examines the experience of practitioners from one of those intervention sites. In-depth interviews with eight practitioners revealed that there was a rigidity with which they had experienced previous health promotion jobs relative to the flexibility and fluidity of HTV. While the health promotion literature does not indicate that health promotion should be overly prescriptive, the experience of these practitioners suggests it is being applied as such in real world settings. Within HTV, asking people to work with 'systems thinking', without giving a prescription about what systems thinking is, enabled practitioners to be 'practice entrepreneurs' by choosing from a variety of systems thinking methods (mapping, reflection) to engage actively in their positions. This highlights the importance of understanding how key concepts, both traditional planning approaches and systems science concepts, are interpreted and then implemented in real world settings.

Revealing complete complex KIR haplotypes phased by long-read sequencing technology.

The killer cell immunoglobulin-like receptor (KIR) region of human chromosome 19 contains up to 16 genes for natural killer (NK) cell receptors that recognize human leukocyte antigen (HLA)/peptide complexes and other ligands. The KIR proteins fulfill functional roles in infections, pregnancy, autoimmune diseases and transplantation. However, their characterization remains a constant challenge. Not only are the genes highly homologous due to their recent evolution by tandem duplications, but the region is structurally dynamic due to frequent transposon-mediated recombination. A sequencing approach that precisely captures the complexity of KIR haplotypes for functional annotation is desirable. We present a unique approach to haplotype the KIR loci using single-molecule, real-time (SMRT) sequencing. Using this method, we have-for the first time-comprehensively sequenced and phased sixteen KIR haplotypes from eight individuals without imputation. The information revealed four novel haplotype structures, a novel gene-fusion allele, novel and confirmed insertion/deletion events, a homozygous individual, and overall diversity for the structural haplotypes and their alleles. These KIR haplotypes augment our existing knowledge by providing high-quality references, evolutionary informers, and source material for imputation. The haplotype sequences and gene annotations provide alternative loci for the KIR region in the human genome reference GrCh38.p8.

Disruptive de novo mutations of DYRK1A lead to a syndromic form of autism and ID.

Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A) maps to the Down syndrome critical region; copy number increase of this gene is thought to have a major role in the neurocognitive deficits associated with Trisomy 21. Truncation of DYRK1A in patients with developmental delay (DD) and autism spectrum disorder (ASD) suggests a different pathology associated with loss-of-function mutations. To understand the phenotypic spectrum associated with DYRK1A mutations, we resequenced the gene in 7162 ASD/DD patients (2446 previously reported) and 2169 unaffected siblings and performed a detailed phenotypic assessment on nine patients. Comparison of our data and published cases with 8696 controls identified a significant enrichment of DYRK1A truncating mutations (P=0.00851) and an excess of de novo mutations (P=2.53 × 10(-10)) among ASD/intellectual disability (ID) patients. Phenotypic comparison of all novel (n=5) and recontacted (n=3) cases with previous case reports, including larger CNV and translocation events (n=7), identified a syndromal disorder among the 15 patients. It was characterized by ID, ASD, microcephaly, intrauterine growth retardation, febrile seizures in infancy, impaired speech, stereotypic behavior, hypertonia and a specific facial gestalt. We conclude that mutations in DYRK1A define a syndromic form of ASD and ID with neurodevelopmental defects consistent with murine and Drosophila knockout models.