Use of temporary tracheostomy occlusion to reduce the risk of sternal wound infection after sternotomy in congenital cardiac surgery.

OBJECTIVE: To describe a method of reducing the risk of sternal wound infection after sternotomy in children with a pre-existing tracheostomy. To report our outcomes using this method from 1 January, 2013 to 31 August, 2023. METHODS: We describe a method for temporarily occluding the tracheal stoma with a removable implant with the primary goal of reducing the risk of sternotomy wound infection by preventing soilage due to tracheostomal secretions. We then performed a retrospective review of all children who underwent temporary tracheostomal occlusion between 1 January, 2013 and 31 August, 2023 at our quaternary care children's hospital. Clinical variables were extracted from the hospital medical records. The rates of antibiotic use and minor and major complications during the period when the stoma plug was in place were recorded. RESULTS: Totally, 19 patients underwent tracheal stoma plugging prior to sternotomy and were included in our analysis. There were two cases of sternal wound infection; one case occurred while the stoma plug was in place, and one developed four days following plug removal. There was one minor complication, with one patient requiring stoma revision via serial dilation at bedside at the time of recannulation. There were no deaths. CONCLUSION: Temporary occlusion of the tracheal stoma with an impermeable plug is a viable option for reducing the risk of sternal wound infection in children with a pre-existing tracheostomy who are undergoing sternotomy.

Pediatric Aerodigestive Medicine: Advancing Collaborative Care for Children With Oropharyngeal Dysphagia.

OBJECTIVES: Aerodigestive disorders encompass various pathological conditions affecting the lungs, upper airway, and gastrointestinal tract in children. While advanced care has primarily occurred in specialty centers, many children first present to general pediatric gastroenterologists with aerodigestive symptoms necessitating awareness of these conditions. At the 2021 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the aerodigestive Special Interest Group held a full-day symposium entitled, Pediatric Aerodigestive Medicine: Advancing Collaborative Care of Children with Aerodigestive Disorders. The symposium aimed to underline the significance of a multidisciplinary approach to achieve better outcomes for these complex patients. METHODS: The symposium brought together leading experts to highlight the growing aerodigestive field, promote new scientific and therapeutic strategies, share the structure and benefits of a multidisciplinary approach in diagnosing common and rare aerodigestive disorders, and foster multidisciplinary discussion of complex cases while highlighting the range of therapeutic and diagnostic options. In this article, we showcase the diagnostic and therapeutic approach to oropharyngeal dysphagia (OPD), one of the most common aerodigestive conditions, emphasizing the role of a collaborative model. CONCLUSIONS: The aerodigestive field has made significant progress and continues to grow due to a unique multidisciplinary, collaborative model of care for these conditions. Despite diagnostic and therapeutic challenges, the multidisciplinary approach has enabled and greatly improved efficient, high-quality, and evidence-based care for patients, including those with OPD.

The Fungal Pathogen Gnomoniopsis castaneae Induces Damaging Cankers in Multiple Domestic Fagaceae Species.

Gnomoniopsis castaneae is internationally recognized as a destructive pathogen of chestnut species. Primarily associated with nut rot, it has also been associated with branch and stem cankers of chestnut and as an endophyte of multiple additional hardwood species. The present study evaluated implications of the recently reported United States presence of the pathogen for domestic Fagaceae species. Stem inoculation assays of Castanea dentata, C. mollissima, C. dentata × C. mollissima, and Quercus rubra (red oak) seedlings were utilized to examine the cankering ability of a regional isolate of the pathogen. The pathogen induced damaging cankers in all assessed species and significant stem girdling in all chestnut species. No previous study has associated the pathogen with damaging infection in Quercus species, and its presence in the United States has the potential to compound ongoing chestnut recovery programs and oak regeneration problems within forest systems.

Early childhood deprivation is associated with alterations in adult brain structure despite subsequent environmental enrichment.

Early childhood deprivation is associated with higher rates of neurodevelopmental and mental disorders in adulthood. The impact of childhood deprivation on the adult brain and the extent to which structural changes underpin these effects are currently unknown. To investigate these questions, we utilized MRI data collected from young adults who were exposed to severe deprivation in early childhood in the Romanian orphanages of the Ceaușescu era and then, subsequently adopted by UK families; 67 Romanian adoptees (with between 3 and 41 mo of deprivation) were compared with 21 nondeprived UK adoptees. Romanian adoptees had substantially smaller total brain volumes (TBVs) than nondeprived adoptees (8.6% reduction), and TBV was strongly negatively associated with deprivation duration. This effect persisted after covarying for potential environmental and genetic confounds. In whole-brain analyses, deprived adoptees showed lower right inferior frontal surface area and volume but greater right inferior temporal lobe thickness, surface area, and volume than the nondeprived adoptees. Right medial prefrontal volume and surface area were positively associated with deprivation duration. No deprivation-related effects were observed in limbic regions. Global reductions in TBV statistically mediated the observed relationship between institutionalization and both lower intelligence quotient (IQ) and higher levels of attention deficit/hyperactivity disorder symptoms. The deprivation-related increase in right inferior temporal volume seemed to be compensatory, as it was associated with lower levels of attention deficit/hyperactivity disorder symptoms. We provide compelling evidence that time-limited severe deprivation in the first years of life is related to alterations in adult brain structure, despite extended enrichment in adoptive homes in the intervening years.

GABA receptor associated protein changes the electrostatic environment around the GABA type A receptor.

We have performed fully atomistic molecular dynamics simulations of the intracellular domain of a model of the GABAA receptor with and without the GABA receptor associated protein (GABARAP) bound. We have also calculated the electrostatic potential due to the receptor, in the absence and presence of GABARAP. We find that GABARAP binding changes the electrostatic properties around the GABAA receptor and could lead to increased conductivity of chloride ions through the receptor. We also find that ion motions that would result in conducting currents are observed nearly twice as often when GABARAP binds. These results are consistent with data from electrophysiological experiments.

The impact of childhood deprivation on adult neuropsychological functioning is associated with ADHD symptom persistence.

BACKGROUND: Institutional deprivation in early childhood is associated with neuropsychological deficits in adolescence. Using 20-year follow-up data from a unique natural experiment - the large-scale adoption of children exposed to extreme deprivation in Romanian institutions in the 1980s -we examined, for the first time, whether such deficits are still present in adulthood and whether they are associated with deprivation-related symptoms of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). METHODS: Adult neuropsychological functioning was assessed across five domains (inhibitory control, emotion recognition, decision-making, prospective memory and IQ) in 70 previously institutionalized adoptees (mean age = 25.3, 50% female) and 22 non-deprived UK adoptees (comparison group, mean age = 24.6, 41% female). ADHD and ASD symptoms were assessed using parent-completed questionnaires. RESULTS: Early institutionalization was associated with impaired performance on all tasks in adulthood. Prospective memory deficits persisted after controlling for IQ. ADHD and ASD symptoms were positively correlated. After controlling for ASD symptoms, ADHD symptoms remained associated with deficits in IQ, prospective memory, proactive inhibition, decision-making quality and emotion recognition. ASD symptoms were not independently associated with neuropsychological deficits when accounting for their overlap with ADHD symptoms. Multiple regression analysis revealed that the link between childhood deprivation and adult ADHD symptoms was statistically explained by deprivation-related differences in adult IQ and prospective memory. CONCLUSIONS: These results represent some of the most compelling evidence to date of the enduring power of early, time-limited childhood adversity to impair long-term neuropsychological functioning across the lifespan - effects that are linked specifically to deprivation-related adult ADHD symptoms.

Why does early childhood deprivation increase the risk for depression and anxiety in adulthood? A developmental cascade model.

BACKGROUND: Using data from the English & Romanian Adoptees (ERA) study, we recently reported that early time-limited exposure to severe institutional deprivation is associated with early-onset and persistent neurodevelopmental problems and later-onset emotional problems. Here, we examine possible reasons for the late emergence of emotional problems in this cohort. Our main focus is on testing a developmental cascade mediated via the functional impact of early-appearing neurodevelopmental problems on late adolescent functioning. We also explore a second putative pathway via sensitization to stress. METHODS: The ERA study includes 165 Romanian individuals who spent their early lives in grossly depriving institutions and were subsequently adopted into UK families, along with 52 UK adoptees with no history of deprivation. Age six years symptoms of neurodevelopmental problems and age 15 anxiety/depression symptoms were assessed via parental reports. Young adult symptoms of depression and anxiety were assessed by both parent and self-reports; young adults also completed measures of stress reactivity, exposure to adverse life events, and functioning in work and interpersonal relationships. RESULTS: The path between early institutional deprivation and adult emotional problems was mediated via the impact of early neurodevelopmental problems on unemployment and poor friendship functioning during the transition to adulthood. The findings with regard to early deprivation, later life stress reactivity, and emotional problems were inconclusive. CONCLUSIONS: Our analysis suggests that the risk for adult depression and anxiety following extreme institutional deprivation is explained through the effects of early neurodevelopmental problems on later social and vocational functioning. Future research should more fully examine the role of stress susceptibility in this model.

Complete Tracheal Ring Deformity. A Translational Genomics Approach to Pathogenesis.

Rationale: Complete tracheal ring deformity (CTRD) is a rare congenital abnormality of unknown etiology characterized by circumferentially continuous or nearly continuous cartilaginous tracheal rings, variable degrees of tracheal stenosis and/or shortening, and/or pulmonary arterial sling anomaly.Objectives: To test the hypothesis that CTRD is caused by inherited or de novo mutations in genes required for normal tracheal development.Methods: CTRD and normal tracheal tissues were examined microscopically to define the tracheal abnormalities present in CTRD. Whole-exome sequencing was performed in children with CTRD and their biological parents ("trio analysis") to identify gene variants in patients with CTRD. Mutations were confirmed by Sanger sequencing, and their potential impact on structure and/or function of encoded proteins was examined using human gene mutation databases. Relevance was further examined by comparison with the effects of targeted deletion of murine homologs important to tracheal development in mice.Measurements and Main Results: The trachealis muscle was absent in all of five patients with CTRD. Exome analysis identified six de novo, three recessive, and multiple compound-heterozygous or rare hemizygous variants in children with CTRD. De novo variants were identified in SHH (Sonic Hedgehog), and inherited variants were identified in HSPG2 (perlecan), ROR2 (receptor tyrosine kinase-like orphan receptor 2), and WLS (Wntless), genes involved in morphogenetic pathways known to mediate tracheoesophageal development in mice.Conclusions: The results of the present study demonstrate that absence of the trachealis muscle is associated with CTRD. Variants predicted to cause disease were identified in genes encoding Hedgehog and Wnt signaling pathway molecules, which are critical to cartilage formation and normal upper airway development in mice.

Do natural experiments have an important future in the study of mental disorders?

There is an enormous interest in identifying the causes of psychiatric disorders but there are considerable challenges in identifying which risks are genuinely causal. Traditionally risk factors have been inferred from observational designs. However, association with psychiatric outcome does not equate to causation. There are a number of threats that clinicians and researchers face in making causal inferences from traditional observational designs because adversities or exposures are not randomly allocated to individuals. Natural experiments provide an alternative strategy to randomized controlled trials as they take advantage of situations whereby links between exposure and other variables are separated by naturally occurring events or situations. In this review, we describe a growing range of different types of natural experiment and highlight that there is a greater confidence about findings where there is a convergence of findings across different designs. For example, exposure to hostile parenting is consistently found to be associated with conduct problems using different natural experiment designs providing support for this being a causal risk factor. Different genetically informative designs have repeatedly found that exposure to negative life events and being bullied are linked to later depression. However, for exposure to prenatal cigarette smoking, while findings from natural experiment designs are consistent with a causal effect on offspring lower birth weight, they do not support the hypothesis that intra-uterine cigarette smoking has a causal effect on attention-deficit/hyperactivity disorder and conduct problems and emerging findings highlight caution about inferring causal effects on bipolar disorder and schizophrenia.

Trends in Liver and Skin Tumor Prevalence in Brown Bullhead ( Ameiurus nebulosus) from the Anacostia River, Washington, DC, and Nearby Waters.

The prevalence of liver and skin tumors in brown bullhead ( Ameiurus nebulosus) from the Anacostia River (Washington, DC) and nearby areas was determined in 2014, 2015, and 2016. The objectives were to (1) compare tumor prevalence across space and time; (2) analyze the 1992-2016 Chesapeake Bay Tumor Database to identify reference locations and test age, length, weight, and sex as covariates; and (3) explore whether changes in bullhead exposure to contaminants can explain the observed trends. With logistic regression, we reported large statistically significant decreases in liver tumor probabilities in bullheads from the Anacostia CSX Bridge (ANAC) area between 1996 and 2001 (merged: female, 77.8%; male, 48.6%), 2009 to 2011 (female, 42.5%; male, 16.6%), and 2014 to 2016 (female, 18.0%; male, 5.7%). Skin tumors decreased by a factor of six in both females and males. Polycyclic aromatic compounds (PAC) initiate liver neoplasms and polychlorinated biphenyls (PCBs) and DDT compounds are promoters. The causes of skin tumors in bullhead are uncertain. Biomarker and tissue data show decreases in PAC-DNA adducts and PCB and DDT contamination in ANAC bullheads. It is likely that the decreased liver tumor prevalence is associated with decreased exposure to these contaminants.

Differentiated Thyroid Cancer in the Pediatric/Adolescent Population: Evolution of Treatment.

Differentiated thyroid cancer (DTC) is the most common cancer in adolescents and young adults. In 2015, the American Thyroid Association published guidelines for management of pediatric DTC. We report our institutional experience and highlight changing practices and new opportunities. A retrospective analysis of all patients diagnosed with DTC from 2001 to 2016 was performed. Among 59 eligible patients, 31 (53%), 15 (25%), and 13 (22%) had low-risk, intermediate-risk, and high-risk disease, respectively. Half (15/31) of low-risk and all intermediate-risk/high-risk patients received radioactive iodine (I-131) ablation. For low-risk patients, average I-131 dose decreased from 80 to 42.05 mCi, and the percentage of patients who received I-131 decreased over time. Eleven of 16 patients with tumor genomic data were found to have somatic targetable (n=6) or germline (n=5) mutations. Persistent/recurrent disease was only present in high-risk (n=8) and intermediate-risk (n=1) patients. Two patients with iodine-refractory disease received trametinib to enhance radioiodine uptake. All patients were alive at follow-up (median, 5 y; range, 1 to 15 y). Coincident with the recent American Thyroid Association guidelines, the use of I-131 in low-risk patients has decreased over time in our practice. Tumor sequencing and cancer genetic evaluation may help redefine opportunities for treatment of high-risk patients and family counseling.

The Use of Preoperative Dynamic Ultrasound to Predict Ulnar Nerve Stability Following In Situ Decompression for Cubital Tunnel Syndrome.

PURPOSE: To assess the use of preoperative, dynamic ultrasound to predict ulnar nerve instability following in situ decompression for cubital tunnel syndrome. METHODS: Prior to undergoing in situ decompression, 43 consecutive patients underwent dynamic ultrasound to assess the stability of the ulnar nerve during elbow flexion. The dynamic ultrasound findings were compared with the intraoperative assessment of nerve stability following in situ decompression. RESULTS: The preoperative dynamic ultrasound agreed with intraoperative findings in 38 of 43 patients (88%). Physical examination of ulnar nerve stability agreed with the intraoperative findings in 5 of 43 patients (12%). For the 5 of 43 cases in which the dynamic ultrasound did not correlate with the degree of ulnar nerve stability after in situ decompression, dynamic ultrasound overestimated the degree of ulnar nerve stability in 4 cases. CONCLUSIONS: Preoperative dynamic ultrasound can be used to accurately predict the degree of ulnar nerve instability following in situ decompression. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II.

Child-to-adult neurodevelopmental and mental health trajectories after early life deprivation: the young adult follow-up of the longitudinal English and Romanian Adoptees study.

BACKGROUND: Time-limited, early-life exposures to institutional deprivation are associated with disorders in childhood, but it is unknown whether effects persist into adulthood. We used data from the English and Romanian Adoptees study to assess whether deprivation-associated adverse neurodevelopmental and mental health outcomes persist into young adulthood. METHODS: The English and Romanian Adoptees study is a longitudinal, natural experiment investigation into the long-term outcomes of individuals who spent from soon after birth to up to 43 months in severe deprivation in Romanian institutions before being adopted into the UK. We used developmentally appropriate standard questionnaires, interviews completed by parents and adoptees, and direct measures of IQ to measure symptoms of autism spectrum disorder, inattention and overactivity, disinhibited social engagement, conduct or emotional problems, and cognitive impairment (IQ score <80) during childhood (ages 6, 11, and 15 years) and in young adulthood (22-25 years). For analysis, Romanian adoptees were split into those who spent less than 6 months in an institution and those who spent more than 6 months in an institution. We used a comparison group of UK adoptees who did not experience deprivation. We used mixed-effects regression models for ordered-categorical outcome variables to compare symptom levels and trends between groups. FINDINGS: Romanian adoptees who experienced less than 6 months in an institution (n=67 at ages 6 years; n=50 at young adulthood) and UK controls (n=52 at age 6 years; n=39 at young adulthood) had similarly low levels of symptoms across most ages and outcomes. By contrast, Romanian adoptees exposed to more than 6 months in an institution (n=98 at ages 6 years; n=72 at young adulthood) had persistently higher rates than UK controls of symptoms of autism spectrum disorder, disinhibited social engagement, and inattention and overactivity through to young adulthood (pooled p<0·0001 for all). Cognitive impairment in the group who spent more than 6 months in an institution remitted from markedly higher rates at ages 6 years (p=0·0001) and 11 years (p=0·0016) compared with UK controls, to normal rates at young adulthood (p=0·76). By contrast, self-rated emotional symptoms showed a late-onset pattern with minimal differences versus UK controls at ages 11 years (p=0·0449) and 15 years (p=0·17), and then marked increases by young adulthood (p=0·0005), with similar effects seen for parent ratings. The high deprivation group also had a higher proportion of people with low educational achievement (p=0·0195), unemployment (p=0·0124), and mental health service use (p=0·0120, p=0·0032, and p=0·0003 for use when aged <11 years, 11-14 years, and 15-23 years, respectively) than the UK control group. A fifth (n=15) of individuals who spent more than 6 months in an institution were problem-free at all assessments. INTERPRETATION: Notwithstanding the resilience shown by some adoptees and the adult remission of cognitive impairment, extended early deprivation was associated with long-term deleterious effects on wellbeing that seem insusceptible to years of nurturance and support in adoptive families. FUNDING: Economic and Social Research Council, Medical Research Council, Department of Health, Jacobs Foundation, Nuffield Foundation.

Adult disinhibited social engagement in adoptees exposed to extreme institutional deprivation: examination of its clinical status and functional impact.

BackgroundEarly-life institutional deprivation produces disinhibited social engagement (DSE). Portrayed as a childhood condition, little is known about the persistence of DSE-type behaviours into, presentation during, and their impact on, functioning in adulthood.AimsWe examine these issues in the young adult follow-up of the English and Romanian Adoptees study.MethodA total of 122 of the original 165 Romanian adoptees who had spent up to 43 months as children in Ceausescu's Romanian orphanages and 42 UK adoptees were assessed for DSE behaviours, neurodevelopmental and mental health problems, and impairment between ages 2 and 25 years.ResultsYoung adult DSE behaviour was strongly associated with early childhood deprivation, with a sixfold increase for those who spent more than 6 months in institutions. However, although DSE overlapped with autism spectrum disorder and attention-deficit hyperactivity disorder symptoms it was not, in itself, related to broader patterns of mental health problems or impairments in daily functioning in young adulthood.ConclusionsDSE behaviour remained a prominent, but largely clinically benign, young adult feature of some adoptees who experienced early deprivation.

Annual Research Review: Threats to the validity of child psychiatry and psychology.

BACKGROUND: Suggestions have been made that many claims concern false-positive findings in the field of child psychology and psychiatry. FINDINGS: The literature was searched for concepts and findings on the validity of child psychiatry and psychology. Substantial progress has been made in some, but not all, areas and considerable challenges remain in all. CONCLUSIONS: The two major threats to validity concern the inability to examine brain tissues in life and the evidence that there is a high overlap among disorders. We emphasize the need to follow published guidelines on preplanned analyses and we note the dangers associated with unregulated flexibility in data analysis. We note the very important clinical and developmental findings that have been ignored, perhaps partly because of an excessive focus on technologies. Nevertheless, we are positive about both the accomplishments and the ways in which challenges are being met.

Heritability of autism spectrum disorders: a meta-analysis of twin studies.

BACKGROUND: The etiology of Autism Spectrum Disorder (ASD) has been recently debated due to emerging findings on the importance of shared environmental influences. However, two recent twin studies do not support this and instead re-affirm strong genetic effects on the liability to ASD, a finding consistent with previous reports. This study conducts a systematic review and meta-analysis of all twin studies of ASD published to date and explores the etiology along the continuum of a quantitative measure of ASD. METHODS: A PubMed Central, Science Direct, Google Scholar, Web of Knowledge structured search conducted online, to identify all twin studies on ASD published to date. Thirteen primary twin studies were identified, seven were included in the meta-analysis by meeting Systematic Recruitment criterion; correction for selection and ascertainment strategies, and applied prevalences were assessed for these studies. In addition, a quantile DF extremes analysis was carried out on Childhood Autism Spectrum Test scores measured in a population sample of 6,413 twin pairs including affected twins. RESULTS: The meta-analysis correlations for monozygotic twins (MZ) were almost perfect at .98 (95% Confidence Interval, .96-.99). The dizygotic (DZ) correlation, however, was .53 (95% CI .44-.60) when ASD prevalence rate was set at 5% (in line with the Broad Phenotype of ASD) and increased to .67 (95% CI .61-.72) when applying a prevalence rate of 1%. The meta-analytic heritability estimates were substantial: 64-91%. Shared environmental effects became significant as the prevalence rate decreased from 5-1%: 07-35%. The DF analyses show that for the most part, there is no departure from linearity in heritability. CONCLUSIONS: We demonstrate that: (a) ASD is due to strong genetic effects; (b) shared environmental effects become significant as a function of lower prevalence rate; (c) previously reported significant shared environmental influences are likely a statistical artefact of overinclusion of concordant DZ twins.

The risk of attention deficit hyperactivity disorder in children exposed to maternal smoking during pregnancy - a re-examination using a sibling design.

BACKGROUND: Conventional cohort studies have consistently shown that exposure to maternal smoking in pregnancy is associated with about twice the risk of attention deficit hyperactivity disorder (ADHD) in the offspring. However, recent studies using alternative designs to disentangle the effect of social and genetic confounders have suggested that confounding may account for the association. In this study we aimed to estimate the association by a sibling design. METHODS: We used a design with half and full siblings in a Danish national register-based cohort on all singletons born between January 1991 and December 2006 and followed until January 2011. Data were available for 90% (N = 968,665) of the singleton live births in the period. We used the combination of the International Classification of Diseases (10th version) diagnosis of hyperkinetic disorder (HKD) and ADHD medication to identify children. We used sibling-matched (conditional) Cox regression to control social and genetic confounding. RESULTS: Using conventional cohort analyses, we found the expected association between pregnancy smoking and offspring ADHD (adjusted HR 2.01, 95% CI 1.94-2.07). In the sibling analysis, however, we did not detect such a strong association (adjusted HR 1.07, 95% CI 0.94-1.22). There was no difference between results for half- and full sibling analyses. The link between pregnancy smoking and low birth weight remained robust in the sibling design (adjusted OR 1.68, 95% CI 1.33-2.12). CONCLUSIONS: We found no support for prenatal smoking as a strong causal factor in ADHD. Our findings suggest that the strong association found in most previous epidemiological studies is likely to be due to a strong link between maternal smoking and maternal ADHD genetics or shared family environment. Pregnant women should still be encouraged to stop smoking because of other risks, but we have no reason to believe that this would reduce the risk of ADHD in the offspring.

Early severe institutional deprivation is associated with a persistent variant of adult attention-deficit/hyperactivity disorder: clinical presentation, developmental continuities and life circumstances in the English and Romanian Adoptees study.

BACKGROUND: Early-life institutional deprivation is associated with attention-deficit/hyperactivity disorder (ADHD) later in childhood and adolescence. In this article, we examine, for the first time, the persistence of deprivation-related ADHD into young adulthood in a sample of individuals adopted as young children by UK families after periods in extremely depriving Romanian orphanages. METHODS: We estimated rates of ADHD at age 15 years and in young adulthood (ages 22-25 years) in individuals at low (LoDep; nondeprived UK adoptees and Romanian adoptees with less than 6-month institutional exposure) and high deprivation-related risk (HiDep; Romanian adoptees with more than 6-month exposure). Estimates were based on parent report using DSM-5 childhood symptom and impairment criteria. At age 15, data were available for 108 LoDep and 86 HiDep cases, while in young adulthood, the numbers were 83 and 60, respectively. Data on education and employment status, IQ, co-occurring symptoms of young adult disinhibited social engagement (DSE), autism spectrum disorder (ASD), cognitive impairment, conduct disorder (CD), callous-unemotional (CU) traits, anxiety, depression and quality of life (QoL) were also collected. RESULTS: ADHD rates in the LoDep group were similar to the general population in adolescence (5.6%) and adulthood (3.8%). HiDep individuals were, respectively, nearly four (19%) and over seven (29.3%) times more likely to meet criteria, than LoDep. Nine 'onset' young adult cases emerged, but these had a prior childhood history of elevated ADHD behaviours at ages 6, 11 and 15 years. Young adult ADHD was equally common in males and females, was predominantly inattentive in presentation and co-occurred with high levels of ASD, DSE and CU features. ADHD was associated with high unemployment and low educational attainment. CONCLUSION: We provide the first evidence of a strong persistence into adulthood of a distinctively complex and impairing deprivation-related variant of ADHD. Our results confirm the powerful association of early experience with later development in a way that suggests a role for deep-seated alterations to brain structure and function.

Why is the topic of the biological embedding of experiences important for translation?

Translational research focuses on innovation in healthcare settings, but this is a two-way process that may have implications for either treatment or prevention. Smoking and lung cancer and the fetal alcohol syndrome are used as examples. Experimental medicine that budges basic and clinical science often constitutes a key way forward. Areas of scientific progress and challenge are discussed in relation to drug action, social cognition, cognitive neuroscience, molecular genetics, gene-environment interaction, and epigenetics. Key concepts and challenges in relation to stress include toxicity, allostatic load, the hypothalamus-pituitary-adrenal axis, and objectives versus subjective stress. The reasons for the need to test causal inferences are discussed. Various kinds of "natural experiments" are discussed in illustration using the assisted conception design, the discordant monozygotic twin design, and the study of universal exposure. Animal models are discussed in relation to enrichment and deprivation effects and the effects of infant separation experiences, epigenetic effects, and the biological embedding of experiences. Translational issues are discussed in relation to the hypothalamic-pituitary-adrenal axis, epigenetics, and inflammation. In conclusion, it is suggested that there are immediate possibilities for experimental medicine but caution is needed with respect to moving into translation too quickly.

Official American Thoracic Society technical standards: flexible airway endoscopy in children.

BACKGROUND: Flexible airway endoscopy (FAE) is an accepted and frequently performed procedure in the evaluation of children with known or suspected airway and lung parenchymal disorders. However, published technical standards on how to perform FAE in children are lacking. METHODS: The American Thoracic Society (ATS) approved the formation of a multidisciplinary committee to delineate technical standards for performing FAE in children. The committee completed a pragmatic synthesis of the evidence and used the evidence synthesis to answer clinically relevant questions. RESULTS: There is a paucity of randomized controlled trials in pediatric FAE. The committee developed recommendations based predominantly on the collective clinical experience of our committee members highlighting the importance of FAE-specific airway management techniques and anesthesia, establishing suggested competencies for the bronchoscopist in training, and defining areas deserving further investigation. CONCLUSIONS: These ATS-sponsored technical standards describe the equipment, personnel, competencies, and special procedures associated with FAE in children.