'They don't think I can do it': Experiences of self-advocates, employment specialists, and employers on employment of adults with intellectual disability.

BACKGROUND: A multi-phase Canadian study was conducted as part of a large-scale community and academic research partnership focused on understanding and improving the employment experiences of people with intellectual disabilities. METHOD: This multi-method study utilized a sequential approach, using findings from qualitative interviews (n = 28) to inform an online survey (n = 149). Participants were invited to share their experiences with paid employment or with persons with intellectual disabilities. RESULTS: Thematic analysis of data across interview and survey findings resulted in six themes: (1) assumptions and attitudes, (2) knowledge and awareness, (3) accessibility of processes, (4) use of accommodations, (5) workplace relationships, and (6) supports and resources. CONCLUSIONS: A holistic and systemic approach has the potential to improve inclusive employment experiences of people with intellectual disabilities. Action is needed mainly at the policy and employer level to reduce barriers and improve on facilitating measures reinforced by the themes shared in this study.

Changes in Cardiac Function During a Swallow Exercise Program in Patients with Coronary Artery Disease.

Research regarding risks of swallow treatment suggests that patients with coronary artery disease (CAD) experience changes in heart rate/rhythm when completing the supraglottic swallow and super-supraglottic swallow. The current study evaluated cardiac function during multiple swallowing exercises in patients with dysphagia and CAD. Eligible patients had CAD and confirmed pharyngeal dysphagia from VFS and sufficient cognitive ability to follow direction. The protocol included an a priori concealed randomized order of seven swallowing exercises (supraglottic swallow, super-supraglottic swallow, Mendelsohn and Masako maneuvers, effortful swallow with and without breath hold, and jaw opening exercise). Objective measures of heart rate/rhythm, oxygen saturation, and blood pressure were compared before vs after the overall session and each exercise using the Wilcoxon signed-rank test, and McNemar's and Cochran's Q tests with alpha at 0.05 and power at 0.80. Participants were 20 adults (15 male), aged 28-88 (median 76.5 years). 90% were intubated during their hospital stay (44% > 1 intubation) and 20% suffered post-op stroke. Severe dysphagia, marked by NPO status, occurred in 30% of patients. Sessions were 26 min long (mean; SD = 2.29). With few exceptions, objective measures were stable pre vs post overall and after each exercise. Potential vulnerability was noted with increased heart rate after the super-supraglottic swallow and increased arrhythmias after the effortful swallow (p < 0.05 for both). The order that swallowing exercises were completed did not significantly impact cardiovascular function. Telemetry and pulse oximetry proved to be feasible tools to monitor for subtle changes in cardiovascular function during completion of swallowing exercises.

Pediatric Endocrinology Milestones 2.0-guide to their implementation.

The Milestones were initiated by the Accreditation Council for Graduate Medical Education (ACGME) to provide a framework for monitoring a trainee's progression throughout residency/fellowship. The Milestones describe stepwise skill progression through six core domains of clinical competency: Patient Care, Medical Knowledge, Interpersonal and Communication Skills, Practice-based Learning and Improvement, Professionalism, and Systems-based Practice. Since their introduction in 2013, several barriers to implementation have emerged. Thus, the ACGME launched the Milestones 2.0 project to develop updated specialty-specific milestones. The Pediatric Endocrinology Milestones 2.0 project aimed to improve upon Milestones 1.0 by addressing common limitations, providing resources for faculty to easily incorporate milestones into their assessment of trainees, and adding sub-competencies in health disparities, patient safety, and physician well-being.This paper reviews the development of the Pediatric Endocrinology Milestones 2.0 including the major changes from Milestones 1.0, development of the Supplemental Guide, and how Milestones 2.0 can be applied at the program level. Although use of the Milestones are required only for ACGME programs, the tools provided in Milestones 2.0 are applicable to fellowship programs worldwide.

Hepatic abnormalities in youth with Turner syndrome.

BACKGROUND & AIMS: Liver disease in children with Turner Syndrome (TS) is poorly understood relative to associated growth, cardiac and reproductive complications. This study sought to better characterize hepatic abnormalities in a large national cohort of youth with TS. METHODS: Using electronic health record data from PEDSnet institutions, 2145 females with TS were matched to 8580 females without TS on eight demographic variables. Outcomes included liver enzymes (AST and ALT) stratified as normal, 1-2 times above the upper limit of normal (ULN), 2-3 times ULN and >3 times ULN, as well as specific liver disease diagnoses. RESULTS: Fifty-eight percent of youth with TS had elevated liver enzymes. Patients with TS had higher odds of enzymes 1-2 times ULN (OR: 1.7, 95% CI: 1.4-1.9), 2-3 times ULN (OR: 2.7, 95% CI: 1.7-3.3) and >3 times ULN (OR: 1.7, 95% CI: 1.3-2.2). They also had higher odds of any liver diagnosis (OR: 2.4, 95% CI: 1.7-3.3), fatty liver disease (OR: 1.9, 95% CI: 1.1-3.2), hepatitis (OR: 3.7, 95% CI: 1.9-7.1), cirrhosis/fibrosis (OR: 5.8, 95% CI: 1.3-25.0) and liver tumour/malignancy (OR: 4.8, 95% CI: 1.4-17.0). In a multinomial model, age, BMI and presence of cardiovascular disease or diabetes significantly increased the odds of elevated liver enzymes in girls with TS. CONCLUSIONS: Youth with TS have higher odds for elevated liver enzymes and clinically significant liver disease compared with matched controls. These results emphasize the need for clinical screening and additional research into the aetiology and treatment of liver disease in TS. LAY SUMMARY: Turner Syndrome, a chromosomal condition in which females are missing the second sex chromosome, is often associated with short stature, infertility and cardiac complications. Liver abnormalities are less well described in the literature. In this study, nearly 60% of youth with TS have elevated liver enzymes. Furthermore, patients with TS had a diagnosis of liver disease more often than patients without TS. Our results support the importance of early and consistent liver function screening and of additional research to define mechanisms that disrupt liver function in paediatric TS females.

Clinical phenotype and management of individuals with mosaic monosomy X with Y chromosome material stratified by genital phenotype.

Individuals mosaic for monosomy X and a cell line with Y chromosome material can have genitalia that appear phenotypical female, male, or ambiguous. Those with this karyotype and typical female genitalia are diagnosed with Turner syndrome; however, this definition specifically excludes those with genitalia other than typical female. There is limited information on whether medical and neurodevelopmental risks are similar among individuals with monosomy X and Y chromosome material across genital phenotypes. This multicenter retrospective study compared comorbidities and clinical management in individuals with monosomy X and Y material and male/ambiguous genitalia to those with typical female genitalia. Electronic medical records for all patients with monosomy X and Y material (n = 76) at two large U.S. pediatric centers were abstracted for predetermined data and outcomes. Logistic regression was used to compare the two phenotypic groups adjusting for site and duration of follow-up. The male/ambiguous genitalia group was just as likely to have congenital heart disease (RR 1.0, 95%CI [0.5-1.9]), autoimmune disease (RR 0.6 [0.2-1.3]), and neurodevelopmental disorders (RR 1.4 [0.8-1.2]) as those with female genitalia. Despite similar risks, they were less likely to receive screening and counseling. In conclusion, individuals with monosomy X and Y chromosome material have similar medical and neurodevelopmental risks relative to individuals with Turner syndrome regardless of genitalia, but there are notable differences in clinical management.

Neurocognitive responses to a single session of static squats with whole body vibration.

The purpose of this study was to determine if the head accelerations using a common whole body vibration (WBV) exercise protocol acutely reduced neurocognition in healthy subjects. Second, we investigated differential responses to WBV plates with 2 different delivery mechanisms: vertical and rotational vibrations. Twelve healthy subjects (N = 12) volunteered and completed a baseline (BASE) neurocognitive assessment: the Immediate Postconcussion Assessment and Cognitive Test (ImPACT). Subjects then participated in 3 randomized exercise sessions separated by no more than 2 weeks. The exercise sessions consisted of five 2-minute sets of static hip-width stance squats, with the knees positioned at a 45° angle of flexion. The squats were performed with no vibration (control [CON]), with a vertically vibrating plate (vertical vibration [VV]), and with a rotational vibrating plate (rotational vibration [RV]) set to 30 Hz with 4 mm of peak-to-peak displacement. The ImPACT assessments were completed immediately after each exercise session and the composite score for 5 cognitive domains was analyzed: verbal memory, visual memory, visual motor speed, reaction time, and impulse control. Verbal memory scores were unaffected by exercise with or without vibration (p = 0.40). Likewise, visual memory was not different (p = 0.14) after CON, VV, or RV. Significant differences were detected for visual motor speed (p = 0.006); VV was elevated compared with BASE (p = 0.01). There were no significant differences (p = 0.26) in reaction time or impulse control (p = 0.16) after exercise with or without vibration. In healthy individuals, 10 minutes of 30 Hz, 4-mm peak-to-peak displacement vibration exposure with a 45° angle of knee flexion did not negatively affect neurocognition.

Congenital adrenal hyperplasia and the second newborn screen.

OBJECTIVE: To evaluate the effectiveness of a second newborn screen for congenital adrenal hyperplasia (CAH) in the state of Colorado and report characteristics associated with cases identified on the first versus second screen. STUDY DESIGN: Colorado implemented newborn screening for CAH with 17-hydroxyprogesterone beginning August 2000. The first screening is performed within 72 hours of life and the second between 8 and 14 days of life. We compared infants diagnosed on the basis of the first versus second newborn screen. RESULTS: The first screen identified 29 cases of which 28 represented classical CAH. The incidence of classical CAH on the first screen was 1:24,766. The second screen identified 17 additional cases, of which 11 represented classical CAH. Combined, the incidence of classical CAH was 1:17,789. The sensitivity of the first screen was 71.79%. The false negative rate of the first screen was 28.2%. In the absence of a second screen, 1:47,824 infants would have been missed. Infants diagnosed on the first screen had higher 17-hydroxyprogesterone values compared with those diagnosed on the second screen (P = .0008). CONCLUSIONS: The use of a single newborn screen for CAH missed nearly 30% of classical CAH cases in Colorado. Addition of a second screen, therefore, can improve the operating characteristics of the newborn screening program.

Androgens and estrogens synergistically regulate the expression of doublecortin and enhance neuronal recruitment in the song system of adult female canaries.

Vocal control nuclei in songbirds display seasonal changes in volume that are regulated by testosterone (T) and its androgenic (5α-dihydrotestosterone; DHT) or estrogenic (17ß-estradiol; E(2)) metabolites. In male canaries, T regulates expression of the microtubule-associated protein doublecortin (DCX), a marker of neurogenesis. We examined the effect of T and its two metabolites alone or in combination on DCX expression in adult female canaries. Treatment with T or with DHT+E(2) increased HVC volume and neuron numbers as well as the total numbers of fusiform (migrating) and round (differentiating) DCX neurons in the nucleus but generally not in adjacent areas. DHT or E(2) alone did not increase these measures but increased the density of fusiform DCX cells per section. Similar results were observed in area X, although some effects did not reach significance, presumably because plasticity in X is mediated transsynaptically and follows HVC changes with some delay. There was no effect of any treatment on the total number of neurons in area X, and no change in DCX cell densities was detected in the lateral magnocellular nucleus of the anterior nidopallium, nor in other parts of the nidopallium. DHT and E(2) by themselves thus increase density of DCX cells migrating through HVC but are not sufficient in isolation to induce the recruitment of these newborn neurons in the nucleus. These effects are generally not observed in the rest of the nidopallium, implying that steroids only act on the attraction and recruitment of new neurons in HVC without having any major effects on their production at the ventricle wall.

Predicting the onset of Addison's disease: ACTH, renin, cortisol and 21-hydroxylase autoantibodies.

CONTEXT: Autoantibodies to 21-hydroxylase (21OH-AA) precede onset of autoimmune Addison's disease (AD). Progression to AD can take months to years, and early detection of metabolic decompensation may prevent morbidity and mortality. OBJECTIVE: To define optimal methods of predicting progression to overt AD (defined by subnormal peak cortisol response to Cosyntropin) in 21OH-AA+ individuals. DESIGN, SETTING AND PARTICIPANTS: Individuals were screened for 21OH-AA at the Barbara Davis Center from 1993 to 2011. Subjects positive for 21OH-AA (n = 87) were tested, and the majority prospectively followed for the development of Addison's disease, including seven diagnosed with AD upon 21OH-AA discovery (discovered), seven who progressed to AD (progressors) and 73 nonprogressors. MAIN OUTCOME MEASURED: Plasma renin activity (PRA), ACTH, baseline cortisol, peak cortisol and 21OH-AA were measured at various time points relative to diagnosis of AD or last AD-free follow-up. RESULTS: Compared with nonprogressors, in the time period 2 months-2 years prior to the onset of AD, progressors were significantly more likely to have elevated ACTH (11-22 pM, P < 1E-4), with no significant differences in mean PRA (P = 0·07) or baseline cortisol (P = 0·08), and significant but less distinct differences seen with 21OH-AA levels (P < 1E-4) and poststimulation cortisol levels (P = 6E-3). CONCLUSION: Moderately elevated ACTH is a more useful early indicator of impending AD than 21OH-AA, PRA or peak cortisol, in the 2 months-2 years preceding the onset of AD.

Parental leave during pediatric fellowship training: A national survey.

BACKGROUND: Until recently, no uniform requirements for parental leave (PL) existed in graduate medical education. We implemented a national survey, with the objective of ascertaining fellows' perceptions of PL policies and their impact. This is the first study to focus exclusively on pediatric subspecialty fellows. METHODS: An online survey instrument was created targeting pediatric fellows. RESULTS: The survey was accessed by 1003 (25%) of the estimated 4078 pediatric subspecialty fellows and 853 (21%) submitted surveys. Respondent demographic data paralleled the data reported by the American Board of Pediatrics. Half of respondents did not know whether their program had a written PL policy. Over 40% reported ≥ 5 weeks of paid PL. Most indicated that fellows use vacation, sick leave, and unpaid time for PL. Almost half of respondents (45%) indicated that their program's PL policy increases the stress of having a child. Fellows chose establishing/extending paid leave and intentionally fostering a more supportive program culture as the most crucial candidate improvements. The importance of equitable PL polices between parent fellows and co-fellows was an important theme of our qualitative data. Fellows feel there is a moral misalignment between the field of pediatrics' dedication to maternal and child health and current PL policies governing pediatric trainees. CONCLUSIONS: PL policies vary widely among pediatric fellowship programs and are often not known by fellows. Fellows are not satisfied with PL policies, which often exacerbate stress for new parents and burden their co-fellows. Targeted modification of several aspects of PL policies may improve their acceptance.

From pattern to purpose: how comparative studies contribute to understanding the function of adult neurogenesis.

The study of adult neurogenesis has had an explosion of fruitful growth. Yet numerous uncertainties and challenges persist. Our review begins with a survey of species that show evidence of adult neurogenesis. We then discuss how neurogenesis varies across brain regions and point out that regional specializations can indicate functional adaptations. Lifespan and aging are key life-history traits. Whereas 'adult neurogenesis' is the common term in the literature, it does not reflect the reality of neurogenesis being primarily a 'juvenile' phenomenon. We discuss the sharp decline with age as a universal trait of neurogenesis with inevitable functional consequences. Finally, the main body of the review focuses on the function of neurogenesis in birds and mammals. Selected examples illustrate how our understanding of avian and mammalian neurogenesis can complement each other. It is clear that although the two phyla have some common features, the function of adult neurogenesis may not be similar between them and filling the gaps will help us understand neurogenesis as an evolutionarily conserved trait to meet particular ecological pressures.

Sex steroid-induced neuroplasticity and behavioral activation in birds.

The brain of adult homeothermic vertebrates exhibits a higher degree of morphological neuroplasticity than previously thought, and this plasticity is especially prominent in birds. In particular, incorporation of new neurons is widespread throughout the adult avian forebrain, and the volumes of specific nuclei vary seasonally in a prominent manner. We review here work on steroid-dependent plasticity in birds, based on two cases: the medial preoptic nucleus (POM) of Japanese quail in relation to male sexual behavior, and nucleus HVC in canaries, which regulates song behavior. In male quail, POM volume changes seasonally, and in castrated subjects testosterone almost doubles POM volume within 2 weeks. Significant volume increases are, however, already observable after 1 day. Steroid receptor coactivator-1 is part of the mechanism mediating these effects. Increases in POM volume reflect changes in cell size or spacing and dendritic branching, but are not associated with an increase in neuron number. In contrast, seasonal changes in HVC volume reflect incorporation of newborn neurons in addition to changes in cell size and spacing. These are induced by treatments with exogenous testosterone or its metabolites. Expression of doublecortin, a microtubule-associated protein, is increased by testosterone in the HVC but not in the adjacent nidopallium, suggesting that neuron production in the subventricular zone, the birthplace of newborn neurons, is not affected. Together, these data illustrate the high degree of plasticity that extends into adulthood and is characteristic of avian brain structures. Many questions still remain concerning the regulation and specific function of this plasticity.

The importance of clinical documentation improvement for Australian hospitals.

Clinical documentation improvement (CDI) is a recent initiative gaining increased momentum in Australia. The benefits surrounding its success internationally include improved quality and patient safety outcomes and increased reimbursement. The premise of CDI is simple: engage clinicians to improve the clinical documentation in the medical record in "real time" so that it is fit for reporting, analysis and reimbursement. Every country has differing healthcare systems and this article has focused on validating the relevancy of CDI for the Australian healthcare environment.

Running wild: neurogenesis in the hippocampus across the lifespan in wild and laboratory-bred Norway rats.

The dogmatic view that new neurons are not produced in the adult mammalian brain has been overturned in light of mounting evidence that neurogenesis continues to occur within two neurogenic niches, the subventricular zone and the hippocampus. In mammals, new neurons are incorporated into the hippocampus throughout life and are influenced by environmental and genetic factors. Most studies use captive-bred animals, and no previous studies have examined neurogenesis in free-living rats despite the common use of laboratory rats. In particular, exercise upregulates neurogenesis in the hippocampus and exercise levels would certainly differ between wild and captive populations. Therefore, it is unclear whether results from captive populations can be generalized to natural populations or reflect variations from an artificial and inappropriate "baseline" level. To address this, we compared levels of cell proliferation and the number of immature neurons (using the endogenous markers Ki67 and doublecortin, respectively) in captured wild juvenile and adult Norway rats to three captive strains (Sprague-Dawley, Long-Evans, and Brown Norway) of the same species. Here, we show that the level of cell proliferation and young immature neuron survival in the dentate gyrus of juvenile wild rats is significantly higher than in Sprague-Dawley rats, but not Long-Evans or Brown Norway rats. However, cell proliferation and the number of immature neurons in the hippocampus of adult wild rats are within the normal range of captive-bred rats at all adult ages examined. This finding is surprising given the dissimilar environments, including stressors and opportunities for exercise, encountered by each population.

Comparison of insulin autoantibody: polyethylene glycol and micro-IAA 1-day and 7-day assays.

BACKGROUND: Older studies of diabetes development typically utilized a 7-day incubation polyethylene glycol competitive insulin autoantibody assay (CIAA). Our standard micro-IAA assay (mIAA) utilizes precipitation with proteins A/G and 1-day incubation (1-day mIAA), but is less sensitive compared to the CIAA assay. METHODS: We performed CIAA and mIAA assays in various conditions. We analyzed serum samples from 446 type 1 diabetes patients, from another set of 247 type 1 diabetes patients within 2 weeks of initiation of insulin treatment, from 150 healthy control donors, from 22 healthy participants in the diabetes autoimmunity study in the young (DAISY), and also coded sera from 50 patients with newly diagnosed type 1 diabetes and 50 blood donor control samples. RESULTS: In the process of our study, we found that the key condition was the incubation time. Therefore, we extended the incubation time to 7 days (7-day mIAA assay). No CIAA-negative control was positive with either 1-day or 7-day mIAA. In a new onset type 1 diabetes and at risk cohorts (DAISY study), the 7-day mIAA identified an additional 18% as being positive along with 16% of those who were initially 1-day mIAA negative and CIAA positive. Most subjects detectable only with the 7-day mIAA assay had intermediate levels of CIAA (80-300 nU/mL) (p = 0.01). CONCLUSIONS: The 7-day mIAA assay identifies a small but significant additional subset of individuals positive on the CIAA assay, while preserving specificity.

Primary central nervous system lymphoma mimicking pituitary apoplexy: case report.

Lymphoma involving the pituitary gland is very rare and usually results from metastatic spread of systemic lymphoma. We present a case of primary central nervous system (CNS) large B cell lymphoma that manifested as pituitary apoplexy. A 45-year-old woman presented with headache, and then rapidly developed a third nerve palsy and bitemporal hemianopsia. Imaging suggested a pituitary macroadenoma, with spontaneous necrosis, extending into the suprasellar region, compressing the optic chiasm and invading the right cavernous sinus. The patient underwent transsphenoidal resection which revealed a vascular, firm tumor. An aggressive decompression of the optic chiasm was performed with complete resolution of both visual fields and third nerve palsy. Final pathology showed B cell lymphoma. Systemic work-up including bone marrow aspiration and CSF studies showed no other foci of lymphoma, and the patient was HIV-negative. Chemotherapy with methotrexate, vincristine, procarbazine, and dexamethasone was administered for primary CNS lymphoma. This is an uncommon diagnosis of which the clinician should be aware in order to tailor surgical intervention and provide early institution of proper therapy.

Sex and regional differences in estradiol content in the prefrontal cortex, amygdala and hippocampus of adult male and female rats.

In general, the behavioral and neural effects of estradiol administration to males and females differ. While much attention has been paid to the potential structural, cellular and sub-cellular mechanisms that may underlie such differences, as of yet there has been no examination of whether the differences observed may be related to differential uptake or storage of estradiol within the brain itself. We administered estradiol benzoate to gonadectomized male and female rats, and compared the concentration of estradiol in serum and brain tissue found in these rats to those of gonadectomized, oil-treated rats and intact rats of both sexes. Long-term gonadectomy (3 weeks) reduced estradiol concentration in the male and female hippocampus, but not in the male or female amygdala or in the female prefrontal cortex. Furthermore, exogenous treatment with estradiol increased estradiol content to levels above intact animals in the amygdala, prefrontal cortex and the male hippocampus. Levels of estradiol were undetectable in the prefrontal cortex of intact males, but were detectable in all other brain regions of intact rats. Here we demonstrate (1) that serum concentrations of estradiol are not necessarily reflective of brain tissue concentrations, (2) that within the brain, there are regional differences in the effects of gonadectomy and estradiol administration, and (3) that there is less evidence for local production of estradiol in males than females, particularly in the prefrontal cortex and perhaps the hippocampus. Thus there are regional differences in estradiol concentration in the prefrontal cortex, amygdala and hippocampus that are influenced by sex and hormone status.

Incidence and impact of dysphagia in patients receiving prolonged endotracheal intubation after cardiac surgery.

BACKGROUND: Cardiac surgery is frequently associated with prolonged endotracheal intubation. Because oral feeding is an important component of patient recovery after high-risk surgery, we sought to examine the contribution of dysphagia in the recuperation process after prolonged endotracheal intubation. METHODS: All 254 adult patients who survived cardiac surgery between 2001 and 2004 at the Toronto General Hospital and in whom endotracheal intubation lasted for 48 hours or longer were eligible for our retrospective review. We used multivariate regression analysis and parametric modelling to identify patient-specific characteristics associated with postextubation dysphagia and the subsequent resumption of normal oral feeding. RESULTS: Dysphagia was diagnosed in 130 (51%) patients. Incremental factors associated with an increased risk for postextubation dysphagia included duration of endotracheal intubation (p < 0.001), the occurrence of a perioperative cerebrovascular event (p = 0.014) and the presence of perioperative sepsis (p = 0.016). Neither preoperative patient risks nor index procedural characteristics were influential factors. The occurrence of dysphagia (p < 0.001) and the duration of endotracheal intubation (p < 0.001) were the only independent factors associated with a delayed return to normal oral feeding. In contrast, several independent factors were associated with a delay to hospital discharge, including the presence of dysphagia (p < 0.001), occurrence of perioperative stroke (p < 0.001), duration of endotracheal intubation (p < 0.001) and number of endotracheal intubation events (p < 0.006). CONCLUSION: Dysphagia is more common in patients with prolonged endotracheal intubation after cardiac surgery than has previously been reported. The duration of postoperative endotracheal intubation is a strong predictor of subsequent dysphagia that both prolongs the return to normal oral feeding and delays subsequent hospital discharge. Patient-or procedure-specific factors are not good predictors. To accelerate discharge of high-risk patients, aggressive nutritional supplementation should pre-empt extubation and swallowing surveillance should follow.

Translating mucosal antigen based prevention of autoimmune diabetes to human.

Mucosal administration of autoantigen (insulin) to animal models has been demonstrated to be effective in preventing autoimmune diabetes. Efficacy is dependent upon the dose and the age at which it is delivered. Because of its low toxicity, mucosal administration of insulin represents an attractive preventive therapy in human. Translation of what is efficacious in animal models is, however, challenging. We have proposed mucosal insulin vaccination as a primary prevention strategy in children on the basis that children with extreme type 1 diabetes risk (> 50%) can be identified and that insulin has been shown to be the first target of autoimmunity in children. Novel, and similar to what is efficacious in mice, is that insulin will be administered when the children are still autoantibody negative in order to induce protective immunity prior to initiation of autoimmunity. The efficacy of increasing doses of mucosal insulin to induce protective immunity will be assessed as the primary end point of the trial. The rationale for primary vaccination and the trial strategy are discussed.