Predictive impact of rare genomic copy number variations in siblings of individuals with autism spectrum disorders.

Identification of genetic biomarkers associated with autism spectrum disorders (ASDs) could improve recurrence prediction for families with a child with ASD. Here, we describe clinical microarray findings for 253 longitudinally phenotyped ASD families from the Baby Siblings Research Consortium (BSRC), encompassing 288 infant siblings. By age 3, 103 siblings (35.8%) were diagnosed with ASD and 54 (18.8%) were developing atypically. Thirteen siblings have copy number variants (CNVs) involving ASD-relevant genes: 6 with ASD, 5 atypically developing, and 2 typically developing. Within these families, an ASD-related CNV in a sibling has a positive predictive value (PPV) for ASD or atypical development of 0.83; the Simons Simplex Collection of ASD families shows similar PPVs. Polygenic risk analyses suggest that common genetic variants may also contribute to ASD. CNV findings would have been pre-symptomatically predictive of ASD or atypical development in 11 (7%) of the 157 BSRC siblings who were eventually diagnosed clinically.

Residual effect of community antimicrobial exposure on risk of hospital onset healthcare-associated Clostridioides difficile infection: a case-control study using national linked data.

BACKGROUND: Associations between antimicrobial exposure in the community and community-associated Clostridioides difficile infection (CA-CDI) are well documented but associations with healthcare-associated CDI (HA-CDI) are less clear. This study estimates the association between antimicrobial prescribing in the community and HA-CDI. METHODS: A matched case-control study was conducted by linking three national patient level datasets covering CDI cases, community prescriptions and hospitalizations. All validated cases of HA-CDI (August 2010 to July 2013) were extracted and up to three hospital-based controls were matched to each case on the basis of gender, age, hospital and date of admission. Conditional logistic regression was applied to estimate the association between antimicrobial prescribing in the community and HA-CDI. A sensitivity analysis was conducted to consider the impact of unmeasured hospital antimicrobial prescribing. RESULTS: Nine-hundred and thirty unique cases of HA-CDI with onset in hospital and no hospital discharge in the 12 weeks prior to index admission were linked with 1810 matched controls. Individuals with prior prescription of any antimicrobial in the community had an odds ratio (OR) = 1.41 (95% confidence interval (CI) 1.13-1.75) for HA-CDI compared with those without. Individuals exposed to high-risk antimicrobials (cephalosporins, clindamycin, co-amoxiclav or fluoroquinolones) had an OR = 1.86 (95% CI: 1.33-2.59). After accounting for the likely impact of unmeasured hospital prescribing, the community exposure, particulary to high-risk antimicrobials, was still associated with elevated HA-CDI risk. CONCLUSIONS: Community antimicrobial exposure is an independent risk factor for HA-CDI and should be considered as part of the risk assessment of patients developing diarrhoea in hospital.

Infants at Risk for Autism Spectrum Disorder: Frequency, Quality, and Variety of Joint Attention Behaviors.

Initiation of joint attention is a critical developmental function related to further social communicative development in infancy. Joint attention appears to be impaired very early in life for children with autism spectrum disorder (ASD), well before a formal diagnosis is established. To observe the early development of joint attention, we prospectively followed infant siblings at high risk for ASD (HR) and low-risk (LR) infants. Initiations of joint attention behaviors were coded with respect to frequency, quality, and variety from videos taken during the administration of the Autism Observation Schedule for Infants. Participants were further stratified based on the presence of ASD (n = 17) or language delay (n = 19) at 3 years of age. Our results revealed that initiations of joint attention are impaired from 12 months of age in both children with ASD and those with language delay, especially for use of gestures (i.e., showing and pointing). At 18 months, fewer initiations of joint attention in all three dimensions distinguished infants with ASD, compared to infants with language delay and HR and LR infants without a diagnosis. Beyond the definition of initiation of joint attention as an early sign for ASD, clinical implications of these results concern the importance of intervening on frequency, quality, and variety of joint attention as early as possible in infants at heightened risk for ASD.

Variability in Verbal and Nonverbal Communication in Infants at Risk for Autism Spectrum Disorder: Predictors and Outcomes.

Early communication impairment is among the most-reported first concerns in parents of young children with autism spectrum disorder (ASD). Using a parent-report questionnaire, we derived trajectory groups for early language and gesture acquisition in siblings at high risk for ASD and in children at low risk, during their first 2 years of life. Developmental skills at 6 months were associated with trajectory group membership representing growth in receptive language and gestures. Behavioral symptoms also predicted gesture development. All communication measures were strongly related to clinical and developmental outcomes. Trajectory groups further indicated slowest language/gesture acquisition in infants with later ASD diagnoses, in particular when associated with language delay. Overall, our results confirm considerable variability in communication development in high-risk infants.

Does family-based treatment reduce the need for hospitalization in adolescent anorexia nervosa?

OBJECTIVE: We examined the timing and number of days of hospitalization during the course of treatment, hospitalization effects on outcome, and predictors and moderators of the use of hospitalization in adolescents with anorexia nervosa (AN). METHOD: Data used in this study were collected from 158 adolescents (ages 12 to 18 years of age) who met DSM-IVTR criteria for AN (exclusive of the amenorrhea criteria) randomized to receive either Family Based Treatment (FBT) or Systemic Family Therapy (SyFT) in a 7 site study. RESULTS: The trajectory of hospital day use is similar in the first 5 weeks irrespective of treatment allocation. However, days of hospitalization continued to increase throughout SyFT but leveled off in FBT after ∼5 weeks of treatment. Early hospitalization was a negative predictor for improvements in percent weight change for both treatment groups (t(1)=2.6, p = 0.011). Co-morbid psychopathology predicted early hospital use in both treatments. Higher levels of eating related obsessions and depression moderated hospitalization rates suggesting that FBT reduces early hospitalization rates compared to SyFT for these subgroups. DISCUSSION: These data support and extend findings from previous studies by identifying patterns of hospital use, and predictors and moderators of treatment effect for early hospitalization use in adolescent AN. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:891-894).

Service utilization in a sample of preschool children with autism spectrum disorder: A Canadian snapshot.

OBJECTIVE: To describe services received by preschool children diagnosed with autism spectrum disorder (ASD) during the five-year period following their diagnosis. METHOD: An inception cohort of preschoolers diagnosed with ASD from Halifax (Nova Scotia), Montreal (Quebec), Hamilton (Ontario), Edmonton (Alberta) and Vancouver (British Columbia) were invited to participate. Parents/caregivers (n=414) described the services provided to their children at four time points: baseline (T1; within four months of diagnosis; mean age three years); six months later (T2); 12 months later (T3); and at school entry (T4). Data were first coded into 11 service types and subsequently combined into four broader categories (no services, behavioural, developmental and general) for analysis. RESULTS: More than 80% of children at T1, and almost 95% at T4 received some type of service, with a significant number receiving >1 type of service at each assessment point. At T1, the most common service was developmental (eg, speech-language therapy). Subsequently, the most common services were a combination of behavioural and developmental (eg, intensive therapy based on applied behaviour analysis and speech-language therapy). Service provision varied across provinces and over time. DISCUSSION: Although most preschool children with ASD residing in urban centres were able to access specialized services shortly after diagnosis, marked variation in services across provinces remains a concern.

OBJECTIF: Décrire les services qu'ont reçus des enfants d'âge préscolaire ayant un trouble du spectre autistique (TSA) pendant la période de cinq ans suivant leur diagnostic. MÉTHODOLOGIE: Une cohorte initiale d'enfants d'âge préscolaire ayant un TSA diagnostiqué et qui provenaient de Halifax (Nouvelle-Écosse), de Montréal (Québec), de Hamilton (Ontario), d'Edmonton (Alberta) ou de Vancouver (Colombie-Britannique) a été invitée à participer à l'étude. Les parents et les tuteurs (n=414) ont décrit les services fournis à leur enfant à quatre moments : au début (T1; dans les quatre mois suivant le diagnostic, âge moyen de trois ans); six mois plus tard (T2); 12 mois plus tard (T3) et à l'entrée à l'école (T4). Les chercheurs ont d'abord codé les données en 11 types de services, pour ensuite les regrouper en quatre catégories plus vastes (absence de services, comportementaux, développementaux et généraux) en vue de leur analyse. RÉSULTATS: Plus de 80 % des enfants ont reçu certains services à T1, et près de 95 % à T4, et un nombre significatif a reçu plus d'un type de services à chaque évaluation. À T1, le service le plus courant était de type développemental (p. ex., orthophonie). Par la suite, les services les plus courants étaient un mélange de services comportementaux et développementaux (p. ex., thérapie intensive selon l'analyse de comportement appliquée et orthophonie). La prestation des services variait selon les provinces et au fil du temps. EXPOSÉ: Même si la plupart des enfants d'âge préscolaire ayant un TSA qui habitaient dans un centre urbain avaient accès à des services spécialisés peu après le diagnostic, les variations marquées des services entre les provinces demeurent préoccupantes.

Language impairment and early social competence in preschoolers with autism spectrum disorders: a comparison of DSM-5 profiles.

Children with autism spectrum disorder (ASD) and structural language impairment (LI) may be at risk of more adverse social-developmental outcomes. We examined trajectories of early social competence (using the Vineland-II) in 330 children aged 2-4 years recently diagnosed with ASD, and compared 3 subgroups classified by: language impairment (ASD/LI); intellectual disability (ASD/ID) and ASD without LI or ID (ASD/alone). Children with ASD/LI were significantly more socially impaired at baseline than the ASD/alone subgroup, and less impaired than those with ASD/ID. Growth in social competence was significantly slower for the ASD/ID group. Many preschool-aged children with ASD/LI at time of diagnosis resembled "late talkers" who appeared to catch up linguistically. Children with ASD/ID were more severely impaired and continued to lag further behind.

HD 181068: a red giant in a triply eclipsing compact hierarchical triple system.

Hierarchical triple systems comprise a close binary and a more distant component. They are important for testing theories of star formation and of stellar evolution in the presence of nearby companions. We obtained 218 days of Kepler photometry of HD 181068 (magnitude of 7.1), supplemented by ground-based spectroscopy and interferometry, which show it to be a hierarchical triple with two types of mutual eclipses. The primary is a red giant that is in a 45-day orbit with a pair of red dwarfs in a close 0.9-day orbit. The red giant shows evidence for tidally induced oscillations that are driven by the orbital motion of the close pair. HD 181068 is an ideal target for studies of dynamical evolution and testing tidal friction theories in hierarchical triple systems.

Who is really at risk? Identifying risk factors for subthreshold and full syndrome eating disorders in a high-risk sample.

BACKGROUND: Numerous longitudinal studies have identified risk factors for the onset of most eating disorders (EDs). Identifying women at highest risk within a high-risk sample would allow for focusing of preventive resources and also suggests different etiologies. METHOD: A longitudinal cohort study over 3 years in a high-risk sample of 236 college-age women randomized to the control group of a prevention trial for EDs. Potential risk factors and interactions between risk factors were assessed using the methods developed previously. Main outcome measures were time to onset of a subthreshold or full ED. RESULTS: At the 3-year follow-up, 11.2% of participants had developed a full or partial ED. Seven of 88 potential risk factors could be classified as independent risk factors, seven as proxies, and two as overlapping factors. Critical comments about eating from teacher/coach/siblings and a history of depression were the most potent risk factors. The incidence for participants with either or both of these risk factors was 34.8% (16/46) compared to 4.2% (6/144) for participants without these risk factors, with a sensitivity of 0.75 and a specificity of 0.82. CONCLUSIONS: Targeting preventive interventions at women with high weight and shape concerns, a history of critical comments about eating weight and shape, and a history of depression may reduce the risk for EDs.

A 1-year follow-up of a multi-center treatment trial of adults with anorexia nervosa.

OBJECTIVE: To examine maintenance of recovery following treatment in an adult anorexia nervosa (AN) population. METHOD: One year follow-up of a randomized clinical trial with 122 participants treated with: cognitive behavioral therapy (CBT), drug therapy (fluoxetine), or a combination (CBT+fluoxetine) for 12 months. Participants were assessed at baseline, end of treatment, and follow-up. The primary outcomes were weight and the global scores from the Eating Disorder Examination (EDE) separately and combined. RESULTS: Fifty-two participants completed the follow-up. Mean weight increased from end of treatment to follow-up. Seventy-five percent (75%) of those weight recovered at end of treatment maintained this recovery at follow-up. Recovery of eating disorder psychopathology was stable from end of treatment to follow-up, with 40% of participants with a global EDE score within normal range. Using the most stringent criteria for recovery, only 21% of the completer sample was recovered. DISCUSSION: The findings suggest that while adults with AN improve with treatment and maintain these improvements during follow-up, the majority is not recovered. Additionally, further research is needed to understand barriers to treatment and assessment completion.

Laparoscopic excision of a cystic retroperitoneal adenocarcinoma arising in a focus of extra-ovarian endometriosis.

We report an unusual case of a retroperitoneal cystic adenocarcinoma arising in a focus of extra-ovarian retroperitoneal endometriosis. The lesion was completely excised using a transperitoneal laparoscopic approach without the need for any adjuvant chemotherapy or radiation therapy. The patient remains clinically well with no evidence of recurrent or metastatic disease after 3 years of follow-up. To our knowledge, this is the first reported case of this type of rare extra-gonadal endometriosis-associated neoplasm with successful laparoscopic excision.

The optimum organization for the delivery of colposcopy service in Ontario: a systematic review.

OBJECTIVE: To determine the optimum organization for colposcopy service delivery in Ontario, Canada. METHODS: A multidisciplinary expert panel was convened to develop a systematic review to inform organizational guidelines. MEDLINE, EMBASE, CINAHL, HealthSTAR, and the Cochrane Library databases were searched from 1996 to February 2006 for articles that reported guidance or outcomes relating to improved outcomes in colposcopy training, qualifications, accreditation, maintenance of competency, the delivery of colposcopy, reducing default from colposcopy clinics, and/or strategies to improve patient satisfaction or comfort. In addition, an environmental scan identified unpublished documents related to the delivery of colposcopy services. RESULTS: Sixteen guidance documents related to the delivery of colposcopy services were identified; 5 from the published literature and 11 from the environmental scan. These documents were used by the panel to inform the systematic review and companion guidelines. CONCLUSIONS: Overall, the Ontario Colposcopy Guidelines Development Group believes that the benefits associated with the implementation of colposcopy recommendations in Ontario will result in greater organization of care and improved patient outcomes. In addition, the group anticipates that these recommendations will provide useful guidance to regional planning authorities, hospital administrators, and Cancer Care Ontario, as well as colposcopists and other practitioners, in the planning of integrated regional and provincial cancer screening services.

Validity of autism diagnoses using administrative health data.

It is necessary to monitor autism prevalence in order to plan education support and health services for affected children. This study was conducted to assess the accuracy of administrative health databases for autism diagnoses. Three administrative health databases from the province of Nova Scotia were used to identify diagnoses of autism spectrum disorders (ASD): the Hospital Discharge Abstract Database, the Medical Services Insurance Physician Billings Database and the Mental Health Outpatient Information System database. Seven algorithms were derived from combinations of requirements for single or multiple ASD claims from one or more of the three administrative databases. Diagnoses made by the Autism Team of the IWK Health Centre, using state-of-the-art autism diagnostic schedules, were compared with each algorithm, and the sensitivity, specificity and C-statistic (i.e. a measure of the discrimination ability of the model) were calculated. The algorithm with the best test characteristics was based on one ASD code in any of the three databases (sensitivity=69.3%). Sensitivity based on an ASD code in either the hospital or the physician billing databases was 62.5%. Administrative health databases are potentially a cost efficient source for conducting autism surveillance, especially when compared to methods involving the collection of new data. However, additional data sources are needed to improve the sensitivity and accuracy of identifying autism in Canada.

Clinical assessment of autism in high-risk 18-month-olds.

Earlier intervention improves outcomes for children with autism spectrum disorders (ASDs), but existing identification tools are at the limits of standardization with 18-month-olds. We assessed potential behavioural markers of ASD at 18 months in a high-risk cohort of infant siblings of children with ASD. Prospective data were collected using the Autism Diagnostic Observation Schedule (ADOS) and Autism Observation Scale for Infants (AOSI) on 155 infant siblings and 73 low-risk controls at 18 months. Infants were classified into three groups (ASD sibs, non-ASD sibs, controls) based on blind best-estimate diagnosis at age 3. Fisher's exact tests, followed by discriminant function analyses, revealed that the majority of informative ADOS items came from the social and behavioural domains, and AOSI items measuring behavioural reactivity and motor control contributed additional information. Findings highlight the importance of considering not only social-communication deficits, but also basic dimensions of temperament including state regulation and motor control when assessing toddlers with suspected ASD.

Human papillomavirus--lessons from history and challenges for the future.

Human papillomavirus (HPV) is the most common sexually transmitted infection, and HPV-associated cervical cancer is a significant cause of morbidity and mortality worldwide. Recent advances in molecular biology have facilitated testing for HPV infection. Over the last decade, national and international cervical cancer screening programs have added HPV testing to their guidelines. The use of HPV prophylactic and therapeutic immunization may expand the need for systematic HPV testing to help define eligible subgroups for intervention. Given the worldwide variation in HPV subtype prevalence, basic Pap testing will continue to play an important role in cervical cancer screening, and methods to improve Pap smear sensitivity may help to improve screening in the future. This review focuses on the genetics and cellular biology of HPV infection, the natural history and prevalence of HPV infections, cervical cancer screening around the world and in Canada in particular, and evolving research to improve screening methods.

Development of a continuous cell line, PBLE, from an American eel peripheral blood leukocyte preparation.

A continuous cell line, PBLE, was developed from the adherent cells in a culture of peripheral blood leukocytes from the American eel, Anguilla rostrata. The cells were grown in Leibovitz's L-15 basal medium supplemented with 20% fetal bovine serum (FBS). Under normal culture conditions at 18 degrees C, the morphology of PBLE was fibroblast-like. The cultures have been subcultured over 80 times and have been cryopreserved successfully. These cells have a diploid karyotype of 38 chromosomes, survived temperatures from 5 to 36 degrees C, and proliferated at temperatures from 5 degrees C to at least 30 degrees C. PBLE underwent apoptosis in response to gliotoxin, but did not show a respiratory burst. Results suggest that PBLE may have arisen from a circulating mesenchymal stem cell. PBLE was susceptible to Chum salmon reovirus (CSV) and supported CSV replication. Therefore this cell line should be useful in studying eel specific virus-host interactions.

Predictors of outcome among high functioning children with autism and Asperger syndrome.

BACKGROUND: The objective of this paper is to assess the extent to which measures of cognitive abilities taken in an inception cohort of young high functioning children with autism and Asperger syndrome predict outcome roughly two and six years later. METHOD: Children who received a diagnosis of autism or Asperger syndrome (AS) and who had a nonverbal IQ score in the 'non-retarded' range were included in the inception cohort. Measures of language and nonverbal skills were taken when the children were 4-6 years of age and outcome assessments were completed when the children were 6-8 and 10-13 years of age. The three outcome measures consisted of scales of adaptive behaviours in socialisation and communication and a composite measure of autistic symptoms (abnormal language, abnormal body and object use, difficulties relating to others, sensory issues and social and self-help difficulties). RESULTS: The explanatory power of the predictor variables was greater for communication and social skills than for autistic symptoms. The power of prediction was stable over time but did differ by PDD subtype. In general, the association between language skills and outcome was stronger in the autism group than in the AS group. CONCLUSIONS: These results support the emphasis of early intervention programmes on language but more work needs to be done on understanding variables that influence outcome in social skills and autistic behaviours, particularly in those with AS.

Inhibitory mechanisms in autism spectrum disorders: typical selective inhibition of location versus facilitated perceptual processing.

BACKGROUND: This study examined the inhibitory control mechanisms of selective attention in autism spectrum disorders. Two issues were engaged: First, we extend previous findings of normal inhibition of distractor identity in autism by examining whether inhibition of spatial location is also spared. The second issue concerns the selectivity of inhibition. In non-clinical participants inhibition is selectively directed to the properties of the distractor that compete for the control of action; we examined whether individuals with autism also show normal selectivity of inhibition. METHOD: A negative priming task was used to examine selective spatial inhibition in participants with autism relative to matched non-clinical controls. RESULTS: We discovered that inhibition of distractor spatial location is within normal limits in autism, as is the ability to selectively direct inhibition to task-relevant stimulus features. In addition, we unexpectedly found that the irrelevant perceptual feature of colour produced a facilitation effect in autism, which has not been observed previously in typical controls. CONCLUSIONS: Evidence of colour facilitation implicates more fluent, but presumably less adaptive, perceptual processes in autism.

Pharmaceutical care needs of patients with angina.

OBJECTIVE: The aim of this study was to evaluate patient knowledge and assess the management of angina for patients receiving sublingual glyceryl trinitrate (GTN) METHOD: Prospective data collection and patient interview was undertaken in 17 community pharmacies. RESULTS: During the study 488 angina patients presented to the participating pharmacies. Data were collected for 347 patients receiving sublingual GTN. Problems with administration technique were identified for 108 patients (31%) and knowledge of when to seek medical help appropriately after failed GTN use was unsure for 134 patients (39%) or poor for 88 patients (25%). Eighty five patients (24%) were not receiving regular symptomatic therapy. Aspirin was prescribed or purchased by 253 patients (73%). Seven pharmacies participated in GP referral (data collected for 201 patients); 31 patients (15%) were referred usually with a recommendation to add aspirin. The outcome of 20 of these referrals was assessed; advice was taken for 13 patients, 3 patients failed to attend GP, aspirin was contraindicated for 3 patients and one patient already attended pharmacist medication review. CONCLUSION: This study demonstrated the potential contribution community pharmacists could make at the time of dispensing to the management of patients with angina.

Prolonged bottle feeding in a cohort of children: does it affect caloric intake and dietary composition?

Little is known about the consequences to children of bottle feeding prolonged beyond age 1 year on caloric intake and overall dietary composition. To obtain these data, 165 children, followed up from infancy, were assessed in these respects for a 24-hour period at age 3 1/2 years. Bottle-fed children (n = 14) consumed more milk than their weaned counterparts (p < 0.001), had a higher mean daily calcium intake (p < 0.05), received fewer calories from carbohydrates (p = 0.034), and received a greater percentage of calories from protein (p = 0.033). There were no significant differences between the groups in total caloric intake, total iron intake, total volume ofjuice, or calories from fat. Pediatricians questioned about the effects of continuing to offer children nutritive liquids from bottles as well as cups (versus offering cups alone) may inform parents that this feeding practice is associated with significantly greater milk consumption and daily calcium intake. However, this study could not find evidence that prolonged bottle feeding at age 3 1/2 years is associated with a significantly decreased total daily iron intake or an increased risk for factors associated with adiposity such as a greater daily calorie intake, a higher body mass index, or greater percentage of total calories derived from fat.