Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human Phenotype Ontology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.

PURPOSE We wanted to identify published randomized trials of interventions to alter the interaction between patients and practitioners, develop taxonomies of the interventions and outcomes, and assess the evidence that such interventions improve patients' health and well-being. METHODSUndertaking a systematic review of randomized trials, we sought trials in primary and secondary care with health-related outcomes, which we found by searching MEDLINE, HealthSTAR, and PsycINFO bibliographic databases through 1999. We also completed one round of manual citation searching.RESULTS Thirty-fi ve trials were included. Most were set in primary care in North America. Trials were heterogeneous in populations, settings, interventions, and measures. Interventions frequently combined several poorly described elements. Explicit theoretical underpinning was rare, and only one study linked intervention through process to outcome measures. Health outcomes were rarely measured objectively (6 of 35), and only 4 trials with health outcomes met predefi ned quality criteria.Interventions frequently altered the process of interactions (signifi cantly in 73%, 22 of 30 trials). Principal outcomes favored the intervention group in 74% of trials (26 of 35), reaching statistical signifi cance in 14 (40%). Positive effects on health outcomes achieved statistical signifi cance in 44% of trials (11 of 25); negative effects were uncommon (5 of 25, 20%). Simple approaches to increasing the participation of patients in the clinical encounter, such as providing practitioners with a note from patients about their concerns beforehand, showed promise, as did more complex programs providing specifi c information about disease and attention to emotion. Apparently similar interventions varied in effectiveness across studies.CONCLUSIONS Successful interactions between patients and their practitioners lie at the heart of medicine, yet there are few rigorous trials of well-specifi ed interventions to inform best practice. Trial evidence suggests that a range of approaches can achieve changes in this interaction, and some show promise in improving patients' health. To advance knowledge further, we need to replicate promising studies using rigorous methods. These should include explicit theoretical frameworks designed to link effects on key communication and interaction characteristics through to effects on health outcomes. INTRODUCTION It is now generally accepted that effective communication is as essential to high-quality medical practice as is clinical knowledge.1-4 A body of evidence suggests that participation of the patient in all stages of the Simon J. Griffi n, MSc 596 OUTCOMES OF INTERVENTIONS TO ALTER INTERACTIONclinical encounter improves effectiveness and effi ciency. Despite this evidence, practitioners often fail to listen or to elicit patients' concerns or to negotiate treatment options. [5][6][7] This failure may be in part because skills are not effectively taught, 1 but there may remain skepticism about the importance of partnersh...

This study investigated the phenotypic manifestations of interstitial duplications of chromosome 15 that involve the Prader-Willi/Angelman syndrome critical region (PWACR). Twenty-one affected individuals from six families were evaluated in detail, using standardized and semi-standardized measures of intelligence, psychopathology, and physical anomalies. Special attention was placed on determining the prevalence of autism spectrum disorders as well as the relationship between the parental origin of the duplication and the phenotypic effects. Assessments of the affected individuals were compared with evaluations of the unaffected relatives from the same families. Results indicated that duplications in the region were associated with variable degrees of intellectual impairments and motor coordination problems. Four of the subjects received a diagnosis of pervasive developmental disorder. Three of these cases were probands and only one met criteria for classic autism. There was very little evidence of the duplication cosegregating with autism spectrum disorder diagnosis. Paternally inherited duplications were significantly less likely to give rise to phenotypic effects. The findings indicate that duplications in the PWACR give rise to developmental delay but not necessarily autism spectrum disorders. They also suggest that phenotypic expression is dependent on the parental origin of the duplication and implicate maternally active genes in the pathogenesis of the developmental impairments. Further research will be required to clarify the range and basis of the phenotypic manifestations.

Findings from a large study comparing deletion and UPD forms of Prader-Willi syndrome were consistent with other evidence in indicating that paternally imprinted genes in the 15q11-13 region constitute a genetic risk factor for aspects of autistic symptomatology. These genes may therefore play a role in the aetiology of autism. By contrast with another report, there was no clear-cut relationship between the size of the deletion and the form of cognitive and behavioural phenotype.

Autism spectrum disorders (ASDs) have been linked with maternally derived duplications/triplications of chromosome 15q11-13 and therefore might occur more frequently in people with Prader-Willi syndrome (PWS) when due to uniparental disomy (UPD), than in other forms of chromosomal abnormality involving this region [i.e. deletion (DEL) forms of PWS and DEL+UPD forms of Angelman's syndrome -(AS)]. Twelve studies regarding ASD in PWS and AS were reviewed. It was noteworthy that among the genetically confirmed UPD and DEL cases of PWS and AS, the rate of ASD was 25.3% (38/150; range 0-36.5%) in PWS and 1.9% in AS (2/104; range 0-100%) (Fisher's exact P<0.0001). Among the subset of cases with confirmed UPD or DEL, the rate of ASD in the UPD cases of PWS was significantly higher (20/53) than in the remaining combined samples (i.e. DEL PWS+UPD AS+DEL AS cases; 20/201) (Fisher's exact P<0.0001). ASD in UPD PWS cases (20/53) compared with DEL PWS cases (18/97) was also statistically significant (Fisher's exact P=0.0176). Thus, the limited available evidence supported the prediction that overexpression of maternally imprinted genes in 15q11-13 confers a risk for ASD. Further research will be required to confirm these findings.