Systematic reanalysis of genomic data improves quality of variant interpretation.

As genomic sequencing expands, so does our knowledge of the link between genetic variation and disease. Deeper catalogs of variant frequencies improve identification of benign variants, while sequencing affected individuals reveals disease-associated variation. Accumulation of human genetic data thus makes reanalysis a means to maximize the benefits of clinical sequencing. We implemented pipelines to systematically reassess sequencing data from 494 individuals with developmental disability. Reanalysis yielded pathogenic or likely pathogenic (P/LP) variants that were not initially reported in 23 individuals, 6 described here, comprising a 16% increase in P/LP yield. We also downgraded 3 LP and 6 variants of uncertain significance (VUS) due to updated population frequency data. The likelihood of identifying a new P/LP variant increased over time, as ~22% of individuals who did not receive a P/LP variant at their original analysis subsequently did after 3 years. We show here that reanalysis and data sharing increase the diagnostic yield and accuracy of clinical sequencing.

Coping over time: the parents of children with autism.

BACKGROUND: Although coping with autism has been examined in a number of papers, virtually no research exists on how families cope over time. This paper reports the results of a longitudinal study of parents coping with autism over a period of approximately a decade. METHODS: The research method for the study was based on ethnographic methods that emphasized in-depth interviews and participant observation. The sample for this study consisted of 28 parents (19 mothers and nine fathers) of children with autism. The instrument for the interviews consisted of questions concerning: the child's medical history and referral experience, the child's present symptomatology, the effects of the child's problems on the parent's well-being, the effects of autism on the family's social life, parental coping strategies, illness conceptualization and the parents' expectations for the future. RESULTS AND CONCLUSIONS: Coping strategies changed from the time of the initial study, as fewer parents coped through reliance on service providers, family support, social withdrawal and individualism and relatively more parents coped through their religious faith and other emotion-focused strategies. The results tentatively support previous research on coping that indicates that aging is linked to the use of more emotion-focused coping strategies.

Quantitative analysis of flavonol glycosides in Ginkgo biloba: a comparison of two analytical methods.

A comparison of testing methods for constituents of Ginkgo biloba was performed as part of the process for determining which of the many available analytical methods was most appropriate for inclusion in the American Herbal Pharmacopoeia (AHP). Three primary methods were reviewed: those adopted by the European Pharmacopoeia, the National Science Foundation-Institute for Nutraceutical Advancement (NSF-INA) and the United States Pharmacopeia. Methods were compared by evaluating sample preparation and hydrolysis, precision and methods of total flavonol glycoside calculation by two independent laboratories. The AHP adopted the method of NSF-INA for inclusion in the AHP monograph owing to observed superiority of this method in terms of precision, glycoside calculation, ease of sample preparation and chromatographic parameters.

Accommodation, resistance and transcendence: three narratives of autism.

This paper presents a narrative analysis of autism. It follows much of the literature on illness and narrative by emphasising the moral quality of illness narratives and the role it plays in creating coherence out of the disordering effects of autism on family life. In particular, the significance of narratives as "moralizing antidotes" to the experience of marginality and their linkages to the cultural "master narratives" of science, politics and faith are stressed. The three narratives presented display both conformity and non-conformity with the official narrative of autism offered by the autistic treatment centre where the research was based. Accordingly, they are described as narratives of accommodation, resistance and transcendence.

Simultaneous determination of the predominant hyperforins and hypericins in St. John's Wort (Hypericum perforatum L.) by liquid chromatography.

Hypericin and hyperforin are believed to be among the active constituents in common St. John's wort (Hypericum perforatum L.). Presently, dietary supplements are generally standardized to contain specified levels of hypericin and hyperforin, and the related compounds, pseudohypericin and adhyperforin. A rapid method was developed for simultaneous determination of these 4 active constituents by liquid chromatography (LC). A 1 g portion of dried, finely ground leaf/flower sample is extracted with 20 mL methanol for 2 h. A 0.6 mL aliquot of the crude extract is combined with 5.4 mL acetonitrile-methanol (9 + 1) and passed through a mixed solid-phase cleanup column. The eluate is examined by LC for hyperforin, adhyperforin, hypericin, and pseudohypericin on a Hypersil reversed-phase column by using simultaneous ultraviolet (284 nm) and fluorescence detection (excitation, 470 nm; emission, 590 nm). The compounds are easily separated isocratically within 8 min with a mobile phase of acetonitrile-aqueous 0.1 M triethylammonium acetate (8 + 2). Average recoveries of hyperforin and adhyperforin were 101.9 and 98.4%, respectively, for 3 sample mixtures containing concentrations ranging from approximately 0.2 to 1.5% combined hyperforins per gram dry weight. Average relative standard deviation (RSD) values for hyperforin and adhyperforin for all 3 mixtures were 18.9 and 18.0%, respectively. Average recoveries of hypericin and pseudohypericin were 88.6 and 93.3% respectively, from 3 sample mixtures containing concentrations ranging from approximately 0.2 to 0.4% combined hypericins per gram dry weight. Average RSD values for hypericin and pseudohypericin for all 3 mixtures were 3.8 and 4.2%, respectively.

High functioning autistic children and the construction of "normal family life".

This study examines the social construction of normal family life among the parents of children with high functioning autism or Asperger's syndrome. The meaning of the concept of normal family life is reviewed, and a constructionist perspective is employed to understand the parents' evaluations of their families. The results present a description of the factors used as evidence for or against family normality and the variations in such perceptions according to the gender of the parent and the child's autistic symptoms.

The use of arm vein as an alternative conduit for lower-extremity bypass.

A 4-year retrospective review of all cases utilizing arm vein for lower-extremity bypass was undertaken. Thirty-six cases were reviewed. The patients had portions of the basilic or cephalic arm veins, or both, harvested and used as a bypass for limb salvage. Composite grafts using a portion of arm vein were excluded. Information on demographics, risk factors, vascular surgical history, presenting signs and symptoms, surgical complications, patient comfort (arm vs. leg pain), and patency rates was studied. We found that all patients were initially seen with claudication or rest pain, that 22% had gangrenous changes, that there was a male dominance (75%), and that all had previous coronary artery bypass grafts or lower-extremity bypass. Limb salvage rate was 85% at 4 years. Primary patency rate was 71% at 4 years. We conclude that arm vein is a useful and durable conduit for bypass. Patient acceptance and comfort is high.

Lay conceptions of autism: parents' explanatory models.

This article reports the results of a study of lay conceptions of autism. The subjects were 33 parents of autistic children. The study utilized Kleinman's explanatory model perspective and examined parents' beliefs about autism with respect to the nature and onset of symptoms, the etiology of the affliction and the illness outcomes for their children. The parents' explanatory models varied in significant ways from the biomedical perspective on autism. The results also identified gender based differences regarding parental beliefs about the etiology of the illness.

Negotiating autism: relations between parents and treatment staff.

This study examines the relationship between parents of autistic children and the treatment centre staff at a state autistic association. There are three main points of disagreement between parents and staff including: the prospect of a cure, the nature of the child's affection, and the uniqueness of the child and how this is related to the possibility of institutionalisation. The nature of these disagreements, and the means by which they are negotiated, are examined and discussed.