DECIDE: a Decision Support Tool to Facilitate Parents' Choices Regarding Genome-Wide Sequencing.

We describe the rationale, development, and usability testing for an integrated e-learning tool and decision aid for parents facing decisions about genome-wide sequencing (GWS) for their children with a suspected genetic condition. The online tool, DECIDE, is designed to provide decision-support and to promote high quality decisions about undergoing GWS with or without return of optional incidental finding results. DECIDE works by integrating educational material with decision aids. Users may tailor their learning by controlling both the amount of information and its format - text and diagrams and/or short videos. The decision aid guides users to weigh the importance of various relevant factors in their own lives and circumstances. After considering the pros and cons of GWS and return of incidental findings, DECIDE summarizes the user's responses and apparent preferred choices. In a usability study of 16 parents who had already chosen GWS after conventional genetic counselling, all participants found DECIDE to be helpful. Many would have been satisfied to use it alone to guide their GWS decisions, but most would prefer to have the option of consulting a health care professional as well to aid their decision. Further testing is necessary to establish the effectiveness of using DECIDE as an adjunct to or instead of conventional pre-test genetic counselling for clinical genome-wide sequencing.

The Prx1 homeobox gene is critical for molar tooth morphogenesis.

The paired-related homeobox genes, Prx1 and Prx2, encode transcription factors critical for orofacial development. Prx1(-/-)/Prx2(-/-) neonates have mandibular hypoplasia and malformed mandibular incisors. Although the mandibular incisor phenotype has been briefly described (ten Berge et al., 1998, 2001; Lu et al., 1999), very little is known about the role of Prx proteins during tooth morphogenesis. Since the posterior mandibular region was relatively normal, we examined molar tooth development in Prx1(-/-)/Prx2(-/-) embryos to determine whether the tooth malformation is primary to the loss of Prx protein or secondary to defects in surrounding tissues. Three-dimensional (3D) morphological reconstructions demonstrated that Prx1(-/-)/Prx2(-/-) embryos had molar malformations, including cuspal changes and ectopic epithelial projections. Although we demonstrate that Prx1 protein is expressed only mesenchymally, 3D reconstructions showed important morphological defects in epithelial tissues at the cap and bell stages. Analysis of these data suggests that the Prx homeoproteins are critical for mesenchymal-epithelial signaling during tooth morphogenesis.

Convergent validity of alternative MMPI-2 personality disorder scales.

The Morey, Waugh, and Blashfield (1985) MMPI (Hathaway et al., 1989) personality disorder scales provided a significant contribution to personality disorder research and assessment. However, the subsequent revisions to the MMPI and the multiple revisions to the diagnostic criteria sets that have since occurred may have justified comparable revisions to these scales. Somwaru and Ben-Porath (1995) selected a substantially different set of items from the MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989) to assess Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) personality disorder diagnostic criteria. In our study, we compared the convergent validity of these alternative MMPI-2 personality disorder scales with respect to 3 self-report measures of personality disorder symptomatology in a sample of 82 psychiatric outpatients. The results suggested that Somwaru and Ben-Porath's scales are as valid as the original Morey et al. scales and might be even more valid for the assessment of borderline, antisocial, and schizoid personality disorder symptomatology.

Objective measurement of motion in patients undergoing spiral CT examinations.

PURPOSE: To develop and evaluate an objective measurement of patient motion during spiral computed tomography (CT). MATERIALS AND METHODS: An acrylic rod was attached along the length of the torso in 109 patients (56 women, 53 men; age range, 21-79 years; mean age, 51 years) who underwent abdominal spiral CT examinations. Subjective evaluation of motion was graded on a five-point scale by two radiologists. Objective measurements of motion were determined by means of computer reconstruction of the rod in three dimensions and calculation of the deviation of the rod from its estimated position in the motionless state with time. RESULTS: Complete data were available in 98 patients. Subjective and objective measurements of patient motion showed a moderately high Spearman correlation coefficient of .49 (P < .001). The correlation between either observer and objective measurements was similar to the correlation between one observer and the other. CONCLUSION: This objective technique for assessing patient motion correlated well with subjective methods and may be useful in evaluating scanning parameters that may affect patient motion and hence scan quality.

Spiral CT with ionic and nonionic contrast material: evaluation of patient motion and scan quality.

PURPOSE: To assess the effect of rapidly injected ionic or nonionic contrast material on patient motion and scan quality in spiral computed tomography (CT). MATERIALS AND METHODS: One hundred nine patients were prospectively, randomly chosen to receive ionic or nonionic contrast material. An acrylic rod was attached to the anterior abdomen with tape, which allowed an objective measurement of motion. Abdominal spiral CT was performed after intravenous injection of contrast material at a rate of 0.9 g of iodine per second. Scans were evaluated subjectively and objectively for motion and subjectively for quality. Complete data were available in 98 patients (47 in the ionic and 51 in the nonionic group). RESULTS: The acrylic rod moved an average of 0.44 mm per section in the nonionic group and 0.71 mm per section in the ionic group. Both subjective and objective measurements showed a statistically significant difference in patient motion. Use of nonionic contrast material resulted in less patient motion. Scan quality was better with nonionic contrast material. CONCLUSION: Less patient motion occurs and scan quality improves when spiral CT is performed with nonionic contrast material.

Distribution of disease in cystic fibrosis: correlation with pulmonary function.

STUDY OBJECTIVE: We hypothesized that the radiographic distribution of disease is important in determining pulmonary function, with the lower lung zones of more importance than the upper lung zones. To test this hypothesis, we retrospectively studied patients with cystic fibrosis, a disease with a known proclivity for the upper lung zones. SUBJECTS AND METHODS: Two hundred seventy-six chest radiographs obtained at 2- to 3-year intervals from 51 patients were scored by two radiologists using a 100-point visual severity scale. The distribution of disease was assessed by dividing the lungs into four equal horizontal zones and scoring each zone for the severity of disease. There were 146 concurrent chest radiographs and pulmonary function tests from which multiple linear regression was used to correlate these zonal scores with FEV1/FVC percent predicted. RESULTS: There was excellent interobserver agreement, intraclass correlation coefficients >0.7. The distribution of disease became predominant in the upper lung zones as the patients aged. Although the median score in the upper lung zones was nearly twice that of the lower lung zones, the lower lung zones were nearly three times (partial F ratio; 6.9 lower zone score vs 2.4 upper lung zone score) as important in determining pulmonary function. CONCLUSION: The regional distribution of disease is important in determining pulmonary function. Sparing of the lower lung zones is important in preserving pulmonary function.

Clinicopathologic study of the effect of radial tears and loop fixation on intraocular lens decentration.

PURPOSE: The purpose of this study is to determine the effect of loop fixation and anterior capsular tears on intraocular lens (IOL) decentration. METHODS: A retrospective measurement of IOL decentration was performed on 144 human eyes with posterior chamber (PC) IOLs obtained after death. RESULTS: Decentration in eyes with asymmetrical bag-sulcus fixation (mean +/- standard deviation, 0.64 +/- 0.39 mm) was significantly higher than eyes with symmetrical fixation. In the presence of radial tears, symmetrically fixated IOLs in either the capsular bag or the ciliary sulcus decentered to a similar degree, 0.35 +/- 0.25 mm and 0.4 +/- 0.26 mm, respectively. The least decentration was observed with capsular fixation and no radial tears (0.18 +/- 0.09 mm). This was significantly less decentration than with any other form of fixation in the presence of radial tears. CONCLUSION: This study shows that capsular fixation with no radial tears, as can be achieved by using the continuous curvilinear capsulorhexis, is associated with the least decentration.

Combined therapy with ascorbic acid and calcitonin for the relief of bone pain in Paget's disease.

In a short trial, 24 patients with Paget's disease of the bone were treated for 2 weeks with either ascorbic acid and calcitonin in combination, or with calcitonin alone. Pain relief was then assessed subjectively by the patients and classified as nil, some, or a marked reduction in pain. There were 11 patients in the group on combined therapy and 73% of them experienced pain relief, compared with 85% of the 13 patients in the group on calcitonin alone. In the patients who experienced pain relief, however, 62% of those on the ascorbic acid and calcitonin combination claimed a marked relief of pain compared with only 36% of the patients who responded to calcitonin alone. These results indicate that when calcitonin and ascorbic acid are used in combination they may provide an increase in the extent of pain relief, but do not increase the total proportion of patients actually obtaining relief. Urinary hydroxyproline excretion was reduced in the calcitonin treated group, but there was little change in the patients on the combined therapy.

Relationship of plasma salicylate levels to pain relief with two different salicylates.

In a preliminary open study of salsalate (3 g daily for 4 weeks) in 61 patients with rheumatoid arthritis or osteoarthrosis, it was found that although the drug produced satisfactory analgesia in 64% of patients, the incidence of side-effects was high (57% of patients): most were symptoms of salicylism and probably related to the high plasma salicylate levels achieved. In a second open study, 20 patients with osteoarthrosis were treated for 4 weeks with 250 mg diflunisal twice daily and then crossed over to salsalate (3 g daily) for a further 2 weeks. The results of subjective assessments of pain relief showed that both drugs produced satisfactory analgesia, and neither was associated with a significant level of gastro-intestinal bleeding. During the diflunisal treatment period there were no reports of salicylism, and plasma salicylate levels were very much lower than those measured after salsalate. The pain relieving effects of both drugs, assessed from patient preference for one or the other treatment, were unrelated to the plasma salicylate levels and it is suggested that plasma levels may have more relationship to the incidence of side-effects than with therapeutic effects.

Ascorbic acid therapy for the relief of bone pain in Paget's disease.

Sixteen patients with painful Paget's disease of the bone were treated with high doses of ascorbic acid. Of these patients, 8 experienced lessening of pain within a period of 5 to 7 days after commencing the vitamin therapy. In 3 of these patients pain was completely abolished. Subsequent treatment with calcitonin caused improvement in most cases. There was little change in plasma alkaline phosphatase levels but the excretion of hydroxyproline was elevated following administration of the vitamin. The highest excretions were found in those patients who experienced complete relief of pain. In patients treated with calcitonin alone, the excretion of hydroxyproline was reduced and urinary levels of ascorbic acid dropped in parallel. It seems clear that ascorbic acid and calcitonin have different effects upon bone metabolism.

Positional information and pattern regulation in Hydra. Dynamics of regions at the boundary.

The dynamics of boundary regions have been investigated mainly by axial grafting and with the emphasis on the head end. The time to resist inhibition of head-end formation and the ability to inhibit head-end formation have been assayed under a variety of conditions. The times increase with distance from the head end. The times required by a boundary region to aquire the inhibitory properties of a head end are longer than those required to aquire resistance to inhibition. Determination of a head end is faster at a cut surbface and at higher temperatures. The results are discussed in terms of a model involving two gradients. Some anomalous results are reported.

Positional information and pattern formation in Hydra. Dynamics of regions away from the boundary.

The dynamics of regions away from the head-end boundary have been investigated by a variety of assays, and the changes appear to be slow. If, for example, a head end is grafted onto a peduncle to give H/56F, region 5 does not become a region 1 with 72 h. Such results support a gradient type model, and exclude a head end inducing a region 1 in the tissue adjacent to it. The changes can be interpreted if the positional value were effectively slowly diffusible: about 10 times more slowly than the positional signal. The results also have implications for studies on polarity reversal.