DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study

PurposePrenatal screening for Down syndrome has improved, but the number of resulting invasive diagnostic procedures remains problematic. Measurement of circulating cell-free DNA in maternal plasma might offer improvement.MethodsA blinded, nested case-control study was designed within a cohort of 4664 pregnancies at high risk for Down syndrome. Fetal karyotyping was compared with an internally validated, laboratory-developed test based on next-generation sequencing in 212 Down syndrome and 1484 matched euploid pregnancies. None had been previously tested. Primary testing occurred at a CLIA-certified commercial laboratory, with cross validation by a CLIA-certified university laboratory.ResultsDown syndrome detection rate was 98.6% (209/212), the false-positive rate was 0.20% (3/1471), and the testing failed in 13 pregnancies (0.8%); all were euploid. Before unblinding, the primary testing laboratory also reported multiple alternative interpretations. Adjusting chromosome 21 counts for guanine cytosine base content had the largest impact on improving performance.ConclusionWhen applied to high-risk pregnancies, measuring maternal plasma DNA detects nearly all cases of Down syndrome at a very low false-positive rate. This method can substantially reduce the need for invasive diagnostic procedures and attendant procedure-related fetal losses. Although implementation issues need to be addressed, the evidence supports introducing this testing on a clinical basis.     

Comparison of serum markers in first-trimester down syndrome screening

OBJECTIVE: To estimate patterns of total hCG and inhibin A levels in the late first trimester of Down syndrome pregnancies, compare them with that of free beta-hCG, and assess screening performance of these markers individually and in combination with pregnancy-associated plasma protein-A (PAPP-A) and nuchal translucency. METHODS: Seventy-nine matched case-control sets of maternal serum samples (each Down syndrome case matched to 5 controls) from 11 through 13 completed weeks of gestation were taken from the sample bank of the First and Second Trimester Evaluation of Risk Consortium, a population-based study, and assayed for levels of free beta-hCG, total hCG, and inhibin A. Distribution characteristics and correlations of the multiples of the median values were estimated in cases and controls. Screening performance for each marker, alone and in combination with PAPP-A, nuchal translucency, and maternal age, was calculated. RESULTS: Median multiples of the median levels of free beta-hCG, total hCG, and inhibin A in cases were more elevated as gestation increased from 11 to 13 weeks, with univariate detection rates of 31%, 23%, and 29%, respectively, at a 5% false-positive rate. At 12 weeks, the multivariate detection rates at a 5% false-positive rate for nuchal translucency and PAPP-A (with maternal age) with either free beta-hCG, total hCG, or inhibin A were 84%, 83%, and 85%, respectively. The improvement in performance from nuchal translucency and PAPP-A to any of the three-marker tests was significant, while performance of any of the three-marker combinations was not significantly different from each other. CONCLUSION: Although levels of free beta-hCG in affected pregnancies were higher earlier than the levels of either total hCG or inhibin A, there was no significant difference in screening performance when either of the three markers was used with nuchal translucency and PAPP-A at 11-13 weeks of pregnancy. LEVEL OF EVIDENCE: II-2.     

Managing change in dental education: is there a method to the madness?

The literature surrounding dental education in the United States is replete with calls for change in the way that dental students are being educated. These calls are being echoed with curriculum models and examples of best practices, but what is missing is specific information about how to implement a desired change-that is, discussion of the change process itself. Knowledge of the organizational change process in other settings, particularly in higher education and professional education, may be of interest to academic program managers in dental schools who are planning or are engaged in change. Historical and theoretical perspectives on organizations and change are presented in this article as groundwork for more detailed discussion about management of change. Seventeen research-based principles of change in higher education and factors in dental education that influence change processes and outcomes are presented and synthesized into guidelines for a hypothetical model for change in a dental school environment. Issues pertinent to the practical management of change are presented, including reframing organizational complexity, change leadership, values/competence/commitment, and organizational learning. An appreciation for change as an ongoing and manageable process will enhance a dental school's viability in a rapidly changing world and ultimately benefit dental graduates and the communities they serve.     

Building bridges: an innovative academic-service partnership

Academic and service entities can create sustainable models of collaboration that realign relationships and resources to enhance the critical competencies essential for entry into practice. Our hospital and school collaborated to implement an innovative academic-service partnership model in which the academic and the care delivery enterprises intersected to accomplish goals of mutual interest and enhance and enrich the practice environment. Two existing resources-the staff nurse and faculty-were used to realign the educational process with the realities of nursing practice in an interpretive, contextual, live unfolding clinical environment that was relevant and memorable. The students were better integrated into the clinical operations and showed increased levels of critical thinking, clinical decision-making, and clinical inquiry skills. The model holds promise to improve transition to practice, make better use of existing resources, and foster collaborative relationships among the academic, practice, and regulatory enterprises.     

The effectiveness of multi-component goal setting interventions for changing physical activity behaviour: a systematic review and meta-analysis

Drawing from goal setting theory (Latham &; Locke, 1991; Locke &; Latham, 2002; Locke et al., 1981), the purpose of this study was to conduct a systematic review and meta-analysis of multi-component goal setting interventions for changing physical activity (PA) behaviour. A literature search returned 41,038 potential articles. Included studies consisted of controlled experimental trials wherein participants in the intervention conditions set PA goals and their PA behaviour was compared to participants in a control group who did not set goals. A meta-analysis was ultimately carried out across 45 articles (comprising 52 interventions, 126 effect sizes, n?=?5912) that met eligibility criteria using a random-effects model. Overall, a medium, positive effect (Cohen's d(SE)?=?.552(.06), 95% CI?=?.43–.67, Z?=?9.03, p?相似文献