The impact of obstructive sleep apnea variability measured in-lab versus in-home on sample size calculations

<p>Abstract</p> <p>Background</p> <p>When conducting a treatment intervention, it is assumed that variability associated with measurement of the disease can be controlled sufficiently to reasonably assess the outcome. In this study we investigate the variability of Apnea-Hypopnea Index obtained by polysomnography and by in-home portable recording in untreated mild to moderate obstructive sleep apnea (OSA) patients at a four- to six-month interval.</p> <p>Methods</p> <p>Thirty-seven adult patients serving as placebo controls underwent a baseline polysomnography and in-home sleep study followed by a second set of studies under the same conditions. The polysomnography studies were acquired and scored at three independent American Academy of Sleep Medicine accredited sleep laboratories. The in-home studies were acquired by the patient and scored using validated auto-scoring algorithms. The initial in-home study was conducted on average two months prior to the first polysomnography, the follow-up polysomnography and in-home studies were conducted approximately five to six months after the initial polysomnography.</p> <p>Results</p> <p>When comparing the test-retest Apnea-hypopnea Index (AHI) and apnea index (AI), the in-home results were more highly correlated (r = 0.65 and 0.68) than the comparable PSG results (r = 0.56 and 0.58). The in-home results provided approximately 50% less test-retest variability than the comparable polysomnography AHI and AI values. Both the overall polysomnography AHI and AI showed a substantial bias toward increased severity upon retest (8 and 6 events/hr respectively) while the in-home bias was essentially zero. The in-home percentage of time supine showed a better correlation compared to polysomnography (r = 0.72 vs. 0.43). Patients biased toward more time supine during the initial polysomnography; no trends in time supine for in-home studies were noted.</p> <p>Conclusion</p> <p>Night-to-night variability in sleep-disordered breathing can be a confounding factor in assessing treatment outcomes. The sample size of this study was small given the night-to-night variability in OSA and limited understanding of polysomnography reliability. We found that in-home studies provided a repeated measure of sleep disordered breathing less variable then polysomnography. Investigators using polysomnography to assess treatment outcomes should factor in the increased variability and bias toward increased AHI values upon retest to ensure the study is adequately powered.</p

Multiple conformations of SAM-II riboswitch detected with SAXS and NMR spectroscopy

Riboswitches are a newly discovered large family of structured functional RNA elements that specifically bind small molecule targets out of a myriad of cellular metabolites to modulate gene expression. Structural studies of ligand-bound riboswitches by X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy have provided insights into detailed RNA–ligand recognition and interactions. However, the structures of ligand-free riboswitches remain poorly characterized. In this study, we have used a variety of biochemical, biophysical and computational techniques including small-angle X-ray scattering and NMR spectroscopy to characterize the ligand-free and ligand-bound forms of SAM-II riboswitch. Our data demonstrate that the RNA adopts multiple conformations along its folding pathway and suggest that the RNA undergoes marked conformational changes upon Mg2+ compaction and S-adenosylmethionine (SAM) metabolite binding. Further studies indicated that Mg2+ ion is not essential for the ligand binding but can stabilize the complex by facilitating loop/stem interactions. In the presence of millimolar concentration of Mg2+ ion, the RNA samples a more compact conformation. This conformation is near to, but distinct from, the native fold and competent to bind the metabolite. We conclude that the formation of various secondary and tertiary structural elements, including a pseudoknot, occur to sequester the putative Shine–Dalgarno sequence of the RNA only after metabolite binding

Development and Growth of a Large Multispecialty Certification Examination: Sleep Medicine Certification—Results of the First Three Examinations

This paper summarizes the results of the first three examinations (2007, 2009, and 2011) of the Sleep Medicine Certification Examination, administered by its six sponsoring American Board of Medical Specialty Boards. There were 2,913 candidates who took the 2011 examination through one of three pathways—self-attested practice experience, previous certification by the American Board of Sleep Medicine, or formal Sleep Medicine fellowship training. The 2011 exam was the last administration in which candidates who had not previously been admitted could take it without completion of formal Sleep Medicine fellowship training. As expected, the number of candidates admitted to the 2011 examination through the practice experience pathway increased, and the overall scores of these candidates were on average lower than the other candidates. Consequently, the pass rate for all first takers of the 2011 examination (65%) was lower than that observed from the 2009 examination (78%) and the 2007 examination (73%). For each administration, candidates admitted through the fellowship training pathway scored the highest; over 90% of them passed the 2011 and 2009 examinations

Disease-Associated Mutations That Alter the RNA Structural Ensemble

Genome-wide association studies (GWAS) often identify disease-associated mutations in intergenic and non-coding regions of the genome. Given the high percentage of the human genome that is transcribed, we postulate that for some observed associations the disease phenotype is caused by a structural rearrangement in a regulatory region of the RNA transcript. To identify such mutations, we have performed a genome-wide analysis of all known disease-associated Single Nucleotide Polymorphisms (SNPs) from the Human Gene Mutation Database (HGMD) that map to the untranslated regions (UTRs) of a gene. Rather than using minimum free energy approaches (e.g. mFold), we use a partition function calculation that takes into consideration the ensemble of possible RNA conformations for a given sequence. We identified in the human genome disease-associated SNPs that significantly alter the global conformation of the UTR to which they map. For six disease-states (Hyperferritinemia Cataract Syndrome, β-Thalassemia, Cartilage-Hair Hypoplasia, Retinoblastoma, Chronic Obstructive Pulmonary Disease (COPD), and Hypertension), we identified multiple SNPs in UTRs that alter the mRNA structural ensemble of the associated genes. Using a Boltzmann sampling procedure for sub-optimal RNA structures, we are able to characterize and visualize the nature of the conformational changes induced by the disease-associated mutations in the structural ensemble. We observe in several cases (specifically the 5′ UTRs of FTL and RB1) SNP–induced conformational changes analogous to those observed in bacterial regulatory Riboswitches when specific ligands bind. We propose that the UTR and SNP combinations we identify constitute a “RiboSNitch,” that is a regulatory RNA in which a specific SNP has a structural consequence that results in a disease phenotype. Our SNPfold algorithm can help identify RiboSNitches by leveraging GWAS data and an analysis of the mRNA structural ensemble

BIOL 114: The Effect of Variegation Mutation of Brassica Rapa on Plant Growth

Brassica rapa is a small flowering plant that is often used in classroom experiments due to its small size, low-maintenance growing conditions, and quick life cycle. Several mutant lines have been bred and briefly described, although not much is known about the actual genetic changes and therefore all the downstream effects of that mutation. Nine different mutant lines of Brassica rapa were grown to more carefully identify the phenotypes affected by the mutations. Wild type and variegated Brassica rapa plants were grown over 4 weeks and Height and variation were measured. The data from this study concluded that the wild type plants were significantly taller than the variegated plants. This data supports the hypothesis that variegation slows or inhibits growth of Brassica rapa