Public validation and its impact on the initial Affordable Care Act enrollment.

The 2010 Affordable Care Act (ACA) resulted in the creation of state-based marketplaces (SBMs) and federally facilitated marketplaces (FFMs), and provided financial assistance to a portion of those eligible to enroll. This study looks at how choosing to create a SBM rather than a FFM, and the financial assistance provided to some, influenced enrollments rates as signals of support for the ACA in the eyes of those eligible to enroll. The findings show that the enrollment behavior of those most strongly in support of the ACA legislation was influenced by those external signals of support for the ACA.

Systematic Computational Identification of Variants That Activate Exonic and Intronic Cryptic Splice Sites.

We developed a variant-annotation method that combines sequence-based machine-learning classification with a context-dependent algorithm for selecting splice variants. Our approach is distinctive in that it compares the splice potential of a sequence bearing a variant with the splice potential of the reference sequence. After training, classification accurately identified 168 of 180 (93.3%) canonical splice sites of five genes. The combined method, CryptSplice, identified and correctly predicted the effect of 18 of 21 (86%) known splice-altering variants in CFTR, a well-studied gene whose loss-of-function variants cause cystic fibrosis (CF). Among 1,423 unannotated CFTR disease-associated variants, the method identified 32 potential exonic cryptic splice variants, two of which were experimentally evaluated and confirmed. After complete CFTR sequencing, the method found three cryptic intronic splice variants (one known and two experimentally verified) that completed the molecular diagnosis of CF in 6 of 14 individuals. CryptSplice interrogation of sequence data from six individuals with X-linked dyskeratosis congenita caused by an unknown disease-causing variant in DKC1 identified two splice-altering variants that were experimentally verified. To assess the extent to which disease-associated variants might activate cryptic splicing, we selected 458 pathogenic variants and 348 variants of uncertain significance (VUSs) classified as high confidence from ClinVar. Splice-site activation was predicted for 129 (28%) of the pathogenic variants and 75 (22%) of the VUSs. Our findings suggest that cryptic splice-site activation is more common than previously thought and should be routinely considered for all variants within the transcribed regions of genes.

Thoracic manipulation versus mobilization in patients with mechanical neck pain: a systematic review.

OBJECTIVES: Thoracic manipulation is widely used in physical therapy and has been shown to be effective at addressing mechanical neck pain. However, thoracic mobilization may produce similar effects. The purpose of this systematic review was to evaluate the current literature regarding the effectiveness of thoracic manipulation versus mobilization in patients with mechanical neck pain. METHODS: ProQuest, NCBI-PubMed, APTA's Hooked on Evidence, Cochrane Library, CINAHL and SPORTDiscus were searched to identify relevant studies. Fourteen studies meeting the inclusion criteria were analyzed using the Physiotherapy Evidence Database (PEDro) scale and the GRADE approach. RESULTS: The literature as assessed by the PEDro scale was fair and the GRADE method showed overall quality ranging from very low to moderate quality. The 14 included studies showed positive outcomes on cervical pain levels, range of motion, and/or disability with the use of thoracic manipulation or mobilization. There was a paucity of literature directly comparing thoracic manipulation and mobilization. DISCUSSION: Current limitations in the body of research, specifically regarding the use of thoracic mobilization, limit the recommendation of its use compared to thoracic manipulation for patients with mechanical neck pain. There is, however, a significant amount of evidence, although of varied quality, for the short-term benefits of thoracic manipulation in treating patients with this condition. Further high quality research is necessary to determine which technique is more effective in treating patients with mechanical neck pain.

Big drinkers: how BMI, gender and rules of thumb influence the free pouring of wine.

BACKGROUND: This research examines free pouring behavior and provides an account of how Body Mass Index (BMI) and gender might lead to the overpouring, and consequently the overconsumption of wine. METHODS: An observational study with young adults investigated how BMI and gender affect free-pouring of wine over a variety of pouring scenarios, and how rules-of-thumb in pouring affect the quantities of alcohol poured by men and women across BMI categories. RESULTS: For men, the amount poured was positively related to BMI. However, BMI did not affect pours by women. The use of the "half glass" rule-of-thumb in pouring reduced the volume of wine poured by over 20% for both men and women. Importantly, this rule-of-thumb substantially attenuated the pours by men at high BMI levels. CONCLUSION: Increasing awareness of pouring biases represents an early and effective step toward curbing alcohol consumption among men, and especially those who are overweight. Additionally, using a simple "half glass" rule-of-thumb may be an effective way to curb overpouring, despite non-standard glass sizes.

Half full or empty: cues that lead wine drinkers to unintentionally overpour.

Wine drinkers often pour their own wine, but is the amount they pour influenced by the shape of the glass, the color of the wine, or how they pour? Building on research involving visual illusions and haptic cues, an exploratory field study shows that while wine drinkers typically poured 3.95 fl. oz. of wine into a standard baseline (10 fl. oz.) glass, they poured 11.9% more into a wider glass, 9.2% more when the wine was white (the low contrast with the glass makes it difficult to see), and 12.2% more when the wine glass was held in their hand rather than sitting on the table. Using narrower wine glasses and not pouring while holding one's glass may be steps toward modestly reducing the amount of wine a social drinker pours and drinks.

Dual activation of CFTR and CLCN2 by lubiprostone in murine nasal epithelia.

Multiple sodium and chloride channels on the apical surface of nasal epithelial cells contribute to periciliary fluid homeostasis, a function that is disrupted in patients with cystic fibrosis (CF). Among these channels is the chloride channel CLCN2, which has been studied as a potential alternative chloride efflux pathway in the absence of CFTR. The object of the present study was to use the nasal potential difference test (NPD) to quantify CLCN2 function in an epithelial-directed TetOn CLCN2 transgenic mouse model (TGN-K18rtTA-hCLCN2) by using the putative CLCN2 pharmacological agonist lubiprostone and peptide inhibitor GaTx2. Lubiprostone significantly increased chloride transport in the CLCN2-overexpressing mice following activation of the transgene by doxycycline. This response to lubiprostone was significantly inhibited by GaTx2 after CLCN2 activation in TGN-CLCN2 mice. Cftr(-/-) and Clc2(-/-) mice showed hyperpolarization indicative of chloride efflux in response to lubiprostone, which was fully inhibited by GaTx2 and CFTR inhibitor 172 + GlyH-101, respectively. Our study reveals lubiprostone as a pharmacological activator of both CFTR and CLCN2. Overexpression and activation of CLCN2 leads to improved mouse NPD readings, suggesting it is available as an alternative pathway for epithelial chloride secretion in murine airways. The utilization of CLCN2 as an alternative chloride efflux channel could provide clinical benefit to patients with CF, especially if the pharmacological activator is administered as an aerosol.

Converging prescription brand shares as evidence of physician learning.

Within a drug category, there is an optimal brand the physician could choose to prescribe based on the patient's particular condition and characteristics. Physicians desire to prescribe the best brand for each patient for professional, moral, and legal reasons. Ideally, detailing provides information that supports this effort. This study finds that, over time, the proportion of prescriptions written for each brand moves toward a stable distribution--a convergence in which each brand's share in the category appears to match the proportion of prescription writing opportunities where the brand is the best choice for the patient. Detailing supports this convergence.