14 research outputs found
An Estimate of the Numbers and Density of Low-Energy Structures (or Decoys) in the Conformational Landscape of Proteins
The conformational energy landscape of a protein, as calculated by known potential energy functions, has several minima, and one of these corresponds to its native structure. It is however difficult to comprehensively estimate the actual numbers of low energy structures (or decoys), the relationships between them, and how the numbers scale with the size of the protein.We have developed an algorithm to rapidly and efficiently identify the low energy conformers of oligo peptides by using mutually orthogonal Latin squares to sample the potential energy hyper surface. Using this algorithm, and the ECEPP/3 potential function, we have made an exhaustive enumeration of the low-energy structures of peptides of different lengths, and have extrapolated these results to larger polypeptides.We show that the number of native-like structures for a polypeptide is, in general, an exponential function of its sequence length. The density of these structures in conformational space remains more or less constant and all the increase appears to come from an expansion in the volume of the space. These results are consistent with earlier reports that were based on other models and techniques
Illness Mapping: A time and cost effective method to estimate healthcare data needed to establish community-based health insurance
Background: Most healthcare spending in developing countries is private out-of-pocket. One explanation for low penetration of health insurance is that poorer individuals doubt their ability to enforce insurance contracts. Community-based health insurance schemes (CBHI) are a solution, but launching CBHI requires obtaining accurate local data on morbidity, healthcare utilization and other details to inform package design and pricing. We developed the "Illness Mapping" method (IM) for data collection (faster and cheaper than household surveys). Methods. IM is a modification of two non-interactive consensus group methods (Delphi and Nominal Group Technique) to operate as interactive methods. We elicited estimates from "Experts" in the target community on morbidity and healthcare utilization. Interaction between facilitator and experts became essential to bridge literacy constraints and to reach consensus.The study was conducted in Gaya District, Bihar (India) during April-June 2010. The intervention included the IM and a household survey (HHS). IM included 18 women's and 17 men's groups. The HHS was conducted in 50 villages with1,000 randomly selected households (6,656 individuals). Results: We found good agreement between the two methods on overall prevalence of illness (IM: 25.9% ±3.6; HHS: 31.4%) and on prevalence of acute (IM: 76.9%; HHS: 69.2%) and chronic illnesses (IM: 20.1%; HHS: 16.6%). We also found good agreement on incidence of deliveries (IM: 3.9% ±0.4; HHS: 3.9%), and on hospital deliveries (IM: 61.0%. ± 5.4; HHS: 51.4%). For hospitalizations, we obtained a lower estimate from the IM (1.1%) than from the HHS (2.6%). The IM required less time and less person-power than a household survey, which translate into reduced costs. Conclusions: We have shown that our Illness Mapping method can be carried out at lower financial and human cost for sourcing essential local data, at acceptably accurate levels. In view of the good fit of results obtained, we assume that the method could work elsewhere as well
Triple Therapy of Fluticasone Furoate, Umeclidinium, Vilanterol- A Compelling Choice in Severe Chronic Obstructive Pulmonary Disease
Trelegy Ellipta (GlaxoSmithKlineTM) is the first single inhaler triple combination therapy comprising of umeclidinium, vilanterol
and fluticasone approved by the United States Food and Drug Administration (US FDA) for patients with severe COPD in 2019.
Clinical trials comparing this triple combination with dual therapy including a Long Acting b2-Agonist/Long Acting Muscarinic
Antagonist (LABA/LAMA) or Long Acting b2-Agonist/Inhaled Corticosteroids (LABA/ICS) were evaluated. Triple combination
did show improvement through the mean Forced Expiratory Volume per second (FEV1), St. George questionnaire, and reduced
hospitalisation due to acute exacerbation of COPD. This medication should be prescribed cautiously for certain populations.
Although this triple combination is used only in patients with the most advanced forms of disease who have frequent exacerbations
and remain uncontrolled, there are certain additional indications that may be explored in future trials. The convenience associated
with using a single device for three different classes of drugs could be its biggest trump card and it will not be surprising to see its
preference among patients avoiding the need for multiple dosing. Nevertheless, it remains to be seen if this improved adherence
would translate into improved outcomes such as reduced mortality in real world practice among patients with severe COPD. The
availability of a single inhaler device for delivering a triple combination of LABA/LAMA/ICS is a small success story in the quest to
identify better therapies for patients with severe COPD, who are so prone to repeat acute exacerbations which could eventually
turn fatal
Cardiovascular MR imaging after surgical correction of tetralogy of fallot: approach based on understanding of surgical procedures
Tetralogy of Fallot (TOF) is one of the most common congenital heart diseases for which patients are referred for postoperative magnetic resonance (MR) imaging evaluation. The most common surgical procedures for TOF repair include infundibulectomy, transannular pulmonary artery patch repair, and right ventricle–pulmonary artery conduit placement. In the past few decades, surgery has proved successful, but most patients require repeat imaging throughout their lives. MR imaging is now frequently used for morphologic and functional evaluation after TOF repair. The most common late postoperative sequelae and residual lesions include right ventricular outflow tract aneurysm and dyskinesis, conduit failure, pulmonary regurgitation, tricuspid regurgitation, right ventricular failure, residual main and branch pulmonary artery stenosis, branch pulmonary artery aneurysm, left pulmonary artery kinking, and residual or recurrent ventricular septal defect. The imaging approach for the evaluation of patients with repaired TOF should be guided by the surgical procedure used and the complications that are expected. Knowledge of the most common postoperative problems and their cardiovascular MR imaging appearances is essential for good radiology practice in this clinical setting