Alien Registration- Coffield, Patrick (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/25320/thumbnail.jp

Alien Registration- Coffield, Patrick (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/25320/thumbnail.jp

Analysis of Hepatitis C Virus Decline during Treatment with the Protease Inhibitor Danoprevir Using a Multiscale Model

The current paradigm for studying hepatitis C virus (HCV) dynamics in patients utilizes a standard viral dynamic model that keeps track of uninfected (target) cells, infected cells, and virus. The model does not account for the dynamics of intracellular viral replication, which is the major target of direct-acting antiviral agents (DAAs). Here we describe and study a recently developed multiscale age-structured model that explicitly considers the potential effects of DAAs on intracellular viral RNA production, degradation, and secretion as virus into the circulation. We show that when therapy significantly blocks both intracellular viral RNA production and virus secretion, the serum viral load decline has three phases, with slopes reflecting the rate of serum viral clearance, the rate of loss of intracellular viral RNA, and the rate of loss of intracellular replication templates and infected cells, respectively. We also derive analytical approximations of the multiscale model and use one of them to analyze data from patients treated for 14 days with the HCV protease inhibitor danoprevir. Analysis suggests that danoprevir significantly blocks intracellular viral production (with mean effectiveness 99.2%), enhances intracellular viral RNA degradation about 5-fold, and moderately inhibits viral secretion (with mean effectiveness 56%). The multiscale model can be used to study viral dynamics in patients treated with other DAAs and explore their mechanisms of action in treatment of hepatitis C

Weight-management interventions in primary care: a pilot randomised controlled trial

BACKGROUND: There is a paucity of randomised controlled trials of weight management in primary care. AIM: To ascertain the feasibility of a full trial of a nurse-led weight-management programme in general practice. DESIGN OF STUDY: Factorial randomised control trial. SETTING: Primary care, UK. METHOD: A total of 123 adults (80.3% women, mean age 47.2 years) with body mass index > or =27 kg/m(2), recruited from eight practices, were randomised to receive structured lifestyle support (n = 30), structured lifestyle support plus pedometer (n = 31), usual care (n = 31), or usual care plus pedometer (n = 31) for a 12-week period. RESULTS: A total of 103 participants were successfully followed up. The adjusted mean difference in weight in structured support compared to usual care groups was -2.63 kg (95% confidence interval [CI] = -4.06 to -1.20 kg), and for pedometer compared to no pedometer groups it was -0.11 kg (95% CI = -1.52 to 1.30 kg). One in three participants in the structured-support groups (17/50, 34.0%) lost 5% or more of their initial weight, compared to less than one in five (10/53, 18.9%) in usual-care groups; provision of a pedometer made little difference (14/48, 29.2% pedometer; 13/55, 23.6% no pedometer). Difference in waist circumference change between structured-support and usual-care groups was -1.80 cm (95% CI = -3.39 to -0.20 cm), and between the pedometer and no pedometer groups it was -0.84 cm (95% CI = -2.42 to 0.73 cm). When asked about their experience of study participation, most participants found structured support helpful. CONCLUSION: The structured lifestyle support package could make substantial contributions to improving weight-management services. A trial of the intervention in general practice is feasible and practicable

The approximate and the numerical solutions of the multiscale model.

<p><b>A.</b> The short-term approximation (blue solid) is compared with the solution of the multiscale PDE model (black dashed). <b>B.</b> Difference between the long-term approximation and the solution of the multiscale PDE model. Parameter values, chosen from <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002959#pcbi-1002959-t002" target="_blank">Table 2</a> and <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002959#pcbi.1002959-Rong3" target="_blank">[30]</a>, are , , , , , , , , , , , , and .</p

Parameter values with standard errors in parenthesis estimated by fitting the standard biphasic model to viral load data.

1<p>Corresponding to a half-life <i>t</i>_1/2 = 0.067 days.</p>2<p>Corresponding to a half-life <i>t</i>_1/2 = 1.65 days.</p

Parameter values with standard errors in parenthesis estimated by fitting the long-term approximation to viral load data and assuming , , and other fixed parameters as given in Table 2 caption.

1<p>This value is not significantly smaller than 0.</p