Comments on "finite-time stability theorem of stochastic nonlinear systems" [Automatica 46 (2010) 2105-2108]

In this comment, we will point out some errors existing in Chen and Jiao (2010) from definitions to the proof of the main result, where the authors discussed the finite-time stability of stochastic nonlinear systems and proved a Lyapunov theorem on the finitetime stability.

The packaging and maturation of the HIV-1 Pol proteins

The Pol protein of human immunodeficiency virus type 1 (HIV-1) harbours the viral enzymes critical for viral replication; protease (PR), reverse transcriptase (RT), and integrase (IN). PR, RT and IN are not functional in their monomeric forms and must come together as either dimers (PR), heterodimers (RT) or tetramers (IN) to be catalytically active. Our knowledge of the tertiary structures of the functional enzymes is well advanced, and substantial progress has recently been made towards understanding the precise steps leading from Pol protein synthesis through viral assembly to the release of active viral enzymes. This review will summarise our current understanding of how the Pol proteins, which are initially expressed as a Gag-Pol fusion product, are packaged into the assembling virion and discuss the maturation process that results in the release of the viral enzymes in their active forms. Our discussion will focus on the relationship between structure and function for each of the viral enzymes. This review will also provide an overview of the current status of inhibitors against the HIV-1 Pol proteins. Effective inhibitors of PR and RT are well established and we will discuss the next generation inhibitors of these enzymes as well recent investigations that have highlighted the potential of IN and RNase H as antiretroviral targets.

Mutations in the kissing-loop hairpin of human immunodeficiency virus type 1 reduce viral infectivity as well as genomic RNA packaging and dimerization

A stem-loop termed the kissing-loop hairpin is one of the most highly conserved structures within the leader of human immunodeficiency virus type 1 (HIV-1) and chimpanzee immunodeficiency virus genomic RNA. Because it plays a key role in the in vitro dimerization of short HIV-1 RNA transcripts (M. Laughrea and L. Jette, Biochemistry 35:1589-1598, 1996, and references therein; M. Laughrea and L. Jette, Biochemistry 35:9366-9374, 1996, and references therein) and because dimeric RNAs may be preferably encapsidated into the HIV-1 virus, alterations of the kissing-loop hairpin might affect the in vivo dimerization and encapsidation processes. Accordingly, substitution and deletion mutations were introduced into the kissing-loop hairpin of an infectious HIV-1 molecular clone in order to produce viruses by transfection methods. The infectivity of the resulting viruses was decreased by at least 99%, the amount of genomic RNA packaged per virus was decreased by 50 to 75%, and the proportion of dimeric genomic RNA was reduced from >80 to 40 to 50%, but the dissociation temperature of the genomic RNA was unchanged. There is evidence suggesting that the deletion mutations moderately inhibited CAp24 production but had no significant effect on RNA splicing. These results are consistent with the kissing-loop model of HIV-1 RNA dimerization. In fact, because intracellular viral RNAs are probably more concentrated in transfected cells than in cells infected by one virus and because the dimerization and encapsidation processes are concentration dependent, it is likely that much larger dimerization and encapsidation defects would have been manifested within cells infected by no more than one virus.

The conformation of the mature dimeric human immunodeficiency virus type 1 RNA genome requires packaging of pol protein

The packaging of a mature dimeric RNA genome is an essential step in human immunodeficiency virus type 1 (HIV-1) replication. We have previously shown that overexpression of a protease (PR)-inactive HIV-1 Gag-Pro-Pol precursor protein generates noninfectious virions that contain mainly monomeric RNA (M. Shehu-Xhilaga, S. M. Crowe, and J. Mak, J. Virol. 75:1834-1841, 2001). To further define the contribution of HIV-1 Gag and Gag-Pro-Pol to RNA maturation, we analyzed virion RNA dimers derived from Gag particles in the absence of Gag-Pro-Pol. Compared to wild-type (WT) dimeric RNAs, these RNA dimers have altered mobility and low stability under electrophoresis conditions, suggesting that the HIV-1 Gag precursor protein alone is not sufficient to stabilize the dimeric virion RNA structure. The inclusion of an active viral PR, without reverse transcriptase (RT) and integrase (IN), rescued the stability of the virion RNA dimers in the Gag particles but did not restore the mobility of the RNAs, suggesting that RT and IN are also required for virion RNA dimer maturation. Thin-section electron microscopy showed that viral particles deficient in RT and IN contain empty cone-shaped cores. The abnormal core structure indicates a requirement for Gag-Pro-Pol packaging during core maturation. Supplementing viral particles with either RT or IN via Vpr-RT or Vpr-IN alone did not correct the conformation of the dimer RNAs, whereas expression of both RT and IN in trans as a Vpr-RT-IN fusion restored RNA dimer conformation to that of the WT virus and also restored the electron-dense, cone-shaped virion core characteristic of WT virus. Our data suggest a role for RT-IN in RNA dimer conformation and the formation of the electron-dense viral core.

Short-term changes in quitting-related cognitions and behaviours after the implementation of plain packaging with larger health warnings : findings from a national cohort study with Australian adult smokers

ABSTRACT
Background: Plain packaging (PP) with larger graphic health warnings (GHWs) was implemented in Australia in late 2012. This study examined effects of these packaging changes on short-term changes in quitting-related cognitions and behaviours.
Methods: We used a series of cohorts of Australian adult cigarette smokers originally sourced from a nationally representative cross-sectional tracking survey, followed up approximately 1 month after their baseline interview (n(weighted)=5441). Logistic regression analyses compared changes in seven quitting-related outcomes over this 1-month follow-up period for the cohorts surveyed before PP, over the period of transition to PP, and during the first year of PP, adjusting for baseline levels of the outcome and covariates.
Results: Compared to the referent group of smokers who completed their follow-up survey pre-PP, those who were followed-up in the early transition period showed greater increases in rates of stopping themselves from smoking (OR=1.51, 95% CI (1.08 to 2.10)) and higher quit attempt rates (OR=1.43, 95% CI (1.00 to 2.03)), those followed-up in the late transition period showed greater increases in intentions to quit (OR=1.42, 95% CI (1.06 to 1.92)) and pack concealment (OR=1.55, 95% CI (1.05 to 2.31)), and those followed- up in the first year of PP showed higher levels of pack concealment (OR=1.65, 95% CI (1.01 to 2.72)), more premature stubbing out of cigarettes (OR=1.55, 95% CI (1.01 to 2.36)), and higher quit attempt rates (OR=1.52, 95% CI (1.01 to 2.30)).
Conclusions: These findings provide some of the strongest evidence to date that implementation of PP with larger GHWs was associated with increased rates of quitting cognitions, microindicators of concern and quit attempts among adult cigarette smokers.

Are quitting-related cognitions and behaviours predicted by proximal responses to plain packaging with larger health warnings? Findings from a national cohort study with Australian adult smokers

Background: Implementation of tobacco plain packaging (PP) with larger graphic health warnings (GHWs) in Australia had positive effects on responses reflecting the specific objectives of the PP policy and on follow-up quitting-related cognitions and behaviours. The aim of this study was to examine predictive relationships bewteen these proximal and distal outcomes.
Methods: A nationally representative sample of Australian adult cigarette smokers completed a baseline survey and a 1-month follow-up survey within the first year of policy implementation (n(weighted)=3215). Logistic regression analyses tested whether baseline measures of cigarette appeal, GHW effectiveness, perceived harm and concern/enjoyment predicted each of seven follow-up measures of quitted-related cognitions and behaviours, adjusting for baseline levels of the outcome and covariates.
Results: In multivariable models, we found consistent evidence that several baseline measures of GHW effectiveness positively and significantly predicted the likelihood that smokers at follow-up reported thinking about quitting at least daily, intending to quit, having a firm date to quit, stubbing out cigarettes prematurely, stopping oneself from smoking and having attempted to quit. Two of the quitting-related outcomes were also predicted by feeling more smoking-related concern than enjoyment. A smaller number of the appeal variables were prospectively associated with quitting-related outcomes, while believing that brands do not differ in harmlessness did not positively predict any outcomes.
Conclusions: These findings provide an initial insight into the pathways through which PP with larger GHWs may lead to changes in smoking behaviour. Future research should examine whether the effects are conditional on individual demographic and smoking characteristics.

Australian adult smokers' responses to plain packaging with larger graphic health warnings 1 year after implementation: results from a national cross-sectional tracking survey

Abstract
Background We assessed whether the Australian plain packs with larger graphic health warnings (GHWs) achieved three specific objectives of reducing the appeal of tobacco, increasing health warning effectiveness and reducing the ability of packaging to mislead about smoking harms.
Methods We compared responses from continuous cross-sectional telephone surveys of n=2176 cigarette smokers during pre-plain packaging (April–September 2012, pre-PP) with n=759 surveyed in the transition period (October–November 2012) and n=4240 during the first year of implementation (December 2012–November 2013, PP year 1), using multivariate logistic regression analyses.
Results From pre-PP to PP year 1, more smokers disliked their pack (p<0.001), perceived lower pack appeal (p<0.001), lower cigarette quality (p<0.001), lower satisfaction (p<0.001) and lower value (p<0.001) and disagreed brands differed in prestige (p=0.003). There was no change in perceived differences in taste of different brands. More smokers noticed GHWs (p<0.001), attributed much motivation to quit to GHWs (p<0.001), avoided specific GHWs when purchasing (p<0.001), and covered packs (p<0.001), with no change in perceived exaggeration of harms. PP year 1 saw an increased proportion believing that brands do not differ in harmfulness (p=0.004), but no change in the belief that variants do not differ in strength or the perceived harmfulness of cigarettes compared with a year ago. Interactions signified greater change for four outcomes assessing aspects of appeal among young adults and two appeal outcomes among mid-aged adults.
Conclusions The specific objectives of plain packaging were achieved and generally sustained among adult smokers up to 12 months after implementation.

Changes in use of types of tobacco products by pack sizes and price segments, prices paid and consumption following the introduction of plain packaging in Australia

Objectives: To describe changes among smokers in use of various types of tobacco products, reported prices paid and cigarette consumption following the standardisation of tobacco packaging in Australia.
Methods: National cross-sectional telephone surveys of adult smokers were conducted from April 2012 (6 months before transition to plain packaging (PP) to March 2014 (15 months afterwards). Multivariable logistics regression assessed changes in products, brands and pack types/sizes; multivariable linear regression examined changes in inflation-adjusted prices paid and reported cigarette consumption between the pre-PP and three subsequent periods – the transition phase, PP year 1 and PP post-tax (post a 12.5% tax increase in December 2013).
Results: The proposition of current smokers using roll-your-own (RYO) products fluctuated over the study period. Proportions using value brands of factory-made (FM) cigarettes increased from pre-PP (21.4%) to PP year 1 (25.5%; p=0.002) and PP post-tax (27.8%; p<0.001). Inflation-adjusted prices paid increased in the PP year 1 and PP post-tax phases; the largest increases were among premium FM brands, the smallest among value brands. Consumption did not change in PP year 1 among daily, regular or current smokers declined significantly in PP post-tax (mean=14.0, SE=0.33) compared to PP year 1 (mean=14.8, SE=0.17; p=0.037).
Conclusions: Introduction of PP was associated with an increase in use of value brands, likely due to increased numbers available and smaller increases in prices for value relative to premium brands. Reported consumption declined following the December 2013 tax increase.

Standardised packaging and new enlarged graphic health warnings for tobacco products in Australia--legislative requirements and implementation of the Tobacco Plain Packaging Act 2011 and the Competition and Consumer (Tobacco) Information Standard, 2011

This paper describes the development, content and implementation of two pieces of Australian tobacco control legislation: one to standardise the packaging of tobacco products and the other to introduce new, enlarged graphic health warnings. It describes the process of legislative drafting, public consultation and parliamentary consideration. It summarises exactly how tobacco products have been required to look since late 2012. Finally, it describes implementation, most particularly, the extent to which packs compliant with the legislation became available to consumers over time.

Use of illicit tobacco following introduction of standardised packaging of tobacco products in Australia: results from a national cross-sectional survey

ABSTRACT
Objectives: To assess whether following standardisation of tobacco packaging in Australia, smokers were, as predicted by the tobacco industry, more likely to use illicit tobacco.
Methods: National cross-sectional telephone surveys conducted continuously from April 2012 (6 months before implementation of plain packaging (PP)) to March 2014 (15 months after) using responses from current cigarette smokers (n=8679). Changes between pre-PP, the transition to PP and PP phase were examined using logistic regression models.
Results: Among those whose factory-made cigarettes were purchased in Australia, compared with pre-PP, there were no significant increases in the PP phase in use of: ‘cheap whites’ (<0.1%; OR=0.24, 95% CI 0.04 to 1.56, p=0.134); international brands purchased for 20% or more below the recommended retail price (0.2%; OR=3.49, 95% CI 0.66 to 18.35, p=0.140); or packs purchased from informal sellers (<0.1%; OR=0.24, 95% CI 0.04 to 1.47, p=0.124). The prevalence of any use of unbranded illicit tobacco remained at about 3% (adjusted OR=0.79, 95% CI 0.58 to 1.08, p=0.141).
Conclusions: While unable to quantify the total extent of use of illicit manufactured cigarettes, in this large national survey we found no evidence in Australia of increased use of two categories of manufactured cigarettes likely to be contraband, no increase in purchase from informal sellers and no increased use of unbranded illicit ‘chop-chop’ tobacco.