Second-Hand Smoke: The Evolution of Children's Exposure

Second-hand smoke exposure (SHSe) causes significant morbidity and mortality in children. A large proportion of children with smoking parents do not live in smoke-free homes, however, to date, little is known about the prevalence of partial smoking restrictions and their efficacy in reducing children’s SHSe. Given the lack of convincing evidence on how to achieve further reductions in children’s SHSe in the home, the identification of the modifiable factors associated with childhood SHSe is imperative to reduce the burden of disease resulting from childhood SHSe. Analysis of the Omnibus Survey (OS) revealed that the prevalence of smoke-free homes in England did not increase significantly between 2006 and 2008. Only 30% of smokers reported a smoke-free home in 2008. However, during the same time period, the proportion of smokers (who did not have a smoke-free home) reporting that they did not smoke when in the same room as a child increased significantly from 62.5% to 74.8%. Using the Health Survey for England, biologically validated self-reported measures of child SHSe revealed that in 2008 and 2009 approximately 50% of children living with a smoking parent were not exposed to SHSe in the home (0.30ng/ml, 95% confidence interval 0.27-0.32ng/ml). Of the 50% of children who remained exposed inside the home, 29% had a parent that smoked in one room only in the home. These children had significantly lower cotinine concentrations (1.13ng/ml, 95% CI 1.05-1.22) than the 21% of children with smoking parents who smoked in 2 or more rooms in the home (2.36ng/ml, 95% CI 2.08-2.68ng/ml). Although smoking in one room equates to lower risk it does not equate to no risk and so interventions are required to change indoor smoking to outdoor smoking. The OS data found that good knowledge of SHS-related illnesses was predictive of both full and partial smoking restrictions in the home. Increases in the proportion of respondents with good knowledge occurred during 2003-2006, a period when frequent anti-SHS mass media campaigns were aired. A case-study evaluation of a brief mass media campaign in the North West and North East of England, which aimed to move smoking parents to smoke outside, was found to have no statistically significant effect on home smoking behaviour in the short term, however knowledge that SHS caused both heart attack and Sudden Infant Death Syndrome increased in this region following the campaign whilst simultaneous decreases were found in the rest of England. Following the identification of those children most exposed to SHS, and the modifiable factors associated with this exposure, this thesis suggests that a comprehensive multi-level approach to tobacco control policy, which includes emotive media campaigns which include information on SHS-related illnesses, will contribute to the continued reduction of childhood SHSe.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Digital phenotyping and the development and delivery of health guidelines and behaviour change interventions

Lovatt and colleagues make the case that drinking guidelines informed by the experiences and behaviours of drinkers are likely to have increased relevance, credibility and efficacy. There is reason to believe that digital technologies such as crowdsourcing, social media, mobile digital devices and biosensing devices measure behaviours such as drinking with a level of detail and on a scale that has not been possible previously. The intensive measurement of behaviours enabled by these approaches, combined with appropriate modelling techniques, can reveal patterns of behaviours that, together with knowledge of the resultant negative or harmful consequences, can inform the development of improved guidelines

Tweeting about public health policy::social media response to the UK Government's announcement of a Parliamentary vote on draft standardised packaging regulations

BackgroundStandardised tobacco packaging has been, and remains, a contentious policy globally, attracting corporate, public health, political, media and popular attention. In January 2015, the UK Government announced it would vote on draft regulations for the policy before the May 2015 General Election. We explored reactions to the announcement on Twitter, in comparison with an earlier period of little UK Government activity on standardised packaging.MethodsWe obtained a random sample of 1038 tweets in two 4-week periods, before and after the UK Government's announcement. Content analysis was used to examine the following Tweet characteristics: support for the policy, purpose, Twitter-user's geographical location and affiliation, and evidence citation and quality. Chi-squared analyses were used to compare Tweet characteristics between the two periods.ResultsOverall, significantly more sampled Tweets were in favour of the policy (49%) in comparison to those opposed (19%). Yet, at Time 2, following the announcement, a greater proportion of sampled tweets opposed standardised packaging compared to the period sampled at Time 1, prior to the announcement (pConclusionsMicroblogging sites can reflect offline policy debates and are used differently by policy proponents and opponents dependent on the policy context. Twitter-users opposed to standardised packaging increased their activity following the Government's announcement, while those in support broadly maintained their rate of Twitter engagement. The findings offer insight into the public health community's options for using Twitter to influence policy and disseminate research. In particular, proliferation of Twitter activity following pro-public health policy announcements could be considered to ensure pro-health messages are not overshadowed by anti-regulation voices

Paired helical filament-forming region of tau (297–391) influences endogenous tau protein and accumulates in acidic compartments in human neuronal cells

Assembly of tau protein into paired helical filaments and straight filaments is a key feature of Alzheimer's disease. Aggregation of tau has been implicated in neurodegeneration, cellular toxicity and the propagation, which accompanies disease progression. We have reported previously that a region of tau (297–391), referred to as dGAE, assembles spontaneously in physiological conditions to form paired helical filament-like fibres in vitro in the absence of additives such as heparin. This provides a valuable tool with which to explore the effects of tau in cell culture. Here we have studied the cellular uptake of soluble oligomeric and fibrillar forms of dGAE and examined the downstream consequences of tau internalisation into differentiated SH-SY5Y neuroblastoma cells using fluorescence and electron microscopy alongside structural and biochemical analyses. The assembled dGAE shows more acute cytotoxicity than the soluble, non-aggregated form. Conversely, the soluble form is much more readily internalised and, once within the cell, is able to associate with endogenous tau resulting in increased phosphorylation and aggregation of endogenous tau, which accumulates in lysosomal/endosomal compartments. It appears that soluble oligomeric forms are able to propagate tau pathology without being acutely toxic. The model system we have developed now permits the molecular mechanisms of propagation of tau pathology to be studied in vitro in a more physiological manner with a view to development of novel therapeutic approaches

Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease A Randomized Clinical Trial

Importance Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. Objective To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. Design, Setting, and Participants Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. Interventions Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. Main Outcomes and Measures Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form– physical functioning subscale score (SF-36), and the change in the Berg Balance Test. Results Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was –2.5 units (95% CI, –3.7 to –1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, –0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. Conclusions and Relevance Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead