Characteristics in stages of change and decisional balance among smokers: The burden of obstructive lung diseases (BOLD)-Australia study

Smoking cessation remains a health promotion target. Applying the Transtheoretical Model to Australian Burden of Obstructive Lung Diseases (BOLD) data, we examined differences in stages of change (SoC) and readiness to quit decisional behaviours. Factors were identified likely to influence readiness of smokers, ≥40 years old, to quit. Analysis was restricted to current smokers classified to one of three stages: pre-contemplation (PC), contemplation (C) or preparation (P) to quit. Their ability to balance positive and negative consequences was measured using decisional balance. Among 314 smokers, 43.0% females and 60.8% overweight/obese, the distribution of SoC was: 38.1% PC, 38.3% C and 23.5% P. Overweight/obesity was associated with readiness to quit in stages C and P and there were more negative than positive attitudes towards smoking in those stages. Males were significantly heavier smokers in PC and C stages. Females used smoking cessation medication more frequently in PC stage, were more embarrassed about smoking and had greater negative reinforcements from smoking. Age started smoking and factors related to smoking history were associated with readiness to quit and increased the odds of being in stage C or P. An overweight/obese smoker was likely to be contemplating or preparing to quit. In these stages, smokers have more negative attitudes toward smoking. Starting smoking later, taking advice on cessation from health providers and using quit medications indicate increased readiness to quit. Evaluating these factors in smokers and developing cessation gain-framed messages may prove useful to healthcare providers

Relationship between early development of spelling and reading

The research reported in this thesis examined the relationship between beginning spelling and reading. More specifically, it focussed on the relationship between the development of early reading and spelling in a context where the approach to early reading instruction includes systematic phonological awareness and decoding instruction. A critical assumption made by proponents of developmental early literacy models is that transfer of skills and knowledge from reading to spelling will occur spontaneously and without formal instruction (Frith, 1980). By contrast instruction-centred approaches make the assumption that there are critical pre-requisite skills that can and should be taught explicitly (Carnine, Silbert & Kameenui, 1997). The difference between these approaches is highlighted in the treatment of invented spelling, a popular activity in Western Australian junior primary classes. A series of studies was undertaken to examine the effect on invented and standard spelling performance of teaching Year 1 children phonological awareness and the strategy of sounding out words. Data were gathered from a range of settings using different research tools. The relationship between phonological awareness and beginning reading and spelling performance was explored initially through a single case study. A post-hoc study was then undertaken with a cohort of students who had received systematic decoding instruction to examine whether proficiency in the decoding of nonwords was related to spelling performance. This permitted an analysis of common sub-skills of decoding and encoding. In the main study the effect on different aspects of reading and spelling performance of using Let\u27s Decode, an approach that includes explicit phonological awareness and systematic decoding instruction, was investigated. In addition, an analysis was made of whether students who received explicit instruction in skills known to contribute to beginning reading and spelling produced superior invented spelling samples. A qualitative analysis was made of the. pre and post invented spelling tests of two pairs of students from the control and intervention groups matched on invented spelling and phonological awareness skills at the beginning of the year, and re tested at the end of Year 1. The final research question involved a single-subject research design to examine the effect of explicit instruction in isolating phonemes in words and prompts to \u27listen for sounds\u27 prior to, and during, the process of spelling words. The single case study revealed a child who was regarded as a competent speller and reader but who could only read words in a familiar context and who had developed a strategy for spelling words based on copying an adult model. This was interpreted as evidence supporting the need for phonological awareness instruction as a pre-requisite for spelling. The post-hoc analysis of a class of students who had received systematic decoding instruction showed that no student classified as a \u27good decoder\u27 could also be classified as a \u27poor speller\u27. This result was considered evidence of a strong link between the phonological knowledge that is required to decode and the role of alphabetic knowledge in spelling. The main study revealed phonological awareness and systematic decoding instruction was associated with superior invented and conventional spelling and reading performance on all reading and spelling measures. Of particular importance was the finding that students who commenced the study with very weak phonological awareness and who subsequently received systematic phonological and decoding instruction showed greater gains in invented spelling than matched students in the control condition. The single subject design showed the effectiveness of phonological awareness individualised instruction on invented spelling for weak students from both intervention and control conditions. It was concluded that the ability to invent spelling is improved when students receive explicit instruction in phonological awareness and systematic decoding but that some students, namely those with persistent weakness in phonological awareness, also require explicit prompts to apply their alphabetic knowledge to spelling words. The implications for instruction of these findings are discussed

Randomized trial to compare the efficacy and toxicity of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) with methotrexate mitoxantrone (MM) in advanced carcinoma of the breast

One hundred and sixteen patients with locally advanced or metastatic breast cancer were randomized to receive CMF (cyclophosphamide 600 mg m−2 day 1 and 8 i.v., 5-fluorouracil 600 mg m−2 day 1 and 8 i.v.,, methotrexate 40 mg m−2 day 1 and 8 i.v., monthly for 6 cycles) or MM (methotrexate 30 mg m−2, mitoxantrone 6.5 mg m−2, both i.v. day 1 3-weekly for 8 cycles) as first line treatment with chemotherapy. Objective responses occurred in 17 patients out of 58 (29%) who received CMF and nine out of 58 (15%) who received MM; 95% confidence interval for difference in response rates (–1%–29%), P = 0.07. No statistically significant differences were seen in overall survival or time to progression between the two regimes although a tendency towards a shorter progression time on the MM regime must be acknowledged. There was, however, significantly reduced haematological toxicity (P < 0.001) and alopecia (P < 0.001) and fewer dose reductions and delays in patients randomized to MM. No statistically significant differences were seen between the two regimes in terms of quality of life (QOL). However, some association between QOL and toxicity was apparent overall with pooled QOL estimates tending to indicate a worsening in psychological state with increasing maximum toxicity over treatment. Despite the fact that results surrounding response rates and time to progression did not reach statistical significance, their possible compatibility with an improved outcome on CMF treatment must be borne in mind. However, MM is a well-tolerated regimen with fewer side-effects than CMF, which with careful patient management and follow-up, therefore, may merit consideration as a first-line treatment to palliate patients with metastatic breast cancer who are infirm or elderly. © 1999 Cancer Research Campaig

Learning to Learn: Theta Oscillations Predict New Learning, which Enhances Related Learning and Neurogenesis

Animals in the natural world continuously encounter learning experiences of varying degrees of novelty. New neurons in the hippocampus are especially responsive to learning associations between novel events and more cells survive if a novel and challenging task is learned. One might wonder whether new neurons would be rescued from death upon each new learning experience or whether there is an internal control system that limits the number of cells that are retained as a function of learning. In this experiment, it was hypothesized that learning a task that was similar in content to one already learned previously would not increase cell survival. We further hypothesized that in situations in which the cells are rescued hippocampal theta oscillations (3–12 Hz) would be involved and perhaps necessary for increasing cell survival. Both hypotheses were disproved. Adult male Sprague-Dawley rats were trained on two similar hippocampus-dependent tasks, trace and very-long delay eyeblink conditioning, while recording hippocampal local-field potentials. Cells that were generated after training on the first task were labeled with bromodeoxyuridine and quantified after training on both tasks had ceased. Spontaneous theta activity predicted performance on the first task and the conditioned stimulus induced a theta-band response early in learning the first task. As expected, performance on the first task correlated with performance on the second task. However, theta activity did not increase during training on the second task, even though more cells were present in animals that had learned. Therefore, as long as learning occurs, relatively small changes in the environment are sufficient to increase the number of surviving neurons in the adult hippocampus and they can do so in the absence of an increase in theta activity. In conclusion, these data argue against an upper limit on the number of neurons that can be rescued from death by learning

Assembly PCR synthesis of optimally designed, compact, multi-responsive promoters suited to gene therapy application

MRC-DTA studentship award British Pharmacological Society Integrative Awar

AAV-mediated photoreceptor transduction of the pig cone-enriched retina

Recent success in clinical trials supports the use of adeno-associated viral (AAV) vectors for gene therapy of retinal diseases caused by defects in the retinal pigment epithelium (RPE). In contrast, evidence of the efficacy of AAV-mediated gene transfer to retinal photoreceptors, the major site of inherited retinal diseases, is less robust. In addition, although AAV-mediated RPE transduction appears efficient, independently of the serotype used and species treated, AAV-mediated photoreceptor gene transfer has not been systematically investigated thus so far in large animal models, which also may allow identifying relevant species-specific differences in AAV-mediated retinal transduction. In the present study, we used the porcine retina, which has a high cone/rod ratio. This feature allows to properly evaluate both cone and rod photoreceptors transduction and compare the transduction characteristics of AAV2/5 and 2/8, the two most efficient AAV vector serotypes for photoreceptor targeting. Here we show that AAV2/5 and 2/8 transduces both RPE and photoreceptors. AAV2/8 infects and transduces photoreceptor more efficiently than AAV2/5, similarly to what we have observed in the murine retina. The use of the photoreceptor-specific rhodopsin promoter restricts transgene expression to porcine rods and cones, and results in photoreceptor transduction levels similar to those obtained with the ubiquitous promoters tested. Finally, immunological, toxicological and biodistribution studies support the safety of AAV subretinal administration to the large porcine retina. The data presented here on AAV-mediated transduction of the cone-enriched porcine retina may affect the development of gene-based therapies for rare and common severe photoreceptor diseases

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Antibody-based protection against HIV infection by vectored immunoprophylaxis

Despite tremendous efforts, development of an effective vaccine against human immunodeficiency virus (HIV) has proved an elusive goal. Recently, however, numerous antibodies have been identified that are capable of neutralizing most circulating HIV strains. These antibodies all exhibit an unusually high level of somatic mutation, presumably owing to extensive affinity maturation over the course of continuous exposure to an evolving antigen. Although substantial effort has focused on the design of immunogens capable of eliciting antibodies de novo that would target similar epitopes, it remains uncertain whether a conventional vaccine will be able to elicit analogues of the existing broadly neutralizing antibodies. As an alternative to immunization, vector-mediated gene transfer could be used to engineer secretion of the existing broadly neutralizing antibodies into the circulation. Here we describe a practical implementation of this approach, which we call vectored immunoprophylaxis (VIP), which in mice induces lifelong expression of these monoclonal antibodies at high concentrations from a single intramuscular injection. This is achieved using a specialized adeno-associated virus vector optimized for the production of full-length antibody from muscle tissue. We show that humanized mice receiving VIP appear to be fully protected from HIV infection, even when challenged intravenously with very high doses of replication-competent virus. Our results suggest that successful translation of this approach to humans may produce effective prophylaxis against HIV

Asbestos-related pleural and lung fibrosis in patients with retroperitoneal fibrosis

<p>Abstract</p> <p>Background</p> <p>Retroperitoneal fibrosis (RPF) is a rare fibroinflammatory disease that leads to hydronephrosis and renal failure. In a case-control study, we have recently shown that asbestos exposure was the most important risk factor for RPF in the Finnish population. The aim of this study was to evaluate the relation of asbestos exposure to radiologically confirmed lung and pleural fibrosis among patients with RPF.</p> <p>Methods</p> <p>Chest high-resolution computed tomography (HRCT) was performed on 16 unexposed and 22 asbestos-exposed RPF patients and 18 asbestos-exposed controls. Parietal pleural plaques (PPP), diffuse pleural thickening (DPT) and parenchymal fibrosis were scored separately.</p> <p>Results</p> <p>Most of the asbestos-exposed RPF patients and half of the asbestos-exposed controls had bilateral PPP, but only a few had lung fibrosis. Minor bilateral plaques were detected in two of the unexposed RPF patients, and none had lung fibrosis. DPT was most frequent and thickest in the asbestos-exposed RPF-patients. In three asbestos-exposed patients with RPF we observed exceptionally large pleural masses that were located anteriorly in the pleural space and continued into the anterior mediastinum.</p> <p>Asbestos exposure was associated with DPT in comparisons between RPF patients and controls (case-control analysis) as well as among RPF patients (case-case analysis).</p> <p>Conclusion</p> <p>The most distinctive feature of the asbestos-exposed RPF patients was a thick DPT. An asbestos-related pleural finding was common in the asbestos-exposed RPF patients, but only a few of these patients had parenchymal lung fibrosis. RPF without asbestos exposure was not associated with pleural or lung fibrosis. The findings suggest a shared etiology for RPF and pleural fibrosis and furthermore possibly a similar pathogenetic mechanisms.</p

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO