Cost-effectiveness of a melanoma screening programme using whole disease modelling

OBJECTIVE: To assess the potential impact of a melanoma screening programme, compared with usual care, on direct costs and life expectancy in the era of targeted drugs and cancer immunotherapy. METHODS: Using a Whole Disease Model approach, a Markov simulation model with a time horizon of 25 years was devised to analyse the cost-effectiveness of a one-time, general practitioner-based melanoma screening strategy in the population aged over 20, compared with no screening. The study considered the most up-to-date drug therapy and was conducted from the perspective of the Veneto regional healthcare system within the Italian National Health Service. Only direct costs were considered. Sensitivity analyses, both one-way and probabilistic, were performed to identify the parameters with the greatest impact on cost-effectiveness, and to assess the robustness of our model. RESULTS: Over a 25-year time horizon, the screening intervention dominated usual care. The probabilistic sensitivity analyses confirmed the robustness of these findings. The key drivers of the model were the proportion of melanomas detected by the screening procedure and the adherence of the target population to the screening programme. CONCLUSIONS: The screening programme proved to be a dominant option compared with usual care. These findings should prompt serious consideration of the design and implementation of a regional or national melanoma screening strategy within a National Health Service

Inherited biotic protection in a Neotropical pioneer plant

Chelonanthus alatus is a bat-pollinated, pioneer Gentianaceae that clusters in patches where still-standing, dried-out stems are interspersed among live individuals. Flowers bear circum-floral nectaries (CFNs) that are attractive to ants, and seed dispersal is both barochorous and anemochorous. Although, in this study, live individuals never sheltered ant colonies, dried-out hollow stems - that can remain standing for 2 years - did. Workers from species nesting in dried-out stems as well as from ground-nesting species exploited the CFNs of live C. alatus individuals in the same patches during the daytime, but were absent at night (when bat pollination occurs) on 60.5% of the plants. By visiting the CFNs, the ants indirectly protect the flowers - but not the plant foliage - from herbivorous insects. We show that this protection is provided mostly by species nesting in dried-out stems, predominantly Pseudomyrmex gracilis. That dried-out stems remain standing for years and are regularly replaced results in an opportunistic, but stable association where colonies are sheltered by one generation of dead C. alatus while the live individuals nearby, belonging to the next generation, provide them with nectar; in turn, the ants protect their flowers from herbivores. We suggest that the investment in wood by C. alatus individuals permitting stillstanding, dried-out stems to shelter ant colonies constitutes an extended phenotype because foraging workers protect the flowers of live individuals in the same patch. Also, through this process these dried-out stems indirectly favor the reproduction (and so the fitness) of the next generation including both their own offspring and that of their siblings, alladding up to a potential case of inclusive fitness in plants

The effect of verbalization strategy on wisconsin card sorting test performance in schizophrenic patients receiving classical or atypical antipsychotics

BACKGROUND: A number of reports showed en encouraging remediation in some patients' executive deficits thanks to the use of 'information processing strategies'. Moreover the impact of antipsychotics on cognitive functions of the schizophrenics is an important issue, especially if an integrated psychosocial treatment is needed. The aim of this paper is to evaluate different executive performance and response to verbalization, a strategy of the Wisconsin Card Sorting Test (WCST) remediation, in subjects on classical vs atypical antipsychotic (AP) treatment. METHODS: Sixty-three schizophrenic subjects undertook the WCST under standard and modified (verbalization) administration. Subjects were stratified by the kind of WCST response (i.e. good, poor and remediable) and AP treatment (i.e. atypical vs. classical). RESULTS: Subjects on atypical APs showed a better performance than those on classical ones. More poor performers who did not remediate were seen in the sample with classical Aps while subjects who remediated the performance were seen in the subgroup with atypical APs only. An increase of perseverative and total errors was seen in poor performers subjects on classical APs. CONCLUSION: Subjects on atypicals showed a better cognitive pattern in terms of WCST performance. Since the naturalistic assignment of medication we cannot draw conclusions about its effect on cognitive performance and its interaction with cognitive remediation potential. However the data lead us to hypothesize that subjects with potential room for remediation did so with the atypical APs

Genetic Background Can Result in a Marked or Minimal Effect of Gene Knockout (GPR55 and CB2 Receptor) in Experimental Autoimmune Encephalomyelitis Models of Multiple Sclerosis

PMCID: PMC379391

Signs and symptoms of acute mania: a factor analysis

<p>Abstract</p> <p>Background</p> <p>The major diagnostic classifications consider mania as a uni-dimensional illness. Factor analytic studies of acute mania are fewer compared to schizophrenia and depression. Evidence from factor analysis suggests more categories or subtypes than what is included in the classification systems. Studies have found that these factors can predict differences in treatment response and prognosis.</p> <p>Methods</p> <p>The sample included 131 patients consecutively admitted to an acute psychiatry unit over a period of one year. It included 76 (58%) males. The mean age was 44.05 years (SD = 15.6). Patients met International Classification of Diseases-10 (ICD-10) clinical diagnostic criteria for a manic episode. Patients with a diagnosis of mixed bipolar affective disorder were excluded. Participants were evaluated using the Young Mania Rating Scale (YMRS). Exploratory factor analysis (principal component analysis) was carried out and factors with an eigenvalue > 1 were retained. The significance level for interpretation of factor loadings was 0.40. The unrotated component matrix identified five factors. Oblique rotation was then carried out to identify three factors which were clinically meaningful.</p> <p>Results</p> <p>Unrotated principal component analysis extracted five factors. These five factors explained 65.36% of the total variance. Oblique rotation extracted 3 factors. Factor 1 corresponding to 'irritable mania' had significant loadings of irritability, increased motor activity/energy and disruptive aggressive behaviour. Factor 2 corresponding to 'elated mania' had significant loadings of elevated mood, language abnormalities/thought disorder, increased sexual interest and poor insight. Factor 3 corresponding to 'psychotic mania' had significant loadings of abnormalities in thought content, appearance, poor sleep and speech abnormalities.</p> <p>Conclusions</p> <p>Our findings identified three clinically meaningful factors corresponding to 'elated mania', 'irritable mania' and 'psychotic mania'. These findings support the multidimensional nature of manic symptoms. Further evidence is needed to support the existence of corresponding clinical subtypes.</p

Polymerase II Promoter Strength Determines Efficacy of microRNA Adapted shRNAs

Since the discovery of RNAi and microRNAs more than 10 years ago, much research has focused on the development of systems that usurp microRNA pathways to downregulate gene expression in mammalian cells. One of these systems makes use of endogenous microRNA pri-cursors that are expressed from polymerase II promoters where the mature microRNA sequence is replaced by gene specific duplexes that guide RNAi (shRNA-miRs). Although shRNA-miRs are effective in directing target mRNA knockdown and hence reducing protein expression in many cell types, variability of RNAi efficacy in cell lines has been an issue. Here we show that the choice of the polymerase II promoter used to drive shRNA expression is of critical importance to allow effective mRNA target knockdown. We tested the abundance of shRNA-miRs expressed from five different polymerase II promoters in 6 human cell lines and measured their ability to drive target knockdown. We observed a clear positive correlation between promoter strength, siRNA expression levels, and protein target knockdown. Differences in RNAi from the shRNA-miRs expressed from the various promoters were particularly pronounced in immune cells. Our findings have direct implications for the design of shRNA-directed RNAi experiments and the preferred RNAi system to use for each cell type

Measurement of Beam-Spin Asymmetries for Deep Inelastic π+\pi^+ Electroproduction

We report the first evidence for a non-zero beam-spin azimuthal asymmetry in the electroproduction of positive pions in the deep-inelastic region. Data have been obtained using a polarized electron beam of 4.3 GeV with the CLAS detector at the Thomas Jefferson National Accelerator Facility (JLab). The amplitude of the $\sin\phi$ modulation increases with the momentum of the pion relative to the virtual photon, $z$, with an average amplitude of $0.038 \pm 0.005 \pm 0.003$ for $0.5 < z < 0.8$ range.Comment: 5 pages, RevTEX4, 3 figures, 2 table