Costi del trattamento con oloprazina nelle fasi iniziali della schizofrenia

Objective: In Italy, use of olanzapine in the public sector was limited by law to patients that had failed treatment with conventional antipsychotics, due to the higher purchase price of the drug. This restriction prevented first-episode patients and patients early in the course of their illness from being treated with olanzapine. The present study investigates economic consequences of this policy. Design: The present study retrospectively outlines treatment costs of patients switched to olanzapine during the early stages of schizophrenia as compared to the costs of patients switched during a later stage of the illness. Setting: The study was conducted within Italian Community Mental Health Services. Patients: The cost of pharmacological and non-pharmacological treatment was retrospectively calculated in 25 out-patients with schizophrenia and related disorders over a one-year span. Thirteen patients were switched to olanzapine in the early stage of their illness, prior to drug approval under a compassionate use regimen. Twelve patients started olanzapine under the restriction in a later stage of illness following failed treatment with a conventional antipsychotic. Results: While total treatment costs between the two groups was similar, cost distribution was different. Early Switch patients had higher drug costs and higher rehabilitation costs, while Late Switch patients had higher hospitalisation costs. Conclusions: Small patient numbers and design limitations prevent conclusions being drawn regarding the ultimate impact on outcome and total treatment cost of restriction of olanzapine to second-line use. Despite this, our findings demonstrate that within the context of the Italian CMHS, patients treated with olanzapine while still in the early stages of schizophrenia do not necessarily cost more overall compared to patients who receive olanzapine after failing treatment with a conventional antipsychotic

Homing endonuclease I-TevIII: dimerization as a means to a double-strand break

Homing endonucleases are unusual enzymes, capable of recognizing lengthy DNA sequences and cleaving site-specifically within genomes. Many homing endonucleases are encoded within group I introns, and such enzymes promote the mobility reactions of these introns. Phage T4 has three group I introns, within the td, nrdB and nrdD genes. The td and nrdD introns are mobile, whereas the nrdB intron is not. Phage RB3 is a close relative of T4 and has a lengthier nrdB intron. Here, we describe I-TevIII, the H–N–H endonuclease encoded by the RB3 nrdB intron. In contrast to previous reports, we demonstrate that this intron is mobile, and that this mobility is dependent on I-TevIII, which generates 2-nt 3′ extensions. The enzyme has a distinct catalytic domain, which contains the H–N–H motif, and DNA-binding domain, which contains two zinc fingers required for interaction with the DNA substrate. Most importantly, I-TevIII, unlike the H–N–H endonucleases described so far, makes a double-strand break on the DNA homing site by acting as a dimer. Through deletion analysis, the dimerization interface was mapped to the DNA-binding domain. The unusual propensity of I-TevIII to dimerize to achieve cleavage of both DNA strands underscores the versatility of the H–N–H enzyme family

Negative Impressions of Childbirth in a North-West England Student Population

Background: Socio-cultural childbirth representations can influence perceptions of childbirth negatively. In this paper we report on a survey study to explore factors associated with negative impressions of childbirth in a North-West England University student sample. We also explored whether different sources and perceptions of childbirth information were linked to fear of childbirth. Methods: All students received a survey link via an online messaging board and/or direct email. Female students who were 18-40 years of age and childless (but planned to have children in the future) were invited to participate. Demographics, birth preferences, a fear of birth and general anxiety measures were included as well as questions about what sources of information shaped students’ attitudes towards pregnancy and birth (i.e. visual/written media, experiences of friends/family members, school-based education, and other) and impressions of birth from these sources (i.e. positive, negative, both positive and negative and not applicable). Results: Eligible students (n=276) completed the online questionnaire. The majority were Caucasian (87%) with a mean age of 22.6 years. Ninety-two students (33.3%) reported negative childbirth impressions through direct or vicarious sources. Students with negative impressions were significantly more likely to report higher fear of birth scores. Negatively perceived birth stories of friends/family members, and mixed perceptions of visual media representations of birth were associated with higher fear of birth scores. Having witnessed a birth first-hand and describing the experience as amazing was linked to lower fear scores. Conclusion: First-hand observations of birth, especially positive experiences, had implications for salutary outcomes. Negative or conflicting perceptions of vicarious experiences were associated with increased levels of childbirth fear. While further research is needed, these 3 insights suggest a need for positive birth stories and messages to be disseminated to mitigate negative effects of indirect accounts

Evaluation of midkine and anterior gradient 2 in a multimarker panel for the detection of ovarian cancer

The aims of this study were: to characterise and compare plasma concentrations of midkine (MDK) in normal healthy women with concentrations observed in women with ovarian cancer; and to establish and compare the performance of MDK with that of anterior gradient 2 protein (AGR2) and CA125 in the development of multi-analyte classification algorithms for ovarian cancer. Median plasma concentrations of immunoreactive MDK, AGR2 and CA125 were significantly greater in the case cohort (909 pg/ml, 765 pg/ml and 502 U/ml, respectively n = 46) than in the control cohort (383 pg/ml, 188 pg/ml and 13 U/ml, respectively n = 61) (p < 0.001). The area under the receiver operator characteristic curve (AUC) for MDK and AGR2 was not significantly different (0.734 ± 0.046 and 0.784 ± 0.049, respectively, mean ± SE) but were both significantly less than the AUC for CA125 (0.934 ± 0.030, p < 0.003). When subjected to stochastic gradient boosted logistic regression modelling, the AUC of the multi-analyte panel (MDK, AGR2 and CA125, 0.988 ± 0.010) was significantly greater than that of CA125 alone (0.934 ± 0.030, p = 0.035). The sensitivity and specificity of the multi-analyte algorithm were 95.2 and 97.7%, respectively. Within the study cohort, CA125 displayed a sensitivity and specificity of 87.0 and 94.6%, respectively. The data obtained in this study confirm that both MDK and AGR2 individually display utility as biomarkers for ovarian cancer and that in a multi-analyte panel significantly improve the diagnostic utility of CA125 in symptomatic women

Estimating the evidence of selection and the reliability of inference in unigenic evolution

<p>Abstract</p> <p>Background</p> <p>Unigenic evolution is a large-scale mutagenesis experiment used to identify residues that are potentially important for protein function. Both currently-used methods for the analysis of unigenic evolution data analyze 'windows' of contiguous sites, a strategy that increases statistical power but incorrectly assumes that functionally-critical sites are contiguous. In addition, both methods require the questionable assumption of asymptotically-large sample size due to the presumption of approximate normality.</p> <p>Results</p> <p>We develop a novel approach, termed the Evidence of Selection (EoS), removing the assumption that functionally important sites are adjacent in sequence and and explicitly modelling the effects of limited sample-size. Precise statistical derivations show that the EoS score can be easily interpreted as an expected log-odds-ratio between two competing hypotheses, namely, the hypothetical presence or absence of functional selection for a given site. Using the EoS score, we then develop selection criteria by which functionally-important yet non-adjacent sites can be identified. An approximate power analysis is also developed to estimate the reliability of inference given the data. We validate and demonstrate the the practical utility of our method by analysis of the homing endonuclease <monospace>I-Bmol</monospace>, comparing our predictions with the results of existing methods.</p> <p>Conclusions</p> <p>Our method is able to assess both the evidence of selection at individual amino acid sites and estimate the reliability of those inferences. Experimental validation with <monospace>I-Bmol</monospace> proves its utility to identify functionally-important residues of poorly characterized proteins, demonstrating increased sensitivity over previous methods without loss of specificity. With the ability to guide the selection of precise experimental mutagenesis conditions, our method helps make unigenic analysis a more broadly applicable technique with which to probe protein function.</p> <p>Availability</p> <p>Software to compute, plot, and summarize EoS data is available as an open-source package called 'unigenic' for the 'R' programming language at <url>http://www.fernandes.org/txp/article/13/an-analytical-framework-for-unigenic-evolution</url>.</p

Critical perspectives on ‘consumer involvement’ in health research: epistemological dissonance and the know-do gap

Researchers in the area of health and social care (both in Australia and internationally) are encouraged to involve consumers throughout the research process, often on ethical, political and methodological grounds, or simply as ‘good practice’. This paper presents findings from a qualitative study in the UK of researchers’ experiences and views of consumer involvement in health research. Two main themes are presented in the paper. Firstly, we explore the ‘know-do gap’ which relates to the tensions between researchers’ perceptions of the potential benefits of, and their actual practices in relation to, consumer involvement. Secondly, we focus on one of the reasons for this ‘know-do gap’, namely epistemological dissonance. Findings are linked to issues around consumerism in research, lay/professional knowledges, the (re)production of professional and consumer identities and the maintenance of boundaries between consumers and researchers

The influence of the political environment and destination governance on sustainable tourism development: a study of Bled, Slovenia

In the context of sustainable tourism development, there are many studies about the exchange process between residents and tourism, yet this issue is practically unexplored with respect to the political environment of tourism. Therefore, this paper introduces and posits that the political environment is a necessary enabler for implementing sustainable tourism. The authors extend the established three-pillar sustainability concept by adding in the political dimension. Then they surveyed how residents' positive and negative perceptions of tourism impacts determine their satisfaction with life in the tourism destination and thus their support for tourism in their community. The model was empirically tested within the context of the long-established Alpine destination of Bled in Slovenia. The findings confirm the importance of the political environment and question the sustainability of Bled's tourism development. It is suggested that the community has relatively weak destination governance due to the underdeveloped political environment. The survey expands and deepens the tourism sustainability debate by adding in the political environment and how it relates to the emerging growth of research on destination governance. The proposed model can be adapted and applied to any destination in order to improve its governance, including the implementation of sustainable tourism development

Application of 4,5-diaminofluorescein to reliably measure nitric oxide released from endothelial cells in vitro

Here we describe in more depth the previously published application of the fluorescent probe 4,5-diaminofluorescein (DAF-2) in order to reliably measure low levels of nitric oxide (NO) as released from human endothelial cells in vitro. The used approach is based on the following considerations a) use low concentrations of DAF-2 (0.1 µM) in order to reduce the contribution of DAF-2 auto-fluorescence to the measured total fluorescence, and b) subtract the DAF-2 auto-fluorescence from the measured total fluorescence. The advantage of this method is the reliable quantification of NO in a biological system in the nanomolar range once thoroughly validated. Here we focus in addition to the previous publication (Leikert et al., FEBS Lett 2001, 506:131-134) on aspects of validation procedures as well as limitations and pitfalls of this method