Why worry about awareness in choice problems? Econometric analysis of screening for cervical cancer

Cervical cancer is one of the most preventable and curable forms of cancer. Since 1991 there has been a concerted effort in Australia to recommend and encourage women to have Pap smears every two years. Part of the success of this National Cervical Screening Program can be gauged by exploring the determinants of screening for cervical cancer among high-risk women and by addressing the specific question of whether screening is associated with socio-economic status. Accessibility to health services remains a core goal in health policy in Australia but evidence on whether the goal is being met is limited. Using unit record data from the 1995 National Health Survey, an econometric model is developed for whether women have ever screened or not. A proportion of women in the sample contend that they have never heard of a Pap test. The analysis characterizes this group of women and accounts for their presence in our modellingScreening choice; Awareness; Censored probit; Cervical cancer

Natural variation in gene expression in the early development of dauer larvae of Caenorhabditis elegans

<p>Abstract</p> <p>Background</p> <p>The free-living nematode <it>Caenorhabditis elegans </it>makes a developmental decision based on environmental conditions: larvae either arrest as dauer larva, or continue development into reproductive adults. There is natural variation among <it>C. elegans </it>lines in the sensitivity of this decision to environmental conditions; that is, there is variation in the phenotypic plasticity of dauer larva development. We hypothesised that these differences may be transcriptionally controlled in early stage larvae. We investigated this by microarray analysis of different <it>C. elegans </it>lines under different environmental conditions, specifically the presence and absence of dauer larva-inducing pheromone.</p> <p>Results</p> <p>There were substantial transcriptional differences between four <it>C. elegans </it>lines under the same environmental conditions. The expression of approximately 2,000 genes differed between genetically different lines, with each line showing a largely line-specific transcriptional profile. The expression of genes that are markers of larval moulting suggested that the lines may be developing at different rates. The expression of a total of 89 genes was putatively affected by dauer larva or non-dauer larva-inducing conditions. Among the upstream regions of these genes there was an over-representation of DAF-16-binding motifs.</p> <p>Conclusion</p> <p>Under the same environmental conditions genetically different lines of <it>C. elegans </it>had substantial transcriptional differences. This variation may be due to differences in the developmental rates of the lines. Different environmental conditions had a rather smaller effect on transcription. The preponderance of DAF-16-binding motifs upstream of these genes was consistent with these genes playing a key role in the decision between development into dauer or into non-dauer larvae. There was little overlap between the genes whose expression was affected by environmental conditions and previously identified loci involved in the plasticity of dauer larva development.</p

Breaking up is hard to do: Why disinvestment in medical technology is harder than investment

Healthcare technology is a two-edged sword - it offers new and better treatment to a wider range of people and, at the same time, is a major driver of increasing costs in health systems. Many countries have developed sophisticated systems of health technology assessment (HTA) to inform decisions about new investments in new healthcare interventions. In this paper, we question whether HTA is also the appropriate framework for guiding or informing disinvestment decisions. In exploring the issues related to disinvestment, we first discuss the various HTA frameworks which have been suggested as a means of encouraging or facilitating disinvestment. We then describe available means of identifying candidates for disinvestment (comparative effectiveness research, clinical practice variations, clinical practice guidelines) and for implementing the disinvestment process (program budgeting and marginal analysis (PBMA) and related techniques). In considering the possible reasons for the lack of progress in active disinvestment, we suggest that HTA is not the right framework as disinvestment involves a different decision making context. The key to disinvestment is not just what to stop doing but how to make it happen - that is, decision makers need to be aware of funding disincentives. What is known about this topic? Disinvestment is an increasingly popular topic amongst academics and policy makers. Most discussions focus on the need to increase disinvestment as a corollary of investment, the lack of overt disinvestment decisions and the use of a framework based on health technology assessment (HTA) to implement disinvestment. What does this paper add? This paper focusses on the difficulties associated with deciding which technologies to disinvest in, and the problems in using an HTA framework to make such decisions, when disinvestment involves a different decision making context from that of investment. What are the implications for practitioners? The key to disinvestment is not just what to stop doing but how to implement such decisions. Making it happen means being aware of funding disincentives. © 2012 AHHA

Does the structure of the medical consultation align with an educational model of clinical communication? A study of physicians’ consultations from a postgraduate examination

OBJECTIVE: This study examined whether the structure of consultations in which physicians were tasked with sharing information corresponded to the chronological stages proposed by an established educational model of clinical communication. METHOD: Seventy six simulated consultations from a postgraduate examination for general medical hospital physicians were transcribed verbatim and converted into diagrams showing consultation structure. All doctor-patient/relative talk was allocated into six phases: Initiating, Gathering information, Summary, Explanation, Planning and Closing, using the ‘communication process skills’ from the Calgary-Cambridge Guide to the Medical Interview. RESULTS: The majority of consultations included four or five of the expected phases, with most talk (41-92%) in Explanation and Planning. There was no discernible consistency of structure across the consultations or in consultations from the same scenario. Consultations varied in the presence, sequential order, size, location and reappearance of phases. CONCLUSIONS: The structure of consultations in this standardised setting bore little resemblance to the chronological order of phases predicted by an educational model. PRACTICE IMPLICATIONS: Educational guidance and interventions to support patients in preparing for consultations need to take account of doctors’ behaviour in practice. Assumptions about the organisation of medical consultations should be queried in the absence of an evidence base

Synaptic targets of medial septal projections in the hippocampus and extrahippocampal cortices of the mouse

Temporal coordination of neuronal assemblies among cortical areas is essential for behavioral performance. GABAergic projections from the medial septum and diagonal band complex exclusively innervate GABAergic interneurons in the rat hippocampus, contributing to the coordination of neuronal activity, including the generation of theta oscillations. Much less is known about the synaptic target neurons outside the hippocampus. To reveal the contribution of synaptic circuits involving the medial septum of mice, we have identified postsynaptic cortical neurons in wild-type and parvalbumin-Cre knock-in mice. Anterograde axonal tracing from the septum revealed extensive innervation of the hippocampus as well as the subiculum, presubiculum, parasubiculum, the medial and lateral entorhinal cortices, and the retrosplenial cortex. In all examined cortical regions, many septal GABAergic boutons were in close apposition to somata or dendrites immunopositive for interneuron cell-type molecular markers, such as parvalbumin, calbindin, calretinin, N-terminal EF-hand calcium-binding protein 1, cholecystokinin, reelin, or a combination of these molecules. Electron microscopic observations revealed septal boutons forming axosomatic or axodendritic type II synapses. In the CA1 region of hippocampus, septal GABAergic projections exclusively targeted interneurons. In the retrosplenial cortex, 93% of identified postsynaptic targets belonged to interneurons and the rest to pyramidal cells. These results suggest that the GABAergic innervation from the medial septum and diagonal band complex contributes to temporal coordination of neuronal activity via several types of cortical GABAergic interneurons in both hippocampal and extrahippocampal cortices. Oscillatory septal neuronal firing at delta, theta, and gamma frequencies may phase interneuron activity. SIGNIFICANCE STATEMENT Diverse types of GABAergic interneurons coordinate the firing of cortical principal cells required for memory processes. During wakefulness and rapid eye movement sleep, the rhythmic firing of cortical GABAergic neurons plays a key role in governing network activity. We investigated subcortical GABAergic projections in the mouse that extend from the medial septum/diagonal band nuclei to GABAergic neurons in the hippocampus and related extrahippocampal cortical areas, including the medial entorhinal cortex. These areas contribute to navigation and show theta rhythmic activity. We found selective GABAergic targeting of different groups of cortical GABAergic neurons, immunoreactive for combinations of cell-type markers. As septal GABAergic neurons also fire rhythmically, their selective innervation of cortical GABAergic neurons suggests an oscillatory synchronization of neuronal activity across functionally related areas

La responsabilité civile du détenteur contractuel de la chose d&#039;autrui en droit privé français

Etudier la responsabilité civile du détenteur contractuel de la chose d\u27autrui consiste à préciser son fondement et son régime. Or, une telle démarche se heurte à des obstacles majeurs. D\u27une part tout détenteur est tenu, en tant que débiteur d\u27un corps certain, de deux obligations : conserver et restituer. D\u27autre part, le détenteur est soumis à des régimes variés de responsabilité : responsabilité pour faute, pour faute présumée, sans faute. Confrontée à la dualité d\u27obligations du détenteur, nous avons tranché la difficulté en démontrant que si l\u27obligation de restitution est le fondement de la responsabilité en cas de retard et de refus injustifié de restituer, seule l\u27obligation de conservation doit servir de fondement à la responsabilité en cas de détérioration comme de perte de la chose. Confrontée à la diversité du droit positif, nous avons tout d\u27abord été obligée de constater qu\u27elle ne concerne que la responsabilité pour défaut de conservation, la responsabilité pour défaut de restitution pouvant être identiquement engagée de plein droit, quel que soit le contrat ayant conféré la détention. Ensuite, nous avons pris conscience que seule une classification des contrats selon leur finalité économique confère cohérence aux différents régimes de responsabilité pour défaut de conservation. Il s\u27agit alors d\u27accorder son attention à l\u27objet du contrat entendu comme l\u27opération économique recherchée par les parties et de distinguer entre les contrats conférant la détention dans le but d\u27utiliser la chose d\u27autrui et ceux conférant la détention dans le but d\u27organiser une prestation de service sur la chose d\u27autrui. Un tel regroupement des contrats spéciaux par familles permet d\u27expliquer le régime de responsabilité grâce aux particularités propres à chaque catégorie et de substituer à la qualification contractuelle une méthode de détermination du régime de responsabilité dans les contrats complexes ou innomés.

A metabolic signature of long life in Caenorhabditis elegans

<p>Abstract</p> <p>Background</p> <p>Many <it>Caenorhabditis elegans </it>mutations increase longevity and much evidence suggests that they do so at least partly via changes in metabolism. However, up until now there has been no systematic investigation of how the metabolic networks of long-lived mutants differ from those of normal worms. Metabolomic technologies, that permit the analysis of many untargeted metabolites in parallel, now make this possible. Here we use one of these, ¹H nuclear magnetic resonance spectroscopy, to investigate what makes long-lived worms metabolically distinctive.</p> <p>Results</p> <p>We examined three classes of long-lived worms: dauer larvae, adult Insulin/IGF-1 signalling (IIS)-defective mutants, and a translation-defective mutant. Surprisingly, these ostensibly different long-lived worms share a common metabolic signature, dominated by shifts in carbohydrate and amino acid metabolism. In addition the dauer larvae, uniquely, had elevated levels of modified amino acids (hydroxyproline and phosphoserine). We interrogated existing gene expression data in order to integrate functional (metabolite-level) changes with transcriptional changes at a pathway level.</p> <p>Conclusions</p> <p>The observed metabolic responses could be explained to a large degree by upregulation of gluconeogenesis and the glyoxylate shunt as well as changes in amino acid catabolism. These responses point to new possible mechanisms of longevity assurance in worms. The metabolic changes observed in dauer larvae can be explained by the existence of high levels of autophagy leading to recycling of cellular components.</p> <p>See associated minireview: <url>http://jbiol.com/content/9/1/7</url></p

European respiratory society international congress 2021: Highlights from best-abstract awardees

This article provides an overview of some of the highlights of the @EuroRespSoc Congress 2021 from the perspective of the best-abstract awardees of the ERS Assemblies @EarlyCareerERS @OrphaLung https://bit.ly/3JCjHYS Every year, the European Respiratory Society (ERS) offers grants to recognise the best overall abstracts of the 14 ERS Assemblies submitted for the ERS International Congress, covering all respiratory areas. The authors of the best abstract (i.e. the highest average score of abstract reviewers and only those who have not applied or were not eligible for a sponsored award) were invited to write a short summary about their virtual Congress experience and view on the evolving field of research in light of their respective Assembly. This article provides an overview of some of the Congress highlights and gives the stage to the promising best-abstract awardees as they are the future of the ERS

High risk prescribing in older adults: Prevalence, clinical and economic implications and potential for intervention at the population level

Background: High risk prescribing can compromise independent wellbeing and quality of life in older adults. The aims of this project are to determine the prevalence, risk factors, clinical consequences, and costs of high risk prescribing, and to assess the impact of interventions on high risk prescribing in older people. Methods. The proposed project will utilise data from the 45 and Up Study, a large scale cohort of 267,153 men and women aged 45 and over recruited during 2006-2009 from the state of New South Wales, Australia linked to a range of administrative health datasets. High risk prescribing will be assessed using three indicators: polypharmacy (use of five or more medicines); Beers Criteria (an explicit measure of potentially inappropriate medication use); and Drug Burden Index (a pharmacologic dose-dependent measure of cumulative exposure to anticholinergic and sedative medicines). Individual risk factors from the 45 and Up Study questionnaire, and health system characteristics from health datasets that are associated with the likelihood of high risk prescribing will be identified. The main outcome measures will include hospitalisation (first admission to hospital, total days in hospital, cause-specific hospitalisation); admission to institutionalised care; all-cause mortality, and, where possible, cause-specific mortality. Economic costs to the health care system and implications of high risk prescribing will be also investigated. In addition, changes in high risk prescribing will be evaluated in relation to certain routine medicines-related interventions. The statistical analysis will be conducted using standard pharmaco-epidemiological methods including descriptive analysis, univariate and multivariate regression analysis, controlling for relevant confounding factors, using a number of different approaches. Discussion. The availability of large-scale data is useful to identify opportunities for improving prescribing, and health in older adults. The size of the 45 and Up Study, along with linkage to health databases provides an important opportunity to investigate the relationship between high risk prescribing and adverse outcomes in a real-world population of older adults. © 2013 Gnjidic et al.; licensee BioMed Central Ltd

Deriving a preference-based utility measure for cancer patients from the European Organisation for the Research and Treatment of Cancer's Quality of Life Questionnaire C30: a confirmatory versus exploratory approach

Background: Multi attribute utility instruments (MAUIs) are preference-based measures that comprise a health state classification system (HSCS) and a scoring algorithm that assigns a utility value to each health state in the HSCS. When developing a MAUI from a health-related quality of life (HRQOL) questionnaire, first a HSCS must be derived. This typically involves selecting a subset of domains and items because HRQOL questionnaires typically have too many items to be amendable to the valuation task required to develop the scoring algorithm for a MAUI. Currently, exploratory factor analysis (EFA) followed by Rasch analysis is recommended for deriving a MAUI from a HRQOL measure. Aim: To determine whether confirmatory factor analysis (CFA) is more appropriate and efficient than EFA to derive a HSCS from the European Organisation for the Research and Treatment of Cancer’s core HRQOL questionnaire, Quality of Life Questionnaire (QLQ-C30), given its well-established domain structure. Methods: QLQ-C30 (Version 3) data were collected from 356 patients receiving palliative radiotherapy for recurrent/metastatic cancer (various primary sites). The dimensional structure of the QLQ-C30 was tested with EFA and CFA, the latter informed by the established QLQC30 structure and views of both patients and clinicians on which are the most relevant items. Dimensions determined by EFA or CFA were then subjected to Rasch analysis. Results: CFA results generally supported the proposed QLQ-C30 structure (comparative fit index =0.99, Tucker–Lewis index =0.99, root mean square error of approximation =0.04). EFA revealed fewer factors and some items cross-loaded on multiple factors. Further assessment of dimensionality with Rasch analysis allowed better alignment of the EFA dimensions with those detected by CFA. Conclusion: CFA was more appropriate and efficient than EFA in producing clinically interpretable results for the HSCS for a proposed new cancer-specific MAUI. Our findings suggest that CFA should be recommended generally when deriving a preference-based measure from a HRQOL measure that has an established domain structure