5,315 research outputs found
Valuing the ICECAP capability index for older people
This paper reports the first application of the capabilities approach to the development and valuation of an instrument for use in the economic evaluation of health and social care interventions. The ICECAP index of capability for older people focuses on quality of life rather than health or other influences on quality of life, and is intended to be used in decision making across health and social care in the UK. The measure draws on previous qualitative work in which five conceptual attributes were developed: attachment, security, role, enjoyment and control. This paper details the innovative use within health economics of further iterative qualitative work in the UK among 19 informants to refine lay terminology for each of the attributes and levels of attributes used in the eventual index. For the first time within quality of life measurement for economic evaluation, a best-worst scaling exercise has been used to estimate general population values (albeit for the population of those aged 65+ years) for the levels of attributes, with values anchored at one for full capability and zero for no capability. Death was assumed to be a state in which there is no capability. The values obtained indicate that attachment is the attribute with greatest impact but all attributes contribute to the total estimation of capability. Values that were estimated are feasible for use in practical applications of the index to measure the impact of health and social care interventions. © 2008 Elsevier Ltd. All rights reserved
Estimating preferences for a dermatology consultation using Best-Worst Scaling: Comparison of various methods of analysis
Background: Additional insights into patient preferences can be gained by supplementing discrete choice experiments with best-worst choice tasks. However, there are no empirical studies illustrating the relative advantages of the various methods of analysis within a random utility framework.
Methods: Multinomial and weighted least squares regression models were estimated for a discrete choice experiment. The discrete choice experiment incorporated a best-worst study and was conducted in a UK NHS dermatology context. Waiting time, expertise of doctor, convenience of attending and perceived thoroughness of care were varied across 16 hypothetical appointments. Sample level preferences were estimated for all models and differences between patient subgroups were investigated using ovariateadjusted multinomial logistic regression.
Results: A high level of agreement was observed between results from the paired model (which is theoretically consistent with the 'maxdiff' choice model) and the marginal model (which is only an approximation to it). Adjusting for covariates showed that patients who felt particularly affected by their skin condition during the previous week displayed extreme preference for short/no waiting time and were less concerned about other aspects of the appointment. Higher levels of educational attainment were associated with larger differences in utility between the levels of all attributes, although the attributes per use had the same impact upon choices as those with lower levels of attainment. The study also demonstrated the high levels of agreement between summary analyses using weighted least squares and estimates from multinomial models.
Conclusion: Robust policy-relevant information on preferences can be obtained from discrete choice
experiments incorporating best-worst questions with relatively small sample sizes. The separation of the
effects due to attribute impact from the position of levels on the latent utility scale is not possible using
traditional discrete choice experiments. This separation is important because health policies to change the
levels of attributes in health care may be very different from those aiming to change the attribute impact
per se. The good approximation of summary analyses to the multinomial model is a useful finding, because weighted least squares choice totals give better insights into the choice model and promote greater familiarity with the preference data
Autonomous decision-making against induced seismicity in deep fluid injections
The rise in the frequency of anthropogenic earthquakes due to deep fluid
injections is posing serious economic, societal, and legal challenges to
geo-energy and waste-disposal projects. We propose an actuarial approach to
mitigate this risk, first by defining an autonomous decision-making process
based on an adaptive traffic light system (ATLS) to stop risky injections, and
second by quantifying a "cost of public safety" based on the probability of an
injection-well being abandoned. The ATLS underlying statistical model is first
confirmed to be representative of injection-induced seismicity, with examples
taken from past reservoir stimulation experiments (mostly from Enhanced
Geothermal Systems, EGS). Then the decision strategy is formalized: Being
integrable, the model yields a closed-form ATLS solution that maps a risk-based
safety standard or norm to an earthquake magnitude not to exceed during
stimulation. Finally, the EGS levelized cost of electricity (LCOE) is
reformulated in terms of null expectation, with the cost of abandoned
injection-well implemented. We find that the price increase to mitigate the
increased seismic risk in populated areas can counterbalance the heat credit.
However this "public safety cost" disappears if buildings are based on
earthquake-resistant designs or if a more relaxed risk safety standard or norm
is chosen.Comment: 8 pages, 4 figures, conference (International Symposium on Energy
Geotechnics, 26-28 September 2018, Lausanne, Switzerland
Neuromodulation and the role of electrodiagnostic techniques
Electrodiagnostic techniques have been utilized in surgery since the early 1960s. These techniques have been primarily used in neurosurgery; however, with the introduction of neuromodulation for voiding dysfunction, these techniques have now found their way into the field of female pelvic medicine. This article will review techniques applicable to evaluate pelvic floor function as it relates to neuromodulation. It will also review the literature describing how these techniques are used to help determine appropriate candidates as well as improve surgical outcomes. A PubMed search was conducted using the terms neuromodulation, Interstim, electrodiagnosis, electrodiagnostic techniques, electromyography with limits to the pelvic floor, and voiding dysfunction. Eight articles and three abstracts were found that directly related to the use of electrodiagnostic techniques as they apply to neuromodulation. Electrodiagnostic techniques may play a role in helping predict appropriate candidates for neuromodulation as well as improve surgical outcomes
Rationale, design and conduct of a randomised controlled trial evaluating a primary care-based complex intervention to improve the quality of life of heart failure patients: HICMan (Heidelberg Integrated Case Management) : study protocol
Background: Chronic congestive heart failure (CHF) is a complex disease with rising prevalence, compromised quality of life (QoL), unplanned hospital admissions, high mortality and therefore high burden of illness. The delivery of care for these patients has been criticized and new strategies addressing crucial domains of care have been shown to be effective on patients' health outcomes, although these trials were conducted in secondary care or in highly organised Health Maintenance Organisations. It remains unclear whether a comprehensive primary care-based case management for the treating general practitioner (GP) can improve patients' QoL. Methods/Design: HICMan is a randomised controlled trial with patients as the unit of randomisation. Aim is to evaluate a structured, standardized and comprehensive complex intervention for patients with CHF in a 12-months follow-up trial. Patients from intervention group receive specific patient leaflets and documentation booklets as well as regular monitoring and screening by a prior trained practice nurse, who gives feedback to the GP upon urgency. Monitoring and screening address aspects of disease-specific selfmanagement, (non)pharmacological adherence and psychosomatic and geriatric comorbidity. GPs are invited to provide a tailored structured counselling 4 times during the trial and receive an additional feedback on pharmacotherapy relevant to prognosis (data of baseline documentation). Patients from control group receive usual care by their GPs, who were introduced to guidelineoriented management and a tailored health counselling concept. Main outcome measurement for patients' QoL is the scale physical functioning of the SF-36 health questionnaire in a 12-month follow-up. Secondary outcomes are the disease specific QoL measured by the Kansas City Cardiomyopathy questionnaire (KCCQ), depression and anxiety disorders (PHQ-9, GAD-7), adherence (EHFScBS and SANA), quality of care measured by an adapted version of the Patient Chronic Illness Assessment of Care questionnaire (PACIC) and NTproBNP. In addition, comprehensive clinical data are collected about health status, comorbidity, medication and health care utilisation. Discussion: As the targeted patient group is mostly cared for and treated by GPs, a comprehensive primary care-based guideline implementation including somatic, psychosomatic and organisational aspects of the delivery of care (HICMAn) is a promising intervention applying proven strategies for optimal care. Trial registration: Current Controlled Trials ISRCTN30822978
Activation of Human Stearoyl-Coenzyme A Desaturase 1 Contributes to the Lipogenic Effect of PXR in HepG2 Cells
The pregnane X receptor (PXR) was previously known as a xenobiotic receptor. Several recent studies suggested that PXR also played an important role in lipid homeostasis but the underlying mechanism remains to be clearly defined. In this study, we found that rifampicin, an agonist of human PXR, induced lipid accumulation in HepG2 cells. Lipid analysis showed the total cholesterol level increased. However, the free cholesterol and triglyceride levels were not changed. Treatment of HepG2 cells with rifampicin induced the expression of the free fatty acid transporter CD36 and ABCG1, as well as several lipogenic enzymes, including stearoyl-CoA desaturase-1 (SCD1), long chain free fatty acid elongase (FAE), and lecithin-cholesterol acyltransferase (LCAT), while the expression of acyl:cholesterol acetyltransferase(ACAT1) was not affected. Moreover, in PXR over-expressing HepG2 cells (HepG2-PXR), the SCD1 expression was significantly higher than in HepG2-Vector cells, even in the absence of rifampicin. Down-regulation of PXR by shRNA abolished the rifampicin-induced SCD1 gene expression in HepG2 cells. Promoter analysis showed that the human SCD1 gene promoter is activated by PXR and a novel DR-7 type PXR response element (PXRE) response element was located at -338 bp of the SCD1 gene promoter. Taken together, these results indicated that PXR activation promoted lipid synthesis in HepG2 cells and SCD1 is a novel PXR target gene. © 2013 Zhang et al
Considering the Case for Biodiversity Cycles: Reexamining the Evidence for Periodicity in the Fossil Record
Medvedev and Melott (2007) have suggested that periodicity in fossil
biodiversity may be induced by cosmic rays which vary as the Solar System
oscillates normal to the galactic disk. We re-examine the evidence for a 62
million year (Myr) periodicity in biodiversity throughout the Phanerozoic
history of animal life reported by Rohde & Mueller (2005), as well as related
questions of periodicity in origination and extinction. We find that the signal
is robust against variations in methods of analysis, and is based on
fluctuations in the Paleozoic and a substantial part of the Mesozoic.
Examination of origination and extinction is somewhat ambiguous, with results
depending upon procedure. Origination and extinction intensity as defined by RM
may be affected by an artifact at 27 Myr in the duration of stratigraphic
intervals. Nevertheless, when a procedure free of this artifact is implemented,
the 27 Myr periodicity appears in origination, suggesting that the artifact may
ultimately be based on a signal in the data. A 62 Myr feature appears in
extinction, when this same procedure is used. We conclude that evidence for a
periodicity at 62 Myr is robust, and evidence for periodicity at approximately
27 Myr is also present, albeit more ambiguous.Comment: Minor modifications to reflect final published versio
Dendritic Spine Shape Analysis: A Clustering Perspective
Functional properties of neurons are strongly coupled with their morphology.
Changes in neuronal activity alter morphological characteristics of dendritic
spines. First step towards understanding the structure-function relationship is
to group spines into main spine classes reported in the literature. Shape
analysis of dendritic spines can help neuroscientists understand the underlying
relationships. Due to unavailability of reliable automated tools, this analysis
is currently performed manually which is a time-intensive and subjective task.
Several studies on spine shape classification have been reported in the
literature, however, there is an on-going debate on whether distinct spine
shape classes exist or whether spines should be modeled through a continuum of
shape variations. Another challenge is the subjectivity and bias that is
introduced due to the supervised nature of classification approaches. In this
paper, we aim to address these issues by presenting a clustering perspective.
In this context, clustering may serve both confirmation of known patterns and
discovery of new ones. We perform cluster analysis on two-photon microscopic
images of spines using morphological, shape, and appearance based features and
gain insights into the spine shape analysis problem. We use histogram of
oriented gradients (HOG), disjunctive normal shape models (DNSM), morphological
features, and intensity profile based features for cluster analysis. We use
x-means to perform cluster analysis that selects the number of clusters
automatically using the Bayesian information criterion (BIC). For all features,
this analysis produces 4 clusters and we observe the formation of at least one
cluster consisting of spines which are difficult to be assigned to a known
class. This observation supports the argument of intermediate shape types.Comment: Accepted for BioImageComputing workshop at ECCV 201
[89Zr]Oxinate4 for long-term in vivo cell tracking by positron emission tomography
Purpose 111In (typically as [111In]oxinate3) is a gold standard
radiolabel for cell tracking in humans by scintigraphy. A long
half-life positron-emitting radiolabel to serve the same purpose
using positron emission tomography (PET) has long
been sought. We aimed to develop an 89Zr PET tracer for cell
labelling and compare it with [111In]oxinate3 single photon
emission computed tomography (SPECT).
Methods [89Zr]Oxinate4 was synthesised and its uptake and
efflux were measured in vitro in three cell lines and in human
leukocytes. The in vivo biodistribution of eGFP-5T33 murine
myeloma cells labelled using [89Zr]oxinate4 or [111In]oxinate3
was monitored for up to 14 days. 89Zr retention by living
radiolabelled eGFP-positive cells in vivo was monitored by
FACS sorting of liver, spleen and bone marrow cells followed
by gamma counting.
Results Zr labelling was effective in all cell types with yields
comparable with 111In labelling. Retention of 89Zr in cells
in vitro after 24 h was significantly better (range 71 to
>90 %) than 111In (43–52 %). eGFP-5T33 cells in vivo
showed the same early biodistribution whether labelled with
111In or 89Zr (initial pulmonary accumulation followed by
migration to liver, spleen and bone marrow), but later translocation
of radioactivity to kidneys was much greater for 111In.
In liver, spleen and bone marrow at least 92 % of 89Zr
remained associated with eGFP-positive cells after 7 days
in vivo.
Conclusion [89Zr]Oxinate4 offers a potential solution to the
emerging need for a long half-life PET tracer for cell tracking
in vivo and deserves further evaluation of its effects on survival
and behaviour of different cell types
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