Bayesian D-Optimal Choice Designs for Mixtures

__Abstract__ \n \nConsumer products and services can often be described as mixtures of ingredients. Examples are the mixture of ingredients in a cocktail and the mixture of different components of waiting time (e.g., in-vehicle and out-of-vehicle travel time) in a transportation setting. Choice experiments may help to determine how the respondents\' choice of a product or service is affected by the combination of ingredients. In such studies, individuals are confronted with sets of hypothetical products or services and they are asked to choose the most preferred product or service from each set. \n \nHowever, there are no studies on the optimal design of choice experiments involving mixtures. We propose a method for generating an optimal design for such choice experiments. To this end, we first introduce mixture models in the choice context and next present an algorithm to construct optimal experimental designs, assuming the multinomial logit model is used to analyze the choice data. To overcome the problem that the optimal designs depend on the unknown parameter values, we adopt a Bayesian D-optimal design approach. We also consider locally D-optimal designs and compare the performance of the resulting designs to those produced by a utility-neutral (UN) approach in which designs are based on the assumption that individuals are indifferent between all choice alternatives. We demonstrate that our designs are quite different and in general perform better than the UN designs

Donald J. Jamison Sr. v. Utah Home Fire Insurance Company : Brief of Respondent

Appeal from the Judgment of the Third Judicial District Court, Salt Lake County- Honorable Stewart M. Hanson, Jr

Vignette studies of medical choice and judgement to study caregivers' medical decision behaviour: systematic review

BACKGROUND: Vignette studies of medical choice and judgement have gained popularity in the medical literature. Originally developed in mathematical psychology they can be used to evaluate physicians' behaviour in the setting of diagnostic testing or treatment decisions. We provide an overview of the use, objectives and methodology of these studies in the medical field. METHODS: Systematic review. We searched in electronic databases; reference lists of included studies. We included studies that examined medical decisions of physicians, nurses or medical students using cue weightings from answers to structured vignettes. Two reviewers scrutinized abstracts and examined full text copies of potentially eligible studies. The aim of the included studies, the type of clinical decision, the number of participants, some technical aspects, and the type of statistical analysis were extracted in duplicate and discrepancies were resolved by consensus. RESULTS: 30 reports published between 1983 and 2005 fulfilled the inclusion criteria. 22 studies (73%) reported on treatment decisions and 27 (90%) explored the variation of decisions among experts. Nine studies (30%) described differences in decisions between groups of caregivers and ten studies (33%) described the decision behaviour of only one group. Only six studies (20%) compared decision behaviour against an empirical reference of a correct decision. The median number of considered attributes was 6.5 (IQR 4-9), the median number of vignettes was 27 (IQR 16-40). In 17 studies, decision makers had to rate the relative importance of a given vignette; in six studies they had to assign a probability to each vignette. Only ten studies (33%) applied a statistical procedure to account for correlated data. CONCLUSION: Various studies of medical choice and judgement have been performed to depict weightings of the value of clinical information from answers to structured vignettes of care givers. We found that the design and analysis methods used in current applications vary considerably and could be improved in a large number of cases

Correction: Protocol of the Healthy Brain Study:An accessible resource for understanding the human brain and how it dynamically and individually operates in its bio-social context

[This corrects the article DOI: 10.1371/journal.pone.0260952.]

Protocol of a prospective study on the diagnostic value of transcranial duplex scanning of the substantia nigra in patients with parkinsonian symptoms

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease (PD) is the second most common neurodegenerative disorder. As there is no definitive diagnostic test, its diagnosis is based on clinical criteria. Recently transcranial duplex scanning (TCD) of the substantia nigra in the brainstem has been proposed as an instrument to diagnose PD. We and others have found that TCD scanning of substantia nigra duplex is a relatively accurate diagnostic instrument in patients with parkinsonian symptoms. However, all studies on TCD so far have involved well-defined, later-stage PD patients, which will obviously lead to an overestimate of the diagnostic accuracy of TCD.</p> <p>We have therefore set out to conduct a prospective study testing the diagnostic accuracy of TCD in patients with a parkinsonism of unclear origin.</p> <p>Methods/Design</p> <p>We will enrol 250 consecutive patients, who are referred to neurology outpatient clinics of two teaching hospitals, for analysis of clinically unclear parkinsonism. Patients, whose parkinsonism is clearly diagnosable at the first visit, will be excluded from the study. All patients will undergo a TCD of the substantia nigra. As a surrogate gold standard we will use the consensus clinical diagnosis reached by two independent, blinded, movement disorder specialist neurologists after 2 years follow-up. At the time of TCD, patients will also undergo a SPECT scan of the brain.</p> <p>Discussion</p> <p>As this prospective trial enrols only patients with an early-stage parkinsonism, it will yield data on the diagnostic accuracy of TCD that is relevant to daily clinical practice: The neurologist needs a diagnostic tool that provides additional information in patients with a clinically indefinable parkinsonian syndrome. The above described observational longitudinal study was designed to explicitly study this aspect in the diagnostic process.</p> <p>Trial registration</p> <p><b>(ITRSCC) NCT00368199</b></p

Development of Grb2 SH2 Domain Signaling Antagonists: A Potential New Class of Antiproliferative Agents

Aberrant signaling through protein-tyrosine kinase (PTK)-dependent pathways is associated with several proliferative diseases. Accordingly, PTK inhibitors are being developed as new approaches for the treatment of certain cancers. Growth factor receptor bound protein 2 (Grb2) is an important downstream mediator of PTK signaling that serves obligatory roles in many pathogenic processes. One of the primary functions of Grb2 is to bind to specific phosphotyrosyl (pTyr)-containing sequences through its Src homology 2 (SH2) domain. Agents that bind to the Grb2 SH2 domain and prevent its normal function could disrupt associated PTK signaling and serve as alternatives to kinase-directed inhibitors. Starting from the X-ray crystal structure of a lead peptide bound to the Grb2 SH2 domain, this review will summarize important contributions to these efforts. The presentation will be thematically arranged according to the region of peptide modified, proceeding from the N-terminus to the C-terminus, with a special section devoted to aspects of conformational constraint

Identification and Characterization of an Unusual Class I Myosin Involved in Vesicle Traffic in Trypanosoma brucei

Myosins are a multimember family of motor proteins with diverse functions in eukaryotic cells. African trypanosomes possess only two candidate myosins and thus represent a useful system for functional analysis of these motors. One of these candidates is an unusual class I myosin (TbMyo1) that is expressed at similar levels but organized differently during the life cycle of Trypanosoma brucei. This myosin localizes to the polarized endocytic pathway in bloodstream forms of the parasite. This organization is actin dependent. Knock down of TbMyo1 results in a significant reduction in endocytic activity, a cessation in cell division and eventually cell death. A striking morphological feature in these cells is an enlargement of the flagellar pocket, which is consistent with an imbalance in traffic to and from the surface. In contrast TbMyo1 is distributed throughout procyclic forms of the tsetse vector and a loss of ∼90% of the protein has no obvious effects on growth or morphology. These results reveal a life cycle stage specific requirement for this myosin in essential endocytic traffic and represent the first description of the involvement of a motor protein in vesicle traffic in these parasites

Cognition and resective surgery for diffuse infiltrative glioma: an overview

Compared to classical oncological outcome measures such as time to progression and survival, the importance of cognitive functioning in patients with diffuse infiltrative brain tumors has only recently been recognized. Apart from the relatively low incidence and the invariably fatal outcome of gliomas, the general assumption that cognitive assessment is time-consuming and burdensome contributes to this notion. Our understanding of the effects of brain surgery on cognition, for instance, is largely based on studies in surgical patients with refractory epilepsy, with only a limited number of studies in surgical patients with gliomas. The impact of other factors affecting cognition in glioma patients such as direct tumor effects, radiotherapy and chemotherapy, and medical treatment, including anti-epileptic drugs and steroids, have been studied more extensively. The purpose of this paper is to provide an overview of cognition in patients with diffuse infiltrative gliomas and the impact of resective surgery as well as other tumor and treatment-related factors