A Review and Classification of Approaches for Dealing with Uncertainty in Multi-Criteria Decision Analysis for Healthcare Decisions

Multi-criteria decision analysis (MCDA) is increasingly used to support decisions in healthcare involving multiple and conflicting criteria. Although uncertainty is usually carefully addressed in health economic evaluations, whether and how the different sources of uncertainty are dealt with and with what methods in MCDA is less known. The objective of this study is to review how uncertainty can be explicitly taken into account in MCDA and to discuss which approach may be appropriate for healthcare decision makers. A literature review was conducted in the Scopus and PubMed databases. Two reviewers independently categorized studies according to research areas, the type of MCDA used, and the approach used to quantify uncertainty. Selected full text articles were read for methodological details. The search strategy identified 569 studies. The five approaches most identified were fuzzy set theory (45 % of studies), probabilistic sensitivity analysis (15 %), deterministic sensitivity analysis (31 %), Bayesian framework (6 %), and grey theory (3 %). A large number of papers considered the analytic hierarchy process in combination with fuzzy set theory (31 %). Only 3 % of studies were published in healthcare-related journals. In conclusion, our review identified five different approaches to take uncertainty into account in MCDA. The deterministic approach is most likely sufficient for most healthcare policy decisions because of its low complexity and straightforward implementation. However, more complex approaches may be needed when multiple sources of uncertainty must be considered simultaneousl

Prenatal and pubertal testosterone affect brain lateralization

After decades of research, the influence of prenatal testosterone on brain lateralization is still elusive, whereas the influence of pubertal testosterone on functional brain lateralization has not been investigated, although there is increasing evidence that testosterone affects the brain in puberty. We performed a longitudinal study, investigating the relationship between prenatal testosterone concentrations in amniotic fluid, pubertal testosterone concentrations in saliva, and brain lateralization (measured with functional Transcranial Doppler ultrasonography (fTCD)) of the Mental Rotation, Chimeric Faces and Word Generation tasks. Thirty boys and 30 girls participated in this study at the age of 15 years. For boys, we found a significant interaction effect between prenatal and pubertal testosterone on lateralization of Mental Rotation and Chimeric Faces. In the boys with low prenatal testosterone levels, pubertal testosterone was positively related to the strength of lateralization in the right hemisphere, while in the boys with high prenatal testosterone levels, pubertal testosterone was negatively related to the strength of lateralization. For Word Generation, pubertal testosterone was negatively related to the strength of lateralization in the left hemisphere in boys. For girls, we did not find any significant effects, possibly because their pubertal testosterone levels were in many cases below quantification limit. To conclude, prenatal and pubertal testosterone affect lateralization in a task-specific way. Our findings cannot be explained by simple models of prenatal testosterone affecting brain lateralization in a similar way for all tasks. We discuss alternative models involving age dependent effects of testosterone, with a role for androgen receptor distribution and efficiency

Bioconjugation strategies to couple supramolecular exo-functionalized palladium cages to peptides for biomedical applications

Supramolecular Pd2L4 cages (L = ligand) hold promise as drug delivery systems. With the idea of achieving targeted delivery of the metallacages to tumor cells, the bioconjugation of exo-functionalized self-assembled Pd2L4 cages to peptides following two different approaches is reported for the first time. The obtained bioconjugates were analyzed and identified by high-resolution mass spectrometry

The Effect of Provider Density on Lung Cancer Survival Among Blacks and Whites in the United States

IntroductionLung cancer mortality rates may vary with access to specialty providers and local resources. We sought to examine the effect of access to care, using density of lung cancer care providers, on lung cancer mortality among blacks and whites in the United States.MethodsWe examined U.S. county-level data for age-adjusted lung cancer mortality rates from 2003 to 2007. Our primary independent variable was per capita number of thoracic oncologic providers, adjusting for county-level smoking rates, socioeconomic status, and other geographic factors. Data were obtained from 2009 Area Resource File, National Center for Health Statistics, and the County Health Rankings Project.ResultsProviders of lung cancer care were unevenly distributed among the U.S. counties. For example, 41.4% of the U.S. population reside in counties with less than four thoracic surgeons per 100,000 people, 23.4% in counties with 4 to 15 surgeons per 100,000 people, and 35.3% in counties with more than 15 surgeons per 100,000 people. Geographically, 4.3% of whites compared with 11.2% of blacks lived in high lung cancer mortality zones. Lung cancer mortality did not vary by density of thoracic surgeons or oncology services; however, higher primary care provider density was associated with lung cancer mortality reduction of 4.1 per 100,000 for whites.ConclusionVariation in provider density for thoracic oncology in the United States was not associated with a difference in lung cancer mortality. Lower mortality associated with higher primary care provider density suggests that equitable access to primary care may lead to reduced cancer disparities

Approaching the Gamow Window with Stored Ions : Direct Measurement of Xe 124 (p,γ) in the ESR Storage Ring

© 2019 American Physical Society. All rights reserved.We report the first measurement of low-energy proton-capture cross sections of Xe124 in a heavy-ion storage ring. Xe12454+ ions of five different beam energies between 5.5 and 8 AMeV were stored to collide with a windowless hydrogen target. The Cs125 reaction products were directly detected. The interaction energies are located on the high energy tail of the Gamow window for hot, explosive scenarios such as supernovae and x-ray binaries. The results serve as an important test of predicted astrophysical reaction rates in this mass range. Good agreement in the prediction of the astrophysically important proton width at low energy is found, with only a 30% difference between measurement and theory. Larger deviations are found above the neutron emission threshold, where also neutron and γ widths significantly impact the cross sections. The newly established experimental method is a very powerful tool to investigate nuclear reactions on rare ion beams at low center-of-mass energies.Peer reviewedFinal Published versio

Stage-Specific Inhibition of MHC Class I Presentation by the Epstein-Barr Virus BNLF2a Protein during Virus Lytic Cycle

gamma-herpesvirus Epstein-Barr virus (EBV) persists for life in infected individuals despite the presence of a strong immune response. During the lytic cycle of EBV many viral proteins are expressed, potentially allowing virally infected cells to be recognized and eliminated by CD8+ T cells. We have recently identified an immune evasion protein encoded by EBV, BNLF2a, which is expressed in early phase lytic replication and inhibits peptide- and ATP-binding functions of the transporter associated with antigen processing. Ectopic expression of BNLF2a causes decreased surface MHC class I expression and inhibits the presentation of indicator antigens to CD8+ T cells. Here we sought to examine the influence of BNLF2a when expressed naturally during EBV lytic replication. We generated a BNLF2a-deleted recombinant EBV (ΔBNLF2a) and compared the ability of ΔBNLF2a and wild-type EBV-transformed B cell lines to be recognized by CD8+ T cell clones specific for EBV-encoded immediate early, early and late lytic antigens. Epitopes derived from immediate early and early expressed proteins were better recognized when presented by ΔBNLF2a transformed cells compared to wild-type virus transformants. However, recognition of late antigens by CD8+ T cells remained equally poor when presented by both wild-type and ΔBNLF2a cell targets. Analysis of BNLF2a and target protein expression kinetics showed that although BNLF2a is expressed during early phase replication, it is expressed at a time when there is an upregulation of immediate early proteins and initiation of early protein synthesis. Interestingly, BNLF2a protein expression was found to be lost by late lytic cycle yet ΔBNLF2a-transformed cells in late stage replication downregulated surface MHC class I to a similar extent as wild-type EBV-transformed cells. These data show that BNLF2a-mediated expression is stage-specific, affecting presentation of immediate early and early proteins, and that other evasion mechanisms operate later in the lytic cycle