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

Relativistic description of electron scattering on the deuteron

Within a quasipotential framework a relativistic analysis is presented of the deuteron current. Assuming that the singularities from the nucleon propagators are important, a so-called equal time approximation of the current is constructed. This is applied to both elastic and inelastic electron scattering. As dynamical model the relativistic one boson exchange model is used. Reasonable agreement is found with a previous relativistic calculation of the elastic electromagnetic form factors of the deuteron. For the unpolarized inelastic electron scattering effects of final state interactions and relativistic corrections to the structure functions are considered in the impulse approximation. Two specific kinematic situations are studied as examples.Comment: (19 pages in revtex + 15 figures not included, available upon request.) report THU-93-10

Spin-orbit final state interaction in the framework of Glauber theory for (e,e'p) reactions

We investigate the reactions D(e,e'p)n and D(\vec e,e'p)n at GeV energies and discuss the opportunities to distinguish between different models for the nuclear ground state by measuring the response functions. In calculating the final-state interaction (FSI) we employ Glauber theory, and we also include relativistic effects in the electromagnetic current. We include not only the central FSI, but also the spin-orbit FSI which is usually neglected in (e,e'p) calculations within the Glauber framework and we show that this contribution plays a crucial role for the fifth response function. All of the methods developed here can be applied to any target nucleus.Comment: 20 pages, 12 figures, minor change in figures 3 and 4 (changed beam energy), correction of error in figure 4 in the previous replacemen

Nonvanishing univalent functions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46267/1/209_2005_Article_BF01214860.pd

Disruption of PHF21A causes syndromic intellectual disability with craniofacial anomalies, epilepsy, hypotonia, and neurobehavioral problems including autism

BACKGROUND: PHF21A has been associated with intellectual disability and craniofacial anomalies based on its deletion in the Potocki-Shaffer syndrome region at 11p11.2 and its disruption in three patients with balanced translocations. In addition, three patients with de novo truncating mutations in PHF21A were reported recently. Here, we analyze genomic data from seven unrelated individuals with mutations in PHF21A and provide detailed clinical descriptions, further expanding the phenotype associated with PHF21A haploinsufficiency. METHODS: Diagnostic trio whole exome sequencing, Sanger sequencing, use of GeneMatcher, targeted gene panel sequencing, and MiSeq sequencing techniques were used to identify and confirm variants. RT-qPCR was used to measure the normal expression pattern of PHF21A in multiple human tissues including 13 different brain tissues. Protein-DNA modeling was performed to substantiate the pathogenicity of the missense mutation. RESULTS: We have identified seven heterozygous coding mutations, among which six are de novo (not maternal in one). Mutations include four frameshifts, one nonsense mutation in two patients, and one heterozygous missense mutation in the AT Hook domain, predicted to be deleterious and likely to cause loss of PHF21A function. We also found a new C-terminal domain composed of an intrinsically disordered region. This domain is truncated in six patients and thus likely to play an important role in the function of PHF21A, suggesting that haploinsufficiency is the likely underlying mechanism in the phenotype of seven patients. Our results extend the phenotypic spectrum of PHF21A mutations by adding autism spectrum disorder, epilepsy, hypotonia, and neurobehavioral problems. Furthermore, PHF21A is highly expressed in the human fetal brain, which is consistent with the neurodevelopmental phenotype. CONCLUSION: Deleterious nonsense, frameshift, and missense mutations disrupting the AT Hook domain and/or an intrinsically disordered region in PHF21A were found to be associated with autism spectrum disorder, epilepsy, hypotonia, neurobehavioral problems, tapering fingers, clinodactyly, and syndactyly, in addition to intellectual disability and craniofacial anomalies. This suggests that PHF21A is involved in autism spectrum disorder and intellectual disability, and its haploinsufficiency causes a diverse neurological phenotype