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Early health technology assessment is increasingly being used to support health economic evidence development during early stages of clinical research. Such early models can be used to inform research and development about the design and management of new medical technologies to mitigate the risks, perceived by industry and the public sector, associated with market access and reimbursement. Over the past 25 years it has been suggested that health economic evaluation in the early stages may benefit the development and diffusion of medical products. Early health technology assessment has been suggested in the context of iterative economic evaluation alongside phase I and II clinical research to inform clinical trial design, market access, and pricing. In addition, performing early health technology assessment was also proposed at an even earlier stage for managing technology portfolios. This scoping review suggests a generally accepted definition of early health technology assessment to be “all methods used to inform industry and other stakeholders about the potential value of new medical products in development, including methods to quantify and manage uncertainty”. The present review also aimed to identify recent published empirical studies employing an early-stage assessment of a medical product. With most included studies carried out to support a market launch, the dominant methodology was early health economic modeling. Further methodological development is required, in particular, by combining systems engineering and health economics to manage uncertainty in medical product portfolios.

We estimate a collective household model with survey data on financial satisfaction from the European Community Household Panel. Our estimates suggest that cohabitating individuals enjoy returns to scale in consumption that are towards the larger end of the range of estimates reported in the literature. They also suggest that the share of household income provided by the female partner is a significant determinant of her share of household consumption in most countries of the countries we study.

Smiling during talking yields speech with higher formants, and hence larger formant dispersion. Previous studies have shown that motor resonance during perception of words related to smiling can activate muscles responsible for the smiling action. If word perception causes smiling activation for such smile-related words, then this motor resonance may occur also during production, resulting in larger formant dispersion in these smile-related words. This paper reports on formant measurements from tokens of the Corpus of Spoken Dutch. Formant values of smile-related word tokens were compared to semantically different but phonetically similar word tokens. Results suggest that formant dispersion is indeed larger in smile-related words than in control words, although the predicted difference was observed only for female speakers. These findings suggest that motor resonance originating from a word's meaning may affect the articulatory and acoustic realization of affective spoken words. Female speakers tend to produce the word "smile" with a smile.

We consider energy-conserving semi-discretizations of linear wave equations on nonuniform grids. Specifically we study explicit and implicit skew-adjoint finite difference methods, based on the assumption of an underlying smooth mapping from a uniform grid, applied to the first and second order wave equations. Our interest is in internal reflection of energy at abrupt variations in grid spacing. We show that all node-centered finite difference schemes suffer from reflections. Cell-centered finite difference schemes for the first order wave equation do not have reflections if the numerical dispersion relation is monotone. Runge-Kutta-based spatial semi-discretizations are also considered and these never give reflections. Furthermore, for higher order wave equations, even finite difference schemes with compact stencils and monotone dispersion relations may give reflections due to coupling of physically significant dispersion branches. Again RK schemes avoid this. Finally, we note that all schemes which avoid internal reflections are implicit

Frame matroids and lifted-graphic matroids are two interesting generalizations of graphic matroids. Here we introduce a new generalization, quasi-graphic matroids, that unifies these two existing classes. Unlike frame matroids and lifted-graphic matroids, it is easy to certify that a matroid is quasi-graphic. The main result of the paper is that every 3-connected representable quasi-graphic matroid is either a lifted-graphic matroid or a rame matroid.

Fortran 90 programs for the computation of real parabolic cylinder functions are presented. The code computes the functions U(a, x), V (a, x) and their derivatives for real a and $x(xgeq 0)$. The code also computes scaled functions. The range of computation for scaled PCFs is practically unrestricted. The aimed relative accuracy for scaled functions is better than 5 10^{-14}. Exceptions to this accuracy are the evaluation of the functions near their zeros and the error caused by the evaluation of trigonometric functions of large arguments when |a| >> x. The routines always give values for which the Wronskian relation for scaled functions is verified with a relative accuracy better than $5 10^{?14}$. The accuracy of the unscaled functions is also better than $5 10 {?14}$ for moderate values of x and a (except close to the zeros), while for large x and a the error is dominated by exponential and trigonometric function evaluations. For IEEE standard double precision arithmetic, the accuracy is better than $5 10^{?13}$ in the computable range of unscaled PCFs (except close to the zeros).

Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy. Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhi-nitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally-enabled, integrated, person-centred care. Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.

Let $p$ be a prime congruent to 1 modulo~4 and let $t, u$ be rational integers such that $(t+usqrt{p,)/2$ is the fundamental unit of the real quadratic field ${mathbb Q(sqrt{p,)$. The Ankeny-Artin-Chowla Conjecture (AACC) asserts that $p$ will not divide $u$. This is equivalent to the assertion that $p$ will not divide $B_{(p-1)/2$, where $B_{n$ denotes the $n^{th$ Bernoulli number. Although first published in 1952, this conjecture still remains unproved today. Indeed, it appears to be most difficult to prove. Even testing the conjecture can be quite challenging because of the size of the numbers $t, u$; for example, when $p = 40,094,470,441$, then both $t$ and $u$ exceed $10^{330000$. In 1988 the AAC conjecture was verified by computer for all $p < 10^{9$. In this paper we describe a new technique for testing the AAC conjecture and we provide some results of a computer run of the method for all primes $p$ up to $10^{11$.

The paper presents the problem of decentralized control with communication between controllers. It differs from the regularly considered decentralized control problem in that the controllers can communicate information. Major questions are then: What? When? and To Whom? to communicate information. The problem instances of decentralized control with communication between controllers for discrete-event systems and for finite-dimensional linear systems are described in detail.

Coalgebra and coinduction provide new results and insights for the supervisory control of discrete-event systems (DES) with partial observations. The paper is based on the formalism developed for supervisory control of DES in the full observation case, i.e. the notion of bisimulation, its generalizations (partial bisimulation and control relation), and the finality of the automaton of partial languages. The concept of nondeterministic weak transitions introduced in this paper yields a definition of deterministic weak transitions. These are shown to be useful in the study of partially observed DES. They give rise to the relational characterizations of normality and observability. These characterizations lead to new algorithms for supremal normal and supremal normal and controllable sublanguages that are compared to the ones known in the literature. Coinduction is used to define an operation on languages called supervised product, which represents the language of the closed-loop system, where the first language acts as a supervisor and the second as an open-loop system. This technique can be used to define many important languages, e.g. supremal controllable sublanguages, infimal controllable or/and observable superlanguages. A variation of supervised product corresponding to the permissive control policy with full controllability is given. It is shown to be equal to the infimal observable superlanguage. We have obtained as a byproduct coinductive definitions of these important languages. We show that antipermissive control policy cannot be captured by coinduction. However, we present an algorithm based on the antipermissive control policy for the computation of an observable sublanguage that contains the supremal normal sublanguage. Using a similar method monolithic algorithms for computation of supremal normal and supremal normal and controllable sublanguages are developed. Finally, the lattice theoretic continuity of the supervised product (i.e. the distributivity of the supervised product with respect to partial language unions) is studied