An audio FIR-DAC in a BCD process for high power Class-D amplifiers

A 322 coefficient semi-digital FIR-DAC using a 1-bit PWM input signal was designed and implemented in a high voltage, audio power bipolar CMOS DMOS (BCD) process. This facilitates digital input signals for an analog class-D amplifier in BCD. The FIR-DAC performance depends on the ISI-resistant nature of this PWM-signal. An impulse response with only positive coefficients was chosen, because of its resistance to deadzone and mismatch. With a DAC current of 0.5 mA, the dynamic range is 111 dB (A-weighted), with SINAD = 103 dB (A-weighted). The current consumption is 1mA for the analog part and 4.8 mA for the digital part. The power consumption is 29 mW at V/sub dd/ = 5 V and the chip area is 2 mm/sup 2/ including the reference diode that can be shared by more channels

The evolution of age-dependent plasticity

When organisms encounter environments that are heterogeneous in time, phenotypic plasticity is often favored by selection. The degree of such plasticity can vary during an organism's lifetime, but the factors promoting differential plastic responses at different ages or life stages remain poorly understood. Here we develop and analyze an evolutionary model to investigate how environmental information is optimally collected and translated into phenotypic adjustments at different ages. We demonstrate that plasticity must often be expected to vary with age in a nonmonotonic fashion. Early in life, it is generally optimal to delay phenotypic adjustments until sufficient information has been collected about the state of the environment to warrant a costly phenotypic adjustment. Toward the end of life, phenotypic adjustments are disfavored as well because their beneficial effects can no longer be fully reaped before death. Our analysis clarifies how patterns of age-dependent plasticity are shaped by the interplay of environmental uncertainty, the accuracy of perceived information, and the costs of phenotypic adjustments with life-history determinants such as the relative strengths of fecundity and viability selection experienced by the organism over its lifetime. We conclude by comparing our results with expectations for alternative mechanisms, including developmental constraints, that promote age-dependent plasticity

International Guillain-Barré Syndrome Outcome Study (IGOS): protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome in Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multi-centre cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within two weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1000 patients with a follow-up of 1-3 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1400 participants from 143 active centres in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modelling, treatment effects and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS. ClinicalTrials.gov Identifier: NCT01582763

Optimizing adalimumab treatment in psoriasis with concomitant methotrexate (OPTIMAP): study protocol for a pragmatic, single-blinded, investigator-initiated randomized controlled trial

markdownabstract__Background:__ The introduction of anti-tumor necrosis factor medications has revolutionized the treatment of psoriasis with achievement of treatment goals (Psoriasis Area and Severity Index score 75, remission) that are not usually met with conventional systemics. Nevertheless, some patients continue to experience persistent disease activity or treatment failure over time. Strategies to optimize treatment outcomes include the use of concomitant methotrexate, which has demonstrated beneficial effects on pharmacokinetics and treatment efficacy in psoriasis and other inflammatory diseases. __Methods:__ This is an investigator-initiated, multicenter randomized controlled trial (RCT) designed to compare the combination treatment of adalimumab and methotrexate with adalimumab monotherapy in patients with psoriasis. The primary outcome is adalimumab drug survival at week 49. Other outcomes include improvement in disease severity and quality of life, tolerability, and safety. Moreover, anti-adalimumab antibodies and adalimumab serum concentrations will be measured and correlations between genotypes and clinical outcomes will be assessed. Patient recruitment started in March 2014. Up to now, 36 patients have been randomized. Many more patients have been (pre)screened. A total of 93 patients is desired to meet an adequate sample size. In our experience, the main limitation for recruitment is prior adalimumab therapy and intolerability or toxicity for methotrexate in the past. __Discussion:__ OPTIMAP is the first RCT to examine combination therapy with adalimumab and methotrexate in a psoriasis population. With data derived from this study we expect to provide valuable clinical data on long-term treatment outcomes. These data will be supported by assessment of the impact of concomitant methotrexate on adalimumab pharmacokinetics. Furthermore, the influence of several single nucleotide polymorphisms on adalimumab response will be analyzed in order to support the development of a more personalized approach for this targeted therapy. Trial registration:NTR4499. Registered on 7 April 2014

До питання підготовки музейної експозиції з історії культури первісного суспільства

In Europe, water management is moving from flood defense to a risk management approach, which takes both the probability and the potential consequences of flooding into account. In this report, we will look at Directives and (non-)EU- initiatives in place to deal with flood risk in Europe indirectly and directly. Emphasis will lie on the two Directives most specifically aimed at floods: the Water Framework Directive (WFD) and the Floods Directive (FD) – how are they related and how they have been or are implemented in the Member States (MSs)? In February 1995, the Netherlands and France took the initiative for a discussion on streamlining the water legislation of the European Union (EU) which resulted in the creation of the WFD in 2000. The WFD provided a new system for the protection and improvement of Europe’s water environment – its rivers, lakes, estuaries, coastal waters and groundwaters. Its main innovation is the requirement that water be managed in an integrated way, with river basin management as leading managing unit. Since flood protection is not explicitly addressed in the WFD, the need to clarify the role of the WFD in flood protection was put on the European agenda as early as 2003, and in 2007, the FD became a fact. The FD is to be implemented in coordination with the WFD, notably by coordinating Flood Risk Management Plans (FRMPs) and River Basin Management Plans (RBMPs). Both the WFD and the FD reflect a shift in EU-governance. Instead of the more traditional top-down legalistic approach they emphasise the importance of more bottom up initiatives from the actors who have to implement the Directives. Combined with the expanded freedom and flexibility for national and local governments, with this new approach, the FD is the first Water Directive in EU law that does not offer an equal minimum level of protection for EU citizens. While both Directives are meant to harmonise European legislation, much flexibility on objectives and measures in the FD is left to the MSs, justified by the nature of flooding and the subsidiarity principle. This creates multi-actor, multi-level and multi-sector challenges addressed in report D1.1.2 (Hegger et al. 2013). For instance, the FD sets out general obligations for transboundary cooperation, but at the national level, the scope and distributions of duties, rights and powers of the various organizations involved should be set out in law. Other challenges identified in the literature are concrete issues related to mandatory flood risks assessments, flood risk maps, and Flood Risk Management plans, but also the involvement of the public and stakeholders, the science-policy interface, uncertainties related to climate change predictions and effects, the coordination with the WFD, the lack of safety standards, the lack of possibilities for EU citizens to rely on substantive provisions before the administrative courts and finally, transboundary aspects such as issues of scale, mismatches between national policies, the assessment of transboundary effects and division of costs related to this. In sum, this report has clarified the development, content and implementation of the current European flood risk governance policies, possible synergies between the two most important Directives linked to floods, and identified topics and questions for more in-depth questions relevant for the next work packages, pertaining to, in no particular order, a) the level of implementation and level of ambition as well as the competent authorities in the case study countries; b) the transboundary nature of floods; c) synergies and conflicts between FD and WFD and other issues not mentioned in these Directives; d) the degree of harmonization, for instance when it comes to flood safety standards and e) the subsidiarity principle – is this conform the requirements set out in the FD? Because while current European flood regulation specified in the WFD and FD provides several potential opportunities for improving flood risk governance, it is not self-evident that all of these opportunities will materialise in all MSs

Особливості розв’язку задач параметричної ідентифікації динамічних систем в умовах інтервальної невизначеності

Розглянуто задачу параметричної ідентифікації лінійних динамічних систем методами аналізу інтервальних даних. Показано, що у випадку врахування початкових інтервальних наближень дискретних значень прогнозованої характеристики дана задача є задачею розв’язування інтервальної системи нелінійних алгебричних рівнянь. Досліджено особливості формування та властивості розв’язку таких систем.Рассмотрена задача параметрической идентификации линейных динамических систем методами анализа интервальных данных. Показано, что в случае учета начальных интервальных приближений дискретных значений прогнозированной характеристики, данная задача есть задачей решения интервальной системы нелинейных алгебраических уравнений; исследованы особенности формирования и свойства решения таких систем.The problem of parameter identification of linear dynamic systems by methods of analysis of interval data is considered. It is shown that in the case of taking into account the initial interval approximations of discrete values of the predicted characteristics, this problem is the problem of solving interval system of nonlinear algebraic equations

Optimal measurement of visual motion across spatial and temporal scales

Sensory systems use limited resources to mediate the perception of a great variety of objects and events. Here a normative framework is presented for exploring how the problem of efficient allocation of resources can be solved in visual perception. Starting with a basic property of every measurement, captured by Gabor's uncertainty relation about the location and frequency content of signals, prescriptions are developed for optimal allocation of sensors for reliable perception of visual motion. This study reveals that a large-scale characteristic of human vision (the spatiotemporal contrast sensitivity function) is similar to the optimal prescription, and it suggests that some previously puzzling phenomena of visual sensitivity, adaptation, and perceptual organization have simple principled explanations.Comment: 28 pages, 10 figures, 2 appendices; in press in Favorskaya MN and Jain LC (Eds), Computer Vision in Advanced Control Systems using Conventional and Intelligent Paradigms, Intelligent Systems Reference Library, Springer-Verlag, Berli

Two-Body Random Ensembles: From Nuclear Spectra to Random Polynomials

The two-body random ensemble (TBRE) for a many-body bosonic theory is mapped to a problem of random polynomials on the unit interval. In this way one can understand the predominance of 0+ ground states, and analytic expressions can be derived for distributions of lowest eigenvalues, energy gaps, density of states and so forth. Recently studied nuclear spectroscopic properties are addressed.Comment: 8 pages, 4 figures. To appear in Physical Review Letter

Science and Morality: Mind the Gap, Use Happiness as a Safe Bridge! Book review of ‘‘Exploring Happiness: from Aristotle to Brain Science’’ by Sissela Bok, Yale University Press, New Haven and London, 2010

Abstract In 2002 Sissela Bok re-published her book ‘‘Common Values’’, first published in 1995, about her search for a minimal set of values to be respected all over the world. In her view such a set of values is needed to facilitate international communication and cooperation. Values already recognized in every society can be included as a starting point. In her book ‘‘Exploring happiness’’, published in 2010, she explains why she finds happiness unfit to be included. She observes that there are discordant claims about what happiness is. Any particular vision can lead to practical choices that either adhere or violate the values she prefers. In my view subjective happiness should be included, because there are no discordant claims about the meaning of subjective happiness, and subjective happiness is simultaneously attractive as a moral value and as an object of scientific research. Subjective happiness can function as a bridge between science and morality. The only discordant claims are about ‘objective’ happiness, as a wider interpretation of well-being in the context of some specific morality or ideology