Fiscaal beleid en arbeidsparticipatie

De Nederlandse overheid streeft naar een vergroting van de arbeidsdeelname en een verhoging van het kennisniveau van de beroepsbevolking. Dit moet bijdragen aan de betaalbaarheid van het stelsel van collectieve voorzieningen zodat solidariteit in de toekomst gewaarborgd kan blijven. Het belastingstelsel speelt hierbij een belangrijke rol. Immers, herverdelende belastingheffing vermindert de prikkels voor arbeidsaanbod en leren. Dit is echter een onvermijdelijk gevolg van het maatschappelijk streven naar het beperken van ongelijkheid. Toch zijn sommige vormen van herverdeling meer verstorend dan andere. Door slimme gerichte hervormingen kan het fiscale stelsel de negatieve effecten op de arbeidsdeelname verkleinen, zonder dat de koopkracht van de minstbedeelden daalt. Deze bijdrage onderzoekt dergelijke opties. Daarbij maken we gebruik van de inzichten uit de economische theorie alsook van simulaties met het MIMIC model van het CPB. De bijdrage richt zich in het bijzonder op drie doelgroepen: laaggeschoolden, vrouwen en ouderen

Applications of patching to quadratic forms and central simple algebras

This paper provides applications of patching to quadratic forms and central simple algebras over function fields of curves over henselian valued fields. In particular, we use a patching approach to reprove and generalize a recent result of Parimala and Suresh on the u-invariant of p-adic function fields, for p odd. The strategy relies on a local-global principle for homogeneous spaces for rational algebraic groups, combined with local computations.Comment: 48 pages; connectivity now required in the definition of rational group; beginning of Section 4 reorganized; other minor change

Objective Acoustic-Phonetic Speech Analysis in Patients Treated for Oral or Oropharyngeal Cancer

Objective: Speech impairment often occurs in patients after treatment for head and neck cancer. New treatment modalities such as surgical reconstruction or (chemo) radiation techniques aim at sparing anatomical structures that are correlated with speech and swallowing. In randomized trials investigating efficacy of various treatment modalities or speech rehabilitation, objective speech analysis techniques may add to improve speech outcome assessment. The goal of the present study is to investigate the role of objective acoustic-phonetic analyses in a multidimensional speech assessment protocol. Patients and Methods: Speech recordings of 51 patients (6 months after reconstructive surgery and postoperative radiotherapy for oral or oropharyngeal cancer) and of 18 control speakers were subjectively evaluated regarding intelligibility, nasal resonance, articulation, and patient-reported speech outcome (speech subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck 35 module). Acoustic-phonetic analyses were performed to calculate formant values of the vowels /a, i, u/, vowel space, air pressure release of /k/ and spectral slope of /x/. Results: Intelligibility, articulation, and nasal resonance were best predicted by vowel space and /k/. Within patients, /k/ and /x/ differentiated tumor site and stage. Various objective speech parameters were related to speech problems as reported by patients. Conclusion: Objective acoustic-phonetic analysis of speech of patients is feasible and contributes to further development of a speech assessment protocol. Copyright (C) 2009 S. Karger AG, Base

ESAO: A holistic Ecosystem-Driven Analysis Model

The growing importance of software ecosystems and open innovation requires that companies become more intentional about aligning their internal strategy, architecture and organizing efforts with the ecosystem that the company is part of. Few models exist that facilitate analysis and improvement of this alignment. In this paper, we present the ESAO model and describe its six main components. Organizations and researchers can use the model to analyze the alignment between the different parts of their business, technologies and ways of working, internally and in the ecosystem. The model is illustrated and validated through the use of three case studies

Stroke recovery in rats after 24h-delayed intramuscular neurotrophin-3 infusion

Objective Neurotrophin‐3 (NT3) plays a key role in the development and function of locomotor circuits including descending serotonergic and corticospinal tract axons and afferents from muscle and skin. We have previously shown that gene therapy delivery of human NT3 into affected forelimb muscles improves sensorimotor recovery after stroke in adult and elderly rats. Here, to move toward the clinic, we tested the hypothesis that intramuscular infusion of NT3 protein could improve sensorimotor recovery after stroke. Methods Rats received unilateral ischemic stroke in sensorimotor cortex. To simulate a clinically feasible time to treatment, 24 hours later rats were randomized to receive NT3 or vehicle by infusion into affected triceps brachii for 4 weeks using implanted catheters and minipumps. Results Radiolabeled NT3 crossed from the bloodstream into the brain and spinal cord in rodents with or without strokes. NT3 increased the accuracy of forelimb placement during walking on a horizontal ladder and increased use of the affected arm for lateral support during rearing. NT3 also reversed sensory impairment of the affected wrist. Functional magnetic resonance imaging during stimulation of the affected wrist showed spontaneous recovery of peri‐infarct blood oxygenation level–dependent signal that NT3 did not further enhance. Rather, NT3 induced neuroplasticity of the spared corticospinal and serotonergic pathways. Interpretation Our results show that delayed, peripheral infusion of NT3 can improve sensorimotor function after ischemic stroke. Phase I and II clinical trials of NT3 (for constipation and neuropathy) have shown that peripheral high doses are safe and well tolerated, which paves the way for NT3 as a therapy for stroke

Risk stratification by residual enzyme activity after newborn screening for medium-chain acyl-CoA dehyrogenase deficiency: data from a cohort study

<p><b>Abstract</b></p> <p><b>Background</b></p> <p>Since the introduction of medium-chain acyl coenzyme A dehydrogenase (MCAD) deficiency in population newborn bloodspot screening (NBS) programs, subjects have been identified with variant <it>ACADM</it> (gene encoding MCAD enzyme) genotypes that have never been identified in clinically ascertained patients. It could be hypothesised that residual MCAD enzyme activity can contribute in risk stratification of subjects with variant <it>ACADM</it> genotypes.</p> <p><b>Methods</b></p> <p>We performed a retrospective cohort study of all patients identified upon population NBS for MCAD deficiency in the Netherlands between 2007–2010. Clinical, molecular, and enzymatic data were integrated.</p> <p><b>Results</b></p> <p>Eighty-four patients from 76 families were identified. Twenty-two percent of the subjects had a variant <it>ACADM</it> genotype. In patients with classical <it>ACADM</it> genotypes, residual MCAD enzyme activity was significantly lower (median 0%, range 0-8%) when compared to subjects with variant <it>ACADM</it> genotypes (range 0-63%; 4 cases with 0%, remainder 20-63%). Patients with (fatal) neonatal presentations before diagnosis displayed residual MCAD enzyme activities <1%. After diagnosis and initiation of treatment, residual MCAD enzyme activities <10% were associated with an increased risk of hypoglycaemia and carnitine supplementation. The prevalence of MCAD deficiency upon screening was 1/8,750 (95% CI 1/7,210–1/11,130).</p> <p><b>Conclusions</b></p> <p>Determination of residual MCAD enzyme activity improves our understanding of variant <it>ACADM</it> genotypes and may contribute to risk stratification. Subjects with variant <it>ACADM</it> genotypes and residual MCAD enzyme activities <10% should be considered to have the same risks as patients with classical <it>ACADM</it> genotypes. Parental instructions and an emergency regimen will remain principles of the treatment in any type of MCAD deficiency, as the effect of intercurrent illness on residual MCAD enzyme activity remains uncertain. There are, however, arguments in favour of abandoning the general advice to avoid prolonged fasting in subjects with variant <it>ACADM</it> genotypes and >10% residual MCAD enzyme activity.</p

High-Energy Cosmology: gamma rays and neutrinos from beyond the galaxy

Our knowledge of the high-energy universe is undergoing a period of rapid change as new astronomical detectors of high-energy radiation start to operate at their design sensitivities. Now is a boomtime for high-energy astrophysics, with new discoveries from Swift and HESS, results from MAGIC and VERITAS starting to be reported, the upcoming launches of the gamma-ray space telescopes GLAST and AGILE, and anticipated data releases from IceCube and Auger. A formalism for calculating statistical properties of cosmological gamma-ray sources is presented. Application is made to model calculations of the statistical distributions of gamma-ray and neutrino emission from (i) beamed sources, specifically, long-duration GRBs, blazars, and extagalactic microquasars, and (ii) unbeamed sources, including normal galaxies, starburst galaxies and clusters. Expressions for the integrated intensities of faint beamed and unbeamed high-energy radiation sources are also derived. A toy model for the background intensity of radiation from dark-matter annihilation taking place in the early universe is constructed. Estimates for the gamma-ray fluxes of local group galaxies, starburst, and infrared luminous galaxies are briefly reviewed. Because the brightest extragalactic gamma-ray sources are flaring sources, and these are the best targets for sources of PeV -- EeV neutrinos and ultra-high energy cosmic rays, rapidly slewing all-sky telescopes like MAGIC and an all-sky gamma-ray observatory beyond Milagro will be crucial for optimal science return in the multi-messenger age.Comment: 10 pages, 3 figs, accepted for publication in the Barcelona Conference on Multimessenger Astronomy; corrected eq. 27, revised Fig. 3, added 2 ref

The B-Meson Distribution Amplitude in QCD

The B-meson distribution amplitude is calculated using QCD sum rules. In particular we obtain an estimate for the integral relevant to exclusive B-decays \lambda_B = 460 \pm 110 MeV at the scale 1 GeV. A simple QCD-motivated parametrization of the distribution amplitude is suggested.Comment: 17 pages, 8 figures, Latex styl

Ventricular function and biomarkers in relation to repair and pulmonary valve replacement for tetralogy of Fallot

Objective Cardiac surgery may cause temporarily impaired ventricular performance and myocardial injury. We aim to characterise the response to perioperative injury for patients undergoing repair or pulmonary valve replacement (PVR) for tetralogy of Fallot (ToF). Methods We enrolled children undergoing ToF repair or PVR from four tertiary centres in a prospective observational study. Assessment - including blood sampling and speckle tracking echocardiography - occurred before surgery (T1), at the first follow-up (T2) and 1 year after the procedures (T3). Ninety-two serum biomarkers were expressed as principal components to reduce multiple statistical testing. RNA Sequencing was performed on right ventricular (RV) outflow tract samples. Results We included 45 patients with ToF repair aged 4.3 (3.4 - 6.5) months and 16 patients with PVR aged 10.4 (7.8 - 12.7) years. Ventricular function following ToF repair showed a fall-and-rise pattern for left ventricular global longitudinal strain (GLS) (-18±4 to -13±4 to -20±2, p &lt; 0.001 for each comparison) and RV GLS (-19±5 to -14±4 to 20±4, p &lt; 0.002 for each comparison). This pattern was not seen for patients undergoing PVR. Serum biomarkers were expressed as three principal components. These phenotypes are related to: (1) surgery type, (2) uncorrected ToF and (3) early postoperative status. Principal component 3 scores were increased at T2. This increase was higher for ToF repair than PVR. The transcriptomes of RV outflow tract tissue are related to patients' sex, rather than ToF-related phenotypes in a subset of the study population. Conclusions The response to perioperative injury following ToF repair and PVR is characterised by specific functional and immunological responses. However, we did not identify factors relating to (dis)advantageous recovery from perioperative injury. Trial registration number Netherlands Trial Register: NL5129.</p