Context. Future weak lensing surveys, such as the Euclid mission, will attempt to measure the shapes of billions of galaxies in order to derive cosmological information. These surveys will attain ...very low levels of statistical error, and systematic errors must be extremely well controlled. In particular, the point spread function (PSF) must be estimated using stars in the field, and recovered with high accuracy. Aims. The aims of this paper are twofold. Firstly, we took steps toward a nonparametric method to address the issue of recovering the PSF field, namely that of finding the correct PSF at the position of any galaxy in the field, applicable to Euclid . Our approach relies solely on the data, as opposed to parametric methods that make use of our knowledge of the instrument. Secondly, we studied the impact of imperfect PSF models on the shape measurement of galaxies themselves, and whether common assumptions about this impact hold true in an Euclid scenario. Methods. We extended the recently proposed resolved components analysis approach, which performs super-resolution on a field of under-sampled observations of a spatially varying, image-valued function. We added a spatial interpolation component to the method, making it a true 2-dimensional PSF model. We compared our approach to PSFEx , then quantified the impact of PSF recovery errors on galaxy shape measurements through image simulations. Results. Our approach yields an improvement over PSFEx in terms of the PSF model and on observed galaxy shape errors, though it is at present far from reaching the required Euclid accuracy. We also find that the usual formalism used for the propagation of PSF model errors to weak lensing quantities no longer holds in the case of an Euclid -like PSF. In particular, different shape measurement approaches can react differently to the same PSF modeling errors.
To evaluate the results of ventral intermediate (Vim) thalamic deep brain stimulation (DBS) in patients with tremor predominant Parkinson's disease (PD) at 6 years post surgery.
This was a prolonged ...follow-up study of 38 patients from eight centres who participated in a multicentre study, the 1 year results of which have been published previously. Total scores as well as scores for individual items of the motor part and the disability part of the Unified Parkinson's Disease Rating Scale were used for evaluation.
Tremor was still effectively controlled by DBS and appendicular rigidity and akinesia remained stable compared with baseline. Axial scores (speech, gait and postural instability), however, worsened, and in parallel the initial improvement in activities of daily living scores at the 1 year follow-up had disappeared at 6 years, despite sustained improvement of tremor. Remarkably, neither daily doses of dopaminergic medication nor fluctuations and dyskinesias had changed at 6 years compared with baseline in this particular patient group.
This study confirms that patients with tremor dominant PD who do not present with fluctuations and dyskinesias may have a relatively benign progression of the disease. Vim DBS, although having no effect on akinesia and rigidity, is a relatively lenient surgical procedure and may still have a place for long term symptomatic control of PD tremor in selected patients.
INTRODUCTION: In Europe the population is ageing rapidly. Older people are taking many medicinal products daily and these may not necessarily be suitable for them. Publications show that older ...patients are underrepresented in clinical trials, especially those over 75 years, with multiple co-morbidities, concomitant treatments and/or frailty. This document provides a summary of recommendations on ethical aspects of clinical trials with older people, who may in some cases be considered a vulnerable patient population. The EFGCP’s Geriatric Medicine Working Party (GMWP) has developed this guidance to promote such research and to support health care professionals in their efforts. ETHICAL, SCOPE AND CONTEXT: The definition of a geriatric patient is reviewed. Frail and vulnerable patients, who are a minority of geriatric patients, should be included whenever it is relevant. The legal context is described. THE PROCESS OF INFORMED CONSENT: All adults should be presumed capable of consent, unless proven otherwise; informed consent must be sought for all older people who are able to consent. A simple, short and easy-to-understand information sheet and consent form will contribute to improving the readability and understanding of the older participant. A participant guide and the use of a simple tool to ensure decision making capacity, are recommended. Whenever older people are unable to consent, their assent should be sought systematically using adequate information, in addition to seeking the consent of their legal or authorised representative as appropriate. ETHICS COMMITTEES: Research ethics committees need internal and/or external geriatric expertise to balance the benefits and risks of research in older people and to appreciate and recognise their autonomy. DESIGN AND ANALYSES: Design and Analyses should be adapted to the objectives with appropriate outcomes and are not different from other clinical trials. CONCLUSIONS: The absence of proper recruitment or insufficient presence of older patients in clinical development plans for new medicinal products is detrimental; there is a need to improve evidence-based knowledge, understanding and management of their conditions and treatment. The aim of this guidance is to facilitate clinical research for and with the older patient population. The long version of the guidance will be available on the EFGCP’s website: www.efgcp.be/ .
Background and purpose: Pregabalin has demonstrated efficacy in controlled trials as adjunctive treatment in patients with refractory seizures.
Methods: This open‐label, 21‐week study in adults ...with at least two partial seizures in the last 2 months, who were inadequately controlled with one to three antiepileptic drugs, evaluated pregabalin 150–600 mg/day (dosed twice daily). The study comprised a prospective or retrospective 8‐week baseline phase, and 9‐week dose optimization and 12‐week maintenance periods. The primary assessment was the mean percentage change in 28‐day seizure frequency between baseline and end‐point (last 12 weeks of treatment, last observation carried forward, modified intention‐to‐treat population).
Results: Four hundred and seventy‐six patients from Europe were included in this study (51% men; mean age/epilepsy duration 40.1/24.1 years). The median baseline seizure frequency was 5.5/28 days. Amongst the patient population, 78% completed the 21‐week treatment period; 7% discontinued for lack of efficacy and 12% because of adverse events (AEs). The mean last pregabalin dose was 359 mg/day. The mean (95% CI) reduction in seizure frequency was 36% (31%; 41%). The median reduction was 33%, and 39% of patients had a ≥50% reduction in seizure frequency. There were 19% and 8% of patients free of seizures during their last 4 and 12 weeks of treatment, respectively. The three most common AEs were dizziness (17%), somnolence (13%) and weight increase (13%).
Conclusions: This open‐label study of pregabalin demonstrated efficacy that was consistent with that observed in previous controlled epilepsy trials. Pregabalin was well tolerated. The AE profile was also consistent with that reported in previous trials.
Gaia Data Release 1 Crowley, C; Kohley, R; Hambly, N C ...
Astronomy and astrophysics (Berlin),
11/2016, Letnik:
595
Journal Article
Recenzirano
Odprti dostop
The European Space Agency's Gaia satellite was launched into orbit around L2 in December 2013 with a payload containing 106 large-format scientific CCDs. The primary goal of the mission is to ...repeatedly obtain high-precision astrometric and photometric measurements of one thousand million stars over the course of five years. The scientific value of the down-linked data, and the operation of the onboard autonomous detection chain, relies on the high performance of the detectors. As Gaia slowly rotates and scans the sky, the CCDs are continuously operated in a mode where the line clock rate and the satellite rotation spin-rate are in synchronisation. Nominal mission operations began in July 2014 and the first data release is being prepared for release at the end of Summer 2016. In this paper we present an overview of the focal plane, the detector system, and strategies for on-orbit performance monitoring of the system. This is followed by a presentation of the performance results based on analysis of data acquired during a two-year window beginning at payload switch-on. Results for parameters such as readout noise and electronic offset behaviour are presented and we pay particular attention to the effects of the L2 radiation environment on the devices. The radiation-induced degradation in the charge transfer efficiency (CTE) in the (parallel) scan direction is clearly diagnosed; however, an extrapolation shows that charge transfer inefficiency (CTI) effects at end of mission will be approximately an order of magnitude less than predicted pre-flight. It is shown that the CTI in the serial register (horizontal direction) is still dominated by the traps inherent to the manufacturing process and that the radiation-induced degradation so far is only a few per cent. We also present results on the tracking of ionising radiation damage and hot pixel evolution. Finally, we summarise some of the detector effects discovered on-orbit which are still being investigated.
Objective:Multifocal motor neuropathy with persistent conduction blocks is classically described as a chronic neuropathy with progressive onset, and acute forms have not previously been ...characterised. We report four cases of severe motor impairment with acute and generalised onset and with persistent motor conduction blocks. Patients and results:An acute tetraparesis with diffuse areflexia but little or no sensory disturbance was the clinical picture. Serial electrophysiological tests showed persistent multifocal motor conduction blocks with absent F waves in most tested motor nerves. No or minor abnormalities of the sensory nerve action potentials were observed. Cerebrospinal fluid contained normal or mildly increased protein levels (<1 g/l) without cells. Campylobacter jejuni serology was negative in three patients and consistent with past infection in one patient. Anti-ganglioside antibodies were positive in three patients. A five day course of intravenous immunoglobulins produced nearly complete symptom resolution in three patients and was ineffective in one patient. Conclusion:Because of the persistence of multifocal motor conduction blocks for several weeks or months as the isolated electrophysiological feature, these cases could not be consistent with Guillain–Barré syndrome or chronic inflammatory demyelinating polyneuropathy. They suggest an original variant of multifocal motor neuropathy with an acute and generalised initial presentation and persistent motor conduction blocks affecting all four limbs.
An accurate covariance matrix is essential for obtaining reliable cosmological results when using a Gaussian likelihood. In this paper we study the covariance of pseudo-
C
ℓ
estimates of tomographic ...cosmic shear power spectra. Using two existing publicly available codes in combination, we calculate the full covariance matrix, including mode-coupling contributions arising from both partial sky coverage and non-linear structure growth. For three different sky masks, we compare the theoretical covariance matrix to that estimated from publicly available
N
-body weak lensing simulations, finding good agreement. We find that as a more extreme sky cut is applied, a corresponding increase in both Gaussian off-diagonal covariance and non-Gaussian super-sample covariance is observed in both theory and simulations, in accordance with expectations. Studying the different contributions to the covariance in detail, we find that the Gaussian covariance dominates along the main diagonal and the closest off-diagonals, but farther away from the main diagonal the super-sample covariance is dominant. Forming mock constraints in parameters that describe matter clustering and dark energy, we find that neglecting non-Gaussian contributions to the covariance can lead to underestimating the true size of confidence regions by up to 70 per cent. The dominant non-Gaussian covariance component is the super-sample covariance, but neglecting the smaller connected non-Gaussian covariance can still lead to the underestimation of uncertainties by 10–20 per cent. A real cosmological analysis will require marginalisation over many nuisance parameters, which will decrease the relative importance of all cosmological contributions to the covariance, so these values should be taken as upper limits on the importance of each component.
The cosmological surveys that are planned for the current decade will provide us with unparalleled observations of the distribution of galaxies on cosmic scales, by means of which we can probe the ...underlying large-scale structure (LSS) of the Universe. This will allow us to test the concordance cosmological model and its extensions. However, precision pushes us to high levels of accuracy in the theoretical modelling of the LSS observables so that no biases are introduced into the estimation of the cosmological parameters. In particular, effects such as redshift-space distortions (RSD) can become relevant in the computation of harmonic-space power spectra even for the clustering of the photometrically selected galaxies, as has previously been shown in literature. In this work, we investigate the contribution of linear RSD, as formulated in the Limber approximation by a previous work, in forecast cosmological analyses with the photometric galaxy sample of the survey. We aim to assess their impact and to quantify the bias on the measurement of cosmological parameters that would be caused if this effect were neglected. We performed this task by producing mock power spectra for photometric galaxy clustering and weak lensing as is expected to be obtained from the survey. We then used a Markov chain Monte Carlo approach to obtain the posterior distributions of cosmological parameters from these simulated observations. When the linear RSD is neglected, significant biases are caused when galaxy correlations are used alone and when they are combined with cosmic shear in the so-called 3times 2pt approach. These biases can be equivalent to as much as $5\ when an underlying Lambda CDM cosmology is assumed When the cosmological model is extended to include the equation-of-state parameters of dark energy, the extension parameters can be shifted by more than $1\ sigma$.
Objective: To assess the effects of focal motor cortex stimulation on motor performance and cortical excitability in patients with Parkinson's disease (PD).
Methods: Repetitive transcranial magnetic ...stimulation (rTMS) was performed on the left motor cortical area corresponding to the right hand in 12 ‘off-drug’ patients with PD. The effects of subthreshold rTMS applied at 0.5 Hz (600 pulses) or at 10 Hz (2000 pulses) using a ‘real’ or a ‘sham’ coil were compared to those obtained by a single dose of l-dopa. The assessment included a clinical evaluation by the Unified Parkinson's Disease Rating Scale and timed motor tasks, and a neurophysiological evaluation of cortical excitability by single- and paired-pulse TMS techniques.
Results: ‘Real’ rTMS at 10 or 0.5 Hz, but not ‘sham’ stimulation, improved motor performance. High-frequency rTMS decreased rigidity and bradykinesia in the upper limb contralateral to the stimulation, while low-frequency rTMS reduced upper limb rigidity bilaterally and improved walking. Concomitantly, 10 Hz rTMS increased intracortical facilitation, while 0.5 Hz rTMS restored intracortical inhibition.
Conclusions: Low- and high-frequency rTMS of the primary motor cortex lead to significant but differential changes in patients with PD both on clinical and electrophysiological grounds. The effects on cortical excitability were opposite to previous observations made in healthy subjects, suggesting a reversed balance of cortical excitability in patients with PD compared to normals. However, the underlying mechanisms of these changes remain to determine, as well as the relationship with clinical presentation and response to l-dopa therapy.
Significance: The present study gives some clues to appraise the role of the primary motor cortex in PD. Clinical improvement induced by rTMS was too short-lasting to consider therapeutic application, but these results support the perspective of the primary motor cortex as a possible target for neuromodulation in PD.
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