Effectiveness and Safety of rhIGF-1 Therapy in Children: The European Increlex® Growth Forum Database Experience.

BACKGROUND/AIMS: We report data from the EU Increlex® Growth Forum Database (IGFD) Registry, an ongoing, open-label, observational study monitoring clinical practice use of recombinant human insulin-like growth factor-1 (rhIGF-1) therapy in children. METHODS: Safety and effectiveness data on rhIGF-1 treatment of 195 enrolled children with growth failure were collected from December 2008 to September 2013. RESULTS: Mean ± SD (95% CI) height velocity during first year of rhIGF-1 treatment was 6.9 ± 2.2 cm/year (6.5; 7.2) (n = 144); in prepubertal patients naïve to treatment, this was 7.3 ± 2.0 cm/year (6.8; 7.7) (n = 81). Female sex, younger age at start of rhIGF-1 therapy, and lower baseline height SDS predicted first-year change in height SDS. The most frequent targeted treatment-emergent adverse events (% patients) were hypoglycemia (17.6%, predictors: young age, diagnosis of Laron syndrome, but not rhIGF-1 dose), lipohypertrophy (10.6%), tonsillar hypertrophy (7.4%), injection site reactions (6.4%), and headache (5.9%). Sixty-one serious adverse events (37 related to rhIGF-1 therapy) were reported in 31 patients (16.5%). CONCLUSION: Safety and effectiveness data on use of rhIGF-1 in a 'real-world' setting were similar to those from controlled randomized trials. Severe growth phenotype and early start of rhIGF-1 improved height response and predicted risk of hypoglycemia

Ionization scheme development at the ISOLDE RILIS

The resonance ionization laser ion source (RILIS) of the ISOLDE on-line isotope separation facility is based on the method of laser step-wise resonance ionization of atoms in a hot metal cavity. The atomic selectivity of the RILIS complements the mass selection process of the ISOLDE separator magnets to provide beams of a chosen isotope with greatly reduced isobaric contamination. Using a system of dye lasers pumped by copper vapour lasers, ion beams of 24 elements have been generated at ISOLDE with ionization efficiencies in the range of 0.5-15%. As part of the ongoing RILIS development off-line resonance ionization spectroscopy studies carried out in 2003 and 2004 have determined the optimal three-step ionization schemes for scandium, antimony, dysprosium and yttrium

HOLMES: The electron capture decay of 163Ho to measure the electron neutrino mass with sub-eV sensitivity

The European Research Council has recently funded HOLMES, a new experiment to directly measure the neutrino mass. HOLMES will perform a calorimetric measurement of the energy released in the decay of 163Ho. The calorimetric measurement eliminates systematic uncertainties arising from the use of external beta sources, as in experiments with beta spectrometers. This measurement was proposed in 1982 by A. De Rujula and M. Lusignoli, but only recently the detector technological progress allowed to design a sensitive experiment. HOLMES will deploy a large array of low temperature microcalorimeters with implanted 163Ho nuclei. The resulting mass sensitivity will be as low as 0.4 eV. HOLMES will be an important step forward in the direct neutrino mass measurement with a calorimetric approach as an alternative to spectrometry. It will also establish the potential of this approach to extend the sensitivity down to 0.1 eV. We outline here the project with its technical challenges and perspectives.Comment: 11 pages, 9 figure

Direct neutrino mass measurement by the HOLMES experiment

The assessment of the neutrino absolute mass scale is still a crucial challenge in today particle physics and cosmology. Beta or electron capture spectrum end-point study is currently the only experimental method which can provide a model independent measurement of the absolute scale of neutrino mass. HOLMES is an experiment to directly measure the neutrino mass by performing a calorimetric measurement of the energy released in the electron capture decay of the artificial isotope163Ho. In a calorimetric measurement the energy released in the decay process is entirely contained into the detector, except for the fraction taken away by the neutrino. This approach eliminates both the issues related to the use of an external source and the systematic uncertainties arising from decays on excited final states. HOLMES will deploy a large array of low temperature microcalorimeters implanted with163Ho nuclei. The achievable neutrino mass statistical sensitivity is expected in the eV range, thereby making HOLMES an important step forward in the direct neutrino mass measurement with a calorimetric approach as an alternative to spectrometry. HOLMES will also establish the potential of this approach to achieve a sub-eV sensitivity. HOLMES is designed to collect about 3 7 1013decays with an instrumental energy resolution around 1 eV FWHM and a time resolution around 1 \u3bcs. To achieve this in three years of measuring time, HOLMES is going to deploy 16 sub-arrays of TES microcalorimeters. Each sub-array has 64 pixels ion implanted with163Ho nuclei to give a pixel activity of 300 Bq per pixel. The TES arrays are read out using microwave multiplexed rf-SQUIDs in combination with a Software Designed Radio data acquisition system. The commissioning of the first implanted sub-array is scheduled for 2018 and it will provide first high statistics data about the EC decay of163Ho together with a preliminary limit on the neutrino mass. In this contribution we outline the HOLMES project with its physics reach and technical challenges, along with its status and perspectives. In particular we will present the status of the HOLMES activities concerning the163Ho isotope production by neutron irradiation and purification, the TES pixel design and optimization, the multiplexed array read-out characterization, the cryogenic set-up installation, and the setting up of the mass separation and ion implantation system for the isotope embedding in the TES absorbers

Status of the HOLMES Experiment to Directly Measure the Neutrino Mass

The assessment of neutrino absolute mass scale is still a crucial challenge in today particle physics and cosmology. Beta or electron capture spectrum end-point study is currently the only experimental method which can provide a model-independent measurement of the absolute scale of neutrino mass. HOLMES is an experiment funded by the European Research Council to directly measure the neutrino mass. HOLMES will perform a calorimetric measurement of the energy released in the electron capture decay of the artificial isotope163Ho. In a calorimetric measurement, the energy released in the decay process is entirely contained into the detector, except for the fraction taken away by the neutrino. This approach eliminates both the issues related to the use of an external source and the systematic uncertainties arising from decays on excited final states. The most suitable detectors for this type of measurement are low-temperature thermal detectors, where all the energy released into an absorber is converted into a temperature increase that can be measured by a sensitive thermometer directly coupled with the absorber. This measurement was originally proposed by De Rujula and Lusignoli (Nucl Phys B 219:277, 1983. https://doi.org/10.1016/0550-3213(83)90642-9), but only in the last decade the technological progress in detectors development has allowed to design a sensitive experiment. HOLMES plans to deploy a large array of low-temperature microcalorimeters with implanted163Ho nuclei. In this contribution we outline the HOLMES project with its physics reach and technical challenges, along with its status and perspectives

Serpentine differentiation and polyploid evolution in \kur{Knautia arvensis} agg. (Dipsacaceae).

Evolutionary history of an intricate polyploid complex Knautia arvensis agg. in Central Europe has been studied using combined approach of molecular (AFLP, DNA-sequencing) and cytological (flow cytometry, karyology) techniques. Possible evolutionary scenario has been suggested for the whole complex and for the serpentine population in particular, based on critical assessment of results obtained from the different methods

Choices of Stent and Cerebral Protection in the Ongoing ACST-2 Trial: A Descriptive Study (vol 53, pg 617, 2017)

Erratum for : "Choices of Stent and Cerebral Protection in the Ongoing ACST-2 Trial: A Descriptive Study." - http://hdl.handle.net/2078.1/20193

Second asymptomatic carotid surgery trial (ACST-2) : a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86-1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91-1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable