Regional variations in standards – problem or opportunity?

A preliminary analysis and evaluation is made of the differences between the various organic standards and of the different implementation rules of the EU Regulation 2092/91 in Europe. This is part of an EU-funded project on the revision of this regulation. These preliminary results show that many differences have specific justifications, which are strongly influenced by specific national or regional circumstances or policy environment. The potential for more regional variation is discusse

Knospe wird noch sozialer

Im Gegensatz zu vielen anderen Bio-Labels ist die Aussage der Schweizer Knospe klar und deutlich. Sie steht für ökologisch und umweltgerecht hergestellte Produkte. Mit den neuen Sozialstandards steht die Knospe in Zukunft auch für «menschengerecht» hergestellte Lebensmittel

Analysis of EEC Regulation 2092/91 in relation to other national and international organic standards

This Deliverable 3.2 report presents an analysis of differences between EEC Regulation 2092/91 and other organic standards and their implementation, using a specially developed database (www.organicrules.org). It further reports on database development. The work was carried out as part of the “EEC 2092/91 (Organic) Revision” STREP project (No. SSPE-CT- 2004-502397) within the EU 6th Framework Programme. The main objective was to identify differences in organic standards in relation to Regulation (EEC) 2092/91 and to analyse selected national governmental and private organic standards with the aim of identifying specific areas in the (EEC) 2092/91 where revision in terms of harmonisation, regionalisation or simplification may be possible

3D Monte Carlo bone marrow dosimetry for Lu-177-PSMA therapy with guidance of non-invasive 3D localization of active bone marrow via Tc-99m-anti-granulocyte antibody SPECT/CT

Background: The bone marrow (BM) is a main risk organ during Lu-177-PSMA ligand therapy of metastasized castration-resistant prostate cancer (mCRPC) patients. So far, BM dosimetry relies on S values, which are pre-computed for reference anatomies, simplified activity distributions, and a physiological BM distribution. However, mCRPC patients may show a considerable bone lesion load, which leads to a heterogeneous and patient-specific activity accumulation close to BM-bearing sites. Furthermore, the patient-specific BM distribution might be significantly altered in the presence of bone lesions. The aim was to perform BM absorbed dose calculations through Monte Carlo (MC) simulations and to investigate the potential value of image-based BM localization. This study is based on 11 Lu-177-PSMA-617 therapy cycles of 10 patients (10 first cycles), who obtained a pre-therapeutic Ga-68-PSMA-11 PET/CT; quantitative Lu-177 SPECT acquisitions of the abdomen 24 (+CT), 48, and 72 h p.i.; and a Lu-177 whole-body planar acquisition at 24 h post-therapy. Patient-specific 3D volumes of interest were segmented from the Ga-68-PSMA-11 PET/CT, filled with activity information from the Lu-177 data, and imported into the FLUKA MC code together with the patient CT. MC simulations of the BM absorbed dose were performed assuming a physiological BM distribution according to the ICRP 110 reference male (MC1) or a displacement of active BM from the direct location of bone lesions (MC2). Results were compared with those from S values (SMIRD). BM absorbed doses were correlated with the decrease of lymphocytes, total white blood cells, hemoglobin level, and platelets. For two patients, an additional pre-therapeutic Tc-99m-anti-granulocyte antibody SPECT/CT was performed for BM localization. Results: Median BM absorbed doses were 130, 37, and 11 mGy/GBq for MC1, MC2, and SMIRD, respectively. Significant strong correlation with the decrease of platelet counts was found, with highest correlation for MC2 (MC1: r = − 0.63, p = 0.04; MC2: r = − 0.71, p = 0.01; SMIRD: r = − 0.62, p = 0.04). For both investigated patients, BM localization via Tc-99m-anti-granulocyte antibody SPECT/CT indicated a displacement of active BM from the direct location of lesions similar to model MC2 and led to a reduction in the BM absorbed dose of 40 and 41% compared to MC1. Conclusion: Higher BM absorbed doses were observed for MC-based models; however, for MC2, all absorbed doses were still below 2 Gy. MC1 resulted in critical values for some patients, but is suspected to yield strongly exaggerated absorbed doses by neglecting bone marrow displacement. Image-based BM localization might be beneficial, and future studies are recommended to support an improvement for the prediction of hematoxicities

Missense variants in ANO4 cause sporadic encephalopathic or familial epilepsy with evidence for a dominant-negative effect

Anoctamins are a family of Ca$^{2+}$-activated proteins that may act as ion channels and/or phospholipid scramblases with limited understanding of function and disease association. Here, we identified five de novo and two inherited missense variants in ANO4 (alias TMEM16D) as a cause of fever-sensitive developmental and epileptic or epileptic encephalopathy (DEE/EE) and generalized epilepsy with febrile seizures plus (GEFS+) or temporal lobe epilepsy. In silico modeling of the ANO4 structure predicted that all identified variants lead to destabilization of the ANO4 structure. Four variants are localized close to the Ca$^{2+}$ binding sites of ANO4, suggesting impaired protein function. Variant mapping to the protein topology suggests a preliminary genotype-phenotype correlation. Moreover, the observation of a heterozygous ANO4 deletion in a healthy individual suggests a dysfunctional protein as disease mechanism rather than haploinsufficiency. To test this hypothesis, we examined mutant ANO4 functional properties in a heterologous expression system by patchclamp recordings, immunocytochemistry, and surface expression of annexin A5 as a measure of phosphatidylserine scramblase activity. All ANO4 variants showed severe loss of ion channel function and DEE/EE associated variants presented mild loss of surface expression due to impaired plasma membrane trafficking. Increased levels of Ca$^{2+}$-independent annexin A5 at the cell surface suggested an increased apoptosis rate in DEE-mutant expressing cells, but no changes in Ca$^{2+}$-dependent scramblase activity were observed. Co-transfection with ANO4 wild-type suggested a dominant-negative effect. In summary, we expand the genetic base for both encephalopathic sporadic and inherited fever-sensitive epilepsies and link germline variants in ANO4 to a hereditary disease

PTX3 Polymorphisms and Invasive Mold Infections After Solid Organ Transplant

Donor PTX3 polymorphisms were shown to influence the risk of invasive aspergillosis among hematopoietic stem cell transplant recipients. Here, we show that PTX3 polymorphisms are independent risk factors for invasive mold infections among 1101 solid organ transplant recipients, thereby strengthening their role in mold infection pathogenesis and patients' risk stratificatio

The GAPS programme at TNG. LVII. TOI-5076b: A warm sub-Neptune planet orbiting a thin-to-thick-disk transition star in a wide binary system

Aims: We report the confirmation of a new transiting exoplanet orbiting the star TOI-5076. Methods: We present our vetting procedure and follow-up observations which led to the confirmation of the exoplanet TOI-5076b. In particular, we employed high-precision TESS photometry, high-angular-resolution imaging from several telescopes, and high-precision radial velocities from HARPS-N. Results: From the HARPS-N spectroscopy, we determined the spectroscopic parameters of the host star: Teff = (5070±143) K, log = (4.6±0.3), [Fe/H] = (+0.20±0.08), and [α/Fe] = 0.05±0.06. The transiting planet is a warm sub-Neptune with a mass mp = (16±2) M⊙, a radius rp =(3.2±0.l) R⊙ yielding a density ρp = (2.8±0.5) g cm−3. It revolves around its star approximately every 23.445 days. Conclusions: The host star is a metal-rich, K2V dwarf, located at about 82 pc from the Sun with a radius of R⋆ = (0.78±0.01) R⊙ and a mass of M⋆ = (0.80±0.07) M⊙. It forms a common proper motion pair with an M-dwarf companion star located at a projected separation of 2178 au. The chemical analysis of the host-star and the Galactic-space velocities indicate that TOI-5076 belongs to the old population of thin-to-thick-disk transition stars. The density of TOI-5076b suggests the presence of a large fraction by volume of volatiles overlying a massive core. We found that a circular orbit solution is marginally favored with respect to an eccentric orbit solution for TOI-5076b. Full Tables 2 and 3 are available at the CDS via anonymous ftp to cdsarc.cds.unistra.fr (ftp://130.79.128.5) or via https://cdsarc.cds.unistra.fr/viz-bin/cat/J/A+A/687/A226</A

Improved upper limb function in non-ambulant children with SMA type 2 and 3 during nusinersen treatment: a prospective 3-years SMArtCARE registry study

Background The development and approval of disease modifying treatments have dramatically changed disease progression in patients with spinal muscular atrophy (SMA). Nusinersen was approved in Europe in 2017 for the treatment of SMA patients irrespective of age and disease severity. Most data on therapeutic efficacy are available for the infantile-onset SMA. For patients with SMA type 2 and type 3, there is still a lack of sufficient evidence and long-term experience for nusinersen treatment. Here, we report data from the SMArtCARE registry of non-ambulant children with SMA type 2 and typen 3 under nusinersen treatment with a follow-up period of up to 38 months. Methods SMArtCARE is a disease-specific registry with data on patients with SMA irrespective of age, treatment regime or disease severity. Data are collected during routine patient visits as real-world outcome data. This analysis included all non-ambulant patients with SMA type 2 or 3 below 18 years of age before initiation of treatment. Primary outcomes were changes in motor function evaluated with the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM). Results Data from 256 non-ambulant, pediatric patients with SMA were included in the data analysis. Improvements in motor function were more prominent in upper limb: 32.4% of patients experienced clinically meaningful improvements in RULM and 24.6% in HFMSE. 8.6% of patients gained a new motor milestone, whereas no motor milestones were lost. Only 4.3% of patients showed a clinically meaningful worsening in HFMSE and 1.2% in RULM score. Conclusion Our results demonstrate clinically meaningful improvements or stabilization of disease progression in non-ambulant, pediatric patients with SMA under nusinersen treatment. Changes were most evident in upper limb function and were observed continuously over the follow-up period. Our data confirm clinical trial data, while providing longer follow-up, an increased number of treated patients, and a wider range of age and disease severity