Le politiche dell'Unione europea sulle armi da fuoco: profili generali

The European Union has developed a foreign policy on arms, to tackle the accumulation of small arms and light weapons in third countries and prevent it. The policy has been outlined by a 2005 Strategy and has been implemented over the years by an array of actions, taken at the international, regional, bilateral or national level. The aim of this paper is to sketch these actions, in order to offer a better understanding of this policy and of its implementation. Keywords: European Union, arms trade, international law, proliferation, small arms and light weapons   L’Unione europea ha sviluppato una politica estera in materia di armi, per contrastare e prevenire l’accumulazione di armi leggere e di piccolo carico nei paesi terzi. Delineata in una Strategia del 2005, è stata attuata nel corso degli anni attraverso una pluralità di azioni. Il presente contributo intende descrivere sinteticamente tali azioni, distinguendole a seconda del piano (internazionale, regionale, bilaterale o nazionale) in cui si svolgono, per metterne in luce la varietà e offrire una valutazione della loro efficacia. Parole chiave: Unione europea, traffico di armi, diritto internazionale, proliferazione, armi leggere e di piccolo calibr

The Hospital Anxiety and Depression Scale: low sensitivity for depression screening in demented and non-demented hospitalized elderly

Background: We currently use the depression subscale (HADD) of the Hospital Anxiety and Depression Scale (HADS) for depression screening in elderly inpatients. Given recent concerns about the performance of the HADD in this age group, we performed a quality-control study retrospectively comparing HADD with the diagnosis of depression by a psychiatrist. We also studied the effect of dementia on the scale's performance. Methods: HADS produces two 7-item subscales assessing depression or anxiety. The HADD was administered by a neuropsychologist. As "gold standard” we considered the psychiatrist's diagnosis based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. Patients older than 65 years, assessed by both the HADD and the psychiatrist, with a clinical dementia rating (CDR) score lower than 3, were included. The effect of dementia was assessed by forming three groups according to the CDR score (CDR0-0.5, CDR1, and CDR2). Simple and multiple logistic regression models were applied to predict the psychiatrist's depression diagnosis from HADD scores. Areas under the receiver operating characteristics curve (AUC) were plotted and compared by χ2 tests. Results: On both univariate and multiple analyses, HADD predicted depression diagnosis but performed poorly (univariate: p = 0.009, AUC = 0.60 (95% confidence interval (CI) = 0.53-0.66); multiple: p = 0.007, AUC = 0.65 (95% CI = 0.58-0.71)), regardless of cognitive status. Because mood could have changed between the two assessments (they occurred at different points of the hospital stay), the multiple analyses were repeated after limiting time interval at 28, 21, and 14 days. No major improvements were noted. Conclusion: The HADD performed poorly in elderly inpatients regardless of cognitive status. It cannot be recommended in this population for depression screening without further stud

Functional Comparison of Induced Pluripotent Stem Cell- and Blood-Derived GPIIbIIIa Deficient Platelets

Human induced pluripotent stem cells (hiPSCs) represent a versatile tool to model genetic diseases and are a potential source for cell transfusion therapies. However, it remains elusive to which extent patient-specific hiPSC-derived cells functionally resemble their native counterparts. Here, we generated a hiPSC model of the primary platelet disease Glanzmann thrombasthenia (GT), characterized by dysfunction of the integrin receptor GPIIbIIIa, and compared side-by-side healthy and diseased hiPSC-derived platelets with peripheral blood platelets. Both GT-hiPSC-derived platelets and their peripheral blood equivalents showed absence of membrane expression of GPIIbIIIa, a reduction of PAC-1 binding, surface spreading and adherence to fibrinogen. We demonstrated that GT-hiPSC-derived platelets recapitulate molecular and functional aspects of the disease and show comparable behavior to their native counterparts encouraging the further use of hiPSC-based disease models as well as the transition towards a clinical application

Improved SIFTER v2 algorithm for long-term GOME-2A satellite retrievals of fluorescence with a correction for instrument degradation

Solar-induced fluorescence (SIF) data from satellites are increasingly used as a proxy for photosynthetic activity by vegetation and as a constraint on gross primary production. Here we report on improvements in the algorithm to retrieve mid-morning (09:30 LT) SIF estimates on the global scale from the GOME-2 sensor on the MetOp-A satellite (GOME-2A) for the period 2007-2019. Our new SIFTER (Sun-Induced Fluorescence of Terrestrial Ecosystems Retrieval) v2 algorithm improves over a previous version by using a narrower spectral window that avoids strong oxygen absorption and being less sensitive to water vapour absorption, by constructing stable reference spectra from a 6-year period (2007-2012) of atmospheric spectra over the Sahara and by applying a latitude-dependent zero-level adjustment that accounts for biases in the data product. We generated stable, good-quality SIF retrievals between January 2007 and June 2013, when GOME-2A degradation in the near infrared was still limited. After the narrowing of the GOME-2A swath in July 2013, we characterised the throughput degradation of the level-1 data in order to derive reflectance corrections and apply these for the SIF retrievals between July 2013 and December 2018. SIFTER v2 data compare well with the independent NASA v2.8 data product. Especially in the evergreen tropics, SIFTER v2 no longer shows the underestimates against other satellite products that were seen in SIFTER v1. The new data product includes uncertainty estimates for individual observations and is best used for mostly clear-sky scenes and when spectral residuals remain below a certain spectral autocorrelation threshold. Our results support the use of SIFTER v2 data being used as an independent constraint on photosynthetic activity on regional to global scales.</p

Mutant HRAS as novel target for MEK and mTOR inhibitors

HRAS is a frequently mutated oncogene in cancer. However, mutant HRAS as drug target has not been investigated so far. Here, we show that mutant HRAS hyperactivates the RAS and the mTOR pathway in various cancer cell lines including lung, bladder and esophageal cancer. HRAS mutation sensitized toward growth inhibition by the MEK inhibitors AZD6244, MEK162 and PD0325901. Further, we found that MEK inhibitors induce apoptosis in mutant HRAS cell lines but not in cell lines lacking RAS mutations. In addition, knockdown of HRAS by siRNA blocked cell growth in mutant HRAS cell lines. Inhibition of the PI3K pathway alone or in combination with MEK inhibitors did not alter signaling nor had an impact on viability. However, inhibition of mTOR or combined inhibition of MEK and mTOR reduced cell growth in a synergistic manner. Finally, Ba/F3 cells transformed with mutant HRAS isoforms Q61L, Q61R and G12V demonstrated equal sensitivity towards MEK and mTOR inhibition. Our results show that HRAS mutations in cancer activate the RAS and mTOR pathways which might serve as a therapeutic option for patients with HRAS mutant tumors

Kontextwechsel und Bedeutung

Die Bedeutung von materiellen Artefakten, die in ihrer Form unverändert bleiben, kann sich durch räumliche Bezüge und durch den Wechsel des Kontexts verändern. Durch die räumliche Zuordnung inszeniert, können Artefakte inhaltlich festgelegt oder akzentuiert werden bzw. eine neue Bedeutung erlangen. Inhaltlich festgelegte Artefakte können durch ihre Aufstellung einen Raum, manchmal eine ganze Landschaft, neu und spezifisch deuten. Dabei lassen sich verschiedene Ausprägungen von Kontextwechseln finden. In diesem Band werden räumliche, historische, topographische und diskursive Kontextwechsel in Fallbeispielen analysiert und deren Bedeutungen und Überschneidungen kritisch reflektiert. So zeigen Artefakte der Antike, wie Bildwerke gezielt aus ihren ursprünglichen Aufstellungskontexten herausgelöst und neu integriert worden sind, wobei dies entsprechend oder entgegen der älteren Verwendung geschehen konnte. Für die Neuzeit lässt sich zeigen, dass sich durch die Sammlung und die Anordnung von Artefakten Wissenssysteme etablieren und stabilisieren lassen. Hier schließen sich Fragen an: etwa nach der Verwendung von Gegenständen, die eigens für Reisen und den Transfer in andere kulturelle Bereiche geschaffen worden sind; oder nach der Rolle von durch Migrant*innen mitgebrachten Objekten als Identitätsmarker

Patient-rated suitability of a novel electronic device for self-injection of subcutaneous interferon beta-1a in relapsing multiple sclerosis: an international, single-arm, multicentre, Phase IIIb study

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) currently requires long-term treatment with disease-modifying drugs, administered parenterally up to once daily. The need for regular self-injection can be a barrier to treatment for many patients. Autoinjectors can help patients overcome problems or concerns with self-injection and could, therefore, improve treatment adherence. This study was performed to assess the suitability of a new electronic device for the subcutaneous (sc) administration of interferon (IFN) beta-1a, 44 mcg three times weekly, for relapsing MS.</p> <p>Methods</p> <p>In this Phase IIIb, multicentre, single-arm study, patients with relapsing MS who had been consistently self-injecting sc IFN beta-1a using an autoinjector for at least 6 weeks were taught to use the new device and self-administered treatment for 12 weeks thereafter. Patient-rated suitability of the device was assessed at the end of Week 12 using the Patient User Trial Questionnaire. Patient satisfaction with, and evaluation of, the injection process was assessed using the MS Treatment Concern Questionnaire. Trainers evaluated the device using the Trainer User Trial Questionnaire.</p> <p>Results</p> <p>At Week 12, 71.6% (73/102) of patients considered the device 'very suitable' or 'suitable' for self-injection; 92.2% (94/102) reported some degree of suitability and only 7.8% (8/102) found the device 'not at all suitable'. At Weeks 4, 8 and 12, most patients reported that injection preparation and clean-up, performing injections and ease of device use in the previous 4 weeks compared favourably with, or was equivalent to, their previous experience of self-injection. Injection-related pain, injection reactions and 'flu-like' symptoms remained stable over the 12 weeks. Each device feature was rated 'very useful' or 'useful' by at least 80% of patients. All trainers and 95.2% (99/104) of patients found device functions 'very easy' or 'easy' to use. Overall convenience was considered the most important benefit of the device.</p> <p>Conclusions</p> <p>Most patients considered the new electronic injection device suitable for the sc injection of IFN beta-1a. They found the device easy to use with useful features, and reported benefits such as overall convenience. The device may, therefore, increase treatment adherence in patients with MS, particularly those with injection-related issues.</p> <p>Trial registration</p> <p>NCT00735007</p

Predicting which children with juvenile idiopathic arthritis will not attain early remission with conventional treatment: Results from the Reacch-out cohort

Objective. To estimate the probability of early remission with conventional treatment for each child with juvenile idiopathic arthritis (JIA). Children with a low chance of remission may be candidates for initial treatment with biologics or triple disease-modifying antirheumatic drugs (DMARD). Methods. We used data from 1074 subjects in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort. The predicted outcome was clinically inactive disease for ≥ 6 months starting within 1 year of JIA diagnosis in patients who did not receive early biologic agents or triple DMARD. Models were developed in 200 random splits of 75% of the cohort and tested on the remaining 25% of subjects, calculating expected and observed frequencies of remission and c-index values. Results. Our best Cox logistic model combining 18 clinical variables a median of 2 days after diagnosis had a c-index of 0.69 (95% CI 0.67-0.71), better than using JIA category alone (0.59, 95% CI 0.56-0.63). Children in the lowest probability decile had a 20% chance of remission and 21% attained remission; children in the highest decile had a 69% chance of remission and 73% attained remission. Compared to 5% of subjects identified by JIA category alone, the model identified 14% of subjects as low chance of remission (probability \u3c 0.25), of whom 77% failed to attain remission. Conclusion. Although the model did not meet our a priori performance threshold (c-index \u3e 0.70), it identified 3 times more subjects with low chance of remission than did JIA category alone, and it may serve as a benchmark for assessing value added by future laboratory/imaging biomarkers

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

KMOS3D:dynamical constraints on the mass budget in early star-forming disks

We exploit deep integral-field spectroscopic observations with KMOS/Very Large Telescope of 240 star-forming disks at 0.6 &lt;z &lt;2.6 to dynamically constrain their mass budget. Our sample consists of massive (≳109.8M⊙) galaxies with sizes Re ≳ 2kpc. By contrasting the observed velocity and dispersion profiles with dynamical models, we find that on average the stellar content contributes 32-7 +8% of the total dynamical mass, with a significant spread among galaxies (68th percentile range fstar ∼ 18%-62%). Including molecular gas as inferred from CO- and dust-based scaling relations, the estimated baryonic mass adds up to 56-12 +17% of the total for the typical galaxy in our sample, reaching ∼90% at z &gt; 2. We conclude that baryons make up most of the mass within the disk regions of high-redshift star-forming disk galaxies, with typical disks at z &gt; 2 being strongly baryon-dominated within R e. Substantial object-to-object variations in both stellar and baryonic mass fractions are observed among the galaxies in our sample, larger than what can be accounted for by the formal uncertainties in their respective measurements. In both cases, the mass fractions correlate most strongly with measures of surface density. High-Σstar galaxies feature stellar mass fractions closer to unity, and systems with high inferred gas or baryonic surface densities leave less room for additional mass components other than stars and molecular gas. Our findings can be interpreted as more extended disks probing further (and more compact disks probing less far) into the dark matter halos that host them.</p