Global well-posedness of the Kirchhoff equation and Kirchhoff systems

This article is devoted to review the known results on global well-posedness for the Cauchy problem to the Kirchhoff equation and Kirchhoff systems with small data. Similar results will be obtained for the initial-boundary value problems in exterior domains with compact boundary. Also, the known results on large data problems will be reviewed together with open problems.Comment: arXiv admin note: text overlap with arXiv:1211.300

Urothelial bladder carcinoma metastasizing to the eye: A systematic review and case report

The eye is a rare site for disseminated malignancies; nevertheless, several tumors may metastasize to ocular structures. Few cases of urothelial and bladder cancer with eye involvement have been described in the literature thus far. The rarity of metastatic ocular localization implies an accurate differential diagnosis among the possible primary tumor sites. However, a specific diagnostic algorithm is not currently available, nor a defined therapeutic approach. Eye metastases are associated with advanced disease and poor prognosis. Physicians should be made aware of the possibility of eye involvement in patients with a past medical history of urothelial bladder cancer associated with ocular symptoms. The present case reports discusses the first documented case, to the best of our knowledge, of an urothelial bladder cancer metastasizing to the retro bulbar region that infiltrates the lacrimal gland. Furthermore, the report provides a systematic qualitative review of the current literature on eye metastases from urothelial bladder cancer using the Preferred Reporting Items for Systematic Reviews and Meta Analyses

JAK/Stat5-mediated subtype-specific lymphocyte antigen 6 complex, locus G6D (LY6G6D) expression drives mismatch repair proficient colorectal cancer

Background: Human microsatellite-stable (MSS) colorectal cancers (CRCs) are immunologically "cold" tumour subtypes characterized by reduced immune cytotoxicity. The molecular linkages between immune-resistance and human MSS CRC is not clear. Methods: We used transcriptome profiling, in silico analysis, immunohistochemistry, western blot, RT-qPCR and immunofluorescence staining to characterize novel CRC immune biomarkers. The effects of selective antagonists were tested by in vitro assays of long term viability and analysis of kinase active forms using anti-phospho antibodies. Results: We identified the lymphocyte antigen 6 complex, locus G6D (LY6G6D) as significantly overexpressed (around 15-fold) in CRC when compared with its relatively low expression in other human solid tumours. LY6G6D up-regulation was predominant in MSS CRCs characterized by an enrichment of immune suppressive regulatory T-cells and a limited repertoire of PD-1/PD-L1 immune checkpoint receptors. Coexpression of LY6G6D and CD15 increases the risk of metastatic relapse in response to therapy. Both JAK-STAT5 and RAS-MEK-ERK cascades act in concert as key regulators of LY6G6D and Fucosyltransferase 4 (FUT4), which direct CD15-mediated immune-resistance. Momelotinib, an inhibitor of JAK1/JAK2, consistently abrogated the STAT5/LY6G6D axis in vitro, sensitizing MSS cancer cells with an intact JAK-STAT signaling, to efficiently respond to trametinib, a MEK inhibitor used in clinical setting. Notably, colon cancer cells can evade JAK2/JAK1-targeted therapy by a reversible shift of the RAS-MEK-ERK pathway activity, which explains the treatment failure of JAK1/2 inhibitors in refractory CRC. Conclusions: Combined targeting of STAT5 and MAPK pathways has superior therapeutic effects on immune resistance. In addition, the new identified LY6G6D antigen is a promising molecular target for human MSS CRC

Start of SPIDER operation towards ITER neutral beams

Heating Neutral Beam (HNB) Injectors will constitute the main plasma heating and current drive tool both in ITER and JT60-SA, which are the next major experimental steps for demonstrating nuclear fusion as viable energy source. In ITER, in order to achieve the required thermonuclear fusion power gain Q=10 for short pulse operation and Q=5 for long pulse operation (up to 3600s), two HNB injectors will be needed [1], each delivering a total power of about 16.5 MW into the magnetically-confined plasma, by means of neutral hydrogen or deuterium particles having a specific energy of about 1 MeV. Since only negatively charged particles can be efficiently neutralized at such energy, the ITER HNB injectors [2] will be based on negative ions, generated by caesium-catalysed surface conversion of atoms in a radio-frequency driven plasma source. A negative deuterium ion current of more than 40 A will be extracted, accelerated and focused in a multi-aperture, multi-stage electrostatic accelerator, having 1280 apertures (~ 14 mm diam.) and 5 acceleration stages (~200 kV each) [3]. After passing through a narrow gas-cell neutralizer, the residual ions will be deflected and discarded, whereas the neutralized particles will continue their trajectory through a duct into the tokamak vessels to deliver the required heating power to the ITER plasma for a pulse duration of about 3600 s. Although the operating principles and the implementation of the most critical parts of the injector have been tested in different experiments, the ITER NBI requirements have never been simultaneously attained. In order to reduce the risks and to optimize the design and operating procedures of the HNB for ITER, a dedicated Neutral Beam Test Facility (NBTF) [4] has been promoted by the ITER Organization with the contribution of the European Union\u2019s Joint Undertaking for ITER and of the Italian Government, with the participation of the Japanese and Indian Domestic Agencies (JADA and INDA) and of several European laboratories, such as IPP-Garching, KIT-Karlsruhe, CCFE-Culham, CEA-Cadarache. The NBTF, nicknamed PRIMA, has been set up at Consorzio RFX in Padova, Italy [5]. The planned experiments will verify continuous HNB operation for one hour, under stringent requirements for beam divergence (< 7 mrad) and aiming (within 2 mrad). To study and optimise HNB performances, the NBTF includes two experiments: MITICA, full-scale NBI prototype with 1 MeV particle energy and SPIDER, with 100 keV particle energy and 40 A current, aiming at testing and optimizing the full-scale ion source. SPIDER will focus on source uniformity, negative ion current density and beam optics. In June 2018 the experimental operation of SPIDER has started

Establishing a Large-Scale Field Experiment to Assess the Effects of Artificial Light at Night on Species and Food Webs

Artificial light at night (ALAN) is one of the most obvious hallmarks of human presence in an ecosystem. The rapidly increasing use of artificial light has fundamentally transformed nightscapes throughout most of the globe, although little is known about how ALAN impacts the biodiversity and food webs of illuminated ecosystems. We developed a large-scale experimental infrastructure to study the effects of ALAN on a light-naïve, natural riparian (i.e., terrestrial-aquatic) ecosystem. Twelve street lights (20 m apart) arranged in three rows parallel to an agricultural drainage ditch were installed on each of two sites located in a grassland ecosystem in northern Germany. A range of biotic, abiotic, and photometric data are collected regularly to study the short- and long-term effects of ALAN on behavior, species interactions, physiology, and species composition of communities. Here we describe the infrastructure setup and data collection methods, and characterize the study area including photometric measurements. None of the measured parameters differed significantly between sites in the period before illumination. Results of one short-term experiment, carried out with one site illuminated and the other acting as a control, demonstrate the attraction of ALAN by the immense and immediate increase of insect catches at the lit street lights. The experimental setup provides a unique platform for carrying out interdisciplinary research on sustainable lighting

A cluster randomised control trial to evaluate the effectiveness and cost-effectiveness of the Italian medicines use review (I-MUR) for asthma patients

Background The economic burden of asthma, which relates to the degree of control, is €5 billion annually in Italy. Pharmacists could help improve asthma control, reducing this burden. This study aimed to evaluate the effectiveness and cost-effectiveness of Medicines Use Reviews provided by community pharmacists in asthma. Methods This cluster randomised, multi-centre, controlled trial in adult patients with asthma was conducted in 15 of the 20 regions of Italy between September 2014 and July 2015. After stratification by region, community pharmacists were randomly allocated to group A (trained in and delivered the intervention at baseline) or B (training and delivery 3 months later), using computerised random number generation in blocks of 10. Each recruited up to five patients, with both groups followed for 9 months. The intervention consisted of a systematic, structured face-to-face consultation with a pharmacist, covering asthma symptoms, medicines used, attitude towards medicines and adherence, recording pharmacist-identified pharmaceutical care issues (PCIs). The primary outcome was asthma control, assessed using the Asthma-Control-Test (ACT) score (ACT ≥ 20 represents good control). Secondary outcomes were: number of active ingredients, adherence, cost-effectiveness compared with usual care. Although blinding was not possible for either pharmacists or patients, assessment of outcomes was conducted by researchers blind to group allocation. Results Numbers of pharmacists and patients enrolled were 283 (A = 136; B = 147) and 1263 (A = 600; B = 663), numbers completing were 201 (A = 97; B = 104) and 816 (A = 400; B = 416), respectively. Patients were similar in age and gender and 56.13% (458/816) had poor/partial asthma control. Pharmacists identified 1256 PCIs (mean 1.54/patient), mostly need for education, monitoring and potentially ineffective therapy. Median ACT score at baseline differed between groups (A = 19, B = 18; p < 0.01). Odds ratio for improved asthma control was 1.76 (95% CI 1.33–2.33) and number needed to treat 10 (95% CI 6–28). Number of active ingredients reduced by 7.9% post-intervention (p < 0.01). Adherence improved by 35.4% 3 months post-intervention and 40.0% at 6 months (p < 0.01). The probability of the intervention being more cost-effective than usual care was 100% at 9 months. Conclusions This community pharmacist-based intervention demonstrated both effectiveness and cost-effectiveness. It has since been implemented as the first community pharmacy cognitive service in Italy

Pre-flight qualification tests of the Mini-EUSO telescope engineering model

International audienceMini-EUSO is part of the JEM-EUSO program and operates on board the International Space Station (ISS). It is a UV-telescope with single-photon counting capability looking at nighttime downwards to the Earth through a nadir-facing UV-transparent window. As part of the pre-flight tests, the Mini-EUSO engineering model, a telescope with 1/9 of the original focal surface and a lens of 2.5 cm diameter, has been built and tested. Tests of the Mini-EUSO engineering model have been made in laboratory and in open-sky conditions. Laboratory tests have been performed at the TurLab facility, located at the Physics Department of the University of Turin, equipped with a rotating tank containing different types of materials and light sources. In this way, the configuration for the observation of the Earth from space was emulated, including the Mini-EUSO trigger schemes. In addition to the qualification and calibration tests, the Mini-EUSO engineering model has also been used to evaluate the possibility of using a JEM-EUSO-type detector for applications such as observation of space debris. Furthermore, observations in open-sky conditions allowed the studies of natural light sources such as stars, meteors, planets, and artificial light sources such as airplanes, satellites reflecting the sunlight, and city lights. Most of these targets could be detected also with Mini-EUSO. In this paper, the tests in laboratory and in open-sky conditions are reported, as well as the obtained results. In addition, the contribution that such tests provided to foresee and improve the performance of Mini-EUSO on board the ISS is discussed

Impact of social determinants on antiretroviral therapy access and outcomes entering the era of universal treatment for people living with HIV in Italy

Background: Social determinants are known to be a driving force of health inequalities, even in high income countries. Aim of our study was to determine if these factors can limit antiretroviral therapy (ART) access, outcome and retention in care of people living with HIV (PLHIV) in Italy. Methods: All ART naïve HIV+ patients (pts) of Italian nationality enrolled in the ICONA Cohort from 2002 to 2016 were included. The association of socio-demographic characteristics (age, sex, risk factor for HIV infection, educational level, occupational status and residency area) with time to: ART initiation (from the first positive anti-HIV test), ART regimen discontinuation, and first HIV-RNA &lt; 50 cp/mL, were evaluated by Cox regression analysis, Kaplan Meier method and log-rank test. Results: A total of 8023 HIV+ pts (82% males, median age at first pos anti-HIV test 36 years, IQR: 29-44) were included: 6214 (77.5%) started ART during the study period. Women, people who inject drugs (PWID) and residents in Southern Italy presented the lowest levels of education and the highest rate of unemployment compared to other groups. Females, pts aged &gt; 50 yrs., unemployed vs employed, and people with lower educational levels presented the lowest CD4 count at ART initiation compared to other groups. The overall median time to ART initiation was 0.6 years (yrs) (IQR 0.1-3.7), with a significant decrease over time [2002-2006 = 3.3 yrs. (0.2-9.4); 2007-2011 = 1.0 yrs. (0.1-3.9); 2012-2016 = 0.2 yrs. (0.1-2.1), p &lt; 0.001]. By multivariate analysis, females (p &lt; 0.01) and PWID (p &lt; 0.001), presented a longer time to ART initiation, while older people (p &lt; 0.001), people with higher educational levels (p &lt; 0.001), unemployed (p = 0.02) and students (p &lt; 0.001) were more likely to initiate ART. Moreover, PWID, unemployed vs stable employed, and pts. with lower educational levels showed a lower 1-year probability of achieving HIV-RNA suppression, while females, older patients, men who have sex with men (MSM), unemployed had higher 1-year risk of first-line ART discontinuation. Conclusions: Despite median time to ART start decreased from 2002 to 2016, socio-demographic factors still contribute to disparities in ART initiation, outcome and durability

Simulations studies for the Mini-EUSO detector

Mini-EUSO is a mission of the JEM-EUSO program flying onboard the International Space Station since August 2019. Since the first data acquisition in October 2019, more than 35 sessions have been performed for a total of 52 hours of observations. The detector has been observing Earth at night-time in the UV range and detected a wide variety of transient sources all of which have been modelled through Monte Carlo simulations. Mini-EUSO is also capable of detecting meteors and potentially space debris and we performed simulations for such events to estimate their impact on future missions for cosmic ray science from space. We show here examples of the simulation work done in this framework to analyse the Mini-EUSO data. The expected response of Mini-EUSO with respect to ultra high energy cosmic ray showers has been studied. The efficiency curve of Mini-EUSO as a function of primary energy has been estimated and the energy threshold for Cosmic Rays has been placed to be above 10^{21} eV. We compared the morphology of several transient events detected during the mission with cosmic ray simulations and excluded that they can be due to cosmic ray showers. To validate the energy threshold of the detector, a system of ground based flashers is being used for end-to-end calibration purposes. We therefore implemented a parameterisation of such flashers into the JEM-EUSO simulation framework and studied the response of the detector with respect to such sources