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Background Timely vaccination is essential to protect infants from vaccine-preventable diseases. The aim of the study was to evaluate the determinants of vaccination timeliness for hexavalent (HEXA) and measles-mumps-rubella (MMR) vaccines. Methods The study is part of the PREHMO project funded by Tuscany Region, Italy. Data on the 2017 and 2018 full birth cohorts of Tuscany (N = 41,493) were retrieved from the Birth Registry and linked to those of the Vaccine Registry up to 24 months after birth. Sociodemographic and at birth characteristics of mothers and infants were retrieved. The primary outcome was the timeliness of HEXA 1st and 3rd doses, and MMR 1st dose. Timeliness was defined as the administration of the dose a day after the period recommended by the vaccination schedule. Multiple logistic regression models were performed. Results For all the vaccines considered, a significantly increased risk of delayed vaccination was observed in preterm infants and in infants born in hospital of second level of newborn care, while infants conceived by assisted reproductive technologies and first-born infants showed a significantly decreased risk for delayed vaccination. Multiple births, small for gestational age status, maternal unemployment, and rural residence were significantly associated with an increased risk of delayed HEXA-1 vaccination (OR 1.31, 95%CI 1.13-1.51; OR 1.12, 95%CI 1.03-1.22; OR 1.06, 95%CI 1.01-1.13; and OR 1.1, 95%CI 1.03-1.16). As for MMR vaccination, a low maternal education was significantly associated with high risk of delay (OR 1.12, 95%CI 1.06-1.18), while rural residence, maternal foreign nationality and female sex were significantly associated with a decreased risk of delay (OR 0.91, 95%CI 0.87-0.96; OR 0.82, 95%CI 0.78-0.87; and OR 0.95, 95%CI 0.91-0.99). Conclusions Several common and vaccine-specific predictors of vaccination timeliness were identified. Strategies to improve a timely vaccination should take into account these predictors. Key messages • Several maternal and infants factors may influence vaccination timeliness of routine immunization in childhood. • Tailored vaccination strategies are needed to improve vaccination timeliness in infants at high-risk of delayed vaccination.

The CALorimetric Electron Telescope (CALET) on the International Space Station (ISS) consists of a high-energy cosmic ray CALorimeter (CAL) and a lower-energy CALET Gamma ray Burst Monitor (CGBM). CAL is sensitive to electrons up to 20 TeV, cosmic ray nuclei from Z = 1 through Z $\sim$ 40, and gamma rays over the range 1 GeV - 10 TeV. CGBM observes gamma rays from 7 keV to 20 MeV. The combined CAL-CGBM instrument has conducted a search for gamma ray bursts (GRBs) since Oct. 2015. We report here on the results of a search for X-ray/gamma ray counterparts to gravitational wave events reported during the LIGO/Virgo observing run O3. No events have been detected that pass all acceptance criteria. We describe the components, performance, and triggering algorithms of the CGBM - the two Hard X-ray Monitors (HXM) consisting of LaBr$_{3}$(Ce) scintillators sensitive to 7 keV to 1 MeV gamma rays and a Soft Gamma ray Monitor (SGM) BGO scintillator sensitive to 40 keV to 20 MeV - and the high-energy CAL consisting of a CHarge-Detection module (CHD), IMaging Calorimeter (IMC), and fully active Total Absorption Calorimeter (TASC). The analysis procedure is described and upper limits to the time-averaged fluxes are presented., 27 pages, 10 figures. Accepted for publication in ApJ

To evaluate the role of tacrolimus ointment in the management of patients on dupilumab therapy for severe atopic dermatitis, in a real-life setting.Consecutive patients with severe AD treated with dupilumab were enrolled. Topical treatment was associated according to the clinical practice. Eczema Area and Severity Index (EASI), itching and sleep Numerical Rating Scale (NRS) and Dermatologic quality of Life (DLQI) were recorded at baseline and after 4, 16 and 52 weeks of treatment with dupilumab.Overall, 342 patients were enrolled, and 307 were evaluable. Tacrolimus was used by 6.5% (n=20) of patients at baseline, 11%, 13.5%, and 11.3% after 1, 4 and 12 months, respectively; the mean time to introduce tacrolimus after initiation of dupilumab was 8.3 ± 0.3 months. Low EASI score (7; mild disease) after 1 month of systemic therapy was more frequent in patients who applied tacrolimus at baseline than in patients who did not (72.2% vs. 55.8%, p=0.027). Female sex, low DLQI scores, low age at dupilumab initiation, and non-generalized AD were correlated with an increased probability to start tacrolimus at any time during the study.Data suggested that early treatment of localized areas with tacrolimus improves systemic treatment efficacy.

We present the measurement of the energy dependence of the boron flux in cosmic rays and its ratio to the carbon flux in an energy interval from 8.4 GeV/n to 3.8 TeV/n based on the data collected by the Calorimetric Electron Telescope (CALET) during ∼6.4 yr of operation on the International Space Station. An update of the energy spectrum of carbon is also presented with an increase in statistics over our previous measurement. The observed boron flux shows a spectral hardening at the same transition energy E_{0}∼200 GeV/n of the C spectrum, though B and C fluxes have different energy dependences. The spectral index of the B spectrum is found to be γ=-3.047±0.024 in the interval 25E200 GeV/n. The B spectrum hardens by Δγ_{B}=0.25±0.12, while the best fit value for the spectral variation of C is Δγ_{C}=0.19±0.03. The B/C flux ratio is compatible with a hardening of 0.09±0.05, though a single power-law energy dependence cannot be ruled out given the current statistical uncertainties. A break in the B/C ratio energy dependence would support the recent AMS-02 observations that secondary cosmic rays exhibit a stronger hardening than primary ones. We also perform a fit to the B/C ratio with a leaky-box model of the cosmic-ray propagation in the Galaxy in order to probe a possible residual value λ_{0} of the mean escape path length λ at high energy. We find that our B/C data are compatible with a nonzero value of λ_{0}, which can be interpreted as the column density of matter that cosmic rays cross within the acceleration region.

A broca Diaphania nitidalis (Cramer, 1781) (Lepidoptera - Pyralidae), constitui-se numa das mais importantes pragas que atacam as cucurbitáceas cultivadas. Entretanto, os estudos sobre este inseto são bastante escassos, principalmente no tocante a sua biologia. Por esse motivo, no presente trabalho, propôs-se estudar a biologia deste inseto, bem como alguns aspectos de seu comportamento. Verificou-se ainda, a possibilidade de criação massal em dieta artificial, a ocorrência de inimigos naturais e alguns aspectos morfológicos de importância taxonômica apresentados pelas lagartas do último instar. Os estudos das diferentes fases da biologia, foram conduzidos em laboratório, sob condições controladas de umidade e temperatura. O alimento natural proporcionado às lagartas se constituiu, durante os dois primeiros instares de folhas tenras e posteriormente de fatias de frutos de Cucurbita pepo L. variedade Caserta. Os principais resultados obtidos foram os seguintes: 1. O período embrionário dos ovos variou de 3 a 4 dias, sendo mais frequente 3 dias; 2. A fase larval apresentou 5 instares, com um período médio de duração de 10,35 ± 0,16 dias em dieta natural e 11,88 ± 0,12 dias em dieta artificial; 3. O estágio de pré-pupa durou 1,89 ± 0,08 dias para lagartas oriundas de dieta natural e 2,18 ± 0,86 dias para a lagartas de dieta artificial; 4. A duração média do estágio de pupa foi de 9,43 ± 0,65 dias para machos e 9,97 ± 0,63 dias para as fêmeas oriundas de dieta natural e 9,50 ± 0,29 dias para machos e 9,75 ± 0,38 dias para fêmeas, quando oriundas de lagartas em dieta artificial; 5. Os adultos alimentaram-se numa solução de mel de abelha a 10% nas gaiolas de acasalamento e postura; 6. Os adultos copularam uma única vez durante todo o seu ciclo de vida. A duração da cópula foi em média de 127,5 minutos; 7. O período de pré-oviposição foi de 2,14 dias com as fêmeas ovipositando em média, 236,64 ovos; 8. Houve um estimulo na oviposição quando as gaiolas foram expostas por algumas horas aos raios solares; 9. O período médio de vida dos adultos virgens, foi de 6,90 dias para machos e 7,60 dias para fêmeas. Para adultos acasalados este período foi de 8 dias para machos e 6,71 dias para as fêmeas; 10. A proporção quanto ao sexo foi de 1 macho para 1 fêmea (1:1); 11. O ciclo de vida em condições de laboratório, proporcionando-se alimento natural para as lagartas e considerando-se adultos acasalados alimentados com solução de mel de abelha a 10% foi de 32,67 dias para os machos e 31,92 dias para as fêmeas. 12. O parasito de lagarta encontrado com maior frequência foi Petrargyrops punctiger Townsend (Diptera, Tachinidae). The pickleworm Diaphania nitidalis (Cramer, 1781) (Lepidoptera, Pyralidae) is one of the most important pests on Cucurbitaceae. However, the works concerning this insect are scarce, specially those on its biology. This research aimed to study the biology of Diaphania nitidalis as well as some aspects of its behavior. The possibility of massal rearing as artificial diet, the occurrence of natural enemies and the morphological features of the last instar larvae were also studied. The experiment was carried out in laboratory under controlled conditions of humidity and temperature. The larvae of the first two instars were reared on tender leaves and the following ones os slices of fruits of Cucurbita pepo L. var. Caserta. The results were as follows: 1. The period of egg evolution varied from 3 to 4 days, being the 3-day period the most frequent; 2. The larval stage has five instars with a mean period of 10.35 ± 0.16 days on natural diet and 11.88 ± 0.12 days on artificial diet; 3. The pre-pupal periods averages 1.89 ± 0.08 days for larvae reared on natural diet and 2.18 ± 0.86 days for larvae reared on artificial diet; 4. The pupal period averages 9.43 ± 0.65 days for the males and 9.97 ± 0.63 days for the females when the larvae are reared on natural diet, and 9.50 ± 0.29 days for the males and 9.75 ± 0.38 days for the females when the larvae are reared on artificial diet; 5. The adults were fed with a 10% honey solution; 6. The adults mate only once and the mating period averages 127.5 minutes; 7. The oviposition period is 2.14 days and the average number of eggs per female is 236.64; 8. The oviposition is stimulated when the cages are placed in the sun for some hours; 9. The longevity of unmated adults is 6.90 days for the males and 7.60 days for the females whereas for mated adults it is 8.00 days for the males and 6.71 days for the females; 10. The sex ratio is 1 male : 1 female; 11. The life span in laboratory conditions, considering natural diet for the larvae and mated adults fed with a 10% honey solution is 32.67 days for the males and 31.92 days for the females; 12. The most frequently found larval parasite was Petrargyrops punctiger Townsend (Diptera, Tachinidae).

The High Energy cosmic-Radiation Detection (HERD) facility is a China-led international space mission that will start its operation around 2027 aboard the future China’s Space Station. The mission is expected to extend the direct measurements on cosmic rays and gamma rays by at least one order of magnitude in energy respect to the limits of the experiments currently operating in space. This is possible thanks to its novel design, based on a 3D, homogeneous, isotropic and finely-segmented calorimeter, with good energy resolution (< 1% for electromagnetic showers, < 30% for hadronic showers) and a good effective geometric factor (> 3 m2sr for electromagnetic showers, > 2 m2sr for hadronic showers). The main challenge of the hardware design is the implementation of the read-out system for each of the almost 8000 LYSO crystals of the calorimeter, since a large dynamic range of 107 is needed and absolute energy scale calibration is crucial for space instruments. In this contribution, we describe the double read-out scheme chosen for the final configuration, made of wave-length shifting fibers coupled with an intensified scientific CMOS and photodiodes connected to a specifically designed front-end electronics. In particular, we will discuss the advantages of both read-out systems and the benefits offered to the apparatus by this double read-out scheme.

The Calorimetric Electron Telescope (CALET), in operation on the International Space Station since 2015, collected a large sample of cosmic-ray iron over a wide energy interval. In this Letter a measurement of the iron spectrum is presented in the range of kinetic energy per nucleon from 10 GeV$/n$ to 2.0 TeV$/n$ allowing the inclusion of iron in the list of elements studied with unprecedented precision by space-borne instruments. The measurement is based on observations carried out from January 2016 to May 2020. The CALET instrument can identify individual nuclear species via a measurement of their electric charge with a dynamic range extending far beyond iron (up to atomic number $Z$ = 40). The energy is measured by a homogeneous calorimeter with a total equivalent thickness of 1.2 proton interaction lengths preceded by a thin (3 radiation lengths) imaging section providing tracking and energy sampling. The analysis of the data and the detailed assessment of systematic uncertainties are described and results are compared with the findings of previous experiments. The observed differential spectrum is consistent within the errors with previous experiments. In the region from 50 GeV$/n$ to 2 TeV$/n$ our present data are compatible with a single power law with spectral index -2.60 $\pm$ 0.03., Comment: main text: 7 pages, 4 figures; supplemental material: 10 pages, 12 figures, 1 table. arXiv admin note: text overlap with arXiv:2012.10319

In this paper, we report the measurement of the energy flow, the cross section and the average inelasticity of forward neutrons (+ antineutrons) produced in $\sqrt{s} = 13$ TeV proton-proton collisions. These quantities are obtained from the inclusive differential production cross section, measured using the LHCf Arm2 detector at the CERN Large Hadron Collider. The measurements are performed in six pseudorapidity regions: three of them ($��> 10.75$, $8.99 < ��< 9.21$ and $8.80 < ��< 8.99$), albeit with smaller acceptance and larger uncertainties, were already published in a previous work, whereas the remaining three ($10.06 < ��< 10.75$, $9.65 < ��< 10.06$ and $8.65 < ��< 8.80$) are presented here for the first time. The analysis was carried out using a data set acquired in June 2015 with a corresponding integrated luminosity of $\mathrm{0.194~nb^{-1}}$. Comparing the experimental measurements with the expectations of several hadronic interaction models used to simulate cosmic ray air showers, none of these generators resulted to have a satisfactory agreement in all the phase space selected for the analysis. The inclusive differential production cross section for $��> 10.75$ is not reproduced by any model, whereas the results still indicate a significant but less serious deviation at lower pseudorapidities. Depending on the pseudorapidity region, the generators showing the best overall agreement with data are either SIBYLL 2.3 or EPOS-LHC. Furthermore, apart from the most forward region, the derived energy flow and cross section distributions are best reproduced by EPOS-LHC. Finally, even if none of the models describe the elasticity distribution in a satisfactory way, the extracted average inelasticity is consistent with the QGSJET II-04 value, while most of the other generators give values that lie just outside the experimental uncertainties., 22 pages, 11 figures

In this paper, we report the measurement relative to the production of forward neutrons in proton-proton collisions at s = 13 $$ \sqrt{s}=13 $$ TeV obtained using the LHCf Arm2 detector at the Large Hadron Collider. The results for the inclusive differential production cross section are presented as a function of energy in three different pseudorapidity regions: η > 10.76, 8.99 < η < 9.22 and 8.81 < η < 8.99. The analysis was performed using a data set acquired in June 2015 that corresponds to an integrated luminosity of 0.194 nb−1. The measurements were compared with the predictions of several hadronic interaction models used to simulate air showers generated by Ultra High Energy Cosmic Rays. None of these generators showed good agreement with the data for all pseudorapidity intervals. For η > 10.76, no model is able to reproduce the observed peak structure at around 5 TeV and all models underestimate the total production cross section: among them, QGSJET II-04 shows the smallest deficit with respect to data for the whole energy range. For 8.99 < η < 9.22 and 8.81 < η < 8.99, the models having the best overall agreement with data are SIBYLL 2.3 and EPOS-LHC, respectively: in particular, in both regions SIBYLL 2.3 is able to reproduce the observed peak structure at around 1.5–2.5 TeV.

Background Mycosis fungoides (MF) and Sezary Syndrome (SS) are the most common cutaneous T-cell lymphomas. MF/SS is accompanied by considerable morbidity from pain, itching and disfigurement. Aim To identify factors associated with poorer health-related quality of life (HRQoL) in patients newly diagnosed with MF/SS. Methods Patients enrolled into Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI; an international observational study in MF/SS) had their HRQoL assessed using the Skindex-29 questionnaire. Skindex-29 scores were analysed in relation to patient- and disease-specific characteristics. Results The study population consisted of 237 patients [60·3% male; median age 60 years, (interquartile range 49-70)], of whom 179 had early MF and 58 had advanced MF/SS. In univariate analysis, HRQoL, as measured by Skindex-29, was worse in women, SS, late-stage MF, those with elevated lactate dehydrogenase, alopecia, high modified Severity Weighted Assessment Tool and confluent erythema. Linear regression models only identified female gender (β = 8·61; P = 0·003) and alopecia (β = 9·71, P = 0·02) as independent predictors of worse global HRQoL. Item-level analysis showed that the severe impairment in symptoms [odds ratio (OR) 2·14, 95% confidence interval (CI) 1·19-3·89] and emotions (OR 1·88, 95% CI 1·09-3·27) subscale scores seen in women was caused by more burning/stinging, pruritus, irritation and greater feelings of depression, shame, embarrassment and annoyance with their diagnosis of MF/SS. Conclusions HRQoL is significantly more impaired in newly diagnosed women with MF/SS and in those with alopecia. As Skindex-29 does not include existential questions on cancer, which may cause additional worry and distress, a comprehensive validated cutaneous T-cell lymphoma-specific questionnaire is urgently needed to more accurately assess disease-specific HRQoL in these patients. What's already known about this topic? Cross-sectional studies of mixed populations of known and newly diagnosed patients with mycosis fungoides (MF)/Sezary syndrome (SS) have shown significant impairment in health-related quality of life (HRQoL). Previous studies on assessing gender-specific differences in HRQoL in MF/SS are conflicting. More advanced-stage disease and pruritus is associated with poorer HRQoL in patients with MF/SS. What does this study add? This is the first prospective study to investigate HRQoL in a homogenous group of newly diagnosed patients with MF/SS. In patients newly diagnosed with MF/SS, HRQoL is worse in women and in those with alopecia and confluent erythema. MF/SS diagnosis has a multidimensional impact on patient HRQoL, including a large burden of cutaneous symptoms, as well as a negative impact on emotional well-being.

Background Survival in mycosis fungoides (MF) is varied and may be poor. The PROCLIPI (PROspective Cutaneous Lymphoma International Prognostic Index) study is a web‐based data collection system for early‐stage MF with legal data‐sharing agreements permitting international collaboration in a rare cancer with complex pathology. Clinicopathological data must be 100% complete and in‐built intelligence in the database system ensures accurate staging. Objectives To develop a prognostic index for MF. Methods Predefined datasets for clinical, haematological, radiological, immunohistochemical, genotypic, treatment and quality of life are collected at first diagnosis of MF and annually to test against survival. Biobanked tissue samples are recorded within a Federated Biobank for translational studies. Results In total, 430 patients were enrolled from 29 centres in 15 countries spanning five continents. Altogether, 348 were confirmed as having early‐stage MF at central review. The majority had classical MF (81·6%) with a CD4 phenotype (88·2%). Folliculotropic MF was diagnosed in 17·8%. Most presented with stage I (IA: 49·4%; IB: 42·8%), but 7·8% presented with enlarged lymph nodes (stage IIA). A diagnostic delay between first symptom development and initial diagnosis was frequent [85·6%; median delay 36 months (interquartile range 1290)]. This highlights the difficulties in accurate diagnosis, which includes lack of a singular diagnostic test for MF. Conclusions This confirmed early‐stage MF cohort is being followed‐up to identify prognostic factors, which may allow better management and improve survival by identifying patients at risk of disease progression. This study design is a useful model for collaboration in other rare diseases, especially where pathological diagnosis can be complex.

Given the good performances in terms of geometrical acceptance and energy resolution, calorimeters are the best suited detectors to measure high energy cosmic rays directly in space. However, in order to exploit this potential, the design of calorimeters must be carefully optimized to take into account all limitations related to space missions, due mainly to the mass of the experimental apparatus. CaloCube is a three years R&D project, approved and financed by INFN in 2014, aiming to optimize the design of a space-borne calorimeter by the use of a cubic, homogeneous and isotropic geometry. In order to maximize detector performances with respect to the total mass of the apparatus, comparative studies on different scintillating materials, different sizes of crystals and different spacings among them have been performed making use of Monte Carlo simulations. In parallel to this activity, several prototypes instrumented with CsI:Tl cubic crystals have been constructed and tested with particle beams (muons, electrons, protons and ions). Both simulations and prototypes showed that the CaloCube design leads to a good particle energy resolution (< 2% for electromagnetic showers, < 40% for hadronic showers) and a good effective geometric factor (> 3:5 m2 sr for electromagnetic showers, > 2:5 m2 sr for hadronic showers). Thanks to these performances, in 5 years of operation it would be possible to measure the ux of electrons+positrons up to some tens of TeV and the uxes of protons and nuclei up to some units of PeV/nucleon, hence extending these measurements by at least one order of magnitude in energy compared to the experiments currently operating in space.

In this paper, we report the measurement relative to the production of forward neutrons in proton-proton collisions at $ \sqrt{s}=13 $ TeV obtained using the LHCf Arm2 detector at the Large Hadron Collider. The results for the inclusive differential production cross section are presented as a function of energy in three different pseudorapidity regions: η > 10.76, 8.99 < η < 9.22 and 8.81 < η < 8.99. The analysis was performed using a data set acquired in June 2015 that corresponds to an integrated luminosity of 0.194 nb$^{−1}$. The measurements were compared with the predictions of several hadronic interaction models used to simulate air showers generated by Ultra High Energy Cosmic Rays. None of these generators showed good agreement with the data for all pseudorapidity intervals. For η > 10.76, no model is able to reproduce the observed peak structure at around 5 TeV and all models underestimate the total production cross section: among them, QGSJET II-04 shows the smallest deficit with respect to data for the whole energy range. For 8.99 < η < 9.22 and 8.81 < η < 8.99, the models having the best overall agreement with data are SIBYLL 2.3 and EPOS-LHC, respectively: in particular, in both regions SIBYLL 2.3 is able to reproduce the observed peak structure at around 1.5–2.5 TeV. In this paper, we report the measurement relative to the production of forward neutrons in proton-proton collisions at $\mathrm{\sqrt{s} = 13~TeV}$ obtained using the LHCf Arm2 detector at the Large Hadron Collider. The results for the inclusive differential production cross section are presented as a function of energy in three different pseudorapidity regions: $\eta > 10.76$, $8.99 < \eta < 9.22$ and $8.81 < \eta < 8.99$. The analysis was performed using a data set acquired in June 2015 that corresponds to an integrated luminosity of $\mathrm{0.194~nb^{-1}}$. The measurements were compared with the predictions of several hadronic interaction models used to simulate air showers generated by Ultra High Energy Cosmic Rays. None of these generators showed good agreement with the data for all pseudorapidity intervals. For $\eta > 10.76$, no model is able to reproduce the observed peak structure at around $\mathrm{5~TeV}$ and all models underestimate the total production cross section: among them, QGSJET II-04 shows the smallest deficit with respect to data for the whole energy range. For $8.99 < \eta < 9.22$ and $8.81 < \eta < 8.99$, the models having the best overall agreement with data are SIBYLL 2.3 and EPOS-LHC, respectively: in particular, in both regions SIBYLL 2.3 is able to reproduce the observed peak structure at around $\mathrm{1.5-2.5~TeV}$.

The GAMMA-400 gamma-ray telescope is intended to measure the fluxes of gamma-rays and cosmic-ray electrons and positrons in the energy range from 100 MeV to several TeV. Such measurements concern the following scientific tasks: investigation of point sources of gamma-rays, studies of the energy spectra of Galactic and extragalactic diffuse emission, studies of gamma-ray bursts and gamma-ray emission from the Sun, as well as high precision measurements of spectra of high-energy electrons and positrons. Also the GAMMA- 400 instrument provides the possibility for protons and nuclei measurements up to knee. But the main goal for the GAMMA-400 mission is to perform a sensitive search for signatures of dark matter particles in high-energy gamma-ray emission. To fulfill these measurements the GAMMA-400 gamma-ray telescope possesses unique physical characteristics in comparison with previous and present experiments. The major advantage of the GAMMA-400 instrument is excellent angular and energy resolution for gamma-rays above 10 GeV. The GAMMA-400 experiment will be installed onboard of the Navigator space platform, manufactured by the NPO Lavochkin Association. The expected orbit will be a highly elliptical orbit (with apogee 300.000 km and perigee 500 km) with 7 days orbital period. An important profit of such an orbit is the fact that the full sky coverage will always be available for gamma ray astronomy.

The GAMMA-400 gamma-ray telescope with excellent angular and energy resolutions is designed to search for signatures of dark matter in the fluxes of gamma-ray emission and electrons + positrons. Precision investigations of gamma-ray emission from Galactic Center, Crab, Vela, Cygnus, Geminga, and other regions will be performed, as well as diffuse gamma-ray emission, along with measurements of high-energy electron + positron and nuclei fluxes. Furthermore, it will study gamma-ray bursts and gamma-ray emission from the Sun during periods of solar activity. The GAMMA-400 energy range is expected to be from ~20 MeV up to TeV energies for gamma rays, up to 10 TeV for electrons + positrons, and up to 1015 eV for cosmic-ray nuclei. For 100-GeV gamma rays, the GAMMA-400 angular resolution is ~0.01° and energy resolution is ~1%; the proton rejection factor is ~5x105. GAMMA-400 will be installed onboard the Russian space observatory.[object Object]

Introduction La proteinose alveolaire pulmonaire (PAP) est une maladie rare due a un dysfonctionnement du macrophage alveolaire. Methodes Nous reportons le premier cas de PAP post allogreffe de cellules souches hematopoietiques (CSH), associe a une infection a Mycobacterium abscessus, suspecte d’etre secondaire a un traitement par ruxolitinib. Resultats Une patiente de 66 ans beneficiait d’une allogreffe de CSH en 2013 pour une myelodysplasie. Elle developpait une GVH cutanee severe, stabilisee par corticoides, ciclosporine, methotrexate et ruxolitinib. Une dyspnee chronique et un trouble de la diffusion s’installaient a partir de mai 2016. Le scanner thoracique montrait du verre depoli et des epaississements des septas. Le bilan infectieux etait negatif. L’atteinte pulmonaire s’aggravait malgre l’arret du methotrexate. Une biopsie pulmonaire chirurgicale revelait un materiel proteique eosinophile granulaire obstruant les alveoles et prenant la coloration PAS. La culture etait positive pour M. abscessus. L’etat de la patiente s’aggravait avec fievre, oxygenodependance, majoration des anomalies scannographiques. Le chimerisme sanguin restait 100 % donneur. Un myelogramme ne montrait pas de myelodyspasie, la recherche d’anticorps anti GM-CSF et anti GATA2 etait negative. Un traitement de la mycobacterie etait instaure et le ruxolitinib etait interrompu. L’evolution etait rapidement favorable avec apyrexie et sevrage de l’oxygene, amelioration radiologique et fonctionnelle. Conclusion Des cas de PAP survenant precocement apres allogreffe ont deja ete decrits. Ce cas est particulier par son caractere tardif et le role causal suppose du ruxolitinib. Le ruxolitinib est un inhibiteur des Janus Kinases (JAK) 1–2, utilise dans les myelofibroses et les GVH severes. GM-CSF est un facteur de croissance essentiel pour les macrophages ; son recepteur est couple a une JAK 2. Par l’inhibition des JAK, le ruxolitinib pourrait interrompre le signal du GM-CSF et entrainer un dysfonctionnement des macrophages alveolaires et l’apparition d’une PAP. L’infection a M. abscessus aurait egalement pu etre favorisee par le ruxolitinib qui altere la fonction des cellules immunitaires locales. Il a ete precedemment associe a un risque accru de reactivation tuberculeuse. La chronologie suggere l’implication du ruxolitinib dans l’apparition de la PAP et de l’infection a M. abscessus. Le signalement de ces effets secondaires est essentiel pour cerner le profil de toxicite de ces nouveaux traitements.

The Large Hadron Collider forward experiment measured very forward neutral particle spectra in LHC proton-proton collisions in early 2010. In this paper we will discuss the energy and transverse momentum spectra of neutral pion at the 7TeV proton-proton collision, and the inclusive photon energy spectra taken at the 900GeV collisions. The spectra in both collision energies are also compared with the predictions of several hadronic interaction models that are often used for high energy particle physics and for modeling ultra high energy cosmic ray showers.

This work presents an electrocardiogram ECG data reduction method based on Walsh spectrum double logarithmic quantization. The technique is theoretically justified for a simulated ECG and its practical efficiency confirmed using MIT/BIH arrhythmia database signals. By classifying a "good" compression as one with MSE/spl les/0.005 for 1:1 spectral reduction, a normal/abnormal ECG mix returned an 87% success rate for waveforms stored with 8- to 11-bit resolution.

Carbonic anhydrase (CA; EC 4.2.1.1) is a zinc metalloenzyme catalysing the reversible hydration of CO2. Its activity is virtually ubiquitous in nature and is envolved in a wide variety of physiological processes. Until today, fourteen CA isozymes (CA I-XIV) were characterised in animals, plants and certain bacteria. Pollutants like heavy metals are considered strong CA activity inhibitors, however few works have studied the sensitivity of CA from aquatic organisms to cadmium and comparatively much less studies on invertebrates are available. In Mytilus galloprovincialis (widely used in marine pollution monitoring programmes as sentinel organisms), we previously demonstrated a significant tissue-specific alteration of CA activity following in vivo cadmium (Cd) exposure, with a significant increase in the digestive gland. In order to establish if protein expression was involved in the observed metal activation of the enzymatic activity, in the present work immuno-precipitation and western blot analysis were applied to the tissue extract of control and Cd exposed mussels. Mussels were exposed to 1.8 µM CdCl2 for 14 days. Digestive gland CA activity was measured applying a simple and low cost electrometric method (Caricato et al., ESCPB Congress, 2003). Immunoprecipitation and western blot analysis (using the polyclonal anti-Carbonic Anhydrase II antibody) revealed in mussel digestive gland a protein that immunoreacts with the antibody at a molecular mass of approximate 42 kDa (the sequencing analysis is in progress). 42 kDa corresponds to the molecular weight of native CA VI (Parkkila S. et al., 1997), whose presence in invertebrates has never been revealed before. Interestingly the 42 KDa band, ascribed to CA, appeared strongly increased in the digestive gland of mussel after 14 day exposure, thus leading to a induction of CA expression in accordance with the observed enzymatic activity increase. To our knowledge this is the first time that Cd inducible CA activity and expression are reported. In conclusion, obtained results represent a good starting point for future potential biomarker application of the CA activity in the sentinel organism M. galloprovincialis.

A total of 675 Pseudoscorpiones, representing nine species, were captured during 12 months in an inundation forest near Manaus, which is covered by several meters of mixedwater for 5-7 months each year. In the terrestrial phase, the average abundance of pseudoscorpions in the soil (0-14 depth) was three times higher during the rainy season (140 ind./m2/month) when compared to the season with less rainfall (48 ind./m2/month). A survival strategy in response to flooding was observed in the terricolous and univoltine Tyrannochthonius amazonicus (Chthoniidae): immature tritonymphs, representing a migrating stage, moved from the soil to the trunk/canopy region where they passed the aquatic phase. Pseudochthonius homodentatus (Chthoniidae) changed from a terricolous mode of life in Central Amazonian upland forests to an arboricolous living in the inundation forest. Six other species, obtained in low numbers predominantly in the trunk/canopy region, are considered arboricolous as well. Our data reconfirm that seasonally inundated forests of the mixedwater type near Manaus represent an ecotone: Pachychernes baileyi (Chernetidae), Tyrannochthonius amazonicus (Chthoniidae), Geogarypus amazonicus (Geogarypidae), Pachyolpium irmgardae (Olpiidae) and Dolichowithius minutus (Withiidae) inhabit blackwater inundation forests in the valley of the Negro River. Parachernes adisi (Chernetidae) was collected from whitewater inundation forests along the lower Solimões River. Paratemnoides minor (Atemnidae) occurs in black- and whitewater inundation forests. Pseudochthonius homodentatus (Chthoniidae) lives in primary and secondary (non-flooded) upland forests of Central Amazonia. The occasionally phoretic Lechytia chthoniiformis (Chthoniidae) is found throughout South America.