Air pollution attributable postneonatal infant mortality in U.S. metropolitan areas: a risk assessment study

BACKGROUND: The impact of outdoor air pollution on infant mortality has not been quantified. METHODS: Based on exposure-response functions from a U.S. cohort study, we assessed the attributable risk of postneonatal infant mortality in 23 U.S. metropolitan areas related to particulate matter <10 μm in diameter (PM(10)) as a surrogate of total air pollution. RESULTS: The estimated proportion of all cause mortality, sudden infant death syndrome (normal birth weight infants only) and respiratory disease mortality (normal birth weight) attributable to PM(10 )above a chosen reference value of 12.0 μg/m(3 )PM(10 )was 6% (95% confidence interval 3–11%), 16% (95% confidence interval 9–23%) and 24% (95% confidence interval 7–44%), respectively. The expected number of infant deaths per year in the selected areas was 106 (95% confidence interval 53–185), 79 (95% confidence interval 46–111) and 15 (95% confidence interval 5–27), respectively. Approximately 75% of cases were from areas where the current levels are at or below the new U.S. PM(2.5 )standard of 15 μg/m(3 )(equivalent to 25 μg/m(3 )PM(10)). In a country where infant mortality rates and air pollution levels are relatively low, ambient air pollution as measured by particulate matter contributes to a substantial fraction of infant death, especially for those due to sudden infant death syndrome and respiratory disease. Even if all counties would comply to the new PM(2.5 )standard, the majority of the estimated burden would remain. CONCLUSION: Given the inherent limitations of risk assessments, further studies are needed to support and quantify the relationship between infant mortality and air pollution

PD-1+ natural killer cells in human non-small cell lung cancer can be activated by PD-1/PD-L1 blockade

Natural killer (NK) cells are critically involved in anti-tumor immunity by targeting tumor cells. In this study, we show that intratumoral NK cells from NSCLC patients expressed elevated levels of the immune checkpoint receptor PD-1 on their cell surface. In contrast to the expression of activating receptors, PD-1; +; NK cells co-expressed more inhibitory receptors compared to PD-1; -; NK cells. Intratumoral NK cells were less functional compared to peripheral NK cells, and this dysfunction correlated with PD-1 expression. Tumor cells expressing PD-L1 inhibited the functionality of PD-1; +; NK cells in ex vivo models and induced PD-1 clustering at the immunological synapse between NK cells and tumor cells. Notably, treatment with PD-1 blockade was able to reverse PD-L1-mediated inhibition of PD-1; +; NK cells. Our findings highlight the therapeutic potential of PD-1; +; NK cells in immune checkpoint blockade and could guide the development of NK cell-stimulating agents in combination with PD-1 blockade

Перебіг анемії вагітних у хворих на туберкульоз легень

В статье представлены данные течения анемии беременных и нарушения фетоплацентарного комплекса у 86 женщин, больных туберкулезом легких. Выявлено, что анемия на фоне туберкулезного процесса приводит к существенным функциональным и морфологическим нарушениям в плаценте. показано диагностическое значение оценки плацентарной дисфункции для профилактики и лечения анемии у данного контингента женщин.The article presents the data of course of pregnancy anemia and failures of fetoplacental complex in 86 women with pulmonary tuberculosis. It is found that anemia under tuberculous process leads to significant functional and morphological disturbances in placenta. Diagnostic significance of assessment of placental dysfunction for the prevention and treatment of anemia in this contingent of women is shown

Treatment of Older Patients With Mantle Cell Lymphoma (MCL):Long-Term Follow-Up of the Randomized European MCL Elderly Trial

PURPOSE: In an update of the randomized, open-label, phase III European Mantle Cell Lymphoma (MCL) Elderly trial (ClinicalTrials.gov identifier: NCT00209209), published in 2012, we aimed to confirm results on long-term outcome focusing on efficacy and safety of long-term use of rituximab maintenance. PATIENTS AND METHODS: Five hundred sixty patients with newly diagnosed MCL underwent a first random assignment between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab, fludarabine, and cyclophosphamide (R-FC) induction, followed by a second random assignment in 316 responders between rituximab and interferon alfa maintenance, to be continued until progression. We compared progression-free survival from the second randomization and overall survival (OS) from the first or second randomizations. RESULTS: After a median follow-up time of 7.6 years, the previously described difference in OS between the induction arms persisted (median, 6.4 years after R-CHOP [n = 280] v 3.9 years after R-FC [n = 280]; P = .0054). Patients responding to R-CHOP had median progression-free survival and OS times of 5.4 and 9.8 years, respectively, when randomly assigned to rituximab (n = 87), compared with 1.9 years (P < .001) and 7.1 years (P = .0026), respectively, when randomly assigned to interferon alfa (n = 97). In 58% and 32% of patients treated with R-CHOP, rituximab maintenance was still ongoing 2 and 5 years from start of maintenance, respectively. After R-FC, rituximab maintenance was associated with an unexpectedly high cumulative incidence of death in remission (22% at 5 years). Toxicity of rituximab maintenance was low after R-CHOP (grade 3-4 leukopenia or infection < 5%) but more prominent in patients on rituximab maintenance after R-FC, in whom grade 3-4 leukopenia (up to 40%) and infections were frequent (up to 15%). CONCLUSION: The excellent results of R-CHOP followed by rituximab maintenance until progression for older patients with MCL persisted in a mature follow-up. Prolongation of rituximab maintenance beyond 2 years is effective and safe

The Resonance Frequency Shift, Pattern Formation, and Dynamical Network Reorganization via Sub-Threshold Input

We describe a novel mechanism that mediates the rapid and selective pattern formation of neuronal network activity in response to changing correlations of sub-threshold level input. The mechanism is based on the classical resonance and experimentally observed phenomena that the resonance frequency of a neuron shifts as a function of membrane depolarization. As the neurons receive varying sub-threshold input, their natural frequency is shifted in and out of its resonance range. In response, the neuron fires a sequence of action potentials, corresponding to the specific values of signal currents, in a highly organized manner. We show that this mechanism provides for the selective activation and phase locking of the cells in the network, underlying input-correlated spatio-temporal pattern formation, and could be the basis for reliable spike-timing dependent plasticity. We compare the selectivity and efficiency of this pattern formation to a supra-threshold network activation and a non-resonating network/neuron model to demonstrate that the resonance mechanism is the most effective. Finally we show that this process might be the basis of the phase precession phenomenon observed during firing of hippocampal place cells, and that it may underlie the active switching of neuronal networks to locking at various frequencies

Advancing global & regional reanalyses

This report outlines the structure of and summarizes the recommendations made at the 5th International Conference on Reanalysis (ICR5), attended by 259 participants from 37 countries, in Rome (Italy), on 13-17 November 2017. It first summarizes the conference structure. Then, the key recommendations of ICR5 are given for the five main conference topics: production; observations (data rescue and preparation); data assimilation methods; quality assurance of reanalysis; and applications in science, services, and policymaking. Lastly, five high-level recommendations are proposed to managing agencies on how best to advance the field of reanalyses, which serves tens of thousands of users, via enhanced research, development, and operations

Comparison of Classifier Fusion Methods for Predicting Response to Anti HIV-1 Therapy

BACKGROUND: Analysis of the viral genome for drug resistance mutations is state-of-the-art for guiding treatment selection for human immunodeficiency virus type 1 (HIV-1)-infected patients. These mutations alter the structure of viral target proteins and reduce or in the worst case completely inhibit the effect of antiretroviral compounds while maintaining the ability for effective replication. Modern anti-HIV-1 regimens comprise multiple drugs in order to prevent or at least delay the development of resistance mutations. However, commonly used HIV-1 genotype interpretation systems provide only classifications for single drugs. The EuResist initiative has collected data from about 18,500 patients to train three classifiers for predicting response to combination antiretroviral therapy, given the viral genotype and further information. In this work we compare different classifier fusion methods for combining the individual classifiers. PRINCIPAL FINDINGS: The individual classifiers yielded similar performance, and all the combination approaches considered performed equally well. The gain in performance due to combining methods did not reach statistical significance compared to the single best individual classifier on the complete training set. However, on smaller training set sizes (200 to 1,600 instances compared to 2,700) the combination significantly outperformed the individual classifiers (p<0.01; paired one-sided Wilcoxon test). Together with a consistent reduction of the standard deviation compared to the individual prediction engines this shows a more robust behavior of the combined system. Moreover, using the combined system we were able to identify a class of therapy courses that led to a consistent underestimation (about 0.05 AUC) of the system performance. Discovery of these therapy courses is a further hint for the robustness of the combined system. CONCLUSION: The combined EuResist prediction engine is freely available at http://engine.euresist.org

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal