Longitudinal functional connectivity changes related to dopaminergic decline in Parkinson’s disease

Background: Resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated that basal ganglia functional connectivity is altered in Parkinson’s disease (PD) as compared to healthy controls. However, such functional connectivity alterations have not been related to the dopaminergic deficits that occurs in PD over time. Objectives: To examine whether functional connectivity impairments are correlated with dopaminergic deficits across basal ganglia subdivisions in patients with PD both cross-sectionally and longitudinally. Methods: We assessed resting-state functional connectivity of basal ganglia subdivisions and dopamine transporter density using 11C-PE2I PET in thirty-four PD patients at baseline. Of these, twenty PD patients were rescanned after 19.9 ± 3.8 months. A seed-based approach was used to analyze resting-state fMRI data. 11CPE2I binding potential (BPND) was calculated for each participant. PD patients were assessed for disease severity. Results: At baseline, PD patients with greater dopaminergic deficits, as measured with 11C-PE2I PET, showed larger decreases in posterior putamen functional connectivity with the midbrain and pallidum. Reduced functional connectivity of the posterior putamen with the thalamus, midbrain, supplementary motor area and sensorimotor cortex over time were significantly associated with changes in DAT density over the same period. Furthermore, increased motor disability was associated with lower intraregional functional connectivity of the posterior putamen. Conclusions: Our findings suggest that basal ganglia functional connectivity is related to integrity of dopaminergic system in patients with PD. Application of resting-state fMRI in a large cohort and longitudinal scanning may be a powerful tool for assessing underlying PD pathology and its progression

Replication in Cells of Hematopoietic Origin Is Necessary for Dengue Virus Dissemination

Dengue virus (DENV) is a mosquito-borne pathogen for which no vaccine or specific therapeutic is available. Although it is well established that dendritic cells and macrophages are primary sites of DENV replication, it remains unclear whether non-hematopoietic cellular compartments serve as virus reservoirs. Here, we exploited hematopoietic-specific microRNA-142 (miR-142) to control virus tropism by inserting tandem target sites into the virus to restrict replication exclusively in this cell population. In vivo use of this virus restricted infection of CD11b+, CD11c+, and CD45+ cells, resulting in a loss of virus spread, regardless of the route of administration. Furthermore, sequencing of the targeted virus population that persisted at low levels, demonstrated total excision of the inserted miR-142 target sites. The complete conversion of the virus population under these selective conditions suggests that these immune cells are the predominant sources of virus amplification. Taken together, this work highlights the importance of hematopoietic cells for DENV replication and showcases an invaluable tool for the study of virus pathogenesis

GrailQuest & HERMES: Hunting for Gravitational Wave Electromagnetic Counterparts and Probing Space-Time Quantum Foam

Within Quantum Gravity theories, different models for space-time quantisation predict an energy dependent speed for photons. Although the predicted discrepancies are minuscule, GRB, occurring at cosmological distances, could be used to detect this signature of space-time granularity with a new concept of modular observatory of huge overall collecting area consisting in a fleet of small satellites in low orbits, with sub-microsecond time resolution and wide energy band (keV-MeV). The enormous number of collected photons will allow to effectively search these energy dependent delays. Moreover, GrailQuest will allow to perform temporal triangulation of high signal-to-noise impulsive events with arc-second positional accuracies: an extraordinary sensitive X-ray/Gamma all-sky monitor crucial for hunting the elusive electromagnetic counterparts of GW. A pathfinder of GrailQuest is already under development through the HERMES project: a fleet of six 3U cube-sats to be launched by 2021/22

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050

Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached$8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total,$40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this,$13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and$1.4 billion was repurposed from existing health projects. $3.1 billion (22.4$2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7$1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Hypertriton Production in p-Pb Collisions at √sNN = 5.02 TeV

The study of nuclei and antinuclei production has proven to be a powerful tool to investigate the formation mechanism of loosely bound states in high-energy hadronic collisions. The first measurement of the production of ${\rm ^{3}_{\Lambda}\rm H}$ in p-Pb collisions at $\sqrt{s_{\rm{NN}}}$ = 5.02 TeV is presented in this Letter. Its production yield measured in the rapidity interval -1 < y < 0 for the 40% highest multiplicity p-Pb collisions is ${\rm d} N /{\rm d} y =[\mathrm{6.3 \pm 1.8 (stat.) \pm 1.2 (syst.) ] \times 10^{-7}}$. The measurement is compared with the expectations of statistical hadronisation and coalescence models, which describe the nucleosynthesis in hadronic collisions. These two models predict very different yields of the hypertriton in small collision systems such as p-Pb and therefore the measurement of ${\rm d} N /{\rm d} y$ is crucial to distinguish between them. The precision of this measurement leads to the exclusion with a significance larger than 6$\sigma$ of some configurations of the statistical hadronisation, thus constraining the production mechanism of loosely bound states

Measurement of the non-prompt D-meson fraction as a function of multiplicity in proton-proton collisions at s \sqrt{s} = 13 TeV

The fractions of non-prompt (i.e. originating from beauty-hadron decays) D0 and D+ mesons with respect to the inclusive yield are measured as a function of the charged-particle multiplicity in proton-proton collisions at a centre-of-mass energy of √s = 13 TeV with the ALICE detector at the LHC. The results are reported in intervals of transverse momentum (pT) and integrated in the range 1 < pT < 24 GeV/c. The fraction of non-prompt D0 and D+ mesons is found to increase slightly as a function of pT in all the measured multiplicity intervals, while no significant dependence on the charged- particle multiplicity is observed. In order to investigate the production and hadronisation mechanisms of charm and beauty quarks, the results are compared to PYTHIA 8 as well as EPOS 3 and EPOS 4 Monte Carlo simulations, and to calculations based on the colour glass condensate including three-pomeron fusion

Characterizing the initial conditions of heavy-ion collisions at the LHC with mean transverse momentum and anisotropic flow correlations

Correlations between mean transverse momentum and anisotropic flow coefficients or are measured as a function of centrality in Pb–Pb and Xe–Xe collisions at sqrt(sNN) = 5.02 TeV and 5.44 TeV, respectively, with ALICE. In addition, the recently proposed higher-order correlation between [pt], v2, and v3 is measured for the first time, which shows an anticorrelation for the presented centrality ranges. These measurements are compared with hydrodynamic calculations using IP-Glasma and TRENTO initial-state shapes, the former based on the Color Glass Condensate effective theory with gluon saturation, and the latter a parameterized model with nucleons as the relevant degrees of freedom. The data are better described by the IP-Glasma rather than the TRENTO based calculations. In particular, Trajectum and JETSCAPE predictions, both based on the TRENTO initial state model but with different parameter settings, fail to describe the measurements. As the correlations between [pt] and vn are mainly driven by the correlations of the size and the shape of the system in the initial state, these new studies pave a novel way to characterize the initial state and help pin down the uncertainty of the extracted properties of the quark–gluon plasma recreated in relativistic heavy-ion collisions

General balance functions of identified charged hadron pairs of (pi,K,p) in Pb-Pb collisions at 2.76 TeV

First measurements of balance functions (BFs) of all combinations of identified charged hadron ( π , K, p) pairs in Pb–Pb collisions at √sNN = 2.76 TeV recorded by the ALICE detector are presented. The BF measurements are carried out as two-dimensional differential correlators versus the relative rapidity (delta-y) and azimuthal angle (delta-φ) of hadron pairs, and studied as a function of collision centrality. The delta-φ dependence of BFs is expected to be sensitive to the light quark diffusivity in the quark–gluon plasma. While the BF azimuthal widths of all pairs substantially decrease from peripheral to central collisions, the longitudinal widths exhibit mixed behaviors: BFs of π π and cross-species pairs narrow significantly in more central collisions, whereas those of KK and pp are found to be independent of collision centrality. This dichotomy is qualitatively consistent with the presence of strong radial flow effects and the existence of two stages of quark production in relativistic heavy-ion collisions. Finally, the first measurements of the collision centrality evolution of BF integrals are presented, with the observation that charge balancing fractions are nearly independent of collision centrality in Pb–Pb collisions. Overall, the results presented provide new and challenging constraints for theoretical models of hadron production and transport in relativistic heavy-ion collisions