Estimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes. An Individual-Participant Data Meta-Analysis

IMPORTANCE: Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US. OBJECTIVE: To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes. DESIGN, SETTING, AND PARTICIPANTS: Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021. EXPOSURES: The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR). MAIN OUTCOMES AND MEASURES: The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses. RESULTS: Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10 mg/g, an eGFR of 45 to 59 mL/min/1.73 m2 based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73 m2 (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years]). CONCLUSIONS AND RELEVANCE: In this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations

RESCUhE Project: Cultural Heritage vulnerability in a changing and directional climate

[EN] RESCUhE Project (Improving structural RESilience of Cultural HEritage to directional extreme hydro-meteorological events in the context of the Climate Change) is a coordinated IGME-UAM research project funded by Spanish Government (MCIN/AEI/10.13039/501100011033). The framework of this research is the predicted increase in climate change vulnerability of heritage sites and the current disconnection between both environmental research on material decay and the practical aspects of designing preventive conservation measurements.RESCUhE Project (Improving structural RESilience of Cultural HEritage to directional extreme hydro-meteorological events in the context of the Climate Change) is a coordinated IGME-UAM research project funded by Spanish Government (MCIN/AEI/10.13039/501100011033).Peer reviewe

The ALICE experiment at the CERN LHC

ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries. Its overall dimensions are 161626 m3 with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Rhythmic Changes in Synapse Numbers in <i>Drosophila melanogaster</i> Motor Terminals

<div><p>Previous studies have shown that the morphology of the neuromuscular junction of the flight motor neuron MN5 in <i>Drosophila melanogaster</i> undergoes daily rhythmical changes, with smaller synaptic boutons during the night, when the fly is resting, than during the day, when the fly is active. With electron microscopy and laser confocal microscopy, we searched for a rhythmic change in synapse numbers in this neuron, both under light:darkness (LD) cycles and constant darkness (DD). We expected the number of synapses to increase during the morning, when the fly has an intense phase of locomotion activity under LD and DD. Surprisingly, only our DD data were consistent with this hypothesis. In LD, we found more synapses at midnight than at midday. We propose that under LD conditions, there is a daily rhythm of formation of new synapses in the dark phase, when the fly is resting, and disassembly over the light phase, when the fly is active. Several parameters appeared to be light dependent, since they were affected differently under LD or DD. The great majority of boutons containing synapses had only one and very few had either two or more, with a 70∶25∶5 ratio (one, two and three or more synapses) in LD and 75∶20∶5 in DD. Given the maintenance of this proportion even when both bouton and synapse numbers changed with time, we suggest that there is a homeostatic mechanism regulating synapse distribution among MN5 boutons.</p></div

Proportion of synaptic boutons found along the MN5 axon in LD and DD.

<p>The graphs show means ± s.e.m in all cases. (A–D) For LCM and TEM, the proportion of boutons per time point was calculated as the number of boutons found in each time point divided by the number of boutons found in the experiment. (A–B) In the LCM samples, the proportion of boutons was higher at ZT19 (0.55±0.04) than ZT7 (0.45±0.03) in LD (A, Mann-Whitney U test, P = 0.03), and higher at CT19 (0.53±0.02) than CT7 (0.47±0.02) in DD (B, Student <i>t</i> test, P = 0.04). (C–D) In TEM samples, the proportion of boutons counted in LD and DD showed no significant differences between time points, although the same tendency as in the LCM samples under LD (ZT19, 0.61±0.12 vs. ZT7, 0.39±0.06) and DD (CT19, 0.54±0.08 vs. CT7, 0.46±0.04). Number of flies used in LCM per ZT: ZT19, n = 38; ZT7, n = 43; CT19, n = 33; CT7, n = 37. In TEM: ZT19/ZT7 n = 7 and CT19/CT7 n = 6.</p

Diagrammatic representation of the daily changes in bouton and synapse numbers found in this study.

<p>The bars do not represent exact values and they are only meant to provide a simplified graphic summary of the results detailed in Figs. 4 and 5. In both LD and DD conditions, we found more boutons at midnight than at midday. Synapses, instead, were more abundant at midnight in LD samples and at midday in DD samples. Abbreviations: Boutons (B, gray bars); synapses (S, black bars); light:darkness (LD); constant darkness (DD).</p

Visualization of synapses in the MN5 terminal based on synaptic markers and LCM.

<p>(A) Example of the staining of the MN5 neuromuscular junction with anti-Horseradish Peroxidase (HRP, blue) and anti-nc82 (BRP, magenta) in some of the thinnest branches, located deeply inside the muscle. The bar scale represents 10 µm. (B) Example of the same staining in a branch of this neuromuscular junction showing boutons with synapses (white arrowheads), and boutons without them (outlined arrowheads) at larger magnification. The bar scale represents 2 µm. (C) Triple staining done at CT19 and CT7 confirming the presence of synaptic vesicles (Syn, magenta) and synapses (BRP, green) in the presynaptic side of synapses in each bouton (see outlined boutons b1, b2 and b3). Orange dotted lines in b1, b2 and b3 show the places where the analysis of fluorescence intensity was done to confirm the presence of Synorf1 in the proximity of the synapses. Details of the signals obtained are shown for HRP (D), BRP (E) and Syn (F). In (E and F) orange outlines mark selected synapses (S1, S2 and S3) located in boutons marked as b1, b2 and b3. (G) The graph shows the profiles of fluorescence intensity measured for the immunofluorescence corresponding to HRP, BRP and Syn, detailed in (C), (E) and (F). Syn and BRP signals match their location in b1, b2 and b3 and confirm that synaptic vesicles are in the proximity of S1, S2 and S3 synapses. (H) Triple staining confirming the accumulation of glutamate receptors (GluRIIA, magenta) apposed to the accumulation of BRP signals (see outlined boutons b1, b2 and b3). Orange dotted lines in b1, b2 and b3 show the places where the analysis of fluorescence intensity was done to confirm the presence of GluRIIA in the proximity of the synapses. Details of the signals obtained are shown for HRP (I), BRP (J) and GluRIIA (K). In (J and K) orange outlines mark selected synapses (S1, S2 and S3) analyzed in b1, b2 and b3. (L) The graph shows the profiles of fluorescence intensity measured for HRP, BRP and GluRIIA, detailed in (H), (J) and (K). GluRIIA and BRP signals match their location in b1, b2 and b3 and confirm that the accumulations of glutamate receptors correspond with accumulations of BRP in the synapses marked S1, S2 and S3.</p