Patterns of urinary β2-microglobulin excretion by patients treated with aminoglycosides

Patterns of urinary β2-microglobulin excretion in patients treated with aminoglycosides. Aminoglycoside antibiotics are relatively mild nephrotoxins, but their action is site-specific to the proximal tubule. Therefore, use of these drugs presents a unique opportunity to study the temporal relation between the damage to the cells lining the renal proximal tubule and the subsequent rise in the serum creatinine concentration. Our study of 52 aminoglycoside-treated patients included measurements of daily serum creatinine, daily 24-hour urinary β2-microglobulin (β2M) excretion, and determination of aminoglycoside tissue accumulation. An elevation in β2M excretion above the baseline value occurred in 37 of 52 (71%), whereas the serum creatinine concentration rose in only 17 of 52 (33%) of patients. Even fewer patients (10 of 52) demonstrated all three criteria for aminoglycoside nephrotoxicity. These 10 patients had elevated tissue accumulation, evidence of renal tubular damage, and arise in serum creatinine concentration. The increased β2M excretion greater than 50 mg/day preceded the serum creatinine rise by 2 to 7 days. An abnormal baseline β2M was not a risk factor for a subsequent rise in creatinine concentration or vice versa. Although each test is primarily site specific, widespread and severe renal proximal tubular damage, regardless of cause, will eventually lead to an elevation of serum creatinine. Thus, serial monitoring of proximal tubular function with urinary β2M excretion has potential value in the assessment of insults to this site, but cannot be expected to explain all changes in serum creatinine.Modalités de l'excrétion urinaire de β2-microglobulines chez les malades traités par les aminoglycosides. Les aminoglycosides ont une action néphrotoxique de sévérité moyenne spécifiquement localisée au tube proximal. L'emploi de ces drogues offre l'opportunité d'étudier la relation dans le temps entre la lésion des cellules tubulaires proximales et l'élévation consécutive de la créatininémie. L'étude de 52 malades traités par les aminoglycosides a comporté la détermination quotidienne de la créatininémie et de l'excrétion urinaire de β2-microglobuline (β2M) ainsi que la détermination de l'accumulation tissulaire d'aminoglycoside. Une élévation de l'excrétion de β2M au dessus de la valeur basale a été observée chez 37 malades (71%) alors que l'élévation de la créatinine n'est survenue que chez 17 malades (33%). Dix malades seulement ont eu les trois critères de néphrotoxicité par l'aminoglycoside. Ces 10 malades avaient une accumulation tissulaire, des signes de lésions tubulaires et une élévation de la créatinine. Une augmentation de l'excrétion deβ2M, au dessus de 50 mg/24 hr a précédé de 2 à 7 jours l'élévation de la créatininémie. Une excrétion basale anormale de β2M n'est pas un facteur de risque d'élévation ultérieure de la créatininémie, ou réciproquement. Bien que chacun de ces tests soit spécifique d'un site, des lésions tubulaires proximales sévères et étendues doivent déterminer une élévation de la créatinine, quelle que soit leur cause. La surveillance itérative de la fonction tubulaire proximale par la mesure de l'excrétion urinaire de β2M a une valeur potentielle dans l'évaluation des lésions mais ne peut pas expliquer la totalité des modifications de la créatininémie

The thermal expansion coeffcient of monolayer, bilayer and trilayer graphene derived from the strain induced by cooling to cryogenic temperatures

This is the author accepted manuscript. The final version is available from the American Institute of Physics via the DOI in this recordData availability: The data that support the findings of this study are available from the corresponding author upon reasonable request.While thermally cycling monolayer, bilayer and trilayer graphene between 5 K and 300 K Raman spectroscopy has shown that cooling to 5 K induces a strain in these graphene flakes of −0.081 ± 0.003%. This strain was used to measure the graphene thermal expansion coefficient (TEC) which was found to be (−3.2±0.2)×10−6 K −1 for monolayers, (−3.4 ± 0.4) × 10−6 K −1 for bilayers and (−3.8 ± 0.6) × 10−6 K −1 for trilayers at room temperature. The TEC showed a similar temperature dependence across all graphene thicknesses and was found to be in good agreement with theoretical predictions. This study thus represents the first measurement of the TEC of bilayer and trilayer graphene. Modification of graphene flakes of all thicknesses with various electrical contact designs was found to have no significant impact on the resulting strain, and thus the TEC, compared to the pristine graphene.Engineering and Physical Sciences Research Council (EPSRC)Leverhulme Trus

Remembering 'zeal' but not 'thing':reverse frequency effects as a consequence of deregulated semantic processing

More efficient processing of high frequency (HF) words is a ubiquitous finding in healthy individuals, yet frequency effects are often small or absent in stroke aphasia. We propose that some patients fail to show the expected frequency effect because processing of HF words places strong demands on semantic control and regulation processes, counteracting the usual effect. This may occur because HF words appear in a wide range of linguistic contexts, each associated with distinct semantic information. This theory predicts that in extreme circumstances, patients with impaired semantic control should show an outright reversal of the normal frequency effect. To test this prediction, we tested two patients with impaired semantic control with a delayed repetition task that emphasised activation of semantic representations. By alternating HF and low frequency (LF) trials, we demonstrated a significant repetition advantage for LF words, principally because of perseverative errors in which patients produced the previous LF response in place of the HF target. These errors indicated that HF words were more weakly activated than LF words. We suggest that when presented with no contextual information, patients generate a weak and unstable pattern of semantic activation for HF words because information relating to many possible contexts and interpretations is activated. In contrast, LF words tend are associated with more stable patterns of activation because similar semantic information is activated whenever they are encountered

Loss of high-level perceptual knowledge of object structure in DAT

Peer reviewe

The anterior temporal lobe semantic hub is a part of the language neural network: selective disruption of irregular past tense verbs by rTMS

There is growing evidence from patient and neuroimaging studies that the anterior temporal lobe (ATL) should be considered a crucial part of the neural network that underpins language. Specifically, this region supports semantic representations that play a key role in various aspects of language processing. In this study, we tested the critical importance of this region for language processing in normal participants by applying repetitive transcranial magnetic stimulation over the left ATL semantic region. The ability to generate the past tense of English verbs has often been used as a test case for neurocognitive models of language. Accordingly, we used this aspect of language to investigate the impact of repetitive transcranial magnetic stimulation (rTMS) over the left ATL. As predicted by single mechanism accounts of past-tense generation, ATL rTMS had a selective impact on participants' ability to generate the past tense of irregular verbs. When combined with other evidence, these results confirm that the ATL semantic hub is a key component of the neural network for language

Mars Express science highlights and future plans

21st EGU General Assembly, EGU2019, proceedings from the conference held 7-12 April, 2019 in Vienna, Austria, id.11100After 15 years in orbit Mars Express remains one of ESA's most scientifically productive Solar System missions whose publication record now exceeds 1200 papers. Characterization of the geological processes on a local-to-regional scale by HRSC, OMEGA and partner experiments on NASA spacecraft has allowed constraining land-forming processes in space and time. Recent results suggest episodic geological activity as well as the presence of large bodies of liquid water in several provinces (e.g. Eridania Planum, Terra Chimeria) in the early and middle Amazonian epoch and formation of vast sedimentary plains north of the Hellas basin. Mars Express observations and experimental teams provided essential contribution to the selection of the Mars-2020 landing sites. Recent discovery of subglacial liquid water underneath the Southern polar cap has proven that the mission science potential is still not exhausted. More than a decade-long record of the atmospheric parameters such as temperature, dust loading, water vapor and ozone abundance, water ice and CO2 clouds distribution, collected by SPICAM, PFS, OMEGA, HRSC and VMC together with subsequent modeling have provided key contributions to our understanding of the martian climate. Recent spectroscopic monitoring of the 2018 dust storm revealed dust properties, their spatial and temporal variations and atmospheric circulation. More than 10,000 crossings of the bow shock by Mars Express allowed ASPERA-3 to characterize complex behavior of the magnetic boundary topology as function of the solar EUV flux. Observations of the ion escape during complete solar cycle revealed important dependencies of the atmospheric erosion rate on parameters of the solar wind and EUV flux and established global energy balance between the solar wind and escaping ion flow. The observations showed that ion escape can be responsible for removal of about 10 mbar over the Mars history that implies existence of other more effective escape channels. The structure of the ionosphere sounded by the MARSIS radar and the MaRS radio science experiment was found to be significantly affected by the solar activity, the crustal magnetic field, as well as by the influx of meteorite and cometary dust. MARSIS and ASPERA-3 observations suggest that the sunlit ionosphere over the regions with strong crustal fields is denser and extends to higher altitudes as compared to the regions with no crustal anomalies. Several models of the upper atmosphere and plasma environment are being developed based on and in support of the collected experimental data. The models aim at creating user-friendly data base of plasma parameters similar to the Mars Climate Database that would be of great service to the planetary community. A significant recent achievement was the flawless transition to the >gyroless> attitude control and operations mode on the spacecraft, that would allow mitigating the onboard gyros aging and extending the mission lifetime. In November 2018 ESA's Science Programme Committee (SPC) confirmed the mission operations till the end of 2020 and notionally approved its extension till the end of 2022. The talk will give the Mars Express status, review the recent science highlights, and outline future plans focusing on synergistic science with TGO

Mars EXpress: status and recent findings

Mars Express has entered its second decade in orbit in excellent health. The mission extension in 2015-2016 aims at augmenting of the surface coverage by imaging and spectral imaging instruments, continuing monitoring of the climate parameters and their variability, study of the upper atmosphere and its interaction with the solar wind in collaboration with NASA's MAVEN mission. Characterization of geological processes and landforms on Mars on a local-to-regional scale by HRSC camera constrained the martian geological activity in space and time and suggested its episodicity. Six years of spectro-imaging observations by OMEGA allowed correction of the surface albedo for presence of the atmospheric dust and revealed changes associated with the dust storm seasons. Imaging and spectral imaging of the surface shed light on past and present aqueous activity and contributed to the selection of the Mars-2018 landing sites. More than a decade long record of climatological parameters such as temperature, dust loading, water vapor, and ozone abundance was established by SPICAM and PFS spectrometers. Observed variations of HDO/H2O ratio above the subliming North polar cap suggested seasonal fractionation. The distribution of aurora was found to be related to the crustal magnetic field. ASPERA observations of ion escape covering a complete solar cycle revealed important dependences of the atmospheric erosion rate on parameters of the solar wind and EUV flux. Structure of the ionosphere sounded by MARSIS radar and MaRS radio science experiment was found to be significantly affected by the solar activity, crustal magnetic field as well as by influx of meteorite and cometary dust. The new atlas of Phobos based on the HRSC imaging was issued. The talk will give the mission status and review recent science highlights

Investigating the impact of CO2 on low-frequency variability of the AMOC in HadCM3

This study investigates the impact of CO2 on the amplitude, frequency, and mechanisms of Atlantic meridional overturning circulation (AMOC) variability in millennial simulations of the HadCM3 coupled climate model. Multichannel singular spectrum analysis (MSSA) and empirical orthogonal functions (EOFs) are applied to the AMOC at four quasi-equilibrium CO2 forcings. The amount of variance explained by the first and second eigenmodes appears to be small (i.e., 11.19%); however, the results indicate that both AMOC strength and variability weaken at higher CO2 concentrations. This accompanies an apparent shift from a predominant 100–125-yr cycle at 350 ppm to 160 yr at 1400 ppm. Changes in amplitude are shown to feed back onto the atmosphere. Variability may be linked to salinity-driven density changes in the Greenland–Iceland– Norwegian Seas, fueled by advection of anomalies predominantly from the Arctic and Caribbean regions. A positive density anomaly accompanies a decrease in stratification and an increase in convection and Ekman pumping, generating a strong phase of the AMOC (and vice versa). Arctic anomalies may be generated via an internal ocean mode that may be key in driving variability and are shown to weaken at higher CO2, possibly driving the overall reduction in amplitude. Tropical anomalies may play a secondary role in modulating variability and are thought to be more influential at higher CO2, possibly due to an increased residence time in the subtropical gyre and/or increased surface runoff driven by simulated dieback of the Amazon rain forest. These results indicate that CO2 may not only weaken AMOC strength but also alter the mechanisms that drive variability, both of which have implications for climate change on multicentury time scales