Early Trends in Cystatin C and Outcomes in Patients with Cirrhosis and Acute Kidney Injury

Background. Acute kidney injury (AKI) is a common and severe complication in patients with cirrhosis. Progression of AKI to a higher stage associates with increased mortality. Intervening early in AKI when renal dysfunction is worsening may improve outcomes. However, serum creatinine correlates poorly with glomerular filtration in patients with cirrhosis and fluctuations may mask progression early in the course of AKI. Cystatin C, a low-molecular-weight cysteine proteinase inhibitor, is a potentially more accurate marker of glomerular filtration. Methods. We conducted a prospective multicenter study in patients with cirrhosis comparing changes in cystatin and creatinine immediately following onset of AKI as predictors of a composite endpoint of dialysis or mortality. Results. Of 106 patients, 37 (35%) met the endpoint. Cystatin demonstrated less variability between samples than creatinine. Patients were stratified into four groups reflecting changes in creatinine and cystatin: both unchanged or decreased 38 (36%) (Scr−/CysC−); only cystatin increased 25 (24%) (Scr−/CysC+); only creatinine increased 15 (14%) (Scr+/CysC−); and both increased 28 (26%) (Scr+/CysC+). With Scr−/CysC− as the reference, in both instances where cystatin rose, Scr−/CysC+ and Scr+/CysC+, the primary outcome was significantly more frequent in multivariate analysis, and , respectively. However, when only creatinine rose, outcomes were similar to the reference group. Conclusions. Changes in cystatin levels early in AKI are more closely associated with eventual dialysis or mortality than creatinine and may allow more rapid identification of patients at risk for adverse outcomes

Turbulent flow at 190 m height above London during 2006-2008: A climatology and the applicability of similarity theory

Flow and turbulence above urban terrain is more complex than above rural terrain, due to the different momentum and heat transfer characteristics that are affected by the presence of buildings (e.g. pressure variations around buildings). The applicability of similarity theory (as developed over rural terrain) is tested using observations of flow from a sonic anemometer located at 190.3 m height in London, U.K. using about 6500 h of data. Turbulence statistics—dimensionless wind speed and temperature, standard deviations and correlation coefficients for momentum and heat transfer—were analysed in three ways. First, turbulence statistics were plotted as a function only of a local stability parameter z/Λ (where Λ is the local Obukhov length and z is the height above ground); the σ_i/u_* values (i = u, v, w) for neutral conditions are 2.3, 1.85 and 1.35 respectively, similar to canonical values. Second, analysis of urban mixed-layer formulations during daytime convective conditions over London was undertaken, showing that atmospheric turbulence at high altitude over large cities might not behave dissimilarly from that over rural terrain. Third, correlation coefficients for heat and momentum were analyzed with respect to local stability. The results give confidence in using the framework of local similarity for turbulence measured over London, and perhaps other cities. However, the following caveats for our data are worth noting: (i) the terrain is reasonably flat, (ii) building heights vary little over a large area, and (iii) the sensor height is above the mean roughness sublayer depth

In-street wind direction variability in the vicinity of a busy intersection in central London

We present results from fast-response wind measurements within and above a busy intersection between two street canyons (Marylebone Road and Gloucester Place) in Westminster, London taken as part of the DAPPLE (Dispersion of Air Pollution and Penetration into the Local Environment; www.dapple.org.uk) 2007 field campaign. The data reported here were collected using ultrasonic anemometers on the roof-top of a building adjacent to the intersection and at two heights on a pair of lamp-posts on opposite sides of the intersection. Site characteristics, data analysis and the variation of intersection flow with the above-roof wind direction (θref) are discussed. Evidence of both flow channelling and recirculation was identified within the canyon, only a few metres from the intersection for along-street and across-street roof-top winds respectively. Results also indicate that for oblique rooftop flows, the intersection flow is a complex combination of bifurcated channelled flows, recirculation and corner vortices. Asymmetries in local building geometry around the intersection and small changes in the background wind direction (changes in 15-min mean θref of 5–10 degrees) were also observed to have profound influences on the behaviour of intersection flow patterns. Consequently, short time-scale variability in the background flow direction can lead to highly scattered in-street mean flow angles masking the true multi-modal features of the flow and thus further complicating modelling challenges

NTPDases in the neuroendocrine hypothalamus: Possible energy regulators of the positive gonadotrophin feedback

<p>Abstract</p> <p>Background</p> <p>Brain-derived ectonucleoside triphosphate diphosphohydrolases (NTPDases) have been known as plasma membrane-incorporated enzymes with their ATP-hydrolyzing domain outside of the cell. As such, these enzymes are thought to regulate purinergic intercellular signaling by hydrolyzing ATP to ADP-AMP, thus regulating the availability of specific ligands for various P2X and P2Y purinergic receptors. The role of NTPDases in the central nervous system is little understood. The two major reasons are the insufficient knowledge of the precise localization of these enzymes in neural structures, and the lack of specific inhibitors for the various NTPDases. To fill these gaps, we recently studied the presence of neuron-specific NTPDase3 in the mitochondria of hypothalamic excitatory neurons by morphological and functional methods. Results from those studies suggested that intramitochondrial regulation of ATP levels may play a permissive role in the neural regulation of physiological functions by tuning the level of ATP-carried energy that is needed for neuronal functions, such as neurotransmission and/or intracellular signaling.</p> <p>Presentation of the hypothesis</p> <p>In the lack of highly specific inhibitors, the determination of the precise function and role of NTPDases is hardly feasable. Yet, here we attempt to find an approach to investigate a possible role for hypothalamic NTPDase3 in the initiation of the midcycle luteinizing hormone (LH) surge, as such a biological role was implied by our recent findings. Here we hypothesize that NTPDase-activity in neurons of the AN may play a permissive role in the regulation of the estrogen-induced pituitary LH-surge.</p> <p>Testing the hypothesis</p> <p>We propose to test our hypothesis on ovariectomized rats, by stereotaxically injecting 17beta-estradiol and/or an NTPDase-inhibitor into the arcuate nucleus and determine the consequential levels of blood LH, mitochondrial respiration rates from arcuate nucleus synaptosomal preparations, NTPDase3-expression from arcuate nucleus tissue samples, all compared to sham and intact controls.</p> <p>Implications of the hypothesis</p> <p>Results from these studies may lead to the conclusion that estrogen may modulate the activity of mitochondrial, synapse-linked NTPDase3, and may show a correlation between mitochondrial NTPDase3-activity and the regulation of LH-release by estrogen.</p

Evaluation of fast atmospheric dispersion models in a regular street network

The need to balance computational speed and simulation accuracy is a key challenge in designing atmospheric dispersion models that can be used in scenarios where near real-time hazard predictions are needed. This challenge is aggravated in cities, where models need to have some degree of building-awareness, alongside the ability to capture effects of dominant urban flow processes. We use a combination of high-resolution large-eddy simulation (LES) and wind-tunnel data of flow and dispersion in an idealised, equal-height urban canopy to highlight important dispersion processes and evaluate how these are reproduced by representatives of the most prevalent modelling approaches: (i) a Gaussian plume model, (ii) a Lagrangian stochastic model and (iii) street-network dispersion models. Concentration data from the LES, validated against the wind-tunnel data, were averaged over the volumes of streets in order to provide a high-fidelity reference suitable for evaluating the different models on the same footing. For the particular combination of forcing wind direction and source location studied here, the strongest deviations from the LES reference were associated with mean over-predictions of concentrations by approximately a factor of 2 and with a relative scatter larger than a factor of 4 of the mean, corresponding to cases where the mean plume centreline also deviated significantly from the LES. This was linked to low accuracy of the underlying flow models/parameters that resulted in a misrepresentation of pollutant channelling along streets and of the uneven plume branching observed in intersections. The agreement of model predictions with the LES (which explicitly resolves the turbulent flow and dispersion processes) greatly improved by increasing the accuracy of building-induced modifications of the driving flow field. When provided with a limited set of representative velocity parameters, the comparatively simple street-network models performed equally well or better compared to the Lagrangian model run on full 3D wind fields. The study showed that street-network models capture the dominant building-induced dispersion processes in the canopy layer through parametrisations of horizontal advection and vertical exchange processes at scales of practical interest. At the same time, computational costs and computing times associated with the network approach are ideally suited for emergency-response applications

A review of planting principles to identify the right place for the right tree for ‘net zero plus’ woodlands: Applying a place‐based natural capital framework for sustainable, efficient and equitable (SEE) decisions

This is the final version. Available from Wiley via the DOI in this record. DATA AVAILABILITY STATEMENT: This is a review paper and has no original data to archive.We outline the principles of the natural capital approach to decision making and apply these to the contemporary challenge of very significantly expanding woodlands as contribution to attaining net zero emissions of greenhouse gases. Drawing on the case of the UK, we argue that a single focus upon carbon storage alone is likely to overlook the other ‘net zero plus’ benefits which woodlands can deliver. A review of the literature considers the wide variety of potential benefits which woodlands can provide, together with costs such as foregone alternative land uses. We argue that decision making must consider all of these potential benefits and costs for the right locations to be planted with the right trees. The paper closes by reviewing the decision support systems necessary to incorporate this information into policy and decision making. Read the free Plain Language Summary for this article on the Journal blog.Biotechnology and Biological Sciences Research CouncilTuring-HSBC-ONS Economic Data Science Awar

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Remineralization of particulate organic carbon in an ocean oxygen minimum zone

This work was funded by a NERC standard grant NE/E01559X/1