On the need for bias correction in regional climate scenarios to assess climate change impacts on river runoff

In climate change impact research, the assessment of future river runoff as well as the catchment scale water balance is impeded by different sources of modeling uncertainty. Some research has already been done in order to quantify the uncertainty of climate 5 projections originating from the climate models and the downscaling techniques as well as from the internal variability evaluated from climate model member ensembles. Yet, the use of hydrological models adds another layer of incertitude. Within the QBic3 project (Qu´ebec-Bavaria International Collaboration on Climate Change) the relative contributions to the overall uncertainty from the whole model chain (from global climate 10 models to water management models) are investigated using an ensemble of multiple climate and hydrological models. Although there are many options to downscale global climate projections to the regional scale, recent impact studies tend to use Regional Climate Models (RCMs). One reason for that is that the physical coherence between atmospheric and land-surface 15 variables is preserved. The coherence between temperature and precipitation is of particular interest in hydrology. However, the regional climate model outputs often are biased compared to the observed climatology of a given region. Therefore, biases in those outputs are often corrected to reproduce historic runoff conditions from hydrological models using them, even if those corrections alter the relationship between temperature and precipitation. So, as bias correction may affect the consistency between RCM output variables, the use of correction techniques and even the use of (biased) climate model data itself is sometimes disputed among scientists. For those reasons, the effect of bias correction on simulated runoff regimes and the relative change in selected runoff indicators is explored. If it affects the conclusion of climate change analysis in 25 hydrology, we should consider it as a source of uncertainty. If not, the application of bias correction methods is either unnecessary in hydro-climatic projections, or safe to use as it does not alter the change signal of river runoff. The results of the present paper highlight the analysis of daily runoff simulated with four different hydrological models in two natural-flow catchments, driven by different regional climate models for a reference and a future period. As expected, bias correction of climate model outputs is important for the reproduction of the runoff regime of the 5 past regardless of the hydrological model used. Then again, its impact on the relative change of flow indicators between reference and future period is weak for most indicators with the exception of the timing of the spring flood peak. Still, our results indicate that the impact of bias correction on runoff indicators increases with bias in the climate simulations

An ensemble approach to assess hydrological models’ contribution to uncertainties in the analysis of climate change impact on water resources

Over the recent years, several research efforts investigated the impact of climate change on water resources for different regions of the world. The projection of future river flows is affected by different sources of uncertainty in the hydro-climatic modelling chain. One of the aims of the QBic3 5 project (Que´bec-Bavarian International Collaboration on Climate Change) is to assess the contribution to uncertainty of hydrological models by using an ensemble of hydrological models presenting a diversity of structural complexity (i.e. lumped, semi distributed and distributed models). The study investigates two humid, mid-latitude catchments with natural flow conditions; one located in 10 Southern Que´bec (Canada) and one in Southern Bavaria (Germany). Daily flow is simulated with four different hydrological models, forced by outputs from regional climate models driven by a given number of GCMs’ members over a reference (1971–2000) and a future (2041–2070) periods. The results show that the choice of the hydrological model does strongly affect the climate change response of selected hydrological indicators, especially those related to low flows. Indicators related to high flows seem less sensitive on the choice of the hydrological model. Therefore, the computationally less demanding models (usually simple, lumped and conceptual) give a significant level of trust for high and overall mean flows

Multicentre, prospective, double-blind, randomised controlled clinical trial comparing different non-opioid analgesic combinations with morphine for postoperative analgesia: the OCTOPUS study

BACKGROUND: Head-to-head comparisons of combinations of more than one non-opioid analgesic (NOA) with morphine alone, for postoperative analgesia, are lacking. The objective of this multicentre, randomised, double-blind controlled trial was to compare the morphine-sparing effects of different combinations of three NOAs-paracetamol (P), nefopam (N), and ketoprofen (K)-for postoperative analgesia. METHODS: Patients from 10 hospitals were randomised to one of eight groups: control (C) received saline as placebo, P, N, K, PN, PK, NK, and PNK. Treatments were given intravenously four times a day during the first 48 h after surgery, and morphine patient-controlled analgesia was used as rescue analgesia. The outcome measures were morphine consumption, pain scores, and morphine-related side-effects evaluated 24 and 48 h after surgery. RESULTS: Two hundred and thirty-seven patients undergoing a major surgical procedure were included between July 2013 and November 2016. Despite a failure to reach a calculated sample size, 24 h morphine consumption [median (inter-quartile range)] was significantly reduced in the PNK group [5 (1-11) mg] compared with either the C group [27 (11-42) mg; P<0.05] or the N group [21 (12-29) mg; P<0.05]. Results were similar 48 h after surgery. Patients experienced less pain in the PNK group compared with the C, N, and P groups. No difference was observed in the incidence of morphine-related side-effects. CONCLUSIONS: Combining three NOAs with morphine allows a significant morphine sparing for 48 h after surgery associated with superior analgesia the first 24 h when compared with morphine alone. CLINICAL TRIAL REGISTRATION: EudraCT: 2012-004219-30; NCT01882530

Adaptation strategy to mitigate the impact of climate change on water resources in arid and semi-arid regions : a case study

Climate change and drought phenomena impacts have become a growing concern for water resources engineers and policy makers, mainly in arid and semi-arid areas. This study aims to contribute to the development of a decision support tool to prepare water resources managers and planners for climate change adaptation. The Hydrologiska Byråns Vattenbalansavdelning (The Water Balance Department of the Hydrological Bureau) hydrologic model was used to define the boundary conditions for the reservoir capacity yield model comprising daily reservoir inflow from a representative example watershed with the size of 14,924 km2 into a reservoir with the capacity of 6.80 Gm3. The reservoir capacity yield model was used to simulate variability in climate change-induced differences in reservoir capacity needs and performance (operational probability of failure, resilience, and vulnerability). Owing to the future precipitation reduction and potential evapotranspiration increase during the worst case scenario (−40% precipitation and +30% potential evapotranspiration), substantial reductions in streamflow of between −56% and −58% are anticipated for the dry and wet seasons, respectively. Furthermore, model simulations recommend that as a result of future climatic conditions, the reservoir operational probability of failure would generally increase due to declined reservoir inflow. The study developed preparedness plans to combat the consequences of climate change and drought

An ensemble approach to assess hydrological models' contribution to uncertainties in the analysis of climate change impact on water resources

Over the recent years, several research efforts investigated the impact of climate change on water resources for different regions of the world. The projection of future river flows is affected by different sources of uncertainty in the hydro-climatic modelling chain. One of the aims of the QBic<sup>3</sup> project (Québec-Bavarian International Collaboration on Climate Change) is to assess the contribution to uncertainty of hydrological models by using an ensemble of hydrological models presenting a diversity of structural complexity (i.e., lumped, semi distributed and distributed models). The study investigates two humid, mid-latitude catchments with natural flow conditions; one located in Southern Québec (Canada) and one in Southern Bavaria (Germany). Daily flow is simulated with four different hydrological models, forced by outputs from regional climate models driven by global climate models over a reference (1971–2000) and a future (2041–2070) period. The results show that, for our hydrological model ensemble, the choice of model strongly affects the climate change response of selected hydrological indicators, especially those related to low flows. Indicators related to high flows seem less sensitive on the choice of the hydrological model

Hemodynamic impact of isobaric levobupivacaine versus hyperbaric bupivacaine for subarachnoid anesthesia in patients aged 65 and older undergoing hip surgery

BackgroundThe altered hemodynamics, and therefore the arterial hypotension is the most prevalent adverse effect after subarachnoid anesthesia. The objective of the study was to determine the exact role of local anesthetic selection underlying spinal anesthesia-induced hypotension in the elderly patient. We conducted a descriptive, observational pilot study to assess the hemodynamic impact of subarachnoid anesthesia with isobaric levobupivacaine versus hyperbaric bupivacaine for hip fracture surgery.DescriptionHundred twenty ASA status I-IV patients aged 65 and older undergoing hip fracture surgery were enrolled. The primary objective of our study was to compare hemodynamic effects based on systolic blood pressure (SBP) and dyastolic blood pressure (DBP) values, heart rate (HR) and hemoglobin (Hb) and respiratory effects based on partial oxygen saturation (SpO2%) values. The secondary objective was to assess potential adverse events with the use of levobupivacaine versus bupivacaine. Assessments were performed preoperatively, at 30 minutes into surgery, at the end of anesthesia and at 48 hours and 6 months after surgery.Among intraoperative events, the incidence of hypotension was statistically significantly higher (p <0.05) in group BUPI (38.3%) compared to group LEVO (13.3%). There was a decrease (p <0.05) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at 30 minutes intraoperatively (19% in group BUPI versus 17% in group LEVO). SpO2% increased at 30 minutes after anesthesia onset (1% in group BUPI versus 1.5% in group LEVO). Heart rate (HR) decreased at 30 minutes after anesthesia onset (5% in group BUPI versus 9% in group L). Hemoglobin (Hb) decreased from time of operating room (OR) admission to the end of anesthesia (9.3% in group BUPI versus 12.5% in group LEVO). The incidence of red blood cell (RBC) transfusion was 13.3% in group BUPI versus 31.7% in group LEVO, this difference was statistically significant. Among postoperative events, the incidence of congestive heart failure (CHF) was significantly higher in group BUPI (8,3%). At 6 months after anesthesia, no differences were found.ConclusionsGiven the hemodynamic stability and lower incidence of intraoperative hypotension observed, levobupivacaine could be the agent of choice for subarachnoid anesthesia in elderly patients

StearoylCoA Desaturase-5: A Novel Regulator of Neuronal Cell Proliferation and Differentiation

Recent studies have demonstrated that human stearoylCoA desaturase-1 (SCD1), a Δ9-desaturase that converts saturated fatty acids (SFA) into monounsaturated fatty acids, controls the rate of lipogenesis, cell proliferation and tumorigenic capacity in cancer cells. However, the biological function of stearoylCoA desaturase-5 (SCD5), a second isoform of human SCD that is highly expressed in brain, as well as its potential role in human disease, remains unknown. In this study we report that the constitutive overexpression of human SCD5 in mouse Neuro2a cells, a widely used cell model of neuronal growth and differentiation, displayed a greater n-7 MUFA-to-SFA ratio in cell lipids compared to empty-vector transfected cells (controls). De novo synthesis of phosphatidylcholine and cholesterolesters was increased whereas phosphatidylethanolamine and triacylglycerol formation was reduced in SCD5-expressing cells with respect to their controls, suggesting a differential use of SCD5 products for lipogenic reactions. We also observed that SCD5 expression markedly accelerated the rate of cell proliferation and suppressed the induction of neurite outgrowth, a typical marker of neuronal differentiation, by retinoic acid indicating that the desaturase plays a key role in the mechanisms of cell division and differentiation. Critical signal transduction pathways that are known to modulate these processes, such epidermal growth factor receptor (EGFR)Akt/ERK and Wnt, were affected by SCD5 expression. Epidermal growth factor-induced phosphorylation of EGFR, Akt and ERK was markedly blunted in SCD5-expressing cells. Furthermore, the activity of canonical Wnt was reduced whereas the non-canonical Wnt was increased by the presence of SCD5 activity. Finally, SCD5 expression increased the secretion of recombinant Wnt5a, a non-canonical Wnt, whereas it reduced the cellular and secreted levels of canonical Wnt7b. Our data suggest that, by a coordinated modulation of key lipogenic pathways and transduction signaling cascades, SCD5 participates in the regulation of neuronal cell growth and differentiation

Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments.

BACKGROUND: Enhanced macromolecule biosynthesis is integral to growth and proliferation of cancer cells. Lipid biosynthesis has been predicted to be an essential process in cancer cells. However, it is unclear which enzymes within this pathway offer the best selectivity for cancer cells and could be suitable therapeutic targets. RESULTS: Using functional genomics, we identified stearoyl-CoA desaturase (SCD), an enzyme that controls synthesis of unsaturated fatty acids, as essential in breast and prostate cancer cells. SCD inhibition altered cellular lipid composition and impeded cell viability in the absence of exogenous lipids. SCD inhibition also altered cardiolipin composition, leading to the release of cytochrome C and induction of apoptosis. Furthermore, SCD was required for the generation of poly-unsaturated lipids in cancer cells grown in spheroid cultures, which resemble those found in tumour tissue. We also found that SCD mRNA and protein expression is elevated in human breast cancers and predicts poor survival in high-grade tumours. Finally, silencing of SCD in prostate orthografts efficiently blocked tumour growth and significantly increased animal survival. CONCLUSIONS: Our data implicate lipid desaturation as an essential process for cancer cell survival and suggest that targeting SCD could efficiently limit tumour expansion, especially under the metabolically compromised conditions of the tumour microenvironment