Statistical bias correction for daily precipitation in regional climate models over Europe

We design, apply, and validate a methodology for correcting climate model output to produce internally consistent fields that have the same statistical intensity distribution as the observations. We refer to this as a statistical bias correction. Validation of the methodology is carried out using daily precipitation fields, defined over Europe, from the ENSEMBLES climate model dataset. The bias correction is calculated using data from 1961 to 1970, without distinguishing between seasons, and applied to seasonal data from 1991 to 2000. This choice of time periods is made to maximize the lag between calibration and validation within the ERA40 reanalysis period. Results show that the method performs unexpectedly well. Not only are the mean and other moments of the intensity distribution improved, as expected, but so are a drought and a heavy precipitation index, which depend on the autocorrelation spectra. Given that the corrections were derived without seasonal distinction and are based solely on intensity distributions, a statistical quantity oblivious of temporal correlations, it is encouraging to find that the improvements are present even when seasons and temporal statistics are considered. This encourages the application of this method to multi-decadal climate projections

Unusual compulsive motor activity during treatment with clothiapine in a mentally retarded adolescent

Atypical antipsychotic agents, specifically those with a high hyposerotonergic activity such as clozapine and clothiapine, have been associated with de novo obsessive–compulsive symptoms. We report the case of a 16-year-old adolescent male with severe mental impairment and disruptive behaviour who developed a compulsive head and body turning disorder on clothiapine. Such a symptom had to be distinguished from epileptic partial seizures; it promptly disappeared with the drug discontinuation

Comparison of the Toxicological Effects of Pesticides in Non-Tumorigenic MCF-12A and Tumorigenic MCF-7 Human Breast Cells

Humans are exposed to residues of organophosphate and neonicotinoid pesticides, commonly used in agriculture. Children are particularly vulnerable and, among possible adverse outcomes, the increased incidence of premature mammary gland development (thelarche) has raised concern. We evaluated the toxicological effects of chlorpyrifos (CPF), imidacloprid (IMI) and glyphosate (GLY) at exposure concentrations occurring in children on the tumorigenic MCF-7 and non-tumorigenic MCF-12A breast cell lines, as representative of the target organ model, assessing cytotoxicity, apoptosis, necrosis, intracellular reactive oxygen species (ROS) and ATP levels, 17β-estradiol secretion and gene expression of nuclear receptors involved in mammary gland development. The pesticides decreased cell vitality in MCF-7 and cell proliferation in MCF-12A cells. ATP levels were decreased in MCF-7 cells by pesticides and apoptosis was increased in MCF-12A cells only by GLY (2.3 nM). ROS production was decreased by pesticides in both cell lines, except IMI (1.6 nM) in MCF-7 cells. Endocrine disrupting activity was highlighted by induction of 17β-estradiol secretion and modulation of the gene expression of estrogen alpha and beta, progesterone, androgen, and aryl hydrocarbon receptors in both cell lines. The use of MCF-7 and MCF-12A cells highlighted dissimilar modes of action of each pesticide at low human relevant concentrations

Effects of balloon injury on neointimal hyperplasia in steptozotocin-induced diabetes and in hyperinsulinemic nondiabetic pancreatic islet-transplanted rats.

BACKGROUND: The mechanisms of increased neointimal hyperplasia after coronary interventions in diabetic patients are still unknown. METHODS AND RESULTS: Glucose and insulin effects on in vitro vascular smooth muscle cell (VSMC) proliferation and migration were assessed. The effect of balloon injury on neointimal hyperplasia was studied in streptozotocin-induced diabetic rats with or without adjunct insulin therapy. To study the effect of balloon injury in nondiabetic rats with hyperinsulinemia, pancreatic islets were transplanted under the kidney capsule in normal rats. Glucose did not increase VSMC proliferation and migration in vitro. In contrast, insulin induced a significant increase in VSMC proliferation and migration in cell cultures. Furthermore, in VSMC culture, insulin increased MAPK activation. A reduction in neointimal hyperplasia was consistently documented after vascular injury in hyperglycemic streptozotocin-induced diabetic rats. Insulin therapy significantly increased neointimal hyperplasia in these rats. This effect of hyperinsulinemia was totally abolished by transfection on the arterial wall of the N17H-ras-negative mutant gene. Finally, after experimental balloon angioplasty in hyperinsulinemic nondiabetic islet-transplanted rats, a significant increase in neointimal hyperplasia was observed. CONCLUSIONS: In rats with streptozotocin-induced diabetes, balloon injury was not associated with an increase in neointimal formation. Exogenous insulin administration in diabetic rats and islet transplantation in nondiabetic rats increased both blood insulin levels and neointimal hyperplasia after balloon injury. Hyperinsulinemia through activation of the ras/MAPK pathway, rather than hyperglycemia per se, seems to be of crucial importance in determining the exaggerated neointimal hyperplasia after balloon angioplasty in diabetic animals

The effects of claw ligatures in American lobster (Homarus americanus) storage: a preliminary study of haemolymph parameters

American lobsters are crustaceans that are offered for sale live and are stored in controlled temperature recirculating aquaria. During their marketing they are subjected to stressors that can affect their welfare, such as air exposure, confinement and handling. European legislation does not provide specific criteria or retention requirements, and so their management depends largely on the common sense of food business operators. Claw ligatures before and during storage are not legally required but are recommended because they prevent lobsters from damaging each other and ensure workers\u2019 safety. The aim of the present study is to evaluate the effect of claw ligatures on lobsters\u2019 welfare by analysing eight different haemolymph stress parameters, vitality and weight. The calcium level showed statistical differences in the two experimental groups (P < 0.05). Our results suggested that the absence of rubber bands did not offer any significant contribution to the lobsters\u2019 welfare

Low- vs high-dose ARNI effects on clinical status, exercise performance and cardiac function in real-life HFrEF patients

Purpose: Only a few studies are available on dose-related effects of sacubitril/valsartan (angiotensin receptor neprilysin inhibition (ARNI)) in real-life patients with heart failure and reduced ejection fraction (HFrEF). We sought to investigate clinical and functional effects in real-life HFrEF patients receiving ARNI at a different cumulative dose. Methods: This was an observational study in consecutive outpatients admitted for HFrEF from October 2017 to June 2019. The PARADIGM criteria were needed for enrolment. ARNI was uptitrated according to blood pressure, drug tolerability, renal function and kaliemia. At least 10-month follow-up was required in each patient. Clinical assessment, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, 6-min walk test and strain echocardiography were performed in each patient on a regular basis during the observational period. At the end of the study, patients were divided into two groups based on the median yearly dose of the ARNI medication. Results: A total of 90 patients, 64 \ub1 11 years, 82% males, were enrolled. The cut-off dose was established in 75 mg BID, and the study population was divided into group A ( 64 75 mg), 52 patients (58%), and group B (> 75 mg), 38 patients (42%). The follow-up duration was 12 months (range 11\u201313). NYHA class, KCCQ score and 6MWT performance ameliorated in both groups, with a quicker time to benefit in group B. The proportion of patients walking > 350 m increased from 21 to 58% in group A (p < 0.001), and from 29 to 82% in group B (p < 0.001). A positive effect was also disclosed in the left ventricular remodelling, strain deformation and diastolic function. Conclusion: One-year ARNI treatment was effective in our real-life HFrEF patient population, leading to clinical and functional improvement in both study groups, slightly greater and with a shorter time to benefit in group B

International earth science information network for global change decision making

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77259/1/AIAA-1991-154-296.pd