Weather derivatives pricing and risk management applications

The main objective of this paper is to discuss suitable methods for the modelling of weather variables and to bring together much of the current thinking in terms of the pricing of their respective derivative contracts (CDD, HDD) with payoffs depending on temperature. In addition to the theoretical overview provided, an empirical investigation is undertaken using historical data from the De Bilt meteorological station: we use the aforementioned data to first suggest a stochastic process that describes the evolution of the temperature. Further, such temperature modelling phase is accompanied by the numerical technique of Monte Carlo simulation for derivatives pricing. Finally, we will analyse some weather-sensitive industries and discuss possible weather hedging strategies they could apply

Subanesthetic IV ketamine reduces acute suicidal ideation in patients with mood disorders

Background. Depression and suicide are common in the United States and present a significant problem in the healthcare landscape. Currently, there are few options that can rapidly reduce suicidal ideation in patients with depression. Ketamine, a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to reduce acute suicidality in patients with depression. Previous studies have a reduction of suicidal ideation compared to saline placebo, but few studies have shown a significant effect compared to a similar psychoactive drug such as midazolam. Method. A search of PubMed and PsychNET was performed in September 2018 using the terms “ketamine,” “suicide,” and “depression” with a filter for human clinical trials. Three randomized controlled trials were discovered that compared the effects of intravenous (IV) ketamine or midazolam on active, acute suicidal ideation in patients with a history of depression. Suicidal ideation and depression were measured using similar scales to allow for relative comparison between studies. Baseline measurements of suicidal ideation were assessed before IV administration of the randomized medications, and repeat assessments were obtained 24 hours after administration of the medication. Results. All three studies evaluated showed a reduction in suicidal ideation in patients that received ketamine compared to those that received midazolam. Grunebaum et al. and Price et al. both saw statistically significant reductions in SI in patients who received ketamine and assessed with the Beck Scale for Suicidal Ideation (BSI) or the Scale for Suicidal Ideation (SSI). Murrough et al. observed a nonsignificant reduction in SI at 24 hours using the BSI, but did see a statistically significant reduction using the Montgomery-Asberg Depression Rating Scale (MADRS-SI). SI was reduced in the midazolam group in all studies, but none were significant, and none as extensive as the ketamine groups. Conclusion. Ketamine administered at subanesthetic doses can provide acute relief of suicidal ideation in patients with depression within 24 hours

transferable drug resistance in escherichia coli isolated from antibiotic fed chickens

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Silver fir (Abies alba Mill.) is able to thrive and prosper under meso-Mediterranean conditions

The potential ecological envelope of silver fir (Abies alba Mill.) based on its present distribution suggests a high suitability for moist rather than warm and dry environments. This contrasts with paleoecological evidence reporting its former presence at low elevations under meso-Mediterranean conditions. In this study, we evaluated the growth performance of silver fir at low elevation (20–60 m a.s.l.) under meso-Mediterranean climatic conditions in Tuscany (central Italy). We conducted a dendroecological analysis on Abies alba trees along a geomorphological gradient (from depression to upper slope conditions). Climate-growth relationships were assessed by means of correlations, response functions, pointer years, and superposed epoch analysis. Silver fir was found to grow and regenerate well in these stands mixed with evergreen (e.g., Quercus ilex L.) and thermophilous deciduous Mediterranean tree species (e.g., Q. cerris L.). Summer drought was the most growth-influencing factor, with immediate (i.e., current season) negative impacts on tree-ring widths (TRW). No significant impacts were observed in the four years following extreme summer droughts, but the TRW series (which started between the 1930s and 1950s) showed a growth decline since the mid-1990s that is likely drought-related. Our results show that, provided there is a sufficiently large soil water holding capacity, silver fir provenances exist which are able to withstand Mediterranean summer droughts, can naturally and regularly regenerate in these systems, and may even dominate over typical meso-Mediterranean species. As long as annual precipitation is not too low (i.e., >850 mm) and summer drought conditions not too extreme (i.e., less than three months), silver fir has thus the potential to thrive under warm Mediterranean conditions.ISSN:0378-1127ISSN:1872-704

sodium calcium exchanger as main effector of endogenous neuroprotection elicited by ischemic tolerance

Abstract The ischemic tolerance (IT) paradigm represents a fundamental cell response to certain types or injury able to render an organ more "tolerant" to a subsequent, stronger, insult. During the 16th century, the toxicologist Paracelsus described for the first time the possibility that a noxious event might determine a state of tolerance. This finding was summarized in one of his most important mentions: "The dose makes the poison". In more recent years, ischemic tolerance in the brain was first described in 1991, when it was demonstrated by Kirino and collaborators that two minutes of subthreshold brain ischemia in gerbils produced tolerance against global brain ischemia. Based on the time in which the conditioning stimulus is applied, it is possible to define preconditioning, perconditioning and postconditioning, when the subthreshold insult is applied before, during or after the ischemic event, respectively. Furthermore, depending on the temporal delay from the ischemic event, two different modalities are distinguished: rapid or delayed preconditioning and postconditioning. Finally, the circumstance in which the conditioning stimulus is applied on an organ distant from the brain is referred as remote conditioning. Over the years the "conditioning" paradigm has been applied to several brain disorders and a number of molecular mechanisms taking part to these protective processes have been described. The mechanisms are usually classified in three distinct categories identified as triggers, mediators and effectors. As concerns the putative effectors, it has been hypothesized that brain cells appear to have the ability to adapt to hypoxia by reducing their energy demand through modulation of ion channels and transporters, which delays anoxic depolarization. The purpose of the present review is to summarize the role played by plasmamembrane proteins able to control ionic homeostasis in mediating protection elicited by brain conditioning, particular attention will be deserved to the role played by Na+/Ca2+ exchanger

Models and methods for conditioning the ischemic brain

Abstract Background In the last decades the need to find new neuroprotective targets has addressed the researchers to investigate the endogenous molecular mechanisms that brain activates when exposed to a conditioning stimulus. Indeed, conditioning is an adaptive biological process activated by those interventions able to confer resistance to a deleterious brain event through the exposure to a sub-threshold insult. Specifically, preconditioning and postconditioning are realized when the conditioning stimulus is applied before or after, respectively, the harmul ischemia. Aims and Results The present review will describe the most common methods to induce brain conditioning, with particular regards to surgical, physical exercise, temperature-induced and pharmacological approaches. It has been well recognized that when the subliminal stimulus is delivered after the ischemic insult, the achieved neuroprotection is comparable to that observed in models of ischemic preconditioning. In addition, subjecting the brain to both preconditioning as well as postconditioning did not cause greater protection than each treatment alone. Conclusions The last decades have provided fascinating insights into the mechanisms and potential application of strategies to induce brain conditioning. Since the identification of intrinsic cell‐survival pathways should provide more direct opportunities for translational neuroprotection trials, an accurate examination of the different models of preconditioning and postconditioning is mandatory before starting any new project

Resveratrol via sirtuin-1 downregulates RE1-silencing transcription factor (REST) expression preventing PCB-95-induced neuronal cell death

Resveratrol (3,5,4'-trihydroxystilbene) (RSV), a polyphenol widely present in plants, exerts a neuroprotective function in several neurological conditions; it is an activator of class III histone deacetylase sirtuin1 (SIRT1), a crucial regulator in the pathophysiology of neurodegenerative diseases. By contrast, the RE1-silencing transcription factor (REST) is involved in the neurotoxic effects following exposure to polychlorinated biphenyl (PCB) mixture A1254. The present study investigated the effects of RSV-induced activation of SIRT1 on REST expression in SH-SY5Y cells. Further, we investigated the possible relationship between the non-dioxin-like (NDL) PCB-95 and REST through SIRT1 to regulate neuronal death in rat cortical neurons. Our results revealed that RSV significantly decreased REST gene and protein levels in a dose- and time-dependent manner. Interestingly, overexpression of SIRT1 reduced REST expression, whereas EX-527, an inhibitor of SIRT1, increased REST expression and blocked RSV-induced REST downregulation. These results suggest that RSV downregulates REST through SIRT1. In addition, RSV enhanced activator protein 1 (AP-1) transcription factor c-Jun expression and its binding to the REST promoter gene. Indeed, c-Jun knockdown reverted RSV-induced REST downregulation. Intriguingly, in SH-SY5Y cells and rat cortical neurons the NDL PCB-95 induced necrotic cell death in a concentration-dependent manner by increasing REST mRNA and protein expression. In addition, SIRT1 knockdown blocked RSV-induced neuroprotection in rat cortical neurons treated with PCB-95. Collectively, these results indicate that RSV via SIRT1 activates c-Jun, thereby reducing REST expression in SH-SY5Y cells under physiological conditions and blocks PCB-95-induced neuronal cell death by activating the same SIRT1/c-Jun/REST pathway

isolated aldosterone deficiency in two infants mistakes and dilemmas in the diagnosis and treatment of a rare disease

In this article, we describe the clinical picture and follow-up of two children diagnosed as suffering from pseudohypoaldosteronism when they were infants, and it was later recognized as isolated aldosterone deficiency in both. We illustrate the clinical differences between the two patients in terms of hydroelectrolytic balance, laboratory data and growth. In fact, while the growth and hematological parameters of the electrolytes and acid-base balance were normal in the first patient, and also without treatment with fludrocortisone thanks to very high renin activity, in the second patient, this treatment was vitally necessary to maintain normal growth and biochemical data. Despite the absence of a molecular analysis which could have confirmed this diagnosis, we believe that the description of the clinical evolution of these two cases from the moment of the incorrect diagnosis until the correct diagnosis and action taken, could be useful to highlight the extreme clinical variability of this rare disease

Changes in the expression of extracellular regulated kinase (ERK 1/2) in the R6/2 mouse model of Huntington's disease after phosphodiesterase IV inhibition

The mitogen-activated protein kinases (MAPKs) superfamily comprises three major signaling pathways: the extracellular signal-regulated protein kinases (ERKs), the c-Jun N-terminal kinases or stress-activated protein kinases (JNKs/SAPKs) and the p38 family of kinases.ERK 1/2 signaling has been implicated in a number of neurodegenerative disorders, including Huntington's disease (HD). Phosphorylation patterns of ERK 1/2 and JNK are altered in cell models of HD. In this study, we aimed at studying the correlations between ERK 1/2 and the neuronal vulnerability to HD degeneration in the R6/2 transgenic mouse model of HD. Single and double-label immunofluorescence for phospho-ERK (pERK, the activated form of ERK) and for each of the striatal neuronal markers were employed on perfusion-fixed brain sections from R6/2 and wild-type mice. Moreover, Phosphodiesterase 4 inhibition through rolipram was used to study the effects on pERK expression in the different types of striatal neurons. We completed our study with western blot analysis. Our study shows that pERK levels increase with age in the medium spiny striatal neurons and in the parvalbumin interneurons, and that rolipram counteracts such increase in pERK. Conversely, cholinergic and somatostatinergic interneurons of the striatum contain higher levels of pERK in the R6/2 mice compared to the controls. Rolipram induces an increase in pERK expression in these interneurons. Thus, our study confirms and extends the concept that the expression of phosphorylated ERK 1/2 is related to neuronal vulnerability and is implicated in the pathophysiology of cell death in HD. (C) 2012 Elsevier Inc. All rights reserved

Immune Checkpoints as Therapeutic Targets in Autoimmunity

Antibodies that block the immune checkpoint receptors PD1 and CTLA4 have revolutionized the treatment of melanoma and several other cancers, but in the process, a new class of drug side effect has emerged—immune related adverse events. The observation that therapeutic blockade of these inhibitory receptors is sufficient to break self-tolerance, highlights their crucial role in the physiological modulation of immune responses. Here, we discuss the rationale for targeting immune checkpoint receptors with agonistic agents in autoimmunity, to restore tolerance when it is lost. We review progress that has been made to date, using Fc-fusion proteins, monoclonal antibodies or other novel constructs to induce immunosuppressive signaling through these pathways. Finally, we explore potential mechanisms by which these receptors trigger and modulate immune cell function, and how understanding these processes might shape the design of more effective therapeutic agents in future