\u27Those Who Cling in Queer Corners To The Forgotten Tongues and Memories of an Elder Day\u27: J.R.R. Tolkien, Finns and Elves

Abstract Those Who Cling in Queer Corners To The Forgotten Tongues and Memories of an Elder Day\u27 J.R.R. Tolkien, Finns and Elves Dr. Andrew Higgins In this paper I will explore how several historic, literary and mythic associations of the Finnish people with elements of magic, the supernatural and the \u27other\u27 influenced J.R.R. Tolkien in imbuing the character and language of his own Elves with a similar quality of magic and \u27arresting strangeness\u27.I will explore several characterisations of the Finns, the People of Kalevala, Tolkien would have encountered in his early study of the Kalevala, several Old Norse and Anglo-Saxon texts as well as other characterisations drawn from more contemporary treatments of the supernatural elements of the Finns in Victorian and Edwardian sources.I will argue that the greatest influence of this connection can be see in two key elements of Tolkien\u27s mythology: first in Tolkien\u27s use of the Finnish language to create a phonetic sound-sense for his own invented language for the Elves of Qenya/Q(u)enya which would evoke a sense of \u27a forgotten tongue\u27. Secondly, in Tolkien\u27s early attempt to incorporate into his own mythology the character of the artisan Volundr, in his Anglo-Saxon characterization Weland, known to be both a son of a Finnish King and a \u27prince of Elves\u27 and who has survived to be one of the few known characters of the lost English mythology Tolkien was seeking to reimagine and repurpose. My paper will show how the literary constructions and mythic representations of the otherness and supernatural qualities of the Finns played its part in inspiring Tolkien to imbue his own Elves with a similar \u27queer\u27 and \u27strange\u27 quality in both their character, history and language who by the third age of Middle-earth did \u27cling in queer corners\u27 while remembering \u27the memories of an elder day\u27 until they were called back to Valinor

Osmotic response during kidney perfusion with cryoprotectant in isotonic or hypotonic vehicle solution

Organ cryopreservation would revolutionize transplantation by overcoming the shelf-life limitations of conventional organ storage. To prepare an organ for cryopreservation, it is first perfused with cryoprotectants (CPAs). These chemicals can enable vitrification during cooling, preventing ice damage. However, CPAs can also cause toxicity and osmotic damage. It is a major challenge to find the optimal balance between protecting the cells from ice and avoiding CPA-induced damage. In this study, we examined the organ perfusion process to shed light on phenomena relevant to cryopreservation protocol design, including changes in organ size and vascular resistance. In particular, we compared perfusion of kidneys (porcine and human) with CPA in either hypotonic or isotonic vehicle solution. Our results demonstrate that CPA perfusion causes kidney mass changes consistent with the shrink-swell response observed in cells. This response was observed when the kidneys were relatively fresh, but disappeared after prolonged warm and/or cold ischemia. Perfusion with CPA in a hypotonic vehicle solution led to a significant increase in vascular resistance, suggesting reduced capillary diameter due to cell swelling. This could be reversed by switching to perfusion with CPA in isotonic vehicle solution. Hypotonic vehicle solution did not cause notable osmotic damage, as evidenced by low levels of lactate dehydrogenase (LDH) in the effluent, and it did not have a statistically significant effect on the delivery of CPA into the kidney, as assessed by computed tomography (CT). Overall, our results show that CPA vehicle solution tonicity affects organ size and vascular resistance, which may have important implications for cryopreservation protocol design

Kynurenine monooxygenase blockade reduces endometriosis-like lesions, improves visceral hyperalgesia, and rescues mice from a negative behavioural phenotype in experimental endometriosis.

Endometriosis is a common and debilitating neuro-inflammatory disorder that is associated with chronic pain. Definitive diagnosis is based on the presence of endometrial-like tissue (lesions) in sites outside the uterus. Kynurenine monooxygenase (KMO) is a mitochondrial enzyme of tryptophan metabolism that regulates inflammation and immunity. Here, we show that KMO is expressed in epithelial cells in human endometriosis tissue lesions and in corresponding lesions in a mouse model of endometriosis. In mice, oral treatment with the potent KMO inhibitor KNS898 induced a biochemical state of KMO blockade with accumulation of kynurenine, diversion to kynurenic acid and ablation of 3-hydroxykynurenine production. In the mouse model of endometriosis, KMO inhibition improved histological outcomes and endometriosis pain-like behaviours, even when KNS898 treatment commenced one week after initiation of lesions. Taken together, these results suggest that KMO blockade is a promising new non-hormonal therapeutic modality for endometriosis

Trends and patterns in surface water chemistry in Europe and North America between 1990 and 2020, with a focus on calcium

Prosjektleder: Rolf David VogtThe report presents trends in major anions and cations, pH, TOC and bicarbonate in surface waters in Europe and North America from 1990 to 2020. Special attention is given to trends in calcium, which showed some unexpected increases. The trends in calcium are analysed in relation to changes in bicarbonates, organic anions, and deposition loads. The surface waters show strong signs of chemical recovery.Norwegian Ministry of Climate and Environment, United Nations Economic Commission for Europe (UNECE)publishedVersio

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease

Objective: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. Methods: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach. Results: An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study. Conclusions: These data do not justify use of CoQ as a treatment to slow functional decline in HD

STrengthening the REporting of Genetic Association Studies (STREGA)— An Extension of the STROBE Statement

Julian Little and colleagues present the STREGA recommendations, which are aimed at improving the reporting of genetic association studies

Identifying the need for good practices in Health Technology Assessment : summary of the ISPOR HTA Council Working Group Report on Good Practices in HTA

The systematic use of evidence to inform healthcare decisions, particularly health technology assessment (HTA), has gained increased recognition. HTA has become a standard policy tool for informing decision makers who must manage the entry and use of pharmaceuticals, medical devices, and other technologies (including complex interventions) within health systems, for example, through reimbursement and pricing. Despite increasing attention to HTA activities, there has been no attempt to comprehensively synthesize good practices or emerging good practices to support populationbased decision-making in recent years. After the identification of some good practices through the release of the ISPOR Guidelines Index in 2013, the ISPOR HTA Council identified a need to more thoroughly review existing guidance. The purpose of this effort was to create a basis for capacity building, education, and improved consistency in approaches to HTA-informed decision-making. Our findings suggest that although many good practices have been developed in areas of assessment and some other key aspects of defining HTA processes, there are also many areas where good practices are lacking. This includes good practices in defining the organizational aspects of HTA, the use of deliberative processes, and measuring the impact of HTA. The extent to which these good practices are used and applied by HTA bodies is beyond the scope of this report, but may be of interest to future researchers