Distinguishing Discourses of the Dísir

ABSTRACT: Previous studies of the dísir have tended to focus on either their links with fertility or use of the term to designate a wide range of supranatural female figures. This study reassesses the textual evidence for the nature of these beings, applying Jens Peter Schjødt’s notion of “discourse” to argue that we should not be searching for a single coherent category of beings. Rather, it argues, our sources depict three semidistinct “dísir” discourses: a group of prosperity-focused female figures with strong links to local landscapes worshipped during the late pagan Iron Age; the use of the signifier “dís” as a poetic synonym for a range of female figures in verse; and a medieval textual discourse of “martial dísir” construed on the basis of poetic texts, but which has no basis in pre-Christian religion. RESUME: Tidligere studier af diserne har haft en tendens til at fokusere enten på deres forbindelse til frugtbarhed eller på brugen af termen til at beskrive en bred vifte af overnaturlige kvindeskikkelser. Dette studier revurderer tekstgrundlaget for disse væseners natur og benytter Jens Peter Schjødts begreb ”diskurs” til at argumentere for, at der ikke er tale om én standardiseret kategori af væsener. I stedet argumenteres der for, at kilderne afslører tre mere eller mindre særskilte diskurser om ”dísir”: En gruppe kvindefigurer med fokus på velstand med stærke bånd til lokale landskaber, som blev dyrket i den sene jernalder; brugen af termen ”dís” som et poetisk synonym for diverse kvindeskikkelser i digte; og en middelalderlig tekstdiskurs omkring ”krigeriske dísir” konstrueret ud fra poetiske tekster, men uden understøttelse in førkristen religion

Processioner i førkristen nordisk religion

English abstract: No systematic survey of processions in pre-Christian Scandinavian religion has yet been attempted, in line with the lack of research on processions in the Study of Religion more generally. This article examines the written, archaeological, and iconographic material and applies Bernhard Lang’s typology of processions in order to describe the functions of the pre-Christian Scandinavian processions. The tentative conclusion it offers is that processions in the pre-Christian North can be divided into two categories: a group of circulatory processions of a predominantly hierophoric type often connected with fertility; and a group of linear processions of a predominantly hierophoric-functional type often connected with funerary rituals.Dansk resume: En undersøgelse af processioner i førkristen nordisk religion er ikke tidligere blevet gjort systematisk ‒ i lighed med den generelle mangel på forskning om processioner i Religionsvidenskaben. Både det skriftlige, arkæologiske og ikonografiske materiale undersøges, og Bernhard Langs processionstypologi benyttes til at beskrive de fundne processioners funktion. Den tentative konklusion er, at processioner i det førkristne Norden kan ses i to grupper: En gruppe af cirkulerende, overvejende hierofore processioner forbundet med frugtbarhed og en anden gruppe af lineære, overvejende hierofor-funktionelle processioner, ofte forbundet med begravelsesritualer

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CaMKK2 as an emerging treatment target for bipolar disorder

Current pharmacological treatments for bipolar disorder are inadequate and based on serendipitously discovered drugs often with limited efficacy, burdensome side-effects, and unclear mechanisms of action. Advances in drug development for the treatment of bipolar disorder remain incremental and have come largely from repurposing drugs used for other psychiatric conditions, a strategy that has failed to find truly revolutionary therapies, as it does not target the mood instability that characterises the condition. The lack of therapeutic innovation in the bipolar disorder field is largely due to a poor understanding of the underlying disease mechanisms and the consequent absence of validated drug targets. A compelling new treatment target is the Ca2+-calmodulin dependent protein kinase kinase-2 (CaMKK2) enzyme. CaMKK2 is highly enriched in brain neurons and regulates energy metabolism and neuronal processes that underpin higher order functions such as long-term memory, mood, and other affective functions. Loss-of-function polymorphisms and a rare missense mutation in human CAMKK2 are associated with bipolar disorder, and genetic deletion of Camkk2 in mice causes bipolar-like behaviours similar to those in patients. Furthermore, these behaviours are ameliorated by lithium, which increases CaMKK2 activity. In this review, we discuss multiple convergent lines of evidence that support targeting of CaMKK2 as a new treatment strategy for bipolar disorder

Humanity’s Best Friend: A Dog-Centric Approach to Addressing Global Challenges

No other animal has a closer mutualistic relationship with humans than the dog (Canis familiaris). Domesticated from the Eurasian grey wolf (Canis lupus), dogs have evolved alongside humans over millennia in a relationship that has transformed dogs and the environments in which humans and dogs have co-inhabited. The story of the dog is the story of recent humanity, in all its biological and cultural complexity. By exploring human-dog-environment interactions throughout time and space, it is possible not only to understand vital elements of global history, but also to critically assess our present-day relationship with the natural world, and to begin to mitigate future global challenges. In this paper, co-authored by researchers from across the natural and social sciences, arts and humanities, we argue that a dog-centric approach provides a new model for future academic enquiry and engagement with both the public and the global environmental agenda

Superiority and cost-effectiveness of monthly extended-release buprenorphine versus daily standard of care medication: a pragmatic, parallel-group, open-label, multicentre, randomised, controlled, phase 3 trial

BACKGROUND: Daily methadone maintenance or buprenorphine treatment is the standard-of-care (SoC) medication for opioid use disorder (OUD). Subcutaneously injected, extended-release buprenorphine (BUP-XR) may be more effective-but there has been no superiority evaluation.METHODS: This pragmatic, parallel-group, open-label, multi-centre, effectiveness superiority randomised, controlled, phase 3 trial was conducted at five National Health Service community-based treatment clinics in England and Scotland. Participants (adults aged ≥ 18 years; all meeting DSM-5 diagnostic criteria for moderate or severe OUD at admission to their current maintenance treatment episode) were randomly assigned (1:1) to receive continued daily SoC (liquid methadone (usual dose range: 60-120 mg) or sublingual/transmucosal buprenorphine (usual dose range: 8-24 mg) for 24 weeks; or monthly BUP-XR (Sublocade;® two injections of 300 mg, then four maintenance injections of 100 mg or 300 mg, with maintenance dose selected by response and preference) for 24 weeks. In the intent-to-treat population (senior statistician blinded to blinded to treatment group allocation), and with a seven-day grace period after randomisation, the primary endpoint was the count of days abstinent from non-medical opioids between days 8-168 (i.e., weeks 2-24; range: 0-161 days). Safety was reported for the intention-to- treat population. Adopting a broad societal perspective inclusive of criminal justice, NHS and personal social service costs, a trial-based cost-utility analysis estimated the Incremental Cost-effectiveness Ratio (ICER) per quality-adjusted life year (QALY) of BUP-XR versus SoC at the National Institute for Health and Care Excellence threshold. The study was registered EudraCT (2018-004460-63) and ClinicalTrials.gov (NCT05164549), and is completed.FINDINGS: Between Aug 9, 2019 and Nov 2, 2021, 314 participants were randomly allocated to receive SoC (n = 156) or BUP-XR (n = 158). Participants were abstinent from opioids for an adjusted mean of 104.37 days (standard error [SE] 9.89; range: 0-161 days) in the SoC group and an adjusted mean of 123.43 days (SE 4.76; range: 24-161 days) in the BUP-XR group (adjusted incident rate ratio [IRR] 1.18, 95% confidence interval [CI] 1.05-1.33; p-value 0.004). The incidence of any adverse event was higher in the BUP-XR group than the SoC group (128 [81.0%] of 158 participants versus 67 [42.9%] of 156 participants, respectively-most commonly rapidly-resolving (mild-moderate range) pain from drug administration in the BUP-XR group (121 [26.9%] of 450 adverse events). There were 11 serious adverse events (7.0%) in the 158 participants in the BUP-XR group, and 18 serious adverse events (11.5%) in the 156 participants in the SoC group-none judged to be related to study treatment. The BUP-XR treatment group had a mean incremental cost of £1033 (95% central range [CR] -1189 to 3225) and was associated with a mean incremental QALY of 0.02 (95% CR 0.00-0.05), and an ICER of £47,540 (0.37 probability of being cost-effective at the £30,000/QALY gained willingness-to-pay threshold). However, BUP-XR dominated the SoC among participants who were rated more severe at study baseline, and among participants in maintenance treatment for more that 28 days at study enrolment.INTERPRETATION: Evaluated against the daily oral SoC, monthly BUP-XR is clinically superior, delivering greater abstinence from opioids, and with a comparable safety profile. BUP-XR was not cost-effective in a base case cost-utility analysis using the societal perspective, but it was more effective and less costly (dominant) among participants with more severe OUD, or those whose current treatment episode was longer than 28 days. Further trials are needed to evaluate if BUP-XR is associated with better clinical and health economic outcomes over the longer term.FUNDING: Indivior.</p

Extended-release pharmacotherapy for opioid use disorder (EXPO):protocol for an open-label randomised controlled trial of the effectiveness and cost-effectiveness of injectable buprenorphine versus sublingual tablet buprenorphine and oral liquid methadone

BACKGROUND: Sublingual tablet buprenorphine (BUP-SL) and oral liquid methadone (MET) are the daily, standard-of-care (SOC) opioid agonist treatment medications for opioid use disorder (OUD). A sizable proportion of the OUD treatment population is not exposed to sufficient treatment to attain the desired clinical benefit. Two promising therapeutic technologies address this deficit: long-acting injectable buprenorphine and personalised psychosocial interventions (PSI). This study will determine (A) the effectiveness and cost-effectiveness — monthly injectable, extended-release (BUP-XR) in a head-to-head comparison with BUP-SL and MET, and (B) the effectiveness of BUP-XR with adjunctive PSI versus BUP-SL and MET with PSI. Safety, retention, craving, substance use, quality-adjusted life years, social functioning, and subjective recovery from OUD will be also evaluated. METHODS: This is a pragmatic, multi-centre, open-label, parallel-group, superiority RCT, with a qualitative (mixed-methods) evaluation. The study population is adults. The setting is five National Health Service community treatment centres in England and Scotland. At each centre, participants will be randomly allocated (1:1) to BUP-XR or SOC. At the London study co-ordinating centre, there will also be allocation of participants to BUP-XR with PSI or SOC with PSI. With 24 weeks of study treatment, the primary outcome is days of abstinence from non-medical opioids during study weeks 2–24 combined with up to 12 urine drug screen tests for opioids. For 90% power (alpha, 5%; 15% inflation for attrition), 304 participants are needed for the BUP-XR versus SOC comparison. With the same planning parameters, 300 participants are needed for the BUP-XR and PSI versus SOC and PSI comparison. Statistical and health economic analysis plans will be published before data-lock on the Open Science Framework. Findings will be reported in accordance with the Consolidated Standards of Reporting Trials and Consolidated Health Economic Evaluation Reporting Standards. DISCUSSION: This pragmatic randomised controlled trial is the first evaluation of injectable BUP-XR versus the SOC medications BUP-SL and MET, with personalised PSI. If there is evidence for the superiority of BUP-XR over SOC medication, study findings will have substantial implications for OUD clinical practice and treatment policy in the UK and elsewhere. TRIAL REGISTRATION: EU Clinical Trials register 2018-004460-63. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06595-0

Ag colloids and arrays for plasmonic non-radiative energy transfer from quantum dots to a quantum well

Non-radiative energy transfer (NRET) can be an efficient process of benefit to many applications including photovoltaics, sensors, light emitting diodes and photodetectors. Combining the remarkable optical properties of quantum dots (QDs) with the electrical properties of quantum wells (QWs) allows for the formation of hybrid devices which can utilize NRET as a means of transferring absorbed optical energy from the QDs to the QW. Here we report on plasmon-enhanced NRET from semiconductor nanocrystal QDs to a QW. Ag nanoparticles in the form of colloids and ordered arrays are used to demonstrate plasmon-mediated NRET from QDs to QWs with varying top barrier thicknesses. Plasmon-mediated energy transfer. (ET) efficiencies of up to similar to 25% are observed with the Ag colloids. The distance dependence of the plasmon-mediated ET is found to follow the same d-4 dependence as the direct QD to QW ET. There is also evidence for an increase in the characteristic distance of the interaction, thus indicating that it follows a Frster-like model with the Ag nanoparticle-QD acting as an enhanced donor dipole. Ordered Ag nanoparticle arrays display plasmon-mediated ET efficiencies up to similar to 21%. To explore the tunability of the array system, two arrays with different geometries are presented. It is demonstrated that changing the geometry of the array allows a transition from overall quenching of the acceptor QW emission to enhancement, as well as control of the competition between the QD donor quenching and ET rates