Search

• DORA and CoARA are redefining academic evaluation standards. • Europe is adopting narrative scientific assessment methods. • Narrative CVs have originated a new field of evaluation. • Narrative Bibliometrics is a new discipline for mapping scientific evidence through data. • Narrative Bibliometrics is a research method adaptable and scalable to any evaluation. The document 'Foundations of Narrative Bibliometrics' provides an analysis of the evolution of scientific assessment, highlighting the influence of manifestos such as DORA and CoARA in shaping ethical and responsible practices in academia, as well as their assimilation by Spanish scientific policies. It connects this context with the contributions of evaluative bibliometrics, emphasising the transition towards a more integrative approach that advocates for a balance between quantitative and qualitative methods in research evaluation. Furthermore, it underscores how the Narrative Curriculum has emerged as one of the fundamental tools in new evaluation processes, as it allows for the description of the complexity and context of academic achievements. Narrative Bibliometrics is proposed, defined as the use of bibliometric indicators to generate stories that support the defence and exposition of a scientific curriculum and/or its individual contributions within the framework of a scientific evaluation process, which demands narratives. To introduce the reader, it presents, in a non-exhaustive manner, sources, indicators, and practical cases for effectively applying Narrative Bibliometrics in various scientific evaluation contexts. Hence, this document contributes to the responsible use of bibliometric indicators, serving as a tool for evaluators and researchers. [ABSTRACT FROM AUTHOR]

Information technology (IT) as a regulatory object is defined and viewed differently across various domains of European IT security law. However, common definitions and methods for the demarcation and separation of operational information technology can contribute to coherence in the historically grown body of regulation. This paper identifies three different general approaches for the treatment of information technology within the existing body of law: information technology as a means, as a service and as a product. Furthermore, we compile a general definition of information technology , which consists of three logical subentities: components, systems , and services. Additionally, steps for the practical identification of the operational information technology addressed by material law requirements are shown. First, all services that affect an articulated protected good must be identified. Within the identification of the systems used to realize those services , two dimensions must be considered. There is the functional dimension as well as the control and power of the disposal dimension. An identified weakness of the current state of IT security law is a lack of clearly formulated protected goods within the existing regulations, which contributes to the difficulties of addressing information technology in general. Furthermore, this paper discusses which actors are responsible for a demarcated piece of information technology and what responsibilities are assigned to them. This section also elaborates on the difficulty of appropriately addressing commercial and non-commercial actors. [ABSTRACT FROM AUTHOR]

The use of cloud services by financial institutions has become increasingly prevalent due to its economic benefits. However, this comes with the inherent drawbacks of increased security risks and potential financial stability risks from the cloud market concentration. The EU has introduced specific legal instruments that place responsibilities on financial institutions to mitigate these risks. This paper analyses how the regulation of cloud service providers in the EU financial sector has evolved from the regulation of operational risk to the regulation of systemic risk. The Digital Operational Resilience Act, adopted in December 2022 and effective from January 17, 2025, plays a key role in enabling this transformation by recognizing the systemic risk aspect of the use of cloud service providers. It responds to this risk by creating a new oversight regime of critical cloud service providers. However, new oversight of critical cloud service providers brings about novel problems, particularly concerning the ne bis in idem principle in the case of overlapping oversight and enforcement by different authorities responsible for respective legislative instruments in cybersecurity and data protection. The overlapping oversight shall respect the principle. This paper evaluates to what extent the overlapping regime respects the principle under Article 50 of the Charter of Fundamental Rights of the European Union by analysing the Digital Operational Resilience Act and provides suggestions to improve coordination among different competent authorities in the case of overlapping supervision and enforcement to respect the principle. [ABSTRACT FROM AUTHOR]

Orexin is a neuromodulatory peptide produced by lateral hypothalamic orexin neurons and binds to G-protein-coupled orexin-1 receptor and orexin-2 receptors. Whether orexin modulates learning and memory is not fully understood. Orexin has biphasic effects on learning and memory: promoting learning and memory at homeostatic levels and inhibiting at supra- and sub-homeostatic levels. Hippocampal sharp wave-ripples encode memory information and are essential for memory consolidation and retrieval. The role of orexin on sharp wave-ripples in hippocampal CA1 remains unknown. Here, we used multi-electrode array recordings in acute ex vivo hippocampal slices to determine the effects of orexin receptor antagonists on sharp wave-ripples. Bath-application of either the orexin-1 receptor antagonist N-(2-Methyl-6-benzoxazolyl)-N'-1,5-naphthyridin-4-yl urea (SB-334867) or the orexin-2 receptor antagonist N-Ethyl-2-[(6-methoxy-3-pyridinyl)[(2-methylphenyl)sulfonyl]amino]-N-(3-pyridinylmethyl)-acetamide (EMPA) reduced sharp wave and ripple incidence, sharp wave amplitude, and sharp wave duration. SB-334867 and EMPA effects on sharp wave amplitude and duration were equivalent, whereas EMPA exhibited a greater reduction of sharp wave and ripple incidence. EMPA also increased ripple duration, whereas SB-334867 had no effect. Inhibition of both orexin receptors with a dual orexin receptor antagonist N-[1,1'-Biphenyl]-2-yl-1-[2-[(1-methyl-1H-benzimidazol-2-yl)thio]acetyl-2-pyrrolidinedicarboxamide (TCS-1102) had effects similar to EMPA, however, sharp wave amplitude and duration were unaffected. Region-specific expression of orexin receptors suggests orexin may regulate sharp wave generation in CA3, dentate gyrus-mediated sharp wave modification, sharp wave propagation to CA1, and local ripple emergence in CA1. Our study indicates an orexin contribution to hippocampal sharp wave-ripple complexes and suggests a mechanism by which sub-homeostatic concentrations of orexin may inhibit learning and memory function. [ABSTRACT FROM AUTHOR]

Orexin contributes to the expression of the cardiovascular and behavioural response of some forms of stress, including novelty stress. Thus, Almorexant, a dual receptor antagonist that blocks the two known orexin receptors, Ox1R and Ox2R, reduces these responses. However, it is not known if the reduction results from blockade of one receptor only or both. To answer this question, the selective Ox1R antagonist ACT335827 and the selective Ox2R antagonist EMPA were injected intragastrically (300 mg/kg) or intraperitoneally (30 and 100 mg/kg) either alone or as a cocktail and compared to Almorexant in rats exposed to novelty stress. Cardiovascular and locomotor responses were recorded by radio-telemetry. Triple immunolabelling was also conducted to establish the distribution of Ox1R and Ox2R in sympathetic preganglionic neurons and orexin neurons. Intraperitoneal injections of ACT335827 (100 mg/kg) reduced the pressor and tachycardic but not the locomotor response of novelty (by 32% and 48%, respectively). Intraperitoneal injections of EMPA (100 mg/kg) only reduced the pressor response (42%). However when given together, ACT335827 and EMPA reduced all 3 components (65%, 60% and 57% of the tachycardic, pressor and locomotor responses, respectively) as Almorexant (100 mg/kg) did (69%, 87% and 72%, respectively). Triple immunolabelling revealed that sympathetic preganglionic neurons were mainly Ox1R positive only while orexin neurons were both Ox1R and Ox2R positive. This study shows that orexin's contribution to the cardiovascular and locomotor components of the novelty stress response is not mediated by one receptor alone, but by both receptors and at different levels of the neuraxis. [ABSTRACT FROM AUTHOR]

Abstract: Starting from a orexin 1 receptor selective antagonist 4,4-disubstituted piperidine series a novel potent 5-azaspiro[2.4]heptane dual orexin 1 and orexin 2 receptor antagonist class has been discovered. SAR and Pharmacokinetic optimization of this series is herein disclosed. Lead compound 15 exhibits potent activity against orexin 1 and orexin 2 receptors along with low cytochrome P450 inhibition potential, good brain penetration and oral bioavailability in rats. [Copyright &y& Elsevier]

Background: The present study investigated the effects of the dual orexin receptor antagonist (DORA) almorexant, a sleep-modulating drug, on the sleep-disrupting effects of methamphetamine in adult rhesus monkeys.Methods: Monkeys were fitted with primate collars to which actigraphy monitors were attached. To determine the effects of methamphetamine on daytime activity and sleep-like parameters, monkeys were given acute injections of vehicle or methamphetamine (0.03, 0.1 or 0.3 mg/kg, i.m.) in the morning (9:00 h) (n = 4 males). We then determined the ability of almorexant to alter the daytime and/or sleep-like effects of the largest (effective) dose of methamphetamine. Vehicle or almorexant (1, 3 or 10 mg/kg, i.m.) were administered in the evening (16:30 h, 1.5 h before "lights off") following morning (9:00 h) administration of methamphetamine (0.3 mg/kg, i.m.), or as a pretreatment (8:30 h) before methamphetamine injections (9:00 h) (n = 4 males). The ability of almorexant (10 mg/kg) to improve sleep-like behaviors also was assessed in a group of monkeys quantitatively identified with short-duration sleep (n = 2 males, 2 females).Results: Morning methamphetamine administration dose-dependently impaired sleep in rhesus monkeys (0.3 mg/kg significantly increased sleep latency and decreased sleep efficiency). Administration of almorexant, both as a pretreatment or as an evening treatment, improved methamphetamine-induced sleep impairment in a dose dependent manner. Morning pretreatment with almorexant also blocked the daytime stimulant effects of methamphetamine. Evening, but not morning, treatment with almorexant in a group of monkeys with baseline short-duration sleep improved sleep measures.Conclusions: Our findings indicate that orexin receptor systems are involved in methamphetamine-induced hyperarousal and sleep disruption. [ABSTRACT FROM AUTHOR]

Here, we present the design, synthesis, and SAR of dual orexin 1 and 2 receptor antagonists, which were optimized by balancing the antagonistic activity for orexin receptors and lipophilicity. Based on the prototype compound 1 , ring construction and the insertion of an additional heteroatom into the resulting ring led to the discovery of orexin 1 and 2 receptor antagonists, which were 3-benzoyl-1,3-oxazinane derivatives. Within these derivatives, (−)- 3h enabled a high dual orexin receptor antagonistic activity and a low lipophilicity. Compound (−)- 3h exhibited potent sleep-promoting effects at a po dose of 1 mg/kg in a rat polysomnogram study, and optimal PK properties with a rapid T max and short half-lives in rats and dogs were observed, indicating a predicted human half-life of 0.9–2.0 h. Thus, (−)- 3h (ORN0829 ; investigation code name, TS-142) was selected as a viable candidate and is currently in clinical development for the treatment of insomnia. [ABSTRACT FROM AUTHOR]