Alder (United States)

Among children and young people, girls in particular sing in choirs. Some girls’ choirs can refer to a particularly high artistic level that falls into the sub-category semi-professional choirs or «elite choirs». One might say that Sandefjord girls’ choir (1956–1997) belonged to this category. This chapter is based on material from a survey among Sandefjord girls’ choir former members, qualitative interviews and supplementary sources based on the following research question: How is a girls’ choir practice constituted over time, and which values in the social practice emerge as lifelong learning for the choristers? In Bourdieu’s cultural sociology, values are understood as accumulated resources or capital. The purpose of the study is to contribute to the development of knowledge about the values which generates in the semi-professional girls’ choir culture as a specific practice in the field of music. Implicitly, this involves a contextualization of the girls’ choir practice in historical time and in geographical place. The study shows that «vocal-musical», co-singing and educational values are most prominent in girls’ choir practice, also as a foundation for lifelong learning. Through this, habitus emerge as a specific kind of «girl’s-choir-singers’ habitus». Despite significant structural changes since the 1950s and into the present, both in the field of music and in society in general, it is clear that new generations of choristers have been regulated and shaped through a reproduction of the values that exist in the social practice.

Abstract We aimed to investigate a potentially sexually dimorphic role of Calcitonin Gene-Related Peptide (CGRP) in mouse and rat models of pain. Based on findings in migraine where CGRP has a preferential pain-promoting effect in female rodents, we hypothesized that CGRP antagonists and antibodies would attenuate pain sensitization more efficaciously in female than male mice and rats. In hyperalgesic priming induced by activation of interleukin 6 (IL-6) signaling, CGRP receptor antagonists, olcegepant and CGRP8-37, both given intrathecally, blocked and reversed hyperalgesic priming only in females. A monoclonal antibody against CGRP, given systemically, blocked priming specifically in female rodents but failed to reverse it. In the spared nerve injury (SNI) model, there was a transient effect of both CGRP antagonists, given intrathecally, on mechanical hypersensitivity in female mice only. Consistent with these findings, intrathecally applied CGRP caused a long-lasting, dose-dependent mechanical hypersensitivity in female mice but more transient effects in males. This CGRP-induced mechanical hypersensitivity was reversed by the KCC2 activator, CLP257 suggesting a role for anionic plasticity in the dorsal horn in the pain-promoting effects of CGRP in females. In spinal dorsal horn slices, CGRP shifted GABAA reversal potentials to significantly more positive values but, again, only in female mice. Therefore, CGRP may regulate KCC2 expression and/or activity specifically in females. However, KCC2 hypofunction promotes mechanical pain hypersensitivity in both sexes because CLP257 alleviated hyperalgesic priming in male and female mice. We conclude that CGRP promotes pain plasticity in female mice, but has a limited impact in male mice.Significance StatementThe majority of patients impacted by chronic pain are women. Mechanistic studies in rodents are creating a clear picture that molecular events promoting chronic pain are different in male and female animals. Far more is known about chronic pain mechanisms in male animals. We sought to build on recent evidence showing that CGRP is a more potent and efficacious promoter of headache pain in female than in male rodents. To test this, we used hyperalgesic priming and the spared nerve injury (SNI) neuropathic pain models in mice. Our findings show a clear sex dimorphism wherein CGRP promotes pain in female but not male mice. Our work suggests that CGRP antagonists could be tested for efficacy in women for a broader variety of pain conditions.

To confirm that the percentage of patients with a migraine on Day 1 after eptinezumab administration measures onset of full preventive effect.

To evaluate the impact of eptinezumab on HRQoL across the spectrum of episodic migraine (EM) and chronic migraine (CM).

Compared with conventional (monospecific) therapeutics, bispecific protein therapeutics present unique challenges for pharmacokinetic (PK) characterization - namely, the characterization of multiple functional domains as well as the consideration of biotransformation or interference by the formation of antitherapeutic antibodies against each functional domain. PK characterization is essential to the success of the overall drug development plan and for molecules with multiple binding domains; multiple bioanalytical methods may be needed to answer critical questions for each phase of drug development. The number of bispecific protein therapeutics entering drug development continues to increase, and therefore, a bioanalytical strategy for the PK characterization of bispecific molecules and study of their in vivo structure-function relationship is needed. This review presents case studies and a regulatory perspective.

Explore effects of eptinezumab on migraine activity from Day 1 post iv infusion through Week 12 in patients with frequent episodic migraine.

Much of the embedded software development market has necessarily tight constraints on program size and processor power, hence developers use handwritten C rather than autocode. They rely primarily on testing to find errors in their code. We have an established software development tool known commercially as Perfect Developer, which uses a powerful automatic theorem prover and inference engine to reason about requirements and specifications. We have found that automated reasoning can be used to discharge a very high proportion of verification conditions arising from the specification and refinement of software components described in our formal specification language, Perfect. The Perfect Developer tool set can also generate code in a C++ subset or in Java, and the output code is then virtually certain to meet the stated specification, reducing the need for exhaustive testing. However, this is not helpful to developers of embedded software who are constrained to write code by hand. We therefore decided to investigate whether automated reasoning could provide a similar degree of success in the verification of annotated C code. We present our preliminary findings.