The search for translational pain outcomes to refine analgesic development: Where did we come from and where are we going?

Pain measures traditionally used in rodents record mere reflexes evoked by sensory stimuli; the results thus may not fully reflect the human pain phenotype. Alterations in physical and emotional functioning, pain-depressed behaviors and facial pain expressions were recently proposed as additional pain outcomes to provide a more accurate measure of clinical pain in rodents, and hence to potentially enhance analgesic drug development. We aimed to review how preclinical pain assessment has evolved since the development of the tail flick test in 1941, with a particular focus on a critical analysis of some nonstandard pain outcomes, and a consideration of how sex differences may affect the performance of these pain surrogates. We tracked original research articles in Medline for the following periods: 1973-1977, 1983-1987, 1993-1997, 2003-2007, and 2014-2018. We identified 606 research articles about alternative surrogate pain measures, 473 of which were published between 2014 and 2018. This indicates that preclinical pain assessment is moving toward the use of these measures, which may soon become standard procedures in preclinical pain laboratories.FPU grant from the Spanish Ministry of Education, Culture and SportsSpanish Ministry of Economy and Competitiveness (MINECO, grant SAF2016-80540-R)Ramón Areces FoundationJunta de Andalucía (grant CTS 109)Esteve PharmaceuticalsEuropean Regional Development Fund (ERDF

Comparing Notes: Recording and Criticism

This chapter charts the ways in which recording has changed the nature of music criticism. It both provides an overview of the history of recording and music criticism, from the advent of Edison’s Phonograph to the present day, and examines the issues arising from this new technology and the consequent transformation of critical thought and practice

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Technological elites, the meritocracy, and postracial myths in Silicon Valley

Entre as modernas elites tecnológicas digitais, os mitos da meritocracia e da façanha intelectual são usados como marcadores de raça e gênero por uma supremacia branca masculina que consolida recursos de forma desproporcional em relação a pessoas não brancas, principalmente negros, latinos e indígenas. Os investimentos em mitos meritocráticos suprimem os questionamentos de racismo e discriminação, mesmo quando os produtos das elites digitais são infundidos com marcadores de raça, classe e gênero. As lutas históricas por inclusão social, política e econômica de negros, mulheres e outras classes desprotegidas têm implicado no reconhecimento da exclusão sistêmica, do trabalho forçado e da privação de direitos estruturais, além de compromissos com políticas públicas dos EUA, como as ações afirmativas, que foram igualmente fundamentais para reformas políticas voltadas para participação e oportunidades econômicas. A ascensão da tecnocracia digital tem sido, em muitos aspectos, antitética a esses esforços no sentido de reconhecer raça e gênero como fatores cruciais para inclusão e oportunidades tecnocráticas. Este artigo explora algumas das formas pelas quais os discursos das elites tecnocráticas do Vale do Silício reforçam os investimentos no pós racialismo como um pretexto para a re-consolidação do capital em oposição às políticas públicas que prometem acabar com práticas discriminatórias no mundo do trabalho. Por meio de uma análise cuidadosa do surgimento de empresas de tecnologias digitais e de uma discussão sobre como as elites tecnológicas trabalham para mascarar tudo, como inscrições algorítmicas e genéticas de raça incorporadas em seus produtos, mostramos como as elites digitais omitem a sua responsabilidade por suas reinscrições pós raciais de (in)visibilidades raciais. A partir do uso de análise histórica e crítica do discurso, o artigo revela como os mitos de uma meritocracia digital baseados em um “daltonismo racial” tecnocrático emergem como chave para a manutenção de exclusões de gênero e raça.Palavras-chave: Tecnologia. Raça. Gênero.Among modern digital technology elites, myths of meritocracy and intellectual prowess are used as racial and gender markers of white male supremacy that disproportionately consolidate resources away from people of color, particularly African Americans, Latino/as and Native Americans. Investments in meritocratic myths suppress interrogations of racism and discrimination even as the products of digital elites are infused with racial, class, and gender markers. Longstanding struggles for social, political, and economic inclusion for African Americans, women, and other legally protected classes have been predicated upon the recognition of systemic exclusion, forced labor, and structural disenfranchisement, and commitments to US public policies like affirmative action have, likewise, been fundamental to political reforms geared to economic opportunity and participation. The rise of the digital technocracy has, in many ways, been antithetical to these sustained efforts to recognize race and gender as salient factors structuring technocratic opportunity and inclusion. This paper explores some of the ways in which discourses of Silicon Valley technocratic elites bolster investments in post-racialism as a pretext for re-consolidations of capital, in opposition to public policy commitments to end discriminatory labor practices. Through a careful analysis of the rise of digital technology companies, and a discussion of how technology elites work to mask everything from algorithmic to genetic inscriptions of race embedded in their products, we show how digital elites elide responsibility for their post-racial re-inscriptions of racial visibilities (and invisibilities). Using historical and critical discourse analysis, the paper reveals how myths of a digital meritocracy premised on a technocratic colorblindness emerge key to perpetuating gender and racial exclusions.Keywords: Technology. Race. Gender

Wider Still and Wider: British Music Criticism since the Second World War

This chapter provides the first historical examination of music criticism in Britain since the Second World War. In the process, it also challenges the simplistic prevailing view of this being a period of decline from a golden age in music criticism

Droplet impact onto a spring-supported plate: analysis and simulations

The high-speed impact of a droplet onto a flexible substrate is a highly non-linear process of practical importance, which poses formidable modelling challenges in the context of fluid–structure interaction. We present two approaches aimed at investigating the canonical system of a droplet impacting onto a rigid plate supported by a spring and a dashpot: matched asymptotic expansions and direct numerical simulation (DNS). In the former, we derive a generalisation of inviscid Wagner theory to approximate the flow behaviour during the early stages of the impact. In the latter, we perform detailed DNS designed to validate the analytical framework, as well as provide insight into later times beyond the reach of the proposed analytical model. Drawing from both methods, we observe the strong influence that the mass of the plate, resistance of the dashpot, and stiffness of the spring have on the motion of the solid, which undergo forced damped oscillations. Furthermore, we examine how the plate motion affects the dynamics of the droplet, predominantly through altering its internal hydrodynamic pressure distribution. We build on the interplay between these techniques, demonstrating that a hybrid approach leads to improved model and computational development, as well as result interpretation, across multiple length and time scales

Validity and reliability of the Nintendo Wii Fit Stillness score for assessment of standing balance

Background/objective: Standing balance has become an important clinical measure in patient populations who are at risk of falls or have osteoarthritis. With custom-written software, the Wii Balance Board (WBB) has been shown to be a valid and reliable force platform that can be used to assess standing balance. However, no studies to date have assessed the use of the more readily available Wii Stillness Score (WSS) as a measure of balance. Methods: Twenty-four individuals without lower limb pathology performed a combination of unilateral and double leg standing balance tests with eyes open or closed on two separate occasions. At each session, data from the WBB were acquired on a laptop computer running custom software and then by Wii-Fit software on a Wii console. The reliability of the WSS was determined by assessing reproducibility, while the validity of the WSS was determined by comparing the results of the WSS to that of the custom-written software. Results: We found that the WSS exhibited excellent intra and inter device reliability in three out of four stances tested. The Bland-Altman plots also showed good concurrent validity for the three analysed stances. However, there remain significant limitations with the use of the WSS such as its rigid thirty-second time parameter and single score result. Conclusion: The readily available WBB may be a used as a portable and inexpensive device to assess standing balance with custom written software. However, with the current limitations of the WSS, we would discourage its use as a clinical measure of balance. Keywords: Wii-fit, Standing, Balance, Stillness score, Wii balance board, Co