MID3: Mission Impossible or Model-Informed Drug Discovery and Development? Point-Counterpoint Discussions on Key Challenges

MID3: Mission Impossible, or Model‐Informed, Drug Discovery and Development? At the 2019 American Society for Clinical Pharmacology and Therapeutics (ASCPT) annual meeting, point‐counterpoint discussions were held on key challenges that limit, and future directions that enhance the adoption of model‐informed drug discovery and development (MID3) across the drug discovery, development, regulatory, and utilization continuum. We envision that the opportunities discussed and lessons learned from having contrasting perspectives on issues that lack consensus may aid our discipline in more effectively implementing MID3 principles

Sperm Competition, Sperm Numbers and Sperm Quality in Muroid Rodents

Sperm competition favors increases in relative testes mass and production efficiency, and changes in sperm phenotype that result in faster swimming speeds. However, little is known about its effects on traits that contribute to determine the quality of a whole ejaculate (i.e., proportion of motile, viable, morphologically normal and acrosome intact sperm) and that are key determinants of fertilization success. Two competing hypotheses lead to alternative predictions: (a) sperm quantity and quality traits co-evolve under sperm competition because they play complementary roles in determining ejaculate's competitive ability, or (b) energetic constraints force trade-offs between traits depending on their relevance in providing a competitive advantage. We examined relationships between sperm competition levels, sperm quantity, and traits that determine ejaculate quality, in a comparative study of 18 rodent species using phylogenetically controlled analyses. Total sperm numbers were positively correlated to proportions of normal sperm, acrosome integrity and motile sperm; the latter three were also significantly related among themselves, suggesting no trade-offs between traits. In addition, testes mass corrected for body mass (i.e., relative testes mass), showed a strong association with sperm numbers, and positive significant associations with all sperm traits that determine ejaculate quality with the exception of live sperm. An “overall sperm quality” parameter obtained by principal component analysis (which explained 85% of the variance) was more strongly associated with relative testes mass than any individual quality trait. Overall sperm quality was as strongly associated with relative testes mass as sperm numbers. Thus, sperm quality traits improve under sperm competition in an integrated manner suggesting that a combination of all traits is what makes ejaculates more competitive. In evolutionary terms this implies that a complex network of genetic and developmental pathways underlying processes of sperm formation, maturation, transport in the female reproductive tract, and preparation for fertilization must all evolve in concert

Scientific assessment of animal welfare

Published online: 11 Dec 2014Animal welfare is a state within the animal and a scientific perspective provides methodologies for evidence-based assessment of an animal's welfare. A simplistic definition of animal welfare might be how the animal feels now. Affective experiences including emotions, are subjective states so cannot be measured directly in animals, but there are informative indirect physiological and behavioural indices that can be cautiously used to interpret such experiences. This review enunciates several key science-based frameworks for understanding animal welfare. The biological functioning and affective state frameworks were initially seen as competing, but a recent more unified approach is that biological functioning is taken to include affective experiences and affective experiences are recognised as products of biological functioning, and knowledge of the dynamic interactions between the two is considered to be fundamental to managing and improving animal welfare. The value of these two frameworks in understanding the welfare of group-housed sows is reviewed. The majority of studies of the welfare of group-housed sows have employed the biological functioning framework to infer compromised sow welfare, on the basis that suboptimal biological functioning accompanies negative affective states such as sow hunger, pain, fear, helplessness, frustration and anger. Group housing facilitates social living, but group housing of gestating sows raises different welfare considerations to stall housing, such as high levels of aggression, injuries and stress, at least for several days after mixing, as well as subordinate sows being underfed due to competition at feeding. This paper highlights the challenges and potential opportunities for the continued improvement in sow management through well-focused research and multidisciplinary assessment of animal welfare. In future the management of sentient animals will require the promotion of positive affective experiences in animals and this is likely to be a major focus for animal welfare science activity in the early twenty-first century.PH Hemsworth, DJ Mellor, GM Cronin and AJ Tilbroo

The experiences of women of reproductive age regarding health-promoting behaviours: A qualitative study

<p>Abstract</p> <p>Background</p> <p>Health promotion is critical for community and family health. Health-promoting behaviours provide solutions for maintaining and promoting health. Although several studies have addressed the frequency and different types of health-promoting behaviours in women, little information is available about their experiences. This study aimed to explore the experiences of women of reproductive age regarding health-promoting behaviours.</p> <p>Methods</p> <p>In the present study, which was conducted in Tehran, Iran, 15 females, who were selected purposefully, participated in individual in-depth, semi-structured interviews. The interviews were recorded, transcribed verbatim, and analysed using conventional content analysis.</p> <p>Results</p> <p>Nine main categories were derived from the analysis, including establishing an appropriate eating pattern, establishing a balanced rest/activity pattern, spirituality, stress management, personal sensitivity and responsibility, establishing an appropriate pattern of social interactions, practicing safe and healthy recreations, feeling improvement in physical-functional health, and feeling improvement in emotional and psychological health. The first 7 categories represent the nature and types of real health-promoting behaviours in women of reproductive age, whereas the last 2 constitute feeling and understanding of the implementation of these behaviours.</p> <p>Conclusion</p> <p>The study findings show that the women experience improvement in physical-functional, emotional, and psychological health by implementing health-promoting behaviours. It is therefore necessary to introduce strategies in the context of the community culture for improving different aspects of health-promoting behaviours in women of reproductive age to maintain and improve their overall health.</p