Brokerage at the science–policy interface: from conceptual framework to practical guidance

This article analyses the conceptual framework of brokerage at the science–policy interface as an important boundary function to support trusted and transparent government decision-making. Policymaking involves a broad range of considerations, but science advice and evidence is critical to help inform decisions. However, mechanisms for requesting and receiving advice from the scientific community are not straightforward, considering that the knowledge needed generally spans multiple disciplines of the natural and social sciences. Once evidence has been appropriately synthesized, there remains the need to ensure an effective and unbiased translation to the policy and political community. The concept of knowledge brokerage revolves around an understanding of the ontologies, cultures and languages of both the policy community and the science community, in order to effectively link the two bidirectionally. In practical terms, this means ensuring that the information needs of the former are understood, and that the type and form of information offered by the latter aligns with those needs. Ideally, knowledge brokers act at the interface between researchers/experts and decision-makers to present evidence in a way that informs policy options but does not determine policy development. Conceptually, negotiating this interface involves acknowledging that values are embedded in the scientific process and evidentiary synthesis, and in particular, in considering the inferential risks inherent in making evidence claims. Brokers are faced with navigating complex policy dynamics and balancing information asymmetries between research providers and users. Building on the conceptual analysis and examination of the nuances of brokerage observed in practice, we propose a set of guidelines to translate the concepts of brokerage to practical application.publishedVersio

Impaired Perinatal Growth and Longevity: A Life History Perspective

Life history theory proposes that early-life cues induce highly integrated responses in traits associated with energy partitioning, maturation, reproduction, and aging such that the individual phenotype is adaptively more appropriate to the anticipated environment. Thus, maternal and/or neonatally derived nutritional or endocrine cues suggesting a threatening environment may favour early growth and reproduction over investment in tissue reserve and repair capacity. These may directly affect longevity, as well as prioritise insulin resistance and capacity for fat storage, thereby increasing susceptibility to metabolic dysfunction and obesity. These shifts in developmental trajectory are associated with long-term expression changes in specific genes, some of which may be underpinned by epigenetic processes. This normative process of developmental plasticity may prove to be maladaptive in human environments in transition towards low extrinsic mortality and energy-dense nutrition, leading to the development of an inappropriate phenotype with decreased potential for longevity and/or increased susceptibility to metabolic disease

Prenatal factors contribute to the emergence of kwoshiorkor or marasmus in severe undernutrition: evidence for the predictive adaptation model

Severe acute malnutrition in childhood manifests as oedematous (kwashiorkor, marasmic kwashiorkor) and non-oedematous (marasmus) syndromes with very different prognoses. Kwashiorkor differs from marasmus in the patterns of protein, amino acid and lipid metabolism when patients are acutely ill as well as after rehabilitation to ideal weight for height. Metabolic patterns among marasmic patients define them as metabolically thrifty, while kwashiorkor patients function as metabolically profligate. Such differences might underlie syndromic presentation and prognosis. However, no fundamental explanation exists for these differences in metabolism, nor clinical pictures, given similar exposures to undernutrition. We hypothesized that different developmental trajectories underlie these clinical-metabolic phenotypes: if so this would be strong evidence in support of predictive adaptation model of developmental plasticity

Thrifty metabolic programming in rats is induced by both maternal undernutrition and postnatal leptin treatment, but masked in the presence of both: implications for models of developmental programming.

BACKGROUND: Maternal undernutrition leads to an increased risk of metabolic disorders in offspring including obesity and insulin resistance, thought to be due to a programmed thrifty phenotype which is inappropriate for a subsequent richer nutritional environment. In a rat model, both male and female offspring of undernourished mothers are programmed to become obese, however postnatal leptin treatment gives discordant results between males and females. Leptin treatment is able to rescue the adverse programming effects in the female offspring of undernourished mothers, but not in their male offspring. Additionally, in these rats, postnatal leptin treatment of offspring from normally-nourished mothers programmes their male offspring to develop obesity in later life, while there is no comparable effect in their female offspring. RESULTS: We show by microarray analysis of the female liver transcriptome that both maternal undernutrition and postnatal leptin treatment independently induce a similar thrifty transcriptional programme affecting carbohydrate metabolism, amino acid metabolism and oxidative stress genes. Paradoxically, however, the combination of both stimuli restores a more normal transcriptional environment. This demonstrates that "leptin reversal" is a global phenomenon affecting all genes involved in fetal programming by maternal undernourishment and leptin treatment. The thrifty transcriptional programme was associated with pro-inflammatory markers and downregulation of adaptive immune mediators, particularly MHC class I genes, suggesting a deficit in antigen presentation in these offspring. CONCLUSIONS: We propose a revised model of developmental programming reconciling the male and female observations, in which there are two competing programmes which collectively drive liver transcription. The first element is a thrifty metabolic phenotype induced by early life growth restriction independently of leptin levels. The second is a homeostatic set point calibrated in response to postnatal leptin surge, which is able to over-ride the metabolic programme. This "calibration model" for the postnatal leptin surge, if applicable in humans, may have implications for understanding responses to catch-up growth in infants. Additionally, the identification of an antigen presentation deficit associated with metabolic thriftiness may relate to a previously observed correlation between birth season (a proxy for gestational undernutrition) and infectious disease mortality in rural African communities

The future of evolutionary medicine: sparking innovation in biomedicine and public health

Evolutionary medicine - i.e. the application of insights from evolution and ecology to biomedicine - has tremendous untapped potential to spark transformational innovation in biomedical research, clinical care and public health. Fundamentally, a systematic mapping across the full diversity of life is required to identify animal model systems for disease vulnerability, resistance, and counter-resistance that could lead to novel clinical treatments. Evolutionary dynamics should guide novel therapeutic approaches that target the development of treatment resistance in cancers (e.g., via adaptive or extinction therapy) and antimicrobial resistance (e.g., via innovations in chemistry, antimicrobial usage, and phage therapy). With respect to public health, the insight that many modern human pathologies (e.g., obesity) result from mismatches between the ecologies in which we evolved and our modern environments has important implications for disease prevention. Life-history evolution can also shed important light on patterns of disease burden, for example in reproductive health. Experience during the COVID-19 (SARS-CoV-2) pandemic has underlined the critical role of evolutionary dynamics (e.g., with respect to virulence and transmissibility) in predicting and managing this and future pandemics, and in using evolutionary principles to understand and address aspects of human behavior that impede biomedical innovation and public health (e.g., unhealthy behaviors and vaccine hesitancy). In conclusion, greater interdisciplinary collaboration is vital to systematically leverage the insight-generating power of evolutionary medicine to better understand, prevent, and treat existing and emerging threats to human, animal, and planetary health

Developmental synchrony of thalamocortical circuits in the neonatal brain

10.1016/j.neuroimage.2015.03.039Neuroimage116168-176GUSTO (Growing up towards Healthy Outcomes

Impaired perinatal growth and longevity: a life history perspective

Life history theory proposes that early-life cues induce highly integrated responses in traits associated with energy partitioning, maturation, reproduction, and aging such that the individual phenotype is adaptively more appropriate to the anticipated environment. Thus, maternal and/or neonatally derived nutritional or endocrine cues suggesting a threatening environment may favour early growth and reproduction over investment in tissue reserve and repair capacity. These may directly affect longevity, as well as prioritise insulin resistance and capacity for fat storage, thereby increasing susceptibility to metabolic dysfunction and obesity. These shifts in developmental trajectory are associated with long-term expression changes in specific genes, some of which may be underpinned by epigenetic processes. This normative process of developmental plasticity may prove to be maladaptive in human environments in transition towards low extrinsic mortality and energy-dense nutrition, leading to the development of an inappropriate phenotype with decreased potential for longevity and/or increased susceptibility to metabolic disease

Developmental contributions to macronutrient selection: A randomized controlled trial in adult survivors of malnutrition

Background and objectives: Birthweight differences between kwashiorkor and marasmus suggest that intrauterine factors influence the development of these syndromes of malnutrition and may modulate risk of obesity through dietary intake. We tested the hypotheses that the target protein intake in adulthood is associated with birthweight, and that protein leveraging to maintain this target protein intake would influence energy intake (EI) and body weight in adult survivors of malnutrition.Methodology: Sixty-three adult survivors of marasmus and kwashiorkor could freely compose a diet from foods containing 10, 15 and 25 percentage energy from protein (percentage of energy derived from protein (PEP); Phase 1) for 3 days. Participants were then randomized in Phase 2 (5 days) to diets with PEP fixed at 10%, 15% or 25%.Results: Self-selected PEP was similar in both groups. In the groups combined, selected PEP was 14.7, which differed significantly (P < 0.0001) from the null expectation (16.7%) of no selection. Self-selected PEP was inversely related to birthweight, the effect disappearing after adjusting for sex and current body weight. In Phase 2, PEP correlated inversely with EI (P = 0.002) and weight change from Phase 1 to 2 (P = 0.002). Protein intake increased with increasing PEP, but to a lesser extent than energy increased with decreasing PEP.Conclusions and implications: Macronutrient intakes were not independently related to birthweight or diagnosis. In a free-choice situation (Phase 1), subjects selected a dietary PEP significantly lower than random. Lower PEP diets induce increased energy and decreased protein intake, and are associated with weight gain