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Transformation toward a sustainable future requires an earth stewardship approach to shift society from its current goal of increasing material wealth to a vision of sustaining built, natural, human, and social capital-equitably distributed across society, within and among nations. Widespread concern about earth's current trajectory and support for actions that would foster more sustainable pathways suggests potential social tipping points in public demand for an earth stewardship vision. Here, we draw on empirical studies and theory to show that movement toward a stewardship vision can be facilitated by changes in either policy incentives or social norms. Our novel contribution is to point out that both norms and incentives must change and can do so interactively. This can be facilitated through leverage points and complementarities across policy areas, based on values, system design, and agency. Potential catalysts include novel democratic institutions and engagement of non-governmental actors, such as businesses, civic leaders, and social movements as agents for redistribution of power. Because no single intervention will transform the world, a key challenge is to align actions to be synergistic, persistent, and scalable.

The multiple myeloma treatment landscape has changed dramatically. This change, paralleled by an increase in scientific knowledge, has resulted in significant improvement in survival. However, heterogeneity remains in clinical outcomes, with a proportion of patients not benefiting from current approaches and continuing to have a poor prognosis. A significant proportion of the variability in outcome can be predicted on the basis of clinical and biochemical parameters and tumor-acquired genetic variants, allowing for risk stratification and a more personalized approach to therapy. This article discusses the principles that can enable the rational and effective development of therapeutic approaches for high-risk multiple myeloma.

The increasing frequency of extreme events, exogenous and endogenous, poses challenges for our societies. The current pandemic is a case in point; but "once-in-a-century" weather events are also becoming more common, leading to erosion, wildfire and even volcanic events that change ecosystems and disturbance regimes, threaten the sustainability of our life-support systems, and challenge the robustness and resilience of societies. Dealing with extremes will require new approaches and large-scale collective action. Preemptive measures can increase general resilience, a first line of protection, while more specific reactive responses are developed. Preemptive measures also can minimize the negative effects of events that cannot be avoided. In this paper, we first explore approaches to prevention, mitigation and adaptation, drawing inspiration from how evolutionary challenges have made biological systems robust and resilient, and from the general theory of complex adaptive systems. We argue further that proactive steps that go beyond will be necessary to reduce unacceptable consequences.

The increasing frequency of extreme events, exogenous and endogenous, poses challenges for our societies. The current pandemic is a case in point; but "once-in-a-century" weather events are also becoming more common, leading to erosion, wildfire and even volcanic events that change ecosystems and disturbance regimes, threaten the sustainability of our life-support systems, and challenge the robustness and resilience of societies. Dealing with extremes will require new approaches and large-scale collective action. Preemptive measures can increase general resilience, a first line of protection, while more specific reactive responses are developed. Preemptive measures also can minimize the negative effects of events that cannot be avoided. In this paper, we first explore approaches to prevention, mitigation and adaptation, drawing inspiration from how evolutionary challenges have made biological systems robust and resilient, and from the general theory of complex adaptive systems. We argue further that proactive steps that go beyond will be necessary to reduce unacceptable consequences.

We consider two aspects of the human enterprise that profoundly affect the global environment: population and consumption. We show that fertility and consumption behavior harbor a class of externalities that have not been much noted in the literature. Both are driven in part by attitudes and preferences that are not egoistic but socially embedded; that is, each household's decisions are influenced by the decisions made by others. In a famous paper, Garrett Hardin [G. Hardin, Science 162, 1243-1248 (1968)] drew attention to overpopulation and concluded that the solution lay in people "abandoning the freedom to breed." That human attitudes and practices are socially embedded suggests that it is possible for people to reduce their fertility rates and consumption demands without experiencing a loss in wellbeing. We focus on fertility in sub-Saharan Africa and consumption in the rich world and argue that bottom-up social mechanisms rather than top-down government interventions are better placed to bring about those ecologically desirable changes.

Myocardial infarction (MI) leads to a multi-phase reparative process at the site of damaged heart that ultimately results in the formation of non-conductive fibrous scar tissue. Despite the widespread use of electroconductive biomaterials to increase the physiological relevance of bioengineered cardiac tissues in vitro, there are still several limitations associated with engineering biocompatible scaffolds with appropriate mechanical properties and electroconductivity for cardiac tissue regeneration. Here, we introduce highly adhesive fibrous scaffolds engineered by electrospinning of gelatin methacryloyl (GelMA) followed by the conjugation of a choline-based bio-ionic liquid (Bio-IL) to develop conductive and adhesive cardiopatches. These GelMA/Bio-IL adhesive patches were optimized to exhibit mechanical and conductive properties similar to the native myocardium. Furthermore, the engineered patches strongly adhered to murine myocardium due to the formation of ionic bonding between the Bio-IL and native tissue, eliminating the need for suturing. Co-cultures of primary cardiomyocytes and cardiac fibroblasts grown on GelMA/Bio-IL patches exhibited comparatively better contractile profiles compared to pristine GelMA controls, as demonstrated by over-expression of the gap junction protein connexin 43. These cardiopatches could be used to provide mechanical support and restore electromechanical coupling at the site of MI to minimize cardiac remodeling and preserve normal cardiac function.

Electroconductive hydrogels (ECHs) are highly hydrated 3D networks generated through the incorporation of conductive polymers, nanoparticles, and other conductive materials into polymeric hydrogels. ECHs combine several advantageous properties of inherently conductive materials with the highly tunable physical and biochemical properties of hydrogels. Recently, the development of biocompatible ECHs has been investigated for various biomedical applications, such as tissue engineering, drug delivery, biosensors, flexible electronics, and other implantable medical devices. Several methods for the synthesis of ECHs have been reported, which include the incorporation of electrically conductive materials such as gold and silver nanoparticles, graphene, and carbon nanotubes, as well as various conductive polymers (CPs), such as polyaniline, polypyrrole, and poly(3,4-ethylenedioxyythiophene) into hydrogel networks. Theses electroconductive composite hydrogels can be used as scaffolds with high swellability, tunable mechanical properties, and the capability to support cell growth both in vitro and in vivo. Furthermore, recent advancements in microfabrication techniques such as three dimensional (3D) bioprinting, micropatterning, and electrospinning have led to the development of ECHs with biomimetic microarchitectures that reproduce the characteristics of the native extracellular matrix (ECM). In addition, smart ECHs with controlled structures and healing properties have also been engineered into devices with prolonged half-lives and increased durability. The combination of sophisticated synthesis chemistries and modern microfabrication techniques have led to engineer smart ECHs with advanced architectures, geometries, and functionalities that are being increasingly used in drug delivery systems, biosensors, tissue engineering, and soft electronics. In this review, we will summarize different strategies to synthesize conductive biomaterials. We will also discuss the advanced microfabrication techniques used to fabricate ECHs with complex 3D architectures, as well as various biomedical applications of microfabricated ECHs.

A primary goal in the management of burn wounds is early wound closure. The use of skin allografts represents a lifesaving strategy for severe burn patients, but their ultimate rejection limits their potential efficacy and utility. IL-6 is a major pleiotropic cytokine which critically links innate and adaptive immune responses. Here, we devised anti-IL-6 receptor eluting gelatin methacryloyl (GelMA) biomaterials (GelMA/anti-IL-6), which were implanted at the interface between the wound beds and skin allografts. Our visible light crosslinked GelMA/anti-IL-6 immunomodulatory biomaterial (IMB) demonstrated a stable kinetic release profile of anti-IL-6. In addition, the incorporation of anti-IL-6 within the GelMA hydrogel had no effect on the mechanical properties of the hydrogels. Using a highly stringent skin transplant model, the GelMA/anti-IL-6 IMB almost doubled the survival of skin allografts. The use of GelMA/anti-IL-6 IMB was far superior to systemic anti-IL-6 receptor treatment in prolonging skin allograft survival. As compared to the untreated control group, skin from the GelMA/anti-IL-6 IMB group contained significantly fewer alloreactive T cells and macrophages. Interestingly, the environmental milieu of the draining lymph nodes (DLNs) of the mice implanted with the GelMA/anti-IL-6 IMB was also considerably less pro-inflammatory. The percentage of CD4+ IFNγ+ cells was much lower in the DLNs of the GelMA/anti-IL-6 IMB group in comparison to the GelMA group. These data highlight the importance of localized immune delivery in prolonging skin allograft survival and its potential utility in treating patients with severe burns.

Bioengineered tissues have become increasingly more sophisticated owing to recent advancements in the fields of biomaterials, microfabrication, microfluidics, genetic engineering, and stem cell and developmental biology. In the coming years, the ability to engineer artificial constructs that accurately mimic the compositional, architectural, and functional properties of human tissues, will profoundly impact the therapeutic and diagnostic aspects of the healthcare industry. In this regard, bioengineered cardiac tissues are of particular importance due to the extremely limited ability of the myocardium to self-regenerate, as well as the remarkably high mortality associated with cardiovascular diseases worldwide. As novel microphysiological systems make the transition from bench to bedside, their implementation in high throughput drug screening, personalized diagnostics, disease modeling, and targeted therapy validation will bring forth a paradigm shift in the clinical management of cardiovascular diseases. Here, we will review the current state of the art in experimental in vitro platforms for next generation diagnostics and therapy validation. We will describe recent advancements in the development of smart biomaterials, biofabrication techniques, and stem cell engineering, aimed at recapitulating cardiovascular function at the tissue- and organ levels. In addition, integrative and multidisciplinary approaches to engineer biomimetic cardiovascular constructs with unprecedented human and clinical relevance will be discussed. We will comment on the implementation of these platforms in high throughput drug screening, in vitro disease modeling and therapy validation. Lastly, future perspectives will be provided on how these biomimetic platforms will aid in the transition towards patient centered diagnostics, and the development of personalized targeted therapeutics.

Florida's coral reefs are facing a multi-year outbreak of stony coral tissue loss disease (SCTLD) with dramatic consequences for coral communities. However, potential anthropogenic and environmental drivers of SCTLD progression and severity remain poorly understood. This study was designed to determine the potential impacts of nutrient amendments on the progression and spread of SCTLD on reefs in Southeast Florida. In situ fertilizer amendments with 30 g of Osmocote™ slow-release fertilizer were used to mimic the effects of agricultural and urban runoff. Fifteen healthy and thirty SCTLD-affected Montastraea cavernosa coral colonies were tagged and divided into three experimental groups: apparently healthy colonies, SCTLD-affected nutrient-amended colonies, and SCTLD-affected control colonies. SCTLD lesion progression, coral tissue loss, and disease prevalence were tracked over a 30-day nutrient amendment period and for an additional 40 days after nutrient amendment removal to determine if there were any latent or recovery effects. Coral tissue loss was tracked over time using Structure-from-Motion photogrammetry and disease prevalence was recorded from diver surveys within a 3-m radius surrounding five centroid colonies from each experimental group. Throughout the experiment, temperature, nutrient concentrations, and SCTLD status of the coral colonies were also monitored. Ultimately, we observed no significant differences in SCTLD progression or surrounding SCTLD prevalence between the nutrient-amended and control groups, suggesting that nutrient amendment had no effect on SCTLD severity during this experiment in Southeast Florida. [ABSTRACT FROM AUTHOR]

Individuals with psychiatric disorders have elevated rates of autoimmune comorbidity and altered immune signaling. It is unclear whether these altered immunological states have a shared genetic basis with those psychiatric disorders. The present study sought to use existing summary-level data from previous genome-wide association studies to determine if commonly varying single nucleotide polymorphisms are shared between psychiatric and immune-related phenotypes. We estimated heritability and examined pair-wise genetic correlations using the linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics methods. Using LDSC, we observed significant genetic correlations between immune-related disorders and several psychiatric disorders, including anorexia nervosa, attention deficit-hyperactivity disorder, bipolar disorder, major depression, obsessive compulsive disorder, schizophrenia, smoking behavior, and Tourette syndrome. Loci significantly mediating genetic correlations were identified for schizophrenia when analytically paired with Crohn's disease, primary biliary cirrhosis, systemic lupus erythematosus, and ulcerative colitis. We report significantly correlated loci and highlight those containing genome-wide associations and candidate genes for respective disorders. We also used the LDSC method to characterize genetic correlations among the immune-related phenotypes. We discuss our findings in the context of relevant genetic and epidemiological literature, as well as the limitations and caveats of the study.

El Niño Southern Oscillation events (ENSO) and the subsequent opposite weather patterns in the following months and years (La Niña) have major climatic impacts, especially on oceanic habitats, affecting breeding success of both land and sea birds. We assessed corticosterone concentrations from blood samples during standardized protocols of capture, handling and restraint to simulate acute stress from 12 species of Galapagos Island birds during the ENSO year of 1998 and a La Niña year of 1999. Plasma levels of corticosterone were measured in samples collected at capture (to represent non-stressed baseline) and subsequently up to 1 h post-capture to give maximum corticosterone following acute stress, and total amount of corticosterone that the individual was exposed to during the test period (integrated corticosterone). Seabird species that feed largely offshore conformed to the brood value hypothesis whereas inshore feeding species showed less significant changes. Land birds mostly revealed no differences in the adrenocortical responses to acute stress from year to year with the exception of two small species (

Conventional methods to engineer electroconductive hydrogels (ECHs) through the incorporation of conductive nanomaterials and polymers exhibit major technical limitations. These are mainly associated with the cytotoxicity, as well as poor solubility, processability, and biodegradability of their components. Here, we describe the engineering of a new class of ECHs through the functionalization of non-conductive polymers with a conductive choline-based bio-ionic liquid (Bio-IL). Bio-IL conjugated hydrogels exhibited a wide range of highly tunable physical properties, remarkable in vitro and in vivo biocompatibility, and high electrical conductivity without the need for additional conductive components. The engineered hydrogels could support the growth and function of primary cardiomyocytes in both two dimentinal (2D) and three dimensional (3D) cultures in vitro. Furthermore, they were shown to be efficiently biodegraded and possess low immunogenicity when implanted subcutaneously in rats. Taken together, our results suggest that Bio-IL conjugated hydrogels could be implemented and readily tailored to different biomedical and tissue engineering applications.

Arctic weather in spring is unpredictable and can also be extreme, so Arctic-breeding birds must be flexible in their breeding to deal with such variability. Unpredictability in weather conditions will only intensify with climate change and this in turn could affect reproductive capability of migratory birds. Adjustments to coping strategies are therefore crucial, so here we examined the plasticity of the adrenocorticotropic stress response in two Arctic songbird species-the snow bunting (Plectrophenax nivalis) and Lapland longspur (Calcarius lapponicus)-breeding in northwest Greenland. Across the breeding season, the stress response was strongest at arrival and least robust during molt in male snow buntings. Snow bunting females had higher baseline but similar stress-induced corticosterone levels compared to males. Modification of the stress response was not due to adrenal insensitivity, but likely regulated at the anterior pituitary gland. Compared to independent nestlings and adult snow buntings, parental-dependent chicks had a more robust stress response. For Lapland longspurs, baseline corticosterone was highest at arrival in both male and females, and arriving males displayed a higher stress response compared to arriving females. Comparison of male corticosterone profiles collected at arrival in Greenland (76°N) and Alaska (67-71°N;) reveal that both species have higher stress responses at the more northern location. Flexibility in the stress response may be typical for birds nesting at the leading edges of their range and this ability will become more relevant as global climate change results in major shifts of breeding habitat and phenology for migratory birds.