Modelling the impact of wastewater flows and management practices on antimicrobial resistance in dairy farms.

Dairy slurry is a major source of environmental contamination with antimicrobial resistant genes and bacteria. We developed mathematical models and conducted on-farm research to explore the impact of wastewater flows and management practices on antimicrobial resistance (AMR) in slurry. Temporal fluctuations in cephalosporin-resistant Escherichia coli were observed and attributed to farm activities, specifically the disposal of spent copper and zinc footbath into the slurry system. Our model revealed that resistance should be more frequently observed with relevant determinants encoded chromosomally rather than on plasmids, which was supported by reanalysis of sequenced genomes from the farm. Additionally, lower resistance levels were predicted in conditions with lower growth and higher death rates. The use of muck heap effluent for washing dirty channels did not explain the fluctuations in cephalosporin resistance. These results highlight farm-specific opportunities to reduce AMR pollution, beyond antibiotic use reduction, including careful disposal or recycling of waste antimicrobial metals.

Maintaining High-Touch in High-Tech Digital Health Monitoring and Multi-Omics Prognostication: Ethical, Equity, and Societal Considerations in Precision Health for Palliative Care.

Advances in digital health, systems biology, environmental monitoring, and artificial intelligence (AI) continue to revolutionize health care, ushering a precision health future. More than disease treatment and prevention, precision health aims at maintaining good health throughout the lifespan. However, how can precision health impact care for people with a terminal or life-limiting condition? We examine here the ethical, equity, and societal/relational implications of two precision health modalities, (1) integrated systems biology/multi-omics analysis for disease prognostication and (2) digital health technologies for health status monitoring and communication. We focus on three main ethical and societal considerations: benefits and risks associated with integration of these modalities into the palliative care system; inclusion of underrepresented and marginalized groups in technology development and deployment; and the impact of high-tech modalities on palliative care's highly personalized and "high-touch" practice. We conclude with 10 recommendations for ensuring that precision health technologies, such as multi-omics prognostication and digital health monitoring, for palliative care are developed, tested, and implemented ethically, inclusively, and equitably.

Antimicrobial resistance in dairy slurry tanks: A critical point for measurement and control.

Waste from dairy production is one of the largest sources of contamination from antimicrobial resistant bacteria (ARB) and genes (ARGs) in many parts of the world. However, studies to date do not provide necessary evidence to inform antimicrobial resistance (AMR) countermeasures. We undertook a detailed, interdisciplinary, longitudinal analysis of dairy slurry waste. The slurry contained a population of ARB and ARGs, with resistances to current, historical and never-used on-farm antibiotics; resistances were associated with Gram-negative and Gram-positive bacteria and mobile elements (ISEcp1, Tn916, Tn21-family transposons). Modelling and experimental work suggested that these populations are in dynamic equilibrium, with microbial death balanced by fresh input. Consequently, storing slurry without further waste input for at least 60 days was predicted to reduce ARB spread onto land, with > 99 % reduction in cephalosporin resistant Escherichia coli. The model also indicated that for farms with low antibiotic use, further reductions are unlikely to reduce AMR further. We conclude that the slurry tank is a critical point for measurement and control of AMR, and that actions to limit the spread of AMR from dairy waste should combine responsible antibiotic use, including low total quantity, avoidance of human critical antibiotics, and choosing antibiotics with shorter half-lives, coupled with appropriate slurry storage.

The phytochemical plumbagin reciprocally modulates osteoblasts and osteoclasts.

Bone metabolism is essential for maintaining bone mineral density and bone strength through a balance between bone formation and bone resorption. Bone formation is associated with osteoblast activity whereas bone resorption is linked to osteoclast differentiation. Osteoblast progenitors give rise to the formation of mature osteoblasts whereas monocytes are the precursors for multi-nucleated osteoclasts. Chronic inflammation, auto-inflammation, hormonal changes or adiposity have the potential to disturb the balance between bone formation and bone loss. Several plant-derived components are described to modulate bone metabolism and alleviate osteoporosis by enhancing bone formation and inhibiting bone resorption. The plant-derived naphthoquinone plumbagin is a bioactive compound that can be isolated from the roots of the Plumbago genus. It has been used as traditional medicine for treating infectious diseases, rheumatoid arthritis and dermatological diseases. Reportedly, plumbagin exerts its biological activities primarily through induction of reactive oxygen species and triggers osteoblast-mediated bone formation. It is plausible that plumbagin's reciprocal actions - inhibiting or inducing death in osteoclasts but promoting survival or growth of osteoblasts - are a function of the synergy with bone-metabolizing hormones calcitonin, Parathormone and vitamin D. Herein, we develop a framework for plausible molecular modus operandi of plumbagin in bone metabolism.

Sociotechnical imaginaries of low-carbon waste-energy futures: UK techno-market fixes displacing public accountability.

To implement EU climate policy, the UK's New Labour government (1997-2010) elaborated an ecomodernist policy framework. It promoted technological innovation to provide low-carbon renewable energy, especially by treating waste as a resource. This framework discursively accommodated rival sociotechnical imaginaries, understood as visions of feasible and desirable futures available through technoscientific development. According to the dominant imaginary, techno-market fixes stimulate low-carbon technologies by making current centralized systems more resource-efficient (as promoted by industry incumbents). According to the alternative eco-localization imaginary, a shift to low-carbon systems should instead localize resource flows, output uses and institutional responsibility (as promoted by civil society groups). The UK government policy framework gained political authority by accommodating both imaginaries. As we show by drawing on three case studies, the realization of both imaginaries depended on institutional changes and material-economic resources of distinctive kinds. In practice, financial incentives drove technological design towards trajectories that favour the dominant sociotechnical imaginary, while marginalizing the eco-localization imaginary and its environmental benefits. The ecomodernist policy framework relegates responsibility to anonymous markets, thus displacing public accountability of the state and industry. These dynamics indicate the need for STS research on how alternative sociotechnical imaginaries mobilize support for their realization, rather than be absorbed into the dominant imaginary.

Regenerative medicine in India: trends and challenges in innovation and regulation.

The government of India has heavily promoted research and development in regenerative medicine together with domestic innovation and business development initiatives. Together, these promise a revolution in healthcare and public empowerment in India. Several national and transnational linkages have emerged to develop innovative capacity, most prominently in stem cell and cord blood banking, as well as in gene therapy, tissue engineering, biomaterials and 3D printing. However, challenges remain of achieving regulatory oversight, viable outputs and equitable impacts. Governance of private cord blood banking, nanomaterials and 3D bioprinting requires more attention. A robust social contract is also needed in healthcare more generally, so that participation in research and innovation in regenerative medicine is backed up by treatments widely accessible to all.

Integrating social and value dimensions into sustainability assessment of lignocellulosic biofuels.

The paper clarifies the social and value dimensions for integrated sustainability assessments of lignocellulosic biofuels. We develop a responsible innovation approach, looking at technology impacts and implementation challenges, assumptions and value conflicts influencing how impacts are identified and assessed, and different visions for future development. We identify three distinct value-based visions. From a techno-economic perspective, lignocellulosic biofuels can contribute to energy security with improved GHG implications and fewer sustainability problems than fossil fuels and first-generation biofuels, especially when biomass is domestically sourced. From socio-economic and cultural-economic perspectives, there are concerns about the capacity to support UK-sourced feedstocks in a global agri-economy, difficulties monitoring large-scale supply chains and their potential for distributing impacts unfairly, and tensions between domestic sourcing and established legacies of farming. To respond to these concerns, we identify the potential for moving away from a one-size-fits-all biofuel/biorefinery model to regionally-tailored bioenergy configurations that might lower large-scale uses of land for meat, reduce monocultures and fossil-energy needs of farming and diversify business models. These configurations could explore ways of reconciling some conflicts between food, fuel and feed (by mixing feed crops with lignocellulosic material for fuel, combining livestock grazing with energy crops, or using crops such as miscanthus to manage land that is no longer arable); different bioenergy applications (with on-farm use of feedstocks for heat and power and for commercial biofuel production); and climate change objectives and pressures on farming. Findings are based on stakeholder interviews, literature synthesis and discussions with an expert advisory group.

Randomised trials in context: practical problems and social aspects of evidence-based medicine and policy.

Randomised trials can provide excellent evidence of treatment benefit in medicine. Over the last 50 years, they have been cemented in the regulatory requirements for the approval of new treatments. Randomised trials make up a large and seemingly high-quality proportion of the medical evidence-base. However, it has also been acknowledged that a distorted evidence-base places a severe limitation on the practice of evidence-based medicine (EBM). We describe four important ways in which the evidence from randomised trials is limited or partial: the problem of applying results, the problem of bias in the conduct of randomised trials, the problem of conducting the wrong trials and the problem of conducting the right trials the wrong way. These problems are not intrinsic to the method of randomised trials or the EBM philosophy of evidence; nevertheless, they are genuine problems that undermine the evidence that randomised trials provide for decision-making and therefore undermine EBM in practice. Finally, we discuss the social dimensions of these problems and how they highlight the indispensable role of judgement when generating and using evidence for medicine. This is the paradox of randomised trial evidence: the trials open up expert judgment to scrutiny, but this scrutiny in turn requires further expertise.

Governing stem cell therapy in India: regulatory vacuum or jurisdictional ambiguity?

Stem cell treatments are being offered in Indian clinics although preclinical evidence of their efficacy and safety is lacking. This is attributed to a governance vacuum created by the lack of legally binding research guidelines. By contrast, this paper highlights jurisdictional ambiguities arising from trying to regulate stem cell therapy under the auspices of research guidelines when treatments are offered in a private market disconnected from clinical trials. While statutory laws have been strengthened in 2014, prospects for their implementation remain weak, given embedded challenges of putting healthcare laws and professional codes into practice. Finally, attending to the capacities of consumer law and civil society activism to remedy the problem of unregulated treatments, the paper finds that the very definition of a governance vacuum needs to be reframed to clarify whose rights to health care are threatened by the proliferation of commercial treatments and individualized negligence-based remedies for grievances.

Biofuels and the role of space in sustainable innovation journeys.

This paper aims to identify the lessons that should be learnt from how biofuels have been envisioned from the aftermath of the oil shocks of the 1970s to the present, and how these visions compare with biofuel production networks emerging in the 2000s. Working at the interface of sustainable innovation journey research and geographical theories on the spatial unevenness of sustainability transition projects, we show how the biofuels controversy is linked to characteristics of globalised industrial agricultural systems. The legitimacy problems of biofuels cannot be addressed by sustainability indicators or new technologies alone since they arise from the spatial ordering of biofuel production. In the 1970-80s, promoters of bioenergy anticipated current concerns about food security implications but envisioned bioenergy production to be territorially embedded at national or local scales where these issues would be managed. Where the territorial and scalar vision was breached, it was to imagine poorer countries exporting higher-value biofuel to the North rather than the raw material as in the controversial global biomass commodity chains of today. However, controversy now extends to the global impacts of national biofuel systems on food security and greenhouse gas emissions, and to their local impacts becoming more widely known. South/South and North/North trade conflicts are also emerging as are questions over biodegradable wastes and agricultural residues as global commodities. As assumptions of a food-versus-fuel conflict have come to be challenged, legitimacy questions over global agri-business and trade are spotlighted even further. In this context, visions of biofuel development that address these broader issues might be promising. These include large-scale biomass-for-fuel models in Europe that would transform global trade rules to allow small farmers in the global South to compete, and small-scale biofuel systems developed to address local energy needs in the South.

Antimicrobial activity of silica coated silicon nano-tubes (SCSNT) and silica coated silicon nano-particles (SCSNP) synthesized by gas phase condensation.

Silica-coated, silicon nanotubes (SCSNTs) and silica-coated, silicon nanoparticles (SCSNPs) have been synthesized by catalyst-free single-step gas phase condensation using the arc plasma process. Transmission electron microscopy and scanning tunneling microscopy showed that SCSNTs exhibited a wall thickness of less than 1 nm, with an average diameter of 14 nm and a length of several 100 nm. Both nano-structures had a high specific surface area. The present study has demonstrated cheaper, resistance-free and effective antibacterial activity in silica-coated silicon nano-structures, each for two Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration (MIC) was estimated, using the optical densitometric technique, and by determining colony-forming units. The MIC was found to range in the order of micrograms, which is comparable to the reported MIC of metal oxides for these bacteria. SCSNTs were found to be more effective in limiting the growth of multidrug-resistant Staphylococcus aureus over SCSNPs at 10 µg/ml (IC 50 = 100 µg/ml).

Lessons from first generation biofuels and implications for the sustainability appraisal of second generation biofuels.

AIMS: The emergence of second generation (2G) biofuels is widely seen as a sustainable response to the increasing controversy surrounding the first generation (1G). Yet, sustainability credentials of 2G biofuels are also being questioned. Drawing on work in Science and Technology Studies, we argue that controversies help focus attention on key, often value-related questions that need to be posed to address broader societal concerns. This paper examines lessons drawn from the 1G controversy to assess implications for the sustainability appraisal of 2G biofuels. SCOPE: We present an overview of key 1G sustainability challenges, assess their relevance for 2G, and highlight the challenges for policy in managing the transition. We address limitations of existing sustainability assessments by exploring where challenges might emerge across the whole system of bioenergy and the wider context of the social system in which bioenergy research and policy are done. CONCLUSIONS: Key lessons arising from 1G are potentially relevant to the sustainability appraisal of 2G biofuels depending on the particular circumstances or conditions under which 2G is introduced. We conclude that sustainability challenges commonly categorised as either economic, environmental or social are, in reality, more complexly interconnected (so that an artificial separation of these categories is problematic).