Analytical Challenges and Metrological Approaches to Ensuring Dietary Supplement Quality: International Perspectives

The increased utilization of metrology resources and expanded application of its’ approaches in the development of internationally agreed upon measurements can lay the basis for regulatory harmonization, support reproducible research, and advance scientific understanding, especially of dietary supplements and herbal medicines. Yet, metrology is often underappreciated and underutilized in dealing with the many challenges presented by these chemically complex preparations. This article discusses the utility of applying rigorous analytical techniques and adopting metrological principles more widely in studying dietary supplement products and ingredients, particularly medicinal plants and other botanicals. An assessment of current and emerging dietary supplement characterization methods is provided, including targeted and non-targeted techniques, as well as data analysis and evaluation approaches, with a focus on chemometrics, toxicity, dosage form performance, and data management. Quality assessment, statistical methods, and optimized methods for data management are also discussed. Case studies provide examples of applying metrological principles in thorough analytical characterization of supplement composition to clarify their health effects. A new frontier for metrology in dietary supplement science is described, including opportunities to improve methods for analysis and data management, development of relevant standards and good practices, and communication of these developments to researchers and analysts, as well as to regulatory and policy decision makers in the public and private sectors. The promotion of closer interactions between analytical, clinical, and pharmaceutical scientists who are involved in research and product development with metrologists who develop standards and methodological guidelines is critical to advance research on dietary supplement characterization and health effects

The imperative for controlled mechanical stresses in unraveling cellular mechanisms of mechanotransduction

BACKGROUND: In vitro mechanotransduction studies are designed to elucidate cell behavior in response to a well-defined mechanical signal that is imparted to cultured cells, e.g. through fluid flow. Typically, flow rates are calculated based on a parallel plate flow assumption, to achieve a targeted cellular shear stress. This study evaluates the performance of specific flow/perfusion chambers in imparting the targeted stress at the cellular level. METHODS: To evaluate how well actual flow chambers meet their target stresses (set for 1 and 10 dyn/cm(2 )for this study) at a cellular level, computational models were developed to calculate flow velocity components and imparted shear stresses for a given pressure gradient. Computational predictions were validated with micro-particle image velocimetry (μPIV) experiments. RESULTS: Based on these computational and experimental studies, as few as 66% of cells seeded along the midplane of commonly implemented flow/perfusion chambers are subjected to stresses within ±10% of the target stress. In addition, flow velocities and shear stresses imparted through fluid drag vary as a function of location within each chamber. Hence, not only a limited number of cells are exposed to target stress levels within each chamber, but also neighboring cells may experience different flow regimes. Finally, flow regimes are highly dependent on flow chamber geometry, resulting in significant variation in magnitudes and spatial distributions of stress between chambers. CONCLUSION: The results of this study challenge the basic premise of in vitro mechanotransduction studies, i.e. that a controlled flow regime is applied to impart a defined mechanical stimulus to cells. These results also underscore the fact that data from studies in which different chambers are utilized can not be compared, even if the target stress regimes are comparable

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

Urban Safety, Anti-Social Behaviour and the Night-Time Economy

The contemporary city is a contested space and its governance is the subject of complex global economic forces, local interests and political struggles as well as a response to the changing face of governing alliances in residential and commercial areas, forms of consumption, commercially-generated crime and disorder and cultural expressions of leisure. This article seeks to provide a thematic introduction to the manner in which the regulation of contemporary British cities has been influenced by concerns with tackling anti-social behaviour and promoting civility. It argues that in governing urban safety, the normative governmental agendas that seek to remoralise and cleanse city spaces and promote certain values of appropriate consumer-citizen, often clash with commercially-driven imperatives to (excessive) consumption and the allure of cities, for some, as places of difference that exhibit relaxed normative constraints; most notably in the night-time economy. It argues that the manner in which these forces are played out is conditioned by the interplay between different actors and organisations, as both regulators and regulated, some of whom have assumed new responsibilities in the governance of urban safety. The resultant pressures have produced mixed experiences of the city as a meeting place for loosely connected strangers, as a place of indulgence and as a place of cultural expression

Bumpy black holes

We study six-dimensional rotating black holes with bumpy horizons: these are topologically spherical, but the sizes of symmetric cycles on the horizon vary nonmonotonically with the polar angle. We construct them numerically for the first three bumpy families, and follow them in solution space until they approach critical solutions with localized singularities on the horizon. We find strong evidence of the conical structures that have been conjectured to mediate the transitions to black rings, to black Saturns, and to a novel class of bumpy black rings. For a different, recently identified class of bumpy black holes, we find evidence that this family ends in solutions with a localized singularity that exhibits apparently universal properties, and which does not seem to allow for transitions to any known class of black holes

Improving natural product research translation:from source to clinical trial

While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a September, 2018 transdisciplinary workshop. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for NP characterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. Natural product clinical trials prioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research