Regulatory Readiness Level: a Tool to Enhance Early Regulatory Adoption in Academic Discovery

The development of pharmaceuticals products is a complex and arduous process. It requires significant investment (both financial and time). The costs of developing products range from $314 million to$2.8 billion, with the time of bringing a new drug to market up to 15 years. The overall probability of success from phase 1 to approval is estimated at between 9% to 12%. Concerns have been raised in the fall off of new approvals and the decreasing number of innovative therapies coming through pharmaceutical R&D divisions. Academia is recognised as a source of such new therapies, but their strengths do not lie in successfully getting product to market. Difficulties arise in the academic setting, due to their lack of understanding and knowledge of the rigorous regulatory requirements that are needed to gain clearance to market pharmaceutical products. Additional tools are needed to aid academic researchers navigate the necessary regulatory pathways. Whilst Technology Readiness Level (TRL) tools exist, they are simplistic in nature and do not provide the necessary detail to facilitate this process. An expansion of the TRL is proposed as one such solution, in the form of a Regulatory Readiness (RRL) tool. This tool will serve as a suitable method to ensure academics have the knowledge and skills to incorporate regulatory science into their product development processes

The examination of developmental potential in forest species through in vitro grafting of oak (Quercus robur and Quercus petraea)

As plants get older they go through a gradual developmental ageing process, from a juvenile phase characterised by rapid growth, good rooting potential, and orthotropic growth, to a mature phase characterised by slow growth, poor rooting potential and plagiotropic growth. This is of considerable importance from the viewpoint of propagation of 'elite' trees , since it is usually impossible to identify high quality plants at the seedling stage and difficulties in the vegetative propagation of adult woody plants arise due the physiological changes associated with maturation. The process of such maturation is very complex and poorly understood. The development of tissue culture techniques, has allowed for the mechanisms underlying maturation and rejuvenation of woody species to be better understood. The technique of cascade grafting of mature tissue to juvenile tissue has yielded ‘rejuvenated’ in several woody plant species. However the techniques of ‘rejuvenation’ rely on the availability of good quantitative markers for juvenile and mature plants. This study was concerned with two aspects of rejuvenation of mature oak material. The establishment of good quantitative and qualitative markers for in vitro growing juvenile and mature Quercus robur and Quercus petraea plants to enable the progress of rejuvenation to be assesed and the development of a system for in vitro cascade grafting of Quercus material. Shoot cultures of Quercus species of juvenile, adolescent and mature origin were examined for a range of morphological and physiological markers of juvenility and maturity in vitro. Morphological Criteria examined were angle of the shoot to the horizontal, stem length, stem diameter (tip, mid, base), leaf number, scale leaf number and shoot number. Image analysis was also carried out to determine leaf area, size, and breadth and length of leaves. Mature Q. robur clones showed a larger mid-stem diameter than juvenile clones, while mature Q. petraea clones were characterised by larger stem diameters at the apex, greater number of leaves on the shoot, shorter shoots and plagiotropic growth. Discriminant analysis on data for Q. robur and Q. petraea allows us to propose the following formulae for discrimination of juvenile and mature shoots where a negative value for Discriminant Score (D) indicates juvenility. Q. petraea Discriminant Score D = - 1.308 - 0.035l*Angle(°) + 2.41*Tip diameter(mm) + 1.435*Mid - Stem diameter(mm) Q. robur Discriminant Score D = - 3.546 + 2.418*Tip diameter(mm) + 2.202it=Mid-Stem Diameter(mm

The making of India's COVID-19 disaster: A Disaster Risk Management (DRM) Assemblage analysis

This article analyses the suite of policies and measures enacted by the Indian Union Government in response to the COVID-19 pandemic through apparatuses of disaster management. We focus on the period from the onset of the pandemic in early 2020, until mid-2021. This holistic review adopts a Disaster Risk Management (DRM) Assemblage conceptual approach to make sense of how the COVID-19 disaster was made possible and importantly how it was responded to, managed, exacerbated, and experienced as it continued to emerge. This approach is grounded in literature from critical disaster studies and geography. The analysis also draws on a wide range of other disciplines, ranging from epidemiology to anthropology and political science, as well as grey literature, newspaper reports, and official policy documents. The article is structured into three sections that investigate in turn and at different junctures the role of governmentality and disaster politics; scientific knowledge and expert advice, and socially and spatially differentiated disaster vulnerabilities in shaping the COVID-19 disaster in India. We put forward two main arguments on the basis of the literature reviewed. One is that both the impacts of the virus spread and the lockdown-responses to it affected already marginalised groups disproportionately. The other is that managing the COVID-19 pandemic through disaster management assemblage/apparatuses served to extend centralised executive authority in India. These two processes are demonstrated to be continuations of pre-pandemic trends. We conclude that evidence of a paradigm shift in India's approach to disaster management remains thin on the ground

The Neogene and Quaternary : chronostratigraphic compromise or non-overlapping magisteria?

Author Posting. © Micropaleontology Press, 2009. This article is posted here by permission of Micropaleontology Press for personal use, not for redistribution. The definitive version was published in Stratigraphy 6 (2009): 1-16.The International Commission on Stratigraphy (ICS) together with its subcommissions on Neogene Stratigraphy (SNS) and Quaternary Stratigraphy (SQS) are facing a persistent conundrum regarding the status of the Quaternary, and the implications for the Neogene System/Period and the Pleistocene Series/Epoch. The SQS, in seeking a formal role for the Quaternary in the standard time scale, has put forward reasons not only to truncate and redefine the Neogene in order to accommodate this unit as a third System/Period in the Cenozoic, but furthermore to shift the base of the Pleistocene to c. 2.6 Ma to conform to a new appreciation of when “Quaternary climates” began. The present authors, as members of SNS, support the well-established concept of a Neogene extending to the Recent, as well as the integrity of the Pleistocene according to its classical meaning, and have published arguments for workable options that avoid this conflict. In this paper, we return to the basic principles involved in the conversion of the essentially marine biostratigraphic/ biochronologic units of Lyell and other 19th-century stratigraphers into the modern hierarchical arrangement of chronostratigraphic units, embodied in the Global Standard Stratotype-section and Point (GSSP) formulation for boundary definitions. Seen in this light, an immediate problem arises from the fact that the Quaternary, either in its original sense as a state of consolidation or in the more common sense as a paleoclimatic entity, is conceptually different from a Lyellian unit, and that a Neogene/Quaternary boundary may therefore be a non sequitur. Secondly, as to retaining the base of the Pleistocene at 1.8 Ma, the basic hierarchical principles dictate that changing the boundary of any non-fundamental or “higher” chronostratigraphic unit is not possible without moving the boundary of its constituent fundamental unit. Therefore, to move the base of the Pleistocene, which is presently defined by the Calabrian GSSP at 1.8 Ma, to be identified with the Gelasian GSSP at 2.6 Ma, requires action to formally redefine the Gelasian as part of the Pleistocene. Finally, it is important to keep in mind that the subject under discussion is chronostratigraphy, not biostratigraphy. Both systems are based on the fossil record, but biostratigraphic units are created to subdivide and correlate stratigraphic sequences. The higher-level units of chronostratigraphy, however, were initially selected to reflect the history of life through geological time. The persistence of a characteristic biota in the face of environmental pressures during the last 23 my argues strongly for the concept of an undivided Neogene that extends to the present. Several ways to accommodate the Quaternary in the standard time scale can be envisaged that preserve the original concepts of the Neogene and Pleistocene. The option presently recommended by SNS, and most compatible with the SQS position, is to denominate the Quaternary as a subperiod/subsystem of the Neogene, decoupled from the Pleistocene so that its base can be identified with the Gelasian GSSP at c. 2.6 Ma. A second option is to retain strict hierarchy by restricting a Quaternary subperiod to the limits of the Pleistocene at 1.8 Ma. As a third option, the Quaternary could be a subera/suberathem or a supersystem/ superperiod, decoupled from the Neogene and thus with its base free to coincide with a convenient marker such as the base of the Pleistocene at 1.8 Ma, or to the Gelasian at 2.6 Ma, as opinions about paleoclimatology dictate. If no compromise can be reached within hierarchical chronostratigraphy, however, an alternative might be to consider Quaternary and Neogene as mutually exclusive categories (climatostratigraphic vs. chronostratigraphic) in historical geology. In this case, we would recommend the application of the principle of NOMA, or Non-Overlapping Magisteria, in the sense of the elegant essay by the late Stephen J. Gould (1999) on the mutually exclusive categories of Religion and Science. In this case the Quaternary would have its own independent status as a climatostratigraphic unit with its own subdivisions based on climatic criteria

What, if anything, is Quaternary?

The formal recognition of Quaternary as a Period/ System was approved by IUGS in June 2009, in accordance with a proposal originated by INQUA. There are reasons to believe that this will have destabilizing consequences for the geological time scale. Until now, the primary divisions of the stratigraphic record, at the Period level and above, have been based on the progressive change of Earth’s biota. The Quaternary, on the other hand, is a paleoclimatic concept based on glacial-interglacial variability, expressed in lithological change. The IUGS vote holds that this paradigm now supersedes the biochronological identity of the Neogene Period/System. Furthermore, to accommodate the most recent INQUA opinion about “when the Ice Ages began”, the ICS agreed to relocate the base of the Pleistocene to 2.59 Ma from 1.81 Ma, enlarging the epoch by 43% and again without regard for its original paleontological definition, or for the vast literature in other fields of Pleistocene research. If history is a guide, the resulting disruption in late Cenozoic marine and vertebrate paleontology, human evolution, paleoceanography and paleoclimatology will be widely resisted, with potential impact on the authority of IUGS. The consequence of abandoning basic principles in order to satisfy the interest of a special group deserves a wider consideration than it has so far received

Integrated stratigraphy of the Waitakian-Otaian Stage boundary stratotype, Early Miocene, New Zealand

The base of the type section of the Otaian Stage at Bluecliffs, South Canterbury, is recognised as the stratotype for the boundary between the Waitakian and Otaian Stages. Principal problems with the boundary are the restriction of existing bioevent proxies to shelf and upper slope environments and its uncertain age. These topics are addressed by a multidisplinary study of a 125 m section about the boundary, which examines its lithostratigraphy, depositional setting, biostratigraphy, correlation, and geochronology. The lower siltstone lithofacies (0-38.5 m) was deposited at upper bathyal depths (200-600 m) in a marginal basin which was partially sheltered from fully oceanic circulation by a submarine high and islands. The site was covered by cool-temperate water and was probably adjacent to the Subtropical Convergence. This unit is succeeded by the banded lithofacies (38.5-106 m) and the upper siltstone lithofacies (basal 19 m studied). Paleodepth probably declined up-sequence, but deposition at shelf depths is not definitely indicated. A cyclic pattern of abundance spikes in benthic and planktonic foraminifera commences 9 m above base and extends to 73 m in the banded lithofacies. Oxygen isotope excursions (up to 2.08%) in Euuvigerina miozea and Cibicides novozelandicus are greatest within the interval containing the abundance spikes. The stage boundary occurs in the banded lithofacies at the highest abundance spike (73 m). Although condensed intervals might affect the completeness of the section, they are not associated with sedimentary discontinuities, and we consider that the section is suitable as a biostratigraphic reference. Spores, pollens, dinoflagellates, calcareous nannofossils, foraminifera, bryozoans, and ostracods are preserved near the boundary, but molluscs principally occur higher, in the shallower upper siltstone lithofacies. Siliceous microfossils are rare. There is considerable scope for further biostratigraphic research. The primary event marking the boundary at 73 m is the appearance of the benthic foraminifer Ehrenbergina marwicki. This is a distinctive and widely distributed event but is restricted to shelf and upper bathyal environments. Supplementary events in planktonic foraminifera and calcareous nannofossils were researched. Highest occurrences of Globigerina brazieri and G. euapertura are recorded at 47 and 58 m. There is a marked decline in relative abundance of Paragloborotalia spp. at 62 m. Helicosphaera carteri becomes more abundant than H. euphratis between 56 and 87 m. These events are not exact proxies for the boundary but they may usefully indicate proximity to it. They occur in the interval of prominent spikes in foraminiferal abundance. The Waitakian-Otaian boundary is dated at 21.7 Ma by strontium isotopes. Stable primary remanence could not be determined in a pilot paleomagnetic study of Bluecliffs specimens. However, specimens trended towards reversed polarity, and remagnetisation great circle analysis will allow directions to be calculated in future collections

Table 2: Measurements (mm) of NTM P91171-1, Baru wickeni

New records of the Oligo–Miocene mekosuchine crocodylian, Baru, from Queensland and the Northern Territory are described. Baru wickeni and Baru darrowi are accepted as valid species in the genus and their diagnoses are revised. Both species are present in Queensland and the Northern Territory but are restricted in time, with B. wickeni known from the late Oligocene and B. darrowi from the middle Miocene. The broad geographic distributions and restricted time spans of these species indicate that this genus is useful for biochronology. The record of B. wickeni from the Pwerte Marnte Marnte Local Fauna in the Northern Territory establishes that the species inhabited the north-western margin of the Lake Eyre Basin (LEB) drainage system. More southerly Oligo–Miocene sites in the LEB contain only one crocodylian species, Australosuchus clarkae. The Pwerte Marnte Marnte occurrence of B. wickeni indicates that the separation of Baru and Australosuchus did not correspond with the boundaries of drainage basins and that palaeolatitude was a more likely segregating factor

The 3rd Global Summit of Research Institutes for Disaster Risk Reduction: Expanding the Platform for Bridging Science and Policy Making

The Global Alliance of Disaster Research Institutes held its 3rd Global Summit of Research Institutes for Disaster Risk Reduction at the Disaster Prevention Research Institute, Kyoto University, Japan, 19–21 March, 2017. The Global Alliance seeks to contribute to enhancing disaster risk reduction (DRR) and disaster resilience through the collaboration of research organizations around the world. The summit aim was to expand the platform for bridging science and policy making by evaluating the evidence base needed to meet the expected outcomes and actions of the Sendai Framework for Disaster Risk Reduction 2015–2030 and its Science and Technology Roadmap. The summit reflected the international nature of collaborative research and action. A pre-conference questionnaire filled out by Global Alliance members identified 323 research projects that are indicative of current research. These were categorized to support seven parallel discussion sessions related to the Sendai Framework priorities for action. Four discussion sessions focused on research that aims to deepen the understanding of disaster risks. Three cross-cutting sessions focused on research that is aimed at the priorities for action on governance, resilience, and recovery. Discussion summaries were presented in plenary sessions in support of outcomes for widely enhancing the science and policy of DRR

Eocene biogenic silica accumulation rates at the Pacific equatorial divergence zone

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94733/1/palo1454.pd

Environmental Forcings of Paleogene Southern Ocean Dinoflagellate Biogeography

Despite warm polar climates and low meridional temperature gradients, a number of different high-latitude plankton assemblages were, to varying extents, dominated by endemic species during most of the Paleogene. To better understand the evolution of Paleogene plankton endemism in the high southern latitudes, we investigate the spatiotemporal distribution of the fossil remains of dinoflagellates, i.e., organic-walled cysts (dinocysts), and their response to changes in regional sea surface temperature (SST). We show that Paleocene and early Eocene (∼65–50 Ma) Southern Ocean dinocyst assemblages were largely cosmopolitan in nature but that a distinct switch from cosmopolitan-dominated to endemic-dominated assemblages (the so-called “transantarctic flora”) occurred around the early-middle Eocene boundary (∼50 Ma). The spatial distribution and relative abundance patterns of this transantarctic flora correspond well with surface water circulation patterns as reconstructed through general circulation model experiments throughout the Eocene. We quantitatively compare dinocyst assemblages with previously published TEX86–based SST reconstructions through the early and middle Eocene from a key locality in the southwest Pacific Ocean, ODP Leg 189 Site 1172 on the East Tasman Plateau. We conclude that the middle Eocene onset of the proliferation of the transantarctic flora is not linearly correlated with regional SST records and that only after the transantarctic flora became fully established later in the middle Eocene, possibly triggered by large-scale changes in surface-ocean nutrient availability, were abundances of endemic dinocysts modulated by regional SST variations