Normalisation to Blood Activity Is Required for the Accurate Quantification of Na/I Symporter Ectopic Expression by SPECT/CT in Individual Subjects

The utilisation of the Na/I symporter (NIS) and associated radiotracers as a reporter system for imaging gene expression is now reaching the clinical setting in cancer gene therapy applications. However, a formal assessment of the methodology in terms of normalisation of the data still remains to be performed, particularly in the context of the assessment of activities in individual subjects in longitudinal studies. In this context, we administered to mice a recombinant, replication-incompetent adenovirus encoding rat NIS, or a human colorectal carcinoma cell line (HT29) encoding mouse NIS. We used 99mTc pertechnetate as a radiotracer for SPECT/CT imaging to determine the pattern of ectopic NIS expression in longitudinal kinetic studies. Some animals of the cohort were culled and NIS expression was measured by quantitative RT-PCR and immunohistochemistry. The radioactive content of some liver biopsies was also measured ex vivo. Our results show that in longitudinal studies involving datasets taken from individual mice, the presentation of non-normalised data (activity expressed as %ID/g or %ID/cc) leads to ‘noisy’, and sometimes incoherent, results. This variability is due to the fact that the blood pertechnetate concentration can vary up to three-fold from day to day. Normalisation of these data with blood activities corrects for these inconsistencies. We advocate that, blood pertechnetate activity should be determined and used to normalise the activity measured in the organ/region of interest that expresses NIS ectopically. Considering that NIS imaging has already reached the clinical setting in the context of cancer gene therapy, this normalisation may be essential in order to obtain accurate and predictive information in future longitudinal clinical studies in biotherapy

What we talk about when we talk about "global mindset": managerial cognition in multinational corporations

Recent developments in the global economy and in multinational corporations have placed significant emphasis on the cognitive orientations of managers, giving rise to a number of concepts such as “global mindset” that are presumed to be associated with the effective management of multinational corporations (MNCs). This paper reviews the literature on global mindset and clarifies some of the conceptual confusion surrounding the construct. We identify common themes across writers, suggesting that the majority of studies fall into one of three research perspectives: cultural, strategic, and multidimensional. We also identify two constructs from the social sciences that underlie the perspectives found in the literature: cosmopolitanism and cognitive complexity and use these two constructs to develop an integrative theoretical framework of global mindset. We then provide a critical assessment of the field of global mindset and suggest directions for future theoretical and empirical research

Movement patterns and habitat selection of invasive African sharptooth catfish

Information on the movement behaviour and habitat use by non-native invasive African catfish Clarias gariepinus is crucial in understanding and possibly mitigating its potential impacts. The aim of this study was to examine catfish movement and habitat selection within an invaded impoundment in the Eastern Cape, South Africa. Acoustic telemetry data for 10 tagged catfish were analyzed to identify spatial patterns in home ranges and seasonal changes in habitat associations. Long-distance movements were observed for most catfish from common central release point, whereas short-distance movements defined their home ranges and utilization distributions that were categorized as localized within single or multiple habitats. Habitat selection was non-random with most catfish utilizing the shallow river mouth and upper section of the reservoir that were dominated by a rocky substratum interspersed with submerged trees. These localities were likely to be preferred for spawning and/or feeding. Utilization of these habitats by catfish is likely to be associated with probable impact due to predation and interference competition for feeding and breeding grounds with other species. Although most catfish maintained their home ranges throughout the study, seasonal shifts in habitat use, which was reflected by the utilization of deep and silt-dominated habitats, were also observed for some catfish. Non-random habitat use and homing behaviour within single and multiple habitats by non-native sharptooth catfish suggests that its impact within the invaded habitats may be associated with particular habitats both at broad spatial and temporal scales. Protection of habitats from catfish invasion should be considered as a management option to conserve native biota

Cryptic Diversity of African Tigerfish (Genus Hydrocynus) Reveals Palaeogeographic Signatures of Linked Neogene Geotectonic Events

The geobiotic history of landscapes can exhibit controls by tectonics over biotic evolution. This causal relationship positions ecologically specialized species as biotic indicators to decipher details of landscape evolution. Phylogeographic statistics that reconstruct spatio-temporal details of evolutionary histories of aquatic species, including fishes, can reveal key events of drainage evolution, notably where geochronological resolution is insufficient. Where geochronological resolution is insufficient, phylogeographic statistics that reconstruct spatio-temporal details of evolutionary histories of aquatic species, notably fishes, can reveal key events of drainage evolution. This study evaluates paleo-environmental causes of mitochondrial DNA (mtDNA) based phylogeographic records of tigerfishes, genus Hydrocynus, in order to reconstruct their evolutionary history in relation to landscape evolution across Africa. Strong geographical structuring in a cytochrome b (cyt-b) gene phylogeny confirms the established morphological diversity of Hydrocynus and reveals the existence of five previously unknown lineages, with Hydrocynus tanzaniae sister to a clade comprising three previously unknown lineages (Groups B, C and D) and H. vittatus. The dated phylogeny constrains the principal cladogenic events that have structured Hydrocynus diversity from the late Miocene to the Plio-Pleistocene (ca. 0–16 Ma). Phylogeographic tests reveal that the diversity and distribution of Hydrocynus reflects a complex history of vicariance and dispersals, whereby range expansions in particular species testify to changes to drainage basins. Principal divergence events in Hydrocynus have interfaced closely with evolving drainage systems across tropical Africa. Tigerfish evolution is attributed to dominant control by pulses of geotectonism across the African plate. Phylogenetic relationships and divergence estimates among the ten mtDNA lineages illustrates where and when local tectonic events modified Africa's Neogene drainage. Haplotypes shared amongst extant Hydrocynus populations across northern Africa testify to recent dispersals that were facilitated by late Neogene connections across the Nilo-Sahelian drainage. These events in tigerfish evolution concur broadly with available geological evidence and reveal prominent control by the African Rift System, evident in the formative events archived in phylogeographic records of tigerfish

The Murrow Legend as Metaphor: The Creation, Appropriation, and Usefulness of Edward R. Murrow\u27s Life Story

Gary Edgerton\u27s contribution to the Journal of American Culture, Vol. 15

Detecting impacts of invasive non-native sharptooth catfish, Clarias gariepinus, within invaded and non-invaded rivers.

In aquatic ecosystems, impacts by invasive introduced fish can be likened to press disturbances that persistently influence communities. This study examined invasion disturbances by determining the relationship between non-native sharptooth catfish Clarias gariepinus and aquatic macroinvertebrates in the Eastern Cape, South Africa. A Multiple Before–After Control–Impact (MBACI) experimental design was used to examine macroinvertebrate communities within two rivers: one with catfish and another one without catfish. Within the invaded river, macroinvertebrates showed little response to catfish presence, whereas predator exclusion appeared to benefit community structure. This suggests that the macroinvertebrate community within the invaded river was adapted to predation impact because of the dominance of resilient taxa, such as Hirudinea, Oligochaeta and Chironomidae that were abundant in the Impact treatment relative to the Control treatment. High macroinvertebrate diversity and richness that was observed in the Control treatment, which excluded the predator, relative to the Impact treatment suggests predator avoidance behaviour within the invaded river. By comparison, within the uninvaded river, catfish introduction into the Impact treatment plots indicated negative effects on macroinvertebrate community that was reflected by decrease in diversity, richness and biomass. A community level impact was also reflected in the multivariate analysis that indicated more variation in macroinvertebrate composition within the Impact treatment relative to the Control in the uninvaded river. Catfish impact within the uninvaded river suggests the dominance of vulnerable taxa, such as odonates that were less abundant in the Impact treatment plots after catfish introduction. From a disturbance perspective, this study revealed different macroinvertebrate responses to catfish impact, and suggests that within invaded habitats, macroinvertebrates were less responsive to catfish presence, whereas catfish introduction within uninvaded habitats demonstrated invasion impact that was shown by a decrease in the abundance of vulnerable taxa. The occurrence of non-native sharptooth catfish within many Eastern Cape rivers is a concern because of its predation impact and potential to influence trophic interrelationships, and efforts should be taken to protect uninvaded rivers, and, where possible, eradicate the invader

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome