Project description:The scientific community has made great efforts in advancing magnetic hyperthermia for the last two decades after going through a sizeable research lapse from its establishment. All the progress made in various topics ranging from nanoparticle synthesis to biocompatibilization and in vivo testing have been seeking to push the forefront towards some new clinical trials. As many, they did not go at the expected pace. Today, fruitful international cooperation and the wisdom gain after a careful analysis of the lessons learned from seminal clinical trials allow us to have a future with better guarantees for a more definitive takeoff of this genuine nanotherapy against cancer. Deliberately giving prominence to a number of critical aspects, this opinion review offers a blend of state-of-the-art hints and glimpses into the future of the therapy, considering the expected evolution of science and technology behind magnetic hyperthermia.
Project description:MotivationIn cluster analysis, the validity of specific solutions, algorithms, and procedures present significant challenges because there is no null hypothesis to test and no 'right answer'. It has been noted that a replicable classification is not necessarily a useful one, but a useful one that characterizes some aspect of the population must be replicable. By replicable we mean reproducible across multiple samplings from the same population. Methodologists have suggested that the validity of clustering methods should be based on classifications that yield reproducible findings beyond chance levels. We used this approach to determine the performance of commonly used clustering algorithms and the degree of replicability achieved using several microarray datasets.MethodsWe considered four commonly used iterative partitioning algorithms (Self Organizing Maps (SOM), K-means, Clutsering LARge Applications (CLARA), and Fuzzy C-means) and evaluated their performances on 37 microarray datasets, with sample sizes ranging from 12 to 172. We assessed reproducibility of the clustering algorithm by measuring the strength of relationship between clustering outputs of subsamples of 37 datasets. Cluster stability was quantified using Cramer's v2 from a kXk table. Cramer's v2 is equivalent to the squared canonical correlation coefficient between two sets of nominal variables. Potential scores range from 0 to 1, with 1 denoting perfect reproducibility.ResultsAll four clustering routines show increased stability with larger sample sizes. K-means and SOM showed a gradual increase in stability with increasing sample size. CLARA and Fuzzy C-means, however, yielded low stability scores until sample sizes approached 30 and then gradually increased thereafter. Average stability never exceeded 0.55 for the four clustering routines, even at a sample size of 50. These findings suggest several plausible scenarios: (1) microarray datasets lack natural clustering structure thereby producing low stability scores on all four methods; (2) the algorithms studied do not produce reliable results and/or (3) sample sizes typically used in microarray research may be too small to support derivation of reliable clustering results. Further research should be directed towards evaluating stability performances of more clustering algorithms on more datasets specially having larger sample sizes with larger numbers of clusters considered.
Project description:Land use change in rangeland ecosystems is pervasive throughout the western United States with widespread ecological, social and economic implications. In California, rangeland habitats have high biodiversity value, provide significant habitat connectivity and form the foundation for a number of ecosystem services. To comprehensively assess the conservation status of these habitats, we analyzed the extent and drivers of habitat loss and the degree of protection against future loss across a 13.5 M ha study area in California. We analyzed rangeland conversion between 1984 and 2008 using time series GIS data and classified resulting land uses with aerial imagery. In total, over 195,000 hectares of rangeland habitats were converted during this period. The majority of conversions were to residential and associated commercial development (49% of the area converted), but agricultural intensification was surprisingly extensive and diverse (40% across six categories). Voluntary enrollment in an agricultural tax incentive program provided widespread protection from residential and commercial conversions across 37% of the remaining rangeland habitat extent (7.5 M ha), though this program did not protect rangeland from conversion to more intensive agricultural uses. Additionally, 24% of the remaining rangeland was protected by private conservation organizations or public agencies through land or easement ownership while 38% had no protection status at all. By developing a spatial method to analyze the drivers of loss and patterns of protection, this study demonstrates a novel approach to prioritize conservation strategies and implementation locations to avert habitat conversion. We propose that this approach can be used in other ecosystem types, and can serve as a regional conservation baseline assessment to focus strategies to effect widespread, cost-effective conservation solutions.
Project description:The foundational concept of habitat lies at the very root of the entire science of ecology, but inaccurate use of the term compromises scientific rigor and communication among scientists and nonscientists. In 1997, Hall, Krausman & Morrison showed that 'habitat' was used correctly in only 55% of articles. We ask whether use of the term has been more accurate since their plea for standardization and whether use varies across the broader range of journals and taxa in the contemporary literature (1998-2012). We searched contemporary literature for 'habitat' and habitat-related terms, ranking usage as either correct or incorrect, following a simplified version of Hall et al.'s definitions. We used generalized linear models to compare use of the term in contemporary literature with the papers reviewed by Hall et al. and to test the effects of taxa, journal impact in the contemporary articles and effects due to authors that cited Hall et al. Use of the term 'habitat' has not improved; it was still only used correctly about 55% of the time in the contemporary data. Proportionately more correct uses occurred in articles that focused on animals compared to ones that included plants, and papers that cited Hall et al. did use the term correctly more often. However, journal impact had no effect. Some habitat terms are more likely to be misused than others, notably 'habitat type', usually used to refer to vegetation type, and 'suitable habitat' or 'unsuitable habitat', which are either redundant or nonsensical by definition. Inaccurate and inconsistent use of the term can lead to (1) misinterpretation of scientific findings; (2) inefficient use of conservation resources; (3) ineffective identification and prioritization of protected areas; (4) limited comparability among studies; and (5) miscommunication of science-based findings. Correct usage would improve communication with scientists and nonscientists, thereby benefiting conservation efforts, and ecology as a science.
Project description:Background and purposeThe hippocampus is a widely recognized area of early change in AD, yet voxelwise analyses of FDG-PET activity differences between AD and CN controls have consistently failed to identify hippocampal hypometabolism. In this article, we propose a high-dimensional PET-specific analysis framework to determine whether important hippocampal metabolic FDG-PET activity differences between patients with AD and CN subjects are embedded in the Jacobian information generated during spatial normalization.Materials and methodsResting FDG-PET data were obtained from 102 CN and 92 participants with AD from the ADNI data base. A PET-study-specific template was constructed using symmetric diffeomorphic registration. Spatially normalized raw FDG maps, Jacobian determinant maps, and modulated maps were generated for all subjects. Statistical parametric mapping and tensor-based morphometry were performed, comparing patients with AD with CN subjects.ResultsWhole-brain spatially normalized raw FDG maps demonstrated robust hypometabolism in cingulate gyrus and bilateral parietal areas. No hippocampal differences were present, except on ROI-based analyses with a hippocampal mask. Whole-brain modulated maps demonstrated robust bilateral hippocampal hypometabolism, and some hypometabolism in the posterior cingulate. Tensor-based morphometry demonstrated robust hippocampal differences only.ConclusionsThese results demonstrate that hippocampal metabolic differences are embedded in the Jacobian information from the spatial normalization procedure. We introduce a voxelwise PET-specific analysis framework based on the use of a PET-population-specific template, high-dimensional symmetric diffeomorphic normalization, and the use of Jacobian information, which can provide substantially increased statistical power and an order of magnitude decrease in imaging costs.
Project description:MNCs often engage in international research collaborations with foreign universities through one of their central R&D laboratories (at headquarters or elsewhere) even though they operate a local R&D unit close to that university, and hence forego the benefits of geographic proximity and local collaboration. Drawing on the knowledge-based theory of the firm, we hypothesize that the choice between distant and local collaboration systematically relates to the knowledge capabilities of the firms' R&D units, the characteristics of the focal knowledge, and local knowledge leakage risks. Analysis of close to 13,000 research collaborations with foreign universities by the world's major biopharmaceutical firms (1995-2015) confirms that collaboration at distance occurs if this allows the firm to benefit from scale and knowledge diversity advantages, if the central unit has strong basic research capabilities, and if collaboration is in a core research domain of the MNC while rival firms are locally present. Maturity of the focal research domain is associated with local collaboration. Our findings qualify the common arguments in favor of collaboration in proximity and suggest that (distant) central R&D units are important orchestrators of research collaboration with universities around the globe.
Project description:The long-term fiscal and economic damage of eurobonds in a rule-based fiscal architecture — as history corroborates — would be greater than the historical challenge of the coronavirus pandemic, unless there is a political union in Europe.