Qualitatively different approaches to simple arithmetic

This study explores the qualitative difference in performance between those who are more successful and those who are less successful in simple arithmetic. In the event that children are unable to retrieve a basic number combination the study identifies that there is a spectrum of performance between children who mainly use procedures, such as count-all in addition and take-away in subtraction, to those who handle simple arithmetic in a much more flexible way. Two independent studies are described The first contrasts the performances of children in simple arithmetic. It considers teacher selected pupils of different ability from within each year group from 7+ to 12+. It takes a series of snapshots of different groups of children and considers their responses to a series of simple number combinations. This first experiment shows qualitatively different thinking in which the less successful children are seen to focus more on the use of procedures and in the development of competence in utilising them. The more successful appear to have developed a flexible mode of thinking which is not only capable of stimulating their selection of more efficient procedures but, the procedures they select are then used in an efficient and competent way. However, the use of procedures amongst the more successful is seen to be only one of two alternative approaches that they use. The other approach involves the flexible use of mathematical objects, numbers, that are derived from encapsulated processes. The below-average children demonstrate little evidence of the flexible use of encapsulated processes. It is the ability of the more able children to demonstrate flexibility through the use of efficient procedures and/or the use of encapsulated processes that stimulates the development of the theory of procepts. This theory utilises the duality which is ambiguously inherent in arithmetical symbolism to establish a framework from which we may identify the notion of proceptual thinking. The second study considers the development of a group of children over a period of nearly a year. This study relates to aspects of the numerical component of the standardised tests in mathematics which form part of the National Curriculum. It provides the data which gives support to the theory and provides evidence to confirm the snap shots taken of children at the age of 7+ and 8+. It indicates that children who possess procedural competence may achieve the same level of attainment as those who display proceptual flexibility at one level of difficulty but they may not possess the appropriate mental tools to cope with the next. The evidence of the study supports the hypothesis that there is a qualitative difference in children's arithmetical thinking

What is the object of the encapsulation of a process?

Several theories have been proposed to describe the transition from process to object in mathematical thinking. Yet, what is the nature of this ''object'' produced by the ''encapsulation'' of a process? Here, we outline the development of some of the theories (including Piaget, Dienes, Davis, Greeno, Dubinsky, Sfard, Gray, and Tall) and consider the nature of the mental objects (apparently) produced through encapsulation and their role in the wider development of mathematical thinking. Does the same developmental route occur in geometry as in arithmetic and algebra? Is the same development used in axiomatic mathematics? What is the role played by imagery

Symbols and the bifurcation between procedural and conceptual thinking

Symbols occupy a pivotal position between processes to be carried out and concepts to be thought about. They allow us both to d o mathematical problems and to think about mathematical relationships. In this presentation we consider the discontinuities that occur in the learning path taken by different students, leading to a divergence between conceptual and procedural thinking. Evidence will be given from several different contexts in the development of symbols through arithmetic, algebra and calculus, then on to the formalism of axiomatic mathematics. This is taken from a number of research studies recently performed for doctoral dissertations at the University of Warwick by students from the USA, Malaysia, Cyprus and Brazil, with data collected in the USA, Malaysia and the United Kingdom. All the studies form part of a broad investigation into why some students succeed yet others fail

Discovery of chlamydial peptidoglycan reveals bacteria with murein sacculi but without FtsZ

Chlamydiae are important pathogens and symbionts with unique cell biological features. They lack the cell-division protein FtsZ, and the existence of peptidoglycan (PG) in their cell wall has been highly controversial. FtsZ and PG together function in orchestrating cell division and maintaining cell shape in almost all other bacteria. Using electron cryotomography, mass spectrometry and fluorescent labelling dyes, here we show that some environmental chlamydiae have cell wall sacculi consisting of a novel PG type. Treatment with fosfomycin (a PG synthesis inhibitor) leads to lower infection rates and aberrant cell shapes, suggesting that PG synthesis is crucial for the chlamydial life cycle. Our findings demonstrate for the first time the presence of PG in a member of the Chlamydiae. They also present a unique example of a bacterium with a PG sacculus but without FtsZ, challenging the current hypothesis that it is the absence of a cell wall that renders FtsZ non-essential

Changes in serogroup and genotype prevalence among carried meningococci in the United Kingdom during vaccine implementation.

BACKGROUND: Herd immunity is important in the effectiveness of conjugate polysaccharide vaccines against encapsulated bacteria. A large multicenter study investigated the effect of meningococcal serogroup C conjugate vaccine introduction on the meningococcal population. METHODS: Carried meningococci in individuals aged 15-19 years attending education establishments were investigated before and for 2 years after vaccine introduction. Isolates were characterized by multilocus sequence typing, serogroup, and capsular region genotype and changes in phenotypes and genotypes assessed. RESULTS: A total of 8462 meningococci were isolated from 47 765 participants (17.7%). Serogroup prevalence was similar over the 3 years, except for decreases of 80% for serogroup C and 40% for serogroup 29E. Clonal complexes were associated with particular serogroups and their relative proportions fluctuated, with 12 statistically significant changes (6 up, 6 down). The reduction of ST-11 complex serogroup C meningococci was probably due to vaccine introduction. Reasons for a decrease in serogroup 29E ST-254 meningococci (from 1.8% to 0.7%) and an increase in serogroup B ST-213 complex meningococci (from 6.7% to 10.6%) were less clear. CONCLUSIONS: Natural fluctuations in carried meningococcal genotypes and phenotypes a can be affected by the use of conjugate vaccines, and not all of these changes are anticipatable in advance of vaccine introduction

TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup.

Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer–associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient\u27s progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts (n = 1,900), two metastatic castration-resistant prostate cancer datasets (n = 293), and one prospective cohort (n = 1,385) to assess the impact of TOP2A and EZH2 expression on prostate cancer cellular program and patient outcomes. We also performed IHC staining for TOP2A and EZH2 in a cohort of primary prostate cancer patients (n = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel prostate cancer–derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic prostate cancer datasets that concurrent TOP2A and EZH2 mRNA and protein upregulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in prostate cancer cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data support further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neoadjuvant targeted therapy approaches. ©2017 AACR

Transnational cult paratexts : Exploring audience readings of Tartan’s Asia Extreme brand

Recent scholarship on the branding of contemporary cult Asian cinema for western audiences has frequently drawn on Said’s seminal treatise Orientalism as a means to critique sensationalist marketing materials. Whilst the excessive character of paratexts produced by film distributors such as Tartan clearly facilitates such readings, in this article I argue that this oft-repeated criticism becomes problematic when employed indiscriminately to theorise, by extension, the audiences for these films. Drawing on a recent empirical study of responses to Asian Extreme cinema and its distribution in the UK and North America, I offer an intervention in this debate by constructing a more nuanced interpretation of the ways in which cult audiences articulate their attraction to cinematic representations of cultural differenc

A One Health overview, facilitating advances in comparative medicine and translational research.

Table of contentsA1 One health advances and successes in comparative medicine and translational researchCheryl StroudA2 Dendritic cell-targeted gorilla adenoviral vector for cancer vaccination for canine melanomaIgor Dmitriev, Elena Kashentseva, Jeffrey N. Bryan, David T. CurielA3 Viroimmunotherapy for malignant melanoma in the companion dog modelJeffrey N. Bryan, David Curiel, Igor Dmitriev, Elena Kashentseva, Hans Rindt, Carol Reinero, Carolyn J. HenryA4 Of mice and men (and dogs!): development of a commercially licensed xenogeneic DNA vaccine for companion animals with malignant melanomaPhilip J. BergmanA5 Successful immunotherapy with a recombinant HER2-expressing Listeria monocytogenes in dogs with spontaneous osteosarcoma paves the way for advances in pediatric osteosarcomaNicola J. Mason, Josephine S. Gnanandarajah, Julie B. Engiles, Falon Gray, Danielle Laughlin, Anita Gaurnier-Hausser, Anu Wallecha, Margie Huebner, Yvonne PatersonA6 Human clinical development of ADXS-HER2Daniel O'ConnorA7 Leveraging use of data for both human and veterinary benefitLaura S. TremlA8 Biologic replacement of the knee: innovations and early clinical resultsJames P. StannardA9 Mizzou BioJoint Center: a translational success storyJames L. CookA10 University and industry translational partnership: from the lab to commercializationMarc JacobsA11 Beyond docking: an evolutionarily guided OneHealth approach to drug discoveryGerald J. Wyckoff, Lee Likins, Ubadah Sabbagh, Andrew SkaffA12 Challenges and opportunities for data applications in animal health: from precision medicine to precision husbandryAmado S. GuloyA13 A cloud-based programmable platform for healthHarlen D. HaysA14 Comparative oncology: One Health in actionAmy K. LeBlancA15 Companion animal diseases bridge the translational gap for human neurodegenerative diseaseJoan R. Coates, Martin L. Katz, Leslie A. Lyons, Gayle C. Johnson, Gary S. Johnson, Dennis P. O'BrienA16 Duchenne muscular dystrophy gene therapyDongsheng DuanA17 Polycystic kidney disease: cellular mechanisms to emerging therapiesJames P. CalvetA18 The domestic cat as a large animal model for polycystic kidney diseaseLeslie A. Lyons, Barbara GandolfiA19 The support of basic and clinical research by the Polycystic Kidney Disease FoundationDavid A. BaronA20 Using naturally occurring large animal models of human disease to enable clinical translation: treatment of arthritis using autologous stromal vascular fraction in dogsMark L. WeissA21 Regulatory requirements regarding clinical use of human cells, tissues, and tissue-based productsDebra A. WebsterA22 Regenerative medicine approaches to Type 1 diabetes treatmentFrancis N. KaranuA23 The zoobiquity of canine diabetes mellitus, man's best friend is a friend indeed-islet transplantationEdward J. RobbA24 One Medicine: a development model for cellular therapy of diabetesRobert J. Harman

Association of a Bacteriophage with Meningococcal Disease in Young Adults

Despite being the agent of life-threatening meningitis, Neisseria meningitidis is usually carried asymptomatically in the nasopharynx of humans and only occasionally causes disease. The genetic bases for virulence have not been entirely elucidated and the search for new virulence factors in this species is hampered by the lack of an animal model representative of the human disease. As an alternative strategy we employ a molecular epidemiological approach to establish a statistical association of a candidate virulence gene with disease in the human population. We examine the distribution of a previously-identified genetic element, a temperate bacteriophage, in 1288 meningococci isolated from cases of disease and asymptomatic carriage. The phage was over-represented in disease isolates from young adults indicating that it may contribute to invasive disease in this age group. Further statistical analysis indicated that between 20% and 45% of the pathogenic potential of the five most common disease-causing meningococcal groups was linked to the presence of the phage. In the absence of an animal model of human disease, this molecular epidemiological approach permitted the estimation of the influence of the candidate virulence factor. Such an approach is particularly valuable in the investigation of exclusively human diseases