Tornado damage and impacts on nuclear facilities in the United States

This report provides an overview of the tornado impact on the safe operation and shutdown of nuclear power plants in the United States. The motivation for this review stems from the damage and failure of the Fukushima nuclear power plant on March 11, 2011. That disaster warrants comparison of the safety measures in place within the global nuclear power industry.

Who is the good high school student?

Schooling is one of the core experiences of most young people in the Western world. This study examines the ways that students inhabit subjectivities defined in their relationship to some normalised good student. The idea that schools exist to produce students who become good citizens is one of the basic tenets of modernist educational philosophies that dominate the contemporary education world. The school has become a political site where policy, curriculum orientations, expectations and philosophies of education contest for the ‘right’ way to school and be schooled. For many people, schools and schooling only make sense if they resonate with past experiences. The good student is framed within these aspects of cultural understanding. However, this commonsense attitude is based on a hegemonic understanding of the good, rather than the good student as a contingent multiplicity that is produced by an infinite set of discourses and experiences. In this book, author Greg Thompson argues that this understanding of subjectivities and power is crucial if schools are to meet the needs of a rapidly changing and challenging world. As a high school teacher for many years, Thompson often wondered how students responded to complex articulations on how to be a good student. How a student can be considered good is itself an articulation of powerful discourses that compete within the school. Rather than assuming a moral or ethical citizen, this study turns that logic on it on its head to ask students in what ways they can be good within the school. Visions of the good student deployed in various ways in schools act to produce various ways of knowing the self as certain types of subjects. Developing the postmodern theories of Foucault and Deleuze, this study argues that schools act to teach students to know themselves in certain idealised ways through which they are located, and locate themselves, in hierarchical rationales of the good student. Problematising the good student in high schools engages those institutional discourses with the philosophy, history and sociology of education. Asking students how they negotiate or perform their selves within schools challenges the narrow and limiting ways that the good is often understood. By pushing the ontological understandings of the self beyond the modernist philosophies that currently dominate schools and schooling, this study problematises the tendency to see students as fixed, measurable identities (beings) rather than dynamic, evolving performances (becomings). Who is the Good High School Student? is an important book for scholars conducting research on high school education, as well as student-teachers, teacher educators and practicing teachers alike.

Swings and round-abouts: Student connectedness in secondary schools

Connectedness is a complex idea that seems to mean different things for each individual. For the purposes of this dissertation, connectedness can best be understood as the ways that an individual feels an affiliation with the community of the institution that he/she experiences. This dissertation seeks to uncover the discourses that various stakeholder groups have within the site of a single school concerning connectedness. One of the precepts that this dissertation holds is that connectedness to school has benefits for the individual as learner, the school as a community and potentially the wider community in years to come. This is a theoretical position in the lineage of such theorists as Plato, Rousseau, and Dewey who have argued that education is a transformative practice that could be a tool for solving some of the issues that contemporary societies face. This work uses the theories of Foucault to extend the analysis to argue that connectedness is not a monolithic constant, but rather a complex set of converging and diverging discourses that students must contend with.

Wrestling with schools, schooling and educational research (Personal Reflections on the European Union-supported Educational Research 1995-2003: Briefing Papers for Policy Makers)

I must admit that I approached the European Union-supported educational research 1995-2003: Briefing papers for policy makers with a sense of trepidation. As a researcher who defines himself as socially critical, I wondered about the dynamics of a policy document that was published by the bureaucracy that has, in some form, a vested interest in the structure and operation of education in its various guises. In turning my attention to this review, I decided to focus my attention on the third guiding question that argues education and training "are strongly interconnected with concerns that include citizenship and democratic participation, inequalities and social justice, cultural diversity and quality of life" (Millei, 2005). The Briefing Papers include recommendations on democracy and citizenship, social exclusion and equality, gender and dealing with mental illness in schools...

EVERSUN: A phase 2 trial of alternating sunitinib and everolimus as first-line therapy for advanced renal cell carcinoma

Background We hypothesised that alternating inhibitors of the vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin pathways would delay the development of resistance in advanced renal cell carcinoma (aRCC). Patients and methods A single-arm, two-stage, multicentre, phase 2 trial to determine the activity, feasibility, and safety of 12-week cycles of sunitinib 50 mg daily 4 weeks on / 2 weeks off, alternating with everolimus 10 mg daily for 5 weeks on / 1 week off, until disease progression or prohibitive toxicity in favourable or intermediate-risk aRCC. The primary end point was proportion alive and progression-free at 6 months (PFS6m). The secondary end points were feasibility, tumour response, overall survival (OS), and adverse events (AEs). The correlative objective was to assess biomarkers and correlate with clinical outcome. Results We recruited 55 eligible participants from September 2010 to August 2012. Demographics: mean age 61, 71% male, favourable risk 16%, intermediate risk 84%. Cycle 2 commenced within 14 weeks for 80% of participants; 64% received ≥22 weeks of alternating therapy; 78% received ≥22 weeks of any treatment. PFS6m was 29/55 (53%; 95% confidence interval [CI] 40% to 66%). Tumour response rate was 7/55 (13%; 95% CI 4% to 22%, all partial responses). After median follow-up of 20 months, 47 of 55 (86%) had progressed with a median progression-free survival of 8 months (95% CI 5–10), and 30 of 55 (55%) had died with a median OS of 17 months (95% CI 12–undefined). AEs were consistent with those expected for each single agent. No convincing prognostic biomarkers were identified. Conclusions The EVERSUN regimen was feasible and safe, but its activity did not meet pre-specified values to warrant further research. This supports the current approach of continuing anti-VEGF therapy until progression or prohibitive toxicity before changing treatment.

The tensor distribution function

Diffusion weighted magnetic resonance imaging is a powerful tool that can be employed to study white matter microstructure by examining the 3D displacement profile of water molecules in brain tissue. By applying diffusion-sensitized gradients along a minimum of six directions, second-order tensors (represented by three-by-three positive definite matrices) can be computed to model dominant diffusion processes. However, conventional DTI is not sufficient to resolve more complicated white matter configurations, e.g., crossing fiber tracts. Recently, a number of high-angular resolution schemes with more than six gradient directions have been employed to address this issue. In this article, we introduce the tensor distribution function (TDF), a probability function defined on the space of symmetric positive definite matrices. Using the calculus of variations, we solve the TDF that optimally describes the observed data. Here, fiber crossing is modeled as an ensemble of Gaussian diffusion processes with weights specified by the TDF. Once this optimal TDF is determined, the orientation distribution function (ODF) can easily be computed by analytic integration of the resulting displacement probability function. Moreover, a tensor orientation distribution function (TOD) may also be derived from the TDF, allowing for the estimation of principal fiber directions and their corresponding eigenvalues.

Developing pictorial conceptual metaphors as a means of understanding and changing the Australian health system for Indigenous people

This paper describes the development of Pictorial Conceptual Metaphors, created out of a literature review on gendered Indigenous health and wellbeing that depicts the inherited effects of the ‘system’ past, present and future. The Pictorial Conceptual Metaphors are pictures that were created to tell the story of colonisation and its inherited and ongoing impacts on Indigenous people’s health and wellbeing. Aboriginal historical experiences, past, present and future are briefly overviewed in order to unpack and communicate to readers the significance and impact of these experiences on Aboriginal health, and ultimately, to bring about understanding to initiate change within the Australian health system. Systemic racism, embedded in the Australian health system, excludes and discriminates against Indigenous peoples through a lack of cultural consideration resulting in a cumulative and ongoing negative effect on Indigenous people’s health (Dudgeon et al. 2014; Fredericks 2008; Marmot 2011; Queensland Government 2012). Systemic action research identifies actions and processes in large systems such as health and education in order to bring about systemic change. Our intention to highlight the systemic changes needed in the Australian health system to improve Indigenous people’s health and wellbeing require us to understand the processes involved in bringing about systemic change. For this to occur, we needed to ‘see the system’ in order to identify the system dynamics in operation. The Pictorial Conceptual Metaphors are the first step in ‘seeing the system’; they illustrate the past and the present, and identify the preferred future for Indigenous health and wellbeing outcomes

Correction: Genome-wide association studies of asthma in population-based cohorts confirm known and suggested loci and identify an additional association near HLA

Read the original article via 'related work' link below

Genome-Wide Association Studies of Asthma in Population-Based Cohorts Confirm Known and Suggested Loci and Identify an Additional Association near HLA

Rationale: Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies. Objectives: To test if population-based cohorts with self-reported physician-diagnosed asthma and genome-wide association (GWA) data could be used to validate known associations with asthma and identify novel associations. Methods: The APCAT (Analysis in Population-based Cohorts of Asthma Traits) consortium consists of 1,716 individuals with asthma and 16,888 healthy controls from six European-descent population-based cohorts. We examined associations in APCAT of thirteen variants previously reported as genome-wide significant (P<5x10-8) and three variants reported as suggestive (P<5×10-7). We also searched for novel associations in APCAT (Stage 1) and followed-up the most promising variants in 4,035 asthmatics and 11,251 healthy controls (Stage 2). Finally, we conducted the first genome-wide screen for interactions with smoking or hay fever. Main Results: We observed association in the same direction for all thirteen previously reported variants and nominally replicated ten of them. One variant that was previously suggestive, rs11071559 in RORA, now reaches genome-wide significance when combined with our data (P = 2.4×10-9). We also identified two genome-wide significant associations: rs13408661 near IL1RL1/IL18R1 (PStage1+Stage2 = 1.1x10-9), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (PStage1+Stage2 = 1.1x10-8), which appears to be independent of previously reported associations in this locus. Finally, we found no strong evidence for gene-environment interactions with smoking or hay fever status. Conclusions: Population-based cohorts with simple asthma phenotypes represent a valuable and largely untapped resource for genetic studies of asthma. © 2012 Ramasamy et al.

Populations of models, experimental designs and coverage of parameter space by Latin Hypercube and Orthogonal Sampling

In this paper we have used simulations to make a conjecture about the coverage of a t-dimensional subspace of a d-dimensional parameter space of size n when performing k trials of Latin Hypercube sampling. This takes the form P(k,n,d,t) = 1 - e^(-k/n^(t-1)). We suggest that this coverage formula is independent of d and this allows us to make connections between building Populations of Models and Experimental Designs. We also show that Orthogonal sampling is superior to Latin Hypercube sampling in terms of allowing a more uniform coverage of the t-dimensional subspace at the sub-block size level. These ideas have particular relevance when attempting to perform uncertainty quantification and sensitivity analyses.

Adding paths to resilience and daily accounts to an already rich field of inquiry: A brief commentary on James Jackson's "Social structure and health disparities"

In absolute terms, there have been improvements in social resources for all racial and ethnic groups in the United States. The rise in education levels among blacks and Hispanics, for instance, suggests a lessening of the gap between classes, beginning in the later part of the 1960’s (Kao & Thompson, 2003). Yet the divide in income and to a lesser extent education between peoples who differ in gender, skin color and ethnic origin continues and in many ways is greater now than ever (Danziger & Gottschalk, 1997); (Gottschalk, 1997). The psychological distance between those high and those low in social-economic status continues unabated and threatens to undermine the capacity of communities to foster the positive architecture of hope, optimism and equal opportunity that holds us together as a nation...

Australian patients using a cardiac-diabetes web-based intervention program: Contributions to person-centered clinical practice

Rationale, aims and objectives: Patients with both cardiac disease and diabetes have poorer health outcomes than patients with only one chronic condition. While evidence indicates that internet based interventions may improve health outcomes for patients with a chronic disease, there is no literature on internet programs specific to cardiac patients with comorbid diabetes. Therefore this study aimed to develop a specific web-based program, then to explore patients’ perspectives on the usefulness of a new program. Methods: The interpretive approach using semi-structured interviews on a purposive sample of eligible patients with type 2 diabetes and a cardiac condition in a metropolitan hospital in Brisbane, Australia. Thematic analysis was undertaken to describe the perceived usefulness of a newly developed Heart2heart webpage. Results: Themes identified included confidence in hospital health professionals and reliance on doctors to manage conditions. Patients found the webpage useful for managing their conditions at home. Conclusions: The new Heart2heart webpage provided a positive and useful resource. Further research on to determine the potential influence of this resource on patients’ self-management behaviours is paramount. Implications for practice include using multimedia strategies for providing information to patients’ comorbidities of cardiac disease and type 2 diabetes, and further development on enhancement of such strategies

Monoclonal antibody screening of a phage-displayed random peptide library reveals mimotopes of chemokine receptor CCR5: Implications for the tertiary structure of the receptor and for an n-terminal binding site for HIV-1 gp120

The chemokine receptor CCR5 contains seven transmembrane-spanning domains. It binds chemokines and acts as co-receptor for macrophage (m)-tropic (or R5) strains of HIV-1. Monoclonal antibodies (mAb) to CCR5, 3A9 and 5C7, were used for biopanning a nonapeptide cysteine (C)-constrained phage-displayed random peptide library to ascertain contact residues and define tertiary structures of possible epitopes on CCR5. Reactivity of antibodies with phagotopes was established by enzyme-linked immunosorbent assay (ELISA). mAb 3A9 identified a phagotope C-HASIYDFGS-C (3A9/1), and 5C7 most frequently identified C-PHWLRDLRV-C (5C7/1). Corresponding peptides were synthesized. Phagotopes and synthetic peptides reacted in ELISA with corresponding antibodies and synthetic peptides inhibited antibody binding to the phagotopes. Reactivity by immunofluorescence of 3A9 with CCR5 was strongly inhibited by the corresponding peptide. Both mAb 3A9 and 5C7 reacted similarly with phagotopes and the corresponding peptide selected by the alternative mAb. The sequences of peptide inserts of phagotopes could be aligned as mimotopes of the sequence of CCR5. For phage 3A9/1, the motif SIYD aligned to residues at the N terminus and FG to residues on the first extracellular loop; for 5C7/1, residues at the N terminus, first extracellular loop, and possibly the third extracellular loop could be aligned and so would contribute to the mimotope. The synthetic peptides corresponding to the isolated phagotopes showed a CD4-dependent reactivity with gp120 of a primary, m-tropic HIV-1 isolate. Thus reactivity of antibodies raised to CCR5 against phage-displayed peptides defined mimotopes that reflect binding sites for these antibodies and reveal a part of the gp120 binding sites on CCR5.

Estimates on the coverage of parameter space using populations of models

In this paper we provide estimates for the coverage of parameter space when using Latin Hypercube Sampling, which forms the basis of building so-called populations of models. The estimates are obtained using combinatorial counting arguments to determine how many trials, k, are needed in order to obtain specified parameter space coverage for a given value of the discretisation size n. In the case of two dimensions, we show that if the ratio (Ø) of trials to discretisation size is greater than 1, then as n becomes moderately large the fractional coverage behaves as 1-exp-ø. We compare these estimates with simulation results obtained from an implementation of Latin Hypercube Sampling using MATLAB.

Targeting EMT in cancer: opportunities for pharmacological intervention

•EMT is important for embryonic development, wound healing, and placentation. •Some cancers appear to exploit this process for increased metastatic potential. •Therefore, this pathway is of great therapeutic interest in the treatment of cancer. The spread of cancer cells to distant organs represents a major clinical challenge in the treatment of cancer. Epithelial–mesenchymal transition (EMT) has emerged as a key regulator of metastasis in some cancers by conferring an invasive phenotype. As well as facilitating metastasis, EMT is thought to generate cancer stem cells and contribute to therapy resistance. Therefore, the EMT pathway is of great therapeutic interest in the treatment of cancer and could be targeted either to prevent tumor dissemination in patients at high risk of developing metastatic lesions or to eradicate existing metastatic cancer cells in patients with more advanced disease. In this review, we discuss approaches for the design of EMT-based therapies in cancer, summarize evidence for some of the proposed EMT targets, and review the potential advantages and pitfalls of each approach