Teaching politics after the practice turn

The ‘practice turn’ and its associated ontology, epistemology and methodology are now well established in political research. In this article, we identify and explore a corollary pedagogy. After outlining the principal components of practice theory, we compare case- and placement-based approaches to learning, designed to develop skills for use in practice. We introduce and describe our own rather different course, which we designed to develop an understanding of the nature of practice as such. We discuss its scope and dynamics, particularly with regard to power in the classroom, and identify broader opportunities and challenges for the development of practice-based pedagogy

Computer simulation of syringomyelia in dogs

Syringomyelia is a pathological condition in which fluid-filled cavities (syringes) form and expand in the spinal cord. Syringomyelia is often linked with obstruction of the craniocervical junction and a Chiari malformation, which is similar in both humans and animals. Some brachycephalic toy breed dogs such as Cavalier King Charles Spaniels (CKCS) are particularly predisposed. The exact mechanism of the formation of syringomyelia is undetermined and consequently with the lack of clinical explanation, engineers and mathematicians have resorted to computer models to identify possible physical mechanisms that can lead to syringes. We developed a computer model of the spinal cavity of a CKCS suffering from a large syrinx. The model was excited at the cranial end to simulate the movement of the cerebrospinal fluid (CSF) and the spinal cord due to the shift of blood volume in the cranium related to the cardiac cycle. To simulate the normal condition, the movement was prescribed to the CSF. To simulate the pathological condition, the movement of CSF was blocked

Multi-parametric MRI zone-specific diagnostic model performance compared with experienced radiologists for detection of prostate cancer

OBJECTIVES: Compare the performance of zone-specific multi-parametric-MRI (mp-MRI) diagnostic models in prostate cancer detection with experienced radiologists. METHODS: A single-centre, IRB approved, prospective STARD compliant 3 T MRI test dataset of 203 patients was generated to test validity and generalisability of previously reported 1.5 T mp-MRI diagnostic models. All patients included within the test dataset underwent 3 T mp-MRI, comprising T2, diffusion-weighted and dynamic contrast-enhanced imaging followed by transperineal template ± targeted index lesion biopsy. Separate diagnostic models (transition zone (TZ) and peripheral zone (PZ)) were applied to respective zones. Sensitivity/specificity and the area under the receiver operating characteristic curve (ROC-AUC) were calculated for the two zone-specific models. Two radiologists (A and B) independently Likert scored test 3 T mp-MRI dataset, allowing ROC analysis for each radiologist for each prostate zone. RESULTS: Diagnostic models applied to the test dataset demonstrated a ROC-AUC = 0.74 (95% CI 0.67–0.81) in the PZ and 0.68 (95% CI 0.61–0.75) in the TZ. Radiologist A/B had a ROC-AUC = 0.78/0.74 in the PZ and 0.69/0.69 in the TZ. Radiologists A and B each scored 51 patients in the PZ and 41 and 45 patients respectively in the TZ as Likert 3. The PZ model demonstrated a ROC-AUC = 0.65/0.67 for the patients Likert scored as indeterminate by radiologist A/B respectively, whereas the TZ model demonstrated a ROC-AUC = 0.74/0.69. CONCLUSION: Zone-specific mp-MRI diagnostic models demonstrate generalisability between 1.5 and 3 T mp-MRI protocols and show similar classification performance to experienced radiologists for prostate cancer detection. Results also indicate the ability of diagnostic models to classify cases with an indeterminate radiologist score. KEY POINTS: • MRI diagnostic models had similar performance to experienced radiologists for classification of prostate cancer. • MRI diagnostic models may help radiologists classify tumour in patients with indeterminate Likert 3 scores

Identification of errors introduced during high throughput sequencing of the T cell receptor repertoire

<p>Abstract</p> <p>Background</p> <p>Recent advances in massively parallel sequencing have increased the depth at which T cell receptor (TCR) repertoires can be probed by >3log10, allowing for saturation sequencing of immune repertoires. The resolution of this sequencing is dependent on its accuracy, and direct assessments of the errors formed during high throughput repertoire analyses are limited.</p> <p>Results</p> <p>We analyzed 3 monoclonal TCR from TCR transgenic, Rag^-/-mice using Illumina^®sequencing. A total of 27 sequencing reactions were performed for each TCR using a trifurcating design in which samples were divided into 3 at significant processing junctures. More than 20 million complementarity determining region (CDR) 3 sequences were analyzed. Filtering for lower quality sequences diminished but did not eliminate sequence errors, which occurred within 1-6% of sequences. Erroneous sequences were pre-dominantly of correct length and contained single nucleotide substitutions. Rates of specific substitutions varied dramatically in a position-dependent manner. Four substitutions, all purine-pyrimidine transversions, predominated. Solid phase amplification and sequencing rather than liquid sample amplification and preparation appeared to be the primary sources of error. Analysis of polyclonal repertoires demonstrated the impact of error accumulation on data parameters.</p> <p>Conclusions</p> <p>Caution is needed in interpreting repertoire data due to potential contamination with mis-sequence reads. However, a high association of errors with phred score, high relatedness of erroneous sequences with the parental sequence, dominance of specific nt substitutions, and skewed ratio of forward to reverse reads among erroneous sequences indicate approaches to filter erroneous sequences from repertoire data sets.</p

Male reproductive health and environmental xenoestrogens

EHP is a publication of the U.S. government. Publication of EHP lies in the public domain and is therefore without copyright. Research articles from EHP may be used freely; however, articles from the News section of EHP may contain photographs or figures copyrighted by other commercial organizations and individuals that may not be used without obtaining prior approval from both the EHP editors and the holder of the copyright. Use of any materials published in EHP should be acknowledged (for example, "Reproduced with permission from Environmental Health Perspectives") and a reference provided for the article from which the material was reproduced.Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention.Supported by EU Contract BMH4-CT96-0314

Gene therapy for carcinoma of the breast: Genetic toxins

Gene therapy was initially envisaged as a potential treatment for genetically inherited, monogenic disorders. The applications of gene therapy have now become wider, however, and include cardiovascular diseases, vaccination and cancers in which conventional therapies have failed. With regard to oncology, various gene therapy approaches have been developed. Among them, the use of genetic toxins to kill cancer cells selectively is emerging. Two different types of genetic toxins have been developed so far: the metabolic toxins and the dominant-negative class of toxins. This review describes these two different approaches, and discusses their potential applications in cancer gene therapy

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes