Particular Resonances: A Review of Jonathan Wyatt’s Therapy, Stand-Up, and the Gesture of Writing: Towards Creative-Relational Inquiry

I want to start with talking a little about resonances. To resonate means to meet. To vibrate with something in some way. Jonathan’s book is full of resonances. It is crafted of them. Resonances between disciplines; therapy, stand-up, writing. Resonances between characters in these worlds. Resonances between knowing, ethics, and the real. Resonances between affective states of personing– which isn’t quite the same as being human. And resonances between the author and the reader; Jonathan’s stories touch us with their humour, their caring for the process of inquiry, and their openness. He confesses things that I’m sure we can all relate to. Anyone who has stood on a stage will, for instance, – and spoiler alert – resonate when Jonathan dies

Structure of amyloid-β (20-34) with Alzheimer's-associated isomerization at Asp23 reveals a distinct protofilament interface.

Amyloid-β (Aβ) harbors numerous posttranslational modifications (PTMs) that may affect Alzheimer's disease (AD) pathogenesis. Here we present the 1.1 Å resolution MicroED structure of an Aβ 20-34 fibril with and without the disease-associated PTM, L-isoaspartate, at position 23 (L-isoAsp23). Both wild-type and L-isoAsp23 protofilaments adopt β-helix-like folds with tightly packed cores, resembling the cores of full-length fibrillar Aβ structures, and both self-associate through two distinct interfaces. One of these is a unique Aβ interface strengthened by the isoaspartyl modification. Powder diffraction patterns suggest a similar structure may be adopted by protofilaments of an analogous segment containing the heritable Iowa mutation, Asp23Asn. Consistent with its early onset phenotype in patients, Asp23Asn accelerates aggregation of Aβ 20-34, as does the L-isoAsp23 modification. These structures suggest that the enhanced amyloidogenicity of the modified Aβ segments may also reduce the concentration required to achieve nucleation and therefore help spur the pathogenesis of AD

Deconfined Fermions but Confined Coherence?

The cuprate superconductors and certain organic conductors exhibit transport which is qualitatively anisotropic, yet at the same time other properties of these materials strongly suggest the existence of a Fermi surface and low energy excitations with substantial free electron character. The former of these features is very difficult to account for if the material possesses three dimensional coherence, while the latter is inconsistent with a description based on a two dimensional fixed point. We therefore present a new proposal for these materials in which they are categorized by a fixed point at which transport in one direction is not renormalization group irrelevant, but is intrinsically incoherent, i.e. the incoherence is present in a pure system, at zero temperature. The defining property of such a state is that single electron coherence is confined to lower dimensional subspaces (planes or chains) so that it is impossible to observe interference effects between histories which involve electrons moving between these subspaces.Comment: 31 pages, REVTEX, 3 eps figures, epsf.tex macr

Double reading in breast cancer screening : cohort evaluation in the CO-OPS trial

Purpose: To investigate the effect of double readings by a second radiologist on recall rates, cancer detection and characteristics of cancers detected in the National Health Service Breast Screening Program in England. Materials and Methods: In this retrospective analysis we evaluated 805,206 women through screening and diagnostic test results by extracting one year of routine data from 33 English breast screening centers. Centers used double reading of digital mammograms, with arbitration if there were discrepant reads. Information on reader decisions, with results of follow-up tests, were used to explore the effect of the second reader. The statistical tests used were the test for equality of proportions, the χ2 test for independence and the t-test. Results: The first reader recalled 4·76%, (38295/805206, 95% CI 4·71%-4·80%) of women. Two readers recalled 6·19% in total, (49857/805206, 95% CI 6·14%- 6·24%), but arbitration of discordant reads reduced recall rate to 4·08%, (32863/805206, 95% CI 4·04%-4·12%, p<0.001). 7055 cancers were detected of which 627 (8·89%, 95% CI 8·22%-9·55%, p<0.001) were detected by the second reader only. These additional cancers were more likely to be ductal carcinoma in situ, (30·5% (183/600) vs 22.0% (1344/6114), p<0.001); and additional invasive cancers were smaller (mean 14·2mm vs 16·7mm, p<0.001), had fewer involved nodes, and were likely to be lower grade. Conclusion: Double reading with arbitration reduces recall and increases cancer detection compared to single reading. Cancers detected only by the second reader were smaller, lower grade, and had less nodal involvement

The Transition Between Quantum Coherence and Incoherence

We show that a transformed Caldeira-Leggett Hamltonian has two distinct families of fixed points, rather than a single unique fixed point as often conjectured based on its connection to the anisotropic Kondo model. The two families are distinguished by a sharp qualitative difference in their quantum coherence properties and we argue that this distinction is best understood as the result of a transition in the model between degeneracy and non-degeneracy in the spectral function of the ``spin-flip'' operator.Comment: some typos corrected and a reference adde

Distinct conformations, aggregation and cellular internalization of different tau strains

The inter-cellular propagation of tau aggregates in several neurodegenerative diseases involves, in part, recurring cycles of extracellular tau uptake, initiation of endogenous tau aggregation, and extracellular release of at least part of this protein complex. However, human brain tau extracts from diverse tauopathies exhibit variant or “strain” specificity in inducing inter-cellular propagation in both cell and animal models. It is unclear if these distinctive properties are affected by disease-specific differences in aggregated tau conformation and structure. We have used a combined structural and cell biological approach to study if two frontotemporal dementia (FTD)-associated pathologic mutations, V337M and N279K, affect the aggregation, conformation and cellular internalization of the tau four-repeat domain (K18) fragment. In both heparin-induced and native-state aggregation experiments, each FTD variant formed soluble and fibrillar aggregates with remarkable morphological and immunological distinctions from the wild type (WT) aggregates. Exogenously-applied oligomers of the FTD tau-K18 variants (V337M and N279K) were significantly more efficiently taken up by SH-SY5Y neuroblastoma cells than WT tau-K18, suggesting mutation-induced changes in cellular internalization. However, shared internalization mechanisms were observed: endocytosed oligomers were distributed in the cytoplasm and nucleus of SH-SY5Y cells and the neurites and soma of human induced pluripotent stem cell-derived neurons where they co-localized with endogenous tau and the nuclear protein nucleolin. Altogether, evidence of conformational and aggregation differences between WT and disease-mutated tau K18 is demonstrated, which may explain their distinct cellular internalization potencies. These findings may account for critical aspects of the molecular pathogenesis of tauopathies involving WT and mutated tau

A Report of Florida’s Cancer History, Risk Factors, and Screening Behaviors: Data from the National Health Interview Survey

To target populations at greatest risk ofdeveloping cancer, it is vital to understand the patterns ofrisk factors and screening behaviors along with cancer surveillance data. This study provides data on the prevalence of self-reported cancer history, can- cer risk factors, and cancer screening behaviors in Florida and compares them to rates in the rest ofthe U.S. Data were ob- tained from the National Health Interview Survey (NHIS), an annual, cross-sectional household survey of the U.S. civilian non-institutionalized population. We analyzed pooled data from the 2000 and 2005 Cancer Control Modules. Compared to the rest ofthe U.S., Floridians reported a lower prevalence ofcurrent smoking, risky drinking, and obesity, and a greater pre- valence ofProstate Specific Antigen (PSA) testing. However, Floridians reported a greater prevalence ofcancer history and a lower prevalence of physical activity, concern for sun protection, lifetime colorectal cancer screening, lifetime breast exam, life- time mammography screening, and lifetime and past year Pap test. The data indicate that Florida lags behind the rest of the U.S. in several areas, particularly cancer screening, and falls short ofthe Healthy People 2020 objectives for health behaviors and screening. These results provide information for key stakeholders and public health policy makers to effectively target Flor- ida residents at greatest risk for cancer and those not receiving recommended cancer screenings. This study also represents a model ofvaluable state-level evaluations that can be conducted using NHIS data. These types ofanalyses can provide a great- er understanding of state-level variations and lead to more effective public health interventions aimed at reducing cancer bur- den