What does poverty feel like? Urban inequality and the politics of sensation

The emergent field of ‘sensory urbanism’ studies how socio-spatial boundaries are policed through sensorial means. Such studies have tended to focus on either formal policies that seek to control territories and populations through a governance of the senses, or on more everyday micro-politics of exclusion where conflicts are articulated in a sensory form. This article seeks to extend this work by concentrating on contexts where people deliberately seek out sensory experiences that disturb their own physical sense of comfort and belonging. While engagement across lines of sensorial difference may often be antagonistic, we argue for a more nuanced exploration of sense disruption that attends to the complex political potential of sensory urbanism. Specifically, we focus on the politics of sensation in tours of low-income urban areas. Tourists enter these areas to immerse themselves in a different environment, to be moved by urban deprivation and to feel its affective force. What embodied experiences do tourists and residents associate with urban poverty? How do guides mobilise these sensations in tourism encounters, and what is their potential to disrupt established hierarchies of socio-spatial value? Drawing on a collaborative research project in Kingston, Mexico City, New Orleans and Rio de Janeiro, the article explores how tours offer tourists a sense of what poverty feels like. Experiencing these neighbourhoods in an intimate, embodied fashion often allows tourists to feel empathy and solidarity, yet these feelings are balanced by a sense of discomfort and distance, reminding tourists in a visceral way that they do not belong

Antiprogestins reduce epigenetic field cancerization in breast tissue of young healthy women

Background: Breast cancer is a leading cause of death in premenopausal women. Progesterone drives expansion of luminal progenitor cells, leading to the development of poor-prognostic breast cancers. However, it is not known if antagonising progesterone can prevent breast cancers in humans. We suggest that targeting progesterone signalling could be a means of reducing features which are known to promote breast cancer formation. Methods: In healthy premenopausal women with and without a BRCA mutation we studied (i) estrogen and progesterone levels in saliva over an entire menstrual cycle (n = 20); (ii) cancer-free normal breast-tissue from a control population who had no family or personal history of breast cancer and equivalently from BRCA1/2 mutation carriers (n = 28); triple negative breast cancer (TNBC) biopsies and healthy breast tissue taken from sites surrounding the TNBC in the same individuals (n = 14); and biopsies of ER+ve/PR+ve stage T1–T2 cancers and healthy breast tissue taken from sites surrounding the cancer in the same individuals (n = 31); and (iii) DNA methylation and DNA mutations in normal breast tissue (before and after treatment) from clinical trials that assessed the potential preventative effects of vitamins and antiprogestins (mifepristone and ulipristal acetate; n = 44). Results: Daily levels of progesterone were higher throughout the menstrual cycle of BRCA1/2 mutation carriers, raising the prospect of targeting progesterone signalling as a means of cancer risk reduction in this population. Furthermore, breast field cancerization DNA methylation signatures reflective of (i) the mitotic age of normal breast epithelium and (ii) the proportion of luminal progenitor cells were increased in breast cancers, indicating that luminal progenitor cells with elevated replicative age are more prone to malignant transformation. The progesterone receptor antagonist mifepristone reduced both the mitotic age and the proportion of luminal progenitor cells in normal breast tissue of all control women and in 64% of BRCA1/2 mutation carriers. These findings were validated by an alternate progesterone receptor antagonist, ulipristal acetate, which yielded similar results. Importantly, mifepristone reduced both the TP53 mutation frequency as well as the number of TP53 mutations in mitotic-age-responders. Conclusions: These data support the potential usage of antiprogestins for primary prevention of poor-prognostic breast cancers

WWER-1000 Nuclear reactor simulator for education. Part A': Overview of simulator physico-mathematical model components

A review of phylogenetic studies carried out together with morphological ones shows that a major problem with most early studies is that they concentrated on techniques and used material or strains of fungi that in most cases were not carefully reference, and in a worrying number of cases wrongly named. Most classical species, particularly of microfungi, are not represented by adequate type material, or other authoritatively identified cultures or specimens, that can serve as DNA sources for phylogenetic study, or for developing robust identification systems. Natural classifications of fungi therefore suffer from the lack of reference strains in resultant phylogenetic trees. In some cases, epitypification and neotypification can solve this problem and these tools are increasingly used to resolve taxonomic confusion and stabilize the understanding of species, genera, families, or orders of fungi. This manuscript discusses epitypification and neotypification, describes how to epitypify or neotypify species and examines the importance of this process. A set of guidelines for epitypification is presented. Examples where taxa have been epitypified are presented and the benefits and problems of epitypification are discussed. As examples of epitypification, or to provide reference specimens, a new epitype is designated for Paraphaeosphaeria michotii and reference specimens are provided for Astrosphaeriella stellata, A. bakeriana, Phaeosphaeria elongata, Ophiobolus cirsii, and O. erythrosporus. In this way we demonstrate how to epitypify taxa and its importance, and also illustrate the value of proposing reference specimens if epitypification is not advisable. Although we provided guidelines for epitypification, the decision to epitypify or not lies with the author, who should have experience of the fungus concerned. This responsibility is to be taken seriously, as once a later typification is made, it may not be possible to undo that, particularly in the case of epitypes, without using the lengthy and tedious formal conservation and rejection processes

National-scale antimicrobial resistance surveillance in wastewater: A comparative analysis of HT qPCR and metagenomic approaches

Wastewater serves as an important reservoir of antimicrobial resistance (AMR), and its surveillance can provide insights into population-level trends in AMR to inform public health policy. This study compared two common high-throughput screening approaches, namely (i) high-throughput quantitative PCR (HT qPCR), targeting 73 antimicrobial resistance genes, and (ii) metagenomic sequencing. Weekly composite samples of wastewater influent were taken from 47 wastewater treatment plants (WWTPs) across Wales, as part of a national AMR surveillance programme, alongside 4 weeks of daily wastewater effluent samples from a large municipal hospital. Metagenomic analysis provided more comprehensive resistome coverage, detecting 545 genes compared to the targeted 73 genes by HT qPCR. It further provided contextual information critical to risk assessment (i.e. potential bacterial hosts). In contrast, HT qPCR exhibited higher sensitivity, quantifying all targeted genes including those of clinical relevance present at low abundance. When limited to the HT qPCR target genes, both methods were able to reflect the spatiotemporal dynamics of the complete metagenomic resistome, distinguishing that of the hospital and the WWTPs. Both approaches revealed correlations between resistome compositional shifts and environmental variables like ammonium wastewater concentration, though differed in their interpretation of some potential influencing factors. Overall, metagenomics provides more comprehensive resistome profiling, while qPCR permits sensitive quantification of genes significant to clinical resistance. We highlight the importance of selecting appropriate methodologies aligned to surveillance aims to guide the development of effective wastewater-based AMR monitoring programmes

The spectrum and clinical impact of epigenetic modifier mutations in myeloma

Epigenetic dysregulation is known to be an important contributor to myeloma pathogenesis but, unlike in other B cell malignancies, the full spectrum of somatic mutations in epigenetic modifiers has not been previously reported. We sought to address this using results from whole-exome sequencing in the context of a large prospective clinical trial of newly diagnosed patients and targeted sequencing in a cohort of previously treated patients for comparison.Whole-exome sequencing analysis of 463 presenting myeloma cases entered in the UK NCRI Myeloma XI study and targeted sequencing analysis of 156 previously treated cases from the University of Arkansas for Medical Sciences. We correlated the presence of mutations with clinical outcome from diagnosis and compared the mutations found at diagnosis with later stages of disease.In diagnostic myeloma patient samples we identify significant mutations in genes encoding the histone 1 linker protein, previously identified in other B-cell malignancies. Our data suggest an adverse prognostic impact from the presence of lesions in genes encoding DNA methylation modifiers and the histone demethylase KDM6A/UTX. The frequency of mutations in epigenetic modifiers appears to increase following treatment most notably in genes encoding histone methyltransferases and DNA methylation modifiers.Numerous mutations identified raise the possibility of targeted treatment strategies for patients either at diagnosis or relapse supporting the use of sequencing-based diagnostics in myeloma to help guide therapy as more epigenetic targeted agents become available

X-Pipeline: An analysis package for autonomous gravitational-wave burst searches

Autonomous gravitational-wave searches -- fully automated analyses of data that run without human intervention or assistance -- are desirable for a number of reasons. They are necessary for the rapid identification of gravitational-wave burst candidates, which in turn will allow for follow-up observations by other observatories and the maximum exploitation of their scientific potential. A fully automated analysis would also circumvent the traditional "by hand" setup and tuning of burst searches that is both labourious and time consuming. We demonstrate a fully automated search with X-Pipeline, a software package for the coherent analysis of data from networks of interferometers for detecting bursts associated with GRBs and other astrophysical triggers. We discuss the methods X-Pipeline uses for automated running, including background estimation, efficiency studies, unbiased optimal tuning of search thresholds, and prediction of upper limits. These are all done automatically via Monte Carlo with multiple independent data samples, and without requiring human intervention. As a demonstration of the power of this approach, we apply X-Pipeline to LIGO data to search for gravitational-wave emission associated with GRB 031108. We find that X-Pipeline is sensitive to signals approximately a factor of 2 weaker in amplitude than those detectable by the cross-correlation technique used in LIGO searches to date. We conclude with the prospects for running X-Pipeline as a fully autonomous, near real-time triggered burst search in the next LSC-Virgo Science Run.Comment: 18 pages, 10 figures. Minor edits and clarifications; added more background on gravitational waves and detectors. To appear in New Journal of Physics

Extensive telomere erosion is consistent with localised clonal expansions in Barrett’s metaplasia

Barrett’s oesophagus is a premalignant metaplastic condition that predisposes patients to the development of oesophageal adenocarcinoma. However, only a minor fraction of Barrett’s oesophagus patients progress to adenocarcinoma and it is thus essential to determine bio-molecular markers that can predict the progression of this condition. Telomere dysfunction is considered to drive clonal evolution in several tumour types and telomere length analysis provides clinically relevant prognostic and predictive information. The aim of this work was to use high-resolution telomere analysis to examine telomere dynamics in Barrett’s oesophagus. Telomere length analysis of XpYp, 17p, 11q and 9p, chromosome arms that contain key cancer related genes that are known to be subjected to copy number changes in Barrett’s metaplasia, revealed similar profiles at each chromosome end, indicating that no one specific telomere is likely to suffer preferential telomere erosion. Analysis of patient matched tissues (233 samples from 32 patients) sampled from normal squamous oesophagus, Z-line, and 2 cm intervals within Barrett’s metaplasia, plus oesophago-gastric junction, gastric body and antrum, revealed extensive telomere erosion in Barrett’s metaplasia to within the length ranges at which telomere fusion is detected in other tumour types. Telomere erosion was not uniform, with distinct zones displaying more extensive erosion and more homogenous telomere length profiles. These data are consistent with an extensive proliferative history of cells within Barrett’s metaplasia and are indicative of localised clonal growth. The extent of telomere erosion highlights the potential of telomere dysfunction to drive genome instability and clonal evolution in Barrett’s metaplasia