Maps, Memories and Manchester: The Cartographic Imagination of the Hidden Networks of the Hydraulic City

The largely unseen channelling, culverting and controlling of water into, through and out of cities is the focus of our cartographic interpretation. This paper draws on empirical material depicting hydraulic infrastructure underlying the growth of Manchester in mapped form. Focusing, in particular, on the 19th century burst of large-scale hydraulic engineering, which supplied vastly increased amounts of clean drinking water, controlled unruly rivers to eliminate flooding, and safely removed sewage, this paper explores the contribution of mapping to the making of a more sanitary city, and towards bold civic minded urban intervention. These extensive infrastructures planned and engineered during Victorian and Edwardian Manchester are now taken-for-granted but remain essential for urban life. The maps, plans and diagrams of hydraulic Manchester fixed particular forms of elite knowledge (around planning foresight, topographical precision, civil engineering and sanitary science) but also facilitated and freed flows of water throughout the city. The survival of these maps and plans in libraries, technical books and obscure reports allows the changing cultural work of water to be explored and evokes a range of socially specific memories of a hidden city. Our aetiology of hydraulic cartographics is conducted using ideas from science and technology studies, semiology, and critical cartography with the goal of revealing how they work as virtual witnesses to an 1 unseen city, dramatizing engineering prowess and envisioning complex and messy materiality into a logical, holistic and fluid network underpinning the urban machine. 1

Assessing the determinants of stillbirths and early neonatal deaths using routinely collected data in an inner city area

BACKGROUND: Within the UK there is considerable variation in the perinatal mortality rate. The objective of this study was to assess the factors associated with stillbirths and early neonatal deaths (ENND) and the suitability of the available databases in a health authority with one of the highest rates in the country. METHODS: Two case-control studies were carried out in three hospital trusts in the Lambeth, Southwark and Lewisham Health Authority, London, using routinely collected information. In one study, 342 stillbirths and 1,368 controls were included, and in the other study, 205 ENND and 820 controls were included. In the two studies cases and controls were matched for hospital trust. RESULTS: A birthweight below 1.5 kg was found in 54% and 48% of the stillbirths and ENND, respectively. More than 50% of the cases, stillbirths and ENND, had a length of gestation below 32 weeks. Length of gestation, birthweight, emergency caesarean section and age of the mother were associated with stillbirths. Birthweight and Apgar score at 1 minute as a categorical variable were associated with ENND. There was no direct evidence of an effect of social deprivation on the outcomes of interest. CONCLUSION: Birthweight and length of gestation are the most influential factors on an unfavourable outcome. Conception at an older age has a serious impact on stillbirth rates. In our health authority social disadvantage did not have a direct impact on stillbirth and ENND. Maternity information systems should collect routine data on fewer variables, but their quality in terms of value, standardization and completion rates must improve

Coaching Models of School-Based Prevention and Promotion Programmes: A Qualitative Exploration of UK Teachers' Perceptions

There has been increased interest in recent years regarding the utility of imported universal prevention and promotion (P&P) programmes in UK schools, many of which have a coaching model attached. However, there have been relatively few studies exploring the cultural transferability and social validity of these models, even though evidence suggests that these factors are important to the successful implementation of the programmes, and thus the achievement of the intended outcomes. The aim of the current study was to explore the coaching practices that teachers report experiencing, and to further understanding of the perceived benefts of these coaching practices to teachers. The sample consisted of 33 teachers implementing one of two universal, school-based P&P programmes, Good Behavior Game and Promoting Alternative Thinking Strategies as part of large-scale, randomised controlled trials. Qualitative, semi-structured interviews were conducted, and data were analysed thematically utilising a hybrid approach. Teachers typically reported engaging in six distinct practices with their coaches. While the majority of these practices were in line with coaching literature, there were some discrepancies between intended coaching practices and teachers’ reports. The coaching practices were generally perceived to be acceptable to teachers. Two unanticipated practices, validation and motivation, appeared to be of particular value to teachers, although these are not currently a prominent feature in existing coaching models. The fndings provide implications for improving the development of socially valid coaching models for UK schools

Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause.

Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell clusters of normal adrenal gland suggests a requirement for codriver mutations in APAs. Here we identified gain-of-function mutations in both CTNNB1 and GNA11 by whole-exome sequencing of 3/41 APAs. Further sequencing of known CTNNB1-mutant APAs led to a total of 16 of 27 (59%) with a somatic p.Gln209His, p.Gln209Pro or p.Gln209Leu mutation of GNA11 or GNAQ. Solitary GNA11 mutations were found in hyperplastic zona glomerulosa adjacent to double-mutant APAs. Nine of ten patients in our UK/Irish cohort presented in puberty, pregnancy or menopause. Among multiple transcripts upregulated more than tenfold in double-mutant APAs was LHCGR, the receptor for luteinizing or pregnancy hormone (human chorionic gonadotropin). Transfections of adrenocortical cells demonstrated additive effects of GNA11 and CTNNB1 mutations on aldosterone secretion and expression of genes upregulated in double-mutant APAs. In adrenal cortex, GNA11/Q mutations appear clinically silent without a codriver mutation of CTNNB1

Mind Perception: Real but Not Artificial Faces Sustain Neural Activity beyond the N170/VPP

Faces are visual objects that hold special significance as the icons of other minds. Previous researchers using event-related potentials (ERPs) have found that faces are uniquely associated with an increased N170/vertex positive potential (VPP) and a more sustained frontal positivity. Here, we examined the processing of faces as objects vs. faces as cues to minds by contrasting images of faces possessing minds (human faces), faces lacking minds (doll faces), and non-face objects (i.e., clocks). Although both doll and human faces were associated with an increased N170/VPP from 175–200 ms following stimulus onset, only human faces were associated with a sustained positivity beyond 400 ms. Our data suggest that the N170/VPP reflects the object-based processing of faces, whether of dolls or humans; on the other hand, the later positivity appears to uniquely index the processing of human faces—which are more salient and convey information about identity and the presence of other minds

Inhibition of TGF-β Signaling and Decreased Apoptosis in IUGR-Associated Lung Disease in Rats

Intrauterine growth restriction is associated with impaired lung function in adulthood. It is unknown whether such impairment of lung function is linked to the transforming growth factor (TGF)-β system in the lung. Therefore, we investigated the effects of IUGR on lung function, expression of extracellular matrix (ECM) components and TGF-β signaling in rats. IUGR was induced in rats by isocaloric protein restriction during gestation. Lung function was assessed with direct plethysmography at postnatal day (P) 70. Pulmonary activity of the TGF-β system was determined at P1 and P70. TGF-β signaling was blocked in vitro using adenovirus-delivered Smad7. At P70, respiratory airway compliance was significantly impaired after IUGR. These changes were accompanied by decreased expression of TGF-β1 at P1 and P70 and a consistently dampened phosphorylation of Smad2 and Smad3. Furthermore, the mRNA expression levels of inhibitors of TGF-β signaling (Smad7 and Smurf2) were reduced, and the expression of TGF-β-regulated ECM components (e.g. collagen I) was decreased in the lungs of IUGR animals at P1; whereas elastin and tenascin N expression was significantly upregulated. In vitro inhibition of TGF-β signaling in NIH/3T3, MLE 12 and endothelial cells by adenovirus-delivered Smad7 demonstrated a direct effect on the expression of ECM components. Taken together, these data demonstrate a significant impact of IUGR on lung development and function and suggest that attenuated TGF-β signaling may contribute to the pathological processes of IUGR-associated lung disease

Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics

In December 2016, a panel of experts in microbiology, nutrition and clinical research was convened by the International Scientific Association for Probiotics and Prebiotics to review the definition and scope of prebiotics. Consistent with the original embodiment of prebiotics, but aware of the latest scientific and clinical developments, the panel updated the definition of a prebiotic: a substrate that is selectively utilized by host microorganisms conferring a health benefit. This definition expands the concept of prebiotics to possibly include non-carbohydrate substances, applications to body sites other than the gastrointestinal tract, and diverse categories other than food. The requirement for selective microbiota-mediated mechanisms was retained. Beneficial health effects must be documented for a substance to be considered a prebiotic. The consensus definition applies also to prebiotics for use by animals, in which microbiota-focused strategies to maintain health and prevent disease is as relevant as for humans. Ultimately, the goal of this Consensus Statement is to engender appropriate use of the term ‘prebiotic’ by relevant stakeholders so that consistency and clarity can be achieved in research reports, product marketing and regulatory oversight of the category. To this end, we have reviewed several aspects of prebiotic science including its development, health benefits and legislation

Anti-angiogenic therapy for cancer: Current progress, unresolved questions and future directions

Tumours require a vascular supply to grow and can achieve this via the expression of pro-angiogenic growth factors, including members of the vascular endothelial growth factor (VEGF) family of ligands. Since one or more of the VEGF ligand family is overexpressed in most solid cancers, there was great optimism that inhibition of the VEGF pathway would represent an effective anti-angiogenic therapy for most tumour types. Encouragingly, VEGF pathway targeted drugs such as bevacizumab, sunitinib and aflibercept have shown activity in certain settings. However, inhibition of VEGF signalling is not effective in all cancers, prompting the need to further understand how the vasculature can be effectively targeted in tumours. Here we present a succinct review of the progress with VEGF-targeted therapy and the unresolved questions that exist in the field: including its use in different disease stages (metastatic, adjuvant, neoadjuvant), interactions with chemotherapy, duration and scheduling of therapy, potential predictive biomarkers and proposed mechanisms of resistance, including paradoxical effects such as enhanced tumour aggressiveness. In terms of future directions, we discuss the need to delineate further the complexities of tumour vascularisation if we are to develop more effective and personalised anti-angiogenic therapies. © 2014 The Author(s)