Creative forms: booklets by the hospital senses collective.

This article details the creation of a series of booklets designed to explore sensory encounters with hospitals and healthcare environments. The booklets were devised as a series of prompts or provocations, created to attend to and examine embodied, sensory encounters with health/care settings rather than to present research findings. Bringing together an expansive range of backgrounds and skill sets the booklets were created to sit within and beyond language through their design, form and content. Within this article we share the ways in which the works are deliberately unfinished and exploratory as this necessitates that those interacting with them create their own meanings and explore how they think and feel about health/care environments. The form and design promote a certain attentiveness and embodied engagement. For example, users must engage with the works carefully, gently turning and unfurling the fragile pages. This is further illustrated through qualitative insights collected from users of the booklets. Throughout this paper we argue for multiplicity in the ways in which we explore and present sensory-focused research. Our attention to multiplicity is supported not only through the design, form and content of the physical booklets but through the creative audio description, text and images created to complement and support these works. These are available online to ensure that our provocations are widely accessible. Within this paper we critique how a reliance on narrative form can limit the ways in which we engage with spatial, sensory and emotional concepts. Such concepts are by their very nature challenging to articulate and arguably require more-than-text-based approaches. We propose that embracing creative, exploratory and seemingly risky routes to examining and presenting such concepts is critical in expanding research.

First-line treatment of advanced epidermal growth factor receptor (EGFR) mutation positive non-squamous non-small cell lung cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation positive (M+) non-small cell lung cancer (NSCLC) is an important subtype of lung cancer comprising 10% to 15% of non-squamous tumours. This subtype is more common in women than men, is less associated with smoking, but occurs at a younger age than sporadic tumours. OBJECTIVES: To assess the clinical effectiveness of single-agent or combination EGFR therapies used in the first-line treatment of people with locally advanced or metastatic EGFR M+ NSCLC compared with other cytotoxic chemotherapy (CTX) agents used alone or in combination, or best supportive care (BSC). The primary outcomes were overall survival and progression-free survival. Secondary outcomes included response rate, symptom palliation, toxicity, and health-related quality of life. SEARCH METHODS: We conducted electronic searches of the Cochrane Register of Controlled Trials (CENTRAL) (2020, Issue 7), MEDLINE (1946 to 27th July 2020), Embase (1980 to 27th July 2020), and ISI Web of Science (1899 to 27th July 2020). We also searched the conference abstracts of the American Society for Clinical Oncology and the European Society for Medical Oncology (July 2020); Evidence Review Group submissions to the National Institute for Health and Care Excellence; and the reference lists of retrieved articles. SELECTION CRITERIA: Parallel-group randomised controlled trials comparing EGFR-targeted agents (alone or in combination with cytotoxic agents or BSC) with cytotoxic chemotherapy (single or doublet) or BSC in chemotherapy-naive patients with locally advanced or metastatic (stage IIIB or IV) EGFR M+ NSCLC unsuitable for treatment with curative intent. DATA COLLECTION AND ANALYSIS: Two review authors independently identified articles, extracted data, and carried out the 'Risk of bias' assessment. We conducted meta-analyses using a fixed-effect model unless there was substantial heterogeneity, in which case we also performed a random-effects analysis as a sensitivity analysis. MAIN RESULTS: Twenty-two trials met the inclusion criteria. Ten of these exclusively recruited people with EGFR M+ NSCLC; the remainder recruited a mixed population and reported results for people with EGFR M+ NSCLC as subgroup analyses. The number of participants with EGFR M+ tumours totalled 3023, of whom approximately 2563 were of Asian origin. Overall survival (OS) data showed inconsistent results between the included trials that compared EGFR-targeted treatments against cytotoxic chemotherapy or placebo. Erlotinib was used in eight trials, gefitinib in nine trials, afatinib in two trials, cetuximab in two trials, and icotinib in one trial. The findings of FASTACT 2 suggested a clinical benefit for OS for participants treated with erlotinib plus cytotoxic chemotherapy when compared to cytotoxic chemotherapy alone, as did the Han 2017 trial for gefitinib plus cytotoxic chemotherapy, but both results were based on a small number of participants (n = 97 and 122, respectively). For progression-free survival (PFS), a pooled analysis of four trials showed evidence of clinical benefit for erlotinib compared with cytotoxic chemotherapy (hazard ratio (HR) 0.31; 95% confidence interval (CI) 0.25 to 0.39 ; 583 participants ; high-certainty evidence). A pooled analysis of two trials of gefitinib versus paclitaxel plus carboplatin showed evidence of clinical benefit for PFS for gefitinib (HR 0.39; 95% CI 0.32 to 0.48 ; 491 participants high-certainty evidence), and a pooled analysis of two trials of gefitinib versus pemetrexed plus carboplatin with pemetrexed maintenance also showed evidence of clinical benefit for PFS for gefitinib (HR 0.59; 95% CI 0.46 to 0.74, 371 participants ; moderate-certainty evidence). Afatinib showed evidence of clinical benefit for PFS when compared with chemotherapy in a pooled analysis of two trials (HR 0.42; 95% CI 0.34 to 0.53, 709 participants high-certainty evidence). All but one small trial showed a corresponding improvement in response rate with tyrosine-kinase inhibitor (TKI) compared to chemotherapy. Commonly reported grade 3/4 adverse events associated with afatinib, erlotinib, gefitinib and icotinib monotherapy were rash and diarrhoea. Myelosuppression was consistently worse in the chemotherapy arms; fatigue and anorexia were also associated with some chemotherapies. Seven trials reported on health-related quality of life and symptom improvement using different methodologies. For each of erlotinib, gefitinib, and afatinib, two trials showed improvement in one or more indices for the TKI compared to chemotherapy. The quality of evidence was high for the comparisons of erlotinib and gefitinib with cytotoxic chemotherapy and for the comparison of afatinib with cytotoxic chemotherapy. AUTHORS' CONCLUSIONS: Erlotinib, gefitinib, afatinib and icotinib are all active agents in EGFR M+ NSCLC patients, and demonstrate an increased tumour response rate and prolonged PFS compared to cytotoxic chemotherapy. We found a beneficial effect of the TKI compared to cytotoxic chemotherapy in adverse effect and health-related quality of life. We found limited evidence for increased OS for the TKI when compared with standard chemotherapy, but the majority of the included trials allowed participants to switch treatments on disease progression, which will have a confounding effect on any OS analysis. Single agent-TKI remains the standard of care and the benefit of combining a TKI and chemotherapy remains uncertain as the evidence is based on small patient numbers. Cytotoxic chemotherapy is less effective in EGFR M+ NSCLC than erlotinib, gefitinib, afatinib or icotinib and is associated with greater toxicity. There are no data supporting the use of monoclonal antibody therapy. Icotinib is not available outside China.

Beyond landscape's visible realm: Recorded sound, nature, and wellbeing.

This article draws on an AHRC/EPSRC funded project called 'A Sense of Place: Exploring nature and wellbeing through the non-visual senses'. The project used sound and smell technologies, as well as material textures and touch, to ask: what does 'wellbeing' mean for people in relation to the non-visual aspects of nature, and how might technology play a role in promoting it (if at all)? This article takes recorded sound as a case study. It argues that recorded soundscapes should be understood on their own terms rather than as 'less than' or a simulation of natural environments. They have specific value in creating space for imagination, particularly when delivered with care and as part of the co-creation of sensory experience. Overall, the article argues that the value of emerging immersive technologies is not to simulate nature better. An 'immersive experience' is richest when it allows for - and reveals - the nuances and complexities of individual responses to natural environments.

Sensing space and making place: the hospital and therapeutic landscapes in two cancer narratives.

This article explores the role of senses in the construction and experience of place, focusing on patients' experiences of hospital care. It compares two cancer narratives for their insights into the heterogeneous ways that hospital environments are made into therapeutic landscapes, arguing that they are a product of dynamic processes rather than something that is simply built. The article draws on a relational model of space and place, alongside literary analysis, to explore the making of un/healthy environments in embodied, affective and sensory terms. It indicates that sensory experiences in hospitals are made (un)therapeutic in relation to illness and recovery, as well as a range of social and human/non-human relations. These conclusions warn against making broad claims about 'good' or 'bad' hospital sensescapes, or against treating the hospital as a homogeneous space. They also offer new opportunities for medical geography and the medical humanities, by showing how illness and recovery are part of the relational making of space and place.

'Humanizing' healthcare environments: architecture, art and design in modern hospitals.

In recent decades, hospital design literature has paid increasing attention to an apparent need to 'humanize' hospital environments. Despite the prevalence of this design goal, the concept of 'humanizing' a space has rarely been defined or interrogated in depth. This article focuses on the meaning of humanization, as a necessary step towards understanding its implementation in practice. It explores the recent history of humanistic design as a goal in healthcare contexts, focusing on the UK in the late twentieth century. It shows that many features of humanistic design were not revolutionary, but that they were thought to serve a new purpose in counterbalancing high-technology, scientific and institutional medical practice. The humanistic hospital, as an ideal, operated as a symbol for wider social concerns about the loss - or decentring - of patients in modern medical practice. Overall, this article indicates a need to interrogate further the language of 'humanization' and its history. The term is not value free; it carries with it assumptions about the dehumanization of modern medicine, and has often been built on implicit binaries between the human and the technological.

Yesterday's Doctors: The Human Aspects of Medical Education in Britain, 1957-93.

In the wake of the Second World War there was a movement to counterbalance the apparently increasingly technical nature of medical education. These reforms sought a more holistic model of care and to put people - rather than diseases - back at the centre of medical practice and medical education. This article shows that students often drove the early stages of education reform. Their innovations focused on relationships between doctors and their communities, and often took the form of informal discussions about medical ethics and the social dimensions of primary care. Medical schools began to pursue 'humanistic' education more formally from the 1980s onwards, particularly within the context of general practice curricula and with a focus on individual doctor-patient relationships. Overall from the 1950s to the 1990s there was a broad shift in discussions of the human aspects of medical education: from interest in patient communities to individuals; from social concerns to personal characteristics; and from the relatively abstract to the measurable and instrumental. There was no clear shift from 'less' to 'more' humanistic education, but rather a shift in the perceived goals of integrating human aspects of medical education. The human aspects of medicine show the importance of student activism in driving forward community and ethical medicine, and provide an important backdrop to the rise of competencies within general undergraduate education.

First-line treatment of advanced epidermal growth factor receptor (EGFR) mutation positive non-squamous non-small cell lung cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation positive (M+) non-small cell lung cancer (NSCLC) is emerging as an important subtype of lung cancer comprising 10% to 15% of non-squamous tumours. This subtype is more common in women than men and is less associated with smoking. OBJECTIVES: To assess the clinical effectiveness of single -agent or combination EGFR therapies used in the first-line treatment of people with locally advanced or metastatic EGFR M+ NSCLC compared with other cytotoxic chemotherapy (CTX) agents used alone or in combination, or best supportive care (BSC). The primary outcome was overall survival. Secondary outcomes included progression-free survival, response rate, toxicity, and quality of life. SEARCH METHODS: We conducted electronic searches of the the Cochrane Register of Controlled Trials (CENTRAL) (2015, Issue 6), MEDLINE (1946 to 1 June 2015), EMBASE (1980 to 1 June 2015), and ISI Web of Science (1899 to 1 June 2015). We also searched the conference abstracts of the American Society for Clinical Oncology and the European Society for Medical Oncology (1 June 2015); Evidence Review Group submissions to the National Institute for Health and Care Excellence; and the reference lists of retrieved articles. SELECTION CRITERIA: Parallel randomised controlled trials comparing EGFR-targeted agents (alone or in combination with cytotoxic agents or BSC) with cytotoxic chemotherapy (single or doublet) or BSC in chemotherapy-naive patients with locally advanced or metastatic (stage IIIB or IV) EGFR M+ NSCLC unsuitable for treatment with curative intent. DATA COLLECTION AND ANALYSIS: Two review authors independently identified articles, extracted data, and carried out the 'Risk of bias' assessment. We conducted meta-analyses using a fixed-effect model unless there was substantial heterogeneity, in which case we also performed a random-effects analysis as a sensitivity analysis. MAIN RESULTS: Nineteen trials met the inclusion criteria. Seven of these exclusively recruited people with EGFR M+ NSCLC; the remainder recruited a mixed population and reported results for people with EGFR M+ NSCLC as subgroup analyses. The number of participants with EGFR M+ tumours totalled 2317, of whom 1700 were of Asian origin.Overall survival (OS) data showed inconsistent results between the included trials that compared EGFR-targeted treatments against cytotoxic chemotherapy or placebo.Erlotinib was the intervention treatment used in eight trials, gefitinib in seven trials, afatinib in two trials, and cetuximab in two trials. The findings of one trial (FASTACT 2) did report a statistically significant OS gain for participants treated with erlotinib plus cytotoxic chemotherapy when compared to cytotoxic chemotherapy alone, but this result was based on a small number of participants (n = 97). For progression-free survival (PFS), a pooled analysis of 3 trials (n = 378) demonstrated a statistically significant benefit for erlotinib compared with cytotoxic chemotherapy (hazard ratio (HR) 0.30; 95% confidence interval (CI) 0.24 to 0.38).In a pooled analysis with 491 participants administered gefitinib, 2 trials (IPASS and NEJSG) demonstrated a statistically significant PFS benefit of gefitinib compared with cytotoxic chemotherapy (HR 0.39; 95% CI 0.32 to 0.48).Afatinib (n = 709) showed a statistically significant PFS benefit when compared with chemotherapy in a pooled analysis of 2 trials (HR 0.42; 95% CI 0.34 to 0.53).Commonly reported grade 3/4 adverse events for afatinib, erlotinib, and gefitinib monotherapy were rash and diarrhoea. Myelosuppression was consistently worse in the chemotherapy arms, fatigue and anorexia were also associated with some chemotherapies.No statistically significant PFS or OS benefit for cetuximab plus cytotoxic chemotherapy (n = 81) compared to chemotherapy alone was reported in either of the two trials.Six trials reported on quality of life and symptom improvement using different methodologies. For each of erlotinib, gefitinib, and afatinib, 2 trials showed improvement in one or more indices for the tyrosine-kinase inhibitor (TKI) compared to chemotherapy.The quality of evidence was high for the comparisons of erlotinib and gefitinib with cytotoxic chemotherapy and for the comparison of afatinib with cytotoxic chemotherapy. AUTHORS' CONCLUSIONS: Erlotinib, gefitinib, and afatinib are all active agents in EGFR M+ NSCLC patients, and demonstrate an increased tumour response rate and prolonged progression-free survival compared to cytotoxic chemotherapy. We also found a beneficial effect of the TKI compared to cytotoxic chemotherapy. However, we found no increase in overall survival for the TKI when compared with standard chemotherapy. Cytotoxic chemotherapy is less effective in EGFR M+ NSCLC than erlotinib, gefitinib, or afatinib and is associated with greater toxicity. There were no data supporting the use of monoclonal antibody therapy.

'Misery loves company': sexual trauma, psychoanalysis and the market for misery.

This article examines sexual 'misery memoirs', focusing on author/reader and genre/market relationships in the context of models of trauma and child sexual abuse. It shows that the success of sexual 'misery memoirs' is inextricably bound up with the popular dissemination of a feminist-psychoanalytic model of traumatic memory that has taken place since the 1970s. It also argues that, as the 'truth' of recovered and traumatic memories has been fundamental to its success, anxieties about false memory and hoax 'misery memoirs' have posed a challenge to the genre and established a market for 'retractor' narratives.

Beach lifeguards: visual search patterns, detection rates and the influence of experience.

PURPOSE: Lifeguard surveillance is critical to any water safety program. This study determined the rates of detection of a 'drowning' individual by beach lifeguards, and whether scanning patterns differed between groups of lifeguards (experienced/less experienced, male/females, surf/non-surf). It was hypothesized that (1) Experienced lifeguards would perform better and produce less fixations of longer duration than inexperienced; (2) A greater detection rate would be seen in a 'biased' compared to a 'non-biased' condition; (3) There would be no differences between the surf compared to non-surf lifeguards, and male compared to female lifeguards with regard to scanning patterns or detection rates. METHOD: A mobile eye tracker was worn by each lifeguard (n = 69, 52 males, 17 females) as they watched 12 min of animated beach footage projected onto a screen in two conditions: a. 'Non-biased' (uniform scene). b. 'Biased' (uniform scene with presumed 'rip' on right side of screen). The lifeguards were informed that at any point during the 12 min a person may or may not disappear and to highlight if and where, a person disappeared. Unknown to the participants, a person always disappeared after 10 min at the same position within, but not between, conditions. Data were analysed using anova, t-tests and binary logistic regression. RESULTS: Experienced lifeguards were five times (p < 0.05) more likely to detect the drowning individual than inexperienced lifeguards. There were no significant differences between the visual search patterns of the groups between 2 and 10 min. The detection rates averaged 16% in the non-biased condition and 29% in biased conditions (p < 0.1), probably because lifeguards searched more on the right of the water. Furthermore, 40% (biased) and 42% (non-biased) did not detect the person disappearing, even though they fixated in the correct location in the 3.5 s before the person completely disappeared. This suggests that some lifeguards may have fixated on, but not processed, relevant visual data ('looked at but not seen'). 25% (biased) and 36% (non-biased) of the lifeguards did not fixate in the location of the person disappearing, but were able to identify their disappearance. CONCLUSIONS: Visual search patterns used by lifeguards can be altered by instruction and detection rates improve as a consequence. Peripheral vision is used effectively by some lifeguards, but cue extraction may be problematic for others.

Glut-1 as a therapeutic target: increased chemoresistance and HIF-1-independent link with cell turnover is revealed through COMPARE analysis and metabolomic studies.

The facilitative glucose transporter Glut-1 is overexpressed and confers poor prognosis in a wide range of solid tumours. The peri-necrotic pattern of expression often seen in human tumour samples is linked with its transcriptional control in hypoxic conditions by hypoxia-inducible factor HIF-1 or through a reduced rate of oxidative phosphorylation. Hypoxia-regulated genes offer promise as novel therapeutic targets as a means of preventing the proliferation and eventual metastatic spread of tissue originating from residual chemically and radio resistant hypoxic cells that have survived treatment. Inhibiting the expression or functionality of Glut-1 may be a way of specifically targeting hypoxic cells within the tumour that depend upon a high rate of glucose uptake for anaerobic glycolysis. We used an array of formalin-fixed, paraffin-embedded samples of the NCI-60 panel of cell lines to carry out immunohistochemical detection of Glut-1 and to select possible candidate lead compounds by COMPARE analysis with agents from the NCI diversity screen, which may work via inhibition of Glut-1 or Glut-1-dependent processes. "Positive" COMPARE hits were mostly conjugated Pseudomonas toxins binding the epidermal growth factor receptor (EGFR). However, correlations with standard anticancer agents were virtually all negative, indicating a link between Glut-1 and chemoresistance. MTT proliferation assays carried out using stable, Glut-1 overexpressing cell lines generated from the bladder EJ138, human fibrosarcoma HT 1080 and the hepatoma wild type Hepa and HIF-1B-deficient c4 tumour cell lines revealed a cell line-dependent increase in chemoresistance to dacarbazine, vincristine and the bioreductive agent EO9 in Glut-1 overexpressing EJ138 relative to WT and empty vector controls. Metabolomic analysis ((31)P-MRS and (1)H MRS) carried out using cell lysates and xenografts generated from Glut-1 overexpressing Hepa and c4 cell lines showed higher glucose levels in Glut-1 overxpressing c4 relative to parental tumour extracts occurred in the absence of an increase in lactate levels, which were in turn significantly higher in the Glut-1 overexpressing Hepa xenografts. This implies that Glut-1 over-expression without a co-ordinate increase in HIF-1-regulated glycolytic enzymes increases glucose uptake but not the rate of glycolysis. Glut-1 overexpressing xenografts also showed higher levels of phosphodiester (PDE), which relates to the metabolite turnover of phospholipids and is involved in membrane lipid degradation, indicating a mechanism by which Glut-1 may increase cell turnover.