Adrenergic factors regulating cell division in the colonic crypt epithelium during carcinogenesis and in colonic adenoma and adenocarcinoma.

Evidence exists implicating adrenergic factors in the control of intestinal epithelial cell proliferation in both normal and diseased states. In this report, attention is focussed on changes in the amine requirements of proliferating cells during the chemical induction of tumours in the colon of mouse. Cell proliferation rates were measured stathmokinetically. Tumours were induced by s.c. injection of dimethylhydrazine (DMH). Results with a series of adrenoceptor agonists and antagonists suggest that there is an alpha 2-adrenoceptor mediated excitatory effect in normal colon but an alpha 2 adrenoceptor mediated inhibitory effect in adenoma and carcinoma. Alpha 1 adrenoceptors, on the other hand, have an inhibitory effect in normal crypts and in adenomas, and an excitatory effect in carcinomas. Beta adrenoceptors have an inhibitory effect in the normal and DMH-treated crypt, and in adenomas, but not in carcinomas. In the crypt epithelium of DMH-treated mice, two regions on cell proliferation, with differing regulatory factors, could be identified. In the upper region of the carcinogen-exposed crypt is a zone where cell proliferation is stimulated by an alpha 2 adrenergic mechanism, thus resembling the basal region of the normal crypt. By contrast, in the basal region of these crypts, cell proliferation is stimulated by an alpha 1 mechanism, thus resembling a malignant tumour

A view through a window: Social relations, material objects and locality

In this article the authors ask what it would mean to think sociologically about the window as a specific material and symbolic object. Drawing on qualitative analysis of a series of comparative interviews with residents in three different streets in a diverse local area of Glasgow, they explore what the use and experience of windows tells us about their respondents’ very different relationships to the places where they live. On the one hand, the window, as a material feature of the home, helps us grasp the lived reality of class inequality and how such inequality shapes people’s day-to-day experience. On the other hand, windows are symbolically charged objects, existing at the border of the domestic and public world. For this reason, they feature in important ways in local debates over the appearance, ownership and conservation of the built environment. The article explores these struggles, and shows what they reveal about the construction of belonging in the neighbourhood, a process which is both classed and racialised at one and the same time.ESR

Have we seen the geneticisation of society? Expectations and evidence

Abby Lippman’s geneticization thesis, of the early 1990s, argued and anticipated that with the rise of genetics, increasing areas of social and health related activities would come to be understood and defined in genetic terms leading to major changes in society, medicine and health care. We review the considerable literature on geneticization and consider how the concept stands both theoretically and empirically across scientific, clinical, popular and lay discourse and practice. Social science scholarship indicates that relatively little of the original claim of the geneticization thesis has been realised, highlighting the development of more complex and dynamic accounts of disease in scientific discourse and the complexity of relationships between bioscientific, clinical and lay understandings. This scholarship represents a shift in social science understandings of the processes of sociotechnical change, which have moved from rather simplistic linear models to an appreciation of disease categories as multiply understood. Despite these shifts, we argue that a genetic imaginary persists, which plays a performative role in driving investments in new gene-based developments. Understanding the enduring power of this genetic imaginary and its consequences remains a key task for the social sciences, one which treats ongoing genetic expectations and predictions in a sceptical yet open way

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Public trust and 'ethics review' as a commodity: the case of Genomics England Limited and the UK's 100,000 genomes project.

The UK Chief Medical Officer's 2016 Annual Report, Generation Genome, focused on a vision to fully integrate genomics into all aspects of the UK's National Health Service (NHS). This process of integration, which has now already begun, raises a wide range of social and ethical concerns, many of which were discussed in the final Chapter of the report. This paper explores how the UK's 100,000 Genomes Project (100 kGP)-the catalyst for Generation Genome, and for bringing genomics into the NHS-is negotiating these ethical concerns. The UK's 100 kGP, promoted and delivered by Genomics England Limited (GEL), is an innovative venture aiming to sequence 100,000 genomes from NHS patients who have a rare disease, cancer, or an infectious disease. GEL has emphasised the importance of ethical governance and decision-making. However, some sociological critique argues that biomedical/technological organisations presenting themselves as 'ethical' entities do not necessarily reflect a space within which moral thinking occurs. Rather, the 'ethical work' conducted (and displayed) by organisations is more strategic, relating to the politics of the organisation and the need to build public confidence. We set out to explore whether GEL's ethical framework was reflective of this critique, and what this tells us more broadly about how genomics is being integrated into the NHS in response to the ethical and social concerns raised in Generation Genome. We do this by drawing on a series of 20 interviews with individuals associated with or working at GEL

Aberrant crypt foci in colorectal carcinogenesis. Cell and crypt dynamics

Aberrant crypt foci (ACF) have been identified on the colonic mucosal surface of rodents treated with colon carcinogens and of humans after methylene-blue staining and observation under a light microscope. Several lines of evidence strongly suggest that ACF with certain morphological, histological, cell kinetics, and genetic features are precursor lesions of colon cancer both in rodents and in humans. Thus, ACF represent the earliest step in colorectal carcinogenesis. This paper has the main purpose of reviewing the evidence supporting this view, with particular emphasis on cell and crypt dynamics in ACF. ACF have been used as intermediate biomarkers of cancer development in animal studies aimed at the identification of colon carcinogens and chemopreventive agents. Recently, evidence has also shown that ACF can be effectively employed in chemopreventive studies also in humans

Quality-of-life outcomes in older patients with early-stage rectal cancer receiving organ-preserving treatment with hypofractionated short-course radiotherapy followed by transanal endoscopic microsurgery (TREC): non-randomised registry of patients unsuitable for total mesorectal excision

Background Older patients with early-stage rectal cancer are under-represented in clinical trials and, therefore, little high-quality data are available to guide treatment in this patient population. The TREC trial was a randomised, open-label feasibility study conducted at 21 centres across the UK that compared organ preservation through short-course radiotherapy (SCRT; 25 Gy in five fractions) plus transanal endoscopic microsurgery (TEM) with standard total mesorectal excision in adults with stage T1–2 rectal adenocarcinoma (maximum diameter ≤30 mm) and no lymph node involvement or metastasis. TREC incorporated a non-randomised registry offering organ preservation to patients who were considered unsuitable for total mesorectal excision by the local colorectal cancer multidisciplinary team. Organ preservation was achieved in 56 (92%) of 61 non-randomised registry patients with local recurrence-free survival of 91% (95% CI 84–99) at 3 years. Here, we report acute and long-term patient-reported outcomes from this non-randomised registry group. Methods Patients considered by the local colorectal cancer multidisciplinary team to be at high risk of complications from total mesorectal excision on the basis of frailty, comorbidities, and older age were included in a non-randomised registry to receive organ-preserving treatment. These patients were invited to complete questionnaires on patient-reported outcomes (the European Organisation for Research and Treatment of Cancer Quality of Life [EORTC-QLQ] questionnaire core module [QLQ-C30] and colorectal cancer module [QLQ-CR29], the Colorectal Functional Outcome [COREFO] questionnaire, and EuroQol-5 Dimensions-3 Level [EQ-5D-3L]) at baseline and at months 3, 6, 12, 24, and 36 postoperatively. To aid interpretation, data from patients in the non-randomised registry were compared with data from those patients in the TREC trial who had been randomly assigned to organ-preserving therapy, and an additional reference cohort of aged-matched controls from the UK general population. This study is registered with the ISRCTN registry, ISRCTN14422743, and is closed. Findings Between July 21, 2011, and July 15, 2015, 88 patients were enrolled onto the TREC study to undergo organ preservation, of whom 27 (31%) were randomly allocated to organ-preserving therapy and 61 (69%) were added to the non-randomised registry for organ-preserving therapy. Non-randomised patients were older than randomised patients (median age 74 years [IQR 67–80] vs 65 years [61–71]). Organ-preserving treatment was well tolerated among patients in the non-randomised registry, with mild worsening of fatigue; quality of life; physical, social, and role functioning; and bowel function 3 months postoperatively compared with baseline values. By 6–12 months, most scores had returned to baseline values, and were indistinguishable from data from the reference cohort. Only mild symptoms of faecal incontinence and urgency, equivalent to less than one episode per week, persisted at 36 months among patients in both groups. Interpretation The SCRT and TEM organ-preservation approach was well tolerated in older and frailer patients, showed good rates of organ preservation, and was associated with low rates of acute and long-term toxicity, with minimal effects on quality of life and functional status. Our findings support the adoption of this approach for patients considered to be at high risk from radical surgery. Funding Cancer Research UK

Intramedullary nails versus distal locking plates for fracture of the distal femur: results from the Trial of Acute Femoral Fracture Fixation (TrAFFix) randomised feasibility study and process evaluation

Objectives: This feasibility study and process evaluation assessed the likely success of a definitive trial of intramedullary fixation with locked retrograde nails versus extramedullary fixation with fixed angle plates for fractures of the distal femur.Design & setting: A multicentre, parallel, two-arm, randomised controlled feasibility study with an embedded process evaluation was conducted at seven NHS hospitals in England. Treatment was randomly allocated in 1:1 ratio, stratified by centre and chronic cognitive impairment. Participants, but not surgeons or research staff, were blinded to the allocation.Participants: Patients 18 years and older with a fracture of the distal femur, who their surgeon believed would benefit from internal fixation, were eligible to take part.Participants were allocated to receive either a retrograde intramedullary nail or an anatomical locking plate.Outcomes: The primary outcomes for this feasibility study were the recruitment rate and completion rate of the EQ-5D-5L at 4?months post-randomisation. Baseline characteristics, disability rating index, quality of life scores, measurements of social support and self-efficacy, resource use and radiographic assessments were also collected. The views of patients and staff were collected during interviews.Results: Recruitment and data completion were lower than expected. 23 of 82 eligible patients were recruited (nail, 11; plate, 12). The recruitment rate was estimated as 0.42 (95% CI 0.27 to 0.62) participants per centre-month. Data completeness of the EQ-5D-5L at 4?months was 61 per cent (95%?CI 43% to 83%). The process evaluation demonstrated that the main barriers to recruitment were variation in treatment pathways across centres, lack of surgeon equipoise and confidence in using both interventions and newly formed research cultures that lacked cohesion.Conclusions: A modified trial design, with embedded recruitment support intervention, comparing functional outcome in cognitively intact adults who have sustained a fragility fracture of the distal femur is feasible

Social meanings and understandings in patient-nurse interaction in the community practice setting: a grounded theory study

Provisional: Background: The patient-nurse relationship is a traditional concern of healthcare research. However, patient-nurse interaction is under examined from a social perspective. Current research focuses mostly on specific contexts of care delivery and experience related to medical condition or illness, or to nurses' speciality. Consequentially, this paper is about the social meanings and understandings at play within situated patient-nurse interaction in the community practice setting in a transforming healthcare service. Methods: Grounded theory methodology was used and the research process was characterised by principles of theoretical sensitivity and constant comparative analysis. The field of study was four health centres in the community. The participants were patients and nurses representative of those attending or working in the health centres and meeting there by scheduled appointment. Data collection methods were observations, informal interviews and semi-structured interviews. Results: Key properties of 'Being a good patient, being a good nurse', 'Institutional experiences' and 'Expectations about healthcare' were associated with the construction of a category entitled 'Experience'. Those key properties captured that in an evolving healthcare environment individuals continually re-constructed their reality of being a patient or nurse as they endeavoured to perform appropriately; articulation of past and present healthcare experiences was important in that process. Modus operandi in role as patient was influenced by past experiences in healthcare and by those in non-healthcare institutions in terms of engagement and involvement (or not) in interaction. Patients' expectations about interaction in healthcare included some uncertainly as they strived to make sense of the changing roles and expertise of nurses and, differentiating between the roles and expertise of nurses and doctors. Conclusions: The importance of social meanings and understandings in patient-nurse interaction is not fully apparent to nurses, but important in the patient experience. Seeking understanding from a social perspective makes a contribution to enhancing knowledge about patient-nurse interaction with subsequent impact on practice, in particular the development of the patient-nurse relationship. The implications are that the meanings and understandings patients and nurses generate from experiences beyond and within their situated interaction are pivotal to the development of their relationship in the transforming community healthcare environment

Global maps of soil temperature

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2&nbsp;m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0\u20135 and 5\u201315&nbsp;cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10\ub0C (mean&nbsp;=&nbsp;3.0&nbsp;\ub1&nbsp;2.1\ub0C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6&nbsp;\ub1&nbsp;2.3\ub0C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler ( 120.7&nbsp;\ub1&nbsp;2.3\ub0C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications