Creating a healthy and sustainable food environment to promote plant-based food consumption: clear barriers and a gradual transition.

BACKGROUND: A shift away from diets high in animal-based foods towards diets high in plant-based foods is desirable considering human health, environmental sustainability, and animal welfare. As the food environment plays a crucial role in shaping consumption patterns, understanding of how changes in the food environment can facilitate plant-based consumption is crucial for the so-called protein transition. The current study aims to garner insight into barriers and facilitators for food outlet managers to take action to stimulate plant-based consumption within a local food environment. METHODS: Using a maximum-variation sample approach, we examined possible barriers and facilitators to promote plant-based consumption across different types of food outlets located within a geographically shared food environment (a city in the Netherlands). We conducted in-depth semi-structured interviews among food outlet managers and applied multi-stage thematic analysis to the interview transcripts. RESULTS: Most managers underscored the urgency of shifting towards more plant-based diets, and perceived a growing demand for plant-based products. However, three barriers hindered most of them from taking decisive action: Managers' perception of low consumer demand for plant-based food options; fear of consumer resistance when stimulating plant-based food options; and limited behavioral agency to offer attractive plant-based food options. The few managers who made changes, or intend to make changes, are individuals with high intrinsic motivation, knowledge and skills. CONCLUSIONS: The present work suggests the key for change towards a food environment stimulating plant-based consumption lies in addressing three (perceived) barriers shared among diverse outlets. These are partly different from barriers for stimulating healthy consumption in general. Furthermore, current changes appear to be driven incidentally by individuals who are motivated and able to stimulate more plant-based purchases among a small targeted group of consumers.

Dirofilariasis mouse models for heartworm preclinical research.

Introduction: Dirofilariasis, including heartworm disease, is a major emergent veterinary parasitic infection and a human zoonosis. Currently, experimental infections of cats and dogs are used in veterinary heartworm preclinical drug research. Methods: As a refined alternative in vivo heartworm preventative drug screen, we assessed lymphopenic mouse strains with ablation of the interleukin-2/7 common gamma chain (γc) as susceptible to the larval development phase of Dirofilaria immitis. Results: Non-obese diabetic (NOD) severe combined immunodeficiency (SCID)γc-/- (NSG and NXG) and recombination-activating gene (RAG)2-/-γc-/- mouse strains yielded viable D. immitis larvae at 2-4 weeks post-infection, including the use of different batches of D. immitis infectious larvae, different D. immitis isolates, and at different laboratories. Mice did not display any clinical signs associated with infection for up to 4 weeks. Developing larvae were found in subcutaneous and muscle fascia tissues, which is the natural site of this stage of heartworm in dogs. Compared with in vitro-propagated larvae at day 14, in vivo-derived larvae had completed the L4 molt, were significantly larger, and contained expanded Wolbachia endobacteria titres. We established an ex vivo L4 paralytic screening system whereby assays with moxidectin or levamisole highlighted discrepancies in relative drug sensitivities in comparison with in vitro-reared L4 D. immitis. We demonstrated effective depletion of Wolbachia by 70%-90% in D. immitis L4 following 2- to 7-day oral in vivo exposures of NSG- or NXG-infected mice with doxycycline or the rapid-acting investigational drug, AWZ1066S. We validated NSG and NXG D. immitis mouse models as a filaricide screen by in vivo treatments with single injections of moxidectin, which mediated a 60%-88% reduction in L4 larvae at 14-28 days. Discussion: Future adoption of these mouse models will benefit end-user laboratories conducting research and development of novel heartworm preventatives via increased access, rapid turnaround, and reduced costs and may simultaneously decrease the need for experimental cat or dog use.

Double pulsed field gradient diffusion MRI to assess skeletal muscle microstructure.

PURPOSE: Preliminary study to determine whether double pulsed field gradient (PFG) diffusion MRI is sensitive to key features of muscle microstructure related to function. METHODS: The restricted diffusion profile of molecules in models of muscle microstructure derived from histology were systematically simulated using a numerical simulation approach. Diffusion tensor subspace imaging analysis of the diffusion signal was performed, and spherical anisotropy (SA) was calculated for each model. Linear regression was used to determine the predictive capacity of SA on the fiber area, fiber diameter, and surface area to volume ratio of the models. Additionally, a rat model of muscle hypertrophy was scanned using a single PFG and a double PFG pulse sequence, and the restricted diffusion measurements were compared with histological measurements of microstructure. RESULTS: Excellent agreement between SA and muscle fiber area (r2 = 0.71; p < 0.0001), fiber diameter (r2 = 0.83; p < 0.0001), and surface area to volume ratio (r2 = 0.97; p < 0.0001) in simulated models was found. In a scanned rat leg, the distribution of these microstructural features measured from histology was broad and demonstrated that there is a wide variance in the microstructural features observed, similar to the SA distributions. However, the distribution of fractional anisotropy measurements in the same tissue was narrow. CONCLUSIONS: This study demonstrates that SA-a scalar value from diffusion tensor subspace imaging analysis-is highly sensitive to muscle microstructural features predictive of function. Furthermore, these techniques and analysis tools can be translated to real experiments in skeletal muscle. The increased dynamic range of SA compared with fractional anisotropy in the same tissue suggests increased sensitivity to detecting changes in tissue microstructure.

Repeat operations in patients with anal fistula, a retrospective study across England and Wales.

AIM: This article reports the frequency of repeat operations including waiting times within the National Health Service (NHS) of England and Wales. METHODS: Retrospective study on repeat operations for anal fistula (AF) performed between 1st January 2010 and 31st December 2016. Data were extracted from the national registry of data entered into Hospital Episode Statistics (HES). Patient factors (age, sex, self-declared ethnicity) and geographical location were tested for association with repeat operations and time to the second operation. RESULTS: We analysed 36,223 patients that had an operation for AF within 148 NHS trusts. The median follow-up time was 28 months. The majority of patients (67.4%) had only one operation. Eighty-five per cent of them remained under the care of a single consultant. Six per cent of the repeat surgeries occurred in at least three different treatment sites. Young age and female sex were associated with higher rates of repeat operations. Non-declared and Black or Black British ethnicity were associated with fewer operations. The median waiting time between the first and second operations was 27.4 weeks (IQR: 14.7-55.3); between the second and third 28.0 weeks (IQR: 14.7-57.0); between the third and fourth 29.0 weeks. CONCLUSION: This large real world population-based study shows that the majority of patients with AF undergo only one operation. Patients requiring multiple procedures tend to stay under the care of a small number of consultants but waiting times between operations are long. There is a geographical variation in the number of operations and the time between them.

The Association between Metabolic Syndrome, Frailty and Disability-Free Survival in Healthy Community-dwelling Older Adults.

OBJECTIVES: To examine the association between metabolic syndrome (MetS) and frailty, and determine whether co-existent MetS and frailty affect disability-free survival (DFS), assessed through a composite of death, dementia or physical disability. DESIGN: Longitudinal study. SETTING AND PARTICIPANTS: Community-dwelling older adults from Australia and the United States (n=18,264) from "ASPirin in Reducing Events in the Elderly" (ASPREE) study. MEASUREMENTS: MetS was defined according to American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines (2018). A modified Fried phenotype and a deficit accumulation Frailty Index (FI) were used to assess frailty. Association between MetS and frailty was examined using multinomial logistic regression. Cox regression was used to analyze the association between MetS, frailty and DFS over a median follow-up of 4.7 years. RESULTS: Among 18,264 participants, 49.9% met the criteria for MetS at baseline. Participants with Mets were more likely to be pre-frail [Relative Risk Ratio (RRR): 1.22; 95%Confidence Interval (CI): 1.14, 1.30)] or frail (RRR: 1.66; 95%CI: 1.32, 2.08) than those without MetS. MetS alone did not shorten DFS while pre-frailty or frailty alone did [Hazard Ratio (HR): 1.68; 95%CI: 1.45, 1.94; HR: 2.65; 95%CI:1.92, 3.66, respectively]. Co-existent MetS with pre-frailty/frailty did not change the risk of shortened DFS. CONCLUSIONS: MetS was associated with pre-frailty or frailty in community-dwelling older individuals. Pre-frailty or frailty increased the risk of reduced DFS but presence of MetS did not change this risk. Assessment of frailty may be more important than MetS in predicting survival free of dementia or physical disability.

Percentage of intrathoracic stomach predicts operative and post-operative morbidity, persistent reflux and PPI requirement following laparoscopic hiatus hernia repair and fundoplication.

PURPOSE: Large hiatus hernias are relatively common and can be associated with adverse symptoms and serious complications. Operative repair is indicated in this patient group for symptom management and the prevention of morbidity. This study aimed to identify predictors of poor outcomes following laparoscopic hiatus hernia repair and fundoplication (LHHRaF) to aid in counselling potential surgical candidates. METHODOLOGY: A retrospective analysis was performed from a prospectively maintained, multicentre database of patients who underwent LHHRaF between 2014 and 2020. Revision procedures were excluded. Hernia size was defined as the intraoperative percentage of intrathoracic stomach, estimated by the surgeon to the nearest 10%. Predictors of outcomes were determined using a prespecified multivariate logistic regression model. RESULTS: 625 patients underwent LHHRaF between 2014 and 2020 with 443 patients included. Median age was 65 years, 62.9% were female and 42.7% of patients had ≥ 50% intrathoracic stomach. In a multivariate regression model, intrathoracic stomach percentage was predictive of operative complications (P = 0.014, OR 1.05), post-operative complications (P = 0.026, OR 1.01) and higher comprehensive complication index score (P = 0.023, OR 1.04). At 12 months it was predictive of failure to improve symptomatic reflux (P = 0.008, OR 1.02) and persistent PPI requirement (P = 0.047, OR 1.02). Operative duration and blood loss were predicted by BMI (P = 0.004 and < 0.001), Type III/IV hernias (P = 0.045 and P = 0.005) and intrathoracic stomach percentage (P = 0.009 and P < 0.001). Post-operative length of stay was predicted by age (P < 0.001) and emergency presentation (P = 0.003). CONCLUSION: In a multivariate regression model, intrathoracic stomach percentage was predictive of operative and post-operative morbidity, PPI use, and failure to improve reflux symptoms at 12 months.

Response of soil respiration to changes in soil temperature and water table level in drained and restored peatlands of the southeastern United States.

BACKGROUND: Extensive drainage of peatlands in the southeastern United States coastal plain for the purposes of agriculture and timber harvesting has led to large releases of soil carbon as carbon dioxide (CO2) due to enhanced peat decomposition. Growth in mechanisms that provide financial incentives for reducing emissions from land use and land-use change could increase funding for hydrological restoration that reduces peat CO2 emissions from these ecosystems. Measuring soil respiration and physical drivers across a range of site characteristics and land use histories is valuable for understanding how CO2 emissions from peat decomposition may respond to raising water table levels. We combined measurements of total soil respiration, depth to water table from soil surface, and soil temperature from drained and restored peatlands at three locations in eastern North Carolina and one location in southeastern Virginia to investigate relationships among total soil respiration and physical drivers, and to develop models relating total soil respiration to parameters that can be easily measured and monitored in the field. RESULTS: Total soil respiration increased with deeper water tables and warmer soil temperatures in both drained and hydrologically restored peatlands. Variation in soil respiration was more strongly linked to soil temperature at drained (R2 = 0.57, p < 0.0001) than restored sites (R2 = 0.28, p < 0.0001). CONCLUSIONS: The results suggest that drainage amplifies the impact of warming temperatures on peat decomposition. Proxy measurements for estimation of CO2 emissions from peat decomposition represent a considerable cost reduction compared to direct soil flux measurements for land managers contemplating the potential climate impact of restoring drained peatland sites. Research can help to increase understanding of factors influencing variation in soil respiration in addition to physical variables such as depth to water table and soil temperature.

Methods of the 7th National Audit Project (NAP7) of the Royal College of Anaesthetists: peri-operative cardiac arrest.

Cardiac arrest in the peri-operative period is rare but associated with significant morbidity and mortality. Current reporting systems do not capture many such events, so there is an incomplete understanding of incidence and outcomes. As peri-operative cardiac arrest is rare, many hospitals may only see a small number of cases over long periods, and anaesthetists may not be involved in such cases for years. Therefore, a large-scale prospective cohort is needed to gain a deep understanding of events leading up to cardiac arrest, management of the arrest itself and patient outcomes. Consequently, the Royal College of Anaesthetists chose peri-operative cardiac arrest as the 7th National Audit Project topic. The study was open to all UK hospitals offering anaesthetic services and had a three-part design. First, baseline surveys of all anaesthetic departments and anaesthetists in the UK, examining respondents' prior peri-operative cardiac arrest experience, resuscitation training and local departmental preparedness. Second, an activity survey to record anonymised details of all anaesthetic activity in each site over 4 days, enabling national estimates of annual anaesthetic activity, complexity and complication rates. Third, a case registry of all instances of peri-operative cardiac arrest in the UK, reported confidentially and anonymously, over 1 year starting 16 June 2021, followed by expert review using a structured process to minimise bias. The definition of peri-operative cardiac arrest was the delivery of five or more chest compressions and/or defibrillation in a patient having a procedure under the care of an anaesthetist. The peri-operative period began with the World Health Organization 'sign-in' checklist or first hands-on contact with the patient and ended either 24 h after the patient handover (e.g. to the recovery room or intensive care unit) or at discharge if this occured earlier than 24 h. These components described the epidemiology of peri-operative cardiac arrest in the UK and provide a basis for developing guidelines and interventional studies.

Enhancing clinician participation in quality improvement training: implementation and impact of an evidence-based initiative to maximise antenatal clinician participation in training regarding women's alcohol consumption during pregnancy.

BACKGROUND: There are significant challenges in ensuring sufficient clinician participation in quality improvement training. Clinician capability has been identified as a barrier to the delivery of evidence-based care. Clinician training is an effective strategy to address this barrier, however, there are significant challenges in ensuring adequate clinician participation in training. This study aimed to assess the extent of participation by antenatal clinicians in evidence-based training to address alcohol consumption during pregnancy, and to assess differences in participation by profession. METHODS: A 7-month training initiative based on six evidence-based principles was implemented in a maternity service in New South Wales, Australia. Descriptive statistics described participation in training (% attending: any training; six evidence-based principles of training; all principles). Regression analyses examined differences by profession. RESULTS: Almost all antenatal clinicians participated in some training (182/186; 98%); 69% participated in ≥1 h of training (µ = 88.2mins, SD:56.56). The proportion of clinicians participating in training that satisfied each of the six principles ranged from 35% (training from peers and experts) to 82% (training was educational and instructional). Only 7% participated in training that satisfied all principles. A significantly higher proportion of midwifery compared to medical clinicians participated in training satisfying five of the six training principles. CONCLUSIONS: A training initiative based on evidence-based principles resulted in almost all clinicians receiving some training and 69% participating in at least 1 h of training. Variability between professions suggests training needs to be tailored to such groups. Further research is required to determine possible associations with care delivery outcomes. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, No. ACTRN12617000882325 (date registered: 16/06/2017).

Susceptibility of the Cowpea Aphid (Hemiptera: Aphididae) to Widely Used Insecticides in Australia.

Globally, 27 aphid species have evolved resistance to almost 100 insecticide active ingredients. A proactive approach to resistance management in pest aphids is needed; this should include risk analysis, followed by regular baseline susceptibility assays for species deemed at high risk of evolving resistance. The cowpea aphid (Aphis craccivora Koch) has evolved insecticide resistance to multiple insecticides outside Australia and was recently identified as a high-risk species in Australia. In this study, we generated toxicity data against four insecticides (representing four unique chemical Mode of Action groups) for populations of A. craccivora collected across Australia. Alpha-cypermethrin was the most toxic chemical to A. craccivora in leaf-dip laboratory bioassays with an average LC50 value across nine populations of 0.008 mg a.i./L, which was significantly lower than dimethoate (1.17 mg a.i./L) and pirimicarb (0.89 mg a.i./L). Small, but significant, differences in sensitivity were detected in some populations against pirimicarb and dimethoate, whereas responses to alpha-cypermethrin and imidacloprid were not significantly different across all aphid populations examined in this study. For all insecticides, the field rate controlled 100% of individuals tested. The data generated will be important for future monitoring of insecticide responses of A. craccivora. Proactive management, including increased reliance on non-chemical pest management approaches and routine insecticide baseline sensitivity studies, is recommended for A. craccivora.

CT angiograms for lower GI bleeding: the experience of a large UK teaching hospital.

INTRODUCTION: The clinical presentation of lower gastrointestinal bleeding (LGIB) is variable in severity, cause and potential investigations. The British Society of Gastroenterology recently published LGIB guidelines, recommending CT angiography (CT-A) for haemodynamically unstable patients, defined by shock index (SI) greater than 1. The aim of this study was to assess the use and role of CT-A in diagnosing LGIB, by assessing the pickup rate of active LGIB defined by contrast extravasation or 'blush' and to determine any association between positive CT-A with various patient and clinical characteristics. METHODS: A retrospective analysis was carried out of 4 years of LGIB admissions. Demographics, inpatient observations and use of blood products were acquired. Vital signs nearest the time of CT-A plus abnormal vital signs preceding imaging were used to calculate SI, Age SI, National Early Warning Score 2 (NEWS2) and Standardised Early Warning Score (SEWS). A consultant gastrointestinal radiologist further reviewed all consultant-reported scans. RESULTS: In total, 930 patients were admitted with LGIB. Median age was 71 years and 51% were male; 179 (19.2%) patients received red blood cell transfusion and 93 patients (10%) underwent CT-A, who were older and were likely to be hypotensive and receive red cell transfusions. Following exclusions, 92 CT-As were included in the analysis. Nine (9.8%) were positive. Univariate analysis showed no association between positive CT-A and any scoring system. A multivariate analysis, including age and gender, showed association between both NEWS2 and SEWS scores with positive CT-A. CONCLUSION: In our analysis of the typical LGIB population, CT-A has shown relatively low pick up rate of active bleeding. CT-A clearly has a role in the investigation of LGIB, but selection remains challenging.

CT angiograms for lower GI bleeding: the experience of a large UK teaching hospital.

INTRODUCTION: The clinical presentation of lower gastrointestinal bleeding (LGIB) is variable in severity, cause and potential investigations. The British Society of Gastroenterology recently published LGIB guidelines, recommending CT angiography (CT-A) for haemodynamically unstable patients, defined by shock index (SI) greater than 1. The aim of this study was to assess the use and role of CT-A in diagnosing LGIB, by assessing the pickup rate of active LGIB defined by contrast extravasation or 'blush' and to determine any association between positive CT-A with various patient and clinical characteristics. METHODS: A retrospective analysis was carried out of 4 years of LGIB admissions. Demographics, inpatient observations and use of blood products were acquired. Vital signs nearest the time of CT-A plus abnormal vital signs preceding imaging were used to calculate SI, Age SI, National Early Warning Score 2 (NEWS2) and Standardised Early Warning Score (SEWS). A consultant gastrointestinal radiologist further reviewed all consultant-reported scans. RESULTS: In total, 930 patients were admitted with LGIB. Median age was 71 years and 51% were male; 179 (19.2%) patients received red blood cell transfusion and 93 patients (10%) underwent CT-A, who were older and were likely to be hypotensive and receive red cell transfusions. Following exclusions, 92 CT-As were included in the analysis. Nine (9.8%) were positive. Univariate analysis showed no association between positive CT-A and any scoring system. A multivariate analysis, including age and gender, showed association between both NEWS2 and SEWS scores with positive CT-A. CONCLUSION: In our analysis of the typical LGIB population, CT-A has shown relatively low pick up rate of active bleeding. CT-A clearly has a role in the investigation of LGIB, but selection remains challenging.

Does a surgery first approach to orthognathic treatment of class III skeletal relations result in a shorter duration of treatment? A systematic review.

The objective of this study was to review the evidence relating to treatment duration and the surgery first approach (SFA) in managing class III skeletal discrepancies to determine whether there is sufficient evidence to show that it results in a shorter duration of treatment compared to a conventional orthodontics first approach (OFA). Analytical and observational studies that compared both approaches and recorded treatment duration as an outcome were included. MEDLINE, EMBASE, CENTRAL and Dental Oral Sciences Source databases were searched along with a review of reference lists. Risk of bias was assessed using the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) tool. Eleven observational studies met the inclusion criteria. No experimental studies were identified. The SFA was reported to have a shorter duration of treatment in all studies. All included studies showed a significant risk of bias, particularly in relation to selection of participants, allocation to groups and in the measurement of treatment duration. There is no quality evidence to suggest that using a surgery first approach to orthognathic treatment of class III skeletal patterns results in a shorter duration of treatment.

A single-centre ten-year retrospective cohort study of malignant small bowel obstruction.

INTRODUCTION: Management of malignant small bowel obstruction (mSBO) is challenging. The decision to perform an operation evaluates the perceived chance of success against a patient's fitness for operation. The aim of this study was to characterise the mSBO patient population in a tertiary UK centre and assess the patient's treatment pathway including use and effects of palliative surgery, total parenteral nutrition (TPN), Gastrografin and dexamethasone as well as preoperative stratification. METHODS: Patients were included if they had mSBO confirmed on computed tomography imaging due to a primary or metastatic neoplasm. Data were collected on pathway and management, and Cox proportional hazard methods were utilised to observe effects on survival. RESULTS: Ninety-four patients were included, with 104 inpatient episodes. Mean age was 67.4 (SD 13.7), with 57 (60.6%) females. Most (89.4%) had only one admission for mSBO. Eighty-four (89.4%) patients died over the ten-year period, 18 (17.3%) within 30 days of admission. Fifty patients (53.1%) underwent operative management: 70% bypass, 24% stoma formation and 6% open-close laparotomies. Log rank testing of survival probability analysis was significant (p = 0.00018), with 50% survival probability at 107.32 days for operative management and 47.87 days for non-operative. DISCUSSION AND CONCLUSION: Operative management forms part of the treatment pathway for a significant proportion of patients with mSBO, offering a survival benefit, though quality of survival is not known. Case selection is good, with few open-close laparotomies. Trials of non-operative interventions such as Gastrografin and dexamethasone are not utilised fully.

Bridging the age gap in breast cancer: impact of omission of breast cancer surgery in older women with oestrogen receptor-positive early breast cancer on quality-of-life outcomes.

BACKGROUND: Primary endocrine therapy may be an alternative treatment for less fit women with oestrogen receptor (ER)-positive breast cancer. This study compared quality-of-life (QoL) outcomes in older women treated with surgery or primary endocrine therapy. METHODS: This was a multicentre, prospective, observational cohort study of surgery or primary endocrine therapy in women aged over 70 years with operable breast cancer. QoL was assessed using European Organisation for Research and Treatment of cancer QoL questionnaires QLQ-C30, -BR23, and -ELD14, and the EuroQol Five Dimensions 5L score at baseline, 6 weeks, and 6, 12, 18, and 24 months. Propensity score matching was used to adjust for baseline variation in health, fitness, and tumour stage. RESULTS: The study recruited 3416 women (median age 77 (range 69-102) years) from 56 breast units. Of these, 2979 (87.2 per cent) had ER-positive breast cancer; 2354 women had surgery and 500 received primary endocrine therapy (125 were excluded from analysis due to inadequate data or non-standard therapy). Median follow-up was 52 months. The primary endocrine therapy group was older and less fit. Baseline QoL differed between the groups; the mean(s.d.) QLQ-C30 global health status score was 66.2(21.1) in patients who received primary endocrine therapy versus 77.1(17.8) among those who had surgery plus endocrine therapy. In the unmatched analysis, changes in QoL between 6 weeks and baseline were noted in several domains, but by 24 months most scores had returned to baseline levels. In the matched analysis, major surgery (mastectomy or axillary clearance) had a more pronounced adverse impact than primary endocrine therapy in several domains. CONCLUSION: Adverse effects on QoL are seen in the first few months after surgery, but by 24 months these have largely resolved. Women considering surgery should be informed of these effects.

Bridging the age gap in breast cancer: cluster randomized trial of two decision support interventions for older women with operable breast cancer on quality of life, survival, decision quality, and treatment choices.

BACKGROUND: Rates of surgery and adjuvant therapy for breast cancer vary widely between breast units. This may contribute to differences in survival. This cluster RCT evaluated the impact of decision support interventions (DESIs) for older women with breast cancer, to ascertain whether DESIs influenced quality of life, survival, decision quality, and treatment choice. METHODS: A multicentre cluster RCT compared the use of two DESIs against usual care in treatment decision-making in older women (aged at least ≥70 years) with breast cancer. Each DESI comprised an online algorithm, booklet, and brief decision aid to inform choices between surgery plus adjuvant endocrine therapy versus primary endocrine therapy, and adjuvant chemotherapy versus no chemotherapy. The primary outcome was quality of life. Secondary outcomes included decision quality measures, survival, and treatment choice. RESULTS: A total of 46 breast units were randomized (21 intervention, 25 usual care), recruiting 1339 women (670 intervention, 669 usual care). There was no significant difference in global quality of life at 6 months after the baseline assessment on intention-to-treat analysis (difference -0.20, 95 per cent confidence interval (C.I.) -2.69 to 2.29; P = 0.900). In women offered a choice of primary endocrine therapy versus surgery plus endocrine therapy, knowledge about treatments was greater in the intervention arm (94 versus 74 per cent; P = 0.003). Treatment choice was altered, with a primary endocrine therapy rate among women with oestrogen receptor-positive disease of 21.0 per cent in the intervention versus 15.4 per cent in usual-care sites (difference 5.5 (95 per cent C.I. 1.1 to 10.0) per cent; P = 0.029). The chemotherapy rate was 10.3 per cent at intervention versus 14.8 per cent at usual-care sites (difference -4.5 (C.I. -8.0 to 0) per cent; P = 0.013). Survival was similar in both arms. CONCLUSION: The use of DESIs in older women increases knowledge of breast cancer treatment options, facilitates shared decision-making, and alters treatment selection. Trial registration numbers: EudraCT 2015-004220-61 (https://eudract.ema.europa.eu/), ISRCTN46099296 (http://www.controlled-trials.com).

Consciousness and the rabbit holes of delirium.

Delirium is a common disorder in hospitalized older adults and the defining characteristic is a disturbance of consciousness. Unfortunately, there are currently no testable measures of consciousness as pertains to its disruption in delirium. Not surprisingly rates of recognition of delirium suffer. Arguably, a greater understanding of the quantum of consciousness may improve delirium diagnosis through better diagnostic tools. Candidate dimensions of consciousness derived from fields of psychology, psychiatry, and philosophy are discussed and relevance to delirium explored. Based upon existing literature in the field of consciousness we identify the pre-reflective state, experiential awareness, and functional networks as candidate sites that may be affected in delirium. Opportunities for clinical instrument development and how these tools can be tested are discussed. We conclude that consciousness content may not hold to a unitary measurement, but facets of its integrity that are impacted in delirium are open to further exploration. Disorders in pre-reflective status, experiential awareness, and functional networks may represent the measurable "rabbit holes" of consciousness disturbance.

Animating inter-organisational resilience communication: A participatory social network analysis of water governance in the UK.

Resilience as a concept and resilience assessment as a practice are being explored across a range of social, ecological and technical systems. In this paper, we propose a new method and visualisation approach for interrogating the communication of resilience within organisational networks, using participatory social network analysis and message passing. Through an examination of the UK water sector organisational network, represented by multiple co-produced network graphs, we identify organisations having a key role in the communication of resilience regulatory and evidence messages, as well as highlighting the potential role of complexity tools in strategy formulation. Animations are presented showing the dynamics of resilience communication, which is discussed. Reflections on the use of participatory social network analysis are explored, as the method opens new doors to potentially examine how network changes could alter communication. Key insights highlight that perceived responsibilities for resilience in the UK water sector rest with a small core of organisations; water customers play a limited role in the two-way communication of resilience and water sector organisations do not communicate widely on resilience with other sectors (such as energy). Additionally, who an organisations' neighbours are and what catalyses a message to be passed are important in determining how quickly messages spread. Results lead to a recommendation that high level governmental and policy organisations should engage to a greater extent with new resilience knowledge and consider the use of complexity tools in policy making. Policy in relation to resilience is not keeping pace with such knowledge, limiting the communication and learning of organisations who ardently follow policy and regulation. For inter-organisational cooperation to make a difference to water governance, such organisations need to be encouraged to communicate and embed the latest approaches in relation to resilience and complexity thinking and practice.

Thermal Control of Spin Excitations in the Coupled Ising-Chain Material RbCoCl_{3}.

We have used neutron spectroscopy to investigate the spin dynamics of the quantum (S=1/2) antiferromagnetic Ising chains in RbCoCl_{3}. The structure and magnetic interactions in this material conspire to produce two magnetic phase transitions at low temperatures, presenting an ideal opportunity for thermal control of the chain environment. The high-resolution spectra we measure of two-domain-wall excitations therefore characterize precisely both the continuum response of isolated chains and the "Zeeman-ladder" bound states of chains in three different effective staggered fields in one and the same material. We apply an extended Matsubara formalism to obtain a quantitative description of the entire dataset, Monte Carlo simulations to interpret the magnetic order, and finite-temperature density-matrix renormalization-group calculations to fit the spectral features of all three phases.

Bridging the Age Gap: a prognostic model that predicts survival and aids in primary treatment decisions for older women with oestrogen receptor-positive early breast cancer.

BACKGROUND: A prognostic model was developed and validated using cancer registry data. This underpins an online decision support tool, informing primary treatment choice for women aged 70 years or older with hormone receptor-positive early breast cancer. METHODS: Data from women diagnosed between 2002 and 2010 in the English Northern and Yorkshire and West Midlands regions were used to develop the model. Primary treatment options of surgery with adjuvant endocrine therapy or primary endocrine therapy were compared. Models predicting the hazard of breast cancer-specific mortality and hazard of other-cause mortality were combined to derive survival probabilities. The model was validated externally using data from the Eastern Cancer Registration and Information Centre. RESULTS: The model was developed using data from 23 842 women, and validated externally on a data set from 14 526 patients. The overall model calibration was good. At 2 and 5 years, predicted mortality from breast cancer and other causes differed from the observed rate by less than 1 per cent. At 5 years, there were slight overpredictions in breast cancer mortality (2629 predicted versus 2556 observed deaths; P = 0·142) and mortality from all causes (6399 versus 6320 respectively; P = 0·583). The discrepancy varied between subgroups. Model discrimination was 0·75 or above for all mortality measures. CONCLUSION: A prognostic model for older women with oestrogen receptor-positive early breast cancer was developed and validated in the present study. This forms a basis for an online decision support tool (https://agegap.shef.ac.uk/).

ANTECEDENTES: Se ha desarrollado y validado un modelo pronóstico utilizando datos del registro de cáncer. Ello ha permitido ofrecer una herramienta online para facilitar la toma de decisiones respecto a la elección del tratamiento inicial en mujeres mayores de 70 años con cáncer de mama precoz y receptores de hormonas positivos. MÉTODOS: Se incluyeron un total de 23.842 mujeres, diagnosticadas entre 2002 y 2010 en las regiones del Norte, Yorkshire y West Midlands inglesas que cumplieron con los criterios de inclusión. Se compararon dos opciones de tratamiento: cirugía primaria asociada a tratamiento endocrino adyuvante o tratamiento primario endocrino. Para estimar la probabilidad de supervivencia se combinaron modelos predictivos para el riesgo de mortalidad específica por cáncer de mama y para el riesgo de mortalidad por otras causas. Se realizó una validación externa con datos del Eastern Cancer Registration and Information Center (n = 14.526). RESULTADOS: La calibración global del modelo fue buena. A los 2 y 5 años, la mortalidad anticipada por cáncer de mama y por otras causas difería de la observada en menos del 1%. A los 5 años, hubo una ligera sobrevaloración de la predicción de mortalidad por cáncer de mama (prevista versus real: 2.629 versus 2.556, P = 0,78) y de la mortalidad por todas las causas (6.399 versus 6.320, P = 0,14). Esta discrepancia varió entre subgrupos. La capacidad discriminativa del modelo fue del 0,75 o superior para todas las medidas de mortalidad. CONCLUSIÓN: En este estudio, se desarrolló y validó un modelo pronóstico para mujeres mayores con cáncer de mama precoz positivo para receptores de estrógenos. Esta herramienta que facilita la toma de decisiones está disponible online (https://agegap.shef.ac.uk/).