A cohort study of the recovery of health and wellbeing following colorectal cancer (CREW study): protocol paper

Background: the number of people surviving colorectal cancer has doubled in recent years. While much of the literature suggests that most people return to near pre-diagnosis status following surgery for colorectal cancer, this literature has largely focused on physical side effects. Longitudinal studies in colorectal cancer have either been small scale or taken a narrow focus on recovery after surgery. There is a need for a comprehensive, long-term study exploring all aspects of health and wellbeing in colorectal cancer patients. The aim of this study is to establish the natural history of health and wellbeing in people who have been treated for colorectal cancer. People have different dispositions, supports and resources, likely resulting in individual differences in restoration of health and wellbeing. The protocol described in this paper is of a study which will identify who is most at risk of problems, assess how quickly people return to a state of subjective health and wellbeing, and will measure factors which influence the course of recovery. Methods: this is a prospective, longitudinal cohort study following 1000 people with colorectal cancer over a period of two years, recruiting from 30 NHS cancer treatment centres across the UK. Questionnaires will be administered prior to surgery, and 3, 9, 15 and 24 months after surgery, with the potential to return to this cohort to explore on-going issues related to recovery after cancer. Discussion: outcomes will help inform health care providers about what helps or hinders rapid and effective recovery from cancer, and identify areas for intervention development to aid this process. Once established the cohort can be followed up for longer periods and be approached to participate in related projects as appropriate and subject to funding<br/

Palaeogeographic controls on climate and proxy interpretation

During the period from approximately 150 to 35?million years ago, the Cretaceous–Paleocene–Eocene (CPE), the Earth was in a “greenhouse” state with little or no ice at either pole. It was also a period of considerable global change, from the warmest periods of the mid-Cretaceous, to the threshold of icehouse conditions at the end of the Eocene. However, the relative contribution of palaeogeographic change, solar change, and carbon cycle change to these climatic variations is unknown. Here, making use of recent advances in computing power, and a set of unique palaeogeographic maps, we carry out an ensemble of 19 General Circulation Model simulations covering this period, one simulation per stratigraphic stage. By maintaining atmospheric CO2 concentration constant across the simulations, we are able to identify the contribution from palaeogeographic and solar forcing to global change across the CPE, and explore the underlying mechanisms. We find that global mean surface temperature is remarkably constant across the simulations, resulting from a cancellation of opposing trends from solar and palaeogeographic change. However, there are significant modelled variations on a regional scale. The stratigraphic stage–stage transitions which exhibit greatest climatic change are associated with transitions in the mode of ocean circulation, themselves often associated with changes in ocean gateways, and amplified by feedbacks related to emissivity and planetary albedo. We also find some control on global mean temperature from continental area and global mean orography. Our results have important implications for the interpretation of single-site palaeo proxy records. In particular, our results allow the non-CO2 (i.e. palaeogeographic and solar constant) components of proxy records to be removed, leaving a more global component associated with carbon cycle change. This “adjustment factor” is used to adjust sea surface temperatures, as the deep ocean is not fully equilibrated in the model. The adjustment factor is illustrated for seven key sites in the CPE, and applied to proxy data from Falkland Plateau, and we provide data so that similar adjustments can be made to any site and for any time period within the CPE. Ultimately, this will enable isolation of the CO2-forced climate signal to be extracted from multiple proxy records from around the globe, allowing an evaluation of the regional signals and extent of polar amplification in response to CO2 changes during the CPE. Finally, regions where the adjustment factor is constant throughout the CPE could indicate places where future proxies could be targeted in order to reconstruct the purest CO2-induced temperature change, where the complicating contributions of other processes are minimised. Therefore, combined with other considerations, this work could provide useful information for supporting targets for drilling localities and outcrop studies

How to involve cancer patients at the end of life as co-researchers

The importance of user involvement in the organisation and delivery of health services and the conduct of research has increased over recent decades. Involving people at the end of life in research remains an under-developed area of research activity. The Macmillan Listening Study, a UK-wide study exploring research views and priorities of people affected by cancer, adopted a participatory research approach. Patients and carers, including two participants receiving palliative care services, collaborated in all aspects of the study as coresearchers. In this paper, we discuss the experience of working with co-researchers to collect data from two hospices. We will discuss practical, ethical and methodological challenges, including specific training needs and the emotional demands of conducting the research. Recommendations are made to facilitate successful collaboration with palliative care service users in end of life research. Palliative Medicine 2006; 20: 821 Á82

Phase I Clinical Trials in Acute Myeloid Leukemia: 23-Year Experience From Cancer Therapy Evaluation Program of the National Cancer Institute

Therapy for acute myeloid leukemia (AML) has largely remained unchanged, and outcomes are unsatisfactory. We sought to analyze outcomes of AML patients enrolled in phase I studies to determine whether overall response rates (ORR) and mortality rates have changed over time

Multimorbidity, polypharmacy, and COVID-19 infection within the UK Biobank cohort

Background: It is now well recognised that the risk of severe COVID-19 increases with some long-term conditions (LTCs). However, prior research primarily focuses on individual LTCs and there is a lack of data on the influence of multimorbidity (≥2 LTCs) on the risk of COVID-19. Given the high prevalence of multimorbidity, more detailed understanding of the associations with multimorbidity and COVID-19 would improve risk stratification and help protect those most vulnerable to severe COVID-19. Here we examine the relationships between multimorbidity, polypharmacy (a proxy of multimorbidity), and COVID-19; and how these differ by sociodemographic, lifestyle, and physiological prognostic factors. Methods and findings: We studied data from UK Biobank (428,199 participants; aged 37–73; recruited 2006–2010) on self-reported LTCs, medications, sociodemographic, lifestyle, and physiological measures which were linked to COVID-19 test data. Poisson regression models examined risk of COVID-19 by multimorbidity/polypharmacy and effect modification by COVID-19 prognostic factors (age/sex/ethnicity/socioeconomic status/smoking/physical activity/BMI/systolic blood pressure/renal function). 4,498 (1.05%) participants were tested; 1,324 (0.31%) tested positive for COVID-19. Compared with no LTCs, relative risk (RR) of COVID-19 in those with 1 LTC was no higher (RR 1.12 (CI 0.96–1.30)), whereas those with ≥2 LTCs had 48% higher risk; RR 1.48 (1.28–1.71). Compared with no cardiometabolic LTCs, having 1 and ≥2 cardiometabolic LTCs had a higher risk of COVID-19; RR 1.28 (1.12–1.46) and 1.77 (1.46–2.15), respectively. Polypharmacy was associated with a dose response higher risk of COVID-19. All prognostic factors were associated with a higher risk of COVID-19 infection in multimorbidity; being non-white, most socioeconomically deprived, BMI ≥40 kg/m2, and reduced renal function were associated with the highest risk of COVID-19 infection: RR 2.81 (2.09–3.78); 2.79 (2.00–3.90); 2.66 (1.88–3.76); 2.13 (1.46–3.12), respectively. No multiplicative interaction between multimorbidity and prognostic factors was identified. Important limitations include the low proportion of UK Biobank participants with COVID-19 test data (1.05%) and UK Biobank participants being more affluent, healthier and less ethnically diverse than the general population. Conclusions: Increasing multimorbidity, especially cardiometabolic multimorbidity, and polypharmacy are associated with a higher risk of developing COVID-19. Those with multimorbidity and additional factors, such as non-white ethnicity, are at heightened risk of COVID-19

Is older age associated with COVID-19 mortality in the absence of other risk factors? General population cohort study of 470,034 participants

Introduction: Older people have been reported to be at higher risk of COVID-19 mortality. This study explored the factors mediating this association and whether older age was associated with increased mortality risk in the absence of other risk factors. Methods: In UK Biobank, a population cohort study, baseline data were linked to COVID-19 deaths. Poisson regression was used to study the association between current age and COVID-19 mortality. Results: Among eligible participants, 438 (0.09%) died of COVID-19. Current age was associated exponentially with COVID-19 mortality. Overall, participants aged ≥75 years were at 13-fold (95% CI 9.13–17.85) mortality risk compared with those &lt;65 years. Low forced expiratory volume in 1 second, high systolic blood pressure, low handgrip strength, and multiple long-term conditions were significant mediators, and collectively explained 39.3% of their excess risk. The associations between these risk factors and COVID-19 mortality were stronger among older participants. Participants aged ≥75 without additional risk factors were at 4-fold risk (95% CI 1.57–9.96, P = 0.004) compared with all participants aged &lt;65 years. Conclusions: Higher COVID-19 mortality among older adults was partially explained by other risk factors. ‘Healthy’ older adults were at much lower risk. Nonetheless, older age was an independent risk factor for COVID-19 mortality

Evaluating the citywide Edinburgh 20mph speed limit intervention effects on traffic speed and volume: A pre-post observational evaluation.

OBJECTIVES: Traffic speed is important to public health as it is a major contributory factor to collision risk and casualty severity. 20mph (32km/h) speed limit interventions are an increasingly common approach to address this transport and health challenge, but a more developed evidence base is needed to understand their effects. This study describes the changes in traffic speed and traffic volume in the City of Edinburgh, pre- and 12 months post-implementation of phased city-wide 20mph speed limits from 2016-2018. METHODS: The City of Edinburgh Council collected speed and volume data across one full week (24 hours a day) pre- and post-20mph speed limits for 66 streets. The pre- and post-speed limit intervention data were compared using measures of central tendency, dispersion, and basic t-tests. The changes were assessed at different aggregations and evaluated for statistical significance (alpha = 0.05). A mixed effects model was used to model speed reduction, in the presence of key variables such as baseline traffic speed and time of day. RESULTS: City-wide, a statistically significant reduction in mean speed of 1.34mph (95% CI 0.95 to 1.72) was observed at 12 months post-implementation, representing a 5.7% reduction. Reductions in speed were observed throughout the day and across the week, and larger reductions in speed were observed on roads with higher initial speeds. Mean 7-day volume of traffic was found to be lower by 86 vehicles (95% CI: -112 to 286) representing a reduction of 2.4% across the city of Edinburgh (p = 0.39) but with the direction of effect uncertain. CONCLUSIONS: The implementation of the city-wide 20mph speed limit intervention was associated with meaningful reductions in traffic speeds but not volume. The reduction observed in road traffic speed may act as a mechanism to lessen the frequency and severity of collisions and casualties, increase road safety, and improve liveability

Marine Mammal Brucella Genotype Associated with Zoonotic Infection

Marine Mammal Brucella Genotype Associated with Zoonotic Infectio

Infrastructural Speculations: Tactics for Designing and Interrogating Lifeworlds

This paper introduces “infrastructural speculations,” an orientation toward speculative design that considers the complex and long-lived relationships of technologies with broader systems, beyond moments of immediate invention and design. As modes of speculation are increasingly used to interrogate questions of broad societal concern, it is pertinent to develop an orientation that foregrounds the “lifeworld” of artifacts—the social, perceptual, and political environment in which they exist. While speculative designs often imply a lifeworld, infrastructural speculations place lifeworlds at the center of design concern, calling attention to the cultural, regulatory, environmental, and repair conditions that enable and surround particular future visions. By articulating connections and affinities between speculative design and infrastructure studies research, we contribute a set of design tactics for producing infrastructural speculations. These tactics help design researchers interrogate the complex and ongoing entanglements among technologies, institutions, practices, and systems of power when gauging the stakes of alternate lifeworlds