Acceptability and Preliminary Efficacy of a Web- and Telephone-Based Personalised Exercise Intervention for Individuals with Metastatic Prostate Cancer: The ExerciseGuide Pilot Randomised Controlled Trial.

Preliminary research has shown the effectiveness of supervised exercise-based interventions in alleviating sequela resulting from metastatic prostate cancer. However, many individuals encounter barriers that limit the uptake of face-to-face exercise. Technology-enabled interventions offer a distance-based alternative. This pilot study aimed to explore the acceptability, safety and preliminary efficacy of a web-based exercise intervention (ExerciseGuide) in individuals with metastatic prostate cancer. Forty participants (70.2 ± 8.5 years) with metastatic prostate cancer were randomised into the 8-week intervention (N = 20) or a wait-list control (N = 20). The intervention arm had access to a computer-tailored website, personalised exercise prescription and remote supervision. ExerciseGuide was deemed acceptable with a score ≥20 on the client satisfaction questionnaire; however, the usability score was just below the pre-specified score of ≥68 on the software usability scale. There were no serious adverse events reported. Moderate-to-vigorous physical activity levels between baseline and follow-ups were significantly higher (10.0 min per day; 95% CI = (1.3-18.6); p = 0.01) in the intervention group compared to wait-list control. There were also greater improvements in step count (1332; 95% CI = (159-2505); p = 0.02) and identified motivation (0.4, 95% CI = (0.0, 0.7); p = 0.04). Our findings provide preliminary evidence that ExerciseGuide is acceptable, safe and efficacious among individuals with metastatic prostate cancer

A covalently crosslinked bioink for multi-materials drop-on-demand 3D bioprinting of three-dimensional cell cultures

In vitro three-dimensional (3D) cell models have been accepted to better recapitulate aspects of in vivo organ environment than 2D cell culture. Currently, the production of these complex in vitro 3D cell models with multiple cell types and microenvironments remains challenging and prone to human error. Here we report a versatile bioink comprised of a 4-arm PEG based polymer with distal maleimide derivatives as the main ink component and a bis-thiol species as the activator that crosslinks the polymer to form the hydrogel in less than a second. The rapid gelation makes the polymer system compatible with 3D bioprinting. The ink is combined with a drop-on-demand 3D bioprinting platform consisting of eight independently addressable nozzles and high-throughput printing logic for creating complex 3D cell culture models. The combination of multiple nozzles and fast printing logic enables the rapid preparation of many complex 3D structures comprising multiple hydrogel environments in the one structure in a standard 96-well plate format. The platform compatibility for biological applications was validated using pancreatic ductal adenocarcinoma cancer (PDAC) cells with their phenotypic responses controlled by tuning the hydrogel microenvironment

Starting-up unregistered and firm performance in Turkey

© 2016 The Author(s) Recent years have seen a questioning of the negative representation of informal sector entrepreneurship and an emergent view that it may offer significant benefits. This paper advances this rethinking by evaluating the relationship between business registration and future firm performance. Until now, the assumption has been that starting-up unregistered is linked to weaker firm performance. Using World Bank Enterprise Survey data on 2494 formal enterprises in Turkey, and controlling for other determinants of firm performance as well as the endogeneity of the registration decision, the finding is that formal enterprises that started-up unregistered and spent longer unregistered have significantly higher subsequent annual sales and productivity growth rates compared with those registered from the outset. This is argued to be because in such weak institutional environments, the advantages of registering from the outset are outweighed by the benefits of deferring business registration and the low risks of detection and punishment. The resultant implication is that there is a need to shift away from the conventional eradication approach based on the negative depiction of informal entrepreneurship as poorly performing, and towards a more facilitating approach that improves the benefits of business registration and tackles the systemic formal institutional deficiencies that lead entrepreneurs to decide to delay the registration of their ventures

Benefits of ICU admission in critically ill patients: Whether instrumental variable methods or propensity scores should be used

<p>Abstract</p> <p>Background</p> <p>The assessment of the causal effect of Intensive Care Unit (ICU) admission generally involves usual observational designs and thus requires controlling for confounding variables. Instrumental variable analysis is an econometric technique that allows causal inferences of the effectiveness of some treatments during situations to be made when a randomized trial has not been or cannot be conducted. This technique relies on the existence of one variable or "instrument" that is supposed to achieve similar observations with a different treatment for "arbitrary" reasons, thus inducing substantial variation in the treatment decision with no direct effect on the outcome. The objective of the study was to assess the benefit in terms of hospital mortality of ICU admission in a cohort of patients proposed for ICU admission (ELDICUS cohort).</p> <p>Methods</p> <p>Using this cohort of 8,201 patients triaged for ICU (including 6,752 (82.3%) patients admitted), the benefit of ICU admission was evaluated using 3 different approaches: instrumental variables, standard regression and propensity score matched analyses. We further evaluated the results obtained using different instrumental variable methods that have been proposed for dichotomous outcomes.</p> <p>Results</p> <p>The physician's main specialization was found to be the best instrument. All instrumental variable models adequately reduced baseline imbalances, but failed to show a significant effect of ICU admission on hospital mortality, with confidence intervals far higher than those obtained in standard or propensity-based analyses.</p> <p>Conclusions</p> <p>Instrumental variable methods offer an appealing alternative to handle the selection bias related to nonrandomized designs, especially when the presence of significant unmeasured confounding is suspected. Applied to the ELDICUS database, this analysis failed to show any significant beneficial effect of ICU admission on hospital mortality. This result could be due to the lack of statistical power of these methods.</p

Hot, Tired and Hungry: The Snacking Behaviour and Food Cravings of Firefighters During Multi-Day Simulated Wildfire Suppression

Firefighters are exposed to numerous stressors during wildfire suppression, including working in hot temperatures and sleep restricted conditions. Research has shown that when sleep restricted, individuals choose foods higher in carbohydrates, fat, and sugar, and have increased cravings for calorie dense foods. However, there is currently no research on the combined effect of heat and sleep restriction on snacking behaviour. Conducting secondary analyses from a larger study, the current study aimed to investigate the impact of heat and sleep restriction on snacking behaviour and food cravings. Sixty-six firefighters completed three days of simulated physically demanding firefighting work and were randomly allocated to either the control (n = 18, CON; 19 °C, 8h sleep opportunity), sleep restricted (n = 16, SR; 19 °C, 4-h sleep opportunity), hot (n = 18, HOT; 33 °C, 8h sleep opportunity), or hot and sleep restricted (n = 14 HOT + SR; 33 °C, 4-h sleep opportunity) condition. During rest periods firefighters were able to self-select sweet, savoury, or healthy snacks from a ration pack and were asked to rate their hunger, fullness, and cravings every two hours (eating block). Mixed model analyses revealed no difference in total energy intake between conditions, however there was a significant interaction between eating block and condition, with those in the CON, HOT, and HOT + SR condition consuming significantly more energy between 1230 and 1430 compared to the SR condition (p = 0.002). Sleep restriction and heat did not impact feelings of hunger and fullness across the day, and did not lead to greater cravings for snacks, with no differences between conditions. These findings suggest that under various simulated firefighting conditions, it is not the amount of food that differs but the timing of food intake, with those that are required to work in hot conditions while sleep restricted more likely to consume food between 1230 and 1430. This has potential implications for the time of day in which a greater amount of food should be available for firefighters.</jats:p

Business Registration and Firm Performance: Some Lessons From India

The aim of this paper is to evaluate the impacts on future firm performance of a firm deciding to register from the outset of its operations. Until now, the assumption has been that starting up registered is linked to higher future firm performance. Reporting World Bank Enterprise Survey (WBES) data collected in 2014 on 9,281 formal enterprises in India, and controlling for other determinants of firm performance as well as the endogeneity of the registration decision, the finding is that formal enterprises that start up unregistered and spend longer unregistered have significantly higher subsequent annual sales and employment growth rates compared with those registered from the outset. When the number of years spent unregistered is included, there are also productivity gains from delaying registration. The tentative explanation is that in this weak institutional environment, the advantages of registering from the outset are outweighed by the benefits of deferring registration. Evaluating the policy implications, the argument is that there is a need to shift away from the conventional eradication approach toward unregistered startups based on the assumption they are unproductive, and toward a more facilitating approach that improves the benefits of being registered and tackles the systemic formal institutional deficiencies that lead entrepreneurs to delay their decision to register

A prospective registry of emergency department patients admitted with infection

<p>Abstract</p> <p>Background</p> <p>Patients with infections account for a significant proportion of Emergency Department (ED) workload, with many hospital patients admitted with severe sepsis initially investigated and resuscitated in the ED. The aim of this registry is to systematically collect quality observational clinical and microbiological data regarding emergency patients admitted with infection, in order to explore in detail the microbiological profile of these patients, and to provide the foundation for a significant programme of prospective observational studies and further clinical research.</p> <p>Methods/design</p> <p>ED patients admitted with infection will be identified through daily review of the computerised database of ED admissions, and clinical information such as site of infection, physiological status in the ED, and components of management abstracted from patients' charts. This information will be supplemented by further data regarding results of investigations, microbiological isolates, and length of stay (LOS) from hospital electronic databases. Outcome measures will be hospital and intensive care unit (ICU) LOS, and mortality endpoints derived from a national death registry.</p> <p>Discussion</p> <p>This database will provide substantial insights into the characteristics, microbiological profile, and outcomes of emergency patients admitted with infections. It will become the nidus for a programme of research into compliance with evidence-based guidelines, optimisation of empiric antimicrobial regimens, validation of clinical decision rules and identification of outcome determinants. The detailed observational data obtained will provide a solid baseline to inform the design of further controlled trials planned to optimise treatment and outcomes for emergency patients admitted with infections.</p

A meta-analysis of long-term effects of conservation agriculture on maize grain yield under rain-fed conditions

Conservation agriculture involves reduced tillage, permanent soil cover and crop rotations to enhance soil fertility and to supply food from a dwindling land resource. Recently, conservation agriculture has been promoted in Southern Africa, mainly for maize-based farming systems. However, maize yields under rain-fed conditions are often variable. There is therefore a need to identify factors that influence crop yield under conservation agriculture and rain-fed conditions. Here, we studied maize grain yield data from experiments lasting 5 years and more under rain-fed conditions. We assessed the effect of long-term tillage and residue retention on maize grain yield under contrasting soil textures, nitrogen input and climate. Yield variability was measured by stability analysis. Our results show an increase in maize yield over time with conservation agriculture practices that include rotation and high input use in low rainfall areas. But we observed no difference in system stability under those conditions. We observed a strong relationship between maize grain yield and annual rainfall. Our meta-analysis gave the following findings: (1) 92% of the data show that mulch cover in high rainfall areas leads to lower yields due to waterlogging; (2) 85% of data show that soil texture is important in the temporal development of conservation agriculture effects, improved yields are likely on well-drained soils; (3) 73% of the data show that conservation agriculture practices require high inputs especially N for improved yield; (4) 63% of data show that increased yields are obtained with rotation but calculations often do not include the variations in rainfall within and between seasons; (5) 56% of the data show that reduced tillage with no mulch cover leads to lower yields in semi-arid areas; and (6) when adequate fertiliser is available, rainfall is the most important determinant of yield in southern Africa. It is clear from our results that conservation agriculture needs to be targeted and adapted to specific biophysical conditions for improved impact

Evolutionary Dynamics of Intratumor Heterogeneity

Intraneoplastic diversity in human tumors is a widespread phenomenon of critical importance for tumor progression and the response to therapeutic intervention. Insights into the evolutionary events that control tumor heterogeneity would be a major breakthrough in our comprehension of cancer development and could lead to more effective prevention methods and therapies. In this paper, we design an evolutionary mathematical framework to study the dynamics of heterogeneity over time. We consider specific situations arising during tumorigenesis, such as the emergence of positively selected mutations (“drivers”) and the accumulation of neutral variation (“passengers”). We perform exact computer simulations of the emergence of diverse tumor cell clones over time, and derive analytical estimates for the extent of heterogeneity within a population of cancer cells. Our methods contribute to a quantitative understanding of tumor heterogeneity and the impact of heritable alterations on this tumor trait