A core challenge in global change biology is to predict how species will respond to future environmental change and to manage these responses. To make such predictions and management actions robust ...to novel futures, we need to accurately characterize how organisms experience their environments and the biological mechanisms by which they respond. All organisms are thermodynamically connected to their environments through the exchange of heat and water at fine spatial and temporal scales and this exchange can be captured with biophysical models. Although mechanistic models based on biophysical ecology have a long history of development and application, their use in global change biology remains limited despite their enormous promise and increasingly accessible software. We contend that greater understanding and training in the theory and methods of biophysical ecology is vital to expand their application. Our review shows how biophysical models can be implemented to understand and predict climate change impacts on species' behavior, phenology, survival, distribution, and abundance. It also illustrates the types of outputs that can be generated, and the data inputs required for different implementations. Examples range from simple calculations of body temperature at a particular site and time, to more complex analyses of species' distribution limits based on projected energy and water balances, accounting for behavior and phenology. We outline challenges that currently limit the widespread application of biophysical models relating to data availability, training, and the lack of common software ecosystems. We also discuss progress and future developments that could allow these models to be applied to many species across large spatial extents and timeframes. Finally, we highlight how biophysical models are uniquely suited to solve global change biology problems that involve predicting and interpreting responses to environmental variability and extremes, multiple or shifting constraints, and novel abiotic or biotic environments.
Predictions of how species respond to climate and other global changes should ideally be based explicitly on known processes. Here we review the field of biophysical ecology, which addresses the most fundamental thermodynamic processes by which organisms respond to environmental change. We contend that greater understanding and training in the theory and methods of biophysical models is vital to expand their application.
Abstract
Endothelial cells (ECs) are sentinels of cardiovascular health. Their function is reduced by the presence of cardiovascular risk factors, and is regained once pathological stimuli are ...removed. In this European Society for Cardiology Position Paper, we describe endothelial dysfunction as a spectrum of phenotypic states and advocate further studies to determine the role of EC subtypes in cardiovascular disease. We conclude that there is no single ideal method for measurement of endothelial function. Techniques to measure coronary epicardial and micro-vascular function are well established but they are invasive, time-consuming, and expensive. Flow-mediated dilatation (FMD) of the brachial arteries provides a non-invasive alternative but is technically challenging and requires extensive training and standardization. We, therefore, propose that a consensus methodology for FMD is universally adopted to minimize technical variation between studies, and that reference FMD values are established for different populations of healthy individuals and patient groups. Newer techniques to measure endothelial function that are relatively easy to perform, such as finger plethysmography and the retinal flicker test, have the potential for increased clinical use provided a consensus is achieved on the measurement protocol used. We recommend further clinical studies to establish reference values for these techniques and to assess their ability to improve cardiovascular risk stratification. We advocate future studies to determine whether integration of endothelial function measurements with patient-specific epigenetic data and other biomarkers can enhance the stratification of patients for differential diagnosis, disease progression, and responses to therapy.
Les sociétés contemporaines sont de plus en plus marquées par les formes de diversité culturelle qui les composent et les distinguent. Si la rencontre avec l’hétérogénéité constitue depuis toujours ...une dimension importante de toute société, elle s’érige dans notre contemporanéité comme le marqueur principal de toute collectivité sociale. Parmi tant d’autres pays, le Canada ne fait pas exception à cette règle, car il s’est aussi forgé dans la mixité. En s’inspirant de la ville de Winnipeg — lieu paradigmatique de la confluence des cultures autochtone, francophone, allophone et anglophone au Canada —, les auteurs de ce recueil s’interrogent sur les nombreuses expressions du brassage culturel non seulement dans l’Ouest canadien, mais aussi à travers le pays. Les contributions en français et en anglais explorent dans une perspective pluridisciplinaire les dimensions historiques, culturelles et discursives du métissage et du transculturalisme au Canada. Dans leur ensemble, les articles cherchent à éclairer la nature de ces deux concepts clés du livre, tout en jetant un regard sur des cas et des exemples caractéristiques de la condition sociohistorique fondamentale du Canada : l’hétérogénéité culturelle.
The United States Preventive Services Task Force supports individualised decision-making for prostate-specific antigen (PSA)-based screening in men aged 55-69. Knowing how the potential benefits and ...harms of screening vary by an individual's risk of developing prostate cancer could inform decision-making about screening at both an individual and population level. This modelling study examined the benefit-harm tradeoffs and the cost-effectiveness of a risk-tailored screening programme compared to age-based and no screening.
A life-table model, projecting age-specific prostate cancer incidence and mortality, was developed of a hypothetical cohort of 4.48 million men in England aged 55 to 69 years with follow-up to age 90. Risk thresholds were based on age and polygenic profile. We compared no screening, age-based screening (quadrennial PSA testing from 55 to 69), and risk-tailored screening (men aged 55 to 69 years with a 10-year absolute risk greater than a threshold receive quadrennial PSA testing from the age they reach the risk threshold). The analysis was undertaken from the health service perspective, including direct costs borne by the health system for risk assessment, screening, diagnosis, and treatment. We used probabilistic sensitivity analyses to account for parameter uncertainty and discounted future costs and benefits at 3.5% per year. Our analysis should be considered cautiously in light of limitations related to our model's cohort-based structure and the uncertainty of input parameters in mathematical models. Compared to no screening over 35 years follow-up, age-based screening prevented the most deaths from prostate cancer (39,272, 95% uncertainty interval UI: 16,792-59,685) at the expense of 94,831 (95% UI: 84,827-105,630) overdiagnosed cancers. Age-based screening was the least cost-effective strategy studied. The greatest number of quality-adjusted life-years (QALYs) was generated by risk-based screening at a 10-year absolute risk threshold of 4%. At this threshold, risk-based screening led to one-third fewer overdiagnosed cancers (64,384, 95% UI: 57,382-72,050) but averted 6.3% fewer (9,695, 95% UI: 2,853-15,851) deaths from prostate cancer by comparison with age-based screening. Relative to no screening, risk-based screening at a 4% 10-year absolute risk threshold was cost-effective in 48.4% and 57.4% of the simulations at willingness-to-pay thresholds of GBP£20,000 (US$26,000) and £30,000 ($39,386) per QALY, respectively. The cost-effectiveness of risk-tailored screening improved as the threshold rose.
Based on the results of this modelling study, offering screening to men at higher risk could potentially reduce overdiagnosis and improve the benefit-harm tradeoff and the cost-effectiveness of a prostate cancer screening program. The optimal threshold will depend on societal judgements of the appropriate balance of benefits-harms and cost-effectiveness.
Objective:
A systematic review and meta-analysis of randomized controlled trials to determine if motivational interviewing leads to increased physical activity, cardiorespiratory fitness or ...functional exercise capacity in people with chronic health conditions.
Data sources:
Seven electronic databases (MEDLINE, PsychINFO, EMBASE, AMED, CINHAL, SPORTDiscus and the Cochrane Central Register of Controlled trials) were searched from inception until January 2014.
Trial selection:
Two reviewers independently examined publications for inclusion. Trials were included if participants were adults (>18 years), had a chronic health condition, used motivational interviewing as the intervention and examined physical activity, cardiorespiratory fitness or functional exercise capacity.
Data extraction:
Two reviewers independently extracted data. Risk of bias within trials was assessed using the Physiotherapy Evidence Database Scale.
Data synthesis:
Meta-analyses were conducted with standardized mean differences and 95% confidence intervals (CIs) were calculated. The Grades of Recommendation, Assessment, Development and Evaluation approach was used to evaluate the quality of the evidence.
Results:
Eleven publications (of ten trials) were included. There was moderate level evidence that motivational interviewing had a small effect in increasing physical activity levels in people with chronic health conditions relative to comparison groups (standardized mean differences = 0.19, 95% CI 0.06 to 0.32, p = 0.004). Sensitivity analysis based on trials that confirmed treatment fidelity produced a larger effect. No conclusive evidence was observed for cardiorespiratory fitness or functional exercise capacity.
Conclusion:
The addition of motivational interviewing to usual care may lead to modest improvements in physical activity for people with chronic health conditions.
The age-based or "one-size-fits-all" breast screening approach does not take into account the individual variation in risk. Mammography screening reduces death from breast cancer at the cost of ...overdiagnosis. Identifying risk-stratified screening strategies with a more favorable ratio of overdiagnoses to breast cancer deaths prevented would improve the quality of life of women and save resources.
To assess the benefit-to-harm ratio and the cost-effectiveness of risk-stratified breast screening programs compared with a standard age-based screening program and no screening.
A life-table model was created of a hypothetical cohort of 364 500 women in the United Kingdom, aged 50 years, with follow-up to age 85 years, using (1) findings of the Independent UK Panel on Breast Cancer Screening and (2) risk distribution based on polygenic risk profile. The analysis was undertaken from the National Health Service perspective.
The modeled interventions were (1) no screening, (2) age-based screening (mammography screening every 3 years from age 50 to 69 years), and (3) risk-stratified screening (a proportion of women aged 50 years with a risk score greater than a threshold risk were offered screening every 3 years until age 69 years) considering each percentile of the risk distribution. All analyses took place between July 2016 and September 2017.
Overdiagnoses, breast cancer deaths averted, quality-adjusted life-years (QALYs) gained, costs in British pounds, and net monetary benefit (NMB). Probabilistic sensitivity analyses were used to assess uncertainty around parameter estimates. Future costs and benefits were discounted at 3.5% per year.
The risk-stratified analysis of this life-table model included a hypothetical cohort of 364 500 women followed up from age 50 to 85 years. As the risk threshold was lowered, the incremental cost of the program increased linearly, compared with no screening, with no additional QALYs gained below 35th percentile risk threshold. Of the 3 screening scenarios, the risk-stratified scenario with risk threshold at the 70th percentile had the highest NMB, at a willingness to pay of £20 000 (US $26 800) per QALY gained, with a 72% probability of being cost-effective. Compared with age-based screening, risk-stratified screening at the 32nd percentile vs 70th percentile risk threshold would cost £20 066 (US $26 888) vs £537 985 (US $720 900) less, would have 26.7% vs 71.4% fewer overdiagnoses, and would avert 2.9% vs 9.6% fewer breast cancer deaths, respectively.
Not offering breast cancer screening to women at lower risk could improve the cost-effectiveness of the screening program, reduce overdiagnosis, and maintain the benefits of screening.
This paper reviews the methods, benefits and challenges associated with the adoption and translation of computational fluid dynamics (CFD) modelling within cardiovascular medicine. CFD, a specialist ...area of mathematics and a branch of fluid mechanics, is used routinely in a diverse range of safety-critical engineering systems, which increasingly is being applied to the cardiovascular system. By facilitating rapid, economical, low-risk prototyping, CFD modelling has already revolutionised research and development of devices such as stents, valve prostheses, and ventricular assist devices. Combined with cardiovascular imaging, CFD simulation enables detailed characterisation of complex physiological pressure and flow fields and the computation of metrics which cannot be directly measured, for example, wall shear stress. CFD models are now being translated into clinical tools for physicians to use across the spectrum of coronary, valvular, congenital, myocardial and peripheral vascular diseases. CFD modelling is apposite for minimally-invasive patient assessment. Patient-specific (incorporating data unique to the individual) and multi-scale (combining models of different length- and time-scales) modelling enables individualised risk prediction and virtual treatment planning. This represents a significant departure from traditional dependence upon registry-based, population-averaged data. Model integration is progressively moving towards 'digital patient' or 'virtual physiological human' representations. When combined with population-scale numerical models, these models have the potential to reduce the cost, time and risk associated with clinical trials. The adoption of CFD modelling signals a new era in cardiovascular medicine. While potentially highly beneficial, a number of academic and commercial groups are addressing the associated methodological, regulatory, education- and service-related challenges.
Display omitted
•Most patients with single HCC ≤3 cm treated by RFA will eventually develop recurrent HCC distant to the ablation site.•Many patients treated with HCC will recur beyond the Milan ...criteria despite close post-RFA surveillance.•Patients with tumors >2 cm and higher serum alpha-fetoprotein are at greater risk of recurrence beyond Milan criteria.
Radiofrequency ablation (RFA) is an effective treatment for single hepatocellular carcinoma (HCC) ≤3 cm. Disease recurrence is common, and in some patients will occur outside transplant criteria. We aimed to assess the incidence and risk factors for recurrence beyond Milan criteria in potentially transplantable patients treated with RFA as first-line therapy.
We performed a retrospective cohort study of potentially transplantable patients with new diagnoses of unifocal HCC ≤3 cm that underwent RFA as first-line therapy between 2000-2015. We defined potentially transplantable patients as those aged <70 years without any comorbidities that would preclude transplant surgery. Incidence of recurrence beyond Milan criteria was compared across 2 groups according to HCC diameter at the time of ablation: (HCC ≤2 cm vs. HCC >2 cm). Competing risks Cox regression was used to identify predictors of recurrence beyond Milan criteria.
We included 301 patients (167 HCC ≤2 cm and 134 HCC >2 cm). Recurrence beyond Milan criteria occurred in 36 (21.6%) and 47 (35.1%) patients in the HCC ≤2 cm and the HCC >2 cm groups, respectively (p = 0.01). The 1-, 3- and 5-year actuarial survival rates after RFA were 98.2%, 86.2% and 79.0% in the HCC ≤2 cm group vs. 93.3%, 77.6% and 70.9% in the HCC >2 cm group (p = 0.01). Tumor size >2 cm (hazard ratio 1.94; 95%CI 1.25–3.02) and alpha-fetoprotein levels at the time of ablation (100–1,000 ng/ml: hazard ratio 2.05; 95%CI 1.10–3.83) were found to be predictors of post-RFA recurrence outside Milan criteria.
RFA for single HCC ≤3 cm provides excellent short- to medium-term survival. However, we identified patients at higher risk of recurrence beyond Milan criteria. For these patients, liver transplantation should be considered immediately after the first HCC recurrence following RFA.
Radiofrequency ablation and liver transplantation are treatment options for early stages of hepatocellular carcinoma (HCC). After ablation some patients will experience recurrence or metastatic spread of the initial tumor or may develop new tumors within the liver. Despite close follow-up, these recurrences can progress rapidly and exceed transplant criteria, preventing the patient from receiving a transplant. We identified that patients with HCC >2 cm and higher serum alpha-fetoprotein are at greater risk of recurrence beyond the transplant criteria. These data suggest that liver transplantation should be considered immediately after the first HCC recurrence for these patients.
PDF
