Determinants of soil organic matter chemistry in maritime temperate forest ecosystems

While the influence of climate, vegetation, management and abiotic site factors on total carbon budgets and turn-over is intensively assessed, the influences of these ecosystem properties on the chemical complexity of soil organic matter (SOM) remains poorly understood. This study addresses the chemical composition of NaOH-extracted SOM from maritime temperate forest sites in Flanders (Belgium) by pyrolysis-GC/MS. The studied forests were chosen based on dominant tree species (Pinus sylvestris, Fagus sylvatica, Quercus robur and Populus spp.), soil texture and soil-moisture conditions. Differences in extractable-SOM pyrolysis products were correlated to site variables including dominant tree species, management of the woody biomass, site history, soil properties, total carbon stocks and indicators for microbial activity. Despite of a typical high intercorrelation between these site variables, the influence of the dominant tree species is prominent. The extractable-SOM composition is strongly correlated to litter quality and available nutrients. In nutrient-poor forests with low litter quality, the decomposition of relatively recalcitrant compounds (i.e. short and mid-chain alkanes/alkenes and aromatic compounds) appears hampered, causing a relative accumulation of these compounds in the soil. However, if substrate quality is favorable, no accumulations of recalcitrant compounds were observed, not even under high soil-moisture conditions. Former heathland vegetation still had a profound influence on extractable-SOM chemistry of young pine forests after a minimum of 60 year

Net benefit approaches to the evaluation of prediction models, molecular markers, and diagnostic tests

Many decisions in medicine involve trade-offs, such as between diagnosing patients with disease versus unnecessary additional testing for those who are healthy. Net benefit is an increasingly reported decision analytic measure that puts benefits and harms on the same scale. This is achieved by specifying an exchange rate, a clinical judgment of the relative value of benefits (such as detecting a cancer) and harms (such as unnecessary biopsy) associated with models, markers, and tests. The exchange rate can be derived by asking simple questions, such as the maximum number of patients a doctor would recommend for biopsy to find one cancer. As the answers to these sorts of questions are subjective, it is possible to plot net benefit for a range of reasonable exchange rates in a "decision curve." For clinical prediction models, the exchange rate is related to the probability threshold to determine whether a patient is classified as being positive or negative for a disease. Net benefit is useful for determining whether basing clinical decisions on a model, marker, or test would do more good than harm. This is in contrast to traditional measures such as sensitivity, specificity, or area under the curve, which are statistical abstractions not directly informative about clinical value. Recent years have seen an increase in practical applications of net benefit analysis to research data. This is a welcome development, since decision analytic techniques are of particular value when the purpose of a model, marker, or test is to help doctors make better clinical decisions

Practical guidance for applying the ADNEX model from the IOTA group to discriminate between different subtypes of adnexal tumors.

All gynecologists are faced with ovarian tumors on a regular basis, and the accurate preoperative diagnosis of these masses is important because appropriate management depends on the type of tumor. Recently, the International Ovarian Tumor Analysis (IOTA) consortium published the Assessment of Different NEoplasias in the adneXa (ADNEX) model, the first risk model that differentiates between benign and four types of malignant ovarian tumors: borderline, stage I cancer, stage II-IV cancer, and secondary metastatic cancer. This approach is novel compared to existing tools that only differentiate between benign and malignant tumors, and therefore questions may arise on how ADNEX can be used in clinical practice. In the present paper, we first provide an in-depth discussion about the predictors used in ADNEX and the ability for risk prediction with different tumor histologies. Furthermore, we formulate suggestions about the selection and interpretation of risk cut-offs for patient stratification and choice of appropriate clinical management. This is illustrated with a few example patients. We cannot propose a generally applicable algorithm with fixed cut-offs, because (as with any risk model) this depends on the specific clinical setting in which the model will be used. Nevertheless, this paper provides a guidance on how the ADNEX model may be adopted into clinical practice

Regression shrinkage methods for clinical prediction models do not guarantee improved performance: simulation study

When developing risk prediction models on datasets with limited sample size, shrinkage methods are recommended. Earlier studies showed that shrinkage results in better predictive performance on average. This simulation study aimed to investigate the variability of regression shrinkage on predictive performance for a binary outcome. We compared standard maximum likelihood with the following shrinkage methods: uniform shrinkage (likelihood-based and bootstrap-based), penalized maximum likelihood (ridge) methods, LASSO logistic regression, adaptive LASSO, and Firth's correction. In the simulation study, we varied the number of predictors and their strength, the correlation between predictors, the event rate of the outcome, and the events per variable. In terms of results, we focused on the calibration slope. The slope indicates whether risk predictions are too extreme (slope 1). The results can be summarized into three main findings. First, shrinkage improved calibration slopes on average. Second, the between-sample variability of calibration slopes was often increased relative to maximum likelihood. In contrast to other shrinkage approaches, Firth's correction had a small shrinkage effect but showed low variability. Third, the correlation between the estimated shrinkage and the optimal shrinkage to remove overfitting was typically negative, with Firth's correction as the exception. We conclude that, despite improved performance on average, shrinkage often worked poorly in individual datasets, in particular when it was most needed. The results imply that shrinkage methods do not solve problems associated with small sample size or low number of events per variable.Development and application of statistical models for medical scientific researc

Random-effects meta-analysis of the clinical utility of tests and prediction models

The use of data from multiple studies or centers for the validation of a clinical test or a multivariable prediction model allows researchers to investigate the test's/model's performance in multiple settings and populations. Recently, meta-analytic techniques have been proposed to summarize discrimination and calibration across study populations. Here, we rather consider performance in terms of net benefit, which is a measure of clinical utility that weighs the benefits of true positive classifications against the harms of false positives. We posit that it is important to examine clinical utility across multiple settings of interest. This requires a suitable meta-analysis method, and we propose a Bayesian trivariate random-effects meta-analysis of sensitivity, specificity, and prevalence. Across a range of chosen harm-to-benefit ratios, this provides a summary measure of net benefit, a prediction interval, and an estimate of the probability that the test/model is clinically useful in a new setting. In addition, the prediction interval and probability of usefulness can be calculated conditional on the known prevalence in a new setting. The proposed methods are illustrated by 2 case studies: one on the meta-analysis of published studies on ear thermometry to diagnose fever in children and one on the validation of a multivariable clinical risk prediction model for the diagnosis of ovarian cancer in a multicenter dataset. Crucially, in both case studies the clinical utility of the test/model was heterogeneous across settings, limiting its usefulness in practice. This emphasizes that heterogeneity in clinical utility should be assessed before a test/model is routinely implemented

Burnout, well-being and defensive medical practice among obstetricians and gynaecologists in the UK: cross-sectional survey study

Objectives: To determine the prevalence of burnout in doctors practising obstetrics and gynaecology, and assess the association with defensive medical practice and self-reported wellbeing. Design: Nationwide online cross-sectional survey study; December 2017-March 2018. Setting: Hospitals in the United Kingdom Participants: 5661 practising Obstetrics and Gynaecology consultants, specialty and associate specialist doctors and trainees registered with the Royal College of Obstetricians and Gynaecologists Primary and Secondary Outcome Measures: Prevalence of burnout using the Maslach Burnout Inventory and defensive medical practice (avoiding cases or procedures, overprescribing, over-referral) using a 12-item questionnaire. The odds ratios of burnout with defensive medical practice and self-reported wellbeing. Results: 3102/5661 doctors (55%) completed the survey. 3073/3102 (99%) met the inclusion criteria (1462 consultants, 1357 trainees and 254 specialty and associate specialist doctors). 1116/3073 (36%) doctors met the burnout criteria, with levels highest amongst trainees (580/1357 [43%]). 258/1116 (23%) doctors with burnout reported increased defensive practice compared to 142/1957 (7%) without (adjusted odds ratio 4.35, 95% CI 3.46 to 5.49). Odds ratios of burnout with wellbeing items varied between 1.38 and 6.37, and were highest for anxiety (3.59, 95% CI 3.07 to 4.21), depression (4.05, 95% CI 3.26 to 5.04), and suicidal thoughts (6.37, 95% CI 95% CI 3.95 to 10.7). In multivariable logistic regression, being of younger age, white or ‘other’ ethnicity, and graduating with a medical degree from the UK or Ireland had the strongest associations with burnout. Conclusions: High levels of burnout were observed in obstetricians and gynaecologists and particularly amongst trainees. Burnout was associated with both increased defensive medical practice and worse doctor wellbeing. These findings have implications for the wellbeing and retention of doctors as well as the quality of patient care, and may help to inform the content of future interventions aimed at preventing burnout and improving patient safety