Common methodological pitfalls in ICI pneumonitis risk prediction studies.

Background: Pneumonitis is one of the most common adverse events induced by the use of immune checkpoint inhibitors (ICI), accounting for a 20% of all ICI-associated deaths. Despite numerous efforts to identify risk factors and develop predictive models, there is no clinically deployed risk prediction model for patient risk stratification or for guiding subsequent monitoring. We believe this is due to systemic suboptimal approaches in study designs and methodologies in the literature. The nature and prevalence of different methodological approaches has not been thoroughly examined in prior systematic reviews. Methods: The PubMed, medRxiv and bioRxiv databases were used to identify studies that aimed at risk factor discovery and/or risk prediction model development for ICI-induced pneumonitis (ICI pneumonitis). Studies were then analysed to identify common methodological pitfalls and their contribution to the risk of bias, assessed using the QUIPS and PROBAST tools. Results: There were 51 manuscripts eligible for the review, with Japan-based studies over-represented, being nearly half (24/51) of all papers considered. Only 2/51 studies had a low risk of bias overall. Common bias-inducing practices included unclear diagnostic method or potential misdiagnosis, lack of multiple testing correction, the use of univariate analysis for selecting features for multivariable analysis, discretization of continuous variables, and inappropriate handling of missing values. Results from the risk model development studies were also likely to have been overoptimistic due to lack of holdout sets. Conclusions: Studies with low risk of bias in their methodology are lacking in the existing literature. High-quality risk factor identification and risk model development studies are urgently required by the community to give the best chance of them progressing into a clinically deployable risk prediction model. Recommendations and alternative approaches for reducing the risk of bias were also discussed to guide future studies.

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.

The compangle: a new goniometer for joint angle measurements of the hand. A technical note.

The accuracy of joint angle measurement of the hand may be negatively influenced by joint swelling, deformation and other obstacles. We developed an alternative goniometer with clear ergonomic advantages, especially for the measurement of small joints. This new concept of goniometry is described and preliminary results on the reliability of the measurements are presented. The intraclass correlation coefficients (ICCs) and the standard error of measurements (SEMs) of the alternative goniometer are greater respectively smaller than a conventional goniometer, indicating a better intratester reliability.

Trends in dating patterns and adolescent development.

A developmental scheme has been proposed which recognizes clusters of variables of adolescent behavior in the area of heterosexual object relationship development. These periods-(I) stage of sexual awakening (13-15), (II) stage of practicing (14-17), (III) stage of acceptance (16-19), (IV) stage of permanent object choice (18-25)-reflect the developing capacity of object relationship and are a a recapitulation on a higher level of functioning of the separation-individuation operations of the infant. The dating patterns at these levels of development provide a sensitive indication of growth, and unworked-through development is reflected in immature patterns. The current trends in dating described are considered to be a function of the prolongation of adolescence and not pathological.