Quality of patient- and proxy-reported outcomes for children with impairment of the lower extremity:A systematic review using the COnsensus-based Standards for selection of health Measurement INstruments methodology

Background: Patient-reported outcome measures have become crucial in the clinical evaluation of patients. Appropriate selection, in a young population, of the instrument is vital to providing evidence-based patient-centered healthcare. This systematic review applies the COnsensus-based Standards for selection of health Measurement INstruments methodology to provide a critically appraised overview of patient-reported outcome measures targeted at pediatric orthopedic patients with lower limb impairment.Method: A systematic search of electronic databases was performed to identify original studies reporting the development and/or validation of patient-reported outcome measures evaluating children with impairment of the lower extremity. Data extraction, quality assessment, and risk of bias evaluation were performed following the COnsensus-based Standards for selection of health Measurement INstruments guidelines and Preferred Reporting Items for Systematic reviews and Meta-Analyses statement.Results: A total of 6919 articles were screened. Thirty-three studies were included, reporting evidence on the measurement properties of 13 different patient-reported outcome measures and 20 translations. Four studies reported on content validity and patient-reported outcome measure development. The methodological quality of studies on structural validity, content validity, or patient-reported outcome measure development was mostly rated as "doubtful" or "very good." The quality of evidence on measurement properties varied noticeably, with most studies needing to perform improve their methodological quality to justify their results.Conclusion: This review provides an extensive overview of all available patient-reported outcome measures for patients with lower extremity impairment within pediatric orthopedics. We cautiously advise the use of four patient-reported outcome measures. However, the scarce availability of research on content validity and patient-reported outcome measure development highlights an area for future research endeavors to improve our knowledge on the currently available patient-reported outcome measures.Level of evidence: Diagnostic level

Organic geochemical studies of soils from the Rothamsted Classical Experiments - V. The fate of lipids in different long-term soil experiments

Lipid extracts from four long-term experiments (Broadbalk Wilderness, Geescroft Wilderness, Hoos®eld Spring Barley and Park Grass) were analysed using a combination of gas chromatography, gas chromatography±mass spectrometry and gas chromatography±combustion±isotope ratio mass spectrometry. The lipid content of the primary organic inputs for each soil were also analysed in order to assess the early diagenetic fate of the various compound classes present. Soil pH was observed to, either directly or indirectly, have a signi®cant e\u80ect on lipids with a relative increase in abundance of n-alkanes at higher pH (7.31) and a large relative increase in n-alkanoic and o-hydroxy acids at low pH (3.74). Triacylglycerols exhibited severe losses irrespective of pH. In an arable soil, n-alkanoic acids showed a temporal decrease in concentration whilst levels of n-alkanols remained static, the di\u80erence was ascribed to a more rapid turnover and possible leachate migration of the n-alkanoic acids. The phytosterol, sitosterol, was observed to rapidly diminish in soils possibly as a result of assimilation by soil dwelling invertebrates. Analysis of 5b-stigmastanol (a faecal biomarker) showed that it remained at levels indicative of manuring even after 113 years. Furthermore, analysis of 5b-stanyl esters revealed a manuring signal even more persistent than that exhibited by the free stanols. Knowledge of the biogeochemical cycling of lipids in the soil environment will help facilitate understanding of the processes which underpin carbon cycling in soils

Organic geochemical studies of soils from the Rothamsted classical experiments VI The occurrence and source of organic acids in an experimental grassland soil

In this work a detailed modeling of three-phase distribution transformers aimed at complementing well-known approaches is presented. Thus, incidence of angular displacement and tapping is taken into account in the proposed models, considering both actual values and per unit. The analysis is based on minimal data requirement: solely short-circuit admittance is needed since three-phase transformers are treated as non-magnetically-coupled single-phase transformers. In order to support the proposed methodology, results obtained through laboratory tests are presented

Biochemical marker research in hemophilic arthropathy: A systematic review

Hemophilic arthropathy (HA) causes major morbidity. Breakthrough therapies reduce the bleeding frequency tremendously, but well-defined joint outcome assessments with a focus on early changes and subclinical damage are lacking. Biomarkers reflecting joint tissue turnover/inflammation might be useful to predict invalidating arthropathy. This systematic review summarized and categorized publications on blood/urinary biomarkers in HA to provide leads for implementation. A PubMed/EMBASE search was performed on September 9, 2019. All publications were assessed and allocated to one or several BIPED-categories, based on the utility of biomarkers. Of the initial 1307 publications found, 27 were eligible for inclusion. The majority (81%, n = 32/42) was cross-sectional in design, including relatively small numbers of patients (median 44, interquartile range 35-78). Fourteen percent (n = 6/42) investigated dynamic changes around a bleeding or treatment. Only two studies investigated the prognostic value of biomarkers. Most promising biomarkers were serum Coll2-1, COL-18N, COMP, C1,2C, C2M, CS846, MIF, plasma sVCAM-1 and urinary CTX-II. Comparing performances and pooling data was not possible due to heterogeneity. Currently, biomarker research in HA is still in an explorative stage and not yet sufficient for translation into daily practice. Clearly, larger homogeneous longitudinal studies in well-defined populations should be performed for further development

Site-specific Activity-based Protein Profiling Using Phosphonate Handles

Most drug molecules target proteins. Identification of the exact drug binding sites on these proteins is essential to understand and predict how drugs affect protein structure and function. To address this challenge, we developed a strategy that uses immobilized metal-affinity chromatography-enrichable phosphonate affinity tags, for efficient and selective enrichment of peptides bound to an activity-based probe, enabling the identification of the exact drug binding site. As a proof of concept, using this approach, termed PhosID-ABPP (activity-based protein profiling), over 500 unique binding sites were reproducibly identified of an alkynylated afatinib derivative (PF-06672131). As PhosID-ABPP is compatible with intact cell inhibitor treatment, we investigated the quantitative differences in approachable binding sites in intact cells and in lysates of the same cell line and observed and quantified substantial differences. Moreover, an alternative protease digestion approach was used to capture the previously reported binding site on the epidermal growth factor receptor, which turned out to remain elusive when using solely trypsin as protease. Overall, we find that PhosID-ABPP is highly complementary to biotin-based enrichment strategies in ABPP studies, with PhosID-ABPP providing the advantage of direct activity-based probe interaction site identification