KJ717942_annotated.gb

The annotated genome of PRV strain Kaplan.<br

A versatile computational pipeline for the preprocessing of cell-free DNA fragmentation data

Cell-free DNA (cfDNA) emerges as a promising liquid biopsy biomarker for cancer diagnosis and patient monitoring. Complementing mutation-based assays, cfDNA carries information about epigenetic modifications from decaying cells. This information is encoded in the shape of the cfDNA fragments. Specifically, fragments from cancer tend to be shorter than those originating from other adult cells, enabling a distinction between cancer patients and healthy individuals. Additional cfDNA features such as fragment end motifs and information on nucleosome positioning provide further insight into cancer biology. These cfDNA measures are typically inferred from low-pass whole genome sequencing and subsequent bioinformatics processing. A key bioinformatics step is the alignment of DNA sequencing reads to the reference genome, which critically depends on preprocessing steps such as read trimming and

The Effect of Preanalytical and Physiological Variables on Cell-Free DNA Fragmentation

Background: Assays that account for the biological properties and fragmentation of cell-free DNA (cfDNA) can improve the performance of liquid biopsy. However, preanalytic and physiological differences between individuals on fragmentomic analysis are poorly defined. Methods: We analyzed the impact of collection tube, plasma processing time, and physiology on the size distribution of cfDNA, their genome-wide representation, and sequence diversity at the cfDNA fragment ends using shallow whole-genome sequencing. Results: Neither different stabilizing collection tubes nor processing times affected the cfDNA fragment sizes, but could impact the genome-wide fragmentation patterns and fragment-end sequences of cfDNA. In addition, beyond differences depending on the gender, the physiological conditions tested between 63 individuals (age, body mass index, use of medication, and chronic conditions) minimally influenced the outcome of fragmentomic methods. Conclusions: Fragmentomic approaches have potential for implementation in the clinic, pending clear traceability of analytical and physiological factors

The Effect of Preanalytical and Physiological Variables on Cell-Free DNA Fragmentation

Background: Assays that account for the biological properties and fragmentation of cell-free DNA (cfDNA) can improve the performance of liquid biopsy. However, preanalytic and physiological differences between individuals on fragmentomic analysis are poorly defined. Methods: We analyzed the impact of collection tube, plasma processing time, and physiology on the size distribution of cfDNA, their genome-wide representation, and sequence diversity at the cfDNA fragment ends using shallow whole-genome sequencing. Results: Neither different stabilizing collection tubes nor processing times affected the cfDNA fragment sizes, but could impact the genome-wide fragmentation patterns and fragment-end sequences of cfDNA. In addition, beyond differences depending on the gender, the physiological conditions tested between 63 individuals (age, body mass index, use of medication, and chronic conditions) minimally influenced the outcome of fragmentomic methods. Conclusions: Fragmentomic approaches have potential for implementation in the clinic, pending clear traceability of analytical and physiological factors

Flächennutzung und Flächennutzungsansprüche in Deutschland

Agricultural land in Germany has continuously declined in recent decades. This was accompanied by an increase in settlement and transport areas as well as forest areas. This process continues. Even if the food supply in Germany is not endangered due to this development, agricultural land is a fundamentally scarce resource that is worth protecting. It must be taken into account that Germany has a global responsibility to use fertile arable land for food production and to protect it accordingly. In view of the fact that national and international sustainability goals are aimed at protecting soils and that the amount of arable land available per capita is decreasing worldwide, Germany should therefore provide an example in dealing with soil as a resource. In recent years, new land use for settlement and transport infrastructure has declined significantly. However, as a result of plans to increase construction of new housing and to expand renewable energies, especially ground-mounted photovoltaics, a sharp increase in new land use is expected by 2030. At the same time, from the perspective of biodiversity and climate protection, increasing demands are being made for the creation of near-natural habitats and carbon sinks. These are associated with land use changes (afforestation, planting of woodlands and hedges, rewetting of peatlands) or with an extensification of agricultural use. Given the numerous uncertainties, it is difficult to predict to what extent the utilised agricultural area will be allocated towards additional land requirements for affordable housing, the energy transition and natural climate protection. An estimate assuming that key goals are achieved by 2030 amounts to a decline of more than 300,000 hectares of utilised agricultural area by 2030. The increasing demands for land are exacerbating the already existing competition between land uses. In the future, land use requirements must be carefully weighed up more closely and synergies and multiple uses of areas should be realized as far as possible. Examples of such synergies include the expansion of photovoltaics (PV) on settlement and transport areas, on rewetted peatlands or in combination with agricultural use. However, governance of PV expansion on open spaces is currently only possible to a limited extent, as planning and approval are in the hands of the municipalities and new systems are increasingly being built outside of the Renewable Energy Act. The expanded privilege under building law for ground-mounted PV on corridors along motorways and railway lines is intended to accelerate expansion. However, it promotes the conversion of agricultural land without taking advantage of the aforementioned synergies. Given the high demands on land for biodiversity and climate protection, synergies must also be realised in this area. Balancing and controlling the various land requirements without slowing down the pace of the energy transition and the transformation towards more sustainable and climate-friendly land use is a major challenge for politicians. For this purpose, a cross-target land use policy must be developed

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine

Critical care admission following elective surgery was not associated with survival benefit: prospective analysis of data from 27 countries

This was an investigator initiated study funded by Nestle Health Sciences through an unrestricted research grant, and by a National Institute for Health Research (UK) Professorship held by RP. The study was sponsored by Queen Mary University of London