Validierung innerklinischer Sichtungsalgorithmen für den Massenanfall von Verletzten

Background In the event of a mass casualty incident (MCI), the situation-related shortage of medical resources does not end when the patients are transported from the scene of the incident. Consequently, an initial triage is required in the receiving hospitals. In the first step, the aim of this study was to create a reference patient vignette set with defined triage categories. This allowed a computer-aided evaluation of the diagnostic quality of triage algorithms for MCI situations in the second step. Methods A total of 250 case vignettes validated in practice were entered into a multistage evaluation process by initially 6 and later 36 triage experts. This algorithm—independent expert evaluation of all vignettes—served as the gold standard for analyzing the diagnostic quality of the following triage algorithms: Manchester triage system (MTS module MCI), emergency severity index (ESI), Berlin triage algorithm (BER), the prehospital algorithms PRIOR and mSTaRT, and two project algorithms from a cooperation between the Federal Office of Civil Protection and Disaster Assistance (BBK) and the Hashemite Kingdom of Jordan—intrahospital Jordanian-German project algorithm (JorD) and prehospital triage algorithm (PETRA). Each patient vignette underwent computerized triage through all specified algorithms to obtain comparative test quality outcomes. Results Of the original 250 vignettes, a triage reference database of 210 patient vignettes was validated independently of the algorithms. These formed the gold standard for comparison of the triage algorithms analyzed. Sensitivities for intrahospital detection of patients in triage category T1 ranged from 1.0 (BER, JorD, PRIOR) to 0.57 (MCI module MTS). Specificities ranged from 0.99 (MTS and PETRA) to 0.67 (PRIOR). Considering Youden’s index, BER (0.89) and JorD (0.88) had the best overall performance for detecting patients in triage category T1. Overtriage was most likely with PRIOR, and undertriage with the MCI module of MTS. Up to a decision for category T1, the algorithms require the following numbers of steps given as the median and interquartile range (IQR): ESI 1 (1–2), JorD 1 (1–4), PRIOR 3 (2–4), BER 3 (2–6), mSTaRT 3 (3–5), MTS 4 (4–5) and PETRA 6 (6–8). For the T2 and T3 categories the number of steps until a decision and the test quality of the algorithms are positively interrelated. Conclusion In the present study, transferability of preclinical algorithm-based primary triage results to clinical algorithm-based secondary triage results was demonstrated. The highest diagnostic quality for secondary triage was provided by the Berlin triage algorithm, followed by the Jordanian-German project algorithm for hospitals, which, however, also require the most algorithm steps until a decision

Distributing CV entanglement over 4 co-propagating orthogonal modes

We propose a scheme for distributing continuous variable entanglement originally established among a pair of mode between a set of four orthogonal co-propagating modes. This is accomplished by exploiting the possibility of coupling polarization with optical angular momentum provided by the q-plate. Here we present the principle of the proposed scheme with a short feasibility study that shows that the four-modes covariance matrix at the scheme output represent an entangled multi mode system.Comment: 8 pages, 1 figur

Comparative Genomic Analysis of the Class \u3ci\u3eEpsilonproteobacteria\u3c/i\u3e and Proposed Reclassification to Epsilonbacteraeota (phyl. nov.)

The Epsilonproteobacteria is the fifth validly described class of the phylum Proteobacteria, known primarily for clinical relevance and for chemolithotrophy in various terrestrial and marine environments, including deep-sea hydrothermal vents. As 16S rRNA gene repositories have expanded and protein marker analysis become more common, the phylogenetic placement of this class has become less certain. A number of recent analyses of the bacterial tree of life using both 16S rRNA and concatenated marker gene analyses have failed to recover the Epsilonproteobacteria as monophyletic with all other classes of Proteobacteria. In order to address this issue, we investigated the phylogenetic placement of this class in the bacterial domain using 16S and 23S rRNA genes, as well as 120 single-copy marker proteins. Single- and concatenated-marker trees were created using a data set of 4,170 bacterial representatives, including 98 Epsilonproteobacteria. Phylogenies were inferred under a variety of tree building methods, with sequential jackknifing of outgroup phyla to ensure robustness of phylogenetic affiliations under differing combinations of bacterial genomes. Based on the assessment of nearly 300 phylogenetic tree topologies, we conclude that the continued inclusion of Epsilonproteobacteria within the Proteobacteria is not warranted, and that this group should be reassigned to a novel phylum for which we propose the name Epsilonbacteraeota (phyl. nov.). We further recommend the reclassification of the order Desulfurellales (Deltaproteobacteria) to a novel class within this phylum and a number of subordinate changes to ensure consistency with the genome-based phylogeny. Phylogenomic analysis of 658 genomes belonging to the newly proposed Epsilonbacteraeota suggests that the ancestor of this phylum was an autotrophic, motile, thermophilic chemolithotroph that likely assimilated nitrogen from ammonium taken up from the environment or generated from environmental nitrate and nitrite by employing a variety of functional redox modules. The emergence of chemoorganoheterotrophic lifestyles in several Epsilonbacteraeota families is the result of multiple independent losses of various ancestral chemolithoautotrophic pathways. Our proposed reclassification of this group resolves an important anomaly in bacterial systematics and ensures that the taxonomy of Proteobacteria remains robust, specifically as genome-based taxonomies become more common

Engineering of a complex bone tissue model with endothelialised channels and capillary-like networks

In engineering of tissue analogues, upscaling to clinically-relevant sized constructs remains a significant challenge. The successful integration of a vascular network throughout the engineered tissue is anticipated to overcome the lack of nutrient and oxygen supply to residing cells. This work aimed at developing a multiscale bone-tissue-specific vascularisation strategy. Engineering pre-vascularised bone leads to biological and fabrication dilemmas. To fabricate channels endowed with an endothelium and suitable for osteogenesis, rather stiff materials are preferable, while capillarisation requires soft matrices. To overcome this challenge, gelatine-methacryloyl hydrogels were tailored by changing the degree of functionalisation to allow for cell spreading within the hydrogel, while still enabling endothelialisation on the hydrogel surface. An additional challenge was the combination of the multiple required cell-types within one biomaterial, sharing the same culture medium. Consequently, a new medium composition was investigated that simultaneously allowed for endothelialisation, capillarisation and osteogenesis. Integrated multipotent mesenchymal stromal cells, which give rise to pericyte-like and osteogenic cells, and endothelial-colony-forming cells (ECFCs) which form capillaries and endothelium, were used. Based on the aforementioned optimisation, a construct of 8 × 8 × 3 mm, with a central channel of 600 µm in diameter, was engineered. In this construct, ECFCs covered the channel with endothelium and osteogenic cells resided in the hydrogel, adjacent to self-assembled capillary-like networks. This study showed the promise of engineering complex tissue constructs by means of human primary cells, paving the way for scaling-up and finally overcoming the challenge of engineering vascularised tissues

Validierung innerklinischer Sichtungsalgorithmen für den Massenanfall von Verletzten – eine simulationsbasierte Studie – deutsche Version

Hintergrund Die situationsbedingte Verknappung medizinischer Ressourcen endet bei einem Massenanfall von Verletzen (MANV) lageabhängig nicht mit dem Abtransport der Patienten von der Einsatzstelle. Folglich ist in den aufnehmenden Kliniken eine Eingangssichtung erforderlich. Ziel dieser Studie war es im ersten Schritt einen Referenz‐Patientenvignettensatz mit definierten Sichtungskategorien zu erstellen. Dies erlaubte im zweiten Schritt, die rechnergestützte Evaluation der diagnostischen Güte klinischer Sichtungsalgorithmen für MANV-Lagen. Methodik In einen mehrstufigen Bewertungsprozess durch zunächst sechs, später 36 Sichtungsexperten gingen 250 in der Übungspraxis validierte Fallvignetten ein. Diese Algorithmen – unabhängige Expertenbewertung aller Vignetten – dienten als Goldstandard für die Analyse der diagnostischen Güte der folgenden innerklinischen Algorithmen: Manchester Triage System (MTS Modul MANV), Emergency severity Index (ESI), Berliner Sichtungsalgorithmus (BER), die prähospitalen Algorithmen PRIOR und mSTaRT, sowie zwei Projektalgorithmen aus einer Kooperation des Bundesamts für Bevölkerungsschutz und Katastrophenhilfe (BBK) mit dem Haschemitischen Königreich Jordanien – innerklinischer jordanisch-deutscher Projektalgorithmus (JorD) und prähospitaler Sichtungsalgorithmus (PETRA). Jede Patientenvignette durchlief computergestützt eine Sichtung durch alle angegeben Algorithmen, um vergleichend die Testgüte für alle Verfahren zu erheben. Ergebnisse Von den ursprünglich 250 Vignetten konnte eine Sichtungsreferenzdatenbank mit 210 Patientenvignetten algorithmenunabhängig validiert werden. Diese bildeten den Goldstandard für den Vergleich der analysierten Sichtungsalgorithmen. Die Sensitivitäten für die innerklinische Detektion von Patienten der Sichtungskategorie I lagen zwischen 1,0 (BER, JorD, PRIOR) und 0,57 (MANV-Modul MTS). Die Spezifitäten lagen zwischen 0,99 (MTS und PETRA) und 0,67 (PRIOR). Gemessen am Youden-Index ergab sich bei BER (0,89) und JorD (0,88) die beste Gesamtperformance für die Detektion von Patienten der Sichtungskategorie I. Eine Übertriage ist am ehesten bei PRIOR, eine Untertriage beim MANV-Modul von MTS zu erwarten. Bis zum Entscheid SK I benötigen die Algorithmen folgende Schrittanzahlen (Median [IQR]): ESI 1 [1–2]; JorD 1 [1–4]; PRIOR 3 [2–4]; BER 3 [2–6]; mSTaRT 3 [3–5]; MTS 4 [4–5]; PETRA 6 [6–8]. Für die SK II und III besteht ein positiver Zusammenhang zwischen der Schrittanzahl bis zum Entscheid und der Testgüte. Schlussfolgerung In der vorliegenden Studie konnte eine Übertragbarkeit prähospitaler algorithmenbasierter Vorsichtungsergebnisse auf die Ergebnisse klinischer Algorithmen gezeigt werden. Die höchste diagnostische Güte für die innerklinischen Sichtung lieferten BER und JorD, die allerdings auch die meisten Algorithmusschritte bis zum Entscheid benötigen

Pyrazolo-triazolo-pyrimidines as adenosine receptor antagonists: Effect of the N-5 bond type on the affinity and selectivity at the four adenosine receptor subtypes

In the last few years, many efforts have been made to search for potent and selective human A3 adenosine antagonists. In particular, one of the most promising human A3 adenosine receptor antagonists is represented by the pyrazolo-triazolo-pyrimidine family. This class of compounds has been strongly investigated from the point of view of structure-activity relationships. In particular, it has been observed that fundamental requisites for having both potency and selectivity at the human A3 adenosine receptors are the presence of a small substituent at the N8 position and an unsubstitued phenyl carbamoyl moiety at the N5 position. In this study, we report the role of the N5-bond type on the affinity and selectivity at the four adenosine receptor subtypes. The observed structure-activity relationships of this class of antagonists are also exhaustively rationalized using the recently published ligand-based homology modeling approach

Adaptations to Submarine Hydrothermal Environments Exemplified by the Genome of Nautilia profundicola

Submarine hydrothermal vents are model systems for the Archaean Earth environment, and some sites maintain conditions that may have favored the formation and evolution of cellular life. Vents are typified by rapid fluctuations in temperature and redox potential that impose a strong selective pressure on resident microbial communities. Nautilia profundicola strain Am-H is a moderately thermophilic, deeply-branching Epsilonproteobacterium found free-living at hydrothermal vents and is a member of the microbial mass on the dorsal surface of vent polychaete, Alvinella pompejana. Analysis of the 1.7-Mbp genome of N. profundicola uncovered adaptations to the vent environment—some unique and some shared with other Epsilonproteobacterial genomes. The major findings included: (1) a diverse suite of hydrogenases coupled to a relatively simple electron transport chain, (2) numerous stress response systems, (3) a novel predicted nitrate assimilation pathway with hydroxylamine as a key intermediate, and (4) a gene (rgy) encoding the hallmark protein for hyperthermophilic growth, reverse gyrase. Additional experiments indicated that expression of rgy in strain Am-H was induced over 100-fold with a 20°C increase above the optimal growth temperature of this bacterium and that closely related rgy genes are present and expressed in bacterial communities residing in geographically distinct thermophilic environments. N. profundicola, therefore, is a model Epsilonproteobacterium that contains all the genes necessary for life in the extreme conditions widely believed to reflect those in the Archaean biosphere—anaerobic, sulfur, H2- and CO2-rich, with fluctuating redox potentials and temperatures. In addition, reverse gyrase appears to be an important and common adaptation for mesophiles and moderate thermophiles that inhabit ecological niches characterized by rapid and frequent temperature fluctuations and, as such, can no longer be considered a unique feature of hyperthermophiles

Management of patients with advanced prostate cancer—metastatic and/or castration-resistant prostate cancer: report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022

Background: Innovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence. Objective: To present the voting results of the APCCC 2022. Design, setting, and participants: The experts voted on controversial questions where high- level evidence is mostly lacking: locally advanced prostate cancer; biochemical recurrence after local treatment; metastatic hormone-sensitive, non-metastatic, and metastatic castration- resistant prostate cancer; oligometastatic prostate cancer; and managing side effects of hormonal therapy. A panel of 105 international prostate cancer experts voted on the consensus questions. Outcome measurements and statistical analysis: The panel voted on 198 pre-defined questions, which were developed by 117 voting and non-voting panel members prior to the conference following a modified Delphi process. A total of 116 questions on metastatic and/or castration- resistant prostate cancer are discussed in this manuscript. In 2022, the voting was done by a web-based survey because of COVID-19 restrictions. Results and limitations: The voting reflects the expert opinion of these panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results are reported in the supplementary material. We report here on topics in metastatic, hormone-sensitive prostate cancer (mHSPC), non-metastatic, castration-resistant prostate cancer (nmCRPC), metastatic castration-resistant prostate cancer (mCRPC), and oligometastatic and oligoprogressive prostate cancer. Conclusions: These voting results in four specific areas from a panel of experts in advanced prostate cancer can help clinicians and patients navigate controversial areas of management for which high-level evidence is scant or conflicting and can help research funders and policy makers identify information gaps and consider what areas to explore further. However, diagnostic and treatment decisions always have to be individualised based on patient characteristics, including the extent and location of disease, prior treatment(s), co-morbidities, patient preferences, and treatment recommendations and should also incorporate current and emerging clinical evidence and logistic and economic factors. Enrolment in clinical trials is strongly encouraged. Importantly, APCCC 2022 once again identified important gaps where there is non-consensus and that merit evaluation in specifically designed trials. Patient summary: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with healthcare providers worldwide. At each APCCC, an expert panel votes on pre-defined questions that target the most clinically relevant areas of advanced prostate cancer treatment for which there are gaps in knowledge. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients and their relatives as part of shared and multidisciplinary decision-making. This report focuses on the advanced setting, covering metastatic hormone-sensitive prostate cancer and both non-metastatic and metastatic castration-resistant prostate cancer. Twitter summary: Report of the results of APCCC 2022 for the following topics: mHSPC, nmCRPC, mCRPC, and oligometastatic prostate cancer. Take-home message: At APCCC 2022, clinically important questions in the management of advanced prostate cancer management were identified and discussed, and experts voted on pre-defined consensus questions. The report of the results for metastatic and/or castration- resistant prostate cancer is summarised here

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Management of patients with advanced prostate cancer. Part I: Intermediate-/high-risk and locally advanced disease, biochemical relapse, and side effects of hormonal treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022

© 2023 The Authors. Published by Elsevier on behalf of European Association of Urology. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1016/j.eururo.2022.11.002Background: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. Objective: To present consensus voting results for select questions from APCCC 2022. Design, setting, and participants: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members (“panellists”) who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1–3. Outcome measurements and statistical analysis: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. Results and limitations: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. Conclusions: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials. Patient summary: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with health care providers and patients worldwide. At each APCCC, a panel of physician experts vote in response to multiple-choice questions about their clinical opinions and approaches to managing advanced prostate cancer. This report presents voting results for the subset of questions pertaining to intermediate- and high-risk and locally advanced prostate cancer, biochemical relapse after definitive treatment, advanced (next-generation) imaging, and management of side effects caused by hormonal therapies. The results provide a practical guide to help clinicians and patients discuss treatment options as part of shared multidisciplinary decision-making. The findings may be especially useful when there is little or no high-level evidence to guide treatment decisions.We gratefully acknowledge the following organisations for providing financial support for the APCCC 2022: The City of Lugano and Movember Foundation. Ros Eeles is supported by a National Institute of Health Research grant to the Biomedical Research Centre at The Institute of Cancer Research and Royal Marsden NHS Foundation Trust. We also acknowledge sponsorship from several for-profit organisations for APCCC 2022, including Advanced Accelerator Applications, Amgen, Astellas, AstraZeneca, Bayer Health Care, Debiopharm, MSD, Janssen Oncology, Myovant Sciences, Orion Pharma, Pfizer Oncology, Roche, Telix Innovations SA, Ferring Pharmaceuticals, Lantheus, and Tolmar. These for-profit organisations supported the conference financially but had no input on the scientific content or the final publication.Accepted versio