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Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI nonresponders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one patient. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma.Significance:Despite treatment advances, melanoma remains a deadly disease at stage IV. Through research autopsy and dense sampling of metastases combined with extensive multiomic profiling, our study elucidates the many mechanisms that melanomas use to evade treatment and the immune system, whether through mutations, widespread copy-number alterations, or extrachromosomal DNA.

Supplementary figure 1: Cohort overview. Number of samples sequenced with whole exome, panel or whole RNA sequencing. Supplementary figure 2: Phylogeny and WGD events in CRUKP1047. Supplementary figure 3: Ploidy and SCNA burden. Supplementary figure 4: Overview of each case. Supplementary figure 5: MEDICC2 copy number sample trees. Supplementary figure 6: MEDICC tree of all exome samples demonstrating that samples cluster together by patient, and not by melanoma subtype. Supplementary figure 7: SCNA frequency of cutaneous (a), acral (b) and melanoma of unknown primary (MUP, c). Supplementary figure 8: Correlation between liver copy number distance to other sites and time of emergence after stage IV diagnosis. Supplementary figure 9: Examination of tumour heterogeneity of alterations to antigen-presentation machinery genes, with site and patient annotation. Supplementary figure 10: Boxplots indicating the proportion of losses in the cohort for each segment. Supplementary figure 11: Balance of expression between nonsynonymous mutations that were not predicted to be neoantigens and clonal predicted neoantigens. Supplementary figure 12: Barplot of TIL infiltration score frequencies, determined by pathologist assessment of histology, across all samples. Supplementary figure 13: Number of samples per patient that are classified as either none-low in terms of TILs or moderate-heavy. Supplementary figure 14: Histogram of purity for samples with RNA-seq data. Supplementary figure 15: TME deconvolution. Supplementary figure 16: The effect of metastatic site on transcriptional profiles. Supplementary figure 17: Association of PHF3 copy number with expression. Supplementary figure 18: Overview of gene fusions identified in RNA-seq data. Supplementary figure 19: Comparison of ploidy estimates from panel sequencing data, exome data and FISH. Supplementary figure 20: Comparison of ploidy estimates in panel, exome, FISH and single cell data. Supplementary figure 21: FACs sort plot for CRUKP2567 diaphragmatic metastasis. Supplementary figure 22: Ploidy and wGII values from single cell sequencing of FACS-sorted tumour cells. Supplementary figure 23: Copy number profiles on chromosome 5 for bulk samples from primary and DI_2_R2, a diaphragmatic metastasis. Supplementary figure 24: Histogram of purity of samples for which RNA-seq was performed faceted by patient. Supplementary figure 25: Histogram of purity of samples for which RNA-seq was performed faceted by tissue site.

S. Table 1: List of PEACE Consortium members. S. Table 2: Sample database used for the study for Panel, Exome and RNASeq samples. S. Table 3: Overview of lines of treatment given to each patient. S. Table 4: Lesions and patients included in the lesion-level response to ICI analysis. S. Table 5: Hallmark genesets significantly upregulated in normal tissue vs tumor tissue. Table shows p-values for tissue type, purity; T value for tissue type, purity; q-value for tissue type, purity (FDR corrected). S. Table 6: Hallmark genesets significantly upregulated in tumor tissue vs normal tissue. Table shows p-values for tissue type, purity; T value for tissue type, purity; q-value for tissue type, purity (FDR corrected). S. Table 7: Genes included in the target panel. S. Table 8: Tree topology comparisons between manually constructed trees and pairtree-constructed trees.

Each year, the National Training Center (NTC) located at Fort Irwin, California, hosts multiple Brigade-level rotational units to conduct training exercises. NTC’s Instrumentation Systems (NTC-IS) digitally capture and store characteristics of movement and maneuver, use of fires, and other tactical operations in a vast database. The Army’s Engineer Research and Development Center (ERDC) recently partnered with Training and Doctrine Command (TRADOC) to make some of the data available for introductory analysis within a relational database. While this data has the potential to expose capability gaps, uncover the truth behind doctrinal assumptions, and create a sophisticated feedback platform for Army leaders at all levels, it is largely unexplored and underutilized. The purpose of this project is to demonstrate the value of this data by developing a prototype information system that supports post-rotation analytics, playback capabilities, and repeatable workflows that measure and expose ground-truth operational and logistical behavior and performance during a rotation. The Army modeling and analysis community will use these products to systematically curate and archive the database and enable future analysis of the NTC-IS data.

Edoxaban, alongside other direct oral anticoagulants (DOAC), is increasingly used for prevention of thromboembolism, including stroke. Despite DOAC therapy, however, annual stroke rate in patients with atrial fibrillation remains 1–2%. Rapid exclusion of relevant anticoagulation is necessary to guide thrombolysis or reversal therapy but, so far, no data exists on the effect of edoxaban on available point-of-care test systems (POCT). To complete our previous investigation on global coagulation-POCT for the detection of DOAC, we evaluated whether CoaguChek®-INR (CC-INR) is capable of safely ruling out edoxaban concentrations above the current treatment thresholds of 30/50 ng/mL in a blood sample. We studied patients receiving a first dose of edoxaban; excluding subjects receiving other anticoagulants. Six blood samples were collected from each patient: before drug intake, 0.5, 1, 2 and 8 h after intake, and at trough (24 h). CC-INR and mass spectrometry for edoxaban concentrations were performed for each time-point. One hundred and twenty blood samples from 20 patients contained 0–302 ng/mL of edoxaban. CC-INR ranged from 0.9 to 2.3. Pearson’s correlation coefficient showed strong correlation between CC-INR and edoxaban concentrations (r = 0.73, p 30 and > 50 ng/mL were ruled out by CC-INR ≤ 1.0 and ≤ 1.1, respectively, with high specificity (> 95%), and a sensitivity of 44% (95%-confidence interval: 30–59%) and 86% (74–93%), respectively. Our study represents the first evaluation of coagulation-POCT in edoxaban-treated patients. CC-POCT is suitable to safely exclude clinically relevant edoxaban concentrations prior to thrombolysis, or guide reversal therapy in stroke patients.

Objective To identify relationships between body shape, body composition, sex and performance on the new US Army Combat Fitness Test (ACFT). Methods Two hundred and thirty-nine United States Military Academy cadets took the ACFT between February and April of 2021. The cadets were imaged with a Styku 3D scanner that measured circumferences at 20 locations on the body. A correlation analysis was conducted between body site measurements and ACFT event performance and evaluated using Pearson correlation coefficients and p-values. A k-means cluster analysis was performed over the circumference data and ACFT performance were evaluated between clusters using t-tests with a Holm-Bonferroni correction. Results The cluster analysis resulted in 5 groups: 1. “V” shaped males, 2. larger males, 3. inverted “V” shaped males and females, 4. “V” shaped smaller males and females, and 5. smallest males and females. ACFT performance was the highest in Clusters 1 and 2 on all events except the 2-mile run. Clusters 3 and 4 had no statistically significant differences in performance but both clusters performed better than Cluster 5. Conclusions The association between ACFT performance and body shape is more detailed and informative than considering performance solely by sex (males and females). These associations may provide novel ways to design training programs from baseline shape measurements.

Background: The vast majority of cancer deaths can be attributed to tumor metastases. Disseminated tumor cells (DTCs) are thought to act as a reservoir of tumor clones which can lie dormant before causing overt metastases. Their presence has been shown to be a poor prognostic indicator in several tumor types. Despite their importance, the timing and source of DTCs is unclear across most solid cancers and even less is known about them in late-stage disease. The Posthumous Evaluation of the Advanced Cancer Environment (PEACE) post-mortem study enables extensive sampling of malignant lesions but also normal tissues, thereby allowing study of DTCs in patients with advanced cancer. Methods: We performed research autopsy sampling of macroscopically normal bone, lung and liver in 3 patients with advanced clear cell renal cell carcinoma (RCC). In addition, we performed bone marrow aspiration at autopsy from vertebral bodies and the ilium using an anterior approach. Mechanical disaggregation followed by collagenase digestion was used to generate single cell suspensions. Detection of tumor cells was carried out using antibodies against known tumor or epithelial markers carbonic anhydrase IX (CAIX). Epithelial cell adhesion molecule (EpCAM) was also used for bone marrow samples as native bone marrow cells do not express this marker. These sub-populations were then isolated using fluorescence activated cell sorting and DNA was extracted and amplified from single cells. Results: We performed and optimised collagenase-based digestion on all solid tissues collected. The percentage of viable cells generated varied significantly between subjects and tissues with bone marrow samples more viable than lung and liver. Rare and distinct populations of CAIX+ and EpCAM+ cells were detected in normal tissues between 0.5-2%. DNA amplification was successful on single cells isolated from normal lung and liver but not from bone tissue. Pilot shallow coverage whole genome sequencing revealed genomically aberrant cells ranging from single chromosome arm losses to widespread copy number aberrations. Conclusion: We demonstrate feasibility of sequencing single cells from autopsy study subjects. Rare populations of single cells with markers of clear cell RCC were detected and isolated both in normal tissues of patients with advanced disease. Genomic analyses of these cells will lead to insights into their relationship to the primary tumor and overt metastatic lesions. Citation Format: Haixi Yan, Cristina Cotobal Martin, Christie English, Annelien Verfaillie, Jonas Demeulemeester, Andrew Rowan, Annika Fendler, Anne-Laure Cattin, Sucheta Mahapatra, Lewis Au, Scott Shepherd, Ben Shum, Charlotte Spencer, Zayd Tippu, Ula Mahadeva, Anna Green, Eleanor Carlyle, Cristina Naceur-Lombardelli, PEACE consortium, Mariam Jamal-Hanjani, Charles Swanton, Samra Turajlic, Peter Van Loo. Detection of disseminated tumor cells in advanced clear cell renal cell carcinoma through research autopsy [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr A011.

Internet-Plattformen wie Facebook, Twitter und YouTube stehen vor der Herausforderung adäquat mit illegalen und unerwünschten Inhalten umzugehen, die über ihre Dienste verbreitet werden. Sie etablieren Gemeinschaftsstandards und komplexe Systeme zur manuellen und technischen Inhaltsregulierung, um problematische Inhalte zu identifizieren, zu filtern, zu löschen und zu kuratieren. Die Plattformen agieren global, aber Inhaltsmoderation wird regional wirksam und hat Auswirkungen auf nationale Öffentlichkeit. Deshalb wird immer öfter eine breite Debatte zum Thema Inhaltsregulierung auf Internet-Plattformen mit Blick auf Öffentlichkeit, Demokratieund regionale Kontextsensibilität eingefordert. Der vorliegende Beitrag zeigt einige der Defizite des aktuellen Regulierungssystems und entwickelt Optionen wie Inhaltsregulierung auf globalen Internet-Plattformen auf nationaler Ebene angebunden werden kann. Zu solchen Optionen zählen z.B. nationale Plattformsprecher/innen, die kommunikative Verantwortung gegenüber nationalen Öffentlichkeiten wahrnehmen; die Förderung und der Ausbau nationaler Meldestellen; der Einsatz von Inhaltsmoderator/innen mit nationalem Kontextwissen; sowie die Einrichtung einer staatsfernen nationalen Ombudsstelle für Inhaltsmoderation, die als Schlichtungsstelle und als Berufungsorgan gegenüber Moderationsentscheidungen der Internet-Plattformen fungiert und Beobachtungs- und Evaluierungsfunktionen übernehmen könnte.

Social media platforms like Facebook, YouTube, and Twitter have become major objects of criticism for reasons such as privacy violations, anticompetitive practices, and interference in public elections. Some of these problems have been associated with algorithms, but the roles that algorithms play in the emergence of different harms have not yet been systematically explored. This article contributes to closing this research gap with an investigation of the link between algorithms and harms on social media platforms. Evidence of harms involving social media algorithms was collected from media reports and academic papers within a two-year timeframe from 2018 to 2019, covering Facebook, YouTube, Instagram, and Twitter. Harms with similar casual mechanisms were grouped together to inductively develop a typology of algorithmic harm based on the mechanisms involved in their emergence: (1) algorithmic errors, undesirable, or disturbing selections; (2) manipulation by users to achieve algorithmic outputs to harass other users or disrupt public discourse; (3) algorithmic reinforcement of pre-existing harms and inequalities in society; (4) enablement of harmful practices that are opaque and discriminatory; and (5) strengthening of platform power over users, markets, and society. Although the analysis emphasizes the role of algorithms as a cause of online harms, it also demonstrates that harms do not arise from the application of algorithms alone. Instead, harms can be best conceived of as socio-technical assemblages, composed of the use and design of algorithms, platform design, commercial interests, social practices, and context. The article concludes with reflections on possible governance interventions in response to identified socio-technical mechanisms of harm. Notably, while algorithmic errors may be fixed by platforms themselves, growing platform power calls for external oversight.

ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal cell carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between tumor molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates with clinical response. T cell receptor (TCR) analysis reveals a significantly higher number of expanded TCR clones pre-treatment in responders suggesting pre-existing immunity. Maintenance of highly similar clusters of TCRs post-treatment predict response, suggesting ongoing antigen engagement and survival of families of T cells likely recognizing the same antigens. In responders, nivolumab-bound CD8+ T cells are expanded and express GZMK/B. Our data suggest nivolumab drives both maintenance and replacement of previously expanded T cell clones, but only maintenance correlates with response. We hypothesize that maintenance and boosting of a pre-existing response is a key element of anti-PD-1 mode of action.

This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Proffered Abstracts section (PR002) of the Conference Proceedings. Citation Format: Alexander Coulton, Irene Lobon, Lavinia Spain, Andrew Rowan, Desiree Shnidrig, Scott Shepherd, Ben Shum, Fiona Byrne, Lewis Au, Kim Edmonds, Ellie Carlyle, Alexandra Renn, Christina Messiou, Charlotte Spencer, Andreas M. Schmidt, Zayd Tippu, Aljosja Rogiers, Max Emmerich, Camille Gerard, Husayn Pallikonda, Cristina Naceur-Lombardelli, Floris Foijer, Hilda van den Bos, René Wardenaar, Diana Spierings, Kate Young, Lisa Pickering, Andrew Furness, Elaine Borg, Miriam Mitchison, David Moore, Mary Falzon, Ian Proctor, Ruby Stewart, Ula Mahadeva, Anna Green, James Larkin, Charles Swanton, Mariam Jamal-Hanjani, Kevin Litchfield, Samra Turajlic. Advanced melanoma exhibits a diversity of evolutionary routes to lethality [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A012.

Background and Purpose— In patients receiving direct oral anticoagulants (DOACs), emergency treatment like thrombolysis for acute ischemic stroke is complicated by insufficient availability of DOAC-specific coagulation tests. Conflicting recommendations have been published concerning the use of global coagulation assays for ruling out relevant DOAC-induced anticoagulation. Methods— Four hundred eighty-one samples from 96 DOAC-treated patients were tested using prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT), DOAC-specific assays (anti-Xa activity, diluted TT), and liquid chromatography–tandem mass spectrometry. Sensitivity and specificity of test results to identify DOAC concentrations Results— Normal PT and aPTT provide insufficient specificity to safely identify DOAC concentrations 95% specificity and a specific TT cutoff enhanced sensitivity for dabigatran to 84%. For apixaban, no cutoffs could be established. Conclusions— Even if highly DOAC-reactive reagents are used, normal results of global coagulation tests are not suited to guide emergency treatment: whereas normal PT and aPTT lack specificity to rule out DOAC-induced anticoagulation, the low sensitivity of normal TT excludes the majority of eligible patients from treatment. However, reagent-specific cutoffs for global coagulation tests ensure high specificity and optimize sensitivity for safe emergency decision making in rivaroxaban- and dabigatran-treated patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifiers: NCT02371044 and NCT02371070.

Online disinformation poses a challenge to democratic societies and has become a prominent issue on the research and political agenda. While many analyses focus on patterns of distribution and reac...

Aim Service evaluation of our dental hospital paediatric liaison nursing (DH-PLN) service which provides an additional route for information sharing about safeguarding concerns via an agreed pathway for two-way communication with public health nurses.Method Retrospective analysis of clinical records of all children referred by DH teams to PLN in the three months October-December 2016.Results One hundred and four children were referred; mean age was 6.2 years, 89.4% from Index of Multiple Deprivation (IMD) quintiles 4 and 5, and 70.2% were attending for dental general anaesthesia. The most common referral reason was dental neglect in 66.3%, followed by missed appointments in 50.0%. The PLN checked child health databases and shared information with health visitors and school nurses (46.2% and 53.8% respectively). Feedback retrieved included known child maltreatment risk factors in 7.7%. This prompted additional child protection referrals to children's social services for seven children (6.7%). Dental outcomes six months later were: treatment complete in 50.0%, treatment ongoing 28.8%, discharged to original referrer with treatment incomplete in 21.1%.Conclusion This DH-PLN service promotes integrated multidisciplinary working, helping overcome barriers to dentistry's involvement in safeguarding. It facilitates more accurate assessments of risk of harm to children receiving dental care and prompts additional child protection referrals to social services.

Background Direct oral anticoagulants (DOACs) are increasingly replacing vitamin K antagonists (VKA) for clinical indications requiring long-term oral anticoagulation. In contrast to VKA, treatment with DOAC including dabigatran—the only direct thrombin inhibitor amongst them—does not require therapeutic drug monitoring. However, in case of treatment complications (e.g., major haemorrhage) and conditions requiring urgent surgery or thrombolytic therapy, information about actual DOAC plasma levels is needed to guide treatment decisions. Due to short reagent stability, limited accuracy at low dabigatran levels and high heparin sensitivity, the applicability of the widely used Hemoclot thrombin inhibitor (HTI) coagulation assay is limited in the emergency setting. Methods Dabigatran concentrations of 288 citrated plasma samples taken from 48 dabigatran-treated patients with drug concentrations of up to 300 ng/mL were measured with the chromogenic anti-IIa Biophen direct thrombin inhibitor (BDTI) assay and results compared with HTI using ultra performance liquid chromatography—tandem mass spectrometry as the reference method for measuring dabigatran plasma concentrations. Results BDTI results showed a very strong correlation with dabigatran concentrations (r = 0.965, p Conclusion The BDTI is an ideal coagulation assay for the around-the-clock determination of dabigatran plasma levels in clinical routine including emergency situations.

Background and Purpose— Specific coagulation assays for non–vitamin K antagonist oral anticoagulants (NOAC) are relatively slow and often lack availability. Although specific point-of-care tests (POCT) are currently not available, NOAC are known to affect established coagulation POCT. This study aimed at determining the diagnostic accuracy of the CoaguChek POCT to rule out relevant concentrations of rivaroxaban, apixaban, and dabigatran in real-life patients. Methods— We consecutively enrolled 60 ischemic stroke patients newly started on NOAC treatment and obtained blood samples at 6 prespecified time points. Samples were tested using the CoaguChek POCT, laboratory-based coagulation assays (prothrombin time and activated partial thromboplastin time, anti-Xa test and Hemoclot), and liquid chromatography–tandem mass spectrometry for direct determination of NOAC concentrations. Results— Three hundred fifty-six blood samples were collected. The CoaguChek POCT strongly correlated ( r =0.82 P Conclusions— If anti-Xa test is not available, we propose the use of the CoaguChek POCT to guide thrombolysis decisions after individual risk assessment in rivaroxaban-treated patients having acute ischemic stroke. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02371044.

Introduction: Non-vitamin K antagonist oral anticoagulants (NOAC) are increasingly replacing vitamin K antagonists for prevention of thromboembolism in atrial fibrillation (AF). Despite treatment, stroke rate in NOAC-treated AF-patients remains 1-2% per year. Subsequently, stroke physicians face a growing number of NOAC-treated patients with acute stroke. Rapid assessment of coagulation in NOAC-treated patients is vital prior to thrombolysis or reversal therapy, but existing point-of-care testing (POCT) is suboptimal. For the first time we evaluate NOAC-specific POCT. Hypothesis: Ecarin clotting time (ECT)- and anti-Xa activity (ENOX)-POCT predict plasma concentrations of dabigatran and apixaban/edoxaban/rivaroxaban. Methods: 80 patients receiving first NOAC-dose and 80 already on NOAC-treatment are enrolled in the SPOCT-NOAC I trial (N=40 for each NOAC). Subjects receiving other anticoagulants are excluded. Six blood samples are collected from each patient: before drug intake, 30min, 1, 2, and 8h after intake, and before next dose. NOAC-concentrations are measured by mass spectrometry. Results: 240 blood samples of 40 dabigatran-treated patients were analyzed. Dabigatran-concentrations ranged from 0-274ng/mL. ECT-POCT ranged from 20-196s. Pearson’s correlation coefficient showed strong correlation between ECT-POCT and dabigatran-concentrations (r=0.87). Performance was improved through the use of citrated in place of non-citrated whole blood (r=0.93). Dabigatran-concentrations >50ng/mL (threshold for thrombolysis according to expert recommendation) were detected by ECT-POCT >50s with 98% sensitivity and 79% specificity. Baseline-samples not containing any dabigatran yielded normal ECT values. Conclusions: This is the first study evaluating NOAC-specific POCT. Final results in the dabigatran group of SPOCT-NOAC show excellent correlation between ECT-POCT and dabigatran plasma concentrations; performance of ECT-POCT is even increased through the use of citrated whole blood. Relevant dabigatran-concentrations are detected with excellent sensitivity and specificity. In addition to ECT-POCT, we will present data on ENOX-POCT from apixaban-, edoxaban- and rivaroxaban-treated patients.

This article summarises work done under Valuing People Now to improve employment prospects and outcomes for people with learning disabilities in England. It summarises the barriers to improvements and explains how understanding these barriers has helped to unlock solutions and new approaches.

Introduction: Non-vitamin K antagonist oral anticoagulants (NOAC) are increasingly replacing vitamin K antagonists for prevention of thromboembolism in atrial fibrillation (AF) and venous thrombosis. Ischemic stroke rate in NOAC-treated AF-patients is 1-2% per year. Subsequently, stroke physicians face a growing number of NOAC-treated patients with acute stroke. Rapid assessment of coagulation in NOAC-treated patients is vital prior to thrombolysis, but existing point-of-care testing (POCT) is suboptimal. For the first time we evaluate NOAC-specific POCT. Hypothesis: Ecarin clotting time (ECT)- and anti-Xa activity-POCT accurately predict plasma concentrations of dabigatran and apixaban/edoxaban/rivaroxaban. Methods: 80 patients receiving first NOAC-dose and 80 already on NOAC-treatment will be enrolled (N=40 for each NOAC). Subjects receiving other anticoagulants will be excluded. 6 blood samples will be collected from each patient: before drug intake, 30min, 1, 2, and 8h after intake, and before next dose. NOAC-concentrations will be measured by mass spectrometry. Results (preliminary): Until now 138 blood samples of 23 dabigatran-treated patients were analyzed. Dabigatran-concentrations ranged from 0-371ng/mL. ECT-POCT ranged from 20-219s. Pearson’s correlation coefficient showed strong correlation for ECT-POCT and dabigatran-concentrations (r=0.94, p50ng/mL (threshold for thrombolysis according to expert recommendation) were detected by ECT-POCT (>50s) with 100% sensitivity and 82% specificity. Baseline-samples not containing any dabigatran yielded normal ECT-POCT. Conclusions: This is the first study evaluating NOAC-specific POCT. Preliminary results show excellent correlation for ECT-POCT and dabigatran; relevant dabigatran-concentrations were detected in 100%. More pioneering results on NOAC-specific POCT will be presented.

Gene expression is an extremely complicated process in which several mechanisms are involved. Owing to its developmental and tissue-specific expression, the β-globin gene is an excellent model for studying gene expression. β-Globin gene expression involves an interplay between several different mechanisms. Chromatin structure is thought to be altered by the locus control region (LCR) located far upstream of the β-globin gene locus. As well, multiple transcription factors come into play both in the LCR and in the individual promoters and enhancers of the β-globin genes. The interaction between these then allows for delicate regulation of β-globin gene expression. In the following review the elaborate system of β-globin gene expression will briefly be examined.Key words: β-globin, gene expression, chromatin, GATA-I, NF-E2, developmental regulation.