Evaluation of Pool-based Testing Approaches to Enable Population-wide Screening for COVID-19

Background: Rapid testing for an infection is paramount during a pandemic to prevent continued viral spread and excess morbidity and mortality. This study aimed to determine whether alternative testing strategies based on sample pooling can increase the speed and throughput of screening for SARS-CoV-2. Methods: A mathematical modelling approach was chosen to simulate six different testing strategies based on key input parameters (infection rate, test characteristics, population size, testing capacity etc.). The situations in five countries (US, DE, UK, IT and SG) currently experiencing COVID-19 outbreaks were simulated to reflect a broad variety of population sizes and testing capacities. The primary study outcome measurements that were finalised prior to any data collection were time and number of tests required; number of cases identified; and number of false positives. Findings: The performance of all tested methods depends on the input parameters, i.e. the specific circumstances of a screening campaign. To screen one tenth of each country's population at an infection rate of 1% - e.g. when prioritising frontline medical staff and public workers -, realistic optimised testing strategies enable such a campaign to be completed in ca. 29 days in the US, 71 in the UK, 25 in Singapore, 17 in Italy and 10 in Germany (ca. eight times faster compared to individual testing). When infection rates are considerably lower, or when employing an optimal, yet logistically more complex pooling method, the gains are more pronounced. Pool-based approaches also reduces the number of false positive diagnoses by 50%. Interpretation: The results of this study provide a clear rationale for adoption of pool-based testing strategies to increase speed and throughput of testing for SARS-CoV-2. The current individual testing approach unnecessarily wastes valuable time and resources.Comment: Revision; 16 pages, 3 figures, 2 tables, 2 supplementary figure

Expedition Anthropocene

Viele Gigabyte gesammelter Daten, verschiedenartigste Eindrücke und Erfahrungen, festgehalten in Fotografien und Audioaufnahmen, und vor allem die Erkenntnis, was Wissenschaft heute leisten kann und leisten muss: Damit reist die Expedition Anthropozän der Jungen Akademie im März 2020 zurück nach Deutschland. Zuvor untersuchen siebzehn Tage lang die Wissenschaftler*innen Miriam Akkermann, Martin-Immanuel Bittner, Christian Hof, Robert Kretschmer, Dirk Pflüger und Ricarda Winkelmann als interdisziplinäres Forschungsteam die Auswirkungen des Anthropozäns in verschiedenen Höhenlagen Ecuadors. Im Fokus der Expedition stehen die folgenden Fragen: Wie verändert der vom Menschen verursachte Klimawandel die belebte und unbelebte Umwelt? Und wie kann der Mensch seiner Verantwortung als geologische Einflussgröße gerecht werden? Diese Fragen führen das Team von der Großstadt über Gletscher in der dünnen Luft es Hochgebirges bis in den artenreichen Nebelwald Ecuadors. Es sind intensive, zum Teil auch von Strapazen und Regenwetter geprägte Tage. Die ungewöhnliche Konstellation von Fachgebieten – von der Musikwissenschaft bis zur Informatik – und Methoden – von Eiskernbohrungen bis zu Klangaufnahmen – erfordert Kooperation, Flexibilität und Anpassung an das übergeordnete Ziel. Nur so wird die Expedition der Komplexität des Themas gerecht – und es ist anzunehmen, dass sich auch die Herausforderungen des globalen Klimawandels nur durch Interdisziplinarität bewältigen lassen werden. Das Anthropozän betrifft alle Menschen, weltweit. Mit dem vorliegenden Dokumentationsband machen die Wissenschaftler*innen ihre Forschung in Ecuador und die daraus gewonnenen Erkenntnisse einem breiten Publikum zugänglich. Die Gliederung des Bandes folgt chronologisch den auf der Expedition beforschten Klimazonen und Siedlungsräumen. Texte, Bilder und weitere Medien laden dazu ein, mitzureisen: Wissenschaftliche Praxis mitzuerleben, beeindruckende Landschaften, Tiere und Pflanzen zu entdecken – und dem Anthropozän dort zu begegnen, wo seine Auswirkungen bereits deutlich spürbar sind.With many gigabytes of collected data, a wide variety of impressions and experiences captured in photographs and audio recordings, and above all the realisation of what science can and must achieve today the Expedition Anthropocene of Die Junge Akademie traveled back to Germany in March 2020. The scientists Miriam Akkermann, Martin-Immanuel Bittner, Christian Hof, Robert Kretschmer, Dirk Pflüger and Ricarda Winkelmann had spent seventeen days as an interdisciplinary research team investigating the effects of the Anthropocene age at various altitudes in Ecuador. The expedition focused on the following questions: How is human-induced climate change altering the living and non-living worlds? And how can humans fulfil their responsibility as a significant influencing factor capable of demarcating an entire geological age? These questions took the team all the way from cities to glaciers in the thin air of the high mountains and to the species-rich cloud forests of Ecuador. It was an intensive trip, and some days were marked by exertion and rainy weather. The unusual constellation of disciplines – from musicology to computer science – and methods – from ice core drilling to sound recording – require cooperation, flexibility and adaptation to the overall goal. Only in this way could the expedition do justice to the complexity of the topic – and it is fair to assume that the challenges of global climate change can likewise only be overcome by means of an interdisciplinary approach. The Anthropocene affects all people, worldwide. In this documentary volume, the scientists make their research in Ecuador and the insights gained from it accessible to a broad audience. The structure of the volume chronologically follows the climatic zones and settlement areas explored on the expedition. Texts, pictures and other media invite you to be part of the journey: to experience scientific practice, to discover impressive landscapes, animals and plants – and to encounter the Anthropocene where its effects are already clearly noticeable

Characterisation of the histone acetyltransferase KAT7 as a novel target for radiosensitisation

Radiotherapy is one of the pillars of modern cancer therapy. However, side effects associated with normal tissue toxicity limit the effectiveness of this treatment. It is therefore desirable to develop tumour-specific radiosensitising agents, which can increase tumour cell kill without increasing the radiosensitivity of the surrounding normal tissue. This project aimed at validating the radiosensitising potential of depletion of the histone acetyltransferase KAT7, and elucidating the underlying mechanism of action. My results showed a radiosensitising effect of KAT7 depletion in seven tumour cell lines. At the same time, a panel of normal tissue cell lines was not radiosensitised. The depletion of KAT7 caused general cell cycle changes, most notably a twofold increase in the proportion of mitotic cells. At the same time, the G2M checkpoint governing entry into mitosis appeared to be impaired. Livecell imaging confirmed a more than threefold increase in mitotic catastrophe following irradiation in KAT7-depleted cells. An oligonucleotide microarray also showed the downregulation of key members of the mitotic pathway, and patient data demonstrated higher expression of KAT7 to be associated with worse prognosis. In summary, this project supports the tumour-specific radiosensitising potential of KAT7 depletion. This novel target for radiosensitisation seems to exert its effects through altering entry into and progression through mitosis.</p

AI3SD Video: Data Generation, Data Standards and Metadata Capture in Drug Discovery

Biomedical research and drug discovery are based on a continuous cycle of scientific findings being made, refined, and translated into new treatments. However, over recent years it has become clear that only a fraction of all published research findings are actually reproducible, causing waste and delays in our efforts to bring new drugs to patients. The answer is changing the way we generate and capture data, including experimental metadata. Especially in light of the increasing role of Artificial Intelligence in drug discovery, it is critical to rethink the way we approach data generation as the most important input for AI-driven drug discovery. The talk will address these recent advances in data and metadata capture based on fully automated experimentation and novel data standards

AI3SD Video: New Trends in Drug Discovery – Robotics &amp; AI

The drug discovery ecosystem is undergoing transformational change. New technologies have an increasing impact on how drugs are being discovered and developed, including in particular Artificial Intelligence and robotics. A critical precondition for successful development of AI applications is having access to large amounts of structured, annotated, machine-learnable data. The talk will cover how recent advances in laboratory automation and robotics enable the generation of biomedical data at scale, providing the most critical input for AI systems. The talk will present real-world case studies, showing how leading AI drug discovery firms benefit from full automation of their discovery processes, delegating experiment execution to advanced robotics, and allowing for projects to move to the next stage faster and more efficiently

Humans of AI3SD: Dr Martin Immanuel-Bittner

Martin-Immanuel Bittner MD DPhil FRSA is the chief executive officer of Arctoris, the world’s first fully automated drug discovery platform that he co-founded in Oxford in 2016. He graduated as a medical doctor from the University of Freiburg in Germany, followed by his DPhil in Oncology as a Rhodes scholar at the University of Oxford. Martin has extensive research experience covering both clinical trials and preclinical drug discovery and is an active member of several leading cancer research organisations. In this Humans of AI3SD interview he discusses how automation can provide fully reproducible, robust and reliable research data, the rise of FAIR data and why experienced postdocs should not be spending eight hours a day pipetting small amounts of liquids

Latest advances in aging research and drug discovery

An increasing aging population poses a significant challenge to societies worldwide. A better understanding of the molecular, cellular, organ, tissue, physiological, psychological, and even sociological changes that occur with aging is needed in order to treat age-associated diseases. The field of aging research is rapidly expanding with multiple advances transpiring in many previously disconnected areas. Several major pharmaceutical, biotechnology, and consumer companies made aging research a priority and are building internal expertise, integrating aging research into traditional business models and exploring new go-to-market strategies. Many of these efforts are spearheaded by the latest advances in artificial intelligence, namely deep learning, including generative and reinforcement learning. To facilitate these trends, the Center for Healthy Aging at the University of Copenhagen and Insilico Medicine are building a community of Key Opinion Leaders (KOLs) in these areas and launched the annual conference series titled “Aging Research and Drug Discovery (ARDD)” held in the capital of the pharmaceutical industry, Basel, Switzerland (www.agingpharma.org). This ARDD collection contains summaries from the 6th annual meeting that explored aging mechanisms and new interventions in age-associated diseases. The 7th annual ARDD exhibition will transpire 2nd-4th of September, 2020, in Basel

Analysis of relation between hypoxia PET imaging and tissue-based biomarkers during head and neck radiochemotherapy.

BACKGROUND Tumor hypoxia is associated with poor prognosis and outcome and can be visualized using 18F-MISO-positron emission tomography (PET) imaging. The goal of this study was to evaluate the correlation between biological markers and biological imaging in a group of patients in whom a correlation between biological imaging and outcome has previously been demonstrated. MATERIAL AND METHODS In a prospective pilot project, 16 patients with locally advanced cancer of the head and neck underwent 18F-MISO-PET scans before and during primary radiochemotherapy in addition to 18F-FDG-PET and computed tomography (CT). Tumor biopsies were stained for three tissue-based markers (Ku80, CAIX, CD44); in addition, human papillomavirus (HPV) status was assessed. H-scores of marker expression were generated and the results were correlated with the biological imaging and clinical outcome. RESULTS No statistically significant correlation was established between the H-scores for Ku80, CD44 and CAIX or between any of the H-scores and the imaging variables (tumor volume on 18F-FDG-PET in ml, hypoxic subvolume as assessed by 18F-MISO-PET in ml, and SUVmax tumor/SUVmean muscle during the 18F-MISO-PET). A statistically significant negative correlation was found between CD44 H-score and HPV status (p = .004). Cox regression analysis for overall survival and recurrence-free survival showed one significant result for CAIX being associated with improved overall survival [hazard ratio 0.96 (0.93-1.00), p = .047]. CONCLUSION Expression of Ku80, CAIX and CD44 as assessed by immunohistochemistry of tumor biopsies were not correlated to one another or the biological imaging data. However, there was a significant influence of CAIX on overall survival and between CD44 and HPV

Serial [18F]-fluoromisonidazole PET during radiochemotherapy for locally advanced head and neck cancer and its correlation with outcome.

PURPOSE The aim was to assess changes of tumour hypoxia during primary radiochemotherapy (RCT) for head and neck cancer (HNC) and to evaluate their relationship with treatment outcome. MATERIAL AND METHODS Hypoxia was assessed by FMISO-PET in weeks 0, 2 and 5 of RCT. The tumour volume (TV) was determined using FDG-PET/MRI/CT co-registered images. The level of hypoxia was quantified on FMISO-PET as TBRmax (SUVmaxTV/SUVmean background). The hypoxic subvolume (HSV) was defined as TV that showed FMISO uptake ⩾1.4 times blood pool activity. RESULTS Sixteen consecutive patients (T3-4, N+, M0) were included (mean follow-up 31, median 44months). Mean TBRmax decreased significantly (p<0.05) from 1.94 to 1.57 (week 2) and 1.27 (week 5). Mean HSV in week 2 and week 5 (HSV2=5.8ml, HSV3=0.3ml) were significantly (p<0.05) smaller than at baseline (HSV1=15.8ml). Kaplan-Meier plots of local recurrence free survival stratified at the median TBRmax showed superior local control for less hypoxic tumours, the difference being significant at baseline and after 2weeks (p=0.031, p=0.016). CONCLUSIONS FMISO-PET documented that in most HNC reoxygenation starts early during RCT and is correlated with better outcome