Low case numbers enable long-term stable pandemic control without lockdowns

The traditional long-term solutions for epidemic control involve eradication or population immunity. Here, we analytically derive the existence of a third viable solution: a stable equilibrium at low case numbers, where test-trace-and-isolate policies partially compensate for local spreading events, and only moderate restrictions remain necessary. In this equilibrium, daily cases stabilize around ten new infections per million people or less. However, stability is endangered if restrictions are relaxed or case numbers grow too high. The latter destabilization marks a tipping point beyond which the spread self-accelerates. We show that a lockdown can reestablish control and that recurring lockdowns are not necessary given sustained, moderate contact reduction. We illustrate how this strategy profits from vaccination and helps mitigate variants of concern. This strategy reduces cumulative cases (and fatalities) 4x more than strategies that only avoid hospital collapse. In the long term, immunization, large-scale testing, and international coordination will further facilitate control.Comment: Final versio

Relaxing restrictions at the pace of vaccination increases freedom and guards against further COVID-19 waves

Mass vaccination offers a promising exit strategy for the COVID-19 pandemic. However, as vaccination progresses, demands to lift restrictions increase, despite most of the population remaining susceptible. Using our age-stratified SEIRD-ICU compartmental model and curated epidemiological and vaccination data, we quantified the rate (relative to vaccination progress) at which countries can lift non-pharmaceutical interventions without overwhelming their healthcare systems. We analyzed scenarios ranging from immediately lifting restrictions (accepting high mortality and morbidity) to reducing case numbers to a level where test-trace-and-isolate (TTI) programs efficiently compensate for local spreading events. In general, the age-dependent vaccination roll-out implies a transient decrease of more than ten years in the average age of ICU patients and deceased. The pace of vaccination determines the speed of lifting restrictions; Taking the European Union (EU) as an example case, all considered scenarios allow for steadily increasing contacts starting in May 2021 and relaxing most restrictions by autumn 2021. Throughout summer 2021, only mild contact restrictions will remain necessary. However, only high vaccine uptake can prevent further severe waves. Across EU countries, seroprevalence impacts the long-term success of vaccination campaigns more strongly than age demographics. In addition, we highlight the need for preventive measures to reduce contagion in school settings throughout the year 2021, where children might be drivers of contagion because of them remaining susceptible..

The challenges of containing SARS-CoV-2 via test-trace-and-isolate

Without a cure, vaccine, or proven long-term immunity against SARS-CoV-2, test-trace-and-isolate (TTI) strategies present a promising tool to contain its spread. For any TTI strategy, however, mitigation is challenged by pre- and asymptomatic transmission, TTI-avoiders, and undetected spreaders, who strongly contribute to hidden infection chains. Here, we studied a semi-analytical model and identified two tipping points between controlled and uncontrolled spread: (1) the behavior-driven reproduction number of the hidden chains becomes too large to be compensated by the TTI capabilities, and (2) the number of new infections exceeds the tracing capacity. Both trigger a self-accelerating spread. We investigated how these tipping points depend on challenges like limited cooperation, missing contacts, and imperfect isolation. Our model results suggest that TTI alone is insufficient to contain an otherwise unhindered spread of SARS-CoV-2, implying that complementary measures like social distancing and improved hygiene remain necessary

Interplay Between Risk Perception, Behavior, and COVID-19 Spread

Pharmaceutical and non-pharmaceutical interventions (NPIs) have been crucial for controlling COVID-19. They are complemented by voluntary health-protective behavior, building a complex interplay between risk perception, behavior, and disease spread. We studied how voluntary health-protective behavior and vaccination willingness impact the long-term dynamics. We analyzed how different levels of mandatory NPIs determine how individuals use their leeway for voluntary actions. If mandatory NPIs are too weak, COVID-19 incidence will surge, implying high morbidity and mortality before individuals react; if they are too strong, one expects a rebound wave once restrictions are lifted, challenging the transition to endemicity. Conversely, moderate mandatory NPIs give individuals time and room to adapt their level of caution, mitigating disease spread effectively. When complemented with high vaccination rates, this also offers a robust way to limit the impacts of the Omicron variant of concern. Altogether, our work highlights the importance of appropriate mandatory NPIs to maximise the impact of individual voluntary actions in pandemic control.BMBF, 01KX2021, Nationales Forschungsnetzwerk der Universitätsmedizin zu Covid-19EC/H2020/101003480/EU/COVID-19-Outbreak Response combining E-health, Serolomics, Modelling, Artificial Intelligence and Implementation Research/CORESM

German evidence-based guidelines for the treatment of Psoriasis vulgaris (short version)

Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1–S126, 2006; or http://www.psoriasis-leitlinie.de)

The IceCube Data Acquisition System: Signal Capture, Digitization, and Timestamping

IceCube is a km-scale neutrino observatory under construction at the South Pole with sensors both in the deep ice (InIce) and on the surface (IceTop). The sensors, called Digital Optical Modules (DOMs), detect, digitize and timestamp the signals from optical Cherenkov-radiation photons. The DOM Main Board (MB) data acquisition subsystem is connected to the central DAQ in the IceCube Laboratory (ICL) by a single twisted copper wire-pair and transmits packetized data on demand. Time calibration is maintained throughout the array by regular transmission to the DOMs of precisely timed analog signals, synchronized to a central GPS-disciplined clock. The design goals and consequent features, functional capabilities, and initial performance of the DOM MB, and the operation of a combined array of DOMs as a system, are described here. Experience with the first InIce strings and the IceTop stations indicates that the system design and performance goals have been achieved.Comment: 42 pages, 20 figures, submitted to Nuclear Instruments and Methods

Multifunctional poly[N-(2-hydroxypropyl)methacrylamide] copolymers via postpolymerization modification and sequential thiol–ene chemistry

Poly[N-(2-hydroxypropyl)methacrylamide] is a promising candidate material for biomedical applications. However, synthesis of functional pHPMA via compolymerization results can lead to variations in monomer composition, molar mass, and dispersity making comparison difficult. Postpolymerization modification routes, most commonly aminolysis of poly[active ester methacrylates], have alleviated some of these problems, but ester hydrolysis can lead to other problems. Here we report the synthesis of multifunctional pHPMA via a simple two-step derivatization of pHPMA homopolymer using readily available standard reagents and atom-efficient procedures. First, treatment with allyl isocyanate yields the corresponding carbamate with predictable incorporation of side-chain functionality. Allyl-pHPMA can then be derivatized further via radical thiol–ene reactions to generate pHPMA with multiple diverse functionalities but without adverse effects on the molecular weight and dispersity of the polymer. The applicability of the method to production of biologically relevant materials is demonstrated by cytocompatibility and cell labeling experiments with easily prepared ligand-functionalized pHPMA in the HCT 116 model cell line

Search for large extra dimensions in the production of jets and missing transverse energy in p(p)over-bar collisions at root s=1.96 TeV

We present the results of a search for new physics in the jets plus missing transverse energy data sample collected from 368 pb(-1) of p (p) over bar collisions at root s = 1.96 TeV recorded by the Collider Detector at Fermilab. We compare the number of events observed in the data with a data-based estimate of the standard model backgrounds contributing to this signature. We observe no significant excess of events, and we interpret this null result in terms of lower limits on the fundamental Planck scale for a large extra dimensions scenario