The benefits, costs and feasibility of a low incidence COVID-19 strategy.

In the summer of 2021, European governments removed most NPIs after experiencing prolonged second and third waves of the COVID-19 pandemic. Most countries failed to achieve immunization rates high enough to avoid resurgence of the virus. Public health strategies for autumn and winter 2021 have ranged from countries aiming at low incidence by re-introducing NPIs to accepting high incidence levels. However, such high incidence strategies almost certainly lead to the very consequences that they seek to avoid: restrictions that harm people and economies. At high incidence, the important pandemic containment measure 'test-trace-isolate-support' becomes inefficient. At that point, the spread of SARS-CoV-2 and its numerous harmful consequences can likely only be controlled through restrictions. We argue that all European countries need to pursue a low incidence strategy in a coordinated manner. Such an endeavour can only be successful if it is built on open communication and trust.

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 or fewer new infections per million people. 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) four times more than strategies that only avoid hospital collapse. In the long term, immunization, large-scale testing, and international coordination will further facilitate control.

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. Strategies that maintain low case numbers, instead of high ones, reduce infections and deaths by factors of eleven and five, respectively. In general, policies with low case numbers significantly benefit from vaccination, as the overall reduction in susceptibility will further diminish viral spread. Keeping case numbers low is the safest long-term strategy because it considerably reduces mortality and morbidity and offers better preparedness against emerging escape or more contagious virus variants while still allowing for higher contact numbers (freedom) with progressing vaccinations.

A look into the future of the COVID-19 pandemic in Europe: an expert consultation.

How will the coronavirus disease 2019 (COVID-19) pandemic develop in the coming months and years? Based on an expert survey, we examine key aspects that are likely to influence the COVID-19 pandemic in Europe. The challenges and developments will strongly depend on the progress of national and global vaccination programs, the emergence and spread of variants of concern (VOCs), and public responses to non-pharmaceutical interventions (NPIs). In the short term, many people remain unvaccinated, VOCs continue to emerge and spread, and mobility and population mixing are expected to increase. Therefore, lifting restrictions too much and too early risk another damaging wave. This challenge remains despite the reduced opportunities for transmission given vaccination progress and reduced indoor mixing in summer 2021. In autumn 2021, increased indoor activity might accelerate the spread again, whilst a necessary reintroduction of NPIs might be too slow. The incidence may strongly rise again, possibly filling intensive care units, if vaccination levels are not high enough. A moderate, adaptive level of NPIs will thus remain necessary. These epidemiological aspects combined with economic, social, and health-related consequences provide a more holistic perspective on the future of the COVID-19 pandemic.

Influence of tree hollow characteristics and forest structure on saproxylic beetle diversity in tree hollows in managed forests in a regional comparison.

Tree hollows are among the rarest habitats in today's Central European managed forests but are considered key structures for high biodiversity in forests. To analyze and compare the effects of tree hollow characteristics and forest structure on diversity of saproxylic beetles in tree hollows in differently structured managed forests, we examined between 41 and 50 tree hollows in beech trees in each of three state forest management districts in Germany. During the two-year study, we collected 283 saproxylic beetle species (5880 individuals; 22% threatened species), using emergence traps. At small spatial scales, the size of hollow entrance and the number of surrounding microhabitat structures positively influenced beetle diversity, while the stage of wood mould decomposition had a negative influence, across all three forest districts. We utilized forest inventory data to analyze the effects of forest structure in radii of 50-500 m around tree hollows on saproxylic beetle diversity in the hollows. At these larger spatial scales, the three forest management districts differed remarkably regarding the parameters that influenced saproxylic beetle diversity in tree hollows. In Ebrach, characterized by mostly deciduous trees, the amount of dead wood positively influenced beetle diversity. In the mostly coniferous Fichtelberg forest district, with highly isolated tree hollows, in contrast, only the proportion of beech trees around the focal tree hollows showed a positive influence on beetle diversity. In Kelheim, characterized by mixed forest stands, there were no significant relationships between forest structure and beetle diversity in tree hollows. In this study, the same local tree hollow parameters influenced saproxylic beetle diversity in all three study regions, while parameters of forest structure at larger spatial scales differed in their importance, depending on tree-species composition.

Effect of cultivation pH on the surface hydrophobicity of Bacillus subtilis spores.

Bacillus subtilis spores are often used as biological indicators (BI) to monitor decontamination processes with gaseous hydrogen peroxide. Results in practical inactivation validation tests, however, vary considerably with no available explanation so far. This study reports on the effect of cultivation pH on spore surface hydrophobicity. Surface hydrophobicity is suspected to have an impact on the decontamination of technical surfaces such as packaging material when gaseous, condensing hydrogen peroxide is applied. It is the aim of this study to examine the impact of different cultivation pH levels on surface hydrophobicity and resistance of B. subtilis spores. Submersed cultivation of B. subtilis in bioreactors at controlled conditions with different static pH levels led to contact angles ranged between 50° and 80°, which was analyzed with water on a homogeneous layer of spores on a filter sheet. Resistance of spores was also affected by the cultivation pH. The results show that the culturing conditions during BI production should be controlled to obtain BI with specified characteristics in inactivation validation tests.

K-t GRAPPA accelerated phase contrast MRI: Improved assessment of blood flow and 3-directional myocardial motion during breath-hold.

PURPOSE: To evaluate spatiotemporal parallel imaging with R = 5 in comparison to conventional parallel imaging with R = 2 applied to phase contrast (PC) magnetic resonance imaging (MRI). This was motivated by the fact that scan times for PC imaging often exceed breath-hold capabilities of patients even with standard parallel imaging using typical reduction factors of R = 2. MATERIALS AND METHODS: K-t generalized autocalibrating partially parallel acquisition (GRAPPA) acquisition was validated in phantom measurements and then applied in 10 volunteer and three patient examinations. Due to the higher reduction factor compared to conventional GRAPPA, k-t GRAPPA measurements could be performed during breath-hold with high spatial and temporal resolution. K-t GRAPPA scans were compared to GRAPPA acquired during free-breathing with navigator respiration control. In addition, spatiotemporally accelerated PC imaging was acquired during free-breathing for comparison of k-t-accelerated breath-held scans. RESULTS: Substantial improvements in image quality for the breath-hold measurements were observed. Significantly reduced peak velocities were found for the GRAPPA protocol compared to the k-t-accelerated breath-hold scans for both flow (8%) and myocardial motion (up to 30%) measurements. CONCLUSION: Spatiotemporal acceleration allows the performance of high temporal or spatial resolution PC imaging during breath-hold while providing high image quality and robust acquisition of functional information that cannot be achieved during breath-hold with standard techniques.

Free-breathing dynamic contrast-enhanced MRI of the abdomen and chest using a radial gradient echo sequence with K-space weighted image contrast (KWIC).

OBJECTIVES: To evaluate the feasibility of free-breathing, dynamic contrast-enhanced (DCE) MRI of the abdomen and thorax using the radial-gradient-echo sequence with k-space weighted image contrast (KWIC) reconstruction. METHODS: Institutional review board approval was obtained. Fourteen patients underwent free-breathing radial DCE-MRI. Radial MRI yielded full-frame images by gridding all k-space data and time-resolved subframe images by using KWIC reconstruction technique. Using subframe KWIC images, voxel-wise perfusion maps were created. For comparison, the breath-hold conventional Cartesian 3D-gradient-echo sequence (VIBE) was also performed during the equilibrium phase. The image qualities of radial and conventional VIBE images were compared quantitatively and qualitatively. RESULTS: Radial DCE-MRI provided high spatial resolution (1.4 × 1.4 mm) and temporal resolution (4.1 s for subframe images) allowing voxel-wise perfusion mapping with negligible motion or streaking artefacts. There were no significant differences in SNR between full-frame radial images and conventional VIBE images (79.08 vs 74.80, P > 0.05). Overall image quality score of full-frame radial images was slightly lower than that of conventional VIBE images (3.88 ± 0.59 vs. 4.31 ± 0.97, P < 0.05), but provided clinically useful images. CONCLUSIONS: The free-breathing radial DCE-MRI can provide high spatial and temporal resolution while maintaining reasonably high image quality and thus is a feasible technique for DCE-MRI in the abdomen and thorax. KEY POINTS: • Dynamic contrast-enhanced magnetic resonance imaging (DCE) MRI is important in oncological imaging • Radial MRI with k-space weighted image contrast (KWIC) reconstruction offers potential improvements • Radial DCE-MRI provides good image quality, reduced artefacts and high spatial/temporal resolution.

Bicuspid aortic valve is associated with altered wall shear stress in the ascending aorta.

BACKGROUND: Hemodynamics may play a role contributing to the progression of bicuspid aortic valve (BAV) aortopathy. This study measured the impact of BAV on the distribution of regional aortic wall shear stress (WSS) compared with control cohorts. METHODS AND RESULTS: Local WSS distribution was measured in the thoracic aorta of 60 subjects using 4-dimensional (4D) flow-sensitive magnetic resonance imaging. WSS analysis included 15 BAV patients: 12 with fusion of the right-left coronary cusp (6 stenotic) and 3 with fusion of the right and noncoronary cusp. The right-left BAV cohort was compared with healthy subjects (n=15), age-appropriate subjects (n=15), and age-/aorta size-controlled subjects (n=15). Compared with the age-appropriate and age-/aorta size-matched controls, WSS patterns in the right-left BAV ascending aorta were significantly elevated, independent of stenosis severity (peak WSS=0.9 ± 0.3 N/m(2) compared with 0.4 ± 0.3 N/m(2) in age-/aorta size-controlled subjects; P<0.001). Time-resolved (cine) 2D images of the bicuspid valves were coregistered with 4D flow data, directly linking cusp fusion pattern to a distinct ascending aortic flow jet pattern. The observation of right-anterior ascending aorta wall/jet impingement in right-left BAV patients corresponded to regions with statistically elevated WSS. Alternative jetting patterns were observed in the right and noncoronary cusp fusion patients. CONCLUSIONS: The results of this study demonstrate that bicuspid valves induced significantly altered ascending aorta hemodynamics compared with age- and size-matched controls with tricuspid valves. Specifically, the expression of increased and asymmetric WSS at the aorta wall was related to ascending aortic flow jet patterns, which were influenced by the BAV fusion pattern.

On the undersampling strategies to accelerate time-resolved 3D imaging using k-t-GRAPPA.

The purpose of this study was to explore how to optimally undersample and reconstruct time-resolved 3D data using a k-t-space-based GRAPPA technique. The performance of different reconstruction strategies was evaluated using data sets with different ratios of phase (N(y)) and partition (N(z)) encoding lines (N(y) × N(z) = 64-128 × 40-64) acquired in a moving phantom. Image reconstruction was performed for different kernel configurations and different reduction factors (R = 5, 6, 8, and 10) and was evaluated using regional error quantification and SNR analysis. To analyze the temporal fidelity of the different kernel configurations in vivo, time-resolved 3D phase contrast data were acquired in the thoracic aorta of two healthy volunteers. Results demonstrated that kernel configurations with a small kernel extension yielded superior results especially for more asymmetric data matrices as typically used in clinical applications. The application of k-t-GRAPPA to in vivo data demonstrated the feasibility of undersampling of time-resolved 3D phase contrast data set with a nominal reduction factors of up to R(net) = 8, while maintaining the temporal fidelity of the measured velocity field. Extended GRAPPA-based parallel imaging with optimized multidimensional reconstruction kernels has the potential to substantially accelerate data acquisitions in time-resolved 3D MRI.

Three-directional acceleration phase mapping of myocardial function.

An optimized acceleration encoded phase contrast method termed "acceleration phase mapping" for the assessment of regional myocardial function is presented. Based on an efficient gradient waveform design using two-sided encoding for in vivo three-directional acceleration mapping, echo and repetition times TE = 12-14 ms and TR = 15-17 ms for low accelerations sensitivity aenc = 5-8 m/s(2) were achieved. In addition to phantom validation, the technique was applied in a study with 10 healthy volunteers at 1.5T and 3T to evaluate its feasibility to assess regional myocardial acceleration at 1.5T and 3T. Results of the acceleration measurements were compared with the temporal derivative of myocardial velocities from three-directional velocity encoded standard phase contrast MRI in the same volunteers. The feasibility to assess myocardial acceleration along the radial, circumferential, and longitudinal direction of the left ventricle was demonstrated. Despite improved signal-to-noise-ratio at 3T (34% increase compared with 1.5T), image quality with respect to susceptibility artifacts was better 1.5T compared with 3T. Analysis of global and regional left ventricular acceleration showed characteristic patterns of systolic and diastolic acceleration and deceleration. Comparisons of directly measured and derived myocardial acceleration dynamics over the cardiac cycle revealed good correlation (r = 0.45-0.68, P < 0.01) between both methods.

In vivo wall shear stress distribution in the carotid artery: effect of bifurcation geometry, internal carotid artery stenosis, and recanalization therapy.

BACKGROUND: the purpose of this study was to analyze the in vivo distribution of absolute wall shear stress (WSS(abs)) and oscillatory shear index (OSI) in the carotid bifurcation and to evaluate its dependence on bifurcation geometry, the presence of internal carotid artery (ICA) stenosis, and recanalization therapy. METHODS AND RESULTS: time-resolved 3D blood flow was acquired with flow-sensitive 4D MRI in 64 normal carotid bifurcations and 17 carotid arteries with moderate ICA stenosis (48±6%) or after surgical recanalization. Among 64 normal arteries, atherogenic wall parameters were consistently concentrated in proximal bulb regions of the common (CCA) and internal (ICA) carotid arteries. The fraction of the carotid bulb exposed to atherosclerosis-prone wall parameters (low WSS(abs) below and high OSI above group-defined 20% and 10% thresholds) was correlated with the individual bifurcation geometry. Multiple regressions revealed significant (P<0.01) relationships (ß, 0.44 to 0.48) between the areas with atherosclerosis-prone wall parameters and the d(ICA)/d(CCA) diameter ratio. The size of regions exposed to high OSI demonstrated highly significant (P≤0.01) relationships with all analyzed geometry parameters (d(ICA)/d(CCA) ß, 0.48; tortuosity ß, ≤-0.56; bifurcation angle ß, ≥0.47). Moderate ICA stenosis altered the distribution of wall parameters (45%/61% reduction of individually low WSS(abs)/high OSI in the proximal ICA), which were relocated to segments distal to the arterial stenosis. WSS(abs)/OSI topology after recanalization was similar compared with the normal wall parameter distribution. CONCLUSIONS: flow-sensitive 4D MRI identified alterations in the segmental in vivo WSS distribution associated with atherosclerotic disease, surgical therapy, and individual bifurcation geometry and could be a valuable technique to assess the individual risk of flow-mediated atherosclerosis and carotid plaque progression.

MR-based visualization and quantification of three-dimensional flow characteristics in the portal venous system.

PURPOSE: To evaluate the feasibility of time-resolved flow-sensitive MRI for the three-dimensional (3D) visualization and quantification of normal and pathological portal venous (PV) hemodynamics. MATERIALS AND METHODS: Portal venous hemodynamics were evaluated in 18 healthy volunteers and 5 patients with liver cirrhosis. ECG- and adaptive respiratory navigator gated flow-sensitive 4D MRI (time-resolved 3D MRI with three-directional velocity encoding) was performed on a 3 Tesla MR system (TRIO, Siemens, Germany). Qualitative flow analysis was achieved using 3D streamlines and time-resolved particle traces originating from seven emitter planes precisely placed at anatomical landmarks in the PV system. Quantitative analysis included retrospective extraction of regional peak and mean velocities and vessel area. Results were compared with standard 2D flow-sensitive MRI and to the reference standard Doppler ultrasound. RESULTS: Qualitative flow analysis was successfully used in the entire PV system. Venous hemodynamics in all major branches in 17 of 18 volunteers and 3 of 5 patients were reliably depicted with good interobserver agreement (kappa = 0.62). Quantitative analysis revealed no significant differences and moderate agreement for peak velocities between 3D MR and 2D MRI (r = 0.46) and Doppler ultrasound (US) (r = 0.35) and for mean velocities between 3D and 2D MRI (r = 0.41). The PV area was significantly (P < 0.01) higher in 3D and 2D MRI compared with US. CONCLUSION: We successfully applied 3D MR velocity mapping in the PV system, providing a detailed qualitative and quantitative analysis of normal and pathological hemodynamics.

Optimized parallel imaging for dynamic PC-MRI with multidirectional velocity encoding.

Phase contrast MRI with multidirectional velocity encoding requires multiple acquisitions of the same k-space lines to encode the underlying velocities, which can considerably lengthen the total scan time. To reduce scan time, parallel imaging is often applied. In dynamic phase contrast MRI using standard generalized autocalibrating partially parallel acquisitions (GRAPPA), several central k-spaces for autocalibration of the reconstruction (autocalibrating signal lines (ACS)) are typically acquired, separately for each velocity direction and each cardiac timeframe, for calculating the reconstruction weights. To further accelerate data acquisition, we developed two methods, which calculated weights with a substantially reduced number of ACSl lines. The effects on image quality and flow quantification were compared to fully sampled data, standard GRAPPA, and time-interleaved sampling scheme in combination with generalized autocalibrating partially parallel acquisitions (TGRAPPA). The results show that the two proposed methods can clearly improve scan efficiency while maintaining image quality and accuracy of measured flow or myocardial tissue velocities. Compared to TGRAPPA, the proposed methods were more accurate in evaluating flow velocity. In conclusion, the proposed reconstruction strategies are promising for dynamic multidirectionally encoded acquisitions and can easily be implemented using the standard GRAPPA reconstruction algorithm.

In vivo assessment of wall shear stress in the atherosclerotic aorta using flow-sensitive 4D MRI.

Our purpose was to correlate atherogenic low wall shear stress (WSS) and high oscillatory shear index (OSI) with the localization of aortic plaques. Flow-sensitive four-dimensional MRI was used to acquire three-dimensional blood flow in the aorta of 62 patients with proven aortic atherosclerosis and 31 healthy volunteers. Multiplanar data analysis of WSS magnitude and OSI in 12 wall segments was performed in analysis planes distributed along the aorta. Disturbed WSS and OSI were defined as areas exposed to low WSS magnitude and high OSI beyond individual 15% thresholds. Planewise analysis revealed a good correlation (r = 0.85) of individual low WSS magnitude but not of high OSI with plaque distribution. Although plaques occurred only rarely in the ascending aorta, the incidence of low WSS magnitude and high OSI was similar to findings in other aortic segments where plaques occurred more frequently. Case-by-case comparisons of plaque location and critical wall parameters revealed a shift of atherogenic WSS magnitude (78% of all cases) and OSI (91%) to wall segments adjacent to the atheroma. Our results indicate that the predictive value of WSS for plaque existence depends on the aortic segment and that locations of critical wall parameters move to neighboring segments of regions affected by atherosclerosis.

Three-dimensional analysis of segmental wall shear stress in the aorta by flow-sensitive four-dimensional-MRI.

PURPOSE: To assess the distribution and regional differences of flow and vessel wall parameters such as wall shear stress (WSS) and oscillatory shear index (OSI) in the entire thoracic aorta. MATERIALS AND METHODS: Thirty-one healthy volunteers (mean age = 23.7 +/- 3.3 years) were examined by flow-sensitive four-dimensional (4D)-MRI at 3T. For eight retrospectively positioned 2D analysis planes distributed along the thoracic aorta, flow parameters and vectorial WSS and OSI were assessed in 12 segments along the vascular circumference. RESULTS: Mean absolute time-averaged WSS ranged between 0.25 +/- 0.04 N/m(2) and 0.33 +/- 0.07 N/m(2) and incorporated a substantial circumferential component (-0.05 +/- 0.04 to 0.07 +/- 0.02 N/m(2)). For each analysis plane, a segment with lowest absolute WSS and highest OSI was identified which differed significantly from mean values within the plane (P < 0.05). The distribution of atherogenic low WSS and high OSI closely resembled typical locations of atherosclerotic lesions at the inner aortic curvature and supraaortic branches. CONCLUSION: The normal distribution of vectorial WSS and OSI in the entire thoracic aorta derived from flow-sensitive 4D-MRI data provides a reference constituting an important perquisite for the examination of patients with aortic disease. Marked regional differences in absolute WSS and OSI may help explaining why atherosclerotic lesions predominantly develop and progress at specific locations in the aorta.

Increasing efficiency of parallel imaging for 2D multislice acquisitions.

Parallel imaging algorithms require precise knowledge about the spatial sensitivity variation of the receiver coils to reconstruct images with full field of view (FOV) from undersampled Fourier encoded data. Sensitivity information must either be given a priori, or estimated from calibration data acquired along with the actual image data. In this study, two approaches are presented, which require very little or no additional data at all for calibration in two-dimensional multislice acquisitions. Instead of additional data, information from spatially adjacent slices is used to estimate coil sensitivity information, thereby increasing the efficiency of parallel imaging. The proposed approaches rely on the assumption that over a small range of slices, coil sensitivities vary smoothly in slice direction. Both methods are implemented as variants of the GRAPPA algorithm. For a given effective acceleration, superior image quality is achieved compared to the conventional GRAPPA method. For the latter calibration lines for coil weight computation must be acquired in addition to the undersampled k-spaces for coil weight computation, thus requiring higher k-space undersampling, that is, a higher reduction factor to achieve the same effective acceleration. The proposed methods are particularly suitable to speed up parallel imaging for clinical applications where the reduction factor is limited to two or three.

Parallel MRI with extended and averaged GRAPPA kernels (PEAK-GRAPPA): optimized spatiotemporal dynamic imaging.

PURPOSE: To evaluate an optimized k-t-space related reconstruction method for dynamic magnetic resonance imaging (MRI), a method called PEAK-GRAPPA (Parallel MRI with Extended and Averaged GRAPPA Kernels) is presented which is based on an extended spatiotemporal GRAPPA kernel in combination with temporal averaging of coil weights. MATERIALS AND METHODS: The PEAK-GRAPPA kernel consists of a uniform geometry with several spatial and temporal source points from acquired k-space lines and several target points from missing k-space lines. In order to improve the quality of coil weight estimation sets of coil weights are averaged over the temporal dimension. RESULTS: The kernel geometry leads to strongly decreased reconstruction times compared to the recently introduced k-t-GRAPPA using different kernel geometries with only one target point per kernel to fit. Improved results were obtained in terms of the root mean square error and the signal-to-noise ratio as demonstrated by in vivo cardiac imaging. CONCLUSION: Using a uniform kernel geometry for weight estimation with the properties of uncorrelated noise of different acquired timeframes, optimized results were achieved in terms of error level, signal-to-noise ratio, and reconstruction time.