Quality assessment of colour fundus and fluorescein angiography images using deep learning.

BACKGROUND/AIMS: Image quality assessment (IQA) is crucial for both reading centres in clinical studies and routine practice, as only adequate quality allows clinicians to correctly identify diseases and treat patients accordingly. Here we aim to develop a neural network for automated real-time IQA in colour fundus (CF) and fluorescein angiography (FA) images. METHODS: Training and evaluation of two neural networks were conducted using 2272 CF and 2492 FA images, with binary labels in four (contrast, focus, illumination, shadow and reflection) and three (contrast, focus, noise) modality specific categories plus an overall quality ranking. Performance was compared with a second human grader, evaluated on an external public dataset and in a clinical trial use-case. RESULTS: The networks achieved a F1-score/area under the receiving operator characteristic/precision recall curve of 0.907/0.963/0.966 for CF and 0.822/0.918/0.889 for FA in overall quality prediction with similar results in most categories. A clear relation between model uncertainty and prediction error was observed. In the clinical trial use-case evaluation, the networks achieved an accuracy of 0.930 for CF and 0.895 for FA. CONCLUSION: The presented method allows automated IQA in real time, demonstrating human-level performance for CF as well as FA. Such models can help to overcome the problem of human intergrader and intragrader variability by providing objective and reproducible IQA results. It has particular relevance for real-time feedback in multicentre clinical studies, when images are uploaded to central reading centre portals. Moreover, automated IQA as preprocessing step can support integrating automated approaches into clinical practice.

Aggregate fluctuations in adaptive production networks.

To counteract the adverse effects of shocks, such as the global pandemic, on the economy, governments have discussed policies to improve the resilience of supply chains by reducing dependence on foreign suppliers. In this paper, we develop and quantify an adaptive production network model to study network resilience and the consequences of reshoring of supply chains. In our model, firms exit due to exogenous shocks or the propagation of shocks through the network, while firms can replace suppliers they have lost due to exit subject to switching costs and search frictions. Applying our model to a large international firm-level production network dataset, we find that restricting buyer-supplier links via reshoring policies reduces output and increases volatility and that volatility can be amplified through network adaptivity.

The impact of government responses to the COVID-19 pandemic on GDP growth: Does strategy matter?

We analyze whether and to what extent strategies employed by governments to fight the COVID-19 pandemic made a difference for GDP growth developments in 2020. Based on the strength and speed with which governments imposed non-pharmaceutical interventions (NPIs) when confronted with waves of infections we distinguish between countries pursuing an elimination strategy and countries following a suppression / mitigation strategy. For a sample of 44 countries fixed effect panel regression results show that NPI changes conducted by elimination strategy countries had a less severe effect on GDP growth than NPI changes in suppression / mitigation strategy countries: strategy matters. However, this result is sensitive to the countries identified as "elimination countries" and to the sample composition. Moreover, we find that exogenous country characteristics drive the choice of strategy. At the same time our results show that countries successfully applying the elimination strategy achieved better health outcomes than their peers without having to accept lower growth.

COVID-19: Lockdowns, Fatality Rates and GDP Growth: Evidence for the First Three Quarters of 2020.

The COVID-19 pandemic has triggered an unprecedented economic crisis. This article analyses the impact of mandatory social distancing imposed by lockdown policies and voluntary social distancing triggered by COVID-19 fatality rates on GDP growth in the first three quarters of 2020 for a sample of 42 countries. OLS and IV results indicate an important role for the fatality rate, while panel regressions show that lockdown stringency is the more important driver of growth. When including lagged variables, more restrictive measures lead to lower GDP growth in the same quarter but are associated with a positive, catching-up effect in the following quarter.

COVID-19 and Economic Growth: Does Good Government Performance Pay Off?

The coronavirus pandemic led to substantial revisions of 2020 GDP growth projections. We analyse whether and to what extent the quality of government policies in handling the health aspects of the crisis influence cross-country differences in the economic impact of the pandemic as projected by the OECD, the IMF and the World Bank. We measure policy quality by a recently published Economist Intelligence Unit index and a COVID-19 Misery index combining the stringency of government-imposed distancing measures with the COVID-19 fatality rate. Moreover, we control for international spillovers captured by trade openness and export exposure to tourism. Results for most specifications show that good government performance pays off as the respective countries record less severe revisions of growth forecasts. Only in a few cases, our findings suggest that the pandemic's global effect might be so strong that actions by individual governments do not affect cross-country differences of growth revisions. Finally, there is broad evidence supporting the view that a country's exposure to the global economy influences its growth outlook relative to other countries.

Matched-Pair Comparison of 68Ga-PSMA-11 PET/CT and 18F-PSMA-1007 PET/CT: Frequency of Pitfalls and Detection Efficacy in Biochemical Recurrence After Radical Prostatectomy.

18F-labeled prostate-specific membrane antigen (PSMA)-ligand PET has several principal advantages over 68Ga-PSMA-11. The purpose of this retrospective study was to evaluate the frequency of non-tumor-related uptake and the detection efficacy comparing 68Ga-PSMA-11 PET/CT and 18F-PSMA-1007 PET/CT in recurrent prostate cancer (PC) patients. Methods: The study included 102 patients with biochemically recurrent PC after radical prostatectomy undergoing 18F-PSMA-1007 PET/CT imaging. On the basis of various clinical variables, patients with corresponding 68Ga-PSMA-11 PET/CT scans were matched. All PET/CT scans (n = 204) were reviewed by 1 nuclear medicine physician. First, all PET-positive lesions were noted. Then, lesions suspected of being recurrent PC were differentiated from lesions attributed to a benign origin on the basis of known pitfalls and information from CT. For each region, the SUVmax of the lesion with the highest PSMA-ligand uptake was noted. Detection rates were determined, and SUVmax was compared separately for 68Ga-PSMA-11 and 18F-PSMA-1007. Results: In total, 18F-PSMA-1007 PET and 68Ga-PSMA-11 PET revealed 369 and 178 PSMA-ligand-positive lesions, respectively. 18F-PSMA-1007 PET revealed approximately 5 times more lesions attributed to a benign origin than did 68Ga-PSMA-11 PET (245 vs. 52 lesions, respectively). The benign lesions most frequently observed were ganglia, unspecific lymph node, and bone lesions, at a rate of 43%, 31%, and 24% for 18F-PSMA-1007 PET and 29%, 42%, and 27% for 68Ga-PSMA-11 PET, respectively. The SUVmax of lesions attributed to a benign origin was significantly higher (P < 0.0001) for 18F-PSMA-1007 PET. Further, a similar number of lesions was attributed to recurrent PC (124/369 for 18F-PSMA-1007 PET and 126/178 for 68Ga-PSMA-11 PET). Conclusion: The number of lesions with increased PSMA-ligand uptake attributed to a benign origin is considerably higher for 18F-PSMA-1007 PET than for 68Ga-PSMA-11 PET. This finding indicates the need for sophisticated reader training emphasizing known pitfalls and reporting within the clinical context.

Degradable, Dendritic Polyols on a Branched Polyphosphazene Backbone.

Herein, we present the design, synthesis, and characterization of fully degradable, hybrid, star-branched dendritic polyols. First multiarmed polyphosphazenes were prepared as a star-branched scaffold which upon functionalization produced globular branched hydroxyl-functionalized polymers with over 1700 peripheral functional end groups. These polyols with unique branched architectures could be prepared with controlled molecular weights and relatively narrow dispersities. Furthermore, the polymers are shown to undergo hydrolytic degradation to low molecular weight degradation products, the rate of which could be controlled through postpolymerization functionalization of the phosphazene backbone.

Nanoscale Imaging Reveals a Tetraspanin-CD9 Coordinated Elevation of Endothelial ICAM-1 Clusters.

Endothelial barriers have a central role in inflammation as they allow or deny the passage of leukocytes from the vasculature into the tissue. To bind leukocytes, endothelial cells form adhesive clusters containing tetraspanins and ICAM-1, so-called endothelial adhesive platforms (EAPs). Upon leukocyte binding, EAPs evolve into docking structures that emanate from the endothelial surface while engulfing the leukocyte. Here, we show that TNF-α is sufficient to induce apical protrusions in the absence of leukocytes. Using advanced quantitation of atomic force microscopy (AFM) recordings, we found these structures to protrude by 160 ± 80 nm above endothelial surface level. Confocal immunofluorescence microscopy proved them positive for ICAM-1, JAM-A, tetraspanin CD9 and f-actin. Microvilli formation was inhibited in the absence of CD9. Our findings indicate that stimulation with TNF-α induces nanoscale changes in endothelial surface architecture and that--via a tetraspanin CD9 depending mechanism--the EAPs rise above the surface to facilitate leukocyte capture.

Biodegradable Polyphosphazene Based Peptide-Polymer Hybrids.

A novel series of peptide based hybrid polymers designed to undergo enzymatic degradation is presented, via macrosubstitution of a polyphosphazene backbone with the tetrapeptide Gly-Phe-Leu-Gly. Further co-substitution of the hybrid polymers with hydrophilic polyalkylene oxide Jeffamine M-1000 leads to water soluble and biodegradable hybrid polymers. Detailed degradation studies, via 31P NMR spectroscopy, dynamic light scattering and field flow fractionation show the polymers degrade via a combination of enzymatic, as well as hydrolytic pathways. The peptide sequence was chosen due to its known property to undergo lysosomal degradation; hence, these degradable, water soluble polymers could be of significant interest for the use as polymer therapeutics. In this context, we investigated conjugation of the immune response modifier imiquimod to the polymers via the tetrapeptide and report the self-assembly behavior of the conjugate, as well as its enzymatically triggered drug release behavior.

Hydrodeoxygenation of Guaiacol over Ceria-Zirconia Catalysts.

The hydrodeoxygenation of guaiacol is investigated over bulk ceria and ceria-zirconia catalysts with different elemental compositions. The reactions are performed in a flow reactor at 1 atm and 275-400 °C. The primary products are phenol and catechol, whereas cresol and benzene are formed as secondary products. No products with hydrogenated rings are formed. The highest conversion of guaiacol is achieved over a catalyst containing 60 mol % CeO2 and 40 mol % ZrO2 . Pseudo-first-order activation energies of 97-114 kJ mol(-1) are observed over the mixed metal oxide catalysts. None of the catalysts show significant deactivation during 72 h on stream. The important physicochemical properties of the catalysts are characterized by X-ray diffraction (XRD), temperature-programmed reduction, titration of oxygen vacancies, and temperature-programmed desorption of ammonia. On the basis of these experimental results, the reasons for the observed reactivity trends are identified.

Size-selected monodisperse nanoclusters on supported graphene: bonding, isomerism, and mobility.

Soft-landing of size-selected Pd(n) (n ≤ 20) nanoclusters on a Moiré-patterned surface of graphene adsorbed on Ru(0001) leads to controlled formation of a truly monodisperse cluster-assembled material. Combined scanning tunneling microscopy and first-principles calculations allow identification of selective adsorption sites, characterization of size-dependent cluster isomers, and exploration of interconversion processes between isomeric forms that manifestly influence cluster surface mobility. Surface-assembled cluster superstructures may be employed in nanocatalytic applications, as well as in fundamental investigations of physical factors controlling bonding, structure, isomerism, and surface mobilities of surface-supported clusters.

Network evolution based on centrality.

We study the evolution of networks when the creation and decay of links are based on the position of nodes in the network measured by their centrality. We show that the same network dynamics arise under various centrality measures, and solve analytically the network evolution. During the complete evolution, the network is characterized by nestedness: the neighborhood of a node is contained in the neighborhood of the nodes with larger degree. We find a discontinuous transition in the network density between hierarchical and homogeneous networks, depending on the rate of link decay. We also show that this evolution mechanism leads to double power-law degree distributions, with interrelated exponents.

Suzuki-Miyaura cross-coupling reaction on copper-trans-A(2)B corroles with excellent functional group tolerance.

The palladium-catalyzed Suzuki-Miyaura cross-coupling reaction has been investigated on meso-substituted trans-A(2)B-corrole using tailored Pd-catalyst systems.We present the first examples of Suzuki-Miyaura cross-coupling reactions on meso-substituted trans-A(2)B-corrole derivatives with neutral, sterically hindered, inactivated and heteroaromatic boronic acids and esters, alkenylboronic acids, as well as quickly deboronating aryl boronic acids and benzo-condensated five membered heterocyclic boronic acids. In addition, we established a high-yield procedure for the Suzuki-Miyaura cross-coupling reaction of corroles with neutral boronic acids.Due to the lability of the free-base corrole macrocycles, functionalization of the corrole periphery was performed with the corresponding Cu-metallated species. meso-Substituted trans-A(2)B-corrole can hence be regarded as highly versatile platform towards more sophisticated corrole systems.X-ray structure analysis of a functionalized meso-substituted trans-A(2)B copper corrole exhibited the typical features of such a Cu-complex: short N-Cu distances and a saddled corrole configuration.Moreover, we observed a sensitivity of the formal oxidation state of the coordinated copper ions towards Suzuki-Miyaura cross-coupling reaction conditions, where the central copper(III) ion approaches the characteristic features of a copper(II) species. This redox behaviour was examined by UV/vis absorption spectra, nuclear magnetic resonance (NMR) experiments and time-dependent density functional theoretical calculations.

Stretched-coordinate PMLs for Maxwell's equations in the discontinuous Galerkin time-domain method.

The discontinuous Galerkin time-domain method (DGTD) is an emerging technique for the numerical simulation of time-dependent electromagnetic phenomena. For many applications it is necessary to model the infinite space which surrounds scatterers and sources. As a result, absorbing boundaries which mimic its properties play a key role in making DGTD a versatile tool for various kinds of systems. Popular techniques include the Silver-Mϋller boundary condition and uniaxial perfectly matched layers (UPMLs). We provide novel instructions for the implementation of stretched-coordinate perfectly matched layers in a discontinuous Galerkin framework and compare the performance of the three absorbers for a three-dimensional test system.

Electromagnetic interaction of split-ring resonators: The role of separation and relative orientation.

Extinction cross-section spectra of split-ring-resonator dimers have been measured at near-infrared frequencies with a sensitive spatial modulation technique. The resonance frequency of the dimer's coupled mode as well as its extinction cross-section and its quality factor depend on the relative orientation and separation of the two split-ring resonators. The findings can be interpreted in terms of electric and magnetic dipole-dipole interaction. Numerical calculations based on a Discontinuous Galerkin Time-Domain approach are in good agreement with the experiments and support our physical interpretation.

Discontinuous Galerkin time-domain computations of metallic nanostructures.

We apply the three-dimensional Discontinuous-Galerkin Time-Domain method to the investigation of the optical properties of bar- and V-shaped metallic nanostructures on dielectric substrates. A flexible finite element-like mesh together with an expansion into high-order basis functions allows for an accurate resolution of complex geometries and strong field gradients. In turn, this provides accurate results on the optical response of realistic structures. We study in detail the influence of particle size and shape on resonance frequencies as well as on scattering and absorption efficiencies. Beyond a critical size which determines the onset of the quasi-static limit we find significant deviations from the quasi-static theory. Furthermore, we investigate the influence of the excitation by comparing normal illumination and attenuated total internal reflection setups. Finally, we examine the possibility of coherently controlling the local field enhancement of V-structures via chirped pulses.

Statistical analysis and verification of forensic age estimation of living persons in the Institute of Legal Medicine of the Berlin University Hospital Charité.

In recent years, the increase in international migration movements has led to a greater demand for forensic age estimation of foreigners without valid identification documents in numerous countries. The growing importance of forensic age determination is underlined by a rapid rise in the number of expert reports by the Institute of Legal Medicine of the Berlin University Hospital Charité. A total of 247 expert opinions on estimated age were given between 1992 and 31 December 2000. Subject to formal court ruling, age is estimated based on the physical inspection, in combination with an X-ray of the left hand and the clavicles as well as dental assessment. However, the statistical proof of the range of scatter for the summarized age diagnosis still remains to be clarified in the context of this assessment procedure. The age estimations made by the Institute of Legal Medicine of the Berlin University Hospital Charité were statistically analyzed with respect to the validity of the different methods. For verification of the age diagnoses, the age estimates were compared with the court records and the age determined in the course of legal proceedings. In 45 cases, the age diagnoses could be verified. In all cases where the age could be verified beyond doubt, deviations from the actual age did not exceed +/-12 months. From this, it can be concluded that the combined application of the above-mentioned methods allows forensic age estimations with a sufficiently high degree of reliability.