Extensions of the SEIR model for the analysis of tailored social distancing and tracing approaches to cope with COVID-19

In the context of the COVID-19 pandemic, governments worldwide face the challenge of designing tailored measures of epidemic control to provide reliable health protection while allowing societal and economic activity. In this paper, we propose an extension of the epidemiological SEIR model to enable a detailed analysis of commonly discussed tailored measures of epidemic control—among them group-specific protection and the use of tracing apps. We introduce groups into the SEIR model that may differ both in their underlying parameters as well as in their behavioral response to public health interventions. Moreover, we allow for different infectiousness parameters within and across groups, different asymptomatic, hospitalization, and lethality rates, as well as different take-up rates of tracing apps. We then examine predictions from these models for a variety of scenarios. Our results visualize the sharp trade-offs between different goals of epidemic control, namely a low death toll, avoiding overload of the health system, and a short duration of the epidemic. We show that a combination of tailored mechanisms, e.g., the protection of vulnerable groups together with a “trace & isolate” approach, can be effective in preventing a high death toll. Protection of vulnerable groups without further measures requires unrealistically strict isolation. A key insight is that high compliance is critical for the effectiveness of a “trace & isolate” approach. Our model allows to analyze the interplay of group-specific social distancing and tracing also beyond our case study in scenarios with a large number of groups reflecting, e.g., sectoral, regional, or age differentiation and group-specific behavioural responses

Global Gene Expression Profiling of Body-Mass Index in Middle-Aged Danish Twins

Objective: The body mass index (BMI) measured as weight in relation to height is an important monitor for obesity and diabetes, with individual variation under control by genetic and environmental factors. In transcriptome-wide association studies on BMI, the genetic contribution calls for controlling of genetic confounding that affects both BMI and gene expression. We performed a global gene expression profiling of BMI on peripheral blood cells using monozygotic twins for efficient handling of genetic make-ups. Methods: We applied a generalized association method to genome-wide gene expression data on 229 pairs of monozygotic twins (age 56-80 years) for detecting diverse patterns of correlation between BMI and gene expression. Results: We detected seven probes associated with BMI with p<1e-04, among them two probes with p<1e-05 (p=2.83e-06 AAK1; p=7.83e-06 LILRA3). In total, the analysis found 1579 probes with nominal p<0.05. Biological pathway analysis of enriched pathways found 50 KEGG and 45 Reactome pathways (FDR<0.05). The identified top functional pathways included immune function, JAK-STAT signalling, insulin signalling and regulation of energy metabolism. Conclusion: This transcriptome-wide association study using monozygotic twins and generalized correlation identified differentially expressed genes and a broad spectrum of enriched biological pathways that may implicate metabolic health

Wide-field HST/ACS images of M81: The Population of Compact Star Clusters

We study the population of compact stellar clusters (CSCs) in M81, using the HST/ACS images in the filters F435W, F606W and F814W covering, for the first time, the entire optical extent of the galaxy. Our sample contains 435 clusters of FWHM less than 10 ACS pixels (9 pc). The sample shows the presence of two cluster populations, a blue group of 263 objects brighter than B=22 mag, and a red group of 172 objects, brighter than B=24 mag. Based on the analysis of colour magnitude diagrams and making use of simple stellar population models, we find the blue clusters are younger than 300 Myr with some clusters as young as few Myr, and the red clusters are as old as globular clusters. The luminosity function of the blue group follows a power-law distribution with an index of 2.0, typical value for young CSCs in other galaxies. The power-law shows unmistakable signs of truncation at I=18.0 mag (M_I=-9.8 mag), which would correspond to a mass-limit of 4x10^4 M_solar if the brightest clusters are younger than 10 Myr. The red clusters have photometric masses between 10^5 to 2x10^7 M_solar for the adopted age of 5 Gyr and their luminosity function resembles very much the globular cluster luminosity function in the Milky Way. The brightest GC in M81 has M_B^0=-10.3 mag, which is ~0.9 mag brighter than w-Cen, the most massive GC in the Milky Way.Comment: Accepted by MNRAS. The paper contains 10 figures and 3 tables. Table 3 will be published in full online onl

Olivine-rich exposures at Bellicia and Arruntia craters on (4) Vesta from Dawn FC

We present an analysis of the olivine-rich exposures at Bellicia and Arruntia craters using Dawn Framing Camera (FC) color data. Our results confirm the existence of olivine-rich materials at these localities as described by Ammannito et al. (2013a) using Visual Infrared Spectrometer (VIR) data. Analyzing laboratory spectra of various Howardite-Eucrite-Diogenite meteorites, high-Ca pyroxenes, olivines and olivine-orthopyroxene mixtures, we derive three FC spectral band parameters that are indicators of olivine-rich materials. Combining the three band parameters allows us, for the first time, to reliably identify sites showing modal olivine contents >40%. The olivine-rich exposures at Bellicia and Arruntia are mapped using higher spatial resolution FC data. The exposures are located on the slopes of outer/inner crater walls, on the floor of Arruntia, in the ejecta, as well as in nearby fresh small impact craters. The spatial extent of the exposures ranges from a few hundred meters to few kilometers. The olivine-rich exposures are in accordance with both the magma ocean and the serial magmatism model (e.g., Righter and Drake 1997; Yamaguchi et al. 1997). However, it remains unsolved why the olivine-rich materials are mainly concentrated in the northern hemisphere (~36-42{\deg} N, 46-74{\deg} E) and are almost absent in the Rheasilvia basin.Comment: Accepted for publication in Meteoritics and Planetary Scienc

Efficacy and outcome of expanded newborn screening for metabolic diseases - Report of 10 years from South-West Germany *

<p>Abstract</p> <p>Background</p> <p>National newborn screening programmes based on tandem-mass spectrometry (MS/MS) and other newborn screening (NBS) technologies show a substantial variation in number and types of disorders included in the screening panel. Once established, these methods offer the opportunity to extend newborn screening panels without significant investment and cost. However, systematic evaluations of newborn screening programmes are rare, most often only describing parts of the whole process from taking blood samples to long-term evaluation of outcome.</p> <p>Methods</p> <p>In a prospective single screening centre observational study 373 cases with confirmed diagnosis of a metabolic disorder from a total cohort of 1,084,195 neonates screened in one newborn screening laboratory between January 1, 1999, and June 30, 2009 and subsequently treated and monitored in five specialised centres for inborn errors of metabolism were examined. Process times for taking screening samples, obtaining results, initiating diagnostic confirmation and starting treatment as well as the outcome variables metabolic decompensations, clinical status, and intellectual development at a mean age of 3.3 years were evaluated.</p> <p>Results</p> <p>Optimal outcome is achieved especially for the large subgroup of patients with medium-chain acyl-CoA dehydrogenase deficiency. Kaplan-Meier-analysis revealed disorder related patterns of decompensation. Urea cycle disorders, organic acid disorders, and amino acid disorders show an early high and continuous risk, medium-chain acyl-CoA dehydrogenase deficiency a continuous but much lower risk for decompensation, other fatty acid oxidation disorders an intermediate risk increasing towards the end of the first year. Clinical symptoms seem inevitable in a small subgroup of patients with very early disease onset. Later decompensation can not be completely prevented despite pre-symptomatic start of treatment. Metabolic decompensation does not necessarily result in impairment of intellectual development, but there is a definite association between the two.</p> <p>Conclusions</p> <p>Physical and cognitive outcome in patients with presymptomatic diagnosis of metabolic disorders included in the current German screening panel is equally good as in phenylketonuria, used as a gold standard for NBS. Extended NBS entails many different interrelated variables which need to be carefully evaluated and optimized. More reports from different parts of the world are needed to allow a comprehensive assessment of the likely benefits, harms and costs in different populations.</p

Global Gene Expression Profiling and Transcription Factor Network Analysis of Cognitive Aging in Monozygotic Twins

Cognitive aging is one of the major problems worldwide, especially as people get older. This study aimed to perform global gene expression profiling of cognitive function to identify associated genes and pathways and a novel transcriptional regulatory network analysis to identify important regulons. We performed single transcript analysis on 400 monozygotic twins using an assumption-free generalized correlation coefficient (GCC), linear mixed-effect model (LME) and kinship model and identified six probes (one significant at the standard FDR < 0.05 while the other results were suggestive with 0.18 ≤ FDR ≤ 0.28). We combined the GCC and linear model results to cover diverse patterns of relationships, and meaningful and novel genes like APOBEC3G, H6PD, SLC45A1, GRIN3B, and PDE4D were detected. Our exploratory study showed the downregulation of all these genes with increasing cognitive function or vice versa except the SLC45A1 gene, which was upregulated with increasing cognitive function. Linear models found only H6PD and SLC45A1, the other genes were captured by GCC. Significant functional pathways (FDR < 3.95e-10) such as focal adhesion, ribosome, cysteine and methionine metabolism, Huntington's disease, eukaryotic translation elongation, nervous system development, influenza infection, metabolism of RNA, and cell cycle were identified. A total of five regulons (FDR< 1.3e-4) were enriched in a transcriptional regulatory analysis in which CTCF and REST were activated and SP3, SRF, and XBP1 were repressed regulons. The genome-wide transcription analysis using both assumption-free GCC and linear models identified important genes and biological pathways implicated in cognitive performance, cognitive aging, and neurological diseases. Also, the regulatory network analysis revealed significant activated and repressed regulons on cognitive function.Peer reviewe

Projecting Antarctic ice discharge using response functions from SeaRISE ice-sheet models

The largest uncertainty in projections of future sea-level change results from the potentially changing dynamical ice discharge from Antarctica. Basal ice-shelf melting induced by a warming ocean has been identified as a major cause for additional ice flow across the grounding line. Here we attempt to estimate the uncertainty range of future ice discharge from Antarctica by combining uncertainty in the climatic forcing, the oceanic response and the ice-sheet model response. The uncertainty in the global mean temperature increase is obtained from historically constrained emulations with the MAGICC-6.0 (Model for the Assessment of Greenhouse gas Induced Climate Change) model. The oceanic forcing is derived from scaling of the subsurface with the atmospheric warming from 19 comprehensive climate models of the Coupled Model Intercomparison Project (CMIP-5) and two ocean models from the EU-project Ice2Sea. The dynamic ice-sheet response is derived from linear response functions for basal ice-shelf melting for four different Antarctic drainage regions using experiments from the Sea-level Response to Ice Sheet Evolution (SeaRISE) intercomparison project with five different Antarctic ice-sheet models. The resulting uncertainty range for the historic Antarctic contribution to global sea-level rise from 1992 to 2011 agrees with the observed contribution for this period if we use the three ice-sheet models with an explicit representation of ice-shelf dynamics and account for the time-delayed warming of the oceanic subsurface compared to the surface air temperature. The median of the additional ice loss for the 21st century is computed to 0.07 m (66% range: 0.02–0.14 m; 90% range: 0.0–0.23 m) of global sea-level equivalent for the low-emission RCP-2.6 (Representative Concentration Pathway) scenario and 0.09 m (66% range: 0.04–0.21 m; 90% range: 0.01–0.37 m) for the strongest RCP-8.5. Assuming no time delay between the atmospheric warming and the oceanic subsurface, these values increase to 0.09 m (66% range: 0.04–0.17 m; 90% range: 0.02–0.25 m) for RCP-2.6 and 0.15 m (66% range: 0.07–0.28 m; 90% range: 0.04–0.43 m) for RCP-8.5. All probability distributions are highly skewed towards high values. The applied ice-sheet models are coarse resolution with limitations in the representation of grounding-line motion. Within the constraints of the applied methods, the uncertainty induced from different ice-sheet models is smaller than that induced by the external forcing to the ice sheets

Use of Vibrio cholerae Vaccine in an Outbreak in Guinea

Producción CientíficaThe use of vaccines to prevent and control cholera is currently under debate. Shanchol is one of the two oral cholera vaccines prequalified by the World Health Organization; however, its effectiveness under field conditions and the protection it confers in the first months after administration remain unknown. The main objective of this study was to estimate the short-term effectiveness of two doses of Shanchol used as a part of the integrated response to a cholera outbreak in Africa. METHODS We conducted a matched case-control study in Guinea between May 20 and October 19, 2012. Suspected cholera cases were confirmed by means of a rapid test, and controls were selected among neighbors of the same age and sex as the case patients. The odds of vaccination were compared between case patients and controls in bivariate and adjusted conditional logistic-regression models. Vaccine effectiveness was calculated as (1-odds ratio) × 100. RESULTS Between June 8 and October 19, 2012, we enrolled 40 case patients and 160 controls in the study for the primary analysis. After adjustment for potentially confounding variables, vaccination with two complete doses was associated with significant protection against cholera (effectiveness, 86.6%; 95% confidence interval, 56.7 to 95.8; P=0.001). CONCLUSIONS In this study, Shanchol was effective when used in response to a cholera outbreak in Guinea. This study provides evidence supporting the addition of vaccination as part of the response to an outbreak. It also supports the ongoing efforts to establish a cholera vaccine stockpile for emergency use, which would enhance outbreak prevention and control strategies