Smart testing and critical care bed sharing for COVID-19 control.

During the early months of the current COVID-19 pandemic, social distancing measures effectively slowed disease transmission in many countries in Europe and Asia, but the same benefits have not been observed in some developing countries such as Brazil. In part, this is due to a failure to organise systematic testing campaigns at nationwide or even regional levels. To gain effective control of the pandemic, decision-makers in developing countries, particularly those with large populations, must overcome difficulties posed by an unequal distribution of wealth combined with low daily testing capacities. The economic infrastructure of these countries, often concentrated in a few cities, forces workers to travel from commuter cities and rural areas, which induces strong nonlinear effects on disease transmission. In the present study, we develop a smart testing strategy to identify geographic regions where COVID-19 testing could most effectively be deployed to limit further disease transmission. By smart testing we mean the testing protocol that is automatically designed by our optimization platform for a given time period, knowing the available number of tests, the current availability of ICU beds and the initial epidemiological situation. The strategy uses readily available anonymised mobility and demographic data integrated with intensive care unit (ICU) occupancy data and city-specific social distancing measures. Taking into account the heterogeneity of ICU bed occupancy in differing regions and the stages of disease evolution, we use a data-driven study of the Brazilian state of Sao Paulo as an example to show that smart testing strategies can rapidly limit transmission while reducing the need for social distancing measures, even when testing capacity is limited.

Optimized delay of the second COVID-19 vaccine dose reduces ICU admissions.

Slower than anticipated, COVID-19 vaccine production and distribution have impaired efforts to curtail the current pandemic. The standard administration schedule for most COVID-19 vaccines currently approved is two doses administered 3 to 4 wk apart. To increase the number of individuals with partial protection, some governments are considering delaying the second vaccine dose. However, the delay duration must take into account crucial factors, such as the degree of protection conferred by a single dose, the anticipated vaccine supply pipeline, and the potential emergence of more virulent COVID-19 variants. To help guide decision-making, we propose here an optimization model based on extended susceptible, exposed, infectious, and removed (SEIR) dynamics that determines the optimal delay duration between the first and second COVID-19 vaccine doses. The model assumes lenient social distancing and uses intensive care unit (ICU) admission as a key metric while selecting the optimal duration between doses vs. the standard 4-wk delay. While epistemic uncertainties apply to the interpretation of simulation outputs, we found that the delay is dependent on the vaccine mechanism of action and first-dose efficacy. For infection-blocking vaccines with first-dose efficacy ≥50%, the model predicts that the second dose can be delayed by ≥8 wk (half of the maximal delay), whereas for symptom-alleviating vaccines, the same delay is recommended only if the first-dose efficacy is ≥70%. Our model predicts that a 12-wk second-dose delay of an infection-blocking vaccine with a first-dose efficacy ≥70% could reduce ICU admissions by 400 people per million over 200 d.

A discussion on electricity prices, or the two sides of the coin.

We examine how different pricing frameworks deal with non-convex features typical of day-ahead energy prices when the power system is hydro-dominated, like in Brazil. For the system operator, requirements of minimum generation translate into feasibility issues that are fundamental to carry the generated power through the network. When utilities are remunerated at a price depending on Lagrange multipliers computed for a system with fixed commitment, the corresponding values sometimes fail to capture a signal that recovers costs. Keeping in mind recent discussions for the Brazilian power system, we analyse mechanisms that provide a compromise between the needs of the generators and those of the system operator. After characterizing when a price supports a generation plan, we explain in simple terms dual prices and related concepts, such as minimal uplifts and bi-dual problems. We present a new pricing mechanism that guarantees cost recovery to all agents, without over-compensations. Instead of using Lagrange multipliers, the price is defined as the solution to an optimization problem. The behaviour of the new rule is compared to two other proposals in the literature on illustrative examples, including a small, yet representative, hydro-thermal system. This article is part of the theme issue 'The mathematics of energy systems'.

TopoMap: A 0-dimensional Homology Preserving Projection of High-Dimensional Data.

Multidimensional Projection is a fundamental tool for high-dimensional data analytics and visualization. With very few exceptions, projection techniques are designed to map data from a high-dimensional space to a visual space so as to preserve some dissimilarity (similarity) measure, such as the Euclidean distance for example. In fact, although adopting distinct mathematical formulations designed to favor different aspects of the data, most multidimensional projection methods strive to preserve dissimilarity measures that encapsulate geometric properties such as distances or the proximity relation between data objects. However, geometric relations are not the only interesting property to be preserved in a projection. For instance, the analysis of particular structures such as clusters and outliers could be more reliably performed if the mapping process gives some guarantee as to topological invariants such as connected components and loops. This paper introduces TopoMap, a novel projection technique which provides topological guarantees during the mapping process. In particular, the proposed method performs the mapping from a high-dimensional space to a visual space, while preserving the 0-dimensional persistence diagram of the Rips filtration of the high-dimensional data, ensuring that the filtrations generate the same connected components when applied to the original as well as projected data. The presented case studies show that the topological guarantee provided by TopoMap not only brings confidence to the visual analytic process but also can be used to assist in the assessment of other projection methods.

Transcriptional alterations related to neuropathology and clinical manifestation of Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia in the human population, characterized by a spectrum of neuropathological abnormalities that results in memory impairment and loss of other cognitive processes as well as the presence of non-cognitive symptoms. Transcriptomic analyses provide an important approach to elucidating the pathogenesis of complex diseases like AD, helping to figure out both pre-clinical markers to identify susceptible patients and the early pathogenic mechanisms to serve as therapeutic targets. This study provides the gene expression profile of postmortem brain tissue from subjects with clinic-pathological AD (Braak IV, V, or V and CERAD B or C; and CDR ≥1), preclinical AD (Braak IV, V, or VI and CERAD B or C; and CDR = 0), and healthy older individuals (Braak ≤ II and CERAD 0 or A; and CDR = 0) in order to establish genes related to both AD neuropathology and clinical emergence of dementia. Based on differential gene expression, hierarchical clustering and network analysis, genes involved in energy metabolism, oxidative stress, DNA damage/repair, senescence, and transcriptional regulation were implicated with the neuropathology of AD; a transcriptional profile related to clinical manifestation of AD could not be detected with reliability using differential gene expression analysis, although genes involved in synaptic plasticity, and cell cycle seems to have a role revealed by gene classifier. In conclusion, the present data suggest gene expression profile changes secondary to the development of AD-related pathology and some genes that appear to be related to the clinical manifestation of dementia in subjects with significant AD pathology, making necessary further investigations to better understand these transcriptional findings on the pathogenesis and clinical emergence of AD.

A feature selection approach for identification of signature genes from SAGE data.

BACKGROUND: One goal of gene expression profiling is to identify signature genes that robustly distinguish different types or grades of tumors. Several tumor classifiers based on expression profiling have been proposed using microarray technique. Due to important differences in the probabilistic models of microarray and SAGE technologies, it is important to develop suitable techniques to select specific genes from SAGE measurements. RESULTS: A new framework to select specific genes that distinguish different biological states based on the analysis of SAGE data is proposed. The new framework applies the bolstered error for the identification of strong genes that separate the biological states in a feature space defined by the gene expression of a training set. Credibility intervals defined from a probabilistic model of SAGE measurements are used to identify the genes that distinguish the different states with more reliability among all gene groups selected by the strong genes method. A score taking into account the credibility and the bolstered error values in order to rank the groups of considered genes is proposed. Results obtained using SAGE data from gliomas are presented, thus corroborating the introduced methodology. CONCLUSION: The model representing counting data, such as SAGE, provides additional statistical information that allows a more robust analysis. The additional statistical information provided by the probabilistic model is incorporated in the methodology described in the paper. The introduced method is suitable to identify signature genes that lead to a good separation of the biological states using SAGE and may be adapted for other counting methods such as Massive Parallel Signature Sequencing (MPSS) or the recent Sequencing-By-Synthesis (SBS) technique. Some of such genes identified by the proposed method may be useful to generate classifiers.

An exact algorithm for optimal MAE stack filter design.

We propose a new algorithm for optimal MAE stack filter design. It is based on three main ingredients. First, we show that the dual of the integer programming formulation of the filter design problem is a minimum cost network flow problem. Next, we present a decomposition principle that can be used to break this dual problem into smaller subproblems. Finally, we propose a specialization of the network Simplex algorithm based on column generation to solve these smaller subproblems. Using our method, we were able to efficiently solve instances of the filter problem with window size up to 25 pixels. To the best of our knowledge, this is the largest dimension for which this problem was ever solved exactly.