An Integer Linear Programming approach to minimize the cost of the refurbishment of a façade to improve the energy efficiency of a building

[EN] Buildings account 40% of the EU's total energy consumption. Therefore, they represent a key potential source of energy savings to fight, among others, against climate change. Furthermore, around 54% of the buildings in Spain date back before 1980, when no thermal regulation was available. The refurbishment of a façade of an old building is usually the most effective way to improve its energy efficiency, by adding layers to the external envelope in order to reduce its thermal transmittance. This paper deals with the problem of minimizing costs for the thermal refurbishment of a façade with thickness and thermal ransmittance bounds and with an intervention both on the opaque part (wall) and the transparent part (windows). Among thousands, even millions of combinations of materials and thicknesses for the different layers to be added to the opaque part, types of frame, and combinations of glasses and air chambers for the transparent part, the aim is to choose the one that minimizes the cost without violating any restriction imposed to the thermal refurbishment, in particular the current energy efficiency regulations in the zone. To optimally solve this problem, it will be modelled as an Integer Linear Programming problem with binary variables. The case study will be Building 1B of the School for Building Engineering of the Polytechnic University of Valencia, Spain. It was built in the late 1960s and has had a very inefficient energy consumption record. The optimal solution will be found among more than 6 million feasible solutions.Salandin, A.; Soler Fernández, D.; Bevivino, M. (2020). 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Deep Convergence, Shared Ancestry, and Evolutionary Novelty in the Genetic Architecture of Heliconius Mimicry

Convergent evolution can occur through different genetic mechanisms in different species. It is now clear that convergence at the genetic level is also widespread, and can be caused by either (i) parallel genetic evolution, where independently evolved convergent mutations arise in different populations or species, or (ii) collateral evolution in which shared ancestry results from either ancestral polymorphism or introgression among taxa. The adaptive radiation of Heliconius butterflies shows color pattern variation within species, as well as mimetic convergence between species. Using comparisons from across multiple hybrid zones, we use signals of shared ancestry to identify and refine multiple putative regulatory elements in Heliconius melpomene and its comimics, Heliconius elevatus and Heliconius besckei, around three known major color patterning genes: optix, WntA, and cortex. While we find that convergence between H. melpomene and H. elevatus is caused by a complex history of collateral evolution via introgression in the Amazon, convergence between these species in the Guianas appears to have evolved independently. Thus, we find adaptive convergent genetic evolution to be a key driver of regulatory changes that lead to rapid phenotypic changes. Furthermore, we uncover evidence of parallel genetic evolution at some loci around optix and WntA in H. melpomene and its distant comimic Heliconius erato. Ultimately, we show that all three of convergence, conservation, and novelty underlie the modular architecture of Heliconius color pattern mimicry

Decomposition techniques with mixed integer programming and heuristics for home healthcare planning

We tackle home healthcare planning scenarios in the UK using decomposition methods that incorporate mixed integer programming solvers and heuristics. Home healthcare planning is a difficult problem that integrates aspects from scheduling and routing. Solving real-world size instances of these problems still presents a significant challenge to modern exact optimization solvers. Nevertheless, we propose decomposition techniques to harness the power of such solvers while still offering a practical approach to produce high-quality solutions to real-world problem instances. We first decompose the problem into several smaller sub-problems. Next, mixed integer programming and/or heuristics are used to tackle the sub-problems. Finally, the sub-problem solutions are combined into a single valid solution for the whole problem. The different decomposition methods differ in the way in which subproblems are generated and the way in which conflicting assignments are tackled (i.e. avoided or repaired). We present the results obtained by the proposed decomposition methods and compare them to solutions obtained with other methods. In addition, we conduct a study that reveals how the different steps in the proposed method contribute to those results. The main contribution of this paper is a better understanding of effective ways to combine mixed integer programming within effective decomposition methods to solve real-world instances of home healthcare planning problems in practical computation time

Pharmacogenetic prediction of clinical outcome in advanced colorectal cancer patients receiving oxaliplatin/5-fluorouracil as first-line chemotherapy

To determine whether molecular parameters could be partly responsible for resistance or sensitivity to oxaliplatin (OX)-based chemotherapy used as first-line treatment in advanced colorectal cancer (CRC). We studied the usefulness of the excision repair cross-complementing 1 (ERCC1), xeroderma pigmentosum group D (XPD), XRCC1 and GSTP1 polymorphisms as predictors of clinical outcome in these patients. We treated 126 CRC patients with a first-line OX/5-fluorouracil chemotherapeutic regimen. Genetic polymorphisms were determined by real-time PCR on an ABI PRISM 7000, using DNA from peripheral blood. Clinical response (CR), progression-free survival (PFS) and overall survival (OS) were evaluated according to each genotype. In the univariate analysis for CR, ERCC1-118 and XPD 751 polymorphisms were significant (P=0.02 and P=0.05, respectively). After adjustment for the most relevant clinical variables, only ERCC1-118 retained significance (P=0.008). In the univariate analysis for PFS, ERCC1-118 and XPD 751 were significant (P=0.003 and P=0.009, respectively). In the multivariant analysis, only the XPD 751 was significant for PFS (P=0.02). Finally, ERCC1-118 and XPD 751 polymorphisms were significant in the univariate analysis for OS (P=0.006 and P=0.015, respectively). Both genetic variables remained significant in the multivariate Cox survival analysis (P=0.022 and P=0.03). Our data support the hypothesis that enhanced DNA repair diminishes the benefit of platinum-based treatments

UNC93B1 Mediates Innate Inflammation and Antiviral Defense in the Liver during Acute Murine Cytomegalovirus Infection

Antiviral defense in the liver during acute infection with the hepatotropic virus murine cytomegalovirus (MCMV) involves complex cytokine and cellular interactions. However, the mechanism of viral sensing in the liver that promotes these cytokine and cellular responses has remained unclear. Studies here were undertaken to investigate the role of nucleic acid-sensing Toll-like receptors (TLRs) in initiating antiviral immunity in the liver during infection with MCMV. We examined the host response of UNC93B1 mutant mice, which do not signal properly through TLR3, TLR7 and TLR9, to acute MCMV infection to determine whether liver antiviral defense depends on signaling through these molecules. Infection of UNC93B1 mutant mice revealed reduced production of systemic and liver proinflammatory cytokines including IFN-α, IFN-γ, IL-12 and TNF-α when compared to wild-type. UNC93B1 deficiency also contributed to a transient hepatitis later in acute infection, evidenced by augmented liver pathology and elevated systemic alanine aminotransferase levels. Moreover, viral clearance was impaired in UNC93B1 mutant mice, despite intact virus-specific CD8+ T cell responses in the liver. Altogether, these results suggest a combined role for nucleic acid-sensing TLRs in promoting early liver antiviral defense during MCMV infection

Foot function during gait and parental perceived outcome in older children with symptomatic club foot deformity

Aims To assess if older symptomatic children with club foot deformity differ in perceived disability and foot function during gait, depending on initial treatment with Ponseti or surgery, compared to a control group. Second aim was to investigate correlations between foot function during gait and perceived disability in this population. Methods In all, 73 children with idiopathic club foot were included: 31 children treated with the Ponseti method (mean age 8.3 years; 24 male; 20 bilaterally affected, 13 left and 18 right sides analyzed), and 42 treated with primary surgical correction (mean age 11.6 years; 28 male; 23 bilaterally affected, 18 left and 24 right sides analyzed). Foot function data was collected during walking gait and included Oxford Foot Model kinematics (Foot Profile Score and the range of movement and average position of each part of the foot) and plantar pressure (peak pressure in five areas of the foot). Oxford Ankle Foot Questionnaire, Disease Specific Index for club foot, Paediatric Quality of Life Inventory 4.0 were also collected. The gait data were compared between the two club foot groups and compared to control data. The gait data were also correlated with the data extracted from the questionnaires. Results Our findings suggest that symptomatic children with club foot deformity present with similar degrees of gait deviations and perceived disability regardless of whether they had previously been treated with the Ponseti Method or surgery. The presence of sagittal and coronal plane hindfoot deformity and coronal plane forefoot deformity were associated with higher levels of perceived disability, regardless of their initial treatment. Conclusion This is the first paper to compare outcomes between Ponseti and surgery in a symptomatic older club foot population seeking further treatment. It is also the first paper to correlate foot function during gait and perceived disability to establish a link between deformity and subjective outcomes.</p

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

Complex modular architecture around a simple toolkit of wing pattern genes

Identifying the genomic changes that control morphological variation and understanding how they generate diversity is a major goal of evolutionary biology. In Heliconius butterflies, a small number of genes control the development of diverse wing colour patterns. Here, we used full-genome sequencing of individuals across the Heliconius erato radiation and closely related species to characterize genomic variation associated with wing pattern diversity. We show that variation around colour pattern genes is highly modular, with narrow genomic intervals associated with specific differences in colour and pattern. This modular architecture explains the diversity of colour patterns and provides a flexible mechanism for rapid morphological diversification.We acknowledge the University of Puerto Rico, the Puerto Rico INBRE grant P20 GM103475 from the National Institute for General Medical Sciences (NIGMS), a component of the National Institutes of Health (NIH); CNRS Nouraugues and CEBA awards (B.A.C.); National Science Foundation awards DEB-1257839 (B.A.C.), DEB-1257689 (W.O.M.), DEB-1027019 (W.O.M.); awards 1010094 and 1002410 from the Experimental Program to Stimulate Competitive Research (EPSCoR) program of the National Science Foundation (NSF) for computational resources; and the Smithsonian Institution. This research was supported in part by Lilly Endowment, Inc., through its support for the Indiana University Pervasive Technology Institute, and in part by the Indiana METACyt Initiative. The Indiana METACyt Initiative at IU is also supported in part by Lilly Endowment, Inc

UK Medical Cannabis Registry: an analysis of clinical outcomes of medicinal cannabis therapy for generalized anxiety disorder

Objectives Anxiety disorders are one of the most common reasons for seeking treatment with cannabis-based medicinal products (CBMPs). Current pharmacological treatments are variable in efficacy and the endocannabinoid system has been identified as a potential therapeutic target. This study aims to detail the changes in health-related quality-of-life (HRQoL) and clinical safety following CBMP therapy for generalized anxiety disorder. Methods A case series from the UK Medical Cannabis Registry was performed. Primary outcomes included changes from baseline in patient-reported outcome measures (the General Anxiety Disorder Scale (GAD-7), EQ-5D-5L (a measure of health-related quality of life), and Sleep Quality Scale (SQS)) at 1, 3 and 6 months. Statistical significance was defined as p<0.050. Results Sixty-seven patients were treated for generalized anxiety disorder. Statistically significant improvements were observed in GAD-7, EQ-5D-5L Index Value, EQ5D Visual Analog Scale, and SQS scores at 1, 3 and 6 months (p<0.050). Twenty-five (39.1%) patients reported adverse events during the follow-up period. Conclusion This study suggests that CBMPs may be associated with improvements in HRQoL outcomes when used as a treatment for generalized anxiety disorder. These findings must be treated with caution considering limitations of study design; however this data may help inform future clinical studies and practice

Unlimited multistability in multisite phosphorylation systems

Reversible phosphorylation on serine, threonine and tyrosine is the most widely studied posttranslational modification of proteins (1, 2). The number of phosphorylated sites on a protein (n) shows a significant increase from prokaryotes, with n less than or equal to 7 sites, to eukaryotes, with examples having n greater than or equal to 150 sites (3). Multisite phosphorylation has many roles (4, 5) and site conservation indicates that increasing numbers of sites cannot be due merely to promiscuous phosphorylation. A substrate with n sites has an exponential number (2^n) of phospho-forms and individual phospho-forms may have distinct biological effects (6, 7). The distribution of these phospho-forms and how this distribution is regulated have remained unknown. Here we show that, when kinase and phosphatase act in opposition on a multisite substrate, the system can exhibit distinct stable phospho-form distributions at steady state and that the maximum number of such distributions increases with n. Whereas some stable distributions are focused on a single phospho-form, others are more diffuse, giving the phospho-proteome the potential to behave as a fluid regulatory network able to encode information and flexibly respond to varying demands. Such plasticity may underlie complex information processing in eukaryotic cells (8) and suggests a functional advantage in having many sites. Our results follow from the unusual geometry of the steady-state phospho-form concentrations, which we show to constitute a rational algebraic curve, irrespective of n. We thereby reduce the complexity of calculating steady states from simulating 3 times 2^n differential equations to solving two algebraic equations, while treating parameters symbolically. We anticipate that these methods can be extended to systems with multiple substrates and multiple enzymes catalysing different modifications, as found in posttranslational modification 'codes' (9) such as the histone code (10, 11). Whereas simulations struggle with exponentially increasing molecular complexity, mathematical methods of the kind developed here can provide a new language in which to articulate the principles of cellular information processing (12)