Visualizing multi-dimensional pareto-optimal fronts with a 3D virtual reality system

In multiobjective optimization, there are several targets that are in conflict, and thus they all cannot reach their optimum simultaneously. Hence, the solutions of the problem form a set of compromised trade-off solutions (a Pareto-optimal front or Pareto-optimal solutions) from which the best solution for the particular problem can be chosen. However, finding that best compromise solution is not an easy task for the human mind. Pareto-optimal fronts are often visualized for this purpose because in this way a comparison between solutions according to their location on the Pareto-optimal front becomes somewhat easier. Visualizing a Pareto-optimal front is straightforward when there are only two targets (or objective functions), but visualizing a front for more than two objective functions becomes a difficult task. In this paper, we introduce a new and innovative method of using three-dimensional virtual reality (VR) facilities to present multi-dimensional Pareto-optimal fronts. Rotation, zooming and other navigation possibilities of VR facilities make easy to compare different trade-off solutions, and fewer solutions need to be explored in order to understand the interrelationships among conflicting objective functions. In addition, it can be used to highlight and characterize interesting features of specific Pareto-optimal solutions, such as whether a particular solution is close to a constraint boundary or whether a solution lies on a relatively steep trade-off region. Based on these additional visual aids for analyzing trade-off solutions, a preferred compromise solution may be easier to choose than by other means

Attenuated Semliki Forest virus for cancer treatment in dogs : safety assessment in two laboratory Beagles

Background: Dogs suffer from spontaneous tumors which may be amenable to therapies developed for human cancer patients, and dogs may serve as large-animal cancer models. A non-pathogenic Semliki Forest virus vector VA7-EGFP previously showed promise in targeting human tumor xenografts in mice, but the oncolytic capacity of the virus in canine cancer cells and the safety of the virus in higher mammals such as dogs, are not known. We therefore assessed the oncolytic potency of VA7-EGFP against canine cancer cells by infectivity and viability assays in two dog solid tumor cell lines. Furthermore we performed a 3-week safety study in two adult Beagles which received a single intravenous injection of similar to 2 x 10(5) plaque forming units of parental A7(74) strain. Results: VA7-EGFP was able to replicate in and kill both canine cancer cell lines tested. No adverse events were observed in either of the two virus-injected adult Beagles and no infective virus could be recovered from any of the biological samples collected over the course of the study. Neutralizing antibodies to Semliki Forest virus became detectable in the dogs at 5 days post infection and remained elevated until study termination. Conclusions: Based on these results, testing of the oncolytic potential of attenuated Semliki Forest virus in canine cancer patients appears feasible.Peer reviewe

A Comparison Between Uwb and Laser-based Pedestrian Tracking

Despite the availability of GNSS on consumer devices enabled personal navigation for most of the World population in most of the outdoor conditions, the problem of precise pedestrian positioning is still quite challenging when indoors or, more in general, in GNSS-challenging working conditions. Furthermore, the covid-19 pandemic also raised of pedestrian tracking, in any environment, but in particular indoors, where GNSS typically does not ensure sufficient accuracy for checking people distance. Motivated by the mentioned needs, this paper investigates the potential of UWB and LiDAR for pedestrian positioning and tracking. The two methods are compared in an outdoor case study, nevertheless, both are usable indoors as well. The obtained results show that the positioning performance of the LiDAR-based approach overcomes the UWB one, when the pedestrians are not obstructed by other objects in the LiDAR view. Nevertheless, the presence of obstructions causes gaps in the LiDAR-based tracking: instead, the combination of LiDAR and UWB can be used in order to reduce outages in the LiDAR-based solution, whereas the latter, when available, usually improves the UWB-based results.Peer reviewe

The effect of dexamethasone on defective nephrin transport caused by ER stress: A potential mechanism for the therapeutic action of glucocorticoids in the acquired glomerular diseases

The mechanism by which glucocorticoids govern antiproteinuric effect in nephrotic syndrome remains unknown. Present study examined the protective role of dexamethasone (DEX) in the intracellular trafficking of nephrin under endoplasmic reticulum (ER) stress. Human embryonic kidney-293 cell line expressing a full-length human nephrin was cultured in mediums containing 5.5 or 25 mM glucose with or without DEX. The result revealed that glucose starvation evoked a rapid ER stress leading to formation of underglycosylated nephrin that was remained in the ER as a complex with calreticulin/calnexin. DEX rescued this interfered trafficking through binding to its receptor and stimulating the mitochondrial transcripts and adenosine 5′ triphosphate (ATP) production, leading to synthesis of fully glycosylated nephrin. These results suggest that ER-stress in podocytes may cause alteration of nephrin N-glycosylation, which may be an underlying factor in the pathomechanism of the proteinuria in nephrotic syndrome. DEX may restore this imbalance by stimulating expression of mitochondrial genes, resulted in the production of ATP that is essential factor for proper folding machinery aided by the ER chaperones

Deep-coverage whole genome sequences and blood lipids among 16,324 individuals.

Large-scale deep-coverage whole-genome sequencing (WGS) is now feasible and offers potential advantages for locus discovery. We perform WGS in 16,324 participants from four ancestries at mean depth >29X and analyze genotypes with four quantitative traits-plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. Common variant association yields known loci except for few variants previously poorly imputed. Rare coding variant association yields known Mendelian dyslipidemia genes but rare non-coding variant association detects no signals. A high 2M-SNP LDL-C polygenic score (top 5th percentile) confers similar effect size to a monogenic mutation (~30 mg/dl higher for each); however, among those with severe hypercholesterolemia, 23% have a high polygenic score and only 2% carry a monogenic mutation. At these sample sizes and for these phenotypes, the incremental value of WGS for discovery is limited but WGS permits simultaneous assessment of monogenic and polygenic models to severe hypercholesterolemia

Optimizing care for children with difficult-to-treat and severe asthma through specialist paediatric asthma centres:expert practical experience and advice

Severe asthma in children carries an unacceptable treatment burden, yet its rarity means clinical experience in treating it is limited, even among specialists. Practical guidance is needed to support clinical decision-making to optimize treatment for children with this condition. This modified Delphi convened 16 paediatric pulmonologists and allergologists from northern Europe, all experienced in treating children with severe asthma. Informed by interviews with stakeholders involved in the care of children with severe asthma (including paediatricians, nurses and carers), and an analysis of European guidelines, the experts built a consensus focused on the gaps in existing guidance. Explored were considerations for optimizing care for patients needing biologic treatment, and for selecting home or hospital delivery of biologics. This consensus is aimed at clinicians in specialist centres, as well as general paediatricians, paediatric allergologists and paediatric pulmonologists who refer children with the most severe asthma to specialist care. Consensus is based on expert opinion and is intended for use alongside published guidelines. Our discussions revealed three key facets to optimizing care. Firstly, early asthma detection in children presenting with wheezing and/or dyspnoea is vital, with a low threshold for referral from primary to specialist care. Secondly, children who may need biologics should be referred to and managed by specialist paediatric asthma centres; we define principles for the specialist team members, tests, and expertise necessary at such centres, as well as guidance on when homecare biologics delivery is and is not appropriate. Thirdly, shared decision-making is essential at all stages of the patient’s journey: clear, concise treatment plans are vital for patient/carer self-management, and structured processes for transition from paediatric to adult services are valuable. The experts identified the potential for specialist paediatric asthma nurses to play a significant role in facilitating multidisciplinary working. Through this project is agreed a framework of practical advice to optimize the care of children with severe asthma. We encourage clinicians and policymakers to implement this practical advice to enhance patient care.</p

Reduced cross-protection against influenza A(H3N2) subgroup 3C.2a and 3C.3a viruses among Finnish healthcare workers vaccinated with 2013/14 seasonal influenza vaccine

Peer reviewe