Robust possibilistic programming to design a closed-loop blood supply chain network considering service-level maximization and lateral resupply.

Reconfiguring the structure of the supply chain network is one of the most strategic and vital decisions in designing a supply chain network. In this study, a Closed-Loop Blood Supply Chain Network (CLBSCN) considering blood group compatibility, ABO-Rh(D), and blood product shelf life has been studied to determine the best strategic and tactical decisions simultaneously considering lateral resupply/transshipment and service-level maximization. Several vital parameters, including supply and demand, are considered fuzzy numbers to approximate reality due to the nature of the world.

Designing a sustainable closed-loop supply chain network considering lateral resupply and backup suppliers using fuzzy inference system.

Sustainability is key factor for transforming traditional supply chain networks into modern ones. This study, for the first time, considers the impacts of the backup suppliers and lateral transshipment/resupply simultaneously on designing a Sustainable Closed-Loop Supply Chain Network (SCLSCN) to decrease the shortage that may occur during the transmission of produced goods in the network. In this manner, the fuzzy multi-objective mixed-integer linear programming model is proposed to design an efficient SCLSCN resiliently.

A novel mouse model of type 2N VWD was developed by CRISPR/Cas9 gene editing and recapitulates human type 2N VWD.

Type 2N von Willebrand disease is caused by mutations in the factor VIII (FVIII) binding site of von Willebrand factor (VWF), resulting in dysfunctional VWF with defective binding capacity for FVIII. We developed a novel type 2N mouse model using CRISPR/Cas9 technology. In homozygous VWF2N/2N mice, plasma VWF levels were normal (1167 ± 257 mU/mL), but the VWF was completely incapable of binding FVIII, resulting in 53 ± 23 mU/mL of plasma FVIII levels that were similar to those in VWF-deficient (VWF-/-) mice.

Platelet-targeted hyperfunctional FIX gene therapy for hemophilia B mice even with preexisting anti-FIX immunity.

Gene therapy may lead to a cure for hemophilia B (HB) if it is successful. Data from clinical trials using adeno-associated virus (AAV)-mediated liver-targeted FIX gene therapy are very encouraging. However, this protocol can be applied only to adults who do not have liver disease or anti-AAV antibodies, which occur in 30% to 50% of individuals.

A rat model of severe VWD by elimination of the VWF gene using CRISPR/Cas9.

Background: Von Willebrand Disease (VWD) is the most common inherited bleeding disorder, caused by quantitative and qualitative changes in von Willebrand factor (VWF). The biology of VWD, studied in canine, porcine, and murine models, differ in species-specific biology of VWF and the amenability to experimental manipulations such as phlebotomy. The factor VIII (FVIII) levels in these models are higher than in humans with type 3 VWD, suggesting functional differences between FVIII and VWF.

The severe spontaneous bleeding phenotype in a novel hemophilia A rat model is rescued by platelet FVIII expression.

Previous studies have shown that platelet-specific factor VIII (FVIII) expression (2bF8) restores hemostasis and induces immune tolerance in hemophilia A (HA) mice even with preexisting inhibitors. Here we investigated for the first time whether platelet FVIII expression can prevent severe spontaneous bleeding in rat HA, a model mimicking the frequent spontaneous bleeding in patients with severe HA. A novel FVIII-/- rat model in a Dahl inbred background (Dahl-FVIII-/-) with nearly the entire rat FVIII gene inverted was created by using a CRISPR/Cas9 strategy.

Aging and Mobility in Rural and Small Urban Areas: A Survey of North Dakota.

To investigate issues of aging and mobility in rural and small urban areas, this study analyzes the results from a survey AARP conducted of its North Dakota members. Specific objectives are to estimate the impact of age and other demographic and geographic characteristics on various measures of mobility, including ability to drive, use of public transportation, trip frequency for both discretionary and nondiscretionary travel, unmet travel demand, barriers to using public transportation, and satisfaction with available transportation options. Although most surveyed still drive, results show decreased mobility with increases in age and for people with disabilities due to decreases in driving and an increased likelihood of lack of transportation limiting the number of trips taken.

Phylogenetic analyses of two mitochondrial metabolic genes sampled in parallel from angiosperms find fundamental interlocus incongruence.

Plant molecular phylogeneticists have supported an analytical approach of combining loci from different genomes, but the combination of mitochondrial sequences with chloroplast and nuclear sequences is potentially problematic. Low substitution rates in mitochondrial genes should decrease saturation, which is especially useful for the study of deep divergences. However, individual mitochondrial loci are insufficiently informative, so that combining congruent loci is necessary.