Zeitschriftenartikel zum Thema „String-nets“

AbstractIn Schweigert and Yang (Methods Appl Symmetry Integr Geom, 2021) it was shown how string-net spaces for the Cardy bulk algebra in the Drinfeld center $${\mathsf {Z}}({\mathsf {C}})$$ Z ( C ) of a modular tensor category $${\mathsf {C}}$$ C give rise to a consistent set of correlators. We extend their results to include open-closed world sheets and allow for more general field algebras, which come in the form of $$({\mathsf {C}}|{\mathsf {Z}}({\mathsf {C}}))$$ ( C | Z ( C ) ) -Cardy algebras. To be more precise, we show that a set of fundamental string-nets with input data from a $$({\mathsf {C}}|{\mathsf {Z}}({\mathsf {C}}))$$ ( C | Z ( C ) ) -Cardy algebra gives rise to a solution of the sewing constraints formulated in Kong et al. (Adv Math 262:604–681, 2014) and that any set of fundamental string-nets solving the sewing constraints determine a $$({\mathsf {C}}|{\mathsf {Z}}({\mathsf {C}}))$$ ( C | Z ( C ) ) -Cardy algebra up to isomorphism. Hence we give an alternative proof of the results in Kong et al. (2014) in terms of string-nets.

Macropods have been captured by a variety of techniques: hand nets, trap yards, baited traps, cannon nets, drugged baits, syringe darts and stunning. These techniques differ in selectivity, in the likelihood of physical trauma or capture myopathy, and in the number of personnel required. Each technique is also limited to particular habitats or environmental conditions. A new draw-string trap was developed to capture kangaroos moving under fences, using a tunnel of soft netting attached to a steel weldmesh floor and suspended from a weldmesh frame. Draw-string closures at each end of the netting allowed selective and safe capture of kangaroos by two operators.

ABSTRACT In the surface waters of sulfidic springs near Regensburg, Bavaria, Germany, the SM1 euryarchaeon, together with filamentous bacteria, forms the recently described unique string-of-pearls community. In addition to naturally occurring string-of-pearls communities, the growth of these communities was also observed on polyethylene nets provided as an artificial attachment material in the streamlets of springs. In order to learn more about the distribution and origin of the SM1 euryarchaeon and its possible occurrence in the subsurface, polyethylene nets were incubated as deeply as possible in different spring holes. After a short residence time, slime-like, milky drops, almost completely composed of SM1 euryarchaeon, were attached to the nets, indicating that this organism grows independent of a partner in deeper earth layers. A newly designed in situ biofilm trapping system allowed the quantitative harvesting of organisms exhibiting this newly discovered lifestyle of the SM1 euryarchaeon for detailed biological studies. The discovery of naturally occurring archaeal biofilms extends our knowledge of the biology and ecological significance of archaea in their environments.

Abstract Sickle cell disease (SCD) is an inherited hemoglobin disorder caused by a single base change (A-T) in the beta-globin gene of hemoglobin with ensuing recurring inflammation that results in progressive end-organ damage and early mortality. Production of neutrophil extracellular traps (NETs) have been shown to be a key component of this inflammatory process in SCD pathophysiology. We sought to determine the relevance of NETosis versus a different type of programmed cell death (apoptosis) in SCD. We used an indirect assay using healthy neutrophils exposed to paired plasma samples (n=16) from SCD patients in steady-state and crisis for 30 min to 7 hrs, and a direct approach of observing neutrophils (3 healthy and 3 SCD) themselves up to 4 hrs. Features of NETosis (histone citrullination, nuclear decondensation, string nets) and apoptosis (piknotic nuclei, c-Parp, membrane damage) were assessed by imaging flow cytometry and fluorescence microscopy. Additionally, plasma titers for 20 inflammatory analytes were determined for the 16 paired SCD samples and 4 healthy controls. High circulating IL-6 levels at crisis found in 9/16 of the paired samples correlated with an increased number of NETs at crisis compared to steady-state. NETs were also observed directly in SCD neutrophils at steady state but not consistently. When NETs or histone citrullination were absent or low, c-Parp was typically detected. Additionally, membrane damage was observed in neutrophils from all SCD donors. The data suggest that the SCD environment disrupts neutrophil homeostasis and activate multiple cell death programs. SCD NETosis appears to be heterogeneous, its contribution to the disease pathophysiology remains to be determined.

Abstract Polymerisation of deoxygenated-HbS in sickle cell disease (SCD) leads to alteration of the shape and function of the red blood cells (RBC), resulting in hemolytic anemia and recurrent episodes of micro-vascular occlusion, triggering a cascade of downstream events and inflammation that underlies the progressive multi-systemic organ damage. Neutrophils have a critical role in promoting sickle pathophysiology; patients with higher leukocyte count, particularly neutrophils, tend to have a higher risk for more severe manifestations as well as earlier mortality. SCD neutrophils display a specific overreactive phenotype, including increased adhesive properties and production of reactive oxygen species. Activated neutrophils can also produce extracellular traps (NETs) in response to pathogens or other inflammatory stimuli. Studies have shown that prolonged exposure of healthy neutrophils to SCD plasma leads to formation of mature string-like NETs. These strings of decondensed chromatin covered with elastase (NE) or myeloperoxidase (MPO) might contribute to SCD pathophysiology. Here, we investigated if SCD neutrophils had enhanced intrinsic potential for NETs formation (i.e. could form NETs in the absence of a stimulus). We evaluated NETosis both indirectly, in which neutrophils isolated from healthy subjects were incubated with plasma from HbSS patients and directly, in which neutrophils isolated from HbSS patients were compared with those isolated from healthy donors. 17 HbSS patients in steady-state (all on hydroxyurea) and 11 race and sex matched healthy donors were included in the direct assays; the NETosis-related events were observed over a period of 7 minutes to 4 hours. For the indirect assay, we used plasma from 19 HbSS patients (14 on hydroxyurea, 5 off hydroxyurea and/or transfused), all of whom provided samples in steady-state and acute pain crisis (paired samples); the healthy neutrophils were treated with SCD plasma for up to 7 hours. A pain crisis was defined as an episode of acute pain that has no evident cause other than SCD, resulting in hospitalization and treatment with parenteral opioids. Steady state was defined as the period from at any time 8 weeks prior to or after a crisis. Patients were excluded when they were <18 or >80 years of age, pregnant or had a history of blood transfusion in the previous 8 weeks. The IRB approved the studies under NIH protocol numbers NCT00081523 (SCD subjects) and 03-H-0015 (healthy controls and SCD subjects). The NETosis features (histone citrullination H4cit3, nuclear decondensation, DNA-NE-MPO strings) were assessed by imaging flow cytometry and fluorescence microscopy. In the indirect assays, healthy neutrophils made more string NETs when treated with the SCD plasma (from both steady state and crisis) compared to plasma from healthy donors (Figure 1A), and NETs response was further increased with plasma from acute compared to their paired steady state sample (N=19, p=0.0114) (Figure 1B). Plasma from patients on or off hydroxyurea induced comparable NETosis responses. This confirmed a higher ability for the crisis milieu to modulate NETosis. Directly, neutrophils isolated from SCD patients as compared to those from healthy controls, showed increased number of decondensed H4cit3 positive nuclei, after only 7 min of incubation in RPMI (N=7, p=0.0688). By comparison the response to high concentration (20 uM) of Hemin - a regular product of hemolysis, was similar in the SCD and the healthy neutrophils (p=0.6871) (Figure 1C). This data suggested that the SCD environment might activate neutrophils to produce NETs in the absence of a specific stimulus. Fluorescence microscopy confirmed that neutrophils isolated from the patients did produce significantly more DNA-NE strings without any stimulation compared to healthy neutrophils (N=9, p=0.0079). After Hemin treatment, NETs response in SCD neutrophils was also higher than that of the healthy controls, but not statistically significant (Figure 1D). Our data provide the first direct in vitro evidence that neutrophils in SCD are innately prone to NETosis but whether and how these might contribute to the initiation or progress of SCD vaso-occlusive crises is yet to be determined. Disclosures No relevant conflicts of interest to declare.

By applying smaller crown sizes and intensive growing techniques, many advantages can be identified compared to the extensive orchards. Also, nursing/pruning and harvest work can be performed more effectively. The outer and inner quality parameters of the fruit and the effectiveness of plant protection techniques are improved. The smaller crown size enables us to apply technologies for ensuring yield safety (e.g. hail, rain, bird nets), resulting in an increase in productivity. The introduction of smaller trees poses a great challenge to cherry production. Trials with dwarfing rootstocks have not yet been successful, therefore, we must use the cv. Mahaleb rootstock, which is excellently adapted to the Hungarian conditions, and also has a stronger growth. In addition, rootstocks with such strong growth are needed for the necessary regeneration of the productive parts of cherry cultivars, there is a need for. At the research garden of the University of Debrecen in Pallag, we planted 21 cherry cultivars on cv. Mahaleb (CT500) rootstock, in a 4 m x 1 m spacing pattern, in the spring of 2000. In our study, we demonstrated the possibilities of developing and maintaining the string super spindle through repeated summer pruning, in terms of growth, bud and fruit formation,. Based on these parameters, we determined which cultivars are the most suitable for intensive production.

This survey aimed to identify the major diseases affecting the Green-the-Home (GTH) vegetable gardens project beneficiaries in Barangays Guadalupe and Marcos in Baybay City, Leyte, and Barangay Liberty, Hilongos, Leyte, Philippines. The study documented the occurrence, incidence, and severity of various vegetable diseases, including the existing pest management practices of vegetable growers. Disease incidence and severity observed in vegetable gardens varied depending on the type of disease, crop, and site. The surveyed crops included okra, upo, ampalaya, tomato, string beans, sweet pepper, chili, eggplant, and cucumber, which are common in the sampling areas. The most common diseases found within the three project sites were okra leaf mold, Cercospora leaf spot of ampalaya, Cercospora leaf spot of sweet pepper, and Cercospora leaf spot of chili. The majority of vegetable growers employed physical and cultural pest management approaches, such as weeds removal (66.6%), the use of nets (63.3%), intercropping (60%), tillage (50%) and bagging (46.6%). Disease occurrence in the areas was influenced by environmental factors such as rainfall, temperature, humidity, and poor management practices of vegetable gardens. Since Baybay and Hilongos have the same climatic pattern, such environmental factors are consistent in both areas. It is recommended that the Government and other lead agencies, such as the Department of Agriculture (DA) and the Agricultural Training Institute (ATI), assist GTH in promoting pests and diseases literacy programs among vegetable growers. They should also provide adequate access to extension services and disseminate appropriate, safe, and long-term pest management strategies to vegetable growers.

Objective. Osteomyelitis (OM) is one of the most risky and challenging diseases. Emerging evidence indicates OM is a risk factor for increasing incidence of venous thromboembolism (VTE) development. However, the mechanisms have not been intensively investigated. Methods. The OM-related dataset GSE30119 and VTE-related datasets GSE19151 and GSE48000 were downloaded from the Gene Expression Omnibus (GEO) database and analyzed to identify the differentially expressed genes (DEGs) (OMGs1 and VTEGs1, respectively). Functional enrichment analyses of Gene Ontology (GO) terms were performed. VTEGs2 and OMGs2 sharing the common GO biological process (GO-BP) ontology between OMGs1 and VTEGs1 were detected. The TRRUST database was used to identify the upstream transcription factors (TFs) that regulate VTEGs2 and OMGs2. The protein-protein interaction (PPI) network between VTEGs2 and OMGs2 was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and then visualized in Cytoscape. Topological properties of the PPI network were calculated by NetworkAnalyzer. The Molecular Complex Detection (MCODE) plugin was utilized to perform module analysis and choose the hub modules of the PPI network. Results. A total of 587 OMGs1 and 382 VTEGs1 were identified from the related dataset, respectively. GO-BP terms of OMGs1 and shared DGEs1 were mainly enriched in the neutrophil-related immune response process, and the shared GO-BP terms of OMGs1 and VTEGs1 seemed to be focused on cell activation, immune, defense, and inflammatory response to stress or biotic stimulus. 230 VTEGs2, 333 OMGs2, and 13 shared DEGs2 were detected. 3 TF-target gene pairs (SP1-LSP1, SPI1-FCGR1A, and STAT1-FCGR1A) were identified. The PPI network contained 1611 interactions among 467 nodes. The top 10 hub proteins were TP53, IL4, MPO, ELANE, FOS, CD86, HP, SOCS3, ICAM1, and SNRPG. Several core nodes (such as MPO, ELANE, and CAMP) were essential components of the neutrophil extracellular traps (NETs) network. Conclusion. This is the first data-mining study to explore shared signatures between OM and VTE by the integrated bioinformatic approach, which can help uncover potential biomarkers and therapeutic targets of OM-related VTE.

We show that string-net models provide a novel geometric method to construct invariants of mapping class group actions. Concretely, we consider string-net models for a modular tensor category C. We show that the datum of a specific commutative symmetric Frobenius algebra in the Drinfeld center Z(C) gives rise to invariant string-nets. The Frobenius algebra has the interpretation of the algebra of bulk fields of the conformal field theory in the Cardy case.

In his PhD thesis [G. Goosen, Oriented 123-tqfts via string-nets and state-sums, PhD thesis, Stellenbosch University, Stellenbosch (2018)], Goosen combined the string-net and the generators-and-relations formalisms for arbitrary once-extended 3-dimensional topological quantum field theories (TQFTs). In this paper, we work this out in detail for the simplest nontrivial example, where the underlying spherical fusion category is the category of [Formula: see text]-graded vector spaces. This allows us to give an elementary string-net description of the linear maps associated to 3-dimensional bordisms. The string-net formalism also simplifies the description of the mapping class group action in the resulting TQFT. We conclude the paper by performing some example calculations from this viewpoint.

We provide a description of virtual non-local matrix product operator (MPO) symmetries in projected entangled pair state (PEPS) representations of string-net models. Given such a PEPS representation, we show that the consistency conditions of its MPO symmetries amount to a set of six coupled equations that can be identified with the pentagon equations of a bimodule category. This allows us to classify all equivalent PEPS representations and build MPO intertwiners between them, synthesising and generalising the wide variety of tensor network representations of topological phases. Furthermore, we use this generalisation to build explicit PEPS realisations of domain walls between different topological phases as constructed by Kitaev and Kong [Commun. Math. Phys. 313 (2012) 351-373]. While the prevailing abstract categorical approach is sufficient to describe the structure of topological phases, explicit tensor network representations are required to simulate these systems on a computer, such as needed for calculating thresholds of quantum error-correcting codes based on string-nets with boundaries. Finally, we show that all these string-net PEPS representations can be understood as specific instances of Turaev-Viro state-sum models of topological field theory on three-manifolds with a physical boundary, thereby putting these tensor network constructions on a mathematically rigorous footing.

BACKGROUND: Subarachnoid hemorrhage (SAH) can lead to acute or delayed cerebral ischemia. Recent findings have revealed that spasm of microvessels, called microvasospasm, may contribute to SAH-related cerebral ischemia, and perivascular inflammation is considered important in the development of microvasospasms. However, owing to the difficulty in investigating the dynamics of vascular and perivascular events, little is known about the mechanisms underlying microvasospasms. METHODS: We established an experimental system aiming to investigate the vascular and perivascular pathology of SAH by combining a SAH mouse model with intravital 2-photon imaging. SAH was induced by intracisternal blood injection, and the distribution of erythrocytes, neutrophil behavior, and morphological changes in the pial arterioles were analyzed over time by 2-photon microscopy imaging. To further explore the role of neutrophils and neutrophil extracellular traps (NETs) in microvasospasm, we performed neutrophil depletion by intraperitoneal administration of neutrophil-specific antibody or NETs removal by intracisternal administration of DNase. RESULTS: Erythrocytes were immediately distributed in the perivascular space of the arterioles after SAH induction; neutrophils intensively infiltrated the perivascular space within 2 days and subsequently showed NETosis; and pial arterioles in the same region developed pearl-string-like microvasospasms in the subacute phase. Neutrophil depletion significantly reduced the number of microvasospasms. Furthermore, the removal of perivascular NETs drastically reduced microvasospasms. CONCLUSIONS: By establishing a unique experimental system, we demonstrated that perivascular NETs could be a new therapeutic target for microvasospasms.

Gauge symmetries play an essential role in determining the interactions of particle physics. Where do they come from? Might the gauge symmetries of the Standard Model unify in the ultraviolet or might they be emergent in the infrared, below some large scale close to the Planck scale? Emergent gauge symmetries are important in quantum many-body systems in quantum phases associated with long range entanglement and topological order, e.g. they arise in high temperature superconductors, with string-net condensation and in the A-phase of superfluid 3 He. String-nets and superfluid 3 He exhibit emergent properties similar to the building blocks of particle physics. Emergent gauge symmetries also play an important role in simulations of quantum field theories. This article discusses recent thinking on possible emergent gauge symmetries in particle physics, commenting also on Higgs phenomena and the vacuum energy or cosmological constant puzzle in emergent gauge systems. This article is part of the theme issue ‘Quantum technologies in particle physics’.

AbstractOne of the most striking features of gapped quantum phases that exhibit topological order is the presence of long-range entanglement that cannot be detected by any local order parameter. The formalism of projected entangled-pair states is a natural framework for the parameterization of gapped ground state wavefunctions which allows one to characterize topological order in terms of the virtual symmetries of the local tensors that encode the wavefunction. In their most general form, these symmetries are represented by matrix product operators acting on the virtual level, which leads to a set of algebraic rules characterizing states with topological quantum order. This construction generalizes the concepts of $${\mathsf {G}}$$ G - and twisted injectivity; the corresponding matrix product operators encode all topological features of the theory and provide a complete picture of the ground state manifold on the torus. We show how the string-net models of Levin and Wen fit within this formalism and in doing so provide a particularly intuitive interpretation of the pentagon equation for F-symbols as the pulling of matrix product operators through the string-net tensor network. Our approach paves the way to finding novel topological phases beyond string nets and elucidates the description of topological phases in terms of entanglement Hamiltonians and edge theories.

AbstractThe bigraph theory, devised by Robin Milner, is a recent mathematical framework for concurrent processes. Its generality is able to subsume many existing process calculi, for example, CCS, CSP, and Petri nets. Further, it provides a uniform proof of bisimilarity, which is a congruence. We present the first canonical string encoding for pure and lean bigraphs by lifting the breadth-first canonical form of rooted unordered trees to a unique representation for bigraphs up to isomorphism (i.e., lean-support equivalence). The encoding’s applicability is limited to atomic alphabets. The time complexity is $$O(n^{2}k\, d \log {d})$$ O ( n 2 k d log d ) , where n is the number of places, d the degree of the place graph and k the maximum arity of a bigraph’s signature. We provide proof of the correctness of our method and also conduct experimental measurements to assess the complexity.

AbstractManipulating intracellular biological processes and organelles has emerged as a pivotal strategy to influence cellular physiological functions. Mitochondria, recognized as the powerhouse of cells, play a crucial role in tumorigenesis and progression. Inspired by the Nature's tyrosinase‐catalyzed melanin formation within melanoma cells, here an approach is developed using a polysaccharide dually‐functionalized with tyrosine and triphenylphosphine (TPP) for targeted mitochondria cross‐linking in melanoma cells. This technique intricately weaves melanin nets within the cells, serving as a tether for the mitochondria and effectively decelerating tumor metabolism through nanoparticle‐net transformation. Tyrosinase acts as the “needle”, while the functionalized polysaccharide serves as the “string” successfully constructing nets within the cell. Furthermore, the tyrosinase‐catalyzed cross‐linking of tyrosine not only facilitates the production of artificial melanin but also enhances the photothermal conversion efficiency of melanoma cells, leading to decrease of the tumor growth. This study unveils a non‐drug method for regulating organelle physiological activity and introduces photothermal treatment. This work not only sheds light on the manipulation of cellular functions but also holds promise for advancing cancer therapeutic strategies.

The recent article by Jones et al. [arXiv:2307.12552 (2023)] gave local topological order (LTO) axioms for a quantum spin system, showed they held in Kitaev’s Toric Code and in Levin-Wen string net models, and gave a bulk boundary correspondence to describe bulk excitations in terms of the boundary net of algebras. In this article, we prove the LTO axioms for Kitaev’s Quantum Double model for a finite group G. We identify the boundary nets of algebras with fusion categorical nets associated to (Hilb(G),C[G]) or (Rep(G),CG) depending on whether the boundary cut is rough or smooth, respectively. This allows us to make connections to the work of Ogata [Ann. Henri Poincaré 25, 2353–2387 (2024)] on the type of the cone von Neumann algebras in the algebraic quantum field theory approach to topological superselection sectors. We show that the boundary algebras can also be calculated from a trivial G-symmetry protected topological phase (G-SPT), and that the gauging map preserves the boundary algebras. Finally, we compute the boundary algebras for the (3 + 1)D Quantum Double model associated to an Abelian group.

Abstract The site Zamostje 2, located in Sergiev-Posad district of Moscow (Russia) on the west bank of the Dubna River, has provided two Mesolithic and one Early Neolithic occupations dated from 7000 to 5400 cal BC. Thanks to the waterlogged environment, the site has an exceptional preservation. The site has yielded fishing screens, fishing fences, wooden fishing traps, and several small cordage remains elaborated with plant fibres, pine bark floats, fragments of paddles, and other wooden objects. In this work, we present the study of the fragments of cordage and fishing nets with the objective of providing new insights into the production and use of implements made of plant fibres. We have characterized the production process by analysing the morphological and technical characteristics by carrying out experimentation with plant fibres in order to obtain reference material to recognize them at an archaeological level. The analysis of 82 knots and 23 fragments of strings has allowed to determine that they were elaborated with single threads from 0.5 to 1.5 mm thick, which is noticeably smaller than most examples from other sites. All of them were elaborated with woody bast fibres.

Regular polyhedra and related structures such as complexes and nets play a prominent role in the study of materials such as crystals, nanotubes and viruses. An abstract regular polyhedron {\cal P} is the combinatorial analog of a classical regular geometric polyhedron. It is a partially ordered set of elements called faces that are completely characterized by a string C-group (G, T), which consists of a group G generated by a set T of involutions. A realization R is a mapping from {\cal P} to a Euclidean G space that is compatible with the associated real orthogonal representation of G. This work discusses an approach to the theory of realizations of abstract regular polyhedra with an emphasis on the construction of a realization and its decomposition as a blend of subrealizations. To demonstrate the approach, it is applied to the polyhedra whose automorphism groups are abstractly isomorphic to the non-crystallographic Coxeter group H 3.

Recent modeling of brain activities encompasses the fusion of different modalities. However, fusing brain modalities requires not only the efficient and compatible representation of the signals but also the benefits associated with it. For instance, the combination of the functional characteristics of EEGs with the structural features of functional magnetic resonance imaging contributes to a better interpretation localization of brain activities. In this paper, we consider the EEG signals as parallel 2D string images from which we extract their visual abstract representations of EEG features. This representation can benefit not only the EEG modeling of the signals but also a future fusion with another modality, like fMRI. In particular, the new methodology, called Bar-LG, provides a reduced discretization of the EEG signals into selected minima/maxima in order to be used in a form of tokens for EEG brain activities of interest. A formal context-free language is used to express and represent the extracted tokens for the selected active brain regions. Then, a Generalized Stochastic Petri-Nets (GSPN) model is used for expressing the functional associations and interactions of these EEG signals as 2D image regions. An illustrative EEG example of epileptic seizure is presented to show the Bar-LG methodology’s abstract capabilities.

Genus Gnetum, of which the majority species are pantropical liana, have broad industrial uses including for string, nets, and paper production. Although numerous studies have investigated anatomical structures during stem development, the underlying molecular mechanisms that regulate this developmental trajectory in Gnetum species remain poorly understood. A total of 12 full-length transcriptomes were generated from four stem developmental stages of an arborescent representative of this genus, Gnetum luofuense, using Oxford Nanopore Technologies. The results of this analysis reveal a total of 24,151 alternative splicing (AS) and 134,391 alternative polyadenylation events. A remarkably dynamic pattern of AS events, especially in the case of intron retentions, was found across the four developmental stages while no dynamic pattern was found among transcript numbers with varied poly(A) sites. A total of 728 long non-coding RNAs were also detected; the number of cis-regulated target genes dramatically increased while no changes were found among trans-regulated target genes. In addition, a K-means clustering analysis of all full-length transcripts revealed that primary growth is associated with carbohydrate metabolism and fungi defense, while secondary growth is closely linked with photosynthesis, nitrogen transportation, and leaf ontogenesis. The use of weighted gene co-expression network analysis as well as differentially expressed transcripts reveals that bHLH, GRF, and MYB-related transcription factors are involved in primary growth, while AP2/ERF, MYB, NAC, PLAZ, and bZIP participate in G. luofuense stem secondary growth. The results of this study provide further evidence that Nanopore sequencing technology provides a cost-effective method for generating full-length transcriptome data as well as for investigating seed plant organ development.

BackgroundOsteoarthritis (OA) is the most common joint disease, which mainly damages articular cartilage and involves the whole joint tissue. It has the characteristics of long course, repeated symptoms and high disability rate, and the incidence trend is gradually increasing. Tetramethylpyrazine (TMP) is the main alkaloid active substance in Ligusticum wallichii, a traditional Chinese medicine, which has the effect of promoting blood circulation and dredging collaterals, and has a good effect on the treatment of early OA, but its molecular mechanism has not been fully clarified so far. Based on network pharmacology, molecular docking simulation and animal experiments, this study explored the target and molecular mechanism of TMP in the treatment of OA.MethodsWe used PubChem, SwissTargetPrediction, and PharmMapper databases to predict the molecular structure and potential targets of TMP. GeneCards and DisGeNET databases were used to predict the relevant targets of OA. Apply UniProt database to convert targets into unified gene names, and proofread and remove duplicate gene names. The intersection targets of TMP and OA obtained on venny2.1.0 website were submitted to the STRING database to construct a PPI network. CytoScape 3.8.2 software was used to analyze the PPI network and obtain the sub-network modules and 10 key targets. The intersection targets of TMP and OA were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment using DAVID 6.8 database. The intersecting targets of TMP and OA, the biological process of GO enrichment, and KEGG signaling pathway were imported into Cytoscape 3.8.2 software to construct the TMP-target-pathway network diagram. Use molecular docking technology to simulate the interaction between TMP molecules and key targets, and predict the binding mode and binding ability. Animal models of rabbit knee osteoarthritis were prepared, and magnetic resonance imager (MRI) and fluorescence quantitative PCR (RT-qPCR) were used to observe the effect of TMP in treating OA as well as the expression of key target genes.Results585 potential targets of TMP, 3,857 potential targets of OA, and 49 intersecting targets of TMP and OA were obtained. The top 10 key target genes were obtained, in order of ranking: ALB, ESR1, IL10, CAT, F2, MPO, C3, CYP3A4, CYP2C9, ANXA1. GO and KEGG analysis implied that the key targets might act on OA by affecting endothelial cell permeability, peri-articular microcirculatory status, NETs production, activation of complement system and coagulation pathway, regulation of immune function of macrophages and T cells, and substance metabolism pathway in vivo, etc. The molecular mechanism might involve the formation of neutrophil extracellular trap, regulation of the actin cytoskeleton, complement and coagulation cascades, and T cell receptor signaling pathways, etc. Molecular docking simulations showed that the binding energy of IL10 and ANXA1 to TMP was greater than -5Kal/mol, but the other key target proteins showed better binding to TMP, and the binding energy was less than -5 kcal/mol. Animal experiments showed that TMP had a significant therapeutic effect on OA. The TMP group had significantly reduced knee joint effusion and bone marrow damage compared to the OA group (p &lt; 0.05). The qRT-PCR results showed that compared with the OA group, the mRNA expression of ESR1, CAT, C3, CYP3A4, CYP2C9, and ANXA1 in the TMP group increased (p &lt; 0.05), while there was no significant difference in mRNA expression of ALB, IL-10, F2, MPO, etc. (p &gt; 0.05).ConclusionTMP is effective in the treatment of OA, with multi-target and multi-pathway interactions. ESR1, CAT, C3, CYP3A4, CYP2C9, and ANXA1 may be potential targets for TMP treatment of OA. The molecular mechanism mainly involves the formation of neutrophil extracellular trap, regulation of the actin cytoskeleton, complement and coagulation cascades, and T cell receptor signaling pathways, etc.

Photo by Tingey Injury Law Firm on Unsplash ABSTRACT The coverage of healthcare costs allegedly brought about by people’s own earlier health-adverse behaviors is certainly a matter of justice. However, this raises the following questions: justice for whom? Is it right to take people’s past behaviors into account in determining their access to healthcare? If so, how do we go about taking those behaviors into account? These bioethical questions become even more complex when we consider them in the context of a commitment to publicly funded, universal healthcare coverage. INTRODUCTION Healthcare coverage of lifestyle-related conditions is certainly a matter of justice. However, this raises the following justice-related question: Is it right to consider people’s past behaviors in determining their access to healthcare? If so, the methods of taking those behaviors into account must be fair and justifiable. This bioethical question becomes even more complex when we consider it in the context of a commitment to publicly funded, universal healthcare coverage. This paper takes an old, classic debate, evaluates newer approaches, and offers an argument favoring a combined approach which alters the liberal-egalitarian solution to account for social justice. ANALYSIS I. Causes of Disease If healthcare coverage were universal, irrespective of socioeconomic status and lifestyle, people would contribute to the cost of remedying the lifestyle-induced health problems of others. In the West, lifestyle-related diseases are burdensome.[i] This paper approaches this concern from a western lens that incorporates both a European tradition of “social safety nets” and an American tradition of personal freedoms. By taking such an approach, solutions to the consequences of one’s past behavior burdening others must consider an individual’s personal freedom to choose to act as he or she wishes, with the distributive social and economic equality of the many. The concept of disease caused by lifestyle and diet is proven. Many health conditions include behavioral risk factors. Multi-pack smoking increases the risk of chronic lung disease, while obesity increases the risk of type 2 diabetes. Inattention to high blood pressure, high cholesterol, and a lack of exercise leads to increased risks of coronary artery disease.[ii] While poor lifestyle choices certainly influence these conditions, their causes are multifactorial, and it is difficult to say that any single string of poor choices led to their development. In a scenario where two men excessively eat fast food for 20 years, several discrete factors impact whether any of them might suffer an ischemic-embolic stroke or not. Genetics, circumstances, and activity will also contribute to outcomes. II. Alcohol-Related End-Stage Liver Disease One paper suggests that alcohol-related end-stage liver disease (ARESLD) differs from other multifactorial disorders as alcohol alone causes the disease.[iii] It justifies attributing personal responsibility to patients with ARESLD because the condition develops only after the cumulative effects of large quantities of alcohol consumed from years to decades.[iv] However, the paper undermines its position by admitting that even the susceptibility to becoming an alcoholic has some degree of genetic predisposition.[v] Given the extreme scarcity of donor livers, some patients may be prioritized over others on the transplant waiting list. Since donor livers cannot be given to everyone, transplanting a liver into an alcoholic may result in death for competing candidates whose liver disease was not their fault. All else being equal, if bioethicists avoid claiming moral deficiency or judgment, those with apparently self-inflicted ARESLD will not be deprived of treatment but will have a lower priority for transplant.[vi] In contrast, another position suggests that it is often difficult to define what behaviors are punishable as these are largely personal and value-laden.[vii] Still, people do not support using their own resources to support the consequences of others’ poor choices, no matter how objective.[viii] In democratic societies, one must take into consideration community morals and values.[ix] Even if we were to punish people for their health-adverse behaviors, we could not logistically employ the vigorous and sustained efforts necessary to determine whose actions are morally weak.[x] III. The Liberal-Egalitarian Proposal One past argument proposes a liberal-egalitarian solution to manage personal responsibility for so-called “lifestyle diseases.”[xi] This Rawlsian system combines the European-style “social safety net” commitment to social and economic equality with the American liberal notion of pluralist toleration and personal freedoms. This idealized system aims to hold people responsible for their choices rather than the consequences to mitigate the downside of blaming those who might not be blameworthy. The approach avoids determining the questionable nature of luck and personal responsibility for health outcomes, fairness in the distribution of economic burden, and the intrusiveness required to practically determine who acts in a morally wrong and health-adverse way. The liberal-egalitarian model, a theory of distributive justice, has two facets: the liberal principle that people should be held accountable for their choices and the egalitarian principle that people who make the same choices should have the same outcomes.[xii] This model attempts to fuse responsibility with equity by seeking to reward good behavior and tax bad behavior rather than punish the consequences of the action and navigate who deserves treatment. For instance, the hospital bedside is not the appropriate place to introduce responsibility for one’s health outcomes.[xiii] This appeals to the reality that, at that time, discerning the true causes of disease was not plausible and to humanity in avoiding a heartless and cruel approach. An argument in favor of the liberal-egalitarian model considers its method of implementation. This approach assumes that the healthcare system treats all individuals regardless of their choices or ability to cover costs. The liberal-egalitarian model also assumes that a certain adverse health condition is related, statistically speaking, to the consumption of a certain good and that good can be taxed. As such, it proposes to tax the consumption of that good to finance the collective burden which arises from that good’s consumption rather than require individuals to pay for their own treatment. In the example of ARESLD, the recommended solution would be taxing all alcohol. While a systematic infrastructure is not explicit, there is the implication that a per-unit tax can be imposed on alcohol so the total tax revenue would make up for the additional healthcare costs due to consumption.[xiv] Upholding the principle that all people who make the same choices should face the same costs, all consumers of alcohol would pay the same tax, regardless of factors such as genetic predisposition to alcoholism, lifestyle, or expected cost of treatment. Upholding the principle of individual responsibility, this model does not deny treatment to anyone, neutralizing factors outside that individual’s control by imposing the tax ex-ante. Other people are not burdened by those who consume the good. People who consume alcohol face a burden proportional to the amount consumed. This tax-based implementation is justified so long as the tax is not prohibitively high for the average consumer. Further, the model mitigates concerns over the intrusiveness of ascribing morality to health-adverse behaviors. IV. Moral and Social Arguments Against the Liberal-Egalitarian Position Arguments against the liberal-egalitarian model concerns its many assumptions. First, this model assumes that consumption of such goods is directly related to the health outcome and that these goods can be taxed.[xv] Certain people genetically predisposed to alcoholism would be predisposed to consume more alcohol. The model falls short when applied to scenarios where health outcomes are not consumption-based, such as engaging in unsafe sex or abstaining from healthy lifestyle choices like exercise. Second, some might argue that the liberal-egalitarian model fails to remain neutral. Residual moral judgments tied to consumption choices introduce non-neutrality. Although taxation in free societies is determined by democratic procedures rather than by individuals in the healthcare system, moral and value-based judgments will be implicit in deciding what behaviors are taxable, such as the purchase of cigarettes. Third, the liberal-egalitarian model fails to determine whether one’s behavior is autonomous, as socio-cultural-economic factors may influence it and behavior is more a product of society, peer pressure, or income. Those also may reflect systemic inequalities. Therefore, this model, which rewards, or taxes based solely on decisions, regardless of their consequences and motivations, fails to consider that a person’s decisions may not be completely autonomous. V. Libertarian Arguments Against the Liberal-Egalitarian Model a. State Intrusiveness as Counter to the Liberal-Egalitarian Model Last, there is a libertarian worry that if the state guarantees universal healthcare coverage to all people, the state will have to become highly intrusive and investigate people’s morals.[xvi] At least one-third of all disease burden in North America, Europe, and the Asia-Pacific is attributable to lifestyle measures such as tobacco smoking, alcohol consumption, high cholesterol, and obesity.[xvii] With these various lifestyles, it is not likely to agree on what conduct to tax or condemn.[xviii] The fine-toothed comb required to determine whether each citizen has been engaging in these behaviors would intrude on daily life and personal freedom. Libertarians champion the argument that impractical intrusiveness would result from universal healthcare, and such a degree of intrusiveness would likely be universally unacceptable.[xix] The liberal-egalitarian model mitigates the libertarian worry about state intrusiveness as it does not involve prying into one’s life and choices other than taxing goods. A liberal state should ideally be neutral to how people decide to live their lives. In all, libertarians can rest assured that the liberal-egalitarian tax-based model, through its ex-ante implementation, will require no prying state eyes. States that provide universal healthcare coverage and wish to condemn certain misconduct do not need to become overly intrusive to carry out measures to hold individuals accountable. b. Fairness Another libertarian worry regarding the guarantee of universal healthcare coverage in the context of lifestyle-driven diseases is that the public will be burdened unfairly with covering others’ ill-advised mistakes or bad luck. An ideal system to address this worry would link treatment or payment for treatment with whatever behavior caused that need.[xx] The distribution of burdens should be linked to how different individuals contributed to the creation of those burdens. Applied to health policy, we should ask how the need for a certain treatment arose when determining how to distribute its cost.[xxi] The liberal-egalitarian model aspires to hold individuals responsible for their choices, not for the consequences of such choices. This model significantly mitigates the libertarian worry over unfair burdens for covering other people’s mistakes or social conditions, which lead to those bad outcomes, by ensuring to not burden others with any of the costs for the treatment of people who decide to engage in certain health-adverse behaviors. The aforementioned taxation-based system would only tax those who also engage in the health-adverse behavior through consumption, and that tax directly pays for the necessary collective treatment. As such, those who do not consume the good are not involved with the payment scheme, while those who do consume the good are responsible for payment in a matter proportional to the amount of the good they have consumed. VI. Universal Coverage Taking a step back, one should consider whether these worries regarding the coverage of apparently self-inflicted health conditions in the context of universal healthcare are worthwhile issues. One perspective raises what is called the culturally imagined objection — an idea erroneously held by many that sick people, especially those who are poor and uneducated, bring these illnesses upon themselves due to poor decision-making and irresponsible risk-taking.[xxii] This perspective critiques the uniquely American view that, since individuals are free to choose their lifestyles, they should bear the costs of their lifestyle.[xxiii] Taking this argument further, some (perhaps the strongly libertarian) would say that the poor health status among many individuals is the price individuals must pay for their American way of life and the liberty and freedom to live as they wish. However, people should not completely punish individuals for their health-adverse behaviors because these choices are largely pre-determined by a person’s socioeconomic influences.[xxiv] The outcomes from these allegedly ill-advised behaviors, which largely affect poorer people, are not just poor behavior but rather a public health crisis. Perhaps the state and its people should take collective responsibility and cover the costs of treatment for those health outcomes without question, as a form of public service. Rather than worrying about accountability and taxing bad behavior or intrusiveness into personal decisions, some might argue that people need to collectively take responsibility for reducing the overarching systemic inequalities and covering the associated treatment costs as a measure of public health. VII. Proposed Solution Given the strengths of the liberal-egalitarian model and taking into account libertarian and social justice-oriented objections, an ideal solution for the coverage of lifestyle-related health problems needs to consider the complex relationship between a person’s behaviors and their apparent health outcomes. It must consider how society as a whole passes judgment on behaviors and how to take into account that many health-adverse decisions are not truly autonomous decisions, as various genetic and socioeconomic factors influence them. An ideal solution combines the liberal-egalitarian tax-based model with the social justice concerns of universal coverage. Whatever the cost for the treatment of medical issues resulting in part or entirely from lifestyle and diet, taxes collected from spending associated with the behavior (like the purchase of alcohol, junk food, and cigarettes) ex-ante should fund 50 percent of the cost of treatment, while the universal healthcare taxation scheme should include the other 50 percent. Such a system would provide an incentive to avoid the purchases that can lead to unhealthy consumption and make healthier choices, slightly punish and discourage such purchases through taxation, yet not overly punish people whose outcomes may have more to do with socioeconomic factors and genetics. Adding public responsibility demonstrates acknowledgement that health care is in the public interest and can mitigate public health inequalities. This solution would fuse personal responsibility with the public responsibility of state-sponsored social improvement while ensuring that all people have fair access to necessary treatment, no matter their ability to pay. CONCLUSION The 50-50 system this paper proposes reflects both justice and personal responsibility in covering healthcare costs allegedly brought about by people’s own health-adverse behaviors. By allocating tax revenue from consumption that contributes or even alone causes poor health outcomes, such a system incorporates personal responsibility. By using general tax revenue for health care, such a system would meet the libertarian requirement of providing care without any moral investigation of past behaviors and the social justice consideration of providing health care to those who may have unwittingly ventured into ill-health due to systemic injustice, socioeconomics, or genetics. - [i] Cappelen, A. W. (2005). Responsibility in health care: A liberal egalitarian approach. Journal of Medical Ethics, 31(8), 476–480. https://doi.org/10.1136/jme.2004.010421 [ii] Moss, A. H. (1991). Should alcoholics compete equally for liver transplantation? JAMA: The Journal of the American Medical Association, 265(10), 1295–1298. https://doi.org/10.1001/jama.1991.03460100097032 [iii] Moss, p. 1295-1298. [iv] Moss, p. 1296. [v] Moss, p. 1295-1298. [vi] Moss, p. 1295-1298. [vii] Cohen, C. IS THIS SUPPOSED TO BE COHEN AND BENJAMIN (1991). Alcoholics and liver transplantation. JAMA: The Journal of the American Medical Association, 265(10), 1299–1301. https://doi.org/10.1001/jama.1991.03460100101033 [viii] Cohen, p. 1299-1301. [ix] Moss, p. 1297. [x] Cohen, p. 1300. [xi] Cappelen, p. 478-480. [xii] Cappalen, p. 478-480. [xiii] Cappelen, p.479. [xiv] Cappelen, p. 479. [xv] Cappelen, p. 479 [xvi] Cohen, p. 1301. [xvii] Cappelen, p. 478. [xviii] Cohen, p. 1299-1301. [xix] Cohen, p. 1301. [xx] Cappelen, p. 476-480. [xxi] Cappelen, p. 476-480. [xxii] Kawachi, I. (2005). Why the United States is not number one in Health. Healthy, Wealthy, and Fair, 18–33. https://doi.org/10.1093/acprof:oso/9780195170665.003.0013 [xxiii] Kawachi, p. 18-33. [xxiv] Kawachi, p. 18-33.

Photo by Tingey Injury Law Firm on Unsplash ABSTRACT The coverage of healthcare costs allegedly brought about by people’s own earlier health-adverse behaviors is certainly a matter of justice. However, this raises the following questions: justice for whom? Is it right to take people’s past behaviors into account in determining their access to healthcare? If so, how do we go about taking those behaviors into account? These bioethical questions become even more complex when we consider them in the context of a commitment to publicly funded, universal healthcare coverage. INTRODUCTION Healthcare coverage of lifestyle-related conditions is certainly a matter of justice. However, this raises the following justice-related question: Is it right to consider people’s past behaviors in determining their access to healthcare? If so, the methods of taking those behaviors into account must be fair and justifiable. This bioethical question becomes even more complex when we consider it in the context of a commitment to publicly funded, universal healthcare coverage. This paper takes an old, classic debate, evaluates newer approaches, and offers an argument favoring a combined approach which alters the liberal-egalitarian solution to account for social justice. ANALYSIS l. Causes of Disease If healthcare coverage were universal, irrespective of socioeconomic status and lifestyle, people would contribute to the cost of remedying the lifestyle-induced health problems of others. In the West, lifestyle-related diseases are burdensome.[1] This paper approaches this concern from a western lens that incorporates both a European tradition of “social safety nets” and an American tradition of personal freedoms. By taking such an approach, solutions to the consequences of one’s past behavior burdening others must consider an individual’s personal freedom to choose to act as he or she wishes, with the distributive social and economic equality of the many. The concept of disease caused by lifestyle and diet is proven. Many health conditions include behavioral risk factors. Multi-pack smoking increases the risk of chronic lung disease, while obesity increases the risk of type 2 diabetes. Inattention to high blood pressure, high cholesterol, and a lack of exercise leads to increased risks of coronary artery disease.[2] While poor lifestyle choices certainly influence these conditions, their causes are multifactorial, and it is difficult to say that any single string of poor choices led to their development. In a scenario where two men excessively eat fast food for 20 years, several discrete factors impact whether any of them might suffer an ischemic-embolic stroke or not. Genetics, circumstances, and activity will also contribute to outcomes. ll. Alcohol-Related End-Stage Liver Disease One paper suggests that alcohol-related end-stage liver disease (ARESLD) differs from other multifactorial disorders as alcohol alone causes the disease.[3] It justifies attributing personal responsibility to patients with ARESLD because the condition develops only after the cumulative effects of large quantities of alcohol consumed from years to decades.[4] However, the paper undermines its position by admitting that even the susceptibility to becoming an alcoholic has some degree of genetic predisposition.[5] Given the extreme scarcity of donor livers, some patients may be prioritized over others on the transplant waiting list. Since donor livers cannot be given to everyone, transplanting a liver into an alcoholic may result in death for competing candidates whose liver disease was not their fault. All else being equal, if bioethicists avoid claiming moral deficiency or judgment, those with apparently self-inflicted ARESLD will not be deprived of treatment but will have a lower priority for transplant.[6] In contrast, another position suggests that it is often difficult to define what behaviors are punishable as these are largely personal and value-laden.[7] Still, people do not support using their own resources to support the consequences of others’ poor choices, no matter how objective.[8] In democratic societies, one must take into consideration community morals and values.[9] Even if we were to punish people for their health-adverse behaviors, we could not logistically employ the vigorous and sustained efforts necessary to determine whose actions are morally weak.[10] lll. The Liberal-Egalitarian Proposal One past argument proposes a liberal-egalitarian solution to manage personal responsibility for so-called “lifestyle diseases.”[11] This Rawlsian system combines the European-style “social safety net” commitment to social and economic equality with the American liberal notion of pluralist toleration and personal freedoms. This idealized system aims to hold people responsible for their choices rather than the consequences to mitigate the downside of blaming those who might not be blameworthy. The approach avoids determining the questionable nature of luck and personal responsibility for health outcomes, fairness in the distribution of economic burden, and the intrusiveness required to practically determine who acts in a morally wrong and health-adverse way. The liberal-egalitarian model, a theory of distributive justice, has two facets: the liberal principle that people should be held accountable for their choices and the egalitarian principle that people who make the same choices should have the same outcomes.[12] This model attempts to fuse responsibility with equity by seeking to reward good behavior and tax bad behavior rather than punish the consequences of the action and navigate who deserves treatment. For instance, the hospital bedside is not the appropriate place to introduce responsibility for one’s health outcomes.[13] This appeals to the reality that, at that time, discerning the true causes of disease was not plausible and to humanity in avoiding a heartless and cruel approach. An argument in favor of the liberal-egalitarian model considers its method of implementation. This approach assumes that the healthcare system treats all individuals regardless of their choices or ability to cover costs. The liberal-egalitarian model also assumes that a certain adverse health condition is related, statistically speaking, to the consumption of a certain good and that good can be taxed. As such, it proposes to tax the consumption of that good to finance the collective burden which arises from that good’s consumption rather than require individuals to pay for their own treatment. In the example of ARESLD, the recommended solution would be taxing all alcohol. While a systematic infrastructure is not explicit, there is the implication that a per-unit tax can be imposed on alcohol so the total tax revenue would make up for the additional healthcare costs due to consumption.[14] Upholding the principle that all people who make the same choices should face the same costs, all consumers of alcohol would pay the same tax, regardless of factors such as genetic predisposition to alcoholism, lifestyle, or expected cost of treatment. Upholding the principle of individual responsibility, this model does not deny treatment to anyone, neutralizing factors outside that individual’s control by imposing the tax ex-ante. Other people are not burdened by those who consume the good. People who consume alcohol face a burden proportional to the amount consumed. This tax-based implementation is justified so long as the tax is not prohibitively high for the average consumer. Further, the model mitigates concerns over the intrusiveness of ascribing morality to health-adverse behaviors. lV. Moral and Social Arguments Against the Liberal-Egalitarian Position Arguments against the liberal-egalitarian model concerns its many assumptions. First, this model assumes that consumption of such goods is directly related to the health outcome and that these goods can be taxed.[15] Certain people genetically predisposed to alcoholism would be predisposed to consume more alcohol. The model falls short when applied to scenarios where health outcomes are not consumption-based, such as engaging in unsafe sex or abstaining from healthy lifestyle choices like exercise. Second, some might argue that the liberal-egalitarian model fails to remain neutral. Residual moral judgments tied to consumption choices introduce non-neutrality. Although taxation in free societies is determined by democratic procedures rather than by individuals in the healthcare system, moral and value-based judgments will be implicit in deciding what behaviors are taxable, such as the purchase of cigarettes. Third, the liberal-egalitarian model fails to determine whether one’s behavior is autonomous, as socio-cultural-economic factors may influence it and behavior is more a product of society, peer pressure, or income. Those also may reflect systemic inequalities. Therefore, this model, which rewards, or taxes based solely on decisions, regardless of their consequences and motivations, fails to consider that a person’s decisions may not be completely autonomous. V. Libertarian Arguments Against the Liberal-Egalitarian Model a. State Intrusiveness as Counter to the Liberal-Egalitarian Model Last, there is a libertarian worry that if the state guarantees universal healthcare coverage to all people, the state will have to become highly intrusive and investigate people’s morals.[16] At least one-third of all disease burden in North America, Europe, and the Asia-Pacific is attributable to lifestyle measures such as tobacco smoking, alcohol consumption, high cholesterol, and obesity.[17] With these various lifestyles, it is not likely to agree on what conduct to tax or condemn.[18] The fine-toothed comb required to determine whether each citizen has been engaging in these behaviors would intrude on daily life and personal freedom. Libertarians champion the argument that impractical intrusiveness would result from universal healthcare, and such a degree of intrusiveness would likely be universally unacceptable.[19] The liberal-egalitarian model mitigates the libertarian worry about state intrusiveness as it does not involve prying into one’s life and choices other than taxing goods. A liberal state should ideally be neutral to how people decide to live their lives. In all, libertarians can rest assured that the liberal-egalitarian tax-based model, through its ex-ante implementation, will require no prying state eyes. States that provide universal healthcare coverage and wish to condemn certain misconduct do not need to become overly intrusive to carry out measures to hold individuals accountable. b. Fairness Another libertarian worry regarding the guarantee of universal healthcare coverage in the context of lifestyle-driven diseases is that the public will be burdened unfairly with covering others’ ill-advised mistakes or bad luck. An ideal system to address this worry would link treatment or payment for treatment with whatever behavior caused that need.[20] The distribution of burdens should be linked to how different individuals contributed to the creation of those burdens. Applied to health policy, we should ask how the need for a certain treatment arose when determining how to distribute its cost.[21] The liberal-egalitarian model aspires to hold individuals responsible for their choices, not for the consequences of such choices. This model significantly mitigates the libertarian worry over unfair burdens for covering other people’s mistakes or social conditions, which lead to those bad outcomes, by ensuring to not burden others with any of the costs for the treatment of people who decide to engage in certain health-adverse behaviors. The aforementioned taxation-based system would only tax those who also engage in the health-adverse behavior through consumption, and that tax directly pays for the necessary collective treatment. As such, those who do not consume the good are not involved with the payment scheme, while those who do consume the good are responsible for payment in a matter proportional to the amount of the good they have consumed. Vl. Universal Coverage Taking a step back, one should consider whether these worries regarding the coverage of apparently self-inflicted health conditions in the context of universal healthcare are worthwhile issues. One perspective raises what is called the culturally imagined objection — an idea erroneously held by many that sick people, especially those who are poor and uneducated, bring these illnesses upon themselves due to poor decision-making and irresponsible risk-taking.[22] This perspective critiques the uniquely American view that, since individuals are free to choose their lifestyles, they should bear the costs of their lifestyle.[23] Taking this argument further, some (perhaps the strongly libertarian) would say that the poor health status among many individuals is the price individuals must pay for their American way of life and the liberty and freedom to live as they wish. However, people should not completely punish individuals for their health-adverse behaviors because these choices are largely pre-determined by a person’s socioeconomic influences.[24] The outcomes from these allegedly ill-advised behaviors, which largely affect poorer people, are not just poor behavior but rather a public health crisis. Perhaps the state and its people should take collective responsibility and cover the costs of treatment for those health outcomes without question, as a form of public service. Rather than worrying about accountability and taxing bad behavior or intrusiveness into personal decisions, some might argue that people need to collectively take responsibility for reducing the overarching systemic inequalities and covering the associated treatment costs as a measure of public health. Vll. Proposed Solution Given the strengths of the liberal-egalitarian model and taking into account libertarian and social justice-oriented objections, an ideal solution for the coverage of lifestyle-related health problems needs to consider the complex relationship between a person’s behaviors and their apparent health outcomes. It must consider how society as a whole passes judgment on behaviors and how to take into account that many health-adverse decisions are not truly autonomous decisions, as various genetic and socioeconomic factors influence them. An ideal solution combines the liberal-egalitarian tax-based model with the social justice concerns of universal coverage. Whatever the cost for the treatment of medical issues resulting in part or entirely from lifestyle and diet, taxes collected from spending associated with the behavior (like the purchase of alcohol, junk food, and cigarettes) ex-ante should fund 50 percent of the cost of treatment, while the universal healthcare taxation scheme should include the other 50 percent. Such a system would provide an incentive to avoid the purchases that can lead to unhealthy consumption and make healthier choices, slightly punish and discourage such purchases through taxation, yet not overly punish people whose outcomes may have more to do with socioeconomic factors and genetics. Adding public responsibility demonstrates acknowledgement that health care is in the public interest and can mitigate public health inequalities. This solution would fuse personal responsibility with the public responsibility of state-sponsored social improvement while ensuring that all people have fair access to necessary treatment, no matter their ability to pay. CONCLUSION The 50-50 system this paper proposes reflects both justice and personal responsibility in covering healthcare costs allegedly brought about by people’s own health-adverse behaviors. By allocating tax revenue from consumption that contributes or even alone causes poor health outcomes, such a system incorporates personal responsibility. By using general tax revenue for health care, such a system would meet the libertarian requirement of providing care without any moral investigation of past behaviors and the social justice consideration of providing health care to those who may have unwittingly ventured into ill-health due to systemic injustice, socioeconomics, or genetics. - [1] Cappelen, A. W. (2005). Responsibility in health care: A liberal egalitarian approach. Journal of Medical Ethics, 31(8), 476–480. https://doi.org/10.1136/jme.2004.010421 [2] Moss, A. H. (1991). Should alcoholics compete equally for liver transplantation? JAMA: The Journal of the American Medical Association, 265(10), 1295–1298. https://doi.org/10.1001/jama.1991.03460100097032 [3] Moss, p. 1295-1298. [4] Moss, p. 1296. [5] Moss, p. 1295-1298. [6] Moss, p. 1295-1298. [7] Cohen, C. IS THIS SUPPOSED TO BE COHEN AND BENJAMIN (1991). Alcoholics and liver transplantation. JAMA: The Journal of the American Medical Association, 265(10), 1299–1301. https://doi.org/10.1001/jama.1991.03460100101033 [8] Cohen, p. 1299-1301. [9] Moss, p. 1297. [10] Cohen, p. 1300. [11] Cappelen, p. 478-480. [12] Cappalen, p. 478-480. [13] Cappelen, p.479. [14] Cappelen, p. 479. [15] Cappelen, p. 479 [16] Cohen, p. 1301. [17] Cappelen, p. 478. [18] Cohen, p. 1299-1301. [19] Cohen, p. 1301. [20] Cappelen, p. 476-480. [21] Cappelen, p. 476-480. [22] Kawachi, I. (2005). Why the United States is not number one in Health. Healthy, Wealthy, and Fair, 18–33. https://doi.org/10.1093/acprof:oso/9780195170665.003.0013 [23] Kawachi, p. 18-33. [24] Kawachi, p. 18-33.