Global antimicrobial resistance (AMR) is currently governed by a decentralized regime complex composed of multiple institutions with overlapping and sometimes conflicting principles, norms, rules, and procedures. Such a decentralized regime complex provides certain advantages and disadvantages when compared to a centralized regime. A pandemic instrument can optimize the regime complex for AMR by leveraging the strengths of both centralization and decentralization. Existing climate treaties under the UNFCCC offer lessons for achieving this hybrid approach. Antimicrobial resistance (AMR) is a complex, intersectoral, and long-enduring problem, with no single global institution set to comprehensively govern it. Instead, global efforts for AMR appear to be coalescing around what political science would call “the regime complex for antimicrobial resistance”; that is, a decentralized network of multiple institutions with overlapping and sometimes conflicting principles, norms, rules, and procedures.This paper outlines the anatomy of the emerging regime complex for AMR. It then considers whether strategies applied in climate governance can be leveraged to improve the coherence of global AMR governance while harnessing the benefits offered by decentralization. More specifically, it argues that drawing on a hybrid approach and design elements from treaties within climate governance, namely, the Cancún and Paris Agreements, a pandemic instrument can leverage the responsiveness, flexibility, adaptability, and resilience of decentralization and the consistency, reliability, and efficiency of centralization.1.AMR is currently governed by a decentralized regime complex. Regime complexes are defined as partially overlapping and sometimes conflicting networks of three or more international regimes that relate to a common issue.These seven elemental regimes, moreover, interact with at least one, but more often many other elemental regimes in the complex through bilateral and multilateral partnerships. For example, the human health, animal health, food, and environmental regimes interact through the WHO, FAO, WOAH, and UNEP’s quadripartite partnerships on AMR, the human health and agriculture regimes interact bilaterally through the WHO and FAO’s joint programmes on food standards and safety.Many of the seven elemental regimes have a high degree of overlap in their memberships, but, crucially, there are important divergences in membership across the regime complex. For instance, the WHO and FAO are largely comprised of the same member states; but discrepancies in memberships exist across the trade, development, and biomedical humanitarianism regimes.And finally, across the regime complex, there are several instances of overlapping and sometimes conflicting principles, rules, norms, and procedures. For example, both the human health security and the trade regimes believe that policy objectives such as promoting health should seek to minimize their impact on trade, while the principles of the human health, food, and animal health regimes all acknowledge the interdependencies among human, environmental, and animal health and the importance of One Health approaches. On the other hand, the trade regime’s principle that intellectual property rights improve health innovation, as well as the rules within the Trade Related Aspects of Intellectual Property Rights (TRIPs) that embody that principle, can often pose challenges for the development and humanitarian biomedicine regimes’ principle of access to medicine as human right.The following snapshot further elucidates the characteristics of the emerging regime complex for AMR .2.The AMR governance landscape is currently populated by dozens of actors and institutions, each with their own mandates and initiatives .11 As deThe most obvious challenge is that AMR’s decentralized governance structure makes it very difficult to parse through the many layers and different frontiers of global activity on the issue. In the absence of an overarching framework, such complexity poses challenges for understanding, tracking, and measuring progress on AMR.Without centralized coordination mechanisms to establish and sustain commitments to and investments for innovation, critical health infrastructure, and equitable distribution of medical countermeasures, AMR action will continue to skew toward the interests of high-income countries and not the long-term interests of the global public. This is especially problematic because AMR represents a weakest link challenge: the global response is only as strong as the weakest response in any given setting because it only takes the emergence and spread of one resistant microbe to undermine the efforts of all. This globally shared vulnerability requires centralized coordination and collaboration mechanisms to ensure equitable investments in global preparedness and prevention everywhere.Additionally, decentralization can pose equity challenges related to how priorities are set, decisions made, and resources distributed. In the absence of a global framework, wealthier states who invest in research and development for new antimicrobials and other technologies tend to do so according to their interests and needs. In other words, and as with many matters in global health, money sets the agenda especially in the absence of established global priorities.Without centralized coordination mechanisms to establish and sustain commitments to and investments for innovation, critical health infrastructure, and equitable distribution of medical countermeasures, AMR action will continue to skew toward the interests of high-income countries and not the long-term interests of the global public. This is especially problematic because AMR represents a weakest link challenge: the global response is only as strong as the weakest response in any given setting because it only takes the emergence and spread of one resistant microbe to undermine the efforts of all. This globally shared vulnerability requires centralized coordination and collaboration mechanisms to ensure equitable investments in global preparedness and prevention everywhere.Beyond these challenges, overlapping and uncoordinated initiatives open the possibility for duplications and redundancies, while also leaving important gaps unaddressed — as is the current case with global leadership on crucial AMR initiatives such as surveillance.Despite these challenges, a decentralized regime provides several benefits.Furthermore, the existence of redundancies could mean that there are extra fail-safes as well as multiple ongoing pathways to success.Finally, a decentralized regime complex can be more flexible than a centralized one. Flexibility allows countries to engage selectively with initiatives that are more relevant for their own domestic conditions. Flexibility also lets the rules bend without breaking, enhancing the sustainability of any international agreement. This could make cooperation around AMR more likely to work, since states usually engage with agreements and endeavors that they have faith in.3.One could argue that a decentralized regime complex, with its multiple centers of activity and diffuse initiatives, is the best option for generating and sustaining effective action on AMR quickly and meeting the need for more location specific knowledge and stakeholder driven solutions for AMR in the short run. To be sure, however, certain elements of global AMR require a more centralized governance structure to guide action in the long run. For instance, centralized mechanisms through the pandemic instrument could deliver much needed commitments and a global vision for global AMR efforts. It can also raise awareness based on a shared understanding of the issue and its urgency, enable the tracking of progress, distribute responsibilities and benefits equitably, and hold countries accountable to their promises.Considering the benefits offered by both, the best option for a pandemic instrument is to strike a balance between the responsiveness, flexibility, adaptability, and resilience of decentralization and the consistency, reliability, and efficiency provided by centralization. At the national level at least, studies have found that centralized and decentralized governance arrangements often co-exist.The same holds true for global governance arrangements for complex issues. The enormous regime complex for climate change, for example, has emerged with thousands of multilateral environmental agreements, organizations, and initiatives focused on addressing climate change, but recent efforts through the 2010 Cancún Agreements and, more recently, the 2015 Paris Agreement under the UNFCCC strike a balance between centralization and decentralization.The Cancún and Paris Agreements were negotiated against the backdrop of a growing regime complex for climate change and strategically leverage the benefits of decentralization under unified global frameworks to coordinate the global response to climate change.For example, the Paris Agreement contains a clear vision and a 2-degree Celsius global target that guides and gauges country behavior without necessarily prescribing it. This goal, in combination with the Paris Agreement’s reliance on individually determined contributions, lets countries determine how they will help meet the goal on their own terms. Put differently, the Paris Agreement provides top-down targets but relies on bottom-up implementation to achieve them.Crucially, in relying on nationally determined, bottom-up initiatives as the main driver of global progress, the Cancún Agreements recognize that some countries require financial support to maximize their ability to address climate change and contribute to the universal global goal. In doing so, the Cancún Agreements established a Green Climate Fund, which, with its limitations notwithstanding, acts as a necessary financing mechanism to support less developed countries in implementing domestic climate action in this hybrid approach.Finally, another key example of a hybrid mechanism embraced by both the Cancún and Paris Agreements are their commitments to the multi-stakeholder forum of the UNFCCC. The forum, as part of the UNFCCC’s Conference of Parties, provides a centralized mechanism and agenda for discussion and dialogue, but is inclusive enough such that many NGOs and interests groups can achieve observer status to attend, monitor, and question states-parties during the conference proceedings, thereby uniting a mix of centralized and decentralized elements.Global information sharing and awareness raising mechanisms that are cognizant of location and scale, relevant knowledge, and evidence.A standardized, consistent, and interoperable global surveillance system.Transparency, accountability, and enforcement mechanisms.A diverse and inclusive multi-stakeholder forum.Global financing mechanisms, such as a global pooled fund, for global investments in infection prevention and control, and the innovation and distribution of medical countermeasures including antimicrobials, diagnostics, and alternative therapies. Alternative funding techniques could include a deposit mechanism or multi party-single closing type deals to leverage decentralized funds for AMR initiatives.Global coordination for response to resistant outbreaks.A pandemic instrument could achieve a hybrid of centralized and decentralized elements by leveraging existing national action plans for AMR, while establishing a global goal against which to assess them and crystalizing a process for ratcheting up their ambition. Moreover, a combination of legally enshrined universal commitments that all countries must undertake, as well as a suite of common but differentiated responsibilities could further enshrine a balance of centralized and decentralized elements within the instrument.By adopting similar institutional design elements as the Paris Agreement, a pandemic instrument could provide much needed leadership on these specific issues in need of centralization while also being adequately flexible to encompass and permit location specific initiatives tailored to different national and local circumstances.Addressing AMR as a complex, cross sectoral issue requires coordination across the regime complex for AMR. But, counter-intuitively, the situation of decentralization that currently defines the AMR governance landscape presents some special advantages, and centralization is not necessarily the best option for all aspects of global AMR governance. Instead, a Pandemic Treaty should determine the value added by centralization, including consistency, enforceability, and reliability, and only include aspects of AMR governance that would appropriately benefit from these values, such as surveillance, global priorities, and funding mechanisms. It could then use design elements to benefit from the power of both centralization and decentralization, such as a universal global goal to guide nationally determined contributions; a combination of universal and common but differentiated responsibilities; an inclusive forum for priority setting, dialogue, and decision making; coordinated resource distribution systems; and a system to coordinate the global respond to resistant outbreaks. This hybrid approach could enable more centralized coordination on some activities but still let bottom up- and cross scale linkages thrive while benefiting from the adaptability, flexibility, and resilience provided by decentralization.


Quantum contextuality supports quantum computation and communication. One of its main vehicles is hypergraphs. The most elaborated are the Kochen–Specker ones, but there is also another class of contextual sets that are not of this kind. Their representation has been mostly operator-based and limited to special constructs in three- to six-dim spaces, a notable example of which is the Yu-Oh set. Previously, we showed that hypergraphs underlie all of them, and in this paper, we give general methods—whose complexity does not scale up with the dimension—for generating such non-Kochen–Specker hypergraphs in any dimension and give examples in up to 16-dim spaces. Our automated generation is probabilistic and random, but the statistics of accumulated data enable one to filter out sets with the required size and structure. Quantum contextuality, which precludes assignments of predetermined values to dense sets of states, has found applications in quantum communication ,2,3, quaThere are three classes of contextual sets elaborated on in the literature which are not of the more common kind of Kochen–Specker (KS) sets ,33,34 anThe first class consists of the operator-based state-independent contextual (SIC) sets put forward by Klyachko et al. , Yu and n vectors, where n is the dimension of space in which a hypergraph resides [The second class consists of hypergraphs built by multiples of mutually orthogonal vectors where at least one of the multiples contains less than  resides ,34,41.The third class consists of the so-called true-implies-false and true-implies-true sets ,43.All sets from these three classes as well as their hypergraph generalization that we elaborate on are contextual, and therefore, we call them non-KS contextual sets.We provide a general method for arbitrarily generating many non-KS hypergraphs in spaces of up to 16-dim. In order to achieve these goals, we make use of non-binary non-KS McKay–Megill–Pavičić hypergraphs (MMPHs) and their language. By means of our algorithms and programs, we arbitrarily obtain many MMPHs, which can be used for various applications, e.g., to generate new entropic tests of contextuality or new operator-based contextual sets.The paper is organized as follows.n-dim space correspond to vectors and their orthogonalities, i.e., m-tuples  lines passing through them.Definition 2.An n-dim non-binary MMPH (NBMMPH),  [is an MMPH 1 s and 0 s in such a way thatfor which each hyperedge contains m vertices, 1. No two vertices within any of its edges are both assigned a value of 1;2. In any of its edges, not all of the vertices are assigned a value of 0.H), n≥3,  is an MMDefinition 3.An NBMMPH in which  KS MMPH.For  theorem ,34,45,46Definition 4.An NBMMPH in which  non-KS MMPH.In this paper, we consider only those non-KS MMPHs for which Definition 5.An n-dim binary MMPH (BMMPH),  MMPH for which each hyperedge contains m vertices, 1. No two vertices within any of its edges are both assigned a value of 1;2. In any of its edges, not all of the vertices are assigned a value of 0.Definition 6.A non-KS NBMMPH to which vertices are added so as to make the number of vertices equal to n in every hyperedge is called a filled MMPH.Filled MMPHs are mostly BMMPHs.Definition 7.A critical NBMMPH is an NBMMPH that is minimal in the sense that removing any of its hyperedges turns it into a BMMPH.Definition 8.Vertex multiplicity is the number of hyperedge vertexes “i” belongs to; we denote it by Definition 9.A master is a non-critical MMPH that contains smaller critical and non-critical sub-MMPHs. A collection of sub-MMPHs of an MMPH master forms its class.parity proof ofthe contextuality of a k-l NBMMPH with odd l and where each vertex shares an even number of edges stems from its inherent contradiction: because each vertex shares an even number of hyperedges, there should be an even number of hyperedges with 1 s. At the same time, each edge can contain only one 1 by definition, and since there are an odd number of hyperedges in the MMPH, there should also be an odd number of edges with 1 s.A Definition 10.A coordinatization of a non-KS NBMMPH is a set of vectors assigned to its vertices that is a subset of n-dim vectors in  MMPH or its smallest master (they need not coincide) or any of its masters.n-tuple of orthogonal vectors, while a “coordinatization” of each hyperedge of the original non-KS NBMMPH is represented by a vector m-tuple  or any its masters. In our present approach, a coordinatization is automatically assigned to each hypergraph by the very procedure of its generation from master MMPHs, as we show below.In other words, a “coordinatization” of each hyperedge of a filled MMPH or a smallest master MMPH is represented by an k vertices and l edges is denoted as a k-l MMPH. ASCII string representation is used for computer processing. MMPH strings are handled by means of algorithms embedded in the programs SHORTD, MMPSTRIP, MMPSUBGRAPH, VECFIND, STATES01, and others [An MMPH is encoded with the help of printable ASCII characters, with the exception of “space”, “0”, “+”, “,” and “.”, organized in single strings; its hyperedges are separated by commas, and each string ends with a period. When all ASCII characters are exhausted, one reuses them prefixed by “+”, and then again by “++”, and so forth. An MMPH with d others ,49,50,51To generate non-KS NBMMPHs, we make use of the following methods.M1 consists of dropping vertices contained in single hyperedges (multiplicity ity m=1)  of eitheM2 consists of a random addition of hyperedges to MMPHs so as to obtain bigger ones, which then serve us to generate smaller non-KS NBMMPHs by stripping hyperedges randomly again;M3 consists of the random deletion of vertices in either NBMMPHs or a BMMPHs until a non-KS NBMMPH is reached.We combine all three methods to obtain an arbitrary number of non-KS NBMMPHs in an arbitrary dimension. The methods rely on the property of MMPHs where, by stripping an MMPH or NBMMPH  or BMMPH of its hyperedges, we can arrive at smaller non-KS NBMMPHs in contrast to a critical KS NBMMPH whose stripping of hyperedges can never yield another  NBMMPH.k-l MMPHs refer to hypergraphs with k vertices and l hyperedges (Definition 1), while the corresponding graphs have more than l edges. For example, in ALK corresponds to a graph clique with three edges: AL, LK, and KA.In M1. The 13-16 MMPH is not critical, and it contains four critical sub-MMPHs, the smallest of which is 10-9 [Yu-Oh’s three-dim non-KS NBMMPH, shown in  is 10-9 .Howard, Wallman, Veitech, and Emerson’s four-dim 30-108 non-KS NBMMPH, shown in Cabello, Portillo, Solís, and Svozil’s five-dim 10-9 non-KS NBMMPH, shown in Our methods can generate NBMMPHs that are critical as well as those that are not. Therefore, although none of the aforementioned examples are critical, we focus on critical ones, because they offer the simplest implementation and presentation. The rationale for adopting such an approach is that only minimal contextual sets, i.e., critical NBMMPHs, are relevant for experimental implementations, since their supersets just contain additional orthogonalities that do not change the contextuality property of their smallest critical set. Hence, while designing MMPHs for particular implementations, we should attempt to find the ones that are critical and are provided via automated generations of MMPHs.M1 and M2. Therefore, below, we give distributions and samples of just four- and five-dim critical non-KS NBMMPHs presented in n vertices (n being the dimension of the considered MMPH), none of which has the multiplicity In , we giveM1, we first generate the supermasters from the vector components. In the four-dim space, we obtain the 24-24 supermaster from the To obtain non-KS NBMMPHs via n-dim critical non-KS MMPHs under the requirement that at least one of their hyperedges must contain n vertices, of which none have a multiplicity of 1 , because We generate Cabello, Portillo, Solís, and Svozil also give a number of minimal six-dim TIFS non-KS NBMMPHs in . In dimensions greater than nine, such vertices do not appear, although even here we can avoid their generation by applying M3 to KS NBMMPHs, as shown in In the seven-dim space, masters obtained from simple vector components, such as M1. However, the MMPHs with M3, as shown in M3.The eight-dim MMPH master is big (2768-1346016), but the stripping technique can still provide us with non-KS NBMMPHs via riticals  so as toM1 applicable. Thus, after the random stripping of 12,068,200 hyperedges, we obtained submasters with 505 hyperedges. By requiring that at least one of the hyperedges contains n vertices and that some of them can have the multiplicity 4ac7efhK2 contains nine vertices.  The filled 13-16, i.e., 44-6, also shown in M2 inapplicable.The nine-dim NBMMPH master obtained from n-vertex requirement in full If we wanted to keep our pscaling ,56, as fM3. The procedure consists of removing vertices and/or hyperedges in such a way that an NBMMPH stops being critical, which enables us to generate smaller critical non-KS NBMMPHs from it via STATES01.A 10-dim or any higher-dimensional masters are too big to be generated from vector components. Therefore, to obtain the non-KS MMPH in those dimensions, we rely on minimal KS NBMMPHs obtained via dimensional upscaling  while apIn In M3.In the following sections, we stay with this approach while applying n vertices, none of which has the multiplicity It has been proven that the minimal complexity  of the dimensional upscaling of KS MMPHs does not scale up with dimension . In  5656, we giIn this paper, we first generated non-KS contextual NBMMPHs (non-binary MMP hypergraphs) with the help of master sets generated from simple vector components whose complexity exponentially scales with dimension—for dimensions four to eight—and then by means of methods whose complexity does not scale with dimension. The need for developing such methods and obtaining MMPHs in higher dimensions has emerged from recent elaborations of classes of contextual sets that are not of the KS kind, all of which have an MMP hypergraph representation. Examples of such elaborations in the literature and their correspondence with MMPHs are given in In Therefore, to ensure arbitrarily exhaustive generation of MMPHs in ever higher dimensions, we need a method whose complexity does not grow with the dimensions. For comparatively small KS MMPHs, such a method—dimensional upscaling—was recently developed in  based onhttp://puh.srce.hr/s/Qegixzz2BdjYwFL (accessed on 22 July 2023). MMPHs can be visualized via hypergraph figures consisting of dots and lines and represented as a string of ASCII characters. The latter representation enables the processing of billions of MMPHs simultaneously via supercomputers and clusters. For the latter elaboration, we developed other dynamical programs specifically to handle and parallelize jobs with arbitrary numbers of MMP hypergraph vertices and edges.The methods used to handle quantum contextual sets rely on algorithms and programs within the MMP language: VECFIND, STATES01, MMPSTRIP, MMPSHUFFLE, SUBGRAPH, LOOP, and SHORTD developed in ,51,57,58To summarize, based on elaborations of non-KS sets that recently appeared in the literature and of which we provided several examples in


Z) using the prepared method were very close to the evaluated ones.To prepare a reliable method for predicting the properties of devulcanized rubbers a nitrile rubber (NBR) compound was prepared and masticated before vulcanization for 0, 30 and 60 min under mechanical stress to prepare NBRs with different molecular weights. The masticated samples were vulcanized at different accelerator contents to prepare damples with different crosslink densities. The physical/mechanical/thermal properties  of the samples were experimentally evaluated. In the next step, the prepared samples were assumed as devulcanized NBRs that underwent chains scission (masticated samples) or crosslinks breakage (vulcanized at different accelerator contents). On this basis, hypothetical devulcanization routes were considered between each sample that underwent chains scission or crosslinks breakage. Based on the results, numerical relationships between the number of chains scission or crosslinks breakage and decrease in the properties were obtained. Finally, the numerical reationships were used to calculate the properties of the samples that underwent both of chains scission and crosslinks breakage. It was found that the calculated contents of hardness, modulus at 100% and molecular weight (M Devulcanization is a promising method among other waste rubber recycling methods3. During devulcanization process, crosslinks and polymer chains are broken that enable it to flow and mold again. On this basis, the devulcanized rubber could be re-vulcanized and reused4. Practically, breaking of all crosslinks is impossible and fracture in the polymer backbone also occurs at the same time that this lowers the mechanical properties of recycled rubber6. In fact, the key factor for successful devulcanization of a waste rubber is increasing in the crosslinks breakage and lowering the chains scission7. This makes devulcanization method a smarter recycling process than reclamation.Recycling of waste rubbers is of the great interests of researchers due to environmental, conservation of raw materials and economical aspects8 measured the quality of devulcanized SBRs containing different contents of carbon black through microwave irradiation. They evaluated sol/gel contents of the recycled rubbers and conducted TGA and DMTA analysis on the samples. It was found that carbon black content has a great impact on devulcanization content by microwave irradiation. Ghowsi et al.9 devulcanized waste nitrile rubber powder using different chemical agents. They mechanically devulcanized rubber particles on a two roll mill. The sheet formation time from particles was considered as a criterion for devulcanization performances. It was found that the sheet formation time (i.e. devulcanization content) decreases about 50 and 85% in presence of different devulcanizing agents and heating, respectively. Rios et al.10 devulcanized SBR with a controlled oxidation process via nitric acid. They evaluated the success of the process using IR, CNMR, TG, GPC and TPD-MS analysis. Rooj et al.11 devulcanized NR rubber in presence of benzoyl peroxide as a chemical devulcanizing agent and monitored the process by measuring crosslink density, tensile properties and IR and SEM analysis. They showed that chemo-mechanical devulcanization is more efficient than separate chemical and mechanical methods. Sabzekar et al.12 studied devulcanization of EPDM rubber in presence of a disulfide oil as chemical agent. They used chemo-mechanical devulcanization method and monitored the process by measuring crosslink density (CLD), sol/gel contents, hardness, tensile properties, compression set and resilience of the recycled rubbers. It was found that the best results obtained with 7 phr of disulfide oil at a temperature of 290 °C and screw speed of 120 rpm. The decrease in the CLD and increase in the sol content were introduced as critera for choosing the best devulcanization process. They also blended devulcanized EPDM with virgin rubber at different ratios and claimed that the product could be industrially attractive based on the physical and mechanical properties.In the last decades, many researchers focused on assessing the quality of recycled rubbers through devulcanization process. Hirayama et al.13 devulcanized NR/SBR waste with various devulcanizing agents at different times of MW irradiation. They evaluated qualitatively/quantitatively devulcanization of samples using evaluation of crosslink density before and after devulcanization. They also investigated the effect of the size of waste rubber particles on the devulcanization performances. They claimed that waste rubber particles were partially devulcanized (i.e. devulcanization of the shell of particles) and devulcanization content improved by decrement in the particle size of the particles. Shabani et al.14 devulcanized NR/SBR waste by probe sonication and assessed the success of process using determination of sol/gel contents and crosslink densities before and after devulcanization. They also claimed that partial devulcanization occurred through probe sonication that its performance depend on the sonication power/time and chemical agent type. Molanorouzi et al.15 used different chemical agents for devulcanization of waste tire rubber. The Horikx theory was used to determine the success of devulcanization process for breaking the crosslinks instead of chains scission.Vahdatbin et al.17, rheological properties18 and mechanical features19 have been performed for this purpose, hitherto. Furthermore, some analysis such as CNMR12, GPC20, FTIR20, TGA21, SEM22, DSC23, DMA/DMTA24 have been used to characterize devulcanized rubbers. Some researchers also used Horikx theory for this purpose25.Based on the literature survey, different methods have been conventionally used for qualitative/quantitative evaluation of devulcanization process. For instance, measurment of sol/gel contents and crosslink density26. However, preparing Horikx curve is time-consuming and expensive. Besides, it could not be used for partially devulcanized rubber9.Although, these methods are helpful for evaluation of devulcanization process  but due to the complexity of the process, they are not able to provide a precise explanation on the mechanism of devulcanization, content of crosslinks breakage and chains scission and their relationships to the recycled rubber properties. In fact, most of the efforts have been focused on the optimization of the devulcanization process to achieve higher mechanical properties and devulcanization percentages (or lower crosslink density). The Horikx theory is the lone method that has been used to illustrate the success of crosslinks breakage in devulcanization process that is performed based on statistical calculationsThere are few investigations on evaluation of the crosslinks breakage and chains scission during devulcanization process and their impact on the physical/mechanical properties of the recycled rubber. In fact, it seems to be impossible to separate role of crosslinks breakage and chains scission on the properties of the devulcanized process using the traditional methods.In this work, it was aimed to prepare a method to separate effect of crosslinks breakage and chains scission on decrement in the properties of a nitrile rubber during devulcanization. For this purpose, samples with different molecular weights (but the same formulation) as a simulated devulcanized samples that exposured just to the chains scission were prepared, at first. The mechanical stress (mastication) was applied for three different times  to a masterbatch of NBR (uncured). On this basis, numerical relationships were obtained between the chains scission and the decrement content in the properties of the masticated samples. In the second step, the prepared samples with different chain lengths (molecular weights) were vulcanized at various contents of CBS accelerator . In this way, three category of materials with different molecular weight were prepared that each category contains three samples with different crosslinking contents. In this case, each category could be assumed as the samples with different content of crosslinks breakage without any chains scission. Now, we have three types of samples that exposed just to chain scission, crosslinks breakage or both of them during hypothetical devulcanization processes. The numerical relationship between the crosslink breakage and the decreased properties was achieved. The physical/mechanical properties of the prepared samples  were considered in this study. Finally, based on the relationships between the decreased content of the properties and number of chains scission or crosslinks breakage, the method was used to predict the properties of the samples that experienced both chains scission and crosslinks breakage during devulcanization. Furthermore, the devulcanization mechanism also was studied using Horikx theory for comparison.The raw materials used in this research are listed in Table The used recipe for preparation of NBR compound is given in Table 0, M30 and M60) were mixed with different contents of CBS accelerator  at constant sulfur content (i.e. 1.3 phr) and TMTD (0.8 phr) as curing system. Different CBS contents were used to prepare samples with low (L), medium (M) and high (H) crosslink densities. All the samples were cured at 170 °C for 6 min. On this basis, nine samples in three categories of molecular weights  and three type of crosslink densities  were prepared. Figure The control samples  of the samples is presented in supporting information, section "The method for calculation of average molecular weight (M13 as follows:3), Vr (no unit), Vs (m3/mol) and χl (dimensionless) were crosslink density, rubber volume fraction in the swollen sample, molar volume of the solvent and the Flory–Huggins' interaction parameter, respectively. The value of 27.The crosslink density (CLD) of the samples was measured using the Flory-Rehner relationship28. The extraction was performed before swelling to measure the crosslink density. The isopropanol extraction was done according to the ASTM D29729. After isopropanol extraction, all the samples were immersed in a sufficient amount of benzene solvent for 72 h. Solvents were refreshed every 24 h. Then the weight of the swollen samples was measured with an accuracy of 0.1 mg. Thereafter, the samples were dried at temperature of 70 ± 2 °C for 24 h in a ventilated oven. The weight of the dried samples was measured with an accuracy of 0.1 mg after reaching to ambient temperature. The value of To measure crosslink density of the NBR samples, they were extracted in isopropanol solvent according to ASTM D6814The density of the dried samples was measured in methanol according to ASTM D297 as follows:Based on the results, devulcanization percent of the samples were determined according to ASTM D6814 as follows:30.The average molecular weight between two crosslinks sing Eq. :5\docume see Eq. 30.–sts and analysisc90 and ts2 are time of reaching of compound to its 90% of curing level and scorch time.A moving die rheometer (MDR) was used to evaluate curing behavior and rheology of the samples. The test was performed at 170 °C by a Hiwa MDR rheometer instrument. The curing rate index (CRI) was calculated based on the MDR results as following:31. The hardness test was performed on the cured samples by a Cori duromerer based on ASTM D224032.The tensile tests were performed on the cured samples (i.e. at 170 °C for 6 min) using a Instron universal machine at tension rate of 500 mm/min based on ASTM D412The devulcanization content was calculated for each hypothetical devulcanization route. For this purpose, 10 chains of a sample were considered and the chains scission and crosslinks breakage were determined. These 10 chains were obtained based on a try and error metod that through it the calculated average molecular weight were almost equal to the evaluated one. In fact, cosidering 10 chains gives the closest results for calculated and evaluated average molecular weights.Figure Gel permeation chromatography (GPC) analysis was used to characterize molecular weight of the uncured 90) of the samples are less than 1.1 min. The curing rate and MH-ML content enhanced by increment in the CBS content  of the samples are shown in Fig. The crosslink densities (CLDs) of the cured samples were calculated based on the Flory-Rehner equation that results are shown in Fig. Figure Figure The mastication of NBR sample caused decrement in the Young modulus and modulus at 100% at different crosslink densities see Fig. -b. HowevFigure n, Mw, Mz and Mz+1) of the samples were determined  /chains scission (CS) and decrement in the evaluated properties, the hardness and modulus at 100% of the usually devulcanized samples  have not direct correlation to chains scission/crosslinks breakage that happened during devulcanization process. on this basis, MDR results are not suitable for monitoring of the devulcanization performances.It was found that curing properties .A numerical correlation was obtained between decrease of the evaluated hardness and chains scission/crosslinks breakage that happened during devulcanization.n and MW values, MZ and MZ+1 values showed a direct relationships to the number of crosslinks breakage and chains scission that occurred by devulcanization.In contrary to MThe prepared mathematical method was used to predict the hardness and modulus at 100% of a series of devulcanized samples. The predicted  data were very close to the evaluated hardness and modulus at 100% of the samples.In this research, a facil method was prepared to predict the properties of devulcanized waste nitrile rubber, based on the relashionship between number of crosslinks breakage/chains scission and decline in the properties. For this purpose, nitrile rubber samples were prepared in three categories (i.e. different mastication times) and different crosslink densities (i.e. different CBS accelerator contents). The method was verified using comparing the calculated and evaluated properties for usually devulcanized samples. The following conclusions were obtained:Supplementary Information.


Antimicrobial resistance (AMR) is among the leading global public health threats of the 21st century. Thus, AMR threatens human, animal, and environmental health globally . MoreoveRamamurthy et al. reviewed the genetic network and programmed regulations used by bacterial pathogens in antimicrobial resistance. Mechanisms identified could be cellular  and/or molecular . Once developed, mobile genetic elements  mostly aid in disseminating AMR in the environment, influenced by the presence of stressors such as biocides, antibiotics, heavy metals, and detergents.The development of resistance in bacteria is a complex process involving several mechanisms. Patil et al. assessed the resistance genomics and molecular epidemiology of Pseudomonas aeruginosa in young children, specifically targeting high-risk extended-spectrum beta-lactamase (ESBL)-producing clones. The authors analysed 294 clinical isolates from a paediatric hospital in China using culture-dependent and independent methods and found that 56%, 40%, 39%, 36%, 33%, and 32% of the isolates were resistant to piperacillin-tazobactam, cefepime, ceftazidime, imipenem, meropenem, and ciprofloxacin, respectively. Furthermore, 42% of the isolates were ESBL producers. Polymerase chain reaction and sequencing revealed the presence of numerous genes including blaCTX-M-15, blaNDM-1, aac(3)IIIa, tet(A), and 23 sequence types, as well as a de novo strain. The isolates also harboured various plasmids that could aid in the transmission of these resistance genes. Still in humans, Jia et al. genomically characterised bacteraemia-associated carbapenem-resistant Serratia marcescens isolates and reported the emergence of KPC-2-encoding IncR plasmids in a clinical setting to understand their resistance and transmission dynamics. After sequencing the complete genome of two S. marcescens isolates, the authors observed that the isolates harboured blaKPC-2-bearing IncR plasmids and multiple plasmid-borne antimicrobial resistance genes. Comparative plasmid analysis further suggested common ancestral lineage for both isolates and concluded that the plasmid borne by both isolates could hinder the transmission of KPC-2-producing S. marcescens in clinical settings.Children are vulnerable to infections due to their less developed immune systems. Shi et al. functionally characterised a novel aminoglycoside phosphotransferase, APH(9)-Ic, and its variant from Stenotrophomonas maltophilia. After performing recombinant protein expression and enzyme kinetic studies, the authors used whole-genome sequencing to determine the genetic context of the studied gene. The authors observed that aph(9)-Ic and aph(9)-Ic1 conferred spectinomycin resistance. Furthermore, a recombinant strain harbouring aph(9)-Ic displayed a marked increased minimum inhibitory concentration level against spectinomycin compared with the control strains; aph(9)-Ic was chromosome-borne, with a relatively conserved genetic environment and no mobile genetic element in its surrounding region.While some clinical bacteria may acquire resistance traits due to exposure to external stressors, others are intrinsically resistant to several antimicrobials. Hence, Yasmeen et al. investigated the occurrence of ESBL-harbouring Klebsiella pneumoniae from 793 samples collected from animals, humans, and the environment. Their study found K. pneumoniae in 11.6%, 8.4% and 7.0%, of animal, humans, and environmental samples, respectively, with the animal isolates harbouring more ESBL genes (mostly blaSHV) than their human and environmental counterparts. These results show the potential spread of these pathogens within the three one health compartments.The one health approach has been shown to provide a comprehensive understanding of the spread of AMR in the human–animal–environment triad. Thus, Ahmad et al. reviewed how the one health concept has been implanted and evolved in combating AMR. They identified that pillars of support to combat AMR include instituting robust ABR surveillance in the various sectors individually and in combination and at national and international level, as well as improving laboratory resources and executing and strictly implementing core plans and actions. Furthermore, drawing on lessons from the recent COVID-19 pandemic, Mantegazza et al. proposed a de novo approach based on a convergence model to fight AMR, exploiting the current Sustainable Development Goals (SDG) roadmap, emphasising a circular approach and highlighting win–win scenarios by enforcing existing objectives and targets to strengthen a multidisciplinary synergistic effort towards fighting AMR. They argued that the global importance of AMR warrants that it be an integral part of the SDG roadmap, involving all the SDG objectives, as such efforts could significantly advance health as a system by focusing on a major priority such as AMR.Given the debating effects of AMR, involving humans, animals, and the environment, attempts at curbing this ill must take a holistic approach involving multisectoral stakeholders. Thus, Collectively, these studies contribute to knowledge on the spread of AMR in humans, animals, and the environment. Furthermore, they reveal the various mechanisms involved in AMR in bacteria, including factors triggering their occurrence and factors favouring such spread. Therefore, combining culture and advanced molecular techniques such as genomics would paint a brighter picture regarding the overall AMR burden. Put together, the studies provide evidence that adopting a one health concept for a successful fight against AMR is imperative.AA: Conceptualization, Methodology, Writing – original draft, Writing – review & editing. AT: Conceptualization, Methodology, Writing – review & editing. NP: Conceptualization, Methodology, Writing – review & editing.


Topic models are widely used to discover the latent representation of a set of documents. The two canonical models are latent Dirichlet allocation, and Gaussian latent Dirichlet allocation, where the former uses multinomial distributions over words, and the latter uses multivariate Gaussian distributions over pre-trained word embedding vectors as the latent topic representations, respectively. Compared with latent Dirichlet allocation, Gaussian latent Dirichlet allocation is limited in the sense that it does not capture the polysemy of a word such as “bank.” In this paper, we show that Gaussian latent Dirichlet allocation could recover the ability to capture polysemy by introducing a hierarchical structure in the set of topics that the model can use to represent a given document. Our Gaussian hierarchical latent Dirichlet allocation significantly improves polysemy detection compared with Gaussian-based models and provides more parsimonious topic representations compared with hierarchical latent Dirichlet allocation. Our extensive quantitative experiments show that our model also achieves better topic coherence and held-out document predictive accuracy over a wide range of corpus and word embedding vectors which significantly improves the capture of polysemy compared with GLDA and CGTM. Our model learns the underlying topic distribution and hierarchical structure among topics simultaneously, which can be further used to understand the correlation among topics. Moreover, the added flexibility of our model does not necessarily increase the time complexity compared with GLDA and CGTM, which makes our model a good competitor to GLDA. Topic models are widely used to identify the latent representation of a set of documents. Since latent Dirichlet allocation (LDA)  was intrLDA uses multinomial distributions over words, whereas Gaussian LDA (GLDA)  uses mulA crucial discrepancy of GLDA and CGTM is that they fail to detect the polysemy of a term, such as “bank,” which LDA and hLDA capture well . LDA is In this paper, we show that the ability to capture polysemy in GLDA-type models can be recovered by restricting the set of topics that can be used to represent a given document. One parsimonious implementation of such a restriction can be achieved by incorporating a hierarchical topic structure, as in hLDA , 8. In oAt first glance, our model may seem to have a price to pay in terms of time complexity because of the added complexity of the model. However, because we do not need to sample from the entire set of topics for each word position in a document, the time complexity of our model does not necessarily worsen compared with GLDA and CGTM. Moreover, our model has the benefit of capturing polysemy in addition to being able to learn a compact hierarchical structure that shows the relationships among topics. Additionally, as in hLDA , BayesiaOther works also exist that combine topic modeling and word embeddings.  used infOur contributions are summarized as follows:We propose the Gaussian hLDA, which significantly improves the capture of polysemy compared with GLDA and CGTM.Our model jointly learns the topics, in addition to the hierarchical structure, and characterizes the relationship among the topics. The hierarchical structure can also be used to analyze the correlation structure among topics.The hierarchical tree structure can be estimated in a flexible manner using the nested Chinese restaurant process .Even though our model is far more expressive than GLDA and CGTM, the time complexity does not necessarily worsen compared with that of those two models.We show that our model exhibits a more parsimonious representation of topics than hLDA.Using three real-world corpora and three different pre-trained word embedding vectors, we show that our model outperforms state-of-the-art models both in terms of the held-out predictive likelihood and topic coherence.Although simple and relatively straightforward, our work shows how a simple model modification drastically improves its performance.https://github.com/hisanor471/ghlda).Codes are made online  denote a specific document, word, or topic. θd,k denotes the probability of topic k for document d and, φk,v denotes the probability of word v in topic k. Nd denotes the number of words in a document. For each word position n in document d, zd,n denotes either the topic or level assignment for that word position and wd,n denotes the word that appears in word position n for document d. Furthermore, cd denotes a path assignment to document d and ld denotes the level distribution in d. For path and level assignments, a topic is uniquely defined as shown in d that are assigned to either topic  or level i , excluding zd,n. i. v and topic k, excluding zd,n. GEM denotes the Griffiths, Engen, and McCloskey distribution  denotes the set of word positions assigned to topic c[l], tl denotes the set of word positions assigned to level l in d, and Γd denotes the multivariate gamma function. The probability of a level is defined aswhere , z, H)) , and theThe qualitative characteristics of LDA, hLDA, GLDA, CGTM, and GhLDA are summarized in d. O(M2) using the Cholesky decomposition of a covariance matrix. Because each word position has K topics to consider, and there are Nd words in a document, the total time complexity of GLDA is O(NdKM2). LDA does not require us to calculate the inverse of the posterior covariance matrix, which makes the time complexity O(NdK). For each document, CGTM requires the sampling of document-level parameters ηd and λd. This step adds another O(K3) to the complexity.We compare the running time complexity of all the models. Because hLDA, CGTM, and GhLDA include steps that require us to sample document-level parameters using all the words that appear in a document, we focus on the running time complexity to sample all assignments for a given document O(PLM2), where P denotes the number of paths and L denotes the maximum depth among all paths. However, exploiting the tree structure, we can reduce the calculation to O(KM2). After sampling the path, GhLDA proceeds to sample levels for each word position in a document. Because each path only has a most L topics, sampling-level assignment for all words in a document takes O(NdLM2). Adding both steps leads to O(KM2 + NdLM2) in total. Similar arguments can be used to calculate the time complexity of hLDA, which is O(K + NdL).Compared with these models, GhLDA first evaluates the posterior predictive probability for all paths. The straightforward calculation results in NdK ≤ K + NdL, the time complexity of GhLDA is lower than that of GLDA . Whereas GLDA with K = 20 leads to Nd × K = 2, 000, GhLDA with the branch structure of   results in K + NdL = 422.). Surely enough, this argument does not take into account the number of iterations required for collapsed Gibbs sampling to converge. However, it still highlights the fact that the time complexity of GhLDA is not necessarily worse than that of GLDA.A few points are worth mentioning. All the models that use word embedding vectors are much slower than their plain counterparts because of the additional step of computing the Cholesky decomposition. However, comparing GLDA and GhLDA, we can see that GhLDA does not necessarily increase the time complexity compared with GLDA. If We conducted experiments using three open datasets, which were all included in our source code. One of the datasets  was assembled particularly for the bank polysemy capturing task. We summarize the datasets below.The Wikipedia dataset, abbreviated as Wiki in the table, is a dataset particularly assembled for the bank polysemy capturing task. The corpus was created from DBpedia-2016 long abstract data . Each lohttp://jmcauley.ucsd.edu/data/amazon/). We sampled evenly from the following five categories: “Electronics,” “Video Games,” “Home and Kitchen,” “Sports and Outdoors,” and “Movies and TV,” and created a corpus of 6,000, of which 5,000 were used for training and 1,000 for testing. The other settings were the same as above.Amazon review data is a dataset of gathered ratings and review information   , word2veWe compared GhLDA with LDA, hLDA , GLDA 1, and CGTα = 0.1, β = 0.1 for LDA, and v = 0.1, κ = 0.1, Ψglove = 50 * I, Ψword2vec = 40 * I, Ψfasttext = 20 * I for GLDA and CGTM, where I denotes an identity matrix. We ran the sampler for 50 epochs for these models, where one epoch was equal to sampling all the word positions in the corpus once. The hyperparameters controlling GEM and nCRP were set to m = 0.5, b = 100, γ = 0.1 similar to . A similar strategy was used in GhLDA, where we adjusted Ψ to vary among the levels in the ratio , where the top level was identical to GLDA. We truncated the tree at level four, as in [The hyperparameters that governed the topic distributions were set to milar to . The iniK = 20, topic 10 included terms related to finance, such as “financial,” “banking,” and “central,” and topic 13 contained terms related to the river, such as “creek,” “lake,” and “water.” However, not a single “bank” or “banks” that appeared in the corpus was assigned to the river topic , and all these words were assigned to the finance topic . Similar observations were made, even when K was increased to 40. In this case, we could see terms related to finance, such as “financial,” “market,” and “management,” in topic 21, and terms related to river, such as “river,” “creek,” and “flows,” in topic 0. However, topic 0 also contained financial terms, such as “investment,” “credit,” and “exchange;” hence, the topic was inappropriately mixed. This observation implies that although increasing the number of topics makes the constraint on mutual exclusivity to soften; it does not improve the ability to capture polysemy. Similar observations hold for CGTM as well.We compare the models’ ability to capture polysemy, paying particular attention to the term “bank(s),” using the Wikipedia dataset. We use GloVe as a case study; the other word embeddings provide similar results. First, as shown in By contrast, GhLDA can capture the polysemy of “bank(s).” As is shown in The inability to capture polysemy in GLDA is further illustrated using low-dimensional representations. We further note that, because our corpus does not exclude highly frequent terms as in , LDA canIn this section, we mainly focus on the difference between GhLDA and hLDA. As shown in We calculated the topic coherence score , 13, 33 However, the topics learned from the Reuters dataset using GhLDA were not at all worse than the GLDA and CGTM counterpart. For instance, in GhLDA-word2vec, there were topics such as “trump, republican, coal, party, workers, house, debate, school, bill, bankruptcy,” which indicate the news topic that Trump made a promise to coal miners during his campaign, and “vehicles, water, vw, flint, safety, cars, emissions, volkswagen, detroit, filed,” which indicate the news topics of Volkswagen’s diesel cars and the tap water problem of Flint. Although these news topics were widely reported during the period in which the news dataset was collected, the PMIs of the topics were -1.36 and -2.79, respectively, which shows the limitations of Palmetto for evaluating new combinations of words correctly.Furthermore, even though they connect to real word news, neither Trump nor Volkswagen appeared in the top 15 words of the 40 topics learned from GLDA-word2vec and CGTM-word2vec. Topics in GLDA were much general, such as “rate, dollar, assets, buy, goal, drop” and “government, end, federal, chinese, countries,” which do not take into the word co-occurrence patterns of the corpus that we wish to analyze. As the Reuters examples suggest, even when the underlying word embedding is not in line with the corpus, the added flexibility of our model identifies critical topics that both GLDA and CGTM fail to identify. This observation further highlights the benefit of our model.We further used the predictive held-out likelihood to quantitatively compare our models, as in . We evalSince we could not compare models with different embeddings, we focused on comparing LDA with hLDA and the best-performing model for each word embedding. In this paper, we proposed Gaussian hLDA, which significantly improves the capture of polysemy compared with GLDA and CGTM. Our model learns the underlying topic distribution and hierarchical structure among topics simultaneously, which can be further used to understand the correlation among topics. We demonstrated the validity of our approach using three real-world datasets.Although there are other ways to capture polysemy in the more recent deep learning style models, such as the transformer-based models , captureS1 File(PDF)Click here for additional data file.


An international legal agreement governing the global antimicrobial commons would represent the strongest commitment mechanism for achieving collective action on antimicrobial resistance (AMR). Since AMR has important similarities to climate change—both are common pool resource challenges that require massive, long-term political commitments—the first article in this special issue draws lessons from various climate agreements that could be applicable for developing a grand bargain on AMR. We consider the similarities and differences between the Paris Climate Agreement and current governance structures for AMR, and identify the merits and challenges associated with different international forums for developing a long-term international agreement on AMR. To be effective, fair, and feasible, an enduring legal agreement on AMR will require a combination of universal, differentiated, and individualized requirements, nationally determined contributions that are regularly reviewed and ratcheted up in level of ambition, a regular independent scientific stocktake to support evidence informed policymaking, and a concrete global goal to rally support. International legal agreements are formally the strongest mechanisms through which countries can make commitments to each other , but oftAntimicrobial resistance (AMR) is one of the leading threats to global health and sustainable development . The thrThe historical failure of country-level and voluntary solutions means that binding international legal agreements may have a stronger likelihood of protecting the global antimicrobial commons. A global health treaty has a reasonable chance of being impactful if it meets four criteria: first, there must be a significant transnational dimension to the health challenge; second, the treaty must address multilateral challenges that cannot practically be addressed by a single country and therefore justifies the use of an instrument with coercive features; third, the proposed treaty should have a reasonable chance of achieving benefits by incentivizing action, institutionalizing accountability, and activating interest groups; and fourth, the treaty should represent the best commitment mechanism among the competing alternative strategies . DespiteAlthough examples of health-specific international legal agreements are scarce, recent international climate change agreements offer a useful comparator, since both climate change and AMR require collective action to address problems that resemble a global tragedy-of-the-commons. In this article, we look to recent international climate change agreements to identify design elements that might inform the development of a microbially effective, ethically fair, and politically feasible AMR treaty.universal responsibilities or “one-size-fits-all”—every country is bound by the same targets and obligations for action. This model was used by many environmental treaties prior to the 1990s [Past environmental agreements offer at least three ways of delineating state parties’ responsibilities Table . In the he 1990s , howeverdifferentiated responsibilities—sets different standards for different groups of countries, usually one standard for high-income countries (HICs) and another for LMICs. The 1997 Kyoto Protocol to the United Nations (UN) Framework Convention on Climate Change (FCCC), for instance, set collective emission-reduction targets for HICs and different requirements for LMICs. Given the overconsumption of antimicrobials in HICs, and the need to focus on boosting access to life-saving drugs in many LMICs, some scholars have suggested that a differentiated responsibility model should be applied to AMR (e.g. [The second model of crafting states parties’ responsibilities—MR (e.g. ). HoweveMR  a collective global goal; (2) nationally determined contributions that are pledged, reviewed and ratcheted every 5 years; (3) regular reporting on actions and outcomes; (4) an annual conference of parties; (5) a global scientific stocktake every 5 years; (6) a combination of binding obligations and recommended policies; and (7) an international legal framework.A collective global goal The Paris Agreement codified an overarching goal to keep global warming well below 2 °C compared to pre-industrial levels. This collective goal provides common ground for negotiation, collaboration, and national policymaking. Developing an equally clear and feasible target would be helpful for progress on AMR; however, there is currently no consensus on an analogous, quantifiable goal for AMR containment. Developing such a goal is likely to be the first, and perhaps most important, challenge in developing an international legal agreement on AMR. Numerous AMR indicators have been proposed, and, in a positive development, a new indicator for antimicrobial resistant blood stream infections has been proposed to support the Sustainable Development Goals [(2)Nationally determined contributions that are pledged, reviewed and ratcheted every 5 years Perhaps the most unique design element of the Paris Agreement is the universal responsibility imposed on all countries to articulate their own individualized responsibilities in national action plans. In this system, nationally determined contributions are pledged and then subsequently reviewed and ratcheted-up in level of ambition every 5 years. The requirement that each successive round of pledged contributions must represent a progression beyond earlier contributions ensures that plans are updated in accordance with increasing response capacity.Developing these elements from a blank slate would likely be very difficult. However, some similar elements already exist in global AMR governance. A future international legal agreement on AMR can therefore draw upon many existing elements for momentum, build upon existing institutional structures, and coordinate efforts to reinforce existing action on AMR Table .Table 2Cnt Goals . The intThe global AMR regime includes the foundation for a similar approach. In 2015, WHO’s plenary governing body—the World Health Assembly—called upon all countries to develop national action plans to address the threat of AMR by 2017 . In tota(3)Regular reporting on activities and outcomesParties to the Paris Agreement are legally bound to regularly report on both activities and outcomes related to their commitments using a standard and accepted methodology. In addition to regular reporting, countries are legally obligated to participate in verification processes to ensure high-quality data reporting. While these mechanisms have not yet been activated, from a design point of view, the robust monitoring, reporting and verification mechanisms of the Paris Agreement may provide some useful lessons for overcoming current weaknesses in global AMR monitoring and reporting processes. The tripartite coalition of WHO, FAO, and OIE currently monitors national-level progress in developing and implementing their national action plans through self-assessment surveys; however, these surveys currently lack an effective verification system [(4)An annual conference of partiesThe Paris Agreement reaffirms countries’ previous commitments to meeting annually to discuss their progress, chart further actions, continue working on existing challenges, and address new issues that emerged in the preceding year. These regular meetings enhance cooperation by building trust, offering predictability, and sharing knowledge and best practices—each a valuable aspect from which the AMR regime could benefit. Over the past 80 years, AMR has not maintained a long-term presence on the global health agenda. The closest AMR has come to achieving this kind of sustained attention is the World Health Assembly’s informal custom of revisiting this major health issue roughly every 3 years. The potentially catastrophic loss of life and the devastating economic impacts associated with AMR should merit more frequent ongoing, high-level discussions of the kind mandated by the Paris Agreement on an annual basis.(5)A global scientific stocktake every 5 yearsIn addition to annual meetings, countries also agreed to participate in a science-based “global stocktake” every 5 years for the purpose of assessing progress towards the Paris Agreement’s long-term goals. This stocktake also features a review of relevant scientific evidence, which allows global climate action to evolve as new scientific discoveries come to light and supports countries to make evidence-informed climate policies. No similar mechanism exists to inform AMR policy, yet an AMR agreement could include this stocktake mechanism to support evidence-informed policy. Currently, there is little evidence on the relative effectiveness of AMR interventions, existing evidence is not often used to inform policy action [(6)A combination of binding obligations and recommended policiesThe Paris Agreement achieved broad support by combining legally binding and non-binding provisions. Major carbon emitters, who were reluctant to commit to a rigid set of predetermined emissions reductions, were open to a treaty that combined legal requirements and recommendations [(7)An international legal frameworkThe Paris Agreement, as a binding instrument within the UN FCCC, provides a relatively comprehensive legal framework for climate change action. Despite the predicted suitability of an international legal framework governing the antimicrobial commons, there does not exist a binding legal instrument to hold parties accountable for antimicrobial stewardship. Having been negotiated to overcome a similar global tragedy-of-the-commons challenge, adopting a framework similar to that of the Paris Agreement may provide a robust and adaptable framework for developing and sustaining political commitment to effectively, fairly and feasibly manage the global antimicrobial commons. Yet, the flexibility offered to countries in meeting their individualized responsibilities might also hinder the achievement of the collective goal, and, as previously noted, initial country pledges under the Paris Agreement were insufficient to meet the global target. As such, some incentives or penalties might be desirable in an AMR agreement in order to promote compliance with countries’ targets. Collective action problems that require cooperation of a large number of parties sometimes suffer from a ‘problem of assurance.’ The problem of assurance can arise when individuals are sincere in their willingness to contribute, but skeptical of the sincerity of other parties. When costs of defection are low and benefits non-excludable, as in free-rider-prone issues like AMR, the assurance problem is more likely to arise. If it does, then parties will likely only be willing to contribute if they have the assurance that others are making their fair contribution as well. If countries were legally bound and incentivized to meet their own targets in terms of ensuring access, conservation and innovation for AMR, this could increase the chances of success for an AMR agreement.Yet, if developing global consensus around a goal is the first major challenge, spurring national action to reach this goal is the second. Initial country pledges under the Paris Agreement were insufficient to meet the global target established in that agreement, and similarly, national AMR action plans have to date been insufficiently ambitious. Although most high antimicrobial-using countries have made public commitments to reduce their use of these products, it has thus far proved difficult to translate this engagement into sufficient national or global policy action .(3)Reguln system . Mechanin system .(4)An any action , and thendations . Legal rTo protect the global antimicrobial commons, an effective international legal framework will need to comprise a mix of universal, differentiated and individualized requirements. In creating a global AMR treaty, it is essential to acknowledge that the provisions discussed below will have important implications for gender equity, intergenerational equity, the empowerment of women, the right to health, and the rights of various marginalized groups. At a minimum, any AMR treaty should include language similar to the Paris Agreement that recognizes these essential factors and requires countries to respect and account for this diversity.Many universal requirements of an AMR treaty could mirror the universal requirements of the Paris Agreement; for example, a universal requirement to regularly report AMR related activities and outcomes, or a requirement to pledge, review, and ratchet nationally determined contributions. Other universal treaty requirements could support these activities; for example, establishing universal AMR and antimicrobial usage definitions, compulsory and transparent monitoring standards, and other requirements to improve data collection would support surveillance systems and the development of long-term national action plans. Historically, one of the greatest hurdles for global antimicrobial stewardship has been the lack of internationally standardized and transparent data collection on antimicrobial usage and AMR. The US, EU, and Asian HICs still vary in their approach to AMR and antimicrobial usage definitions, measurement methods, and data processing, and it has proved difficult to reconcile data collected through active monitoring protocols in human medicine with passive monitoring systems often employed in non-human settings. Despite launching GLASS, international organizations like WHO and OIE have faced some unwillingness among countries to openly and transparently report their AMR and antimicrobial usage data , 34.Disease burdens vary significantly between LMICs and HICs, access to antimicrobials is still limited in many parts of the world, and not every country has the economic, bureaucratic, and scientific resources to implement stewardship requirements. Meanwhile, higher levels of per capita consumption and their historical role in spreading antimicrobial consumption mean that HICs have a greater moral obligation to shoulder greater burdens when it comes to tackling the resulting global fallout of AMR , 20. As An international treaty can acknowledge this differentiated responsibility by requiring HICs to make greater or earlier reductions in human, animal, and environmental antimicrobial usage and other targets  as outlined in the treaty’s overarching goal. Furthermore, differentiated requirements might require HICs to finance the development of new antimicrobials, diagnostics, and alternative treatments, or by requiring HIC contributions to an international fund designed to support the integrated development of health care, food, and water, sanitation, and hygiene (WASH) systems in LMICs. Differentiated responsibility is already informing the financing of delinked antibiotic development through public–private partnerships  by countries like the US, UK, and Germany. However, overall funding remains limited and will not be indefinite. New investments could be required either via existing public–private partnerships such as the Global Antibiotic Research and Development Partnership (GARDP) or via a new international body for antimicrobial development .Like the Paris Agreement, an international legal framework on the global antimicrobial commons can also include a process requirement for countries to make individualized commitments towards achieving a common goal. While the requirement to outline nationally determined contributions is universal, domestic mitigation measures addressing the specific contributions proposed by individual countries become legally binding upon only them. Individualized commitments on the part of countries could range from enhanced environmental and stewardship efforts by antimicrobial-producing countries to a restructuring of prescription incentives for health professionals in HICs. A recent systematic review and evidence map identified 17 distinct policy strategies that have been used by national governments to reduce human antimicrobial use —any of wA clear and focused goal is integral to the success of any international agreement, or indeed, any successful public health campaign. To date, the lack of such a goal in the global AMR response has proved problematic both for catalyzing action and measuring success. International goal-setting can take one of two forms. The first, as in the case of the Paris Agreement, is a specific overarching global goal. The second, as in the case of the Sustainable Development Goals (SDGs), are general goals supported by multiple specific targets. Either approach can be effective, provided it is supported by concrete, measurable indicators. A lack of generally accepted and measurable targets has been a challenge in AMR with respect to the general goal set in the 2015 WHO Global Action Plan on Antimicrobial resistance, “To ensure, for as long as possible, continuity of successful treatment and prevention of infectious diseases with effective and safe medicines that are quality-assured, used in a responsible way, and accessible to all who need them,” which lacks the level of specificity needed to be actionable or to measure progress towards globally agreed priorities.absolute goal, for which there is a strict definition of success. In the case of AMR, an absolute goal might be to end all deaths from amenable infections or to end the use of critically important drugs in non-human sectors by 2030. The Paris Agreement goal, and the SDG target 3.4 to “reduce by one-third premature mortality from non-communicable diseases…”, are both examples of relative goals which have specific targets defined in relation to other measures. A relative goal in the case of AMR might be to reduce deaths from drug-resistant infections overall or to reduce the rate of specific drug-resistant infections  below a designated reference year. Finally, SDG target 3.9 to “substantially reduce the number of deaths and illnesses from hazardous chemicals…” provides an example of a directional goal which focus on progress from a starting place without setting a clear benchmark. In the case of AMR, this might include a goal to minimize deaths from preventable infections—which depends on both achieving greater access to antimicrobials and conserving the effectiveness of existing antimicrobials. Achieving a microbially effective, internationally equitable, and politically feasible grand bargain on AMR will require a substantial effort to clearly define AMR priorities in terms of either a single specific and measurable goal, or a broad commitment to reducing AMR through an agreed series of specific AMR targets. At the very least, the goal(s) for AMR will need to address both the access and conservation dimensions of the AMR problem. Two preliminary options for potential AMR goals are presented in Table The examples from the Paris Agreement and the SDGs also illustrate the three approaches to goal setting: directional goals, absolute goals, and relative goals. The SDG target 3.3 to “end the epidemic of AIDS, tuberculosis, malaria and neglected tropical diseases…” is an A legal agreement could potentially be negotiated through any of four forums, including (1) the UN General Assembly, (2) one of the UN’s relevant technical agencies or a treaty body, (3) a partnership of several UN’s agencies or treaty bodies, or 4) as a plurilateral agreement with a small group of countries. Each of these options presents certain strengths and limitations, and each has its own unique strategic considerations . As the primary deliberative, policymaking, and representative body of the UN, UNGA would provide a high-profile forum for an AMR agreement. Such a high-profile agreement could mobilize political will and promote AMR to a higher position on national and international agendas. The UNGA’s high level of legitimacy could also facilitate collaboration among other UN and treaty bodies, including the tripartite of WHO, FAO, OIE, plus the UN Environment Program (UNEP). However, working through the UNGA would require AMR to contend for attention among other high-level security, economic and development issues, and when it gets that attention, it could suffer from a ‘race to the bottom’ in terms of consensus-building in such a large decision-making body. A treaty emerging out of UNGA would also have to properly account for, manage, and integrate ongoing AMR efforts: an overlap of authority could lead to loopholes for accountability; duplication of ongoing work could result in inefficiencies; and omissions of ongoing efforts could result in fragmentation .An international legal agreement could also be created under the authority of one of the UN’s relevant technical agencies. Both WHO and FAO have constitutional mechanisms permitting their members to enact legally binding rules through their plenary decision-making bodies. In fact, WHO’s constitution envisions two such mechanisms Table . For exaWHO’s primary focus is on promoting human health, but equally important for AMR are animal health, agriculture and the environment. Countries could regulate antimicrobial use in animal and agricultural sectors using Article 14 of the FAO’s constitution, which permits members to adopt and implement legally binding conventions contingent on a 2/3 majority vote. Member states have used this FAO tool to adopt 17 conventions governing diverse issues including the regulation and promotion of livestock farming guided by principles of sustainable development and self-reliance in Asia and the Pacific. An international legal agreement on AMR under the aegis of the FAO could follow a similar model by creating a commission to regulate and promote livestock farming around the world according to the principles of AMR stewardship and conservation , 9. AlteAn agreement through one of the WHO, FAO or OIE alone, however, would only address one dimension of the problem. A microbially effective response will adopt a One Health approach to bring together stakeholders across the different sectors of human, animal, agriculture and environmental health. Therefore, while either the WHO, FAO or OIE could oversee an AMR agreement, these efforts would need to be supplemented by a multisectoral partnership to include solutions that address all facets of the problem simultaneously . The UN’Another feasible approach might be to organize a treaty separately from any existing international organization. An initial core-group of leading countries could, most expediently, convene a meeting to begin discussions of an international treaty. While all countries must play a role in the global response to AMR, starting negotiations of an international AMR treaty with a small group of countries might generate momentum, enable more ambitious content, and allow other countries to join when they are ready . A pluriGlobal health policies are successful when they are effective, sustainable, fair, and feasible. These criteria must be judged on a global scale; an AMR treaty cannot be deemed effective if it is effective only in certain parts of the world, and it cannot be deemed fair if it is not fair within and across countries. Finally, regardless of effectiveness, a treaty cannot be considered successful if some countries are unfairly burdened by the measures adopted. There are no cost-free solutions to AMR and some countries will have to bear a greater share of these burdens than others. The question is therefore, how can we maximize the results, minimize the burdens, distribute them fairly, and make sure everyone wins?First, a successful treaty must strike the right balance between access, conservation, and innovation, three conflicting elements that must be addressed to satisfactorily and fairly contain AMR. Conservation compels us to reduce antimicrobial use by reducing reliance on antimicrobials. Improving hygiene standards and implementing effective infection prevention and control measures are integral strategies to achieving this goal, and investments are needed to improve health system capacity and quality of care in resource limited settings. Because the burdens need to be distributed fairly, and because the effectiveness of these measures would benefit both these countries’ populations and the global community more broadly, these investments need to be technically and financially supported by HICs. Supporting these actions would allow HICs to discharge part of their moral obligations to contribute to the solution; this would be an obligation of fairness both because HICs have historically overconsumed antimicrobials  and becaSecond, for all countries to win, measures must be appropriate across the human health, animal, agriculture and environmental sectors. A successful treaty will give due consideration to the health needs of humans and animals and ensure that the burdens associated with promoting both are spread fairly across the actors who have so far benefited more from antimicrobials and who are more responsible for AMR. The large-scale use of antibiotics in industrial agriculture is a significant factor for the selection of AMR in the environment and animal populations , 24. WitThird, an international legal agreement on the antimicrobial commons would need to achieve intergenerational justice in a way that ensures wins for both current and future generations. As with many other global problems—such as climate change—justice requires that the next generations will not have to bear too many of the burdens of the poor choices of the current generation, and that the benefits of scarce resources will last as long as possible. The benefits and burdens of antimicrobials and antimicrobial policies will need to be shared across time. But future generations will have to bear some burdens, as strategies to address the problem on the two previous dimensions will need to be constantly revised and updated, based on an assessment of the progress being made. Keeping AMR under control is a problem humanity will always face. Any treaty will need to have mechanisms in place to ensure that progress is tracked and strategies adjusted on a regular basis, so that at any time a decision can be made on how to achieve a fair distribution of the burdens, not only across countries and across sectors, but also across generations. A treaty like this will have to work over a possibly indefinite period of time so its adaptation mechanisms are essential to guarantee not only effectiveness, fairness and feasibility, but also sustainability.Antimicrobial resistance is a complex and far-reaching threat to human health and development. In this manuscript we focus on what can be learned from the design of the Paris Agreement, which complements our efforts to look at other global policy solutions for AMR , 27, 33.


Escherichia coli that colonized travellers to Laos. Long-read sequencing was used to reconstruct complete plasmid sequences from 48 isolates obtained from the daily stool samples of 23 travellers over a 3 week period. This method revealed a collection of 105 distinct plasmids, 38.1 % (n=40) of which carried AMR genes. The plasmids in this population were diverse, mostly unreported and included 38 replicon types, with F-type plasmids (n=23) the most prevalent amongst those carrying AMR genes. Fine-scale analysis of all plasmids identified numerous AMR gene contexts and emphasized the importance of IS elements, specifically members of the IS6/IS26 family, in the evolution of complex multidrug resistance regions. We found a concerning convergence of ESBL and colistin resistance determinants, with three plasmids from two different F-type lineages carrying blaCTX-M and mcr genes. The extensive diversity seen here highlights the worrying probability that stable new vehicles for AMR will evolve in E. coli populations that can disseminate internationally through travel networks.Increased colonization by antimicrobial-resistant organisms is closely associated with international travel. This study investigated the diversity of mobile genetic elements involved with antimicrobial resistance (AMR) gene carriage in extended-spectrum beta-lactamase (ESBL)-producing  Long-read sequencing data are available through the National Center for Biotechnology Information (NCBI) under the BioProject PRJNA853172. Complete plasmid sequences have been uploaded to GenBank with accession numbers in Table S1 (available in the online version of this article). The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.Escherichia coli isolates found in faecal samples from travellers to Vientiane, Laos. Here we add to known databases of AMR plasmids by adding these MDR plasmids found in Southeast Asia, an area of high AMR prevalence. We characterized novel AMR plasmids, including complex ESBL (blaCTX-M) and colistin (mcr) resistance co-carriage plasmids, emphasizing the potential exposure of travellers to Laos to a wide variety of mobile genetic elements that may facilitate global AMR spread. This in-depth study has revealed further detail concerning the numerous factors that may influence AMR transfer, and therefore potential routes of AMR spread internationally, and is a step towards finding methods to combat AMR spread.The global spread of antimicrobial resistance (AMR) is closely associated with international travel. AMR is a severe global concern and has compromised treatment options for many bacterial pathogens, among them pathogens carrying extended-spectrum beta-lactamase (ESBL) and colistin resistance genes. Colonizing multidrug-resistant (MDR) organisms have the potential to cause serious consequences. Infections caused by antimicrobial-resistant bacteria, including MDR bacteria, are associated with longer hospitalization, poorer patient outcomes, greater mortality and higher costs compared to infections with susceptible bacteria. This study elucidates the numerous different types of plasmids carrying AMR genes in colonizing ESBL-producing Infections caused by antimicrobial-resistant organisms are harder to treat, lengthen hospital stays, increase mortality rates and place a significant financial burden on healthcare institutes . It is iEscherichia coli, a Gram-negative human gut commensal and opportunistic extraintestinal pathogen, is an important vector for AMR  and ant.0.8.10) ] from th.0.8.10) .E. coli were cultured overnight on UTI chromogenic agar (Sigma) at 37 °C. After purity checks single colonies were subcultured overnight in lysogeny broth (LB) (Miller) . For the majority of isolates DNA was extracted using Monarch Genomic DNA Extraction kit (NEB), but in some instances a lower quantity and quality yield was obtained. In these instances, we observed atypical precipitates and opted for extraction using phenol/chloroform with cetyltrimethylammonium bromide (CTAB). The extracted DNA was sequenced over four runs of MinION (Oxford Nanopore Technology) using R9.4.1 flow cells. Three runs were prepared using Ligation Protocol (LSK-SQK109) and one run was prepared with the Rapid Barcoding Sequencing kit (SQK-RBK004), with both protocols modified to a one-pot implementation.https://github.com/nanoporetech/pyguppyclient). The quality of the data was examined using NanoPlot (v1.28.2) . (v0.4.7)  and visu(v0.4.7) . In some(v0.4.7)  to assem(v0.4.7)  and Plas(v0.4.7) . TigSPLIblast. Where possible, plasmid replicons were sub-typed using the PubMLST database (https://pubmlst.org/) , or miniature inverted-repeat tandem elements (MITEs) [tet(A) in pLAO84]. The remaining plasmid, pLAO41, contained mcr-1 but no detectable IS elements.The vast majority . IS3 and IS5 were also common, present in 75 % (n=27) and 78 % (n=28) of AMR plasmids, respectively. Differences in IS6 family element carriage were seen between AMR and non-AMR plasmids, with AMR plasmids containing a mean of five IS6 family elements per plasmid (range 0–9). In contrast, only 24 % (n=4) of non-AMR plasmids carried IS6 family elements, with only 1–2 IS6 elements per plasmid  contained ESBL genes, a colistin resistance gene or both. Our data showed the abundance and importance of F-type, X-type, Q-type and ColE1-like plasmids as vectors for AMR gene spread in E. coli in Laos. AMR plasmids accounted for 38.1 % (n=40) of the 105 distinct plasmids and 17 of these 40 AMR plasmids identified were F-type (42.5 %), highlighting their importance as carriers of AMR genes . F-type plasmids are known to carry AMR genes [In this study we conducted an in-depth investigation of the role of plasmids in the alarmingly high levels of AMR found in  to Laos . We haveMR genes  and are ds n=30, 5 % contaE. coli. Small ColE1-like θ-RNA plasmids are common in E. coli [n=26) were the most prevalent plasmids in the collection, followed by F-types (n=23) (n=3) carried AMR genes. This is consistent with previous findings that ColE1-like plasmids occasionally carry resistance genes, including aminoglycoside and beta-lactam resistance determinants [tet(A)-carrying ColE1-like plasmid pLAO84 clearly demonstrates the capacity these small plasmids have for disseminating resistance genes. pLAO84 was found in multiple E. coli STs in this collection, suggesting that it was circulating in the local E. coli population before being acquired by multiple study participants . Additionally, the presence of a plasmid that was almost identical to pLAO84 in GenBank (GenBank accession CP057097.1) indicates that this ColE1-like plasmid lineage has already spread internationally, as it was present in Escherichia fergusonii isolated from pig faeces in the UK.A variety of less anticipated vehicles for AMR genes were identified in these Lao . coli  and theis (n=23) , but in rminants . While rrminants . The tetE. coli, including tetracycline and sulphonamide resistance genes, which were also found in pLAO59 [A Y-type phage-plasmid  highlighted an additional opportunity for AMR spread, since there is a chance for co-selection of this MDR plasmid due to carriage of metal resistance genes, e.g. for silver and copper. pLAO59 appeared not only to have lost key phage genes required for the lytic lifestyle , apparenn pLAO59 .mcr genes, for example, were found next to multiple TEs (mcr-3.4 is associated with the FII-type [Ecp1 is known to contribute to the spread of blaCTX-M [Ecp1 was identified (pLAO32) as part of a blaCTX-M-55-containing transposition unit flanked by the 5 bp target site duplication TAACA. Most blaCTX-M genes in this collection were associated with complete copies of IS26 and partial ISEcp1 (26 from the IS6/26 family is known to play a key role in AMR gene dissemination [26 carriage predisposes plasmids to insertion of additional IS26 and any associated AMR genes, which facilitates the accumulation of AMR genes at single sites, leading to multidrug resistance phenotypes [26 and, based on what is known of IS26 behaviour [26 is likely to have played an important role in the assembly of their complex co-carriage resistance regions (Multiple combinations of AMR resistance genes were found in multiple genetic contexts associated with various mobile genetic elements. FII-type . ISEcp1 laCTX-M , but intmination . IS26 caenotypes . This apehaviour , IS26 is regions .E. coli hybrid assemblies has confirmed the vast and diverse genetic context of AMR in the Kantele et al. dataset isolated in Laos, and highlighted that in addition to multiple unique colonizing strains [Analysis of plasmid contigs from 49  strains , there aClick here for additional data file.Click here for additional data file.


Pharmaceutics entitled “Biomimetic and Functional Nanomaterials for Molecular Imaging,” which focuses on the exciting advancements in molecular imaging facilitated by biomaterials and nanotechnology. The development of non-invasive imaging technologies has revolutionized disease diagnosis, the study of the mechanisms of action, and the exploration of novel therapeutic approaches. In recent years, the convergence of biomaterials and nanotechnology has paved the way for innovative medical imaging techniques, propelling molecular imaging into a multidisciplinary discipline with tremendous potential.Welcome to this Special Issue of the journal Nanotechnology has played a pivotal role in transforming molecular imaging from a mere image acquisition process to a comprehensive field that combines sensitivity, selectivity, functional imaging, and the integration of therapeutic and diagnostic functions within molecular platforms (known as theranostics). By leveraging nanotechnology and existing imaging modalities such as magnetic resonance imaging (MRI), X-ray computerized tomography (CT), positron emission tomography (PET), and ultrasound imaging, the field of molecular imaging is becoming an essential technology in biomedicine.Given the wide-ranging applications of biomaterials in biomedical research and, specifically, in the field of molecular imaging, this Special Issue aims to present noteworthy research and review articles that showcase the current state-of-the-art in biomaterial assessment, recent technological breakthroughs, and their functions and applications in molecular imaging.“Synthetic Antiferromagnetic Gold Nanoparticles as Contrast Agents for MRI and CT” .“Iron Oxide Conjugation for dual MRI and Fluorescent Imaging of Brain Tumors” .“Divalent Manganese Ions for Cross-Linking and MRI Contrast in Intrathecal Injection of Hydrogel-Embedded Stem Cells” .“Molecular Imaging for Myelin Quantification in Organotypic Cultures” .“Iron Oxide-Bold Nanoparticles for In Vivo Imaging and Photothermal Therapy” .“Quantification of Iron Oxide Nanoparticle Uptake in Mouse Brachiocelphalic Artery Atherosclerotic Plaque using T2-Weighted MRI” .“Review of New Approaches in Nanomedicine for Ischemic Stroke” .We are thrilled to present a collection of insightful papers that exemplify the progress being made in the field. The articles selected for this Special Issue include:These papers highlight the diverse applications and significant contributions that biomaterials and nanotechnology bring to molecular imaging. From enhancing imaging contrast and targeting specific tissues to enabling therapeutic and cell interventions and quantifying disease progression, these studies exemplify the transformative potential of this interdisciplinary field.We extend our gratitude to the authors for their valuable contributions and the reviewers for their diligent efforts in ensuring the high quality of the published work. Their collective efforts have made this Special Issue a comprehensive source of the latest advancements and insights in biomaterials and nanotechnology for molecular imaging.We hope that this Special Issue serves as a valuable resource for researchers, clinicians, and stakeholders interested in the rapidly evolving field of molecular imaging. We anticipate that the findings presented here will inspire further exploration, collaboration, and innovative applications in the ever-expanding realm of biomaterials and nanotechnology for improved disease understanding, diagnosis, and treatment.We hope that readers enjoy reading this Special Issue, and we hope that it will stimulate fruitful discussions and future breakthroughs in the fascinating field of molecular imaging.