Potential Incompatibility Research Articles

Leveraging high-throughput analytics and automation to rapidly develop high-concentration mAb formulations: integrated excipient compatibility and viscosity screening

Abstract Background: Formulation screening is essential to experimentally balance stability and viscosity in high-concentration mAb formulations. We developed a high-throughput approach with automated sample preparation and analytical workflows to enable the integrated assessment of excipient compatibility and viscosity of mAb formulations. Methods: Ninety-six formulations of a trastuzumab biosimilar were screened by combining 8 types of excipient modifiers with 4 types of buffers across a pH range of 4.5 to 7.5. Key stability risks, including high molecular weight (HMW) aggregation and fragmentation, were thoroughly assessed along with viscosity at high concentrations. Additionally, several biophysical parameters were evaluated for their ability to predict stability or viscosity outcomes. Multiple linear regression was applied to fit the data and identify key factors. Results: The optimal pH range for the trastuzumab biosimilar was found to be 5.0 to 6.5, based on opposing pH dependencies for stability and viscosity. Buffer type had a minor effect on viscosity and fragmentation but played a significant role in influencing HMW aggregates, with Na-acetate and histidine-HCl being the best candidates. The impact of excipient modifiers on viscosity, HMW, and fragmentation depended on both pH and buffer type, showing strong interactions among factors. Arginine-HCl and lysine-HCl effectively lowered viscosity of the trastuzumab biosimilar at pH levels above 6.0, while glycine formulations were more effective at reducing viscosity below pH 6.0. Histidine-HCl, arginine-HCl, and lysine-HCl lowered the risk of HMW aggregation, whereas formulations containing Na-phosphate or NaCl showed higher HMW aggregation. Formulations with arginine-HCl, lysine-HCl, and NaCl demonstrated a rapid increase in fragmentation at pH levels below 5.0, while Na-aspartate formulations showed increased fragmentation at pH levels above 6.5. Conclusion: Hence, it is important to optimize the levels of each chosen excipient in the formulation study to balance their benefits against potential incompatibilities. This study serves as a foundation for identifying high-concentration antibody formulations using a high-throughput approach, where minimal materials are required, and optimized formulation design spaces can be quickly identified.

Social Evidence Tampering and the Epistemology of Content Moderation

AbstractSocial media misinformation is widely thought to pose a host of threats to the acquisition of knowledge. One response to these threats is to remove misleading information from social media and to de-platform those who spread it. While content moderation of this sort has been criticized on various grounds—including potential incompatibility with free expression—the epistemic case for the removal of misinformation from social media has received little scrutiny. Here, I provide an overview of some costs and benefits of the removal of misinformation from social media. On the one hand, removing misinformation from social media can promote knowledge acquisition by removing misleading evidence from online social epistemic environments. On the other hand, such removals require the exercise of power over evidence by content moderators. As I argue, such exercises of power can encourage suspicions on the part of social media users and can compromise the force of the evidence possessed by such users. For these reasons, the removal of misinformation from social media poses its own threats to knowledge.

Incompatibility of Y-site-administered drugs: the case of acyclovir and ciprofloxacin

Abstract Objectives Multiple drug administration is a common practice in hospitals and clinics. This is the case when multiple pathologies are treated. In this context, frequently, antivirals and antibiotics are co-administrated either simultaneously or sequentially ignoring potential incompatibilities. In this study, we focused on an antiviral (acyclovir) and an antibiotic (ciprofloxacin) compatibility/incompatibility when they are co-administrated. Methods In this study, we focused on the effect of drug ratio, pH, and delay by implementing robust high-performance liquid chromatography methods to determine the main factors leading to potential modification of concentration of one of the two drugs in the mixture. Key findings The results showed that acyclovir is quantitatively recovered in all conditions related to pH, concentration, and time (up to 24 hours). However, ciprofloxacin is strongly altered depending on the acidic and basic conditions, the quantity of ciprofloxacin used, and the time after mixing the two drugs. The most valuable piece of information is that the ratio of acyclovir/ciprofloxacin is crucial. Conclusions The volume ratio of acyclovir/ciprofloxacin (prepared at 2 mg/ml each) should be calculated and managed to provide at least two-fold quantity of acyclovir versus ciprofloxacin or at least nine-fold quantity of ciprofloxacin versus acyclovir to maintain the administrated doses and prevent physicochemical interactions.

Challenges and Controversies to the European CBAM from a Legal Perspective

The Carbon Border Adjustment Mechanism (CBAM), proposed by the European Union to combat carbon leakage, presents a complex landscape of opportunities and challenges in the realm of global climate governance. This paper explores the problems and controversies surrounding CBAM, including potential WTO incompatibility, violations of UNFCCC principles, and complexities in carbon accounting. It also examines the potential impact of CBAM on developing countries and offers a range of suggested solutions. These solutions encompass designing domestic carbon markets in alignment with the European model, implementing policy and regulatory reforms, fostering China-European bilateral relations, and emphasizing international cooperation and adherence to established legal frameworks. Additionally, at the enterprise level, strategies to invest in green technologies, establish comprehensive carbon accounting systems, and adapt to the evolving low-carbon economy are proposed. By addressing these challenges and embracing these strategies, nations and businesses can contribute to a more sustainable and equitable global climate governance framework.

2142 Shared decision-making on treatment escalation planning in the acute medical setting for older patients: a qualitative study

Abstract Introduction Shared Decision-Making (SDM) is increasingly expected in most aspects of UK medical practice and can be particularly important for older patients to guide goals of care. Treatment Escalation Plans (TEP) summarise medical intervention to be attempted in the event of acute deterioration. Current guidance advocates SDM in TEP but it is unclear whether this is considered practicable by clinicians. This study aims to understand clinicians’ perspectives on SDM in TEP for older patients in the acute medical setting. Methods This was a qualitative study following a relativist constructivist approach. 26 consultant and registrar doctors were recruited from general internal medicine, intensive care, palliative care and emergency medicine. A clinical doctoral student conducted semi-structured interviews including vignettes of older multi-morbid patients with capacity to discuss treatment escalation. Reflexive thematic analysis was performed. Ethics approvals were obtained from the Health Research Authority 22/HRA/4387. Results Three themes were generated: ‘An unequal partnership’, ‘Options without equipoise’ and ‘Decisions with shared understanding’. SDM incorporating patient preferences with clinical opinion was seldom perceived to be appropriate. Clinical complexity and use of intuition, together with lack of perceived moral equipoise, motivated clinicians to develop medically acceptable TEPs. Shared understanding with the patient and family and avoiding conflict were important. Conclusions Contrary to current guidance, SDM was considered a potential barrier to formulating appropriate TEPs in the acute medical setting. This study suggests potential incompatibility between policies prioritising patient autonomy and the right to make unwise decisions, and those stating clinicians’ prerogative to determine realistic chance of treatment success and not provide intervention considered medically inappropriate.

Potential incompatibility of inherited behavior patterns with civilization: Implications for Fermi paradox.

All intelligent organisms presumably originally have a number of inherited behavior patterns (IBPs) that are not fine-tuned for conditions prevailing in civilized communities. Indeed, some IBPs may be highly incompatible with such conditions and have high potential to induce self-destruction. These patterns may include responses of social organisms seeking power over conspecifics in relation to harvesting and consuming energy. It is possible that all emerging civilizations could face problems associated with incompatible IBPs, which may partially explain why civilizations are apparently rare (since we have not detected any others in our galaxy).

Programming utopia: artificial intelligence, judgement, and the prospect of jurisgenesis

ABSTRACT There has been much handwringing about artificial intelligence’s application to law. Much of it regards AI’s potential incompatibility with restrictions on the unauthorized interpretation of law. However, the arguments commonly offered in defence of these restrictions fail to justify curtailing a technology that promises to narrow the ‘justice gap’ and deliver us to a more egalitarian future. Despite this failure, however, I contend that utopian visions of ‘robot lawyers’ nevertheless cast a dystopian shadow, as the increased use of AI encroaches on the space of human judgement. At stake in this encroachment, I contend, is the possibility of jurisgenesis, the interpretive activity by which law’s material power and normative meaning are bound. Preserving this possibility, I conclude, requires that discussions of law and AI must include not only scholars of law and of machine learning, but also humanists, who concern themselves with the connection between our law and our humanity.

Frontal fibrosing alopecia—A new absolute contraindication for deep chemical peels

Frontal fibrosing alopecia (FFA) is characterized by a receding hairline in the frontotemporal region due to the gradual loss of hair follicles and then follicular stem cells and follicular fibrosis. Follicular stem cells are crucial in skin healing after chemical peeling and other resurfacing procedures. Although there is a possible association of FFA with a history of facial and scalp surgical procedures, there is no information on the safety of cosmetic procedures in patients with FFA. We report five patients with FFA who experienced unusual and complicated outcomes after undergoing a deep chemical peel (phenol and croton oil). As the prevalence of FFA continues to increase globally, it is essential to raise awareness about the potential incompatibility of this dermatologic disorder with specific cosmetic procedures, such as deeper peels and other resurfacing modalities.

Principles for embedded emissions accounting to support trade-related climate policy

ABSTRACT Climate policy – though shaped by international regimes – has traditionally been heavily domestic in practice. Accordingly, public emissions accounting frameworks have been designed to support policies targeting emitting processes within the territory, and to facilitate the production of National Accounts. Now, a combination of emissions leakage, competitiveness, and both investor and consumer concerns are driving the rapid emergence of policies targeting emissions embodied in traded products. To support these product-targeted policies, governments are investing in the development of public embedded emissions accounting frameworks (EEFs). While EEFs as an information instrument have enormous potential to support the transition to a net-zero global economy, they equally have the potential to inhibit trade, slow the transition, and have a disproportionate impact on developing countries – both through their design, and through potential incompatibilities between accounting developed in different jurisdictions. This article contributes to addressing these challenges by describing the minimum viable set of principles for an emissions accounting information instrument to be compatible with both international trade law and climate change mitigation regimes. To identify these design principles, our method is a systematic review of carbon accounting and trade law literature. Noting the prominent place of principles in guidelines for carbon accounting practice, we additionally extract principles identified in leading emissions accounting guidelines. Theory-based identification and analysis of these systematically extracted principles is used to develop the synthesized set of key principles for the design of public embedded emissions accounting schemes for traded products. Public agencies developing approaches for product emissions accounting, such as to meet requirements for carbon border adjustment mechanisms, could use these principles to guide design and negotiation.

Investigation of the drug–drug interaction and incompatibility mechanism between Aconitum carmichaelii Debx and Pinellia ternata (Thunb.) Breit

Ethnopharmacological relevanceThe combination of Aconitum carmichaelii Debx (Chuanwu, CW) and Pinellia ternata (Thunb.) Breit (Banxia, BX) forms an herbal pair within the eighteen incompatible medicaments (EIM), indicating that BX and CW are incompatible. However, the scientific understanding of this incompatibility mechanism, especially the corresponding drug–drug interaction (DDI), remains complex and unclear. Aim of the studyThis study aims to explain the DDI and potential incompatibility mechanism between CW and BX based on pharmacokinetics and cocktail approach. Materials and methodsUltraperformance liquid chromatography–tandem mass spectrometry methods were established for pharmacokinetics and cocktail studies. To explore the DDI between BX and CW, in the pharmacokinetics study, 10 compounds were determined in rat plasma after administering CW and BX–CW herbal pair extracts. In the cocktail assay, the pharmacokinetic parameters of five probe substrates were utilized to assess the influence of BX on cytochrome P450 (CYP) isoenzyme (dapsone for CYP3A4, phenacetin for CYP1A2, dextromethorphan for CYP2D6, tolbutamide for CYP2C9, and omeprazole for CYP2C19). Finally, the DDI and incompatibility mechanism of CW and BX were integrated to explain the rationality of EIM theory. ResultsBX not only enhances the absorption of aconitine and benzoylaconine but also accelerates the metabolism of mesaconitine, benzoylmesaconine, songorine, and fuziline. Moreover, BX affects the activity of CYP enzymes, which regulate the metabolism of toxic compounds. ConclusionsBX altered the activity of CYP enzymes, consequently affecting the metabolism of toxic compounds from CW. This incompatibility mechanism may be related to the increased absorption of these toxic compounds in vivo.

Phase separation and gelation of gelatin-glucose syrup mixtures and gummy confections: Effects of moisture content, sugars, citric acid, and citrates

Phase separation is a prevalent phenomenon in gummy confections, often arising from potential molecular incompatibility between gelatin and long-chain polysaccharides in glucose syrups (GS). This study focuses on analyzing the phase separation and gelling behaviors of gelatin-GS mixtures, elucidating the roles played by water content and small molecular weight (MW) additional ingredients. Mixtures with 6% gelatin, 40% GS, and varying portions of water, sucrose/allulose, citric acid (CA), and citrates (soluble/insoluble) were prepared. Phase separation behaviors were observed using inverted fluorescent microscopy, with the gel properties characterized using rheology, texture profile analysis (TPA), and water-holding capacity (WHC) analysis. The results highlight the significant impacts of these small MW components on biopolymer compatibility (cosolubility). In gelatin-GS-water mixtures, reducing the water ratio without the addition of sugars promoted phase separation towards the polysaccharide-rich morphologies, while enhancing the sol-gel transition and gel strength due to increased gelatin/water ratio. The incorporation of sucrose or allulose into gelatin-GS-water mixtures, without altering the gelatin/GS/water ratio, generally improved the protein-polysaccharide co-solubility during mixing but had an adverse overall effect on gel formation. Acidification with CA increased the surface charges of the proteins, enhancing the biopolymer miscibility and gelling performance. Soluble citrates, e.g., sodium citrate (SC) and potassium citrate (PC), promoted protein-polysaccharide miscibility and gelation at low concentrations (1–5%), but led to severe phase separation and weakened gelation at higher dosage levels (7.5–10%). In contrast, insoluble citrate, i.e., calcium citrate (CC), marginally enhanced the protein-polysaccharide miscibility while facilitating gummy gelation as an active filler.

Enhancing quantum metrology for multiple frequencies of oscillating magnetic fields by quantum control

Abstract Quantum multi-parameter estimation has recently attracted increased attention due to its wide applications, with a primary goal of designing high-precision measurement schemes for unknown parameters. While existing research has predominantly concentrated on time-independent Hamiltonians, little has been known about quantum multi-parameter estimation for time-dependent Hamiltonians due to the complexity of quantum dynamics. This work bridges the gap by investigating the precision limit of multi-parameter quantum estimation for a qubit in an oscillating magnetic field model with multiple unknown frequencies. As the well-known quantum Cramér–Rao bound is generally unattainable due to the potential incompatibility between the optimal measurements for different parameters, we use the most informative bound instead which is always attainable and equivalent to the Holevo bound in the asymptotic limit. Moreover, we apply additional Hamiltonian to the system to engineer the dynamics of the qubit. By utilizing the quasi-Newton method, we explore the optimal schemes to attain the highest precision for the unknown frequencies of the magnetic field, including the simultaneous optimization of initial state preparation, the control Hamiltonian and the final measurement. The results indicate that the optimization can yield much higher precisions for the field frequencies than those without the optimizations. Finally, we study the robustness of the optimal control scheme with respect to the fluctuation of the interested frequencies, and the optimized scheme exhibits superior robustness to the scenario without any optimization.

The distinctly zetetic significance of disagreement

Recent debates about disagreement’s significance have largely focused on its epistemic significance. However, given how much attention has already been paid to its epistemic significance, we might well wonder: what significance might disagreement have when we consider other related normative domains? And, in particular, what significance might it have when we consider the broader domain of inquiry, or what some thinkers have called either the “zetetic” or “erotetic” domain? In response, this paper suggest three things. Firstly, it suggests how we might clarify the relations among the epistemic, erotetic, and zetetic domains of normativity, given their potential differences and incompatibilities. Then, it suggests that disagreement’s significance within inquiry can either be tied to erotetic norms or to either of two sorts of zetetic norms: vindication-directed or possession-directed norms. And finally, it suggests preferred answers to the question of what disagreement’s distinctly zetetic significance might be, given the participating inquirers’ ordinarily-conceived zetetic standings and how their sets of dialectically accessible evidence might compare.

Corroboration and contradictions in global biodiversity indicators

Biodiversity indicators measure progress toward global biodiversity goals, including the Kunming-Montreal Global Biodiversity Framework of the UN Convention on Biological Diversity. A suite of indicators is typically needed to capture the complexity of biodiversity. For the suite to be effective, it needs to capture the important aspects of the system, without over-representing some at the expense of others. It is therefore important to identify redundancies and contradictions between indicators within a suite. Comparing indicators derived from independent input data can also serve as a validation of indicator accuracy, or alternatively, identify unexpected behaviour and potential flaws or incompatibilities in data or construction. We examined the relationships between eight widely adopted global biodiversity indicators, all proposed for use in the monitoring framework of the Kunming-Montreal global biodiversity framework. We focused on the relationships between indicators driven by landuse data and those driven by species observations, testing for pairwise and multivariate correlations between indicator values for ecoregions. We used hierarchical clustering to identify spatial patterns in relationships between landuse and species response indicators. We found no strong correlation between landuse and species-response indicators in ecoregions with high landuse. Reasons for disagreement among indicators may include inaccurate, or coarse spatial data and mismatched baselines. We did find strong correlations between indicators sharing input data. We suggest that indicators selected for the Kunming-Montreal framework be systematically reviewed for correlations and recommend that suites of indicators should consider the independence of input data sources to minimise the risk of using correlated or biased measures of conservation progress.

Impact of Arbuscular Mycorrhizal Fungi (AMF) on nutrient uptake and the growth of <i>C. retusa<?i> and <i>S. occidentalis<?i> under phosphorus stress

This study investigates the influence of Arbuscular Mycorrhizal Fungi (AMF) on the growth of Crotallaria retusa and Senna occidentalis under three phosphorus levels (low, medium, and high). Conducted in the experimental garden of Ahmadu Bello University Zaria, the soil samples were collected from a degraded site at the Institute of Agricultural Research, sieved, and sterilized. Perforated buckets were filled with sterilized soil, and the trench method was employed for AMF application. Three phosphorus levels were tested, and seeds of C. retusa and S. occidentalis were planted in individual buckets. Daily watering and observations were carried out for twelve weeks, measuring seedling height, leaf length, width, and number of leaves. The results indicate that high phosphorus concentration (12g/bucket) constrains the growth of C. retusa, while medium concentration (6g/bucket) enhances shoot length, branches, and leaves. AMF inoculation significantly improves growth attributes, but reduced growth in C. retusa under high phosphorus suggests potential incompatibility between phosphorus and AMF. At week 6, medium phosphorus (6g/bucket) resulted in more leaves (122.17±37.61) than low and high levels. Lowest growth occurred at low phosphorus (0g/bucket). Arbuscular mycorrhizal fungi improved overall growth, but high phosphorus hindered C. retusa growth due to potential incompatibility with AMF. Overall, the study highlights the complex interplay between AMF, phosphorus levels, and plant growth, offering insights into optimizing conditions for the cultivation of C. retusa and S. occidentalis.

Mapping restricted introgression across the genomes of admixed indigenous African cattle breeds

BackgroundThe genomes of indigenous African cattle are composed of components with Middle Eastern (taurine) and South Asian (indicine) origins, providing a valuable model to study hybridization and to identify genetic barriers to gene flow. In this study, we analysed indigenous African cattle breeds as models of hybrid zones, considering taurine and indicine samples as ancestors. In a genomic cline analysis of whole-genome sequence data, we considered over 8 million variants from 144 animals, which allows for fine-mapping of potential genomic incompatibilities at high resolution across the genome.ResultsWe identified several thousand variants that had significantly steep clines (‘SCV’) across the whole genome, indicating restricted introgression. Some of the SCV were clustered into extended regions, with the longest on chromosome 7, spanning 725 kb and including 27 genes. We found that variants with a high phenotypic impact (e.g. indels, intra-genic and missense variants) likely represent greater genetic barriers to gene flow. Furthermore, our findings provide evidence that a large proportion of breed differentiation in African cattle could be linked to genomic incompatibilities and reproductive isolation. Functional evaluation of genes with SCV suggest that mitonuclear incompatibilities and genes associated with fitness (e.g. resistance to paratuberculosis) could account for restricted gene flow in indigenous African cattle.ConclusionsTo our knowledge, this is the first time genomic cline analysis has been applied to identify restricted introgression in the genomes of indigenous African cattle and the results provide extended insights into mechanisms (e.g. genomic incompatibilities) contributing to hybrid differentiation. These results have important implications for our understanding of genetic incompatibilities and reproductive isolation and provide important insights into the impact of cross-breeding cattle with the aim of producing offspring that are both hardy and productive.

Systematic review on contract-based safety assurance and guidance for future research

The safety requirements are often described via specifications called contracts. To verify that the system fulfils certain safety requirements, for instance, in the assume-guarantee contract specification, the key safety indicators are organized, so that if certain assumptions hold then the respective behaviour is guaranteed. Safety contracts provide a means of exposing potential incompatibilities early in the development process, selecting components to reuse, certifying systems, and identifying uncertainty sources during the operational phase. There exist several studies on contract-based safety assurance, however, there is not any systematic study in this field. For this, a first Systematic Literature Review (SLR) is carried out to obtain an overview of the various contract-based safety assurance concepts, problems, proposed solutions, and their usefulness. In our study, the identification and selection of the primary studies were based on a well-planned search strategy. The search process identified a total of 2881 studies published between 1969 and 2021, out of which 66 studies were selected through a multi-stage process according to our predefined SLR protocol. This SLR aims to highlight the state-of-the-art of contract-based safety assurance and identify potential gaps for future research. Based on research topics in selected studies, we identified the following main categories: contract type, analysis techniques for system safety, compliance with standards, development stage, domain, level of automation, type of study and evaluation, and tool support. The findings of the systematic review not only highlight that the contracts are even more important for advanced safety-critical systems but also strategies to exploit their full potential should be considered in future studies. The suggestions revealed for future research include the usage of contracts for adapting new behaviour, defining system boundaries, interacting with other systems, managing risk during operation, dynamic/runtime safety assurance, and integration of safety with security.

Visible Light Induced Copper-Catalyzed Enantioselective Deaminative Arylation of Amino Acid Derivatives Assisted by Phenol.

The exploration of value-added conversions of naturally abundant amino acids has received considerable attention from the synthetic community. Compared with the well-established asymmetric decarboxylative transformation, the asymmetric deaminative transformation of amino acids still remains a formidable challenge, mainly due to the lack of effective strategies for the C-N bond activation and the potential incompatibility with chiral catalysts. Here, we disclose a photoinduced Cu-catalyzed asymmetric deaminative coupling reaction of amino acids with arylboronic acids. This new protocol provides a series of significant chiral phenylacetamides in generally good yields and excellent stereoselectivity under mild and green conditions (42-85 % yields, up to 97 % ee). Experimental investigations and theoretical calculations were performed to reveal the crucial role of additional phenols in improving catalytic efficiency and enantiocontrol.

Visible Light Induced Copper‐Catalyzed Enantioselective Deaminative Arylation of Amino Acid Derivatives Assisted by Phenol

AbstractThe exploration of value‐added conversions of naturally abundant amino acids has received considerable attention from the synthetic community. Compared with the well‐established asymmetric decarboxylative transformation, the asymmetric deaminative transformation of amino acids still remains a formidable challenge, mainly due to the lack of effective strategies for the C−N bond activation and the potential incompatibility with chiral catalysts. Here, we disclose a photoinduced Cu‐catalyzed asymmetric deaminative coupling reaction of amino acids with arylboronic acids. This new protocol provides a series of significant chiral phenylacetamides in generally good yields and excellent stereoselectivity under mild and green conditions (42–85 % yields, up to 97 % ee). Experimental investigations and theoretical calculations were performed to reveal the crucial role of additional phenols in improving catalytic efficiency and enantiocontrol.

Risks for Knowledge-uptake in Dutch Marine Spatial Planning: Incompatibilities Between Research and Policy-making

The rapid increase of Offshore Wind Farm (OWF) development in the North-Sea occurs under serious uncertainty, partly due to knowledge gaps concerning the North-Sea’s socio-ecological system. The situation is particularly urgent in the Netherlands due to the intense use of its maritime zone and related conflicts among stakeholders. Optimising the placement of OWFs requires the uptake of multidisciplinary knowledge in Marine Spatial Planning (MSP) policy through ongoing adaptation of policies to new knowledge. Currently, knowledge-uptake from research into policy is widely mentioned as a challenge for MSP, but knowledge management theory has hardly been applied to it. To be useful in the multidisciplinary environment of MSP, a common language about knowledge is needed to allow for cooperation between scientific disciplines and policy sectors. However, many risks exist that may hinder knowledge-uptake between research and policy-making. This thinking-gap between research and policy-making is recognised in many fields. However, MSP and relevant knowledge about the North-Sea is rapidly developing and understudied. This results in a high pressure and dynamic situation in a developing field which can be an insightful case to apply knowledge-management theory and provide new insights for scholars of MSP. This study focuses on risks for knowledge uptake that derive from incompatibilities between researchers and policy-makers in the use and development of knowledge within the context of OWF development and MSP. These incompatibilities range from differing timeframes and uses of data to more fundamental differences in roles between researchers desiring to understand the world, and policy-makers desiring to change it. Characteristics of MSP, such as the high political pressure and relative pioneering practice of MSP may exacerbate the impact of such incompatibilities. Notably, MSP may suffer from a focus on short-term policy-making, limited cumulative understanding and fragmentation in policy. The aim of this article is to consider the effect of incompatibilities between systems of research and policy-making on knowledge-uptake in Dutch MSP and how these may be exacerbated by characteristics of MSP. Using knowledge-management literature, a list of potential incompatibilities between systems of research and policy-making is drawn. Data was collected by means of document analysis, in-depth interviews with researchers and policy-makers, and observations of policy workshops, consortium meetings, and focus groups. Findings suggest that risks to knowledge-uptake are partially caused by the incompatibilities between research and policy-making and that the context of MSP exacerbates these incompatibilities in most instances. Simultaneously, some instances were found where MSP can actually help to decrease differences between researchers and policy-makers. However, the incompatibilities between researchers and policy-makers are so enduring that risks to knowledge-uptake still persist. Better joint understanding and recognition of differences between research and policy-making are required to limit the negative effect of incompatibilities between research and policy-making on knowledge uptake.