We develop and test a formal model of leader political life cycle effects within a selectorate framework. The model leads to novel hypotheses about the provision of public goods, private goods, and freedoms over a leader's tenure in power. The analyses show, as hypothesized, that the total provision of benefits as well as the provision of public goods and freedoms decrease significantly the longer a leader is in power, whereas the proportion of rewards in the form of private goods (such as corruption opportunities) increases.

Infant ALL (iALL) is initiated in utero, most often by rearrangement of the KMT2A gene (KMT2Ar). It carries a very poor prognosis despite a lack of additional oncogenic driver mutations common in childhood ALL. Here, we aimed to identify specific properties of human fetal hematopoietic stem/progenitor cells (HSPC) that promote leukemic transformation in KMT2Ar iALL using molecular, functional and in vivo assays. Through comparison of human fetal HSPC with adult HSPC transcriptomes we derived a fetal-specific gene signature and identified the fetal oncogene LIN28B and its downstream effectors among the top hits. These genes were also expressed in iALL. Functional assays revealed that LIN28B was essential in human fetal liver (FL) CD34+ cells to maintain proliferation and stem-like properties, and support B- and NK-lymphopoiesis. To interrogate the role of LIN28B in iALL, we utilized a human FL-derived CRISPR-Cas9 KMT2A::AFF1 model. In this CRISPRKMT2A::AFF1 model, human FL CD34+ cells fail to transform upon induction of KMT2A::AFF1 translocation in the absence of LIN28B. Furthermore, LIN28B-expressing CRISPRKMT2A::AFF1 leukemias were more proliferative in vitro and in vivo, with this advantage being lost upon LIN28B knockdown. Mechanistic studies showed that LIN28B acts by stabilizing key early B-lymphoid genes, epigenetic regulators, and cell cycle and anti-apoptotic genes. Thus, LIN28B has an essential role in normal human fetal B-lymphopoiesis, and is necessary for the initiation of KMT2A::AFF1 iALL in human fetal cells in the absence of co-operating mutations. LIN28B activity may help explain why KMT2A::AFF1 leukemias are so aggressive, making it a potential target in LIN28B-expressing leukemias.

Based on an extension of selectorate theory, we characterize three structural conditions that make a coup likely: winning coalition size near the size that yields minimum utility to its members (so small or intermediate-sized coalitions), low economic productivity, and a leader relatively new to office. Policy misallocation exacerbates the risk of a coup. The theory and evidence show two mechanisms that increase the risk of coup: policy under-provision and over-provision. Leaders whose policy provisions are commensurate with expectations experience fewer coups. One anticipatory response of leaders to a heightened coup risk is to change the government's institutions. High coup risks increase the likelihood of institution change whether a coup actually occurs or not. The threat of an under-provision coup tends to result in an expansion of the winning coalition size (democratization), while an elevated risk of an over-provision coup typically results in a contraction in coalition size whether a coup actually occurs or not.

Genetic alterations alone cannot account for the diverse phenotypes of cancer cells. Even cancers with the same driver mutation show significant transcriptional heterogeneity and varied responses to therapy. However, the mechanisms underpinning this heterogeneity remain under-explored. Here, we find that novel enhancer usage is a common feature in acute lymphoblastic leukemia (ALL). In particular, KMT2A::AFF1 ALL, an aggressive leukemia with a poor prognosis and a low mutational burden, exhibits substantial transcriptional heterogeneity between individuals. Using single cell multiome analysis and extensive chromatin profiling, we reveal that much transcriptional heterogeneity in KMT2A::AFF1 ALL is driven by novel enhancer usage. By generating high resolution Micro Capture-C data in primary patient samples, we identify patient-specific enhancer activity at key oncogenes such as MEIS1 and RUNX2, driving high levels of expression of both oncogenes in a patient-specific manner. Overall, our data show that enhancer heterogeneity is highly prevalent in KMT2A::AFF1 ALL and may be a mechanism that drives transcriptional heterogeneity in cancer more generally.

We develop a theory of resistance and repression in which citizens face a coordination problem and participation in collective resistance must be large enough for a government to concede rather than repress citizens who participate. Repression is costly for both citizens (the punished) and the government (the punisher). Harsher punishments can sometimes raise participation via a strategic-feedback channel that follows from the credibility of implementing repression: a higher cost to the punisher makes a government less willing to repress larger resistance, and this can encourage citizens’ coordinated participation. We identify three factors that determine whether this channel dominates: the shape of the response of the government’s costs to the intensity and scale of repression, the presence of selective incentives, and the presence or absence of focal optimism. We examine a government’s desired choice of repression technology and the response of the social cost of political instability to harsher punishments.

Although genetic alterations drive carcinogenesis (PMID: 29439951), they alone cannot account for the diverse phenotypes of cancer cells. Even cancers with the same driver mutation show significant transcriptional heterogeneity and varied responses to therapy (PMID: 32807900). However, the mechanisms underpinning this heterogeneity remain under-explored. Aberrant enhancer activity is a hallmark of many cancers, including KMT2A::AFF1 acute lymphoblastic leukemia (ALL; PMID: 37626123), an aggressive leukemia subtype with a poor prognosis (PMID: 32376390) and a nearly mutationally silent genetic landscape (PMID: 25730765). Despite the low mutational burden, KMT2A-rearranged leukemias exhibit substantial heterogeneity between individuals, providing an ideal model to study transcriptional heterogeneity without the confounding effect of numerous cooperating mutations. To validate the extent of transcriptional heterogeneity we first compared two patient-derived KMT2A::AFF1 cell lines (RS4;11 and SEM), identifying 2,361 differentially expressed genes via RNA sequencing. Next, we compared enhancer activity using Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq), identifying 3,342 enhancers with significantly altered activity in these KMT2A::AFF1 ALL cell lines. CRISPR-Cas9-based deletion of representative enhancers confirmed cell line-specific activity on their predicted target genes. Using supervised machine learning, we developed a predictive model that identified the KMT2A-complex as a key factor in enhancer activity differences between cell lines. Our previous work showed that KMT2A::AFF1 binds enhancers and regulates them by recruiting a complex that facilitates transcriptional elongation (PMID: 37626123). In line with this, loss of KMT2A::AFF1 or components of the transcription elongation complex significantly diminishes enhancer-promoter interactions and features of active enhancers, implying that it is essential for maintaining enhancer activity (PMID: 37626123). To confirm differential enhancer usage in patients, we used single-cell multiomics (RNA+ATAC) on KMT2A::AFF1 patient blasts, identifying substantial transcriptional heterogeneity and 3,162 differentially active putative enhancers. As ATAC-seq identifies genomic boundary elements in addition to enhancers and promoters, we performed detailed epigenetic profiling of nine KMT2A::AFF1 patient samples (four infants and five children) with a low-cell number optimized chromatin-immunoprecipitation protocol. Employing a deep-learning-based strategy, we reduced intrinsic sample-to-sample noise and dramatically improved the stringency of differential enhancer identification. This approach revealed 2,647 differentially active enhancers, with 61 displaying activity unique to a single patient. We examined whether any unique enhancers were located near prognostically relevant genes and identified putative patient-specific enhancers near MEIS1 and RUNX2. Single-cell expression data revealed elevated MEIS1 and RUNX2 expression in the patient with these unique enhancers. Using Micro-Capture-C (MCC), we confirmed that these enhancers contact the MEIS1 and RUNX2 promoters, implicating these patient specific enhancers in the overexpression of these genes. Overall, our data suggests that enhancer heterogeneity is highly prevalent in KMT2A::AFF1 ALL and appears to be driven by differential KMT2A-complex binding. We identify differential enhancer activity at key oncogenes such as MEIS1 and RUNX2. Analysis of published microarray data shows that overexpression of either gene is associated with significantly reduced overall survival (PMIDs: 20699438, 19880498, 17312329). Taken together, this indicates that enhancer heterogeneity may significantly contribute to the phenotypic diversity observed between patients in ALL.

Political leaders value public demonstrations of support from foreign leaders and frequently make concessions in order to obtain them. We model the bargaining dynamics surrounding these exchanges and their impact on the recipient leader’s political survival, with a focus on top-level diplomatic visits as a means of signaling international support. Our model addresses two interrelated questions; first, we consider how symbolic displays of support from one leader to another can be informative even when they are “purchased” with concessions, and second, we derive the equilibrium price and political impact of a visit under different bargaining protocols. The incentive to make a concession in exchange for a visit generally undermines a visit’s signaling value. We identify a diplomatic resource curse, where the existence of opportunities for diplomatic exchange can force leaders into accepting visit-for-concession deals that leave them worse off than if they were diplomatically isolated. Visits never occur when negotiations are fully transparent. Mutually beneficial quid pro quo diplomacy requires opacity in negotiations.

Iron is an irreplaceable co-factor for metabolism. Iron deficiency affects >1 billion people, causing symptoms including anaemia and impaired immunity. Nevertheless, precisely how iron deprivation impacts immune cell function remains poorly characterised. We therefore interrogated how physiologically low iron availability affected activated CD8+ T cell metabolism and function, using multi-omic and metabolic labelling approaches. Iron limitation profoundly stalled proliferation without influencing cell viability, altered histone methylation status and disrupted mitochondrial membrane potential. Consistently, metabolism of glucose and glutamine in the TCA cycle was limited, indeed TCA cycle activity was partially reversed to a reductive trajectory. Previous studies have shown mitochondria-derived aspartate is crucial for proliferation of transformed cells. Surprisingly, we found aspartate was increased in stalled iron deficient CD8+ T-cells, but was not utilised cytosolically for nucleotide synthesis, likely due to trapping within depolarised mitochondria. Conversely, exogenous aspartate, which directly accesses the cytosol, markedly rescued the clonal expansion of even severely iron-deficient CD8+ T-cells. Overall, iron scarcity creates a mitochondrial-located metabolic bottleneck impairing T-cells, which can be bypassed by resupplying inhibited biochemical processes with aspartate. These findings reveal molecular consequences of iron deficiency for CD8+ T cell function, providing mechanistic insight into the basis for immune impairment during iron deficiency.### Competing Interest StatementT.A.M. is a paid consultant for and shareholder in Dark Blue Therapeutics Ltd. D.A.T undertakes paid consultancy work for Sitryx Ltd.

United Nations Security Council (UNSC) membership comes with privileges. Existing research shows that the world's most powerful countries funnel financial favors to governments elected to the UNSC, arguably to influence their votes on matters of international importance. This study investigates whether these governments, whose election elevates them to prominent positions of power, also receive security benefits. We argue that elected UNSC members win the attention and protection of the world's super powers, and, as a result, are less likely to be attacked. But we further argue that the General Assembly and the world's super powers prefer pacific countries on the UNSC. In support of our theory, we find empirically that temporary membership on the UNSC is associated with lower rates of being targeted and lower rates of initiating conflict. We conclude that UNSC membership has existential benefits and is associated with a reduced likelihood of militarized disputes.

ABSTRACT Dysregulation of cellular differentiation is a hallmark of cancer. Isocitrate dehydrogenase (IDH) is commonly mutated multiple cancers including glioma, cholangiocarcinoma, lymphoma and Acute Myeloid Leukaemia (AML). Mutant IDH generates d-2-hydroxyglutarate that inhibits enzymes including Jumonji histone demethylases and TET2. Using primary human IDH2-mutant AML cells as a model, single cell RNA-seq and ATAC-seq, we demonstrated the continuum of cell states during restoration of neutrophilic differentiation to leukaemic progenitors by Enasidenib, a mutant IDH2 inhibitor. In cells which ultimately differentiate, there is co-expression of competing GATA2/RUNX3/SOX4-driven stem-progenitor and pro-differentiation EGR1/JUN/FOS programmes, followed by expression of cell cycle and terminal neutrophil programmes involving CEBP family and SPI1/PU.1. Genes upregulated during differentiation display loss of H3K27me3 in bivalent chromatin but not of H3K4me3, while downregulated genes are enriched for PRC2/EZH2 targets. In contrast to previous reports of a TET2-dependent mechanism for IDH-mutations, we observed only a modest link between promoter DNA CpG methylation and gene expression. For the first time in primary AML, we describe the lifting of differentiation block by de-repression of pro-differentiation genes through modulation of H3K27 demethylation in bivalent chromatin, and thus highlight a novel and important mechanism in how IDH mutations disrupt cell fates in cancer.

Aberrant enhancer activation is a key mechanism driving oncogene expression in many cancers. While much is known about the regulation of larger chromosome domains in eukaryotes, the details of enhancer-promoter interactions remain poorly understood. Recent work suggests co-activators like BRD4 and Mediator have little impact on enhancer-promoter interactions. In leukemias controlled by the MLL-AF4 fusion protein, we use the ultra-high resolution technique Micro-Capture-C (MCC) to show that MLL-AF4 binding promotes broad, high-density regions of enhancer-promoter interactions at a subset of key targets. These enhancers are enriched for transcription elongation factors like PAF1C and FACT, and the loss of these factors abolishes enhancer-promoter contact. This work not only provides an additional model for how MLL-AF4 is able to drive high levels of transcription at key genes in leukemia but also suggests a more general model linking enhancer-promoter crosstalk and transcription elongation.

Cellular ontogeny and MLL breakpoint site influence the capacity of MLL-edited CD34+ hematopoietic cells to initiate and recapitulate infant patients' features in pro-B-cell acute lymphoblastic leukemia (B-ALL). We provide key insights into the leukemogenic determinants of MLL-AF4+ infant B-ALL.

Leaders shift political institutions to ameliorate threats to their tenure. The masses might rebel to replace the leader and change institutions. Disloyalty by political insiders might result in a coup. Leaders liberalize when the masses present a greater threat and ‘autocratize’ to dissipate threats from elites. A two-step procedure tests these arguments: (1) The risks of revolution and coup are estimated as a function of leader health, experience, economic conditions and extant institutions. (2) These risks are used to predict institutional change in a heteroskedastic regression model. The magnitude and direction of institutional change depends upon whether the masses or elites pose the greater threat. When both risks are high, leaders must gamble as to which risk they believe is greatest. In such circumstances, institutions are highly volatile even as the aggregate direction of change becomes unclear.

Background: Infant acute lymphoblastic leukaemia (iALL) has a dismal prognosis, and its characteristic MLL gene rearrangement (MLLr) invariably arises before birth. MLLr alone appears sufficient to transform human fetal liver haematopoietic cells suggesting that fetal molecular programmes may co-operate with MLLr to produce the aggressive phenotype of iALL. One such oncofetal gene, LIN28B is normally expressed exclusively before birth but is known to be aberrantly expressed in a range of malignancies. LIN28B is an RNA binding protein and its canonic oncogenic mechanism is believed to be through repression of let-7 micro RNAs, which act as tumour suppressors for oncogenes such as the MYC and RAS families. The role of LIN28B expression/function in MLLr iALL initiation and maintenance is unknown. Aims: We hypothesise that the oncofetal gene, LIN28B, is required for the initiation and maintenance of iALL. Methods: Molecular: Bulk and scRNAseq datasets were interrogated for LIN28B expression in healthy human fetal liver (FL), fetal bone marrow (BM) and postnatal BM; publicly available bulk RNAseq datasets were analysed for infant (<1year age) and childhood (1-18 years) MLLr ALL. RNAseq, ATACseq and ChIPseq was performed for a human FL-derived MLL-AF4 iALL model (CRISPRMLL-AF4 ALL), SEM cell line and primary patient samples. Functional: SEM cells transduced with lentivirus encoding YFP and (a) control or (b) LIN28B knockdown shRNA(KD) were characterised using RNA sequencing, liquid culture proliferation, apoptosis assay, colony forming assays, and in vivo xenotransplantation in NSG mice. Results:LIN28B is selectively expressed in human fetal HSC, MPP, LMPP and myeloid and erythroid precursor cells, but not B-progenitors or B-cells. It is not expressed in any postnatal HSPC. A subset of iALL patients express LIN28B but there was no LIN28B expression in childhood MLLr ALL. Similarly, a subset of CRISPRMLL-AF4 ALLs expressed LIN28B; further analysis revealed that LIN28B was accessible and bound by MLL-AF4 in CRISPRMLL-AF4 ALLs. In the cell-lines screened: SEM (MLL-AF4+), RCH-ACV (TCF3-PBX1+), and KOPN-8 (MLL-ENL+), only SEM cells express LIN28B. Knockdown of LIN28B in MLL-AF4+ SEM cells (confirmed by qPCR and western blot), caused rapid cell death by apoptosis in liquid culture (Fig 1a&b) and a severe reduction in colony formation in semi-solid medium (n=5, p=0.0004) (Fig 1c). It also significantly prolonged survival in an in vivo ALL model produced by transplantation of control YFP+ or LIN28B KD YFP+ SEM cells, with median survival being 38 days (n= 9 mice) and 58 days (n=12 mice) respectively (p<0.0001) (Fig 1d). When culled LIN28B KD recipients had a predominantly YFP-ve LIN28B+ leukaemia, suggesting a LIN28B KD escape. By contrast the control SEM cells remained YFP+ve. Gene set enrichment analysis of bulk RNA sequencing for SEM control and LIN28B KD cells showed LIN28B KD was negatively associated with let-7 target genes, consistent with knockdown causing an increase in let-7 miRNAs and suppression of their targets. MYC targets, E2F and G2M gene sets are also negatively associated with LIN28B knockdown, which may be let 7 mediated or a direct LIN28B effect. Summary: Aberrant LIN28B expression is seen in a subset of iALL. LIN28B is essential in vitro and in vivo for SEM cells (MLL-AF4+ cell line). Transcriptomic data suggests let-7 axis may cause these changes. Further work is needed to elucidate the role of LIN28B in iALL. As LIN28B is not expressed in postnatal HSPC, targeting LIN28B or downstream effectors could offer an attractive option for therapy with minimal off target effects.Keywords: Infant, Children, Acute lymphoblastic leukemia

In KMT2A-rearranged acute lymphoblastic leukemia (ALL), an aggressive malignancy, oncogenic KMT2A-fusion proteins inappropriately recruit DOT1L to promote leukemogenesis, highlighting DOT1L as an attractive therapeutic target. Unfortunately, treatment with the first-in-class DOT1L inhibitor pinometostat eventually leads to non-responsiveness. To understand this we established acquired pinometostat resistance in pediatric KMT2A::AFF1+ B-ALL cells. Interestingly, these cells became mostly independent of DOT1L-mediated H3K79 methylation, but still relied on the physical presence of DOT1L, HOXA9 and the KMT2A::AFF1 fusion. Moreover, these cells selectively lost the epigenetic regulation and expression of various KMT2A-fusion target genes such as PROM1/CD133, while other KMT2A::AFF1 target genes, including HOXA9 and CDK6 remained unaffected. Concomitantly, these pinometostat-resistant cells showed upregulation of several myeloid-associated genes, including CD33 and LILRB4/CD85k. Taken together, this model comprehensively shows the adaptive potential of KMT2A-rearranged ALL cells upon losing dependency on one of its main oncogenic properties.

States often form battlefield coalitions to combat a shared foe, but are frequently frustrated by their partners' underwhelming efforts while fighting. Why? Using selectorate theory, this chapter contends regime type conditions belligerents' composition of forces and war aims, which then shape provision of effort in combat. Democratic states, with capital-heavy forces and war aims emphasising international collective goods, tend to shirk and free-ride on their partners' efforts during the fighting. Non-democratic states, relying on labour-heavy forces and emphasising private goods war aims, are reluctant to form coalitions and push for operations that benefit them more than the collective. In mixed-regime battlefield coalitions, belligerents' divergent types of forces and war aims create conflicting pressures that undermine cohesion and coordination. The argument is assessed through case studies of three coalition combat efforts during the World Wars. The results strongly support the claim laid out in this chapter and have implications for scholarship on coalition duration and termination, burden-sharing, and democratic warfighting.

Within a formal model of international agreements in the shadow of renegotiations and domestic competition, we highlight three important ways elections shape international agreements. Elections determine who will be in control of policy in the future, which affects how leaders bargain today. Elections also determine the deals policymakers will agree to. Finally, proposers have the opportunity to shape the contours of domestic political competition with what is offered in pre-electoral bargaining. We identify that several canonical results in the literature – like the Schelling conjecture or the idea that hawkish leaders have an innate bargaining advantage over dovish leaders – only hold under certain restrictions on how voters evaluate their leaders. In contrast, we show paradoxically that when voters are prospective, electoral incentives shade the ability for domestic leaders to negotiate better deals for their publics. Counterintuitively, this leads to hawks agreeing to more conciliatory agreements than doves.

Aberrant enhancer activity is a hallmark of many cancers including KMT2A-rearranged acute lymphoblastic leukemia (ALL), an aggressive leukemia subtype with an event-free survival of 19-45% in infant-ALL (<1 year of age) and 50-59% in childhood-ALL cases. Targeting enhancer activity may provide a novel therapeutic strategy for this hard-to-treat disease. Transcription factors are key effectors of enhancer activity. They recognise and bind to specific DNA sequences at enhancers, driving the expression of target genes from these distal loci. MYB is an important hematopoietic transcription factor that is commonly overexpressed in KMT2A-rearranged leukemias and is required for leukemia survival, where loss of MYB has been shown to abrogate the leukemia phenotype. However, the precise mechanism by which MYB contributes to enhancer function, and the stages of enhancer activation at which it acts are unknown. We employed a well-characterized chromatin anchoring system to interrogate MYB function and determine whether it can recruit specific enhancer activities de novo. By fusing the MYB transactivation domain (MYB TA) to the Tet repressor (TetR) DNA binding domain, MYB TA is directed to an array of Tet operator ( TetO) sequences incorporated into a neutral genomic region devoid of native gene regulatory elements. We found that MYB TA alone is sufficient to recruit key enhancer-associated proteins, including P300, Brd4 and Mediator to the TetO locus. We observed MYB TA-dependent deposition of H3K27ac, increased chromatin accessibility and transcription not just at the TetO locus, but remarkably, also at regions more than 50kb away. Using the chromosome conformation capture (3C) technique NG Capture-C, we observed MYB TA-induced DNA interactions between TetO and the distal sites of transcription, as well as more long-range interactions up to 400kb distal to where MYB TA is bound. Together, these observations suggest that MYB TA binding alone is sufficient to establish an enhancer-like regulatory element, which activates distant cryptic promoters. This activity is dependent on the continued presence of MYB TA, as disruption of MYB TA binding results in a rapid loss of transcription and acquired chromatin features, implicating MYB in enhancer maintenance as well as initiation. To confirm our observations in a disease context, we tested the requirement for MYB at endogenous enhancers in SEM cells, a model of KMT2A-rearranged ALL. By stably introducing a degradation tag (FKBP12 F36V) to the endogenous MYB gene, we were able to rapidly induce protein degradation and observe the immediate effects on chromatin features. Using transient transcriptome sequencing, we noted significant transcriptional downregulation of known MYB target genes, including BCL2, MYC, LMO4 and CDK6. We also observed decreases in enhancer H3K27ac levels and eRNA transcription, most marked at MYB-bound loci. To investigate the requirement for MYB in maintaining physical proximity between enhancer and promoter, we performed the base pair-resolution 3C technique Micro-Capture-C (MCC). MCC revealed highly punctate interactions between enhancer elements and their target promoters. At BCL2 and MYC, MYB degradation results in a reduction in interactions with the promoter at discrete regions within the enhancers. This argues for highly localised MYB-dependent activity at enhancers, driving interaction with and activation of distal target promoters. Overall, our data argue for a role for MYB in establishing enhancers de novo, indicating that MYB overexpression may directly result in onco-enhancer activity at key genes in vivo. At a subset of MYB-bound enhancers, the continued presence of MYB is absolutely required to maintain enhancer activity and oncogene upregulation. Further exploration of associated co-factors that mediate MYB-dependent enhancer activity may identify novel targets for therapeutic exploitation.

Introduction: While hip osteoarthritis is a disease of the whole synovial joint, cartilage defects are considered a hallmark feature. A high proportion of young adult football players have hip cartilage defects. However, the role that other intra-articular features play in the pathogenesis of cartilage defects in football players remains unknown. This study had two aims: 1) examine the relationship between imaging-defined intra-articular features (labral tears, bone marrow edema pattern, subchondral cysts, effusion-synovitis and ligamentum teres tears) and cartilage defects (presence and severity) in football players; 2) investigate if the relationship between imaging-defined intra-articular features and cartilage defects is stronger in football players with hip/groin pain Methods: 182 semi-elite football (soccer/Australian football) players (288 hips; 50% soccer; age:26yrs; height:1.79m; weight:78kg; 20% women) with hip/groin pain (>6 months of pain and +ve flexion-adduction-internal-rotation test) and 55 semi-elite control football players (110 control hips; 55% soccer; age:26yrs; height:1.79m; weight:79kg; 25% women) without hip/groin pain underwent 3-tesla MRI. Cartilage defects, labral tears, bone marrow edema pattern (BMEP), subchondral cysts, effusion-synovitis and ligamentum teres tears were scored semi-quantitatively. Logistic and negative binomial regression with generalised estimating equations were used to determine whether intra-articular features were associated with presence and severity of cartilage defects. Results: Hips with minor (OR 1.8, 95%CI 1.2,2.9) and severe (OR 5.1, 95%CI 2.5,10.3) labral tears had a higher prevalence of cartilage defects than hips without. Only hips with severe labral tears (IRR 2.1, 95%CI 1.4,3.2) had higher (greater severity) cartilage defects scores than hips without. Hips with BMEP or subchondral cysts had a higher prevalence (OR 7.7, 95%CI 3.1,20.0) and more severe (IRR 1.8 95%CI 1.4,2.3) cartilage defects than hips without. Effusion synovitis was not associated with a higher prevalence or greater severity of cartilage defects. For ligamentum teres tears only, a significant feature by symptoms interaction was present. Symptomatic football players without a ligamentum teres tear had a greater severity of cartilage defects when compared to those with symptoms and ligamentum teres tears. Discussion: Labral tears, BMEP and subchondral cysts were associated with the presence and severity of cartilage defects in active adult football players. Effusion-synovitis was not associated with cartilage defects. With the exception of ligament teres tears, the relationship between imaging-defined intra-articular features and cartilage defects was no stronger in football players with hip/groin pain when compared to those without. Conflict of interest statement: My co-authors and I acknowledge that we have no conflict of interest of relevance to the submission of this abstract.

Drugi tom antologii tekstów źródłowych zawiera starannie wybrane i po raz pierwszy przetłumaczone na język polski fragmenty 40 prac naukowych, po 1989 roku kształtujących naukę o stosunkach międzynarodowych. Zbiór otwiera fragment słynnej książki Cynthii