Henry II and Ganelon

Paul R. Hyams was educated at Oxford University and is now a fellow of Pembroke College, Oxford. He is interested in the development of English law in the twelfth and thirteenth centuries and is the author of King, Lords and Peasants in Medieval England: The Common Law of Vtfleinage in the Twelfth and Thirteenth Centuries (Oxford: Clarendon Press, 1980)

Warranty and good lordship in twelfth-century England

Already in the twelfth century, men canvassed different views on the ways in which they thought lordship ought to be exercised. They used their picture of how an idealised "Good Lord" -- a familiar label in later times -- comported himself to assess the treatment they actually received from their lords. This Good Lordship had both Positive and Negative aspects: the "good lord" maintained his vassals in their honours and renounced his right to revoke grants afterwards. One excellent way to study the pursuit of this double ideal is through the language of charters, more particularly through the warranty clauses by which Good Lordship was often implemented. The transformation of warranty into its familiar Common-Law shape reflects corresponding and complex changes in both lord-vassal relations and the role of the King and his justice. Warranty actually began as a security device, designed to keep men to their word, and is found used in this sense over wide areas of sub-Carolingian Europe. It was probably imported to England by the French, and can be seen in twelfth-century charters progressively superseding other forms of words to become the classic "guarantee" of Good Lordship. In this manner it came by 1200 to be virtually equated with the lordship it had originally been used to enforce. Warranty was lordship seen from the vassal's point of view, that is, tenant-right. Despite this origin in very personal relations, warranty probably always created between the parties' heirs some kind of obligation, which sharpened and was made infinitely more clear-cut with the emergence of full legal inheritance rights. Warranty swelled to full tenant-right, a full guarantee of the Right to Good Lordship. As the heir's claim grew into an enforceable right of inheritance through increasing access to remedies by royal justice, and because such justice tended to strict construction, warranty became a contractual addition to which claimants had to prove their entitlement. The narrative of legal change from 1150 argues for gradual evolution but also suggests 1153-4 8S the decisive turning-point in this development. Detailed (sometimes technical) examination of evidence for some relevant cases, royal writs concerning warranty and the turning-point of 1153-4 is reserved for three appendixes

Streptococcus pneumoniae Septic Arthritis in adults in Bristol and Bath, United Kingdom, 2006-2018:a 13-year retrospective observational cohort study

Few studies on adult pneumococcal septic arthritis are sufficiently large enough to assess both epidemiological trends following routine pneumococcal immunization and clinical disease. With major shifts in serotypes causing invasive pneumococcal disease (IPD), we wanted to determine the clinical phenotype of adult septic arthritis caused by Streptococcus pneumoniae. We conducted a retrospective cohort study of pneumococcal infections in Bristol and Bath, UK, 2006–2018. We defined pneumococcal septic arthritis as adults with clinically-confirmed septic arthritis, with pneumococcus isolated from sterile-site culture or urinary antigen test positivity. Clinical records were reviewed for each patient in the cohort. Septic arthritis accounted for 1.7% of all IPD cases. 45 cases of adult pneumococcal septic arthritis occurred, with disease typically affecting older adults and those with underlying comorbidity. 67% patients had another focus of infection during their illness. 66% patients required increased care on discharge and 43% had reduced range of movement. In-hospital case fatality rate was 6.7%. One-year patient mortality was 31%. Currently most cases of adult pneumococcal septic arthritis are due to non-PCV13 serotypes which are associated with more severe disease. Non-PCV-13 serotypes had higher prevalence of concomitant pneumococcal infection at another site (73.7% versus 36.6%), increased intensive care or high-dependency unit requirement (32.4% versus 0%), and increased inpatient and 1-year case fatality rate (8.8% versus 0%, and 32.4% versus 27.4% respectively) compared to PCV-13 serotypes. Pneumococcal septic arthritis remains a small proportion of IPD. However, there is significant associated morbidity and mortality, and pneumococcal septic arthritis requires monitoring in coming years

Analysis of Using the Total White Blood Cell Count to Define Severe New-onset Ulcerative Colitis in Children

Objectives: The aim of this study was to assess common laboratory tests in identifying severe ulcerative colitis in children at diagnosis. Methods: A cohort of 427 children 4 to 17 years of age newly diagnosed with ulcerative colitis (UC) was prospectively enrolled. Boosted classification trees were used to characterize predictive ability of disease attributes based on clinical disease severity using Pediatric Ulcerative Colitis Activity Index (PUCAI), severe (65+) versus not severe (<65) and total Mayo score, severe (10-12) versus not severe (<10); mucosal disease by Mayo endoscopic subscore, severe (3) versus not severe (<3); and extensive disease versus not extensive (left-sided and proctosigmoiditis). Results: Mean age was 12.7 years; 49.6% (n = 212) were girls, and 83% (n = 351) were Caucasian. Severe total Mayo score was present in 28% (n = 120), mean PUCAI score was 49.8 ± 20.1, and 33% (n = 142) had severe mucosal disease with extensive involvement in 82% (n = 353). Classification and regression trees identified white blood cell count, erythrocyte sedimentation rate, and platelet count (PLT) as the set of 3 best blood laboratory tests to predict disease extent and severity. For mucosal severity, albumin (Alb) replaced PLT. Classification models for PUCAI and total Mayo provided sensitivity of at least 0.65 using standard clinical cut-points with misclassification rates of approximately 30%. Conclusions: A combination of the white blood cell count, erythrocyte sedimentation rate, and either PLT or albumin is the best predictive subset of standard laboratory tests to identify severe from nonsevere clinical or mucosal disease at diagnosis in relation to objective clinical scores

Chemical inhibition of bacterial protein tyrosine phosphatase suppresses capsule production

Capsule polysaccharide is a major virulence factor for a wide range of bacterial pathogens, including Streptococcus pneumoniae. The biosynthesis of Wzy-dependent capsules in both Gram-negative and –positive bacteria is regulated by a system involving a protein tyrosine phosphatase (PTP) and a protein tyrosine kinase. However, how the system functions is still controversial. In Streptococcus pneumoniae, a major human pathogen, the system is present in all but 2 of the 93 serotypes found to date. In order to study this regulation further, we performed a screen to find inhibitors of the phosphatase, CpsB. This led to the observation that a recently discovered marine sponge metabolite, fascioquinol E, inhibited CpsB phosphatase activity both in vitro and in vivo at concentrations that did not affect the growth of the bacteria. This inhibition resulted in decreased capsule synthesis in D39 and Type 1 S. pneumoniae. Furthermore, concentrations of Fascioquinol E that inhibited capsule also lead to increased attachment of pneumococci to a macrophage cell line, suggesting that this compound would inhibit the virulence of the pathogen. Interestingly, this compound also inhibited the phosphatase activity of the structurally unrelated Gram-negative PTP, Wzb, which belongs to separate family of protein tyrosine phosphatases. Furthermore, incubation with Klebsiella pneumoniae¸ which contains a homologous phosphatase, resulted in decreased capsule synthesis. Taken together, these data provide evidence that PTPs are critical for Wzydependent capsule production across a spectrum of bacteria, and as such represents a valuable new molecular target for the development of anti-virulence antibacterials.Alistair J. Standish, Angela A. Salim, Hua Zhang, Robert J. Capon and Renato Moron

Salmonella bongori provides insights into the evolution of the Salmonellae.

The genus Salmonella contains two species, S. bongori and S. enterica. Compared to the well-studied S. enterica there is a marked lack of information regarding the genetic makeup and diversity of S. bongori. S. bongori has been found predominantly associated with cold-blooded animals, but it can infect humans. To define the phylogeny of this species, and compare it to S. enterica, we have sequenced 28 isolates representing most of the known diversity of S. bongori. This cross-species analysis allowed us to confidently differentiate ancestral functions from those acquired following speciation, which include both metabolic and virulence-associated capacities. We show that, although S. bongori inherited a basic set of Salmonella common virulence functions, it has subsequently elaborated on this in a different direction to S. enterica. It is an established feature of S. enterica evolution that the acquisition of the type III secretion systems (T3SS-1 and T3SS-2) has been followed by the sequential acquisition of genes encoding secreted targets, termed effectors proteins. We show that this is also true of S. bongori, which has acquired an array of novel effector proteins (sboA-L). All but two of these effectors have no significant S. enterica homologues and instead are highly similar to those found in enteropathogenic Escherichia coli (EPEC). Remarkably, SboH is found to be a chimeric effector protein, encoded by a fusion of the T3SS-1 effector gene sopA and a gene highly similar to the EPEC effector nleH from enteropathogenic E. coli. We demonstrate that representatives of these new effectors are translocated and that SboH, similarly to NleH, blocks intrinsic apoptotic pathways while being targeted to the mitochondria by the SopA part of the fusion. This work suggests that S. bongori has inherited the ancestral Salmonella virulence gene set, but has adapted by incorporating virulence determinants that resemble those employed by EPEC.We thank the core sequencing and informatics teams at the Sanger Institute for their assistance and The Wellcome Trust for its support of the Sanger Institute Pathogen Genomics and Biology groups and the MRC for their support of GF, KSR and GNS. MCF, GCL, TRC, HSS, GSV, MS, NKP, RAK, JP, GD and NRT were supported by Wellcome Trust grant 076964 and MICROME, an EU Framework Programme 7 Collaborative Project, Grant Agreement Number 222886-2. Work was also supported by Grant ADI-08/2006 from Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) and The World Bank, and grant 1100092 from Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT). CJB was supported by fellowships from CONICYT (21080373 and AT-24091015)

La joie de la liberté et le prix de la respectabilité : autour des chartes d’affranchissement anglaises et d’actes français analogues (v. 1160-1307)

Hyams Paul R. La joie de la liberté et le prix de la respectabilité : autour des chartes d’affranchissement anglaises et d’actes français analogues (v. 1160-1307). In: Bibliothèque de l'école des chartes. 2006, tome 164, livraison 2. pp. 371-389