The Medieval ‘Marches' of Normandy and Wales

This article explores the striking links and parallels which existed between the frontiers of Normandy and of Wales, particularly between 1066 and 1204. It takes its cue from the fact that both frontiers were identified as ‘marches' at that time. It argues that while the frontier of Normandy was not a precursor of the March of Wales, experiences made by the Normans on their ‘home frontier' did help shape their contribution to the making of the Welsh March. Moreover, this essay contends that during the twelfth century, the borders of Normandy and of Wales evolved, in important respects, along similar lines. Thus, both ‘marches' came to be characterized by an exceptional density of castles and uniquely long-established castellan dynasties controlling compact lordships (to the best of their ability). By 1204, these features had helped foster the notion that the marches of Normandy and Wales were similar kinds of frontiers, despite the differences that undeniably existed between them. By implication, the famous liberties of the Welsh Marcher lords were, at first, irrelevant to the concept of the ‘march' of Wales. This supports Professor Sir Rees Davies's view that the Welsh Marcher liberties only became an issue in the thirteenth century. Finally, therefore, this article argues that it was the very features shared by the Norman and Welsh ‘marches', rather than claims to immunity, which first paved the way for the inclusion of the conquest lordships of southern Wales within the region identified as Marchia Walli

Smoking, season, and detection of chlamydia pneumoniae DNA in clinically stable COPD patients

BACKGROUND: The prevalence and role of Chlamydia pneumoniae in chronic obstructive pulmonary disease (COPD) remain unclear. METHODS: Peripheral blood mononuclear cells were obtained from 100 outpatients with smoking-related, clinically stable COPD, and induced sputum was obtained in 62 patients. RESULTS: Patients had mean age (standard deviation) of 65.8 (10.7) years, mean forced expiratory volume in one second of 1.34 (0.61) L, and 61 (61.0%) were male. C. pneumoniae nucleic acids were detected by nested polymerase chain reaction in 27 (27.0%). Current smoking (odds ratio {OR} = 2.6, 95% confidence interval {CI}: 1.1, 6.6, P = 0.04), season (November to April) (OR = 3.6, 95% CI: 1.4, 9.2, P = 0.007), and chronic sputum production (OR = 6.4, 95% CI: 1.8, 23.2, P = 0.005) were associated with detection of C. pneumoniae DNA. CONCLUSIONS: Prospective studies are needed to examine the role of C. pneumoniae nucleic acid detection in COPD disease symptoms and progression

The frequency-dependent Wright-Fisher model: diffusive and non-diffusive approximations

We study a class of processes that are akin to the Wright-Fisher model, with transition probabilities weighted in terms of the frequency-dependent fitness of the population types. By considering an approximate weak formulation of the discrete problem, we are able to derive a corresponding continuous weak formulation for the probability density. Therefore, we obtain a family of partial differential equations (PDE) for the evolution of the probability density, and which will be an approximation of the discrete process in the joint large population, small time-steps and weak selection limit. If the fitness functions are sufficiently regular, we can recast the weak formulation in a more standard formulation, without any boundary conditions, but supplemented by a number of conservation laws. The equations in this family can be purely diffusive, purely hyperbolic or of convection-diffusion type, with frequency dependent convection. The particular outcome will depend on the assumed scalings. The diffusive equations are of the degenerate type; using a duality approach, we also obtain a frequency dependent version of the Kimura equation without any further assumptions. We also show that the convective approximation is related to the replicator dynamics and provide some estimate of how accurate is the convective approximation, with respect to the convective-diffusion approximation. In particular, we show that the mode, but not the expected value, of the probability distribution is modelled by the replicator dynamics. Some numerical simulations that illustrate the results are also presented

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo