The Old in the New: Urban Castle Imposition in Anglo-Norman England, AD1050-1150

In the aftermath of the Norman Conquest of the kingdom of England in the late eleventh century a series of castle structures were imposed on the fabric of a large number of Late Saxon towns. In the late 1980s this specific group of castles were archaeologically termed ‘urban castles’, being perceived as distinct from other forms of such structures encountered in the UK. The interpretation of these castles, whose design is widely accepted as being imported in this period from northern France, is closely entwined with culturally and nationalistically-loaded historical narrative of the Norman Conquest. This interpretive position has had a dominant role in how the urban castle is studied in historical and archaeological discourse, which in turn reinforces the validity and legitimacy of this approach. The present study will seek to question the rationale and evidence behind the present interpretive framework. This will include a historiographical analysis of the development of the study of Late Saxon and Norman England over the last century and how the conditions of research in this period has influenced and often proved divisive in how the urban castle is understood and encapsulated within perceptions of radical change in English history. In turn it will offer an alternative, interdisciplinary approach to the encounter and interpretation of the urban castle. Detailed examinations of the urban castles and settlements of Wallingford (Oxon.) and Huntingdon (Cambs.) will be followed by broader, regional studies of Sussex and the Severn Vale. The castles in these examples will be studied in the wider context of urban development across the period c.AD900-1150 which will allow them to be considered as one element amongst a hetregenous, fluid process of settlement evolution. This original methodology will be utilised to demonstrate how these sites can be used as a subject for understanding the wider phenomenon of Saxo-Norman urbanism, and that the castle is an integral, if physically distinct, element in this process.Arts and Humanities Research Council (AHRC

Impact of global budget payments on cardiovascular care in Maryland: an interrupted time series analysis

Background Global budget payments (GBP) are considered effective in containing health care expenditures; however, information on their impact on quality of cardiovascular care is limited. We aimed to evaluate the effects of GBP on utilization, outcomes, and costs for 3 major cardiovascular conditions. Methods We analyzed claims data of hospital admissions in Maryland from fiscal year 2013 to 2018. Using segmented regression, we evaluated temporal trends in hospitalizations, length of stay, percutaneous coronary intervention and coronary artery bypass grafting volumes, case mix-adjusted 30-day readmission rates, risk-standardized mortality rates, and hospitalization charges in patients with principal diagnosis of heart failure, acute ischemic stroke, and acute myocardial infarction (AMI) in relation to GBP implementation. Trends in global cardiovascular procedure charges/volumes were also studied. Results Hospitalization rates for congestive heart failure and AMI remained unaffected by GBP, while the gradient of ischemic stroke admissions decreased (Ptrend<0.0001). Length of stay slightly increased for patients with congestive heart failure (Ptrend=0.03). Inpatient coronary artery bypass grafting surgeries decreased (Ptrend<0.0001). We observed a significant decrease in casemix-adjusted 30-day readmission rate in the AMI cohort beyond the prepolicy trend (Ptrend=0.0069). There were no significant changes in mortality for any of the 3 conditions. Hospitalization charges increased for ischemic stroke (Ptrend<0.0001), remained constant for congestive heart failure (Ptrend=0.1), and decreased for AMI (Ptrend=0.0005). We observed a significant increase in electrocardiography rate charges (Ptrend<0.0001), coincidentally with a reduction in volumes (Ptrend=0.0003). Conclusions Introducing GBP in Maryland had no perceivable adverse effects on inpatient outcomes and quality indicators for 3 major cardiovascular conditions. Savings were observed in the AMI cohort, possibly due to reduced unnecessary readmissions, efficiency improvements, or shifts to outpatient care. Reduced cardiovascular procedure volumes were counterbalanced by a proportional rise in charges. State-level adoption of GBP with pay-for-performance incentives may be effective for cost containment without adversely impacting quality of cardiovascular care

Bortezomib-Induced Complete Heart Block and Myocardial Scar: The Potential Role of Cardiac Biomarkers in Monitoring Cardiotoxicity

Bortezomib is a proteasome inhibitor used to treat multiple myeloma and mantle cell lymphoma. Traditionally, bortezomib was thought to have little cardiovascular toxicity; however, there is increasing evidence that bortezomib can lead to cardiac complications including left ventricular dysfunction and atrioventricular block. We present the case of a 66-year-old man with multiple myeloma and persistent asymptomatic elevations of cardiac biomarkers who developed complete heart block and evidence of myocardial scar after his eighth cycle of bortezomib, requiring permanent pacemaker placement. In addition to discussing the cardiovascular complications of bortezomib therapy, we propose a potential role for biomarkers in the prediction and monitoring of bortezomib cardiotoxicity

Endangered Archaeology in the Middle East and North Africa: Introducing the EAMENA Project

This project uses satellite imagery and historic aerial photographs to discover and interpret archaeological sites. It has created an open access database of archaeological records that provides basic information so that the sites can be better under- stood and preserved in the future. The threats to sites in the Middle East and North Africa are increasing and creating a record of previously unrecorded sites using this methodology may be our the last chance before they are destroyed

Endangered Archaeology in the Middle East and North Africa: Introducing the EAMENA Project

This project uses satellite imagery and historic aerial photographs to discover and interpret archaeological sites. It has created an open access database of archaeological records that provides basic information so that the sites can be better under- stood and preserved in the future. The threats to sites in the Middle East and North Africa are increasing and creating a record of previously unrecorded sites using this methodology may be our the last chance before they are destroyed

Cardiovascular adverse events associated with BRAF versus BRAF/MEK inhibitor: Cross-sectional and longitudinal analysis using two large national registries

BACKGROUND: Cardiovascular adverse events (CVAEs) associated with BRAF inhibitors alone versus combination BRAF/MEK inhibitors are not fully understood. METHODS: This study included all adult patients who received BRAF inhibitors (vemurafenib, dabrafenib, encorafenib) or combinations BRAF/MEK inhibitors (vemurafenib/cobimetinib; dabrafenib/trametinib; encorafenib/binimetinib). We utilized the cross-sectional FDA\u27s Adverse Events Reporting System (FAERS) and longitudinal Truven Health Analytics/IBM MarketScan database from 2011 to 2018. Various CVAEs, including arterial hypertension, heart failure (HF), and venous thromboembolism (VTE), were studied using adjusted regression techniques. RESULTS: In FAERS, 7752 AEs were reported (40% BRAF and 60% BRAF/MEK). Median age was 60 (IQR 49-69) years with 45% females and 97% with melanoma. Among these, 567 (7.4%) were cardiovascular adverse events (mortality rate 19%). Compared with monotherapy, combination therapy was associated with increased risk for HF (reporting odds ratio [ROR] = 1.62 (CI = 1.14-2.30); p = 0.007), arterial hypertension (ROR = 1.75 (CI = 1.12-2.89); p = 0.02) and VTE (ROR = 1.80 (CI = 1.12-2.89); p = 0.02). Marketscan had 657 patients with median age of 53 years (IQR 46-60), 39.3% female, and 88.7% with melanoma. There were 26.2% CVAEs (CI: 14.8%-36%) within 6 months of medication start in those receiving combination therapy versus 16.7% CVAEs (CI: 13.1%-20.2%) among those receiving monotherapy. Combination therapy was associated with CVAEs compared to monotherapy (adjusted HR: 1.56 (CI: 1.01-2.42); p = 0.045). CONCLUSIONS AND RELEVANCE: In two independent real-world cohorts, combination BRAF/MEK inhibitors were associated with increased CVAEs compared to monotherapy, especially HF, and hypertension

Myocarditis in Patients Treated With Immune Checkpoint Inhibitors.

BACKGROUND: Myocarditis is an uncommon, but potentially fatal, toxicity of immune checkpoint inhibitors (ICI). Myocarditis after ICI has not been well characterized. OBJECTIVES: The authors sought to understand the presentation and clinical course of ICI-associated myocarditis. METHODS: After observation of sporadic ICI-associated myocarditis cases, the authors created a multicenter registry with 8 sites. From November 2013 to July 2017, there were 35 patients with ICI-associated myocarditis, who were compared to a random sample of 105 ICI-treated patients without myocarditis. Covariates of interest were extracted from medical records including the occurrence of major adverse cardiac events (MACE), defined as the composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically significant complete heart block. RESULTS: The prevalence of myocarditis was 1.14% with a median time of onset of 34&nbsp;days after starting ICI (interquartile range: 21 to 75 days). Cases were 65 ± 13 years of age, 29% were female, and 54% had no other immune-related side effects. Relative to controls, combination ICI (34% vs. 2%; p&nbsp;&lt; 0.001) and diabetes (34% vs. 13%; p&nbsp;=&nbsp;0.01) were more common in cases. Over 102&nbsp;days (interquartile range: 62 to 214 days) of median follow-up, 16 (46%) developed MACE; 38% of MACE occurred with normal ejection fraction. There was a 4-fold increased risk of MACE with troponin T of&nbsp;≥1.5&nbsp;ng/ml (hazard ratio: 4.0; 95% confidence interval: 1.5 to 10.9; p&nbsp;=&nbsp;0.003). Steroids were administered in 89%, and lower steroids doses were associated with higher residual troponin and higher MACE rates. CONCLUSIONS: Myocarditis after ICI therapy may be more common than appreciated, occurs early after starting treatment, has a malignant course, and responds to higher steroid doses

News from the field ou como um projeto internacional começa a sair do papel

This paper presents the main research issues of Jê Landscapes of Southern Brazil project and also brings preliminary results of the first year of Archaeology and Palaeoecology research activities.O presente texto apresenta as questões centrais de pesquisa do projeto Paisagens Jê do Sul do Brasil e também traz resultados preliminares do primeiro ano de atividades de pesquisa em Arqueologia e Paleoecologia