A grid-enabled problem solving environment for parallel computational engineering design

This paper describes the development and application of a piece of engineering software that provides a problem solving environment (PSE) capable of launching, and interfacing with, computational jobs executing on remote resources on a computational grid. In particular it is demonstrated how a complex, serial, engineering optimisation code may be efficiently parallelised, grid-enabled and embedded within a PSE. The environment is highly flexible, allowing remote users from different sites to collaborate, and permitting computational tasks to be executed in parallel across multiple grid resources, each of which may be a parallel architecture. A full working prototype has been built and successfully applied to a computationally demanding engineering optimisation problem. This particular problem stems from elastohydrodynamic lubrication and involves optimising the computational model for a lubricant based on the match between simulation results and experimentally observed data

Real-World Utilization of Oral Anticancer Agents and Related Costs in Older Adults with Metastatic Renal Cell Carcinoma in the United States

BACKGROUND: Substantial racial and socioeconomic disparities in metastatic RCC (mRCC) have persisted following the introduction of targeted oral anticancer agents (OAAs). The relationship between patient characteristics and OAA access and costs that may underlie persistent disparities in mRCC outcomes have not been examined in a nationally representative patient population. METHODS: Retrospective SEER-Medicare analysis of patients diagnosed with mRCC between 2007-2015 over age 65 with Medicare part D prescription drug coverage. Associations between patient characteristics, OAA receipt, and associated costs were analyzed in the 12 months following mRCC diagnosis and adjusted to 2015 dollars. RESULTS: 2,792 patients met inclusion criteria, of which 32.4%received an OAA. Most patients received sunitinib (57%) or pazopanib (28%) as their first oral therapy. Receipt of OAA did not differ by race/ethnicity or socioeconomic indicators. Patients of advanced age (>80 years), unmarried patients, and patients residing in the Southern US were less likely to receive OAAs. The mean inflation-adjusted 30-day cost to Medicare of a patient's first OAA prescription nearly doubled from $3864 in 2007 to$7482 in 2015, while patient out-of-pocket cost decreased from $2409 to$1477. CONCLUSION: Race, ethnicity, and socioeconomic status were not associated with decreased OAA receipt in patients with mRCC; however, residing in the Southern United States was, as was marital status. Surprisingly, the cost to Medicare of an initial OAA prescription nearly doubled from 2007 to 2015, while patient out-of-pocket costs decreased substantially. Shifts in OAA costs may have significant economic implications in the era of personalized medicine

Patterns and Predictors of Oral Anticancer Agent Use in Diverse Patients with Metastatic Renal Cell Carcinoma

PURPOSE Availability of targeted oral anticancer agents (OAAs) has transformed care for patients with metastatic renal cell carcinoma (mRCC). Our objective was to identify patterns and predictors of OAA use within 12 months after mRCC was detected to understand real-world adoption of OAAs. METHODS We used a novel, North Carolina cancer registry–linked multipayer claims data resource to examine patterns of use of five oral therapies among patients with mRCC diagnosed in 2006-2015, with claims through 2016. Patients were required to have 12 months of continuous enrollment before metastatic index date. Log-Poisson models estimated unadjusted and adjusted risk ratios (RRs) for associations between patient characteristics and OAA use. In sensitivity analyses, we used a competing risk framework to estimate adjusted risk differences in OAA use. RESULTS Our population-based study of 713 patients demonstrated low (37%) OAA use during the first year after metastatic index date among both publicly and privately insured patients, with shifting patterns of use consistent with regulatory approvals over time. Compared with patients age 18-49 years, patients age 70-74 years were half likely to use OAAs (95% confidence limit [CL], 0.34 to 0.78) and patients age 801 years were 71% less likely to use OAAs (95% CL, 0.17 to 0.50). Patients with two comorbidities (RR, 0.73; 95% CL, 0.55 to 0.98) and those with 31 comorbidities (RR, 0.68; 95% CL, 0.50 to 0.91) were less likely to receive OAA than those without comorbidities. Patients with higher frailty also had lower OAA utilization (RR, 0.67; 95% CL, 0.52 to 0.85). CONCLUSION These findings suggest a need to better understand the system-level and provider-level drivers of OAA underuse, as well as OAA adherence and associated survival

Oral Anticancer Agent (OAA) Adherence and Survival in Elderly Patients With Metastatic Renal Cell Carcinoma (mRCC)

Objective: To examine real-world adherence to oral anticancer agents (OAAs) and its association with outcomes among Medicare beneficiaries with metastatic renal cell carcinoma (mRCC). Methods: SEER-Medicare retrospective cohort study of patients with metastatic renal cell carcinoma (mRCC) who received an OAA between 2007 and 2015. We examined A) adherence and B) overall and disease-specific 2-year survival landmarked at 3 months after OAA initiation. Adherence was assessed by calculating the proportion of days covered (PDC) within 3 months of OAA initiation, with adherent use being defined as PDC > 80%. Results: A total of 905 patients met study criteria, of whom 445 patients (49.2%) were categorized as adherent to initial OAA treatment. Adjusting for clinical and demographic factors revealed decreased odds of adherence associated with living within an impoverished neighborhood (OR 0.49, CI 0.0.33 – 0.74) and out-of-pocket costs > $200 (OR 0.68, CI 0.47-.98). Adherence was associated with improved 2-year survival in univariate analysis (logrank test, P = .01) and a non-significant trend toward an association with decreased all-cause (HR 0.87, CI 0.72 – 1.05) and RCC-specific survival (HR 0.84, CI 0.69 – 1.03) in multivariable analysis. Conclusion: Local poverty levels and high out-of-pocket costs are associated with poor initial adherence to OAA therapy in Medicare beneficiaries with mRCC, which in turn, suggests a trend toward poor overall and disease-specific survival. Efforts to improve outcomes in the broader mRCC population should incorporate OAA adherence and economic factors

Provider- and patient-level predictors of oral anticancer agent initiation and adherence in patients with metastatic renal cell carcinoma

Background: Improving oral anticancer agent (OAA) initiation and adherence is the important quality-of-care issues, particularly since one fourth of anticancer agents being developed will be administered orally. Our objective was to identify provider- and patient-level characteristics associated with OAA initiation and adherence among individuals with metastatic renal cell carcinoma (mRCC). Methods: We used state cancer registry data linked to multi-payer claims data to identify patients with mRCC diagnosed in 2004–2015. Provider data were obtained from North Carolina Health Professions Data System and the National Plan & Provider Enumeration System. We estimated risk ratios (RRs) and corresponding 95% confidence limits (CLs) using modified Poisson regression to evaluate factors associated with OAA initiation and adherence. Results: Among the 207 (out of 687) patients who initiated an OAA following mRCC diagnosis and survived 90 days, median proportion of days covered was 0.91. Patients with a modal provider specializing in hematology/medical oncology were much more likely to initiate OAAs than those seen by other specialties. Additionally, patients with a female provider were more likely to initiate OAAs than those with a male provider. Compared to patients treated by providers practicing in both urban and rural areas, patients with providers practicing solely in urban areas were more likely to initiate OAAs, after controlling for patient-level factors (RR = 1.37; 95% CL: 1.09–1.73). Medicare patients were less likely to be adherent than those with private insurance (RR = 0.61; 95% CL: 0.42–0.87). Conclusions: Our results suggest that provider- and patient-level factors influence OAA initiation in patients with mRCC but only insurance type was associated with adherence

Late medieval Germany: an under-Stated nation?

The following text is taken from the publisher's website. "Few would doubt the central importance of the nation in the making and unmaking of modern political communities. The long history of 'the nation' as a concept and as a name for various sorts of 'imagined community' likewise commands such acceptance. But when did the nation first become a fundamental political factor? This is a question which has been, and continues to be, far more sharply contested. A deep rift still separates 'modernist' perspectives, which view the political nation as a phenomenon limited to modern, industrialised societies, from the views of scholars concerned with the pre-industrial world who insist, often vehemently, that nations were central to pre-modern political life also. This book represents the first attempt to engage with these questions by drawing on the expertise of leading medieval, early modern and modern historians.

At the margin of community: Germans in pre-Hussite Bohemia

Arguably, the single most important dimension in the existence of any community, medieval or modern, is its members' shared conviction that it exists, and that its existence represents a significant bond between them. The central and later Middle Ages have been viewed as a period of particular importance for the growth of such self-consciousness - and for its growth, particularly among those large political communities which Susan Reynolds suggests we call ‘regnal’, and which many medievalists appear happy to refer to as ‘national’. As Reynolds showed, communities of this sort evolved legitimising mythologies which overlay existing structures of government with notions of ancient and primal ethnic solidarity, and thus placed such communities, imaginatively, outside the normal processes of contingency and change. Challenging questions therefore arise if we call to mind the many new political formations which were established during this period, which saw the extension into neighbouring regions, by both violent and peaceful means, of the political and social forms characteristic of continental western Europe. The new settlements had not only to be organised and defended physically, but also explained and justified. A vocabulary of argument thus evolved to account for their existence and to illuminate their relationships with existing political and social structures. In formulating this vocabulary, however, writers were con-fronted by the strong impulse in medieval thought to lay upon all significant communities a veneer of timelessness, or at least of antiquity. How this obstacle was overcome for particular new communities doubtless has many specific answers. But an obstacle it must surely have been, and the study of how — or whether — it was surmounted in any given instance is thus inherently worth while