The Impact Of September 11 On Terrorism Insurance: Comparing Senate Bill 2600, House Of Representatives Bill 3210, And the United Kingdom\u27s Pool Re.

If insurance is a small world that reflects the purposes of the larger world outside it, \u27 then the events of September 11 have dealt a devastating blow to both worlds

General practice ethnicity data: evaluation of a tool

INTRODUCTION: There is evidence that the collection of ethnicity data in New Zealand primary care is variable and that data recording in practices does not always align with the procedures outlined in the Ethnicity Data Protocols for the Health and Disability Sector. In 2010, The Ministry of Health funded the development of a tool to audit the collection of ethnicity data in primary care. The aim of this study was to pilot the Ethnicity Data Audit Tool (EAT) in general practice. The goal was to evaluate the tool and identify recommendations for its improvement. METHODS: Eight general practices in the Waitemata District Health Board region participated in the EAT pilot. Feedback about the pilot process was gathered by questionnaires and interviews, to gain an understanding of practices’ experiences in using the tool. Questionnaire and interview data were analysed using a simple analytical framework and a general inductive method. FINDINGS: General practice receptionists, practice managers and general practitioners participated in the pilot. Participants found the pilot process challenging but enlightening. The majority felt that the EAT was a useful quality improvement tool for handling patient ethnicity data. Larger practices were the most positive about the tool. CONCLUSION: The findings suggest that, with minor improvements to the toolkit, the EAT has the potential to lead to significant improvements in the quality of ethnicity data collection and recording in New Zealand general practices. Other system-level factors also need to be addressed

Making Health Data Work for Maori: attitudes and current challenges

This article explores the experience of health services decision makers using Mäori health data to inform decision making. It draws on selected findings from the second phase of a three-year Health Research Council-funded study and discusses how Mäori health data identification, data analysis and data interpretation processes are being used by decision makers to help to identify the most promising strategies to improve Mäori health. Data is critical to monitoring inequity and has the potential to drive health service change. However, improvement is needed at all steps in the decisionmaking process to better facilitate utilising data to leverage change in Mäori health outcomes

Brain microvessel endothelial cells in tissue culture: A model for study of blood-brain barrier permeability

Endothelial cells were prepared from bovine brain microvessels and grown in tissue culture. They contained factor VIII/von Willebrand antigen, the most specific marker available for determination of the endothelial origin of cells in culture. The cultured cells formed complex tight junctions and contained few pinocytotic vessels. These properties are responsible for formation of the blood-brain barrier in vivo. When monolayers of the endothelial cells were exposed briefly to a calcium-free solution or treated with 1.6 M arabinose, distinctive morphological changes occurred in the intercellular contacts. In either case, a normal structure was reestablished following return to control medium. To assess the effect of these treatments on transcellular permeability, we measured the movement of sucrose labeled with carbon 14 across a monolayer of endothelial cells cultured on a collagen-coated nylon mesh. Removal of external calcium increased the rate of sucrose movement by 120%; the arabinose treatment increased transcellular flux by 40%.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50304/1/410140403_ftp.pd

Regression of experimental NIS-expressing breast cancer brain metastases in response to radioiodide/gemcitabine dual therapy.

Treating breast cancer brain metastases (BCBMs) is challenging. Na+/I- symporter (NIS) expression in BCBMs would permit their selective targeting with radioiodide (131I-). We show impressive enhancement of tumor response by combining131I- with gemcitabine (GEM), a cytotoxic radiosensitizer. Nude mice mammary fat-pad (MFP) tumors and BCBMs were generated with braintropic MDA-MB-231Br cells transduced with bicistronically-linked NIS and firefly luciferase cDNAs. Response was monitored in vivo via bioluminescent imaging and NIS tumor expression.131I-/GEM therapy inhibited MFP tumor growth more effectively than either agent alone. BCBMs were treated with: high or low-dose GEM (58 or 14.5 mg/Kg×4); 131I- (1mCi or 2×0.5 mCi 7 days apart); and 131I-/GEM therapy. By post-injection day (PID) 25, 82-86% of controls and 78-83% of 131I--treated BCBM grew, whereas 17% low-dose and 36% high-dose GEM regressed. The latter tumors were smaller than the controls with comparable NIS expression (~20% of cells). High and low-dose 131I-/ GEM combinations caused 89% and 57% tumor regression, respectively. High-dose GEM/131I- delayed tumor growth: tumors increased 5-fold in size by PID45 (controls by PID18). Although fewer than 25% of cells expressed NIS, GEM/131I- caused dramatic tumor regression in NIS-transduced BCBMs. This effect was synergistic, and supports the hypothesis that GEM radiosensitizes cells to 131I-

A Novel Biosensor for Evaluation of Apoptotic or Necrotic Effects of Nitrogen Dioxide during Acute Pancreatitis in Rat

The direct and accurate estimation of nitric dioxide levels is an extremely laborious and technically demanding procedure in the molecular diagnostics of inflammatory processes. The aim of this work is to demonstrate that a stop-flow technique utilizing a specific spectroscopic biosensor can be used for detection of nanomolar quantities of NO2 in biological milieu. The use of novel compound cis-[Cr(C2O4)(AaraNH2)(OH2)2]+ increases NO2 estimation accuracy by slowing down the rate of NO2 uptake. In this study, an animal model of pancreatitis, where nitrosative stress is induced by either 3g/kg bw or 1.5 g/kg bw dose of l-arginine, was used. Biochemical parameters and morphological characteristics of acute pancreatitis were monitored, specifically assessing pancreatic acinar cell death mode, NO2 generation and cellular glutathione level. The severity of the process correlated positively with NO2 levels in pancreatic acinar cell cytosol samples, and negatively with cellular glutathione levels

Hyperosmotic stress induces axl activation and cleavage in cerebral endothelial cells

Due to the relative impermeability of the blood-brain barrier many drugs are unable to reach the CNS in therapeutically relevant concentration. One method to deliver drugs to the CNS is the osmotic opening of the blood-brain barrier using mannitol. Hyperosmotic mannitol induces a strong phosphorylation on tyrosine residues in a broad spectrum of proteins in cerebral endothelial cells, the principal components of the blood-brain barrier. Previously we have shown that among targets of tyrosine phosphorylation are ?-catenin, extracellular signal-regulated kinase 1/2 and the non-receptor tyrosine kinase Src. The aim of this study was to identify new signaling pathways activated by hypertonicity in cerebral endothelial cells. Using an antibody array and immunoprecipitation we identified the receptor tyrosine kinase Axl to become tyrosine phosphorylated in response to hyperosmotic mannitol. Besides activation, Axl was also cleaved in response to osmotic stress. Degradation of Axl proved to be metalloproteinase- and proteasome-dependent and resulted in 50-55 kDa C-terminal products which remained phosphorylated even after degradation. Specific knockdown of Axl increased the rate of apoptosis in hyperosmotic mannitol-treated cells, therefore we assume that activation of Axl may be a protective mechanism against hypertonicity-induced apoptosis. Our results identify Axl as an important element of osmotic stress-induced signaling

Dose escalation study of intravenous and intra-arterial N-acetylcysteine for the prevention of oto- and nephrotoxicity of cisplatin with a contrast-induced nephropathy model in patients with renal insufficiency.

BACKGROUND: Cisplatin neuro-, oto-, and nephrotoxicity are major problems in children with malignant tumors, including medulloblastoma, negatively impacting educational achievement, socioemotional development, and overall quality of life. The blood-labyrinth barrier is somewhat permeable to cisplatin, and sensory hair cells and cochlear supporting cells are highly sensitive to this toxic drug. Several chemoprotective agents such as N-acetylcysteine (NAC) were utilized experimentally to avoid these potentially serious and life-long side effects, although no clinical phase I trial was performed before. The purpose of this study was to establish the maximum tolerated dose (MTD) and pharmacokinetics of both intravenous (IV) and intra-arterial (IA) NAC in adults with chronic kidney disease to be used in further trials on oto- and nephroprotection in pediatric patients receiving platinum therapy. METHODS: Due to ethical considerations in pediatric tumor patients, we used a clinical population of adults with non-neoplastic disease. Subjects with stage three or worse renal failure who had any endovascular procedure were enrolled in a prospective, non-randomized, single center trial to determine the MTD for NAC. We initially aimed to evaluate three patients each at 150, 300, 600, 900, and 1200 mg/kg NAC. The MTD was defined as one dose level below the dose producing grade 3 or 4 toxicity. Serum NAC levels were assessed before, 5 and 15 min post NAC. Twenty-eight subjects (15 men; mean age 72.2 +/- 6.8 years) received NAC IV (N = 13) or IA (N = 15). RESULTS: The first participant to experience grade 4 toxicity was at the 600 mg/kg IV dose, at which time the protocol was modified to add an additional dose level of 450 mg/kg NAC. Subsequently, no severe NAC-related toxicity arose and 450 mg/kg NAC was found to be the MTD in both IV and IA groups. Blood levels of NAC showed a linear dose response (p < 0.01). Five min after either IV or IA NAC MTD dose administration, serum NAC levels reached the 2-3 mM concentration which seemed to be nephroprotective in previous preclinical studies. CONCLUSIONS: In adults with kidney impairment, NAC can be safely given both IV and IA at a dose of 450 mg/kg. Additional studies are needed to confirm oto- and nephroprotective properties in the setting of cisplatin treatment. Clinical Trial Registration URL: https://eudract.ema.europa.eu . Unique identifier: 2011-000887-92