Automated Gamma Knife dose planning using polygon clipping and adaptive simulated annealing

The Gamma Knife (Elekta Instruments, Inc., Norcross, GA), a neurosurgical, highly focused radiation delivery device, is used to eradicate deep-seated anomalous tissue within the human brain by delivering a lethal dose of radiation to target tissue. This dose is the accumulated result of delivering sequential "shots" of radiation to the target, where each shot is approximately three-dimensional (3-D) Gaussian in shape. The size and intensity of each shot can be adjusted by varying the time of radiation exposure and by using one of four collimator sizes ranging from 4-18 mm. Current dose planning requires that the dose plan be developed manually to cover the target, and only the target, with a desired minimum radiation intensity using a minimum number of shots. This is a laborious and subjective process that typically leads to suboptimal conformal target coverage by the dose. We have previously presented a forward-direct-method, which, using adaptive simulated annealing and Nelder-Mead simplex optimizers, automates the selection and placement of generic Gaussian-based kernels or "shots" to form a simulated dose plan. In order to make the computation of the problem tractable, the algorithm exploits 2-D contouring and polygon clipping and takes a 2 1/2-D approach to defining the problem. In the current paper we present the results of four experiments on two historical clinical datasets, where the generic kernels have been replaced by patient specific kernels calculated by Elekta's Leksell Gamma Plan software. For these experiments the user only selects the maximum number of shots to use and the optimizers are then given the freedom to vary the number of shots as well as the weight, collimator size, and 3-D location of each shot. Highly conformal and competitive dose plans were generated for these two difficult cases.     

Adequate Vitamin D Intake Cannot Be Achieved within Carbon Emission Limits Unless Food Is Fortified: A Simulation Study

This study applied linear programming using a Dutch “model diet” to simulate the dietary shifts needed in order to optimize the intake of vitamin D and to minimize the carbon footprint, considering the popularity of the diet. Scenarios were modelled without and with additional fortified bread, milk, and oil as options in the diets. The baseline diet provided about one fifth of the adequate intake of vitamin D from natural food sources and voluntary vitamin D-fortified foods. Nevertheless, when optimizing this diet for vitamin D, these food sources together were insufficient to meet the adequate intake required, unless the carbon emission and calorie intake were increased almost 3-fold and 2-fold, respectively. When vitamin D-fortified bread, milk, and oil were added as options to the diet, along with increases in fish consumption, and decreases in sugar, snack, and cake consumption, adequate intakes for vitamin D and other nutrients could be met within the 2000 kcal limits, along with a relatively unchanged carbon footprint. Achieving vitamin D goals while reducing the carbon footprint by 10% was only possible when compromising on the popularity of the diet. Adding vitamin D to foods did not contribute to the total carbon emissions. The modelling study shows that it is impossible to obtain adequate vitamin D through realistic dietary shifts alone, unless more vitamin D-fortified foods are a necessary part of the diet.     

The economics of alternative payment models for pharmaceuticals

The European Journal of Health Economics - Pharmaceuticals are priced uniformly by convention, but vary in their degree of effectiveness for different disease indications. As more high-cost...     

Qualitätsmanagement und -entwicklung in der Primärprävention und Gesundheitsförderung: Stand,Herausforderungen und Perspektiven

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - In den vergangenen 3 Jahrzehnten nahm die Qualitätsentwicklung in der Primärprävention und...     

Patients Receiving a Primary Unicompartmental Knee Replacement Have a Higher Risk of Revision but a Lower Risk of Mortality Than Predicted Had They Received a Total Knee Replacement: Data From the National Joint Registry for England,Wales, Northern Ireland,and the Isle of Man

BackgroundTo determine unicompartmental (UKR) and total knee replacement (TKR) revision rates, compare UKR revision rates with what they would have been had they received TKR instead, and assess subsequent re-revision and 90-day mortality rates.MethodsUsing National Joint Registry data, we estimated UKR and TKR revision and mortality rates. Flexible parametric survival modeling (FPM) was used to model failure in TKR and make estimates for UKR. Kaplan-Meier estimates were used to compare cumulative re-revision for revised UKRs and TKRs.ResultsTen-year UKR revision rates were 2.5 times higher than expected from TKR, equivalent to 70 excess revisions/1000 cases within 10 years (5861 excess revisions in this cohort). Revision rates were 2.5 times higher for the highest quartile volume UKR surgeons compared to the same quartile for TKR and 3.9 times higher for the lowest quartiles respectively. Re-revision rates of revised TKRs (10 years = 17.5%, 95% confidence interval [CI] 16.4-18.7) were similar to revised UKRs (15.2%, 95% CI 13.4-17.1) and higher than revision rates following primary TKR (3.3%, 95% CI 3.1-3.5). Ninety-day mortality rates were lower after UKR compared with TKR (0.08% vs 0.33%) and lower than predicted had UKR patients received a TKR (0.18%), equivalent to 1 fewer death per 1000 cases.ConclusionUKR revision rates were substantially higher than TKR even when demographics and caseload differences were accounted for; however, fewer deaths occur after UKR. This should be considered when forming treatment guidelines and commissioning services. Re-revision rates were similar between revised UKRs and TKRs, but considerably higher than for primary TKR, therefore UKR cannot be considered an intermediate procedure.     

Clinical and cytogenetic aspects of X-chromosome deletions

Karyotype/phenotype correlations in six non-mosaic patients with dysgenetic ovaries and partial deletions of the X-chromosome (three patients with short arm, and three with long arm deletions) are presented and the pertinent literature is analysed. It would appear that functioning ovarian tissue is present more often in patients with a short arm deletion than in those with a deleted long arm. This may represent a difference in the strength of two sets of controlling factors, but it can also be related to break point position. This in turn may be misinterpreted due to the difficulty in distinguishing between terminal and interstitial deletions in the long arm. Stature may be a heterochromatic effect, but if specific genetic factors influencing stature exist, then they would appear to be situated mostly on the short arm of the X-chromosome, although some 'statural determinants' occur also on the long arm and could be located rather close to the centromere. Deletions of the short arm of the X-chromosome were almost always associated with some features of the Turner phenotype, and could possibly be related to a gene dosage effect.     

High expression of nitric oxide synthases is a favorable prognostic sign in non-small cell lung carcinoma

Immunohistochemical expression of neuronal (n), endothelial (e), and inducible (i) NOS and their association with the type, grade, apoptotic index, proliferation of tumors and the survival of patients were investigated in 89 biopsies of non-small cell lung carcinoma (NSCLC). In tumor cells, expression of iNOS was detected in 35/89 (40%) cases, while 79/89 (89%) and 72/89 (81%) cases showed weak to intense positivity for eNOS and nNOS, respectively. Strong eNOS staining was seen significantly more often in adenocarcinomas than in squamous cells carcinomas (p=0.016), and iNOS immunoreactivity was seen more often in grade I-II tumors than in grade III tumors (p=0.024). There was no significant difference between the low and high apoptotic indexes or between the low and high proliferation rates of tumors in any instance of NOS staining. The patients with tumors showing high nNOS expression tended to have better survival than the others (p=0.06, log-rank; p=0.04, Bresow; p=0.048, Tarone-Ware). Similarly, the patients with tumors showing high expression of iNOS, eNOS and nNOS, as determined by a combined sum index, had a better survival than those with a low sum index for these enzymes (p<0.05). The results show intense expression of eNOS and nNOS, and moderate expression of iNOS in tumor cells of non-small cell carcinoma. Intense NOSs expression seems to be a favorable prognostic sign in non-small cell lung carcinoma.     

Determinants of interest rates on tax-exempt hospital bonds

The aim of this paper is to examine the determinants of interest rates on tax-exempt hospital bonds. The results highlight the potential and actual roles of Federal and state policy in the determination of these rates. The shift to a Prospective Payment System under Medicare has subsidized the borrowing costs of some hospitals at the expense of others. The selection of underwriters by negotiation rather than by competitive bidding results in higher interest rates. The Federal tax act of 1986 raised the cost of hospital debt by encouraging bond issues to contain call features.     

High-dose thiotepa with autologous bone marrow rescue in recurrent malignant oligodendroglioma: A case report

High-dose thiotepa with autologous bone marrow rescue is a new and promising treatment modality in several kinds of solid tumors. We used this regimen in a pediatric patient who had the third recurrence of his malignant oligodendroglioma of brain that developed during 8 in 1 chemotherapy. We achieved complete response after a total dose of 1125 mg/m² of intravenous thiotepa. Good penetration into the CNS renders thiotepa potentially useful for chemosensitive brain tumors, and one course of high-dose thiotepa can be administered with acceptable toxicity by utilizing autologous bone marrow rescue.     

Macrolide transport in Escherichia coli strains having normal and altered OmpC and/or OmpF porins

[(14)C]Erythromycin and [(14)C]azithromycin uptake rates were studied in Escherichia coli strains containing normal OmpC and OmpF porins (strain MRC 106) and altered OmpC porins due to small insertions (strains RAM121 and OC1555) or deletions (strain RAM122) in the ompC alleles and altered OmpF porins due to small ompF deletions (strains OC1555 and PLB3255). Strains RAM121 and RAM122 also lacked OmpF porins in their outer membrane. The porin mutants demonstrated a 2- to 1224-fold increase in macrolide transport and a concurrent 3- to 530-fold decrease in MIC when compared to the parent strain, MCR106. Both strains OC1555 and PLB3255 had enhanced permeability to 1-N-phenylnaphthylamine indicating increased permeability of the outer membrane to hydrophobic molecules. The macrolides, at 2 to 1000 times MIC, failed to displace the cationic probe polymyxin; therefore, drug entry by a self-promoted mechanism was not indicated. Since >95% of macrolide is protonated and thus hydrophilic (logP(i)=-0.89) at neutral pH, the bulk of drug entry may be via the porin channels.