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1.
Jerzy Slowinski Jake Dominik Ryan J. Uitti Zeshan Ahmed Dennis D. Dickson Zbigniew K. Wszolek 《Neuropathology》2007,27(1):73-80
We present a case of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17) harboring the N279K mutation in the MAPT gene from the family known as pallido‐ponto‐nigral degeneration (PPND). This 49‐year‐old man was followed for 17 years. He presented at age 41 years with left leg stiffness and en‐bloc turning. During the course of his illness he developed a constellation of symptoms including parkinsonism, pyramidal signs, vertical gaze palsy, dysphagia, dystonia, personality and cognitive dysfunction, weight loss and mutism. Gross neuropathological examination showed mild atrophy of the cerebral cortex, hippocampal formation, amygdala, thalamus, subthalamic nucleus and depigmentation of the substantia nigra. Microscopy revealed neuronal loss and gliosis in the same regions. Tau immunohistochemistry showed pretangles, numerous threads, grain‐like structures and oligodendroglial tau‐positive inclusions (“coiled bodies”). In the spinal cord the tau pathology was more abundant in gray than white matter. Pretangles and threads were present in the anterior and, to a lesser extent, in the posterior horns. FTDP‐17 should be suspected in patients with a history of familial parkinsonism combined with behavioral and cognitive changes, onset before age 65 years and an aggressive clinical course. 相似文献
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Jake M. Najman 《Australian and New Zealand journal of public health》1988,12(1):31-41
Recent findings have pointed to an association between socioeconomic status and health in Australia but have, in the process, raised important questions about the validity of various methods of determining a respondent's location within the hierarchy. While some of the problems associated with the use of the Australian Bureau of Statistics classification were known, the full extent of these deficiencies was not. This paper reviews past and present methods of measuring socioeconomic inequality in Australia. After pointing to the criteria which should be applied to determine the adequacy of any method of socioeconomic classification, the paper reviews the main strengths and weaknesses of the methods of classification used in health-related research in Australia. 相似文献
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The convolution method can be used to model the effect of random geometric uncertainties into planned dose distributions used in radiation treatment planning. This is effectively done by linearly adding infinitesimally small doses, each with a particular geometric offset, over an assumed infinite number of fractions. However, this process inherently ignores the radiobiological dose-per-fraction effect since only the summed physical dose distribution is generated. The resultant potential error on predicted radiobiological outcome [quantified in this work with tumor control probability (TCP), equivalent uniform dose (EUD), normal tissue complication probability (NTCP), and generalized equivalent uniform dose (gEUD)] has yet to be thoroughly quantified. In this work, the results of a Monte Carlo simulation of geometric displacements are compared to those of the convolution method for random geometric uncertainties of 0, 1, 2, 3, 4, and 5 mm (standard deviation). The alpha/betaCTV ratios of 0.8, 1.5, 3, 5, and 10 Gy are used to represent the range of radiation responses for different tumors, whereas a single alpha/betaOAR ratio of 3 Gy is used to represent all the organs at risk (OAR). The analysis is performed on a four-field prostate treatment plan of 18 MV x rays. The fraction numbers are varied from 1-50, with isoeffective adjustments of the corresponding dose-per-fractions to maintain a constant tumor control, using the linear-quadratic cell survival model. The average differences in TCP and EUD of the target, and in NTCP and gEUD of the OAR calculated from the convolution and Monte Carlo methods reduced asymptotically as the total fraction number increased, with the differences reaching negligible levels beyond the treatment fraction number of > or =20. The convolution method generally overestimates the radiobiological indices, as compared to the Monte Carlo method, for the target volume, and underestimates those for the OAR. These effects are interconnected and attributed to assuming an infinite number of fractions inherent in the implementation of the convolution technique, irrespective of the uniqueness of each treatment schedule. Based on the fraction numbers analyzed (1-50), and the range of fraction numbers normally used clinically (> or =20), the convolution method can be used safely to estimate the effects of random geometric uncertainties on prostate treatment radiobiological outcomes, for both the target and the OAR. Although the results of this study is likely to apply to other clinical sites and treatment techniques other than the four-field, further validation similar to those done in this study may be necessary prior to clinical implementation. 相似文献
5.
Rachel H. Albright Ryan J. Rodela Panah Nabili Chris E. Gentchos N. Jake Summers 《The Journal of foot and ankle surgery》2021,60(1):61-66
Total ankle arthroplasty (TAA) is used as an alternative to ankle arthrodesis for adults with severe ankle arthritis. Numerous orthopedic centers have entered the healthcare market offering fast-tracked joint replacement protocols, meanwhile, TAA has been excluded from these joint centers, and is primarily performed in the inpatient setting. The purpose of this study is to examine short-term complications in the inpatient and outpatient settings following TAA using a systematic review and quantitative analysis. We considered all studies examining short-term complications following TAA performed in the inpatient versus outpatient setting occuring within 1 year of the index operation. We summarized data using a pooled relative risk and random effects model. A pooled sensitivity analysis was performed for studies with data on complication rates for inpatient or outpatient populations, which did not have a control group. The quality of included studies was assessed using the Cochrane risk of bias tool. Nine studies were included in the quantitative analysis, with 4 studies in the final meta-analysis. Subjects undergoing inpatient surgery experienced a 5-times higher risk of short-term complications compared to the outpatient group (risk ratio 5.27, 95% confidence interval 3.31, 8.42). Results did not change after sensitivity analysis (inpatient weighted mean complication rate: 9.62% vs outpatient weighted mean 5.02%, p value <.001). The overall level of evidence of included studies was level III, with a moderate to high risk of bias. Outpatient TAAs do not appear to pose excess complication risks compared to inpatient procedures, and may therefore be a reasonable addition to experienced centers that have established a fast-track outpatient total joint protocol. 相似文献
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Jennifer A. Westwood Geoffrey M. Matthews Jake Shortt David Faulkner Hollie J. Pegram Connie P.M. Duong Marta Chesi P. Leif Bergsagel Leslie L. Sharp Richard D. Huhn Phillip K. Darcy Ricky W. Johnstone Michael H. Kershaw 《Leukemia research》2014
In order to stimulate antigen presentation and T cell activity against cancer, we treated three different tumor models in mice with the monoclonal antibodies anti-CD40 plus anti-CD137 (BiMab). In a subcutaneous transplantable MC38 colon cancer model, there was significant enhancement in the survival of mice following BiMab treatment. Anti-CD40 has shown considerable success against lymphoma in previous studies by other investigators, and we also showed in this study that, in a model of Eμ-Myc lymphoma, there was a statistically significant enhancement of survival of mice following BiMab treatment. Following the success of the BiMab treatment in the previous two models, we wished to determine if it would be successful in a mouse model of multiple myeloma. Firstly, we tested a transplantable model of disease in which multiple myeloma cells derived from Vk*MYC mice were injected intravenously. A minor proportion of anti-CD137 and BiMab treated mice experienced prolongation of life beyond 250 days. Then we tested the therapy in a spontaneously occurring multiple myeloma model, in Vk*MYC transgenic mice. The majority of mice treated survived longer than control mice, although statistical significance was not demonstrated. 相似文献
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Matthias Szabolcs Megan Keniry Laura Simpson Latarsha J. Reid Susan Koujak Sarah C. Schiff Giselle Davidian Scott Licata Sofia Gruvberger-Saal Vundavalli V.V.S. Murty Subhadra Nandula Argiris Efstratiadis Jake A. Kushner Morris F. White Ramon Parsons 《The American journal of pathology》2009,174(1):276-286
Mutations in the phosphatase and tensin homologue (PTEN)/phosphatidylinositol-3 kinase-α (PI3K) signaling pathway are frequently found in human cancer. In addition, Pten+/− mice develop tumors in multiple organs because of the activation of the PI3K signaling cascade. Because activation of PI3K signaling leads to feedback inhibition of insulin receptor substrate-2 (IRS2) expression, an upstream activator of PI3K, we therefore anticipated that IRS2 expression would be low in tumors that lack PTEN. Surprisingly, however, an elevation of IRS2 was often detected in tumor samples in which PTEN levels were compromised. To determine the potential contribution of Irs2 to tumor progression, Pten+/− mice were crossed with Irs2+/− mice. Deletion of Irs2 did not affect the initiation of neoplasia found in Pten+/− mice but suppressed cancer cell growth, proliferation, and invasion through the basement membrane. Deletion of Irs2 also attenuated the expression of Myc in prostatic intraepithelial neoplasia in Pten+/− mice. In addition, the expression levels of IRS2 and MYC were highly correlated in human prostate cancer, and IRS2 could stimulate MYC expression in cultured cells. Our findings provide evidence that the PI3K-activating adaptor Irs2 contributes to tumor progression in Pten+/− mice by stimulating both Myc and DNA synthesis. 相似文献