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221.
Predicting lung radiotherapy-induced pneumonitis using a model combining parametric Lyman probit with nonparametric decision trees 总被引:1,自引:0,他引:1
Das SK Zhou S Zhang J Yin FF Dewhirst MW Marks LB 《International journal of radiation oncology, biology, physics》2007,68(4):1212-1221
PURPOSE: To develop and test a model to predict for lung radiation-induced Grade 2+ pneumonitis. METHODS AND MATERIALS: The model was built from a database of 234 lung cancer patients treated with radiotherapy (RT), of whom 43 were diagnosed with pneumonitis. The model augmented the predictive capability of the parametric dose-based Lyman normal tissue complication probability (LNTCP) metric by combining it with weighted nonparametric decision trees that use dose and nondose inputs. The decision trees were sequentially added to the model using a "boosting" process that enhances the accuracy of prediction. The model's predictive capability was estimated by 10-fold cross-validation. To facilitate dissemination, the cross-validation result was used to extract a simplified approximation to the complicated model architecture created by boosting. Application of the simplified model is demonstrated in two example cases. RESULTS: The area under the model receiver operating characteristics curve for cross-validation was 0.72, a significant improvement over the LNTCP area of 0.63 (p = 0.005). The simplified model used the following variables to output a measure of injury: LNTCP, gender, histologic type, chemotherapy schedule, and treatment schedule. For a given patient RT plan, injury prediction was highest for the combination of pre-RT chemotherapy, once-daily treatment, female gender and lowest for the combination of no pre-RT chemotherapy and nonsquamous cell histologic type. Application of the simplified model to the example cases revealed that injury prediction for a given treatment plan can range from very low to very high, depending on the settings of the nondose variables. CONCLUSIONS: Radiation pneumonitis prediction was significantly enhanced by decision trees that added the influence of nondose factors to the LNTCP formulation. 相似文献
222.
Jianhua Huang Tian Xie Yuming Wu Xianghong Li Sara Lusina En-Sheng Ji Shuanglin Xiang Yuzhen Liu Shiva Gautam J. Woodrow Weiss 《Respiratory physiology & neurobiology》2010,171(2):83-89
To test the hypothesis that central changes in sympathoregulation might contribute to sympathoexcitation after cyclic intermittent hypoxia (CIH) we exposed male Sprague–Dawley rats to CIH or to room air sham (Sham) for 8 h/d for 3 weeks. After completion of the exposure we assessed heart rate, mean arterial pressure and renal sympathetic nerve activity in conscious animals before and after intracerebroventricular (i.c.v.) administration of endothelin-1 (ET-1, 3 pmol). CIH-exposed animals had a significantly greater sympathetic response to ET-1 than did Sham-exposed animals (CIH 137.8 ± 15.6% of baseline; Sham 112.2 ± 10.0% of baseline; CIH vs. Sham, P = 0.0373). This enhanced sympathetic response to i.c.v. ET-1 was associated with greater expression of endothelin receptor A (ETA) protein in the subfornical organs of CIH-exposed relative to Sham-exposed rats. We conclude that 3-week CIH exposure enhances central ET-1 receptor expression and the sympathetic response to i.c.v. ET-1 suggesting central endothelin may contribute to the sympathetic and hemodynamic response to cyclic intermittent hypoxia. 相似文献
223.
Shicong B. Zou Julia Weng Melissa N. Symons Shiva M. Singh 《Alcoholism, clinical and experimental research》2009,33(3):394-399
Background: Inwardly‐rectifying potassium channel protein Kir4.1 is encoded by Kcnj10 which maps to a quantitative trait locus on chromosome 1 for the voluntary alcohol consumption phenotype in mice. Kcnj10 brain expression differences have been established between ethanol‐preferring C57Bl/6J and ethanol‐avoiding BALB/cJ mice, but its differential expression in other tissues and strains have largely been overlooked. A nonsynonymous single nucleotide polymorphism exists between C57Bl/6J and ethanol‐avoiding DBA/2J mice which changes amino acid 262 from threonine (C57Bl/6J) to serine (DBA/2J). This Kcnj10 SNP and its expression may serve as valuable markers in predicting the ethanol preference phenotype in mice. Methods: The evolutionary divergence of the Kir gene family was characterized using phylogenetic analysis involving the 16 mouse Kir channels. Kcnj10 expression differences in the brain, liver, lung, heart, spleen, kidney, testes, and muscle of male C57Bl/6J and DBA/2J mice at different developmental stages were examined using semiquantitative RT‐PCR analysis. A SNP analysis was conducted to assess the association of Kcnj10 Thr262Ser SNP and the ethanol preference phenotype in F2 mice derived from the reciprocal crosses of the C57Bl/6J and DBA/2J strains. Results: Evolutionary analysis supports gene duplication and genetic recombination as likely sources of diversity within the Kir gene family. Semiquantitative RT‐PCR analysis revealed significantly higher Kcnj10 expression in the brain, spleen, and kidney of both strains when compared to other tissues from the same strain. There were no significant differences in tissue‐specific mRNA levels between strains except in the testes. Genotype distributions of the Kcnj10 Thr262Ser SNP were different between low‐ and high‐drinkers. A significant difference in the average ethanol preference level of each genotype was also observed. Conclusion: Our results suggest a role for Kcnj10 in ethanol preference determination in mice. However, further experiments are needed to establish if this association is due to the nonsynonymous SNP or other additional factors associated with Kcnj10. 相似文献
224.
225.
Andrew Shiva Sara C. Haden Jeannie Brooks 《Social psychiatry and psychiatric epidemiology》2009,44(11):979-987
Introduction
The goal of the study was to understand what characteristics of the provider and recipient of psychiatric care on inpatient civil and forensic units impact satisfaction ratings. Specifically, we explored how demographic variables (age, race), psychiatric diagnosis (psychotic, affective, substance-related), and patients’ interactions with staff influence satisfaction ratings. 相似文献226.
Physics and imaging for targeting of oligometastases 总被引:1,自引:0,他引:1
Yin FF Das S Kirkpatrick J Oldham M Wang Z Zhou SM 《Seminars in radiation oncology》2006,16(2):85-101
Oligometastases refer to metastases that are limited in number and location and are amenable to regional treatment. The majority of these metastases appear in the brain, lung, liver, and bone. Although the focus of interest in the past within radiation oncology has been on the treatment of intracranial metastases, there has been growing interest in extracranial sites such as the liver and lung. This is largely because of the rapid development of targeting techniques for oligometastases such as intensity-modulated and image-guided radiation therapy, which has made it possible to deliver single or a few fractions of high-dose radiation treatments, highly conformal to the target. The clinical decision to use radiation to treat oligometastases is based on both radiobiological and physics considerations. The radiobiological considerations involve improvement of treatment schema for time, dose, and volume. Areas of interests are hypofractionation, tumor and normal tissue tolerance, and hypoxia. The physics considerations for oligometastases treatment are focused mainly on ensuring treatment accuracy and precision. This article discusses the physics and imaging aspects involved in each step of the radiation treatment process for oligometastases, including target definition, treatment simulation, treatment planning, pretreatment target localization, radiation delivery, treatment verification, and treatment evaluation. 相似文献
227.
Allen-Ramey FC Bukstein D Luskin A Sajjan SG Markson LE 《Journal of managed care pharmacy : JMCP》2006,12(4):310-321
OBJECTIVE: To compare asthma-related health care resource utilization among a matched cohort of asthma patients using inhaled corticosteroids (ICSs) plus either montelukast (MON) or salmeterol (SAL) as combination therapy for asthma, during a time prior to the availability of fixed-dose combinations of ICS/SAL. METHODS: A retrospective analysis using the PHARMetrics patient-centric claims database was conducted for the period preceding the market introduction of combination fluticasone-SAL in September 2000. Patients had to meet the following criteria for inclusion in the study: they had to be between the ages of 4 and 55 years; they had to have been continuously enrolled for 2 years; they had to have initiated ICS/MON or ICS/SAL therapy between July 1, 1998, and June 30, 1999; and they had to have had either (a) a diagnosis of asthma (based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes of 493.xx) for 2 outpatient visits, 1 or more emergency department (ED) visits, or 1 or more hospitalizations within 1 year or (b) pharmacy claim records that contained a National Drug Code for an antiasthma medication (betaagonist, theophylline, ICS, cromolyn, or leukotriene) 2 or more times within 1 year. ICS/MON and ICS/SAL patients were matched 1 to 1 on age and propensity score. Outcomes included asthma-related hopitalizations and ED visits with ICD-9-CM codes of 493.xx, and oral corticosteroid (OCS) fills and short-acting beta-agonist (SABA) fills. Multivariate regression analyses were performed. Subgroup analyses based on sequential or concurrent initiation of combination therapy were also conducted. RESULTS: A total of 1,216 patients were matched (ICS/MON = 608; ICS/SAL= 608). Decreased odds of ED visits and/or hospitalizations were observed with ICS/MON (adjusted odds ratio [OR] = 0.58; 95% confidence interval [CI], 0.35- 0.98) versus ICS/SAL. The odds of postindex OCS fills were not different for ICS/MON and ICS/SAL patients (adjusted OR = 1.04; 95% CI, 0.79-1.38). Postindex pharmacy claims for SABAs were significantly higher among ICS/MON patients versus ICS/SAL patients (adjusted relative risk [RR] = 1.33; 95% CI, 1.17-1.52), and this difference remained regardless of prior use or no prior use of ICSs. In subgroup analyses, mean change in SABA fills varied by how combination therapy was initiated, with sequential addition of asthma controllers leading to a reduction in SABA fills in both groups. For patients with concurrent initiation of combination therapy, the odds of ED visits/hospitalizations were significantly lower in patients initiating ICS/MON (adjusted OR = 0.25; 95% CI, 0.08-0.79). CONCLUSION: In this matched cohort, use of ICS/MON compared with ICS/SAL resulted in similar odds of OCS fills, decreased odds of ED visits and asthmarelated hospitalizations, but higher utilization of SABA. 相似文献
228.
Hirai K Ohno Y Jindai M Aoki Y Hayashi E Higuchi H Mizuno S Nagata K Tamura T Rai SK Shrestha MP 《Environmental health and preventive medicine》2004,9(1):13-21
Objective The present study examined the levels of serum α-Tocopherol (Toc), retinol (Ret), cholesterol (Chol) and triglycerides (TG),
and their correlations in the sera of people in Nepal.
Methods The survey was conducted on the general populace in the agricultural Terai region in southern Nepal. The study population
consisted of 93 males and 83 females aged 10–68 years. Serum Toc and Ret were measured by high-performance liquid chromatography.
Results No significant differences were observed between the genders for the average of total Chol (T-Chol) (140 and 145 mg/100 ml,
respectively), HDL-C (45 and 47 mg/100 ml), LDL-C (94 and 97 mg/100 ml), and TG (106 and 110 mg/100 ml), and the ratio of
LDL/HDL (2.16). The levels of mean Toc (4.32 and 4.27 μg/ml) were about the same for both genders, while the mean Ret levels
were significantly higher for males (624 ng/ml) than for females (535 ng/ml) (p<0.001). A direct relationship was found between
the levels of Toc and Ret (r=0.46, p<0.001 and r=0.28, p<0.05 for males and females, respectively). Serum levels of Toc and
Ret were positively related to the levels of Chol (r=0.48 and r=0.58, p<0.001 for males and r=0.49, p<0.01 and r-0.28, p<0.05
for females, respectively). The ratio of Toc/TG normalized to serum TG was directly correlated to the ratio of Ret/TG (r=0.79
for males, and r=0.72 for females, p<0.001, respectively) and the ratios of Toc/TG and Ret/TG were negatively related to the
LDL/HDL levels (r=−0.49 and r=−0.43, for males, and r=−0.46 and r=−0.57 for females, p<0.001, respectively).
Conclusion The levels of Toc and Ret were low in the sera of people living in the southern rural Terai region in Nepal, and it was found
that lower levels of Toc and Ret normalized to TG increased the ratio of LDL/HDL. These results suggest that greater intake
of foods rich in Toc and Ret should be encouraged to reduce the erisk of coronary heart disease. 相似文献
229.
Biswas S Chytil A Washington K Romero-Gallo J Gorska AE Wirth PS Gautam S Moses HL Grady WM 《Cancer research》2004,64(14):4687-4692
Deregulation of members of the transforming growth factor (TGF)-beta signaling pathway occurs often in colon cancers and is believed to affect the formation of primary colon cancer. Mutational inactivation of TGFBR2 is the most common genetic event affecting the TGF-beta signaling pathway and occurs in approximately 20-30% of all colon cancers. By mating Fabpl(4xat-132) Cre mice with Tgfbr2(flx/flx) mice, we have generated a mouse model that is null for Tgfbr2 in the colonic epithelium, and in this model system, we have assessed the effect of loss of TGF-beta signaling in vivo on colon cancer formation induced by azoxymethane (AOM). We have observed a significant increase in the number of AOM-induced adenomas and adenocarcinomas in the Fabpl(4xat-132) Cre Tgfbr2(flx/flx) mice compared with Tgfbr2(flx/flx) mice, which have intact TGF-beta receptor type II (TGFBR2) in the colon epithelium, and we have found increased proliferation in the neoplasms occurring in the Fabpl(4xat-132) Cre Tgfbr2(flx/flx) mice. These results implicate the loss of TGF-beta-mediated growth inhibition as one of the in vivo mechanisms through which TGFBR2 inactivation contributes to colon cancer formation. Thus, we have demonstrated that loss of TGFBR2 in colon epithelial cells promotes the establishment and progression of AOM-induced colon neoplasms, providing evidence from an in vivo model system that TGFBR2 is a tumor suppressor gene in the colon. 相似文献
230.
Bacterial diarrheagenic heat-stable enterotoxins induce colon cancer cell cytostasis by targeting guanylyl cyclase C (GCC) signaling. Anticancer actions of these toxins are mediated by cyclic guanosine 3',5'-monophosphate (cGMP)-dependent influx of Ca2+ through cyclic nucleotide-gated channels. However, prolonged stimulation of GCC produces resistance in tumor cells to heat-stable enterotoxin-induced cytostasis. Resistance reflects rapid (tachyphylaxis) and slow (bradyphylaxis) mechanisms of desensitization induced by cGMP. Tachyphylaxis is mediated by cGMP-dependent protein kinase, which limits the conductance of cyclic nucleotide-gated channels, reducing the influx of Ca2+ propagating the antiproliferative signal from the membrane to the nucleus. In contrast, bradyphylaxis is mediated by cGMP-dependent allosteric activation of phosphodiesterase 5, which shapes the amplitude and duration of heat-stable enterotoxin-dependent cyclic nucleotide accumulation required for cytostasis. Importantly, interruption of tachyphylaxis and bradyphylaxis restores cancer cell cytostasis induced by heat-stable enterotoxins. Thus, regimens that incorporate cytostatic bacterial enterotoxins and inhibitors of cGMP-mediated desensitization offer a previously unrecognized therapeutic paradigm for treatment and prevention of colorectal cancer. 相似文献