Research in and application of modern automatic control theory to nuclear rocket dynamics and control, volume I Semiannual status report

Linear optimal feedback control theory for nuclear rocket dynamics and control problem

Endometrial stromal sarcoma: a population-based analysis

To determine independent prognostic factors for the survival of patients with endometrial stromal sarcoma (ESS), data were abstracted from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute from 1988 to 2003. Kaplan–Meier and Cox proportional hazards models were used for analyses. Of 831 women diagnosed with ESS, the median age was 52 years (range: 17–96 years). In total, 59.9% had stage I, 5.1% stage II, 14.9% stage III, and 20.1% had stage IV disease. Overall, 13.0, 36.1, and 34.7% presented with grades 1, 2, and 3, respectively. Patients with stage I–II vs III–IV disease had 5 years DSS of 89.3% vs 50.3% (P<0.001) and those with grades 1, 2, and 3 cancers had survivals of 91.4, 95.4, and 42.1% (P<0.001). In multivariate analysis, older patients, black race, advanced stage, higher grade, lack of primary surgery, and nodal metastasis were independent prognostic factors for poorer survival. In younger women (<50 years) with stage I–II disease, ovarian-sparing procedures did not adversely impact survival (91.9 vs 96.2%; P=0.1). Age, race, primary surgery, stage, and grade are important prognostic factors for ESS. Excellent survival in patients with grade 1 and 2 disease of all stages supports the concept that these tumors are significantly different from grade 3 tumors. Ovarian-sparing surgeries may be considered in younger patients with early-stage disease

Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study.

BACKGROUND: Outcome of low-grade glioma (WHO grade II) is highly variable, reflecting molecular heterogeneity of the disease. We compared two different, single-modality treatment strategies of standard radiotherapy versus primary temozolomide chemotherapy in patients with low-grade glioma, and assessed progression-free survival outcomes and identified predictive molecular factors. METHODS: For this randomised, open-label, phase 3 intergroup study (EORTC 22033-26033), undertaken in 78 clinical centres in 19 countries, we included patients aged 18 years or older who had a low-grade (WHO grade II) glioma (astrocytoma, oligoastrocytoma, or oligodendroglioma) with at least one high-risk feature (aged &gt;40 years, progressive disease, tumour size &gt;5 cm, tumour crossing the midline, or neurological symptoms), and without known HIV infection, chronic hepatitis B or C virus infection, or any condition that could interfere with oral drug administration. Eligible patients were randomly assigned (1:1) to receive either conformal radiotherapy (up to 50·4 Gy; 28 doses of 1·8 Gy once daily, 5 days per week for up to 6·5 weeks) or dose-dense oral temozolomide (75 mg/m(2) once daily for 21 days, repeated every 28 days [one cycle], for a maximum of 12 cycles). Random treatment allocation was done online by a minimisation technique with prospective stratification by institution, 1p deletion (absent vs present vs undetermined), contrast enhancement (yes vs no), age (&lt;40 vs ≥40 years), and WHO performance status (0 vs ≥1). Patients, treating physicians, and researchers were aware of the assigned intervention. A planned analysis was done after 216 progression events occurred. Our primary clinical endpoint was progression-free survival, analysed by intention-to-treat; secondary outcomes were overall survival, adverse events, neurocognitive function (will be reported separately), health-related quality of life and neurological function (reported separately), and correlative analyses of progression-free survival by molecular markers (1p/19q co-deletion, MGMT promoter methylation status, and IDH1/IDH2 mutations). This trial is closed to accrual but continuing for follow-up, and is registered at the European Trials Registry, EudraCT 2004-002714-11, and at ClinicalTrials.gov, NCT00182819. FINDINGS: Between Sept 23, 2005, and March 26, 2010, 707 patients were registered for the study. Between Dec 6, 2005, and Dec 21, 2012, we randomly assigned 477 patients to receive either radiotherapy (n=240) or temozolomide chemotherapy (n=237). At a median follow-up of 48 months (IQR 31-56), median progression-free survival was 39 months (95% CI 35-44) in the temozolomide group and 46 months (40-56) in the radiotherapy group (unadjusted hazard ratio [HR] 1·16, 95% CI 0·9-1·5, p=0·22). Median overall survival has not been reached. Exploratory analyses in 318 molecularly-defined patients confirmed the significantly different prognosis for progression-free survival in the three recently defined molecular low-grade glioma subgroups (IDHmt, with or without 1p/19q co-deletion [IDHmt/codel], or IDH wild type [IDHwt]; p=0·013). Patients with IDHmt/non-codel tumours treated with radiotherapy had a longer progression-free survival than those treated with temozolomide (HR 1·86 [95% CI 1·21-2·87], log-rank p=0·0043), whereas there were no significant treatment-dependent differences in progression-free survival for patients with IDHmt/codel and IDHwt tumours. Grade 3-4 haematological adverse events occurred in 32 (14%) of 236 patients treated with temozolomide and in one (&lt;1%) of 228 patients treated with radiotherapy, and grade 3-4 infections occurred in eight (3%) of 236 patients treated with temozolomide and in two (1%) of 228 patients treated with radiotherapy. Moderate to severe fatigue was recorded in eight (3%) patients in the radiotherapy group (grade 2) and 16 (7%) in the temozolomide group. 119 (25%) of all 477 patients had died at database lock. Four patients died due to treatment-related causes: two in the temozolomide group and two in the radiotherapy group. INTERPRETATION: Overall, there was no significant difference in progression-free survival in patients with low-grade glioma when treated with either radiotherapy alone or temozolomide chemotherapy alone. Further data maturation is needed for overall survival analyses and evaluation of the full predictive effects of different molecular subtypes for future individualised treatment choices. FUNDING: Merck Sharpe &amp; Dohme-Merck &amp; Co, Canadian Cancer Society, Swiss Cancer League, UK National Institutes of Health, Australian National Health and Medical Research Council, US National Cancer Institute, European Organisation for Research and Treatment of Cancer Cancer Research Fund

The course of mental health after miscarriage and induced abortion: a longitudinal, five-year follow-up study

BACKGROUND: Miscarriage and induced abortion are life events that can potentially cause mental distress. The objective of this study was to determine whether there are differences in the patterns of normalization of mental health scores after these two pregnancy termination events. METHODS: Forty women who experienced miscarriages and 80 women who underwent abortions at the main hospital of Buskerud County in Norway were interviewed. All subjects completed the following questionnaires 10 days (T1), six months (T2), two years (T3) and five years (T4) after the pregnancy termination: Impact of Event Scale (IES), Quality of Life, Hospital Anxiety and Depression Scale (HADS), and another addressing their feelings about the pregnancy termination. Differential changes in mean scores were determined by analysis of covariance (ANCOVA) and inter-group differences were assessed by ordinary least squares methods. RESULTS: Women who had experienced a miscarriage had more mental distress at 10 days and six months after the pregnancy termination than women who had undergone an abortion. However, women who had had a miscarriage exhibited significantly quicker improvement on IES scores for avoidance, grief, loss, guilt and anger throughout the observation period. Women who experienced induced abortion had significantly greater IES scores for avoidance and for the feelings of guilt, shame and relief than the miscarriage group at two and five years after the pregnancy termination (IES avoidance means: 3.2 vs 9.3 at T3, respectively, p < 0.001; 1.5 vs 8.3 at T4, respectively, p < 0.001). Compared with the general population, women who had undergone induced abortion had significantly higher HADS anxiety scores at all four interviews (p < 0.01 to p < 0.001), while women who had had a miscarriage had significantly higher anxiety scores only at T1 (p < 0.01). CONCLUSION: The course of psychological responses to miscarriage and abortion differed during the five-year period after the event. Women who had undergone an abortion exhibited higher scores during the follow-up period for some outcomes. The difference in the courses of responses may partly result from the different characteristics of the two pregnancy termination events

Experimental concepts for toxicity prevention and tissue restoration after central nervous system irradiation

Several experimental strategies of radiation-induced central nervous system toxicity prevention have recently resulted in encouraging data. The present review summarizes the background for this research and the treatment results. It extends to the perspectives of tissue regeneration strategies, based for example on stem and progenitor cells. Preliminary data suggest a scenario with individually tailored strategies where patients with certain types of comorbidity, resulting in impaired regeneration reserve capacity, might be considered for toxicity prevention, while others might be "salvaged" by delayed interventions that circumvent the problem of normal tissue specificity. Given the complexity of radiation-induced changes, single target interventions might not suffice. Future interventions might vary with patient age, elapsed time from radiotherapy and toxicity type. Potential components include several drugs that interact with neurodegeneration, cell transplantation (into the CNS itself, the blood stream, or both) and creation of reparative signals and a permissive microenvironment, e.g., for cell homing. Without manipulation of the stem cell niche either by cell transfection or addition of appropriate chemokines and growth factors and by providing normal perfusion of the affected region, durable success of such cell-based approaches is hard to imagine