Phase I study of sorafenib combined with radiation therapy and temozolomide as first-line treatment of high-grade glioma.

BACKGROUND: Sorafenib (Sb) is a multiple kinase inhibitor targeting both tumour cell proliferation and angiogenesis that may further act as a potent radiosensitizer by arresting cells in the most radiosensitive cell cycle phase. This phase I open-label, noncontrolled dose escalation study was performed to determine the safety and maximum tolerated dose (MTD) of Sb in combination with radiation therapy (RT) and temozolomide (TMZ) in 17 patients with newly diagnosed high-grade glioma. METHODS: Patients were treated with RT (60 Gy in 2 Gy fractions) combined with TMZ 75 mg m(-2) daily, and Sb administered at three dose levels (200 mg daily, 200 mg BID, and 400 mg BID) starting on day 8 of RT. Thirty days after the end of RT, patients received monthly TMZ (150-200 mg m(-2) D1-5/28) and Sb (400 mg BID). Pharmacokinetic (PK) analyses were performed on day 8 (TMZ) and on day 21 (TMZ&Sb) (Clinicaltrials ID: NCT00884416). RESULTS: The MTD of Sb was established at 200 mg BID. Dose-limiting toxicities included thrombocytopenia (two patients), diarrhoea (one patient) and hypercholesterolaemia (one patient). Sb administration did not affect the mean area under the curve(0-24) and mean Cmax of TMZ and its metabolite 5-amino-imidazole-4-carboxamide (AIC). Tmax of both TMZ and AIC was delayed from 0.75 (TMZ alone) to 1.5 h (combined TMZ/Sb). The median progression-free survival was 7.9 months (95% confidence interval (CI): 5.4-14.55), and the median overall survival was 17.8 months (95% CI: 14.7-25.6). CONCLUSIONS: Although Sb can be combined with RT and TMZ, significant side effects and moderate outcome results do not support further clinical development in malignant gliomas. The robust PK data of the TMZ/Sb combination could be useful in other cancer settings.

Endocavitary contact radiation therapy for ultrasonographically staged T1 N0 and T2 N0 rectal cancer.

BACKGROUND: The purpose of this study was to determine the long-term outcomes of patients undergoing endocavitary contact radiation therapy (ECR) for stage I rectal cancer. METHODS: A database of patients treated with ECR for biopsy-proven rectal adenocarcinoma from July 1986 to June 2006 was reviewed retrospectively. Only patients with primary, non-metastatic, ultrasonographically staged T1 N0 and T2 N0 cancer who had no adjuvant treatment were included. Patients received a median of 90 (range 60-190) Gy contact radiation, delivered transanally by a 50-kV X-ray tube in two to five fractions. RESULTS: Of 149 patients, 77 (40 T1, 37 T2) met the inclusion criteria. Median age was 74 (range 38-104) years, and median follow-up 69 (range 10-219) months. ECR failed in 21 patients (27 per cent) (persistent disease, four; recurrence, 17), of whom ten remained disease free after salvage therapy. The estimated 5-year disease-free survival rate was 74 (95 per cent confidence interval 63 to 83) per cent after ECR alone, and 87 (76 to 93) per cent when survival after salvage therapy for recurrence was included. CONCLUSION: ECR is a minimally invasive treatment option for early-stage rectal cancer. However, similar to other local therapies, ECR has a worse oncological outcome than radical surgery.

Hollow sphere as a detector of gravitational radiation

The most important features of the proposed spherical gravitational wave detectors are closely linked with their symmetry. Hollow spheres share this property with solid ones, considered in the literature so far, and constitute an interesting alternative for the realization of an omnidirectional gravitational wave detector. In this paper we address the problem of how a hollow elastic sphere interacts with an incoming gravitational wave and find an analytical solution for its normal mode spectrum and response, as well as for its energy absorption cross sections. It appears that this shape can be designed having relatively low resonance frequencies (~ 200 Hz) yet keeping a large cross section, so its frequency range overlaps with the projected large interferometers. We also apply the obtained results to discuss the performance of a hollow sphere as a detector for a variety of gravitational wave signals.

Advanced age increases the failure rate of non-operative management of blunt splenic injuries

Introduction: Non-operative management (NOM) of blunt splenic injuries in hemodynamically stable patients is nowadays considered the standard treatment. Material and Methods: The aim was to clarify the criteria used for primary operative management (OM) and planned NOM. Furthermore, the study aimed to identify risk factors for failure of NOM. All adult patients with blunt splenic injuries treated from 2000-2008 were reviewed and a logistic regression analysis employed. Results: There were 206 patients (146 men, 70.9%). Mean age was 38.2 ± 19.1 years. The mean Injury Severity Score (ISS) was 30.9 ± 11.6. The American Association for the Surgery of Trauma (AAST) classification of the splenic injury was: grade I, n = 43 (20.9%); grade II, n = 52 (25.2%); grade III, n = 60 (29.1%), grade IV, n = 42 (20.4%) and grade V, n = 9 (4.4%). 47 patients (22.8%) required immediate surgery (OM). More than 5 units of red cell transfusions (odds ratio [OR] 13.72, P < 0.001), a Glasgow Coma Scale < 11 (OR 9.88, P = 0.009) and age ? 55 years (OR 3.29, P = 0.038) were associated with primary OM. 159 patients (77.2%) qualified for a non-surgical approach (NOM), which was successful in 89.9% (143/159). The overall splenic salvage rate amounted to 69.4% (143/206). Multiple logistic regression analysis found age ? 40 years to be the only factor significantly and independently related to the failure of NOM (OR 13.58, P = 0.001). Conclusion: Advanced age is associated with an increased failure rate of NOM in patients with blunt splenic injuries.

Contribution of Topography and Incident Solar Radiation to Variation of Soil and Plant Litter at an Area with Heterogeneous Terrain

Natural processes that determine soil and plant litter properties are controlled by multiple factors. However, little attention has been given to distinguishing the effects of environmental factors from the effects of spatial structure of the area on the distribution of soil and litter properties in tropical ecosystems covering heterogeneous topographies. The aim of this study was to assess patterns of soil and litter variation in a tropical area that intercepts different levels of solar radiation throughout the year since its topography has slopes predominantly facing opposing geographic directions. Soil data (pH, C, N, P, H+Al, Ca, Mg, K, Al, Na, sand, and silt) and plant litter data (N, K, Ca, P, and Mg) were gathered together with the geographic coordinates (to model the spatial structure) of 40 sampling units established at two sites composed of slopes predominantly facing northwest and southeast (20 units each). Soil and litter chemical properties varied more among slopes within similar geographic orientations than between the slopes facing opposing directions. Both the incident solar radiation and the spatial structure of the area were relevant in explaining the patterns detected in variation of soil and plant litter. Individual contributions of incident solar radiation to explain the variation in the properties evaluated suggested that this and other environmental factors may play a particularly relevant role in determining soil and plant litter distribution in tropical areas with heterogeneous topography. Furthermore, this study corroborates that the spatial structure of the area also plays an important role in the distribution of soil and litter within this type of landscape, which appears to be consistent with the action of water movement mechanisms in such areas.

Classical predictive electrodynamics of two charges with radiation: General framework. I.

Outgoing radiation is introduced in the framework of the classical predictive electrodynamics using LorentzDiracs equation as a subsidiary condition. In a perturbative scheme in the charges the first radiative self-terms of the accelerations, momentum and angular momentum of a two charge system without external field are calculated.

Classical predictive electrodynamics of two charges with radiation: Energy and 3. momentum balance and scattering crossections-II

We deal with a classical predictive mechanical system of two spinless charges where radiation is considered and there are no external fields. The terms (2,2)Paa of the expansion in the charges of the HamiltonJacobi momenta are calculated. Using these, together with known previous results, we can obtain the paa up to the fourth order. Then we have calculated the radiated energy and the 3-momentum in a scattering process as functions of the impact parameter and the incident energy for the former and 3-momentum for the latter. Scattering cross-sections are also calculated. Good agreement with well known results, including those of quantum electrodynamics, has been found.

Rapid radiation in spiny lobsters (Palinurus spp) as revealed by classic and ABC methods using mtDNA and microsatellite data

Background: Molecular tools may help to uncover closely related and still diverging species from a wide variety of taxa and provide insight into the mechanisms, pace and geography of marine speciation. There is a certain controversy on the phylogeography and speciation modes of species-groups with an Eastern Atlantic-Western Indian Ocean distribution, with previous studies suggesting that older events (Miocene) and/or more recent (Pleistocene) oceanographic processes could have influenced the phylogeny of marine taxa. The spiny lobster genus Palinurus allows for testing among speciation hypotheses, since it has a particular distribution with two groups of three species each in the Northeastern Atlantic (P. elephas, P. mauritanicus and P. charlestoni) and Southeastern Atlantic and Southwestern Indian Oceans (P. gilchristi, P. delagoae and P. barbarae). In the present study, we obtain a more complete understanding of the phylogenetic relationships among these species through a combined dataset with both nuclear and mitochondrial markers, by testing alternative hypotheses on both the mutation rate and tree topology under the recently developed approximate Bayesian computation (ABC) methods. Results Our analyses support a North-to-South speciation pattern in Palinurus with all the South-African species forming a monophyletic clade nested within the Northern Hemisphere species. Coalescent-based ABC methods allowed us to reject the previously proposed hypothesis of a Middle Miocene speciation event related with the closure of the Tethyan Seaway. Instead, divergence times obtained for Palinurus species using the combined mtDNA-microsatellite dataset and standard mutation rates for mtDNA agree with known glaciation-related processes occurring during the last 2 my. Conclusion The Palinurus speciation pattern is a typical example of a series of rapid speciation events occurring within a group, with very short branches separating different species. Our results support the hypothesis that recent climate change-related oceanographic processes have influenced the phylogeny of marine taxa, with most Palinurus species originating during the last two million years. The present study highlights the value of new coalescent-based statistical methods such as ABC for testing different speciation hypotheses using molecular data.

Problème de surcharge de l'articulation coxo-fémorale chez l'adolescent [Overuse injuries of the hip in adolescents].

Painful femoro-acetabular impingement symptoms localized in the groin in flexion, adduction and internal rotation can be explained either by a primary disease of the labrum often post-traumatic, and more frequently as part of femoro-acetabular primary or secondary dysmorphia. The kinematic of the normal hip joint depends of peri-acetabular structures, geometry of joints and possible pathologies that could contribute to modify either the geometry or the proprioceptive function. By combining and analyzing these parameters it is possible to describe a joint concept of centricity, an essential parameter for optimal functions of the joint. The concept of overload is explained as the inability of the hip to ensure its centricity during activities that could lead to the occurrence of any degenerative disorders.

Brain Injuries In Iowa, September 2001

Under Iowa law, hospitals treating persons with a brain or spinal cord injury which results in a hospital admission, patient transfer, or death must report that injury to the Central Registry for Brain and Spinal Cord Injuries of the Iowa Department of Public Health.

High rate of severe radiation dermatitis during radiation therapy with concurrent cetuximab in head and neck cancer: results of a survey in EORTC institutes.

OBJECTIVE: Examination of the rate of grade III or grade IV radiation dermatitis during treatment of head and neck cancer (HNC) with radiotherapy (RT) and concurrent cetuximab in EORTC centres. MATERIALS AND METHOD: A questionnaire was sent to all members of the EORTC Radiation Oncology Group and Head and Neck Group (111 institutions) to evaluate the widespread use of cetuximab and radiotherapy in HNC and to estimate the frequency of grades III and IV skin reactions in the radiation portals associated with this protocol. Co-morbidities, RT schedules and co-medications were also recorded. RESULTS: We received responses from 28 institutions in 11 countries. A total of 125 HNC patients from 15 institutions were treated with cetuximab and concurrent RT. Information about the skin reactions was available from 71 patients. Of these 36 had no grade III/IV adverse effects in the RT field, 15 had a grade III and 20 had grade IV radiation dermatitis. No detectable relation of grades III and IV radiation dermatitis with co-morbidities such as liver insufficiency or renal dysfunction was found. CONCLUSION: According to the results of the questionnaire, grade III/IV radiation dermatitis is observed in 49% of HNC patients treated with cetuximab and concurrent RT. A systematic clinical monitoring of cutaneous side effects during RT plus cetuximab is advised to ensure the safety of this protocol.

Statistical Modeling of the Eye for Multimodal Treatment Planning for External Beam Radiation Therapy of Intraocular Tumors.

PURPOSE: Ocular anatomy and radiation-associated toxicities provide unique challenges for external beam radiation therapy. For treatment planning, precise modeling of organs at risk and tumor volume are crucial. Development of a precise eye model and automatic adaptation of this model to patients' anatomy remain problematic because of organ shape variability. This work introduces the application of a 3-dimensional (3D) statistical shape model as a novel method for precise eye modeling for external beam radiation therapy of intraocular tumors. METHODS AND MATERIALS: Manual and automatic segmentations were compared for 17 patients, based on head computed tomography (CT) volume scans. A 3D statistical shape model of the cornea, lens, and sclera as well as of the optic disc position was developed. Furthermore, an active shape model was built to enable automatic fitting of the eye model to CT slice stacks. Cross-validation was performed based on leave-one-out tests for all training shapes by measuring dice coefficients and mean segmentation errors between automatic segmentation and manual segmentation by an expert. RESULTS: Cross-validation revealed a dice similarity of 95% ± 2% for the sclera and cornea and 91% ± 2% for the lens. Overall, mean segmentation error was found to be 0.3 ± 0.1 mm. Average segmentation time was 14 ± 2 s on a standard personal computer. CONCLUSIONS: Our results show that the solution presented outperforms state-of-the-art methods in terms of accuracy, reliability, and robustness. Moreover, the eye model shape as well as its variability is learned from a training set rather than by making shape assumptions (eg, as with the spherical or elliptical model). Therefore, the model appears to be capable of modeling nonspherically and nonelliptically shaped eyes.