Sediment flux and composition changes in canyons on a carbonate-siliciclastic margin: evidence from turbidite deposits along the Great Barrier Reef margin

The shelf edge and slope of the Great Barrier Reef is heavily incised by submarine canyons which terminate in the Queensland Trough. Traditionally, sedimentation on the margin has been investigated within the framework of idealized siliciclastic or carbonate systems, depending on whether rivers or shallow marine carbonate producers dominate supply. The widely accepted paradigm ('reciprocal' sedimentation) states that sea-level strongly influences shelf, slope and basin sedimentation, with siliciclastics dominating lowstand periods and carbonates dominating transgressions/highstands. However, recent work (e.g., Dunbar and Dickens, 2003) on cores from the slope and basin has challenged this view. These workers argue that accumulation of both siliciclastic and carbonate sediments varies in phase, with the highest rates observed during transgressions, lowest rates during lowstands and moderate sedimentation during highstands. Irrespective of which model is correct, exactly how the sediment (carbonate or siliciclastic) moves from the shelf to the basin, and the role of submarine canyons in this process is not understood. We address this problem directly by investigating sedimentation in the canyons bordering the GBR. Combining new multibeam bathymetry and seismic data with x-radiograph, magnetic susceptibility, insitu reflectance spectroscopy, grain size, CNS, petrologic, pollen and 14C AMS analyses of canyon cores off Cooktown and Cairns, we aim to establish the source, timing and frequency of turbidite events deposited in the canyons over the last glacial to interglacial cycle, thereby testing the competing models. Our preliminary data confirm that: (1) the canyons record a distinct sedimentary shift from siliciclastic turbidites to calciturbidites; (2) the siliciclastic turbidites were deposited before 28 ka - providing strong support for the "reciprocal" model of margin sedimentation; and (3) the canyons have been active throughout the last deglaciation and into the late Holocene

Intensity-Modulated and Image-Guided Radiotherapy in Patients with Locally Advanced Inoperable Pancreatic Cancer after Preradiation Chemotherapy

Background. Radiotherapy (RT) in patients with pancreatic cancer is still a controversial subject and its benefit in inoperable stages of locally advanced pancreatic cancer (LAPC), even after induction chemotherapy, remains unclear. Modern radiation techniques such as image-guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT) may improve effectiveness and reduce radiotherapy-related toxicities. Methods. Patients with LAPC who underwent radiotherapy after chemotherapy between 09/2004 and 05/2013 were retrospectively analyzed with regard to preradiation chemotherapy (PRCT), modalities of radiotherapy, and toxicities. Progression-free (PFS) and overall survival (OS) were estimated by Kaplan-Meier curves. Results. 15 (68%) women and 7 men (median age 64 years; range 40–77) were identified. Median duration of PRCT was 11.1 months (range 4.3–33.0). Six patients (27%) underwent conventional RT and 16 patients (73%) advanced IMRT and IGRT; median dosage was 50.4 (range 9–54) Gray. No grade III or IV toxicities occurred. Median PFS (estimated from the beginning of RT) was 5.8 months, 2.6 months in the conventional RT group (conv-RT), and 7.1 months in the IMRT/IGRT group (P=0.029); median OS was 11.0 months, 4.2 months (conv-RT), and 14.0 months (IMRT/IGRT); P=0.141. Median RT-specific PFS for patients with prolonged PRCT > 9 months was 8.5 months compared to 5.6 months for PRCT < 9 months (P=0.293). This effect was translated into a significantly better median RT-specific overall survival of patients in the PRCT > 9 months group, with 19.0 months compared to 8.5 months in the PRCT  <  9 months group (P=0.049). Conclusions. IGRT and IMRT after PRCT are feasible and effective options for patients with LAPC after prolonged preradiation chemotherapy

Design and evaluation of a hybrid radiofrequency applicator for magnetic resonance imaging and RF induced hyperthermia: electromagnetic field simulations up to 14.0 Tesla and proof-of-concept at 7.0 Tesla

This work demonstrates the feasibility of a hybrid radiofrequency (RF) applicator that supports magnetic resonance (MR) imaging and MR controlled targeted RF heating at ultrahigh magnetic fields (B0>/=7.0T). For this purpose a virtual and an experimental configuration of an 8-channel transmit/receive (TX/RX) hybrid RF applicator was designed. For TX/RX bow tie antenna electric dipoles were employed. Electromagnetic field simulations (EMF) were performed to study RF heating versus RF wavelength (frequency range: 64 MHz (1.5T) to 600 MHz (14.0T)). The experimental version of the applicator was implemented at B0 = 7.0T. The applicators feasibility for targeted RF heating was evaluated in EMF simulations and in phantom studies. Temperature co-simulations were conducted in phantoms and in a human voxel model. Our results demonstrate that higher frequencies afford a reduction in the size of specific absorption rate (SAR) hotspots. At 7T (298 MHz) the hybrid applicator yielded a 50% iso-contour SAR (iso-SAR-50%) hotspot with a diameter of 43 mm. At 600 MHz an iso-SAR-50% hotspot of 26 mm in diameter was observed. RF power deposition per RF input power was found to increase with B0 which makes targeted RF heating more efficient at higher frequencies. The applicator was capable of generating deep-seated temperature hotspots in phantoms. The feasibility of 2D steering of a SAR/temperature hotspot to a target location was demonstrated by the induction of a focal temperature increase (DeltaT = 8.1 K) in an off-center region of the phantom. Temperature simulations in the human brain performed at 298 MHz showed a maximum temperature increase to 48.6C for a deep-seated hotspot in the brain with a size of (19x23x32)mm(3) iso-temperature-90%. The hybrid applicator provided imaging capabilities that facilitate high spatial resolution brain MRI. To conclude, this study outlines the technical underpinnings and demonstrates the basic feasibility of an 8-channel hybrid TX/RX applicator that supports MR imaging, MR thermometry and targeted RF heating in one device

Chiral quark-soliton model in the Wigner-Seitz approximation

In this paper we study the modification of the properties of the nucleon in the nucleus within the quark-soliton model. This is a covariant, dynamical model, which provides a non-linear representation of the spontaneously broken SU(2)_L X SU(2)_R symmetry of QCD. The effects of the nuclear medium are accounted for by using the Wigner-Seitz approximation and therefore reducing the complex many-body problem to a simpler single-particle problem. We find a minimum in the binding energy at finite density, a change in the isoscalar nucleon radius and a reduction of the in-medium pion decay constant. The latter is consistent with a partial restoration of chiral symmetry at finite density, which is predicted by other models.Comment: 30 pages, 13 figures; uses REVTeX and epsfi

Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme

Therapy options at the time of recurrence of glioblastoma multiforme are often limited. We investigated whether treatment with a new intratumoral thermotherapy procedure using magnetic nanoparticles improves survival outcome. In a single-arm study in two centers, 66 patients (59 with recurrent glioblastoma) received neuronavigationally controlled intratumoral instillation of an aqueous dispersion of iron-oxide (magnetite) nanoparticles and subsequent heating of the particles in an alternating magnetic field. Treatment was combined with fractionated stereotactic radiotherapy. A median dose of 30 Gy using a fractionation of 5 × 2 Gy/week was applied. The primary study endpoint was overall survival following diagnosis of first tumor recurrence (OS-2), while the secondary endpoint was overall survival after primary tumor diagnosis (OS-1). Survival times were calculated using the Kaplan–Meier method. Analyses were by intention to treat. The median overall survival from diagnosis of the first tumor recurrence among the 59 patients with recurrent glioblastoma was 13.4 months (95% CI: 10.6–16.2 months). Median OS-1 was 23.2 months while the median time interval between primary diagnosis and first tumor recurrence was 8.0 months. Only tumor volume at study entry was significantly correlated with ensuing survival (P < 0.01). No other variables predicting longer survival could be determined. The side effects of the new therapeutic approach were moderate, and no serious complications were observed. Thermotherapy using magnetic nanoparticles in conjunction with a reduced radiation dose is safe and effective and leads to longer OS-2 compared to conventional therapies in the treatment of recurrent glioblastoma

Towards a single-chip, implantable RFID system: is a single-cell radio possible?

We present an overview of progress towards single-chip RFID solutions. To date heterogeneous integration has been appropriate for non-biological systems. However, for in-vivo sensors and even drug delivery systems, a small form factor is required. We discuss fundamental limits on the size of the form factor, the effect of the antenna, and propose a unified single-chip RFID solution appropriate for a broad range of biomedical in-vivo device applications, both current and future. Fundamental issues regarding the possibility of single cell RF radios to interface with biological function are discussed

Meta-analysis on the effect of the N363S polymorphism of the glucocorticoid receptor gene (GRL) on human obesity

BACKGROUND: Since both excess glucocorticoid secretion and central obesity are clinical features of some obese patients, it is worthwhile to study a possible association of glucocorticoid receptor gene (GRL) variants with obesity. Previous studies have linked the N363S variant of the GRL gene to increased glucocorticoid effects such as higher body fat, a lower lean-body mass and a larger insulin response to dexamethasone. However, contradictory findings have been also reported about the association between this variant and obesity phenotypes. Individual studies may lack statistical power which may result in disparate results. This limitation can be overcome using meta-analytic techniques. METHODS: We conducted a meta-analysis to assess the association between the N363S polymorphism of the GRL gene and obesity risk. In addition to published research, we included also our own unpublished data -three novel case-control studies- in the meta-analysis The new case-control studies were conducted in German and Spanish children, adolescents and adults (total number of subjects: 1,117). Genotype was assessed by PCR-RFLP (Tsp509I). The final formal meta-analysis included a total number of 5,909 individuals. RESULTS: The meta-analysis revealed a higher body mass index (BMI) with an overall estimation of +0.18 kg/m(2 )(95% CI: +0.004 to +0.35) for homo-/heterozygous carriers of the 363S allele of the GRL gene in comparison to non-carriers. Moreover, differences in pooled BMI were statistically significant and positive when considering one-group studies from the literature in which participants had a BMI below 27 kg/m(2 )(+ 0.41 kg/m(2 )[95% CI +0.17 to +0.66]), but the differences in BMI were negative when only our novel data from younger (aged under 45) and normal weight subjects were pooled together (-0.50 kg/m(2 )[95% CI -0.84 to -0.17]). The overall risk for obesity for homo-/heterozygous carriers of the 363S allele was not statistically significant in the meta-analysis (pooled OR = 1.02; 95% CI: 0.56–1.87). CONCLUSION: Although certain genotypic effects could be population-specific, we conclude that there is no compelling evidence that the N363S polymorphism of the GRL gene is associated with either average BMI or obesity risk

Targeted therapy against Bcl-2-related proteins in breast cancer cells

INTRODUCTION: Bcl-2 and Bcl-xL confer resistance to apoptosis, thereby reducing the effectiveness of chemotherapy. We examined the relationship between the expression of Bcl-2 and Bcl-xL and chemosensitivity of breast cancer cells, with the aim of developing specific targeted therapy. METHODS: Four human breast cancer cell lines were examined, and the effects of antisense (AS) Bcl-2 and AS Bcl-xL phosphorothioate oligodeoxynucleotides (ODNs) on chemosensitivity were tested in vitro and in vivo. Chemosensitivity was evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay, and the antitumor effect was assessed in vivo by the success of xenograft transplantation into athymic mice. RESULTS: Treatment with AS Bcl-2 and Bcl-xL ODNs resulted in a sequence-specific decrease in protein expression, compared with controls. Treatment of BT-474, ZR-75-1, and MDA-MB-231 cells with AS Bcl-2 increased chemosensitivity to doxorubicin (DOX), mitomycin C (MMC), paclitaxel (TXL), and docetaxel (TXT). Transfection of the Bcl-2 gene into MDA-MB-453 cells decreased sensitivity to DOX and MMC. Treatment of MDA-MB-231, BT-474, and ZR-75-1 cells with AS Bcl-xL increased chemosensitivity to DOX, MMC and taxanes to a smaller extent than AS Bcl-2. This occurred in the setting of increased Bax and cleaved poly(ADP-ribose) polymerase, as well as decreased Bcl-2 and pAkt. AS Bcl-2 ODNs induced splenomegaly in association with increased serum IL-12, which was attenuated by methylation of the CpG motifs of AS Bcl-2; however, methylated CpG failed to negate the increased antitumor effect of AS Bcl-2. Bcl-2 and Bcl-xL, to a smaller extent, are major determinants of chemosensitivity in breast cancer cells. CONCLUSION: Targeted therapy against Bcl-2 protein with the use of AS ODNs might enhance the effects of chemotherapy in patients with breast cancer

Epigenetic and Genetic Factors Predict Women's Salivary Cortisol following a Threat to the Social Self

10.1371/journal.pone.0048597PLoS ONE711