Measurements of ion-electron energy-transfer cross section in high-energy-density plasmas.

We report on measurements of the ion-electron energy-transfer cross section utilizing low-velocity ion stopping in high-energy-density plasmas at the OMEGA laser facility. These measurements utilize a technique that leverages the close relationship between low-velocity ion stopping and ion-electron equilibration. Shock-driven implosions of capsules filled with D^{3}He gas doped with a trace amount of argon are used to generate densities and temperatures in ranges from 1×10^{23} to 2×10^{24} cm^{-3} and from 1.4 to 2.5 keV, respectively. The energy loss of 1-MeV DD tritons and 3.7-MeV D^{3}He alphas that have velocities lower than the average velocity of the thermal electrons is measured. The energy loss of these ions is used to determine the ion-electron energy-transfer cross section, which is found to be in excellent agreement with quantum-mechanical calculations in the first Born approximation. This result provides an experimental constraint on ion-electron energy transfer in high-energy-density plasmas, which impacts the modeling of alpha heating in inertial confinement fusion implosions, magnetic-field advection in stellar atmospheres, and energy balance in supernova shocks.

Quantifying electron temperature distributions from time-integrated x-ray emission spectra.

K-shell x-ray emission spectroscopy is a standard tool used to diagnose the plasma conditions created in high-energy-density physics experiments. In the simplest approach, the emissivity-weighted average temperature of the plasma can be extracted by fitting an emission spectrum to a single temperature condition. It is known, however, that a range of plasma conditions can contribute to the measured spectra due to a combination of the evolution of the sample and spatial gradients. In this work, we define a parameterized model of the temperature distribution and use Markov Chain Monte Carlo sampling of the input parameters, yielding uncertainties in the fit parameters to assess the uniqueness of the inferred temperature distribution. We present the analysis of time-integrated S and Fe x-ray spectroscopic data from the Orion laser facility and demonstrate that while fitting each spectral region to a single temperature yields two different temperatures, both spectra can be fit simultaneously with a single temperature distribution. We find that fitting both spectral regions together requires a maximum temperature of 1310-70 +90 eV with significant contributions from temperatures down to 200 eV.

Measurements of pressure-induced Kß line shifts in ramp compressed cobalt up to 8 Mbar.

We report measurements of K-shell fluorescence lines induced by fast electrons in ramp-compressed Co targets. The fluorescence emission was stimulated by fast electrons generated through short-pulse laser-solid interaction with an Al target layer. Compression up to 2.1× solid density was achieved while maintaining temperatures well below the Fermi energy, effectively removing the thermal effects from consideration. We observed small but unambiguous redshifts in the Kß fluorescence line relative to unshifted Cu Kα. Redshifts up to 2.6 eV were found to increase with compression and to be consistent with predictions from self-consistent models based on density-functional theory.

Experimental Validation of Low-Z Ion-Stopping Formalisms around the Bragg Peak in High-Energy-Density Plasmas.

We report on the first accurate validation of low-Z ion-stopping formalisms in the regime ranging from low-velocity ion stopping-through the Bragg peak-to high-velocity ion stopping in well-characterized high-energy-density plasmas. These measurements were executed at electron temperatures and number densities in the range of 1.4-2.8 keV and 4×10^{23}-8×10^{23} cm^{-3}, respectively. For these conditions, it is experimentally demonstrated that the Brown-Preston-Singleton formalism provides a better description of the ion stopping than other formalisms around the Bragg peak, except for the ion stopping at v_{i}∼0.3v_{th}, where the Brown-Preston-Singleton formalism significantly underpredicts the observation. It is postulated that the inclusion of nuclear-elastic scattering, and possibly coupled modes of the plasma ions, in the modeling of the ion-ion interaction may explain the discrepancy of ∼20% at this velocity, which would have an impact on our understanding of the alpha energy deposition and heating of the fuel ions, and thus reduce the ignition threshold in an ignition experiment.

Dietary patterns of university students in the UK: a cross-sectional study.

BACKGROUND: University represents a key transition into adulthood for many adolescents but there are associated concerns about health and behaviours. One important aspect relates to diet and there is emerging evidence that university students may consume poor quality diets, with potential implications for body weight and long-term health. This research aimed to characterise dietary patterns of university students in the UK and their sociodemographic and lifestyle antecedents. METHODS: An online, cross-sectional survey was undertaken with a convenience sample of 1448 university students from five UK universities (King's College London, Universities of St Andrews, Southampton and Sheffield, and Ulster University). The survey comprised a validated food frequency questionnaire alongside lifestyle and sociodemographic questions. Dietary patterns were generated from food frequency intake data using principal components analysis. Nutrient intakes were estimated to characterise the nutrient profile of each dietary pattern. Associations with sociodemographic variables were assessed through general linear modelling. RESULTS: Dietary analyses revealed four major dietary patterns: 'vegetarian'; 'snacking'; 'health-conscious'; and 'convenience, red meat & alcohol'. The 'health-conscious' pattern had the most favourable micronutrient profile. Students' gender, age, year of study, geographical location and cooking ability were associated with differences in pattern behaviour. Female students favoured the 'vegetarian' pattern, whilst male students preferred the 'convenience, red meat & alcohol' pattern. Less healthful dietary patterns were positively associated with lifestyle risk factors such as smoking, low physical activity and take-away consumption. The health-conscious pattern had greatest nutrient density. The 'convenience, red meat & alcohol' pattern was associated with higher weekly food spending; this pattern was also identified most consistently across universities. Students reporting greater cooking ability tended towards the 'vegetarian' and 'health-conscious' patterns. CONCLUSIONS: Food intake varied amongst university students. A substantial proportion of students followed health-promoting diets, which had good nutrient profiles obviating a need for dietary intervention. However, some students consumed poor diets, incurred greater food costs and practised unfavourable lifestyle behaviours, which may have long-term health effects. University policy to improve students' diets should incorporate efforts to promote student engagement in cooking and food preparation, and increased availability of low cost healthier food items.

Measurements of Ion Stopping Around the Bragg Peak in High-Energy-Density Plasmas.

For the first time, quantitative measurements of ion stopping at energies around the Bragg peak (or peak ion stopping, which occurs at an ion velocity comparable to the average thermal electron velocity), and its dependence on electron temperature (T(e)) and electron number density (n(e)) in the range of 0.5-4.0 keV and 3×10(22) to 3×10(23) cm(-3) have been conducted, respectively. It is experimentally demonstrated that the position and amplitude of the Bragg peak varies strongly with T(e) with n(e). The importance of including quantum diffraction is also demonstrated in the stopping-power modeling of high-energy-density plasmas.

[Guidelines for gastroenteropancreatic neuroendocrine tumors--what is new? What should be incorporated in daily therapeutic decisions?]. / Leitlinien für gastroenteropankreatische neuroendokrine Tumoren--was ist neu? Was sollte in die Therapierichtlinien aufgenommen werden?

Neuroendocrine neoplasias are seldom, but increasing. This holds true for the incidence but even more for the prevalence, since patients are able to live with their disease for quite a long time. The European Neuroendocrine Tumor Society (ENETS) as well as other societies (NANETS: North American Neuroendocrine Tumor Society; NCCN: National Comprehensive Cancer Network; ESMO: European Society of Medical Oncology) have published diagnostic and therapeutic guidelines that we present in this review. We aim to summarize those actual guidelines in a practice-based diagnostic and therapeutic algorithm, but also wish to point to open questions that have to be discussed in a multidisciplinary approach.

Estimation of local anisotropy of plexiform bone: Comparison between depth sensing micro-indentation and Reference Point Indentation.

The recently developed Reference Point Indentation (RPI) allows the measurements of bone properties at the tissue level in vivo. The goal of this study was to compare the local anisotropic behaviour of bovine plexiform bone measured with depth sensing micro-indentation tests and with RPI. Fifteen plexiform bone specimens were extracted from a bovine femur and polished down to 0.05µm alumina paste for indentations along the axial, radial and circumferential directions (N=5 per group). Twenty-four micro-indentations (2.5µm in depth, 10% of them were excluded for testing problems) and four RPI-indentations (~50µm in depth) were performed on each sample. The local indentation modulus Eind was found to be highest for the axial direction (24.3±2.5GPa) compared to the one for the circumferential indentations (19% less stiff) and for the radial direction (30% less stiff). RPI measurements were also found to be dependent on indentation direction (p<0.001) with the exception of the Indentation Distance Increase (IDI) (p=0.173). In particular, the unloading slope US1 followed similar trends compared to the Eind: 0.47±0.03N/µm for axial, 11% lower for circumferential and 17% lower for radial. Significant correlations were found between US1 and Eind (p=0.001; R(2)=0.58), while no significant relationship was found between IDI and any of the micro-indentation measurements (p>0.157). In conclusion some of the RPI measurements can provide information about local anisotropy but IDI cannot. Moreover, there is a linear relationship between most local mechanical properties measured with RPI and with micro-indentations, but IDI does not correlate with any micro-indentation measurements.

Self-Consistent Simulation of Transport and Energy Deposition of Intense Laser-Accelerated Proton Beams in Solid-Density Matter.

The first self-consistent hybrid particle-in-cell (PIC) simulation of intense proton beam transport and energy deposition in solid-density matter is presented. Both the individual proton slowing-down and the collective beam-plasma interaction effects are taken into account with a new dynamic proton stopping power module that has been added to a hybrid PIC code. In this module, the target local stopping power can be updated at each time step based on its thermodynamic state. For intense proton beams, the reduction of target stopping power from the cold condition due to continuous proton heating eventually leads to broadening of the particle range and energy deposition far beyond the Bragg peak. For tightly focused beams, large magnetic field growth in collective interactions results in self-focusing of the beam and much stronger localized heating of the target.

Use of radiometric (234/238U and 228/226Ra) and mass spectrometry (87/86Sr) methods for studies of the stability of groundwater reservoirs in Central Poland.

The uranium (234U/238U) and radium (228Ra/226Ra) activity ratios and 87Sr/86Sr isotopic ratio in thermal groundwater, subsurface water (groundwater) and river water from Poddebice and Uniejow were determined. The uranium and radium activity ratios and strontium isotopic ratio varied from 0.629 to 1.471, from 0.396 to 4.961 and from 0.708438 to 0.710344, respectively. The results for the thermal groundwater samples showed that the radiometric method together with mass spectrometry stable strontium isotope ratio measurements can be used for underground water transport studies. On the basis of the uranium and radium activity and the strontium isotopic ratio differences in subsurface water (groundwater) and in river water, any possible water influx between these adjacent reservoirs can be observed. The obtained results exclude any water transport from surface and subsurface water to thermal ground water reservoirs in this region of Poland.

Measurement of charged-particle stopping in warm dense plasma.

We measured the stopping of energetic protons in an isochorically heated solid-density Be plasma with an electron temperature of ∼32 eV, corresponding to moderately coupled [(e^{2}/a)/(k_{B}T_{e}+E_{F})∼0.3] and moderately degenerate [k_{B}T_{e}/E_{F}∼2] "warm-dense matter" (WDM) conditions. We present the first high-accuracy measurements of charged-particle energy loss through dense plasma, which shows an increased loss relative to cold matter, consistent with a reduced mean ionization potential. The data agree with stopping models based on an ad hoc treatment of free and bound electrons, as well as the average-atom local-density approximation; this work is the first test of these theories in WDM plasma.

Vandetanib therapy in medullary thyroid cancer.

The U.S. Food and Drug Administration (FDA) approved vandetanib in April 2011 for the treatment of unresectable, locally advanced or metastatic medullary thyroid cancer (MTC). In Europe it was approved in March 2012, but only for the treatment of aggressive and symptomatic MTC. This small molecule is a tyrosine kinase inhibitor of several growth factors involved in cellular proliferation and angiogenesis, including the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptors 2 and 3 (VEGFR-2, VEGFR-3). In addition, vandetanib is an inhibitor of the RET (rearranged during transfection) gene, a proto-oncogene often mutated in familial MTC. Since MTC is a rare disease, for which no previous medical therapies are approved, vandetanib is the first drug shown to be effective in a large phase III trial treating patients with metastatic or locally advanced MTC. Common adverse events are diarrhea, nausea, hypertension, headache and QT prolongation that are manageable and are commonly outweighed by the benefits of vandetanib in terms of delaying disease progression and inducing tumor response.

Uranium isotopes as a tracer of groundwater transport studies.

The activity concentrations of 234U and 238U in thermal groundwater, deep well water and river water samples from Central Poland were determined. Concentration of 234U and 238U in the examined waters varied from <0.013 (LLD) to 16.8 mBq/dm3 and from <0.013 (LLD) to 45.5 mBq/dm3 respectively. The highest uranium activity concentrations were measured in the thermal groundwater from Mszczonow and Cieplice, while the lowest were observed in thermal ground water from Uniejow and Poddebice. In thermal groundwater from Skierniewice, uranium activity concentrations were below lower limit of detection (0.013 mBq/dm3). The 234U/238U activity ratio varied from 0.37 (Cieplice) to 1.30 (Poddebice well water).

Current treatment options for neuroendocrine tumors.

Neuroendocrine tumors are heterogeneous in their clinical behavior and require therapies specially tailored according to staging and grading, origin and expression of peptide receptors. Somatostatin analogues act as antisecretory and antiproliferative agents. Chemotherapy is mandatory for poorly differentiated neuroendocrine carcinomas and is also effective in neuroendocrine tumors of the pancreas and of the bronchial system. For localized neuroendocrine tumors, surgery should be performed with curative intent and is also an option in advanced or metastasized neuroendocrine tumors with the goal to debulk tumor masses. Local ablative therapies may be applied to decrease tumor load in the liver; however, results are often of short duration. Peptide receptor radiotherapy is a new treatment method applying radionuclide-targeted somatostatin receptor agonists for internal cytotoxic radiotherapy in somatostatin receptor-expressing neuroendocrine tumors. Retrospective and prospective clinical studies indicate prolonged progression-free survival and overall survival of patients responding by stable disease or any kind of remission with this innovative treatment, which is, however, available only in a few specialized centers. Finally, small-molecule inhibitors of vascular endothelial growth factor and serine/threonine-protein kinase mTOR pathways have been shown to delay progression in patients with neuroendocrine tumors. In summary, treatment options for neuroendocrine tumors have expanded considerably in the last years leading to prolonged overall survival.

ZM447439, a novel promising aurora kinase inhibitor, provokes antiproliferative and proapoptotic effects alone and in combination with bio- and chemotherapeutic agents in gastroenteropancreatic neuroendocrine tumor cell lines.

BACKGROUND: Therapeutic approaches to gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are still not satisfactory. A new direction in treatment options could be the novel aurora kinase inhibitor ZM447439, which was previously reported to interfere with the mitotic spindle integrity checkpoint and chromosome segregation, but does not interfere with other kinases when used up to 5 muM. METHODS: We evaluated the antineoplastic effects of ZM447439 on growth and apoptosis of the GEP-NET cell lines BON, QGP-1 and MIP-101, representing the different malignant tumor types, using standard cell biological tests as crystal violet assays, caspase activation, DNA fragmentation and cell cycle analysis. RESULTS: ZM447439 dose-dependently inhibited proliferation of all three cell lines with IC(50) values in the nanomolar to low micromolar range. Moreover, aurora kinase inhibition by ZM447439 potently induced apoptosis, which was accompanied by DNA fragmentation and caspase 3 and 7 activation. Furthermore, we observed cell cycle arrest at G(0)/G(1) phase as well as a block in G(2)/M transition. In addition, combined treatment with the chemotherapeutic agents streptozocin and cisplatin augmented significantly the antiproliferative effects of those agents. CONCLUSION: Aurora kinase inhibition by ZM447439 seems to be a promising new therapeutic approach in GEP-NETs, which should be evaluated in further clinical trials.

Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie.

BACKGROUND: This study assessed the activity of the mAb cetuximab in combination with cisplatin and 5-fluorouracil (5-FU) in advanced esophageal squamous cell carcinoma. PATIENTS AND METHODS: For a maximum of six 29-day cycles, patients received cisplatin 100 mg/m(2), day 1, plus 5-FU 1000 mg/m(2), days 1-5 (CF), either alone or in combination with cetuximab (CET-CF; 400 mg/m(2) initial dose followed by 250 mg/m(2) weekly thereafter). The primary end point was tumor response. Tumor material was obtained for analysis of KRAS mutation status. RESULTS: Sixty-two eligible patients were included, 32 receiving CET-CF and 30 CF. Cetuximab did not exacerbate grade 3/4 toxicity, except for rash (6% versus 0%) and diarrhea (16% versus 0%). The overall response rate according to RECIST criteria was 19% and 13% and the disease control rate 75% and 57% for the CET-CF and CF arms, respectively. With a median follow-up of 21.5 months, the median progression-free survival was 5.9 and 3.6 months and median overall survival 9.5 and 5.5 months for CET-CF and CF, respectively. No KRAS codon 12/13 tumor mutations were identified in 37 evaluated samples. CONCLUSION: Cetuximab can be safely combined with CF chemotherapy and may increase the efficacy of standard CF chemotherapy.

[An unusual case of upper GI bleeding: esophageal cancer metastasis at a percutaneous endoscopic gastrostomy site--case report and review of the literature]. / Ungewöhnlicher Fall einer akuten oberen gastrointestinalen Blutung: PEG-Implantationsmetastase eines Osophaguskarzinoms--Fallbericht und Literaturübersicht.

We present the case of a patient with an esophageal squamous cell carcinoma, who was treated primarily by radiotherapy. Due to dysphagia, the patient received a percutaneous endoscopic gastrostomy (PEG) without any sign of tumour at that time. Five months later the patient presented with an upper GI bleeding from a gastric ulcer, which histologically turned out to be a metastasis of the previously diagnosed squamous cell carcinoma. So-called "implantation metastases" at the percutaneous endoscopic gastrostomy site are rare and most of the cases have been described in patients with head and neck tumours. Moreover, the presentation as an upper GI bleed is very uncommon and needs the attention of both endoscopists as well as gastrointestinal oncologists. Clinicopathological features of this case with a brief review of the literature are presented.

Clinical, genetic, and cellular analysis of 49 osteopetrotic patients: implications for diagnosis and treatment.

BACKGROUND: Osteopetrosis, a genetic disease characterised by osteoclast failure, is classified into three forms: infantile malignant autosomal recessive osteopetrosis (ARO), intermediate autosomal recessive osteopetrosis (IRO), and autosomal dominant osteopetrosis (ADO). METHODS: We studied 49 patients, 21 with ARO, one with IRO, and 27 with type II ADO (ADO II). RESULTS: Most ARO patients bore known or novel (one case) ATP6i (TCIRG1) gene mutations. Six ADO II patients had no mutations in ClCN7, the only so far recognised gene implicated, suggesting involvement of yet unknown genes. Identical ClCN7 mutations produced differing phenotypes with variable degrees of severity. In ADO II, serum tartrate resistant acid phosphatase was always elevated. Bone alkaline phosphatase (BALP) was generally low, but osteocalcin was high, suggesting perturbed osteoblast differentiation or function. In contrast, BALP was high in ARO patients. Elevated osteoclast surface/bone surface was noted in biopsies from most ARO patients. Cases with high osteoclasts also showed increased osteoblast surface/bone surface. ARO osteoclasts were morphologically normal, with unaltered formation rates, intracellular pH handling, and response to acidification. Their resorption activity was greatly reduced, but not abolished. In control osteoclasts, all resorption activity was abolished by combined inhibition of proton pumping and sodium/proton antiport. CONCLUSIONS: These findings provide a rationale for novel therapies targeting pH handling mechanisms in osteoclasts and their microenvironment.

Characterization of the Bacillus subtilis spore morphogenetic coat protein CotO.

Bacillus spores are protected by a structurally and biochemically complex protein shell composed of over 50 polypeptide species, called the coat. Coat assembly in Bacillus subtilis serves as a relatively tractable model for the study of the formation of more complex macromolecular structures and organelles. It is also a critical model for the discovery of strategies to decontaminate B. anthracis spores. In B. subtilis, a subset of coat proteins is known to have important roles in assembly. Here we show that the recently identified B. subtilis coat protein CotO (YjbX) has an especially important morphogenetic role. We used electron and atomic force microscopy to show that CotO controls assembly of the coat layers and coat surface topography as well as biochemical and cell-biological analyses to identify coat proteins whose assembly is CotO dependent. cotO spores are defective in germination and partially sensitive to lysozyme. As a whole, these phenotypes resemble those resulting from a mutation in the coat protein gene cotH. Nonetheless, the roles of CotH and CotO and the proteins whose assembly they direct are not identical. Based on fluorescence and electron microscopy, we suggest that CotO resides in the outer coat (although not on the coat surface). We propose that CotO and CotH participate in a late phase of coat assembly. We further speculate that an important role of these proteins is ensuring that polymerization of the outer coat layers occurs in such a manner that contiguous shells, and not unproductive aggregates, are formed.

A molecular code for splicing silencing: configurations of guanosine-rich motifs.

Alternative pre-mRNA splicing is frequently used to expand the protein-coding capacity of genomes, and to regulate gene expression at the post-transcriptional level. It is a significant challenge to decipher the molecular language of tissue-specific splicing because the inherent flexibility of these mechanisms is specified by numerous short sequence motifs distributed in introns and exons. In the present study, we employ the glutamate NMDA (N-methyl-D-aspartate) R1 receptor (GRIN1) transcript as a model system to identify the molecular determinants for a brain region-specific exon silencing mechanism. We identify a set of guanosine-rich motifs that function co-operatively to regulate the CI cassette exon in a manner consistent with its in vivo splicing pattern. Whereas hnRNP (heterogeneous nuclear ribonucleoprotein) A1 mediates silencing of the CI cassette exon in conjunction with the guanosine-rich motifs, hnRNP H functions as an antagonist to silencing. Genome-wide analysis shows that, while this motif pattern is rarely present in human and mouse exons, those exons for which the pattern is conserved are generally found to be skipped exons. The identification of a similar arrangement of guanosine-rich motifs in transcripts of the hnRNP H family of splicing factors has implications for their co-ordinate regulation at the level of splicing.