Clinical Factors Associated with Dense and Wedge-Shaped Nephrograms Detected 24 h After Chemoembolization

This investigation aimed to evaluate patient characteristics and procedural factors associated with abnormal nephrograms encountered on noncontrast computed axial tomography (CAT) obtained 24-h after transarterial chemoembolization (TACE) for primary and metastatic hepatic malignancies. Sixty hepatic chemoembolization procedures were performed in 29 patients who had a median age of 63 years (range 42–79). The male-to-female ratio was 16:13. Noncontrast CAT scans were obtained approximately 24 h after TACE as part of our institutional protocol and were examined for persistent renal nephrograms. These findings were compared with clinical and procedural parameters to determine whether there was any association with these factors or with the occurrence of acute renal failure (ARF). Abnormally persistent CAT nephrograms were observed 24 h after 28 of 60 (46.7%) TACE procedures, of which 14 (23.3%) were persistent, bilaterally dense, global nephrograms, and 14 (23.3%) were small, wedge-shaped, and focal nephrograms. The change in serum creatinine from baseline to 24 h was significantly greater (p = 0.031) in the global nephrogram group. The presence of cirrhosis, Child-Pugh score, procedure time, baseline renal insufficiency, and lower periprocedural mean arterial blood pressure were also statistically significantly associated with the occurrence of bilateral globally dense nephrograms. The procedure time was statistically significantly associated with the occurrence of wedge-like focally persistent nephrograms. Global, persistently dense nephrograms and wedge-shaped focally persistent nephrograms are not infrequently observed after TACE. Persistent global nephrograms can be an important clinical indicator of ARF. The wedge nephrogram may represent focal renal ischemia

Bayesian parameter estimation in the second LISA Pathfinder Mock Data Challenge

A main scientific output of the LISA Pathfinder mission is to provide a noise model that can be extended to the future gravitational wave observatory, LISA. The success of the mission depends thus upon a deep understanding of the instrument, especially the ability to correctly determine the parameters of the underlying noise model. In this work we estimate the parameters of a simplified model of the LISA Technology Package (LTP) instrument. We describe the LTP by means of a closed-loop model that is used to generate the data, both injected signals and noise. Then, parameters are estimated using a Bayesian framework and it is shown that this method reaches the optimal attainable error, the Cramer-Rao bound. We also address an important issue for the mission: how to efficiently combine the results of different experiments to obtain a unique set of parameters describing the instrument.Comment: 14 pages, 4 figures, submitted to PR

Tumor collagenase stimulatory factor (TCSF) expression and localization in human lung and breast cancers.

Tumor cell-derived collagenase stimulatory factor (TCSF) stimulates in vitro the biosynthesis of various matrix metalloproteinases involved in tumor invasion, such as interstitial collagenase, gelatinase A, and stromelysin 1. The expression of TCSF mRNAs was studied in vivo, using in situ hybridization and Northern blotting analysis, in seven normal tissues and in 22 squamous cell carcinomas of the lung, and in seven benign proliferations and in 22 ductal carcinomas of the mammary gland. By in situ hybridization, TCSF mRNAs were detected in 40 of 44 carcinomas, in pre-invasive and invasive cancer cells of both lung and breast cancers. TCSF mRNAs and gelatinase A mRNAs were both visualized in the same areas in serial sections in breast cancers, and were expressed by different cells, tumor cells, and fibroblasts. The histological results were confirmed by Northern blot analysis, which showed a higher expression of TCSF mRNAs in cancers than in benign and normal tissues. These observations support the hypothesis that TCSF is an important factor in lung and breast tumor progression

Sub-femto-g free fall for space-based gravitational wave observatories: LISA pathfinder results

We report the first results of the LISA Pathfinder in-flight experiment. The results demonstrate that two free-falling reference test masses, such as those needed for a space-based gravitational wave observatory like LISA, can be put in free fall with a relative acceleration noise with a square root of the power spectral density of 5.2 ± 0.1 fm s−2/√Hz or (0.54 ± 0.01) × 10−15 g/√Hz, with g the standard gravity, for frequencies between 0.7 and 20 mHz. This value is lower than the LISA Pathfinder requirement by more than a factor 5 and within a factor 1.25 of the requirement for the LISA mission, and is compatible with Brownian noise from viscous damping due to the residual gas surrounding the test masses. Above 60 mHz the acceleration noise is dominated by interferometer displacement readout noise at a level of (34.8 ± 0.3) fm/√Hz, about 2 orders of magnitude better than requirements. At f ≤ 0.5 mHz we observe a low-frequency tail that stays below 12 fm s−2/√Hz down to 0.1 mHz. This performance would allow for a space-based gravitational wave observatory with a sensitivity close to what was originally foreseen for LISA

Angiogenesis and hypoxia in lymph node metastases is predicted by the angiogenesis and hypoxia in the primary tumour in patients with breast cancer

Hypoxia and angiogenesis are important factors in breast cancer progression. Little is known of hypoxia and angiogenesis in lymph node metastases of breast cancer. The aim of this study was to quantify hypoxia, by hypoxia-induced marker expression levels, and angiogenesis, by endothelial cell proliferation, comparing primary breast tumours and axillary lymph node metastases. Tissue sections of the primary tumour and a lymph node metastasis of 60 patients with breast cancer were immunohistochemically stained for the hypoxia-markers carbonic anhydrase 9 (CA9), hypoxia-inducible factor-1α (Hif-1α) and DEC-1 and for CD34/Ki-67. Endothelial cell proliferation fraction (ECP%) and tumour cell proliferation fraction (TCP%) were assessed. On haematoxylin–eosin stain, the growth pattern and the presence of a fibrotic focus were assessed. Hypoxia-marker expression, ECP% and TCP% in primary tumours and in lymph node metastases were correlated to each other and to clinico-pathological variables. Median ECP% and TCP% in primary tumours and lymph node metastases were comparable (primary tumours: ECP%=4.02, TCP%=19.54; lymph node metastases: ECP%=5.47, TCP%=21.26). ECP% correlated with TCP% (primary tumours: r=0.63, P<0.001; lymph node metastases: r=0.76, P<0.001). CA9 and Hif-1α expression were correlated (primary tumours P=0.005; lymph node metastases P<0.001). In primary tumours, CA9 and Hif-1α expression were correlated with DEC-1 expression (P=0.05), presence of a fibrotic focus (P<0.007) and mixed/expansive growth pattern (P<0.001). Primary tumours and lymph node metastases with CA9 or Hif-1α expression had a higher ECP% and TCP% (P<0.003); in primary tumours, mixed/expansive growth pattern and fibrotic focus were characterised by higher ECP% (P=0.03). Furthermore, between primary tumours and lymph node metastases a correlation was found for ECP%, TCP%, CA9 and Hif-1α expression (ECP% r=0.51, P<0.001; TCP r=0.77, P<0.001; CA9 and Hif-1α P<0.001). Our data demonstrate that the growth of breast cancer lymph node metastases is angiogenesis dependent and that angiogenesis and hypoxia in the primary tumour predict angiogenesis and hypoxia in the lymph node metastases. Together with previous findings in breast cancer liver metastases, which grow in 96% of cases angiogenesis independently, these data suggest that both the intrinsic growth characteristics and angiogenic potential of breast cancer cells and the site-specific tumour microenvironment determine angiogenesis and hypoxia in breast cancer

Recent progress towards development of effective systemic chemotherapy for the treatment of malignant brain tumors

Systemic chemotherapy has been relatively ineffective in the treatment of malignant brain tumors even though systemic chemotherapy drugs are small molecules that can readily extravasate across the porous blood-brain tumor barrier of malignant brain tumor microvasculature. Small molecule systemic chemotherapy drugs maintain peak blood concentrations for only minutes, and therefore, do not accumulate to therapeutic concentrations within individual brain tumor cells. The physiologic upper limit of pore size in the blood-brain tumor barrier of malignant brain tumor microvasculature is approximately 12 nanometers. Spherical nanoparticles ranging between 7 nm and 10 nm in diameter maintain peak blood concentrations for several hours and are sufficiently smaller than the 12 nm physiologic upper limit of pore size in the blood-brain tumor barrier to accumulate to therapeutic concentrations within individual brain tumor cells. Therefore, nanoparticles bearing chemotherapy that are within the 7 to 10 nm size range can be used to deliver therapeutic concentrations of small molecule chemotherapy drugs across the blood-brain tumor barrier into individual brain tumor cells. The initial therapeutic efficacy of the Gd-G5-doxorubicin dendrimer, an imageable nanoparticle bearing chemotherapy within the 7 to 10 nm size range, has been demonstrated in the orthotopic RG-2 rodent malignant glioma model. Herein I discuss this novel strategy to improve the effectiveness of systemic chemotherapy for the treatment of malignant brain tumors and the therapeutic implications thereof

The Gravitational Universe

The last century has seen enormous progress in our understanding of the Universe. We know the life cycles of stars, the structure of galaxies, the remnants of the big bang, and have a general understanding of how the Universe evolved. We have come remarkably far using electromagnetic radiation as our tool for observing the Universe. However, gravity is the engine behind many of the processes in the Universe, and much of its action is dark. Opening a gravitational window on the Universe will let us go further than any alternative. Gravity has its own messenger: Gravitational waves, ripples in the fabric of spacetime. They travel essentially undisturbed and let us peer deep into the formation of the first seed black holes, exploring redshifts as large as z ~ 20, prior to the epoch of cosmic re-ionisation. Exquisite and unprecedented measurements of black hole masses and spins will make it possible to trace the history of black holes across all stages of galaxy evolution, and at the same time constrain any deviation from the Kerr metric of General Relativity. eLISA will be the first ever mission to study the entire Universe with gravitational waves. eLISA is an all-sky monitor and will offer a wide view of a dynamic cosmos using gravitational waves as new and unique messengers to unveil The Gravitational Universe. It provides the closest ever view of the early processes at TeV energies, has guaranteed sources in the form of verification binaries in the Milky Way, and can probe the entire Universe, from its smallest scales around singularities and black holes, all the way to cosmological dimensions

Sensor noise in LISA Pathfinder: laser frequency noise and its coupling to the optical test mass readout

The LISA Pathfinder (LPF) mission successfully demonstrated the feasibility of the technology needed for the future space borne gravitational wave observatory LISA. A key subsystem under study was the laser interferometer, which measured the changes in relative distance in between two test masses (TMs). It achieved a sensitivity of 32.0 + 2.4 − 1.7     fm / √ Hz , which was significantly better than the prelaunch tests. This improved performance allowed direct observation of the influence of laser frequency noise in the readout. The differences in optical path lengths between the measurement and reference beams in the individual interferometers of our setup determined the level of this undesired readout noise. Here, we discuss the dedicated experiments performed on LPF to measure these differences with high precision. We reached differences in path length difference between ( 368 ± 5 )     μm and ( 329.6 ± 0.9 )     μm which are significantly below the required level of 1 mm or 1000     μm . These results are an important contribution to our understanding of the overall sensor performance. Moreover, we observed varying levels of laser frequency noise over the course of the mission. We provide evidence that these do not originate from the laser frequency stabilization scheme which worked as expected. Therefore, this frequency stabilization would be applicable to other missions with similar laser frequency stability requirements