Carbon nanofibers/liquid metal composites for high temperature laser ultrasound.

As the demand for clean energy becomes greater worldwide, there will also be an increasing demand for next generation nuclear power plants that incorporate advanced sensors and monitoring equipment. A major challenge posed by nuclear power plants is that, during normal operation, the reactor compartment is subjected to high operating temperatures and radiation flux. Diagnostic sensors monitoring such structures are also subject to temperatures reaching hundreds of degrees Celsius, which puts them at risk for heat degradation. In this work, the ability of carbon nanofibers to work in conjunction with a liquid metal as a photoacoustic transmitter was demonstrated at high temperatures. Fields metal, a Bi-In-Sn eutectic, and gallium are compared as acoustic mediums. Fields metal was shown experimentally to have superior performance over gallium and other reference cases. Under stimulation from a low fluence 6 ns pulse laser at 6 mJ/cm2 with 532 nm green light, the Fields metal transducer transmitted a 200 kHz longitudinal wave with amplitude >5.5 times that generated by a gallium transducer at 300 °C. Each high temperature test was conducted from a hot to cold progression, beginning as high as 300 °C, and then cooling down to 100 °C. Each test shows increasing signal amplitude of the liquid metal transducers as temperature decreases. Carbon nanofibers show a strong improvement over previously used candle-soot nanoparticles in both their ability to produce strong acoustic signals and absorb higher laser fluences up to 12 mJ/cm2.

A phase Ib/II study of cabozantinib (XL184) with or without erlotinib in patients with non-small cell lung cancer.

PURPOSE: Cabozantinib is a multi-kinase inhibitor that targets MET, AXL, and VEGFR2, and may synergize with EGFR inhibition in NSCLC. Cabozantinib was assessed alone or in combination with erlotinib in patients with progressive NSCLC and EGFR mutations who had previously received erlotinib. METHODS: This was a phase Ib/II study (NCT00596648). The primary objectives of phase I were to assess the safety, pharmacokinetics, and pharmacodynamics and to determine maximum tolerated dose (MTD) of cabozantinib plus erlotinib in patients who failed prior erlotinib treatment. In phase II, patients with prior response or stable disease with erlotinib who progressed were randomized to single-agent cabozantinib 100 mg qd vs cabozantinib 100 mg qd and erlotinib 50 mg qd (phase I MTD), with a primary objective of estimating objective response rate (ORR). RESULTS: Sixty-four patients were treated in phase I. Doses of 100 mg cabozantinib plus 50 mg erlotinib, or 40 mg cabozantinib plus 150 mg erlotinib were determined to be MTDs. Diarrhea was the most frequent dose-limiting toxicity and the most frequent AE (87.5% of patients). The ORR for phase I was 8.2% (90% CI 3.3-16.5). In phase II, one patient in the cabozantinib arm (N = 15) experienced a partial response, for an ORR of 6.7% (90% CI 0.3-27.9), with no responses for cabozantinib plus erlotinib (N = 13). There was no evidence that co-administration of cabozantinib markedly altered erlotinib pharmacokinetics or vice versa. CONCLUSIONS: Despite responses with cabozantinib/erlotinib in phase I, there were no responses in the combination arm of phase II in patients with acquired resistance to erlotinib. Cabozantinib did not appear to re-sensitize these patients to erlotinib.

Permanent sensorineural deafness in a patient with chronic myelogenous leukemia secondary to intracranial hemorrhage.

A 52-year-old male presented with tinnitus and fullness in left ear for one day. Workup revealed a white blood cell count of 685 × 10(3)/µL with marked increase in granulocyte series and myeloid precursors on peripheral smear. The initial impression was chronic myelogenous leukemia with hyperleukocytosis, and patient was started on hydration, hydroxyurea, and allopurinol. Patient tolerated bone marrow biopsy well but continued to bleed excessively from the biopsy site. Results confirmed Philadelphia chromosome positive chronic myelogenous leukemia (chronic phase). On day three of hospitalization, patient developed sudden slurred speech along with shaking movements involving extremities. Magnetic resonance imaging revealed multiple hemorrhages throughout the brain. Hydroxyurea was continued until insurance coverage for nilotinib was getting approved. On day nine of hospitalization, patient developed sudden bilateral sensorineural deafness. Repeat magnetic resonance imaging revealed multiple new hemorrhages throughout the brain. Computer tomography of the temporal bones showed inflammatory changes in right and left mastoid cells. Nilotinib was started on day eleven of hospitalization. Patient's white blood cell count continued to decrease, but there was no improvement in hearing. Four months later, patient was treated with bilateral transmastoid cochlear implants. This case highlights permanent deafness as a hemorrhagic complication secondary to chronic myelogenous leukemia.