A 90-102 GHz CMOS based pulsed Fourier transform spectrometer: New approaches for in situ chemical detection and millimeter-wave cavity-based molecular spectroscopy.

We present a system level description of a cavity-enhanced millimeter-wave spectrometer that is the first in its class to combine source and detection electronics constructed from architectures commonly deployed in the mobile phone industry and traditional pulsed Fourier transform techniques to realize a compact device capable of sensitive and specific in situ gas detections. The instrument, which has an operational bandwidth of 90-102 GHz, employs several unique components, including a custom-designed pair of millimeter-wave transmitter and heterodyne receiver integrated circuit chips constructed with 65 nm complementary metal-oxide semiconductor (CMOS) techniques. These elements are directly mated to a hybrid coupling structure that enables free-space interaction of the electronics with a small gas volume while also acting as a cavity end mirror. Instrument performance for sensing of volatile compounds is highlighted with experimental trials taken in bulk gas flows and seeded molecular beam environments.

Long-Term Adverse Effects of Low-Osmolar Compared With Iso-Osmolar Contrast Media After Coronary Angiography.

The relative incidence of long-term adverse effects between low-osmolar contrast media (LOCM) and iso-osmolar contrast media (IOCM) after coronary angiography is still unclear. We analyzed cardiology patients undergoing coronary angiography from January 2006 to July 2013 using either LOCM (iohexol, iopromide) or IOCM (iodixanol) at a single institution. For each contrast medium, primary (all-cause mortality, n = 6,992) and secondary outcomes (long-term renal injury and cardiovascular events beyond 90 days, n = 2,792) were recorded. Inverse probability weighing (IPW) was applied to minimize the selection bias between groups. Unadjusted all-cause mortality was significantly lower for LOCM versus IOCM (hazard ratio [HR] 0.28, 95% CI 0.23 to 0.34). After multivariate Cox regression or IPW, all-cause mortality became comparable and lost statistical significance. Chronic kidney disease subgroup had higher mortality risk when receiving LOCM compared with IOCM (regression adjusted HR 1.80, 95% CI 0.95 to 3.42; IPW-adjusted HR 1.57, 95% CI 0.99 to 2.48). In conclusion, after coronary angiography, patients receiving LOCM had comparable overall long-term mortality compared with IOCM after adjustment. LOCM tended to induce higher long-term mortality than IOCM in chronic kidney disease cohorts.

A CMOS millimeter-wave transceiver embedded in a semi-confocal Fabry-Perot cavity for molecular spectroscopy.

The extension of radio frequency complementary metal oxide semiconductor (CMOS) circuitry into millimeter wavelengths promises the extension of spectroscopic techniques in compact, power efficient systems. We are now beginning to use CMOS millimeter devices for low-mass, low-power instrumentation capable of remote or in situ detection of gas composition during space missions. We have chosen to develop a Flygare-Balle type spectrometer, with a semi-confocal Fabry-Perot cavity to amplify the pump power of a mm-wavelength CMOS transmitter that is directly coupled to the planar mirror of the cavity. We have built a pulsed transceiver system at 92-105 GHz inside a 3 cm base length cavity and demonstrated quality factor up to 4680, allowing for modes with 20 MHz bandwidth, with a sufficient cavity amplification factor for mW class transmitters. This work describes the initial gas measurements and outlines the challenges and next steps.

Phase I study of nintedanib incorporating dynamic contrast-enhanced magnetic resonance imaging in patients with advanced solid tumors.

BACKGROUND: This open-label phase I dose-escalation study investigated the safety, efficacy, pharmacokinetics (PK), and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) effects of the oral angiokinase inhibitor nintedanib in patients with advanced solid tumors. METHODS: Nintedanib was administered once daily continuously, starting at 100 mg and later amended to allow evaluation of 250 mg b.i.d. The primary endpoint was maximum tolerated dose (MTD). DCE-MRI studies were performed at baseline and on days 2 and 28. RESULTS: Fifty-one patients received nintedanib 100-450 mg once daily (n = 40) or 250 mg b.i.d. (n = 11). Asymptomatic reversible liver enzyme elevations (grade 3) were dose limiting in 2 of 5 patients at 450 mg once daily. At 250 mg b.i.d., 2 of 11 patients experienced dose-limiting toxicity (grade 3 liver enzyme elevation and gastrointestinal symptoms). Common toxicities included fatigue, diarrhea, nausea, vomiting, and abdominal pain (mainly grade ≤2). Among 45 patients, 22 (49%) achieved stable disease; 7 remained on treatment for >6 months. DCE-MRI of target lesions revealed effects in some patients at 200 and ≥400 mg once daily. CONCLUSION: Nintedanib is well tolerated by patients with advanced solid malignancies, with MTD defined as 250 mg b.i.d., and can induce changes in DCE-MRI. Disease stabilization >6 months was observed in 7 of 51 patients.

Unfolding the role of PET FDG scan in the management of thyroid incidentaloma in cancer patients.

Thyroid incidentaloma detected on FDG-PET scan has been reported repeatedly in the last several years, though conflicting data are reported. Our aim is to identify the incidence and outcome of incidental FDG-PET detected thyroid lesions in patients undergoing FDG-PET scan for other primary malignancies and to suggest a management algorithm. This is a retrospective review of all patients who had a FDG-PET detected incidental thyroid lesion between January 2002 and December 2009 at Peter MacCallum Cancer Center. Demographics, data relating to PET scan findings, FNA diagnoses, operative details, and histopathology were reviewed. Of the 1,034 subjects who underwent the FDG-PET study, 51 (4.9%) were identified as having thyroid incidentaloma, 31 females and 20 males with a mean age of 60 years. Thyroid malignancy was noted in 39.5% (19/48 patients) who underwent FNAB. Sixteen underwent thyroidectomy. The histopathology revealed 12 patients with papillary carcinoma, 5 with follicular carcinoma and 2 with medullary carcinoma. The high rates are in concordance with analysis of the rates published in the literature. In patients with thyroid PET incidentaloma, the incidence of primary thyroid malignancy is very high as reported in our study and based on analysis of published data, necessitating further investigation. If assessment of these incidentalomas suggests malignancy, then appropriate surgical management may be warranted according to the patient's medical condition.

Significant perturbation in renal functional magnetic resonance imaging parameters and contrast retention for iodixanol compared with iopromide: an experimental study using blood-oxygen-level-dependent/diffusion-weighted magnetic resonance imaging and computed tomography in rats.

OBJECTIVES: The objective of this study was to investigate the renal changes after intravenous administration of a high dose of either iodixanol or iopromide using functional magnetic resonance imaging (MRI) and computed tomography (CT). MATERIALS AND METHODS: The study was approved by the institutional committee on animal research. Seventy-two male Sprague-Dawley rats were divided into 5 cohorts, comprising normal saline (NS), iopromide, iopromide + NS, iodixanol, and iodixanol + NS. Intravenous contrast was administrated at 8 g iodine/kg of body weight. Renal CT, quantitative functional MRI of blood-oxygen-level-dependent (BOLD) imaging and diffusion-weighted imaging (DWI), and histologic examinations were performed for 18 days after contrast administration. Statistical analysis was performed by using 1-way analysis of variance, Mann-Whitney test, and regression analysis. RESULTS: In the renal cortex, BOLD showed persistent elevation of R2* and DWI showed persistent suppression of apparent diffusion coefficient after iodixanol administration for 18 days. Compared with iopromide, adjusted ΔR2* (ΔR2*adj) was significantly higher in the iodixanol group from 1 hour to 18 days (P < 0.04) after contrast; adjusted ΔADC (ΔADCadj) was significantly more pronounced at day 6 (P = 0.01) after contrast. The iodixanol cohort also exhibited persistently higher attenuation in the renal cortex on CT and more severe microscopic renal cortical vacuolization up to 18 days. Intravenous hydration decreased the magnetic resonance changes in both groups but more markedly with iodixanol. CONCLUSIONS: At high doses, iodixanol induced greater changes in renal functional MRI (BOLD and DWI) relative to iopromide. Combined with longer contrast retention within the kidney, this suggests that iodixanol may produce more severe and longer-lasting contrast-induced renal damage.

Phase I and pharmacodynamic trial of the DNA methyltransferase inhibitor decitabine and carboplatin in solid tumors.

PURPOSE: The DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (decitabine) induces DNA demethylation and re-expression of epigenetically silenced genes, and increases carboplatin sensitivity of tumor xenograft models. We designed a clinical study to determine the feasibility of delivering a dose of decitabine, combined with carboplatin, that would be capable of producing equivalent biologic effects in patients with solid tumors. PATIENTS AND METHODS: In a two-stage design, 33 patients received escalating doses of decitabine administered as a 6-hour infusion on day 1 followed by carboplatin, area under the concentration-time curve (AUC) 5 (cohort 1) and AUC 6 (cohort 2), on day 8 of a 28-day cycle. Pharmacodynamic analyses included 5-methyl-2'-deoxycytidine levels, MAGE1A CpG island methylation, and fetal hemoglobin (HbF) expression. RESULTS: The major toxicity was myelosuppression. Dose limiting toxicities, prolonged grade 4 neutropenia (one patient), and sepsis and grade 3 anorexia/fatigue (one patient), were seen in two of four patients treated with decitabine 135 mg/m2 and carboplatin AUC 5. Dose limiting toxicity comprising neutropenic sepsis (one patient) and grade 3 fatigue (one patient) was seen in two of 10 patients treated at decitabine 90 mg/m2 and carboplatin AUC 6. Decitabine induced dose-dependent, reversible demethylation in peripheral-blood cells (PBCs) maximally at day 10. Furthermore, decitabine 90 mg/m2 induced demethylation of the MAGE1A CpG island in PBCs, buccal cells, and tumor biopsies, as well as elevation of HbF expression. CONCLUSION: Decitabine can be combined safely with carboplatin at a dose and schedule that causes epigenetic changes equivalent to or greater than that observed in mice with carboplatin-sensitized xenografts. The recommended dose/schedule for phase II trials is decitabine 90 mg/m2 (day 1) followed by carboplatin AUC 6 (day 8) every 28 days.