HETE-II and the Interplanetary Network

The FREGATE experiment aboard HETE-II has been successfully integrated into the Third Interplanetary Network (IPN) of gamma-ray burst detectors. We show how HETE's timing has been verified in flight, and discuss what HETE can do for the IPN and vice-versa.Comment: To appear in the proceedings of the conference on Gamma-Ray Burst and Afterglow Astronomy 2001: A Workshop Celebrating the First Year of the HETE Mission, to be published by AIP. Figures must be downloaded and printed separatel

In flight performance and first results of FREGATE

The gamma-ray detector of HETE-2, called FREGATE, has been designed to detect gamma-ray bursts in the energy range [6-400] keV. Its main task is to alert the other instruments of the occurrence of a gamma-ray burst (GRB) and to provide the spectral coverage of the GRB prompt emission in hard X-rays and soft gamma-rays. FREGATE was switched on on October 16, 2000, one week after the successful launch of HETE-2, and has been continuously working since then. We describe here the main characteristics of the instrument, its in-flight performance and we briefly discuss the first GRB observations.Comment: Invited lecture at the Woods Hole 2001 GRB Conference, 8 pages, 15 figure

Methods to Standardize a Multicenter Acupuncture Trial Protocol to Reduce Aromatase Inhibitor-related Joint Symptoms in Breast Cancer Patients

AbstractRobust methods are needed to efficiently conduct large, multisite, randomized, controlled clinical trials of acupuncture protocols. The Southwest Oncology Group (SWOG) S1200 trial is a randomized, controlled (i.e., sham-controlled and waitlist-controlled) trial of a standardized acupuncture protocol for treating aromatase inhibitor (AI)-associated arthralgias in early-stage breast cancer patients (n = 228). The primary objective of this study was to determine whether true acupuncture administered twice weekly for 6 weeks, as compared to sham acupuncture or a waitlist control, reduced AI-associated joint pain at 6 weeks as assessed by patient reports. The study was conducted at 11 institutions across the United States. The true acupuncture protocol was developed using a consensus-based process. The true acupuncture and the sham acupuncture protocols each consisted of 12 sessions administered for 6 weeks, followed by one weekly session for 6 weeks. The true acupuncture protocol used standardized protocol points, and the standardized acupoints were tailored to a patient's joint symptoms. The similarly standardized sham acupuncture protocol utilized superficial needling of nonacupoints. Standardized methods were developed to train and monitor acupuncturists and included online and in-person training, study manuals, monthly phone calls, and remote quality assurance monitoring throughout the study period. The research staff similarly received online and in-person training and monthly phone calls

Time-resolved X-ray spectral modeling of an intermediate burst from SGR1900+14 observed by HETE-2/FREGATE and WXM

We present a detailed analysis of a 3.5 s long burst from SGR 1900+14 that occurred on 2001 July 2. The 2-150 keV time-integrated energy spectrum is well described by the sum of two blackbodies whose temperatures are approximately 4.3 and 9.8 keV. The time-resolved energy spectra are similarly well fitted by the sum of two blackbodies. The higher temperature blackbody evolves with time in a manner consistent with a shrinking emitting surface. The interpretation of these results in the context of the magnetar model suggests that the two-blackbody fit is an approximation of an absorbed, multitemperature spectrum expected on theoretical grounds rather than a physical description of the emission. If this is indeed the case, our data provide further evidence for a strong magnetic field and indicate that the entire neutron star was radiating during most of the burst duration

Total hemoglobin reduction in the tumor volume correlates with response to breast cancer neoadjuvant chemotherapy within two weeks of treatment

Optical imaging techniques have emerged as a possible alternative to predict pathological complete response (pCR) in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). Our team developed a so-called diffuse optical tomographic breast imaging system (DOTBIS) which does not require the use of contrast agents or compression, and enables imaging of the whole breast volume using low intensity near infrared light capable to measure tissue concentration of oxy-hemoglobin (ctO2Hb), deoxy-hemoglobin (ctHHb) and water percentage. In this retrospective study, ctTHb changes in the tumor region of 16 breast cancer patients were analyzed across NAC. Both breasts of all patients have been scanned simultaneously with our DOTBIS system, Figure 1, which employs four wavelengths and gathers data from a total of 64 sources and 128 detectors per breast. A PDE-constrained multispectral image reconstruction code creates 3D image maps of total hemoglobin (ctHbT = ctO2Hb+ ctHHb). Tumor volume is selected by entering radiologic information such as tumor side, clock position and distance from the nipple (FN). An automated code was designed to select the highest value from the distance FN and the quadrant referent to the clock position. Subsequently, a region-based image segmentation method is implemented to examine neighboring pixels of the highest value point considering a mask of 90%. After tumor volume segmentation, we calculate the mean ctHbT extracted from the region of interest. An independent-samples t-test was run to determine if there were differences in ctTHb reduction in the tumor region before the third cycle of taxane between responders (n=4) and non-responders (n=12). ctTHb reduction was greater to pCR (45.71 ± 25.16 mM) than non-pCR tumors (-9.67 ± 25.65 mM), a statistically significant difference of 55.38 mM (95% CI, 23.74 to 87), t(14) = 3.755, p = .002, in Figure 2 we can see an example. From the ROC plot results, we can observe that ctTHb reduction in the tumor region after 2 cycles of Taxane is a good indicator to anticipate pCR status. With an area under the curve of 0.958, the best cut-off that maximizes sensitivity and specificity is 16.86mM. At this reduction level, the sensitivity is 100% and specificity is 91.7%. In conclusion, our findings indicate that DOTBIS-measured total hemoglobin in the tumor region may be a strong and independent predictor of treatment response to NAC. Please click Additional Files below to see the full abstract

The hypoxia-inducible genes VEGF and CA9 are differentially regulated in superficial vs invasive bladder cancer

Regulation by hypoxia may underlie the expression of vascular endothelial growth factor in bladder cancer. We have compared the distribution of vascular endothelial growth factor mRNA with a hypoxia marker, carbonic anhydrase 9 (CA IX). vascular endothelial growth factor mRNA was analysed by in situ hybridisation and CA IX by immunochemistry in 22 cases of bladder cancer. The relationship of microvessels to the distribution of CA IX was determined. In a separate series of 49 superficial tumours, CA IX immunostaining was compared with clinico-pathological outcome. In superficial and invasive disease there was overlap in the expression of vascular endothelial growth factor and CA IX, CA IX being more widespread. Both were expressed predominantly on the luminal surface, and surrounding areas of necrosis (invasive tumours). Expression of both factors was greater in superficial disease. Expression was absent within ∼80 μm of microvessels. Unlike vascular endothelial growth factor, CA IX did not predict outcome in superficial disease. Differential responses to reoxygenation provide one explanation: vascular endothelial growth factor mRNA declined rapidly, while CA IX expression was sustained for >72 h. Expression of vascular endothelial growth factor mRNA in bladder tumours is consistent with hypoxic regulation and suggests differential regulation in superficial vs invasive disease. The expression of CA IX on the luminal surface justifies investigation of its utility as a therapeutic target/prognostic indicator

Scientific Highlights of the HETE-2 Mission

The HETE-2 mission has been highly productive. It has observed more than 250 GRBs so far. It is currently localizing 25 - 30 GRBs per year, and has localized 43 GRBs to date. Twenty-one of these localizations have led to the detection of X-ray, optical, or radio afterglows, and as of now, 11 of the bursts with afterglows have known redshifts. HETE-2 has confirmed the connection between GRBs and Type Ic supernovae, a singular achievement and certainly one of the scientific highlights of the mission so far. It has provided evidence that the isotropic-equivalent energies and luminosities of GRBs are correlated with redshift, implying that GRBs and their progenitors evolve strongly with redshift. Both of these results have profound implications for the nature of GRB progenitors and for the use of GRBs as a probe of cosmology and the early universe. HETE-2 has placed severe constraints on any X-ray or optical afterglow of a short GRB. It is also solving the mystery of "optically dark' GRBs, and revealing the nature of X-ray flashes.Comment: 10 pages, 9 figures, to appear in proc. "The Restless High-Energy Universe", Royal Tropical Institute, Amsterdam; revised text, added ref

Phase I trial of intravesical Suramin in recurrent superficial transitional cell bladder carcinoma

Suramin is an antitrypanosomal agent with antineoplastic activity, but with serious systemic side effects. We administered Suramin intravesically to determine a concentration with low toxicity but with evidence of a pharmacodynamic effect, to recommend a dose level for phase II trials. This was an open-labelled, nonrandomised dose-escalation phase I study. In all, 12 patients with a history of recurrent superficial bladder cancer were grouped into four dose levels (10–150 mg ml−1 in 60 ml saline). Six catheter instillations at weekly intervals were used. Cystoscopy and biopsy were performed before and 3 months after the start of treatment. Suramin was assayed using high-performance liquid chromatography, vascular endothelial growth factor (VEGF) using ELISA (enzyme-linked immunosorbent assay), and urinary protein profile using surface-enhanced laser desorption ionisation mass spectroscopy (SELDI). Minimal systemic absorption of Suramin was found at the highest dose of 150 mg ml−1. Urinary VEGF was affected by Suramin at doses above 50 mg ml−1, corresponding to the estimated threshold of saturation of Suramin binding to urine albumin. SELDI showed a specific disappearance of urinary protein peaks during treatment. Intravesical Suramin shows lack of toxicity and low systemic absorption. The results of this phase I trial support expanded clinical trials of efficacy at a dose of 100 mg ml−1 intravesically

The X-ray Afterglows of GRB 020813 and GRB 021004 with Chandra HETGS: Possible Evidence for a Supernova Prior to GRB 020813

We report on the detection of an emission line near 1.3 keV, which we associate with blue-shifted hydrogen-like sulfur (S XVI), in a 76.8 ksec Chandra HETGS spectrum of the afterglow of GRB 020813. The line is detected at 3.3 sigma significance. We also find marginal evidence for a line possibly due to hydrogen-like silicon (Si XIV) with the same blue-shift. A line from Fe is not detected, though a very low significance Ni feature may be present. A thermal model fits the data adequately, but a reflection model may provide a better fit. There is marginal evidence that the equivalent width of the S XVI line decrease as the burst fades. We infer from these results that a supernova likely occurred >~ 2 months prior to the GRB. We find no discrete or variable spectral features in the Chandra HETGS spectrum of the GRB 021004 afterglow.Comment: 26 pages, 11 figures, submitted to Ap