Verification of Laser Heterodyne Interferometric Bench for Chinese Spaceborne Gravitational Wave Detection Missions.

Construction of laser heterodyne interferometric bench to measure tiny translation and tilt with picometer- and nanoradian-level sensitivity in the millihertz band is critical for the success of spaceborne gravitational wave detection, including the LISA, Taiji, and Tianqin missions. In this paper, we report on the construction and testing of a laser heterodyne interferometric bench that contains two optical path designs, the dual-beam heterodyne interferometry and the polarization-multiplexing heterodyne interferometry. The measurement sensitivity of translation and tilt reaches below 3 pm/Hz1/2 and 12 nrad/Hz1/2 for frequencies above 10 mHz, respectively. As a technical verification platform, stabilization loops of amplitude and phase and coherence analysis are also conducted through the bench. Furthermore, we demonstrate initial implements of phase-locking technology and multiple degree of freedom measurements as the extended applications of the constructed bench. The achieved results show that the laser interferometric bench would serve as an excellent experimental platform for the technology demonstration and verification of future Chinese spaceborne gravitational wave detection.

Design and Construction of the Optical Bench Interferometer for the Taiji Program.

A kind of full-function two-sided optical bench interferometer (OBI) is designed to meet the practical requirements of the Taiji Program for space gravitational wave detection. The main optical paths are arranged on the A-side for transmission and interference, and other optical paths and electronic devices are placed on the B-side. According to the design scheme, we successfully constructed two OBIs by using hydrogen-oxygen catalytic stress-free bonding technology. When the OBI is installed and adjusted, the position and Angle error of the interference beam are controlled within 30 µm and 50 µrad through the self-designed precision mechanical clamping mechanism and beam position measuring device. The built OBI was placed on the vibration isolation platform in the vacuum tank for the stability test. The test results show that the noise of the OBI is less than 10 pm/√Hz in the frequency band of 0.1 Hz to 1 Hz, which meets the noise budget requirements of the Taiji Pathfinder in the middle- and high-frequency band.

Study on the Effect of Micro-Force Perturbations and Temperature Fluctuation on Interferometer for the Taiji Program.

To increase the interferometric measurement resolution in the Taiji program, we present a noise suppression method in this paper. Taking the specific micro-force perturbation and temperature fluctuation in the Taiji-1 interferometer as an example, we set up and experimentally verified the corresponding transfer function to quantify the effect of both noise sources on the interferometric results. Consistent results were obtained between the numerical and experimental results for the transfer function. It is instructive to eliminate the micro-force perturbations and temperature fluctuations during on-orbit interferometric measurement for as long as the acquisition of the force or temperature distribution of related surfaces and the corresponding transfer functions. This indicates that the method can be used for noise sensing and more in the field of noise elimination and measurement resolution improvement for future Taiji program interferometers.

Inter-spacecraft offset frequency setting strategy in the Taiji program.

For controlling the beat frequency of heterodyne interferometry so that the Taiji program can detect gravitational waves in space, an offset frequency setting strategy based on a linear programming algorithm is proposed. Considering factors such as Doppler frequency shift, phase-locking scheme, laser relative intensity noise, and phase detector bandwidth, inter-spacecraft offset frequency setting results suitable for the Taiji program are obtained. During the six years of running the detection process, the use of frequency bounds in the range of [5 MHz, 25 MHz] showed that offset frequencies will remain unchanged for a maximum of 1931 days. If the upper and lower bounds are adjusted, and the relative motion between spacecraft is further constrained, the offset frequencies do not need to change during the time of the mission. These results may provide insights into selecting the phase detector and designing operation parameters such as orbit and laser modulation frequency in the Taiji program.

A low-noise analog frontend design for the Taiji phasemeter prototype.

The Taiji program plans to utilize the laser interferometer to measure the movement at the picometer level between free-floating test masses. As the phase readout equipment, the phasemeter needs to obtain the beat note with an accuracy of µrad/Hz. The main source of noise in the phasemeter is the analog frontend of the analog to digital converter. A self-designed phasemeter prototype with a low-noise analog frontend, which includes the theme of the pilot tone correction, has been developed and tested for the Taiji program in this Note. The experimental results show that the performance of the developed phasemeter can satisfy the Taiji sensitivity requirement in the whole frequency range. The sensitivity of the board can reach 0.5 µrad/Hz in the frequency range of 0.1-1 Hz. Therefore, the prototype gives us a good model for the fully functional Taiji phasemeter.

The Influence of Vitamin D on Mammographic Density: Results from CALGB 70806 (Alliance) a Randomized Clinical Trial.

Current therapies for breast cancer prevention only prevent estrogen receptor positive (ER+) disease and toxicity limits use of these agents. Vitamin D is a potential prevention therapy for both ER+ and ER- disease and is safe with few side effects. This study evaluates the effect of 1-year of vitamin D supplementation on mammographic density (MD), a biomarker of breast cancer risk in a multicenter randomized controlled trial. Premenopausal women with ≥25% MD and no history of cancer were randomly assigned to 2,000 international units (IU) of vitamin D or placebo orally daily for 1 year. Change in percent MD was evaluated using Cumulus software after all participants completed treatment. Three hundred women enrolled between January 2011 and December 2013 with a mean age of 43 and diverse ethnicity [14% Hispanic, 12% African American (AA)]. Supplementation significantly increased vitamin D levels compared with placebo (14.5 ng/mL vs. -1.6 ng/mL; P < 0.0001) with all participants on the vitamin D arm achieving vitamin D sufficiency at 12 months. Vitamin D was safe and well tolerated. After adjustment for baseline MD, the mean between-arm difference (vitamin D vs. placebo) at 1 year was -0.75 (-0.26, 1.76; P = 0.56). A greater effect was seen for women with ≥50% MD and AA women, although neither reached significance. This randomized controlled trial demonstrated significant improvement in vitamin D levels with 2,000 IU for 1 year, with 100% of supplemented women achieving sufficiency. However, a null effect was seen regarding change in MD for premenopausal women (the primary outcome of the study). PREVENTION RELEVANCE: Current therapies for breast cancer prevention only prevent estrogen receptor positive (ER+) disease and are underutilized due to toxicity and side effects. Vitamin D is a potential prevention therapy for both ER+ and ER- disease and is safe with few side effects.

Laser acquisition experimental demonstration for space gravitational wave detection missions.

The laser acquisition-pointing technique is one of the most important techniques for space gravitational wave detection missions, like the Taiji program and the LISA (Laser Interferometer Space Antenna) program. The laser acquisition system suppresses the laser deviation angle to 1 µrad at the receiving aperture. Corresponding to 80 times of telescope magnification, the acquisition accuracy should reach 80 µrad at the acquisition camera. In order to verify the feasibility of the laser acquisition scheme, a laser acquisition ground simulation experimental system is designed and constructed. The experimental system simulates the actual acquisition process of the Taiji from three aspects: optical path, acquisition accuracy and acquisition scanning process. In the experiment, the coupling between the laser acquisition system and the laser pointing system is considered by introducing the DWS (Differential Wave-front Sensing) technique to calibrate the reference position of the acquisition camera and read out the acquisition precision. Due to limited beam propagation distance in the ground experiment, the in-flat top properties of the transmitting beam will greatly affect the acquisition precision. Based on the analysis of the influence, an improved acquisition ground simulation scheme is introduced. The experimental results indicate that the experimental system can achieve the acquisition accuracy of sub-10 µrad magnitude at the acquisition camera. The experimental system realizes methodological demonstration of the acquisition scheme. The results offer the experimental foundation and theoretical basis for the acquisition system of the Taiji/LISA program.

Automatic, high-speed, high-precision acquisition scheme with QPD for the Taiji program.

Most of the space gravitational wave detection missions, such as the Taiji program, use space-based laser interferometer to sense the gravitational waves. However, to obtain the interference signal, the inter-satellite laser acquisition scheme is firstly required to establish the laser link. Traditional acquisition sensors are CCD cameras, which cause a serious heating problem and call for high alignment precision. To avoid these questions, a high-speed, high-precision, fully automatic acquisition scheme with quadrant photodetectors (QPD) is proposed in this paper. Incoherent measurement method of the QPD is introduced to fulfill high-speed acquisition, while a dedicated imaging system is involved for automatic acquisition. Also, an improved differential power sensing (DPS) signal is developed. Combined with the down-sampling algorithm and the match filter algorithm, the acquisition scheme can achieve 1 µrad resolution with total scanning time less than 220 s.

Tilt-to-length noise coupled by wavefront errors in the interfering beams for the space measurement of gravitational waves.

The space-based gravitational wave detection programs, like the Laser Interferometer Space Antenna (LISA) or the Taiji program, aim to detect gravitational waves in space with a triangular constellation of three spacecraft. The unavoidable jitters of the spacecraft and the pointing will couple with the misalignment of the interfering beams into the longitudinal path length readout. This effect is called tilt-to-length (TTL) coupling, which is one of the keys to achieving the required measuring accuracy of 1pm/Hz. In terms of two phase definitions (the LISA Pathfinder (LPF) signal and the Average Phase (AP) signal), we implement the comprehensive theoretical analysis concerning the effect of aberrations on TTL coupling noise. In addition, we analytically derive that the proper lateral shift of the interfering beams relative to the detector can partly cancel out the TTL noise coupled with aberrations, especially coma and trefoil aberrations for the AP signal. Based on the above results, the meaningful guidance can be provided for the design and construction of the optical system in LISA or Taiji.

High-precision laser spot center positioning method for weak light conditions.

In the acquisition stage of many space applications, such as the Taiji program, the spot center of weak laser light must be accurately determined. Under weak light conditions, the precision of most traditional positioning methods is greatly affected. In this paper, we present a high-precision laser spot center positioning method based on the theoretical analysis of influence factors of precision. It is shown through experimental study that the method's precision can fulfill the requirement of the Taiji program.

Randomized Trial of Standard Adjuvant Chemotherapy Regimens Versus Capecitabine in Older Women With Early Breast Cancer: 10-Year Update of the CALGB 49907 Trial.

PURPOSE: Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years. PATIENTS AND METHODS: Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician's choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS. RESULTS: The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56% and 50%, respectively (hazard ratio [HR], 0.80; P = .03); breast cancer-specific survival rates were 88% and 82%, respectively (HR, 0.62; P = .03); and overall survival rates were 62% and 56%, respectively (HR, 0.84; P = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor-negative patients (HR, 0.66; P = .02), but not among hormone receptor-positive patients (HR, 0.89; P = .43). Overall, 43.9% of patients have died (13.1% from breast cancer, 16.4% from causes other than breast cancer, and 14.1% from unknown causes). Second nonbreast cancers occurred in 14.1% of patients. CONCLUSION: With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor-negative disease. Competing risks in this older population dilute overall survival benefits.

Effect of Vitamin D Supplementation on Breast Cancer Biomarkers: CALGB 70806 (Alliance) Study Design and Baseline Data.

One in eight women will develop breast cancer over their lifetime with 230,000 women diagnosed in 2015. For this reason, breast cancer prevention efforts are essential. Vitamin D, with anticancer properties, may have a role in prevention of some cancers, including breast cancer. This report discusses the rationale, study protocol, and baseline data for a clinical trial of vitamin D and its effects on breast cancer biomarkers. This study was a randomized controlled trial designed to evaluate the effect of a fixed dose of vitamin D on specfic breast cancer biomarkers. Study participants were randomized to take either vitamin D or placebo for a period of 1 year. All participants had mammograms and blood drawn for serum biomarkers. A subset of participants underwent random periareolar fine needle aspiration to draw tissue for biomarkers. From January 2011 to December 2013, 300 premenopausal women, aged 59 or younger, were recruited from 41 institutions across the United States. A total of 102 women underwent random periareolar fine needle aspiration. The last subject completed the trial in January 2015. Baseline vitamin D levels for all participants ranged from 4-72 ng/mL, with 62% of participants being vitamin D deficient at enrollment (≥30 ng/mL or ≥75 nmo-l/L). The mean body mass index was 27.0 kg/m2 (range 15.1-53.6 kg/m2). 14% and 11.7% of participants were Hispanic or African American, respectively. Accrual and enrollment of participants is feasible for this type of multi-center prevention trial, and it can readily be carried out in a cooperative group setting.

5-year follow-up of a randomized controlled trial of immediate versus delayed zoledronic acid for the prevention of bone loss in postmenopausal women with breast cancer starting letrozole after tamoxifen: N03CC (Alliance) trial.

BACKGROUND: Postmenopausal women with breast cancer receiving aromatase inhibitors are at an increased risk of bone loss. The current study was undertaken to determine whether upfront versus delayed treatment with zoledronic acid (ZA) impacted bone loss. This report described the 5-year follow-up results. METHODS: A total of 551 postmenopausal women with breast cancer who completed tamoxifen treatment and were undergoing daily letrozole treatment were randomized to either upfront (274 patients) or delayed (277 patients) ZA at a dose of 4 mg intravenously every 6 months. In the patients on the delayed treatment arm, ZA was initiated for a postbaseline bone mineral density T-score of <-2.0 or fracture. RESULTS: The incidence of a 5% decrease in the total lumbar spine bone mineral density at 5 years was 10.2% in the upfront treatment arm versus 41.2% in the delayed treatment arm (P<.0001). A total of 41 patients in the delayed treatment arm were eventually started on ZA. With the exception of increased NCI Common Toxicity Criteria (CTC) grade 1/2 elevated creatinine and fever in the patients treated on the upfront arm and cerebrovascular ischemia among those in the delayed treatment arm, there were no significant differences observed between arms with respect to the most common adverse events of arthralgia and back pain. Osteoporosis occurred less frequently in the upfront treatment arm (2 vs 8 cumulative cases), although this difference was not found to be statistically significant. Bone fractures occurred in 24 patients in the upfront treatment arm versus 25 patients in the delayed treatment arm. CONCLUSIONS: Immediate treatment with ZA prevented bone loss compared with delayed treatment in postmenopausal women receiving letrozole and these differences were maintained at 5 years. The incidence of osteoporosis or fractures was not found to be significantly different between treatment arms.

Pilot evaluation of Scrambler therapy for the treatment of chemotherapy-induced peripheral neuropathy.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN), a common side effect of chemotherapy, needs better effective treatments. Preliminary data support the use of Scrambler therapy, a device which treats pain via noninvasive cutaneous electrostimulation, for the treatment of CIPN. The current manuscript reports data from a pilot trial, performed to investigate the effect of Scrambler therapy for the treatment of established CIPN. METHODS: Eligible patients had CIPN symptoms of ≥1 month duration with tingling and/or pain ≥4/10 during the prior week. Patients were treated with Scrambler therapy to the affected area(s) for up to ten daily 30-min sessions. Symptoms were monitored using a neuropathy questionnaire consisting of numerical analog scales ranging from 0 to 10, daily before therapy as well as weekly for 10 weeks after therapy. Descriptive summary statistics formed the basis of data analysis. RESULTS: Thirty-seven patients were enrolled. Twenty-five patients were treated primarily on their lower extremities while 12 were treated primarily on their upper extremities. There was a 53 % reduction in pain score from baseline to day 10; a 44 % reduction in tingling; and a 37 % reduction in numbness. Benefit appeared to last throughout 10 weeks of follow-up. There were no substantial adverse events. CONCLUSION: Preliminary data support that Scrambler therapy may be effective for the treatment of CIPN: a prospective placebo-controlled clinical trial should be performed.

Wisconsin Ginseng (Panax quinquefolius) to improve cancer-related fatigue: a randomized, double-blind trial, N07C2.

BACKGROUND: Safe, effective interventions to improve cancer-related fatigue (CRF) are needed because it remains a prevalent, distressing, and activity-limiting symptom. Based on pilot data, a phase III trial was developed to evaluate the efficacy of American ginseng on CRF. METHODS: A multisite, double-blind trial randomized fatigued cancer survivors to 2000mg of American ginseng vs a placebo for 8 weeks. The primary endpoint was the general subscale of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) at 4 weeks. Changes from baseline at 4 and 8 weeks were evaluated between arms by a two-sided, two-sample t test. Toxicities were evaluated by self-report and the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) provider grading. RESULTS: Three hundred sixty-four participants were enrolled from 40 institutions. Changes from baseline in the general subscale of the MFSI-SF were 14.4 (standard deviation [SD] = 27.1) in the ginseng arm vs 8.2 (SD = 24.8) in the placebo arm at 4 weeks (P = .07). A statistically significant difference was seen at 8 weeks with a change score of 20 (SD = 27) for the ginseng group and 10.3 (SD = 26.1) for the placebo group (P = .003). Greater benefit was reported in patients receiving active cancer treatment vs those who had completed treatment. Toxicities per self-report and CTCAE grading did not differ statistically significantly between arms. CONCLUSIONS: Data support the benefit of American ginseng, 2000mg daily, on CRF over an 8-week period. There were no discernible toxicities associated with the treatment. Studies to increase knowledge to guide the role of ginseng to improve CRF are needed.

Pilot study of Panax quinquefolius (American ginseng) to improve cancer-related fatigue: a randomized, double-blind, dose-finding evaluation: NCCTG trial N03CA.

PURPOSE: This pilot trial sought to investigate whether any of three doses of American ginseng (Panax quinquefolius) might help cancer-related fatigue. A secondary aim was to evaluate toxicity. METHODS: Eligible adults with cancer were randomized in a double-blind manner, to receive American ginseng in doses of 750, 1,000, or 2,000 mg/day or placebo given in twice daily dosing over 8 weeks. Outcome measures included the Brief Fatigue Inventory, vitality subscale of the Medical Outcome Scale Short Form-36 (SF-36), and the Global Impression of Benefit Scale at 4 and 8 weeks. RESULTS: Two hundred ninety patients were accrued to this trial. Nonsignificant trends for all outcomes were seen in favor of the 1,000- and 2,000-mg/day doses of American ginseng. Area under the curve analysis of activity interference from the Brief Fatigue Inventory was 460-467 in the placebo group and 750 mg/day group versus 480-551 in the 1,000- and 2,000-mg/day arms, respectively. Change from baseline in the vitality subscale of the SF-36 was 7.3-7.8 in the placebo and the 750-mg/day arm, versus 10.5-14.6 in the 1,000- and 2,000-mg/day arms. Over twice as many patients on ginseng perceived a benefit and were satisfied with treatment over those on placebo. There were no significant differences in any measured toxicities between any of the arms. CONCLUSION: There appears to be some activity and tolerable toxicity at 1,000-2,000 mg/day doses of American ginseng with regard to cancer-related fatigue. Thus, further study of American ginseng is warranted.