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Activatable fluorescence imaging in the second near-infrared window (NIR-II FL, 1000-1700 nm) is of great significance for accurate tumor diagnosis and targeting therapy. However, the clinical translation of most stimulus-activated nanoprobes is severely restricted by insufficient tumor response and out-of-synchronization theranostic process. Herein, an intelligent nanofactory AUC-GOx/Cel that possesses the "external supply, internal promotion" dual H

Background:Chemotherapy has side effects on breast cancer patients, and sleep disturbance is one of the common psychological symptoms. Purpose: This study aimed to examine the incidence of sleep disorders and investigate the relationship between anxiety and depression, hope, social support and sleep disorders in breast cancer patients with chemotherapy in China.Results:Total 350 patients were administered questionnaires, and 329 patients completed the questionnaires. The recovery rate was 94%. The majority of participants reported clinically significant sleep disturbance prior to chemotherapy (67.8%), during chemotherapy (71.8%), and after chemotherapy (72.2%). Pearson correlation analysis showed that the higher the direct support, emotional support, social interaction support, informational support and total social support score, the lower the total PSQI score of breast cancer patients (r = -0.212, -0.292, -0.236, -0.271, and -0.195 p< 0.01, respectively). Multifactorial model analysis showed that direct support, anxiety and age were the three main factors that affected sleep quality in breast cancer patients. Conclusions:social support may provide a powerful tool to reduce anxiety and improve sleep quality in breast cancer patients with chemotherapy. Citation Format: Wenjuan Zhu, Wanling Li, Hui Yang, Linying Wang, Jun Guo, Jinnan Gao. The association of sleep quality with anxiety, depression and social support in breast cancer patients with chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-14.

Tissue hemodynamics, including the blood flow, oxygenation, and oxygen metabolism, are closely associated with many diseases. As one of the portable optical technologies to explore human physiology and assist in healthcare, near-infrared diffuse optical spectroscopy (NIRS) for tissue oxygenation measurement has been developed for four decades. In recent years, a dynamic NIRS technology, namely, diffuse correlation spectroscopy (DCS), has been emerging as a portable tool for tissue blood flow measurement. In this article, we briefly describe the basic principle and algorithms for static NIRS and dynamic NIRS (i.e., DCS). Then, we elaborate on the NIRS instrumentation, either commercially available or custom-made, as well as their applications to physiological studies and clinic. The extension of NIRS/DCS from spectroscopy to imaging was depicted, followed by introductions of advanced algorithms that were recently proposed. The future prospective of the NIRS/DCS and their feasibilities for routine utilization in hospital is finally discussed.

Purpose To assess the status of returning to work (RTW) following breast cancer treatment and to explore its associated factors among female patients. Methods Four-hundred-forty-two eligible patients admitted in a tertiary hospital since 2012 were followed up in 2018. Information about working status after treatment, date of RTW or reason for not RTW was obtained during a 30-min interview. Patients’ sociodemographic, disease, and treatment characteristics were retrieved from the hospital record. Overall prevalence rate and probability of RTW during the follow-up were estimated using Kaplan–Meier method. Factors associated with RTW were identified using regression analyses. Results Three-hundred-ninety-six patients (89.6%) completed the follow-up. The median follow-up was 31 months. Among them, 141 patents (35.6%) RTW of whom 68.1% (n = 96) were back within 12 months after cancer treatment. The reported reasons for not RTW included: prolonged fatigue, low self-esteem, lack of support from family and working unit, or voluntarily quitting. Patients aged under 50 years, being single, having higher level of education, not having extensive axillary node procedure, or without any comorbidities were more likely to RTW. Conclusion The rate of RTW after cancer treatment in this cohort was lower than those reported in others. Both personal and treatment factors were associated with RTW.

Background Follow-up after curative surgery is increasingly recognized as an important component of breast cancer care. Although current guideline regulates the follow-ups, there are no relevant studies on the adherence to it in China. This study investigated the post-surgery follow-up and explored its association with patients, tumor and treatment characteristics. Methods A total of 711 patients underwent surgical treatment in Shanxi Bethune Hospital from March 2012 to May 2018 were included in this study. Baseline sociodemographic, tumor, and treatment characteristics were obtained from the hospital electronic medical records. The post-surgery follow-up was reviewed and assessed from the patient’s follow-up examination record. Factors associated with the first three-year follow up was evaluated using logistic regression analysis. Results The annual follow-up rate after surgery decreased gradually from 67.1% at the 1st year, 60.2% at the 3rd year to 51.9% at the 4th year, and 43.5% at the 5th year. Loss of follow-up during the first 3 years after surgery was significantly associated with older age (> 65 years), lower medical insurance coverage, axillary lymph node dissection, and less intensity of systemic treatment. Conclusion A significant downtrend of annual follow-up rate for breast cancer survivors was confirmed in this study. Loss of follow-up within the first 3 years after surgery was associated with both patient’s characteristics and treatment. These results will provide evidence to help clinicians to develop tailored patient management after curative surgery.

Cancer-related cognitive impairment (CRCI) is a common complaint in breast cancer patients, especially related to chemotherapy. It is characterized as cognitive disorders in areas of memory, attention and executive function, which can negatively affect patients' quality of life and their ability to work. While various assessment methods of CRCI cause highly diverse results in CRCI-related studies. Currently, it is not clear how cerebral structure and function change in breast cancer patients and underlying mechanisms of developing CRCI are still undefined. Intervention research is limited. This article reviews the results of CRCI-related studies and research progress and discusses the advantages and limits of various methods. Besides, the mechanisms and intervention strategies are reviewed.

Purpose: To assess the financial toxicity (FT) and to investigate patients and cancer characteristic that associated with it in patients admitted in a tertiary hospital in central China. Methods: This was a cross-sectional study of 166 patients from 188 with stage 0-III women breast cancer admitted in Bethune hospital in Taiyuan, Shanxi province during January–May 2019. FT was self-reported using of financial Toxicity Comprehensive Rating Scale (COST-FACIT). Patients’ sociodemographic factors, clinical examination, and cancer treatment were collected from questionnaire and hospital record. The financial concern and coping strategy was self-reported. Factors associated with FT were identified using linear regression analysis. Results: Of the 166 completed the survey, the COST score ranged 0–40 with a mean of 21.2 (median 22.5, standard deviation 8.1). On multivariate linear regression analysis, older age (β coefficient: 0.20, 95% CI 0.11–0.29, p < 0.001), higher household income (β coefficient: 3000–5000 Yuan: 7.88, 95% CI 4.74–11.01, p < 0.001; ≥ 5000 Yuan: 12.81, 95% CI 9.54–16.08, p < 0.001) were positively associated with COST scores. Advanced cancer stage was the strongest predictor of FT among the cancer characteristics (β coefficient: − 4.52, 95% CI − 7.13–1.92, p = 0.001). To cope with the FT, 131 (78.8%) patients decreased non-medical expenses, and 56 (33.7%) reduced or quitted treatment. Conclusions: FT was significantly associated with patient’s age, income, and cancer stage. Women having financial concerns after diagnosis were more likely to reduce their non-medical expenses and even quit treatments. Clinicians should take into account the FT levels in all patients and work out appropriate treatment strategies for optimal clinical outcome. Refereed/Peer-reviewed

To investigate the therapeutic effect of anthracycline chemotherapy in advanced breast cancer and its influence on estradiol and tumor size, 136 breast cancer patients in Shan Xi Bethune Hospital were divided into anthracycline chemotherapy group and non anthracycline chemotherapy group. The clinical effects of anthracycline chemotherapy group and non-anthracycline chemotherapy group were observed. The levels of estrone, estradiol and follicle stimulating hormone before and after treatment were measured. The tumor size, adverse reactions and 2-y survival rate of anthracycline chemotherapy group and non anthracycline chemotherapy group were measured after 1-3 courses of treatment. The total effective rate of anthracycline chemotherapy group and non-anthracycline chemotherapy group was 64.7 and 23.5 %, respectively and the total effective rate of non anthracycline chemotherapy group was significantly lower than that of anthracycline chemotherapy group (p 0.05). After treatment, the tumor volume of each group gradually decreased with increased time of drug exposure and the degree of tumor reduction in the non-anthracycline chemotherapy group was lower than that of the anthracycline chemotherapy group (p 0.05). After 2 y of follow-up, the survival rate of anthracycline chemotherapy group was significantly higher than that of non-anthracycline chemotherapy group (p

// Yao Zhang 1, 2, * , Jinzhi Lai 1, * , Zhanwen Du 1 , Jinnan Gao 2 , Shuming Yang 3 , Shashank Gorityala 4 , Xiahui Xiong 1 , Ou Deng 1, 5 , Zhefu Ma 5 , Chunhong Yan 6 , Gonzalo Susana 7 , Yan Xu 3, 4 , Junran Zhang 1 1 Department of Radiation Oncology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA 2 Department of Breast Surgery, Shanxi Academy of Medical Sciences, The Affiliated Shanxi Dayi Hospital of Shanxi Medical University, Shanxi, 030032, PR China 3 Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA 4 Department of Chemistry, Cleveland State University, Cleveland, OH 44115, USA 5 Department of Breast Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, PR China 6 Augusta University, Augusta, 30912, GA, USA 7 Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, St. Louis, MO 63104, USA * These authors contributed equally to this work Correspondence to: Junran Zhang, email: Junran.zhang@case.edu Keywords: double strand break repair, homologous recombination, replication stress, CHK1 inhibitor, radioresistance Received: January 28, 2016 Accepted: April 11, 2016 Published: May 04, 2016 ABSTRACT Radiotherapy (RT) remains a standard therapeutic modality for breast cancer patients. However, intrinsic or acquired resistance limits the efficacy of RT. Here, we demonstrate that CHK1 inhibitor AZD7762 alone significantly inhibited the growth of radioresistant breast cancer cells (RBCC). Given the critical role of ATR/CHK1 signaling in suppressing oncogene-induced replication stress (RS), we hypothesize that CHK1 inhibition leads to the specific killing for RBCC due to its abrogation in the suppression of RS induced by oncogenes. In agreement, the expression of oncogenes c-Myc/CDC25A/c-Src/H-ras/E2F1 and DNA damage response (DDR) proteins ATR/CHK1/BRCA1/CtIP were elevated in RBCC. AZD7762 exposure led to significantly higher levels of RS in RBCC, compared to the parental cells. The mechanisms by which CHK1 inhibition led to specific increase of RS in RBCC were related to the interruptions in the replication fork dynamics and the homologous recombination (HR). In summary, RBCC activate oncogenic pathways and thus depend upon mechanisms controlled by CHK1 signaling to maintain RS under control for survival. Our study provided the first example where upregulating RS by CHK1 inhibitor contributes to the specific killing of RBCC, and highlight the importance of the CHK1 as a potential target for treatment of radioresistant cancer cells.

e19402 Background: The term “Financial toxicity(FT)” is widely used to describe the distress or hardship patients suffering from the financial burden of cancer treatment[1]. Increased evidences have showed that cancer-associated FT is common and has a negative impact on patients’ mental health, quality and length of life[1,2]. The scale of COmprehensive Score for financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT) was used to assess the FT of cancer patients, which has been validated and widely used internationally [3] and China [4]. To our knowledge, little is known about the FT of breast cancer patients in China. The aim of this study is to assess the FT and to investigate patients and cancer characteristic that associated with it in patients in central China. Methods: This was a cross-sectional study among 188 patients with stage 0-III women breast cancer admitted in Bethune hospital in Taiyuan, Shanxi province during January - May 2019. FT was self-reported using the COST-FACIT. Patients’ socio-demographic factors, clinical examination, and cancer treatment were collected from questionnaire and hospital record. The financial concern and coping strategy was self-reported. Factors associated with FT was identified using linear regression analysis. Results: One hundred and sixty-six (88.2%) completed the questionnaire. The COST score ranged 0-40 with a mean of 21.2 (median 22.5, standard deviation 8.1). On multivariate linear regression analysis, older age (β coefficient: 0.19, 95% CI: 0.10-0.29, p

e12617 Background: Pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) is associated with favorable outcomes of patients with triple-negative breast cancer (TNBC). However, the heterogeneous nature of the disease often results in diverse responses to the same NACT protocol. In particular, a proportion of patients with residual disease (RD) develop metastasis at early stages after treatment. Further stratification of TNBC patients without pCR to NACT is needed for the development of novel strategies in the management of these patients. Methods: A retrospective series of ten TNBC patients with locally residual disease after NACT with the EC-T regimen at Shanxi Bethune Hospital between 2014 and 2018 were included. Total RNA from FFPE pre-NACT core biopsies and paired surgical specimens was subjected to the Affymetrix Human Transcriptome Array. Gene Set Enrichment Analysis (GSEA) was used to identify signal pathways and gene signatures associated with early metastasis after NACT followed by surgery. The Cox proportional hazard model and Kaplan-Meier survival curves on DMFS (distant metastasis-free survival) were employed to assess the prognostic value of the identified signature in TNBC patients from GEO datasets. Results: The epithelial-mesenchymal transition (EMT) pathway was markedly more enriched in pre- (NES = 1.92; p.adjust = 0.019) and post-NACT samples (NES = 2.02; p.adjust = 0.010) from patients who developed metastasis at relatively early stages ( < 18 months) after surgery compared with those who had been disease-free. Noticeably, the EC-T NACT differentially affected the expression of EMT genes resulting in global promotion or inhibition of the pathway in a case-dependent manner. Nevertheless, a subset of 6 EMT genes including LUM, SFRP4, DCN, MMP2, CXCL12, and HTRA1 was expressed constantly at higher levels in samples from patients who progressed to metastasis. The potential of this 6-EMT gene signature to predict TNBC metastasis was validated in the MDACC neoadjuvant series (GSE25066) that contained 113 TNBC patients with RD (55 with metastasis; p = 0.0008; HR = 0.36; 95% CI: 0.200-0.685) and the ICO–UMGC dataset (GSE103091) including 107 TNBC patients (31 with metastasis; p = 0.032, HR = 0.46, 95% CI:0.225-0.937). Conclusions: The expression of the 6-EMT gene signature at diagnosis may be a predictive value of metastasis of TNBC. Moreover, the persistently high expression of the signature may signal early metastasis in TNBC patients with residual disease after EC-T NACT.

e19232 Background: The incidence of breast cancer has increased more than 30% in the past decades in China. Epidemiological studies based on international and Chinese data have showed that breast cancer is the most common in female malignant tumors. Breast cancer patients with early breast cancer have better survival, lower recurrence and metastasis rate due to early diagnosis and improved treatment. As an important element in the comprehensive management of breast cancer patients, follow-up can eliminate treatment-related complications, detect recurrence and metastasis as early as possible, and improve mental health and quality of life. It is increasingly recognized as a distinct phase of cancer care. However, follow-up adherence after breast surgery has not been studied in China. The aim of this study is to investigate the loss of follow-up after breast cancer surgery and its association with patients', tumor and treatment characteristics. Methods: A total of 711 patients underwent surgical treatment in Shanxi Bethune Hospital from March 2012 to May 2018 were included in this study. Baseline socio-demographic, tumor, and treatment characteristics were obtained from the hospital electronic medical records. The post-surgery follow-up was reviewed and assessed from the patients’ follow-up examination record. Factors associated with the first three-year follow-up was evaluated using logistic regression analysis. Results: The annual follow-up rate after surgery decreased gradually from 67.1% at the 1st year, 60.2% at the 3rd year to 51.9% at the 4th year, and 43.5% at the 5th year. Loss of follow-up during the first three years after surgery was significantly associated with older age >65 years(OR=2.34, 95% CI:1.14-4.82), lower medical insurance coverage(OR=4.26, 95%CI:1.77-10.25), axillary lymph node dissection(OR=2.52, 95%CI:1.39-4.55), no chemotherapy(OR=3.55, 95% CI:1.87-6.75) and no radiotherapy(OR=3.85, 95%CI:2.11-7.03). Conclusions: This study indicated that the annual follow-up rate after curative surgery for breast cancer survivors decreased significantly within five years, and that the risk of poor adherence to follow-up examinations was significantly increased in patients aged over 65 years with lower medical insurance coverage, having extensive axillary lymph node dissection, and lack of systematic treatments. These results suggest potential for improving adherence to follow-up in higher-risk subgroups and help clinicians to develop tailored patient management.

Lactic acid bacteria and cellulose degrading bacteria play an important role in fermentation process of silage, because they can prevent the rancidity and increase the nutritive value of silage. But the propagation of lactic acid bacteria will inhibit the activity of cellulose degrading bacteria in the silage fermentation system. This problem can be solved by releasing lactic acid bacteria and cellulose degrading bacteria in different time. Therefore, we immobilized lactic acid bacteria as a microbial agent for sustained release. Firstly, the optimal balling concentration of the composite immobilized carrier and composite immobilized carrier were obtained by immobilization of blank balls and corncob adsorbed Lactobacillus plantarum S1 respectively. The best immobilization condition of L. plantarum S1 was obtained by comparing the immobilized rate and balling effect of two kinds of balls, which were embedded by sodium alginate (SA), CMC-Na and embedded-crosslinked by SA, CMC-Na, polyvinyl alcohol (PVA). The results showed that the best balling concentration was achieved by using 6% PVA+0.4% SA+0.3% CMC-Na for embedding-crosslinking and 1.2% SA+0.5% CMC-Na for direct embedding respectively. In addition, comparing with the mechanical strength and embedding rate of five kinds of immobilization process, the best immobilized process was obtained by adding of the mixture of immobilized carriers (1.2%SA+ 0.5%CMC-Na) and corncob adsorbed L. plantarum S1 slowly into 4% CaCl₂ for 24 hours. The corncob adsorption and SA embedding methodology can effectively increase the embedding efficiency of Lactobacillus plantarum S1.乳酸菌与纤维素降解菌因其可防止微贮饲料酸败、增加秸秆饲料的营养价值等优点，在秸秆微贮过程中起重要作用。但由于乳酸菌的繁殖会抑制纤维素降解菌的活性，如何实现微贮过程中两种微生物分时发挥功能是解决上述问题的关键。文中利用固定化技术将乳酸菌制备成含有玉米秸秆粉的固定化菌剂以达到缓释的目的。首先制作固定化空白小球得出复合固定化载体成球的最佳浓度，利用玉米芯吸附植物乳杆菌S1 得到复合固定化载体，以对S1 的包埋率、成球效果等为指标，通过对比两种固定化方法 (包埋法与包埋-交联法)，得到固定化植物乳杆菌S1 的最佳条件。研究表明，使用6% PVA+0.4% SA+0.3% CMC-Na 进行包埋-交联时成球效果最好，使用1.2% SA+0.5% CMC-Na 进行直接包埋时成球效果最好。通过对比5 种固定化工艺，将1.2% SA+0.5% CMC-Na和吸附玉米粉组成的固定化载体混合物逐滴滴入4%氯化钙中直接包埋24 h 得到的固定化小球其机械强度以及包埋率均优于其他工艺。因此，利用玉米芯吸附-海藻酸钠包埋的方法可以有效提高植物乳杆菌包埋效率，为使用固定化技术制备微贮饲料菌剂奠定基础。.

Rationale Wilson disease (WD) is an autosomal recessive hereditary disease in which the patient usually has a reduced risk of developing cancer. In particular, with the exception of hepatocellular carcinoma and cholangiocarcinoma, the incidence of cancer is significantly lower in WD patients compared with the general population. This case study presents a rare case of WD complicated with primary breast cancer. Patient concerns A 40-year-old woman who was diagnosed with WD at 25 years of age found a lump in her left breast. She has a family history of cancer. Diagnoses Ultrasound and mammography results were highly suggestive of a malignant lesion. After core needle biopsy, it was confirmed that she had invasive breast cancer. Interventions A modified radical mastectomy was performed for the left breast. As the tumor was defined as a stage IIa triple negative breast cancer, the patient would have been recommended epirubicin/cyclophosphamide + docetaxel for 8 cycles if WD was not a comorbidity. As the patient had cirrhosis and abnormal liver function, she was given paclitaxel weekly for 6 cycles instead. Outcomes The patient showed good tolerance, and has not had a recurrence in 2 years. Lessons We reviewed the literature for studies of patients with WD complicated with cancers, and to our knowledge, this is the first report on WD complicated with breast cancer. The patient received chemotherapy even with liver dysfunction, which suggests that patients with WD can be safely treated with paclitaxel chemotherapy under close surveillance.

Well-known ‘routing hole’ problem of geographic routing is hardly avoided in wireless sensor networks because of various actual geographical environments. Existing geographic routing protocols use perimeter routing strategies to find a detour path around the boundary of holes when they encounter the local minimum during greedy forwarding. However, this solution may lead to uneven energy consumption around the holes since it consumes more energy of the boundary sensors. It becomes more serious when holes appear in most of routing paths in a large-scale sensor network. In this paper, we propose a novel distributed strategy to balance the traffic load on the boundary of holes by virtually changing the sizes of these holes. The proposed mechanism dynamically controls holes to expand and shrink circularly without changing the underlying forwarding strategy. Therefore, it can be applied to most of the existing geographic routing protocols which detour around holes. Simulation results show that our strategy can effectively balance the load around holes, thus prolonging the network life of sensor networks when an existing geographic routing protocol is used as the underlying routing protocol.

Soaking aqueous ammonia (SAA) pretreatment of corn stover was carried out at three temperatures (30, 50, and 70 ºC) and three concentrations of ammonia solution (5, 15, and 25 wt.%). The delignification kinetic model, based on three first-order reactions, was applied to describe the kinetic behavior of lignin removal from corn stover during SAA pretreatment. The first, second, and third terms were based on the initial, bulk, and residual phases of delignification, respectively. The results showed that the model fitted well with the data obtained from the experiments. The activation energies for the delignification reactions were estimated as 61.05 and 59.46 kJ/mol in the bulk and residual phases, respectively. Delignification selectivity increased with increasing reaction temperature.

Experiments were made to investigate mechanisms by which adenosine 5′-trisphosphate (ATP) enhanced vasomotion in mesenteric lymphatic vessels isolated from young guinea-pigs. ATP (10−8–10−3 M) caused a concentration-dependent increase of perfusion-induced vasomotion with the endothelium mediating a fundamental role at low ATP concentrations (10−8–10−6 M). The response to 10−6 M ATP showed tachyphylaxis when applied at intervals of 10 min but not at intervals of 20 or 30 min. Suramin (10−4 M) or reactive blue 2 (3×10−5 M) but not PPADS (3×10−5 M) abolished the excitatory response to 10−6 M ATP confirming an involvement of P2 purinoceptors. The excitatory response to 10−6 M ATP was abolished by treatment with either pertussis toxin (100 ng ml−1), antiflammin-1 (10−9M), indomethacin (3×10−6 M) or SQ29548 (3×10−7 M), inhibitors of specific G proteins, phospholipase A2, cyclo-oxygenase and thromboxane A2 receptors respectively. ATP simultaneously induced a suramin-sensitive inhibitory response, which was normally masked by the excitatory response. ATP-induced inhibition was mediated by endothelium-derived nitric oxide (EDNO) as the response was abolished by NG-nitro-L-arginine (L-NOARG; 10−4 M), an inhibitor of nitric oxide synthase. We conclude that ATP modulates lymphatic vasomotion by endothelium-dependent and endothelium-independent mechanisms. One of these is a dominant excitation caused through endothelial P2 purinoceptors which because of an involvement of a pertussis toxin sensitive G-protein may be of the P2Y receptor subtype. Their stimulation increases synthesis of phospholipase A2 and production of thromboxane A2, an arachidonic acid metabolite which acts as an endothelium-derived excitatory factor. British Journal of Pharmacology (1999) 127, 1597–1602; doi:10.1038/sj.bjp.0702710

Well known "hole" problem is hardly avoided in wireless sensor networks because of various actual geographical environments. Existing geographic routing protocols (such as GFG [1] and GPSR [2]) use perimeter routing strategies to find a detour path around the boundary of holes when they encounter the "local minimum" during greedy forwarding. However, this solution may lead to uneven energy consumption around the holes since it consumes more energy of the boundary sensors. It becomes more serious when holes appear in most of routing paths in a large scale sensor network. In this paper, we propose a novel distributed strategy to balance the traffic load on the boundary of holes by virtually changing the sizes of these holes. The proposed mechanism dynamically controls holes to expand and shrink circularly without changing the underlying forwarding strategy. Therefore, it can be applied to most of the existing geographic routing protocols which detour around holes. Simulation results show that our new strategy can effectively balance the load around holes thus prolong the network life of sensor networks when using with GPSR.

High mammographic density was an independent risk factor for breast cancer and has a higher associated risk than most other known risk factors. The reproducibility remains a major issue in assessment of breast parenchymal patterns. Misclassification of mammographic pattern can lead to significant underestimation of risk estimates. The purpose of this study was to assess the inter-rater and intra-rater reliability based on visual subjective mammographic density measurements. Three density measures, Wolfe parenchymal pattern, Boyd classification scale, and a percentage of densities in total breast, were investigated. The study included 101 women who were participants of the International Breast Cancer Intervention Study I (IBIS I) for up to 7 years. Seven sets of mammograms were collected for each woman. Left breast mediolateral oblique films were digitized, and the scanned images were independently reviewed by two readers. These images were reassessed by one reader after a year. The agreements of measures were evaluated by Kappa statistics (Wolfe and Boyd scale) and intraclass correlation coefficient (percentage densities). For the inter-rater agreement, Weighted Kappa for Wolfe scale was 0.89 (P < 0.0001) and for Boyd scale was 0.84 (P < 0.0001). The intraclass correlation coefficient was 0.94 for percentage densities. For the intra-rater agreement, Weighted Kappa for Wolfe scale was 0.87 (P < 0.0001) and for Boyd scale was 0.86 (P < 0.0001). The intraclass correlation coefficient was 0.96 for percentage densities. The study concludes that both visual qualitative and quantitative measurements on mammographic density are highly reproducible in the breast cancer research studies if appropriate training is provided. The method is appropriate for risk assessment in a prevention trial.