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In this work, we demonstrate that damage mechanism identification from acoustic emission (AE) signals generated in minicomposites with elastically similar constituents is possible. AE waveforms were generated by SiC/SiC ceramic matrix minicomposites (CMCs) loaded under uniaxial tension and recorded by four sensors (two models with each model placed at two ends). Signals were encoded with a modified partial power scheme and subsequently partitioned through spectral clustering. Matrix cracking and fiber failure were identified based on the frequency information contained in the AE event they produced, despite the similar constituent elastic properties of the matrix and fiber. Importantly, the resultant identification of AE events closely followed CMC damage chronology, wherein early matrix cracking is later followed by fiber breaks, even though the approach is fully domain-knowledge agnostic. Additionally, the partitions were highly precise across both the model and location of the sensors, and the partitioning was repeatable. The presented approach is promising for CMCs and other composite systems with elastically similar constituents. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a bacterial pathogen that causes severe infections among humans. The increasing emergence of antibiotic resistance necessitates the development of new strategies to combat the spread of disease. One approach is photodynamic inactivation using porphyrin photosensitizers, which generate superoxide and other radicals in the presence of light, causing cell death via the oxidation of proteins and lipids. In this study, we analyzed a novel library of meso-substituted and metallated porphyrins for activity against multidrug-resistant S. aureus. From a library of 251 compounds, 51 showed antimicrobial activity, in three discrete classes of activity: those that functioned only in light, those that had toxicity only in darkness, and those that displayed activity regardless of illumination. We further demonstrated the broad-spectrum activity of these compounds against a variety of pathogens, including Bacillus anthracis, Enterococcus faecalis, and Escherichia coli. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) analyses of lead compounds (XPZ-263 and XPZ-271) revealed strong activity and killing towards methicillin-resistant S. aureus (MRSA) strains. An analysis of mutation frequencies revealed low incidences of resistance to lead compounds by E. coli and MRSA. Finally, an exploration of the underlying mechanism of action suggests that these compounds do not depend solely upon light-induced radical generation for toxicity, highlighting their potential for clinical applications. [ABSTRACT FROM AUTHOR]

We reviewed 66 women with poor-risk metastatic breast cancer from 15 centers to describe the efficacy of allogeneic hematopoietic cell transplantation (HCT). Median follow-up for survivors was 40 months (range, 3–64). A total of 39 patients (59%) received myeloablative and 27 (41%) reduced-intensity conditioning (RIC) regimens. More patients in the RIC group had poor pretransplant performance status (63 vs 26%, P=0.002). RIC group developed less chronic GVHD (8 vs 36% at 1 year, P=0.003). Treatment-related mortality rates were lower with RIC (7 vs 29% at 100 days, P=0.03). A total of 9 of 33 patients (27%) who underwent immune manipulation for persistent or progressive disease had disease control, suggesting a graft-vs-tumor (GVT) effect. Progression-free survival (PFS) at 1 year was 23% with myeloablative conditioning and 8% with RIC (P=0.09). Women who developed acute GVHD after an RIC regimen had lower risks of relapse or progression than those who did not (relative risk, 3.05: P=0.03), consistent with a GVT effect, but this did not affect PFS. These findings support the need for preclinical and clinical studies that facilitate targeted adoptive immunotherapy for breast cancer to explore the benefit of a GVT effect in breast cancer.Bone Marrow Transplantation (2008) 41, 537–545; doi:10.1038/sj.bmt.1705940; published online 17 December 2007 [ABSTRACT FROM AUTHOR]

Despite significant advances in prevention and therapy, cytomegalovirus (CMV) infection continues to be an important cause of morbidity and mortality in the hematopoietic stem cell transplant (HSCT) recipient. The standard drug for pre-emptive therapy is intravenous ganciclovir (GCV). Valganciclovir (VGC), the oral pro-drug of GCV, has excellent bioavailability and is ideal for oral therapy. Since March 2002, VGC was adopted in our center for outpatient pre-emptive therapy in all patients undergoing allogeneic HSCT. Fifty-two allogeneic HSCT recipients were followed weekly via Digene hybrid capture assay®. Patients with a positive assay were treated with VGC 900 mg p.o. b.i.d. × 14 days followed by 900 mg p.o. QD until at least 7 days after a negative test. Eighteen patients (14 sib, four MUD) had 30 episodes of CMV DNA detection treated with oral VGC. Median duration of therapy was 21 days (range 10–21 days). The rate of response was 93% (28/30) as confirmed by a negative assay within 14 days. No significant toxicity was encountered. Two patients failed oral VGC. One case of CMV enteritis was diagnosed in a patient with acute GVHD. Pre-emptive therapy of CMV infection with oral VGC is safe and effective in allogeneic HSCT recipients.Bone Marrow Transplantation (2006) 37, 851–856. doi:10.1038/sj.bmt.1705341; published online 13 March 2006 [ABSTRACT FROM AUTHOR]

Summary:We report a pilot study of a home-based aerobic exercise program in a group of 17 adult hematopoietic stem cell transplant (HSCT) recipients. Participants had received no cancer treatment for at least 6 months and reported leisure time physical activity less than 20?min per day and fewer than three times a week during the previous month. Following baseline assessments of aerobic fitness, fatigue symptoms, and quality of life, participants were placed on home-based aerobic exercise programs consisting of 20-40?min of activity in the target heart rate zone (40-60%predicted heart rate reserve) delivered in three to five sessions per week for 12 weeks. Subjects were supplied with electronic heart rate monitors and we encouraged program adherence using weekly telephone contacts and exercise diaries. In all, 32 of the 42 qualified candidates consented (acceptance=76%). Of these, 17 kept appointments for baseline assessments, four did not complete the study (attrition=46%), and no exercise-related adverse events were reported. Scores on measures of aerobic fitness, fatigue severity, and physical well-being improved (signed ranks test; P<0.05) during program participation. Our findings suggest that individually prescribed, home-based aerobic exercise is an acceptable, safe, and potentially effective intervention for improving physical functioning and fatigue in sedentary HSCT recipients.Bone Marrow Transplantation (2005) 35, 721-727. doi:10.1038/sj.bmt.1704815 Published online 7 February 2005 [ABSTRACT FROM AUTHOR]

Summary:Metastatic breast cancer has been a common indication for autologous hematopoietic stem cell transplantation (HSCT). Previous reports indicate 3-year survival and progression-free survival (PFS) rates after autotransplant to be about 30 and 15%, respectively. Most deaths are from recurrent disease. One potential cause for high relapse rates is graft contamination with tumor. We describe 14 women with metastatic breast cancer transplanted between 1991 and 1998 with hematopoietic cells from identical twins. Median age was 41?y (range 34-50). Most women (12 of 14) were treated with mastectomy, and all received anthracycline-based regimens in their pretransplant course; nine women also received a taxane, seven radiotherapy and three hormonal therapy. Four women were in complete remission (one CR, three CRU) at transplant, five were in partial remission, two had stable disease and two had progressive disease. Eight women have died, one of treatment-related causes and seven of progressive breast cancer. Three-year survival was 48% (21-71%) and 3-year PFS was 21% (5-45%). Although the number of patients is small, outcomes for women transplanted with syngeneic grafts are similar to those of women receiving autologous grafts. This suggests that residual cancer in the patient is the major contributor to relapse after transplantation for breast cancer.Bone Marrow Transplantation (2003) 32, 151-155. doi:10.1038/sj.bmt.1704120 [ABSTRACT FROM AUTHOR]

This paper summarizes a pilot, sequential dose-escalation study of PEG-rHuMGDF in patients with advanced malignancies who had delayed platelet recovery after autologous stem cell transplantation (ASCT). Patients were randomized to receive either placebo (n = 11) or PEG-rHuMGDF at 5 (n = 9), 10 (n = 6), or 25 (n = 7) μg/kg/day by subcutaneous injection for 14 days and were monitored for 5 weeks. Across all treatment groups, eight patients had platelet recovery to 20 × 109/l by day 21. The proportion of patients achieving platelet recovery, the median number of days and units of platelet transfusions were similar for the placebo and the PEG-rHuMGDF groups. PEG-rHuMGDF was well tolerated at all dosages. The incidence rates of adverse events in all groups were similar. No deaths on study, no drug-related serious adverse events, and no development of neutralizing antibodies to MGDF occurred. Bone Marrow Transplantation (2000) 26, 1083–1088. [ABSTRACT FROM AUTHOR]

Information regarding the nature, frequency, correlates and temporal trajectory of concerns of stem cell transplantation (SCT) recipients is critical to the development of interventions to enhance quality of life (QOL) in these individuals. This study examined psychosocial concerns in 110 SCT (87% autologous) recipients drawn from two SCT centers. Participants were a mean of 46 years of age and 17 months post-SCT (range 3–62 months). Information regarding current and past SCT-related concerns, performance status, and demographic characteristics was collected by telephone interview or questionnaire. Recipients reported a wide variety of psychosocial concerns following SCT. Recipients who were younger, female and evidenced a poorer performance status reported a larger number of post-SCT concerns. Examination of the temporal trajectory of concerns suggests that some concerns are salient throughout the course of post-SCT recovery (eg disease recurrence, energy level, ‘returning to normal’), some are salient early in the course of recovery (eg quality of medical care, overprotectiveness by others), and others emerge later in the course of recovery (eg feeling tense or anxious, sexual life, sleep, relationship with spouse/partner, ability to be affectionate). Implications for the development of interventions to enhance post-SCT QOL are identified. [ABSTRACT FROM AUTHOR]

Although fatigue is one of the most common and debilitating symptoms experienced by cancer patients, it has received little systematic attention. This situation is due in large part to the lack of adequate instruments to measure fatigue. The primary aim of this study was to validate a newly developed measure of fatigue for use with cancer patients: the Fatigue Symptom Inventory (FSI). This 13 item self-report measure was designed to measure the intensity and duration of fatigue and its impact on quality of life. The psychometric properties of the FSI were assessed in women undergoing treatment for breast cancer, women who had completed treatment for breast cancer and women with no history of cancer. A seven-item interference subscale was found to have good internal consistency, with alpha coefficients above 0.90 in all three groups. The complete FSI was found to have rather weak to moderate test-retest reliability among patients in active treatment and healthy comparison subjects assessed on three separate occasions. Convergent validity was demonstrated using comparisons with existing measures of fatigue. Construct validity was demonstrated using comparisons between and within groups as well as comparisons with measures of anxiety and depression. Overall, the FSI was established as a valid and reliable measure of fatigue in cancer patients and healthy individuals. Suggestions are made for the potential application of the measure in clinical research. [ABSTRACT FROM AUTHOR]

As more women are treated with bone marrow transplantation (BMT) for breast cancer, there is growing interest in quality of life (QOL) following treatment. Although there have been some clinical studies of QOL following BMT, this area has received little systematic attention. In particular, it is unclear how QOL for women treated with BMT for breast cancer differs from that which might be expected for ‘healthy’ women of about the same age. To address this issue, we compared QOL reported by women treated with autologous BMT for breast cancer with that of a group of women of similar age with no history of cancer. In addition, we examined the relationship of demographic factors, medical factors, and self-reported symptom prevalence, severity, and distress to QOL in post-BMT patients. All participants completed the SF-36 Health Survey developed from the Medical Outcomes Study (SF-36). Post-BMT patients also completed the ECOG Performance Status Rating Scale (PSR) and the Memorial Symptom Assessment Scale (MSAS). Results indicated that, compared to the women with no cancer history, post-BMT patients reported significantly impaired physical functioning, physical role functioning, general health, vitality, social functioning, and emotional role functioning. Impaired QOL following BMT was significantly associated with lower income, a longer time to engraftment, longer hospital stay, poor performance status, and greater symptom prevalence, severity, and distress. The problems identified in this study may be important targets for intervention when trying to improve QOL following BMT. [ABSTRACT FROM AUTHOR]

As more individuals undergo autologous bone marrow transplantation (BMT), there is growing interest in the impact of treatment side effects on quality of life. Fatigue is a potentially disruptive treatment side effect that has not been systematically assessed following BMT. The primary aim of this study was to determine whether the severity of fatigue and its impact on quality of life is significantly greater in women who had undergone BMT for breast cancer than in women of similar age with no history of cancer. Another aim was to identify the medical and psychosocial correlates of fatigue in women who had completed BMT. A group of women treated with autologous BMT for breast cancer (n = 43; mean age = 44; mean time since BMT = 20 months) and a group of women of similar age with no history of cancer (n = 43; mean age = 46) participated in this study. Subjects completed measures of fatigue, anxiety, depression, and sleep habits. Medical data were obtained from computerized patient records. Women who had completed BMT for breast cancer reported significantly more frequent and severe fatigue than women with no cancer history. In addition, fatigue had a significantly greater impact on daily functioning and quality of life in BMT recipients than in women with no cancer history. Fatigue following BMT for breast cancer was related to both medical factors (i.e., time since BMT) and psychosocial factors (i.e., anxiety, depressive symptoms and sleep difficulties). Following BMT for breast cancer, women may experience fatigue that is worse than might "normally" be expected and can interfere with daily functioning and quality of life. Future research should focus on identifying the biological correlates of fatigue, psychological and physiological mechanisms by which fatigue is produced, and interventions to alleviate fatigue. [ABSTRACT FROM AUTHOR]

We present improvements of a previously reported method of tracheoesophageal puncture for voice restoration in postlaryngectomy patients. Our method utilizes a flexible endoscope to enable the tracheoesophageal puncture to be made under direct visualization using only local anesthesia and intravenous sedation. After 3 days, the created tracheoesophageal fistula tract is mature enough to allow placement of a voice prosthesis in the office. This allows the entire procedure to be performed in an outpatient setting with minimal risk. [ABSTRACT FROM AUTHOR]