Burden of lymphedema in long-term breast cancer survivors by race and age

Background: Risk assessment for breast cancer–related lymphedema has emphasized upper-limb symptoms and treatment-related risk factors. This article examined breast cancer–related lymphedema after surgery, overall and in association with broader demographic and clinical features. Methods: The Carolina Breast Cancer Study phase 3 followed participants for breast cancer–related lymphedema from baseline (on average, 5 months after breast cancer diagnosis) to 7 years after diagnosis. Among 2645 participants, 552 self-reported lymphedema cases were identified. Time-to-lymphedema curves and inverse probability weighted conditional Cox proportional hazards model were used to evaluate whether demographics and clinical features were associated with breast cancer–related lymphedema. Results: Point prevalence of breast cancer–related lymphedema was 6.8% at baseline, and 19.9% and 23.8% at 2 and 7 years after diagnosis, respectively. Most cases had lymphedema in the arm (88%-93%), whereas 14% to 27% presented in the trunk and/or breast. Beginning approximately 10 months after diagnosis, younger Black women had the highest risk of breast cancer–related lymphedema and older non-Black women had the lowest risk. Positive lymph node status, larger tumor size (>5 cm), and estrogen receptor–negative breast cancer, as well as established risk factors such as higher body mass index, removal of more than five lymph nodes, mastectomy, chemotherapy, and radiation therapy, were significantly associated with increased hazard (1.5- to 3.5-fold) of lymphedema. Conclusions: Findings highlight that hazard of breast cancer–related lymphedema differs by demographic characteristics and clinical features. These factors could be used to identify those at greatest need of lymphedema prevention and early intervention. Lay summary: In this study, the aim was to investigate breast cancer–related lymphedema (BCRL) burden. This study found that risk of BCRL differs by race, age, and other characteristics

Early childhood constraint therapy for sensory/motor impairment in cerebral palsy: a randomised clinical trial protocol.

INTRODUCTION: Cerebral palsy (CP) is the most common physical disability in childhood. It is a disorder resulting from sensory and motor impairments due to perinatal brain injury, with lifetime consequences that range from poor adaptive and social function to communication and emotional disturbances. Infants with CP have a fundamental disadvantage in recovering motor function: they do not receive accurate sensory feedback from their movements, leading to developmental disregard. Constraint-induced movement therapy (CIMT) is one of the few effective neurorehabilitative strategies shown to improve upper extremity motor function in adults and older children with CP, potentially overcoming developmental disregard. METHODS AND ANALYSIS: This study is a randomised controlled trial of children 12-24 months corrected age studying the effectiveness of CIMT combined with motor and sensory-motor interventions. The study population will comprise 72 children with CP and 144 typically developing children for a total of N=216 children. All children with CP, regardless of group allocation will continue with their standard of care occupational and physical therapy throughout the study. The research material collected will be in the form of data from high-density array event-related potential scan, standardised assessment scores and motion analysis scores. ETHICS AND DISSEMINATION: The study protocol was approved by the Institutional Review Board. The findings of the trial will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: NCT02567630

Scratching the scale labyrinth

In this paper, we introduce a new approach to computer-aided microtonal improvisation by combining methods for (1) interactive scale navigation, (2) real-time manipulation of musical patterns and (3) dynamical timbre adaption in solidarity with the respective scales. On the basis of the theory of well-formed scales we offer a visualization of the underlying combinatorial ramifications in terms of a scale labyrinth. This involves the selection of generic well-formed scales on a binary tree (based on the Stern-Brocot tree) as well as the choice of specific tunings through the specification of the sizes of a period (pseudo-octave) and a generator (pseudo-fifth), whose limits are constrained by the actual position on the tree. We also introduce a method to enable transformations among the modes of a chosen scale (generalized and refined “diatonic” and “chromatic” transpositions). To actually explore the scales and modes through the shaping and transformation of rhythmically and melodically interesting tone patterns, we propose a playing technique called Fourier Scratching. It is based on the manipulation of the “spectra” (DFT) of playing gestures on a sphere. The coordinates of these gestures affect score and performance parameters such as scale degree, loudness, and timbre. Finally, we discuss a technique to dynamically match the timbre to the selected scale tuning

Simvastatin suppresses experimental aortic aneurysm expansion

ObjectiveAbdominal aortic aneurysm (AAA) formation is a result of inflammation and extracellular matrix (ECM) remodeling mediated by matrix metalloproteinases (MMPs). Hydroxymethylglutaryl-coenzyme A inhibitors (statins), although clinically used as lipid-lowering agents, have also been demonstrated to have anti-inflammatory effects. This study was designed to determine whether the hydroxymethylglutaryl-coenzyme A inhibitor simvastatin suppresses aneurysm formation in an elastase-induced rat AAA model.MethodsAneurysms were created in adult male Wistar rats by infusion of elastase into isolated infrarenal aortic segments. The rats were randomized to receive either simvastatin (n = 17) or placebo (n = 17) by gastric lavage daily starting the day before surgery. The rats were euthanized and the infrarenal aortas harvested on postoperative day 7. Aortic diameters were measured before infusion, immediately after infusion, and at the time of harvesting. Protein expression was measured by immunoblot analysis. Gene expression profiling using Affymetrix U34A rat genome chips was performed to identify changes in gene expression caused by simvastatin treatment.ResultsMean aneurysm diameter was significantly less in the simvastatin treatment group compared with controls (3.4 ± 0.08 mm vs 4.3 ± 0.19 mm; P = .0001). MMP-9 and nuclear factor-κB protein levels were decreased in the aortas of simvastatin-treated animals. Gene microarray analysis revealed 315 genes with statistically significant changes in expression (P < .05) in the simvastatin group. Genes related to inflammation, ECM remodeling, and oxidative stress function were downregulated. These included genes for interleukin 1, interleukin 4, inducible nitric oxide synthase, P-selectin, platelet-derived growth factor α, tumor necrosis factor, and several chemokines.ConclusionsSimvastatin significantly suppresses experimental aneurysm expansion and reduces protein levels of MMP-9 and nuclear factor-κB. Gene array analysis provides evidence that several mediators of inflammation, matrix remodeling, and oxidative stress are downregulated by simvastatin treatment. This suggests that simvastatin inhibits AAA formation by blocking the expression of certain proinflammatory genes. Simvastatin may be useful as an adjuvant therapy to suppress the growth of small aneurysms.Clinical RelevanceHuman aortic aneurysms are characterized histologically by an inflammatory infiltrate with severe proteolytic destruction. Statins, although used clinically as lipid-lowering agents, have been shown to have anti-inflammatory effects. Simvastatin reduced experimental aneurysm size in this study. It seems that this reduction is mediated by interfering with multiple pathways, including oxidative stress, inflammation, and ECM and matrix remodeling. Further study into the effect of statins in reducing the growth of AAAs in patients is warranted

Integrating Biology and Access to Care in Addressing Breast Cancer Disparities: 25 Years’ Research Experience in the Carolina Breast Cancer Study

Purpose of Review: To review research on breast cancer mortality disparities, emphasizing research conducted in the Carolina Breast Cancer Study, with a focus on challenges and opportunities for integration of tumor biology and access characteristics across the cancer care continuum. Recent Findings: Black women experience higher mortality following breast cancer diagnosis, despite lower incidence compared to white women. Biological factors, such as stage at diagnosis and breast cancer subtypes, play a role in these disparities. Simultaneously, social, behavioral, environmental, and access to care factors are important. However, integrated studies of biology and access are challenging and it is uncommon to have both data types available in the same study population. The central emphasis of phase 3 of the Carolina Breast Cancer Study, initiated in 2008, was to collect rich data on biology (including germline and tumor genomics and pathology) and health care access in a diverse study population, with the long-term goal of defining intervention opportunities to reduce disparities across the cancer care continuum. Summary: Early and ongoing research from CBCS has identified important interactions between biology and access, leading to opportunities to build greater equity. However, sample size, population-specific relationships among variables, and complexities of treatment paths along the care continuum pose important research challenges. Interdisciplinary teams, including experts in novel data integration and causal inference, are needed to address gaps in our understanding of breast cancer disparities

Perspective: Advancing the research agenda for improving understanding of cyanobacteria in a future of global change

Harmful cyanobacterial blooms (=cyanoHABs) are an increasing feature of many waterbodies throughout the world. Many bloom-forming species produce toxins, making them of particular concern for drinking water supplies, recreation and fisheries in waterbodies along the freshwater to marine continuum. Global changes resulting from human impacts, such as climate change, over-enrichment and hydrological alterations of waterways, are major drivers of cyanoHAB proliferation and persistence. This review advocates that to better predict and manage cyanoHABs in a changing world, researchers need to leverage studies undertaken to date, but adopt a more complex and definitive suite of experiments, observations, and models which can effectively capture the temporal scales of processes driven by eutrophication and a changing climate. Better integration of laboratory culture and field experiments, as well as whole system and multiple-system studies are needed to improve confidence in models predicting impacts of climate change and anthropogenic over-enrichment and hydrological modifications. Recent studies examining adaptation of species and strains to long-term perturbations, e.g. temperature and carbon dioxide (CO2) levels, as well as incorporating multi-species and multi-stressor approaches emphasize the limitations of approaches focused on single stressors and individual species. There are also emerging species of concern, such as toxic benthic cyanobacteria, for which the effects of global change are less well understood, and require more detailed study. This review provides approaches and examples of studies tackling the challenging issue of understanding how global changes will affect cyanoHABs, and identifies critical information needs for effective prediction and management

Explicit solution of the (quantum) elliptic Calogero-Sutherland model

We derive explicit formulas for the eigenfunctions and eigenvalues of the elliptic Calogero-Sutherland model as infinite series, to all orders and for arbitrary particle numbers and coupling parameters. The eigenfunctions obtained provide an elliptic deformation of the Jack polynomials. We prove in certain special cases that these series have a finite radius of convergence in the nome $q$ of the elliptic functions, including the two particle (= Lam\'e) case for non-integer coupling parameters.Comment: v1: 17 pages. The solution is given as series in q but only to low order. v2: 30 pages. Results significantly extended. v3: 35 pages. Paper completely revised: the results of v1 and v2 are extended to all order

Risk factors for Luminal A ductal carcinoma in situ (DCIS) and invasive breast cancer in the Carolina Breast Cancer Study

Purpose Invasive breast cancers are thought to arise from in situ lesions, but some ductal carcinoma in situ (DCIS) are indolent with low likelihood of progressing to invasive carcinoma. Comparison of risk factor associations between DCIS and invasive disease may elucidate which factors influence early versus late stages of carcinogenesis. Therefore, we determined whether there were differences in risk factor profiles for screen-detected DCIS and invasive breast cancer among Luminal A lesions. Methods We conducted a case-control analysis using data from the Carolina Breast Cancer Study (1993-2001). Analyses were restricted to Luminal A tumors and screen-detected tumors among mammography-eligible women, to limit confounding by mode of detection (N = 108 DCIS; N = 203 invasive). Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between risk factors and lesion type. Results In stratified analyses, we observed qualitative differences in the direction of association for ever smoking, obese BMI, high waist-To-hip-ratio (WHR), and ?10 years of oral contraceptive use between DCIS and invasive disease. Breastfeeding was inversely associated with invasive disease and was not associated with DCIS. Interaction tests for risk factor associations between Luminal A DCIS and invasive breast cancer were not statistically significant (p>0.05). Conclusions Among Luminal A tumors, established breast cancer risk factors may exert stronger effects on progression of early lesions to invasive disease, with lesser effects on risk of DCIS

Obesity and Breast Cancer Metastasis across Genomic Subtypes

Background: Obese women have higher risk of aggressive breast tumors and distant metastasis. However, obesity has rarely been assessed in association with metastasis in diverse populations. Methods: In the Carolina Breast Cancer Study Phase 3 (2008–2013), waist-to-hip ratio (WHR), body mass index (BMI), and molecular subtype [PAM50 risk-of-recurrence (ROR) score] were assessed. Obesity measures were evaluated in association with metastasis within five years of diagnosis, overall and stratified by race and ROR score. Absolute risk of metastasis and risk differences between strata were calculated using the Kaplan–Meier estimator, adjusted for age, grade, stage, race, and ER status. Relative frequency of metastatic site and multiplicity were estimated in association with obesity using generalized linear models. Results: High-WHR was associated with higher risk of metastasis (5-year risk difference, RD, 4.3%; 95% confidence interval, 2.2–6.5). It was also associated with multiple metastases and metastases at all sites except brain. The 5-year risk of metastasis differed by race (11.2% and 6.9% in Black and non-Black, respectively) and ROR score (19.5% vs. 6.6% in high vs. low-to-intermediate ROR-PT). Non-Black women and those with low-to-intermediate ROR scores had similar risk in high- and low-WHR strata. However, among Black women and those with high ROR, risk of metastasis was elevated among high-WHR (RDBlack/non-Black = 4.6%, RDHigh/Low-Int = 3.1%). Patterns of metastasis were similar by BMI. Conclusions: WHR is associated with metastatic risk, particularly among Black women and those with high-risk tumors. Impact: Understanding how risk factors for metastasis interact may help in tailoring care plans and surveillance among patients with breast cancer

A chemotherapy privileging process for advanced practice providers at an academic medical center

Purpose: Nurse practitioners, physician assistants, and pharmacists are advanced practice providers who are highly trained and qualified healthcare professionals that can help support traditional demands on oncologists' increased time in direct patient care. The purpose of this study was to detail and assess the creation of a privileging process for this group of medical professionals within an academic medical center. Obtaining the designation of limited oncology practice provider (LOPP) gives the right to modify chemotherapy orders and to order supportive care medications. Methods: An interdisciplinary team developed a comprehensive training process inclusive of required educational domains, knowledge goals, and educational activities to become an LOPP. In 2018, five years after the implementation of the privileging process, a survey was distributed to assess perceptions of the training process and integration of LOPPs within oncology practice. Results: Most oncologists noted that working with LOPPs is beneficial to oncology practice (94%) and that they make modifying chemotherapy orders more efficient (87%). Greater than 82% of LOPPs also reported that their privileges streamline the chemotherapy process and make them feel valuable. Conclusion: The creation of the LOPP designation is an effective way to integrate nurse practitioners, physician assistants, and pharmacists within oncology practice. The inclusion of a focused privileging process ensures the safety of cancer care provided and has created a streamlined process for chemotherapy modifications and supportive care