Chemistry plays a key role in many astrophysical situations regulating the cooling and the thermal properties of the gas, which are relevant during gravitational collapse, the evolution of discs and ...the fragmentation process. In order to simplify the usage of chemical networks in large numerical simulations, we present the chemistry package krome, consisting of a python pre-processor which generates a subroutine for the solution of chemical networks which can be embedded in any numerical code. For the solution of the rate equations, we make use of the high-order solver DLSODES, which was shown to be both accurate and efficient for sparse networks, which are typical in astrophysical applications. krome also provides a large set of physical processes connected to chemistry, including photochemistry, cooling, heating, dust treatment and reverse kinetics. The package presented here already contains a network for primordial chemistry, a small metal network appropriate for the modelling of low metallicities environments, a detailed network for the modelling of molecular clouds, a network for planetary atmospheres, as well as a framework for the modelling of the dust grain population. In this paper, we present an extended test suite ranging from one-zone and 1D models to first applications including cosmological simulations with enzo and ramses and 3D collapse simulations with the flash code. The package presented here is publicly available at http://kromepackage.org/ and https://bitbucket.org/krome/krome_stable.
Most research addressing needs and concerns of young patients with breast cancer (≤40 years) is retrospective. The HOHO European protocol is a prospective multicenter cohort study of young women with ...newly diagnosed breast cancer, about fertility, psychosocial and quality of life concerns. Here we report the baseline data and focus on predictors of fertility concerns.
Patient surveys and medical record review were used. The baseline survey included sociodemographic, medical and treatment data as well as questions on fertility concerns and preservation strategies. Subscales from the CAncer Rehabilitation Evaluation System-Short Form (CARES-SF) were administered to measure specific quality of life aspects. Uni- and multivariable modeling were used to investigate predictors of greater fertility concern.
Among 297 eligible respondents, 67% discussed fertility issues before starting therapy, 64% were concerned about becoming infertile after treatment, and 15% decided not to follow prescribed therapies. Fifty-four percent of women wished future children before diagnosis; of these, 71% still desired biologic children afterwards. In multivariable analysis, not having children was the only patient characteristic significantly associated with fertility concerns at diagnosis. Twenty-seven percent used fertility preservation strategies. Women who received chemotherapy reported greater physical (p = 0.021) and sexual difficulties (p = 0.039) than women who did not. Women who were married or had a partner reported less psychosocial problems than single women (p = 0.039).
Young women with newly diagnosed breast cancer have several concerns, including, but not limited to, fertility. The HOHO European study provides valuable information to develop targeted interventions.
•Many young women desire future biologic children after breast cancer.•Sixty-four percent of study patients had fertility concerns.•A low proportion of patients took fertility preservation measures.•Women treated with chemotherapy reported greater physical and sexual difficulties.•Women with stable relationships reported less psychosocial problems than single women.
The TDE focus group seeks to understand how disequilibria are generated in geological, chemical and biological systems, and how these disequilibria can lead to emergent phenomena, such as ...self-organization in bounded conditions eventuating in metabolism. Some planetary water-rock interfaces generate electrochemical disequilibria (e.g. electron, proton and/or ion gradients), and life itself is an out-of-equilibrium system that operates by harnessing such gradients across membranes. Disequilibrium in inorganic chemical systems also leads to the formation of a variety of patterns, structures, and dynamical systems. Understanding geochemical far-from-equilibrium systems and bounded self-organizing processes may be instructive in revealing some of the processes behind lifes origin. In this workshop paper we will detail the outcomes of the 8th TDE meeting in Tokyo, summarizing the focus groups discussions regarding 1) the determination of some of the required conditions for generating geochemical disequilibria for life to originate on a wet, rocky world; 2) the spatial and temporal scales for the origin of life;3) lifes use of disequilibria and the relationship of life itself to self-organizing systems in an aqueous inorganic milieu; and 4) pathways forward for achieving the laboratory simulation of far-from-equilibrium systems concerning prebiotic chemical processes.
We sought to determine whether a high-risk group could be defined among patients with operable breast cancer in whom a search of occult central nervous system (CNS) metastases was justified.
We ...evaluated data from 9524 women with early breast cancer (42% node-negative) who were randomized in International Breast Cancer Study Group clinical trials between 1978 and 1999, and treated without anthracyclines, taxanes, or trastuzumab. We identified patients whose site of first event was CNS and those who had a CNS event at any time.
Median follow-up was 13 years. The 10-year incidence (10-yr) of CNS relapse was 5.2% (1.3% as first recurrence). Factors predictive of CNS as first recurrence included: node-positive disease (10-yr = 2.2% for > 3 N+), estrogen receptor-negative (2.3%), tumor size > 2 cm (1.7%), tumor grade 3 (2.0%), < 35 years old (2.2%), HER2-positive (2.7%), and estrogen receptor-negative and node-positive (2.6%). The risk of subsequent CNS recurrence was elevated in patients experiencing lung metastases (10-yr = 16.4%).
Based on this large cohort we were able to define risk factors for CNS metastases, but could not define a group at sufficient risk to justify routine screening for occult CNS metastases.
Late recurrences in postmenopausal women with hormone receptor-positive breast cancers remain an important challenge. Avoidance or delayed development of resistance represents the main objective in ...extended endocrine therapy (ET). In animal models, resistance was reversed with restoration of circulating estrogen levels during interruption of letrozole treatment. This phase III, randomized, open-label Study of Letrozole Extension (SOLE) studied the effect of extended intermittent letrozole treatment in comparison with continuous letrozole. In parallel, the SOLE estrogen substudy (SOLE-EST) analyzed the levels of estrogen during the interruption of treatment.
SOLE enrolled 4884 postmenopausal women with hormone receptor-positive, lymph node-positive, operable breast cancer between December 2007 and October 2012 and among them, 104 patients were enrolled in SOLE-EST. They must have undergone local treatment and have completed 4-6 years of adjuvant ET. Patients were randomized between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day for 9 months followed by a 3-month interruption in years 1-4 and then 2.5 mg/day during all of year 5).
Intention-to-treat population included 4851 women in SOLE (n = 2425 in the intermittent and n = 2426 in the continuous letrozole groups) and 103 women in SOLE-EST (n = 78 in the intermittent and n = 25 in the continuous letrozole groups). After a median follow-up of 84 months, 7-year disease-free survival (DFS) was 81.4% in the intermittent group and 81.5% in the continuous group (hazard ratio: 1.03, 95% confidence interval: 0.91-1.17). Reported adverse events were similar in both groups. Circulating estrogen recovery was demonstrated within 6 weeks after the stop of letrozole treatment.
Extended adjuvant ET by intermittent administration of letrozole did not improve DFS compared with continuous use, despite the recovery of circulating estrogen levels. The similar DFS coupled with previously reported quality-of-life advantages suggest intermittent extended treatment is a valid option for patients who require or prefer a treatment interruption.
•Disease-free survival after 7 years was similar with extended intermittent or continuous letrozole in breast cancer.•Circulating estrogen level was restored 6 weeks after interruption of extended letrozole treatment.•Extended intermittent letrozole treatment is safe for postmenopausal women with hormone receptor-positive breast cancers.•Results coupled with reported quality-of-life data should be reassuring for patients who need to interrupt extended therapy.
This European phase IIIb, expanded-access multicenter trial evaluated the safety of EVE plus EXE in a patient population similar to BOLERO-2.
Post-menopausal women aged ≥18 years with hormone ...receptor-positive, human epidermal growth factor-receptor-2–negative advanced breast cancer (ABC) recurring/progressing during/after prior non-steroidal aromatase inhibitors were enrolled. The primary objective was safety of EVE plus EXE based on frequency of adverse events (AEs), and serious AEs (SAEs). The secondary objective was to evaluate AEs of grade 3/4 severity.
The median treatment duration was 5.1 months 95% confidence interval (CI) 4.8–5.6 for EVE and 5.3 months (95% CI 4.8–5.6) for EXE. Overall, 2131 patients were included in the analysis; 81.8% of patients experienced EVE- or EXE-related or EVE/EXE-related AEs (investigator assessed); 27.2% were of grade 3/4 severity. The most frequently reported non-hematologic AEs were (overall %, % EVE-related) stomatitis (52.8%; 50.8%) and asthenia (22.8%; 14.6%). The most frequently reported hematologic AEs were (overall %, % EVE-related) anemia (14.4%; 8.1%) and thrombocytopenia (5.9%; 4.6%). AE-related treatment discontinuations were higher in elderly (≥70 years) versus non-elderly patients (23.8% versus 13.0%). The incidence of EVE-related AEs in both elderly and non-elderly patients appeared to be lower in first-line ABC versus later lines. The incidence of AEs (including stomatitis/pneumonitis) was independent of BMI status (post hoc analysis). Overall, 8.5% of patients experienced at least one EVE-related SAE. Of the 121 on-treatment deaths (5.7%), 66 (3.1%) deaths were due to disease progression and 46 (2.2%) due to AEs; 4 deaths were suspected to be EVE-related.
This is the largest ever reported safety dataset on a general patient population presenting ABC treated with EVE plus EXE and included a sizeable elderly subset. Although the patients were more heavily pretreated, the safety profile of EVE plus EXE in BALLET was consistent with BOLERO-2.
EudraCT Number: 2012-000073-23.
Adjuvant Trastuzumab with chemotherapy is the gold standard for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (HER2+ EBC). Older patients have been largely ...under-represented in clinical trials, and few data on Trastuzumab cardiotoxicity have been reported in this subgroup.
Four hundred and ninety-nine consecutive HER2+ EBC patients were treated with adjuvant trastuzumab and chemotherapy (aTrastC) at 10 Italian institutions. We evaluated disease prevalence and patient characteristics in the patients older than 60 years of age (over-60), prevalence of aTrastC cardiotoxicity and risk factors.
There were 160 ‘over-60’ patients (32%), in whom a higher prevalence of hypertension, diabetes, renal dysfunction, dyslipidemia and treatment with ACEi (40 versus 8%) and beta blockers (20 versus 8%) was found than in the younger patients (339 = 68%). Clinical heart failure occurred in 6% of the ‘over-60’ and in 2% of the younger patients. A reduction in left ventricular ejection fraction of >10 points was detected in 33% of the ‘over-60’ and in 23% of the younger patients (all P < 0.05). aTrastC was discontinued in 10% of the ‘over-60’ and in 4% of the younger patients (P = 0.003), restarted in 44% of the ‘over-60’ and in 58% of the younger women (P = ns).
In clinical practice, 32% of HER2+ EBC patients treated with aTrastC are ‘over-60’. These patients have an increased cardiovascular risk profile and develop aTrastC cardiotoxicity commonly.
In recent years, integrated building design practices based on the definition of “green building” criteria as common standards of measurement have been promoted. For example, Green Building Rating ...Systems such as LEED (US) and BREEAM (UK) provide national standards for developing high-performance sustainable buildings. However, integrated environmental accounting methods and global sustainability indicators are still required to evaluate the general environmental performances of buildings, because housing is greatly concerned with global environmental problems such as the use of non-renewable energy, the overexploitation of materials, the exhaustion of resources and the wasting of energy.
In this work, an emergy (spelled with an “m”) analysis has been applied to a building to account for the main energy and material inflows to the processes of building manufacturing, maintenance and use. Building materials, technologies and structural elements have been measured and compared to each other in order to evaluate their impacts and to provide a basic calculation that may be used for evaluation and selection. A comprehensive appraisal of the building industry is then expected through a series of synthetic indices. Results represent a source of information that will also be useful for future studies on the urban and regional scale.
Abstract Purpose The aim of the study was to analyze the modification of total and regional body composition in early breast cancer patients treated with aromatase inhibitors (AIs). Methods This is a ...prospective, single-center, observational, longitudinal study. Four-hundred and twenty-eight patients treated with adjuvant aromatase inhibitors were enrolled at the Medical Oncology and Breast Unit of Spedali Civili Hospital in Brescia from September 2014 to June 2022. Several body composition parameters including total and regional fat and lean body mass were investigated with dual-energy X-ray absorptiometry (DXA) scan at baseline and after 18 months of treatment with aromatase inhibitors. Results A significant increase in fat body mass (mean + 7.2%, 95% confidence interval CI: 5.5;8.9%) and a reduction in lean body mass (mean −3.1%, 95% CI −3.9; −2.4) were documented in this population. The changes in fat and lean body mass varied considerably according to different body districts ranging between + 3.2% to + 10.9% and from−1.3% to −3.9%, respectively. Conclusion Aromatase inhibitor adjuvant therapy in early breast cancer is associated with changes in body composition, with a wide variability among different body districts, leading to a risk of sarcopenic obesity. Supervised physical exercise that focuses on single body parts that may display detrimental variations may be beneficial for AIs treated patients.
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