Pregnancy-associated breast cancer - Special features in diagnosis and treatment

For obvious psychological reasons it is difficult to associate pregnancy - a life-giving period of our existence with life-threatening malignancies. Symptoms pointing to malignancy are often ignored by both patients and physicians, and this, together with the greater difficulty of diagnostic imaging, probably results in the proven delay in the detection of breast cancers during pregnancy. The diagnosis and treatment of breast cancer are becoming more and more important, as the fulfillment of the desire to have children is increasingly postponed until a later age associated with a higher risk of carcinoma, and improved cure rates of solid tumors no longer exclude subsequent pregnancies. The following article summarizes the special features of the diagnosis and primary therapy of pregnancy-associated breast cancer with particular consideration of cytostatic therapy

The potential hazard of staphylococci and micrococci to human subjects in a life support systems evaluator and on a diet of precooked freeze dehydrated foods

Distribution, and hazards of indigenous microbial populations in humans during prolonged space flight simulatio

Preliminary Observations on New Images of the Elysium Frozen Sea Deposits from HRSC Mars Express

Abstract not available

Phototriggered Ru(II)−Dimethylsulfoxide Linkage Isomerization in Crystals and Films

Photochromic materials are of interest because of their potential applications in optical information storage devices. Measurements on photochromic sodium nitroprusside (Na_2[Fe(CN)_5(NO)]) indicate that two metastable states are formed by irradiations of the crystalline solid:  the first is an isonitrosyl (O-bonded NO); the second is an η^2-NO (side-on) complex. Phototriggered linkage isomerizations also occur in dimethylsulfoxide (dmso) complexes: notably, both photochemical Ru−S → Ru−O and thermal Ru−O → Ru−S reactions are observed in dmso solutions of [Ru(bpy)_2(dmso)_2]^(2+) (bpy = 2,2‘-bipyridine); and, as reported here, we find photochromism attributable to Ru−S → Ru−O rearrangement upon visible excitation of [Ru(tpy)(bpy)(dmso)]^(2+) (tpy = 2,2‘:6‘,2‘ ‘-terpyridine) in single crystals and films as well as in solution

Tracking internal temperature and structural dynamics during nail penetration of lithium-ion cells

Mechanical abuse of lithium-ion batteries is widely used during testing to induce thermal runaway, characterize associated risks, and expose cell and module vulnerabilities. However, the repeatability of puncture or ‘nail penetration’ tests is a key issue as there is often a high degree of variability in the resulting thermal runaway process. In this work, the failure mechanisms of 18650 cells punctured at different locations and orientations are characterized with respect to their internal structural degradation, and both their internal and surface temperature, all of which are monitored in real time. The initiation and propagation of thermal runaway is visualized via high-speed synchrotron X-ray radiography at 2000 frames per second, and the surface and internal temperatures are recorded via infrared imaging and a thermocouple embedded in the tip of the penetrating nail, respectively. The influence of the nail, as well as how and where it penetrates the cell, on the initiation and propagation of thermal runaway is described and the suitability of this test method for representing in-field failures is discussed

Characterising thermal runaway within lithium-ion cells by inducing and monitoring internal short circuits

Lithium-ion batteries are being used in increasingly demanding applications where safety and reliability are of utmost importance. Thermal runaway presents the greatest safety hazard, and needs to be fully understood in order to progress towards safer cell and battery designs. Here, we demonstrate the application of an internal short circuiting device for controlled, on-demand, initiation of thermal runaway. Through its use, the location and timing of thermal runaway initiation is pre-determined, allowing analysis of the nucleation and propagation of failure within 18 650 cells through the use of high-speed X-ray imaging at 2000 frames per second. The cause of unfavourable occurrences such as sidewall rupture, cell bursting, and cell-to-cell propagation within modules is elucidated, and steps towards improved safety of 18 650 cells and batteries are discussed

Aberrant regulation of RANKL/OPG in women at high risk of developing breast cancer

Breast cancer is the most common female cancer, affecting approximately one in eight women during their lifetime in North America and Europe. Receptor Activator of NF-kB Ligand (RANKL), its receptor RANK and the natural antagonist osteoprotegerin (OPG) are essential regulators of bone resorption. We have initially shown that RANKL/RANK are essential for hormone-driven mammary epithelial proliferation in pregnancy and RANKL/RANK have been implicated in mammary stem cell biology. Using genetic mouse-models, we and others identified the RANKL/RANK system as a key regulator of sex hormone, BRCA1-mutation, and oncogene-driven breast cancer and we proposed that RANKL/RANK might be involved in the initiation of breast tumors. We now report that in postmenopausal women without known genetic predisposition, high RANKL and progesterone serum levels stratify a subpopulation of women at high risk of developing breast cancer 12-24 months before diagnosis (5.33-fold risk, 95%CI 1.5-25.4; P=0.02). In women with established breast cancer, we demonstrate that RANKL/OPG ratios change dependent on the presence of circulating tumor cells (CTCs). Finally, we show in a prospective human breast cancer cohort that alterations in RANKL/OPG ratios are significantly associated with breast cancer manifestation. These data indicate that the RANKL/RANK/OPG system is deregulated in post-menopausal women at high risk for breast cancer and in women with circulating tumor cells. Thus, serum levels of RANKL/OPG are potentially indicative of predisposition and progression of breast cancer in humans. Advancement of our findings towards clinical application awaits prior validation in independent patient cohorts

Methylation patterns in serum DNA for early identification of disseminated breast cancer

BACKGROUND: Monitoring treatment and early detection of fatal breast cancer (BC) remains a major unmet need. Aberrant circulating DNA methylation (DNAme) patterns are likely to provide a highly specific cancer signal. We hypothesized that cell-free DNAme markers could indicate disseminated breast cancer, even in the presence of substantial quantities of background DNA. METHODS: We used reduced representation bisulfite sequencing (RRBS) of 31 tissues and established serum assays based on ultra-high coverage bisulfite sequencing in two independent prospective serum sets (n = 110). The clinical use of one specific region, EFC#93, was validated in 419 patients (in both pre- and post-adjuvant chemotherapy samples) from SUCCESS (Simultaneous Study of Gemcitabine-Docetaxel Combination adjuvant treatment, as well as Extended Bisphosphonate and Surveillance-Trial) and 925 women (pre-diagnosis) from the UKCTOCS (UK Collaborative Trial of Ovarian Cancer Screening) population cohort, with overall survival and occurrence of incident breast cancer (which will or will not lead to death), respectively, as primary endpoints. RESULTS: A total of 18 BC specific DNAme patterns were discovered in tissue, of which the top six were further tested in serum. The best candidate, EFC#93, was validated for clinical use. EFC#93 was an independent poor prognostic marker in pre-chemotherapy samples (hazard ratio [HR] for death = 7.689) and superior to circulating tumor cells (CTCs) (HR for death = 5.681). More than 70% of patients with both CTCs and EFC#93 serum DNAme positivity in their pre-chemotherapy samples relapsed within five years. EFC#93-positive disseminated disease in post-chemotherapy samples seems to respond to anti-hormonal treatment. The presence of EFC#93 serum DNAme identified 42.9% and 25% of women who were diagnosed with a fatal BC within 3–6 and 6–12 months of sample donation, respectively, with a specificity of 88%. The sensitivity with respect to detecting fatal BC was ~ 4-fold higher compared to non-fatal BC. CONCLUSIONS: Detection of EFC#93 serum DNAme patterns offers a new tool for early diagnosis and management of disseminated breast cancers. Clinical trials are required to assess whether EFC#93-positive women in the absence of radiological detectable breast cancers will benefit from anti-hormonal treatment before the breast lesions become clinically apparent

Magnetic field-assisted solidification of W319 Al alloy qualified by high-speed synchrotron tomography

Magnetic fields have been widely used to control solidification processes. Here, high-speed synchrotron X-ray tomography was used to study the effect of magnetic fields on solidification. We investigated vertically upward directional solidification of an Al-Si-Cu based W319 alloy without and with a transverse magnetic field of 0.5 T while the sample was rotating. The results revealed the strong effect of a magnetic field on both the primary α-Al phase and secondary β-Al5FeSi intermetallic compounds (IMCs). Without the magnetic field, coarse primary α-Al dendrites were observed with a large macro-segregation zone. When a magnetic field is imposed, much finer dendrites with smaller primary arm spacing were obtained, while macro-segregation was almost eliminated. Segregated solutes were pushed out of the fine dendrites and piled up slightly above the solid/liquid interface, leading to a gradient distribution of the secondary β-IMCs. This work demonstrates that rotating the sample under a transversal magnetic field is a simple yet effective method to homogenise the temperature and composition distributions, which can be used to control the primary phase and the distribution of iron-rich intermetallics during solidification