574 research outputs found

    Literature

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    Literature has been proposed as a means to enrich an understanding of ethical issues within medicine and health care and as a resource in medical education. Its proponents argue for the value of understanding human suffering, and the experience of health care, through literature, rather than solely through the more abstract and analytic philosophical methods of bioethics. Literature is claimed to serve as a corrective to the rational and individualist approaches of bioethics, by drawing attention to ‘our vulnerable and interdependent human existence.’ In this essay the history of a relationship between ethics and literature is discussed, along with more recent scholarship on the ethical relevance of literature, and research focusing on the constitution of ethics as literary form. It is apparent that literature, and especially futurist writing and science fiction, has an influence on the construction and understanding of ethical issues for both specialist practitioners and the lay public. It is concluded that literature enhances understanding of ethical issues in health care and research, and the manner in which it does so needs to be better understood through the skills of literary analysis as a necessary complement to bioethical analysis

    Two fundamentally different drivers of dipolarizations at Saturn

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    Solar wind energy is transferred to planetary magnetospheres via magnetopause reconnection, driving magnetospheric dynamics. At giant planets like Saturn, rapid rotation and internal plasma sources from geologically active moons also drive magnetospheric dynamics. In both cases, magnetic energy is regularly released via magnetospheric current redistributions that usually result in a change of the global magnetic field topology (named substorm dipolarization at Earth). Besides this substorm dipolarization, the front boundary of the reconnection outflow can also lead to a strong but localized magnetic dipolarization, named a reconnection front. The enhancement of the north-south magnetic component is usually adopted as the indicator of magnetic dipolarization. However, this field increase alone cannot distinguish between the two fundamentally different mechanisms. Using measurements from Cassini, we present multiple cases whereby we identify the two distinct types of dipolarization at Saturn. A comparison between Earth and Saturn provides new insight to revealing the energy dissipation in planetary magnetospheres

    A Rotating Azimuthally Distributed Auroral Current System on Saturn Revealed by the Cassini Spacecraft

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    Stunning aurorae are mainly produced when accelerated electrons travel along magnetic field lines to collide with the atmosphere. The motion of electrons often corresponds to the evolution of a magnetic field-aligned current system. In the terrestrial magnetosphere, the current system is formed at the night-side sector, and thus produces an auroral bulge at night. Due to the different energy sources between Saturn and the Earth, it is expected that their auroral current systems are fundamentally different, although the specific auroral driver at Saturn is poorly understood. Using simultaneous measurements of the aurora, particles, magnetic fields, and energetic neutral atoms, we reveal that a chain of paired currents, each of which includes a downward and an upward current branch, is formed in Saturn's magnetosphere, which generates separated auroral patches. These findings inform similar auroral current structures between the Earth and Saturn, while the difference is that Saturn's unique mass and energy sources lead to a rotational characteristic

    Ice-sheet collapse and sea-level rise at the BĂžlling warming 14,600 years ago

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    Past sea-level records provide invaluable information about the response of ice sheets to climate forcing. Some such records suggest that the last deglaciation was punctuated by a dramatic period of sea-level rise, of about 20 metres, in less than 500 years. Controversy about the amplitude and timing of this meltwater pulse (MWP-1A) has, however, led to uncertainty about the source of the melt water and its temporal and causal relationships with the abrupt climate changes of the deglaciation. Here we show that MWP-1A started no earlier than 14,650 years ago and ended before 14,310 years ago, making it coeval with the Bolling warming. Our results, based on corals drilled offshore from Tahiti during Integrated Ocean Drilling Project Expedition 310, reveal that the increase in sea level at Tahiti was between 12 and 22 metres, with a most probable value between 14 and 18 metres, establishing a significant meltwater contribution from the Southern Hemisphere. This implies that the rate of eustatic sea-level rise exceeded 40 millimetres per year during MWP-1A

    High nuclear MSK1 is associated with longer survival in breast cancer patients

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    Purpose: Mitogen- and stress- activated kinases (MSKs) are important substrates of the mitogen-activated protein kinase (MAPK)-activated protein kinase family. MSK1 and MSK2 are both nuclear serine/threonine protein kinases, with MSK1 being suggested to potentially play a role in breast cancer cell proliferation, cell cycle progression, cell migration, invasion and tumour growth. The aim of the current study was to assess MSK1 protein expression in breast cancer tumour specimens, evaluating its prognostic significance. Methods: A large cohort of 1902 early stage invasive breast cancer patients was used to explore the expression of MSK1. Protein expression was examined using standard immunohistochemistry on tissue microarrays. Results: Low MSK1 protein expression was associated with younger age (P=0.004), higher tumour grade (P<0.001), higher Nottingham Prognostic Index scores (P=0.007), negative ER (P<0.001) and PR (P<0.001) status, and with triple-negative (P<0.001) and basal-like (P<0.001) phenotypes. Low MSK1 protein expression was significantly associated with shorter time to distant metastasis (P<0.001), and recurrence (P=0.013) and early death due to breast cancer (P=0.01). This association between high MSK1 expression and improved breast cancer-specific survival was observed in the whole cohort (P=0.009) and in the HER2 negative and non-basal like tumours (P=0.006 and P=0.024, respectively). Multivariate analysis including other prognostic variables indicated that MSK1 is not an independent marker of outcome. Conclusions: High MSK1 is associated with improved breast cancer-specific survival in early stage invasive breast cancer patients, and has additional prognostic value in HER2 negative and non-basal like disease. Although not an independent marker of outcome we believe such findings, and significant associations with well-established negative prognostic factors (age, grade, Nottingham Prognostic Index, hormone receptor status, time to distant metastasi

    The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

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    The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future

    Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival

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    Impaired apoptosis is one of the hallmarks of cancer. Caspase-3 and -8 are key regulators of the apoptotic response and have been shown to interact with the calpain family, a group of cysteine proteases, during tumorigenesis. The current study sought to investigate the prognostic potential of caspase-3 and -8 in breast cancer, as well as the prognostic value of combinatorial caspase and calpain expression. A large cohort (n = 1902) of early stage invasive breast cancer patients was used to explore the expression of caspase-3 and -8. Protein expression was examined using standard immunohistochemistry on tissue microarrays. High caspase-3 expression, but not caspase-8, is significantly associated with adverse breast cancer-specific survival (P = 0.008 and P = 0.056, respectively). Multivariate analysis showed that caspase-3 remained an independent factor when confounding factors were included (hazard ratio (HR) 1.347, 95% confidence interval (CI) 1.086–1.670; P = 0.007). The analyses in individual subgroups demonstrated the significance of caspase-3 expression in clinical outcomes in receptor positive (ER, PR or HER2) subgroups (P = 0.001) and in non-basal like subgroup (P = 0.029). Calpain expression had been previously assessed. Significant association was also found between high caspase-3/high calpain-1 and breast cancer-specific survival in the total patient cohort (P = 0.005) and basal-like subgroup (P = 0.034), as indicated by Kaplan–Meier analysis. Caspase-3 expression is associated with adverse breast cancer-specific survival in breast cancer patients, and provides additional prognostic values in distinct phenotypes. Combinatorial caspase and calpain expression can predict worse prognosis, especially in basal-like phenotypes. The findings warrant further validation studies in independent multi-centre patient cohorts

    On the curvature in logarithmic plots of rate coefficients for chemical reactions

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    In terms of the reduced potential energy barrier ζ = ΔuTS/kT, the rate coefficients for chemical reactions are usually expressed as proportional to e-ζ. The coupling between vibrational modes of the medium to the reaction coordinate leads to a proportionality of the regularized gamma function of Euler Q(a,ζ) = Γ(a,ζ)/Γ(a), with a being the number of modes coupled to the reaction coordinate. In this work, the experimental rate coefficients at various temperatures for several chemical reactions were fitted to the theoretical expression in terms of Q(a,ζ) to determine the extent of its validity and generality. The new expression affords lower deviations from the experimental points in 29 cases out of 38 and it accounts for the curvature in the logarithmic plots of rate coefficients versus inverse temperature. In the absence of tunneling, conventional theories predict the curvature of these plots to be identically zero

    Malnutrition and inflammation in acute kidney injury due to earthquake-related crush syndrome

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    <p>Abstract</p> <p>Background</p> <p>Malnutrition and inflammation are common and serious complications in patients with acute kidney injury (AKI). However, the profile of these complications in patients with AKI caused by crush syndrome (CS) remains unclear. This study describes the clinical characteristics of malnutrition and inflammation in patients with AKI and CS due to the Wenchuan earthquake.</p> <p>Methods</p> <p>One thousand and twelve victims and eighteen healthy adults were recruited to the study. They were divided into five groups: Group A was composed of victims without CS and AKI (904 cases); Group B was composed of patients with CS and AKI who haven't received renal replacement therapy (RRT) (57 cases); and Group C was composed of patients with CS and AKI receiving RRT (25 cases); Group D was composed of earthquake victims with AKI but without CS (26 cases); and Group E was composed of 18 healthy adult controls. The C-reactive protein (CRP), prealbumin, transferrin, interleukin-6 and TNF-α were measured and compared between Group E and 18 patients from Group C.</p> <p>Results</p> <p>The results indicate that participants in Group C had the highest level of serum creatinine, blood urea nitrogen and uric acid. Approximately 92% of patients with CS who had RRT were suffering from hypoalbuminemia. The interleukin-6 and CRP levels were significantly higher in patients with CS AKI receiving RRT than in the control group. Patients in Group C received the highest dosages of albumin, plasma or red blood cell transfusions. One patient in Group C died during treatment.</p> <p>Conclusions</p> <p>Malnutrition and inflammation was common in patients with earthquake-related CS and had a negative impact on the prognosis of these subjects. The results of this study indicate that the use of RRT, intensive nutritional supplementation and transfusion alleviated the degree of malnutrition and inflammation in hemodialysis patients with crush syndrome.</p

    Actively evolving subglacial conduits and eskers initiate ice shelf channels at an Antarctic grounding line

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    Ice-shelf channels are long curvilinear tracts of thin ice found on Antarctic ice shelves. Many of them originate near the grounding line, but their formation mechanisms remain poorly understood. Here we use ice-penetrating radar data from Roi Baudouin Ice Shelf, East Antarctica, to infer that the morphology of several ice-shelf channels is seeded upstream of the grounding line by large basal obstacles indenting the ice from below. We interpret each obstacle as an esker ridge formed from sediments deposited by subglacial water conduits, and calculate that the eskers’ size grows towards the grounding line where deposition rates are maximum. Relict features on the shelf indicate that these linked systems of subglacial conduits and ice-shelf channels have been changing over the past few centuries. Because ice-shelf channels are loci where intense melting occurs to thin an ice shelf, these findings expose a novel link between subglacial drainage, sedimentation and ice-shelf stability
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