164 research outputs found

    Aesthetic experience and spiritual well-being: locating the role of theological commitments

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    I discuss three accounts of the spiritual significance of aesthetic experience. Two of these perspectives I have taken from the recent literature in theological aesthetics, and the third I have constructed, building on Thomas Aquinas’s conception of the goods of the infused moral virtues. This broadly Thomistic approach occupies, I argue, a middle ground between the other two, on account of its distinctive understanding of the role of theological context in defining spiritually significant goods. These perspectives are not mutually exclusive, but they do present rather different conceptions of the ways in which aesthetic goods can contribute to spiritual well-being, and provide a focus for religious practice

    How stratospheric are deep stratospheric intrusions? LUAMI 2008

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    A large-scale comparison of water-vapour vertical-sounding instruments took place over central Europe on 17 October 2008, during a rather homogeneous deep stratospheric intrusion event (LUAMI, Lindenberg Upper-Air Methods Intercomparison). The measurements were carried out at four observational sites: Payerne (Switzerland), Bilthoven (the Netherlands), Lindenberg (north-eastern Germany), and the Zugspitze mountain (Garmisch-Partenkichen, German Alps), and by an airborne water-vapour lidar system creating a transect of humidity profiles between all four stations. A high data quality was verified that strongly underlines the scientific findings. The intrusion layer was very dry with a minimum mixing ratios of 0 to 35 ppm on its lower west side, but did not drop below 120 ppm on the higher-lying east side (Lindenberg). The dryness hardens the findings of a preceding study (“Part 1”, Trickl et al., 2014) that, e.g., 73 % of deep intrusions reaching the German Alps and travelling 6 days or less exhibit minimum mixing ratios of 50 ppm and less. These low values reflect values found in the lowermost stratosphere and indicate very slow mixing with tropospheric air during the downward transport to the lower troposphere. The peak ozone values were around 70 ppb, confirming the idea that intrusion layers depart from the lowermost edge of the stratosphere. The data suggest an increase of ozone from the lower to the higher edge of the intrusion layer. This behaviour is also confirmed by stratospheric aerosol caught in the layer. Both observations are in agreement with the idea that sections of the vertical distributions of these constituents in the source region were transferred to central Europe without major change. LAGRANTO trajectory calculations demonstrated a rather shallow outflow from the stratosphere just above the dynamical tropopause, for the first time confirming the conclusions in “Part 1” from the Zugspitze CO observations. The trajectories qualitatively explain the temporal evolution of the intrusion layers above the four stations participating in the campaign

    Beyond Barbour : A Theology of Science from Ancient and Modern Thinkers

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    In this chapter, I will challenge a common background relational assumption behind all of Barbour’s categories as intrinsically unfaithful to the universal nature of both science and religion, arguing instead that it is more fruitful to ask what a ‘theology of science’ might look like. ‘What does science do, and what is it for, within a theological worldview?’ This approach works very well in a teaching context when developed in two ways: (1) historically and (2) using Biblical studies in wisdom, especially in the book of Job. Students of this approach start to think in new ways and ask new questions, suggesting an approach to science or in its more ancient form natural philosophy – the ‘love of wisdom of natural things’ – that can draw on theological and cultural roots. I suggest that deriving a human narrative for science in this way can transform the way political discussions of ‘troubled technologies’ (genetic medicine, genetically modified organisms (GMOs), fracking, etc.) are framed and the way we approach science in education and the media

    Oral capecitabine as an alternative to i.v. 5-fluorouracil-based adjuvant therapy for colon cancer: safety results of a randomized, phase III trial

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    Background: Oral capecitabine achieves a superior response rate with an improved safety profile compared with bolus 5-fluorouracil-leucovorin (5-FU/LV) as first-line treatment for patients with metastatic colorectal cancer. We report here the results of a large phase III trial investigating adjuvant oral capecitabine compared with 5-FU/LV (Mayo Clinic regimen) in Dukes' C colon cancer. Patients and methods: Patients aged 18-75 years with resected Dukes' C colon carcinoma were randomized to receive 24 weeks of treatment with either oral capecitabine 1250 mg/m2 twice daily, days 1-14 every 21 days (n = 993), or i.v. bolus 5-FU 425 mg/m2 with i.v. leucovorin 20 mg/m2 on days 1-5, repeated every 28 days (n = 974). Results: Patients receiving capecitabine experienced significantly (P <0.001) less diarrhea, stomatitis, nausea/vomiting, alopecia and neutropenia, but more hand-foot syndrome than those receiving 5-FU/LV. Fewer patients receiving capecitabine experienced grade 3 or 4 neutropenia, febrile neutropenia/sepsis and stomatitis (P <0.001), although more experienced grade 3 hand-foot syndrome than those treated with 5-FU/LV (P <0.001). Capecitabine demonstrates a similar, favorable safety profile in patients aged <65 years or ≥65 years old. Conclusions: Based on its improved safety profile, capecitabine has the potential to replace 5-FU/LV as standard adjuvant treatment for patients with colon cancer. Efficacy results are expected to be available in 2004. Keywords: Adjuvant treatment, capecitabine, chemotherapy, colorectal cance

    Robo2-Slit1 dependent cell-cell interactions mediate assembly of the trigeminal ganglion

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    Vertebrate cranial sensory ganglia, responsible for sensation of touch, taste and pain in the face and viscera, are composed of both ectodermal placode and neural crest cells. The cellular and molecular interactions allowing generation of complex ganglia remain unknown. Here, we show that proper formation of the trigeminal ganglion, the largest of the cranial ganglia, relies on reciprocal interactions between placode and neural crest cells in chick, as removal of either population resulted in severe defects. We demonstrate that ingressing placode cells express the Robo2 receptor and early migrating cranial neural crest cells express its cognate ligand Slit1. Perturbation of this receptor-ligand interaction by blocking Robo2 function or depleting either Robo2 or Slit1 using RNA interference disrupted proper ganglion formation. The resultant disorganization mimics the effects of neural crest ablation. Thus, our data reveal a novel and essential role for Robo2-Slit1 signaling in mediating neural crest–placode interactions during trigeminal gangliogenesis

    Apoptosis and proliferation in the trigeminal placode

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    The neurogenic trigeminal placode develops from the crescent-shaped panplacodal primordium which delineates the neural plate anteriorly. We show that, in Tupaia belangeri, the trigeminal placode is represented by a field of focal ectodermal thickenings which over time changes positions from as far rostral as the level of the forebrain to as far caudal as opposite rhombomere 3. Delamination proceeds rostrocaudally from the ectoderm adjacent to the rostral midbrain, and contributes neurons to the trigeminal ganglion as well as to the ciliary ganglion/oculomotor complex. Proliferative events are centered on the field prior to the peak of delamination. They are preceded, paralleled and, finally, outnumbered by apoptotic events which proceed rostrocaudally from non-delaminating to delaminating parts of the field. Apoptosis persists upon regression of the placode, thereby exhibiting a massive “wedge” of apoptotic cells which includes the postulated position of the “ventrolateral postoptic placode” (Lee et al. in Dev Biol 263:176–190, 2003), merges with groups of lens-associated apoptotic cells, and disappears upon lens detachment. In conjunction with earlier work (Washausen et al. in Dev Biol 278:86–102, 2005) our findings suggest that apoptosis contributes repeatedly to the disintegration of the panplacodal primordium, to the elimination of subsets of premigratory placodal neuroblasts, and to the regression of placodes

    The Association Between Blood Coagulation Activity and Lung Function: A Population-Based Study

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    &lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Increased in susceptibility to thrombotic disease may be associated with lower lung function. If causal, this association may suggest an area for development of new interventions for lung disease. The aim of this study was to investigate the association between blood coagulation activation as measured by plasma d-dimers and lung function.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology/Principal Findings:&lt;/b&gt; We conducted a cross-sectional study on 2463 randomly selected adults in 1991 and followed up 1252 of these individuals in 2000. Plasma D-dimer levels, a marker of activity of blood coagulation pathways, were analysed in the baseline 1991 samples. There was an inverse cross-sectional association between plasma D-dimer and Forced Expiratory Volume in one second, with a decrease of 71 ml per mg FEU/ml increment in plasma D-dimer (95% confidence intervals CI: -135 to -6), and a decrease in Forced Vital Capacity (97 ml per mg FEU/ml increase in D-dimer, 95% CI: -170 to -24). These associations were attenuated after adjustment for serum highly sensitive CRP. No association was observed between plasma D-dimer and the decline in lung function between 1991 and 2000.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions/Significance:&lt;/b&gt; The cross-sectional findings are consistent with the hypothesis that activation of blood coagulation pathways is associated with decreased lung function, and that systemic inflammation may contribute to this relation. However, the lack of an association with decline in lung function suggests that clotting pathways that involve d-dimers may not be a promising therapeutic target for new interventions for respiratory disease.&lt;/p&gt

    Small Platforms, High Return: The Need to Enhance Investment in Small Satellites for Focused Science, Career Development, and Improved Equity

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    In the next decade, there is an opportunity for very high return on investment of relatively small budgets by elevating the priority of smallsat funding in heliophysics. We've learned in the past decade that these missions perform exceptionally well by traditional metrics, e.g., papers/year/\$M (Spence et al. 2022 -- arXiv:2206.02968). It is also well established that there is a "leaky pipeline" resulting in too little diversity in leadership positions (see the National Academies Report at https://www.nationalacademies.org/our-work/increasing-diversity-in-the-leadership-of-competed-space-missions). Prioritizing smallsat funding would significantly increase the number of opportunities for new leaders to learn -- a crucial patch for the pipeline and an essential phase of career development. At present, however, there are far more proposers than the available funding can support, leading to selection ratios that can be as low as 6% -- in the bottom 0.5th percentile of selection ratios across the history of ROSES. Prioritizing SmallSat funding and substantially increasing that selection ratio are the fundamental recommendations being made by this white paper.Comment: White paper submitted to the Decadal Survey for Solar and Space Physics (Heliophysics) 2024-2033; 6 pages, 1 figur

    NUTMEG: A randomized phase II study of nivolumab and temozolomide versus temozolomide alone in newly diagnosed older patients with glioblastoma.

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    BACKGROUND: There is an immunologic rationale to evaluate immunotherapy in the older glioblastoma population, who have been underrepresented in prior trials. The NUTMEG study evaluated the combination of nivolumab and temozolomide in patients with glioblastoma aged 65 years and older. METHODS: NUTMEG was a multicenter 2:1 randomized phase II trial for patients with newly diagnosed glioblastoma aged 65 years and older. The experimental arm consisted of hypofractionated chemoradiation with temozolomide, then adjuvant nivolumab and temozolomide. The standard arm consisted of hypofractionated chemoradiation with temozolomide, then adjuvant temozolomide. The primary objective was to improve overall survival (OS) in the experimental arm. RESULTS: A total of 103 participants were randomized, with 69 in the experimental arm and 34 in the standard arm. The median (range) age was 73 (65-88) years. After 37 months of follow-up, the median OS was 11.6 months (95% CI, 9.7-13.4) in the experimental arm and 11.8 months (95% CI, 8.3-14.8) in the standard arm. For the experimental arm relative to the standard arm, the OS hazard ratio was 0.85 (95% CI, 0.54-1.33). In the experimental arm, there were three grade 3 immune-related adverse events which resolved, with no unexpected serious adverse events. CONCLUSIONS: Due to insufficient evidence of benefit with nivolumab, the decision was made not to transition to a phase III trial. No new safety signals were identified with nivolumab. This complements the existing series of immunotherapy trials. Research is needed to identify biomarkers and new strategies including combinations
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