“Mapping for Rights”: Indigenous Peoples, Litigation and Legal Empowerment

In the process of adjudication and litigation, indigenous peoples are usually facing a very complex and demanding process to prove their rights to their lands and ancestral territories. Courts and tribunals usually impose a very complex and onerous burden of proof on the indigenous plaintiffs to prove their rights over their ancestral territories. To prove their rights indigenous peoples often have to develop map of their territories to prove their economic, cultural, and spiritual connections to their territories. This article reflects on the role played by the mapping of indigenous territories in supporting indigenous peoples’ land claims. It analyses the importance of mapping within the process of litigation, but also its the impact beyond the courtroom

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

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

Determining the Potential of DNA Damage Response (DDR) Inhibitors in Cervical Cancer Therapy

Cisplatin-based chemo-radiotherapy (CRT) is the standard treatment for advanced cervical cancer (CC) but the response rate is poor (46–72%) and cisplatin is nephrotoxic. Therefore, better treatment of CC is urgently needed. We have directly compared, for the first time, the cytotoxicity of four DDR inhibitors (rucaparib/PARPi, VE-821/ATRi, PF-477736/CHK1i and MK-1775/WEE1i) as single agents, and in combination with cisplatin and radiotherapy (RT) in a panel of CC cells. All inhibitors alone caused concentration-dependent cytotoxicity. Low ATM and DNA-PKcs levels were associated with greater VE-821 cytotoxicity. Cisplatin induced ATR, CHK1 and WEE1 activity in all of the cell lines. Cisplatin only activated PARP in S-phase cells, but RT activated PARP in the entire population. Rucaparib was the most potent radiosensitiser and VE-821 was the most potent chemosensitiser. VE-821, PF-47736 and MK-1775 attenuated cisplatin-induced S-phase arrest but tended to increase G2 phase accumulation. In mice, cisplatin-induced acute kidney injury was associated with oxidative stress and PARP activation and was prevented by rucaparib. Therefore, while all inhibitors investigated may increase the efficacy of CRT, the greatest clinical potential of rucaparib may be in limiting kidney damage, which is dose-limiting

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

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

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

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

How stratospheric are deep stratospheric intrusions? LUAMI 2008

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

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

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

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

&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

Chondrogenic and Gliogenic Subpopulations of Neural Crest Play Distinct Roles during the Assembly of Epibranchial Ganglia

In vertebrates, the sensory neurons of the epibranchial (EB) ganglia transmit somatosensory signals from the periphery to the CNS. These ganglia are formed during embryogenesis by the convergence and condensation of two distinct populations of precursors: placode-derived neuroblasts and neural crest- (NC) derived glial precursors. In addition to the gliogenic crest, chondrogenic NC migrates into the pharyngeal arches, which lie in close proximity to the EB placodes and ganglia. Here, we examine the respective roles of these two distinct NC-derived populations during development of the EB ganglia using zebrafish morphant and mutants that lack one or both of these NC populations. Our analyses of mutant and morphant zebrafish that exhibit deficiencies in chondrogenic NC at early stages reveal a distinct requirement for this NC subpopulation during early EB ganglion assembly and segmentation. Furthermore, restoration of wildtype chondrogenic NC in one of these mutants, prdm1a, is sufficient to restore ganglion formation, indicating a specific requirement of the chondrogenic NC for EB ganglia assembly. By contrast, analysis of the sox10 mutant, which lacks gliogenic NC, reveals that the initial assembly of ganglia is not affected. However, during later stages of development, EB ganglia are dispersed in the sox10 mutant, suggesting that glia are required to maintain normal EB ganglion morphology. These results highlight novel roles for two subpopulations of NC cells in the formation and maintenance of EB ganglia: chondrogenic NC promotes the early-stage formation of the developing EB ganglia while glial NC is required for the late-stage maintenance of ganglion morphology

Face Value: The Rhetoric of Facial Disfigurement in American Film and Popular Culture, 1917-27

This is the author accepted manuscript. The final version is available from Taylor & Francis via the DOI in this record.The return of facially disfigured men from the trenches of World War One occasioned a muted public reaction in the US. However, this article will show that burgeoning discourses concerning plastic surgery in the US also generated a significant reaction in the popular press, and that these were reflected, too, in several feature films dealing with facial surgery on disfigured veterans. Though several of these films depicted miraculous transformations occasioned by the surgeons, Robert Florey’s 1927 film, Face Value, focused on an American veteran with facial scarring that could not be repaired. The article will argue that this film drew strongly upon the increasingly prominent public presence of the gueules cassées in the US during 1926 and 1927. Depicting gueules cassées and their facial injuries prominently in several scenes, the film brought to attention difficult questions concerning the futures of such men, which the US media had hitherto rarely addressed