WORCESTER (Reino Unido). Planos de población. 1780 (1779). 1:2400

Escalas gráficas de 1300 pies ó 433 1/3 yardas [= 16,4 cm]. Orientado con lis en rosa de ocho vientosToponimia de calles y plazasRelación de los edificios religiosos, hospitales, edificios públicos y casas de prebendados, indicados por clave alfanuméricaTabla de los distritos municipales o parroquias con su area y número de casas y habitantes existentesAmplia leyenda explicativa acerca de la situación, historia, división administrativa, industria y diputados de la ciudadNotas explicativas sobre la extension territorial de la ciudad y la batalla que tuvo lugar en sus alrededores el año de 1651, entre los ejércitos de Carlos II y Oliver CromwellTítulo enmarcado en arco conmemorativo coronado por el escudo de la ciudad, tras el cual se observa una vista de la misma y a cuyos pies se encuentran distribuídos objetos alusivos al comercio y la industriaForma parte de la Colección Mendoz

LICHFIELD (Reino Unido). Planos de población. 1781. 1:2400

Escalas gráficas de 440 yardas y 1320 pies [= 16,8 cm]. Coordenads de Lichfield referids al meridiano de Londres (N 52°41'/O 2°45'). Orientado con lis en rosa de ocho vientos prolongadosToponimia de calles y plazasIndica la parcelación del territorio municipalRelación de los principales edificios públicos civiles y religiosos, casas de preendados y puertas valladas, indicados por clave alfanuméricaTabla de distritos en que se divide la ciudad, señalando el número de casas y habitantes de cada uno de ellosAmplia leyenda explicativa sobre el nombre, situación, historia, gobierno municipal, ferias y mercados de la ciudadTítulo enmarcado en pedestal sobre el cual se asientan varias columnas, observándose un edificio al fondo ; al pie de aquél, mitra, manopla, casco y escudo y, en primer termino, libro de sermones de John HacketForma parte de la Colección MendozaInserta : "South West View of the Cathedra

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

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

Modulation of Mouse Coagulation Gene Transcription following Acute In Vivo Delivery of Synthetic Small Interfering RNAs Targeting HNF4α and C/EBPα

Hepatocyte nuclear factor 4α (HNF4α) and CCAAT/enhancer-binding protein α (C/EBPα) are important for the transcriptional control of coagulation factors. To determine in vivo the direct role of HNF4α and C/EBPα in control of genes encoding coagulation factors, a synthetic small interfering (si)RNA approach was used that enabled strong reduction of mouse hepatic HNF4α and C/EBPα under conditions that minimized target-related secondary effects. For both HNF4α and C/EBPα, intravenous injection of specific synthetic siRNAs (siHNF4α and siC/EBPα) resulted in more than 75% reduction in their liver transcript and protein levels 2 days post-injection. For siHNF4α, this coincided with marked and significantly reduced transcript levels of the coagulation genes Hrg, Proz, Serpina5, F11, F12, F13b, Serpinf2, F5, and F9 (in order of magnitude of effect) as compared to levels in control siRNA injected animals. Significant decreases in HNF4α target gene mRNA levels were also observed at 5 days post-siRNA injection, despite a limited level of HNF4α knockdown at this time point. Compared to HNF4α, C/EBPα knockdown had a modest impact on genes encoding coagulation factors. A strong reduction in C/EBPα transcript and protein levels resulted in significantly affected transcript levels of the control genes Pck1 and Fasn and a modest downregulation for coagulation genes Fba, Fbg and F5. F5 and F11 were the sole coagulation genes that were significantly affected upon prolonged (5 day) C/EBPα knockdown. We conclude that in the mouse, HNF4α has a direct and essential regulatory role for multiple hepatic coagulation genes, while a role for C/EBPα is more restricted. In addition, this study demonstrates that synthetic siRNA provides a simple and fast means for determining liver transcription factor involvement in vivo