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Standard chemoradiotherapy with infusional 5FU for locally advanced pancreatic cancer (LAPC) has limited efficacy in this disease. The combination of Capecitabine (Cap) and Gemcitabine (Gem) are synergistic and are potent radiosensitisers. The aim of this phase I trial was thus to determine the highest administered dose of the Cap plus Gem combination with radical radiotherapy (RT) for LAPC. Patients had LAPC, adequate organ function, ECOG PS 0-1. During RT, Gem was escalated from 20-50 mg m-2 day-1 (twice per week), and Cap 800-2000 mg m-2 day-1 (b.i.d, days 1-5 of each week). Radiotherapy 50.4 Gy/28 fractions/5.5 weeks, using 3D-conformal techniques. Three patients were entered to each dose level (DL). Dose-limiting toxicity(s) (DLTs) were based on treatment-related toxicities. Twenty patients were accrued. Dose level (DL) 1: Cap/Gem; 800/20 mg m -2 day-1 (3 patients), DL2: 1000/20 (12 patients), DL3: 1300/30 (5 patients). Dose-limiting toxicities were observed in DL3; grade 3 dehydration (1 patient) and grade 3 diarrhoea and dehydration (1 patient). Dose level 2 was the recommend phase 2 dose. Disease control rate was 75%: PR=15%, SD=60%. Median overall survival was 11.2 months. The addition of Cap and Gem to radical RT was feasible and active and achieved at relatively low doses. © 2009 Cancer Research UK.

Preclinical data indicates that cyclooxygenase-2 (COX-2) inhibition impairs plasma cell growth and potentially synergizes with thalidomide. We performed a trial in previously treated patients with myeloma using thalidomide up to a maximum dose of 800 mg/d with celecoxib (400 mg bid). Outcomes were compared with a prior trial of thalidomide. Sixty-six patients with median age of 67 (range, 43-85) received a median dose of thalidomide and celecoxib of 400 and 800 mg/d, respectively, with median durations of treatment of 27 and 13 weeks, respectively. The most common toxicities associated with premature discontinuation of celecoxib (n = 30 of 53, 57%) were fluid retention and deterioration of renal function. Overall response rate (RR) was 42% and with 20 months median follow-up; the actuarial median progression-free survival and overall survival were 6.8 and 21.4 months, respectively. Unlike our prior study, age >65 years was not predictive of inferior RR due to improvement in RR in older patients with the combination (37% versus 15%, P = 0.08). The RR was superior in patients who received a total dose of celecoxib exceeding 40 g in the first 8 weeks of therapy (62% versus 30%, P = 0.021). Progression-free survival and overall survival were also improved. Other predictors for inferior progression-free survival were age >65 years (P = 0.016) and elevated beta2-microglobulin (P = 0.017). This study provides evidence that the addition of high-dose celecoxib adds to the antimyeloma activity of thalidomide but this comes with unacceptable toxicity. Future studies should use newer COX-2 inhibitors with thalidomide, or their respective derivatives. © 2005 American Association for Cancer Research.

We report a functional magnetic resonance imaging (fMRI) adaptation study of two well-described patients, DF and PS, who present face identity recognition impairments (prosopagnosia) following brain-damage. Comparing faces to non-face objects elicited activation in all visual areas of the cortical face processing network that were spared subsequent to brain damage. The common brain lesion in the two patients was in the right inferior occipital cortex, in the territory of the right "occipital face area" ('OFA'), which strengthens the critical role of this region in processing faces. Despite the lesion to the right 'OFA', there was normal range of sensitivity to faces in the right "fusiform face area" ('FFA') in both patients, supporting a non-hierarchical model of face processing at the cortical level. At the same time, however, sensitivity to individual face representations, as indicated by release from adaptation to identity, was abnormal in the right 'FFA' of both patients. This suggests that the right 'OFA' is necessary to individualize faces, perhaps through reentrant interactions with other cortical face sensitive areas. The lateral occipital area (LO) is damaged bilaterally in patient DF, who also shows visual object agnosia. However, in patient PS, in whom LO was spared, sensitivity to individual representations of non-face objects was still found in this region, as in the normal brain, consistent with her preserved object recognition abilities. Taken together, these observations, which fruitfully combine functional imaging and neuropsychology, place strong constraints on the possible functional organization of the cortical areas mediating face processing in the human brain.

We sought to determine the effects of prism adaptation on peripherally cued visual attention shifting in patients with spatial neglect, using a task devised by Egly et al. (J Exp Psychol Gen 123:161–177, 1994) based on the classic Posner paradigm. This task allowed a comparison of “within-object” versus “between-object” attention shifts. A display was presented containing two parallel outline rectangles, and subjects were asked to make rapid responses to a target, which would appear at one end of one of the rectangles. The target location was pre-cued with 75% validity: on invalid trials attention was directed either to the other end of the same rectangle, or to the other rectangle. Healthy subjects and right-hemisphere patients without neglect showed a left-right symmetrical pattern, with a larger validity effect when required to shift attention between rectangles, thus indicating a greater difficulty of attention-shifting between than within the respective shapes. The neglect patients showed the typical leftward “disengage deficit” previously observed in neglect, but only for attention shifts between objects, indicating that the effect is object-based rather than purely spatial. A comparison of vertical and horizontal shift costs showed that this attention-shifting deficit for left-hemifield target stimuli was directional rather than hemifield-based: it was absent for vertical shifts of attention within the left hemifield. Finally, we found that prism adaptation abolished the disengage deficit. We found no effects of prism adaptation in the control subjects. We argue that prism adaptation has a powerful effect on one of the fundamental manifestations of the neglect syndrome.

Eleven laboratories have collaborated to study chloroplast DNA (cpDNA) variation in black poplar (Populus nigra L.) across Europe in order to improve our understanding of the location of glacial refugia and the subsequent postglacial routes of recolonisation. A common analysis based on the restricted fragments produced by five primer pairs was used to determine the cpDNA haplotype of 637 samples obtained from genebank collections established in nine European countries. Haplotype 2 was particularly common and was found in 46% of the non-hybrid samples. A total of 81 non-hybrid chloroplast variants were detected. Three haplotypes (from four trees believed to originate from Eastern Europe) clustered together and were very different from the rest of the samples. The remaining samples were divided into two groups, one of which had a largely eastern distribution and samples from the other group were mostly located in the west. This, along with the fact that Spain in the southwest and Austria and Italy in the southeast had high diversity, suggest that there were ice age refugia of black poplar in both southwestern (Spain) and southeastern Europe (Italy and/or Balkan). Results also indicate that the Pyrenees formed a significant barrier, since only 7 of the 45 haplotypes in Spain exist elsewhere in Europe