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Negligent delay in the diagnosis and treatment of infected cervical discitis leading to a permanent and partial C5 tetraplegia. Settlement: 8 March 2012. Christopher Wilson-Smith QC and Caroline Hallissey of Outer Temple Chambers, instructed by Antonia Jones of Stewarts Law LLP for the claimant. Sarah Pritchard of Kings Chambers, instructed by Vanessa Splaine of Weightmans LLP for the defendant.

Clinical negligence: Delayed delivery at birth causing chronic partial hypoxia probably due to cord compression during labour and the failure to deliver before the Claimant sustained injury. Settlement for approximately £9.2 m over the Claimant's lifetime. Liability: Clinical Negligence: Delayed delivery at birth causing chronic partial hypoxia probably due to cord compression during labour and the failure to deliver before the Claimant sustained injury. Quantum: Cerebral palsy. Settlement: 4 September 2012.

Analyses of chromosomal translocation and inversion breakpoints in sporadic acute myeloid leukemias have identified many transcription factors as playing a role in leukemogenesis. Studies of families with a Mendelian predisposition to hematological malignancies have identified the gene coding for the transcription factor RUNX1 as a leukemia-predisposing gene involved in the first steps of leukemogenesis. Using two families, another autosomal dominant familial leukemia locus was linked to chromosome band 16q22 where the CBFB gene maps. Although CBFB forms a core-binding factor transcriptional complex with RUNX1, previous analyses have excluded the CBFB gene as the leukemia-predisposing gene in these families. In the current study, we performed an extended molecular analysis in these families of the four other transcription factor genes in the 16q22 critical region as well as of two other genes with a known association with leukemia. Several previously undescribed but nonpathogenic sequence variants were identified. We demonstrated that the transcription factors E2F4, CTCF, NFATC3, and NFAT5, and the genes coding for NAD(P)H:quinone oxido-reductase 1 (NQO1) and for E-cadherin are not responsible for the leukemia susceptibility in these families. The presence of NQO1 polymorphisms may suggest a role for this gene in disease risk modification in these families. © 2004 Wiley-Liss, Inc.

Background Bisphosphonates (BPs) were designed for the prevention of skeletal-related events secondary to bone metastases. The purpose of this study was to show that zoledronic acid (ZA) directly eradicates highly tumorigenic and potentially metastatic cancer cells. Materials and methods Human prostate and breast highly tumorigenic (PC3, MCF 7) and low- or non-tumorigenic (LNCaP, MCF 10a) cell lines, respectively, were exposed to different concentrations of ZA (0-10 μM). Reverse transcriptase double quantitative polymerase chain reaction was used for quantitative gene expression analysis. Apoptosis and cell proliferation were determined using microscopic observation and MTS assays. Western blot was used to confirm the translational effects of apoptotic genes on protein expression. Results Human prostate and breast highly tumorigenic (PC3, MCF 7) and low- or non-tumorigenic (LNCaP, MCF 10a) cell lines, respectively, showed multiple genes demonstrating differential expressions, including TRAF, TRADD, BCL2, CASPASES and IAP families. Increasing ZA concentrations showed a greater concentration-time response on cell proliferation and apoptosis in the highly tumorigenic cells. These results were confirmed by both reversing and enhancing the effect of ZA on cell proliferation with caspase 3, 7 or survivin siRNA, respectively. Pro-apoptotic proteins bax and caspase 2, 3, 7 and 9 were up-regulated, while the anti-apoptotic proteins bcl2, birc3 and survivin were down-regulated only in the highly tumorigenic cells. Conclusions This explains the ability of ZA to inhibit bony metastasis in highly tumorigenic cells compared with the low- or non-tumorigenic cells through a significant decrease in cell proliferation and increase in apoptosis through gene-regulated and translational-mediated down-regulation of survivin coupled with the inhibition of caspase 3 or 7. This has significant implications toward understanding the pharmacophysiology of BPs in metastasis and supports the clinically observed effect of BPs when administered adjunctively with anticancer drugs such as cyclophosphamide/methotrexate/5-fluorouracil, epirubicin in combination with cyclophosphamide or docetaxel, and doxorubicin.

N-tuple nets are conceptually a highly parallel architecture. However, high-speed serial emulations of N-tuple nets offer considerable advantages of flexibility and cost efficiency in applications requiring only moderate bandwidth. In the paper a software technique for designing dynamically evolved N-tuple nets is described and the process whereby the designed structure can be progressively mapped into hardware to a level determined by the application requirements is illustrated.