Bulk Superconductivity and Disorder in Single Crystals of LaFePO

We have studied the intrinsic normal and superconducting properties of the oxypnictide LaFePO. These samples exhibit bulk superconductivity and the evidence suggests that stoichiometric LaFePO is indeed superconducting, in contrast to other reports. We find that superconductivity is independent of the interplane residual resistivity {rho}{sub 0} and discuss the implications of this on the nature of the superconducting order parameter. Finally we find that, unlike T{sub c}, other properties in single-crystal LaFePO including the resistivity and magnetoresistance, can be very sensitive to disorder

Pre-Clinical Evaluation of a 213Bi-Labeled 2556 Antibody to HIV-1 gp41 Glycoprotein in HIV-1 Mouse Models as a Reagent for HIV Eradication

Any strategy for curing HIV infection must include a method to eliminate viral-infected cells. Based on our earlier proof-of-principle results targeting HIV-1 infected cells with radiolabeled antibody (mAb) to gp41 viral antigen, we embarked on identifying a suitable candidate mAb for preclinical development.Among the several human mAbs to gp41 tested, mAb 2556 was found to have high affinity, reactivity with multimeric forms of gp41 present on both the surface of virus particles and cells expressing HIV-1 Env, and recognition of a highly conserved epitope of gp41 shared by all HIV-1 subtypes. Also, mAb 2556 was the best in competition with HIV-1+ serum antibodies, which is an extremely important consideration for efficacy in the treatment of HIV patients. When radiolabeled with alpha-emitting radionuclide 213-Bismuth ((213)Bi) - (213)Bi-2556 efficiently and specifically killed ACH-2 human lymphocytes chronically infected with HIV-1, and HIV-1 infected human peripheral blood mononuclear cells (hPBMCs). The number of binding sites for (213)Bi-2556 on the surface of the infected cells was >10(6). The in vivo experiments were performed in two HIV-1 mouse models--splenic and intraperitoneal. In both models, the decrease in HIV-1 infected hPBMCs from the spleens and peritoneum, respectively, was dose-dependent with the most pronounced killing of hPBMCs observed in the 100 µCi (213)Bi-2556 group (P = 0.01). Measurement of the blood platelet counts and gross pathology of the treated mice demonstrated the lack of toxicity for (213)Bi-2556.We describe the preclinical development of a novel radiolabeled mAb reagent that could potentially be part of an HIV eradication strategy that is ready for translation into the clinic as the next step in its development. As viral antigens are very different from "self" human antigens - this approach promises high selectivity, increased efficacy and low toxicity, especially in comparison to immunotoxins

Primary chemo-radiotherapy in the treatment of locally advanced and inflammatory breast cancer

BACKGROUND: The best management of large, diffuse or inflammatory breast cancers is uncertain and the place of radiotherapy and/or surgery is not clearly defined. METHODS: A cohort of 123 patients with non-metastatic locally advanced or inflammatory breast cancer 3 cm or more in diameter or T4, was treated between 1989 and 2006. All patients received primary chemotherapy followed by radiotherapy, 40 Gy in 15 fractions with 10 Gy boost. Patients with ER positive tumours received Tamoxifen. Assessment was carried out 8 weeks post-treatment and surgery was reserved for residual or recurrent disease. RESULTS: For each stage there were T2/3: 63, T4b: 31 and T4d: 29 patients. 80 had complete clinical response (65%) but 18 patients were never free of inoperable local disease. 25 patients had residual operable disease at assessment and 12 patients who initially had a complete response developed operable local recurrence (LR). 37 Patients (30%) had surgery at a mean of 15 months post diagnosis. At 5 years, overall survival (OS) of the two surgical groups was not significantly different from those 68 patients who had complete remission without surgery, p=0.218, HR 1.46 (0.80-2.55). Surgery as an independent variable to predict survival was not significant on a Cox proportional hazards model (p=0.97). LR in the surgical groups was 13.5% vs 17.5% in the non-surgical patients. The median OS was 64.5 months and disease-free survival (DFS) was 52.5 months. 5-Year OS was 54% and DFS survival 43%. CONCLUSION: In patients with a complete or partial response to chemo-radiotherapy for locally advanced or inflammatory breast cancer, reserving surgery for those with residual or recurrent local disease did not appear to compromise survival. This finding would support examination of this treatment strategy by a randomised controlled trial

DNA methylation and body mass index from birth to adolescence : meta-analyses of epigenome-wide association studies

Background DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits. Methods We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment. Results DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P <1.06 x 10(-7), with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth P-enrichment = 1; childhood P-enrichment = 2.00 x 10(-4); adolescence P-enrichment = 2.10 x 10(-7)). Conclusions There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.Peer reviewe

Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

Background Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P <1.06 x 10(- 7), of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.Peer reviewe

Some aspects of the antibacterial activity of bovine neutrophils in relation to staphylococcal mastitis /

Diss. Ph.D.: veterinary medicin

Welfare reform and lone parents

Includes bibliographical referencesAvailable from British Library Document Supply Centre- DSC:9349. 99092(no 03/072) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo