Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: strong graft-versus-leukemia effect and risk factors determining outcome

Between 1988 and 1999, 127 patients with poor-risk acute lymphoblastic leukemia (ALL) received a matched unrelated donor transplant using marrow procured by National Marrow Donor Program (NMDP) collection centers and sent out to 46 transplant centers worldwide. Poor risk was defined by the presence of the translocations t(9;22) (n = 97), or t(4;11) (n = 25), or t(1;19) (n = 5). Sixty-four patients underwent transplantation in first remission (CR1), 16 in CR2 or CR3, and 47 patients had relapsed ALL or primary induction failure (PIF). Overall survival at 2 years from transplant was 40% for patients in CR1, 17% in CR2/3, and 5% in PIF or relapse. Treatment-related mortality (TRM) and relapse mortality, estimated as competing risk factors, were 54% and 6%, respectively, in CR1, 75% and 8% in CR2/3, and 64% and 31% in PIF or relapse. Currently 23 CR1 patients are alive and free of disease with a median follow-up of 24 months (range, 3-97). Multivariable analysis showed that CR1, shorter interval from di

Differential role for trehalose metabolism in salt-stressed maize

Little is known about how salt impacts primary metabolic pathways of C4 plants, particularly related to kernel development and seed set. Osmotic stress was applied to maize (Zea mays) B73 by irrigation with increasing concentrations of NaCl from the initiation of floral organs until 3 d after pollination. At silking, photosynthesis was reduced to only 2% of control plants. Salt treatment was found to reduce spikelet growth, silk growth, and kernel set. Osmotic stress resulted in higher concentrations of sucrose (Suc) and hexose sugars in leaf, cob, and kernels at silking, pollination, and 3 d after pollination. Citric acid cycle intermediates were lower in salt-treated tissues, indicating that these sugars were unavailable for use in respiration. The sugar-signaling metabolite trehalose-6-phosphate was elevated in leaf, cob, and kernels at silking as a consequence of salt treatment but decreased thereafter even as Suc levels continued to rise. Interestingly, the transcripts of trehalose pathway genes were most affected by salt treatment in leaf tissue. On the other hand, transcripts of the SUCROSE NONFERMENTING-RELATED KINASE1 (SnRK1) marker genes were most affected in reproductive tissue. Overall, both source and sink strength are reduced by salt, and the data indicate that trehalose-6-phosphate and SnRK1 may have different roles in source and sink tissues. Kernel abortion resulting from osmotic stress is not from a lack of carbohydrate reserves but from the inability to utilize these energy reserves

Who Meets Whom: Access and Lobbying During the Coalition Years

In 2010, the incoming Coalition government announced that it would publish details of meetings between ministers and outside interests. We have collated and coded these data and, in this article, describe patterns of access between 2010 and 2015. In some respects, access is notably fragmented. No single organisation attends more than 2.5% of the 6292 meetings held by ministers. On the contrary, business, collectively, attends fully 45% of all meetings: more than twice the share of any other category of organisation. We also find evidence of distinctive policy communities characterised by high levels of access between particular interests and ministers within specific departments

Safety, efficacy and glucose turnover of reduced prandial boluses during closed-loop therapy in adolescents with type 1 diabetes: a randomized clinical trial.

AIMS: To evaluate safety, efficacy and glucose turnover during closed-loop with meal announcement using reduced prandial insulin boluses in adolescents with type 1 diabetes (T1D). METHODS: We conducted a randomized crossover study comparing closed-loop therapy with standard prandial insulin boluses versus closed-loop therapy with prandial boluses reduced by 25%. Eight adolescents with T1D [3 males; mean (standard deviation) age 15.9 (1.5) years, glycated haemoglobin 74 (17) mmol/mol; median (interquartile range) total daily dose 0.9 (0.7, 1.1) IU/kg/day] were studied on two 36-h-long visits. In random order, subjects received closed-loop therapy with either standard or reduced insulin boluses administered with main meals (50-80 g carbohydrates) but not with snacks (15-30 g carbohydrates). Stable-label tracer dilution methodology measured total glucose appearance (Ra_total) and glucose disposal (Rd). RESULTS: The median (interquartile range) time spent in target (3.9-10 mmol/l) was similar between the two interventions [74 (66, 84)% vs 80 (65, 96)%; p = 0.87] as was time spent above 10 mmol/l [21.8 (16.3, 33.5)% vs 18.0 (4.1, 34.2)%; p = 0.87] and below 3.9 mmol/l [0 (0, 1.5)% vs 0 (0, 1.8)%; p = 0.88]. Mean plasma glucose was identical during the two interventions [8.4 (0.9) mmol/l; p = 0.98]. Hypoglycaemia occurred once 1.5 h post-meal during closed-loop therapy with standard bolus. Overall insulin delivery was lower with reduced prandial boluses [61.9 (55.2, 75.0) vs 72.5 (63.6, 80.3) IU; p = 0.01] and resulted in lower mean plasma insulin concentration [186 (171, 260) vs 252 (198, 336) pmol/l; p = 0.002]. Lower plasma insulin was also documented overnight [160 (136, 192) vs 191 (133, 252) pmol/l; p = 0.01, pooled nights]. Ra_total was similar [26.3 (21.9, 28.0) vs 25.4 (21.0, 29.2) µmol/kg/min; p = 0.19] during the two interventions as was Rd [25.8 (21.0, 26.9) vs 25.2 (21.2, 28.8) µmol/kg/min; p = 0.46]. CONCLUSIONS: A 25% reduction in prandial boluses during closed-loop therapy maintains similar glucose control in adolescents with T1D whilst lowering overall plasma insulin levels. It remains unclear whether closed-loop therapy with a 25% reduction in prandial boluses would prevent postprandial hypoglycaemia.US National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK085621). Support for the Artificial Pancreas research programme by the JDRF, Diabetes UK, NIHR Cambridge Biomedical Research Centre, and Wellcome Trust Strategic Award (100574/Z/12/Z) is acknowledged.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/dom.1254

Lesbian and bisexual women's human rights, sexual rights and sexual citizenship: negotiating sexual health in England.

Lesbian and bisexual women's sexual health is neglected in much Government policy and practice in England and Wales. This paper examines lesbian and bisexual women's negotiation of sexual health, drawing on findings from a small research project. Themes explored include invisibility and lack of information, influences on decision-making and sexual activities and experiences of services and barriers to sexual healthcare. Key issues of importance in this respect are homophobic and heterosexist social contexts. Drawing on understandings of lesbian, gay and bisexual human rights, sexual rights and sexual citizenship, it is argued that these are useful lenses through which to examine and address lesbian and bisexual women's sexual health and related inequalities

Competing for the Platform: How Organized Interests affect Party Positioning in the United States

What explains which groups are included in a party coalition in any given election cycle? Recent advances in political party theory suggest that policy demanders comprise parties, and that the composition of a party coalition varies from election to election. We theorize three conditions under which parties articulate an interest group?s preferred positions in its quadrennial platform: when groups are ideologically proximate to the party median, when groups display party loyalty, and when groups are flush with resources. Using computer-assisted content analysis on a unique and rich data source, we examine three cycles of testimony that 80 organized groups provided to the Democratic Party. The analysis compares group requests with the content of Democratic and Republican National Committee platforms in 1996, 2000, and 2004. Results show that parties reward loyal groups and those that are ideologically proximate to the party, but offer no confirmation of a resource effect

Diphenyl Urea Derivatives as Inhibitors of Transketolase: A Structure-Based Virtual Screening

Transketolase is an enzyme involved in a critical step of the non-oxidative branch of the pentose phosphate pathway whose inhibition could lead to new anticancer drugs. Here, we report new human transketolase inhibitors, based on the phenyl urea scaffold, found by applying structure-based virtual screening. These inhibitors are designed to cover a hot spot in the dimerization interface of the homodimer of the enzyme, providing for the first time compounds with a suggested novel binding mode not based on mimicking the thiamine pyrophosphate cofactor

Inflow Speed Analysis of Interchange Injections in Saturn's Magnetosphere

During its more than 13 years in orbit, the Cassini spacecraft detected a large number of plasma and energetic charged particle injections in Saturn's inner magnetosphere. In the corotating frame of the planet, the plasma contained within an injection moves radially inward with the component particles gaining energy. The highest energy particles in the injection experience stronger gradient‐curvature drifts in the longitudinal direction and can drift out of the main body of the injection. We have used these drift‐out effects to estimate the inflow speed of 19 injections by surveying cases from the available plasma data. We find that the average inflow speed from our sample is 22 km/s, and the values are well distributed between 0 and 50 km/s, with a few higher estimates. We have also computed the radial travel distance of interchange events and found that these are typically one to two Saturn radii. We discuss the implications of these quantifications on our understanding of transport