Long-term outcomes of allogeneic haematopoietic stem cell transplantation for adult cerebral X-linked adrenoleukodystrophy

The adult cerebral inflammatory form of X-linked adrenoleukodystrophy is a rapidly progressive neurodegenerative disease, as devastating as childhood cerebral adrenoleukodystrophy. Allogeneic haematopoietic stem cell transplantation has been demonstrated to provide long-term neurological benefits for boys with the childhood cerebral form, but results in adults are sparse and inconclusive. We analysed data from 14 adult males with adult cerebral adrenoleukodystrophy treated with allogeneic haematopoietic stem cell transplantation on a compassionate basis in four European centres. All presented with cerebral demyelinating lesions and gadolinium enhancement. Median age at diagnosis of adult cerebral adrenoleukodystrophy was 33 years (range 21–48 years). In addition to cerebral inflammation, five patients had established severe motor disability from adrenomyeloneuropathy affecting only the spinal cord and peripheral nerves (Expanded Disability Status Scale score ≥ 6). Eight patients survived (estimated survival 57 ± 13%) with a median follow-up of 65 months (minimum 38 months). Death was directly transplant-/infection-related (n = 3), due to primary disease progression in advanced adult cerebral adrenoleukodystrophy (n = 1), or secondary disease progression (n = 2) after transient multi-organ failure or non-engraftment. Specific complications during stem cell transplantation included deterioration of motor and bladder functions (n = 12) as well as behavioural changes (n = 8). Arrest of progressive cerebral demyelination and prevention of severe loss of neurocognition was achieved in all eight survivors, but deterioration of motor function occurred in the majority (n = 5). Limited motor dysfunction (Expanded Disability Status Scale score < 6) prior to transplantation was associated with significantly improved survival [78 ± 14% (n = 9) versus 20 ± 18%(n = 5); P < 0.05] and maintenance of ambulation (Expanded Disability Status Scale score < 7) post-transplant (78% versus 0%; P = 0.021). In contrast, bilateral involvement of the internal capsule on brain MRI was associated with poorer survival [20 ± 18% (n = 5) versus 78 ± 14% (n = 9); P < 0.05]. This study is the first to support the feasibility, complications and potential long-term neurological benefit of allogeneic haematopoietic stem cell transplantation in adult cerebral adrenoleukodystrophy. Further studies are warranted to attempt to improve outcomes through patient selection and optimization of transplantation protocols

Evaluation of soybean for resistance to soybean rust in Vietnam

Soybean rust, caused by Phakopsora pachyrhizi Sydow, is a severe foliar disease of soybean [Glycine max (L.) Merr.] that occurs throughout most soybean producing regions of the world. The objective of this research was to evaluate selected soybean genotypes for resistance to soybean rust in Vietnam. Five field experiments in Vietnam were completed from 2006 to 2009. The area-under-the-disease-progress-curve (AUDPC) was calculated for each soybean genotype based on four disease assessments taken during the reproductive growth stages. AUDPC units among soybean genotypes in each experiment differed (P < 0.05). Over the five experiments, the resistant check DT 2000 was most often the genotype with the lowest AUDPC units while the sources of rust resistance (Rpp1-5) did not always have low AUDPC units in each experiment, although PI 230970 (Rpp2) appeared to be more stable. A few genotypes with non-characterized genes for resistance, such as PI 398998, PI 437323, and PI 549017, had the lowest AUDPC units in at least one of the experiments. These genetic resources may be useful for host plant resistance studies and breeding soybeans for rust resistance in Vietnam and other locations like Brazil and the United States that have more recently been inundated with soybean rust. A significant (P < 0.001) experiment×genotype interaction was found when the AUDPC data of 14 soybean genotypes tested in Experiments 1, 2, and 3 were combined and analyzed. This result indicates the potential importance of changing fungal races and/or biotypes that occur in the rust population.T.A. Pham, C.B. Hill, M.R. Miles, B.T. Nguyen, T.T. Vu, T.D. Vuong, T.T. VanToai, H.T. Nguyen, G.L. Hartma

Reactivation of hepatitis E infection in a patient with acute lymphoblastic leukaemia after allogeneic stem cell transplantation

Hepatitis E virus (HEV) is the major cause of several outbreaks of waterborne hepatitis in tropical and subtropical countries and of sporadic cases of viral hepatitis in endemic and industrialised countries. Generally, HEV causes an acute self-limiting hepatitis. The clinical course is characterised by transient viraemia and transaminasaemia followed by a full hepatic recovery. Recent studies describe prolonged and chronic HEV infections in some immunosuppressed patients after solid organ transplantation. Here, an indigenous acute limited hepatitis E in a patient with Philadelphia chromosome-positive acute lymphoblastic leukaemia prior to allogeneic stem cell transplantation is reported. Fourteen weeks after stem cell transplantation, reappearance of HEV viraemia was observed, with increasing viral load and modestly elevated serum transaminases. Sequence analysis of the viral RNAs revealed a reactivation of endogenous HEV genotype 3, indicating viral persistence after recovery from acute hepatitis E

DUNE Offline Computing Conceptual Design Report

International audienceThis document describes Offline Software and Computing for the Deep Underground Neutrino Experiment (DUNE) experiment, in particular, the conceptual design of the offline computing needed to accomplish its physics goals. Our emphasis in this document is the development of the computing infrastructure needed to acquire, catalog, reconstruct, simulate and analyze the data from the DUNE experiment and its prototypes. In this effort, we concentrate on developing the tools and systems thatfacilitate the development and deployment of advanced algorithms. Rather than prescribing particular algorithms, our goal is to provide resources that are flexible and accessible enough to support creative software solutions as HEP computing evolves and to provide computing that achieves the physics goals of the DUNE experiment

DUNE Offline Computing Conceptual Design Report

This document describes Offline Software and Computing for the Deep Underground Neutrino Experiment (DUNE) experiment, in particular, the conceptual design of the offline computing needed to accomplish its physics goals. Our emphasis in this document is the development of the computing infrastructure needed to acquire, catalog, reconstruct, simulate and analyze the data from the DUNE experiment and its prototypes. In this effort, we concentrate on developing the tools and systems thatfacilitate the development and deployment of advanced algorithms. Rather than prescribing particular algorithms, our goal is to provide resources that are flexible and accessible enough to support creative software solutions as HEP computing evolves and to provide computing that achieves the physics goals of the DUNE experiment