Clonorchiasis in bone marrow transplant recipients

Among 380 bone marrow transplant (BMT) recipients, five cases (1.3%) of clonorchiasis were observed from 1991 to 1996. Clonorchis sinensis infection was evident in the results of stool examinations performed for screening purposes 7 days before bone marrow transplantation. Salmonella species were isolated concomitantly from the stools of two of the five patients. None of the patients had symptoms due to clonorchiasis. Ultrasonography did not show dilated hepatobiliary ducts, stones, or periportal fibrosis. Fatty liver changes were detected in one patient. All five patients received praziquantel (25 mg/kg po t.i.d. for 1 day) before bone marrow transplantation. Only two patients who underwent allogeneic transplantation had mild venoocclusive disease of the liver with transient hyperbilirubinemia and mildly elevated liver enzyme levels, whereas hyperbilirubinemia or elevated serum alanine aminotransferase levels, related to conditioning toxicity, occurred in two other patients. After treatment with praziquantel, stool examinations for all five patients were negative for C. sinensis ova. In addition, Salmonella species were not detected after ciprofloxacin prophylaxis. All five patients survived for >300 days. Given the availability of effective therapy and in the absence of excessive complications, clonorchiasis is not a contraindication to bone marrow transplantation.published_or_final_versio

Epigenetic inactivation of the miR-34a in hematological malignancies

miR-34a is a transcriptional target of p53 and implicated in carcinogenesis. We studied the role of miR-34a methylation in a panel of hematological malignancies including acute leukemia [acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)], chronic leukemia [chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML)], multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). The methylation status of miR-34a promoter was studied in 12 cell lines and 188 diagnostic samples by methylation-specific polymerase chain reaction. miR-34a promoter was unmethylated in normal controls but methylated in 75% lymphoma and 37% myeloma cell lines. Hypomethylating treatment led to re-expression of pri-miR-34a transcript in lymphoma cells with homozygous miR-34a methylation. In primary samples at diagnosis, miR-34a methylation was detected in 4% CLL, 5.5% MM samples and 18.8% of NHL at diagnosis but none of ALL, AML and CML (P = 0.011). In MM patients with paired samples, miR-34a methylation status remained unchanged at progression. Amongst lymphoid malignancies, miR-34a was preferentially methylated in NHL (P = 0.018), in particular natural killer (NK)/T-cell lymphoma. In conclusion, amongst hematological malignancies, miR-34a methylation is preferentially hypermethylated in NHL, in particular NK/T-cell lymphoma, in a tumor-specific manner, therefore the role of miR-34a in lymphomagenesis warrants further study. © The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]

Stage-specific manifestation of mold infections in bone marrow transplant recipients: Risk factors and clinical significance of positive concentrated smears

Potassium hydroxide-concentrated smears, prepared from sedimented remains of clinical specimens, were used to distinguish between mold infection and exogenous contamination in fungal culture-positive specimens. This method was applied in the study of 3,857 clinical specimens from 230 bone marrow transplant recipients who were followed up prospectively for infectious complications. Concentrated smears of only 86 (from 21 infected patients) of 149 fungal culture-positive specimens were positive for hyphae; 82 of the strains were Aspergillus species. Concentrated smears of the remaining 63 fungal culture-positive specimens were negative; the strains identified by culture were considered as exogenous contaminants (87% of which were Penicillium species). A stage-specific manifestation of mold infection was observed: 67% of mold infections occurred during acute graft-vs.-host disease (GVHD) a median of 47 days after transplantation, whereas 9% of mold infections occurred as rapidly fatal invasive disease before engraftment. Overall, of the 21 patients with mold infection, 17 (81%) had invasive mold disease, and four (19%) had mold colonization of airways secondary to chronic GVHD after day 100. The significant risk factors for mold infection were total-body irradiation and grade 2-4 acute GVHD. Because of our high mortality rate (82%), the consideration of antimold prophylaxis for such patients may be warranted.published_or_final_versio

Feedback Stabilization of a Class of Diagonal Infinite-Dimensional Systems with Delay Boundary Control

This paper studies the boundary feedback stabilization of a class of diagonal infinite-dimensional boundary control systems. In the studied setting, the boundary control input is subject to a constant delay while the open loop system might exhibit a finite number of unstable modes. The proposed control design strategy consists in two main steps. First, a finite-dimensional subsystem is obtained by truncation of the original Infinite-Dimensional System (IDS) via modal decomposition. It includes the unstable components of the infinite-dimensional system and allows the design of a finite-dimensional delay controller by means of the Artstein transformation and the pole-shifting theorem. Second, it is shown via the selection of an adequate Lyapunov function that 1) the finite-dimensional delay controller successfully stabilizes the original infinite-dimensional system; 2) the closed-loop system is exponentially Input-to-State Stable (ISS) with respect to distributed disturbances. Finally, the obtained ISS property is used to derive a small gain condition ensuring the stability of an IDS-ODE interconnection.Comment: Preprin

Radial Growth of Qilian Juniper on the Northeast Tibetan Plateau and Potential Climate Associations

There is controversy regarding the limiting climatic factor for tree radial growth at the alpine treeline on the northeastern Tibetan Plateau. In this study, we collected 594 increment cores from 331 trees, grouped within four altitude belts spanning the range 3550 to 4020 m.a.s.l. on a single hillside. We have developed four equivalent ring-width chronologies and shown that there are no significant differences in their growth-climate responses during 1956 to 2011 or in their longer-term growth patterns during the period AD 1110–2011. The main climate influence on radial growth is shown to be precipitation variability. Missing ring analysis shows that tree radial growth at the uppermost treeline location is more sensitive to climate variation than that at other elevations, and poor tree radial growth is particularly linked to the occurrence of serious drought events. Hence water limitation, rather than temperature stress, plays the pivotal role in controlling the radial growth of Sabina przewalskii Kom. at the treeline in this region. This finding contradicts any generalisation that tree-ring chronologies from high-elevation treeline environments are mostly indicators of temperature changes

Lymphatic Filariasis Control in Tanzania: Effect of Six Rounds of Mass Drug Administration with Ivermectin and Albendazole on Infection and Transmission.

Control of lymphatic filariasis (LF) in most countries of sub-Saharan Africa is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. We present findings from a detailed study on the effect of six rounds of MDA with this drug combination as implemented by the National Lymphatic Filariasis Elimination Programme (NLFEP) in a highly endemic rural area of north-eastern Tanzania.\ud The effect of treatment on transmission and human infection was monitored in a community- and a school-based study during an 8-year period (one pre-intervention and 7 post-intervention years) from 2003 to 2011. Before intervention, 24.5% of the community population had microfilariae (mf) in the blood, 53.3% had circulating filarial antigens (CFA) and 78.9% had specific antibodies to the recombinant filarial antigen Bm14. One year after the sixth MDA, these values had decreased considerably to 2.7%, 19.6% and 27.5%, respectively. During the same period, the CFA prevalence among new intakes of Standard 1 pupils in 10 primary schools decreased from 25.2% to 5.6%. In line with this, transmission by the three vectors (Anopheles gambiae, An. funestus and Culex quinquefasciatus) as determined by dissection declined sharply (overall vector infectivity rate by 99.3% and mean monthly transmission potential by 99.2% between pre-intervention and fifth post-intervention period). A major shift in vector species composition, from predominantly anopheline to almost exclusively culicine was observed over the years. This may be largely unrelated to the MDAs but may have important implications for the epidemiology of LF in the area. Six MDAs caused considerable decrease in all the measured indices for transmission and human infection. In spite of this, indices were still relatively high in the late period of the study, and it may take a long time to reach the recommended cut-off levels for interruption of transmission unless extra efforts are made. These should include increased engagement of the target population in the control activities, to ensure higher treatment coverage. It is expected that the recent initiative to distribute insecticide impregnated bed nets to every household in the area will also contribute towards reaching the goal of successful LF elimination

Meta-analysis of binary outcomes via generalized linear mixed models: a simulation study

Background: Systematic reviews and meta-analyses of binary outcomes are widespread in all areas of application. The odds ratio, in particular, is by far the most popular effect measure. However, the standard meta-analysis of odds ratios using a random-effects model has a number of potential problems. An attractive alternative approach for the meta-analysis of binary outcomes uses a class of generalized linear mixed models (GLMMs). GLMMs are believed to overcome the problems of the standard random-effects model because they use a correct binomial-normal likelihood. However, this belief is based on theoretical considerations, and no sufficient simulations have assessed the performance of GLMMs in meta-analysis. This gap may be due to the computational complexity of these models and the resulting considerable time requirements. Methods: The present study is the first to provide extensive simulations on the performance of four GLMM methods (models with fixed and random study effects and two conditional methods) for meta-analysis of odds ratios in comparison to the standard random effects model. Results: In our simulations, the hypergeometric-normal model provided less biased estimation of the heterogeneity variance than the standard random-effects meta-analysis using the restricted maximum likelihood (REML) estimation when the data were sparse, but the REML method performed similarly for the point estimation of the odds ratio, and better for the interval estimation. Conclusions: It is difficult to recommend the use of GLMMs in the practice of meta-analysis. The problem of finding uniformly good methods of the meta-analysis for binary outcomes is still open

A cautionary note regarding count models of alcohol consumption in randomized controlled trials

BACKGROUND: Alcohol consumption is commonly used as a primary outcome in randomized alcohol treatment studies. The distribution of alcohol consumption is highly skewed, particularly in subjects with alcohol dependence. METHODS: In this paper, we will consider the use of count models for outcomes in a randomized clinical trial setting. These include the Poisson, over-dispersed Poisson, negative binomial, zero-inflated Poisson and zero-inflated negative binomial. We compare the Type-I error rate of these methods in a series of simulation studies of a randomized clinical trial, and apply the methods to the ASAP (Addressing the Spectrum of Alcohol Problems) trial. RESULTS: Standard Poisson models provide a poor fit for alcohol consumption data from our motivating example, and did not preserve Type-I error rates for the randomized group comparison when the true distribution was over-dispersed Poisson. For the ASAP trial, where the distribution of alcohol consumption featured extensive over-dispersion, there was little indication of significant randomization group differences, except when the standard Poisson model was fit. CONCLUSION: As with any analysis, it is important to choose appropriate statistical models. In simulation studies and in the motivating example, the standard Poisson was not robust when fit to over-dispersed count data, and did not maintain the appropriate Type-I error rate. To appropriately model alcohol consumption, more flexible count models should be routinely employed