114 research outputs found
Epidemiology and outcomes of Clostridium difficile infection in allogeneic hematopoietic cell and lung transplant recipients
BackgroundClostridium difficile infection (CDI) is a common complication of lung and allogeneic hematopoietic cell (HCT) transplant, but the epidemiology and outcomes of CDI after transplant are poorly described.MethodsWe performed a prospective, multicenter study of CDI within 365Â days postâallogeneic HCT or lung transplantation. Data were collected via patient interviews and medical chart review. Participants were followed weekly in the 12Â weeks postâtransplant and while hospitalized and contacted monthly up to 18Â months postâtransplantation.ResultsSix sites participated in the study with 614 total participants; 4 enrolled allogeneic HCT (385 participants) and 5 enrolled lung transplant recipients (229 participants). One hundred and fifty CDI cases occurred within 1Â year of transplantation; the incidence among lung transplant recipients was 13.1% and among allogeneic HCTs was 31.2%. Median time to CDI was significantly shorter among allogeneic HCT than lung transplant recipients (27Â days vs 90Â days; PÂ =Â .037). CDI was associated with significantly higher mortality from 31 to 180Â days postâindex date among the allogeneic HCT recipients (Hazard ratio [HR]Â =Â 1.80; PÂ =Â .007). There was a trend towards increased mortality among lung transplant recipients from 120 to 180Â days postâindex date (HRÂ =Â 4.7, PÂ =Â .09).ConclusionsThe epidemiology and outcomes of CDI vary by transplant population; surveillance for CDI should continue beyond the immediate postâtransplant period.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143790/1/tid12855_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143790/2/tid12855.pd
Blue laser cooling transitions in Tm I
We have studied possible candidates for laser cooling transitions in
Tm in the spectral region 410 -- 420 nm. By means of saturation
absorption spectroscopy we have measured the hyperfine structure and rates of
two nearly closed cycling transitions from the ground state
to upper states
at
410.6 nm and
at
420.4 nm and evaluated the life times of the excited levels as 15.9(8) ns and
48(6) ns respectively. Decay rates from these levels to neighboring
opposite-parity levels are evaluated by means of Hartree-Fock calculations. We
conclude, that the strong transition at 410.6 nm has an optical leak rate of
less then and can be used for efficient laser cooling of
Tm from a thermal atomic beam. The hyperfine structure of two other
even-parity levels which can be excited from the ground state at 409.5 nm and
418.9 nm is also measured by the same technique. In addition we give a
calculated value of s for the rate of magnetic-dipole transition
at 1.14 m between the fine structure levels
of the ground state which can be
considered as a candidate for applications in atomic clocks.Comment: 8 pages, 5 figure
Slow Light in Doppler Broadened Two level Systems
We show that the propagation of light in a Doppler broadened medium can be
slowed down considerably eventhough such medium exhibits very flat dispersion.
The slowing down is achieved by the application of a saturating counter
propagating beam that produces a hole in the inhomogeneous line shape. In
atomic vapors, we calculate group indices of the order of 10^3. The
calculations include all coherence effects.Comment: 6 pages, 5 figure
Application of the 2008 definitions for invasive fungal diseases to the trial comparing voriconazole versus amphotericin B for therapy of invasive aspergillosis: a collaborative study of the Mycoses Study Group (MSG 05) and the European Organization for Research and Treatment of Cancer Infectious Diseases Group.
BACKGROUND: Strict definition of invasive aspergillosis (IA) cases is required to allow precise conclusions about the efficacy of antifungal therapy. The Global Comparative Aspergillus Study (GCAS) compared voriconazole to amphotericin B (AmB) deoxycholate for the primary therapy of IA. Because predefined definitions used for this trial were substantially different from the consensus definitions proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group in 2008, we recategorized the 379 episodes of the GCAS according to the later definitions.
METHODS: The objectives were to assess the impact of the current definitions on the classification of the episodes and to provide comparative efficacy for probable/proven and possible IA in patients treated with either voriconazole or AmB. In addition to original data, we integrated the results of baseline galactomannan serum levels obtained from 249 (65.7%) frozen samples. The original response assessment was accepted unchanged.
RESULTS: Recategorization allowed 59 proven, 178 probable, and 106 possible IA cases to be identified. A higher favorable 12-week response rate was obtained with voriconazole (54.7%) than with AmB (29.9%) (P < .0001). Survival was higher for voriconazole for mycologically documented (probable/proven) IA (70.2%) than with AmB (54.9%) (P = .010). Higher response rates were obtained in possible IA treated with voriconazole vs AmB with the same magnitude of difference (26.2%; 95% confidence interval [CI], 7.2%-45.3%) as in mycologically documented episodes (24.3%; 95% CI, 11.9%-36.7%), suggesting that possible cases are true IA.
CONCLUSIONS: Recategorization resulted in a better identification of the episodes and confirmed the higher efficacy of voriconazole over AmB deoxycholate in mycologically documented IA
Endemic fungal infections in solid organ and hematopoietic cell transplant recipients enrolled in the TransplantâAssociated Infection Surveillance Network ( TRANSNET )
Background Invasive fungal infections are a major cause of morbidity and mortality among solid organ transplant ( SOT ) and hematopoietic cell transplant ( HCT ) recipients, but few data have been reported on the epidemiology of endemic fungal infections in these populations. Methods Fifteen institutions belonging to the TransplantâAssociated Infection Surveillance Network prospectively enrolled SOT and HCT recipients with histoplasmosis, blastomycosis, or coccidioidomycosis occurring between March 2001 and March 2006. Results A total of 70 patients (64 SOT recipients and 6 HCT recipients) had infection with an endemic mycosis, including 52 with histoplasmosis, 9 with blastomycosis, and 9 with coccidioidomycosis. The 12âmonth cumulative incidence rate among SOT recipients for histoplasmosis was 0.102%. Occurrence of infection was bimodal; 28 (40%) infections occurred in the first 6Â months post transplantation, and 24 (34%) occurred between 2 and 11Â years post transplantation. Three patients were documented to have acquired infection from the donor organ. Seven SOT recipients with histoplasmosis and 3 with coccidioidomycosis died (16%); no HCT recipient died. Conclusions This 5âyear multicenter prospective surveillance study found that endemic mycoses occur uncommonly in SOT and HCT recipients, and that the period at risk extends for years after transplantation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106980/1/tid12186.pd
Bi-allelic variants in NAE1 cause intellectual disability, ischiopubic hypoplasia, stress-mediated lymphopenia and neurodegeneration
Neddylation has been implicated in various cellular pathways and in the pathophysiology of numerous diseases. We identified four individuals with bi-allelic variants in NAE1, which encodes the neddylation E1 enzyme. Pathogenicity was supported by decreased NAE1 abundance and overlapping clinical and cellular phenotypes. To delineate how cellular consequences of NAE1 deficiency would lead to the clinical phenotype, we focused primarily on the rarest phenotypic features, based on the assumption that these would best reflect the pathophysiology at stake. Two of the rarest features, neuronal loss and lymphopenia worsening during infections, suggest that NAE1 is required during cellular stress caused by infections to protect against cell death. In support, we found that stressing the proteasome system with MG132ârequiring upregulation of neddylation to restore proteasomal function and proteasomal stressâled to increased cell death in fibroblasts of individuals with NAE1 genetic variants. Additionally, we found decreased lymphocyte counts after CD3/CD28 stimulation and decreased NF-ÎșB translocation in individuals with NAE1 variants. The rarest phenotypic featureâdelayed closure of the ischiopubic ramiâcorrelated with significant downregulation of RUN2X and SOX9 expression in transcriptomic data of fibroblasts. Both genes are involved in the pathophysiology of ischiopubic hypoplasia. Thus, we show that NAE1 plays a major role in (skeletal) development and cellular homeostasis during stress. Our approach suggests that a focus on rare phenotypic features is able to provide significant pathophysiological insights in diseases caused by mutations in genes with pleiotropic effects.</p
Bi-allelic variants in NAE1 cause intellectual disability, ischiopubic hypoplasia, stress-mediated lymphopenia and neurodegeneration
Neddylation has been implicated in various cellular pathways and in the pathophysiology of numerous diseases. We identified four individuals with bi-allelic variants in NAE1, which encodes the neddylation E1 enzyme. Pathogenicity was supported by decreased NAE1 abundance and overlapping clinical and cellular phenotypes. To delineate how cellular consequences of NAE1 deficiency would lead to the clinical phenotype, we focused primarily on the rarest phenotypic features, based on the assumption that these would best reflect the pathophysiology at stake. Two of the rarest features, neuronal loss and lymphopenia worsening during infections, suggest that NAE1 is required during cellular stress caused by infections to protect against cell death. In support, we found that stressing the proteasome system with MG132ârequiring upregulation of neddylation to restore proteasomal function and proteasomal stressâled to increased cell death in fibroblasts of individuals with NAE1 genetic variants. Additionally, we found decreased lymphocyte counts after CD3/CD28 stimulation and decreased NF-ÎșB translocation in individuals with NAE1 variants. The rarest phenotypic featureâdelayed closure of the ischiopubic ramiâcorrelated with significant downregulation of RUN2X and SOX9 expression in transcriptomic data of fibroblasts. Both genes are involved in the pathophysiology of ischiopubic hypoplasia. Thus, we show that NAE1 plays a major role in (skeletal) development and cellular homeostasis during stress. Our approach suggests that a focus on rare phenotypic features is able to provide significant pathophysiological insights in diseases caused by mutations in genes with pleiotropic effects.</p
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