| 41. |
- Brunstein, Claudio G, et al.
(författare)
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Effect of Conditioning Regimen Dose Reduction in Obese Patients Undergoing Autologous Hematopoietic Cell Transplantation
- 2019
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 25:3, s. 480-487
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Tidskriftsartikel (refereegranskat)abstract
- Data are limited on whether to adjust high-dose chemotherapy before autologous hematopoietic cell transplant (autoHCT) in obese patients. This study explores the effects of dose adjustment on the outcomes of obese patients, defined as body mass index (BMI) ≥ 30 kg/m2. Dose adjustment was defined as a reduction in standard dosing ≥ 20%, based on ideal, reported dosing and actual weights. We included 2 groups of US patients who had received autoHCT between 2008 and 2014. Specifically, we included patients with multiple myeloma (MM, n = 1696) treated with high-dose melphalan and patients with Hodgkin or non-Hodgkin lymphomas (n = 781) who received carmustine, etoposide, cytarabine, and melphalan conditioning. Chemotherapy dose was adjusted in 1324 patients (78%) with MM and 608 patients (78%) with lymphoma. Age, sex, BMI, race, performance score, comorbidity index, and disease features (stage at diagnosis, disease status, and time to transplant) were similar between dose groups. In multivariate analyses for MM, adjusting for melphalan dose and for center effect had no impact on overall survival (P = .894) and treatment-related mortality (TRM) (P = .62), progression (P = .12), and progression-free survival (PFS; P = .178). In multivariate analyses for lymphoma, adjusting chemotherapy doses did not affect survival (P = .176), TRM (P = .802), relapse (P = .633), or PFS (P = .812). No center effect was observed in lymphoma. This study demonstrates that adjusting chemotherapy dose before autoHCT in obese patients with MM and lymphoma does not influence mortality. These results do not support adjusting chemotherapy dose in this population.
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| 42. |
- Campbell, C., et al.
(författare)
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Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy
- 2020
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Ingår i: Journal of Comparative Effectiveness Research. - : Becaris Publishing Limited. - 2042-6305 .- 2042-6313. ; 9:14
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Tidskriftsartikel (refereegranskat)abstract
- Aim:Assess the totality of efficacy evidence for ataluren in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD).Materials & methods:Data from the two completed randomized controlled trials (ClinicalTrials.gov: NCT00592553; NCT01826487) of ataluren in nmDMD were combined to examine the intent-to-treat (ITT) populations and two patient subgroups (baseline 6-min walk distance [6MWD] >= 300-<400 or <400 m). Meta-analyses examined 6MWD change from baseline to week 48.Results:Statistically significant differences in 6MWD change with ataluren versus placebo were observed across all three meta-analyses. Least-squares mean difference (95% CI): ITT (n = 342), +17.2 (0.2-34.1) m, p = 0.0473; >= 300-<400 m (n = 143), +43.9 (18.2-69.6) m, p = 0.0008; <400 m (n = 216), +27.7 (6.4-49.0) m, p = 0.0109.Conclusion:These meta-analyses support previous evidence for ataluren in slowing disease progression versus placebo in patients with nmDMD over 48 weeks. Treatment benefit was most evident in patients with a baseline 6MWD >= 300-<400 m (the ambulatory transition phase), thereby informing future trial design.
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| 43. |
- Hogan, C. J., et al.
(författare)
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Fission yeast Iec1-Ino80-mediated nucleosome eviction regulates nucleotide and phosphate metabolism
- 2010
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Ingår i: Molecular and Cellular Biology. - 0270-7306 .- 1098-5549. ; 30:3, s. 657-674
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Tidskriftsartikel (refereegranskat)abstract
- Ino80 is an ATP-dependent nucleosome-remodeling enzyme involved in transcription, replication, and the DNA damage response. Here, we characterize the fission yeast Ino80 and find that it is essential for cell viability. We show that the Ino80 complex from fission yeast mediates ATP-dependent nucleosome remodeling in vitro. The purification of the Ino80-associated complex identified a highly conserved complex and the presence of a novel zinc finger protein with similarities to the mammalian transcriptional regulator Yin Yang 1 (YY1) and other members of the GLI-Krüppel family of proteins. Deletion of this Iec1 protein or the Ino80 complex subunit arp8, ies6, or ies2 causes defects in DNA damage repair, the response to replication stress, and nucleotide metabolism. We show that Iec1 is important for the correct expression of genes involved in nucleotide metabolism, including the ribonucleotide reductase subunit cdc22 and phosphate- and adenineresponsive genes. We find that Ino80 is recruited to a large number of promoter regions on phosphate starvation, including those of phosphate- and adenine-responsive genes that depend on Iec1 for correct expression. Iec1 is required for the binding of Ino80 to target genes and subsequent histone loss at the promoter and throughout the body of these genes on phosphate starvation. This suggests that the Iec1-Ino80 complex promotes transcription through nucleosome eviction.
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| 44. |
- Karthik, K. R. G., et al.
(författare)
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Physical and Electrical Properties of Single Zn2SnO4 Nanowires
- 2011
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Ingår i: Electrochemical and solid-state letters. - Pennington, NJ : Electrochemical Society. - 1099-0062 .- 1944-8775. ; 14:1, s. K5-K7
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Tidskriftsartikel (refereegranskat)abstract
- Electrical characterizations of single Zn2SnO4 (ZTO) nanowire devices are presented. These include resistivity, mobility, and photosensing measurements. The resistivity and the mobility of the Zn2SnO4 nanowire were measured to be 5.6 cm and 0.2 cm2/Vs, respectively. These values were found to be strongly dependent on the amount of electron-donating defects and less dependent on the thickness of the nanowires. An increase in the resistivity when changing the ambient atmosphere is observed. This change is caused by defect states lying in the bandgap, as shown by photoluminescence. The results imply the potential of ZTO nanowires as phototransistors and other photosensitive devices. © 2010 The Electrochemical Society.
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| 45. |
- Lagomarsino, L. P., et al.
(författare)
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Phylogeny, classification, and fruit evolution of the species-rich Neotropical bellflowers (Campanulaceae: Lobelioideae)
- 2014
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Ingår i: American Journal of Botany. - : Wiley. - 0002-9122 .- 1537-2197. ; 101:12, s. 2097-2112
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Tidskriftsartikel (refereegranskat)abstract
- Premise of the study: The species-rich Neotropical genera Centropogon, Burmeistera, and Siphocampylus represent more than half of the similar to 1200 species in the subfamily Lobelioideae (Campanulaceae). They exhibit remarkable morphological variation in floral morphology and habit. Limited taxon sampling and phylogenetic resolution, however, obscures our understanding of relationships between and within these genera and underscores our uncertainty of the systematic value of fruit type as a major diagnostic character. Methods: We inferred a phylogeny from five plastid DNA regions (rpl32-trnL, ndhF-rpl32, rps16-trnK, trnG-trnG-trns, rbcL) using maximum-likelihood and Bayesian inference. Ancestral character reconstructions were applied to infer patterns of fruit evolution. Key results: Our results demonstrate that the majority of species in the genera Centropogon, Burmeistera, and Siphocampylus together form a primarily mainland Neotropical clade, collectively termed the "centropogonids." Caribbean Siphocampylus, however, group with other Caribbean lobelioid species. We find high support for the monophyly of Burmeistera and the polyphyly of Centropogon and mainland Siphocampylus. The ancestral fruit type of the centropogonids is a capsule; berries have evolved independently multiple times. Conclusions: Our plastid phylogeny greatly improves the phylogenetic resolution within Neotropical Lobelioideae and highlights the need for taxonomic revisions in the subfamily. Inference of ancestral character states identifies a dynamic pattern of fruit evolution within the centropogonids, emphasizing the difficulty of diagnosing broad taxonomic groups on the basis of fruit type. Finally, we identify that the centropogonids, Lysipomia, and Lobelia section Tupa form a Pan-Andean radiation with broad habitat diversity. This clade is a prime candidate for investigations of Neotropical biogeography and morphological evolution.
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| 46. |
- Rhodes, Olin E., et al.
(författare)
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Integration of ecosystem science into radioecology : A consensus perspective
- 2020
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 740
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Tidskriftsartikel (refereegranskat)abstract
- In the Fall of 2016 a workshop was held which brought together over 50 scientists from the ecological and radiological fields to discuss feasibility and challenges of reintegrating ecosystem science into radioecology. There is a growing desire to incorporate attributes of ecosystem science into radiological risk assessment and radioecological research more generally, fueled by recent advances in quantification of emergent ecosystem attributes and the desire to accurately reflect impacts of radiological stressors upon ecosystem function. This paper is a synthesis of the discussions and consensus of the workshop participant's responses to three primary questions, which were: 1) How can ecosystem science support radiological risk assessment? 2) What ecosystem level endpoints potentially could be used for radiological risk assessment? and 3) What inference strategies and associated methods would be most appropriate to assess the effects of radionuclides on ecosystem structure and function? The consensus of the participants was that ecosystem science can and should support radiological risk assessment through the incorporation of quantitative metrics that reflect ecosystem functions which are sensitive to radiological contaminants. The participants also agreed that many such endpoints exit or are thought to exit and while many are used in ecological risk assessment currently, additional data need to be collected that link the causal mechanisms of radiological exposure to these endpoints. Finally, the participants agreed that radiological risk assessments must be designed and informed by rigorous statistical frameworks capable of revealing the causal inference tying radiological exposure to the endpoints selected for measurement.
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| 47. |
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| 48. |
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| 49. |
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| 50. |
- Allen-Philbey, Kimberley, et al.
(författare)
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Subcutaneous cladribine to treat multiple sclerosis : experience in 208 patients
- 2021
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Ingår i: Therapeutic Advances in Neurological Disorders. - : SAGE Publications. - 1756-2856 .- 1756-2864. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To report on safety and effectiveness of subcutaneous cladribine (Litak®) in multiple sclerosis (MS) patients. Methods: Litak® was offered to MS-patients irrespective of disease course. Litak® 10 mg was administered for 3–4 days during week 1. Based on lymphocyte count at week 4, patients received another 0–3 doses at week 5. A second course was administered 11 months later. Follow-up included adverse events, relapses, expanded disability status scale (EDSS), 9-hole-peg and Timed-25-foot-walking tests, no-evidence-of-disease-activity (NEDA), no-evidence-of-progression-or-active-disease (NEPAD), MRI, cerebrospinal fluid (CSF) neurofilament light chain (NfL), and lymphocyte counts. Results: In all, 208 patients received at least one course of treatment. Age at baseline was 44 (17–72) years and EDSS 0–8.5. Cladribine was generally well tolerated. One myocardial infarction, one breast cancer, and three severe skin reactions occurred without long-term sequelae. Two patients died (one pneumonia, one encephalitis). Lymphopenia grade 3 occurred in 5% and grade 4 in 0.5%. In 94 out of 116 pwMS with baseline and follow-up (BaFU) data after two treatment courses, EDSS remained stable or improved. At 18 months, 64% of patients with relapsing MS and BaFU data (n = 39) had NEDA. At 19 months, 62% of patients with progressive MS and BaFU data (n = 13) had NEPAD. Of n = 13 patients whose CSF-NfL at baseline was elevated, 77% were normalised within 12 months. Conclusions: Litak® was well tolerated. Effectiveness in relapsing MS appeared similar to cladribine tablets and was encouraging in progressive MS. Our data suggest cladribine may be safe and effective in MS-patients irrespective of their disease stage.
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