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Akaagerger, NB, DK Kaki, AI Philip e BA Ikyo. "Assessment of Radiofrequency Radiation Exposure Levels from Mobile Phones and Wireless Hotspots in Some Parts of Makurdi-Nigeria". NIGERIAN ANNALS OF PURE AND APPLIED SCIENCES 3, n.º 3b (15 de novembro de 2020): 138–43. http://dx.doi.org/10.46912/napas.204.
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Radio waves and Microwaves also known as Radio Frequency Radiations (RFR) have been associated with health hazards. This research was carried out to assess the safety level of these radiations in Makurdi, Benue State. Measurement of RFR power density and electric field strength were carried out for mobile phones. A Cornet 15SA Electrosmog meter was used for assessing RFR exposure levels. Measurements of RFR power density (mWm-2) and electric field strength (Vm-1) for wireless hotspots were carried out within 10m radius to offices and open areas with high occupancy. Radiation levels from mobile phones were measured on the surface with mobile phones in contact with the meter in a normal direction such that maximum readings are obtained. A survey questionnaire was also designed to assess the level of knowledge of the residents concerning the effects of exposure to RF radiations. The field strength and Power density from mobile phones were found to range from 0.1946 Vm-1 to 26.2446 Vm-1 and 0.1004 mWm-2 to 1.827 Wm-2 respectively. These are within ICNIRP recommended value of 10 Wm-2 for members of the public. Environmental levels of RFR in areas with RFR generating devices showed that RFR levels ranged from 5.0595Vm-1 (0.0679 Wm-1) to 7.3961Vm-1 (0.145 Wm1). Also, assessment of areas with Wi-Fi hotspots showed that the presence of hotspots significantly increased background levels of RFR. These values were compared with measurements carried out in areas without RF devices which ranged from 0.10212Vm-1 (0.02766 mWm-2) to 1.7334 Vm-1 (0.0079 Wm-2). The presence of devices was seen to increase the amount of radiation in the environment. The questionnaire results indicated that there was need to further educate the public on the effects of these radiations and precautionary to be adopted for safety.
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Rasmussen, Kelli M., Vikas Patil, Hsu-Chih Chien, Deborah Kay Morreall, Catherine Li, Zachary R. Burningham, Brian C. Sauer e Ahmad S. Halwani. "Real-World Practice Patterns in a Nationwide Cohort of Veterans with Waldenström's Macroglobulinemia". Blood 134, Supplement_1 (13 de novembro de 2019): 5270. http://dx.doi.org/10.1182/blood-2019-127738.
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Background Waldenström's macroglobulinemia (WM) is a rare indolent cancer. Because of its low incidence, the treatment practices for WM primarily rely on data from phase 2 trials, which often have no consensus as to how to best treat this uncommon disease. The heterogeneity of treatments available can be observed in clinical practice guidelines, which recommend traditional chemotherapies, second-generation proteasome inhibitors, multiagent immunotherapies, and the novel Bruton's tyrosine kinase inhibitor, ibrutinib (IBR). Yet, despite clinical evidence and treatment guidelines recommending multiagent chemoimmunotherapy in first-line (1L) patients with WM, a majority of patients still receive monotherapy, namely chlorambucil in Europe and monotherapy rituximab (R) in the United States. To date, there have been no reports on the real-world treatment practices in 1L of WM since the introduction of IBR. The primary objective of this study is to understand the 1L treatment practices for WM in a nationwide cohort of Veterans treated in the largest integrated healthcare system in the United States, the Veterans Health Administration (VA). Methods Using the VA Cancer Registry System and electronic healthcare records, we identified Veterans diagnosed with WM between January 1, 2006, to December 31, 2018. Treatment regimens were classified in accordance with the National Comprehensive Cancer Network (NCCN) guidelines for WM (versions 1.2006, 2.2013, and 2.2019). Eligible patients were followed until loss to follow-up, death or the end of the study observation period (June 30, 2019). The 1L of treatment was examined; with the start date for 1L being the index date. Patients with a cancer diagnosis other than WM and patients who did not receive 1L treatment were excluded from the study. Results We identified 340 patients who were diagnosed with WM and received a 1L treatment regimen between 2006-2019 in the VA. Median age at diagnosis was 68 years (range: 37-92); 334 (98%) of patients were male. Demographics are further described in Table 1. At diagnosis, the median serum IgM was 3083 mg/dl (range: 10-11500), the median hemoglobin was 11 g/dl (range: 5-17), and the platelet count was 204 k/dl (range: 5-732). A noticeable shift in the adoption of treatments can be observed when comparing treatment practices in patients treated between 2006-2009, 2010-2014, and those treated between 2015-2019. From 2006-2009 the majority of 1L patients received monotherapy with R (23, 37%) or chlorambucil (14, 22%). Between 2010-2014, the majority of patients received monotherapy R (43, 34%), with increasing adoption of bendamustine + R (8, 6%) and bortezomib (27, 21%). Between 2015-2019, IBR became the leading 1L treatment (38, 25%), followed by bendamustine + R (33, 22%), monotherapy R (33, 22%), and bortezomib + R (28, 19%). The estimated survival rate of WM patients treated with 1L was 79% at three-years, 68% at 5-years, and 55% at 7-years. Conclusions Our study is one of the first to examine the real-world treatment practices of WM patients treated with 1L after the approval of novel agent IBR. Our results highlight the heterogeneity of treatment options available for WM patients. We also describe the evolution of treatment choices in 1L over the last decade: from chlorambucil and rituximab monotherapy, to ibrutinib, bendamustine, and bortezomib. Retrospective and/or observational studies examining treatments and outcomes in WM patients should take these shifts in treatment practices into consideration. Given the persistent utilization of monotherapy R as a treatment in 1L, despite the superior efficacy of other treatment options such as ibrutinib, bendamustine and bortezomib regimens, our results indicate the need for continued efforts to educate clinicians about the appropriate treatment options available for this rare disease. Acknowledgments: The study was sponsored by Pharmacyclics Disclosures Sauer: University of Utah and SLC VA Medical Center: Employment. Halwani:Genentech, Inc.: Research Funding; Bristol-Myers Squibb: Research Funding; AbbVie: Research Funding; Pharmacyclics: Research Funding; Immune Design: Research Funding; Amgen: Research Funding; Kyowa Hakko Kirin: Research Funding; Seattle Genetics: Research Funding; Takeda: Research Funding; Miragen: Research Funding.
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Chen, Jiaji G., Xia Liu, Jie Chen, Lian Xu, Nicholas Tsakmaklis, Maria Demos, Christopher J. Patterson et al. "Acquisition of BTK C481S Produces Resistance to Ibrutinib in MYD88 Mutated WM and ABC DLBCL Cells That Is Accompanied By ERK1/2 Hyperactivation, and Is Targeted By the Addition of the ERK1/2 Inhibitor Ulixertinib". Blood 128, n.º 22 (2 de dezembro de 2016): 2764. http://dx.doi.org/10.1182/blood.v128.22.2764.2764.
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Abstract Activating mutations in MYD88 mutations trigger BTK (Yang et al, Blood 2013; Wilson et al, Nat. Med. 2015) and HCK (Yang et al, Blood 2016) activation in Waldenström's macroglobulinemia (WM) and ABC-DLBCL, which activate multiple downstream pro-survival signaling cascades that include NFkB, AKT, and ERK1/2. Ibrutinib targets BTK and HCK, and shows high levels of activity in MYD88 mutated WM and ABC DLBCL. Resistance to ibrutinib has been observed in CLL, MCL, and in WM (Xu et al, submitted) due to acquisition of mutations that impact the binding of ibrutinib to BTK at Cysteine 481, which include the C481S mutation. To explore the functional impact of the BTK C481S mutation on ibrutinib treatment in MYD88 mutated WM and ABC DLBCL cells, we transduced MYD88 L265P mutated BCWM.1 and MWCL-1 WM, and TMD-8 and HBL-1 ABC DLBCL cell lines with either lentiviral vector alone, or lentiviral vectors expressing BTK wild-type (BTK WT) or BTK with C481S (BTK C481S) mutation. Transduction with BTK C481S led to a 1-3 log fold increase in EC50 for ibrutinib versus vector only or BTK WT transduced cells. BTK C481S expressing cells showed hyperphosphorylation of PLCγ2 (Tyr 1217) which is immediately downstream of BTK, and ERK1/2 (Thr 202/Tyr 204) versus vector only or BTK WT cells in all four MYD88 mutated cell lines following ibrutinib (0.1, 0.5 uM) treatment for 2 hrs. In contrast, no changes in the phospho-IKBa (Ser 32), the gatekeeper of NFkB, nor phospho-AKT (Ser 473) or p38MAPK (Thr 180/Tyr 182) were observed between vector only, BTK WT or BTK C481S transduced cells following ibrutinib treatment. Given the hyperactivation of ERK1/2 in BTK C481S transduced cells treated with ibrutinib, we next evaluated the activity of ulixertinib (BVD-523, VRT752271), a highly selective ERK1/2 inhibitor that is currently under clinical investigation. Ulixertinib blocked ERK1/2 activity as evidenced by reduction of phospho-p90RSK (Ser 380) by western blot analysis in BTK C481S transduced BCWM.1 and TMD-8 cells. The combination of ulixertinib with ibrutinib produced higher levels of tumor cell killing than either agent alone, and showed synergistic interactions with combination index (CI) values below 1.0 at pharmacologically relevant concentrations. Our data indicate that acquisition of BTK C481S produces resistance to ibrutinib in MYD88 mutated WM and ABC DLBCL cells that is accompanied by ERK1/2 hyperactivation. The addition of the ERK1/2 inhibitor ulixertinib to ibrutinib at pharmacologically relevant concentrations produced synergistic tumor cell killing in BTK C481S ibrutinib resistant cells. The findings provide rationale for the investigation of ERK1/2 inhibitors in ibrutinib resistant MYD88 driven WM and ABC DLBCL disease mediated by BTK mutations. Disclosures Castillo: Pharmacyclics: Honoraria; Janssen: Honoraria; Millennium: Research Funding; Biogen: Consultancy; Otsuka: Consultancy; Abbvie: Research Funding. Treon:Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy.
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Varettoni, Marzia, Luca Arcaini, Silvia Zibellini, Emanuela Boveri, Sara Rattotti, Roberta Riboni, Alessandro Corso et al. "Prevalence and Clinical Significance of the MYD88 (L265P) Somatic Mutation in Patients with Waldenström Macroglobulinemia, IgM-Monoclonal Gammopathy of Undetermined Significance or Other Mature B-Cell Neoplasms." Blood 120, n.º 21 (16 de novembro de 2012): 2667. http://dx.doi.org/10.1182/blood.v120.21.2667.2667.
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Abstract Abstract 2667 Waldenström Macroglobulinemia (WM) is a B-cell lymphoproliferative disorder characterized by bone marrow infiltration by lymphoplasmacytic lymphoma associated with a monoclonal component of IgM type in the serum. WM is often preceded by an IgM monoclonal gammopathy of undetermined significance (IgM-MGUS). The cumulative probability of progression of IgM-MGUS to WM or to other lymphoproliferative disorders is approximately 1.5% per year. Other mature B-cell neoplasms such as splenic marginal zone lymphoma (SMZL) and B-cell chronic lymphoproliferative disorders (B-CLPD) can carry an IgM monoclonal component and should therefore be considered in differential diagnosis with WM. In a study based on parallel sequencing of the whole genome of lymphoplasmacytic cells and paired normal tissue from WM patients, Treon et al (Blood. 2011;118:Abstract 300) have identified a highly recurrent somatic mutation with oncogenic activity in the myeloid differentiation primary response (MYD88) gene, leading to a change from leucine to proline at position 265 of the aminoacid sequence [MYD88 (L265P)]. Targeted Sanger resequencing showed MYD88 (L265P) in 90% of WM patients, but only in a minority of patients with IgM-MGUS or other mature B-cell neoplasms such as SMZL. We developed an allele-specific PCR for the MYD88 (L265P) mutation, and studied 58 patients with WM, 77 with IgM-MGUS, 84 with splenic marginal zone lymphoma (SMZL) and 52 with B-cell chronic lymphoproliferative disorders (B-CLPD). DNA was obtained from bone marrow cells (n=204) and peripheral blood (n=67). The aims of this study were: i) to assess the prevalence of the mutation in WM, IgM-MGUS, SMZL, and B-CLPD; ii) to analyze the relationship between MYD88 (L265P) mutation and clinical phenotype; iii) to evaluate the impact of the mutation on the risk of progression from IgM-MGUS WM or other lymphoproliferative disorders. The MYD88 (L265P) mutation was detected in 58/58 (100%) patients with WM, either asymptomatic (n=39) or symptomatic (n=18), and in 36/77 (47%) patients with IgM-MGUS. In addition, it was detected in 5/84 (6%) patients with SMZL and in 3/52 (6%) with B-CLPD; of these MYD88 (L265P)-positive subjects, 4 SMZL and 2 B-CLPD patients carried a serum IgM monoclonal component, while the remaining B-CLPD patient carried a double (IgM and IgG) monoclonal component. Compared with IgM-MGUS patients with wild-type MYD88, those carrying MYD88 (L265P) had significantly higher levels of IgM (P<.0001), lower levels of IgG (P=.04) and IgA (P=.04), and higher incidence of Bence-Jones proteinuria at diagnosis (P=.002). During the follow-up, 9 patients with IgM-MGUS progressed to WM (7 cases) or to marginal zone lymphoma (2 cases). Using a case-control approach, the risk of evolution of patients with MYD88 (L265P) was significantly higher as compared to that of patients with wild-type MYD88 sequence (OR 4.7, 95% confidence interval 0.8–48.7, P=.047). In conclusion, the findings of this study indicate that: i) the allele-specific PCR we developed is able to detect the MYD88 (L265P) mutation in all patients with WM and in nearly half the patients with IgM-MGUS, and therefore represents a useful diagnostic tool; ii) MYD88 (L265P) is an uncommon molecular lesion in SMZL and in B-CLPD, but is associated with an IgM monoclonal component in the few positive patients, suggesting that some cases of B-CLPD might be included in the spectrum of WM; iii) in IgM-MGUS, the mutation is associated with greater disease burden and higher risk of disease progression, and therefore represents a useful prognostic marker. Disclosures: No relevant conflicts of interest to declare.
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Klimanova, E. A., e T. V. Konovalova. "Polymorphism of the BMP-15 locus in Romanov sheep in Western Siberia". Bulletin of NSAU (Novosibirsk State Agrarian University), n.º 2 (26 de julho de 2023): 197–204. http://dx.doi.org/10.31677/2072-6724-2023-67-2-197-204.
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Currently, selective selection takes into account gene polymorphisms associated not only with multiple pregnancies (growth differentiation factor 9 (GDF-9), bone morphogenetic protein receptor (BMPR-IB), etc.) but also with milk parameters (β-lactoglobulin (β-lg), αS1-casein) and meat (myostatin (MSTN), calpastatin (CAST), calpain (CAPN1)) productivity. Thus, genes associated with the transforming growth factor began to be monitored to improve reproductive performance in sheep breeding: BMP-15, GDF-9, and BMPR-IB. Genetic markers related to animal reproduction are exciting, with several productive indicators and other evaluation criteria that have not been previously studied. Work on the relationship of animal gene inheritance with biochemical, haematological, environmental and zootechnical indicators is particularly relevant. In this paper, we consider genotypic variability in Romanov sheep for the BMP-15 gene locus, which belongs to the genes of the β-growth factor family. The distribution of genotypes in sheep of the Romanov breed in the conditions of Western Siberia was as follows: for ewes, the frequencies of genotypes WW–25%, WM–75, and MM–0%; for sheep - 0, 80 and 20%, respectively. All three genotypes (WW, WM, and MM) were identified in the studied sheep. The results differ from the data obtained in several other works on foreign sheep breeds (short-tailed sheep Khan, Awassi, Barki, Ossimi, Rahmani, etc.). It is interesting to study the BMP-15 locus further to establish its associations with biochemical and haematological parameters and the hormonal status of sheep.
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Kwak, Sung-Gyu, Go-Eun Lee e Il-Ho Kim. "Electronic Transport and Thermoelectric Properties of Te-Doped Tetrahedrites Cu12Sb4-yTeyS13". Korean Journal of Metals and Materials 59, n.º 8 (5 de agosto de 2021): 560–66. http://dx.doi.org/10.3365/kjmm.2021.59.8.560.
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Tetrahedrite is a promising thermoelectric material mainly due to its low thermal conductivity, a consequence of its complicated crystal structure. However, tetrahedrite has a high hole concentration; therefore, optimizing carrier concentration through doping is required to maximize the power factor. In this study, Te-doped tetrahedrites Cu12Sb4-yTeyS13 (0.1 ≤ y ≤ 0.4) were prepared using mechanical alloying and hot pressing. The mechanical alloying successfully prepared the tetrahedrites doped with Te at the Sb sites without secondary phases, and the hot pressing produced densely sintered bodies with a relative density >99.7%. As the Te content increased, the lattice constant increased from 1.0334 to 1.0346 nm, confirming the successful substitution of Te at the Sb sites. Te-doped tetrahedrites exhibited p-type characteristics, which were confirmed by the positive signs of the Hall and Seebeck coefficients. The carrier concentration decreased but the mobility increased with Te content. The electrical conductivity was relatively constant at 323–723 K, and decreased with Te substitution from 2.6 × 104 to 1.6 × 104 Sm-1 at 723 K. The Seebeck coefficient increased with temperature and Te content, achieving values of 184–204 μVK-1 at 723 K. The thermal conductivity was <1.0 Wm-1K-1, and decreased with increasing Te content. Cu12Sb3.9Te0.1S13 exhibited the highest dimensionless figure of merit (ZT = 0.80) at 723 K, achieving a high power factor (0.91 mWm-1K-2) and a low thermal conductivity (0.80 Wm-1K-1).
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Nelson, Sydney, Lawrence H. Boise, Jonathan L. Kaufman, Leonard T. Heffner, Nishi N. Shah, Mary Jo Lechowicz, Sagar Lonial e Ajay K. Nooka. "Changing Epidemiology and Improved Survival In Patients With Waldenstrom Macroglobulinemia: Review Of Surveillance, Epidemiology, and End Results (SEER) Data". Blood 122, n.º 21 (15 de novembro de 2013): 3135. http://dx.doi.org/10.1182/blood.v122.21.3135.3135.
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Abstract Background Waldenstrom Macroglobulinemia (WM) is a hematological malignancy that affects 1500 people each year in the United States. Due to lack of literature on era comparative population-based analysis, we have analyzed Surveillance Epidemiology and End Results (SEER) data to evaluate the changes in incidence and survival patterns in the new millennium where modern therapeutic agents such as rituximab, immunomodulatory drugs and proteasome inhibitors were offered to WM patients; in contrast to the earlier period when they were non-existent. Methods The SEER 18 registry which includes data from 1973-2010 from 18 geographic areas including 28% of US representative population was used in analysis. ICD-O-3 code 9761 was used for identifying patients for this analysis. SEER* Stat 8.0.4 is used to calculate age-adjusted incidence and mortality rates based on race, gender, and age for patients. Age adjusted rates were used in this anlaysis to avoid confounding variables when comparing rates over time. Results We have included 4304 patients in the analysis (1244 patients diagnosed before 2000 and 3060 patients after 2000). The incidence rate of WM increased with age. The 10 year cumulative incidence rate per 100,000 by age stratification (<50 yrs, 50-59 yrs, 60-69 yrs, 70-79 yrs and >80) are 0.02%, 0.40%, 1.01%, 2.14% and 2.98% respectively. Over the last decade the trend of incidence rate in WM has been steadily decreasing across all age groups (Figure 1). Median survival for all WM patients is 74 months (m) (70.2-77.8). Significant survival improvement was seen in the current era (median survival ≥2000 vs. <2000: 84 m (79.8-92.2) vs. 64 m (57-67); p=0.000) Survival difference ≥2000 vs. <2000 was seen across most groups (male: 83 m vs. 58 m, p=0.000; female: 87 m vs. 70 m, p=0.004; white: 85 m vs. 62 m, p=0.000; age 50-59: 122 vs NR; p=0.002; age 60-69: 123 vs. 81 m; p=0.000; age 70-79: 69 vs. 53 m; p=0.001; age >80: 36 vs. 31 m; p=0.05). Younger patients <50 (NR vs. 204 m, p=0.53) and African American patients (75 m vs. 62 m, p=0.72) did not see survival benefit. Conclusion The incidence rates of Waldenstrom's macroglobulinemia are trending down over the last decade for reasons unclear. The survival rates have significantly improved across most stratifications of age, sex, gender in the new millennium. These results could be secondary to the favorable impact of new drugs used in treating patients with Waldenstrom's macroglobulinemia. Also should be taken into consideration, that the current classification for WM took place in the new millennium which is a limitation for interpretation of this survival benefit observed. Disclosures: Boise: Onyx Pharmaceuticals: Consultancy. Kaufman:Onyx: Consultancy; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Janssen: Consultancy; Millenium: Consultancy; Merck: Research Funding. Heffner:Genentech: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Biotest: Honoraria, Research Funding; Onyx: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Pharmacyclics: Honoraria, Research Funding. Lonial:Millennium: Consultancy; Celgene: Consultancy; Novartis: Consultancy; BMS: Consultancy; Sanofi: Consultancy; Onyx: Consultancy.
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Sullivan-Dunbar, Sandra. "Grenholm, Cristina. Motherhood and Love: Beyond the Gendered Stereotypes of Theology. Translated by, Marie Tåqvist. Grand Rapids, MI: Wm. B. Eerdmans, 2011. xx+204 pp. $25.00 (paper)." Journal of Religion 93, n.º 1 (janeiro de 2013): 105–6. http://dx.doi.org/10.1086/669836.
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Barnard, D. L., V. D. Hubbard, D. F. Smee, R. W. Sidwell, K. G. W. Watson, S. P. T. Tucker e P. A. R. Reece. "In Vitro Activity of Expanded-Spectrum Pyridazinyl Oxime Ethers Related to Pirodavir: Novel Capsid-Binding Inhibitors with Potent Antipicornavirus Activity". Antimicrobial Agents and Chemotherapy 48, n.º 5 (maio de 2004): 1766–72. http://dx.doi.org/10.1128/aac.48.5.1766-1772.2004.
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ABSTRACT Picornaviruses (PV) include human rhinovirus (HRV), the primary cause of the common cold, and the enteroviruses (EV), which cause serious diseases such as poliomyelitis, meningoencephalitis, and systemic neonatal disease. Although no compounds for PV infections have been approved in the United States, pirodavir was one of the most promising capsid-binding compounds to show efficacy in human clinical trials for chemoprophylaxis of the common cold. Susceptibility to hydrolysis precluded its use as an oral agent. We have developed orally bioavailable pyridazinyl oxime ethers that are as potent as pirodavir. Compounds BTA39 and BTA188 inhibited a total of 56 HRV laboratory strains and three clinical isolates as determined by neutral red uptake assay. At concentrations of <100 nM, BTA39 inhibited 69% of the HRV serotypes and isolates evaluated, BTA188 inhibited 75%, and pirodavir inhibited 59% of the serotypes and isolates. The 50% inhibitory concentrations (IC50s) for the two compounds ranged from 0.5 nM to 6,701 nM. The compounds also inhibited EV, including coxsackie A and B viruses (IC50 = 773 to 3,608 nM) and echoviruses (IC50 = 193 to 5,155 nM). BTA39 only inhibited poliovirus strain WM-1 at 204 nM, and BTA188 only inhibited poliovirus strain Chat at 82 nM. EV 71 was inhibited by BTA39 and BTA188, with IC50s of 1 and 82 nM, respectively. Both compounds were relatively nontoxic in actively growing cells (50% cytotoxic doses, ≥4,588 nM). These data suggest that these oxime ethers warrant further investigation as potential agents for treating selected PV infections.
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Buske, Christian, Meletios A. Dimopoulos, Alexander Grunenberg, Efstathios Kastritis, Cecile Tomowiak, Béatrice Mahé, Xavier Troussard et al. "Bortezomib in Combination with Dexamethasone, Rituximab and Cyclophosphamide (B-DRC) As First - Line Treatment of Waldenstrom's Macroglobulinemia: Results of a Prospectively Randomized Multicenter European Phase II Trial". Blood 136, Supplement 1 (5 de novembro de 2020): 26. http://dx.doi.org/10.1182/blood-2020-140933.
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Background: Rituximab/chemotherapy is still one of the cornerstones of treatment for patients with Waldenström's macroglobulinemia (WM) despite the emergence of BTK inhibitors. Beside Rituximab-Bendamustine the combination Dexamethasone, Rituximab and Cyclophospamide (DRC) is the most widely recommended immunochemotherapy in national and international guidelines based on its low myelotoxicity and anti-lymphoma activity in WM. In addition, the proteasome inhibitor Bortezomib (B) has shown significant activity in WM as single agent or combined with Rituximab and/or Dexamethasone. This study aimed at evaluating the efficacy and toxicity of Bortezomib-DRC (B-DRC) as first line treatment in WM. Methods: In this prospective randomized multicenter European phase II study, patients with the diagnosis of WM confirmed by reference pathology and in need of treatment were randomized 1:1 to DRC (Dexamethasone 20 mg orally d1, Rituximab 375 mg/m2 IV d1 cycle 1 and 1400 mg SC d1 cycle 2-6, Cyclophosphamide 100 mg/m2 x 2 orally d1-5) or to B-DRC (DRC plus Bortezomib SC 1,6mg/m2 day 1, 8, 15) for 6 cycles (28d interval). Primary endpoint was progression free survival (PFS). Secondary endpoints included response rates, overall survival (OS), and toxicity. Results: Of 204 registered patients, 2 patients were excluded due to incorrect randomization. Median follow-up was 27.5 months at the time of the data cut. Median age was 68 years (range 34-89) in both arms. According to the ISSWM prognostic score 14 % of patients were at low, 73 % at intermediate and 13 % at high risk in both treatment arms. Median baseline hemoglobin for B-DRC and DRC was 10.0 and 9.8 g/dl and median baseline IgM 31.7 and 31.9 g/dl, respectively. Mutational status was available for 72 patients: in the B-DCR vs DRC treatment arm 26 and 16 patients were MYD88 mutated (MYD88MT) and CXCR4 wildtype (CXCR4WT), 8 and 12 patients were MYD88MT/CXCR4MT and 5 and 5 patients MYD88WT/CXCR4WT, respectively. Median PFS has not been reached in the B-DRC arm (95% CI: 33.5; --) compared to 50.1 months in the DRC arm (95% CI: 31.1; --) with an estimated PFS at 24 months of 80.6 % (95% CI: 69.5; 88.0) and 72.8 % (95% CI: 61.3; 81.3), respectively (p=0.32). Median OS has not been reached in either treatment arm with 5 deaths and 6 deaths in the B-DRC and DRC arm, respectively. At the end of treatment B-DRC induced major responses (at least PR) in 79.1 % of patients (vs 68.9% for DRC) and a CR/VGPR in 18.7 % of patients (vs 11.1 % for DRC) with an overall response of 91.2 compared to 86.7 % for DRC. Compared to baseline IgM decreased by 79 % and 73 % and Hb increased by 28 % and 32 % in the B-DRC and DRC arm, respectively. Responses and PFS were independent of the mutational status in both treatment arms. B-DRC and DRC were well tolerated: grade ≥3 AEs occurred in 48% of all patients (B-DRC 48%, DRC 47%). Most common grade ≥3 AEs included neutropenia (25%), anemia (6%), and thrombocytopenia (5%). Overall, 16 pts (8%) developed infections (1% grade ≥3). Serious AEs occurred in 40 pts (20%) (DRC: 26 (26%), B-DRC: 14 (14%)). Peripheral sensory neuropathy occurred in 18 patients treated with B-DRC (2 patients with grade 3, 16 patients grade 1-2) and in 3 patients treated with DRC (all grade 1 and 2). Conclusions: This is the first and largest prospective randomized trial to evaluate bortezomib in combination with standard immunochemotherapy, demonstrating that B-DRC is a well-tolerated regimen which induces a high rate of major responses including deep remissions after 6 months of treatment with a 2-year PFS of 81%, independently of the mutational status of MYD88 and CXCR4. At this time point of analysis, adding Bortezomib to DRC did not induce significant differences in PFS compared to DRC alone. Future trials will have to compare chemotherapy-free approaches such as continuous treatment with BTK inhibitors with fixed duration treatments exemplified by B-DRC to understand which of the two treatment approaches offers the highest long - term sustained clinical benefit to WM patients. Disclosures Buske: Roche, Janssen, Bayer, MSD: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Roche, Janssen, AbbVie, Pfizer, Celltrion: Honoraria, Speakers Bureau. Dimopoulos:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau. Kastritis:Genesis Pharma: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Tomowiak:Roche: Research Funding; Gilead: Research Funding; Janssen: Honoraria; AbbVie: Honoraria; Beigene: Honoraria; Takeda: Honoraria. Hajek:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria; PharmaMar: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Research Funding; Oncopeptides: Consultancy. Viardot:Roche: Honoraria, Other: advisory board; Kite/Gilead: Honoraria, Other: advisory board; Novartis: Honoraria, Other: advisory board; Amgen: Honoraria, Other: advisory board. Aurran:Janssen: Honoraria. Lepretre:Gilead: Honoraria; Astra Zeneca: Honoraria; AbbVie: Honoraria; Janssen: Honoraria. Leblond:AbbVie: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Lilly: Honoraria; Janssen: Honoraria; Roche: Honoraria; Astra Zeneca: Honoraria; Amgen: Honoraria; Gilead: Honoraria; Beigene: Honoraria; Beigene: Membership on an entity's Board of Directors or advisory committees. de Guibert:Gilead Sciences: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Garcia-Sanz:Amgen: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Gilead: Honoraria, Research Funding; Incyte: Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria; Pharmacyclics: Honoraria; Takeda: Consultancy, Research Funding. Gomes da Silva:roche: Consultancy; abbvie: Consultancy; BMS: Consultancy; MSD: Consultancy; Janssen: Consultancy; Gilead: Consultancy. Morel:Janssen: Honoraria. OffLabel Disclosure: Bortezomib in combination with DRC in Waldenström's Macroglobulinemia
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Macedo, Alice Dos Santos, e Gilberto Fisch. "Variabilidade Espacial da Radiação Solar na Região de Manaus - AM durante o Experimento GOAmazon 2014/15 (Spatial variability of solar radiation in Manaus-AM region during GOAmazon Experiment 2014/15)". Revista Brasileira de Geografia Física 10, n.º 6 (9 de novembro de 2017): 1802. http://dx.doi.org/10.26848/rbgf.v10.6.p1802-1811.
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Este trabalho realizou um estudo da variabilidade espacial em 2014 da irradiância solar na região de Manaus-AM, através de dados observacionais, inserido no Projeto GOAmazon 2014/15. Também, como forma complementar, foi realizada a análise da cobertura de nuvens, chuva e aerossóis e suas interrelações com a irradiância solar. Como resultado, observa-se que os menores valores médios da irradiância solar ocorreram na área urbana,o que é justificado, em parte pela urbanização que altera os fluxos envolvidos, diminuindo a irradiância solar à superfície. Os valores típicos são entre 400 e 600 Wm-2na estação chuvosa (fevereiro/março) com um desvio padrão de 200 e 380 Wm-2e entre 650 e 800 Wm-2na estação seca (agosto-setembro) com desvio padrão de 190 e 300 Wm-2. A B S T R A C T The solar radiation is an important climatic element in the Amazon region, as it has a strong impact for ecological (by the preservation of the biodiversity) and technological (as a renewable energy) areas. Consequently, this study contributes for these themes, conducting an observational study of the spatial variability of the solar irradiance for Manaus-AM area, with data collected during the project GOAmazon 2014/15. The cloud cover and rainfall and their relationships with solar radiation were also analysed. The maximum values observed for the wet season (february and march) are in the range 450 and 600 Wm-2 with high standart deviation (300 - 350 Wm-2 ), while they are in the range from 650 and 800 Wm-2 during the dry period (august - september) with lower standart deviation (200 - 300 Wm-2). These values are directly associated with cloud cover and rainfall. In general, the urban area (Manaus city) showed the low values of solar radiation at the surface compared with its neighborhood, inducing a horizontal gradient of clouds/rainfall and solar energy between the city and the semi rural areas. Keywords: piranometer, global solar radiation, cloud cover, total sky imager
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Pethes, Nicolas. "WM in Brasilien". POP 3, n.º 1 (1 de março de 2014): 13–18. http://dx.doi.org/10.14361/pop-2014-0103.
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Cheng, Chi-Han, e Fidelia Nnadi. "Predicting Downward Longwave Radiation for Various Land Use in All-Sky Condition: Northeast Florida". Advances in Meteorology 2014 (2014): 1–12. http://dx.doi.org/10.1155/2014/525148.
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Accurate estimate of the surface longwave radiation is important for the surface radiation budget, which in turn controls evaporation and sensible heat fluxes. Regional land use changes can impact local weather conditions; for example, heterogeneous land use patterns and temporal changes in atmospheric circulation patterns would affect air temperature and water vapor pressure, which are more commonly used as inputs in existing models for estimating downward longwave radiation (LWd). In this study, first, we analyzed the cloud cover and land use covers impacts onLWd. Next,LWdon all-sky conditions were developed by using the existing land use-adapted model and cloud cover data from the region of Saint Johns River Water Management District (SJRWMD), FL. The results show that factors, such as, seasonal effects, cloud cover, and land use, are of importance in the estimation ofLWdand they cannot be ignored when developing a model forLWdprediction. The all-sky land use-adapted model with all factors taken into account performs better than other existing models statistically. The results of the statistical analyses indicated that the BIAS, RMSE, MAE, and PMRE are −0.18 Wm−2, 10.81 Wm−2, 8.00 Wm−2, and 2.30%; −2.61 Wm−2, 14.45 Wm−2, 10.64 Wm−2, and 3.19%; −0.07 Wm−2, 10.53 Wm−2, 8.03 Wm−2, and 2.27%; and −0.62 Wm−2, 13.97 Wm−2, 9.76 Wm−2, and 2.87% for urban, rangeland, agricultural, and wetland areas, respectively.
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Ostrowski, Janusz, Wojciech Stefan Zgliczyński, Jarosław Pinkas e Ryszard Gellert. "History of the School of Public Health at the Centre of Postgraduate Medical Education (1971 to 2021)". Wiedza Medyczna 4, n.º 1 (28 de junho de 2022): 1–7. http://dx.doi.org/10.36553/wm.132.
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The 50th anniversary of the Centre of Postgraduate Medical Education (CMKP) was celebrated in 2021. Since the beginning, the School of Public Health (SZP) has been inseparable linked with the CMKP. Throughout this period, the position of the SZP director has been held by eight persons i.e. Bogusław Kożusznik (1971 to 1977), Marek Sanecki (1978 to 1991), Andrzej Wojtczak (1991 to 1996), Jerzy Leowski (1996 to 2003), Janusz Opolski (2003 to 2004 and 2005 to 2011), Maria Miller (2005 to 2005), Dorota Cianciara (2011 to 2018) and Jarosław Pinkas (since 2018). In the paper, the consecutive directors and the SZP modifications during the period of the recent 50 years is presented.
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Yoon, Hae-chang. "A study on the characteristics of patients with facial palsy treated with Korean medicine - Based on the Korean National Health Insurance statistical yearbook". Journal of Korean Medicine 44, n.º 2 (1 de junho de 2023): 10–19. http://dx.doi.org/10.13048/jkm.23013.
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Objectives: This study aimed to find out the characteristics of patients with facial palsy based on the National Health Insurance(NHI) statistical yearbook and provide the information pertaining to supplement Coverage of NHI.Methods: Based on the data of NHI between 2004 to 2021 for facial palsy(G51) obtained from the Ministry of Health and Welfare, the analyses were carried out according to the distribution of gender and the number of patients, visits, reimbursed days, and medical expenses by using the SAS 9.4.Results: The crude rate of facial palsy was reported as 361.71(2021) comparable with 419.60(2004) and 534.11(2009). The rate of men increased from 293.96(2004) to 302.27(2021) but the rate of women decreased from 450.88(2014) to 420.80(2021). The number of patients maintained around 190,000, however, it declined for patients treated Korean medicine(KM) after 2010. As the medical expenses were elevated, especially Western medicine(WM), that of WM exceeded KM’s since 2018. The expenses of women were higher than men’s in KM. By contrast, there was no difference with gender in WM. For reimbursed days per visits, it has been increased in WM but there was no difference in KM.Conclusion: Although the rate of patients with facial palsy in KM was high with no difference in the whole number of patients and reimbursed days per visits in KM annually, the number of patients in KM decreased but medical expenses elevated. According to this, it is necessary for reinforcing Coverage of NHI to research other factors related to KM.
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Powell, Tamara L., Marie Arsalidou, Vanessa M. Vogan e Margot J. Taylor. "Letter and Colour Matching Tasks: Parametric Measures of Developmental Working Memory Capacity". Child Development Research 2014 (30 de novembro de 2014): 1–9. http://dx.doi.org/10.1155/2014/961781.
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We investigated the mediating role of interference in developmental assessments of working memory (WM) capacity across childhood, adolescence, and young adulthood. One hundred and forty-two participants completed two versions of visuospatial (colour matching task, CMT) and verbal (letter matching task, LMT) WM tasks, which systematically varied cognitive load in a high and low interference condition. Results showed similar developmental trajectories across high interference contexts (CMT- and LMT-Complex) and divergent developmental growth patterns across low interference contexts (CMT- and LMT-Simple). Performance on tasks requiring greater cognitive control was in closer agreement with developmental predictions relative to simple recall guided tasks that rely solely on the storage components of WM. These findings suggest that developmental WM capacity, as measured by the CMT and LMT paradigms, can be better quantified using high interference contexts, in both content domains, and demonstrate steady increases in WM through to mid-adolescence.
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Bett, K. E., A. Vandenberg, S. Banniza, Q. Lu, B. Barlow e S. Ife. "CDC WM-2 common bean". Canadian Journal of Plant Science 94, n.º 2 (março de 2014): 469–71. http://dx.doi.org/10.4141/cjps2013-313.
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Bett, K. E., Vandenberg, A., Banniza, S., Lu, Q., Barlow, B. and Ife, S. 2014. CDC WM-2 common bean. Can. J. Plant Sci. 94: 469–471. CDC WM-2 is a short-season, slow-darkening, pinto bean cultivar (CFIA Registration #6593) with indeterminate growth habit and tolerance to common bacterial blight and anthracnose races 73 and 105. It was developed using marker-assisted backcrossing and field testing.
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Paiva, Bruno, Luis A. Corchete, Maria-Belen Vidriales, Ramón García-Sanz, Jose J. Perez, Irene Aires-Mejia, Maria-Luz Sanchez et al. "The cellular origin and malignant transformation of Waldenström macroglobulinemia". Blood 125, n.º 15 (9 de abril de 2015): 2370–80. http://dx.doi.org/10.1182/blood-2014-09-602565.
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Key Points Benign (ie, IgM MGUS and smoldering WM) clonal B cells already harbor the phenotypic and molecular signatures of the malignant WM clone. Multistep transformation from benign (ie, IgM MGUS and smoldering WM) to malignant WM may require specific copy number abnormalities.
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Lee, Ho Sup, Kihyun Kim, Dok Hyun Yoon, Jin Seok Kim, Soo-Mee Bang, Jeong-Ok Lee, Hyeon Seok Eom et al. "Clinical Factors Associated with Response or Survival after Chemotherapy in Patients with Waldenström Macroglobulinemia in Korea". BioMed Research International 2014 (2014): 1–7. http://dx.doi.org/10.1155/2014/253243.
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Waldenström’s macroglobulinemia (WM) is a B-cell proliferative malignancy characterized by immunoglobulin M monoclonal gammopathy and bone marrow infiltration by lymphoplasmacytic cells. Clinical features and cytogenetics of WM in Asia including Republic of Korea remain unclear. Moreover, no study has reported treatment outcomes in patients with WM treated with novel agent combined with conventional chemotherapy. This study investigated clinical features and assessed treatment outcomes with novel agent and conventional chemotherapy in Republic of Korea. Data from all (n=71) patients with newly diagnosed WM at 17 hospitals who received chemotherapy between January 2005 and December 2012 were collected retrospectively. The median age of patients was 66 years (range: 37–92 years) and male to female ratio was 5 : 1. Patients treated with novel agent combined chemotherapy displayed higher overall response rate (ORR) compared to conventional chemotherapy alone (92.9% versus 52.6%,P=0.006). The 5-year overall survival rate was 62.6% (95% confidence interval: 34.73–111.07). Use of novel agents produced higher ORR but survival benefit was not apparent due to the small number of patients and short follow-up duration. Further studies are needed to confirm the efficacy of novel agents in patients with WM.
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Tassone, Pierfrancesco, Paola Neri, Jeffery L. Kutok, Olivier Tournilhac, Daniel Ditzel Santos, Evdoxia Hatjiharissi, Vidit Munshi et al. "A SCID-hu in vivo model of human Waldenström macroglobulinemia". Blood 106, n.º 4 (15 de agosto de 2005): 1341–45. http://dx.doi.org/10.1182/blood-2004-11-4477.
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AbstractThe preclinical evaluation of investigational agents for Waldenström macroglobulinemia (WM) has been limited by the lack of in vivo models that enable the use of explanted patient cells. We describe here a novel in vivo model of human WM in severe combined immunodeficient (SCID) mice implanted with human fetal bone chips (SCID-hu mice) into which WM cells from patient bone marrow are engrafted directly into the human bone marrow (huBM) microenvironment. WM cells in SCID-hu mice produced human monoclonal paraprotein (immunoglobulin M [IgM] and/or κ or λ chain) detectable in mice sera. Immunohistochemical analysis of human bone retrieved from SCID-hu mice showed infiltration with CD20+, IgM+, and monotypic light chain+ lymphoplasmacytic cells. Mast cells were observed to be associated with the infiltrate in these sections. Treatment of SCID-hu mice bearing WM with rituximab induced tumor regression, associated with a decrease in serum paraprotein. This model, therefore, recapitulates the in vivo biology of WM and allows the study of novel investigational drugs targeting WM cells in the huBM milieu. (Blood. 2005;106:1341-1345)
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Li, Xiufeng, Subhendra N. Sarkar, David E. Purdy e Richard W. Briggs. "Quantifying Cerebellum Grey Matter and White Matter Perfusion Using Pulsed Arterial Spin Labeling". BioMed Research International 2014 (2014): 1–12. http://dx.doi.org/10.1155/2014/108691.
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To facilitate quantification of cerebellum cerebral blood flow (CBF), studies were performed to systematically optimize arterial spin labeling (ASL) parameters for measuring cerebellum perfusion, segment cerebellum to obtain separate CBF values for grey matter (GM) and white matter (WM), and compare FAIR ASST to PICORE. Cerebellum GM and WM CBF were measured with optimized ASL parameters using FAIR ASST and PICORE in five subjects. Influence of volume averaging in voxels on cerebellar grey and white matter boundaries was minimized by high-probability threshold masks. Cerebellar CBF values determined by FAIR ASST were 43.8 ± 5.1 mL/100 g/min for GM and 27.6 ± 4.5 mL/100 g/min for WM. Quantitative perfusion studies indicated that CBF in cerebellum GM is 1.6 times greater than that in cerebellum WM. Compared to PICORE, FAIR ASST produced similar CBF estimations but less subtraction error and lower temporal, spatial, and intersubject variability. These are important advantages for detecting group and/or condition differences in CBF values.
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Kowalska, Iwona. "Edukacja na rzecz rozwoju regionu – ocena założeń wieloletnich ram finansowych 2014–2020 w RPO województwa mazowieckiego". Turystyka i Rozwój Regionalny, n.º 3 (15 de janeiro de 2005): 53–66. http://dx.doi.org/10.22630/tirr.2015.3.5.
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Głównym celem Regionalnego Programu Operacyjnego Województwa Mazowieckiego 2014–2020 (RPO WM) jest inteligentny, zrównoważony rozwój zwiększający spójność społeczną i terytorialną przy wykorzystaniu potencjału mazowieckiego rynku pracy. Program stanowi narzędzie realizacji polityki rozwoju prowadzonej przez Samorząd Województwa Mazowieckiego. Polityka ta obejmuje również rozwój w obszarze edukacji. Warto zatem podjąć się wstępnej oceny założeń wieloletnich ram finansowych 2014–2020 w RPO WM w części dotyczącej edukacji. Celem artykułu jest próba dokonania tej oceny z uwzględnieniem trzech aspektów: – zakresu przedmiotowego w konfrontacji z zapisami RPO WM 2007–2013, obszarem inteligentnych specjalizacji dla Mazowsza 2014–2020 oraz z założeniami Programu Operacyjnego Wiedza, Edukacja Rozwój 2014–2020 (POWER); – procedury pozyskania wsparcia finansowego (konkurencyjność versus preferencje programowe); – nakłady i instrumenty finansowe (środki bezzwrotne versus środki zwrotne). W artykule poddano weryfikacji następującą hipotezę: zakres przedmiotowy finansowania Osi Priorytetowej X: Edukacja dla regionu w RPO WM 2014–2020 nie pokrywa się z zakresami innych programów operacyjnych w tej perspektywie, a kwestia konkurencyjności jest osłabiona szeroką skalą preferencyjności w wyborze projektów przy zastosowaniu bezzwrotnych instrumentów finansowych (dotacji). Przy opracowaniu artykułu korzystano z materiałów źródłowych Komisji Europejskiej, krajowych dokumentów dotyczących strategii rozwoju oraz literatury przedmiotu dotyczącej absorpcji środków unijnych na projekty społeczne.
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Petrikkos, Loizos, Marie-Christine Kyrtsonis, Maria Roumelioti, George Georgiou, Anna Efthymiou, Tatiana Tzenou e Panayiotis Panayiotidis. "Clonotypic Analysis of Immunoglobulin Heavy Chain Sequences in Patients with Waldenström’s Macroglobulinemia: Correlation withMYD88L265P Somatic Mutation Status, Clinical Features, and Outcome". BioMed Research International 2014 (2014): 1–6. http://dx.doi.org/10.1155/2014/809103.
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We performedIGHclonotypic sequence analysis in WM in order to determine whether a preferentialIGHgene rearrangement was observed and to assessIGHVmutational status in blood and/or bone marrow samples from 36 WM patients. In addition we investigated the presence ofMYD88L265P somatic mutation. AfterIGHVDJ locus amplification, monoclonal VDJ rearranged fragments were sequenced and analyzed.MYD88L265P mutation was detected by AS-PCR. The most frequent family usage wasIGHV3(74%);IGHV3-23andIGHV3-74segments were used in 26% and 17%, respectively. Somatic hypermutation was seen in 91% of cases.MYD88L265P mutation was found in 65,5% of patients and absent in the 3 unmutated. These findings did not correlate with clinical findings and outcome. Conclusion.IGH genes’repertoire differed in WM from those observed in other B-cell disorders with a recurrentIGHV3-23andIGHV3-74usage; monoclonalIGHVwas mutated in most cases, and a high but not omnipresent prevalence ofMYD88L265P mutation was observed. In addition, the identification of 3 patients with unmutatedIGHVgene segments, negative for theMYD88L265P mutation, could support the hypothesis that an extra-germinal B-cell may represent the originating malignant cell in this minority of WM patients.
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Kim, Jung-Ah, Kyongok Im, Si Nae Park, Jiseok Kwon, Qute Choi, Sang Mee Hwang, Naohiro Sekiguchi, Sung-Soo Yoon, Dong Soon Lee e Seon Young Kim. "MYD88 L265P Mutations Are Correlated with 6q Deletion in Korean Patients with Waldenström Macroglobulinemia". BioMed Research International 2014 (2014): 1–7. http://dx.doi.org/10.1155/2014/363540.
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Waldenström macroglobulinemia (WM) is a malignant lymphoplasma-proliferative disorder with IgM monoclonal gammopathy. A recent whole-genome study identified MYD88 L265P as the key mutation in WM. We investigatedMYD88mutations in conjunction with cytogenetic study in 22 consecutive Korean WM patients. Conventional G-banding and interphase fluorescencein situhybridization (FISH) were performed at regions including 6q21 using bone marrow (BM) aspirates. Sixteen patients were subjected to Sanger sequencing-basedMYD88mutation study. Five patients (28%) showed cytogenetic aberrations in G-banding. The incidence of 6q21 deletion was 17% by conventional G-banding and 37% by FISH. Ten patients (45%) showed cytogenetic aberrations using FISH: 6q deletion in eight (37%) andIGHrearrangement in four (18%). Two patients had both the 6q deletion andIGHrearrangement, and two had only theIGHrearrangement. Eleven patients (69%) presented with the MYD88 L265P mutation.MYD88mutations were significantly associated with the presence of 6q deletions (P=0.037). Six patients with the 6q deletion for whom sequencing was possible were found to harborMYD88mutations. The MYD88 L265P mutation was also associated with increased lymphocyte burden in BM biopsy. This is the first report of high frequency MYD88 L265P mutations in Korean WM patients.
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Fulciniti, Mariateresa, Nicola Amodio, Rajya Lakshmi Bandi, Mansa Munshi, Guang Yang, Lian Xu, Zachary Hunter et al. "MYD88-independent growth and survival effects of Sp1 transactivation in Waldenström macroglobulinemia". Blood 123, n.º 17 (24 de abril de 2014): 2673–81. http://dx.doi.org/10.1182/blood-2014-01-550509.
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Wang, Zhen, Yan-Jun Du, Yan-Jun Ding, Zheng Li e Zhi-Min Peng. "Monitoring of ambient carbon monoxide concentrations based on wavelength modulation direct absorption spectroscopy". Acta Physica Sinica 71, n.º 4 (2022): 044205. http://dx.doi.org/10.7498/aps.71.20211772.
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Wavelength modulation-direct absorption spectroscopy (WM-DAS) has the advantages of both direct absorption spectroscopy (DAS) measurable absorptivity function and wavelength modulation spectrum (WMS) with high signal-to-noise ratio (SNR). In this paper, the WM-DAS spectrum is used to measure the absorptivity of 4300.7 cm<sup>–1</sup> line of CO molecule and the detection limit is as low as 4 × 10<sup>–7</sup> (200 s) at 0.5 m optical path, room temperature and low pressure. Then, through combining the WM-DAS spectrum with a 120 m long optical path Herriott cell, at room temperature and atmospheric pressure, the standard deviation of the fitting residual error of the absorptivity function is reduced down to ~5.1 × 10<sup>–5</sup> (1 s). Finally, different concentrations of CO are continuously monitored by long-path WM-DAS measurement system, and compared with the results obtained from the cavity ring-down spectroscopy (CRDS). The experimental results show that the measurement results from the long-path WM-DAS and CRDS method are the same. The detection limit of CO concentration in long-path WM-DAS system is as low as 0.9 ppb (200 s), and the WM-DAS system is simple and the measurement speed is much faster than CRDS. At the same time, the long-path WM-DAS system is used to continuously monitor the atmospheric trace CO concentration and trend for one month, and the measured results are highly consistent with those from the China Environmental Monitoring Station.
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Peng, Syu-Jyun, Tomor Harnod, Jang-Zern Tsai, Chien-Chun Huang, Ming-Dou Ker, Jun-Chern Chiou, Herming Chiueh, Chung-Yu Wu e Yue-Loong Hsin. "Through Diffusion Tensor Magnetic Resonance Imaging to Evaluate the Original Properties of Neural Pathways of Patients with Partial Seizures and Secondary Generalization by Individual Anatomic Reference Atlas". BioMed Research International 2014 (2014): 1–8. http://dx.doi.org/10.1155/2014/419376.
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To investigate white matter (WM) abnormalities in neocortical epilepsy, we extract supratentorial WM parameters from raw tensor magnetic resonance images (MRI) with automated region-of-interest (ROI) registrations. Sixteen patients having neocortical seizures with secondarily generalised convulsions and 16 age-matched normal subjects were imaged with high-resolution and diffusion tensor MRIs. Automated demarcation of supratentorial fibers was accomplished with personalized fiber-labeled atlases. From the individual atlases, we observed significant elevation of mean diffusivity (MD) in fornix (cres)/stria terminalis (FX/ST) and sagittal stratum (SS) and a significant difference in fractional anisotropy (FA) among FX/ST, SS, posterior limb of the internal capsule (PLIC), and posterior thalamic radiation (PTR). For patients with early-onset epilepsy, the diffusivities of the SS and the retrolenticular part of the internal capsule were significantly elevated, and the anisotropies of the FX/ST and SS were significantly decreased. In the drug-resistant subgroup, the MDs of SS and PTR and the FAs of SS and PLIC were significantly different. Onset age was positively correlated with increases in FAs of the genu of the corpus callosum. Patients with neocortical seizures and secondary generalisation had microstructural anomalies in WM. The changes in WM are relevant to early onset, progression, and severity of epilepsy.
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Zhu, Li Bing, Wai Chung Chan, Kwai Ching Lo, Tin Pui Yum e Lei Li. "Wrist-Ankle Acupuncture for the Treatment of Pain Symptoms: A Systematic Review and Meta-Analysis". Evidence-Based Complementary and Alternative Medicine 2014 (2014): 1–9. http://dx.doi.org/10.1155/2014/261709.
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Routine acupuncture incorporates wrist-ankle acupuncture (WAA) for its analgesic effect, but WAA is not widely used in clinics due to incomplete knowledge of its effectiveness and concerns about less clinical research and because less people know it. This study aimed to assess the efficacy and possible adverse effects of WAA or WAA adjuvants in the treatment of pain symptoms. This study compared WAA or WAA adjuvant with the following therapies: western medication (WM), sham acupuncture (SA), or body acupuncture (BA). Randomized controlled trials (RCTs) were searched systematically in related electronic databases by two independent reviewers. 33 RCTs were finally included, in which 7 RCTs were selected for meta-analysis. It was found that WAA or WAA adjuvant was significantly more effective than WM, SA, or BA in pain relief. There was nothing different between WAA and SA in adverse events, but WAA was marginally significantly safer than WM. Although both WAA and WAA adjuvant appeared to be more effective than WM, SA, or BA in the treatment of pain symptoms with few side effects, further studies with better and more rigorously designed are still necessary to ensure the efficacy and safety issue of WAA due to the poor methodology and small sample size of previous studies.
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Morra, Enrica. "Carfilzomib: a new opportunity for WM patients". Blood 124, n.º 4 (24 de julho de 2014): 468–69. http://dx.doi.org/10.1182/blood-2014-06-578625.
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Messina, Silvia, e Francesco Patti. "Gray Matters in Multiple Sclerosis: Cognitive Impairment and Structural MRI". Multiple Sclerosis International 2014 (2014): 1–9. http://dx.doi.org/10.1155/2014/609694.
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Multiple sclerosis (MS) is an immune-mediated disease affecting central nervous system (CNS). Although MS is classically considered a white matter (WM) disease, the involvement of gray matter (GM) in the pathogenic process has been confirmed by pathology studies and MRI studies. Impairment of cognitive domains such as memory, mental processing speed, attention, and executive function can occur from the early stage of the disease and tends to worsen over time, despite stable physical symptoms. WM demyelination is moderately correlated with CI, suggesting that probably WM abnormalities alone cannot fully explain the extent of clinical symptoms in MS, including CI. Several MRI techniques have shown the involvement of GM in MS and the association between GM damage, physical disability, and CI. The aim of this review is to provide an overview of CI and GM damage assessed by structural brain MRI.
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Manson, Eric Naab, Stephen Inkoom, Abdul Nashirudeen Mumuni, Issahaku Shirazu e Adolf Kofi Awua. "Assessment of the Impact of Turbo Factor on Image Quality and Tissue Volumetrics in Brain Magnetic Resonance Imaging Using the Three-Dimensional T1-Weighted (3D T1W) Sequence". International Journal of Biomedical Imaging 2023 (15 de novembro de 2023): 1–9. http://dx.doi.org/10.1155/2023/6304219.
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Background. The 3D T1W turbo field echo sequence is a standard imaging method for acquiring high-contrast images of the brain. However, the contrast-to-noise ratio (CNR) can be affected by the turbo factor, which could affect the delineation and segmentation of various structures in the brain and may consequently lead to misdiagnosis. This study is aimed at evaluating the effect of the turbo factor on image quality and volumetric measurement reproducibility in brain magnetic resonance imaging (MRI). Methods. Brain images of five healthy volunteers with no history of neurological diseases were acquired on a 1.5 T MRI scanner with varying turbo factors of 50, 100, 150, 200, and 225. The images were processed and analyzed with FreeSurfer. The influence of the TFE factor on image quality and reproducibility of brain volume measurements was investigated. Image quality metrics assessed included the signal-to-noise ratio (SNR) of white matter (WM), CNR between gray matter/white matter (GM/WM) and gray matter/cerebrospinal fluid (GM/CSF), and Euler number (EN). Moreover, structural brain volume measurements of WM, GM, and CSF were conducted. Results. Turbo factor 200 produced the best SNR ( median = 17.01 ) and GM/WM CNR ( median = 2.29 ), but turbo factor 100 offered the most reproducible SNR ( IQR = 2.72 ) and GM/WM CNR ( IQR = 0.14 ). Turbo factor 50 had the worst and the least reproducible SNR, whereas turbo factor 225 had the worst and the least reproducible GM/WM CNR. Turbo factor 200 again had the best GM/CSF CNR but offered the least reproducible GM/CSF CNR. Turbo factor 225 had the best performance on EN (-21), while turbo factor 200 was next to the most reproducible turbo factor on EN (11). The results showed that turbo factor 200 had the least data acquisition time, in addition to superior performance on SNR, GM/WM CNR, GM/CSF CNR, and good reproducibility characteristics on EN. Both image quality metrics and volumetric measurements did not vary significantly ( p > 0.05 ) with the range of turbo factors used in the study by one-way ANOVA analysis. Conclusion. Since no significant differences were observed in the performance of the turbo factors in terms of image quality and volume of brain structure, turbo factor 200 with a 74% acquisition time reduction was found to be optimal for brain MR imaging at 1.5 T.
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Nilsson, Jonna, Alan J. Thomas, John T. O'Brien e Peter Gallagher. "White Matter and Cognitive Decline in Aging: A Focus on Processing Speed and Variability". Journal of the International Neuropsychological Society 20, n.º 3 (17 de fevereiro de 2014): 262–67. http://dx.doi.org/10.1017/s1355617713001458.
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AbstractWhite matter (WM) change plays an important role in age-related cognitive decline. In this review, we consider methodological advances with particular relevance to the role of WM in age-related changes in processing speed. In this context, intra-individual variability in processing speed performance has emerged as a sensitive proxy of cognitive and neurological decline while neuroimaging techniques used to assess WM change have become increasingly more sensitive. Together with a carefully designed task protocol, we emphasize that the combined implementation of intra-individual variability and neuroimaging techniques hold promise for specifying the WM-processing speed relationship with implications for normative and clinical samples. (JINS, 2014, 20, 1–6)
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Hu, Y., e J. Yang. "Uncertainty of the CO<sub>2</sub> threshold for melting a hard Snowball Earth". Climate of the Past Discussions 6, n.º 4 (12 de julho de 2010): 1337–50. http://dx.doi.org/10.5194/cpd-6-1337-2010.
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Abstract. One of the critical issues of the Snowball Earth hypothesis is how high level of CO2 is required for triggering the deglaciation. Using Community Atmospheric Model version 3 (CAM3), we study the problem for the CO2 threshold. Our simulations show large differences from previous results (Pierrehumbert, 2004, 2005). At 0.2 bars of CO2, the January maximum near-surface temperature is about 268 K, about 13 K higher than that in Pierrehumbert (2004, 2005), but lower than the value of 270 K for 0.1 bar of CO2 in Le Hir et al. (2007). It is found that the diversity of simulation results is mainly due to model sensitivity of greenhouse effect and longwave cloud forcing to increasing CO2. At 0.2 bar of CO2, CAM3 yields 117 Wm −2 of clear-sky greenhouse effect and 32 Wm−2 of longwave cloud forcing, versus only about 77 Wm−2 and 10.5 Wm−2 in Pierrehumbert (2004, 2005), respectively. CAM3 has comparable clear-sky greenhouse effect to that in Le Hir et al. (2007), but lower longwave cloud forcing. CAM3 also produces much stronger Hadley cells than in Pierrehumbert (2005).
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Mano, Quintino R., Gregory G. Brown, Heline Mirzakhanian, Khalima Bolden, Kristen S. Cadenhead e Gregory A. Light. "Not All Distraction Is Bad: Working Memory Vulnerability to Implicit Socioemotional Distraction Correlates with Negative Symptoms and Functional Impairment in Psychosis". Schizophrenia Research and Treatment 2014 (2014): 1–6. http://dx.doi.org/10.1155/2014/320948.
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This study investigated implicit socioemotional modulation of working memory (WM) in the context of symptom severity and functional status in individuals with psychosis (N=21). A delayed match-to-sample task was modified wherein task-irrelevant facial distracters were presented early and briefly during the rehearsal of pseudoword memoranda that varied incrementally in load size (1, 2, or 3 syllables). Facial distracters displayed happy, sad, or emotionally neutral expressions. Implicit socioemotional modulation of WM was indexed by subtracting task accuracy on nonfacial geometrical distraction trials from facial distraction trials. Results indicated that the amount of implicit socioemotional modulation ofhighWM load accuracy was significantly associated with negative symptoms (r=0.63,P<0.01), role functioning (r=−0.50,P<0.05), social functioning (r=−0.55,P<0.01), and global assessment of functioning (r=−0.53,P<0.05). Specifically,greaterattentional distraction ofhighWM load was associated withlesssevere symptoms and functional impairment. This study demonstrates the importance of the WM-socioemotional interface in influencing clinical and psychosocial functional status in psychosis.
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Roccaro, Aldo M., Antonio Sacco, Cristina Jimenez, Patricia Maiso, Michele Moschetta, Yuji Mishima, Yosra Aljawai et al. "C1013G/CXCR4 acts as a driver mutation of tumor progression and modulator of drug resistance in lymphoplasmacytic lymphoma". Blood 123, n.º 26 (26 de junho de 2014): 4120–31. http://dx.doi.org/10.1182/blood-2014-03-564583.
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Key Points C1013G/CXCR4 acts as an activating mutation in WM leading to enhanced tumor growth, and as an inducer of drug resistance. BMS936564/MDX1338, a novel anti-CXCR4 moAb, successfully targets WM cells, either C1013G/CXCR4 mutated or wild-type.
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Tournilhac, Oliver, Steven Le Gouill, Daniel Ditzel Santos, Klaus Podar, Lian Xu, Evdoxia Hatjiharissi, Yu-Tzu Tai et al. "Vascular Endothelial Growth Factor (VEGF) Is a Growth and Survival Factor in Waldenstrom’s Macroglobulinemia." Blood 104, n.º 11 (16 de novembro de 2004): 4892. http://dx.doi.org/10.1182/blood.v104.11.4892.4892.
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Abstract Waldenstrom’s macroglobulinemia (WM) is a B-cell disorder characterized by excess of bone marrow (BM) IgM secreting lymphoplasmacytic cells (LPC). In previous studies, we and others have demonstrated that VEGF within the BM micro-environment plays a role in the growth, survival and migration of myeloma plasma cells. Conversely, we demonstrated that BM mast cells (MC), which produce and secrete VEGF (Boesiger, J Exp Med, 1998) support growth and survival of WM LPC (Tournilhac et al, JCO2004; 22:517S). In the present studies we therefore explored the role of VEGF in WM pathogenesis. Using RT-PCR analysis, we detected VEGF receptors R1 (Flt-1) and R2 (flk1/KDR) transcripts in sorted LPC from 4/4 (100%) and 15/16 (94%) WM patients respectively. Moreover, we showed functionality for VEGF as a growth and survival factor in WM. Specifically, recombinant human VEGF (rh-VEGF) at 25 ng/ml induced dose dependent proliferation of sorted LPC from WM patients and prevented serum starvation- induced apoptosis. Inhibition of VEGF signaling pathways both induced apoptosis and blocked mast cell- induced proliferation of sorted WM LPCs in 4 of 6 and 4 of 4 patients, respectively. Besides the known MC-derived WM LPC growth and survival factors CD40 ligand (CD40L) (JCO2004; 22;517S) and B-lymphocyte stimulator protein (BLYS) (Ditzel Santos et al, ASH 2004 submitted), the present study demonstrates also a role of VEGF in WM pathogenesis. We therefore suggest VEGF as an additional therapeutic target in WM treatment regimens.
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Guerrera, Maria Luisa, Guang Yang, Xia Liu, Nickolas Tsakmaklis, Maria G. Demos, Amanda Kofides, Manit Munshi et al. "The ERK1/2 Regulator WNK2 Shows Differential Expression and Isoform Usage, Primarily Driven By Aberrant Methylation, in MYD88 Mutated Waldenström's Macroglobulinemia". Blood 138, Supplement 1 (5 de novembro de 2021): 2692. http://dx.doi.org/10.1182/blood-2021-154160.
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Abstract MYD88 mutations (MYD88 MUT) are present in 95-97% of patients with Waldenström's Macroglobulinemia (WM). Transgenic mouse studies show that MYD88 MUT alone is insufficient to drive oncogenesis. We previously reported the occurrence of non-overlapping somatic mutations in either CXCR4 (CXCR4 MUT) or deletions in 6q (del6q) in MYD88 mutated (MYD88 MUT) WM patients, suggesting either event may serve as a secondary driver of WM oncogenesis. Intersecting the lists of genes differentially modulated by either CXCR4 MUT or del6q revealed WNK2 as a top hit (Guerrera ML et al, Haematologica 2018). WNK2 is a serine/threonine protein kinase that negatively regulates ERK1/2 activation and has known tumor suppressor function in several solid tumors, wherein its expression is primarily silenced by aberrant promoter methylation. ERK1/2 pathway plays an important pro-survival role, its activation is accompanied by the release of inflammatory cytokines and can mediate ibrutinib resistance in WM (Chen et al, Blood 2018). We therefore sought to investigate the expression of WNK2, and clarify the mechanisms underlying its aberrant expression by genomic subtypes in WM. To study the regulation of WNK2 gene expression, we analyzed our previously published RNA-Seq data (Hunter ZH et al, Blood 2016) and validated findings in 47 WM patients by RT-qPCR. Compared to healthy donor (HD) B and plasma cells (PC), we observed marked upregulation of WNK2 expression in bone marrow (BM) CD19-selected tumor cells from MYD88 MUTCXCR4 WT patients (p<0.0001). Conversely, WNK2 expression was silenced in tumor cells from MYD88 MUTCXCR4 MUT and MYD88 WTCXCR4 WT (p<0.001 vs HD PC) patients, with less pronounced suppression of WNK2 also observed in MYD88 MUTdel6q cases. Immunohistochemistry analysis on patient BM biopsies confirmed the findings observed at the mRNA level per patient genotype. To assess the impact of alternative splice variants on overall gene expression, we then studied the relative composition of the 16 documented isoforms (Figure 1). RNA-Seq showed a prevalence of protein-coding transcripts, particularly those coding for isoforms missing the ERK regulatory kinase domain, in MYD88 MUT vs MYD88 WT WM. By RT-PCR, we validated the preferential use of the protein-coding WNK2-208, WNK2-203 and WNK2-205 transcripts in 32 of 47 WM samples with detectable total WNK2 levels. Of those, WNK2-208 and WNK2-203 lack the region coding for the functional kinase domain. Analysis of known post-translational modification (PTM) sites annotated for the canonical isoform WNK2-201 in the 3 isoforms of interest demonstrated that C-terminal PTM sites are highly conserved across all isoforms even in the absence of the kinase domain, alluding to novel protein regulatory sites yet to be characterized. Analysis of CpG methylation using enhanced reduced representation bisulfite sequencing from 62 WM patients identified 3 clusters of differentially methylated CpG islands (CpGs) between MYD88 MUTCXCR4 WT and MYD88 MUTCXCR4 MUT patients. Three CpGs in the WNK2 promoter, four in intron 1 and one in intron 11 constituted clusters 1, 2 and 3, respectively (Figure 1). Compared to healthy donor memory B-cell and PC, we observed aberrant hypermethylation in cluster 1 in MYD88 MUTCXCR4 MUT and hypomethylation at a putative enhancer in cluster 2 in MYD88 MUTCXCR4 WT patients, while del6q cases showed a mixed methylation pattern. A higher degree of methylation, particularly in cluster 2, significantly correlated with reduction in total and transcript-specific WNK2 mRNA levels that affected expression of transcripts encoding for kinase domain-containing isoforms. Furthermore, we validated the differential methylation status of 3 of 4 methylated CpGs in cluster 2 in 10 patients, including MYD88 MUTCXCR4 WT, MYD88 MUTCXCR4 MUT and MYD88 MUTdel6q, and 3 MYD88 MUT(BCWM.1, TMD-8) and MYD88 WT (Ramos) cell lines by means of bisulfite PCR followed by Sanger sequencing. Taken together, our findings reveal that the ERK1/2 regulator WNK2 shows differential expression and isoform usage in distinct genomic subsets of MYD88 MUT WM; is primarily driven by aberrant methylation; and may serve as a key driver of disease progression in WM. Figure 1 Figure 1. Disclosures Yang: Blueprint Medicines Corporations: Current Employment, Current holder of individual stocks in a privately-held company. Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding. Treon: BeiGene: Consultancy, Research Funding; Eli Lily: Research Funding; Abbvie/Pharmacyclics: Consultancy, Research Funding.
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Wang, Michael, Yuhong Zhou, Haijun Wang, Qing Yi, Yanxia Zhang, Raymond Alexanian, Larry Kwak e Xin Du. "Trend and Geographic Variations in the Incidence of Waldenstrom’s Macroglobulinemia in the United States over 17 Years from 1988 to 2004." Blood 110, n.º 11 (16 de novembro de 2007): 5174. http://dx.doi.org/10.1182/blood.v110.11.5174.5174.
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Abstract Background: Waldenstrom’s Macroglobulinemia (WM) is an uncommon subtype of B cell malignancy. The updated trend of its incidence in the United States has not been reported. Objective: To better understand the incidence and epidemiological features of WM in the United States. Methods: We conducted a population-based incidence study with 1463 patients (pts) with WM identified from the Surveillance, Epidemiology, and End Results (SEER) tumor registries over 17 years. From the SEER data, 78,558 pts of all ages diagnosed with non-Hodgkin’s lymphoma (NHL) were identified between 1988 and 2004 in 9 SEER areas. Of these pts, 1463 had pathologically confirmed WM, accounting for 2% of NHL. The incidence with 95% confidence intervals were generated from SEER*Stat Software and was age-adjusted to the U.S. year 2000 standard population. Annual Percent Change (APC)for the incidence was calculated and considered to be statistically significant if p value was less than 0.05. The crude 1-year survival rate was calculated as the ratio of the number of pts who survived over 1 year and the number of pts diagnosed with WM. Results: Of the1463 pts with WM, median age at diagnosis was 73. Overall incidence rate was 0.37/100,000/year, which increased with age from 0.03 in pts aged <50 to 1.03 in pts aged 60–69 and 2.76 in pts aged 80 or older. The age-adjusted incidence did not change significantly from 0.34 in 1988 compared with 0.36 in 2004. Therefore was no significant Annual Percent Change (0.97%, p>0.05). Incidence of WM was higher in men (0.52) than in women (0.26) (P<0.001). There were substantial geographic variations (p<0.001) in the incidence of WM. The age-adjusted incidence was highest in Seattle (0.49) and lowest in Atlanta (0.19). The incidence was higher in Caucasians (0.40) than in African-Americans (0.17) and other races (0.20). Annual Percentage Change was 1.3% in Caucasians (p<0.05). Conclusion: The overall incidence of Waldenstrom’s Macroglobulinemia did not change significantly from 1988 to 2004, and was significantly higher in male Caucasians. There were substantial geographical variations in the incidence of Waldenstrom’s Macroglobulinemia in the United States.
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Treon, Steven P., Christina K. Tripsas, Kirsten Meid, Sandra Kanan, Patricia Sheehy, Stacey Chuma, Lian Xu et al. "Carfilzomib, rituximab, and dexamethasone (CaRD) treatment offers a neuropathy-sparing approach for treating Waldenström's macroglobulinemia". Blood 124, n.º 4 (24 de julho de 2014): 503–10. http://dx.doi.org/10.1182/blood-2014-03-566273.
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Key Points Carfilzomib, rituximab, and dexamethasone (CaRD) produce overall and CR/VGPR responses in 87% and 36% of frontline WM patients, respectively. CaRD activity was not impacted by MYD88 and CXCR4 mutations and represents a neuropathy-sparing option for treating WM patients.
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Zhou, Jiang, e Peng Li. "Compactness of the Commutator of Multilinear Fourier Multiplier Operator on Weighted Lebesgue Space". Journal of Function Spaces 2014 (2014): 1–10. http://dx.doi.org/10.1155/2014/606504.
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LetTσbe the multilinear Fourier multiplier operator associated with multiplierσsatisfying the Sobolev regularity thatsupl∈ZσlWs1,…,sm(Rmn)<∞for somesk∈(n/2,n] (k=1,…,m). The authors prove that ifb1,…,bm∈BMO(Rn)andw⃗∈∏k=1mApk/tk(tk=n/sk), then the commutatorTσ,Σbis bounded fromLp1(Rn,w1)×⋯×Lpm(Rn,wm)toLp(Rn,νw⃗). Moreover, the authors also prove that ifb1,…,bm∈VMO(Rn)andw⃗∈∏k=1mApk/tk(tk=n/sk), then the commutatorTσ,Σbis compact operator fromLp1(Rn,w1)×⋯×Lpm(Rn,wm)toLp(Rn,νw⃗).
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Hatzianastassiou, N., A. Fotiadi, Ch Matsoukas, K. Pavlakis, E. Drakakis, D. Hatzidimitriou e I. Vardavas. "Long-term global distribution of earth’s shortwave radiation budget at the top of atmosphere". Atmospheric Chemistry and Physics Discussions 4, n.º 3 (14 de maio de 2004): 2671–726. http://dx.doi.org/10.5194/acpd-4-2671-2004.
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Abstract. The mean monthly shortwave (SW) radiation budget at the top of atmosphere (TOA) was computed on 2.5° longitude-latitude resolution for the 14-year period from 1984 to 1997, using a radiative transfer model with long-term climatological data from the International Satellite Cloud Climatology Project (ISCCP-D2) supplemented by data from the National Centers for Environmental Prediction - National Center for Atmospheric Research (NCEP-NCAR) Global Reanalysis project, and other global data bases such as TIROS Operational Vertical Sounder (TOVS) and Global Aerosol Data Set (GADS). The model radiative fluxes at TOA were validated against Earth Radiation Budget Experiment (ERBE) S4 scanner satellite data (1985–1989). The model is able to predict the seasonal and geographical variation of SW TOA fluxes. On a mean annual and global basis, the model is in very good agreement with ERBE, overestimating the outgoing SW radiation at TOA (OSR) by 0.93 Wm−2 (or by 0.92%), within the ERBE uncertainties. At pixel level, the OSR differences between model and ERBE are mostly within ±10 Wm−2, with ±5 Wm−2 over extended regions, while there exist some geographic areas with differences of up to 40 Wm−2, associated with uncertainties in cloud properties and surface albedo. The 14-year average model results give a planetary albedo equal to 29.6% and a TOA OSR flux of 101.2 Wm-2. A significant linearly decreasing trend in OSR and planetary albedo was found, equal to 2.3 Wm−2 and 0.6% over the 14-year period (from January 1984 to December 1997), indicating an increasing solar planetary warming. This planetary SW radiative heating occurs in the tropical and sub-tropical areas (20° S–20° N), with clouds being the most likely cause. The computed global mean OSR anomaly ranges within ±4 Wm−2, with signals from El Niño and La Niña events or Pinatubo eruption, whereas significant negative OSR anomalies, starting from year 1992, are also detected.
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Hatzianastassiou, N., A. Fotiadi, Ch Matsoukas, K. Pavlakis, E. Drakakis, D. Hatzidimitriou e I. Vardavas. "Long-term global distribution of earth's shortwave radiation budget at the top of atmosphere". Atmospheric Chemistry and Physics 4, n.º 5 (3 de agosto de 2004): 1217–35. http://dx.doi.org/10.5194/acp-4-1217-2004.
Texto completo da fonteResumo:
Abstract. The mean monthly shortwave (SW) radiation budget at the top of atmosphere (TOA) was computed on 2.5° longitude-latitude resolution for the 14-year period from 1984 to 1997, using a radiative transfer model with long-term climatological data from the International Satellite Cloud Climatology Project (ISCCP-D2) supplemented by data from the National Centers for Environmental Prediction – National Center for Atmospheric Research (NCEP-NCAR) Global Reanalysis project, and other global data bases such as TIROS Operational Vertical Sounder (TOVS) and Global Aerosol Data Set (GADS). The model radiative fluxes at TOA were validated against Earth Radiation Budget Experiment (ERBE) S4 scanner satellite data (1985–1989). The model is able to predict the seasonal and geographical variation of SW TOA fluxes. On a mean annual and global basis, the model is in very good agreement with ERBE, overestimating the outgoing SW radiation at TOA (OSR) by 0.93 Wm-2 (or by 0.92%), within the ERBE uncertainties. At pixel level, the OSR differences between model and ERBE are mostly within ±10 Wm-2, with ±5 Wm-2 over extended regions, while there exist some geographic areas with differences of up to 40 Wm-2, associated with uncertainties in cloud properties and surface albedo. The 14-year average model results give a planetary albedo equal to 29.6% and a TOA OSR flux of 101.2 Wm-2. A significant linearly decreasing trend in OSR and planetary albedo was found, equal to 2.3 Wm-2 and 0.6% (in absolute values), respectively, over the 14-year period (from January 1984 to December 1997), indicating an increasing solar planetary warming. This planetary SW radiative heating occurs in the tropical and sub-tropical areas (20° S–20° N), with clouds being the most likely cause. The computed global mean OSR anomaly ranges within ±4 Wm-2, with signals from El Niño and La Niña events or Pinatubo eruption, whereas significant negative OSR anomalies, starting from year 1992, are also detected.
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Leblond, Veronique, Julie Lejeune, Olivier Tournilhac, Pierre Morel, marie Sarah Dilhuydy, Caroline Dartigeas, Marion Malphette et al. "International Phase III Study of Chlorambucil Versus Fludarabine As Initial Therapy for Waldenstrom's Macroglobulinemia and Related Disorders: Results in 414 Patients on Behalf of FCG CLL/ WM, GOELAMS, GELA, NCRI, ALLG". Blood 118, n.º 21 (18 de novembro de 2011): 776. http://dx.doi.org/10.1182/blood.v118.21.776.776.
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Abstract Abstract 776 Background: Waldenstrom's macroglobulinemia (WM) and related-disorders (Marginal Zone Lymphoma: MZL, and non immunoglobulin IgM lymphoplasmacytic lymphoma: LPL) are rare diseases Very few randomized trials were reported in this setting. Most commonly patients with WM are initially treated with an alkylating agent, such as chlorambucil (CBL) or with a nucleoside analogue such as fludarabine (F) or 2CdA, alone or in association with monoclonal antibody. Methods: WM1 study was a prospective international randomized open-label study that included patients with previously untreated WM MZL and LPL. At registration, patients were stratified as having WM, SLVL, or LPL, and were randomized in the two arms. The aim of the study was to compare the efficacy of oral CBL at a dose of 8 mg/m2 for 10 days every 28 days to a maximum of 12 cycles with oral F at a dose of 40 mg/m2 orally for 5 days every 28 days to a maximum of 6 cycles. 418 patients were enrolled into the study from 07/01 to12/09. 414 patients were included and 405 received at least one course of chemotherapy. There were 339 WM, 37 MZL and 38 LPL with a median age of 68 years (40-89). 207 patients were randomized in the F arm and 207 patients in the CBL arm. At inclusion, the median of haemoglobin (g/l), platelets (Giga/l), albumin (g/l) and beta 2 microglobulin (mg/l) were 9.9, 218, 37.1 and 3.47 respectively. Results: In intention to treat basis, the overall response rate (CR+PR) was 47.8 % in the F arm versus 38.6% in the CBL arm (p=0.06). With a median follow-up time of 35.9 months, the median of progression free survival time (PFS) and disease free survival (DFS) were statistically longer in the F arm: PFS 36.3m vs 27.1 m ( p=0.01) and DFS 38.3m vs 19. 9m (p= 0.0006). In WM group, factors influencing negatively PFS were CBL arm, albumin< 35g/l, platelets<100 G/l and age> 70 years. Main toxicity was haematological with 17/203 (8.3%) vs 18/203 (9%) of grade III- IV thrombocytopenia and 50/203 (24.6%) vs 39/202 (19.3%) of grade III-IV anemia in F and CBL arms respectively. Overall survival rate at 5 years was 61.4% [52.9;71.3] in CBL arm and 70.3% [62.7-78.8] in F arm (p=0.04) (Fig 1). Cumulative Incidence of second malignancies (solid tumors and haematological malignancies except Richter syndrome (RS)) was statistically higher in the chlorambucil arm (25 versus 8, p= 0.004) (Fig 2). The number of RS was 8 in F arm and 9 in CBL arm. Conclusion: F by oral route is a safe and effective ambulatory treatment in WM and close related disorders patients, even in the elderly and more effective than CBL with a duration of response over 3 years. An unexpected finding was a statistically higher number of second malignancies in the C arm and we cannot rule out an oncogenic role of CBL in this setting. Of note, we stress that it is the first time that a front- line treatment has a significant impact on overall survival in WM patients. Disclosures: Leblond: mundipharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Tournilhac:Amgen: Research Funding; Mundipharma: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees.
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Tam, Constantine, Andrew P. Grigg, Stephen Opat, Matthew Ku, Michael Gilbertson, Mary Ann Anderson, John F. Seymour et al. "The BTK Inhibitor, Bgb-3111, Is Safe, Tolerable, and Highly Active in Patients with Relapsed/ Refractory B-Cell Malignancies: Initial Report of a Phase 1 First-in-Human Trial". Blood 126, n.º 23 (3 de dezembro de 2015): 832. http://dx.doi.org/10.1182/blood.v126.23.832.832.
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Abstract Introduction: Bruton's tyrosine kinase (BTK) is a downstream intermediary of B cell receptor (BCR) signaling. As revealed by ibrutinib, disruption of BCR signaling results in significant anti-tumor activity in various B cell malignancies. BGB-3111 is a potent, specific and irreversible BTK inhibitor. In biochemical and cellular assays, BGB-3111 was more selective than ibrutinib for BTK vs. EGFR, FGR, FRK, HER2, HER4, ITK, JAK3, LCK, BLK and TEC. Activity against these other kinases is implicated in ibrutinib-associated toxicities such as diarrhea, bleeding, and atrial fibrillation. In preclinical animal studies, BGB-3111 demonstrated superior oral bioavailability, achieving higher exposure and more complete target inhibition in the tissues than ibrutinib. We report here the initial results of an ongoing phase 1 trial of BGB-3111 in patients (pts) with advanced B cell malignancies. Patients/Methods: This first-in-human, open label phase 1 study comprised a dose-escalation (DE) component, followed by an ongoing safety, schedule and efficacy expansion component. The results of the planned interim analysis performed at the end of DE are reported here. During DE, pts with relapsed or refractory World Health Organization (WHO) classification defined B-lymphoid malignancies were enrolled to 1 of 5 dose cohorts of BGB-3111 (40, 80, 160, 320mg PO QD; 160mg PO BID) in a modified 3+3 dose escalation design. Adverse events (AEs) were reported per CTCAE v4.03 (patients with baseline cytopenias remained evaluable for neutropenia and thrombocytopenia) and responses per histology-specific standard criteria (NHL IWG criteria 2014; modified CLL IWG criteria 2015; WM IWWM criteria 2013). BGB-3111 pharmacokinetics (PK) was analyzed by dose level, and BTK occupancy determined using an irreversible binding assay in PBMCs. Results: 25 pts were enrolled in DE: 40mg (n=4), 80mg (n=5), 160mg (n=6) and 320mg (n=6) QD, and 160mg BID (n=4). Pts had received a median 2 (range: 1-7) prior therapies, for diagnoses listed in Table 1. As of 30 July 2015, all were evaluable for AE and response. BGB-3111 exposure increased in a dose-proportional manner from 40mg to 320mg daily. The Cmax and AUC0-24h of BGB-3111 at 80mg QD was comparable to that reported for ibrutinib at 560mg QD, and the free drug concentration of BGB-3111 at 40mg QD was comparable for that reported for ibrutinib 560mg QD. Sustained 24 hour BTK occupancy in PBMCs was demonstrated in all pts at 40mg QD (24 hour BTK occupancy 98.6 +/-1.1%), and at all higher dose levels. No dose limiting toxicities (DLT) were encountered, and the maximum tolerated dose (MTD) was not reached. The recommended phase 2 dose (320mg daily) was determined based on the pharmacokinetics, pharmacodynamics, safety and efficacy of BGB-3111. Three pts discontinued BGB-3111 due to disease progression. There were no drug-related SAEs, AEs leading to drug discontinuation, or AE-related deaths. Of 21 ≥grade 3 AEs, 3 were assessed by investigators as potentially drug-related - all were self-limiting neutropenia in CLL pts, two of whom had neutropenia at baseline. No G3/4 bleeding events were recorded. Four pts had a baseline history of atrial fibrillation/flutter (AF); no exacerbation or new event of AF was reported. 16 responses, including 1 complete remission, have been observed. Response by histology is summarized in Table 1 and Figure 1. 22/25 pts remain on study treatment, free of progression, at a median of 204 days (range 138-321). Table. Response by Histology to BGB-3111 Histology n Objective Response (no. in CR) SD Continuing Treatment (as of 30th July 2015) Days on treatment (median; range) CLL 8 6 (0) 2 8 199 (140-252) MCL 6 4 (1) 1 5 227 (165-315) Waldenström's 6 5 (0) 0 5 232 (152-321) DLBCL 2 0 (0) 1 1 159 FL 1 0 (0) 1 1 194 MZL 1 0 (0) 1 1 138 HCL 1 1 (0) 0 1 285 Conclusions: These preliminary Phase 1 results suggest that the selective BTK inhibitor BGB-3111 is safe and highly clinically active. Complete blockade of BTK in PBMC at low doses and excellent tolerability at higher doses raises the possibility that BTK blockade in deep tissue sites will be complete. This question is currently being explored in the expansion phase. Figure 1. Best response in 22 pts evaluated by CT scan (SPD, CLL and NHL) or IgM levels (WM). Not included here are 1 responder with HCL (PR), and 2 pts who progressed before restaging. Figure 1. Best response in 22 pts evaluated by CT scan (SPD, CLL and NHL) or IgM levels (WM). Not included here are 1 responder with HCL (PR), and 2 pts who progressed before restaging. Disclosures Tam: Janssen: Consultancy, Honoraria, Research Funding. Off Label Use: BGB-3111 is not licensed for treatment of B-cell malignancies. Grigg:BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Opat:Janssen Pharmaceuticals: Other: Provision of subsidized medications only. Seymour:Phebra: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Infinity: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hedrick:Beigene: Employment. Yang:Beigene: Employment, Equity Ownership. Wang:Beigene: Employment, Equity Ownership. Luo:Beigene: Employment, Equity Ownership. Xue:Beigene: Employment, Equity Ownership. Roberts:Walter and Eliza Hall Institute of Medical Research: Employment; AbbVie: Research Funding; Servier: Research Funding; Genentech: Research Funding.
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Su, W., J. Corbett, Z. Eitzen e L. Liang. "Next-generation angular distribution models for top-of-atmosphere radiative flux calculation from CERES instruments: validation". Atmospheric Measurement Techniques 8, n.º 8 (14 de agosto de 2015): 3297–313. http://dx.doi.org/10.5194/amt-8-3297-2015.
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Abstract. Radiative fluxes at the top of the atmosphere (TOA) from the Clouds and the Earth's Radiant Energy System (CERES) instrument are fundamental variables for understanding the Earth's energy balance and how it changes with time. TOA radiative fluxes are derived from the CERES radiance measurements using empirical angular distribution models (ADMs). This paper evaluates the accuracy of CERES TOA fluxes using direct integration and flux consistency tests. Direct integration tests show that the overall bias in regional monthly mean TOA shortwave (SW) flux is less than 0.2 Wm−2 and the RMSE is less than 1.1 Wm−2. The bias and RMSE are very similar between Terra and Aqua. The bias in regional monthly mean TOA LW fluxes is less than 0.5 Wm−2 and the RMSE is less than 0.8 Wm−2 for both Terra and Aqua. The accuracy of the TOA instantaneous flux is assessed by performing tests using fluxes inverted from nadir- and oblique-viewing angles using CERES along-track observations and temporally and spatially matched MODIS observations, and using fluxes inverted from multi-angle MISR observations. The averaged TOA instantaneous SW flux uncertainties from these two tests are about 2.3 % (1.9 Wm−2) over clear ocean, 1.6 % (4.5 Wm−2) over clear land, and 2.0 % (6.0 Wm−2) over clear snow/ice; and are about 3.3 % (9.0 Wm−2), 2.7 % (8.4 Wm−2), and 3.7 % (9.9 Wm−2) over ocean, land, and snow/ice under all-sky conditions. The TOA SW flux uncertainties are generally larger for thin broken clouds than for moderate and thick overcast clouds. The TOA instantaneous daytime LW flux uncertainties derived from the CERES-MODIS test are 0.5 % (1.5 Wm−2), 0.8 % (2.4 Wm−2), and 0.7 % (1.3 Wm−2) over clear ocean, land, and snow/ice; and are about 1.5 % (3.5 Wm−2), 1.0 % (2.9 Wm−2), and 1.1 % (2.1 Wm−2) over ocean, land, and snow/ice under all-sky conditions. The TOA instantaneous nighttime LW flux uncertainties are about 0.5–1 % (< 2.0 Wm−2) for all surface types. Flux uncertainties caused by errors in scene identification are also assessed by using the collocated CALIPSO, CloudSat, CERES and MODIS data product. Errors in scene identification tend to underestimate TOA SW flux by about 0.6 Wm−2 and overestimate TOA daytime (nighttime) LW flux by 0.4 (0.2) Wm−2 when all CERES viewing angles are considered.
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Lund, Sigrun Helga, Malin Hultcrantz, Lynn Goldin, Ola Landgren, Magnus Björkholm, Ingemar Turesson e Sigurdur Y. Kristinsson. "Patterns of Infectious Morbidity in Patients with Waldenström’s Macroglobulinaemia/Lymphoplasmacytic Lymphoma: A Population-Based Study". Blood 124, n.º 21 (6 de dezembro de 2014): 3350. http://dx.doi.org/10.1182/blood.v124.21.3350.3350.
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Abstract Background Infections are a major cause of morbidity and mortality in patients with hematologic malignancies. However, largely due to the rarity of Waldenström’s macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL), the literature on infectious morbidity is limited. Using population-based data from Sweden, we estimated the risk of bacterial and viral infections among 2,608 LPL/WM patients compared to 10,433 matched controls. Patients and Methods We identified all WM/LPL patients diagnosed 1980-2005 in the nationwide Swedish Cancer and Patient Registries, as well as a national network database including all major hematology/oncology centers; duplicate records were removed. Follow-up time was up to 2006. For each WM/LPL patient, four population-based controls (matched by age, sex, and county of residence) were identified randomly from the Swedish population database. Information on type of infection and date of infection was obtained from the Patient Registry which captures information on all individual patient-based discharge diagnosis from inpatient (since 1964) and outpatient care (since 2000). Through linkage to the nationwide Cause of Death Registry, we identified dates of death for WM/LPL patients and controls. Cox proportional hazard models were used to estimate the overall risk of infections. Models were adjusted for sex, age, and calendar period. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for individual infections. Results Overall, WM/LPL patients had a 3.4-fold (95% CI=3.1-3.6) elevated risk of developing any infection than controls (Figure). Compared to controls, the risk of developing bacterial and viral infections was 3.2-fold (95%; CI=2.9-3.5) and 6.0-fold (95% CI=4.9-7.3) higher, respectively. More specifically, WM/LPL patients had an increased risk (p<0.05) of the following types of bacterial infections: septicaemia (HR=9.3; 95% CI 3.7-23.5), endocarditis (HR=5.0; 95% CI 2.5-10.0), pneumonia (HR=3.8; 95% CI 3.4-4.2), meningitis (HR=3.4; 95% CI 1.1-10.3), cellulitis (HR=2.6; 95% CI 2.0-3.4), osteomyelitis (HR=1.9; 95% CI 1.01-3.6), and pyelonephritis (HR=1.6; 95% CI 1.2-2.4). Regarding viral infections, WM/LPL patients had an increased risk of herpes zoster (HR=9.2; 95% CI 6.7-12.6) and influenza (HR=2.3; 95% CI 1.5-3.5). The risk of infections was highest during the first year after diagnosis. Interestingly, WM/LPL patients diagnosed in the more recent calendar periods had significantly higher risk of infections (Figure). Compared to WM/LPL patients diagnosed in 1980-1989, patients diagnosed in 1990-1999 and 2000-2004 had a 1.5-fold (95% CI=1.3-1.6) and 1.8-fold (95% CI=1.6-2.1) increased risk of any infection, respectively. The same patterns were observed when bacterial infections were analyzed separately. In analysis focusing on viral infections; there was only a significant increased risk during the most recent calendar period (p=0.027). Females had a significantly lower risk of infections compared to males (p<0.001). Increasing age was significantly associated with a higher risk of infections (p<0.001). Discussion In this large population-based study including over 2,600 WM/LPL patients and 10,000 matched controls, we found that bacterial and viral infections represent a major threat to WM/LPL patients. This was particularly true during the first years following diagnosis. Importantly, the risk of infections increased in more recent years. The effects on infectious complications due to novel drugs in the treatment of WM/LPL need to be better defined and trials on prophylactic measures are needed. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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Brunfaut, Tineke, Judit Kormos, Marije Michel e Michael Ratajczak. "Testing young foreign language learners’ reading comprehension: Exploring the effects of working memory, grade level, and reading task". Language Testing 38, n.º 3 (25 de fevereiro de 2021): 356–77. http://dx.doi.org/10.1177/0265532221991480.
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Extensive research has demonstrated the impact of working memory (WM) on first language (L1) reading comprehension across age groups (Peng et al., 2018), and on foreign language (FL) reading comprehension of adults and older adolescents (Linck et al., 2014). Comparatively little is known about the effect of WM on young FL readers’ comprehension, and even less within testing contexts. Young FL readers are still developing their L1 reading skills and general cognitive skills (e.g., attentional regulation abilities). Completing FL reading tests might be particularly taxing on their WM, and differences in WM capacity – as well as other learner and task characteristics – might create construct-irrelevant variance in test performance. In this study, we investigate the effects of WM, grade level, and reading task on young learners’ FL reading test performances. Ninety-four young English language learners (Grades 6–7) in Hungary completed the TOEFL® Junior™ Comprehensive’s reading test and a WM test battery. Our mixed-effects model predicted significantly higher comprehension accuracy among learners with higher WM capacity, and among learners in Grade 7 compared to learners in Grade 6. Reading task differences were not associated with significant comprehension accuracy differences. We discuss the implications of our findings for testing young learners’ FL reading comprehension.
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Wang, X., C. L. Heald, D. A. Ridley, J. P. Schwarz, J. R. Spackman, A. E. Perring, H. Coe, D. Liu e A. D. Clarke. "Exploiting simultaneous observational constraints on mass and absorption to estimate the global direct radiative forcing of black carbon and brown carbon". Atmospheric Chemistry and Physics 14, n.º 20 (20 de outubro de 2014): 10989–1010. http://dx.doi.org/10.5194/acp-14-10989-2014.
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Abstract. Atmospheric black carbon (BC) is a leading climate warming agent, yet uncertainties on the global direct radiative forcing (DRF) remain large. Here we expand a global model simulation (GEOS-Chem) of BC to include the absorption enhancement associated with BC coating and separately treat both the aging and physical properties of fossil-fuel and biomass-burning BC. In addition we develop a global simulation of brown carbon (BrC) from both secondary (aromatic) and primary (biomass burning and biofuel) sources. The global mean lifetime of BC in this simulation (4.4 days) is substantially lower compared to the AeroCom I model means (7.3 days), and as a result, this model captures both the mass concentrations measured in near-source airborne field campaigns (ARCTAS, EUCAARI) and surface sites within 30%, and in remote regions (HIPPO) within a factor of 2. We show that the new BC optical properties together with the inclusion of BrC reduces the model bias in absorption aerosol optical depth (AAOD) at multiple wavelengths by more than 50% at AERONET sites worldwide. However our improved model still underestimates AAOD by a factor of 1.4 to 2.8 regionally, with the largest underestimates in regions influenced by fire. Using the RRTMG model integrated with GEOS-Chem we estimate that the all-sky top-of-atmosphere DRF of BC is +0.13 Wm−2 (0.08 Wm−2 from anthropogenic sources and 0.05 Wm−2 from biomass burning). If we scale our model to match AERONET AAOD observations we estimate the DRF of BC is +0.21 Wm−2, with an additional +0.11 Wm−2 of warming from BrC. Uncertainties in size, optical properties, observations, and emissions suggest an overall uncertainty in BC DRF of −80%/+140%. Our estimates are at the lower end of the 0.2–1.0 Wm−2 range from previous studies, and substantially less than the +0.6 Wm−2 DRF estimated in the IPCC 5th Assessment Report. We suggest that the DRF of BC has previously been overestimated due to the overestimation of the BC lifetime (including the effect on the vertical profile) and the incorrect attribution of BrC absorption to BC.
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Mateos, David, e Manuel Antón. "Worldwide Evaluation of Ozone Radiative Forcing in the UV-B Range between 1979 and 2014". Remote Sensing 12, n.º 3 (29 de janeiro de 2020): 436. http://dx.doi.org/10.3390/rs12030436.
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Ultraviolet (UV) radiation plays a key role in different planetary mechanisms, thus necessitating a worldwide analysis of this solar spectrum interval. This study offers a worldwide and long-term analysis of ozone radiative forcing (ORF) in the UV-B range between 1979 and 2014. The method uses monthly total ozone column (TOC) values obtained from the ERA-Interim reanalysis data collection and radiative transfer simulations. A global mean ORF of 0.011 Wm−2 is obtained, with marked differences between mid-latitude and tropical areas. The mid-latitude belts in the Northern and Southern Hemispheres exhibit the following statistically significant ORF trends between 1982 and 2014 with respect to pre-1980 values: 0.007 Wm−2 per decade in the 60–45°S belt and around 0.004 Wm−2 per decade in the 45–30°S and 45–60°N belts. The increase observed in the net UV-B radiation levels at the troposphere might have relevant photochemical effects that impact climate change.
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Bristow, Michael S., Jessica E. Simon, Robert A. Brown, Michael Eliasziw, Michael D. Hill, Shelagh B. Coutts, Richard Frayne, Andrew M. Demchuk e J. Ross Mitchell. "MR Perfusion and Diffusion in Acute Ischemic Stroke: Human Gray and White Matter have Different Thresholds for Infarction". Journal of Cerebral Blood Flow & Metabolism 25, n.º 10 (11 de maio de 2005): 1280–87. http://dx.doi.org/10.1038/sj.jcbfm.9600135.
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It is thought that gray and white matter (GM and WM) have different perfusion and diffusion thresholds for cerebral infarction in humans. We sought to determine these thresholds with voxel-by-voxel, tissue-specific analysis of coregistered acute and follow-up magnetic resonance (MR) perfusion- and diffusion-weighted imaging. Quantitative cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and apparent diffusion coefficient (ADC) maps were analyzed from nine acute stroke patients (imaging acquired within 6 h of onset). The average values of each measure were calculated for GM and WM in normally perfused tissue, the region of recovered tissue and in the final infarct. Perfusion and diffusion thresholds for infarction were determined on a patient-by-patient basis in GM and WM separately by selecting thresholds with equal sensitivities and specificities. Gray matter has higher thresholds for infarction than WM ( P<0.009) for CBF (20.0 mL/100 g min in GM and 12.3 mL/100 g min in WM), CBV (2.4 mL/100 g in GM and 1.7 mL/100 g in WM), and ADC (786 × 10−6 mm2/s in GM and 708 × 10−6 mm2/s in WM). The MTT threshold for infarction in GM is lower ( P = 0.014) than for WM (6.8 secs in GM and 7.1 secs in WM). A single common threshold applied to both tissues overestimates tissue at risk in WM and underestimates tissue at risk in GM. This study suggests that tissue-specific analysis of perfusion and diffusion imaging is required to accurately predict tissue at risk of infarction in acute ischemic stroke.