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BACKGROUND: Odronextamab, a CD20×CD3 bispecific antibody that engages cytotoxic T cells to destroy malignant B cells, has demonstrated encouraging activity across multiple subtypes of relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. PATIENTS AND METHODS: This phase II study (ELM-2; NCT03888105) evaluated odronextamab in patients with R/R follicular lymphoma (FL) after ≥2 lines of systemic therapy. Patients received intravenous odronextamab in 21-day cycles, with step-up dosing in Cycle 1 to help mitigate the risk of cytokine release syndrome (CRS), until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review. RESULTS: Among 128 patients evaluated, 95% completed Cycle 1, and 85% completed ≥4 cycles. At 20.1 months' efficacy follow-up, ORR was 80.0% and complete response rate was 73.4%. Median duration of complete response was 25.1 months. Median progression-free survival was 20.7 months, and median overall survival was not reached. Discontinuation of odronextamab due to adverse events (AEs) occurred in 16% of patients. The most common treatment-emergent AEs were CRS (56%; grade ≥3 1.7% [1/60] with 0.7/4/20 mg step-up), neutropenia (39%), and pyrexia (38%). CONCLUSIONS: Odronextamab achieved high complete response rates with generally manageable safety in patients with heavily pretreated R/R FL.
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BACKGROUND: Optimal consolidation for young patilents with relapsed/refractory (R/R) follicular lymphoma (FL) remains uncertain in the rituximab era, with an unclear benefit of autologous stem cell transplantation (ASCT). The multicenter, randomized, phase III FLAZ12 (NCT01827605) trial compared anti-CD20 radioimmunotherapy (RIT) with ASCT as consolidation after chemoimmunotherapy, both followed by rituximab maintenance. PATIENTS AND METHODS: Patients (age 18-65 years) with R/R FL and without significant comorbidities were enrolled and treated with three courses of conventional, investigator-chosen chemoimmunotherapies. Those experiencing at least a partial response were randomized 1 : 1 to ASCT or RIT before CD34+ collection, and all received postconsolidation rituximab maintenance. Progression-free survival (PFS) was the primary endpoint. The target sample size was 210 (105/group). RESULTS: Between August 2012 and September 2019, of 164 screened patients, 159 were enrolled [median age 57 (interquartile range 49-62) years, 55% male, 57% stage IV, 20% bulky disease]. The study was closed prematurely because of low accrual. Data were analyzed on 8 June 2023, on an intention-to-treat basis, with a 77-month median follow-up from enrollment. Of the 141 patients (89%), 70 were randomized to ASCT and 71 to RIT. The estimated 3-year PFS in both groups was 62% (hazard ratio 1.11, 95% confidence interval 0.69-1.80, P = 0.6662). The 3-year overall survival also was similar between the two groups. Rates of grade ≥3 hematological toxicity were 94% with ASCT versus 46% with RIT (P < 0.001), and grade ≥3 neutropenia occurred in 94% versus 41%, respectively (P < 0.001). Second cancers occurred in nine patients after ASCT and three after radioimmunotherapy (P = 0.189). CONCLUSIONS: Even if prematurely discontinued, our study did not demonstrate the superiority of ASCT versus RIT. ASCT was more toxic and demanding for patients and health services. Both strategies yielded similar, favorable long-term outcomes, suggesting that consolidation programs milder than ASCT require further investigation in R/R FL.
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Trasplante de Células Madre Hematopoyéticas , Linfoma Folicular , Humanos , Masculino , Persona de Mediana Edad , Adolescente , Adulto Joven , Adulto , Anciano , Femenino , Linfoma Folicular/radioterapia , Radioinmunoterapia , Rituximab , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia sin Enfermedad , Trasplante Autólogo , Trasplante de Células MadreRESUMEN
We report a fast pump modulation scheme in a terahertz time domain spectroscopy (THz-TDS) system by utilizing the intensity modulation from the megahertz repetition rate of the pump pulse for lock-in detection. In conventional THz-TDS, the modulation required for the high signal-to-noise ratio lock-in detection is achieved through the use of an optical chopper or an AC bias. Here, we propose the use of an electro-optic modulator (EOM), operated as a pulse picker, to vary the repetition rate of the pump pulse, relative to the probe pulse, allowing us to directly use the megahertz laser repetition rate as the reference modulation frequency for lock-in detection. Our proposed scheme is applicable to all types of pulsed THz emitters, including those that cannot be electronically biased. Since the maximum allowable modulation frequency is limited only by the laser repetition rate and/or by the bandwidth of the EOM, megahertz modulation rates, and, consequently, rapid data acquisition times, become possible. Using our technique, we were able to detect an oscillating signal with frequencies up to 10 kHz, using â¼1 µs integration time per point, â¼100× faster than previously reported values for THz-TDS systems.
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OBJECTIVES: This study aimed to investigate the influences of living arrangements on the association between dietary variety and frailty by gender in community-dwelling older people. DESIGN: A cross-sectional study. SETTING: Nishinomiya city, Hyogo prefecture, Japan. PARTICIPANTS: A total of 4,996 randomly selected community-dwelling older people aged 65 years and older and living in Nishinomiya City. MEASUREMENTS: Survey questionnaires were distributed via mail. The frailty score was evaluated by the 5-item frailty screening index. Dietary variety was assessed using the dietary variety score developed for the general older Japanese population. RESULTS: A total of 2,764 community-dwelling participants aged ≥ 65 years responded to the questionnaires. After excluding missing data, 1,780 participants were included in the study analysis. The frailty scores in older men living alone were significantly higher than those in older men living with someone (P < 0.001). The dietary variety scores in older men living alone were significantly lower than those in older men living with someone (P < 0.001). However, differences in the frailty and dietary variety scores between living alone and living with someone were not were observed in older women (P = 0.360 and P = 0.265, respectively). In the multivariable regression analysis, the associations between dietary variety score and frailty score in living alone (ß= -0. 271, P = 0.011) were stronger than those in living with someone in the case of older men (ß= -0.131, P = 0.045). Similar associations between dietary variety and frailty were presented in older women living alone than in those living with someone (ß -0.114, P = 0.002; ß -0.088, P = 0.012, respectively). CONCLUSIONS: Older men who live alone had higher frailty score and lower dietary variety. The associations between dietary variety and frailty were different according to living arrangements in both older men and older women.
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Fragilidad , Masculino , Humanos , Femenino , Anciano , Fragilidad/diagnóstico , Fragilidad/epidemiología , Vida Independiente , Estudios Transversales , Factores Sexuales , Conducta AlimentariaRESUMEN
Estimation of whole root biomass including coarse and larger roots and root balls can provide better understanding of carbon and nitrogen stocks in floodplain forests. Whole root systems of nine ash trees (Fraxinus angustifolia Vahl.) and six alder trees (Alnus glutinosa L.) trees ranging in diameter breast height (dbh) from 29.1 to 72.0 cm for ash and from 29.1 to 44.3 cm for alder were excavated, and their small < 1 cm, medium 1-4 cm, larger > 4 cm and root-ball biomass, and root carbon and nitrogen stocks were determined in Karacabey floodplain forest in Bursa, Turkey. In addition, for the method comparison, small root biomass (< 1 cm) was also determined using soil-core method. The whole root biomass of ash trees varied from 167.7 to 186.8 Mg ha-1. Alder trees had lower whole root biomass than ash trees ranging from 49.0 to 63.6 Mg ha-1. The determination of small root biomass by soil excavation method was nearly two-fold higher than by soil core method. Both root carbon and nitrogen stocks showed an increase with increasing root diameter. Among the tree characteristics (dbh, age, height, and volume), the dbh showed the highest correlation with whole root biomass and root carbon and nitrogen stocks for both tree species. It is concluded that young trees can have higher small, medium, and large root biomass and store more C and N in those roots, whereas older trees can have higher root-ball biomass and root-ball carbon and nitrogen stocks in Karacabey floodplain forests.
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Carbono , Fraxinus , Nitrógeno , Biomasa , Turquía , Monitoreo del Ambiente , Bosques , Árboles , SueloRESUMEN
We propose and experimentally prove efficient high-resolution electro-optic sampling measurement of broadband terahertz waveforms in a LiNbO3 crystal in the configuration with the probe laser beam propagating along the optical axis of the crystal. This configuration allows one to avoid the detrimental effect of strong intrinsic birefringence of LiNbO3 without any additional optical elements. To achieve velocity matching of the terahertz wave and the probe beam, the terahertz wave is introduced into the crystal through a Si prism at the Cherenkov angle to the probe beam. The workability of the scheme at different wavelengths of the probe optical beam (800 and 1550 nm) is demonstrated.
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This study aimed to clarify the effectiveness of foetal body weight estimation by measuring foetal coronet width using transrectal ultrasonography in beef cows during near-term pregnancy. A characteristic 'gull wing' pattern was obtained from the foetal coronet cross-section from the dewclaw side using ultrasonography. This pattern was matched to the bone surface of the distal part of the middle phalanx. Then, the relationship between coronet width and body weight at birth of 22 Japanese Brown calves was analysed and a high correlation coefficient of 0.8965 (P < 0.001) was obtained. In conclusion, the coronet width of the fetus is depicted as a 'gull wing' hyperechoic structure and can be measured by ultrasonography per rectum during near-term pregnancy. This technique may be a useful tool to identify high-risk cows with dystocia before calving. High foetal coronet values may predispose cattle to dystocia.
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Enfermedades de los Bovinos , Distocia , Animales , Peso Corporal , Bovinos , Distocia/diagnóstico por imagen , Distocia/veterinaria , Femenino , Peso Fetal , Proyectos Piloto , Embarazo , Ultrasonografía/veterinariaRESUMEN
We study the capillary adhesion of a spherical elastic cap on a rigid sphere of a different radius. Caps of small area accommodate the combination of flexural and in-plane strains induced by the mismatch in curvature, and fully adhere to the sphere. Conversely, wider caps delaminate and exhibit only partial contact. We determine the maximum size of the cap enabling full adhesion and describe its dependence on experimental parameters through a balance of stretching and adhesion energies. Beyond the maximum size, complex adhesion patterns such as blisters, bubbles or star shapes are observed. We rationalize these different states in configuration diagrams where stretching, bending and adhesion energies are compared through two dimensionless parameters.
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Abstract Objective: The aim of this study was to identify the causes of congenital microcephaly in Rio Grande do Sul, a state in southern Brazil, where no ZIKV outbreak was detected, from December 2015 to December 2016, which was the period when ZIKV infection was at its peak in northeast Brazil. Methods: This was a cross-sectional study where all notifications of congenital microcephaly in the state of Rio Grande do Sul were included for analysis. Evaluation of cases followed the guidelines of the Brazilian Ministry of Health. Dysmorphological and neurological evaluations were performed by a specialized team, and genetic tests and neuroimaging were performed when clinically indicated. STORCH infections were diagnosed using standard tests. ZIKV infection was diagnosed through maternal serum RT-PCR and/or neuroimaging associated with clinical/epidemiological criteria. Results: From 153 744 registered live births in the study period, 148 cases were notified, but 90 (60.8%) of those were later excluded as "non-confirmed" microcephaly. In the 58 confirmed cases of microcephaly (prevalence = 3.8/10 000 live births), congenital infections (syphilis, toxoplasmosis, cytomegalovirus, and ZIKV) constituted the predominant etiology (50.0%), followed by isolated CNS (15.5%), and genetic syndromes (10.3%). Congenital ZIKV syndrome (CZS) with typical phenotype was diagnosed in three cases (5.2% of all confirmed microcephaly cases or 10.4% of all congenital infections). Conclusion: In Rio Grande do Sul, where no outbreak of ZIKV infection was recorded, congenital infections were the leading cause of congenital microcephaly, and the attributable risk for CZS in the etiology of microcephaly was 5.2%.
Resumo: Objetivo: Identificar as causas da microcefalia congênita no Rio Grande do Sul, Região Sul do Brasil, onde não foi detectado surto de ZIKV, de dezembro de 2015 a dezembro de 2016. Esse foi o período em que a infecção por ZIKV estava em seu auge no Nordeste do Brasil. Métodos: Este é um estudo transversal no qual todas as notificações de microcefalia congênita no estado do Rio Grande do Sul foram incluídas para análise. A avaliação dos casos seguiu as orientações do Ministério da Saúde. A avaliação dismorfológica e neurológica foi feita por uma equipe especializada e os testes genéticos e as neuroimagens foram feitos quando indicado clinicamente. As infecções STORCH (Sífilis, Toxoplasmose, Rubéola, Citomegalovírus e Herpes simples) foram diagnosticadas utilizando testes padrão. A infecção por ZIKV foi diagnosticada por meio da transcriptase reversa seguida de reação em cadeia da polimerase (RT-PCR) no soro materno e/ou neuroimagem associada a critérios clínicos/epidemiológicos. Resultados: De 153.744 nascidos vivos registrados no período do estudo, 148 bebês foram casos notificados, porém 90 (60,8%) casos foram excluídos posteriormente como microcefalia "não confirmada". Nos 58 casos confirmados de microcefalia (prevalência = 3,8/10.000 nascidos vivos), as infecções congênitas (sífilis, toxoplasmose, citomegalovírus e ZIKV) constituíram a etiologia predominante (50,0%), seguidas de doenças ligadas ao SNC isolado (15,5%) e síndromes genéticas (10,3%). A síndrome congênita do ZIKV (SCZ) com fenótipo típico foi diagnosticada em três casos (5,2% de todos os casos confirmados de microcefalia ou 10,4% de todas as infecções congênitas). Conclusão: No Rio Grande do Sul, Brasil, onde não foi registrado surto de infecção por ZIKV, a principal causa de microcefalia congênita foram infecções congênitas e o risco atribuível para SCZ na etiologia de microcefalia foi de 5,2%.
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Humanos , Masculino , Femenino , Embarazo , Recién Nacido , Complicaciones Infecciosas del Embarazo/epidemiología , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/epidemiología , Microcefalia/epidemiología , Microcefalia/virología , Complicaciones Infecciosas del Embarazo/virología , Brasil/epidemiología , Prevalencia , Brotes de Enfermedades , Estudios Transversales , Factores de Riesgo , Edad Gestacional , Distribución por SexoRESUMEN
OBJECTIVE: The aim of this study was to identify the causes of congenital microcephaly in Rio Grande do Sul, a state in southern Brazil, where no ZIKV outbreak was detected, from December 2015 to December 2016, which was the period when ZIKV infection was at its peak in northeast Brazil. METHODS: This was a cross-sectional study where all notifications of congenital microcephaly in the state of Rio Grande do Sul were included for analysis. Evaluation of cases followed the guidelines of the Brazilian Ministry of Health. Dysmorphological and neurological evaluations were performed by a specialized team, and genetic tests and neuroimaging were performed when clinically indicated. STORCH infections were diagnosed using standard tests. ZIKV infection was diagnosed through maternal serum RT-PCR and/or neuroimaging associated with clinical/epidemiological criteria. RESULTS: From 153744 registered live births in the study period, 148 cases were notified, but 90 (60.8%) of those were later excluded as "non-confirmed" microcephaly. In the 58 confirmed cases of microcephaly (prevalence = 3.8/10000 live births), congenital infections (syphilis, toxoplasmosis, cytomegalovirus, and ZIKV) constituted the predominant etiology (50.0%), followed by isolated CNS (15.5%), and genetic syndromes (10.3%). Congenital ZIKV syndrome (CZS) with typical phenotype was diagnosed in three cases (5.2% of all confirmed microcephaly cases or 10.4% of all congenital infections). CONCLUSION: In Rio Grande do Sul, where no outbreak of ZIKV infection was recorded, congenital infections were the leading cause of congenital microcephaly, and the attributable risk for CZS in the etiology of microcephaly was 5.2%.
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Microcefalia/epidemiología , Microcefalia/virología , Complicaciones Infecciosas del Embarazo/epidemiología , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/epidemiología , Brasil/epidemiología , Estudios Transversales , Brotes de Enfermedades , Femenino , Edad Gestacional , Humanos , Recién Nacido , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Prevalencia , Factores de Riesgo , Distribución por SexoRESUMEN
We report efficient high-resolution electro-optic sampling detection of broadband terahertz radiation by measuring direct intensity modulation of a femtosecond fiber laser beam induced by terahertz field in a 1-cm thick GaAs crystal.
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Adalimumab/uso terapéutico , Antiinflamatorios/uso terapéutico , Enfermedades de la Uña/diagnóstico por imagen , Uñas/diagnóstico por imagen , Psoriasis/diagnóstico por imagen , Ultrasonografía , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Uña/tratamiento farmacológico , Psoriasis/tratamiento farmacológicoRESUMEN
We report on a new constraint on gravitylike short-range forces, in which the interaction charge is mass, obtained by measuring the angular distribution of 5 Å neutrons scattering off atomic xenon gas. Around 10^{7} scattering events were collected at the 40 m small angle neutron scattering beam line located at the HANARO research reactor of the Korean Atomic Energy Research Institute. The extracted coupling strengths of new forces in the Yukawa-type parametrization are g[over ^]^{2}=(0.2±6.8±2.0)×10^{-15} GeV^{-2} and g[over ^]^{2}=(-5.3±9.0_{-2.8}^{+2.7})×10^{-17} GeV^{-2} for interaction ranges of 0.1 and 1.0 nm, respectively. These strengths correspond to 95% confidence level limits of g^{2}<(1.4±0.2)×10^{-14} GeV^{-2} and g^{2}<(1.3±0.2)×10^{-16} GeV^{-2}, improving the current limits for interaction ranges between 4 and 0.04 nm by a factor of up to 10.
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BACKGROUND: Poor adherence is thought to be one of the major common causes of uncontrolled high blood pressure over the world leading to useless drug dose or class changes which may lead to increased adverse effects and medical costs. The current study aimed to investigate the relationship between knowledge about complications related to hypertension and adherence to antihypertensive treatment. MATERIALS AND METHODS: A cross-sectional study was carried out between May and November 2013 on a representative sample of 453 hypertensive patients at public primary care outpatients in the department of Tlemcen in Algeria. The adherence was assessed with the adherence evaluation scale of Girerd which contains six items with closed dichotomous responses (yes/no). The degree of adherence was calculated according to the score resulting from the sum of all "yes" answers. A cut-off value of 80% was used to categorize patients as "adherent" or "non-adherent". To do so, a structured questionnaire has been performed including patients' knowledge about hypertension complications and the other factors which may affect adherence therapy. RESULTS: Among the 453 patients included in the study, only 35.5% were adherents. Univariate analysis has shown a positive relationship between knowledge about hypertension complications and adherence. However, comorbidities, and number of antihypertensive drugs prescribed, were associated with poor adherence. In a multivariate analysis, a significant difference was shown between adherents and non-adherents according to the factors mentioned above and the insurance status. CONCLUSION: This study has shown a positive relationship between patients' knowledge about the hypertensive complications and adherence. In contrast, increased number of antihypertensive drugs taken May affect negatively the adherence to therapy.