Radioimmunotherapy versus autologous hematopoietic stem cell transplantation in relapsed/refractory follicular lymphoma: a Fondazione Italiana Linfomi multicenter, randomized, phase III trial.

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.

Megahertz repetition rate-based lock-in detection scheme for rapid data acquisition in terahertz time domain spectroscopy.

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 ∼1 µs integration time per point, ∼100× faster than previously reported values for THz-TDS systems.

Associations between Dietary Variety and Frailty in Community-Dwelling Older People Who Live Alone: Gender Differences.

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.

First assessment of root biomass and root carbon and nitrogen stocks in Turkish floodplain forests.

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.

Noncollinear electro-optic sampling detection of terahertz pulses in a LiNbO3 crystal while avoiding the effect of intrinsic birefringence.

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.

Correlation of foetal body weight by coronet width measurement using ultrasonography in prepartum cows: a pilot study.

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.

Elastocapillary adhesion of a soft cap on a rigid sphere.

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.

Prevalence and causes of congenital microcephaly in the absence of a Zika virus outbreak in southern Brazil / Prevalência e causas da microcefalia congênita sem a presença do surto do vírus Zika no Sul do Brasil

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%.

Prevalence and causes of congenital microcephaly in the absence of a Zika virus outbreak in southern Brazil.

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%.

Nonellipsometric electro-optic sampling of terahertz waves in GaAs.

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.

Constraints on new gravitylike forces in the nanometer range.

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.

Impact of patient knowledge of hypertension complications on adherence to antihypertensive therapy.

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.

Randomized clinical trial of isolated Roux-en-Y versus conventional reconstruction after pancreaticoduodenectomy.

BACKGROUND: Pancreaticoduodenectomy (PD) is associated with a high incidence of postoperative complications including pancreatic fistula. This randomized clinical trial compared the incidence of pancreatic fistula between the isolated Roux-en-Y (IsoRY) and conventional reconstruction (CR) methods. METHODS: Patients admitted for PD between June 2009 and September 2012 in a single centre were assigned randomly to CR or IsoRY. The primary endpoint was the incidence of pancreatic fistula (grade A-C) defined according to the International Study Group on Pancreatic Fistula. Secondary endpoints were complication rates, mortality and hospital stay. Multiple logistic regression analysis was performed to identify factors associated with pancreatic fistula. RESULTS: Some 153 patients were randomized, 76 to CR and 77 to IsoRY; two patients from the IsoRY group were excluded after randomization. Pancreatic fistula occurred in 26 patients (34 per cent) in the CR group and 25 (33 per cent) in the IsoRY group (P = 0·909). The number of patients with a clinically relevant pancreatic fistula (grade B or C) was similar in the two groups (10 and 11 patients respectively; P = 0·789), as were complication rates (42 versus 40 per cent; P = 0·793) and mortality (none in either group; P = 0·999). Soft pancreas was the only independent risk factor for pancreatic fistula (odds ratio 4·42, 95 per cent confidence interval 1·85 to 10·53; P <0·001). CONCLUSION: This study showed that IsoRY reconstruction does not reduce the incidence of pancreatic fistula compared with CR. REGISTRATION NUMBER: NCT00915863 (http://www.clinicaltrials.gov/) and UMIN000001967 (http://www.umin.ac.jp/).

Surveillance for yellow Fever virus in non-human primates in southern Brazil, 2001-2011: a tool for prioritizing human populations for vaccination.

In Brazil, epizootics among New World monkey species may indicate circulation of yellow fever (YF) virus and provide early warning of risk to humans. Between 1999 and 2001, the southern Brazilian state of Rio Grande do Sul initiated surveillance for epizootics of YF in non-human primates to inform vaccination of human populations. Following a YF outbreak, we analyzed epizootic surveillance data and assessed YF vaccine coverage, timeliness of implementation of vaccination in unvaccinated human populations. From October 2008 through June 2009, circulation of YF virus was confirmed in 67 municipalities in Rio Grande do Sul State; vaccination was recommended in 23 (34%) prior to the outbreak and in 16 (24%) within two weeks of first epizootic report. In 28 (42%) municipalities, vaccination began more than two weeks after first epizootic report. Eleven (52%) of 21 laboratory-confirmed human YF cases occurred in two municipalities with delayed vaccination. By 2010, municipalities with confirmed YF epizootics reported higher vaccine coverage than other municipalities that began vaccination. In unvaccinated human populations timely response to epizootic events is critical to prevent human yellow fever cases.

Observation of the spatial distribution of gravitationally bound quantum states of ultracold neutrons and its derivation using the Wigner function.

Ultracold neutrons (UCNs) can be bound by the potential of terrestrial gravity and a reflecting mirror. The wave function of the bound state has characteristic modulations. We carried out an experiment to observe the vertical distribution of the UCNs above such a mirror at the Institut Laue-Langevin in 2011. The observed modulation is in good agreement with that prediction by quantum mechanics using the Wigner function. The spatial resolution of the detector system is estimated to be 0.7 µm. This is the first observation of gravitationally bound states of UCNs with submicron spatial resolution.

One-year follow-up of zoster-associated pain in 764 immunocompetent patients with acute herpes zoster treated with famciclovir (FAMILIAR study).

BACKGROUND: Herpes zoster (HZ), a reactivation of varicella zoster virus manifested by skin blisters and neuralgia, can lead to postherpetic neuralgia in 10-20% of affected subjects. METHOD: In this study, a cohort of 764 patients with HZ was treated with 1500 mg/day of famciclovir for 7 days, and zoster-associated pain (ZAP) was monitored monthly thereafter for up to 12 months until pain resolution was achieved. Patients were questioned monthly by telephone, and pain was recorded using a numerical rating scale (NRS, 0-10). KEY RESULTS: A total of 751 of 764 (98.3%) patients completed follow-up. The percentage of patients with ZAP was 12.4% at day 90, 7.1% at 6 months and 4.0% at 1 year. After the third month, the NRS were 3 or less in most of the remaining patients with ZAP. Stratified analysis revealed significant persistence of ZAP in patients aged ≥50 years and in those aged ≥65 years, and in patients with either moderate-to-severe skin symptoms or severe pain at the initial consultation.Stratified analyses unexpectedly showed patients who commenced famciclovir at 0-2 days after onset of the eruption had a higher prevalence of ZAP at day 90 than those treated at 3-5 days or ≥6 days after rash onset (P = 0.0164, log-rank test). On further analysis, a higher proportion of patients (45.4%) treated at 0-2 days had moderate to severe symptoms compared with those treated at 3-5 days (40.5%) or ≥6 days (37.0%) (P = 0.0987, Cochran-Armitage test). CONCLUSION & INFERENCE: This study, with an exceptionally high follow-up rate, revealed several new findings, including the influence of disease severity on the delay between the onset of symptoms and seeking medical attention. Six adverse drug reactions were reported in five of 721 patients in the safety analysis, including two severe cases of vomiting and convulsions.