Technical note: Quantifying radionuclide residues in hospital wastewater: A case study on [131I]I and [177mLu]Lu/[177Lu]Lu.

BACKGROUND: Historically, [131I]I has been a common isotope in radionuclide therapy, with [177Lu]Lu-labelled radiopharmaceuticals now seeing a surge in use. These can include no-carrier-added or carrier-added [177Lu]Lu with slight impurities of [177mLu]Lu with a significantly longer half-life than [131I]I. Wastewater from therapy wards can contain a mixture of these radioisotopes. In some countries, national regulations require wastewater to be stored in dedicated systems before it is discharged into the public sewage system. To fulfill legal requirements, the nuclide specific activity concentration must be verified. PURPOSE: We evaluate a method for determining the activity concentration of [177mLu]Lu /[177Lu]Lu at equilibrium and [131I]I in pure and mixed samples in order to prove that the determined values are reliably below the limits for release. METHODS: We analysed the emitted energy spectrum of 1 L samples with a wastewater counter using an energy window-based approach by evaluating measurements from two different time points. Based on the law of decay and the time and energy-dependent measured values, equation systems were set up to calculate the count rates for [131I]I and [177mLu]Lu, which were converted into activity concentration using calibration factors. RESULTS: There is strong linear correlation between the nominal and determined activity concentrations (correlation coefficients R = 0.99; coefficient of determinations R2 = 0.99). We underestimate the actual activity concentration by a median of -1.4% for [177mLu]Lu and overestimate the activity concentration for [131I]I by a median of 7.1%. CONCLUSION: We show that an undercut of the clearance levels for material release is measurable. We analyse and determine activity concentrations of mixed samples consisting of [131I]I and [177mLu]Lu/[177Lu]Lu in equilibrium. The method is simple to implement using a conventional wastewater counter, however with a slightly increased effort, as two samples and measurements are required. The methodology can be adapted for the analysis of other nuclide mixtures.

Dealing with dry waste disposal issues associated with 177mLu impurities: a long-term challenge for nuclear medicine departments.

PURPOSE: A strategy for management of radioactive waste associated with 177Lu-dotatate (Lutathera®) treatments was established in our institution, based on predicted storage times of 3-5 years extrapolated from the results of a 2-year measurement study. The aim of this work was to validate this strategy by identifying contaminants and confirming disposal based on the clearance level twice-the-background was within expected time frames. METHODS: We conducted a prospective series of measurements of radioactive waste associated with the first 65 treatments administered. Sequential measurements of the first 45 vials used were performed on a dose calibrator to identify contaminants. Exposure rates in contact were monitored with a dose ratemeter on a 6-monthly basis for all waste stored: 46 empty vials, 19 vials partially used and 61 biohazard containers. RESULTS: Initial median activity of the first vials used was 118 MBq [4-4188 MBq]. For each vial, the decay curve of activity obtained was adjusted to a bi-exponential model. The major component, representing 99.7% of the activity, has a median half-life of 6.6 days [5.7-7.2 days] corresponding to 177Lu. The second, representing only 0.3% of the activity and having a median half-life of 152 days [104-205 days] corresponding to 177mLu, determines necessary storage times. Partially used vials can be disposed of after 5 years, other waste after 3 years. Compliance with the regulatory clearance level is achieved within expected time frames. CONCLUSION: Although only present as traces, 177mLu associated with the direct production route results in major radioactive waste disposal issues for hospitals. Availability of radiopharmaceuticals without impurities appears to be crucial for an expanding use of targeted radionuclide therapy.

Technical note: Assessment of radiation measurement devices for the detection of [177 Lu]Lu-labeled radiopharmaceuticals containing [177m Lu]Lu-impurities.

BACKGROUND: Nuclear medicine therapies using [177 Lu]Lu-labeled radiopharmaceuticals have increased significantly in recent years. Some of these radiopharmaceuticals contain long-lived impurities of [177m Lu]Lu. Identification of this specific contamination and its quantification is important in different scenarios. PURPOSE: In this study, standard measurement hardware used for handling radioisotopes was evaluated for the measurement of [177m Lu]Lu and [177 Lu]Lu at equilibrium. Device-specific detection limits (LODs) for [177m Lu]Lu were determined according to international standards and then validated. METHODS: The LODs were determined according to the international standard ISO 11929-1 for [177m Lu]Lu for five identical portable contamination monitors (PCMs), a wastewater counter (WWC), and a release counter system (RCS) at different measuring times. Subsequent activity measurements of the defined samples were used to validate the linearity of the measurement instruments down to the LOD for each system. RESULTS: The average LOD across all PCMs was 0.249 ± 0.009 and 0.129 ± 0.005 Bq/cm2 for 10 and 30 s measurements, respectively. The LODs of WWC varied between 3.3 and 4.7 Bq/L for measurement times of 300 s and 0.8-1.3 Bq/L for 3600 s depending on the energy window studied. The LOD of the RCS depended on the container volume and was 0.08 Bq/g for the 50 L container at 60 s measurement. The measurements for all examined devices were linear down to the LOD (correlation coefficient R ≥ 0.96; coefficient of determination R2  ≥ 0.92). CONCLUSIONS: All investigated measuring instruments (PCM, WWC, RCS) were suitable for the determination of [177m Lu]Lu at equilibrium, and their specific LODs were determined. Based on the measurements performed, activity is overestimated; however, this is tolerable because assumptions and measurements in the context of radiation protection should be conservative.

Language therapy outcomes in deaf children with cochlear implant using a new developed program: A pilot study.

BACKGROUND: Cochlear implanted (CI) children have problems in most aspects of language and in particular with regards to grammar. Considering the lack of studies in the field of grammar treatment in CI children and bearing in the mind that CI children have the potential to develop language, the aim of the present study was to investigate the effect of treating grammar in CI children using a treatment grammar program. METHODOLOGY: first, the literature related to grammar were reviewed so as to extract different grammatical components for developing grammar treatment program and to make sentences for each element as well as to compile a manual for its implementation. Second, the validity of the sentences was examined using the Delphi method. Third, grammar treatment was performed on five CI children. Persian Developmental Sentence Scoring(PDSS) and Mean Length of Utterance(MLU) were used to evaluate them before and after treatment. RESULTS: Five grammatical classes were extracted, and the grammatical elements were classified in each category according to age. For all of the grammatical items, 2076 sentences were constructed. After applying the Delphi method, a total of 1936 sentences with Kendall's coefficient of concordance (W) of 71%, remained. Using this program, grammar treatment was effective in all five children. The PDSS and MLU increased in all five children during the treatment phase, which was confirmed by Percentage of Non-overlapping Data (PND), Improvement Rate Difference (IRD). During the follow-up period, the children showed that they were able to maintain the trained components. CONCLUSION: Cochlear implants have the potential to learn language skills, and the present study confirms their ability to learn grammar, using a comprehensive grammar treatment program.

Radionuclide generator-based production of therapeutic 177Lu from its long-lived isomer 177mLu.

BACKGROUND: In this work, a lutetium-177 (177Lu) production method based on the separation of nuclear isomers, 177mLu & 177Lu, is reported. The 177mLu-177Lu separation is performed by combining the use of DOTA & DOTA-labelled peptide (DOTATATE) and liquid-liquid extraction. METHODS: The 177mLu cations were complexed with DOTA & DOTATATE and kept at 77 K for periods of time to allow 177Lu production. The freed 177Lu ions produced via internal conversion of 177mLu were then extracted in dihexyl ether using 0.01 M di-(2-ethylhexyl) phosphoric acid (DEHPA) at room temperature. The liquid-liquid extractions were performed periodically for a period up to 35 days. RESULTS: A maximum 177Lu/177mLu activity ratio of 3500 ± 500 was achieved with [177mLu]Lu-DOTA complex, in comparison to 177Lu/177mLu activity ratios of 1086 ± 40 realized using [177mLu]Lu-DOTATATE complex. The 177Lu-177mLu separation was found to be affected by the molar ratio of lutetium and DOTA. A 177Lu/177mLu activity ratio up to 3500 ± 500 was achieved with excess DOTA in comparison to 177Lu/177mLu activity ratio 1500 ± 600 obtained when lutetium and DOTA were present in molar ratio of 1:1. Further, the 177Lu ion extraction efficiency, decreases from 95 ± 4% to 58 ± 2% in the presence of excess DOTA. CONCLUSION: The reported method resulted in a 177Lu/ 177mLu activity ratio up to 3500 after the separation. This ratio is close to the lower end of 177Lu/177mLu activity ratios, attained currently during the direct route 177Lu production for clinical applications (i.e. 4000-10,000). This study forms the basis for further extending the liquid-liquid extraction based 177mLu-177Lu separation in order to lead to a commercial 177mLu/177Lu radionuclide generator.

Retelling stories: Grammatical and lexical measures for identifying monolingual spanish speaking children with specific language impairment (SLI).

Children with Specific Language Impairment (SLI) have grammatical and lexical difficulties when telling stories. The aim of this work was to explore whether language productivity measures, such as mean length of utterance (MLU), percentage of ungrammatical sentences (%UGS), total number of words (TNW), and number of different words (NDW) produced by young children during a story retell task, can be used to accurately differentiate monolingual Spanish-speaking children with SLI from children with typical language development (TLD). Fifty monolingual Spanish-speaking children between 4; 0 and 6; 11 years were assigned to one of two groups: 25 children with SLI and 25 TLD age-matched peers. A scripted picture book was read to each child and the child was subsequently asked to retell the story using pictures. Story retells were analyzed for MLU, %UGS, TNW, and NDW. Results showed significant differences between groups on all four measures. Children with SLI showed significantly lower MLU, TNW and NDW, and significantly higher%UGS when compared with age-matched peers with TLD. Results suggest that measures of language productivity obtained during story retells may be used to accurately detect differences in language performance and differentiate monolingual Spanish-speaking children with SLI from their typical peers. The findings from this study have clinical implications for assessment and identification of monolingual Spanish-speaking children with language impairments.

Length of Utterance, in Morphemes or in Words?: MLU3-w, a Reliable Measure of Language Development in Early Basque.

The mean length of utterace (MLU), which was proposed by Brown (1973) as a better index for language development in children than age, has been regularly reported in case studies as well as in cross-sectional studies on early spontaneous language production. Despite the reliability of MLU as a measure of (morpho-)syntactic development having been called into question, its extensive use in language acquisition studies highlights its utility not only for intra- and inter-individual comparison in monolingual language acquisition, but also for cross-linguistic assessment and comparison of bilinguals' early language development (Müller, 1993; Yip and Matthews, 2006; Meisel, 2011). An additional issue concerns whether MLU should be measured in words (MLU-w) or morphemes (MLU-m), the latter option being the most difficult to gauge, since new challenges have arisen regarding how to count zero morphemes, suppletive and fused morphemes. The different criteria have consequences, especially when comparing development in languages with diverging morphological complexity. A variant of MLU, the MLU3, which is calculated out of the three longest sentences produced (MLU3-w and MLU3-m), is included among the subscales of expressive language development in CDI parental reports (Fenson et al., 1993, 2007). The aim of the study is to investigate the consistency and utility of MLU3-w and MLU3-m as a measure for (morpho-)syntactic development in Basque, an agglutinative language. To that end, cross-sectional data were obtained using either the Basque CDI-2 instrument (16- to 30-month-olds) or the Basque CDI-3 (30- to 50-month-olds). The results of analyzing reports on over 1,200 children show three main findings. First, MLU3-w and MLU3-m can report equally well on very young children's development. Second, the strong correlations found between MLU3 and expressive vocabulary in the Basque CDI-2 and CDI-3 instruments, as well as between MLU3 and both nominal and verbal morphology scales, confirm the consistency not only of MLU3 but also of the two Basque CDI instruments. Finally, both MLU3-w and MLU3-m subscales appear sensitive to input after age 2, which emphasizes their utility for identifying developmental patterns in Basque bilinguals.

Syntagmatic and paradigmatic development of cochlear implanted children in comparison with normally hearing peers up to age 7.

OBJECTIVE: Grammatical development is shown to be delayed in CI children. However, the literature has focussed mainly on one aspect of grammatical development, either morphology or syntax, and on standard tests instead of spontaneous speech. The aim of the present study was to compare grammatical development in the spontaneous speech of Dutch-speaking children with cochlear implants and normally hearing peers. Both syntagmatic and paradigmatic development will be assessed and compared with each other. METHOD: Nine children with cochlear implants were followed yearly between ages 2 and 7. There was a cross-sectional control group of 10 normally hearing peers at each age. Syntactic development is measured by means of Mean Length of Utterance (MLU), morphological development by means of Mean Size of Paradigm (MSP). This last measure is relatively new in child language research. RESULTS: MLU and MSP of children with cochlear implants lag behind that of their normally hearing peers up to age 4 and up to age 6 respectively. By age 5, CI children catch up on MSP and by age 7 they caught up on MLU. CONCLUSION: Children with cochlear implants catch up with their normally hearing peers for both measures of syntax and morphology. However, it is shown that inflection is earlier age-appropriate than sentence length in CI children. Possible explanations for this difference in developmental pace are discussed.

Learning language in autism: maternal linguistic input contributes to later vocabulary.

It is well established that children with typical development (TYP) exposed to more maternal linguistic input develop larger vocabularies. We know relatively little about the linguistic environment available to children with autism spectrum disorders (ASD), and whether input contributes to their later vocabulary. Children with ASD or TYP and their mothers from English and French-speaking families engaged in a 10 min free-play interaction. To compare input, children were matched on language ability, sex, and maternal education (ASD n = 20, TYP n = 20). Input was transcribed, and the number of word tokens and types, lexical diversity (D), mean length of utterances (MLU), and number of utterances were calculated. We then examined the relationship between input and children's spoken vocabulary 6 months later in a larger sample (ASD: n = 19, 50-85 months; TYP: n = 44, 25-58 months). No significant group differences were found on the five input features. A hierarchical multiple regression model demonstrated input MLU significantly and positively contributed to spoken vocabulary 6 months later in both groups, over and above initial language levels. No significant difference was found between groups in the slope between input MLU and later vocabulary. Our findings reveal children with ASD and TYP of similar language levels are exposed to similar maternal linguistic environments regarding number of word tokens and types, D, MLU, and number of utterances. Importantly, linguistic input accounted for later vocabulary growth in children with ASD.

Input materno e aquisição da linguagem: Análise das díades comunicativas entre mães e filhos / Maternal input and language acquisition: Analysis of communicative mother-child dyads

Este trabalho trata da interação verbal entre mães e filhos, objetivando estudar a extensão e quantidade de enunciados diretivos das mães no desenvolvimento da linguagem dos filhos com ou sem retardo na aquisição da linguagem verbal. Participaram da pesquisa oito crianças acompanhadas de suas mães, de ambos os sexos, com idades entre 2:10 e 5:3 anos e divididas em dois grupos. Quatro apresentavam retardo na aquisição da linguagem e as outras quatro desenvolvimento normal da linguagem. Para a análise da interação lingüística propuseram-se três tarefas de interação entre as díades. Obtiveram-se a média de extensão do enunciado (MLU), os enunciados diretivos das mães e realizou-se a análise estatística para determinar a relevância de cada item analisado. A partir desta pesquisa concluiu-se que o MLU não foi uma medida que refletiu as diferenças na fala dirigida à criança nos dois grupos; a variável que melhor reproduziu a diferença no input materno foi a avaliação dos enunciados diretivos.(AU)

This work is about the mother-child verbal interaction, aiming to study the extension and amount of mother’s directive utterances upon language development, with or without delay in the acquisition of verbal language. Eight children of both genders, whose ages varied between 2:10 and 5:3 years, accompanied by the mothers, participated in the research divided in two groups. One group was composed by four children who showed delay in the acquisition of verbal language and the remaining four who had normal development of language acquisition. Three tasks were proposed for analysis of linguistic interactions of the dyad. MLU and directives utterances of mothers were obtained. The statistical analysis was made in order to obtain the relevance of each item. It was found that the MLU, in this study, was not a measure reflecting differences in directed speech to the child in both groups; the variable that better reproduced the difference in the mother’s input was the directive utterance.(AU)

Input materno e aquisição da linguagem: Análise das díades comunicativas entre mães e filhos / Maternal input and language acquisition: Analysis of communicative mother-child dyads

Este trabalho trata da interação verbal entre mães e filhos, objetivando estudar a extensão e quantidade de enunciados diretivos das mães no desenvolvimento da linguagem dos filhos com ou sem retardo na aquisição da linguagem verbal. Participaram da pesquisa oito crianças acompanhadas de suas mães, de ambos os sexos, com idades entre 2:10 e 5:3 anos e divididas em dois grupos. Quatro apresentavam retardo na aquisição da linguagem e as outras quatro desenvolvimento normal da linguagem. Para a análise da interação lingüística propuseram-se três tarefas de interação entre as díades. Obtiveram-se a média de extensão do enunciado (MLU), os enunciados diretivos das mães e realizou-se a análise estatística para determinar a relevância de cada item analisado. A partir desta pesquisa concluiu-se que o MLU não foi uma medida que refletiu as diferenças na fala dirigida à criança nos dois grupos; a variável que melhor reproduziu a diferença no input materno foi a avaliação dos enunciados diretivos.

This work is about the mother-child verbal interaction, aiming to study the extension and amount of mother’s directive utterances upon language development, with or without delay in the acquisition of verbal language. Eight children of both genders, whose ages varied between 2:10 and 5:3 years, accompanied by the mothers, participated in the research divided in two groups. One group was composed by four children who showed delay in the acquisition of verbal language and the remaining four who had normal development of language acquisition. Three tasks were proposed for analysis of linguistic interactions of the dyad. MLU and directives utterances of mothers were obtained. The statistical analysis was made in order to obtain the relevance of each item. It was found that the MLU, in this study, was not a measure reflecting differences in directed speech to the child in both groups; the variable that better reproduced the difference in the mother’s input was the directive utterance.