Long-term oncological outcomes of endoscopic full-thickness resection after previous incomplete resection of low-risk T1 CRC (LOCAL-study): study protocol of a national prospective cohort study.

BACKGROUND: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization. METHODS/DESIGN: In this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate. DISCUSSION: Since the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation. Trial registration Nederlands Trial Register, NL 7879, 16 July 2019 ( https://trialregister.nl/trial/7879 ).

Severe Complication of Thiopurine Treatment in a Young Woman with Crohn's Disease.

CASE DESCRIPTION: A 28-year old woman receiving thiopurine treatment for Crohn's disease presented with a systemic primo cytomegalovirus (CMV) infection affecting the gut (colitis), liver (hepatitis), lungs (pneumonitis) and eyes (retinitis). Secondary to this systemic infection, she developed splenomegaly, pancytopenia and lymphadenopathy. Anti-viral treatment resulted in complete resolution of clinical, biochemical and radiological abnormalities within 6 weeks. CONCLUSION: Early recognition is crucial since CMV infection in a patient receiving thiopurine treatment may result in serious complications. LEARNING POINTS: Cytomegalovirus (CMV) infection in patients receiving thiopurine treatment may result in serious complications.This case report describes extensive primo CMV infection causing colitis, hepatitis, pneumonitis and retinitis in a patient receiving thiopurine treatment.Early recognition and treatment of the infection is crucial.

The balance of storage and computation in morphological processing: the role of word formation type, affixal homonymy, and productivity.

This article is concerned with the way in which the balance of storage-storing and processing words through full-form representations-and computation-storing and processing words through morpheme-based representations-in lexical processing in the visual modality is affected by the following 3 factors: word formation type (roughly, inflection vs. derivation), productivity, and affixal homonymy. Experimental results for 5 different Dutch suffixes, combined with previous results obtained for 4 comparable Finnish suffixes (R. Bertram, M. Laine, & K. Karvinen, 1999) and 2 Dutch suffixes (R. H. Baayen, T. Dijkstra, & R. Schreuder, 1997), show that none of these factors in isolation is a reliable cross-linguistic predictor of the balance of storage and computation. The authors offer a general framework that outlines how morphological processing is influenced by the interaction of word formation type, productivity, and affixal homonymy.

Affixal homonymy triggers full-form storage, even with inflected words, even in a morphologically rich language.

This paper investigates whether affixal homonymy, the phenomenon that one affix form serves two or more semantic/syntactic functions, affects lexical processing of inflected words in a similar way for a morphologically rich language such as Finnish as for morphologically restricted languages such as Dutch and English. For the latter two languages, there is evidence that affixal homonymy triggers full-form storage for inflected words (Bertram, R., Schreuder, R., and Baayen, R. H. (in press). The balance of storage and computation in morphological processing: the role of word formation type, affixal homonymy, and productivity. Journal of Experimental Psychology: Learning, Memory, and Cognition; Sereno and Jongman (1997). Processing of English inflectional morphology. Memory and Cognition, 25, 425-437). Two visual lexical decision experiments show the same pattern for Finnish. Apparently, the substantially richer morphology in Finnish does not prevent full-form storage for inflected words when the affix is homonymic.

War and peace: morphemes and full forms in a noninteractive activation parallel dual-route model.

This article introduces a computational tool for modeling the process of morphological segmentation in visual and auditory word recognition in the framework of a parallel dual-route model.

Towards a standardised assessment procedure for developmental apraxia of speech.

This study addresses the assessment of developmental apraxia of speech (DAS) in children. For this, 11 children with a clear diagnosis of DAS were selected, based on documented speech history and perceptual evaluation of speech. The children with DAS, as well as 11 normal-speaking children, produced singleton real word and nonsense word imitations elicited in a standardised way. Phonetic transcriptions were analysed and errors in consonants classified. The results showed, firstly, that the children with DAS produced similar types of consonant errors as has been reported in the literature, which corroborates the method of elicitation as a valid procedure to assess relevant speech symptoms of DAS. Secondly, a large quantitative difference between children with DAS and normal-speaking children was found, in that children with DAS produced an overall higher rate of singleton consonant errors (substitutions, omissions, distortions) and cluster errors (cluster reductions) than the normal-speaking children. For the DAS group, the substitution-rate, particularly in real words (as opposed to nonsense words), was significantly correlated with severity as rated by two speech and language pathologists. This suggests that substitution-rate yields an adequate measure of severity of DAS. Thirdly, a qualitative difference between both subject groups emerged. Children with DAS did not benefit from the lexical status of the utterance (real versus nonsense word) to the same extent as normal-speaking children. Based on these findings the nature of the underlying deficits in speech production in DAS is discussed.

Feature analysis of singleton consonant errors in developmental verbal dyspraxia (DVD).

The aim of this study is to quantify diagnostic characteristics related to consonant production of developmental verbal dyspraxia (DVD). For this, a paradigmatic and syntagmatic feature-value analysis of the consonant substitution and omission errors in DVD speech was conducted. Following a three-step procedure, eleven clear cases were selected from a group of 24 children with DVD. The consonants produced in a word and nonsense-word imitation task were phonetically transcribed and transferred to confusion matrices, which allows for a feature and feature-value analysis. The analysis revealed that children with DVD (a) show low percentages of retention for place and manner of articulation and voicing, due to high substitution and omission rates; (b) show a particularly low percentage of retention of place of articulation in words, which, together with error rate, is strongly related to severity of involvement; (c) are inconsistent in their feature realization and feature preference; and (d) show a high syntagmatic error rate. These results form a quantification of diagnostic characteristics. Unexpectedly, however, very few qualitative differences in error pattern were found between children with DVD and a group of 11 age-matched children with normal speech. Thus, although the children with DVD produced higher substitution and omission rates than children with normal speech, the speech profiles of both subject groups are similar. This result stresses the importance of interpreting profiles, not isolated symptoms. The hypothesis to consider DVD as a deficit in the phonological encoding process is discussed.

The pharmacodynamics and activity of intranasally administered insulin in healthy male volunteers.

The objective of the study was to assess the bioavailability and absorption dynamics of intranasal insulin (with di-decanoyl-alpha-phosphatidylcholine, DDPC, as absorption enhancer) in two potencies (U200 and U500). Toward this aim, the euglycemic clamp technique combined with somatostatin (100 micrograms/h) was used. Insulin was administered to 12 healthy males: 5 IU intravenously (20-min infusion); 10 IU subcutaneously; 50 IU (U200) and 50 IU, 100 IU, and 150 IU (U500) intranasally. Peak insulin levels (mean +/- SD) were reached at 17.9 +/- 2.6, 77.9 +/- 38.3, 23.3 +/- 5.4, 25.4 +/- 8.4, 26.2 +/- 8.3, and 27.5 +/- 5.8 min, respectively. For the 50 IU dose, peak glucose requirements during the clamp and time to peak were not significantly different for U200 and U500: 548.8 +/- 279.5 vs. 452.4 +/- 232.9 mg/min and 41.3 +/- 16.2 vs. 51.5 +/- 29.9 min, respectively. Compared with intravenous insulin, the bioavailability calculated from the total area under the insulin curve was 13.2% (95% confidence interval 7.9, 21.9) and 8.8% (95% confidence interval 5.6, 13.8), and compared with subcutaneous insulin, the bioavailability was 14.8% (95% confidence interval 8.7, 25.2) and 9.9% (95% confidence interval 6.4, 15.4) for the U200 and U500 preparations, respectively. An apparent nonlinear dose-dependent relation was found for the U500 potency. The within-subject variability of the areas under the curves of plasma insulin after the administration of 100 IU was 43.6% (range 20.7-85.7). In conclusion, this nasal insulin preparation has promising absorption and action profiles in both potencies, which makes it suitable for further exploration of clinical applications.

Bidirectional grapheme-phoneme activation in a bimodal detection task.

A divided attention paradigm was used to investigate whether graphemes and phonemes can mutually activate or inhibit each other during bimodal processing. In 3 experiments, Dutch subjects reacted to visual and auditory targets in single-channel or bimodal stimuli. In some bimodal conditions, the visual and auditory targets were nominally identical or redundant (e.g., visual A and auditory /a/); in others they were not (e.g., visual U and auditory /a/). Temporal aspects of cross-modal activation were examined by varying the stimulus onset asynchrony of visual and auditory stimuli. Cross-modal facilitation--but not inhibition--occurred rapidly and automatically between phoneme and grapheme representations. Implications for current models of bimodal processing and word recognition are discussed.

Processing novel compounds: evidence for interactive meaning activation of ambiguous nouns.

In three experiments, the meaning activation of ambiguous nouns in novel nominal compounds was investigated. Ambiguous nouns were unbalanced homographs occurring as the second members of the compound. Meaningful interpretations of the compounds were based on either the dominant or the subordinate meaning of the ambiguous noun. In Experiment 1, visually presented novel compounds serving as primes were followed at varying intervals by targets associatively related to distinct meanings of the ambiguous noun. In a lexical decision task, facilitation effects were found only for targets related to the meaning that was relevant for the interpretation of the compound. Experiment 2 showed that interactive activation could not be attributed to differences in semantic relatedness between the first members of compounds and targets. Experiment 3 demonstrated equal intralexical relatedness between members for both types of compounds. It is proposed that interactive activation may facilitate the interpretation of the novel compound. Compatible meaning aspects of the nouns may become more strongly activated, and incompatible meaning aspects may not become activated. The selection of meaning aspects relevant for interpretation would thereby be simplified.

From concepts to lexical items.

In this paper we address the question how in language production conceptual structures are mapped onto lexical items. First we describe the lexical system in a fairly abstract way. Such a system consists of, among other things, a fixed set of basic lexical entries characterized by four groups of information: phonetic form, grammatical features, argument structure, and semantic form. A crucial assumption of the paper is that the meaning in a lexical entry has a complex internal structure composed of more primitive elements (decomposition). Some aspects of argument structure and semantic form and their interaction are discussed with respect to the issue of synonymy. We propose two different mappings involved in lexical access. One maps conceptual structures to semantic forms, and the other maps semantic forms to conceptual structures. Both mappings are context dependent and are many-to-many mappings. We present an elaboration of Levelt's (1989) model in which these processes interact with the grammatical encoder and the mental lexicon. Then we address the consequences of decomposition for processing models, especially the nature of the input of lexical access and the time course. Processing models that use the activation metaphor may have difficulties accounting for certain phenomena where a certain lemma triggers not one, but two or more word forms that have to be produced with other word forms in between.

The interpretation of isolated novel nominal compounds.

The lexical decision task was used to investigate interpretative processing of isolated novel compounds (noun-noun nominals). On the basis of interpretability ratings, novel compounds were classified as being of either high or low interpretability. In a lexical decision task in which novel compounds functioned as nonwords, a significant interference effect was found for compounds of high interpretability. In a naming task, no differences were found between the two types of novel compounds, but lexicalized compounds resulted in shorter latencies than did novel compounds. Novel compounds were also shown to be interpreted under conditions unfavorable to morphological decomposition, suggesting that the interpretation process is beyond strategic control by the subject. Equal semantic priming effects were obtained for members of established semantic categories and nouns of highly interpretable compounds. Interpretative processes dealing with a limited set of basic semantic relations and analogy with lexicalized compounds are discussed.

Determination of diisobutyl- and diisopropylnaphthalenesulphonates in pesticide wettable powders and dispersible granules by high-performance liquid chromatography.

Methods are presented for determining diisobutyl and diisopropylnaphthalenesulphonates in pesticides formulated as wettable powders or water dispersible granules. The dispersing agents were concentrated on anion-exchange cartridges and after removal of interfering substances eluted with methanol containing 5% hydrochloric acid. The various isomers were separated by reversed-phase high-performance liquid chromatography on an octyl-modified column using a water-methanol gradient or on a cyanoalkyl-modified column with water-methanol. Quantitative results were obtained by comparing the peaks with those of the standard technical material. Various groups of peaks were identified as mono-, di- and triisobutylnaphthalenesulphonates respectively.

Context-dependent migrations in visual word perception.

In the present study we investigate the effect of context--that is, a prime--on migration errors. Migration errors, or migrations, are caused by perceptual interactions between two words in a visual display, such as line-lace. After postcuing, subjects sometimes report lane or lice, instead of the requested word line. This phenomenon has been demonstrated by previous studies. In the experiments reported here, we replicate this phenomenon. We also find that more migrations of the lane type occur (compared with lice type), when the display line-lace is preceded by a prime related to lane (but not to lice). This shows that higher order word knowledge, in the form of semantic relations between words, influences the migration phenomenon. Further, we show that the number of migration errors are not a result of only a summation of activation from the letters in the display. The method we developed to isolate context-dependent migrations also gives valuable information about the effect of contextual information on word perception.

Scenarios for health planning and management: the Dutch experience.

The processes of health planning and management require a clear insight into: future developments in society at large; the magnitude of disease categories (mortality and morbidity patterns); the rapid developments in medical technology; and, changing concepts of "good" health care delivery systems. In 1983, the Dutch Secretary of Welfare, Health and Cultural Affairs decided to establish a Steering Committee for Future Health Scenarios (STG). The chief task of this Committee is to create alternative pictures of possible futures in the field of public health and health care. These health scenarios are used to increase the anticipatory capability of policymakers and health managers. This paper evaluates the Dutch experience with scenario- projects on "health and ageing", "cardiovascular diseases", and "cancer". After a short introduction on the structure of the STG, and the concept of scenarios, the scenario-projects are described and analysed. The conclusions to date of the projects are mentioned briefly. This article ends with some recommendations, with respect to the methodology of scenarios in the field of health, the structural prerequisites for successful projects, and the communication aspects of these types of studies.

Determination of dodecylbenzenesulphonates and ethoxylated alkylphenols in liquid pesticide formulations by high-performance liquid chromatography.

A method is presented for determining mixtures of calcium dodecylbenzene-sulphonate (CaDBS) and ethoxylated alkylphenols in pesticidal emulsifiable concentrates. The pesticide formulations are adsorbed on a pre-concentration column. The active ingredients, the solvents and the emulsifiers are eluted successively by using solvents with increasing polarities. The various homologues of CaDBS and the ethoxylated alkylphenols are separated by reversed-phase high performance liquid chromatography using methanol-water containing tetramethylammonium bromide. The oligomers of the ethoxylated phenols are separated on an aminopropyl-modified column using a solvent gradient (propan-2-ol-water and hexane-tetrahydrofuran). Quantitative results are given for synthetic samples. The degree of ethoxylation of the ethoxylated alkylphenols has been determined and the CaDBS components characterized.