Cerebellar mutism syndrome in children with brain tumours of the posterior fossa

Background: Central nervous system tumours constitute 25% of all childhood cancers; more than half are located in the posterior fossa and surgery is usually part of therapy. One of the most disabling late effects of posterior fossa tumour surgery is the cerebellar mutism syndrome (CMS) which has been reported in up to 39% of the patients but the exact incidence is uncertain since milder cases may be unrecognized. Recovery is usually incomplete. Reported risk factors are tumour type, midline location and brainstem involvement, but the exact aetiology, surgical and other risk factors, the clinical course and strategies for prevention and treatment are yet to be determined. Methods: This observational, prospective, multicentre study will include 500 children with posterior fossa tumours. It opened late 2014 with participation from 20 Nordic and Baltic centres. From 2016, five British centres and four Dutch centres will join with a total annual accrual of 130 patients. Three other major European centres are invited to join from 2016/17. Follow-up will run for 12 months after inclusion of the last patient. All patients are treated according to local practice. Clinical data are collected through standardized online registration at pre-determined time points pre- and postoperatively. Neurological status and speech functions are examined pre- operatively and postoperatively at 1-4 weeks, 2 and 12 months. Pre- and postoperative speech samples are recorded and analysed. Imaging will be reviewed centrally. Pathology is classified according to the 2007 WHO system. Germline DNA will be collected from all patients for associations between CMS characteristics and host genome variants including pathway profiles. Discussion: Through prospective and detailed collection of information on 1) differences in incidence and clinical course of CMS for different patient and tumour characteristics, 2) standardized surgical data and their association with CMS, 3) diversities and results of other therapeutic interventions, and 4) the role of host genome variants, we aim to achieve a better understanding of risk factors for and the clinical course of CMS - with the ultimate goal of defining strategies for prevention and treatment of this severely disabling condition.Peer reviewe

On describing

The overarching topic of this dissertation is the semantics and pragmatics of definite descriptions. It focuses on the question whether sentences such as ‘the king of France is bald’ literally assert the existence of a unique king (and therefore are false) or simply presuppose the existence of such a king (and thus fail to express propositions). One immediate obstacle to resolving this question is that immediate truth value judgments about such sentences (sentences with non-denoting descriptions) are particularly unstable; some elicit a clear intuition of falsity whereas others simply seem awkward or strange. Because of these variations, truth value judgments are generally considered unreliable. In the first chapter of the dissertation, an explanation of this phenomenon is developed. It is observed that when these types of sentences are considered in the context of a discourse, a systematic pattern in judgments emerges. This pattern, it is argued, should be explained in terms of certain pragmatic factors, e.g. whether a speaker’s utterance is interpreted as cooperative. A detailed and general explanation of the phenomenon is then presented which draws importantly on recent research in the semantics and pragmatics of questions and focus. It is shown that the behavior of these judgments can be systematically explained, that truth value judgments are not as unreliable as standardly assumed, and that the proposed explanation best supports the conclusion that definite descriptions presuppose rather than assert existence. In the second chapter, the following problem is investigated. If definite descriptions are assumed to literally assert existence, a sentence such as ‘Hans wants the ghost in his attic to be quiet’ is incorrectly predicted to be true only if Hans wants there to be a (unique) ghost in his attic. This prediction is often considered evidence against Russell’s quantificational analysis and evidence in favor of the referential analysis of Frege and Strawson. Against this claim, it is demonstrated that this problem is a general problem about the existence commitments of natural language determiners, i.e. not an argument in favor of a referential analysis. It is shown that in order to avoid these undesirable predictions, quite radical changes to the semantic framework are required. For example, it must be assumed that a sentence of the form ‘The F is G’ has the open sentence ‘x is G’ as its asserted content. A uniform quantificational and presuppositional analysis of definites and indefinites is outlined which by exploiting certain features of so-called dynamic semantics unproblematically assumes that the asserted contents indeed are open sentences. In view of the proposed quantificational/presuppositional analysis, the dissertation is concluded by a rejection of the argument put forward by Reimer (1998) and Devitt (2004) that definite descriptions are ambiguous between attributive (quantificational) and referential (indexical) uses. Reimer and Devitt’s argument is (in contrast to Donnellan, 1966) based primarily on the assumption that definite descriptions are conventionally used to communicate singular thoughts and that the conventional meaning of a definite description therefore must be fundamentally indexical/directly referential. I argue that this argument relies crucially on tacit assumptions about semantic processing for which no empirical evidence is provided. I also argue that the argument is too general; if sound, it would be an argument for an indexical treatment of most, if not all, other determiners. I then conclude by demonstrating that the view does not explain any new data and thus has no clear motivation. In short, this dissertation provides a detailed pragmatic explanation of a long-standing puzzle about truth value judgments and then outlines a novel dynamic semantic analysis of definites and indefinites. This analysis solves a significant problem about existence commitments — a problem that neither Russell’s nor the Frege/Strawson analysis are equipped to handle. This analysis is then defended against the claim that definite descriptions are ambiguous.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor in Norway from 1974 through 2013: Unexplainable regional differences in survival

Background A previous study based on Norwegian Cancer Registry data suggested regional differences in overall survival (OS) after treatment for medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor (CNS‐PNET) in Norway. The purpose of the present study was to confirm in an extended cohort whether there were regional differences in outcome or not, and if so try to identify possible explanations. Material and methods Data from patients aged 0–20 years diagnosed with and treated for MB/CNS‐PNET at all four university hospitals in Norway from 1974 to 2013 were collected and compared. Results Of 266 identified patients, 251 fulfilled inclusion criteria. MB was diagnosed in 200 and CNS‐PNET in 51 patients. Five‐year OS and event‐free survival (EFS) were 59% and 52%, respectively. There was a significant difference in five‐year OS and EFS between MB and CNS‐PNET patients; 62% versus 47% (P = 0.007) and 57% versus 35% (P < 0.001). In multivariable analysis, two factors were found to significantly contribute to improved five‐year OS and EFS, whereas one factor contributed to improved five‐year OS only. Gross total resection (GTR) versus non‐GTR (hazard ratio [HR] 0.53, P = 0.003; HR 0.46, P < 0.001) and cerebrospinal irradiation (CSI) versus non‐CSI (HR 0.24, P < 0.001; HR 0.28, P < 0.001) for both, and treatment outside Oslo University Hospital for OS only (HR 0.64, P = 0.048). Conclusion Survival was comparable with data from other population‐based studies, and the importance of GTR and CSI was confirmed. The cause for regional survival differences could not be identified