A Diagnostic Algorithm for Posterior Fossa Tumors in Children: A Validation Study

BACKGROUND AND PURPOSE: Primary posterior fossa tumors comprise a large group of neoplasias with variable aggressiveness and short and long-term outcomes. This study aimed to validate the clinical usefulness of a radiologic decision flow chart based on previously published neuroradiologic knowledge for the diagnosis of posterior fossa tumors in children. MATERIALS AND METHODS: A retrospective study was conducted (from January 2013 to October 2019) at 2 pediatric referral centers, Children's Hospital of Philadelphia, United States, and Great Ormond Street Hospital, United Kingdom. Inclusion criteria were younger than 18 years of age and histologically and molecularly confirmed posterior fossa tumors. Subjects with no available preoperative MR imaging and tumors located primarily in the brain stem were excluded. Imaging characteristics of the tumors were evaluated following a predesigned, step-by-step flow chart. Agreement between readers was tested with the Cohen κ, and each diagnosis was analyzed for accuracy. RESULTS: A total of 148 cases were included, with a median age of 3.4 years (interquartile range, 2.1-6.1 years), and a male/female ratio of 1.24. The predesigned flow chart facilitated identification of pilocytic astrocytoma, ependymoma, and medulloblastoma sonic hedgehog tumors with high sensitivity and specificity. On the basis of the results, the flow chart was adjusted so that it would also be able to better discriminate atypical teratoid/rhabdoid tumors and medulloblastoma groups 3 or 4 (sensitivity = 75%-79%; specificity = 92%-99%). Moreover, our adjusted flow chart was useful in ruling out ependymoma, pilocytic astrocytomas, and medulloblastoma sonic hedgehog tumors. CONCLUSIONS: The modified flow chart offers a structured tool to aid in the adjunct diagnosis of pediatric posterior fossa tumors. Our results also establish a useful starting point for prospective clinical studies and for the development of automated algorithms, which may provide precise and adequate diagnostic tools for these tumors in clinical practice

Suppression of ovarian hormones in adolescent rats has no effect on anxiety-like behaviour or c-fos activation in the amygdala

Support was provided the British Society for Neuroendocrinology, Carnegie Trust for the Universities of Scotland and School of Psychology & Neuroscience, University of St Andrews.In humans, sex differences in mood disorders emerge during adolescence, with prevalence rates being consistently higher in females than males. It has been hypothesised that exposure to endogenous ovarian hormones during adolescence enhances the susceptibility of females to mood disorders from this stage of life onwards. However, experimental evidence in favour of this hypothesis is lacking. In the present study, we examined the long‐term effects of suppressing adolescent gonadal hormone levels in a group of female Lister‐hooded rats via administration of a gonadotrophin‐releasing hormone antagonist (Antide; administered on postnatal day [PND] 28 and 42) compared to control females and males (n = 14 per group). We predicted that, in adulthood, Antide‐treated female rats would exhibit more male‐like behaviour than control females in novel environments (elevated‐plus maze, open field and light‐dark box), in response to novel objects and novel social partners, and in an acoustic startle task. Progesterone and luteinising hormone assays (which were conducted on blood samples collected on PND 55/56 and 69/70) confirmed that the hypothalamic‐pituitary‐gonadal axis was temporarily suppressed by Antide treatment. In addition, Antide‐treated females were found to exhibit a modest pubertal delay, as measured by vaginal opening, which was comparable in length to the pubertal delay that has been induced by adolescent exposure to alcohol or stress in previous studies of female rats. However, Antide‐treated females did not substantially differ from control females on any of the behavioural tests, despite the evidence for predicted sex differences in some measures. Following the acoustic startle response task, all subjects were culled and perfused, and c‐Fos staining was conducted in the medial and basolateral amygdala, with the results showing no significant differences in cell counts between the groups. These findings suggest that ovarian hormone exposure during adolescence does not have long‐term effects on anxiety‐related responses in female rats.Publisher PDFPeer reviewe

Centre selection for clinical trials and the generalisability of results: a mixed methods study.

BACKGROUND: The rationale for centre selection in randomised controlled trials (RCTs) is often unclear but may have important implications for the generalisability of trial results. The aims of this study were to evaluate the factors which currently influence centre selection in RCTs and consider how generalisability considerations inform current and optimal practice. METHODS AND FINDINGS: Mixed methods approach consisting of a systematic review and meta-summary of centre selection criteria reported in RCT protocols funded by the UK National Institute of Health Research (NIHR) initiated between January 2005-January 2012; and an online survey on the topic of current and optimal centre selection, distributed to professionals in the 48 UK Clinical Trials Units and 10 NIHR Research Design Services. The survey design was informed by the systematic review and by two focus groups conducted with trialists at the Birmingham Centre for Clinical Trials. 129 trial protocols were included in the systematic review, with a total target sample size in excess of 317,000 participants. The meta-summary identified 53 unique centre selection criteria. 78 protocols (60%) provided at least one criterion for centre selection, but only 31 (24%) protocols explicitly acknowledged generalisability. This is consistent with the survey findings (n = 70), where less than a third of participants reported generalisability as a key driver of centre selection in current practice. This contrasts with trialists' views on optimal practice, where generalisability in terms of clinical practice, population characteristics and economic results were prime considerations for 60% (n = 42), 57% (n = 40) and 46% (n = 32) of respondents, respectively. CONCLUSIONS: Centres are rarely enrolled in RCTs with an explicit view to external validity, although trialists acknowledge that incorporating generalisability in centre selection should ideally be more prominent. There is a need to operationalize 'generalisability' and incorporate it at the design stage of RCTs so that results are readily transferable to 'real world' practice