Neuroendocrine morbidity after pediatric optic gliomas: a longitudinal analysis of 166 children over 30 years

Context: 50% of pediatric low-grade gliomas affect the optic pathway, hypothalamus and suprasellar areas (OP/HSGs) resulting in significant long-term neuroendocrinopathy. Objective: To dissect tumor- from treatment-related risk factors for OP/HSG-associated neuroendocrinopathy. Design: Retrospective case notes analysis of 166 children with newly-diagnosed OP/HSGs at our quaternary center between 1980 –2010 by multivariate Cox, linear and logistic regression. Results: Patients were of median (range) age 4.9 (0.2–15.4) years at diagnosis and followed up for 8.3 (0.04 –26.8) years. Despite high 20-year overall survival (81.0%), progression-free and endocrine event-free (EEFS) survival were 47.2% and 20.8% respectively. EEFS declined up to 15 years postdiagnosis, with hypothalamic involvement (p0.001) being implicated more than radiotherapy (p0.008) in earlier endocrinopathy; the reverse being true of its density (radiotherapy p0.001; hypothalamic involvement p0.006). GH deficiency (GHD) was commonest (40.3%), followed by central precocious puberty (CPP, 26.0%), gonadotropin (GnD, 20.4%), TSH (13.3%), and ACTH (13.3%) deficiencies. GHD increased with later treatment eras (p0.01), but replacement did not increase progression. CPP was associated with future GnD (p0.05). Posterior pituitary dysfunction (PPD, 7.2%) occurred in 57.9% after only biopsies or shunt procedures, and was associated with 6/13 deaths. 50.2% became obese. Tumor extent, surgery and increased endocrinopathy, rather than radiotherapy, predicted visuo-cognitive morbidity. Conclusions: This first longitudinal OP/HSG-specific study demonstrates that hypothalamo-pituitary dysfunction evolves hierarchically over decades. Tumor location predicts its speed of onset and radiotherapy its density. GnD can evolve from previous CPP, whilst life-threatening PPD can occur after any surgery. Our data suggest that recent radiation-avoiding chemotherapeutic strategies have increased GHD without improving survival

Violent and victimized bodies: sexual violence policy in England and Wales

This paper uses the notion of the body to frame an archaeology of sexual violence policy in England and Wales, applying and developing Pillow’s ideas. It argues that the dominant construction is of sexual violence as an individualized crime, with the solution being for a survivor to report, and with support often instrumentalized in relation to criminal justice objectives. However, criminal justice proceedings can intensify or create further trauma for sexual violence survivors. Furthermore, in addition to criminalizing the violent body and supporting the victimized one, there is a need for policy to produce alternative types of bodies through preventative interventions. Much sexual violence is situated within (hetero) sexual dynamics constructing a masculine aggressor and a feminine body which eventually yields. Prevention must therefore focus on developing embodied boundaries, and narratives at the margins of policy could underpin such efforts

Phosphorylation: The Molecular Switch of Double-Strand Break Repair

Repair of double-stranded breaks (DSBs) is vital to maintaining genomic stability. In mammalian cells, DSBs are resolved in one of the following complex repair pathways: nonhomologous end-joining (NHEJ), homologous recombination (HR), or the inclusive DNA damage response (DDR). These repair pathways rely on factors that utilize reversible phosphorylation of proteins as molecular switches to regulate DNA repair. Many of these molecular switches overlap and play key roles in multiple pathways. For example, the NHEJ pathway and the DDR both utilize DNA-PK phosphorylation, whereas the HR pathway mediates repair with phosphorylation of RPA2, BRCA1, and BRCA2. Also, the DDR pathway utilizes the kinases ATM and ATR, as well as the phosphorylation of H2AX and MDC1. Together, these molecular switches regulate repair of DSBs by aiding in DSB recognition, pathway initiation, recruitment of repair factors, and the maintenance of repair mechanisms

Linguistic incompetence: giving an account of researching multilingually

This paper considers the place of linguistic competence and incompetence in the context of researching multilingually. It offers a critique of the concept of competence and explores the performative dimensions of multilingual research and its narration, through the philosophy of Judith Butler, and in particular her study Giving an account of oneself. It explores aspects of risk, justice, narrative limit and a morality of multilingualism in emergent multilingual research frameworks. These theoretical dimensions are explored through consideration of ‘linguistically incompetent’ ethnographic work with refugees and asylum seekers, in contexts of hospitality and in life long learning research in the Gaza Strip, and of early attempts to learn new languages. The paper offers a prospect of a relational approach to researching multilingually and affirms the vulnerability at the heart of linguistic hospitality

'Lad culture' in higher education: agency in the sexualisation debates

This paper reports on research funded by the National Union of Students, which explored women students’ experiences of ‘lad culture’ through focus groups and interviews. We found that although laddism is only one of various potential masculinities, for our participants it dominated social and sexual spheres of university life in problematic ways. However, their objections to laddish behaviours did not support contemporary models of ‘sexual panic’, even while oppugning the more simplistic celebrations of young women’s empowerment which have been observed in debates about sexualisation. We argue that in their ability to reject ‘lad culture’, our respondents expressed a form of agency which is often invisibilised in sexualisation discussions and which could be harnessed to tackle some of the issues we uncovered

Fourth ventricle tumors in children: complications and influence of surgical approach

OBJECTIVES: The goal of this study was to characterize the complications and morbidity related to the surgical management of pediatric fourth ventricle tumors. / METHODS: All patients referred to the authors’ institution with posterior fossa tumors from 2002 to 2018 inclusive were screened to include only true fourth ventricle tumors. Preoperative imaging and clinical notes were reviewed to extract data on presenting symptoms; surgical episodes, techniques, and adjuncts; tumor histology; and postoperative complications. / RESULTS: Three hundred fifty-four children with posterior fossa tumors were treated during the study period; of these, 185 tumors were in the fourth ventricle, and 167 fourth ventricle tumors with full data sets were included in this analysis. One hundred patients were male (mean age ± SD, 5.98 ± 4.12 years). The most common presenting symptom was vomiting (63.5%). The most common tumor types, in order, were medulloblastoma (94 cases) > pilocytic astrocytoma (30 cases) > ependymoma (30 cases) > choroid plexus neoplasms (5 cases) > atypical teratoid/rhabdoid tumor (4 cases), with 4 miscellaneous lesions. Of the 67.1% of patients who presented with hydrocephalus, 45.5% had an external ventricular drain inserted (66.7% of these prior to tumor surgery, 56.9% frontal); these patients were more likely to undergo ventriculoperitoneal shunt (VPS) placement at a later date (p = 0.00673). Twenty-two had an endoscopic third ventriculostomy, of whom 8 later underwent VPS placement. Overall, 19.7% of patients had a VPS sited during treatment. Across the whole series, the transvermian approach was more frequent than the telovelar approach (64.1% vs 33.0%); however, the telovelar approach was significantly more common in the latter half of the series (p < 0.001). Gross-total resection was achieved in 70.7%. The most common postoperative deficit was cerebellar mutism syndrome (CMS; 28.7%), followed by new weakness (24.0%), cranial neuropathy (18.0%), and new gait abnormality/ataxia (12.6%). Use of intraoperative ultrasonography significantly reduced the incidence of CMS (p = 0.0365). There was no significant difference in the rate of CMS between telovelar or transvermian approaches (p = 0.745), and multivariate logistic regression modeling did not reveal any statistically significant relationships between CMS and surgical approach. / CONCLUSIONS: Surgical management of pediatric fourth ventricle tumors continues to evolve, and resection is increasingly performed through the telovelar route. CMS is enduringly the major postoperative complication in this patient population

Preliminary archaeoentomological analyses of permafrost-preserved cultural layers from the pre-contact Yup’ik Eskimo site of Nunalleq, Alaska : implications, potential and methodological considerations

Acknowledgements Site excavation and samples collection were conducted by archaeologists from the University of Aberdeen, with the help of archaeologists and student excavators from the University of Aberdeen University of Alaska Fairbanks and Bryn Mawr College, Kuskokwim Campus, College of Rural Alaska and residents of Quinhagak and Mekoryuk. This study is funded through AHRC grant to the project ‘Understanding Cultural Resilience and Climate Change on the Bering Sea through Yup’ik Ecological Knowledge, Lifeways, Learning and Archaeology’ to Rick Knecht, Kate Britton and Charlotta Hillderal (University of Aberdeen; AH/K006029/1). Thanks are due to Qanirtuuq Inc. and Quinhagak, Alaska for sampling permissions and to entomologists working at the CNC in Ottawa for allowing access to reference collections of beetles, lice and fleas. Yves Bousquet, Ales Smetana and Anthony E. Davies are specially acknowledged for their help with the identification of coleopteran specimens. Finally, we would also like to thank Scott Elias for useful comments on the original manuscript.Peer reviewedPublisher PD

Increased strontium uptake in trabecular bone of ovariectomized calcium-deficient rats treated with strontium ranelate or strontium chloride

Based on clinical trials showing the efficacy to reduce vertebral and non-vertebral fractures, strontium ranelate (SrR) has been approved in several countries for the treatment of postmenopausal osteoporosis. Hence, it is of special clinical interest to elucidate how the Sr uptake is influenced by dietary Ca deficiency as well as by the formula of Sr administration, SrR versus strontium chloride (SrCl2). Three-month-old ovariectomized rats were treated for 90 days with doses of 25 mg kg-1 d-1 and 150 mg kg-1 d-1 of SrR or SrCl2 at low (0.1% Ca) or normal (1.19% Ca) Ca diet. Vertebral bone tissue was analysed by confocal synchrotron-radiation-induced micro X-ray fluorescence and by backscattered electron imaging. Principal component analysis and k-means clustering of the acquired elemental maps of Ca and Sr revealed that the newly formed bone exhibited the highest Sr fractions and that low Ca diet increased the Sr uptake by a factor of three to four. Furthermore, Sr uptake in bone of the SrCl2-treated animals was generally lower compared with SrR. The study clearly shows that inadequate nutritional calcium intake significantly increases uptake of Sr in serum as well as in trabecular bone matrix. This indicates that nutritional calcium intake as well as serum Ca levels are important regulators of any Sr treatment