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

Saturation of absorption in p

A time-resolved measurement on the recovery of saturation in p-Ge was performed with picosecond CO{sub 2} laser pulses. It was directly confirmed that the relaxation of hole excitation in p-Ge was faster than 40 psec and that this type of measurement can provide additional temporal information on picosecond pulses

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

Dynamic tissue analysis using time- and wavelength-resolved fluorescence spectroscopy for atherosclerosis diagnosis

Simultaneous time- and wavelength-resolved fluorescence spectroscopy (STWRFS) was developed and tested for the dynamic characterization of atherosclerotic tissue ex vivo and arterial vessels in vivo. Autofluorescence, induced by a 337 nm, 700 ps pulsed laser, was split to three wavelength sub-bands using dichroic filters, with each sub-band coupled into a different length of optical fiber for temporal separation. STWRFS allows for fast recording/analysis (few microseconds) of time-resolved fluorescence emission in these sub-bands and rapid scanning. Distinct compositions of excised human atherosclerotic aorta were clearly discriminated over scanning lengths of several centimeters based on fluorescence lifetime and the intensity ratio between 390 and 452 nm. Operation of STWRFS blood flow was further validated in pig femoral arteries in vivo using a single-fiber probe integrated with an ultrasound imaging catheter. Current results demonstrate the potential of STWRFS as a tool for real-time optical characterization of arterial tissue composition and for atherosclerosis research and diagnosis

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

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

Effects of Risedronate in Runx2 Overexpressing Mice, an Animal Model for Evaluation of Treatment Effects on Bone Quality and Fractures

Young mice overexpressing Runx2 specifically in cells of the osteoblastic lineage failed to gain bone mass and exhibited a dramatic increase in bone resorption, leading to severe osteopenia and spontaneous vertebral fractures. The objective of the current study was to determine whether treatment with a bisphosphonate (risedronate, Ris), which reduces fractures in postmenopausal as well as in juvenile osteoporosis, was able to improve bone quality and reduce vertebral fractures in mice overexpressing Runx2. Four-week-old female Runx2 mice received Ris at 2 and 10 μg/kg subcutaneously twice a week for 12 weeks. Runx2 and wild-type mice received vehicle (Veh) as control. We measured the number of new fractures by X-ray and bone mineral density (BMD) by DEXA. We evaluated bone quality by histomorphometry, micro-CT, and Fourier transform infrared imaging (FTIRI). Ris at 20 μg/kg weekly significantly reduced the average number of new vertebral fractures compared to controls. This was accompanied by significantly increased BMD, increased trabecular bone volume, and reduced bone remodeling (seen in indices of bone resorption and formation) in the vertebrae and femoral metaphysis compared to Runx2 Veh. At the femur, Ris also increased cortical thickness. Changes in collagen cross-linking seen on FTIRI confirmed that Runx2 mice have accelerated bone turnover and showed that Ris affects the collagen cross-link ratio at both forming and resorbing sites. In conclusion, young mice overexpressing Runx2 have high bone turnover-induced osteopenia and spontaneous fractures. Ris at 20 μg/kg weekly induced an increase in bone mass, changes in bone microarchitecture, and decreased vertebral fractures

Time on a Rotating Platform

Traditional clock synchronisation on a rotating platform is shown to be incompatible with the experimentally established transformation of time. The latter transformation leads directly to solve this problem through noninvariant one-way speed of light. The conventionality of some features of relativity theory allows full compatibility with existing experimental evidence.Comment: 12 pages, Latex, no figure. Copies available at [email protected] accepted for publication in Found. Phys. Let