Novel dual single sided silicon strip detector chip for radiotherapy verification

A novel dual single sided silicon strip detector (SSSSD) chip was designed to meet clinical requirements in radiotherapy verification. An available design from Micron Semiconductor Ltd. (BB7, 500 µ m thick) was the base of a two-dimensional detector adapted into a special configuration with the aim of uniforming and minimizing foreing materials around the active area (64 × 64 mm2). With this purpose, two independent BB7 SSSSDs were mounted in a perpendicular configuration, separated by a 500 µ m kapton dielectric film with the same dimensions as the silicon wafers, thus minimizing air gaps in between. This new configuration, called the dual SSSSD chip design, was mounted on kapton printed circuit board (PCB). Both silicon wafers were divided into 32 strips, 2 mm width each. The aim of developing this detector was to allow 2D dose measurements, improve spatial resolution and perform radiotherapy treatment verification faster than with a previous prototype. Characteristics and performance of the novel detector are presented

Radia2: A New Tool for Radiotherapy Verification

Radiotherapy is nowadays a proven technique in cancer treatments. Within the evolution of radiotherapy treatments towards more complex techniques, the need of new dosimetric methods for treatment verifications has appeared. In order to reach an improved dosimetric method, a collaboration was started to transfer knowledge from nuclear reaction instrumentation to medical applications, involving several departments from the University of Seville, Centro Nacional de Aceleradores (CNA), the Hospital Universitario Virgen Macarena and the company Inabensa. The first prototype, patent pending [2], gave very promising results. Currently, a critical review is being carried out to create an improved system

Cutaneous skeletal hypophosphatemia syndrome: clinical spectrum, natural history, and treatment

© 2016, International Osteoporosis Foundation and National Osteoporosis Foundation. Summary: Cutaneous skeletal hypophosphatemia syndrome (CSHS), caused by somatic RAS mutations, features excess fibroblast growth factor-23 (FGF23) and skeletal dysplasia. Records from 56 individuals were reviewed and demonstrated fractures, scoliosis, and non-congenital hypophosphatemia that in some cases were resolved. Phosphate and calcitriol, but not skin lesion removal, were effective at controlling hypophosphatemia. No skeletal malignancies were found. Purpose: CSHS is a disorder defined by the association of epidermal and/or melanocytic nevi, a mosaic skeletal dysplasia, and an FGF23-mediated hypophosphatemia. To date, somatic RAS mutations have been identified in all patients whose affected tissue has undergone DNA sequencing. However, the clinical spectrum and treatment are poorly defined in CSHS. The purpose of this study is to determine the spectrum of the phenotype, natural history of the disease, and response to treatment of hypophosphatemia. Methods: Five CSHS subjects underwent prospective data collection at clinical research centers. A review of the literature identified 45 reports that included a total of 51 additional patients, in whom the findings were compatible with CSHS. Data on nevi subtypes, bone histology, mineral and skeletal disorders, abnormalities in other tissues, and response to treatment of hypophosphatemia were analyzed. Results: Fractures, limb deformities, and scoliosis affected most CSHS subjects. Hypophosphatemia was not present at birth. Histology revealed severe osteomalacia but no other abnormalities. Skeletal dysplasia was reported in all anatomical compartments, though less frequently in the spine; there was no clear correlation between the location of nevi and the skeletal lesions. Phosphate and calcitriol supplementation was the most effective therapy for rickets. Convincing data that nevi removal improved blood phosphate levels was lacking. An age-dependent improvement in mineral abnormalities was observed. A spectrum of extra-osseous/extra-cutaneous manifestations that included both benign and malignant neoplasms was present in many subjects, though osteosarcoma remains unreported. Conclusion: An understanding of the spectrum, natural history, and efficacy of treatment of hypophosphatemia in CSHS may improve the care of these patients

Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia

Pathologically elevated serum levels of fibroblast growth factor-23 (FGF23), a bone-derived hormone that regulates phosphorus homeostasis, result in renal phosphate wasting and lead to rickets or osteomalacia. Rarely, elevated serum FGF23 levels are found in association with mosaic cutaneous disorders that affect large proportions of the skin and appear in patterns corresponding to the migration of ectodermal progenitors. The cause and source of elevated serum FGF23 is unknown. In those conditions, such as epidermal and large congenital melanocytic nevi, skin lesions are variably associated with other abnormalities in the eye, brain and vasculature. The wide distribution of involved tissues and the appearance of multiple segmental skin and bone lesions suggest that these conditions result from early embryonic somatic mutations. We report five such cases with elevated serum FGF23 and bone lesions, four with large epidermal nevi and one with a giant congenital melanocytic nevus. Exome sequencing of blood and affected skin tissue identified somatic activating mutations of HRAS or NRAS in each case without recurrent secondary mutation, and we further found that the same mutation is present in dysplastic bone. Our finding of somatic activating RAS mutation in bone, the endogenous source of FGF23, provides the first evidence that elevated serum FGF23 levels, hypophosphatemia and osteomalacia are associated with pathologic Ras activation and may provide insight in the heretofore limited understanding of the regulation of FGF23