Some Remarks on IBNR Evaluation Techniques

In this short paper we discuss a new methodology for estimating reserves for IBNR (incurred but not reported) claims.

The Next Generation of Orthotopic Thyroid Cancer Models: Immunocompetent Orthotopic Mouse Models of BRAF

Background: While the development of new treatments for aggressive thyroid cancer has advanced in the last 10 years, progress has trailed headways made with other malignancies. A lack of reliable authenticated human cell lines and reproducible animal models is one major roadblock to preclinical testing of novel therapeutics. Existing xenograft and orthotopic mouse models of aggressive thyroid cancer rely on the implantation of highly passaged human thyroid carcinoma lines in immunodeficient mice. Genetically engineered models of papillary and undifferentiated (anaplastic) thyroid carcinoma (PTC and ATC) are immunocompetent; however, slow and stochastic tumor development hinders high-throughput testing. Novel models of PTC and ATC in which tumors arise rapidly and synchronously in immunocompetent mice would facilitate the investigation of novel therapeutics and approaches. Methods: We characterized and utilized mouse cell lines derived from PTC and ATC tumors arising in genetically engineered mice with thyroid-specific expression of endogenous BrafV600E/WTand deletion of either Trp53 (p53) or Pten. These murine thyroid cancer cells were transduced with luciferase- and GFP-expressing lentivirus and implanted into the thyroid glands of immunocompetent syngeneic B6129SF1/J mice in which the growth characteristics were assessed. Results: Large locally aggressive thyroid tumors form within one week of implantation. Tumors recapitulate their histologic subtype, including well-differentiated PTC and ATC, and exhibit CD3+, CD8+, B220+, and CD163+ immune cell infiltration. Tumor progression can be followed in vivo using luciferase and ex vivo using GFP. Metastatic spread is not detected at early time points. Conclusions: We describe the development of the next generation of murine orthotopic thyroid cancer models. The implantation of genetically defined murine BRAF-mutated PTC and ATC cell lines into syngeneic mice results in rapid and synchronous tumor formation. This model allows for preclinical investigation of novel therapeutics and/or therapeutic combinations in the context of a functional immune system

Some remarks on IBNR Evaluation Techniques

In this short note we give some comments and general remarks on the methodology of IBNR computations, as presented at the workshop on IBNR computations at the 2000 ASTIN Meeting, Porto Cervo, Sardinia

Some remarks on IBNR evaluation techniques

status: publishe

An Open-Label Study of Risperidone in the Improvement of Quality of Life and Treatment of Symptoms of Violent and Self-Injurious Behaviour in Adults with Intellectual Disability

Background We examined the benefits of risperidone, including quality of life (QoL), in the treatment of violent and self-injurious behaviour in adults with moderate, severe or profound intellectual disability. Methods Twenty-four participants received open-label, oral, flexible-dose risperidone of 0.5–6 mg/day for 12 weeks. Efficacy was measured primarily using the Aberrant Behaviour Checklist (ABC) and secondarily using validated measures of depression, autism, QoL and global condition. Safety and tolerability were also assessed. Results Total ABC significantly improved from baseline by week 1. This improvement was maintained throughout the study (final visit, P < 0.001). Secondary efficacy measures were also improved with risperidone, including QoL measures (final visit: home life, P < 0.001; activity, P = 0.002; skills, P = 0.014). Risperidone was generally well tolerated, with no unexpected adverse events. Conclusions In this open-label trial, risperidone was efficacious and well tolerated for managing violent and self-injurious behaviour and improving QoL in adults with moderate, severe or profound intellectual disabilit