Temperature-dependent Characterization of Power Amplifiers Using an Efficient Electrothermal Analysis Technique

In this paper, we propose an efficient methodology for the electrothermal characterization of power amplifier (PA) integrated circuits. The proposed electrothermal analysis method predicts the effect of temperature variations on the key performances of PAs, such as gain and linearity, under realistic dynamic operating conditions. A comprehensive technique for identifying an equivalent compact thermal model, using data from 3-D finite element method thermal simulation and nonlinear curve fitting algorithms, is described. Two efficient methods for electrothermal analysis applying the developed compact thermal model are reported. The validity of the methods is evaluated using commercially available electrothermal computer-aided design (CAD) tools and through extensive pulsed RF signal measurements of a PA device under test. The measurement results confirm the validity of the proposed electrothermal analysis methods. The proposed methods show significantly faster simulation speed comparing to available CAD tools for electrothermal analysis. Moreover, the results reveal the importance of electrothermal characterization in the prediction of the temperature-aware PA dynamic operation

A telegeriatric service in a small rural hospital: A case study and cost analysis

Introduction Small hospitals in rural areas usually have an insufficient caseload of frail old people to justify the regular presence of a geriatrician. This study examined the costs of providing a telegeriatric service by videoconference in a rural hospital, compared to the costs of a visiting geriatrician that travels to undertake in-person consultations. Methods A cost analysis was undertaken to compare the costs of the telegeriatric service model with the costs of a visiting geriatrician service model. A recently established telegeriatric service at Warwick Hospital was used as a case study. Results In the base case model (assuming four patients per round and a round-trip travel distance of 312 kilometres), an estimated AUD$131 per patient consultation can be saved in favour of the telegeriatric service model. Key drivers of costs are the number of patients per round and the travel distance and time in the visiting geriatrician model. At a workload of four patients per round, it is less expensive to conduct a telegeriatric service than a visiting geriatrician service when the round-trip travel time exceeds 76 minutes. Discussion Even under quite conservative assumptions, a telegeriatric service offers an economically feasible approach to the delivery of specialist geriatric assessment in rural and remote settings

Sarcoma treatment in the era of molecular medicine

Sarcomas are heterogeneous and clinically challenging soft tissue and bone cancers. Although constituting only 1% of all human malignancies, sarcomas represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. More than 100 histological subtypes have been characterized to date, and many more are being discovered due to molecular profiling. Owing to their mostly aggressive biological behavior, relative rarity, and occurrence at virtually every anatomical site, many sarcoma subtypes are in particular difficult-to-treat categories. Current multimodal treatment concepts combine surgery, polychemotherapy (with/without local hyperthermia), irradiation, immunotherapy, and/or targeted therapeutics. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the latest advances in the molecular biology of sarcomas and their effects on clinical oncology; it is meant for a broad readership ranging from novices to experts in the field of sarcoma.Peer reviewe

Sarcoma classification by DNA methylation profiling

Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate. Here, we demonstrate classification of soft tissue and bone tumours using a machine learning classifier algorithm based on array-generated DNA methylation data. This sarcoma classifier is trained using a dataset of 1077 methylation profiles from comprehensively pre-characterized cases comprising 62 tumour methylation classes constituting a broad range of soft tissue and bone sarcoma subtypes across the entire age spectrum. The performance is validated in a cohort of 428 sarcomatous tumours, of which 322 cases were classified by the sarcoma classifier. Our results demonstrate the potential of the DNA methylation-based sarcoma classification for research and future diagnostic applications

Non-cytotoxic systemic treatment in malignant peripheral nerve sheath tumors (MPNST): A systematic review from bench to bedside

Contains fulltext : 204282.pdf (publisher's version ) (Open Access)BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas. Once metastasized, prognosis is poor despite regular treatment with conventional cytotoxic drugs. This study reviews the preclinical and clinical results of non-cytotoxic systemic therapy in MPNST. METHODS: A systematic search was performed in PubMed and Embase databases according to the PRISMA guidelines. Search terms related to 'MPNST', 'targeted therapy', 'immunotherapy', and 'viral therapy' were used. Only in vivo studies and clinical trials were included. Clinicaltrials.gov was also searched for any ongoing trials including MPNST patients. Qualitative synthesis was performed on all studies stratifying per target: membrane, cytoplasmic, nuclear, immunotherapy and oncolytic viruses, and other. In vivo studies were assessed for treatment effect on tumor growth (low/intermediate/high), survival, and metastases. Clinical trials were assessed on response rate, progression-free survival, and overall survival. RESULTS: After full-text screening, 60 in vivo studies and 19 clinical trials were included. A total of 13 trials are ongoing and unpublished. The included trials displayed relatively poor response rates thus far, with patients achieving stable disease at best. Inhibiting cytoplasmic targets most commonly yielded high treatment effect, predominantly after mTOR inhibition. Oncolytic viruses and angiogenesis inhibition also demonstrate intermediate to high effect. Therapies including a combination of drugs were most effective in controlling tumor growth. Several ongoing trials investigate potentially promising pathways, while others have yet to be established. CONCLUSION: Targeting the PI3K/Akt/mTOR pathway seems most promising in the treatment of MPNSTs. Oncolytic viruses and angiogenesis inhibition represent emerging therapies that require further study. Combinations of targeted therapies are most likely key to maximize treatment effect

Non-cytotoxic systemic treatment in malignant peripheral nerve sheath tumors (MPNST) : A systematic review from bench to bedside

Background: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas. Once metastasized, prognosis is poor despite regular treatment with conventional cytotoxic drugs. This study reviews the preclinical and clinical results of non-cytotoxic systemic therapy in MPNST. Methods: A systematic search was performed in PubMed and Embase databases according to the PRISMA guidelines. Search terms related to ‘MPNST’, ‘targeted therapy’, ‘immunotherapy’, and ‘viral therapy’ were used. Only in vivo studies and clinical trials were included. Clinicaltrials.gov was also searched for any ongoing trials including MPNST patients. Qualitative synthesis was performed on all studies stratifying per target: membrane, cytoplasmic, nuclear, immunotherapy and oncolytic viruses, and other. In vivo studies were assessed for treatment effect on tumor growth (low/intermediate/high), survival, and metastases. Clinical trials were assessed on response rate, progression-free survival, and overall survival. Results: After full-text screening, 60 in vivo studies and 19 clinical trials were included. A total of 13 trials are ongoing and unpublished. The included trials displayed relatively poor response rates thus far, with patients achieving stable disease at best. Inhibiting cytoplasmic targets most commonly yielded high treatment effect, predominantly after mTOR inhibition. Oncolytic viruses and angiogenesis inhibition also demonstrate intermediate to high effect. Therapies including a combination of drugs were most effective in controlling tumor growth. Several ongoing trials investigate potentially promising pathways, while others have yet to be established. Conclusion: Targeting the PI3K/Akt/mTOR pathway seems most promising in the treatment of MPNSTs. Oncolytic viruses and angiogenesis inhibition represent emerging therapies that require further study. Combinations of targeted therapies are most likely key to maximize treatment effect

Prognostic and therapeutic relevance of the IGF pathway in Ewing's sarcoma patients

Contains fulltext : 125804.pdf (publisher's version ) (Closed access)The optimal target and timing of drugs interfering with the insulin-like growth factor (IGF) signaling system in Ewing's sarcoma (ES) remain undetermined. We examined the expression of IGF signaling proteins in ES samples taken before and after chemotherapy, and speculate about the optimal way of treating ES patients in the future. Tumor material (36 initial biopsies and 24 resection specimens after neoadjuvant chemotherapy) and follow-up data of 41 patients treated for ES at the Radboud University Nijmegen Medical Centre were analyzed. Immunohistochemical staining was done for IGF1, IGF2, IGFBP3, IGF-1R, phosphorylated AKT (pAKT), phosphorylated mTOR (pmTOR), and phosphorylated ERK (pERK), and staining intensity was scored semiquantitatively. Change of protein expression during treatment, correlations of effector cascade signaling, and influence on progression-free (PFS) and overall survival (OS) were tested. All potential targets were widely expressed at both time points. After chemotherapy, pmTOR expression decreased significantly (p = 0.021) while IGFBP3 increased (p = 0.005). Correlations exist between IGF-1R and pERK (rho = 0.286, p = 0.031), IGF-1R and pAKT (rho = 0.269, p = 0.045), pAKT and pERK (rho = 0.460, p = 0.000), and pERK and pmTOR (rho = 0.273, p = 0.038). In therapy-naive samples, combined expression of pAKT, pmTOR, and pERK predicted worse PFS (median, 11 vs. 32 months; p = 0.039) and OS (median, 18 vs. 83 months; p = 0.023). We identify an unfavorable prognostic group of ES patients with widely activated IGF-effector cascades, demonstrate cooperation between the different downstream pathways, and show how expression of IGF-related proteins may change after exposure to chemotherapy. These findings should be taken into account when designing future trials with IGF-targeting agents. We suggest the prospective exploration of chemotherapy and multi-target tyrosine kinase inhibitors in the first-line setting