Therapeutic approach in glioblastoma multiforme with primitive neuroectodermal tumor components: case report and review of the literature

Glioblastoma multiforme (GBM) is the most common and aggressive malignant glioma that is treated with first-line therapy, using surgical resection followed by local radiotherapy and concomitant/adjuvant temozolomide (TMZ) treatment. GBM is characterised by a high local recurrence rate and a low response to therapy. Primitive neuroectodermal tumour (PNET) of the brain revealed a low local recurrence rate; however, it also exhibited a high risk of cerebrospinal fluid (CSF) dissemination. PNET is treated with surgery followed by craniospinal irradiation (CSI) and platinum-based chemotherapy in order to prevent CSF dissemination. GBM with PNET-like components (GBM/PNET) is an emerging variant of GBM, characterised by a PNET-like clinical behaviour with an increased risk of CSF dissemination; it also may benefit from platinum-based chemotherapy upfront or following failure of GBM therapy. The results presented regarding the management of GBM/PNET are based on case reports or case series, so a standard therapeutic approach for GBM/PNET is not defined, constituing a challenging diagnostic and therapeutic dilemma. In this report, a case of a recurrent GBM/PNET treated with surgical resection and radiochemotherapy as Stupp protocol, and successive platinum-based chemotherapy due to the development of leptomeningeal dissemintation and an extracranial metastasis, is discussed. A review of the main papers regarding this rare GBM variant and its therapeutic approach are also reported. In conclusion, GBM/PNET should be treated with a multimodal approach including surgery, chemoradiotherapy, and/or the early introduction of CSI and platinum-based chemotherapy upfront or at recurrence

Predicting the effects of climate change on water yield and forest production in the northeastern United States

Rapid and simultaneous changes in temperature, precipitation and the atmospheric concentration of CO2 are predicted to occur over the next century. Simple, well-validated models of ecosystem function are required to predict the effects of these changes. This paper describes an improved version of a forest carbon and water balance model (PnET-II) and the application of the model to predict stand- and regional-level effects of changes in temperature, precipitation and atmospheric CO2 concentration. PnET-II is a simple, generalized, monthly time-step model of water and carbon balances (gross and net) driven by nitrogen availability as expressed through foliar N concentration. Improvements from the original model include a complete carbon balance and improvements in the prediction of canopy phenology, as well as in the computation of canopy structure and photosynthesis. The model was parameterized and run for 4 forest/site combinations and validated against available data for water yield, gross and net carbon exchange and biomass production. The validation exercise suggests that the determination of actual water availability to stands and the occurrence or non-occurrence of soil-based water stress are critical to accurate modeling of forest net primary production (NPP) and net ecosystem production (NEP). The model was then run for the entire NewEngland/New York (USA) region using a 1 km resolution geographic information system. Predicted long-term NEP ranged from -85 to +275 g C m-2 yr-1 for the 4 forest/site combinations, and from -150 to 350 g C m-2 yr-1 for the region, with a regional average of 76 g C m-2 yr-1. A combination of increased temperature (+6*C), decreased precipitation (-15%) and increased water use efficiency (2x, due to doubling of CO2) resulted generally in increases in NPP and decreases in water yield over the region

The photosynthesis-foliar nitrogen relationship in deciduous and evergreen forests in New Hampshire

Biomass production in forests is a key process in the global carbon (C) cycle that is strongly linked to photosynthesis and related leaf traits. Spatially, relationships among leaf traits can vary as a function of climate, soils and species composition. As modeling approaches to estimate C gain improve, the need to understand variability in leaf traits becomes increasingly important. Here, we characterized the relationship between photosynthetic capacity (Amax), foliar nitrogen and leaf mass per area (LMA) within and across species in northern hardwood and evergreen stands of the White Mountain National Forest in New Hampshire, a region that has been underrepresented in past leaf trait studies. Results were used to parameterize a forest ecosystem model (PnET) that has been widely used in the Northeast region to predict ecosystem C fluxes. Within all species, Amax was strongly and positively related to mass-based foliar percent nitrogen (%N). The observed relationship between foliar %N and Amax differed significantly from the previously used model parameterization that was based on leaf trait data from forest stands in Wisconsin, and was largely a function of differences in leaf mass per area. Using site-specific foliar %N and LMA to estimate Amax in PnET improved the estimation of GPP by 5.5% in comparison with GPP estimates derived from an eddy covariance tower

Treatment options for PNET liver metastases. a systematic review

Pancreatic neuroendocrine tumors (PNETs) are rare pancreatic neoplasms. About 40-80% of patients with PNET are metastatic at presentation, usually involving the liver (40-93%). Liver metastasis represents the most significant prognostic factor. The aim of this study is to present an up-to-date review of treatment options for patients with liver metastases from PNETs

Molecular pathogenesis and targeted therapy of sporadic pancreatic neuroendocrine tumors

Over the past few years, knowledge regarding the molecular pathology of sporadic pancreatic neuroendocrine tumors (PNETs) has increased substantially, and a number of targeted agents have been tested in clinical trials in this tumor type. For some of these agents there is a strong biological rationale. Among them, the mammalian target of rapamycin inhibitor Everolimus and the antiangiogenic agent Sunitinib have both been approved for the treatment of PNETs. However, there is lack of knowledge regarding biomarkers able to predict their efficacy, and mechanisms of resistance. Other angiogenesis inhibitors, such as Pazopanib, inhibitors of Src, Hedgehog or of PI3K might all be useful in association or sequence with approved agents. On the other hand, the clinical significance, and potential for treatment of the most common mutations occurring in sporadic PNETs, in the MEN-1 gene and in ATRX and DAXX, remains uncertain. The present paper reviews the main molecular changes occurring in PNETs and how they might be linked with treatment options

A mechanized proof of loop freedom of the (untimed) AODV routing protocol

The Ad hoc On-demand Distance Vector (AODV) routing protocol allows the nodes in a Mobile Ad hoc Network (MANET) or a Wireless Mesh Network (WMN) to know where to forward data packets. Such a protocol is 'loop free' if it never leads to routing decisions that forward packets in circles. This paper describes the mechanization of an existing pen-and-paper proof of loop freedom of AODV in the interactive theorem prover Isabelle/HOL. The mechanization relies on a novel compositional approach for lifting invariants to networks of nodes. We exploit the mechanization to analyse several improvements of AODV and show that Isabelle/HOL can re-establish most proof obligations automatically and identify exactly the steps that are no longer valid.Comment: The Isabelle/HOL source files, and a full proof document, are available in the Archive of Formal Proofs, at http://afp.sourceforge.net/entries/AODV.shtm

Calibration and validation of a combustion-cogeneration

This paper describes the calibration and validation of a combustion cogeneration model for whole-building simulation. As part of IEA Annex 42, we proposed a combustion cogeneration model for studying residentialscale cogeneration systems based on both Stirling and internal combustion engines. We implemented this model independently in the EnergyPlus, ESP-r and TRNSYS building simulation programs, and undertook a comprehensive effort to validate the model's predictions. Using established comparative testing and empirical validation principles, we vetted the model's theoretical basis and its software implementations. The results demonstrate acceptable-to-excellent agreement, and suggest the calibrated model can be used with confidence