Prognosis of localised gastrointestinal stromal tumour (GIST) is heterogeneous, notably for patients with AFIP intermediate or high risk of relapse, who are candidates to adjuvant imatinib. We ...hypothesised that gene expression profiles might improve the prognostication and help to refine the indications for imatinib.
We collected gene expression and histoclinical data of 146 pre-treatment localised GIST samples treated with surgery alone. We searched for a gene expression signature (GES) predictive for relapse-free survival (RFS) and compared its performances to that of three published prognostic proliferation-based GES (Genomic Grade Index (GGI), 16-Kinase, and CINSARC) and AFIP classification. We also analysed a data set from 28 patients with advanced GIST treated with neo-adjuvant imatinib.
We identified a 275-gene GES (gene expression signature) predictive of RFS in a learning set and validated its robustness in an independent set. However, the GGI outperformed its prognostic performances, and those of the two other signatures and the AFIP intermediate-risk classification in two independent tests sets in uni- and multivariate analyses. Importantly, GGI could split the AFIP intermediate/high-risk samples into two groups with different RFS. Genomic Grade Index 'high-risk' tumours were more proliferative and genetically unstable than 'low-risk' tumours, and more sensitive to imatinib.
GGI refines the prediction of RFS in localised GIST and might help tailor adjuvant imatinib.
This paper compares different operating strategies for small scale (100 kWe) combined heat and power (CHP) plants fired by natural gas and solid biomass to serve a residential energy demand. The ...focus is on a dual fuel micro gas turbine (MGT) cycle. Various biomass/natural gas energy input ratios are modelled, in order to assess the trade-offs between: (i) lower energy conversion efficiency and higher investment cost when increasing the biomass input rate; (ii) higher primary energy savings and revenues from feed-in tariff available for biomass electricity fed into the grid. The strategies of baseload (BL), heat driven (HD) and electricity driven (ED) plant operation are compared, for an aggregate of residential end-users in cold, average and mild climate conditions. On the basis of the results from thermodynamic assessment and simulation at partial load operation, CAPEX and OPEX estimates, and Italian energy policy scenario (incentives available for biomass electricity, on-site and high efficiency CHP), the maximum global energy efficiency, primary energy savings and investment profitability is found, as a function of biomass/natural gas ratio, plant operating strategy and energy demand typology. The thermal and electric conversion efficiency ranged respectively between 46 and 38% and 30 and 19% for the natural gas and biomass fired case studies. The IRR of the investment was highly influenced by the load/CHP thermal power ratio and by the operation mode. The availability of high heat demand levels was also a key factor, to avoid wasted cogenerated heat and maximize CHP sales revenues. BL operation presented the highest profitability because of the higher revenues from electricity sales. Climate area was another important factor, mainly in case of low load/CHP ratios. Moreover, at low load/CHP power ratio and for the BL operation mode, the dual fuel option presented the highest profitability. This is due to the lower cost of biomass fuel in comparison to natural gas and the high subsidies available for biomass electricity by feed-in tariffs. The results show that dual fuel MT can be an interesting option to increase efficiencies, flexibility and plant reliability at low cost in comparison to only biomass systems, facilitating an integration of renewable and fossil fuel systems.
•A natural gas/biomass fired 100 kWe microturbine serving residential energy demand is investigated.•Energy efficiency, capex, opex and electricity revenues trade-offs are assessed.•Various CHP plant operating strategies are compared.•The optimal biomass energy input is 70% of total CHP consumption.•The heat driven operation is the most profitable operation mode in the Italian energy framework.
Patients treated with platinum compounds are subject to hypersensitivity reactions. Our study has highlighted the reactions related to oxaliplatin (OHP) infusion. One hundred and twenty-four patients ...affected by advanced colorectal cancer were treated with different schedules containing OHP, at the Institute of Haematology and Medical Oncology 'L. and A. Seragnoli' of Bologna and at the Medical Oncology Division of Livorno Hospital. Seventeen patients (13%) showed hypersensitivity reactions after a few minutes from the start of the OHP infusion. Usually, these reactions were seen after 2-17 exposures to OHP (Mean+/-s.e.: 9.4+/-1.07). No patient experienced allergic reactions at his/her first OHP infusion. Eight patients developed a mild reaction consisting of flushing and swelling of the face and hands, itching, sweating and lachrymation. The remaining nine patients showed a moderate-severe reaction with dyspnoea, wheezing, laryngospasm, psycho-motor agitation, tachycardia, precordial pain, diffuse erythema, itching and sweating. Six patients out of 17 were re-exposed to the drug with premedication of steroids and all except one developed the hypersensitivity reaction again. The cumulative dose, the time of exposure to OHP and the clinical features are variable and unpredictable. The risk of developing hypersensitivity reactions in patients treated with a short infusion of OHP cannot be underestimated.
At present no reports on gene expression profiling of liver metastases from colorectal cancer are available. We identified two different signatures using Affymetrix platform: epidermal growth factor ...receptor pathway was upregulated in metachronous lesions, whereas the pathway mainly related to angiogenesis was in synchronous lesions. Synchronous or metachronous liver metastases could be treated differently on the basis of different molecular pathways.
•A novel hybrid CSP/biomass combined cycle is modelled in Cycle-tempo.•Input data for costs and profitability assessment are taken from real pilot plants.•Thermal storage, collectors sizing and ...operational strategies are compared.•CSP integration increases efficiency but not investment profitability.
This paper focuses on the thermo-economic analysis of a 2.1-MWe and 960kWt hybrid solar-biomass combined heat and power (CHP) system composed of a 1.4-MWe Externally Fired Gas-Turbine (EFGT) and a 0.7-MWe bottoming Organic Rankine Cycle (ORC) power plant. The primary thermal energy input is provided by a hybrid Concentrating Solar Power (CSP) collector array covering a total ground area of 22,000–32,000m2, coupled to a biomass boiler. The CSP collector array is based on parabolic-trough concentrators (PTCs) with molten salts as the heat transfer fluid (HTF), upstream of a 4.5–9.1MWt fluidized-bed furnace for direct biomass combustion. In addition, two molten-salt tanks are considered that provide 4.8–18MWh (corresponding to 1.3–5.0h) of Thermal Energy Storage (TES), as a means of reducing the variations in the plant’s operating conditions, increasing the plant’s capacity factor and total operating hours (from 5500–6000 to 8000h per year). On the basis of the results of the thermodynamic simulations, upfront and operational costs assessments, and considering an Italian energy policy scenario (feed-in tariffs, or FiTs, for renewable electricity), the global energy conversion efficiency and investment profitability of this plant are estimated for different sizes of CSP and biomass furnaces, different operation strategies (baseload and modulating) and cogenerative vs. electricity-only system configurations. Upfront costs in the range 4.3–9.5MEur are reported, with operating costs in the range 1.5–2.3MEur annually. Levelized costs of energy from around 100Eur/MWh to above 220Eur/MWh are found, along with net present values (NPVs) from close to 13,000 to −3000kEur and internal rates of return (IRRs) from 30% down to almost zero when prioritizing electrical power generation (i.e., not in cogenerative mode). In all cases the economic viability of the systems deteriorate for larger CSP section sizes. The results indicate the low economic profitability of CSP integration in comparison to biomass-only plants, due to high investment costs of the former, which are not compensated by the higher global energy conversion efficiency and energy sales revenues.
The epidermal growth factor receptor (EGFr) is one of the most studied molecules as a target for cancer therapy. Over these last few years, several studies attempting to identify predictive ...biomarkers of treatment response, such as the receptor status or other molecules related to the downstream signalling pathway, have been conducted. However, from a clinical point of view, the information obtained from ex vivo analyses still has various limitations that may be overcome by the combination with molecular imaging technologies which may provide a noninvasive, global, in vivo evaluation of the molecular tumour background. The aim of this review is to report the preclinical results of all positron emission tomography (PET) tracers synthesized until now for in vivo detection of EGFr in cancer. Two classes of PET compounds have been developed: labelled small molecules such as tyrosine kinase inhibitors and labelled monoclonal antibodies. The in vitro and in vivo results of these PET tracers are very different depending on the chemical properties, positron emission radionuclide, or animal models. As a consequence, various critical questions are still open, and the implications of a translation in the clinical setting for EGFr imaging in cancer patients is discussed.
PurposeDespite the extensive research on post-disaster reconstruction projects (PDRP), there is a paucity of studies that examine critical challenges for the project practices in post-war-developing ...countries, particularly, Africa. The purpose of this research is to investigate the key project management challenges impacting the post-disaster reconstruction projects (PDRP) during the construction and planning stages in Angola, with an aim to fill the knowledge gap.Design/methodology/approachThe primary data was collected from 130 project management practitioners working with planning, provincial government organisations including consultants, and contractors within the Angolan public sectors organisations. Response data was subjected to descriptive statistics, mean scores, and inferential statistics (One sample t-tests) and Kendall's concordance.FindingsThe descriptive and empirical analysis demonstrated a disparity of the ranking of the 21challenges affecting the PDRP among the groups; with statistically significant differences amongst the 10 challenges. Based on the overall sample, 6 out of 10 critical challenges are between (24–25) levels of agreement close to the mean. The results of the mean score ranking indicate that “working with poor or restricted access to location”, “project culture that fits the needs of local people”; “improving the capacity of local government”, “minimizing the negative effects of local people” and “relocation issues by establishing property rights during the reconstruction project” were the five critical challenges to managing PDRP whereas “improving information and communication processes”, “securing adequate resources (material and machinery)”, “dealing with rising costs of materials and labour” were considered to be the least critical.Research limitations/implicationsThe study was restricted to one province and Country (out of 18) namely, Luanda, Angola. Therefore, the findings may not be generalized to public sector organisations operating in different countries with different contexts, political settings and disaster complexities.Practical implicationsThe establishment of challenges in PDRPs helps the key stakeholders by providing the foundation to project teams to address the challenges during planning and construction stages, and thus improving project delivery in the future. Understanding the uniqueness of PDRPs and interdependency of project management from the implementing organization is of particular value for the managers of future projects and other decision-makers, especially in the emerging countries. Moreover, the findings could be used to reflect on the need to formulate policies appropriate to post disaster environments, which among other issues could address building policies, which could include land ownership regulations and procedures together with property rights.Originality/valueThis study contributes to the body of knowledge on the subject within a previously unexplored post-war context with a focus on public organizations perspective. The study provides insights on the challenges affecting the post-disaster reconstruction across the Angolan public sector.
Purpose
Nowadays, no human neuroendocrine cell models derived from the neural crest are available. In this study, we present non-transformed long-term primary Neural Crest Cells (NCCs) isolated from ...the trunk region of the neural crest at VIII–XII gestational weeks of human foetuses obtained from voluntary legal abortion.
Methods and results
In NCC, quantitative real-time RT PCR demonstrated the expression of neural crest specifier genes, such as Snail1, Snail2/SLUG, Sox10, FoxD3, c-Myc, and p75NTR. Moreover, these cell populations expressed stemness markers (such as Nanog and nestin), as well as markers of motility and invasion (TAGLN, MMP9, CXCR4, and CXCR7), and of neuronal/glial differentiation (MAP2, GFAP, SYP, and TAU). Functional analysis demonstrated that these cells not only possessed high migration properties, but most importantly, they expressed markers of sympatho-adrenal lineage, such as ASCL1 and tyrosine hydroxylase (TH). Moreover, the expression of TH increased after the induction with two different protocols of differentiation towards neuronal and sympatho-adrenal phenotypes. Finally, exposure to conditioned culture media from NCC induced a mature phenotype in a neuronal cell model (namely SH-SY5Y), suggesting that NCC may also act like Schwann precursors.
Conclusion
This unique human cell model provides a solid tool for future studies addressing the bases of human neural crest-derived neuroendocrine tumours.
Background
Adrenal lipid-poor adenomas (LPA) are defined by high unenhanced density (≥ 10 HU), and absolute and relative contrast medium washout > 60% and > 40%, respectively, at computerized ...tomography (CT). To date, no thorough histopathological characterization has been performed in those frequent lesions (one-third of adrenal adenomas). Our aim was to analyze the histopathological characteristics of adrenal LPA.
Methods
Patients with LPA (
n
= 57) were selected among consecutive subjects referred for an adrenal incidentaloma or ACTH-independent Cushing syndrome. FluoroDeoxyGlucose-Positron Emission Tomography (FDG-PET) was performed in 37 patients. In patients treated by adrenalectomy (
n
= 17), Weiss score and Lin–Weiss–Bisceglia score (in tumors composed entirely or predominantly of oncocytes) were calculated.
Results
Radiological parameters did not differ among patients with ACTH-independent Cushing syndrome (
n
= 6) and those with adrenal incidentalomas associated with primary aldosteronism (
n
= 2), autonomous cortisol secretion (
n
= 14), or non-functioning (
n
= 35). Patients treated by adrenalectomy had larger tumors (28.9 ± 11.2
vs
17.3 ± 8.4 mm,
P
< 0.001), higher CT unenhanced density (29.1 ± 11.0
vs
23.1 ± 9.0 HU,
P
= 0.043), and FDG-PET adrenal uptake (9.0 ± 6.4
vs
4.4 ± 2.3 SUV,
P
= 0.003) than non-operated ones. Oncocytic features > 75% of the tumor were detected in 12/17 cases (70.6%). Five of those showed borderline-malignant histopathological characteristics by Lin–Weiss–Bisceglia score. Among remaining non-oncocytic tumors, 1/5 had a Weiss score ≥ 3. Overall, 6/17 tumors (35.3%) had borderline-malignant potential. Radiological parameters were similar between patients with benign and borderline-malignant tumors.
Conclusions
Adrenal LPA are a heterogeneous group of tumors, mostly composed of oncocytomas. Up to 1/3 of those tumors may have a borderline-malignant potential at histopathology.
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