Epithelial ovarian carcinoma diagnosis by desorption electrospray ionization mass spectrometry imaging

Ovarian cancer is highly prevalent among European women, and is the leading cause of gynaecological cancer death. Current histopathological diagnoses of tumour severity are based on interpretation of, for example, immunohistochemical staining. Desorption electrospray mass spectrometry imaging (DESI-MSI) generates spatially resolved metabolic profiles of tissues and supports an objective investigation of tumour biology. In this study, various ovarian tissue types were analysed by DESI-MSI and co-registered with their corresponding haematoxylin and eosin (H&E) stained images. The mass spectral data reveal tissue type-dependent lipid profiles which are consistent across the n = 110 samples (n = 107 patients) used in this study. Multivariate statistical methods were used to classify samples and identify molecular features discriminating between tissue types. Three main groups of samples (epithelial ovarian carcinoma, borderline ovarian tumours, normal ovarian stroma) were compared as were the carcinoma histotypes (serous, endometrioid, clear cell). Classification rates >84% were achieved for all analyses, and variables differing statistically between groups were determined and putatively identified. The changes noted in various lipid types help to provide a context in terms of tumour biochemistry. The classification of unseen samples demonstrates the capability of DESI-MSI to characterise ovarian samples and to overcome existing limitations in classical histopathology

Striving for Freedom: an Incarcerated Existence

Presented in this project is a detailed study of the effects of long term incarceration on inmates and society. This researcher examined the life of a fictitious inmate, through the form of a novella, as he endured long term incarceration. His innermost thoughts and feelings shed light into the criminal lifestyle through the careful examination of his experiences related to: (a) childhood, (b) family dysfunction, (c) socioeconomic status, (c) peer relations, and (d) education. The purpose of long term incarceration prevention should be focused on: (a) prevention, in order to stop at risk individuals from becoming institutionalized; (b) intervention, to try and offer services to help at risk individual to lead a stable lifestyle; (c) rehabilitation, to provide training and educational opportunities for the inmate population; and (d) alternatives to incarceration, for nonviolent offenders

Multitarget drug design strategy in Alzheimer’s disease: focus on cholinergic transmission and amyloid-β aggregation

Background: Alzheimer pathogenesis has been associated with a network of processes working simultaneously and synergistically. Over time, much interest has been focused on cholinergic transmission and its mutual interconnections with other active players of the disease. Besides the cholinesterase mainstay, the multifaceted interplay between nicotinic receptors and amyloid is actually considered to have a central role in neuroprotection. Thus, the multitarget drug-design strategy has emerged as a chance to face the disease network. Results: By exploiting the multitarget approach, the present study provides new molecules able to target the cholinergic pathway, by joining direct nicotinic receptor stimulation to acetylcholinesterase inhibition, and to inhibit Aβ aggregation. Conclusions: These new compounds emerged as a suitable starting point for a further optimization process

A systemic design application for resources management in urban green spaces

Urban green spaces are often analyzed by the quantity of provided services, the kind of benefits they supply for the community and the human actions that modify the urban ecosystems. Moreover, urban green spaces and green infrastructures can produce important resources, even if these latter are not always considered during the preparation of management plans. To this extent, the Systemic Design can help to show the qualitative aspects of these resources and how they can be managed. Aim of this study is therefore to illustrate how a holistic approach like the Systemic Design can be applied to the management of urban green infrastructure, their ecosystem services and the raw materials and resources useful for the community.With an application to a real case, we will show how a Systemic Design approach is able to state resources' availability in a green urban area with the consequent identification of the area in which these resources can be employed. This identification is the essential prerequisite for the creation of a plan that stress the links among ecosystem services, resources and urban dwellers and the consequent best management practices, with particular emphasis on challenges related to climate changes and increasing urbanization.When necessary, Systemic Design can also provide viable indications to redesign a new context with different fluxes of materials and energy and can contribute to the creation of a set of new activities deeply connected with local green spaces. The final results can be identified in the creation of work tools for administrators and urban designers interested in the integrated management of green infrastructures and the suggestion of a new urban model, with stronger connections between society and territory, for more sustainable and resilient cities

Primary Voltage and Frequency Regulation in Inverter Based Islanded Microgrids through a Model Predictive Control Approach

A frequency and voltage control strategy based on a decentralized and communication-less approach is proposed in this work and applied to Photovoltaic-Storage-Microturbine islanded Microgrids (MGs). The approach is based on the Model Predictive Control (MPC) technique. Thanks to the use of local measurements, each source can nullify the steady-state voltage and frequency errors by means of a dedicated MPC controller. Consequently, the proposed approach unifies the advantages of classic droop and master/slave controllers due to the absence of communication links among devices and due to the absence of a secondary centralized control loop

A model predictive control design for power generation heavy-duty gas turbines

The new electric power generation scenario, characterized by growing variability due to the greater presence of renewable energy sources (RES), requires more restrictive dynamic requirements for conventional power generators. Among traditional power generators, gas turbines (GTs) can regulate the output electric power faster than any other type of plant; therefore, they are of considerable interest in this context. In particular, the dynamic performance of a GT, being a highly nonlinear and complex system, strongly depends on the applied control system. Proportional–integral–derivative (PID) controllers are the current standard for GT control. However, since such controllers have limitations for various reasons, a model predictive control (MPC) was designed in this study to enhance GT performance in terms of dynamic behavior and robustness to model uncertainties. A comparison with traditional PID-based controllers and alternative model-based control approaches (feedback linearization control) found in the literature demonstrated the effectiveness of the proposed approach

Treatment of malignant hypercalcaemia with aminohexane bisphosphonate (neridronate).

Twenty patients with hypercalcaemia due to malignancy, which persisted following rehydration, were treated with the bisphosphonate, aminohexane bisphosphonate (AHBP), which is structurally similar to pamidronate. The treatment given was a single infusion of 125 mg of AHBP in 500 ml of normal saline infused over 4 h. Serum and urine biochemistry were measured before and after treatment. Acute toxicity was evaluated with particular attention to gastrointestinal symptoms, acute-phase reaction and change in renal function, as judged by serum creatinine. The infusion of AHBP induced a rapid fall apparent by day 3 (P < 0.001), with a nadir at day 7. The serum calcium remained lower at days 14 and 28 than at day 0, but the numbers followed up were low (n = 5 and n = 4). In all 20 patients there was a fall in serum calcium after treatment, and in 13 (65%) normocalcaemia was achieved. Failure to respond completely to AHBP appeared to be associated with a renal mechanism of hypercalcaemia. Treatment was associated with a significant decrease in fasting urinary calcium excretion (P < 0.05). There was no change in white cell count or renal function following AHBP and only two cases of mild pyrexia after infusion. We conclude that aminohexane bisphosphonate is an effective agent in the treatment of tumour-induced hypercalcaemia, with rapid onset of effect and low toxicity

Chromogenic In Situ Hybridization and p16/Ki67 Dual Staining on Formalin-Fixed Paraffin-Embedded Cervical Specimens: Correlation with HPV-DNA Test, E6/E7 mRNA Test, and Potential Clinical Applications.

Although HPV-DNA test and E6/E7 mRNA analyses remain the current standard for the confirmation of human papillomavirus (HPV) infections in cytological specimens, no universally adopted techniques exist for the detection of HPV in formalin-fixed paraffin-embedded samples. Particularly, in routine laboratories, molecular assays are still time-consuming and would require a high level of expertise. In this study, we investigated the possible use of a novel HPV tyramide-based chromogenic in situ hybridization (CISH) technology to locate HPV on tissue specimens. Then, we evaluate the potential usefulness of p16(INK4a)/Ki-67 double stain on histological samples, to identify cervical cells expressing HPV E6/E7 oncogenes. In our series, CISH showed a clear signal in 95.2% of the specimens and reached a sensitivity of 86.5%. CISH positivity always matched with HPV-DNA positivity, while 100% of cases with punctated signal joined with cervical intraepithelial neoplasia grade 2 or worse (CIN2+). p16/Ki67 immunohistochemistry gave an interpretable result in 100% of the cases. The use of dual stain significantly increased the agreement between pathologists, which reached 100%. Concordance between dual stain and E6/E7 mRNA test was 89%. In our series, both CISH and p16(INK4a)/Ki67 dual stain demonstrated high grade of performances. In particular, CISH would help to distinguish episomal from integrated HPV, in order to allow conclusions regarding the prognosis of the lesion, while p16(INK4a)/Ki67 dual stain approach would confer a high level of standardization to the diagnostic procedur