Multi-scale Modelling of Natural Composites Using Thermodynamics-Based Artificial Neural Networks and Dimensionality Reduction Techniques

Modelling natural composites, as the majority of real geomaterials, requires facing their intrinsic multiscale nature. This allows to consider multiphysics coupling occurring at the microscale, then reflected onto the macroscopic behavior. Geotechnics is constantly requiring reliable constitutive models of natural compolve large-scale engineering problems accurately and efficiently. This need motivates the contribution. To capture in detail the macroscopic effects of microssites to socopic processes, many authors have developed multi-scale numerical schemes. A common drawback of such methods is the prohibitive computational cost. Recently,Machine Learning based approaches have raised as promising alternatives to traditional methods. Artificial Neural Networks – ANNs – have been used to predict the constitutive behaviour of complex, heterogeneous materials, with reduced calculation costs. However, a major weakness of ANN is the lack of a rigorous framework based on principles of physics. This often implies a limited capability to extrapolate values ranging outside the training set and the need of large, high-quality datasets, on which performing the training. This work focuses on the use of Thermodynamics-based Artificial Neural Networks – TANN – to predict the constitutive behaviour of natural composites. Dimensionality reduction techniques – DRTs – are used to embed information of microscopic processes into a lower dimensional manifold. The obtained set of variables is used to characterize the state of the material at the macroscopic scale. Entanglement of DRTs with TANN allows to reproduce the complex nonlinear material response with reduced computational costs and guarantying thermodynamic admissibility. To demonstrate the method capabilities an application to a heterogeneous material model is presented

Market Access for Medical Devices: Adapting to Change

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Water retention and characteristic curves representing tropical clay soils from Africa

Soil water retention curves (SWRCs) form an essential component of frameworks coupling the hydromechanical behaviour of unsaturated soils. The curves describe how suction changes with variables such as degree of saturation, void ratio and volumetric/gravimetric water content. SWRCs can be determined from incrementally drying initially saturated reconstituted samples to a final residual state, thus developing the primary drying curve (PDC). The primary wetting curve (PWC) is established from subsequent incremental wetting from residual state and is hysteretic compared with the PDC. SWRCs for reconstituted, high-plasticity, tropical clays from Africa (Sudan, Tanzania and South Africa) will be produced using suction measuring instruments, a tensiometer, filter paper and a dew point potentiometer. The development of SWRCs under various subsequent cycles of drying will be presented and discussed along with details concerning volumetric changes and cracking during drying. In order to investigate the uniqueness of the PDC and PWC and the effect of initial void ratio, SWRCs will be determined for samples formed by reconstituted from slurry under different applied energy levels.</jats:p

ALERT Doctoral School 2012: advanced experimental techniques in geomechanics

The twenty-second session of the European Graduate School 2012 (called usually ALERT Doctoral School) entitled Advanced experimental techniques in geomechanics is organized by Cino Viggiani, Steve Hall and Enrique Romero.Postprint (published version

Faciliating More Efficient Negotiations for Innovative Therapies: A Value-Based Negotiation Framework

OBJECTIVES: An increasing number of innovative therapies (e.g., gene- and cell-based treatments) have been developed in the past 20 years. Despite the significant clinical potential of these therapies, access delays may arise because of differing perspectives of manufacturers and payers regarding issues such as the value of the product, clinical and financial uncertainties, and sustainability.Managed entry agreements (MEAs) can enable access to treatments that would not be reimbursed by conventional methods because of such concerns. However, although MEA typologies exist, there is currently no structured process to come to agreements on MEAs, which can be difficult to decide upon and implement.To facilitate more structured MEA negotiations, we propose a conceptual "value-based negotiation framework" with corresponding application tools. METHODS: The framework was developed based on an iterative process of scientific literature review and expert input. RESULTS: The framework aims to (i) systematically identify and prioritize manufacturer and payer concerns about a new treatment, and (ii) select a mutually acceptable combination of MEA terms that can best address priority concerns, with the lowest possible implementation burden. CONCLUSIONS: The proposed framework will be tested in practice, and is a step toward supporting payers and manufacturers to engage in more structured, transparent negotiations to balance the needs of both sides, and enabling quicker, more transparent MEA negotiations and patient access to innovative products

Next-Generation Sequencing in Clinical Practice. Is It a Cost-Saving Alternative to a Single-Gene Testing Approach?

Objectives: This study aimed to compare the costs of a next-generation sequencing-based (NGS-based) panel testing strategy to those of a single-gene testing-based (SGT-based) strategy, considering different scenarios of clinical practice evolution. Methods: Three Italian hospitals were analysed, and four different testing pathways (paths 1, 2, 3, and 4) were identified: two for advanced non-small-cell lung cancer (aNSCLC) patients and two for unresectable metastatic colon-rectal cancer (mCRC) patients. For each path, we explored four scenarios considering the current clinical practice and its expected evolution. The 16 testing cases (4 scenarios × 4 paths) were then compared in terms of differential costs between the NGS-based and SGT-based approaches considering personnel, consumables, equipment, and overhead costs. Break-even and sensitivity analyses were performed. Data gathering, aimed at identifying the hospital setup, was performed through a semi-structured questionnaire administered to the professionals involved in testing activities. Results: The NGS-based strategy was found to be a cost-saving alternative to the SGT-based strategy in 15 of the 16 testing cases. The break-even threshold, the minimum number of patients required to make the NGS-based approach less costly than the SGT-based approach, varied across the testing cases depending on molecular alterations tested, techniques adopted, and specific costs. The analysis found the NGS-based approach to be less costly than the SGT-based approach in nine of the 16 testing cases at any volume of tests performed; in six cases, the NGS-based approach was found to be less costly above a threshold (and in one case, it was found to be always more expensive). Savings obtained using an NGS-based approach ranged from €30 to €1249 per patient; in the unique testing case where NGS was more costly, the additional cost per patient was €25. Conclusions: An NGS-based approach may be less costly than an SGT-based approach; also, generated savings increase with the number of patients and different molecular alterations tested

The association of financial difficulties with clinical outcomes in cancer patients: secondary analysis of 16 academic prospective clinical trials conducted in Italy

Background: Cancer may cause financial difficulties, but its impact in countries with public health systems is unknown. We evaluated the association of financial difficulties with clinical outcomes of cancer patients enrolled in academic clinical trials performed within the Italian public health system. Patients and methods: Data were pooled from 16 prospective multicentre trials in lung, breast or ovarian cancer, using the EORTC quality of life (QOL) C30 questionnaire. Question 28 scores financial difficulties related to disease or treatment in four categories from 'not at all' to 'very much'. We defined financial burden (FB) as any financial difficulty reported at baseline questionnaire, and financial toxicity (FT) as score worsening in a subsequent questionnaire. We investigated (i) the association of FB with clinical outcomes (survival, global QOL response [questions 29/30] and severe toxicity), and (ii) the association of FT with survival. Multivariable analyses were performed using logistic regression models or the Cox model adjusting for trial, gender, age, region and period of enrolment, baseline global QOL and, where appropriate, FB and global QOL response. Results are reported as odds ratio (OR) or hazard ratio (HR) with 95% confidence intervals (CI). Results: At baseline 26% of the 3670 study patients reported FB, significantly correlated with worse baseline global QOL. FB was not associated with risks of death (HR 0.94, 95% CI 0.85-1.04, P = 0.23) and severe toxicity (OR 0.90, 95% CI 0.76-1.06, P = 0.19) but was predictive of a higher chance of worse global QOL response (OR 1.35, 95% CI 1.08-1.70, P = 0.009). During treatment, 2735 (74.5%) patients filled in subsequent questionnaires and 616 (22.5%) developed FT that was significantly associated with an increased risk of death (HR 1.20, 95% CI 1.05-1.37, P = 0.007). Several sensitivity analyses confirmed these findings. Conclusion: Even in a public health system, financial difficulties are associated with relevant cancer patients outcomes like QOL and survival

Italian hospitals on the web: a cross-sectional analysis of official websites

<p>Abstract</p> <p>Background</p> <p>Although the use of the Internet for health purposes has increased steadily in the last decade, only a few studies have explored the information provided by the websites of health institutions and no studies on the on-line activities of Italian hospitals have been performed to date. The aim of this study was to explore the characteristics of the contents and the user-orientation of Italian hospital websites.</p> <p>Methods</p> <p>The cross-sectional analysis considered all the Italian hospitals with a working website between December 2008 and February 2009. The websites were coded using an <it>ad hoc </it>Codebook, comprising eighty-nine items divided into five sections: technical characteristics, hospital information and facilities, medical services, interactive on-line services and external activities. We calculated a website evaluation score, on the basis of the items satisfied, to compare private (PrHs) and public hospitals, the latter divided into ones with their own website (PubHs-1) and ones with a section on the website of their Local Health Authority (PubHs-2). Lastly, a descriptive analysis of each item was carried out.</p> <p>Results</p> <p>Out of the 1265 hospitals in Italy, we found that 419 of the 652 public hospitals (64.3%) and 344 of the 613 PrHs (56.1%) had a working website (p = 0.01). The mean website evaluation score was 41.9 for PubHs-1, 21.2 for PubHs-2 and 30.8 for PrHs (p < 0.001).</p> <p>Only 5 hospitals out of 763 (< 1%) provided specific clinical performance indicators, such as the nosocomial infection rate or the surgical mortality rates. Regarding interactive on-line services, although nearly 80% of both public and private hospitals enabled users to communicate on-line, less than 18% allowed the reservation of medical services, and only 8 websites (1%) provided a health-care forum.</p> <p>Conclusions</p> <p>A high percentage of hospitals did not provide an official website and the majority of the websites found had several limitations. Very few hospitals provided information to increase the credibility of the hospital and user confidence in the institution. This study suggests that Italian hospital websites are more a source of information on admissions and services than a means of communication between user and hospital.</p

Can we use the pharmacy data to estimate the prevalence of chronic conditions? a comparison of multiple data sources

<p>Abstract</p> <p>Background</p> <p>The estimate of the prevalence of the most common chronic conditions (CCs) is calculated using direct methods such as prevalence surveys but also indirect methods using health administrative databases.</p> <p>The aim of this study is to provide estimates prevalence of CCs in Lazio region of Italy (including Rome), using the drug prescription's database and to compare these estimates with those obtained using other health administrative databases.</p> <p>Methods</p> <p>Prevalence of CCs was estimated using pharmacy data (PD) using the Anathomical Therapeutic Chemical Classification System (ATC).</p> <p>Prevalences estimate were compared with those estimated by hospital information system (HIS) using list of ICD9-CM diagnosis coding, registry of exempt patients from health care cost for pathology (REP) and national health survey performed by the Italian bureau of census (ISTAT).</p> <p>Results</p> <p>From the PD we identified 20 CCs. About one fourth of the population received a drug for treating a cardiovascular disease, 9% for treating a rheumatologic conditions.</p> <p>The estimated prevalences using the PD were usually higher that those obtained with one of the other sources. Regarding the comparison with the ISTAT survey there was a good agreement for cardiovascular disease, diabetes and thyroid disorder whereas for rheumatologic conditions, chronic respiratory illnesses, migraine and Alzheimer's disease, the prevalence estimates were lower than those estimated by ISTAT survey. Estimates of prevalences derived by the HIS and by the REP were usually lower than those of the PD (but malignancies, chronic renal diseases).</p> <p>Conclusion</p> <p>Our study showed that PD can be used to provide reliable prevalence estimates of several CCs in the general population.</p