Assuring measurement traceability to ATE systems for MEMS temperature sensors testing and calibration

In the framework of an EMPIR joint research project (MET4FoF - Metrology for Factory of Future), a facility is being developed to provide in-situ measurement traceability to next-generation of Automated Test Equipment (ATE) systems used in MEMS temperature sensors testing and calibration. The above measurement traceability concepts are demonstrated in a testbed developed by SPEA in collaboration with INRIM and IPQ. The experimental work comprises both the factory-side implementation and the laboratory-side developments of a special calibration facility, to cover the temperature range between approximately -60 °C and 200 °C. On the factory side, SPEA develops a novel ATE prototype system, based on the concepts of good metrology practice, with the possibility to calibrate/validate in-situ the electronic circuitry and the on-board reference temperature sensors. The novel ATE prototype implements: • An improved temperature control system, with a new design of heaters, temperature sensors and MEMS temperature conditioning features. • A CPU software/firmware improvements to store sensors’ calibration coefficients and allow a “one-touch calibration” feature (i.e. a fully automatic process able to perform a comparison calibration of the ATE on-board reference temperature sensors). • An assessment of thermal conditions (homogeneity, heat losses, boundary effects) to estimate temperature calibration uncertainty. • A so-called “reference fixture”, i.e. an instrumented sensor socket equipped with a network of laboratory-calibrated reference sensors. On the laboratory side, INRIM develops calibration facilities and measurements methods to provide traceable temperature and electrical measurements to the above ATE systems. A custom equipment is developed to accommodate the sensors belonging to the reference fixture in order to calibrate them by comparison in a thermostatic bath. IPQ deals with the numerical simulation, by means of a 3D model of the temperature uniformity of the thermal chuck i.e. the ATE component providing the thermal stimulus to the MEMS under test. The simulation data will be used to help the SPEA hardware designer to improve the type, number and position of reference sensors on the thermal chuck to provide a more reliable and metrologically characterized thermal stimulus. The final paper will describe how an ATE machine works and in which parts it consists and how it is modified to reach the final goal. Furthermore, simulation data will be cross-compared with experimental data coming from metrological characterization before and after the ATE improvements in order to demonstrate their effectiveness. Also the method to assure traceability in large-scale temperature MEMS testing will be detailed and an example of application will be reported. Finally, it is expected that the outcome of this work will impact the quality and reliability of the MEMS sensors largely used in consumer electronics and will extend the calibration capability provided by INRIM to such an expanding industrial sector

An evaluation of morphological and functional multi-parametric MRI sequences in classifying non-muscle and muscle invasive bladder cancer

Objectives: Our goal is to determine the ability of multi-parametric magnetic resonance imaging (mpMRI) to differentiate muscle invasive bladder cancer (MIBC) from non-muscle invasive bladder cancer (NMIBC). Methods: Patients underwent mpMRI before tumour resection. Four MRI sets, i.e. T2-weighted (T2W) + perfusion-weighted imaging (PWI), T2W plus diffusion-weighted imaging (DWI), T2W + DWI + PWI, and T2W + DWI + PWI + dif-fusion tensor imaging (DTI) were interpreted qualitatively by two radiologists, blinded to histology results. PWI, DWI and DTI were also analysed quantitatively. Accuracy was determined using histopathology as the reference standard. Results: A total of 82 tumours were analysed. Ninety-six percent of T1-labeled tumours by the T2W + DWI + PWI image set were confirmed to be NMIBC at histopathology. Overall accuracy of the complete mpMRI protocol was 94% in differentiating NMIBC from MIBC. PWI, DWI and DTI quantitative parameters were shown to be significantly different in cancerous versus non-cancerous areas within the bladder wall in T2-labelled lesions. Conclusions: MpMRI with DWI and DTI appears a reliable staging tool for bladder cancer. If our data are validated, then mpMRI could precede cystoscopic resection to allow a faster recognition of MIBC and accelerated treatment pathways. Key Points: • A critical step in BCa staging is to differentiate NMIBC from MIBC. • Morphological and functional sequences are reliable techniques in differentiating NMIBC from MIBC. • Diffusion tensor imaging could be an additional tool in BCa staging

Multiparametric MRI of the bladder: inter-observer agreement and accuracy with the Vesical Imaging-Reporting and Data System (VI-RADS) at a single reference center

Objectives: To evaluate accuracy and inter-observer variability using Vesical Imaging-Reporting and Data System (VI-RADS) for discrimination between non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Methods: Between September 2017 and July 2018, 78 patients referred for suspected bladder cancer underwent multiparametric MRI of the bladder (mpMRI) prior to transurethral resection of bladder tumor (TURBT). All mpMRI were reviewed by two radiologists, who scored each lesion according to VI-RADS. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each VI-RADS cutoff. Receiver operating characteristics curves were used to evaluate the performance of mpMRI. The Ƙ statistics was used to estimate inter-reader agreement. Results: Seventy-five patients were included in the final analysis, 53 with NMIBC and 22 with MIBC. Sensitivity and specificity were 91% and 89% for reader 1 and 82% and 85% for reader 2 respectively when the cutoff VI-RADS > 2 was used to define MIBC. At the same cutoff, PPV and NPV were 77% and 96% for reader 1 and 69% and 92% for reader 2. When the cutoff VI-RADS > 3 was used, sensitivity and specificity were 82% and 94% for reader 1 and 77% and 89% for reader 2. Corresponding PPV and NPV were 86% and 93% for reader 1 and 74% and 91% for reader 2. Area under curve was 0.926 and 0.873 for reader 1 and 2 respectively. Inter-reader agreement was good for the overall score (Ƙ = 0.731). Conclusions: VI-RADS is accurate in differentiating MIBC from NMIBC. Inter-reader agreement is overall good. Key Points: • Traditionally, the local staging of bladder cancer relies on transurethral resection of bladder tumor. • However, transurethral resection of bladder tumor carries a significant risk of understaging a cancer; therefore, more accurate, faster, and non-invasive staging techniques are needed to improve outcomes. • Multiparametric MRI has proved to be the best imaging modality for local staging; therefore, its use in suitable patients has the potential to expedite radical treatment when necessary and non-invasive diagnosis in patients with poor fitness

MicroRNA 193b-3p as a predictive biomarker of chronic kidney disease in patients undergoing radical nephrectomy for renal cell carcinoma

Background: A significant proportion of patients undergoing radical nephrectomy (RN) for clear-cell renal cell carcinoma (RCC) develop chronic kidney disease (CKD) within a few years following surgery. Chronic kidney disease has important health, social and economic impact and no predictive biomarkers are currently available. MicroRNAs (miRs) are small non-coding RNAs implicated in several pathological processes. Methods: Primary objective of our study was to define miRs whose deregulation is predictive of CKD in patients treated with RN. Ribonucleic acid from formalin-fixed paraffin embedded renal parenchyma (cortex and medulla isolated separately) situated >3 cm from the matching RCC was tested for miR expression using nCounter NanoString technology in 71 consecutive patients treated with RN for RCC. Validation was performed by RT–PCR and in situ hybridisation. End point was post-RN CKD measured 12 months post-operatively. Multivariable logistic regression and decision curve analysis were used to test the statistical and clinical impact of predictors of CKD. Results: The overexpression of miR-193b-3p was associated with high risk of developing CKD in patients undergoing RN for RCC and emerged as an independent predictor of CKD. The addition of miR-193b-3p to a predictive model based on clinical variables (including sex and estimated glomerular filtration rate) increased the sensitivity of the predictive model from 81 to 88%. In situ hybridisation showed that miR-193b-3p overexpression was associated with tubule-interstitial inflammation and fibrosis in patients with no clinical or biochemical evidence of pre-RN nephropathy. Conclusions: miR-193b-3p might represent a useful biomarker to tailor and implement surveillance strategies for patients at high risk of developing CKD following RN

Climate-sensitive health priorities in Nunatsiavut, Canada

Background: This exploratory study used participatory methods to identify, characterize, and rank climate-sensitive health priorities in Nunatsiavut, Labrador, Canada. Methods: A mixed method study design was used and involved collecting both qualitative and quantitative data at regional, community, and individual levels. In-depth interviews with regional health representatives were conducted throughout Nunatsiavut (n = 11). In addition, three PhotoVoice workshops were held with Rigolet community members (n = 11), where participants took photos of areas, items, or concepts that expressed how climate change is impacting their health. The workshop groups shared their photographs, discussed the stories and messages behind them, and then grouped photos into re-occurring themes. Two community surveys were administered in Rigolet to capture data on observed climatic and environmental changes in the area, and perceived impacts on health, wellbeing, and lifestyles (n = 187). Results: Climate-sensitive health pathways were described in terms of inter-relationships between environmental and social determinants of Inuit health. The climate-sensitive health priorities for the region included food security, water security, mental health and wellbeing, new hazards and safety concerns, and health services and delivery. Conclusions: The results highlight several climate-sensitive health priorities that are specific to the Nunatsiavut region, and suggest approaching health research and adaptation planning from an EcoHealth perspective

Natural scaffolds with potential metal chelating activity for the multi-target therapy of Alzheimer's Disease: a preliminary study

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Identification of Natural Scaffolds as New Multi-Functional Agents for the Treatment of Alzheimer’s Disease

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Natural Scaffolds with Multi-Target Activity for the Potential Treatment of Alzheimer’s Disease

A few symptomatic drugs are currently available for Alzheimer’s Disease (AD) therapy, but these molecules are only able to temporary improve the cognitive capacity of the patients if administered in the first stages of the pathology. Recently, important advances have been achieved about the knowledge of this complex condition, which is now considered a multi-factorial disease. Researchers are, thus, more oriented toward the preparation of molecules being able to contemporaneously act on different pathological features. To date, the inhibition of acetylcholinesterase (AChE) and of β-amyloid (Aβ) aggregation as well as the antioxidant activity and the removal and/or redistribution of metal ions at the level of the nervous system are the most common investigated targets for the treatment of AD. Since many natural compounds show multiple biological properties, a series of secondary metabolites of plants or fungi with suitable structural characteristics have been selected and assayed in order to evaluate their potential role in the preparation of multi-target agents. Out of six compounds evaluated, 1 showed the best activity as an antioxidant (EC50 = 2.6 ± 0.2 µmol/µmol of DPPH) while compound 2 proved to be effective in the inhibition of AChE (IC50 = 6.86 ± 0.67 µM) and Aβ1–40 aggregation (IC50 = 74 ± 1 µM). Furthermore, compound 6 inhibited BChE (IC50 = 1.75 ± 0.59 µM) with a good selectivity toward AChE (IC50 = 86.0 ± 15.0 µM). Moreover, preliminary tests on metal chelation suggested a possible interaction between compounds 1, 3 and 4 and copper (II). Molecules with the best multi-target profiles will be used as starting hit compounds to appropriately address future studies of Structure-Activity Relationships (SARs)