Microstructure,Phase Formation and Heat-Treating of Novel Cast Al-Mg-Zn-Cu-Si Lightweight Complex Concentrated Aluminum Based Alloy

In the current work, a novel complex concentrated aluminum alloy is designed and studied. In order to investigate the unknown region of the multicomponent phase diagrams, thermo-physical parameters and the CALPHAD method were used to understand the phase formation of the Al₅₈Mg₁₈Zn₁₂Cu₅Si₇ at.% (Al₄₇.₄Mg₁₃.₃Zn₂₃.₈Cu₉.₆Si₆wt.%) alloy with a low-density of 2.63 g/cm³. The CALPHAD methodology showed good agreement with both the investigated microstructure and the thermodynamic parameters. The designed alloy was manufactured using an induction furnace and pour mold casting process. This study avoids the use of expensive, dangerous or scarce alloying elements and focuses instead on the utilization of widely available relatively cheaper elements. The microstructural evolution as a function of the heat-treatment was studied by means of different microstructural characterization techniques. The hardness, compressive strength and electrical conductivity of the as-cast and heat-treated alloy at room temperature were studied and correlated with the previously characterized microstructure. The alloy is characterized by a multiphase microstructure with major α-Al matrix reinforced with various secondary phases. In terms of mechanical properties, the developed alloy exhibited a high hardness value of 249 Vickers and compressive strength of 588 MPa. The present work provides a valuable insight for researchers, who aim to design and produce industry-like Aluminum based complex concentrated alloys (CCAs).     

Immunohistochemical localization of interleukin-6 in peripheral human endocrine glands

Interleukin-6 (IL-6) is a pleiotropic cytokine with differentiation and growth-promoting effects. Extensive studies in experimental animals denote that IL-6 is produced in various endocrine organs and participates in the local control of endocrine cell function. The expression of this cytokine in human endocrine glands, however, has only been examined in a limited number of studies. We investigated the immunohistochemical expression and localization of IL-6 in a variety of peripheral human endocrine glands. In the adrenals, IL-6 immunoreactivity was detected in all three zones of the cortex. The reticularis and glomerulosa zones were more heavily stained as compared with the slight immunoreactivity of the fasciculata zone. In the adrenal medulla, chromaffin and sustentacular cells were variably positive. A substantial number of follicular thyroid cells were strongly immunoreactive for IL-6 in all normal and hyperplastic thyroids examined. Parafollicular cells were negative. Parathyroid chief cells were mildly positive; selective and more intense staining was observed in acidophilic cells. Pancreatic islet cells were variably positive. In the testis positive staining was selectively observed in both Leydig and Sertoli cells. In conclusion, IL-6 immunoreactivity is present in almost all the human endocrine glands and it expressed in a cell-specific manner. These observations provide further support for the existence of local immune-endocrine interactions.     

RPE65-Associated Retinopathies in the Italian Population: A Longitudinal Natural History Study

PurposeTo investigate the course of inherited retinal degenerations (IRD) due to mutations in the RPE65 gene.MethodsThis longitudinal multicentric retrospective chart-review study was designed to collect best corrected visual acuity (BCVA), Goldman visual field, optical coherence tomography (OCT), and electroretinography (ERG) measurements. The data, including imaging, were collected using an electronic clinical research form and were reviewed at a single center to improve consistency.ResultsFrom an overall cohort of 60 Italian patients with RPE65-associated IRD, 43 patients (mean age, 27.8 ± 19.7 years) were included and showed a mean BCVA of 2.0 ± 1.0 logMAR. Time-to-event analysis revealed a median age of 33.8 years and 41.4 years to reach low vision and blindness based on BCVA, respectively. ERG (available for 34 patients) showed undetectable responses in most patients (26; 76.5%). OCT (available for 31 patients) revealed epiretinal membranes in five patients (16.1%). Central foveal thickness significantly decreased with age at a mean annual rate of −0.6%/y (P = 0.044). We identified 43 different variants in the RPE65 gene in the entire cohort. Nine variants were novel. Finally, to assess genotype-phenotype correlations, patients were stratified according to the number of RPE65 loss-of-function (LoF) alleles. Patients without LoF variants showed significantly (P < 0.05) better BCVA compared to patients with one or two LoF alleles.ConclusionsWe described the natural course of RPE65-associated IRD in an Italian cohort showing for the first time a specific genotype-phenotype association. Our findings can contribute to a better management of RPE65-associated IRD patients.     

Selecting information in electronic health records for knowledge acquisition

Knowledge acquisition of relations between biomedical entities is critical for many automated biomedical applications, including pharmacovigilance and decision support. Automated acquisition of statistical associations from biomedical and clinical documents has shown some promise. However, acquisition of clinically meaningful relations (i.e. specific associations) remains challenging because textual information is noisy and co-occurrence does not typically determine specific relations. In this work, we focus on acquisition of two types of relations from clinical reports: disease-manifestation related symptom (MRS) and drug-adverse drug event (ADE), and explore the use of filtering by sections of the reports to improve performance. Evaluation indicated that applying the filters improved recall (disease-MRS: from 0.85 to 0.90; drug-ADE: from 0.43 to 0.75) and precision (disease-MRS: from 0.82 to 0.92; drug-ADE: from 0.16 to 0.31). This preliminary study demonstrates that selecting information in narrative electronic reports based on the sections improves the detection of disease-MRS and drug-ADE types of relations. Further investigation of complementary methods, such as more sophisticated statistical methods, more complex temporal models and use of information from other knowledge sources, is needed.     

Advanced Model Predictive Feedforward/Feedback Control of a Tablet Press

In continuous pharmaceutical manufacturing, real-time precise control of critical quality attributes (CQAs) is necessary for quality by design (QbD)-based manufacturing and real-time release (RTR) with minimum consumption of time, space, and resources. Pharmaceutical tablets can be produced through different routes with a common tablet press unit operation always placed at the end of the manufacturing process. Therefore, the tablet press is a crucial unit operation directly influencing the CQAs irrespective of manufacturing routes. Despite this, little attention has been paid to the development of an advanced efficient control system for the tablet press. Process modeling can be used as an efficient virtual experimentation tool to design, compare, and evaluate different control systems. We developed a model in Simulink (Mathworks) that includes two master control loops for tablet weight and hardness and a slave feedback loop controlling the compaction force applied to each tablet. We examined the performance of different control strategies based on proportional integral derivative (PID) control and model predictive control (MPC), as well as feedforward/feedback control. We found that a hybrid MPC-PID control strategy outperforms the PID-only control strategy. We also observed that the addition of a feedforward controller further improves the performance of the hybrid MPC-PID control strategy.     

Design Space of Pharmaceutical Processes Using Data-Driven-Based Methods

Introduction  

The identification and graphical representation of process design space are critical in locating not only feasible but also optimum operating variable ranges and design configurations. In this work, the mapping of the design space of pharmaceutical processes is achieved using the ideas of process operability and flexibility under uncertainty.     

Primary pleural epithelioid mesothelioma of clear cell type: a case report and review of current literature

Primary pleural epithelioid mesothelioma with clear cell morphology is a particularly rare neoplasm, with only a few documented cases. Here, the authors report a case of a 76-year-old man, with a history of asbestos exposure, admitted for mild dyspnea. Radiologic examination revealed right pleural effusion and pleural thickening. Cytological examination of aspirated pleural samples was consistent with non-small cell carcinoma. Histological examination of the resected, via VATS, plural specimens was consistent with the diagnosis of clear cell epithelioid mesothelioma. The authors further analyze the main morphological and immunohistochemical features of clear cell epithelioid mesothelioma, emphasizing the algorithm for excluding other clear cell tumors metastatic to the pleura.