The microstructure and hardness of case-hardened steel were investigated after carburizing and austenitizing at 820-900 °C, and oil quenching and tempering at 180 °C. The carburized case had a multiphase microstructure consisting of martensite, carbides, and retained austenite, and the maximum content of the retained austenite was 30%; the particle size range was 2-3 μm. The nano-hardness decreased from about 12 GPa near the surface to about 7 GPa in the core, and the microhardness decreased from 800 HV0.2 to 450 HV0.2. The in-depth distribution of the microhardness and nano-hardness showed a similar trend, and the ratio of nano-hardness to microhardness was about 15. The results were attributed to the fine particle size of the retained austenite and its even distribution in the martensite matrix and it could not lower the nano-hardness. The nano-hardness was relatively low in areas of the retained austenite (about 5.5 GPa), and pop-in effects were observed, indicating the phase transformation of the retained austenite during nanoindentation loading.

Our assessment of 30 water bodies in the vicinity of the Mae Moh coal mine and power station in northern Thailand does not indicate substantial water quality management challenges to developing fisheries/aquaculture in peripheral reservoirs and streams. Negative water quality issues such as high concentrations of arsenic (2-17 μg/L) and ions including sulfate (868-2605 mg/L), sodium (217-552 mg/L), and total ammonia (<1-5 mg/L) were associated with groundwater and surface water resources on the facility, as well as the stream network draining from it. Total dissolved solids were also very high, ranging from 658 to 3610 mg/L. Six of seven ponds tested had As concentrations in the range of 5-17 μg/L. Although these levels are less than the Thai regulation for industrial effluent, they are elevated over background surface water concentrations. The highest concentration in a contaminated stream was 10.54 μg/L As, which is only slightly above the WHO (2017) regulation of 10 μg/L for drinking water. Ponds, contaminated streams, and deep subsurface water should not be used for fisheries/aquaculture without extensive remediation/treatment. Concentrations of these water parameters in peripheral streams and reservoirs were not of environmental concern. High water hardness (161-397 mg/L CaCO3 and potential ionic imbalances may be the greatest hindrances to developing sustainable fisheries and aquaculture in reservoirs in the study area. Routine monitoring of inorganic As species and other contaminants in water is needed to assess the full extent of arsenic risk at the site following closure.

Continuous manufacturing of oral-dosage drug products is increasing the need for rigorous process understanding both from a process design and control perspective. The purpose of this study is to develop a methodology that analyzes the effects of upstream process parameters on continuous tablet compaction and then correlates associated upstream variables to the final tablet attributes (e.g. relative density and hardness). The impact of three process parameters (system throughput, blender speed, and compaction force) on tablet attributes is investigated using a full factorial experimental design. As expected, the compaction force was found to be the most significant process parameter. However, importantly, throughput was discovered to have a non-negligible impact which was previously unaccounted for. This impact is proposed to be related to differing levels of powder pre-compression. An empirical model for this relationship is regressed and incorporated into a flowsheet model. The flowsheet model is then used to develop an in silico design space which is compared favorably to that built from experiments. Moreover, in the future, the in silico design space based on the validated flowsheet model can provide better manufacturing flexibility and make control strategy development simpler.

Continuous Manufacturing (CM) of pharmaceutical drug products is a rather new approach within the pharmaceutical industry. In the presented paper, a GMP continuous wet granulation line used for clinical production of solid dosage forms was investigated with a thorough monitoring strategy regarding process performance and robustness. The line was composed of the subsequent continuous unit operations feeding - twin-screw wet-granulation - fluid-bed drying - sieving and tableting; the formulation of a new pharmaceutical entity in development was selected for this study. In detail, a Design of Experiments (DoE) was used to evaluate the impact of the three main factors (amount of water, filling rate, and shear force in twin-screw granulator) on the tablet quality. The process was monitored via in-process control (IPC) tests (e.g. weight, hardness, disintegration, and loss-on-drying), Process Analytical Technologies (PAT), and through the analysis of the process parameters (multivariate process control). The tested formulation was very robust to the large process variation of the DoE: all IPC results were in specification, the PAT probes provided stable results for the content uniformity and no critical variations can be detected in the process parameters. An adequate monitoring strategy was presented and the robustness of the process with one formulation has been demonstrated. In summary, this continuous process in combination with smart formulation development allows the robust production of constant quality tablets. The synergy between PAT, process data science and IPC creates an adequate monitoring framework of the continuous manufacturing line.

This study applied the concept of Quality by Design (QbD) to tablet dissolution. Its goal was to propose a quality control strategy to model dissolution testing of solid oral dose products according to International Conference on Harmonization guidelines. The methodology involved the following three steps: (1) a risk analysis to identify the material- and process-related parameters impacting the critical quality attributes of dissolution testing, (2) an experimental design to evaluate the influence of design factors (attributes and parameters selected by risk analysis) on dissolution testing, and (3) an investigation of the relationship between design factors and dissolution profiles. Results show that (a) in the case studied, the two parameters impacting dissolution kinetics are active pharmaceutical ingredient particle size distributions and tablet hardness and (b) these two parameters could be monitored with PAT tools to predict dissolution profiles. Moreover, based on the results obtained, modeling dissolution is possible. The practicality and effectiveness of the QbD approach were demonstrated through this industrial case study. Implementing such an approach systematically in industrial pharmaceutical production would reduce the need for tablet dissolution testing.

BACKGROUND: Previous studies have suggested that masticatory forces are associated with cracked teeth, but it is not clear which specific poor oral masticatory habits may be more likely to cause cracks. The aim of this study was to quantitatively assess risk factors for cracked teeth among poor oral masticatory habits and create a model for individualized risk predictions.
METHODS: We enrolled 35 patients with cracked teeth matched to 70 controls without cracked teeth by age, sex, position of the affected tooth, presence/absence of systemic disease, and diagnosis of symptomatic irreversible pulpitis from the Stomatology Hospital of Tianjin Medical University, Tianjin, China. Odds ratios (ORs) were calculated using conditional logistic regression analysis.
RESULTS: Thermal cycling eating habits (OR = 3.296; 95% confidence interval [CI], 1.684-6.450), eating coarse foods (OR = 2.727; 95% CI, 1.340-5.548), chewing on hard objects (OR = 2.087; 95% CI, 1.041-4.182), and unilateral mastication (OR = 2.472; 95% CI, 1.255-4.869) were independent risk factors for cracked teeth. The corresponding risk scores were 2.182, 1.691, 1.467, and 1.589, respectively. The area under the receiver operating characteristic curve and its 95% CI were 0.920 (0.868-0.973); the sensitivity and specificity were 0.943 and 0.800, respectively.
CONCLUSIONS: Thermal cycling eating habits were strongly associated with cracked teeth, whereas eating coarse foods, chewing on hard objects, and unilateral mastication were also independent risk factors for cracked teeth. These findings yield insights into ways to promote the prevention of risky behaviors for cracked teeth.

We believe cultural group selection is an elegant theoretical framework to study the evolution of complex human behaviours, including large-scale cooperation. However, the empirical evidence on key theoretical issues - such as levels of within- and between-group variation and effects of intergroup competition - is so far patchy, with no clear case where all the relevant assumptions and predictions of cultural group selection are met, to the exclusion of other explanations.

Effects of different oils on physicochemical properties, consumer liking, emotion, and purchase intent of sponge cakes were evaluated. Three healthy oils (extra virgin coconut oil, EVCO; extra virgin olive oil, EVOO; rice bran oil, RBO) compared with butter (the control), were used at 20% (w/w, wheat flour basis) in sponge cake formulations. Five positive (calm, good, happy, pleased, satisfied) and 3 negative (guilty, unsafe, worried) emotion terms, selected from the EsSense Profile(®) with slight modification using an online (N = 234) check-all-that-apply questionnaire, were used for consumer testing. Consumers (N = 148) evaluated acceptability of 9 sensory attributes on a 9-point hedonic scale, 8 emotion responses on a 5-point rating scale, and purchase intent on a binomial scale. Overall liking, emotion, and purchase intent were evaluated before compared with after health benefit statement of oils had been given to consumers. Overall liking and positive emotion (except calm) scores of sponge cake made with EVCO were higher than those made with EVOO and RBO. Specific volume, expansion ratio, and moisture content of control, EVCO, and EVOO were not significantly different, but higher than RBO sponge cake. JAR results showed that sponge cake made with RBO had the least softness that was reflected by the highest hardness (6.61 to 9.69 compared with. 12.76N). Oil (EVCO/EVOO/RBO) health benefit statement provided to consumer significantly increased overall liking, positive emotion, and purchase intent scores while decreased negative emotion scores. Overall liking and pleased emotion were critical attributes influencing purchase intent (odds ratio = 2.06 to 3.75), whereas calm and happy became not critical after health benefit statement had been given.

The present work focuses on the development of biomaterials that support the adhesion and the proliferation of adipose-tissue derived stem cells. Therefore, gelatin and starch are selected as starting materials. Both hydrogel building blocks are of great interest as they provide a general chemical structure comparable to the protein and the polysaccharide constituting part of the extracellular matrix. Crosslinkable side groups are incorporated on both biopolymers to enable the subsequent chemical crosslinking, thereby ensuring their stability at physiological temperature. An in vitro cellular assay revealed that the hydrogels developed are biocompatible and supported cell adhesion of adipose-tissue derived mesenchymal stem cells. The presence of the starch phase tempered the adhesion resulting in local cell detachment. The results thus indicate that by carefully varying the ratio of the two building blocks, hydrogels can be developed possessing a controllable cell adhesion behavior.

Crystals of voriconazole, an antifungal drug, are soft in nature, and this is disadvantageous during compaction studies where pressure is applied on the solid. Crystal engineering is used to make cocrystals and salts with modified mechanical properties (e.g., hardness). Cocrystals with biologically safe coformers such as fumaric acid, 4-hydroxybenzoic acid, and 4-aminobenzoic acid and salts with hydrochloric acid and oxalic acid are prepared through solvent assisted grinding. The presence (salt) or absence (cocrystal) of proton transfer in these multicomponent crystals is unambiguously confirmed with single crystal X-ray diffraction. All the cocrystals have 1:1 stoichiometry, whereas salts exhibit variable stoichiometries such as HCl salt (1:2) and oxalate salts (1:1.5 and 1:1). The nanoindentation technique was applied on single crystals of the salts and cocrystals. The salts exhibit better hardness than the drug and cocrystals in the order salts ≫ drug > cocrystals. The molecular origin of this mechanical modulation is explained on the basis of slip planes in the crystal structure and relative orientations of the molecules with respect to the nanoindentation direction. The hydrochloride salt is the hardest solid in this family. This may be useful for tableting of the drug during formulation and in drug development.