Effect of Annealing Temperature on Electrochemical Properties of Zr56Cu19Ni11Al9Nb5 in PBS Solution.

The electrochemical properties of as-cast Zr56Cu19Ni11Al9Nb5 metallic glass and samples annealed at different temperatures were investigated using potentiodynamic polarization tests and electrochemical impedance spectroscopy (EIS) in phosphate buffer saline (PBS) solution. It was shown that passivation occurred for the as-cast sample and the samples annealed at 623-823 K, indicating good corrosion resistance. At higher annealing temperature, the corrosion resistance first increased, and then decreased. The sample annealed at 823 K exhibited the best corrosion resistance, with high spontaneous corrosion potential Ecorr at -0.045 VSCE, small corrosion current density icorr at 1.549 × 10-5 A·cm-2, high pitting potential Epit at 0.165 VSCE, the largest arc radius, and the largest sum of Rf and Rct at 5909 Ω·cm2. For the sample annealed at 923 K, passivation did not occur, with low Ecorr at -0.075 VSCE, large icorr at 1.879 × 10-5 A·cm-2, the smallest arc radius, and the smallest sum of Rf and Rct at 2173 Ω·cm2, which suggested the worst corrosion resistance. Proper annealing temperature led to improved corrosion resistance due to structural relaxation and better stability of the passivation film, however, if the annealing temperature was too high, the corrosion resistance deteriorated due to the chemical inhomogeneity between the crystals and the amorphous matrix. Optical microscopy and scanning electron microscopy (SEM) examinations indicated that localized corrosion occurred. Results of energy dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) illustrated that the main corrosion products were ZrO2, CuO, Cu2O, Ni(OH)2, Al2O3, and Nb2O5.

An integrated data management and informatics framework for continuous drug product manufacturing processes: A case study on two pilot plants.

The pharmaceutical industry continuously looks for ways to improve its development and manufacturing efficiency. In recent years, such efforts have been driven by the transition from batch to continuous manufacturing and digitalization in process development. To facilitate this transition, integrated data management and informatics tools need to be developed and implemented within the framework of Industry 4.0 technology. In this regard, the work aims to guide the data integration development of continuous pharmaceutical manufacturing processes under the Industry 4.0 framework, improving digital maturity and enabling the development of digital twins. This paper demonstrates two instances where a data integration framework has been successfully employed in academic continuous pharmaceutical manufacturing pilot plants. Details of the integration structure and information flows are comprehensively showcased. Approaches to mitigate concerns in incorporating complex data streams, including integrating multiple process analytical technology tools and legacy equipment, connecting cloud data and simulation models, and safeguarding cyber-physical security, are discussed. Critical challenges and opportunities for practical considerations are highlighted.

Developing a Virtual Flowability Sensor for Monitoring a Pharmaceutical Dry Granulation Line.

Current technologies to measure granule flowability involve at-line methods that can take hours to perform. This is problematic for a continuous dry granulation tableting line, where the quality assurance and control of the final tablet products depend on real-time monitoring and control of powder flowability. Hence, a real-time alternative is needed for measuring the flowability of the granular products coming out of the roller compactor, which is the unit operation immediately preceding the tablet press. Since particle analyzers have the potential to take inline measurements of the size and shape of granules, they can potentially serve as real-time flowability sensors, given that the size and shape measurements can be used to reliably predict flowability measurements. This paper reports on the use of Partial Least Squares (PLS) regression to utilize distributions of size and shape measurements in predicting the output of three different types of flowability measurements: rotary drum flow, orifice flow, and tapped density analysis. The prediction performance of PLS had a coefficient of determination ranging from 0.80 to 0.97, which is the best reported performance in the literature. This is attributed to the ability of PLS to handle high collinearity in the datasets and the inclusion of multiple shape characteristics-eccentricity, form factor, and elliptical form factor-into the model. The latter calls for a change in industry perspective, which normally dismisses the importance of shape in favor of size; and the former suggests the use of PLS as a better way to reduce the dimensionality of distribution datasets, instead of the widely used practice of pre-selecting distribution percentiles.

Application of MHE-based NMPC on a Rotary Tablet Press under Plant-Model Mismatch.

Active control strategies play a vital role in modern pharmaceutical manufacturing. Automation and digitalization are revolutionizing the pharmaceutical industry and are particularly important in the shift from batch operations to continuous operation. Active control strategies provide real-time corrective actions when departures from quality targets are detected or even predicted. Under the concept of Quality-by-Control (QbC), a three-level hierarchical control structure can be applied to achieve effective setpoint tracking and disturbance rejection in the tablet manufacturing process through the development and implementation of a moving horizon estimation-based nonlinear model predictive control (MHE-NMPC) framework. When MHE is coupled with NMPC, historical data in the past time window together with real-time data from the sensor network enable model parameter updating and control. The adaptive model in the NMPC strategy compensates for process uncertainties, further reducing plant-model mismatch effects. The frequency and constraints of parameter updating in the MHE window should be determined cautiously to maintain control robustness when sensor measurements are degraded or unavailable. The practical applicability of the proposed MHE-NMPC framework is demonstrated via using a commercial scale tablet press, Natoli NP-400, to control tablet properties, where the nonlinear mechanistic models used in the framework can predict the essential powder properties and provide physical interpretations.

A Hierarchical Approach to Monitoring Control Performance and Plant-Model Mismatch.

Controllers are often tuned during plant commissioning, with a fixed process model. However, over time degradation can occur in the process, the process model and the controller, making it necessary to either re-tune the controller or re-identify the process model. Authors have proposed a variety of approaches to identify plant-model mismatch (PMM) and control performance degradation (CPD). While each approach may have its own advantages and disadvantages, they are generally designed to function on different timescales. The differing timescales result in the need for a multi-level hierarchical approach to monitor, detect, and manage PMM and CPD, as illustrated through a continuous pharmaceutical manufacturing application, i.e., a direct compression tablet manufacturing process. This work also highlights the requirement for index-based metrics, that enable the impact of PMM and CPD to be quantified and assessed from a control performance monitoring perspective, to aid fault diagnosis through root cause analysis to guide maintenance decisions for continuous manufacturing applications.

Development of a Virtual Sensor for Real-Time Prediction of Granule Flow Properties.

We report progress of an ongoing work to develop a virtual sensor for flowability, which is a critical tool for enabling real time process monitoring in a granulation line. The sensor is based on camera imaging to measure the size and shape distribution of granules produced by wet granulation. Then, statistical methods were used to correlate them with flowability measurements such as ring shear tests, drained angle of repose, dynamic angle of repose, and tapped density. The virtual sensor addresses the issue with these flowability measurements, which are based on off-line characterization methods that can take hours to perform. With a virtual sensor based on real-time measurement methods, the prediction of granule flowability become faster, allowing for timely decisions regarding process control and the supply chain.

Real-Time Monitoring of Powder Mass Flowrates for Plant-Wide Control of a Continuous Direct Compaction Tablet Manufacturing Process.

While measurement and monitoring of powder/particulate mass flow rate are not essential to the execution of traditional batch pharmaceutical tablet manufacturing, in continuous operation, it is an important additional critical process parameter. It has a key role both in establishing that the process is in a state of control, and as a controlled variable in process control system design. In current continuous tableting line operations, the pharmaceutical community relies on loss-in-weight feeders to monitor and understand upstream powder flow dynamics. However, due to the absence of established sensing technologies for measuring particulate flow rates, the downstream flow of the feeders is monitored and controlled using various indirect strategies. For example, the hopper level of the tablet press is maintained as a controlled process output by adjusting the turret speed of the tablet press, which indirectly controlling the flow rate. This gap in monitoring and control of the critical process flow motivates our investigation of a novel PAT tool, a capacitance-based sensor (ECVT), and its effective integration into the plant-wide control of a direct compaction process. First, the results of stand-alone experimental studies are reported, which confirm that the ECVT sensor can provide real-time measurements of mass flow rate with measurement error within -1.8 ~ 3.3% and with RMSE of 0.1 kg/h over the range of flow rates from 2 to 10 kg/h. The key caveat is that the powder flowability has to be good enough to avoid powder fouling on the transfer line walls. Next, simulation case studies are carried out using a dynamic flowsheet model of a continuous direct compression line implemented in Matlab/Simulink to demonstrate the potential structural and performance advantages in plant-wide process control enabled by mass flow sensing. Finally, experimental studies are performed on a direct compaction pilot plant in which the ECVT sensor is located at the exit of the blender, to confirm that the powder flow can be monitored instantaneously and controlled effectively at the specified setpoint within a plant-wide feedback controller system.

Evaluation of a Combined MHE-NMPC Approach to Handle Plant-Model Mismatch in a Rotary Tablet Press.

The transition from batch to continuous processes in the pharmaceutical industry has been driven by the potential improvement in process controllability, product quality homogeneity, and reduction of material inventory. A quality-by-control (QbC) approach has been implemented in a variety of pharmaceutical product manufacturing modalities to increase product quality through a three-level hierarchical control structure. In the implementation of the QbC approach it is common practice to simplify control algorithms by utilizing linearized models with constant model parameters. Nonlinear model predictive control (NMPC) can effectively deliver control functionality for highly sensitive variations and nonlinear multiple-input-multiple-output (MIMO) systems, which is essential for the highly regulated pharmaceutical manufacturing industry. This work focuses on developing and implementing NMPC in continuous manufacturing of solid dosage forms. To mitigate control degradation caused by plant-model mismatch, careful monitoring and continuous improvement strategies are studied. When moving horizon estimation (MHE) is integrated with NMPC, historical data in the past time window together with real-time data from the sensor network enable state estimation and accurate tracking of the highly sensitive model parameters. The adaptive model used in the NMPC strategy can compensate for process uncertainties, further reducing plant-model mismatch effects. The nonlinear mechanistic model used in both MHE and NMPC can predict the essential but complex powder properties and provide physical interpretation of abnormal events. The adaptive NMPC implementation and its real-time control performance analysis and practical applicability are demonstrated through a series of illustrative examples that highlight the effectiveness of the proposed approach for different scenarios of plant-model mismatch, while also incorporating glidant effects.

Sociodemographic factors associated with attitudes towards abortion in New Zealand.

AIMS: The present study examined the sociodemographic correlates of support for legalised abortion in New Zealand. METHOD: Data (N=19,973) were from the 2016/17 New Zealand Attitudes and Values Study, a national longitudinal panel sample of New Zealand adults aged 18 and older. The survey measured support for legalised abortion (a) regardless of the reason and (b) when the woman's life is endangered, as well as (c) focal sociodemographic correlates. RESULTS: Our sample expressed moderate-to-high support for legalised abortion regardless of the reason and high support for abortion when the woman's life is endangered. Being religious, living in a more deprived neighbourhood and having more children all correlated negatively with support for both measures of abortion. Men were less supportive of abortion for any reason but did not differ from women's support for legalised abortion when the woman's life is endangered. Furthermore, age correlated negatively with support for abortion for any reason, but positively with support for abortion when a woman's life is endangered. CONCLUSIONS: A majority of our respondents expressed high levels of support for legalised abortion. Several sociodemographic factors were significantly associated with support for legalised abortion.

Public support and sociodemographic correlates of public breastfeeding support in New Zealand.

AIMS: The present study examined levels of support for public breastfeeding and sociodemographic correlates of public breastfeeding attitudes in New Zealand. METHOD: Data (N=19,598) were from the 2016/17 New Zealand Attitudes and Values Study, a nationwide longitudinal panel study of the social attitudes of New Zealand adults aged 18 and older. The survey included an item measuring support for women breastfeeding in public alongside relevant sociodemographic variables. RESULTS: Most New Zealanders (75.3%) supported breastfeeding in public, whereas a small minority (5.2%) were opposed (a further 19.5% were neutral on the issue). In terms of sociodemographic correlates of public breastfeeding support, men (relative to women), being older, identifying with a religion and being of Asian ethnicity (relative to European/Pakeha) were associated with lower support. Conversely, being a parent, having more children (given birth to, fathered or adopted), being in a serious romantic relationship, having attained higher education and being of Maori ethnicity (relative to European/Pakeha) were associated with greater support for public breastfeeding. CONCLUSIONS: New Zealanders expressed high levels of support for public breastfeeding. Reliable sociodemographic correlates of public breastfeeding support were also identified. These results provide the first comprehensive overview of New Zealanders' support towards breastfeeding in public.

Properties of Single-Walled Aluminosilicate Nanotube/Poly(vinyl alcohol) Aqueous Dispersions.

The properties of (synthesized) single-walled aluminosilicate nanotube (AlSiNT; light-scattering characterized length ∼2000 ± 230 nm and diameter ∼35 ± 4 nm) dispersed in an aqueous poly(vinyl alcohol) (PVA) solution (10 wt %) are systematically explored using a comprehensive combination of (polarized/depolarized) dynamic light scattering, rheological, rheo-optical, and scanning electron microscopy analysis schemes. The nanotube/polymer dispersions under investigation are promising for their fair nanotube dispersion in pristine aqueous media (e.g., without salt or acid addition), as well as for the optical transparency that greatly facilitates systematic exploration of structural features and dispersion state that are practically inaccessible for many of their (opaque) companions such as carbon nanotube dispersions. We provide the first in-depth analysis revealing excellent dispersion state of (unmodified) AlSiNT in the PVA matrix, giving rise to (critical) gel-like features and substantially promoted elasticity that can be utilized, as a practical assessment, to produce uniform and defect-free electrospun nanofibers. Additionally, there is unambiguous evidence of nematic liquid crystal-like "wagging" (strain-invariant, periodic oscillation) under steady shear flow, a phenomenon previously unreported for nanotube composite materials. Overall, the present findings suggest that AlSiNT/PVA dispersions possess promising rheological, optical, and electrospinning properties that are highly desirable for current nanotechnological applications, and may serve as an ideal model system for establishing structure-performance relationships for like nanotube/polymer composite materials.

Asexual Identity in a New Zealand National Sample: Demographics, Well-Being, and Health.

Academic interest in asexuality has increased in recent years; however, there is yet to be a national probability study exploring the correlates of self-identifying as asexual. Here, we utilized data from the 2014/15 New Zealand Attitudes and Values Study. Past research has typically used attraction-based measures; however, we asked participants to describe their sexual orientation using a self-generated, open-ended item, and 0.4% (n = 44) self-identified as asexual. We then compared self-identified asexual participants with a heterosexual reference group (n = 11,822) across a large number of demographic, psychological, and health variables. Relative to heterosexuals, self-identified asexual participants were (1) more likely to be women, and (2) substantially less likely to be cisgender, (3) in a serious romantic relationship, or (4) a parent. No deleterious mental or physical health effects were associated with asexuality when compared to heterosexuality. This study provides the first attempt at measuring self-identification as asexual in a national sample and highlights core similarities and differences between those who identify as asexual and heterosexual.

The Diversity and Prevalence of Sexual Orientation Self-Labels in a New Zealand National Sample.

In this study, we asked participants to "describe their sexual orientation" in an open-ended measure of self-generated sexual orientation. The question was included as part of the New Zealand Attitudes and Values Study (N = 18,261) 2013/2014 wave, a national probability survey conducted shortly after the first legal same-sex marriages in New Zealand. We present a two-level classification scheme to address questions about the prevalence of, and demographic differences between, sexual orientations. At the most detailed level of the coding scheme, 49 unique categories were generated by participant responses. Of those who responded with the following, significantly more were women: bisexual (2.1 % of women, compared to 1.5 % of men), bicurious (0.7 % of women, 0.4 % of men), and asexual (0.4 % of women and less than 0.1 % of men). However, significantly fewer women than men reported being lesbian or gay (1.8 % of women, compared to 3.5 % of men). Those openly identifying as bicurious, bisexual, or lesbian/gay were significantly younger than those with a heterosexual orientation. This study shows diversity in the terms used in self-generated sexual orientations, and provides up-to-date gender, age, and prevalence estimates for the New Zealand population. Finally, results reveal that a substantial minority of participants may not have understood the question about sexual orientation.

Benevolent Sexism, Attitudes Toward Motherhood, and Reproductive Rights: A Multi-Study Longitudinal Examination of Abortion Attitudes.

Although Benevolent Sexism (BS)-an ideology that highly reveres women who conform to traditional gender roles-is cloaked in a superficially positive tone, being placed upon a pedestal is inherently restrictive. Accordingly, because the paternalistic beliefs associated with BS are based on the idealization of traditional gender roles (which include motherhood), BS should predict people's attitudes toward women's reproductive rights. Using data from a nationwide longitudinal panel study (N = 12,299), Study 1 showed that BS (but not Hostile Sexism) had cross-lagged effects on opposition to both elective and traumatic abortion. Study 2 (N = 309) extended these findings by showing that the relationship between BS and support for abortion was fully mediated by attitudes toward motherhood. These results highlight the pernicious nature of BS by demonstrating that the idealization of women-and motherhood, in particular-comes at a substantial cost (namely, the restriction of women's reproductive rights).

Regional differences in the psychological recovery of Christchurch residents following the 2010/2011 earthquakes: a longitudinal study.

We examined changes in psychological distress experienced by residents of Christchurch following two catastrophic earthquakes in late 2010 and early 2011, using data from the New Zealand Attitudes and Values Study (NZAVS), a national probability panel study of New Zealand adults. Analyses focused on the 267 participants (172 women, 95 men) who were living in central Christchurch in 2009 (i.e., before the Christchurch earthquakes), and who also provided complete responses to our yearly panel questionnaire conducted in late 2010 (largely between the two major earthquakes), late 2011, and late 2012. Levels of psychological distress were similar across the different regions of central Christchurch immediately following the September 2010 earthquake, and remained comparable across regions in 2011. By late 2012, however, average levels of psychological distress in the regions had diverged as a function of the amount of property damage experienced within each given region. Specifically, participants in the least damaged region (i.e., the Fendalton-Waimairi and Riccarton-Wigram wards) experienced greater drops in psychological distress than did those in the moderately damaged region (i.e., across the Spreydon-Heathcote and Hagley-Ferrymead wards). However, the level of psychological distress reported by participants in the most damaged region (i.e., across Shirley-Papanui and Burwood-Pegasus) were not significantly different to those in the least damaged region of central Christchurch. These findings suggest that different patterns of psychological recovery emerged across the different regions of Christchurch, with the moderately damaged region faring the worst, but only after the initial shock of the destruction had passed.

Demographic and psychological predictors of panel attrition: evidence from the New Zealand attitudes and values study.

This study examines attrition rates over the first four years of the New Zealand Attitudes and Values Study, a longitudinal national panel sample of New Zealand adults. We report the base rate and covariates for the following four distinct classes of respondents: explicit withdrawals, lost respondents, intermittent respondents and constant respondents. A multinomial logistic regression examined an extensive range of demographic and socio-psychological covariates (among them the Big-Six personality traits) associated with membership in these classes (N = 5,814). Results indicated that men, Maori and Asian peoples were less likely to be constant respondents. Conscientiousness and Honesty-Humility were also positively associated with membership in the constant respondent class. Notably, the effect sizes for the socio-psychological covariates of panel attrition tended to match or exceed those of standard demographic covariates. This investigation broadens the focus of research on panel attrition beyond demographics by including a comprehensive set of socio-psychological covariates. Our findings show that core psychological covariates convey important information about panel attrition, and are practically important to the management of longitudinal panel samples like the New Zealand Attitudes and Values Study.