Control Package Research Articles

Scientific and Regulatory Lessons Learnt on Building a Chemistry, Manufacturing, and Controls (CMC) Package for COVID-19 Variant Vaccine Updates in the EU—A Regulator’s Perspective

During the COVID-19 pandemic, eight COVID-19 vaccines were authorised in the European Union (EU); as a result of emerging SARS-CoV-2 variants and waning immunity, some of these have been adapted to broaden the immunity against circulating variants. The pace at which variants emerge challenges the technical feasibility to make adapted vaccines available in a suitable timeframe and in sufficient quantities. Despite the current absence of a clear-cut seasonal spread for COVID-19, the EU regulatory approach thus far is a pragmatic approach following a pathway similar to that of seasonal influenza. This approach currently requires chemistry, manufacturing, and controls (CMC—the design, development and consistent manufacture of a specified medicinal product of good quality) and non-clinical data (from product laboratory and animal studies), as well as demonstrating that updated vaccines induce an immune response that can predict clinical efficacy and safety in humans. For CMC data, COVID-19 mRNA vaccine adaptations generally made use of the same formulation, control strategy, manufacturing process, and inclusion of registered manufacturing sites for the drug product; therefore assessment was generally streamlined. The experience gained from the vaccine adaptations, combined with a continuous early regulator-developer scientific discussion, permits increasingly greater predictability for timing and positive regulatory outcomes. Here, we review key aspects of the quality control and manufacture of updating COVID-19 vaccines to protect against new variants. Although most experience has been gained with mRNA vaccines, we note that investment in the streamlining of manufacturing processes for recombinant protein vaccines would facilitate future strain updates/adaptations thereby safeguarding availability of different COVID-19 vaccine types, which is considered of value for public health. We also reflect on the challenges and opportunities in establishing more predictable regulatory mechanisms for future COVID-19 vaccine adaptions and more widely for future vaccines containing rapidly evolving pathogens with the potential to cause health threats.

Exploring Management Control Systems for Biodiversity: Insights from Three Food Companies

ABSTRACT Despite growing recognition of the pressing need for companies to protect biodiversity, research has not yet provided a comprehensive overview to help guide companies on effective biodiversity management. This study identifies a package of intra-organisational biodiversity management controls that may be effective across multiple organisational contexts as well as individual controls that companies can choose from according to their specific contexts. For this purpose, we undertook an exploratory multiple case-study, selecting critical cases from the food sector on the basis of this industry’s enormous impacts on biodiversity loss and its existential dependence on preserving biodiversity. In analysing our interview and archival data we applied a framework of management control categories to investigate the research question ‘How do food companies use management control systems to address biodiversity?’ Our study contributes to practice and theory by providing a systematic overview of management controls and practices targeting key issues of biodiversity loss. Whilst confirming there is no one-size-fits-all approach, our findings indicate that companies should strive to integrate biodiversity-related controls with their core business, interlink biodiversity controls with existing sustainability controls, and complement informal with formal controls.

Exploring the heterogeneity of interstitial cells of Cajal and their properties in gastrointestinal mesenchymal tumors applying single-cell RNA sequencing analysis

BackgroundGastrointestinal mesenchymal stromal tumors (GISTs) are a group of intramural tumors that exhibit a wide range of morphologies. Dysfunction or loss of interstitial cells of Cajal (ICCs) is correlated with the disorders of gastrointestinal motility. At present, the characterization and molecular mechanisms underlying the role of ICCs in GIST are still not clear.MethodsThe GSE162115 dataset from Gene Expression Omnibus database was processed using Seurat package for quality control, data normalization, and cell clustering. Differential expression and functional enrichment analyses were performed using the FindAllMarkers function and clusterProfiler package. Cellular heterogeneity was assessed by CytoTRACE and potential regulatory mechanisms of ICCs in GISTs were investigated using SCENIC. Cellular communication was inferred and analyzed applying the CellChat package.ResultsEight clusters were identified based on 34,861 cells. Intra-tumor samples had a higher proportion of ICCs than peri-tumor. ICCs were related to cell cycle and glycolytic activity in intra-tumor samples, while those in peri-tumor samples were involved in immune response. Further analysis identified four ICC subgroups (subcluster 1–4), of which subcluster 3 showed the most typical stem cell properties and interacted with the rest of the cells through the MIF-CD74 (CD44) protein.ConclusionThis study analyzed the heterogeneity and stem cell properties of ICCs in GISTs, revealing the molecular mechanisms and potential therapeutic targets for GISTs.

P204 BANGLADESH HEARTS: LESSONS LEARNED FROM A NATIONAL HYPERTENSION CONTROL PROGRAM, 2018-2024

Background and Objective: In Bangladesh, 21% of all adults aged >=18 years have hypertension but among hypertensives, only 14.1% have blood pressure (BP) controlled (<140/90 mmHg) .1 To improve hypertension control and prevent cardiovascular disease, the Non-Communicable Disease Control Program under the Ministry of Health & Family Welfare launched the Bangladesh Hypertension Control Initiative (BHCI) with technical support from the National Heart Foundation of Bangladesh and Resolve to Save Lives. Method: The BHCI gradually implemented the World Health Organization (WHO) HEARTS standardized hypertension control package in 172 sub-district facilities (35% of all sub-district facilities) & 10 district-level facilities in 23 districts from 2018 to 2024. BHCI facilities implemented a simple, evidence-based, step-by-step, and drug & dose-specific hypertension treatment protocol, a reliable supply of protocol medicines free of charge to patients, team-based care including non-physician members, and the Simple digital hypertension management app to collect real-time data and facilitate patient and program monitoring over time. A continuous quality improvement initiated in 2020 focused on lowering missed visit rate and raising blood pressure control. Missed visit rate was the proportion of all enrolled patients failing to attend a scheduled clinic visit in the prior three months; BP control was proportion with BP <140/90 mmHg at their last visit in the prior three months. Results: From March 2019 to February 2024, the BHCI had enrolled 364,038 hypertensive patients in treatment (Figure). Facility-based BP control increased from 37% in July 2020 when the quality improvement program started to 57% by April 2024. Missed visits decreased from 53% in July 2020 to 29% by April 2024. Conclusion: BHCI is on track for national scale-up in Bangladesh and can serve as a model for WHO-HEARTS hypertension control programs in other LMIC countries. Reference: 1. World Health Organization. National STEPS survey for non-communicable diseases risk factors in Bangladesh 2018. Panel A: number of hypertension patients enrolled in treatment. Panel B: rates of missed hypertension management visits and blood pressure controlled <140/90

Evaluation of the World Health Organization-HEARTS hypertension control package in Bangladesh: a quasi-experimental trial

BackgroundThe World Health Organization (WHO) promotes the HEARTS technical package for improving hypertension control worldwide, but its effectiveness has not been rigorously evaluated.ObjectiveTo compare hypertension outcomes in clinics implementing HEARTS...

Massively parallel sample preparation for multiplexed single-cell proteomics using nPOP.

Single-cell proteomics by mass spectrometry (MS) allows the quantification of proteins with high specificity and sensitivity. To increase its throughput, we developed nano-proteomic sample preparation (nPOP), a method for parallel preparation of thousands of single cells in nanoliter-volume droplets deposited on glass slides. Here, we describe its protocol with emphasis on its flexibility to prepare samples for different multiplexed MS methods. An implementation using the plexDIA MS multiplexing method, which uses non-isobaric mass tags to barcode peptides from different samples for data-independent acquisition, demonstrates accurate quantification of ~3,000-3,700 proteins per human cell. A separate implementation with isobaric mass tags and prioritized data acquisition demonstrates analysis of 1,827 single cells at a rate of >1,000 single cells per day at a depth of 800-1,200 proteins per human cell. The protocol is implemented by using a cell-dispensing and liquid-handling robot-the CellenONE instrument-and uses readily available consumables, which should facilitate broad adoption. nPOP can be applied to all samples that can be processed to a single-cell suspension. It takes 1 or 2 d to prepare >3,000 single cells. We provide metrics and software (the QuantQC R package) for quality control and data exploration. QuantQC supports the robust scaling of nPOP to higher plex reagents for achieving reliable and scalable single-cell proteomics.

골판지 포장지의 알루미늄 코팅이 팽이버섯의 저온저장 중 품질 특성에 미치는 영향

We examined the physicochemical properties and microbial safety of Enoki mushrooms during storage at 5°C for 9 weeks, with different packaging containers that are corrugated, Al-coated, and without packaging (control). The weight change of Enoki mushrooms in the different containers due to moisture loss was 1.9%, 0.9%, 0.6% for control, corrugated, and Al-coated packaging, respectively. The degree of browning rapidly increased as the storage period increased in the control sample. However, corrugated and Al-coated packaging suppressed the browning degree. The changes of color L-, a-, and b-vlaues were minimal changes in Al-coated packaging. There was no significant difference in the total amino acids, polyphenol oxidase, and peroxidase in corrugated packaging and Al-coated packaging, regardless of the storage period. The microbial growth such as total aerobic bacteria, yeast, and mold of Enoki mushroom during the storage period, were significantly suppressed in Al-coated packaging samples as compared to the control and corrugated packaging. In conclusion, Al-coated packaging has beneficial effects such as preventing moisture loss, maintaining browning degree, inhibiting oxidative enzyme reaction, and ensuring microbial safety of Enoki mushrooms during the storage period. Al-coated packaging is considered effective for extending the shelf-life and improving the storage and distribution of mushrooms.

골판지 포장지의 알루미늄 코팅이 팽이버섯의 저온저장 중 품질 특성에 미치는 영향

We examined the physicochemical properties and microbial safety of Enoki mushrooms during storage at 5°C for 9 weeks, with different packaging containers that are corrugated, Al-coated, and without packaging (control). The weight change of Enoki mushrooms in the different containers due to moisture loss was 1.9%, 0.9%, 0.6% for control, corrugated, and Al-coated packaging, respectively. The degree of browning rapidly increased as the storage period increased in the control sample. However, corrugated and Al-coated packaging suppressed the browning degree. The changes of color L-, a-, and b-vlaues were minimal changes in Al-coated packaging. There was no significant difference in the total amino acids, polyphenol oxidase, and peroxidase in corrugated packaging and Al-coated packaging, regardless of the storage period. The microbial growth such as total aerobic bacteria, yeast, and mold of Enoki mushroom during the storage period, were significantly suppressed in Al-coated packaging samples as compared to the control and corrugated packaging. In conclusion, Al-coated packaging has beneficial effects such as preventing moisture loss, maintaining browning degree, inhibiting oxidative enzyme reaction, and ensuring microbial safety of Enoki mushrooms during the storage period. Al-coated packaging is considered effective for extending the shelf-life and improving the storage and distribution of mushrooms.

Enhanced stability of encapsulated lemongrass essential oil in chitosan-gelatin and pectin-gelatin biopolymer matrices containing ZnO nanoparticles

The use of essential oils is widespread in various fields such as pharmacy, pest control, and active packaging. However, their instability and short-term effects require methods to enhance their durability and effectiveness. Encapsulation in biopolymer matrices appears to be a promising approach due to the environmental safety and cost-effectiveness of such formulations. In this study, different oil-in-water emulsions were prepared by mixing chitosan-gelatin (C-G) or pectin-gelatin (P-G) solutions with lemongrass essential oil (LG). ZnO NPs were used as an additional active component. Encapsulation in biopolymer matrices resulted in stable emulsions with a significantly slower release of LG, and ZnO NPs further suppressed LG release, particularly in the P-G emulsion. They also contributed to the stability of the emulsions and a decrease in the average droplet size of LG. Furthermore, the presence of LG and ZnO NPs improved the smoothness of the films prepared from the emulsions and dispersions using the casting technique. SEM/EDS analysis confirmed the homogeneous distribution of ZnO NPs in both C-G and P-G films. By adjusting the type and content of the biopolymers and NPs, such emulsions could be effectively utilized in various applications where controlled release of active components is required.

Enterprise Risk Management as Part of the Organizational Control Package: Review and Implications for Management Accounting Research

ABSTRACT Research on enterprise risk management (ERM) has increased considerably in the past two decades. Although management accounting researchers have substantially contributed to these advancements, previous reviews of the ERM literature have not discussed in depth the role of ERM as part of the organizational control package and how management accounting research could build on its research traditions to further our collective understanding of ERM. In this paper, we therefore adopt a management control perspective to critically analyze both quantitative and qualitative empirical ERM research and specifically focus on the integration of ERM in organizational control packages. Taking a complementarity perspective and accounting for the decision-facilitating and decision-influencing purposes of management accounting and control systems (MACS), we recommend several broader avenues for future management accounting research on ERM.

Inner struggle or identity fit – control configurations that improve management accountants’ sense of their identity

PurposeThis study aims to investigate which configurations of organizational-level and group-level management controls support an identity fit for management accountants in the management accounting profession. It aims to complement recent qualitative management accounting research. This stream just begun to use role and identity theory to investigate role expectations, conflicts and coping strategies of management accountants when they struggle with their work identity.Design/methodology/approachBased on configuration theory, this study uses a fuzzy-set qualitative comparative analysis to indicate all possible configurations of formal and informal management controls that improve management accountants’ sense of their identity in an organization. The analyses are based on the results of a cross-sectional survey of 277 management accountants from Germany, Austria, Switzerland and Liechtenstein.FindingsThe results show that a strong group culture and high psychological safety at the group level are relevant conditions for a high identity fit. Further, the configurations differ regarding the career stages of management accountants.Originality/valueThis study contributes to work identity research of management accountants and to research on formal and informal control configurations as a control package. It is of particular importance for various professions that are affected by role change, as from the findings on management accountants’ identity fit, implications can also be made for other organizational functions that need to engage in identity work.

Agweather-qaqc: An Interactive Python Package for Quality Assurance and Quality Control of Daily Agricultural Weather Data and Calculation of Reference Evapotranspiration

agweather-qaqc: An Interactive Python Package for Quality Assurance and Quality Control of Daily Agricultural Weather Data and Calculation of Reference Evapotranspiration

MISTER-T: An open-source software package for quantum optimal control of multi-electron systems on arbitrary geometries

We present an open-source software package, MISTER-T (Manipulating an Interacting System of Total Electrons in Real-Time), for the quantum optimal control of interacting electrons within a time-dependent Kohn-Sham formalism. In contrast to other implementations restricted to simple models on rectangular domains, our method enables quantum optimal control calculations for multi-electron systems (in the effective mass formulation) on nonuniform meshes with arbitrary two-dimensional cross-sectional geometries. Our approach is enabled by forward and backward propagator integration methods to evolve the Kohn-Sham equations with a pseudoskeleton decomposition algorithm for enhanced computational efficiency. We provide several examples of the versatility and efficiency of the MISTER-T code in handling complex geometries and quantum control mechanisms. The capabilities of the MISTER-T code provide insight into the implications of varying propagation times and local control mechanisms to understand a variety of strategies for manipulating electron dynamics in these complex systems. Program summaryProgram Title: MISTER-TCPC Library link to program files:https://doi.org/10.17632/psymy4ddnw.1Licensing provisions: GNU General Public License 3Programming language: MATLABSupplementary material: animated movies of total electron densities under the influence of optimal control fields for (1) an asymmetric double-well potential for long propagation times, (2) an asymmetric double-well potential for short propagation times, and (3) a triple-well potential with a position-dependent effective mass.Nature of problem: The MISTER-T code solves quantum optimal control problems for interacting electrons within a time-dependent Kohn-Sham formalism. It can handle two-dimensional systems with arbitrary cross-sectional geometries within the effective mass formulation. The user-friendly code uses forward and backward propagator integration methods to evolve the Kohn-Sham equations with a pseudoskeleton decomposition algorithm for enhanced computational efficiency.Solution method: iterative solution of the quantum optimal control equations using finite element methods, effective mass formulation, pseudoskeleton decomposition, sparse matrix linear algebra, and nonuniform fast Fourier transforms.

A fairy tale with an unhappy ending: the organizational regulation of “Latina accountant identity” in Spain

PurposeIdentity regulation is part of a management control package. Organizations regulate employees’ self-identity to influence their behaviors. The success of this regulation depends on its trade-off with employees’ work identities and personalities. Organizational discourse nurtures this dynamic and interactive process. We focus on the regulation of an (undesired) organizational identity that is born at the intersection of race/ethnicity, gender, sex and migrant discrimination in accounting-related positions. We aim to analyze how Latina accountants who migrate to Spain perceive that their triple status as Latina, women and migrants affects their careers as accountants and interpret whether this triple intersectional discrimination aims to create a Latina accountant’s self-identity.Design/methodology/approachThis critical study follows a phenomenological approach to analyze the experiences of women born in Latin America who migrated to Spain to occupy accounting-related positions. A thematic analysis of their semi-structured interviews allowed us to examine the challenges faced by Latina accountants in their accounting careers in Spain.FindingsOur interviewees' narratives display an internalization of, even resignation to, a self-identity that we label “Latina accountant identity.” This identity is based on explicit discrimination discourses that cause them to suffer from the intersection of racism, sexism and migrant conditions and is nurtured by the discourses of their senior managers, co-workers and subordinates.Originality/valueTo the best of our knowledge, this is the first study to frame the regulation of an intersectional discriminatory identity that is used to control Latina accountants from the inside, acting on the triple condition of Latinas, women and foreigners, influencing their self-perceptions regarding work and personal lives.

A Cost-Effective Integrated Methodology for Electromagnetic Actuation via Visual Feedback.

Electromagnetic actuation can support many fields of technology, such as robotics or biomedical applications. In this context, fully understanding the system behavior and proposing a low-cost package for feedback control is challenging. Modeling the electromagnetic force is particularly tricky because it is a nonlinear function of the actuated object's position and coil's current. Measuring in real time the position of the actuated object with the precision required for accurate motion control is also nontrivial. In this study, we propose a novel, cost-effective electromagnetic set-up to achieve position control via visual feedback. We actuated vertically and under different experimental conditions a 10 mm diameter steel ball hanging on a low-stiffness spring, demonstrating good tracking performance (the position error remained within ±0.5 mm, with a negligible phase delay in the best scenarios). The experimental results confirm the feasibility of the proposed set-up, which is characterized by minimum complexity and realized with off-the-shelf and cost-effective components. For these reasons, such a contribution helps to understand and apply electromagnetic actuation even further.

Classification of LED Packages for Quality Control by Discriminant Analysis, Neural Network and Decision Tree.

This study investigates supervised learning to improve LED classification. A hardware system for testing was built. The data for learning were acquired and then analyzed to show their characteristics. An LED was tested, and the results were categorized into three defective LED groups and one normal LED group. Before classification, electrical and optical data were examined to identify their characteristics. To find out the best way for quality control, an ensemble of methods was used. First, the discriminant analysis using the validation data achieved a 77.9% true positive rate for normal products, inadequate for quality control. Second, neural network-based learning boosted this rate to 97.8%, but the 2.2% false negative rate remained problematic. Finally, a binary decision tree was constructed, achieving a 99.4% true positive rate from just 14 splits, proving highly effective in product classification. The training time was measured as 8.1, 18.2 and 8.2 s for discriminant analysis, neural network and decision tree, respectively. This work has found the binary decision tree is advantageous considering both learning and classification efficiencies.

VO2 nano-rod coated mica composite pearlescent pigment for temperature control packaging

A temperature control mica/VO2 functional pearlescent pigment was designed for the packaging industry. Firstly, a layer of VO2 nanorod film was coated on the surface of flake mica powder by hydrothermal method. Then, the surface of pure mica was modified by silane coupling agent KH-570 and sandwiched between inorganic powders to strengthen the combination. Secondly, the mica/VO2 composite pearlescent powder with gray-green pearlescent effect were successfully obtained by thermal annealing. The crystal structure of the VO2 coating and the chemical valence state of vanadium were verified by X-ray diffraction and X-ray photoelectron spectroscopy. Finally, powders were mixed with polyurethane resin to obtain a functional film. The infrared transmittance of film at 28 °C and 70 °C showed that the composite film with mica content of 3 g had greater temperature control properties, and the difference between high and low temperature transmittance was about 16%. Most importantly, the shiny decorative effect of pearlescent pigment can be still be maintained after being endowed with temperature control property. This work proposes the preparation of functional mica/VO2 composite with pearlescent effect and temperature control property.

Mechatronic Spatial Atomic Layer Deposition for Closed‐Loop and Customizable Process Control

AbstractA customized atmospheric‐pressure spatial atomic layer deposition (AP‐SALD) system is designed and implemented, which enables mechatronic control of key process parameters, including gap size and parallel alignment. A showerhead depositor delivers precursors to the substrate while linear actuators and capacitance probe sensors actively maintain gap size and parallel alignment through multiple‐axis tilt and closed‐loop feedback control. Digital control of geometric process variables with active monitoring is facilitated with a custom software control package and user interface. AP‐SALD of TiO2 is performed to validate self‐limiting deposition with the system. A novel multi‐axis printing methodology is introduced using x‐y position control to define a customized motion path, which enables an improvement in the thickness uniformity by reducing variations from 8% to 2%. In the future, this mechatronic system will enable experimental tuning of parameters that can inform multi‐physics modeling to gain a deeper understanding of AP‐SALD process tolerances, enabling new pathways for non‐traditional SALD processing that can push the technology towards large‐scale manufacturing.

Re-Fining Citrus Leaf and Fruit Spot Disease Control Options in Northern Uganda

Citrus leaf and fruit spot disease, caused by Pseudocercospora angolensis has, since 2010, come about as the most dreadful disease of citrus in Northern Uganda. Over the last few years, feedback from citrus farmers has helped in re-fining management strategies. In the first years of citrus leaf and fruit spot disease outbreak in Northern Uganda, chemical treatment was promoted as part of a control package, in addition to the destruction of heavily diseased plants and buckthorn to remove inoculum. Buck horning and destruction of diseased plants is labour-intensive and time-consuming, especially when many infected citrus trees have to be taken out, or buck horned. Research findings indicate citrus leaf and fruit spot disease fungus can be weakened with fungicide sprays to the extent that even when disease symptoms are present on leaves, it does not automatically lead to infection of fruits. This gave rise to a new control strategy where only infected plants in an orchard are pruned, and all the citrus trees in the orchard are treated with fungicides. The pruning of visibly infected plants in an orchard will lessen the inoculum load, and the fungicide sprays will stop pathogen replication. This method is not labour intensive and takes less time when equated to severe buck horning of all the trees in the orchard. However, pruning and fungicide treatment need to move together with the control of new infections that can happen via unrestricted entry during harvesting

The integration of risk into management control systems: towards a deeper understanding across multiple levels of analysis

The integration of risk into management control has recently received increased attention in the management accounting and control literature. Much of this research has focused on the organizational and individual actor level. However, some studies suggest that the integration of risk into the organizational control package may equally be influenced by forces operating at other levels of analysis– including the economic and political level and the organizational field level. In this guest editorial for the special issue on “Courageous Risk Governance: Enabling Resilience, Autonomy, and New Thinking,” I therefore discuss how our collective understanding of the integration of risk into management control could be enhanced by research at multiple levels of analysis. The papers included in this special issue show that when this integration is successfully managed, organizations can achieve valuable outcomes, such as increased resilience. For both practitioners and academics, future research on such integration therefore seems fruitful and necessary. This article provides ideas for particularly relevant questions about this integration and for theories that can guide such research.