Johnson & Johnson (Ireland)

Industrial IoT (IIoT) is a novel concept of a fully connected, transparent, automated, and intelligent factory setup improving manufacturing processes and efficiency. To achieve this, existing hierarchical models must transition to a fully connected vertical model. Since IIoT is a novel approach, the environment is susceptible to cyber threat vectors, standardization, and interoperability issues, bridging the gaps at the IT/OT ICS (industrial control systems) level. IIoT M2M communication relies on new communication models (5G, TSN ethernet, self-driving networks, etc.) and technologies which require challenging approaches to achieve the desired levels of data security. Currently there are no methods to assess the vulnerabilities/risk impact which may be exploited by malicious actors through system gaps left due to improper implementation of security standards. The authors are currently working on an Industry 4.0 cybersecurity project and the insights provided in this paper are derived from the project. This research enables an understanding of converged/hybrid cybersecurity standards, reviews the best practices, and provides a roadmap for identifying, aligning, mapping, converging, and implementing the right cybersecurity standards and strategies for securing M2M communications in the IIoT.

The development of advanced autonomous mobile robots (AMRs) is essential for achieving the flexible work environment necessary for smart manufacturing. Complex perception, locomotion and navigation systems comprised of many sensors and powerful processors allow AMRs to continuously monitor their surroundings and internal systems. AMRs that can move freely around an industrial facility are increasingly required for 24/7 industrial processes. The energy requirements of AMRs can include the need for high power for tasks such as lifting and transporting as well as low power for the various onboard sensors. Total operating time between charges is dependent on factors such as distance travelled, payload power consumption, payload/cargo mass and AMR attachments such as tilt trays or robotic arms. This review discusses pre-existing commercial AMRs, their power consumption and compares the specifications of battery packs which are being used in the current generation of AMRs. This is followed by a detailed discussion about lithium-ion battery operation and recommendations for cathode and anode materials to replace traditionally used electrode materials to meet the growing power demands of next generation AMRs in the short to medium term (5–10 years) and in the long term (10+ years).

BACKGROUND: Initial studies investigating correlations between stroke etiology and clot composition are conflicting and do not account for clot size as determined by area. Radiological studies have shown that cardioembolic strokes are associated with shorter clot lengths and lower clot burden than non-cardioembolic clots. OBJECTIVE: To report the relationship between stroke etiology, extracted clot area, and histological composition at each procedural pass. METHODS: As part of the multi-institutional RESTORE Registry, the Martius Scarlett Blue stained histological composition and extracted clot area of 612 per-pass clots retrieved from 441 patients during mechanical thrombectomy procedures were quantified. Correlations with clinical and procedural details were investigated. RESULTS: Clot composition varied significantly with procedural passes; clots retrieved in earlier passes had higher red blood cell content (H4=11.644, p=0.020) and larger extracted clot area (H4=10.730, p=0.030). Later passes were associated with significantly higher fibrin (H4=12.935, p=0.012) and platelets/other (H4=15.977, p=0.003) content and smaller extracted clot area. Large artery atherosclerotic (LAA) clots were significantly larger in the extracted clot area and more red blood cell-rich than other etiologies in passes 1-3. Cardioembolic and cryptogenic clots had similar histological composition and extracted clot area across all procedural passes. CONCLUSION: LAA clots are larger and associated with a large red blood cell-rich extracted clot area, suggesting soft thrombus material. Cardioembolic clots are smaller in the extracted clot area, consistent in composition and area across passes, and have higher fibrin and platelets/other content than LAA clots, making them stiffer clots. The per-pass histological composition and extracted clot area of cryptogenic clots are similar to those of cardioembolic clots, suggesting similar formation mechanisms.

Smart manufacturing is a vision and major driver for change in today's industry. The goal of smart manufacturing is to optimize manufacturing processes through constantly monitoring, controlling, and adapting processes towards more efficient and personalised manufacturing. This requires and relies on technologies for connected machines incorporating a variety of computation, sensing, actuation, and machine to machine communications modalities. As such, understanding the change towards smart manufacturing requires knowledge of the enabling technologies, their applications in real world scenarios and the communication protocols and their performance to meet application requirements. Particularly, wireless communication is becoming an integral part of modern smart manufacturing and is expected to play an important role in achieving the goals of smart manufacturing. This paper presents an extensive review of wireless communication protocols currently applied in manufacturing environments and provides a comprehensive review of the associated use cases whilst defining their expected impact on the future of smart manufacturing. Based on the review, we point out a number of open challenges and directions for future research in wireless communication technologies for smart manufacturing.

Industry 5.0 envisions close cooperation between humans and machines requiring ultra-reliable low-latency communications (URLLC). The intelligent reflecting surface (IRS) has the potential to play a crucial role in realizing wireless URLLC for Industry 5.0. IRS is forecast to be a key enabler of 6G wireless communication networks as it can significantly improve wireless network performance by creating a controllable radio environment. In this article, we first provide an over-view of IRS technology and then conceptualize the potential for IRS implementation in a future smart manufacturing environment to support the emergence of Industry 5.0 with a series of applications. Finally, to stimulate future research in this area, we discuss the strength, open challenges, and opportunities of IRS technology in modern smart manufacturing.

BACKGROUND: Acute ischaemic stroke due to distal medium vessel occlusion (AIS-DMVO) causes significant morbidity. Endovascular thrombectomy advancement has made treating AIS-DMVO with stent retrievers (SR) and aspiration catheters (AC) possible, however the optimal technique remains unknown. We performed a systematic review and meta-analysis to investigate the efficacy and safety of SR use compared to purely AC use in patients with AIS-DMVO. METHODS: We systematically searched PubMed, Cochrane Library and EMBASE, from inception to 2nd September 2022, for studies comparing SR or primary combined (SR/PC) against AC in AIS-DMVO. We adopted the Distal Thrombectomy Summit Group's definition of DMVO. Efficacy outcomes were functional independence (modified Rankin Scale (mRS) 0-2 at 90 days), first pass effect (modified Thrombolysis in Cerebral Infarction scale (mTICI) 2c-3 or expanded Thrombolysis in Cerebral Infarction scale (eTICI) 2c-3 at first pass), successful final recanalisation (mTICI or eTICI 2b-3), and excellent final recanalisation (mTICI or eTICI 2c-3). Safety outcomes were symptomatic intracranial haemorrhage (sICH) and 90-day mortality. RESULTS: 12 cohort studies and 1 randomised-controlled trial were included, involving 1881 patients with 1274 receiving SR/PC and 607 receiving AC only. SR/PC achieved higher odds of functional independence (odds ratio (OR) 1.33, 95% confidence interval (CI) 1.06-1.67) and lower odds of mortality (OR 0.69, 95% CI 0.50-0.94) than AC. Odds of successful/excellent recanalisation and sICH were similar between both groups. Stratified to compare only SR and only AC, the use of only SR, achieved significantly higher odds of successful recanalisation as compared to only AC (OR 1.80, 95% CI 1.17-2.78). CONCLUSION: There is potential for efficacy and safety benefits in SR/PC use as compared to AC only in AIS-DMVO. Further trials are necessary to validate the efficacy and safety of SR use in AIS-DMVO.

This work aims to apply the Theory of Critical Distances (TCD) to the fatigue assessment of additively manufactured (AM) Ti-6Al-4V material produced via the selective laser melting (SLM) process. Modified alternatives to traditional TCD methods are considered. In this sense, it is sought to develop a fatigue prediction model that is better suited to assessing the impact of multiple stress-rising features which are located in close proximity to each other. Hereby, consideration has been given to modelling process-inherent surface roughness in combination with an internally positioned artificial defect, shaped as a feature that is reminiscent of a pore. Simultaneously, the research also seeks to circumnavigate a potential issue with respect to the current TCD methodology. This concerns the matter of applying TCD practices to components whereby the area of interest for conducting stress-distance analytics is on a size scale that is smaller than that of the critical distance length parameter itself. Several different strategies were attempted as a way to try and achieve meaningful modifications to the TCD process. Results show that it is possible to overcome such challenges that can often present themselves during the fatigue appraisal of AM metal parts. In this sense, the optimal novel strategy that was experimented with returned average error margins of 13.7% or better. It is anticipated that such models may assist in further optimising the accuracy of service life evaluation for metallic AM components that are intended for industry.

As the pharmaceutical industry seeks more efficient methods for the production of higher value therapeutics, the associated data analysis, data visualization, and predictive modeling require dependable data origination, management, transfer, and integration. As a result, the management and integration of data in a consistent, organized, and reliable manner is a big challenge for the pharmaceutical industry. In this work, an ontological information infrastructure is developed to integrate data within manufacturing plants and analytical laboratories. The ANSI/ISA-88.01 batch control standard has been adapted in this study to deliver a well-defined data structure that will improve the data communication inside the system architecture for continuous processing. All the detailed information of the lab-based experiment and process manufacturing, including equipment, samples and parameters, are documented in the recipe. This recipe model is implemented into a process control system (PCS), data historian, as well as Electronic Laboratory Notebook (ELN) system. Data existing in the recipe can be eventually exported from this system to cloud storage, which could provide a reliable and consistent data source for data visualization, data analysis, or process modeling.

In-vitro neurovascular models of large vessel occlusions (LVOs) causing acute ischemic stroke (AIS) are used extensively for pre-clinical testing of new treatment devices. They enable physicians and engineers to examine device performance and the response of the occlusion to further advance design solutions for current unmet clinical needs. These models also enable physicians to train on basic skills, to try out new devices and new procedural approaches, and for the stroke team to practice workflows together in the comfort of a controlled environment in a non-clinical setting. Removal of the occlusive clot in its entirety is the primary goal of the endovascular treatment of LVOs via mechanical thrombectomy (MT) and the medical treatment via thrombolysis. In MT, recanalization after just one pass is associated with better clinical outcomes than procedures that take multiple passes to achieve the same level of recanalization, commonly known as first pass effect (FPE). To achieve this, physicians and engineers are continually investigating new devices and treatment approaches. To distinguish between treatment devices in the pre-clinical setting, test models must also be optimized and expanded become more nuanced and to represent challenging patient cohorts that could be improved through new technology or better techniques. The aim of this paper is to provide a perspective review of the recent advancements in the in-vitro modeling of stroke and to outline how these models need to advance further in future. This review provides an overview of the various in-vitro models used for the modeling of AIS and compares the advantages and limitations of each. In-vitro models remain an extremely useful tool in the evaluation and design of treatment devices, and great strides have been made to improve replication of physiological conditions. However, further advancement is still required to represent the expanding indications for thrombectomy and thrombolysis, and the generation of new thrombectomy devices, to ensure that smaller treatment effects are captured.

Meniscus injuries are a common problem in orthopedic medicine and are associated with a significantly increased risk of developing osteoarthritis. While developments have been made in the field of meniscus regeneration, the engineering of cell-laden constructs that mimic the complex structure, composition and biomechanics of the native tissue remains a significant challenge. This can be linked to the use of cells that are not phenotypically representative of the different zones of the meniscus, and an inability to direct the spatial organization of engineered meniscal tissues. In this study we investigated the potential of zone-specific meniscus progenitor cells (MPCs) to generate functional meniscal tissue following their deposition into melt electrowritten (MEW) scaffolds. We first confirmed that fibronectin selected MPCs from the inner and outer regions of the meniscus maintain their differentiation capacity with prolonged monolayer expansion, opening their use within advanced biofabrication strategies. By depositing MPCs within MEW scaffolds with elongated pore shapes, which functioned as physical boundaries to direct cell growth and extracellular matrix production, we were able to bioprint anisotropic fibrocartilaginous tissues with preferentially aligned collagen networks. Furthermore, by using MPCs isolated from the inner (iMPCs) and outer (oMPCs) zone of the meniscus, we were able to bioprint phenotypically distinct constructs mimicking aspects of the native tissue. An iterative MEW process was then implemented to print scaffolds with a similar wedged-shaped profile to that of the native meniscus, into which we deposited iMPCs and oMPCs in a spatially controlled manner. This process allowed us to engineer sulfated glycosaminoglycan and collagen rich constructs mimicking the geometry of the meniscus, with MPCs generating a more fibrocartilage-like tissue compared to the mesenchymal stromal/stem cells. Taken together, these results demonstrate how the convergence of emerging biofabrication platforms with tissue-specific progenitor cells can enable the engineering of complex tissues such as the meniscus.

Digitalization in manufacturing is the conversion of information into digital format, the integration of this digital data and technologies into the manufacturing process and the use of those technologies (eg: simulation) to change a business model to provide new revenue and value-producing opportunities. Digitalization may be seen as the increased generation, analysis, and use of data to improve the efficiency of the overall manufacturing system. Simulation in manufacturing is often applied in situations where conducting experiments on a real system is impossible or very difficult due to cost or time to carry out the experiment is too long. A key input to the simulation model of automated equipment is the acquisition of valid data in relation to cycle time and reliability of various workstations on this line. As a consequence of being able to simulate equipment processes and interact with this validated simulation model, both the understanding of how the production system will perform under varying reliability and cycle time conditions is achieved. The simulation model then enables the experimentation of ‘what if scenarios’ that can be tested easily, while also providing a valuable tool to inform the maintenance personnel what station reliabilities they need to target in order to sustain a high performing manufacturing line. Simulation metamodeling is an approach to line design which is of great interest to design engineers and research experts. However, its application in automated medical devices manufacturing line design has never been well explored. The author has adopted an open-source simulation tool (JaamSim) to develop a digital model of an automated medical devices manufacturing line in the Johnson & Johnson Vision Care (JJVC) manufacturing facility. This paper demonstrates with a high level of rigour, fidelity and overall system design/approach, how a digital model along with the use of a metamodel can be used for the development of an automated manufacturing line in the medical devices industry. The digital model and metamodel can be used by manufacturing engineering teams to perform scenario testing during the design and development phase of the line or as part of the continuous improvement stage when the line is in full operation. The overall average absolute error when comparing the simulation model outputs to the metamodel outputs was 0.87% was achieved with the metamodel for the actual industrial application used by the author.

The meniscus is a fibrocartilage tissue that is integral to the correct functioning of the knee joint. The tissue possesses a unique collagen fiber architecture that is integral to its biomechanical functionality. In particular, a network of circumferentially aligned collagen fibers function to bear the high tensile forces generated in the tissue during normal daily activities. The limited regenerative capacity of the meniscus has motivated increased interest in meniscus tissue engineering; however, the in vitro generation of structurally organized meniscal grafts with a collagen architecture mimetic of the native meniscus remains a significant challenge. Here we used melt electrowriting (MEW) to produce scaffolds with defined pore architectures to impose physical boundaries upon cell growth and extracellular matrix production. This enabled the bioprinting of anisotropic tissues with collagen fibers preferentially oriented parallel to the long axis of the scaffold pores. Furthermore, temporally removing glycosaminoglycans (sGAGs) during the early stages of in vitro tissue development using chondroitinase ABC (cABC) was found to positively impact collagen network maturation. Specially we found that temporal depletion of sGAGs is associated with an increase in collagen fiber diameter without any detrimental effect on the development of a meniscal tissue phenotype or subsequent extracellular matrix production. Moreover, temporal cABC treatment supported the development of engineered tissues with superior tensile mechanical properties compared to empty MEW scaffolds. These findings demonstrate the benefit of temporal enzymatic treatments when engineering structurally anisotropic tissues using emerging biofabrication technologies such as MEW and inkjet bioprinting.

We are investigating the characteristics of wireless channels in a factory floor environment through simulation and experimentation. We simulate the communication coverage of 5G indoor factory (InF) networks using both, ray tracing and statistical channel models. A ray tracing model requires detailed models of the environment, including their properties and locations, whereas an empirical statistical model does not need such details. Through simulation, we compare the InF wireless channel characteristics obtained from ray tracing and statistical models. Different channel characterization metrics are considered in the comparison, including Reference Signal Received Power (RSRP), channel gain, and SNR. For the purpose of validating the simulation results, we have conducted experiments with a private 5G test-bed on a real-world factory floor. For our use case, we used a factory hall with two 5G radio heads in different positions. Our study demonstrates the viability of the 3GPP InF model, providing more accurate predictions than ray tracing while using less data and significantly quicker simulation run times.

BACKGROUND: Patients with relapsed/refractory multiple myeloma (RRMM) who develop extramedullary disease (EMD) generally have a poor prognosis, highlighting the urgent need for new therapies. We report effectiveness outcomes and safety in patients with and without EMD from the pooled analysis of LocoMMotion and MoMMent. METHODS: LocoMMotion and MoMMent-1 are prospective, noninterventional, consecutive studies assessing the evolving standard of care from 20192022 in patients with triple-class exposed RRMM. RESULTS: Of 302 patients, 29 had EMD per investigator discretion and only 15 patients were assessed as having true extramedullary plasmacytoma (EMP; defined as patients with ≥1 EMP lesion) by the response review committee. The 29 EMD patients received 21 unique regimens (most commonly chemotherapy-based regimens). Of the 29 patients with EMD, overall response rate (ORR) was 24.1%, median progression-free survival (PFS) was 2.66 months, median overall survival (OS) was 7.16 months, and median time to next treatment (TTNT) was 3.09 months. All responses were lower (ORR) and shorter (median PFS, OS, and TTNT) in patients with EMD vs patients without EMD. Nineteen (65.5%) patients with EMD received ≥1 subsequent lines of therapy. Of those, two (10.5%) patients received bispecific antibodies and achieved a partial response or better; three (15.8%) patients received antibody-drug conjugates (responses were unknown or not determined at data cut-off), and no patients received chimeric antigen receptorT cell therapy. CONCLUSIONS: These results demonstrate the urgent need for more effective novel therapies for patients with EMD and highlight the need to use clear definitions of EMD and EMD response criteria for clinical trials.

As manufacturing capital equipment is expensive, it is necessary that the equipment once in operation is reliable and delivers to the business plan targets. Simulation along with an optimization system is an invaluable tool to confirm that an automated manufacturing line can produce to the required business objectives before and after it goes into operation. Simulation in manufacturing is often applied in situations where conducting experiments on a real system is very difficult often because of cost or the time to carry out the experiment is too long. Optimization is the organized search for such designs and operating modes to find the best available solution from a set of feasible solutions. It determines the set of actions or elements that must be implemented to achieve an optimized manufacturing line. As a result of being able to concurrently simulate and optimize equipment processes, the understanding of how the actual production system will perform under varying conditions is achieved. Implementing the actual changes to equipment to improve reliability can be both time consuming and expensive. Simulation in conjunction with optimization can be used to verify these improvements before the equipment is modified. This study has adopted an open-source simulation tool (JaamSim) to develop a digital model of an automated tray loader manufacturing system in the Johnson & Johnson Vision Care (JJVC) manufacturing facility. This paper demonstrates how this digital model was integrated with SimWrapper optimization and how both tools can be used for the optimization and development of an automated manufacturing line in the medical devices industry.

Digitalization in manufacturing is the conversion of information into digital format, the integration of this digital data and technologies into the manufacturing process and the use of those technologies (eg: simulation) to change a business model to provide new revenue and value-producing opportunities. Digitalization may be seen as the increased generation, analysis, and use of data to improve the efficiency of the overall manufacturing system. Simulation in manufacturing is often applied in situations where conducting experiments on a real system is impossible or very difficult due to cost or time to carry out the experiment is too long. A key input to the simulation model of automated equipment is the acquisition of valid data in relation to cycle time and reliability of various workstations on this line. As a consequence of being able to simulate equipment processes and interact with this validated simulation model, both the understanding of how the production system will perform under varying reliability and cycle time conditions is achieved. The simulation model then enables the experimentation of ‘what if scenarios’ that can be tested easily, while also providing a valuable tool to inform the maintenance personnel what station reliabilities they need to target in order to sustain a high performing manufacturing line. The author has adopted an open source simulation tool (JaamSim) to develop a digital model of an automated production line in a Johnson & Johnson Vision Care (JJVC) manufacturing facility. This research demonstrated how a digital model was validated for use. The validated digital model can then be used by the author/facility engineering teams to perform scenario testing during the design stage of the line. This simulation model can also be used as a subset of an optimization system to determine recommended optimum line parameters to maximize line performance, either during the line design or when line is in operation.

Abstract Thrombus fragmentation during endovascular stroke treatment, such as mechanical thrombectomy, leads to downstream emboli, resulting in poor clinical outcomes. Clinical studies suggest that fragmentation risk is dependent on clot composition. This current study presents the first experimental characterization of the fracture properties of blood clots, in addition to the development of a predictive model for blood clot fragmentation. A bespoke experimental test-rig and compact tension specimen fabrication has been developed to measure fracture toughness of thrombus material. Fracture tests are performed on three physiologically relevant clot compositions: a high fibrin 5% H clot, a medium fibrin 20% H clot, a low-fibrin 40% H clot. Fracture toughness is observed to significantly increase with increasing fibrin content, i.e. red blood cell-rich clots are more prone to tear during loading compared to the fibrin-rich clots. Results also reveal that the mechanical behaviour of clot analogues is significantly different in compression and tension. Finite element cohesive zone modelling of clot fracture experiments show that fibrin fibres become highly aligned in the direction perpendicular to crack propagation, providing a significant toughening mechanism. The results presented in this study provide the first characterization of the fracture behaviour of blood clots and are of key importance for development of next-generation thrombectomy devices and clinical strategies.

Moving surface interactions between rigid and compliant materials have a wide range of functional applications in the automotive, aerospace and medical industries. This study investigates the cutting and frictional performance of textured stainless steel scalpel blades using polyurethane as the counterpart material. Groove textures of controlled geometries, oriented parallel and tangential to the primary cutting edge were produced using DLW and DLIP processes. Empirical investigations were conducted to study the influences of groove width, depth, separation distance and orientation on the performance of the textured blades under dry conditions. The results reveal that for both the DLW and DLIP generated textures, groove width and orientation have the largest influences on blade performance. The investigated textures showed significant improvements in friction and cutting forces compared to untextured blades, producing reductions of up to 17.0% and 5.8% for the DLW and 33.2% and 24.1% for the DLIP in the parallel orientation respectively.

Abstract Background. Teclistamab is a subcutaneous bispecific IgG4 antibody targeting BCMA on myeloma cells and CD3 on T cells, enabling T-cell–mediated cytotoxicity. Daratumumab is an anti-CD38 monoclonal antibody used in combination with standard agents. The current standard-of-care regimens in elderly patients with newly diagnosed multiple myeloma (NDMM) include the triplet DRd (MAIA) or quadruplet combinations of anti-CD38 antibodies with RVd. These regimens show remarkable efficacy with 32% to 61% MRD negativity at 10-5 and prolonged PFS. However, further optimization of treatment strategies remains a key focus of research efforts for patients with MM. Recently, the combination of teclistamab and daratumumab (Tec-Dara) has demonstrated strong efficacy in the relapsed setting with deep responses. Most trials currently evaluate triplet combinations of BCMA-directed bispecific antibodies with daratumumab and lenalidomide (MajesTEC-7 and MagnetisMM-6). The IFM2021-01 trial is a phase 2 study evaluating the doublets teclistamab-daratumumab (Cohort A) and teclistamab-lenalidomide (Cohort B) in frontline transplant-ineligible patients. Here, we report Cohort A (Tec-Dara), an “all-antibody-based” frontline treatment for patients with NDMM. Methods. IFM2021-01 is an open-label, multicenter, single-arm phase 2 study enrolling patients aged ≥65 years with NDMM, ineligible for high-dose chemotherapy with autologous stem cell transplantation. Teclistamab was administered subcutaneously with step-up doses (0.06 mg/kg and 0.3 mg/kg) followed by 1.5 mg/kg treatment doses on Days 8 and 15 of Cycle 1. Maintenance dosing continued at 3 mg/kg every 4 weeks thereafter. Daratumumab SC (1800 mg) was given weekly in Cycles 1–2, every 2 weeks in Cycles 3–6, and every 4 weeks thereafter. The primary endpoint was the rate of very good partial response (VGPR) or better after 4 cycles per IMWG criteria. Secondary endpoints include overall response rate (ORR), complete response (CR) rate, MRD-negativity by NGS at 10-5 and 10-6, progression-free survival (PFS), and overall survival (OS). Safety was assessed per CTCAE v5.0. The protocol was approved by the French Agency (ANSM) and an external Ethics Committee. The study is conducted by Lille University Hospital and the IFM French Myeloma group in collaboration and with financial support from Janssen Pharmaceutica NV, a member of the Johnson & Johnson group of companies (EU CT 2024-514101-65; ClinicalTrial.gov NCT05572229). Results. A total of 37 patients were enrolled in Cohort A. The median age was 73 years, with 11 (30%) patients above the age of 75 years, and 20 (54%) were female. Overall, 33 (89%) patients had ECOG 0 or 1 and 4 (11%) had ECOG 2; 16 (44%) patients were fit, 12 (33%) were intermediate, and 8 (22%) were frail based on the IMWG frailty score. A total of 25 (68%) patients had standard-risk cytogenetics and 12 (32%) had high-risk features (according to the new IMS/IMWG consensus). The primary endpoint - rate of VGPR or better after 4 cycles was 78%. At data cut-off (08/07/2025), the median follow-up time was 7.6 months (13.1 months for 18 patients; 6 months for 19 patients). The ORR at best response was 100%, with 36 (97%) achieving VGPR or better. The MRD negativity rate at 6 months by NGS at 10-6 was 51% in the intention-to-treat population and 100% in the 21 evaluable patients (16 were not evaluable for MRD at 6 months due to missing or invalid samples). Median DOR, PFS, and OS were not reached. No progression or death occurred during the follow up. The rates of PFS, and OS were 100% each. Regarding safety, 28 (76%) of patients had grade ≥3 adverse events (AEs) and 8 (22%) had serious AEs (SAE) – with no grade 5 AEs. The rate of grade ≥3 hematologic AEs was 46%, with 27% neutropenia. Overall, 5 (14%) patients had grade ≥3 infections. All patients received immunoglobulin replacement therapy at inception of treatment. Treatment discontinuation due to AEs occurred in 1 (3%) patient. Conclusions. IFM2021-01 Cohort A demonstrates that an “all-antibody–based” doublet regimen of teclistamab and daratumumab is highly effective and well-tolerated in elderly patients with NDMM, with deep responses, high MRD negativity, and a favorable safety profile.

There are fewer women than men in Science, Technology, Engineering and Mathematics (STEM). To address this imbalance, numerous STEM intervention programmes have been implemented worldwide. These programmes are aimed at helping girls and women to reach their full potential in terms of school and work.Planning and implementing a STEM intervention programme is a complex process. There are many different stakeholders, and their needs can be varied and evolving. This paper discusses STEM interventions, and it presents our experience with a specific intervention, the University of Limerick-Lero/Johnson & Johnson WiSTEM <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> D (Women in STEM, Manufacturing and Design) programme. This programme has evolved based on the learnings identified in areas such as participant group dynamics, invited speaker engagement and presentation delivery, and teamwork-centered activities. Such learnings can be applied across a range of STEM fields, including software engineering. We believe that initiatives, such as WiSTEM <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> D, which support and promote gender equality in STEM <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> D fields, and specifically Computer Science (CS) education and industry, are of key importance. Our review of the programme has identified three primary lessons: (1) individuals did not benefit as strongly as those working in groups (2) online events allow for more speakers and greater transfer of knowledge and (3) working in teams provides the students with the opportunity to socialise with other women in a work environment.