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A consistent and transparent approach is essential for quality decision-making in the review and approval of medicines. This is achieved through the use of a standard and well-defined framework, as the decisions made should not be influenced by any biases. While most National Medicines Regulatory Authorities (NMRAs) have designed frameworks to assess the quality of their decisions, many have not been implemented. A well-structured framework improves consistency and predictability in the decision-making process. The Quality of Decision-Making Orientation Scheme (QoDoS) has been widely adopted as a leading framework for this purpose. This study aimed to assess the decision-making processes of two technical committees operating within the Zambia Medicines Regulatory Authority (ZAMRA) using the QoDoS framework developed by the Centre for Innovation in Regulatory Science (CIRS); determine areas of improvement for routine assessment of quality of decision-making and its acceptability with respect to ZAMRA; and suggest ways of improving the lowest-scoring Quality Decision-Making Practices (QDMPs) and how these may be implemented into the decision-making framework to ensure consistency. The framework was used to assess the quality of the decision-making process and subsequent implementation of the ten QDMPs. The study included five members from the Technical Committee for Human Medicines (TCHM) and seven members from the Technical Committee for Veterinary Medicines (TCVM) at ZAMRA, all responsible for recommending the approval or rejection of applications following scientific review. The validated QoDoS questionnaire was electronically distributed to the members, and data were analysed using descriptive statistics. Analysis of the QDMPs across the 12 committee members indicated that both human and veterinary medicines technical committees generally perceived their individual and organizational decision-making practices as favourable. Favourable QDMPs included QDMP 2 (assigning clear roles and responsibilities of the stakeholders involved in the review and approval of medicines), QDMP 4 (evaluate both internal and external influences or biases), QDMP 6 (considering uncertainty), QDMP 7 (re-evaluate new information as it becomes available), QDMP 9, (ensure transparency and keep a record trail) and QDMP 10 (effective communication of the basis of the decision). However, areas for improvement were identified in QDMP 1 (systematic structured approach), QDMP 3 (decision criteria), QDMP 5 (alternatives) and QDMP 8 (impact analysis) within the TCVM, as well as in QDMP 3 and QDMP 8 within the TCHM. This study assessed committee members' perceptions of the implementation of QDMPs in the review and approval of medicines. It was demonstrated that most of the best QDMPs were implemented, except for four QDMPs that needed improvement, namely having a systematic structured approach, decision criteria, alternatives and impact analysis.

Adverse effects can disrupt early treatment in first-episode psychosis and precipitate discontinuation. We report the use of the five-step precision medicine (5SPM) method in personalised precision psychiatry to guide antipsychotic decision-making in a patient with first-episode psychosis. A 26-year-old woman with regular tobacco and cannabis use was admitted to an acute psychiatric ward with persecutory delusions, behavioural dysregulation, anxiety and insomnia. Olanzapine (7.5 mg) was initiated and aripiprazole (20 mg) added to transition to aripiprazole monotherapy. Soon after aripiprazole introduction, she developed pain and cramps circumscribed to her arms, rejected treatment, and symptoms did not remit. A 5SPM-guided assessment, including pharmacogenetic testing and a structured review of pharmacokinetic interactions and environmental factors, provided a coherent basis to interpret an uncommon tolerability signal and to rationalise a change in antipsychotic strategy. Following shared decision-making, aripiprazole was withdrawn and olanzapine optimised; arm symptoms resolved within days, psychotic symptoms ceased, and she was discharged. At six months, she remained adherent to pharmacological treatment, which was eventually switched to long-acting injectable olanzapine following the patient's preference, had stopped cannabis and returned to work. In this case, precision-guided shared decision-making was associated with treatment continuity in early psychosis by resolving an atypical adverse effect and improving clinical and functional outcomes.

Following recent research in the United Kingdom (UK) on the prevalence of parental alienating behaviors (PABs) as reported by separated parents, this study presents the first nationally representative investigation of the prevalence and impacts of PABs as reported by young adults in the United Kingdom. A sample of 1,004 participants aged 18-25 completed an online survey assessing exposure to 30 established PABs, parental acceptance and rejection, and mental health outcomes, including post-traumatic stress, depression, and suicidality. Results revealed that 98.3% of participants reported experiencing at least one PAB from a parent during childhood, with over half reporting exposure to ten or more behaviors. Approximately one-quarter experienced twenty or more behaviors. Males reported significantly higher exposure to PABs than females, though no other demographic differences were found. Exposure to PABs was significantly correlated with increased parental rejection and decreased parental acceptance, as well as elevated symptoms of PTSD, depression, and suicidal ideation. These findings provide robust evidence that PABs are both widespread and psychologically harmful, underscoring their recognition as a form of family violence with long-term consequences. Implications include the need for comprehensive legal frameworks, enhanced clinical training, and public awareness initiatives to address and mitigate the effects of PABs on children and families. Future longitudinal research is needed to better understand trajectories of resilience and vulnerability among affected individuals.

Cationic surfactants from quaternary ammonium compounds (QACs) are increasingly recognized as relevant micropollutants particularly following their widespread use during and after the COVID-19 pandemic. The new EU Urban Wastewater Treatment Directive (2024/3019) highlights micropollutant removal as a regulatory priority, mandating advanced treatment for their elimination. In this context, this study examined benzalkonium chloride (BAC) retention and membrane response during nanofiltration (NF) and reverse osmosis (RO), across concentrations ranging from monomeric to micellar. RO membranes achieved >97% rejection, whereas NF showed 65-96% removal strongly affected by micelle formation. Flux decline was most pronounced in RO, with relative permeability (J/J0) decreasing to ~0.12 at 1.0 CMC, while NF membranes exhibited better hydraulic stability. Membrane active layer zeta potential measurements confirmed adsorption and charge neutralization, with shifts toward less negative values after BAC exposure. Hermia model analysis revealed that fouling was governed by cake layer formation or pore blocking, depending on membrane type and feed concentration.

Quadrotor UAVs present a significant control challenge due to their underactuated nature; strong coupling effects; nonlinear dynamics; and high sensitivity to unknown effect parameters, external disturbances, and uncertainties. To address this issue, this study proposes a Lyapunov-based backstepping (LYP) controller that ensures robust stability and precise trajectory tracking. The controller employs an inner- and outer-loop architecture for coupled position and attitude control. Its performance is compared with Proportional-Integral-Derivative (PID) and Fractional-Order PID (FOPID) controllers under three scenarios: nominal conditions, external disturbances, and model parameter uncertainties. All controller gains are optimized using Particle Swarm Optimization (PSO). Simulation results, which are evaluated using time-domain metrics and root mean square error (RMSE), demonstrate that the proposed LYP controller achieves superior robustness, faster disturbance rejection, and improved tracking accuracy compared to both PID and FOPID controllers.

Calcineurin is a serine/threonine phosphatase that classically regulates T cell activation and modulates immune response by targeting transcription factors of the NFaT family. Activation of calcineurin for example by angiotensin II, phenylephrine, endothelin-1 or mechanical stress can influence vascular smooth muscle cell function and stimulates proliferation and migration or affect the phenotype of these respective cells. This can lead to vessel wall remodeling, increased vascular tone or fibrosis, which contribute to the development of cardiovascular diseases. Based on its classical function, inhibition of calcineurin activity by calcineurin inhibitors is a common treatment in the clinics for autoimmune and inflammatory disease or to prevent graft rejection. Classical calcineurin inhibitors can promote pathological effects in vasculature that resemble calcineurin activation, namely the development of systemic hypertension or inflammatory processes, making the interpretation of the role of calcineurin in vascular smooth muscle cells difficult. In this mini review, we provide a summary of known pathological outcomes of calcineurin activation and calcineurin inhibitor-induced effects in vascular smooth muscle cells. Knowledge about these functional alterations can provide a useful tool to avoid negative effects for the vasculature during pharmacological intervention. Overall, maintenance of a balanced calcineurin activity is essential for proper vascular smooth muscle cell function.

Cytomegalovirus (CMV), a prevalent member of the herpesvirus family, poses significant risks to immunocompromised patients, particularly those undergoing hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT). This study aimed to assess the prevalence and genotype distribution of CMV among transplant recipients in Jordan. A retrospective observational study conducted at the Jordan Royal Medical Service's Virology Department from January to October 2024, included all patients who underwent HSCT or SOT. Blood samples collected in EDTA tubes were analyzed for CMV detection and genotyping. Real-time PCR facilitated CMV amplification, while multiplex nested PCR identified gB and gN genotypes. Among 80 transplant recipients with positive CMV DNA, 15 (18.8%) were from SOT kidney transplants (KT), and 65 (81.2%) were HSCT recipients. Genotype analysis of 44 samples revealed that 21 had the gN genotype and 27 had the gB genotype. Mixed genotypes gB and gN were present in 15 samples. The mixed genotype gN1+gN2 (42.86%) was most common in KT recipients, while gB2 (31%) was prevalent among HSCT recipients. CMV is a common opportunistic virus that often leads to severe, life-threatening illness and is associated with an increased risk of transplant rejection. Our study demonstrated that the most prevalent genotypes in Jordanian HSCT and SCT recipients with CMV infection were gB2 and gN1+gN2, respectively.

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To enhance the tracking accuracy and control stability of virtually coupled train sets (VCTS) in metros under uncertain disturbances, such as track vibrations and adverse weather, a distributed event-triggered model predictive control (MPC) strategy based on a high-gain disturbance observer (HGDO) is developed, with consideration of both the computational efficiency and disturbance rejection capability of the control system. First, a cooperative control cost function is designed based on the dynamic model of virtual coupling trains. To alleviate the high computational burden of conventional MPC, an event-triggered mechanism is introduced, where adaptive trigger threshold sets are designed according to train's real-time speed, thereby reducing the computational load. Simultaneously, an HGDO is employed to observe and compensate external disturbances in real time, enhancing both disturbance rejection and control precision. The effectiveness and superiority of the proposed approach are validated through cooperative train control simulations conducted in MATLAB/Simulink. The results demonstrate that the proposed approach achieves computational efficiency improvements of 54.23%, 41.79%, and 29.35% under three distinct trigger threshold sets, compared to conventional MPC. Furthermore, relative to the advanced Input Blocking Robust MPC, the proposed method reduces the speed root mean square error by 26.43%, the distance root mean square error by 27.14%, and the average solution time by 18.75%, demonstrating its strong potential for practical metro applications.

Graft-versus-host disease (GVHD) remains the most severe complications following allogeneic hematopoietic cell transplantation (allo-HCT). Mesenchymal stromal cells (MSCs) have shown therapeutic potential in GVHD due to their immunomodulatory properties. However, their clinical application is constrained by safety concerns, including ectopic engraftment, microvascular obstruction, rejected by host, and potential tumor-supportive effects. Increasing evidence suggests that MSC-derived exosomes (MSC-Exos), as cell-free mediators, retain many of the beneficial effects of MSCs while exhibiting improved safety and stability profiles. MSC-Exos carry diverse bioactive cargo, including nucleic acids, lipids, and proteins, and can modulate immune responses, promote tissue repair, and restore barrier integrity. In this review, we place particular emphasis on both immunoregulation and tissue barrier protection as dual mechanisms underlying MSC-Exos efficacy in GVHD. We further discuss emerging preclinical and clinical evidence, as well as key challenges in translation.

The crystallization of monoclonal antibodies is deemed particularly challenging due to their large size and structural flexibility. An additional challenge is represented by the tendency of mAb crystals to rapidly lose their crystallinity when removed from liquid and exposed to air or nitrogen, which complicates filtration. This study aims to develop crystallization design strategies for mAbs using the caffeine cocrystal of pembrolizumab as a model. Optimal crystallization conditions are identified by minimizing cycle times for crystallization and filtration. Metrics are introduced to rank the filtration performance of the different crystalline particle populations. This work focuses on the crystallization of caffeine cocrystal-1 of pembrolizumab, which is consistently generated upon charge of the crystallizing agent poly(ethylene glycol) 3350 (PEG) and of mediating salts, among others, dextran sodium sulfate (DSS). This study also demonstrates that seeding is feasible in the crystallization of mAbs and consistently shortens the cycle times for crystallization and improves the robustness of the process. As a proof of concept, seeded semicontinuous crystallizations are performed to enhance supersaturation control during crystallization when stringent impurity rejection and particle attribute specifications must be met. The isolation of crystalline mAb particles presents considerable challenge, and there are no documented studies that have established precedent for this aspirational goal. Finally, to avoid amorphization of the particles during isolation, a conservative approach is adopted to only partially deliquor the filter cake and to leave enough supernatant to fully submerge the filter cake to prevent air or nitrogen exposure. Assuming multiple filtration steps may be required to meet drug substance specifications, this study demonstrates that the crystal form can be retained through successive filtration and dilution/wash cycles with the supernatant composition adjusted after each filtration. This outcome demonstrates that the particles are resistant to changes in the solvent composition, such that the final product could be swapped from the matrix best suited for crystallization to a matrix more suitable for product delivery.

Liposomes can act as drug carriers because of their ability to encapsulate both hydrophilic and lipophilic substances, protect them from external factors, and facilitate controlled drug delivery or release. However, the physical properties and encapsulation efficiencies are strongly influenced by the choice of the liposome formation and the solute loading process. During liposome assembly, poorly permeable solutes can be rejected by the phospholipid membrane, resulting in a poor encapsulation efficiency. In this study, five different liposome formulation process routes have been directly experimentally compared: the heating method with sonication, the lipid film hydration method with either extrusion or sonication, and the freeze-thawing method applied to either preloaded or blank liposomes. 5(6)-Carboxyfluorescein and D-(+)-glucose were used as model solutes with different permeability and hydrophilicity profiles to assess the encapsulation efficiency and concentration retention factor of each formulation process route. The film hydration method followed by extrusion was found to be the most effective for carboxyfluorescein as a more permeable solute. In contrast, the film hydration method followed by sonication was found to be a more effective process for glucose, which is less permeable. The quantity of encapsulated solute per mass of lipids was found to increase with an increasing solute concentration in the loading solution, indicating a clear dependence on the concentration driving force.

This article challenges standard accounts about technological disillusionment in the late 1960s and 1970s that locate opposition to new technologies primarily in environmentalists and the "New Left" or declining trust in expertise. Looking at the critics of the Anglo-French supersonic jet Concorde in Britain, it argues for the importance of political economy to understand the demise of techno-nationalism. Drawing on debates within government, Parliament, the press, and extraparliamentary opposition, the article demonstrates that actually economic and industrial critiques-often voiced privately within the state-were decisive. What united these ideologically diverse opponents was not environmentalism but a shared wariness of state power and the conviction that official deception sustained a looming commercial disaster. It also shows how a lack of transparency and powerful state propaganda masked Concorde's effective cancellation, which demonstrated a deep rejection of techno-nationalism. The conclusion reflects on why Britain sustained its supersonic commitment longer than the United States.

This study proposes a critical resilience model for children and youth in Latin American polycrisis contexts, marked by overlapping adversities including poverty, environmental degradation, armed conflict, and institutional abandonment. In this cross-sectional, sequential mixed-methods study, we combined standardized instruments with culturally grounded focusgroups in Indigenous and Afro-descendant communities in Colombia's Chocó region (n = 187, aged 7-29). Quantitative findings reveal a paradox: high resilience scores despite severe structural deprivation-food insecurity, coercive parenting, violence exposure. Regression analysis identified both risk and protective factors, highlighting complex relationships between adversity and adaptive responses. Narratives emphasized resilience not as passive adjustment but as collective resistance, spiritual balance, and political agency, what participants termed "to live is to resist." We therefore distinguish resilience from resistance, political agency, and habituated endurance. Rather than rejecting resilience per se, we critique its depoliticized use: in contexts of polycrisis, standardized resilience scores may register persistence under structural harm without adequately differentiating flourishing from normalized suffering. This convergence challenges dominant individualistic resilience conceptions and supports a relational, culturally situated framework informed by Latin American critical theory. Together, the findings support a relational, culturally situated, and justice-oriented understanding of resilience and call for mental health strategies that strengthen collective life while addressing the structural roots of suffering.

Suicide-related stigma is a public health concern that hinders help-seeking and prevention efforts. This study examined the dimensions of stigma among inpatients admitted for self-poisoning, their families, and healthcare providers. In a cross-sectional study, participants included 60 patients admitted following self-poisoning, one family member per patient, and 31 healthcare providers from the Emergency Department. Data were collected using the Personal Suicide Stigma Questionnaire to examine Rejection, Minimization, and Self-blame subscales in patients, and the Persian version of the Attitudes Toward Suicide Scale to evaluate general acceptance of suicide (Factor1), perceived preventability (Factor2), and communication problems (Factor3) in family members and healthcare providers. Patients had a mean age of 30.87 ± 9.9, and were predominantly female (68.3%). Family members had a mean age of 43.25 ± 11.42 (61.7% female), and healthcare providers had a mean age of 36.26 ± 8.47 (58.1% female). Among patients, females scored higher on Minimization and Self-blame subscales. Employment status and education level were associated with Rejection and Minimization subscales. A psychiatric hospitalization history was linked to higher Self-blame. Age correlated negatively with Self-blame. Among family members, marital status was associated with all three factors, and age was positively correlated with perceived preventability and communication problems. Living status and psychiatric history were associated with communication problems. Among healthcare providers, educational level and occupation were associated with communication problems, while work experience was correlated negatively with general acceptance of suicide factor. Most family members (88.3%) and healthcare providers (58.1%) agreed that suicide is avoided in discussion, and about half believed asking about suicide could increase risk. Suicide-related stigma and communication barriers were evident and varied by demographic and psychosocial factors, highlighting the need for targeted stigma-reduction interventions and training programs among stakeholders.

Simultaneous Localization and Mapping (SLAM) is a fundamental methodology that underpins autonomous navigation in robotic systems. Conventional approaches perform well in static environments but rely on the assumption of environmental rigidity, which leads to significant accuracy degradation in dynamic environments. To address this challenge, this study presents RTS-SLAM, a real-time semantic visual SLAM system designed for dynamic environments. Based on the ORB-SLAM2 framework, a multi-layer, constraint-driven dynamic feature-rejection strategy is introduced. The proposed approach first removes dynamic features by combining semantic information with geometric constraints. Subsequently, residual dynamic points are eliminated via trajectory-consistency constraint analysis, thereby effectively improving localization accuracy. Furthermore, a dense mapping strategy featuring global sparsification and critical region refinement is proposed. By reducing redundancy in the dense point cloud, the method decreases memory usage while preserving important object geometries. Experimental evaluations on the TUM RGB-D and Bonn datasets indicate that RTS-SLAM reduces the average absolute trajectory error by more than 95% compared with ORB-SLAM2 in dynamic environments. Meanwhile, the system maintains real-time performance and achieves high localization accuracy in dynamic environments.

Tight ultrafiltration (TUF) membranes have garnered significant attention for the treatment of printing and dyeing wastewater, owing to their high separation efficiency and water permeance. However, macrovoids in TUF membranes fabricated via conventional non-solvent induced phase separation (NIPS) inherently undergo collapse-induced structural degradation under pressurization, markedly reducing water permeability. In this study, we develop a cuttlebone-inspired poly (m-phenylene isophthalamide) (PMIA) TUF membrane featuring a symmetric porous structure to effectively enhance stability of ultrafiltration (UF) process. The resulting membrane fabricated through a double-sided NIPS process using a continuous microfluidic approach (M-PMIA) demonstrates superior structural robustness compared to conventionally cast PMIA membranes. The M-PMIA membrane achieves superior flux stability for 172 h continuous UF with an exceeding rejection rate for Congo Red and demonstrates a high pure water permeance of 180 L m-2 h-1 bar-1. Furthermore, the membrane exhibits excellent thermal and chemical stability throughout dye removal processes. This work proposes a promising approach for designing high-performance TUF membranes that facilitate efficient and stable purification of printing and dyeing wastewater.

This longitudinal study examined how interactions between both children's negative emotionality predicted parental rejection toward firstborns (Mage = 49.9 months; 55% boys) in 120 Chinese two-child families from 2016 to 2018 in Shanghai (mostly Han ethnicity). Parents reported firstborns' temperament prenatally, secondborns' temperament at 6 months postpartum, and parental rejection prenatally and at 1, 6, and 12 months postpartum. Regression analyses predicting parental rejection toward firstborns at 6 and 12 months postpartum from both children's temperaments controlled for two prior parental rejection. Higher negative emotionality in secondborns predicted greater maternal rejection toward firstborns at 6 months. At 12 months, this association emerged only when firstborns also showed high negative emotionality. No significant effects were observed for paternal rejection. The arrival of a second child is a major transition for families and may change how parents interact with their firstborn. This study followed 120 Chinese families from pregnancy through the first year after the second child's birth to examine how children's emotional characteristics relate to parenting. Results showed that mothers displayed more rejecting behaviors toward firstborn children when the younger sibling had higher negative emotionality, particularly when the firstborn was also emotionally reactive. Fathers' parenting behaviors were less closely associated with children's emotional characteristics. These findings suggest that early siblinghood parenting may be shaped by the combined emotional demands of both children, highlighting the importance of supporting parents—especially mothers—during this transition.