Five-year-old children value reasons in apologies for belief-based accidents.

Accidents can be intent-based (unintended action-unintended outcome) or belief-based (intended action-unintended outcome). As compared to intent-based accidents, giving reasons is more crucial for belief-based accidents because the transgressor appears to have intentionally transgressed. In Study 1, UK-based preschoolers who were native English speakers (N = 96, 53 girls, collected 2020-2021) witnessed two intent-based or belief-based accidents; one transgressor apologized, the other apologized with a reason. Five-year-olds, but not 4-year-olds, favored the reason-giving transgressor following a belief-based accident but not an intent-based accident (where an apology sufficed). In Study 2, 5-year-olds (N = 48, 25 girls, collected 2021) distinguished between "good" and "bad" reasons for the harm caused. Thus, 5-year-old children recognize when reasons should accompany apologies and account for the quality of these reasons.

Finish What you Started: 2-Year-Olds Motivated by a Preference for Completing Others' Unfinished Actions in Instrumental Helping Contexts.

A considerable body of research has documented the emergence of what appears to be instrumental helping behavior in early childhood. The current study tested the hypothesis that one basic psychological mechanism motivating this behavior is a preference for completing unfinished actions. To test this, a paradigm was implemented in which 2-year-olds (n = 34, 16 females/18 males, mostly White middle-class children) could continue an adult's action when the adult no longer wanted to complete the action. The results showed that children continued the adult's actions more often when the goal had been abandoned than when it had been reached (OR = 2.37). This supports the hypothesis that apparent helping behavior in 2-year-olds is motivated by a preference for completing unfinished actions.

Tablet coating by injection molding technology - Optimization of coating formulation attributes and coating process parameters.

We developed and evaluated a solvent-free injection molding (IM) coating technology that could be suitable for continuous manufacturing via incorporation with IM tableting. Coating formulations (coating polymers and plasticizers) were prepared using hot-melt extrusion and screened via stress-strain analysis employing a universal testing machine. Selected coating formulations were studied for their melt flow characteristics. Tablets were coated using a vertical injection molding unit. Process parameters like softening temperature, injection pressure, and cooling temperature played a very important role in IM coating processing. IM coating employing polyethylene oxide (PEO) based formulations required sufficient room humidity (>30% RH) to avoid immediate cracks, whereas other formulations were insensitive to the room humidity. Tested formulations based on Eudrajit E PO and Kollicoat IR had unsuitable mechanical properties. Three coating formulations based on hydroxypropyl pea starch, PEO 1,000,000 and Opadry had favorable mechanical (<700MPa Young's modulus, >35% elongation, >95×104J/m3 toughness) and melt flow (>0.4g/min) characteristics, that rendered acceptable IM coats. These three formulations increased the dissolution time by 10, 15 and 35min, respectively (75% drug release), compared to the uncoated tablets (15min). Coated tablets stored in several environmental conditions remained stable to cracking for the evaluated 8-week time period.

Demonstration of pharmaceutical tablet coating process by injection molding technology.

We demonstrate the coating of tablets using an injection molding (IM) process that has advantage of being solvent free and can provide precision coat features. The selected core tablets comprising 10% w/w griseofulvin were prepared by an integrated hot melt extrusion-injection molding (HME-IM) process. Coating trials were conducted on a vertical injection mold machine. Polyethylene glycol and polyethylene oxide based hot melt extruded coat compositions were used. Tablet coating process feasibility was successfully demonstrated using different coating mold designs (with both overlapping and non-overlapping coatings at the weld) and coat thicknesses of 150 and 300 µm. The resultant coated tablets had acceptable appearance, seal at the weld, and immediate drug release profile (with an acceptable lag time). Since IM is a continuous process, this study opens opportunities to develop HME-IM continuous processes for transforming powder to coated tablets.

Integrated hot-melt extrusion - injection molding continuous tablet manufacturing platform: Effects of critical process parameters and formulation attributes on product robustness and dimensional stability.

This study provides a framework for robust tablet development using an integrated hot-melt extrusion-injection molding (IM) continuous manufacturing platform. Griseofulvin, maltodextrin, xylitol and lactose were employed as drug, carrier, plasticizer and reinforcing agent respectively. A pre-blended drug-excipient mixture was fed from a loss-in-weight feeder to a twin-screw extruder. The extrudate was subsequently injected directly into the integrated IM unit and molded into tablets. Tablets were stored in different storage conditions up to 20 weeks to monitor physical stability and were evaluated by polarized light microscopy, DSC, SEM, XRD and dissolution analysis. Optimized injection pressure provided robust tablet formulations. Tablets manufactured at low and high injection pressures exhibited the flaws of sink marks and flashing respectively. Higher solidification temperature during IM process reduced the thermal induced residual stress and prevented chipping and cracking issues. Polarized light microscopy revealed a homogeneous dispersion of crystalline griseofulvin in an amorphous matrix. DSC underpinned the effect of high tablet residual moisture on maltodextrin-xylitol phase separation that resulted in dimensional instability. Tablets with low residual moisture demonstrated long term dimensional stability. This study serves as a model for IM tablet formulations for mechanistic understanding of critical process parameters and formulation attributes required for optimal product performance.

Development of Maltodextrin-Based Immediate-Release Tablets Using an Integrated Twin-Screw Hot-Melt Extrusion and Injection-Molding Continuous Manufacturing Process.

The combination of hot-melt extrusion and injection molding (HME-IM) is a promising process technology for continuous manufacturing of tablets. However, there has been limited research on its application to formulate crystalline drug-containing immediate-release tablets. Furthermore, studies that have applied the HME-IM process to molded tablets have used a noncontinuous 2-step approach. The present study develops maltodextrin (MDX)-based extrusion-molded immediate-release tablets for a crystalline drug (griseofulvin) using an integrated twin-screw HME-IM continuous process. At 10% w/w drug loading, MDX was selected as the tablet matrix former based on a preliminary screen. Furthermore, liquid and solid polyols were evaluated for melt processing of MDX and for impact on tablet performance. Smooth-surfaced tablets, comprising crystalline griseofulvin solid suspension in the amorphous MDX-xylitol matrix, were produced by a continuous process on a twin-screw extruder coupled to a horizontally opening IM machine. Real-time HME process profiles were used to develop automated HME-IM cycles. Formulation adjustments overcame process challenges and improved tablet strength. The developed MDX tablets exhibited adequate strength and a fast-dissolving matrix (85% drug release in 20 min), and maintained performance on accelerated stability conditions.

Regulatory Perspectives on Continuous Pharmaceutical Manufacturing: Moving From Theory to Practice: September 26-27, 2016, International Symposium on the Continuous Manufacturing of Pharmaceuticals.

Continuous manufacturing plays a key role in enabling the modernization of pharmaceutical manufacturing. The fate of this emerging technology will rely, in large part, on the regulatory implementation of this novel technology. This paper, which is based on the 2nd International Symposium on the Continuous Manufacturing of Pharmaceuticals, describes not only the advances that have taken place since the first International Symposium on Continuous Manufacturing of Pharmaceuticals in 2014, but the regulatory landscape that exists today. Key regulatory concepts including quality risk management, batch definition, control strategy, process monitoring and control, real-time release testing, data processing and management, and process validation/verification are outlined. Support from regulatory agencies, particularly in the form of the harmonization of regulatory expectations, will be crucial to the successful implementation of continuous manufacturing. Collaborative efforts, among academia, industry, and regulatory agencies, are the optimal solution for ensuring a solid future for this promising manufacturing technology.

The nature of prosociality in chimpanzees.

An important debate centres around the nature of prosociality in nonhuman primates. Chimpanzees help other individuals in some experimental settings, yet they do not readily share food. One solution to this paradox is that they are motivated to help others provided there are no competing interests. However, benefits to recipients could arise as by-products of testing. Here we report two studies that separate by-product from intended helping in chimpanzees using a GO/NO-GO paradigm. Actors in one group could help a recipient by releasing a food box, but the same action for another group prevented a recipient from being able to get food. We find no evidence for helping-chimpanzees engaged in the test regardless of the effects on their partners. Illusory prosocial behaviour could arise as a by-product of task design.

Prosociality.

Prosociality refers to behaviours that are intended to benefit others. This definition appears to be so straightforward that it hardly bears mentioning: like certain forms of adult entertainment, we know it when we see it. Yet, determining what counts as prosocial is not as simple as it first appears. There are numerous behaviours that appear prosocial but, on scrutiny, may not have been intended and motivated for the well-being of others. Consider a banal scenario: a seated passenger on a crowded bus stands up and someone takes his seat. Did the person standing up intend that someone else take the seat? Perhaps he was getting off the bus at the next stop and did not care if anyone sat there. But what if he remained standing for several stops, or made an overt gesture such as waving his hand toward the seat? In that case it is more likely that he intended for someone to have his place on the bus. But what about his underlying motives? Maybe he was putting himself in a better position to pick the pocket of the person sitting down. Less sinister possibilities include trying to impress the person who took his seat - trying to improve his reputation, his social standing, as it were. Or maybe, just maybe, he intended for another passenger to sit comfortably, to increase the happiness of a stranger, with no ulterior motives.

Restorative Justice in Children.

An important, and perhaps uniquely human, mechanism for maintaining cooperation against free riders is third-party punishment. Our closest living relatives, chimpanzees, will not punish third parties even though they will do so when personally affected. Until recently, little attention has been paid to how punishment and a sense of justice develop in children. Children respond to norm violations. They are more likely to share with a puppet that helped another individual as opposed to one who behaved harmfully, and they show a preference for seeing a harmful doll rather than a victim punished. By 6 years of age, children will pay a cost to punish fictional and real peers, and the threat of punishment will lead preschoolers to behave more generously. However, little is known about what motivates a sense of justice in children. We gave 3- and 5-year-old children--the youngest ages yet tested--the opportunity to remove items and prevent a puppet from gaining a reward for second- and third-party violations (experiment 1), and we gave 3-year-olds the opportunity to restore items (experiment 2). Children were as likely to engage in third-party interventions as they were when personally affected, yet they did not discriminate among the different sources of harm for the victim. When given a range of options, 3-year-olds chose restoration over removal. It appears that a sense of justice centered on harm caused to victims emerges early in childhood and highlights the value of third-party interventions for human cooperation.

Preschoolers are sensitive to free riding in a public goods game.

Despite the benefits of cooperation, selfish individuals often produce outcomes where everyone is worse off. This "tragedy of the commons" has been demonstrated experimentally in adults with the public goods game. Contributions to a public good decline over time due to free-riders who keep their endowments. Little is known about how children behave when confronted with this social dilemma. Forty-eight preschoolers were tested using a novel non-verbal procedure and simplified choices more appropriate to their age than standard economic approaches. The rate of cooperation was initially very low and rose in the second round for the girls only. Children were affected by their previous outcome, as they free rode more after experiencing a lower outcome compared to the other group members.

The emergence of human prosociality: aligning with others through feelings, concerns, and norms.

The fact that humans cooperate with nonkin is something we take for granted, but this is an anomaly in the animal kingdom. Our species' ability to behave prosocially may be based on human-unique psychological mechanisms. We argue here that these mechanisms include the ability to care about the welfare of others (other-regarding concerns), to "feel into" others (empathy), and to understand, adhere to, and enforce social norms (normativity). We consider how these motivational, emotional, and normative substrates of prosociality develop in childhood and emerged in our evolutionary history. Moreover, we suggest that these three mechanisms all serve the critical function of aligning individuals with others: Empathy and other-regarding concerns align individuals with one another, and norms align individuals with their group. Such alignment allows us to engage in the kind of large-scale cooperation seen uniquely in humans.

Five-year-olds understand fair as equal in a mini-ultimatum game.

In studies of children's resource distribution, it is almost always the case that "fair" means an equal amount for all. In the mini-ultimatum game, players are confronted with situations in which fair does not always mean equal, and so the recipient of an offer needs to take into account the alternatives the proposer had available to her or him. Because of its forced-choice design, the mini-ultimatum game measures sensitivity to unfair intentions in addition to unfair outcomes. In the current study, we gave a mini-ultimatum game to 5-year-old children, allowing us to determine the nature of fairness sensitivity at a period after false belief awareness is typically passed and before formal schooling begins. The only situation in which responders rejected offers was when the proposer could have made an equal offer. But unlike adults, they did not employ more sophisticated notions of fairness that take into account the choices facing the proposer. Proposers, in their turn, were also not adult-like in that they had a very poor understanding that responders would reject unequal offers when an equal one was available. Thus, preschool children seem to understand "fair=equal" in this task, but not much more, and they are not yet skillful at anticipating what others will find fair beyond 50/50 splits.

No third-party punishment in chimpanzees.

Punishment can help maintain cooperation by deterring free-riding and cheating. Of particular importance in large-scale human societies is third-party punishment in which individuals punish a transgressor or norm violator even when they themselves are not affected. Nonhuman primates and other animals aggress against conspecifics with some regularity, but it is unclear whether this is ever aimed at punishing others for noncooperation, and whether third-party punishment occurs at all. Here we report an experimental study in which one of humans' closest living relatives, chimpanzees (Pan troglodytes), could punish an individual who stole food. Dominants retaliated when their own food was stolen, but they did not punish when the food of third-parties was stolen, even when the victim was related to them. Third-party punishment as a means of enforcing cooperation, as humans do, might therefore be a derived trait in the human lineage.

Theft in an ultimatum game: chimpanzees and bonobos are insensitive to unfairness.

Humans, but not chimpanzees, punish unfair offers in ultimatum games, suggesting that fairness concerns evolved sometime after the split between the lineages that gave rise to Homo and Pan. However, nothing is known about fairness concerns in the other Pan species, bonobos. Furthermore, apes do not typically offer food to others, but they do react against theft. We presented a novel game, the ultimatum theft game, to both of our closest living relatives. Bonobos and chimpanzee 'proposers' consistently stole food from the responders' portions, but the responders did not reject any non-zero offer. These results support the interpretation that the human sense of fairness is a derived trait.

Social preference experiments in animals: strengthening the case for human preferences.

Guala appears to take social preferences for granted in his discussion of reciprocity experiments. While he does not overtly claim that social preferences are only by-products that arise in testing environments, he does assert that whatever they are--and how they evolved--they have little value in the real world. Experiments on animals suggest that social preferences may be unique to humans, supporting the idea that they might play a prominent role in our world.

Animal cognition: concepts from apes to bees.

New research shows that honeybees can classify arrangements of two visual patterns according to their spatial configuration. Can bees learn relational concepts of 'above' and 'below'? And are the underlying psychological processes comparable in humans and other primates facing similar tasks?