Development, implementation and evaluation of an evidence-based paediatric early warning system improvement programme: the PUMA mixed methods study

Background Paediatric mortality rates in the United Kingdom are amongst the highest in Europe. Clinically missed deterioration is a contributory factor. Evidence to support any single intervention to address this problem is limited, but a cumulative body of research highlights the need for a systems approach. Methods An evidence-based, theoretically informed, paediatric early warning system improvement programme (PUMA Programme) was developed and implemented in two general hospitals (no onsite Paediatric Intensive Care Unit) and two tertiary hospitals (with onsite Paediatric Intensive Care Unit) in the United Kingdom. Designed to harness local expertise to implement contextually appropriate improvement initiatives, the PUMA Programme includes a propositional model of a paediatric early warning system, system assessment tools, guidance to support improvement initiatives and structured facilitation and support. Each hospital was evaluated using interrupted time series and qualitative case studies. The primary quantitative outcome was a composite metric (adverse events), representing the number of children monthly that experienced one of the following: mortality, cardiac arrest, respiratory arrest, unplanned admission to Paediatric Intensive Care Unit, or unplanned admission to Higher Dependency Unit. System changes were assessed qualitatively through observations of clinical practice and interviews with staff and parents. A qualitative evaluation of implementation processes was undertaken. Results All sites assessed their paediatric early warning systems and identified areas for improvement. All made contextually appropriate system changes, despite implementation challenges. There was a decline in the adverse event rate trend in three sites; in one site where system wide changes were organisationally supported, the decline was significant (ß = -0.09 (95% CI: − 0.15, − 0.05); p = < 0.001). Changes in trends coincided with implementation of site-specific changes. Conclusions System level change to improve paediatric early warning systems can bring about positive impacts on clinical outcomes, but in paediatric practice, where the patient population is smaller and clinical outcomes event rates are low, alternative outcome measures are required to support research and quality improvement beyond large specialist centres, and methodological work on rare events is indicated. With investment in the development of alternative outcome measures and methodologies, programmes like PUMA could improve mortality and morbidity in paediatrics and other patient populations.

Career Adaptability and Career Success

In this study, we contribute to the ongoing incremental validation efforts of the Career Adapt-Abilities Scale (CAAS). Using primary personality and cognition data from 164 German athletes in vocational careers, we intended to replicate Zacher’s (2014) seminal work in an alternative Western environment while also extending it in two significant ways: first, by adding two components of cognitive ability, and second, by introducing an alternative outcome variable – objective career success. In line with Zacher, we observe a significant role of career adaptability in predicting subjective career success. However, we also note that this initially robust relationship stems from a different psychosocial resource than expected. Interestingly, employing CAAS seems not to possess further incremental validity when predicting objective career success.

Emotionally Engaged Learners Are More Satisfied with Online Courses

Research on massive open online courses (MOOCs) has tended to focus on outcome indicators valued in traditional higher education settings, particularly achievement and completion. This study highlights the differences between MOOCs and credit-bearing university courses and shifts this focus to an alternative outcome indicator—learner satisfaction. In this study, engagement is identified as an important antecedent of learner satisfaction and is conceptualised and operationalised as a multidimensional construct. This study built three regression models to identify the relative importance of behavioural, cognitive, emotional, and social engagement for learner satisfaction after controlling for personal characteristics unrelated to the criteria of good teaching. The analysis showed that engagement explained approximately 20% of the variance in learner satisfaction with MOOCs. Emotional engagement was more influential for predicting learner satisfaction than cognitive engagement and behavioural engagement. Social engagement had no significant effect on learner satisfaction. Demographics (age, education level, and origin) and motivation were of limited utility in predicting learner satisfaction with MOOCs, accounting for 4% and 2% of variance, respectively. Based on research findings, the article presents the following propositions: (1) configure the MOOC teaching and learning environment in a way that enhances emotional engagement; (2) statistically adjust for age, education level, origin, and motivation when interpreting learner satisfaction results; and (3) monitor the level of emotional engagement and implement educational interventions to provide support for emotional disengagers.

The Involvement of Oxidative Stress, Neuronal Lesions, Neurotransmission Impairment, and Neuroinflammation in Acrylamide-Induced Neurotoxicity

Acrylamide (ACR) is a typically contaminate during environmental industry and poses potential health hazards that have been attracting increasing attention. Its neurotoxicity is known to cause significant damage to health. However, the mechanisms of ACR-induced neurotoxicity require further clarification. This study explores how ACR-induced oxidative stress, neuronal lesions, neurotransmission impairment, and neuroinflammation mutually contribute to neurotoxicity using a mouse model. According to the results, oxidative stress was indicated by the presence of a distinct increase in cellular reactive oxygen species levels, malondialdehyde, and 8-hydroxy-2-deoxyguanosine content, as well as a significant decrease in the glutathione content after ACR exposure. Moreover, ACR caused neurological defects associated with gait abnormality and neuronal loss while suppressing the levels of acetylcholine and dopamine and increasing the protein expression of α-syn, further inhibiting cholinergic and dopaminergic neuronal function. Additionally, ACR treatment caused an inflammation response via NF-κB activation and increased the protein expression of NLRP3. Consequently, ACR activated the NLRP3 inflammasome constituents, including Caspase-1, ASC, N-GSDMD, IL-1β, and IL-18. The results revealed the underlying molecular mechanism of ACR-induced neurotoxicity via oxidative stress, neurotransmission impairment, and neuroinflammation-related signal cascade. This information will further improve the development of an alternative outcome pathway strategy for investigating the risk posed by ACR.

Salmonella in Chicken Meat: Consumption, Outbreaks, Characteristics, Current Control Methods and the Potential of Bacteriophage Use

The control of Salmonella in chicken processing plants is an ongoing challenge for many factories around the globe, especially with the increasing demand for poultry escalating processing throughputs. Foodborne outbreaks due to Salmonella still pose a prominent risk to public health. As chicken meat is a good reservoir for Salmonella, it is important for chicken processing plants to continuously optimize methods to reduce the incidence of Salmonella on their products. Current methods include the use of chemical antimicrobials such as chlorine-containing compounds and organic acids. However, these current methods are decreasing in popularity due to the rising rate of Salmonella resistance, coupled with the challenge of preserving the sensory properties of the meat, along with the increasing stringency of antimicrobial use. Bacteriophages are becoming more appealing to integrate into the large scale hurdle concept. A few factors s need to be considered for successful implementation, such as legislation, and application volumes and concentrations. Overall, bacteriophages show great potential because of their host specificity, guaranteeing an alternative outcome to the selective pressure for resistant traits placed by chemicals on whole microbial communities.

Can UN Peacekeeping Promote Environmental Quality?

This research focuses on a positive, and previously largely unknown, implication of United Nations (UN) peacekeeping: better environmental quality. While maintaining international peace and security remains the main goal of peacekeeping operations, we contend that they can also be linked to environmentally friendly outcomes. Mission mandates and UN policies increasingly comprise actions that potentially promote environmental quality. At the same time, positive side effects on the environment materialize due to the cooperation with and activities of other UN bodies. The empirical analyses, also correcting for the likely non-random assignment of peace missions and employing several alternative outcome measures, suggest that UN peace missions are indeed substantively associated with better environmental quality. This research has important implications for our understanding of peacekeeping operations, and it contributes to the literatures on the (unintended) consequences of peacekeeping as well as environmental politics.

Cannabinoid Modulation of Dopamine Release During Motivation, Periodic Reinforcement, Exploratory Behavior, Habit Formation, and Attention

Motivational and attentional processes energize action sequences to facilitate evolutionary competition and promote behavioral fitness. Decades of neuropharmacology, electrophysiology and electrochemistry research indicate that the mesocorticolimbic DA pathway modulates both motivation and attention. More recently, it was realized that mesocorticolimbic DA function is tightly regulated by the brain’s endocannabinoid system and greatly influenced by exogenous cannabinoids—which have been harnessed by humanity for medicinal, ritualistic, and recreational uses for 12,000 years. Exogenous cannabinoids, like the primary psychoactive component of cannabis, delta-9-tetrahydrocannabinol, produce their effects by acting at binding sites for naturally occurring endocannabinoids. The brain’s endocannabinoid system consists of two G-protein coupled receptors, endogenous lipid ligands for these receptor targets, and several synthetic and metabolic enzymes involved in their production and degradation. Emerging evidence indicates that the endocannabinoid 2-arachidonoylglycerol is necessary to observe concurrent increases in DA release and motivated behavior. And the historical pharmacology literature indicates a role for cannabinoid signaling in both motivational and attentional processes. While both types of behaviors have been scrutinized under manipulation by either DA or cannabinoid agents, there is considerably less insight into prospective interactions between these two important signaling systems. This review attempts to summate the relevance of cannabinoid modulation of DA release during operant tasks designed to investigate either motivational or attentional control of behavior. We first describe how cannabinoids influence DA release and goal-directed action under a variety of reinforcement contingencies. Then we consider the role that endocannabinoids might play in switching an animal’s motivation from a goal-directed action to the search for an alternative outcome, in addition to the formation of long-term habits. Finally, dissociable features of attentional behavior using both the 5-choice serial reaction time task and the attentional set-shifting task are discussed along with their distinct influences by DA and cannabinoids. We end with discussing potential targets for further research regarding DA-cannabinoid interactions within key substrates involved in motivation and attention.

Oh…So close! Children’s close counterfactual reasoning and emotion inferences

How we feel about an outcome often depends on how close an alternative outcome was to occurring. In four experiments, we investigated whether predominantly White, middle-class, Canadian children (N = 425, Experiments 1-3) and American adults (N = 227, Experiment 4) consider close counterfactual alternatives when inferring other people’s emotions. In Experiment 1, 6-year-olds (but not 4- and 5-year-olds) inferred that an agent would feel sadder about winning a mediocre prize if she later found out that a more attractive one could have easily been won. However, children of all ages failed to judge whether the better outcome could have easily happened. In Experiment 2, when 5- and 6-year-olds knew the locations of the prizes beforehand, they inferred that an agent would be equally happy about winning a mediocre prize regardless if she almost won a better prize or not. Again, they did not recognize when the better outcome was a close counterfactual possibility. In Experiment 3, we included extra cues to the closeness of the alternative and both 5- and 6-year-olds inferred that she would feel sadder about winning a mediocre prize, and 6-year-olds acknowledged that the attractive prize was a close counterfactual alternative. In Experiment 4, adults considered close counterfactuals when inferring emotions. Our findings suggest that close counterfactuals influence children’s emotion inferences before they become able to acknowledge their closeness.

What are the key themes associated with the positive learning experience in MOOCs? An empirical investigation of learners’ ratings and reviews

Past MOOC research has tended to focus on learning outcomes valued in traditional higher education settings, such as achievement and retention. This study recognises that student ratings are an important alternative outcome measure in MOOCs. This paper adopted a semiautomatic text mining approach to collect and analyse 8475 ratings and reviews submitted for 1794 MOOCs. The analysis revealed six important themes that contributed to positive ratings: ‘learning’, ‘understanding’, ‘interesting’, ‘videos’, ‘recommend’, and ‘questions’. The paper then investigated the characteristics of each identified theme based on the proximity of themes, distribution of concepts within themes, and important connections. Based on research findings, the paper presents the following propositions to assist educators and providers to enhance the learning experience in MOOCs: (1) provide realistic learning contexts and instructional conditions in MOOCs to facilitate the acquisition of knowledge that transfers more readily to real-world practices; (2) carefully design the instructional conditions so that some mental challenge and stimulation is required for learners to achieve a full understanding of the content, rather than making MOOCs too simple or effortless to complete; (3) design the course content, materials, and communications to generate interest; (4) allocate sufficient resources to create high-quality video lectures; (5) employ video lectures to elicit positive emotions from MOOC learners and simplify complex, difficult concepts; and (6) incorporate discussion boards in MOOCs and invest in human and digital resources to address learners’ queries.

CRISPR/Cas9-based inactivation of human papillomavirus oncogenes E6 and E7 induces senescence in cervical cancer cells

ABSTRACTHuman papillomaviruses (HPVs) such as HPV16 and HPV18 can cause cancers of the cervix, vagina, vulva, penis, anus and oropharynx. Continuous expression of the HPV viral oncoproteins E6 and E7 are essential for transformation and maintenance of cancer cells. Therefore, therapeutic targeting of E6 and E7 genes can potentially be used to treat HPV-related cancers. Previous CRISPR/Cas9 studies on inactivation of E6 and E7 genes confirmed cell cycle arrest and apoptosis. Here we report that CRISPR/Cas9-based knockout of E6 and E7 can also trigger cellular senescence in HPV18 immortalized HeLa cells. Specifically, HeLa cells in which E6 and E7 were inactivated exhibited characteristic senescence markers like enlarged cell and nucleus surface area, increased β-galactosidase expression, and loss of lamin B1 with detection of cytoplasmic chromatin fragments. Furthermore, the knockout of HPV18 E6 and E7 proteins resulted in upregulation of p53/p21 and pRb/p21 levels in senescent cells. These senescent cells were devoid of characteristic apoptotic markers and re-introduction of codon-modified HPV18 E6 decreased p53 levels. Taken together, our study demonstrates that cellular senescence is as an alternative outcome of HPV oncogene inactivation by the CRISPR/Cas9 methodology.