Single centre observational study evaluating the impact of introducing High Flow Nasal Cannula outside of Paediatric Critical Care Unit.

AIM: To evaluate the impact of High Flow Nasal Cannula (HFNC) introduction outside of Paediatric Critical Care Units (PCCU), on PCCU admissions and intubation rates. Secondarily, to identify escalation predictors. METHODS: Retrospective observational study with matched PCCU admissions and intubation rates, 2-years before (Group 1) and 2-years after (Group 2) HFNC introduction outside of PCCU. Within Group 2, we compared those admitted to PCCU (escalation) and those who did not (non-escalation). Observations, change in observations and time to starting HFNC were analysed. RESULTS: Pre- and post-introduction comparison: Of 980 admissions in Group 1, 55 were admitted to PCCU, whereas of 1209 admission in Group 2, there were 85 admissions, P = 0.188. Group 1 had 25 intubations compared to 23 in Group 2, P = 0.309. Over twice as many children had some form of respiratory support in Group 2. Post-introduction: 104 children commenced HFNC, 72% for bronchiolitis. Median age was 4 months in the non-escalation group and 6.5 months in the escalation group, P = 0.663. Thirty-eight children escalated to PCCU: 33 required CPAP/BiPAP, 4 were intubated with 1 remaining on HFNC. Comparisons of age, gender, comorbidities, observations, change in observations and time to starting HFNC showed no significant escalation predictors. CONCLUSIONS: This study identified no statistically significant predictors of escalation. There was an observed increase in PCCU admissions with decreased intubations. The resource implications of this therapy are significant and further studies should examine cost effectiveness of HFNC use outside of PCCU.

Food Choices, Sustainability and Australian Native Foods: Perceptions among University Students.

(1) Background: Urgent changes in our food choices are needed for more sustainable, resilient and equitable food systems. Australian native plant-based foods have both environmental and health benefits. Including these foods in our diet may reduce both the risk of chronic diseases and the impact of climate change. This study explored the perceptions and attitudes towards food choices, sustainability and Australian native plant-based food among university students. (2) Methods: A cross-sectional online survey was completed by 212 university students in Australia from October to December 2022. Questions included information about sociodemographic characteristics, food choices, Australian native foods and the impact on sustainability. Logistic regression was used for analyses. (3) Results: Most participants recognised the impact of food choices on sustainability. There was a significant association between recognition of the impact of food choices on sustainability and the environmental and nutritional benefits of Australian native foods (OR = 2.89, 95% CI 1.29, 6.46, p = 0.010). Students who were familiar with or had tried Australian native plant-based foods were significantly more likely to recognise their environmental and nutritional benefits (p < 0.001). (4) Conclusions: Students who recognise the impact of food choices on sustainability and the benefits of Australian native foods are more likely to include native foods in their diet. More studies are needed to investigate the specific native foods consumed and the barriers and facilitators to the intake of these foods.

Nutritional supplementation, tooth crown size, and trait expression in individuals from Tezonteopan, Mexico.

Understanding how epigenetic factors impact dental phenotypes can help refine the use of teeth for elucidating biological relationships among human populations. We explored relationships among crown size, principal cusp spacing, and accessory cusp expression in maxillary dental casts of nutritionally supplemented (n = 34) and non-supplemented (n = 39) individuals from Tezonteopan, Mexico. We hypothesized that the non-supplemented group would exhibit smaller molar crowns and reduced intercusp spacing. Since intercusp spacing is thought to be more sensitive to epigenetic influences than crown size, we predicted that the supplemented and non-supplemented groups would differ more in the former than the latter. Previous work suggests that molar accessory cusp expression may be elevated under conditions of stress. We therefore expected evidence of greater Carabelli and Cusp 5 trait expression in the non-supplemented group. We further hypothesized that anterior teeth would be affected by nutritional stress during development, with the non-supplemented group having smaller anterior tooth crowns and therefore limited space to form the tuberculum dentale. Finally, we tested whether the presence of molar accessory traits followed predictions of the Patterning Cascade Model of tooth morphogenesis in the entire sample. Our results supported the expectation that cusp spacing would differ more than molar crown size between the two groups. Carabelli trait showed little evidence of frequency differences between groups, but some evidence of greater trait scores in the non-supplemented group. The non-supplemented group also showed evidence of greater Cusp 5 frequency and expression. In the central incisors and canines, there was strong evidence for smaller crown sizes and reduced tuberculum dentale frequency in the non-supplemented group. With both groups pooled together, there was strong evidence of closer mesiodistal distances among principal cusps in molars with accessory cusps, a finding that is consistent with the PCM. Overall, our findings suggest that nutritional stress may affect accessory cusp expression.

Affect variability and cortisol in context: The moderating roles of mean affect and stress.

Positive and negative affect have been shown to have implications for hormones like cortisol but how moment to moment changes in affect (i.e., affect variability) influence cortisol secretion is less well understood. Additionally, context characteristics such as mean affect and stress may influence the association between affect variability and cortisol output. In the current study, we examined affect, stress, and cortisol data from 113 participants (age range = 25-63, M = 35.63, SD = 11.34; 29% male; 42% White/Caucasian, 37% Asian or Pacific Islander, 13% Hispanic/Latino, 4% Black/African American, 1% Native American, Eskimo, or Aleut, 4% selected "other" for their race/ethnicity). Participants completed ecological momentary assessments assessing positive and negative affect and stress four times per day for five days and provided saliva samples at each time point. Saliva was assayed for cortisol, and area under the curve with respect to ground was computed. In a three-way interaction, both positive affect mean level and stress moderated the association between positive affect variability and cortisol (b = -1.55, t(100) = -3.29, SE = 0.47, p <.01, ß = -4.05). When breaking down this three-way interaction, in the context of low stress and high mean positive affect, variability was positively related to total cortisol output. In contrast, in the context of high stress and high mean positive affect, variability was negatively related to total cortisol output. While greater positive affect variability is generally worse for health-relevant outcomes (as prior research has shown and as we show here at low levels of stress), at high levels of stress, fluctuation in affect may be adaptive. For someone experiencing a high stress week, having fluctuations in positive affect may mean that they are adaptively changing to meet their environmental needs especially when they typically report high mean positive affect levels. There were no associations between negative affect variability and cortisol secretion nor did mean negative affect or stress play a moderating role for negative affect variability. This study provides evidence that positive affect variability's association with cortisol secretion throughout the day may vary based on stress and mean positive affect levels.

ST-2560, a selective inhibitor of the NaV1.7 sodium channel, affects nocifensive and cardiovascular reflexes in non-human primates.

BACKGROUND AND PURPOSE: The voltage-gated sodium channel isoform NaV1.7 is a high-interest target for the development of non-opioid analgesics due to its preferential expression in pain-sensing neurons. NaV1.7 is also expressed in autonomic neurons, yet its contribution to involuntary visceral reflexes has received limited attention. The small molecule inhibitor ST-2560 was advanced into pain behaviour and cardiovascular models to understand the pharmacodynamic effects of selective inhibition of NaV1.7. EXPERIMENTAL APPROACH: Potency of ST-2560 at NaV1.7 and off-target ion channels was evaluated by whole-cell patch-clamp electrophysiology. Effects on nocifensive reflexes were assessed in non-human primate (NHP) behavioural models, employing the chemical capsaicin and mechanical stimuli. Cardiovascular parameters were monitored continuously in freely-moving, telemetered NHPs following administration of vehicle and ST-2560. KEY RESULTS: ST-2560 is a potent inhibitor (IC50 = 39 nM) of NaV1.7 in primates with ≥1000-fold selectivity over other isoforms of the human NaV1.x family. Following systemic administration, ST-2560 (0.1-0.3 mg·kg-1, s.c.) suppressed noxious mechanical- and chemical-evoked reflexes at free plasma concentrations threefold to fivefold above NaV1.7 IC50. ST-2560 (0.1-1.0 mg·kg-1, s.c.) also produced changes in haemodynamic parameters, most notably a 10- to 20-mmHg reduction in systolic and diastolic arterial blood pressure, at similar exposures. CONCLUSIONS AND IMPLICATIONS: Acute pharmacological inhibition of NaV1.7 is antinociceptive, but also has the potential to impact the cardiovascular system. Further work is merited to understand the role of NaV1.7 in autonomic ganglia involved in the control of heart rate and blood pressure, and the effect of selective NaV1.7 inhibition on cardiovascular function.

Co-Designing Research for Sustainable Food Systems and Diets with Aboriginal Communities: A Study Protocol.

(1) Background: Food choices and systems have contributed to various health and environmental issues, resulting in the global syndemic (obesity, undernutrition and climate change). Studies show that revitalizing Indigenous food systems and including native plant-based foods in our diet may be important for promoting health, reducing diet-linked chronic diseases and mitigating environmental changes. However, it is still a challenge to 'Indigenize' research by including Aboriginal people in all project phases to achieve culturally appropriate collaboration. We describe the development of a protocol using co-design methods to explore how knowledge can be exchanged around Aboriginal food practices related to native plant-based foods to facilitate benefits and share opportunities for sustainable food systems and Aboriginal aspirations, as well as to promote health in these communities. (2) Methods: This qualitative study includes five phases. In Phase I, we will start building a trusting relationship with the communities and train the research team. In Phase II, we will receive the consent to co-design and establish the Aboriginal Reference Group to ensure that Aboriginal people will lead this project. In Phase III, the investigators will run the interviews/focus groups and record the discussions about the community's place-based needs, understanding the community aspirations for a sustainable food system and the potential opportunities for doing research and strengthening community between research and community. In Phase IV, the records will be analyzed with the Aboriginal Reference Group, and summaries will be shared with community members. Phase V will establish case studies to support the implementation of community aspirations. (3) Discussion: This study protocol describes the process of ensuring that research for sustainable food systems meets Indigenous aspirations and health promotion in Indigenous communities.

Dental complexity and diet in amniotes: A meta-analysis.

Tooth morphology is among the most well-studied indicators of ecology. For decades, researchers have examined the gross morphology and wear patterns of teeth as indicators of diet, and recent advances in scanning and computer analysis have allowed the development of new and more quantitative measures of tooth morphology. One of the most popular of these new methods is orientation patch count (OPC). OPC, a measure of surface complexity, was originally developed to distinguish the more complex tooth crowns of herbivores from the less complex tooth crowns of faunivores. OPC and a similar method derived from it, orientation patch count rotated (OPCR), have become commonplace in analyses of both modern and fossil amniote dietary ecology. The widespread use of these techniques makes it possible to now re-assess the utility of OPC and OPCR. Here, we undertake a comprehensive review of OPC(R) and diet and perform a meta-analysis to determine the overall difference in complexity between herbivores and faunivores. We find that the relationship between faunivore and herbivore OPC or OPCR values differs substantially across studies, and although some support the initial assessment of greater complexity in herbivores, others do not. Our meta-analysis does not support an overall pattern of greater complexity in herbivores than faunivores across terrestrial amniotes. It appears that the relationship of OPC or OPCR to diet is taxon-specific and dependent on the type of faunivory of the group in question, with insectivores often having values similar to herbivores. We suggest extreme caution in comparing OPC and OPCR values across studies and offer suggestions for how OPCR can constructively be used in future research.

Understanding Post-Esophagectomy Complications and Their Management: The Early Complications.

Esophagectomy is a technically complex operation performed for both benign and malignant esophageal disease. Medical and surgical advancements have led to improved outcomes in esophagectomy patients over the past several decades; however, surgeons must remain vigilant as complications happen often and can be severe. Post-esophagectomy complications can be grouped into early and late categories. The aim of this review is to discuss the early complications of esophagectomy along with their risk factors, work-up, and management strategies with special attention given to anastomotic leaks.

A Critique of Automated Approaches to Code Facial Expressions: What Do Researchers Need to Know?

Facial expression recognition software is becoming more commonly used by affective scientists to measure facial expressions. Although the use of this software has exciting implications, there are persistent and concerning issues regarding the validity and reliability of these programs. In this paper, we highlight three of these issues: biases of the programs against certain skin colors and genders; the common inability of these programs to capture facial expressions made in non-idealized conditions (e.g., "in the wild"); and programs being forced to adopt the underlying assumptions of the specific theory of emotion on which each software is based. We then discuss three directions for the future of affective science in the area of automated facial coding. First, researchers need to be cognizant of exactly how and on which data sets the machine learning algorithms underlying these programs are being trained. In addition, there are several ethical considerations, such as privacy and data storage, surrounding the use of facial expression recognition programs. Finally, researchers should consider collecting additional emotion data, such as body language, and combine these data with facial expression data in order to achieve a more comprehensive picture of complex human emotions. Facial expression recognition programs are an excellent method of collecting facial expression data, but affective scientists should ensure that they recognize the limitations and ethical implications of these programs.

Multi-center validation of an artificial intelligence system for detection of COVID-19 on chest radiographs in symptomatic patients.

OBJECTIVES: While chest radiograph (CXR) is the first-line imaging investigation in patients with respiratory symptoms, differentiating COVID-19 from other respiratory infections on CXR remains challenging. We developed and validated an AI system for COVID-19 detection on presenting CXR. METHODS: A deep learning model (RadGenX), trained on 168,850 CXRs, was validated on a large international test set of presenting CXRs of symptomatic patients from 9 study sites (US, Italy, and Hong Kong SAR) and 2 public datasets from the US and Europe. Performance was measured by area under the receiver operator characteristic curve (AUC). Bootstrapped simulations were performed to assess performance across a range of potential COVID-19 disease prevalence values (3.33 to 33.3%). Comparison against international radiologists was performed on an independent test set of 852 cases. RESULTS: RadGenX achieved an AUC of 0.89 on 4-fold cross-validation and an AUC of 0.79 (95%CI 0.78-0.80) on an independent test cohort of 5,894 patients. Delong's test showed statistical differences in model performance across patients from different regions (p < 0.01), disease severity (p < 0.001), gender (p < 0.001), and age (p = 0.03). Prevalence simulations showed the negative predictive value increases from 86.1% at 33.3% prevalence, to greater than 98.5% at any prevalence below 4.5%. Compared with radiologists, McNemar's test showed the model has higher sensitivity (p < 0.001) but lower specificity (p < 0.001). CONCLUSION: An AI model that predicts COVID-19 infection on CXR in symptomatic patients was validated on a large international cohort providing valuable context on testing and performance expectations for AI systems that perform COVID-19 prediction on CXR. KEY POINTS: • An AI model developed using CXRs to detect COVID-19 was validated in a large multi-center cohort of 5,894 patients from 9 prospectively recruited sites and 2 public datasets. • Differences in AI model performance were seen across region, disease severity, gender, and age. • Prevalence simulations on the international test set demonstrate the model's NPV is greater than 98.5% at any prevalence below 4.5%.

Discovery of Selective Inhibitors of NaV1.7 Templated on Saxitoxin as Therapeutics for Pain.

The voltage-gated sodium channel isoform NaV1.7 has drawn widespread interest as a target for non-opioid, investigational new drugs to treat pain. Selectivity over homologous, off-target sodium channel isoforms, which are expressed in peripheral motor neurons, the central nervous system, skeletal muscle and the heart, poses a significant challenge to the development of small molecule inhibitors of NaV1.7. Most inhibitors of NaV1.7 disclosed to date belong to a class of aryl and acyl sulfonamides that preferentially bind to an inactivated conformation of the channel. By taking advantage of a sequence variation unique to primate NaV1.7 in the extracellular pore of the channel, a series of bis-guanidinium analogues of the natural product, saxitoxin, has been identified that are potent against the resting conformation of the channel. A compound of interest, 25, exhibits >600-fold selectivity over off-target sodium channel isoforms and is efficacious in a preclinical model of acute pain.

A multi-lab test of the facial feedback hypothesis by the Many Smiles Collaboration.

Following theories of emotional embodiment, the facial feedback hypothesis suggests that individuals' subjective experiences of emotion are influenced by their facial expressions. However, evidence for this hypothesis has been mixed. We thus formed a global adversarial collaboration and carried out a preregistered, multicentre study designed to specify and test the conditions that should most reliably produce facial feedback effects. Data from n = 3,878 participants spanning 19 countries indicated that a facial mimicry and voluntary facial action task could both amplify and initiate feelings of happiness. However, evidence of facial feedback effects was less conclusive when facial feedback was manipulated unobtrusively via a pen-in-mouth task.

Why So Serious? An Attempt to Mitigate the Short-Term Harmful Effects of the Film Joker on Prejudice toward People with Mental Illness.

The media perpetuates many harmful stereotypes about people with mental illness. In two studies, we demonstrate the impact of negative media portrayals of mental illness on prejudice and attempt to mitigate these negative effects. Specifically, in Study 1, participants watched the movie Joker, a recent film which associates mental illness with violent behavior, or a control film (Terminator). Participants completed the Prejudice towards People with Mental Illness (PPMI) scale before and after viewing their respective films. The PPMI consists of four dimensions: fear/avoidance (i.e., wanting to avoid people with mental illness), malevolence (i.e., viewing people with mental illness as inferior), authoritarianism (i.e., preference for control over people with mental illness), and unpredictability (i.e., the behavior of people with mental illness is unreliable). We hypothesized that participants who watched the film Joker would display an increase in their fear/avoidance of people with mental illness and their support for authoritarian approaches to their treatment. Consistent with these hypotheses, participants who viewed Joker displayed a significant increase in the fear/avoidance and authoritarian subscales of the PPMI, relative to participants that watched Terminator. In Study 2, in an attempt to mitigate the impact of Joker on prejudice towards people with mental illness, directly after the film we displayed educational and counter-stereotypical statements on-screen that challenged the view that people with mental illness are violent. A control group viewed Joker without these statements. Identical to Study 1, all participants completed the PPMI scale before and after viewing the film. We hypothesized that participants who viewed Joker with the statements would display lower prejudice relative to the control condition. Unfortunately, participants in the experimental and control conditions displayed a comparable increase in prejudice. Together, these studies confirm the negative effect of media portrayals of mental illness (as depicted in Joker) and demonstrate that these effects are not easily mitigated.

Lung Cancer Attracts Greater Stigma than Other Cancer Types in Aotearoa New Zealand.

Background: Lung cancer is the leading cause of cancer death in Aotearoa New Zealand, killing over 1,700 people each year. Despite the burden of lung cancer in Aotearoa New Zealand, the popular press has referred to it as the cancer type that no one talks about. Here, we investigate one factor that may contribute to this state of affairs: lung cancer stigma. Methods: Participants were university students and members of the general public. University students were recruited via an online experiment participation system in 2021. Members of the public were recruited via social media. All participants completed the Cancer Stigma Scale (CSS) for one of five cancer types (lung, cervical, breast, skin, or bowel). The CSS is a 25-item scale with six subscales: awkwardness, avoidance, severity, policy opposition, personal responsibility, and financial discrimination. Results: The mean age of participants was 24.3 (Standard Deviation = 10.4). Data from each subscale were submitted to an analysis of covariance (ANCOVA), with cancer type as a between-participant factor (5: lung, cervical, breast, skin, or bowel) and stigma as the dependent variable. Relative to most other cancer types, people were more likely to avoid someone with lung cancer, view interacting with someone with lung cancer as more awkward, and view people with lung cancer as being responsible for their condition. Conclusion: The Health Research Council of New Zealand recently funded the very first trial of lung cancer screening in Aotearoa New Zealand. The current study suggests that addressing stigma will be essential for the success of such programs, with stigma likely influencing those who engage in such trials.