Engaging communities in addressing air quality: a scoping review.

BACKGROUND: Exposure to air pollution has a detrimental effect on health and disproportionately affects people living in socio-economically disadvantaged areas. Engaging with communities to identify concerns and solutions could support organisations responsible for air quality control, improve environmental decision-making, and widen understanding of air quality issues associated with health. This scoping review aimed to provide an overview of approaches used to engage communities in addressing air quality and identify the outcomes that have been achieved. METHODS: Searches for studies that described community engagement in air quality activities were conducted across five databases (Academic Search Complete, CABI, GreenFILE, MEDLINE, Web of Science). Data on study characteristics, community engagement approach, and relevant outcomes were extracted. The review process was informed by a multi-stakeholder group with an interest in and experience of community engagement in air quality. Thirty-nine papers from thirty studies were included in the final synthesis. CONCLUSION: A range of approaches have been used to engage communities in addressing air quality, most notably air quality monitoring. Positive outcomes included increased awareness, capacity building, and changes to organisational policy and practice. Longer-term projects and further exploration of the impact of community engagement on improving air quality and health are needed as reporting on these outcomes was limited.

The Acute Stroke Therapy by Inhibition of Neutrophils study - Key features and impact.

The Acute Stroke Therapy by Inhibition of Neutrophils (ASTIN) study, initiated in November of the year 2000, is now widely recognized as having been a landmark study in the history of clinical trials. We look at why this is the case by considering its key features and impact. These key features are: the use of Bayesian design and analysis; the use of the normal dynamic linear model; the response adaptive nature of the study; the use of real-time dosing decisions; and the use of an integrated model to predict 90-day response on the Scandinavian Stroke Scale. Our overall conclusion is that the ASTIN study's main impact came from showing the clinical trial community the feasibility of the novel design and analysis used when most of these key features were rarely used in industry trials, let alone used together in one trial in a disease area with a tremendous unmet medical need.

Candidate biomarkers for the diagnosis and prognosis of drug-induced liver injury: An international collaborative effort.

Current blood biomarkers are suboptimal in detecting drug-induced liver injury (DILI) and predicting its outcome. We sought to characterize the natural variabilty and performance characteristics of 14 promising DILI biomarker candidates. Serum or plasma from multiple cohorts of healthy volunteers (n = 192 and n = 81), subjects who safely took potentially hepatotoxic drugs without adverse effects (n = 55 and n = 92) and DILI patients (n = 98, n = 28, and n = 143) were assayed for microRNA-122 (miR-122), glutamate dehydrogenase (GLDH), total cytokeratin 18 (K18), caspase cleaved K18, glutathione S-transferase α, alpha-fetoprotein, arginase-1, osteopontin (OPN), sorbitol dehydrogenase, fatty acid binding protein, cadherin-5, macrophage colony-stimulating factor receptor (MCSFR), paraoxonase 1 (normalized to prothrombin protein), and leukocyte cell-derived chemotaxin-2. Most candidate biomarkers were significantly altered in DILI cases compared with healthy volunteers. GLDH correlated more closely with gold standard alanine aminotransferase than miR-122, and there was a surprisingly wide inter- and intra-individual variability of miR-122 levels among healthy volunteers. Serum K18, OPN, and MCSFR levels were most strongly associated with liver-related death or transplantation within 6 months of DILI onset. Prediction of prognosis among DILI patients using the Model for End-Stage Liver Disease was improved by incorporation of K18 and MCSFR levels. Conclusion: GLDH appears to be more useful than miR-122 in identifying DILI patients, and K18, OPN, and MCSFR are promising candidates for prediction of prognosis during an acute DILI event. Serial assessment of these biomarkers in large prospective studies will help further delineate their role in DILI diagnosis and management.

High-fidelity copying is not necessarily the key to cumulative cultural evolution: a study in monkeys and children.

The unique cumulative nature of human culture has often been explained by high-fidelity copying mechanisms found only in human social learning. However, transmission chain experiments in human and non-human primates suggest that cumulative cultural evolution (CCE) might not necessarily depend on high-fidelity copying after all. In this study, we test whether defining properties of CCE can emerge in a non-copying task. We performed transmission chain experiments in Guinea baboons and human children where individuals observed and produced visual patterns composed of four squares on touchscreen devices. In order to be rewarded, participants had to avoid touching squares that were touched by a previous participant. In other words, they were rewarded for innovation rather than copying. Results nevertheless exhibited fundamental properties of CCE: an increase over generations in task performance and the emergence of systematic structure. However, these properties arose from different mechanisms across species: children, unlike baboons, converged in behaviour over generations by copying specific patterns in a different location, thus introducing alternative copying mechanisms into the non-copying task. In children, prior biases towards specific shapes led to convergence in behaviour across chains, while baboon chains showed signs of lineage specificity. We conclude that CCE can result from mechanisms with varying degrees of fidelity in transmission and thus that high-fidelity copying is not necessarily the key to CCE.

Culture shapes the evolution of cognition.

A central debate in cognitive science concerns the nativist hypothesis, the proposal that universal features of behavior reflect a biologically determined cognitive substrate: For example, linguistic nativism proposes a domain-specific faculty of language that strongly constrains which languages can be learned. An evolutionary stance appears to provide support for linguistic nativism, because coordinated constraints on variation may facilitate communication and therefore be adaptive. However, language, like many other human behaviors, is underpinned by social learning and cultural transmission alongside biological evolution. We set out two models of these interactions, which show how culture can facilitate rapid biological adaptation yet rule out strong nativization. The amplifying effects of culture can allow weak cognitive biases to have significant population-level consequences, radically increasing the evolvability of weak, defeasible inductive biases; however, the emergence of a strong cultural universal does not imply, nor lead to, nor require, strong innate constraints. From this we must conclude, on evolutionary grounds, that the strong nativist hypothesis for language is false. More generally, because such reciprocal interactions between cultural and biological evolution are not limited to language, nativist explanations for many behaviors should be reconsidered: Evolutionary reasoning shows how we can have cognitively driven behavioral universals and yet extreme plasticity at the level of the individual-if, and only if, we account for the human capacity to transmit knowledge culturally. Wherever culture is involved, weak cognitive biases rather than strong innate constraints should be the default assumption.

Testing strategy in phase 3 trials with multiple doses.

In this paper, we consider multiplicity testing approaches mainly for phase 3 trials with two doses. We review a few available approaches and propose some new ones. The doses selected for phase 3 usually have the same or a similar efficacy profile, so they have some degree of consistency in efficacy. We review the Hochberg procedure, the Bonferroni procedure, and a few consistency-adjusted procedures, and suggest new ones by applying the available procedures to the pooled dose and the high dose, the dose that is thought to be more efficacious between two doses. The reason behind the idea is that the pooled dose and the high dose are more consistent than the original two doses if the high dose is more efficacious than the low dose. We compare all approaches via simulations and recommend using a procedure combining 4A and the pooling approach. We also discuss briefly the testing strategy for trials with more than two doses.

Cross-modal associations and synesthesia: Categorical perception and structure in vowel-color mappings in a large online sample.

We report associations between vowel sounds, graphemes, and colors collected online from over 1,000 Dutch speakers. We also provide open materials, including a Python implementation of the structure measure and code for a single-page web application to run simple cross-modal tasks. We also provide a full dataset of color-vowel associations from 1,164 participants, including over 200 synesthetes identified using consistency measures. Our analysis reveals salient patterns in the cross-modal associations and introduces a novel measure of isomorphism in cross-modal mappings. We found that, while the acoustic features of vowels significantly predict certain mappings (replicating prior work), both vowel phoneme category and grapheme category are even better predictors of color choice. Phoneme category is the best predictor of color choice overall, pointing to the importance of phonological representations in addition to acoustic cues. Generally, high/front vowels are lighter, more green, and more yellow than low/back vowels. Synesthetes respond more strongly on some dimensions, choosing lighter and more yellow colors for high and mid front vowels than do nonsynesthetes. We also present a novel measure of cross-modal mappings adapted from ecology, which uses a simulated distribution of mappings to measure the extent to which participants' actual mappings are structured isomorphically across modalities. Synesthetes have mappings that tend to be more structured than nonsynesthetes', and more consistent color choices across trials correlate with higher structure scores. Nevertheless, the large majority (~ 70%) of participants produce structured mappings, indicating that the capacity to make isomorphically structured mappings across distinct modalities is shared to a large extent, even if the exact nature of the mappings varies across individuals. Overall, this novel structure measure suggests a distribution of structured cross-modal association in the population, with synesthetes at one extreme and participants with unstructured associations at the other.

Phonological and orthographic influences in the bouba-kiki effect.

We examine a high-profile phenomenon known as the bouba-kiki effect, in which non-word names are assigned to abstract shapes in systematic ways (e.g. rounded shapes are preferentially labelled bouba over kiki). In a detailed evaluation of the literature, we show that most accounts of the effect point to predominantly or entirely iconic cross-sensory mappings between acoustic or articulatory properties of sound and shape as the mechanism underlying the effect. However, these accounts have tended to confound the acoustic or articulatory properties of non-words with another fundamental property: their written form. We compare traditional accounts of direct audio or articulatory-visual mapping with an account in which the effect is heavily influenced by matching between the shapes of graphemes and the abstract shape targets. The results of our two studies suggest that the dominant mechanism underlying the effect for literate subjects is matching based on aligning letter curvature and shape roundedness (i.e. non-words with curved letters are matched to round shapes). We show that letter curvature is strong enough to significantly influence word-shape associations even in auditory tasks, where written word forms are never presented to participants. However, we also find an additional phonological influence in that voiced sounds are preferentially linked with rounded shapes, although this arises only in a purely auditory word-shape association task. We conclude that many previous investigations of the bouba-kiki effect may not have given appropriate consideration or weight to the influence of orthography among literate subjects.

A comparison of five approaches to decision-making for a first clinical trial of efficacy.

The first trial of clinical efficacy is an important step in the development of a compound. Such a trial gives the first indication of whether a compound is likely to have the efficacy needed to be successful. Good decisions dictate that good compounds have a large probability of being progressed and poor compounds have a large probability of being stopped. In this paper, we consider and contrast five approaches to decision-making that have been used. To illustrate the use of the five approaches, we conduct a comparison for two plausible scenarios with associated assumptions for sample sizing. The comparison shows some large differences in performance characteristics of the different procedures. Which decision-making procedures and associated performance characteristics are preferred will depend on the focus of interest and the decision maker's attitude to risk. Copyright © 2016 John Wiley & Sons, Ltd.

An evolutionary approach to sign language emergence: From state to process.

Understanding the relationship between gesture, sign, and speech offers a valuable tool for investigating how language emerges from a nonlinguistic state. We propose that the focus on linguistic status is problematic, and a shift to focus on the processes that shape these systems serves to explain the relationship between them and contributes to the central question of how language evolves.

Cultural evolution of systematically structured behaviour in a non-human primate.

Culture pervades human life and is at the origin of the success of our species. A wide range of other animals have culture too, but often in a limited form that does not complexify through the gradual accumulation of innovations. We developed a new paradigm to study cultural evolution in primates in order to better evaluate our closest relatives' cultural capacities. Previous studies using transmission chain experimental paradigms, in which the behavioural output of one individual becomes the target behaviour for the next individual in the chain, show that cultural transmission can lead to the progressive emergence of systematically structured behaviours in humans. Inspired by this work, we combined a pattern reproduction task on touch screens with an iterated learning procedure to develop transmission chains of baboons (Papio papio). Using this procedure, we show that baboons can exhibit three fundamental aspects of human cultural evolution: a progressive increase in performance, the emergence of systematic structure and the presence of lineage specificity. Our results shed new light on human uniqueness: we share with our closest relatives essential capacities to produce human-like cultural evolution.

The shrinking or disappearing observed treatment effect.

It is frequently noted that an initial clinical trial finding was not reproduced in a later trial. This is often met with some surprise. Yet, there is a relatively straightforward reason partially responsible for this observation. In this article, we examine this reason by first reviewing some findings in a recent publication in the Journal of the American Medical Association. To help explain the non-negligible chance of failing to reproduce a previous positive finding, we compare a series of trials to successive diagnostic tests used for identifying a condition. To help explain the suspicion that the treatment effect, when observed in a subsequent trial, seems to have decreased in magnitude, we draw a conceptual analogy between phases II-III development stages and interim analyses of a trial with a group sequential design. Both analogies remind us that what we observed in an early trial could be a false positive or a random high. We discuss statistical sources for these occurrences and discuss why it is important for statisticians to take these into consideration when designing and interpreting trial results.

Cultural evolution creates the statistical structure of language.

Human language is unique in its structure: language is made up of parts that can be recombined in a productive way. The parts are not given but have to be discovered by learners exposed to unsegmented wholes. Across languages, the frequency distribution of those parts follows a power law. Both statistical properties-having parts and having them follow a particular distribution-facilitate learning, yet their origin is still poorly understood. Where do the parts come from and why do they follow a particular frequency distribution? Here, we show how these two core properties emerge from the process of cultural evolution with whole-to-part learning. We use an experimental analog of cultural transmission in which participants copy sets of non-linguistic sequences produced by a previous participant: This design allows us to ask if parts will emerge purely under pressure for the system to be learnable, even without meanings to convey. We show that parts emerge from initially unsegmented sequences, that their distribution becomes closer to a power law over generations, and, importantly, that these properties make the sets of sequences more learnable. We argue that these two core statistical properties of language emerge culturally both as a cause and effect of greater learnability.

Evaluating the Relative Importance of Wordhood Cues Using Statistical Learning.

Identifying wordlike units in language is typically done by applying a battery of criteria, though how to weight these criteria with respect to one another is currently unknown. We address this question by investigating whether certain criteria are also used as cues for learning an artificial language-if they are, then perhaps they can be relied on more as trustworthy top-down diagnostics. The two criteria for grammatical wordhood that we consider are a unit's free mobility and its internal immutability. These criteria also map to two cognitive mechanisms that could underlie successful statistical learning: learners might orient themselves around the low transitional probabilities at unit boundaries, or they might seek chunks with high internal transitional probabilities. We find that each criterion has its own facilitatory effect, and learning is best where they both align. This supports the battery-of-criteria approach to diagnosing wordhood, and also suggests that the mechanism behind statistical learning may not be a question of either/or; perhaps the two mechanisms do not compete, but mutually reinforce one another.

Predictability and Variation in Language Are Differentially Affected by Learning and Production.

General principles of human cognition can help to explain why languages are more likely to have certain characteristics than others: structures that are difficult to process or produce will tend to be lost over time. One aspect of cognition that is implicated in language use is working memory-the component of short-term memory used for temporary storage and manipulation of information. In this study, we consider the relationship between working memory and regularization of linguistic variation. Regularization is a well-documented process whereby languages become less variable (on some dimension) over time. This process has been argued to be driven by the behavior of individual language users, but the specific mechanism is not agreed upon. Here, we use an artificial language learning experiment to investigate whether limitations in working memory during either language learning or language production drive regularization behavior. We find that taxing working memory during production results in the loss of all types of variation, but the process by which random variation becomes more predictable is better explained by learning biases. A computational model offers a potential explanation for the production effect using a simple self-priming mechanism.

Increased water temperature contributes to a chondrogenesis response in the eyes of spotted wolffish.

Adult vertebrate cartilage is usually quiescent. Some vertebrates possess ocular scleral skeletons composed of cartilage or bone. The morphological characteristics of the spotted wolffish (Anarhichas minor) scleral skeleton have not been described. Here we assessed the scleral skeletons of cultured spotted wolffish, a globally threatened marine species. The healthy spotted wolffish we assessed had scleral skeletons with a low percentage of cells staining for the chondrogenesis marker sex-determining region Y-box (Sox) 9, but harboured a population of intraocular cells that co-express immunoglobulin M (IgM) and Sox9. Scleral skeletons of spotted wolffish with grossly observable eye abnormalities displayed a high degree of perochondrial activation as evidenced by cellular morphology and expression of proliferating cell nuclear antigen (PCNA) and phosphotyrosine. Cells staining for cluster of differentiation (CD) 45 and IgM accumulated around sites of active chondrogenesis, which contained cells that strongly expressed Sox9. The level of scleral chondrogenesis and the numbers of scleral cartilage PCNA positive cells increased with the temperature of the water in which spotted wolffish were cultured. Our results provide new knowledge of differing Sox9 spatial tissue expression patterns during chondrogenesis in normal control and ocular insult paradigms. Our work also provides evidence that spotted wolffish possess an inherent scleral chondrogenesis response that may be sensitive to temperature. This work also advances the fundamental knowledge of teleost ocular skeletal systems.

The role of artificial intelligence in the treatment of obstructive sleep apnea.

BACKGROUND: The first-line and most common treatment for obstructive sleep apnea is nasal continuous positive airway pressure, which serves as a pneumatic splint to stabilize the upper airway and is effective when used with appropriate adherence. Continuous positive airway pressure compliance rates remain significantly low despite machine improvements and compliance intervention. Other treatment options include oral appliances, myofunctional therapy, and surgery. The aim of this project is to elucidate the role of artificial intelligence within improving the treatment of obstructive sleep apnea. METHODS: Related publications between 1999 and 2022 were reviewed from PubMed and Embase databases utilizing search terms "artificial intelligence," "machine learning," "obstructive sleep apnea," and "treatment." Both authors independently screened the results by title/abstract then by full text review. 126 non-duplicate articles were screened, 38 articles were included after title and abstract screen and 30 articles were included after full text review. The inclusion criteria are outline in the PICO framework and involved studies focused on artificial intelligence application in guiding and evaluating obstructive sleep apnea treatment. Non-English articles were excluded. RESULTS: The role of artificial intelligence in the treatment of OSA was categorized into the following sections: Predicting treatment outcomes of various treatment options, Improving/Evaluating treatment, and Personalizing treatment with improving understanding of underlying mechanisms of OSA. CONCLUSIONS: Artificial intelligence has the capacity to improve the treatment of OSA through predicting outcomes of treatment options, evaluating the treatment the patient is currently utilizing and increasing understanding of the mechanisms that contribute to OSA disease process and physiology. Implementing AI in guiding treatment decisions allows patients to connect with treatment methods that would be most effective on an individual basis.

Intraoperative video recording in otolaryngology for surgical education: evolution and considerations.

BACKGROUND: Otolaryngology is a surgical speciality well suited for the application of intraoperative video recording as an educational tool considering the number procedures within the speciality that utilize digital technology. Intraoperative recording has been utilized in endoscopic surgeries and in evaluating technique in mastoidectomy, myringotomy and grommet insertion. The impact of intra-operative video recording in otolaryngology education is vast in creating access to surgical videos for preparation outside the operating room to individualized coaching and assessment. The purpose of this project is to highlight the role of intraoperative video recording in otolaryngology training and elucidate the challenges and considerations associated with implementation. METHODS: Related publications between 1999 to 2022 were reviewed from PubMed and Embase databases utilizing search terms "intraoperative videography," "video recording surgery," "otolaryngology," and "surgical education." 109 articles were screened independently by HB and SK, by title and abstract then full text review. 28 articles from the original search and 6 from the secondary reference review were included. RESULTS: The application of intraoperative video recording is evident in otolaryngology surgeries including endoscopic sinus surgery, laryngeal surgery, and other endoscopic procedures. There have been significant advancements in recording tools, including devices that can capture the surgeon's perspective. The considerations and challenges identified with utilizing this educational tool were categorized into different themes including ethics/consent, regulation, liability, data, technology, and human resources. CONCLUSION: Intra-operative video recording has been demonstrated to have significant impact within otolaryngology education. It is critical to elucidate the challenges and considerations involved to utilize this educational tool effectively. Future directives will see video-based performance analytics providing comparative metrics to encourage precise coaching of surgical residents.

Documenting a Reduction in Signing Space in Nicaraguan Sign Language Using Depth and Motion Capture.

In this paper, we use motion tracking technology to document the birth of a brand new language: Nicaraguan Sign Language. Languages are dynamic entities that undergo change and growth through use, transmission, and learning, but the earliest stages of this process are generally difficult to observe as most languages have been used and passed down for many generations. Here, we observe a rare case of language emergence: the earliest stages of the new sign language in Nicaragua. By comparing the signing of the oldest and youngest signers of Nicaraguan Sign Language, we can track how the language itself is changing. Using motion tracking technology, we document a decrease in the size of articulatory space of Nicaraguan Sign Language signers over time. The reduction in articulatory space in Nicaraguan Sign appears to be the joint product of several decades of use and repeated transmission of this new language.

Kruppel-family zinc finger proteins as emerging epigenetic biomarkers in head and neck squamous cell carcinoma.

BACKGROUND: Krüppel-type zinc finger protein genes located on chromosome 19q13 are aberrantly hypermethylated with high frequency in all anatomic sub-sites of head and neck cancers as well as other epithelial tumours resulting in decreased expression. METHODS: We examined prognostic significance of ZNF154 and ZNF132 expression and DNA methylation in independent patient cohort of about 500 head and neck cancer patients in the Cancer Genome Atlas (TCGA). We also overexpressed these genes in HEK-293 cells, as well as the oral cancer cell line UM-SCC-1. RESULTS: In 20 patients from the TCGA cohort of HNSCC patients where ZNF154 and ZNF132 DNA methylation and RNA expression could be compared in tumor and adjacent normal tissue, there was increased DNA methylation and decreased expression of both ZNF154 and ZNF132 in primary tumours. Low ZNF154 and low ZNF132 expression were associated with shorter overall survival in both head and neck squamous cell carcinoma (HNSCC) and lung adenocarcinoma (LUAC patients). While expression of these proteins in HEK-293 cells produced full-length protein, only truncated copies could be expressed in head and neck cancer cells (UM-SCC-1). The truncated version of ZNF154 protein increased doubling time and reduced cell migration in UM-SCC-1 cancer cells. CONCLUSIONS: Both ZNF132 and ZNF154 represent novel clinically significant biomarkers in head and neck cancer with potential tumour suppressive properties. Future studies will address the underlying molecular mechanisms by which ZNF154 expression in HNSCC contributes to the control of cell growth and migration.