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Background Carbapenem-resistant Enterobacterales (CRE) are an urgent public health threat in the United States. Objective Describe the clinical and molecular epidemiology of CRE in a multicenter pediatric cohort. Methods CRACKLE-1 and CRACKLE-2 are prospective cohort studies with consecutive enrollment of hospitalized patients with CRE infection or colonization between 24 December 2011 and 31 August 2017. Patients younger than age 18 years and enrolled in the CRACKLE studies were included in this analysis. Clinical data were obtained from the electronic health record. Carbapenemase genes were detected using polymerase chain reaction and whole-genome sequencing. Results Fifty-one children were identified at 18 healthcare system study sites representing all U.S. census regions. The median age was 8 months, with 67% younger than age 2 years. Median number of days from admission to culture collection was 11. Seventy-three percent of patients had required intensive care and 41% had a history of mechanical ventilation. More than half of children had no documented comorbidities (Q1, Q3 0, 2). Sixty-seven percent previously received antibiotics during their hospitalization. The most common species isolated were Enterobacter species (41%), Klebsiella pneumoniae (27%), and Escherichia coli (20%). Carbapenemase genes were detected in 29% of isolates tested, which was lower than previously described in adults from this cohort (61%). Thirty-four patients were empirically treated on the date of culture collection, but only 6 received an antibiotic to which the CRE isolate was confirmed susceptible in vitro. Thirty-day mortality was 13.7%. Conclusions CRE infection or colonization in U.S. children was geographically widespread, predominantly affected children younger than age 2 years, associated with significant mortality, and less commonly caused by carbapenemase-producing strains than in adults. [ABSTRACT FROM AUTHOR]

Issues Addressed: Several national governments are showing interest in policies to promote wellbeing. One common strategy is to devise systems to measure indictors of wellbeing, presuming that governments act on what they measure. This article will argue instead that formation of multisectoral policies to promote psychological wellbeing requires a different kind of theoretical and evidentiary basis. Methods: The article integrates ideas from literature on wellbeing, health in all policies, political science, mental health promotion, and social determinants of health to make a case for place‐based policy as the central feature of multi‐sectoral policy for psychological wellbeing. Results and Discussion: I argue that the required theoretical foundation for policy action on psychological wellbeing lies with understanding certain basic functions of human social psychology including the role of stress arousal. I then draw on policy theory to propose three steps to translate this theoretical understanding of psychological wellbeing into practicable, multi‐sectoral policies. Step one is concerned with adopting a thoroughly revised conception of psychological wellbeing as a policy problem. Step two involves uptake of a theory of change in policy, grounded on recognition of essential social conditions required to promote psychological wellbeing. Proceeding from these, I will argue that a necessary (but not sufficient) third step is to implement place‐based strategies involving government‐community partnerships, to generate essential conditions for psychological wellbeing on a universal basis. Finally, I examine implications of the proposed approach for current theory and practice in mental health promotion policy. Conclusions: Place‐based policy is foundational for effective multi‐sectoral policy to promote psychological wellbeing. So What?: Governments aiming to promote psychological wellbeing should position place‐based policy at the centre of their strategies. [ABSTRACT FROM AUTHOR]

The chromobox-containing protein CBX4 is an important regulator of epithelial cell proliferation and differentiation, and has been implicated in several cancer types. The cancer stem cell (CSC) population is a key driver of metastasis and recurrence. The undifferentiated, plastic state characteristic of CSCs relies on cues from the microenvironment. Cancer-associated fibroblasts (CAFs) are a major component of the microenvironment that can influence the CSC population through the secretion of extracellular matrix and a variety of growth factors. Here we show CBX4 is a critical regulator of the CSC phenotype in squamous cell carcinomas of the skin and hypopharynx. Moreover, CAFs can promote the expression of CBX4 in the CSC population through the secretion of interleukin-6 (IL-6). IL-6 activates JAK/STAT3 signaling to increase ∆Np63α—a key transcription factor that is essential for epithelial stem cell function and the maintenance of proliferative potential that is capable of regulating CBX4. Targeting the JAK/STAT3 axis or CBX4 directly suppresses the aggressive phenotype of CSCs and represents a novel opportunity for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Our understanding of cancer and the key pathways that drive cancer survival has expanded rapidly over the past several decades. However, there are still important challenges that continue to impair patient survival, including our inability to target cancer stem cells (CSCs), metastasis, and drug resistance. The transcription factor p63 is a p53 family member with multiple isoforms that carry out a wide array of functions. Here, we discuss the critical importance of the ΔNp63α isoform in cancer and potential therapeutic strategies to target ΔNp63α expression to impair the CSC population, as well as to prevent metastasis and drug resistance to improve patient survival. ΔNp63α is a p63 isoform in the p53 family that is a master regulator of epithelial stemness in normal tissue. In cancer, ΔNp63α regulates a number of key aspects of cancer progression, including cancer stem cell (CSC) maintenance, metastasis, and drug resistance, through regulation of several downstream pathways. ΔNp63α is difficult to target directly, but multiple pathways upstream of ΔNp63α with druggable targets have been identified that represent potential therapeutic opportunities in cancer. Many pathways upstream of ΔNp63α are involved in crosstalk with the tumor microenvironment. With growing interest in targeting the tumor niche, further investigation into how ΔNp63α is involved in crosstalk with the microenvironment represents an exciting area of future investigation. [ABSTRACT FROM AUTHOR]

Cell turnover in adult tissues is essential for maintaining tissue homeostasis over a life span and for inducing the morphological changes associated with the reproductive cycle. However, the underlying mechanisms that coordinate the balance of cell death and proliferation remain unsolved. Using the mammary gland, we have discovered that Rac1 acts as a nexus to control cell turnover. Postlactational tissue regression is characterised by the death of milk secreting alveoli, but the process is reversible within the first 48 h if feeding recommences. In mice lacking epithelial Rac1, alveolar regression was delayed. This defect did not result from failed cell death but rather increased cell turnover. Fitter progenitor cells inappropriately divided, regenerating the alveoli, but cell death also concomitantly accelerated. We discovered that progenitor cell hyperproliferation was linked to nonautonomous effects of Rac1 deletion on the macrophageal niche with heightened inflammation. Moreover, loss of Rac1 impaired cell death with autophagy but switched the cell death route to apoptosis. Finally, mammary gland reversibility failed in the absence of Rac1 as the alveoli failed to recommence lactation upon resuckling. [ABSTRACT FROM AUTHOR]

Percentage changes greater than 100% are frequently used in consumer contexts; for example, a cordless vacuum cleaner may boast "125% longer runtime" compared to competitors. Via six studies (n  = 2,395) and 11 supplementary studies (n  = 3,249), the current research shows that consumers systematically underestimate the magnitude of percentage changes greater than 100%. Specifically, many consumers apply the relative size usage (e.g. "125% of," equivalent to 25% more) instead of the appropriate relative change (e.g. "125% more," equivalent to 100% more + 25% more), which leads them to be off by exactly 100% in their magnitude estimates. The rate of bias decreases when the difference between these two usages is emphasized. The Off by 100% bias occurs across a variety of consumer contexts, influencing behavioral intentions and incentive-compatible choice. The findings make theoretical contributions to research on processing of percentages, probability versus frequency formats, and magnitude judgments. Finally, understanding how different presentation formats of the same information can lead to different magnitude judgments enables marketers and policymakers to ensure more effective communication. [ABSTRACT FROM AUTHOR]

New technology invariably provokes concerns over potential societal impacts. Even as risks often fail to materialize, the fear continues. The current research explored the psychological underpinnings of this pattern. Across four studies (N = 2,454 adults recruited via Amazon Mechanical Turk), we found evidence for the role of status quo thinking in evaluating technology. In Study 1, we experimentally manipulated the reported age of unfamiliar technology and found that people evaluate it more favorably when it is described as originating before (vs. after) their birth. In Studies 2 through 4, participants' age at the time of invention strongly predicts attitudes toward a wide range of real-world technologies. Finally, we found that individual differences in status-quo-based decision-making moderated evaluations of technology. These studies provide insight into how people respond to the rapidly changing technological landscape. [ABSTRACT FROM AUTHOR]

Makerspace tools and technologies are becoming increasingly popular in K-12 educational settings. While makerspace education has the potential to democratize educational spaces, the integration of these new technologies into the classroom is not trivial. In this paper, we analyze a university-based makerspace apprenticeship program for pre-service teachers to learn makerspace tools and technologies for use in their future classrooms. We demonstrate how apprenticeship in this community of practice led to increased confidence in maker tools and technologies and a mindset toward learning in makerspaces as playful, collaborative, and iterative. We found that pre-service teachers require greater opportunities to see students engaged in making in elementary classrooms. We end with recommendations for supporting pre-service teachers to adopt making for their future classrooms. [ABSTRACT FROM AUTHOR]

In the face of global epidemics of mental ill-health, the future of social policy lies with promotion of public wellbeing. This article aims to provide an explanatory rationale and methods for a fundamental shift in social policy; away from a remedial focus on mental ill-health defined in terms of disease or aberrant behaviour and toward a focus on universal access to social conditions favourable to psychological wellbeing. The paper begins with prefacing argument about the urgent need for such a shift, noting the high rates of mental ill-health globally and the failure of current biomedical responses to reduce these. Building on recent theoretical work on public wellbeing and evidence on social determinants of mental health, the paper then proposes nine domains for social policy and broader public policy action, to create conditions supportive of wellbeing abilities. Finally, the paper presents several conceptual issues relating to the challenge of putting such action into practice and concludes that contemporary understanding of wellbeing offers a theory of change to shift social policy from mental illness to public wellbeing. [ABSTRACT FROM AUTHOR]

Issue addressed: We sought to examine barriers to access to, use of, and benefits from digital health services in an area of socioeconomic disadvantage of Adelaide, Australia. Methods: We conducted waiting room surveys in two hospital diabetes clinics and one hospital antenatal clinic in South Australia, and follow‐up telephone interviews with 20 patients. We examined the extent of access to, use of and benefits from digital health services, and what barriers people encountered. We undertook mixed methods, with quantitative descriptive analysis and qualitative analysis. Results: Thirty‐seven diabetes clinic patients (54% response rate) and 99 antenatal clinic patients (33% response rate) participated. Sixty‐two percent of the patients with diabetes and 27% of antenatal clinic patients had never used digital health services. Seventeen percent of patients with diabetes and 30% of antenatal clinic patients were hesitant users, and 22% of patients with diabetes and 44% of antenatal clinic patients were confident users. Barriers included struggling to afford the technology or to stay connected and a lack of trust in online health information. Potential benefits included feeling more empowered and complementing face‐to‐face care. Conclusions: There are socioeconomic barriers to access, use of, and ability to benefit from digital health strategies that mean not everyone will be able to benefit from digital health services. So What?: As COVID‐19 accelerates the shift towards digital health services, people experiencing socioeconomic disadvantage may be excluded. If barriers to access and use are not addressed, they will exacerbate already increasing health inequities. [ABSTRACT FROM AUTHOR]

The Internet has radically shifted how people access information. Instead of storing information internally, increasingly, people outsource to the Internet and retrieve it when needed. While this is an efficient strategy in many ways, its downstream consequences remain largely unexplored. This research examines how accessing online information impacts how people remember information in a learning context. Across five experiments, participants studied for a quiz either by searching online to access relevant information or by directly receiving that same information without online search. Those who searched the Internet performed worse in the learning assessment, indicating that they stored less new knowledge in internal memory. However, participants who searched the Internet were as confident, or even more confident, that they had mastered the study material compared to those who did not search online. We argue that, by making information retrievability salient, Internet search reduces the likelihood of information being stored in memory. Further, these results suggest that searching online leads to the misattribution of online information to internal memory, thus masking the Internet-induced learning deficits. [ABSTRACT FROM AUTHOR]

Storytelling can stimulate learning by delivering scientific content within a narrative that increases comprehension and engagement. In this article I describe the coevolutionary arms race between toxic newts and predatory garter snakes. This engaging story centers on the use of a deadly neurotoxin called tetrodotoxin (TTX) as an antipredator defense. Some species of newts contain TTX in their tissues, but resistance to TTX has developed through convergent evolution in garter snakes and other species. TTX resistance results from mutated voltage-gated sodium channels. These channels, whether TTX resistant or not, are found in all animals and are vital to the function of nervous and muscle tissues. Through reciprocal selection, coevolution has created phenotypic matching between toxic newts and TTX-resistant garter snakes across their range in the western United States. In other words, as newts became more poisonous, garter snakes became more resistant. These results and the scientific process behind them are discussed in detail. This story can be used by educators to provide a unifying and engaging backdrop as students learn multiple aspects of biology, such as protein structure, genetics, phylogenetics, electrical signaling, evolution, and the process of science. [ABSTRACT FROM AUTHOR]

Ancient enzootic associations between wildlife and their infections allow evolution to innovate mechanisms of pathogenicity that are counterbalanced by host responses. However, erosion of barriers to pathogen dispersal by globalization leads to the infection of hosts that have not evolved effective resistance and the emergence of highly virulent infections. Global amphibian declines driven by the rise of chytrid fungi and chytridiomycosis are emblematic of emerging infections. Here, we review how modern biological methods have been used to understand the adaptations and counteradaptations that these fungi and their amphibian hosts have evolved. We explore the interplay of biotic and abiotic factors that modify the virulence of these infections and dissect the complexity of this disease system. We highlight progress that has led to insights into how we might in the future lessen the impact of these emerging infections. [ABSTRACT FROM AUTHOR]

Although rising rates of obesity are recognized as a major concern for Australian public health, debate on what (if any) responsive action should be undertaken is conceptually and normatively complex. It is shaped by diverse values and interests; different representations of the problem; and many options for action by government, the private sector or individuals. This paper presents research documenting arguments for and against implementing a sugar tax in Australia. It is based on semi-structured interviews with representatives from industry (n  = 4), public health (n  = 4), policy think tanks (n  = 2); and document and media analyses. The research design was informed by framing and agenda setting theory with results reported under four main themes: framing economic impacts, framing equity, framing obesity and framing the 'nanny state' versus individual liberty argument. We found that proposals for a sugar tax as part of policy responses to the issue of overweight and obesity in Australia are framed very differently by actors who either support or oppose it. A conclusion is that policy makers and public health advocates involved in policy debates on a sugar tax need to understand the role of problem and 'solution' framing, and develop positions based on protecting the public interest as a basic ethical responsibility of governments and public agencies. [ABSTRACT FROM AUTHOR]

The effects of timber harvest in the moist coniferous forests of western North America are not well documented for ecologically important arthropods such as moths.We assessed the response of macromoth community structure (abundance, sample size‐corrected estimates of species richness and diversity, and overall community composition) to time since deforestation at 20 previously logged sites (1–95 years post‐harvest), and compared the macromoth communities at these stands to four old growth stands.As stand age increased following timber harvest, the number of macromoths captured in ultraviolet light traps increased and the relative abundance of dietary generalists declined, but sample size‐corrected estimates of species richness and diversity did not vary. Macromoth community composition of the youngest stands (<10 years post‐harvest) differed markedly from each other but converged soon thereafter.Macromoth communities at old growth sites featured higher capture rates, lower dominance by dietary generalists, and higher sample size‐corrected estimates of species richness and diversity than at previously logged sites. Community composition profiles for old growth sites differed from all previously logged sites, but the differences were subtle except in comparison to the youngest logged sites. None of the 188 species we sampled were old growth specialists.Our results reveal dramatic initial impacts of deforestation on macromoth communities in moist coniferous forests of western North America. Such effects are largely reversed within two decades post‐harvest but some effects persist for at least 95‐years following logging. [ABSTRACT FROM AUTHOR]

Governments in Australia and internationally show growing interest in wellbeing as a policy goal; however, such interests raise questions about the theories or definitions of wellbeing they will apply. Choices about how wellbeing is defined for policy purposes are likely to delimit the strategies applied. Wholly individualized conceptualizations of wellbeing may lead to policy focused narrowly on 'improving' individuals rather than on creating favourable social conditions. Also, Indigenous theories of wellbeing may have much to offer policy for public wellbeing, but little research has examined whether this potential is considered in contemporary health policy. We report on research examining Indigenous and non-Indigenous theories of wellbeing in a representative sample of current Australian health policy documents. We examine what theories or definitions of wellbeing are present, whether policies recognize social determinants of health; if 'lifestyle drift' is present; how Indigenous and non-Indigenous theories of wellbeing are positioned; and whether policies propose strategies consistent with their definitions of wellbeing. We discuss implications of current approaches for effective policy to promote Indigenous and non-Indigenous wellbeing. [ABSTRACT FROM AUTHOR]

Cognitive ability consists not only of one's internal competence but also of the augmentation offered by the outside world. How much of our cognitive success is due to our own abilities, and how much is due to external support? Can we accurately draw that distinction? Here, we explored when and why people are unaware of their reliance on outside assistance. Across eight experiments (N = 2,440 participants recruited from Amazon Mechanical Turk), people showed improved metacognitive calibration when assistance occurred after a delay or required active choice. Furthermore, these findings apply across a wide range of cognitive tasks, including semantic memory (Experiments 1a and 1b), episodic memory (Experiments 2a and 2b), and problem solving (Experiments 3a–3d). These experiments offer important insights into how we understand our own abilities when we rely on outside help. [ABSTRACT FROM AUTHOR]

• Tocilizumab was not associated with significantly reduced mortality in mechanically ventilated patients with COVID-19 pneumonia. • Patients who received tocilizumab were younger, presented with higher fever on the day of intubation, and had significantly fewer comorbidities than controls. • Elevated interleukin-6 was associated with greater mortality risk; interleukin-6 levels were similar in the treatment and control group. The purpose of this study is to evaluate clinical outcomes in patients with critical COVID-19 pneumonia requiring invasive mechanical ventilation who were treated with tocilizumab Single-center retrospective cohort study Stony Brook University Hospital, a 600-bed academic tertiary medical center in Suffolk County, New York Consecutive patients with COVID-19 confirmed by nasopharyngeal polymerase chain reaction (PCR) who were admitted to Stony Brook University Hospital between March 10 and April 2 2020 and required mechanical ventilation in any intensive care unit during their hospitalization Treatment with tocilizumab while intubated Overall mortality 30 days from the date of intubation Forty-five patients received tocilizumab compared to seventy controls. Baseline demographic characteristics, inflammatory markers, treatment with corticosteroids, and sequential organ failure assessment (SOFA) scores were similar between the two cohorts. Patients who received tocilizumab had significantly lower Charlson co-morbidity index (2.0 vs 3.0, P = 0.01) than controls. There was a trend towards younger mean age in the tocilizumab exposed group (56.2 vs 60.6; P = 0.09). In logistic regression analysis there was no reduction in mortality associated with receipt of tocilizumab (odds ratio (OR) 1.04; 95% CI, 0.27–3.75). There was no observed increased risk of secondary infection in patients given tocilizumab (28.9 vs 25.7; OR 1.17; 95% CI, 0.51–2.71). When controlling for age, severity of illness, and co-morbidities, tocilizumab was not associated with reduction in mortality in this retrospective cohort study of mechanically ventilated patients with COVID-19 pneumonia. Further studies are needed to determine the role of tocilizumab in the treatment of COVID-19. [ABSTRACT FROM AUTHOR]

Ancient enzootic associations between wildlife and their infections allow evolution to innovate mechanisms of pathogenicity that are counterbalanced by host responses. However, erosion of barriers to pathogen dispersal by globalization leads to the infection of hosts that have not evolved effective resistance and the emergence of highly virulent infections. Global amphibian declines driven by the rise of chytrid fungi and chytridiomycosis are emblematic of emerging infections. Here, we review how modern biological methods have been used to understand the adaptations and counteradaptations that these fungi and their amphibian hosts have evolved. We explore the interplay of biotic and abiotic factors that modifr the virulence of these infections and dissect the complexity of this disease system. We highlight progress that has led to insights into how we might in the future lessen the impact of these emerging infections. [ABSTRACT FROM AUTHOR]

Metacognition and self-regulated learning are skills that contribute to student success, but few studies have examined these topics within a community college context. We addressed this lack of understanding by asking community college biology students to metacognitively reflect on their learning strategies. We took a novel approach in our analysis by investigating how learning strategies potentially differed based on race, age, gender, and final course grade. With some exceptions, we found little evidence to suggest that such differences existed. Notably, we found that learning strategies did not differ between high-achieving and low-achieving students, which contradicts previous studies. We offer several possible explanations for these preliminary results, which include misrepresentation by students in their reflecctions, external and internal barriers to studying, potential flaws in our survey instrument, and students not effectively using learning strategies. We suggest replication of this study with methodological changes to further investigate any potential differences that may exist among these groups of students. Our research is an example of how classroom action research can provide insight into how students learn, which empowers us to make evidence-based changes in our teaching. [ABSTRACT FROM AUTHOR]

p63 (also known as TP63) is a transcription factor of the p53 family, along with p73. Multiple isoforms of p63 have been discovered and these have diverse functions encompassing a wide array of cell biology. p63 isoforms are implicated in lineage specification, proliferative potential, differentiation, cell death and survival, DNA damage response and metabolism. Furthermore, p63 is linked to human disease states including cancer. p63 is critical to many aspects of cell signaling, and in this Cell science at a glance article and the accompanying poster, we focus on the signaling cascades regulating TAp63 and ΔNp63 isoforms and those that are regulated by TAp63 and ΔNp63, as well the role of p63 in disease. [ABSTRACT FROM AUTHOR]

The concept of cultural safety (CS) has been developed as a critical perspective on healthcare provided to Indigenous service users in neo-colonial countries such as New Zealand, Australia and Canada. Unlike other frameworks for culturally competent healthcare, a CS approach recognizes impacts of colonization and power inequalities on Indigenous peoples and asks how these may manifest in healthcare settings. It has been argued that CS thinking is suited to critical analysis of public policy, but there has been limited work in this direction. Drawing on literature on CS in Australian healthcare, we defined a CS framework consisting of five concepts: reflexivity, dialogue, reducing power differences, decolonization and regardful care. Our research examined whether and in what terms this framework could be adapted as a tool for critical analysis of Australian public policy as it affects Aboriginal and Torres Strait Islander peoples. We used a collaborative inquiry process combining perspectives of an Aboriginal researcher and a non-Indigenous researcher. We developed a thematic analysis framework to examine how the five concepts might be reflected in contemporary writings on policy by leading Aboriginal or Torres Strait Islander thinkers. We found the framework is applicable as a tool for policy analysis; bringing together key concerns raised by Aboriginal and Torres Strait Islander leaders and critical concepts such as sovereignty and interface thinking. We concluded the framework is likely to be a useful tool for critical, systemic thinking about public policy as it affects Indigenous peoples and for specifying areas where performance can be improved to achieve culturally safe policy. [ABSTRACT FROM AUTHOR]

• Candida auris is a newly identified and globally emerging fungal infection. • C. auris shows extensive innate and acquired resistance to antifungal drugs. • The fungus is intrinsically resistant to widely used hospital disinfectants leading to high rates of nosocomial transmission. • Research into virulence and treatment of C. auris in susceptible patients is urgently needed. The discovery in 2009 of a new species of yeast, Candida auris , heralded the arrival of a novel emerging human infectious disease. This review highlights the unique characteristics of C. auris that have lled to it being of public health concern worldwide, namely public health concern, namely its global emergence, its ability to cause nosocomial outbreaks in healthcare settings, its innate and emerging resistance to multiple antifungal drugs and its resilience in the face of hygiene and infection control measures. Genomic epidemiology has identified four emergences of C. auris marked by four clades of the pathogen. These clades of C. auris are genetically dissimilar and are associated with differential resistance to antifungal drugs, suggesting that they will continue to phenotypically diverge into the future. The global emergence of C. auris testifies to the unmapped nature of Kingdom Fungi, and represents a new nosocomial threat that will require enhanced infection control across diverse healthcare and community settings. [ABSTRACT FROM AUTHOR]

Critical social and economic resources, such as employment, education, and health services, increasingly require online access, highlighting the growing need to address equity of access to high-speed broadband telecommunications. Ensuring access to broadband requires the necessary infrastructure which, in Australia, is the National Broadband Network (NBN). In this paper, we use policy implementation theory to examine the translation of the government's NBN policy into service delivery, specifically in relation to the choice of policy instruments to install the broadband infrastructure, the associated barriers and enablers to their implementation, and the equity considerations that are emerging as the policy is implemented. We conducted a rapid review of NBN policy documents and academic and grey literature to map the NBN policy instruments and to examine how key contextual, political, and technical aspects of NBN policy implementation are likely to affect equity. Our findings indicate a range of equity concerns in the implementation of NBN policy. The instrument choice of a public–private 'hybrid' organisation to implement NBN policy has created a fertile ground for competing political, social, and commercial priorities, thereby affecting how the policy is implemented and thus increasing the risks to equity as it competes with other priorities. As these mixed public–private instruments become more prevalent as policy tools to deliver major infrastructure, determining the best means to safeguard equity is a vital consideration to ensure the benefits are distributed fairly. [ABSTRACT FROM AUTHOR]

The paper analyses the policy process which enabled the successful adoption of Australia's National Aboriginal and Torres Strait Islander Health Plan 2013–2023 (NATSIHP), which is grounded in an understanding of the Social Determinants of Indigenous Health (SDIH). Ten interviews were conducted with key policy actors directly involved in its development. The theories we used to analyse qualitative data were the Advocacy Coalition Framework, the Multiple Streams Approach, policy framing and critical constructionism. We used a complementary approach to policy analysis. The NATSIHP acknowledges the importance of Aboriginal and Torres Strait Islander (hereafter, Aboriginal) culture and the health effects of racism, and explicitly adopts a human-rights-based approach. This was enabled by a coalition campaigning to 'Close the Gap' (CTG) in health status between Aboriginal and non-Aboriginal Australians. The CTG campaign, and key Aboriginal health networks associated with it, operated as an effective advocacy coalition, and policy entrepreneurs emerged to lead the policy agenda. Thus, Aboriginal health networks were able to successfully contest conventional problem conceptions and policy framings offered by government policy actors and drive a paradigm shift for Aboriginal health to place SDIH at the centre of the NATSIHP policy. Implications of this research for policy theory and for other policy environments are considered along with suggestions for future research. [ABSTRACT FROM AUTHOR]

This study identifies current practices of private health funds (PHFs) in Australian primary health care (PHC), including areas where their involvement is increasing, and examines the risks and benefits of these practices for quality of, and equity of access to PHC. The paper draws on research to investigate equity implications of current PHF involvement in PHC in Australia. We reviewed literature, analysed documents relating to a Senate Committee inquiry and interviewed stakeholders and experts in private health insurance policy from government, private sector and nongovernment organisations. Involvement of PHFs in the PHC sector in Australia is increasing, presenting risk of increased inequities in access to PHC based on insurance status, which could undermine the universality of PHC under Medicare. However, some stakeholders think these risks can be managed within current policy arrangements. There are also risks for quality of PHC services arising from greater involvement of PHFs in service delivery and "preferred provider" models. Differing stakeholder views on equity implications of PHF involvement in PHC are associated with different views on desirable policy action. We conclude that there is a risk of increased involvement of PHFs in PHC risks exacerbating existing inequities in the health system, but this is moderated by public support for Medicare. [ABSTRACT FROM AUTHOR]

One of the mind’s most fundamental tasks is interpreting incoming data and weighing the value of new evidence. Across a wide variety of contexts, we show that when summarizing evidence, people exhibit a binary bias: a tendency to impose categorical distinctions on continuous data. Evidence is compressed into discrete bins, and the difference between categories forms the summary judgment. The binary bias distorts belief formation—such that when people aggregate conflicting scientific reports, they attend to valence and inaccurately weight the extremity of the evidence. The same effect occurs when people interpret popular forms of data visualization, and it cannot be explained by other statistical features of the stimuli. This effect is not confined to explicit statistical estimates; it also influences how people use data to make health, financial, and public-policy decisions. These studies (N = 1,851) support a new framework for understanding information integration across a wide variety of contexts. [ABSTRACT FROM AUTHOR]

Across many different contexts, individuals consult customer ratings to inform their purchase decisions. The present studies document a novel phenomenon, dubbed “the binary bias,” which plays an important role in how individuals evaluate customer reviews. Our main proposal is that people tend to make a categorical distinction between positive ratings (e.g. 4s and 5s) and negative ratings (e.g. 1s and 2s). However, within those bins, people do not sufficiently distinguish between more extreme values (5s and 1s) and less extreme values (4s and 2s). As a result, people’s subjective representations of distributions are heavily impacted by the extent to which those distributions are imbalanced (having more 4s and 5s vs. more 1s and 2s). Ten studies demonstrate that this effect has important consequences for people’s product evaluations and purchase decisions. Additionally, we show this effect is not driven by the salience of particular bars, unrealistic distributions, certain statistical properties of a distribution, or diminishing subjective utility. Furthermore, we demonstrate this phenomenon’s relevance to other domains besides product reviews, and discuss the implications for existing research on how people integrate conflicting evidence. [ABSTRACT FROM AUTHOR]

Studies the behavior of hysteretic current-biased Josephson junction in the vicinity of its return to the zero-voltage states. Information on the general considerations, models and dimensionless parameters; Deterministic return characteristic; Effect of fluctuations.

Open textbooks are free, online resources that can replace traditional textbooks and save students money. The costs of traditional textbooks continue to increase, and this can particularly affect at-risk, low-income students. Few studies have analyzed student perceptions of open textbooks and how they influence academic achievement, but the emerging trend is positive. In the present study, I assessed student perceptions of an open textbook and calculated the subsequent cost savings. Although there were some limitations to my study, such as a low sample size, my results closely mirror previous studies in that most students had favorable opinions of the open textbook and would prefer to use them over traditional textbooks. The average cost savings per student was $81 for one course, determined using a novel method that does not assume all students buy new textbooks. These savings were likely important to the students, the majority of whom worked five hours or more and have received Pell Grants or other tuition waivers. [ABSTRACT FROM AUTHOR]

The receptor tyrosine kinase c-Met, its ligand HGF, and components of the downstream signalling pathway, have all been implicated in the pathogenesis of myeloma, both as modulators of plasma cell proliferation and as agents driving osteoclast differentiation and osteoblast inhibition thus, all these contribute substantially to the bone destruction typically caused by myeloma. Patients with elevated levels of HGF have a poor prognosis, therefore, targeting these entities in such patients may be of substantial benefit. We hypothesized that ARQ-197 (Tivantinib), a small molecule c-Met inhibitor, would reduce myeloma cell growth and prevent myeloma-associated bone disease in a murine model. In vitro we assessed the effects of ARQ-197 on myeloma cell proliferation, cytotoxicity and c-Met protein expression in human myeloma cell lines. In vivo we injected NOD/SCID-γ mice with PBS (non-tumour bearing) or JJN3 cells and treated them with either ARQ-197 or vehicle. In vitro exposure of JJN3, U266 or NCI-H929 cells to ARQ-197 resulted in a significant inhibition of cell proliferation and an induction of cell death by necrosis, probably caused by significantly reduced levels of phosphorylated c-Met. In vivo ARQ-197 treatment of JJN3 tumour-bearing mice resulted in a significant reduction in tumour burden, tumour cell proliferation, bone lesion number, trabecular bone loss and prevented significant decreases in the bone formation rate on the cortico-endosteal bone surface compared to the vehicle group. However, no significant differences on bone parameters were observed in non-tumour mice treated with ARQ-197 compared to vehicle, implying that in tumour-bearing mice the effects of ARQ-197 on bone cells was indirect. In summary, these res ults suggest that ARQ-197 could be a promising therapeutic in myeloma patients, leading to both a reduction in tumour burden and an inhibition of myeloma-induced bone disease. [ABSTRACT FROM AUTHOR]

The recent rate of emergence of pathogenic fungi that are resistant to the limited number of commonly used antifungal agents is unprecedented. The azoles, for example, are used not only for human and animal health care and crop protection but also in antifouling coatings and timber preservation. The ubiquity and multiple uses of azoles have hastened the independent evolution of resistance in many environments. One consequence is an increasing risk in human health care from naturally occurring opportunistic fungal pathogens that have acquired resistance to this broad class of chemicals. To avoid a global collapse in our ability to control fungal infections and to avoid critical failures in medicine and food security, we must improve our stewardship of extant chemicals, promote new antifungal discovery, and leverage emerging technologies for alternative solutions. [ABSTRACT FROM AUTHOR]

Quantum indistinguishability plays a crucial role in many lowenergy physical phenomena, from quantum fluids to molecular spectroscopy. It is, however, typically ignored in most hightemperature processes, particularly for ionic coordinates, implicitly assumed to be distinguishable, incoherent, and thus well approximated classically. We explore enzymatic chemical reactions involving small symmetric molecules and argue that in many situations a full quantum treatment of collective nuclear degrees of freedom is essential. Supported by several physical arguments, we conjecture a "quantum dynamical selection" (QDS) rule for small symmetric molecules that precludes chemical processes that involve direct transitions from orbitally nonsymmetric molecular states. As we propose and discuss, the implications of the QDS rule include (i) a differential chemical reactivity of para- and orthohydrogen, (ii) a mechanism for inducing intermolecular quantum entanglement of nuclear spins, (iii) a mass-independent isotope fractionation mechanism, (iv) an explanation of the enhanced chemical activity of "reactive oxygen species", (v) illuminating the importance of ortho-water molecules in modulating the quantum dynamics of liquid water, and (vi) providing the critical quantumto- biochemical linkage in the nuclear spin model of the (putative) quantum brain, among others. [ABSTRACT FROM AUTHOR]

Two 2-aminoimidazole-based inhibitors, LY3031207 (1) and LY3023703 (2), of the microsomal prostaglandin E synthase-1 (mPGES-1) enzyme were found to cause drug-induced liver injury (DILI) in humans. We studied imidazole ring substitutions to successfully mitigate reactive metabolite (RM) formation. These studies support the conclusion that RM formation may play a role in the observations of DILI and the consideration of 2-aminoimidazoles as structure alerts, due to the high likelihood of bioactivation to generate RMs. [ABSTRACT FROM AUTHOR]

Intersectoral action between public agencies across policy sectors, and between levels of government, is seen as essential for effective action by governments to address social determinants of health (SDH) and to reduce health inequities. The health sector has been identified as having a crucial stewardship role, to engage other policy sectors in action to address the impacts of their policies on health. This article reports on research to investigate intersectoral action on SDH and health inequities in Australian health policy. We gathered and individually analysed 266 policy documents, being all of the published, strategic health policies of the national Australian government and eight State/Territory governments, current at the time of sampling in late 2012-early 2013. Our analysis showed that strategies for intersectoral action were common in Australian health policy, but predominantly concerned with extending access to individualized medical or behavioural interventions to client groups in other policy sectors. Where intersectoral strategies did propose action on SDH (other than access to health-care), they were mostly limited to addressing proximal factors, rather than policy settings affecting the distribution of socioeconomic resources. There was little evidence of engagement between the health sector and those policy sectors most able to influence systemic socioeconomic inequalities in Australia. [ABSTRACT FROM AUTHOR]

Protein arginine methyltransferase 5 (PRMT5) cooperates with methylosome protein 50 (MEP50) to arginine methylate histone H3 and H4 to silence gene expression, and increased PRMT5 activity is associated with enhanced cancer cell survival. We have studied the role of PRMT5 and MEP50 in epidermal squamous cell carcinoma. We show that knockdown of PRMT5 or MEP50 results in reduced H4R3me2s formation, and reduced cell proliferation, invasion, migration and tumor formation. We further show that treatment with sulforaphane (SFN), a cancer preventive agent derived from cruciferous vegetables, reduces PRMT5 and MEP50 level and H4R3me2s formation, and this is associated with reduced cell proliferation, invasion and migration. The SFN-dependent reduction in PRMT5 and MEP50 level requires proteasome activity. Moreover, SFN-mediated responses are partially reversed by forced PRMT5 or MEP50 expression. SFN treatment of tumors results in reduced MEP50 level and H4R3me2s formation, confirming that that SFN impacts this complex in vivo. These studies suggest that the PRMT5/MEP50 is required for tumor growth and that reduced expression of this complex is a part of the mechanism of SFN suppression of tumor formation. [ABSTRACT FROM AUTHOR]

Significant changes have occurred in Australia's national primary healthcare (PHC) policy over the last decade, but little assessment has been made of implications for equity. This research aimed to identify key recent changes in national PHC policy and assess implications for equity of access to PHC. Academic literature was reviewed to identify issues affecting equity of access in national PHC policy, and grey literature was also reviewed to identify significant policy changes during 2005-16 with implications for equitable access. Equity implications of four areas of policy change, set against the existing Medicare system, were assessed. It was found that Medicare supports equitable access to general practice, but there is a risk of reduced equity under current policy settings. Four changes in PHC policy were selected as having particular implications for equity of access and these were assessed as follows: increased involvement of private health insurance presents risks for equity; equity implications of new models of coordinated care are unclear; and regional primary health organisations and current policy on Aboriginal and Torres Strait Islander health have potential equity benefits, but these will depend on further implementation. [ABSTRACT FROM AUTHOR]

We present experimental evidence that people's modes of social interaction influence their construal of truth. Participants who engaged in cooperative interactions were less inclined to agree that there was an objective truth about that topic than were those who engaged in a competitive interaction. Follow-up experiments ruled out alternative explanations and indicated that the changes in objectivity are explained by argumentative mindsets: When people are in cooperative arguments, they see the truth as more subjective. These findings can help inform research on moral objectivism and, more broadly, on the distinctive cognitive consequences of different types of social interaction. [ABSTRACT FROM AUTHOR]

Emerging infections caused by fungi have become a widely recognized global phenomenon. Their notoriety stems from their causing plagues and famines, driving species extinctions, and the difficulty in treating human mycoses alongside the increase of their resistance to antifungal drugs. This special issue comprises a collection of articles resulting from a Royal Society discussion meeting examining why pathogenic fungi are causing more disease now than they did in the past, and how we can tackle this rapidly emerging threat to the health of plants and animals worldwide. [ABSTRACT FROM AUTHOR]

The Latin Trinity ( LT) and the Social Trinity ( ST) represent the two dominant approaches for interpreting the doctrine of the Trinity in contemporary philosophical theology. Both approaches have consequences for Christian theology, however, and I believe that neither sufficiently overcomes the charges of modalism or tritheism, respectively. Moreover, the charge of the overall logical incoherency of the doctrine of the Trinity remains a viable criticism. In order to defend the doctrine of the Trinity against charges of incoherency, while avoiding the modalistic and tritheistic leanings of the LT and ST models, I argue that the unitary nature of God-as-three-hypostases is best understood in terms of a relationship of supervenience between the revelation of (1) Deut. 6:4 and (2) the Gospel of John. The Hypostases of the Trinity supervene on the unitary identity of God insofar as to be ' God' is to entail the perichoretic relationship of unbegottenness, begottenness, and spiratation (procession). The Supervenient Trinity ( SvT), as an analogical model, provides a way to understand God as (1) and (2) that better avoids the modalist and tritheistic difficulties raised by the LT and the ST approaches. [ABSTRACT FROM AUTHOR]

Efforts to reform science education focus on implementing constructivist pedagogy to engage students in scientific practices, promote critical thinking, and provide students with relevant research experiences. In this spirit, this article presents authentic, inquiry-based activities utilizing the real-world bioscience behind wastewater treatment. The activities begin with a tour of a wastewater treatment facility, followed by a guided inquiry activity in which students enumerate E. coli levels from wastewater samples collected from different steps of the treatment process. Students then participate in an open-inquiry experiment to test a unique hypothesis. Learning about wastewater treatment introduces students to important biology content such as bioremediation, microbiology, and nutrient cycling. Additionally, students engage in science practices such as inquiry and constructing evidence-based explanations. [ABSTRACT FROM AUTHOR]

The combretastatins are an important class of tubulin-binding agents. Of this family, a number of compounds are potent tumor vascular disrupting agents (VDAs) and have shown promise in the clinic for cancer therapy. We have developed a modular synthetic route to combretastatin analogs based on a pyrazole core through highly regioselective alkyne cycloaddition reactions of sydnones. These compounds show modest to high potency against human umbilical vein endothelial cell proliferation. Moreover, evidence is presented that these novel VDAs have the same mode of action as CA4P and bind reversibly to β-tubulin, believed to be a key feature in avoiding toxicity. The most active compound from in vitro studies was taken forward to an in vivo model and instigated an increase in tumor cell necrosis. [ABSTRACT FROM AUTHOR]

Does expertise within a domain of knowledge predict accurate self-assessment of the ability to explain topics in that domain? We find that expertise increases confidence in the ability to explain a wide variety of phenomena. However, this confidence is unwarranted; after actually offering full explanations, people are surprised by the limitations in their understanding. For passive expertise (familiar topics), miscalibration is moderated by education; those with more education are accurate in their self-assessments (Experiment 1). But when those with more education consider topics related to their area of concentrated study (college major), they also display an illusion of understanding (Experiment 2). This 'curse of expertise' is explained by a failure to recognize the amount of detailed information that had been forgotten (Experiment 3). While expertise can sometimes lead to accurate self-knowledge, it can also create illusions of competence. [ABSTRACT FROM AUTHOR]

Evidence on social determinants of health and health equity (SDH/HE) is abundant but often not translated into effective policy action by governments. Governments' health policies have continued to privilege medical care and individualised behaviour-change strategies. In the light of these limitations, the 2008 Commission on the Social Determinants of Health called on health agencies to adopt a stewardship role; to take action themselves and engage other government sectors in addressing SDH/HE. This article reports on research using analysis of health policy documents - published by nine Australian national or regional governments - to examine the extent to which the Australian health sector has taken up such a role. We found policies across all jurisdictions commonly recognised evidence on SDH/HE and expressed goals to improve health equity. However, these goals were predominantly operationalised in health care and other individualised strategies. Relatively few strategies addressed SDH/HE outside of access to health care, and often they were limited in scope. National policies on Aboriginal health did most to systemically address SDH/HE. We used Kingdon's (2011)multiple streams theory to examine how problems, policies and politics combine to enable, partially allow, or prevent action on SDH/HE in Australian health policy. [ABSTRACT FROM AUTHOR]

Area-based strategies have been widely employed in efforts to improve population health and take action on social determinants of health (SDH) and health inequities, including in urban areas where many of the social, economic and environmental factors converge to influence health. Increasingly, these factors are recognized as being part of a complex system, where population health outcomes are shaped by multiple, interacting factors operating at different levels of social organization. This article reports on research to assess the extent to which an alliance of health and human service networks is able to promote action on SDH within an Australian urban region, using a complex systems frame. We found that such an alliance was able to promote some effective action which takes into account complex interactions between social factors affecting health, but also identified significant potential barriers to other forms of desired action identified by alliance members. We found that a complex systems lens was useful in assessing a collaborative intervention to address SDH within an urban region. [ABSTRACT FROM AUTHOR]

The possibility that quantum processing with nuclear spins might be operative in the brain is explored. Phosphorus is identified as the unique biological element with a nuclear spin that can serve as a qubit for such putative quantum processing– a neural qubit –while the phosphate ion is the only possible qubit-transporter . We identify the “Posner molecule”, Ca 9 ( PO 4 ) 6 , as the unique molecule that can protect the neural qubits on very long times and thereby serve as a (working) quantum-memory . A central requirement for quantum-processing is quantum entanglement . It is argued that the enzyme catalyzed chemical reaction which breaks a pyrophosphate ion into two phosphate ions can quantum entangle pairs of qubits. Posner molecules, formed by binding such phosphate pairs with extracellular calcium ions, will inherit the nuclear spin entanglement. A mechanism for transporting Posner molecules into presynaptic neurons during vesicle endocytosis is proposed. Quantum measurements can occur when a pair of Posner molecules chemically bind and subsequently melt, releasing a shower of intra-cellular calcium ions that can trigger further neurotransmitter release and enhance the probability of post-synaptic neuron firing. Multiple entangled Posner molecules, triggering non-local quantum correlations of neuron firing rates, would provide the key mechanism for neural quantum processing. Implications, both in vitro and in vivo, are briefly mentioned. [ABSTRACT FROM AUTHOR]

As the Internet has become a nearly ubiquitous resource for acquiring knowledge about the world, questions have arisen about its potential effects on cognition. Here we show that searching the Internet for explanatory knowledge creates an illusion whereby people mistake access to information for their own personal understanding of the information. Evidence from 9 experiments shows that searching for information online leads to an increase in self-assessed knowledge as people mistakenly think they have more knowledge "in the head," even seeing their own brains as more active as depicted by functional MR1 (fMRI) images. [ABSTRACT FROM AUTHOR]

Despite advances in tissue engineering for the knee meniscus, it remains a challenge to match the complex macroscopic and microscopic structural features of native tissue, including the circumferentially and radially aligned collagen bundles essential for mechanical function. To mimic this structural hierarchy, this study developed multi-lamellar mesenchymal stem cell (MSC)-seeded nanofibrous constructs. Bovine MSCs were seeded onto nanofibrous scaffolds comprised of poly(e-caprolactone) with fibers aligned in a single direction (0° or 90° to the scaffold long axis) or circumferentially aligned (C). Multi-layer groups (0°/0°/0°, 90°/90°/90°, 0°/90°/0°, 90°/0°/90°, and C/C/C) were created and cultured for a total of 6 weeks under conditions favoring fibrocartilaginous tissue formation. Tensile testing showed that 0° and C single layer constructs had stiffness values several fold higher than 90° constructs. For multi-layer groups, the stiffness of 0°/0°/0° constructs was higher than all other groups, while 90°/90°/90° constructs had the lowest values. Data for collagen content showed a general positive interactive effect for multi-layers relative to single layer constructs, while a positive interaction for stiffness was found only for the C/C/C group. Collagen content and cell infiltration occurred independent of scaffold alignment, and newly formed collagenous matrix followed the scaffold fiber direction. Structural hierarchies within multi-lamellar constructs dictated biomechanical properties, and only the C/C/C constructs with non-orthogonal alignment within layers featured positive mechanical reinforcement as a consequence of the layered construction. These multi-layer constructs may serve as functional substitutes for the meniscus as well as test beds to understand the complex mechanical principles that enable meniscus function. [ABSTRACT FROM AUTHOR]