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Augmented reality (AR) is an emergent technology beginning to be integrated into many disciplines such as engineering, architecture, and medical fields for educational purposes. The present study builds on a pilot study conducted in the spring of 2022 exploring how AR can be employed in Environmental Education (EE) by providing just-in-time information in context to aid user perception of both the interrelationships present among all members of the place being explored and the environmental issues being faced by that same community. An AR trail experience located in the Sonoran Desert of the Southwest United States was created using the tenets of place-responsive design while drawing on principles from place-based education, critical place inquiry, and the importance of play in learning. Sixteen participants including undergraduate and graduate students from the University of Arizona, some of which were preservice teachers, took part in the AR trail experience guided by a digital javelina where they interacted with activities anchored to GPS coordinates in a choice-based manner. They also collected digital ARtifacts in the experience such as photos, videos, and written responses that were then used to provoke reflective thinking and connections to the ARtifacts others have captured. Semi-structured interviews were conducted later and combined with the digital artifacts along with footage from video glasses worn during the experience to construct themes through reflexive thematic analysis and critical incident reflection of the engagement and interactions taking place in the liminal space between virtual and embodied learning. These themes will aid in exploring the types of connections fostered using AR in the EE context. The study adds to the literature through an examination of these interactions and exploring the implications they have for the use of AR in EE as well as serving as a model for other such experiences. Findings include the use of AR engaged learners

Prologue All authors are disabled scholars with varying experiences of learning disability, long term illness, chronic health conditions. All authors are neurodivergent. Three are currently unemployed, underemployed, and/or precariously employed. Two are from a marginalised ethnic/racial group. Two are the first in their generation to access higher education. Three have known severe poverty. Not all involved could be named on this publication. The lived experience of the authors is woven into a singular cautionary tale to provide an every-person understanding of career-block within academia for disabled scholars. This artistic endeavour, inherently analytic in its documentation of the ‘identity work’ of our authors, draws on past experience (memory) weaved through imagination. The writing and publishing of this piece required a brutal honesty that lays us open, vulnerable, and at risk. However, as you will read, the risk of silence could be greater still. Human experience can be understood through stories. Our work is concerned with performing the narrative of our daily lives (Langellier and Peterson, 2004); making the mundane magical and instilling belief in the unbelievable. Our lived experiences are stranger than fiction, and combined they enchant a fictional narrative that describes the necropolitics of career-blocking (Mbembe 2003) through a new methodology we call PanEthnography. As authors of different disciplines/fields and universities, we were united in our experiences of disability in the academe. We conceived and constructed PanEthnography through a lens of Embodied Inquiry (Bochner & Ellis 2016; Leigh and Brown 2021; Apostolidou and Daskalaki, 2021). During the month of October 2022 we formed a research collective (or writing coven), to explore our collective experiences of career blocking related to disability. The data gathering process was undertaken by digital means by using online video-conferencing and countless WhatsApp (Halliwell and Wilkinson 2

Flash droughts, characterized by rapid onset and intensification, are increasingly occurring as a consequence of climate change and rising temperatures. However, existing hydrometeorological definitions fail to encompass the full range of flash droughts, many of which have distinct local physical attributes. Consequently, these events often go undetected or unforecast in generic global flash drought assessments and are underrepresented in research. To address this gap, we conducted a comprehensive survey to gather information on local nomenclature, characteristics, and impacts of flash droughts worldwide. The survey revealed the widespread occurrence of these phenomena, highlighting their underre-searched nature. By analyzing case studies, through literature review often in local languages to unearth elusive studies, we identified five different types of flash droughts based on their specific characteristics. Our study aims to increase awareness about the complexity and diverse impacts of flash droughts, emphasizing the importance of considering regional contexts and the vulnerability of affected populations. The reported impacts underscore the need for better integration of all flash drought types in drought research, monitoring, and management. Monitoring a combination of indicators is crucial for timely detection and response to this emerging and escalating threat.

Background Given the robust evidence base for the efficacy of evidence-based treatments targeting youth anxiety, researchers have advanced beyond efficacy outcome analysis to identify mechanisms of change and treatment directionality. Grounded in developmental transactional models, interventions for young children at risk for anxiety by virtue of behaviorally inhibited temperament often target parenting and child factors implicated in the early emergence and maintenance of anxiety. In particular, overcontrolling parenting moderates risk for anxiety among highly inhibited children, just as child inhibition has been shown to elicit overcontrolling parenting. Although longitudinal research has elucidated the temporal unfolding of factors that interact to place inhibited children at risk for anxiety, reciprocal transactions between these child and parent factors in the context of early interventions remain unknown. Method This study addresses these gaps by examining mechanisms of change and treatment directionality (i.e., parent-to-child vs. child-to-parent influences) within a randomized controlled trial comparing two interventions for inhibited preschoolers (N = 151): the multicomponent Turtle Program (‘Turtle’) and the parent-only Cool Little Kids program (‘CLK’). Reciprocal relations between parent-reported child anxiety, observed parenting, and parent-reported accommodation of child anxiety were examined across four timepoints: pre-, mid-, and post-treatment, and one-year follow-up (NCT02308826). Results Hypotheses were tested via latent curve models with structured residuals (LCM-SR) and latent change score (LCS) models. LCM-SR results were consistent with the child-to-parent influences found in previous research on cognitive behavioral therapy (CBT) for older anxious youth, but only emerged in Turtle. LCS analyses revealed bidirectional effects of changes in parent accommodation and child anxiety during and after intervention, but only in Turtle. Conclusion Our f

During development, the lymphatic vasculature forms as a second, new vascular network derived from blood vessels. The transdifferentiation of embryonic venous endothelial cells (VECs) into lymphatic endothelial cells (LECs) is the first step in this process. Specification, differentiation and maintenance of LEC fate are all driven by the transcription factor Prox1, yet downstream mechanisms remain to be elucidated. We present a single cell transcriptomic atlas of lymphangiogenesis in zebrafish revealing new markers and hallmarks of LEC differentiation over four developmental stages. We further profile single cell transcriptomic and chromatin accessibility changes in zygotic prox1a mutants that are undergoing a VEC-LEC fate reversion during differentiation. Using maternal and zygotic prox1a/prox1b mutants, we determine the earliest transcriptomic changes directed by Prox1 during LEC specification. This work altogether reveals new transcriptional targets and regulatory regions of the genome downstream of Prox1 in LEC maintenance, as well as showing that Prox1 specifies LEC fate primarily by limiting blood vascular and hematopoietic fate. This extensive single cell resource provides new mechanistic insights into the enigmatic role of Prox1 and the control of LEC differentiation in development.

Flash droughts, characterized by rapid onset and intensification, are increasingly occurring as a consequence of climate change and rising temperatures. However, existing hydrometeorological definitions fail to encompass the full range of flash droughts, many of which have distinct local physical attributes. Consequently, these events often go undetected or unforecast in generic global flash drought assessments and are underrepresented in research. To address this gap, we conducted a comprehensive survey to gather information on local nomenclature, characteristics, and impacts of flash droughts worldwide. The survey revealed the widespread occurrence of these phenomena, highlighting their underre-searched nature. By analyzing case studies, through literature review often in local languages to unearth elusive studies, we identified five different types of flash droughts based on their specific characteristics. Our study aims to increase awareness about the complexity and diverse impacts of flash droughts, emphasizing the importance of considering regional contexts and the vulnerability of affected populations. The reported impacts underscore the need for better integration of all flash drought types in drought research, monitoring, and management. Monitoring a combination of indicators is crucial for timely detection and response to this emerging and escalating threat., Water Resources

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counter-intuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfv\'en waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, $\alpha=2$ as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed $>$600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: pre-flare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that $\alpha = 1.63 \pm 0.03$. This is below the critical threshold, suggesting that Alfv\'en waves are an important driver of coronal heating., Comment: 1,002 authors, 14 pages, 4 figures, 3 tables, published by The Astrophysical Journal on 2023-05-09, volume 948, page 71

Background: Most people experience a diagnostic error at least once in their lifetime. Patients’ experiences with their diagnosis could provide important insights when setting research priorities to reduce diagnostic error. Objective: Our objective was to engage patients in research agenda setting for improving diagnosis. Patient involvement: Patients were involved in generating, discussing, prioritizing, and ranking of research questions for diagnostic error reduction. Methods: We used the prioritization methodology based on the Child Health and Nutrition Research Initiative (CHNRI). We first solicited research questions important for diagnostic error reduction from a large group of patients. Thirty questions were initially prioritized at an in-person meeting with 8 patients who were supported by 4 researchers. The resulting list was further prioritized by patients who scored questions on five predefined criteria. We then applied previously determined weights to these prioritization criteria to adjust the final prioritization score for each question, resulting in 10 highest priority research questions. Results: Forty-one patients submitted 171 research questions. After prioritization, the highest priority topics included better care coordination across the diagnostic continuum and improving care transitions, improved identification and measurement of diagnostic errors and attention for implicit bias towards patients who are vulnerable to diagnostic errors. Discussion: We systematically identified the top-10 patient generated research priorities for diagnostic error reduction using transparent and objective methods. Patients prioritized different research questions than researchers and therefore complemented an agenda previously generated by researchers. Practical value: Research priorities identified by patients can be used by funders and researchers to conduct future research focused on reducing diagnostic errors.

Women have always been interested in science (Fara 2018). However, historically and to this day they have faced barriers that have blocked them from succeeding and progressing. In 2018, the Royal Society of Chemistry (RSC) conducted a review on diversity (and the lack thereof) in the chemical sciences (RSC 2018), and followed this with a report on the particular challenges for women in terms of their progression and retention (RSC 2019a). The RSC found that women faced a multitude of small obstacles throughout the publishing process leading to their publishing less, in lower impact journals, and being cited less than men (RSC 2019b). This catalogue of small barriers could be considered as a series of microaggressions, a term used by Sara Ahmed (2012, 2017) and other critical race scholars. In the United States, various programmes have been funded to combat the attrition of women from the sciences with varying amounts of long-term success (Rosser 2017). While the numbers demonstrate that more women are recruited into undergraduate courses, internationally the growth at the most senior levels is disappointing, and in some subjects and in some universities the numbers of senior women in science are in attrition (Mason and Ekman 2007; Rosser 2017). When considering the lack of progress on gender balance in science, it is important to note that gender cannot be considered in isolation, and that gender is not binary. Women and other marginalized genders face intersectional barriers. ‘Intersectionality’ is a term first used by Kimberlé Crenshaw (1989) to describe the racism and sexism faced by Black women. Protected characteristics, including sexuality, race, ethnicity, religion, and disability, all result in barriers that compound to prevent an individual from reaching their full potential. There is a notable lack of diversity within academia (Fryberg and Martinez 2014; Shelton, Flynn and Grosland 2018), and even more so within science; people of colour and those marginal

Unmyelinated non-peptidergic nociceptors (NP afferents) arborise in lamina II of the spinal cord and receive GABAergic axoaxonic synapses, which mediate presynaptic inhibition. However, until now the source of this axoaxonic synaptic input was not known. Here we provide evidence that it originates from a population of inhibitory calretinin-expressing interneurons (iCRs), which correspond to lamina II islet cells. The NP afferents can be assigned to 3 functionally distinct classes (NP1-3). NP1 afferents have been implicated in pathological pain states, while NP2 and NP3 afferents also function as pruritoceptors. Our findings suggest that all 3 of these afferent types innervate iCRs and receive axoaxonic synapses from them, providing feedback inhibition of NP input. The iCRs also form axodendritic synapses, and their targets include cells that are themselves innervated by the NP afferents, thus allowing for feedforward inhibition. The iCRs are therefore ideally placed to control the input from non-peptidergic nociceptors and pruritoceptors to other dorsal horn neurons, and thus represent a potential therapeutic target for the treatment of chronic pain and itch.

The nucleoporin (NUP) ELYS, encoded by AHCTF1, is a large multifunctional protein with essential roles in nuclear pore assembly and mitosis. Using both larval and adult zebrafish models of hepatocellular carcinoma (HCC), in which the expression of an inducible mutant kras transgene (krasG12V) drives hepatocyte-specific hyperplasia and liver enlargement, we show that reducing ahctf1 gene dosage by 50% markedly decreases liver volume, while non-hyperplastic tissues are unaffected. We demonstrate that in the context of cancer, ahctf1 heterozygosity impairs nuclear pore formation, mitotic spindle assembly and chromosome segregation, leading to DNA damage and activation of a Tp53-dependent transcriptional program that induces cell death and cell cycle arrest. Heterozygous expression of both ahctf1 and ranbp2 (encoding a second nucleoporin), or treatment of heterozygous ahctf1 larvae with the nucleocytoplasmic transport inhibitor, Selinexor, completely blocks krasG12V-driven hepatocyte hyperplasia. Gene expression analysis of patient samples in the Liver hepatocellular carcinoma (LIHC) dataset in The Cancer Genome Atlas shows that high expression of one or more of the transcripts encoding the ten components of the NUP107-160 subcomplex, which includes AHCTF1, is positively correlated with worse overall survival. These results provide a strong and feasible rationale for the development of novel cancer therapeutics that target ELYS function and suggest potential avenues for effective combinatorial treatments.

The nucleoporin (NUP) ELYS, encoded by AHCTF1, is a large multifunctional protein with essential roles in nuclear pore assembly and mitosis. Using both larval and adult zebrafish models of hepatocellular carcinoma (HCC), in which the expression of an inducible mutant kras transgene (krasG12V) drives hepatocyte-specific hyperplasia and liver enlargement, we show that reducing ahctf1 gene dosage by 50% markedly decreases liver volume, while non-hyperplastic tissues are unaffected. We demonstrate that in the context of cancer, ahctf1 heterozygosity impairs nuclear pore formation, mitotic spindle assembly and chromosome segregation, leading to DNA damage and activation of a Tp53-dependent transcriptional program that induces cell death and cell cycle arrest. Heterozygous expression of both ahctf1 and ranbp2 (encoding a second nucleoporin), or treatment of heterozygous ahctf1 larvae with the nucleocytoplasmic transport inhibitor, Selinexor, completely blocks krasG12V-driven hepatocyte hyperplasia. Gene expression analysis of patient samples in the Liver hepatocellular carcinoma (LIHC) dataset in The Cancer Genome Atlas shows that high expression of one or more of the transcripts encoding the ten components of the NUP107-160 subcomplex, which includes AHCTF1, is positively correlated with worse overall survival. These results provide a strong and feasible rationale for the development of novel cancer therapeutics that target ELYS function and suggest potential avenues for effective combinatorial treatments.

Rebecca Moran talks plainly about what it has been like to experience and live beyond a family murder-suicide. Rebecca had a six month old baby when her father and brother died, so her story intertwines death and fresh life. She describes her experiences with existential horror, and how unprepared we are to deal with deeply unsettling blows to our existential frameworks, as well as our understandings of what life and love look like. Rebecca talks about the way big grief and horror can be received – or leaned away from – by friends, family, and the public, and how this can create unintentional isolation and silencing.

'We’re just gonna call it all BPD' three channel video, duration 1h-10min. To enable subtitles, please click on the CC icon in the video status bar. An immersive video installation, created from verbatim scripts, authored by people with lived experience of a diagnosis of Borderline Personality Disorder (BPD). “BPD” is one of the most stigmatised of all mental health diagnoses – both in the public imagination and within the health sector itself. As such, it has been criticised as a “highly contentious and damaging label” (1). Movements campaigning for its abolition point to the high correlation between childhood abuse or neglect and “BPD”, arguing that by labelling someone with a “personality disorder” we focus on what is wrong with the person—the flaws in their personality–rather than on what happened to them. The alternative would be to approach the internal experience of “BPD” as an understandable response to trauma. The characters in this piece share their experiences of this label, describing histories of trauma and illuminating the impact of relationships with caregivers, friends, family and service-providers. Their stories ‘from the inside’, help us to understand experiences such as the urge to self-harm or the feeling of intense emotion, making sense of behaviours that are often simply regarded as symptoms of ‘disorder’. They also reveal the various way in which the longer term impacts of trauma can be supported and effectively managed, highlighting above all the importance of human connection. These moving and inspiring stories of painful experiences are shared in the spirit of openness and compassionate listening. The installation intentionally evokes the space of an imagined group encounter where people commit to holding a space for feelings and for respectful listening without judgement. ‘We’re just gonna call it all BPD’ is designed to be experienced as an immersive installation, in which 3 life-sized figures appear on screens that form a circle complete

Acquiring a better understanding of drought impacts becomes increasingly vital under a warming climate. Traditional drought indices describe mainly biophysical variables and not impacts on social, economic, and environmental systems. We utilized natural language processing and bidirectional encoder representation from Transformers (BERT) based transfer learning to fine-tune the model on the data from the news-based Drought Impact Report (DIR) and then apply it to recognize seven types of drought impacts based on the filtered Twitter data from the United States. Our model achieved a satisfying macro-F1 score of 0.89 on the DIR test set. The model was then applied to California tweets and validated with keyword-based labels. The macro-F1 score was 0.58. However, due to the limitation of keywords, we also spot-checked tweets with controversial labels. 83.5% of BERT labels were correct compared to the keyword labels. Overall, the fine-tuned BERT-based recognizer provided proper predictions and valuable information on drought impacts. The interpretation and analysis of the model were consistent with experiential domain expertise., Comment: 5 pages (+3 in appendix), 5 figures in appendix, 2 tables (+1 in appendix), ICML Workshop on Tackling Climate Change with Machine Learning Workshop, 2021

Dyslexia is estimated to affect ten per cent of the UK population, but there is widespread lack of awareness of the condition by society, which is reflected in the publishing industry through the absence of targeted activity for this readership. The overall aim of this research was to discover how the UK publishing industry can adapt to make its print titles more accessible to adults with dyslexia. The dissertation achieved this aim through an extensive study of relevant literature and the collection and analysis of empirical data. The primary research is comprised of three case studies, and surveys with two target samples. The former involved single interviews with Mairi Kidd, former Managing Director of Barrington Stoke; Susie Dunlop, Publishing Director at Allison & Busby and David Shelley, CEO of Hachette UK. The surveys were conducted by a written questionnaire with UK publishing professionals and a telephone questionnaire with adult dyslexics. This research produced key findings including: confirming the lack of understanding of dyslexia among those working in the UK publishing industry, identifying that adult dyslexics prefer to read in print, and consensus among the latter sample about the importance of text size and spacing as an aid to comprehension. The main conclusions drawn from this research are that publishers bear the responsibility for a cycle of reading deficiency that passes familiarly from dyslexic adults to their children, if left unsupported. It is not enough to be increasing accessibility in digital formats when the readership, as evidenced in this study, favour printed material and, although more costly to modify the existing production workflow to increase spacing and text size, ultimately these changes present a global opportunity for UK publishers to widen readership and thereby increase sales. This research suggests that publishers should collaborate with specialist organisations, such as the British Dyslexia Association, to better unders

Behavioral inhibition (BI), a temperament trait characterized by fear and wariness in novel situations, has been identified as a risk factor for later social reticence and avoidance of peer interactions. However, the ability to regulate fearful responses to novelty may disrupt the link between BI and socially reticent behavior. The present study examined how and whether both behaviorally-manifested and physiological indices of emotion regulation moderate the relation between BI and later social reticence. Participants in this study included 88 children followed longitudinally from ages 2 to 4. At age 2, children completed the BI Paradigm in which children's responses to novel objects and adults were observed. At age 4, children's baseline respiratory sinus arrhythmia (RSA) was assessed and mothers reported on children's negative emotionality and soothability. Social reticence at age 4 was observed during a free play session with 3 unfamiliar peers. Results from saturated path models revealed a significant two-way interaction between BI and baseline RSA and a three-way interaction between BI, negative emotionality, and baseline RSA when predicting socially reticent behavior at age 4. At high levels of baseline RSA and high levels of negative emotionality, the association between BI and social reticence was negative. The relation between BI and later social reticence was only positive and significant at low levels of baseline RSA combined with high levels of negative emotionality. The results suggest that either strong physiological regulation or low negative emotionality seems sufficient to buffer inhibited young children against later social reticence.

Dyslexia is estimated to affect ten per cent of the UK population, but there is widespread lack of awareness of the condition by society, which is reflected in the publishing industry through the absence of targeted activity for this readership. The overall aim of this research was to discover how the UK publishing industry can adapt to make its print titles more accessible to adults with dyslexia. The dissertation achieved this aim through an extensive study of relevant literature and the collection and analysis of empirical data. The primary research is comprised of three case studies, and surveys with two target samples. The former involved single interviews with Mairi Kidd, former Managing Director of Barrington Stoke; Susie Dunlop, Publishing Director at Allison & Busby and David Shelley, CEO of Hachette UK. The surveys were conducted by a written questionnaire with UK publishing professionals and a telephone questionnaire with adult dyslexics. This research produced key findings including: confirming the lack of understanding of dyslexia among those working in the UK publishing industry, identifying that adult dyslexics prefer to read in print, and consensus among the latter sample about the importance of text size and spacing as an aid to comprehension. The main conclusions drawn from this research are that publishers bear the responsibility for a cycle of reading deficiency that passes familiarly from dyslexic adults to their children, if left unsupported. It is not enough to be increasing accessibility in digital formats when the readership, as evidenced in this study, favour printed material and, although more costly to modify the existing production workflow to increase spacing and text size, ultimately these changes present a global opportunity for UK publishers to widen readership and thereby increase sales. This research suggests that publishers should collaborate with specialist organisations, such as the British Dyslexia Association, to better unders

West Nile virus (WNV) is a globally distributed mosquito-borne virus of great public health concern. The number of WNV human cases and mosquito infection patterns vary in space and time. Many statistical models have been developed to understand and predict WNV geographic and temporal dynamics. However, these modeling efforts have been disjointed with little model comparison and inconsistent validation. In this paper, we describe a framework to unify and standardize WNV modeling efforts nationwide. WNV risk, detection, or warning models for this review were solicited from active research groups working in different regions of the United States. A total of 13 models were selected and described. The spatial and temporal scales of each model were compared to guide the timing and the locations for mosquito and virus surveillance, to support mosquito vector control decisions, and to assist in conducting public health outreach campaigns at multiple scales of decision-making. Our overarching goal is to bridge the existing gap between model development, which is usually conducted as an academic exercise, and practical model applications, which occur at state, tribal, local, or territorial public health and mosquito control agency levels. The proposed model assessment and comparison framework helps clarify the value of individual models for decision-making and identifies the appropriate temporal and spatial scope of each model. This qualitative evaluation clearly identifies gaps in linking models to applied decisions and sets the stage for a quantitative comparison of models. Specifically, whereas many coarse-grained models (county resolution or greater) have been developed, the greatest need is for fine-grained, short-term planning models (m-km, days-weeks) that remain scarce. We further recommend quantifying the value of information for each decision to identify decisions that would benefit most from model input.

West Nile virus (WNV) is a globally distributed mosquito-borne virus of great public health concern. The number of WNV human cases and mosquito infection patterns vary in space and time. Many statistical models have been developed to understand and predict WNV geographic and temporal dynamics. However, these modeling efforts have been disjointed with little model comparison and inconsistent validation. In this paper, we describe a framework to unify and standardize WNV modeling efforts nationwide. WNV risk, detection, or warning models for this review were solicited from active research groups working in different regions of the United States. A total of 13 models were selected and described. The spatial and temporal scales of each model were compared to guide the timing and the locations for mosquito and virus surveillance, to support mosquito vector control decisions, and to assist in conducting public health outreach campaigns at multiple scales of decision-making. Our overarching goal is to bridge the existing gap between model development, which is usually conducted as an academic exercise, and practical model applications, which occur at state, tribal, local, or territorial public health and mosquito control agency levels. The proposed model assessment and comparison framework helps clarify the value of individual models for decision-making and identifies the appropriate temporal and spatial scope of each model. This qualitative evaluation clearly identifies gaps in linking models to applied decisions and sets the stage for a quantitative comparison of models. Specifically, whereas many coarse-grained models (county resolution or greater) have been developed, the greatest need is for fine-grained, short-term planning models (m-km, days-weeks) that remain scarce. We further recommend quantifying the value of information for each decision to identify decisions that would benefit most from model input.

The establishment of cardiac function in the developing embryo is essential to ensure blood flow and, therefore, growth and survival of the animal. The molecular mechanisms controlling normal cardiac rhythm remain to be fully elucidated. From a forward genetic screen, we identified a unique mutant, grime, that displayed a specific cardiac arrhythmia phenotype. We show that loss-of-function mutations in tmem161b are responsible for the phenotype, identifying Tmem161b as a regulator of cardiac rhythm in zebrafish. To examine the evolutionary conservation of this function, we generated knockout mice for Tmem161b. Tmem161b knockout mice are neonatal lethal and cardiomyocytes exhibit arrhythmic calcium oscillations. Mechanistically, we find that Tmem161b is expressed at the cell membrane of excitable cells and live imaging shows it is required for action potential repolarization in the developing heart. Electrophysiology on isolated cardiomyocytes demonstrates that Tmem161b is essential to inhibit Ca2+ and K+ currents in cardiomyocytes. Importantly, Tmem161b haploinsufficiency leads to cardiac rhythm phenotypes, implicating it as a candidate gene in heritable cardiac arrhythmia. Overall, these data describe Tmem161b as a highly conserved regulator of cardiac rhythm that functions to modulate ion channel activity in zebrafish and mice.

The cavin proteins are essential for caveola biogenesis and function. Here, we identify a role for the muscle-specific component, Cavin4, in skeletal muscle T-tubule development by analyzing two vertebrate systems, mouse and zebrafish. In both models, Cavin4 localized to T-tubules, and loss of Cavin4 resulted in aberrant T-tubule maturation. In zebrafish, which possess duplicated cavin4 paralogs, Cavin4b was shown to directly interact with the T-tubule–associated BAR domain protein Bin1. Loss of both Cavin4a and Cavin4b caused aberrant accumulation of interconnected caveolae within the T-tubules, a fragmented T-tubule network enriched in Caveolin-3, and an impaired Ca2+ response upon mechanical stimulation. We propose a role for Cavin4 in remodeling the T-tubule membrane early in development by recycling caveolar components from the T-tubule to the sarcolemma. This generates a stable T-tubule domain lacking caveolae that is essential for T-tubule function.

Hogan and colleagues report that the RNA helicase Ddx21 mediates Vegfc-stimulated lymphangiogenesis during zebrafish development through controlling rDNA transcription and ribosome biogenesis in endothelial cells. The development of a functional vasculature requires the coordinated control of cell fate, lineage differentiation and network growth. Cellular proliferation is spatiotemporally regulated in developing vessels, but how this is orchestrated in different lineages is unknown. Here, using a zebrafish genetic screen for lymphatic-deficient mutants, we uncover a mutant for the RNA helicase Ddx21. Ddx21 cell-autonomously regulates lymphatic vessel development. An established regulator of ribosomal RNA synthesis and ribosome biogenesis, Ddx21 is enriched in sprouting venous endothelial cells in response to Vegfc-Flt4 signalling. Ddx21 function is essential for Vegfc-Flt4-driven endothelial cell proliferation. In the absence of Ddx21, endothelial cells show reduced ribosome biogenesis, p53 and p21 upregulation and cell cycle arrest that blocks lymphangiogenesis. Thus, Ddx21 coordinates the lymphatic endothelial cell response to Vegfc-Flt4 signalling by balancing ribosome biogenesis and p53 function. This mechanism may be targetable in diseases of excessive lymphangiogenesis such as cancer metastasis or lymphatic malformation., These authors contributed equally: Katarzyna Koltowska, Kazuhide S. Okuda

West Nile virus (WNV) is a globally distributed mosquito-borne virus of great public health concern. The number of WNV human cases and mosquito infection patterns vary in space and time. Many statistical models have been developed to understand and predict WNV geographic and temporal dynamics. However, these modeling efforts have been disjointed with little model comparison and inconsistent validation. In this paper, we describe a framework to unify and standardize WNV modeling efforts nationwide. WNV risk, detection, or warning models for this review were solicited from active research groups working in different regions of the United States. A total of 13 models were selected and described. The spatial and temporal scales of each model were compared to guide the timing and the locations for mosquito and virus surveillance, to support mosquito vector control decisions, and to assist in conducting public health outreach campaigns at multiple scales of decision-making. Our overarching goal is to bridge the existing gap between model development, which is usually conducted as an academic exercise, and practical model applications, which occur at state, tribal, local, or territorial public health and mosquito control agency levels. The proposed model assessment and comparison framework helps clarify the value of individual models for decision-making and identifies the appropriate temporal and spatial scope of each model. This qualitative evaluation clearly identifies gaps in linking models to applied decisions and sets the stage for a quantitative comparison of models. Specifically, whereas many coarse-grained models (county resolution or greater) have been developed, the greatest need is for fine-grained, short-term planning models (m-km, days-weeks) that remain scarce. We further recommend quantifying the value of information for each decision to identify decisions that would benefit most from model input.

West Nile virus (WNV) is a globally distributed mosquito-borne virus of great public health concern. The number of WNV human cases and mosquito infection patterns vary in space and time. Many statistical models have been developed to understand and predict WNV geographic and temporal dynamics. However, these modeling efforts have been disjointed with little model comparison and inconsistent validation. In this paper, we describe a framework to unify and standardize WNV modeling efforts nationwide. WNV risk, detection, or warning models for this review were solicited from active research groups working in different regions of the United States. A total of 13 models were selected and described. The spatial and temporal scales of each model were compared to guide the timing and the locations for mosquito and virus surveillance, to support mosquito vector control decisions, and to assist in conducting public health outreach campaigns at multiple scales of decision-making. Our overarching goal is to bridge the existing gap between model development, which is usually conducted as an academic exercise, and practical model applications, which occur at state, tribal, local, or territorial public health and mosquito control agency levels. The proposed model assessment and comparison framework helps clarify the value of individual models for decision-making and identifies the appropriate temporal and spatial scope of each model. This qualitative evaluation clearly identifies gaps in linking models to applied decisions and sets the stage for a quantitative comparison of models. Specifically, whereas many coarse-grained models (county resolution or greater) have been developed, the greatest need is for fine-grained, short-term planning models (m–km, days–weeks) that remain scarce. We further recommend quantifying the value of information for each decision to identify decisions that would benefit most from model input.

Although many studies show that peers influence the development of adolescent internalizing and externalizing difficulties, few have considered both internalizing and externalizing difficulties in the same study, and fewer have considered the contributions of parents. Using a longitudinal sample of 385 adolescents, the contributions of best friends’ internalizing and externalizing difficulties (as assessed in Grade 6; G6: Mage = 13.64 years; 53% female; 40% ethnic or racial minority) were examined as they predicted subsequent adolescent internalizing and externalizing difficulties (at G8); in addition, the moderating role of both maternal and paternal support (at G6) was explored. Structural equation modelling revealed that best friend internalizing difficulties predicted decreases, but that best friend externalizing difficulties predicted increases in adolescents’ externalizing difficulties over time. Significant interactions involving both maternal and paternal support revealed that the negative impact of a G6 best friend having internalizing problems on later G8 adolescent externalizing problems was stronger at low levels of maternal and paternal support. The findings highlight the complex, and interactive, influences of friends and parents on the development of internalizing and externalizing symptomatology during adolescence, and underscore the importance of targeting both sources of social influence in research and clinical work.

The establishment of cardiac function in the developing embryo is essential to ensure blood flow and, therefore, growth and survival of the animal. The molecular mechanisms controlling normal cardiac rhythm remain to be fully elucidated. From a forward genetic screen, we identified a unique mutant, grime, that displayed a specific cardiac arrhythmia phenotype. We show that loss-of-function mutations in tmem161b are responsible for the phenotype, identifying Tmem161b as a regulator of cardiac rhythm in zebrafish. To examine the evolutionary conservation of this function, we generated knockout mice for Tmem161b. Tmem161b knockout mice are neonatal lethal and cardiomyocytes exhibit arrhythmic calcium oscillations. Mechanistically, we find that Tmem161b is expressed at the cell membrane of excitable cells and live imaging shows it is required for action potential repolarization in the developing heart. Electrophysiology on isolated cardiomyocytes demonstrates that Tmem161b is essential to inhibit Ca2+ and K+ currents in cardiomyocytes. Importantly, Tmem161b haploinsufficiency leads to cardiac rhythm phenotypes, implicating it as a candidate gene in heritable cardiac arrhythmia. Overall, these data describe Tmem161b as a highly conserved regulator of cardiac rhythm that functions to modulate ion channel activity in zebrafish and mice.

Building compositional explanations requires models to combine two or more facts that, together, describe why the answer to a question is correct. Typically, these "multi-hop" explanations are evaluated relative to one (or a small number of) gold explanations. In this work, we show these evaluations substantially underestimate model performance, both in terms of the relevance of included facts, as well as the completeness of model-generated explanations, because models regularly discover and produce valid explanations that are different than gold explanations. To address this, we construct a large corpus of 126k domain-expert (science teacher) relevance ratings that augment a corpus of explanations to standardized science exam questions, discovering 80k additional relevant facts not rated as gold. We build three strong models based on different methodologies (generation, ranking, and schemas), and empirically show that while expert-augmented ratings provide better estimates of explanation quality, both original (gold) and expert-augmented automatic evaluations still substantially underestimate performance by up to 36% when compared with full manual expert judgements, with different models being disproportionately affected. This poses a significant methodological challenge to accurately evaluating explanations produced by compositional reasoning models., Comment: Accepted to EMNLP 2021

The lymphatic vasculature develops primarily from pre-existing veins. A pool of lymphatic endothelial cells (LECs) first sprouts from cardinal veins followed by migration and proliferation to colonise embryonic tissues. Although much is known about the molecular regulation of LEC fate and sprouting during early lymphangiogenesis, we know far less about the instructive and permissive signals that support LEC migration through the embryo. Using a forward genetic screen, we identified mbtps1 and sec23a, components of the COP-II protein secretory pathway, as essential for developmental lymphangiogenesis. In both mutants, LECs initially depart the cardinal vein but then fail in their ongoing migration. A key cargo that failed to be secreted in both mutants was a type II collagen (Col2a1). Col2a1 is normally secreted by notochord sheath cells, alongside which LECs migrate. col2a1a mutants displayed defects in the migratory behaviour of LECs and failed lymphangiogenesis. These studies thus identify Col2a1 as a key cargo secreted by notochord sheath cells and required for the migration of LECs. These findings combine with our current understanding to suggest that successive cell-to-cell and cell-matrix interactions regulate the migration of LECs through the embryonic environment during development.

Virtual peer interaction is prevalent among adolescents (Anderson & Jiang, 2018), but little is known about how adolescents’ virtual interactions with peers compare to their in-person interactions. The present study aimed to compare adolescents’ in-person and virtual interactions in a multiplayer video game during an initial interaction with an unfamiliar peer to examine differences in social behavior, physiological responding, and perceptions of interaction quality. The study also aimed to investigate how motivations for solitude related to interaction quality, and whether these associations differed across virtual and in-person interaction. Participants were 72 adolescents (78% male, Mage = 12.49) from the Washington, DC metropolitan area who interacted with an unfamiliar peer in the lab using the multiplayer game Minecraft. Pairs of participants were randomly assigned to interact with one another in-person, sitting in the same room next to each other, or virtually, able to communicate using the text-based chat feature. Participants completed questionnaires about their motivations for solitude prior to the interaction. They also completed questionnaires about their self-perceptions and affect before and after the interaction, as well as their perceptions of the interaction quality after the interaction. Participants’ social engagement and their social initiations and the partner’s responses were observed during the interaction, and their respiratory sinus arrhythmia was measured before, during, and after the interaction. Results showed that quantity of social interaction was higher in the in-person condition, but perceived quality of the interaction was higher in the virtual condition. Participants spent more time communicating with one another and made more social initiations in the in-person condition. However, participants in the virtual condition received more successful responses to their social initiations and reported enjoying the interaction marginally mor

Scientists and policy makers need better ways to quantify effects of drought, and recognize that defining drought impacts is often subjective, relative to expectations and what is normal for a given location. This dissertation explores three questions that provide different ways of understanding drought impacts: 1) A statistical analysis to describe, explain and predict a drought signal in the annual number of human cases of West Nile Virus in Nebraska found that a dry year preceded by a wet year, often in combination with warm temperatures, increases the number of human cases. Modelling scenarios found that drought may have increased the number of cases by 38% from 2002–2018. The models were better at explaining than predicting, and better at predicting which counties would have cases (most had none) than how many cases there would be. 2) Collecting, geolocating, filtering and analyzing tweets using #drought and related hashtags, a statistical model described an expected relationship between the number of tweets in each state, each week, and news coverage, drought status, and population. I investigated whether higher-than-expected numbers of tweets, reflecting higher drought awareness, could be of use for early detection of drought, using a diversity statistic threshold to identify broader-based increases in tweet volume. Higher drought awareness in some cases reflected past drought experience, and in some cases reflected emerging drought. 3) The Drought Impact Reporter collected reports from two different networks in Missouri in 2018, one based on citizen science, and the other, tapping into stakeholders, primarily livestock producers, for crowdsourced observations. I examined differences in observations from the two networks over space, time, and drought status, and found that the citizen science reports could help validate the stakeholder reports. I conclude by evaluating how combinations of subjective, qualitative and quantitative data contribute to useful know

The correct assignment of cell fate within fields of multipotent progenitors is essential for accurate tissue diversification. The first lymphatic vessels arise from pre-existing veins after venous endothelial cells become specified as lymphatic progenitors. Prox1 specifies lymphatic fate and labels these progenitors; however, the mechanisms restricting Prox1 expression and limiting the progenitor pool remain unknown. We identified a zebrafish mutant that displayed premature, expanded, and prolonged lymphatic specification. The gene responsible encodes the regulator of alternative splicing, Nova2. In zebrafish and human endothelial cells, Nova2 selectively regulates pre-mRNA splicing for components of signaling pathways and phosphoproteins. Nova2-deficient endothelial cells display increased Mapk/Erk signaling, and Prox1 expression is dynamically controlled by Erk signaling. We identify a mechanism whereby Nova2-regulated splicing constrains Erk signaling, thus limiting lymphatic progenitor cell specification. This identifies the capacity of a factor that tunes mRNA splicing to control assignment of cell fate during vascular differentiation.

Unambiguous cell line authentication is essential to avoid loss of association between data and cells. The risk for loss of references increases with the rapidity that new human pluripotent stem cell (hPSC) lines are generated, exchanged, and implemented. Ideally, a single name should be used as a generally applied reference for each cell line to access and unify cell-related information across publications, cell banks, cell registries, and databases and to ensure scientific reproducibility. We discuss the needs and requirements for such a unique identifier and implement a standard nomenclature for hPSCs, which can be automatically generated and registered by the human pluripotent stem cell registry (hPSCreg). To avoid ambiguities in PSC-line referencing, we strongly urge publishers to demand registration and use of the standard name when publishing research based on hPSC lines. In this article Kurtz, Seltmann and colleagues propose a standard nomenclature and registry for human pluripotent stem cells. The nomenclature is based on fixed name elements and provides a unique identifier for PSC lines suitable for referencing over diverse data sources, registries, publications, and cell banks. Rigorous application is needed to reduce risks from misidentification and false referencing of lines and data.

Unambiguous cell line authentication is essential to avoid loss of association between data and cells. The risk for loss of references increases with the rapidity that new human pluripotent stem cell (hPSC) lines are generated, exchanged, and implemented. Ideally, a single name should be used as a generally applied reference for each cell line to access and unify cell-related information across publications, cell banks, cell registries, and databases and to ensure scientific reproducibility. We discuss the needs and requirements for such a unique identifier and implement a standard nomenclature for hPSCs, which can be automatically generated and registered by the human pluripotent stem cell registry (hPSCreg). To avoid ambiguities in PSC-line referencing, we strongly urge publishers to demand registration and use of the standard name when publishing research based on hPSC lines. In this article Kurtz, Seltmann and colleagues propose a standard nomenclature and registry for human pluripotent stem cells. The nomenclature is based on fixed name elements and provides a unique identifier for PSC lines suitable for referencing over diverse data sources, registries, publications, and cell banks. Rigorous application is needed to reduce risks from misidentification and false referencing of lines and data.

Unambiguous cell line authentication is essential to avoid loss of association between data and cells. The risk for loss of references increases with the rapidity that new human pluripotent stem cell (hPSC) lines are generated, exchanged, and implemented. Ideally, a single name should be used as a generally applied reference for each cell line to access and unify cell-related information across publications, cell banks, cell registries, and databases and to ensure scientific reproducibility. We discuss the needs and requirements for such a unique identifier and implement a standard nomenclature for hPSCs, which can be automatically generated and registered by the human pluripotent stem cell registry (hPSCreg). To avoid ambiguities in PSC-line referencing, we strongly urge publishers to demand registration and use of the standard name when publishing research based on hPSC lines.

Unambiguous cell line authentication is essential to avoid loss of association between data and cells. The risk for loss of references increases with the rapidity that new human pluripotent stem cell (hPSC) lines are generated, exchanged, and implemented. Ideally, a single name should be used as a generally applied reference for each cell line to access and unify cell-related information across publications, cell banks, cell registries, and databases and to ensure scientific reproducibility. We discuss the needs and requirements for such a unique identifier and implement a standard nomenclature for hPSCs, which can be automatically generated and registered by the human pluripotent stem cell registry (hPSCreg). To avoid ambiguities in PSC-line referencing, we strongly urge publishers to demand registration and use of the standard name when publishing research based on hPSC lines. In this article Kurtz, Seltmann and colleagues propose a standard nomenclature and registry for human pluripotent stem cells. The nomenclature is based on fixed name elements and provides a unique identifier for PSC lines suitable for referencing over diverse data sources, registries, publications, and cell banks. Rigorous application is needed to reduce risks from misidentification and false referencing of lines and data.

Unambiguous cell line authentication is essential to avoid loss of association between data and cells. The risk for loss of references increases with the rapidity that new human pluripotent stem cell (hPSC) lines are generated, exchanged, and implemented. Ideally, a single name should be used as a generally applied reference for each cell line to access and unify cell-related information across publications, cell banks, cell registries, and databases and to ensure scientific reproducibility. We discuss the needs and requirements for such a unique identifier and implement a standard nomenclature for hPSCs, which can be automatically generated and registered by the human pluripotent stem cell registry (hPSCreg). To avoid ambiguities in PSC-line referencing, we strongly urge publishers to demand registration and use of the standard name when publishing research based on hPSC lines. In this article Kurtz, Seltmann and colleagues propose a standard nomenclature and registry for human pluripotent stem cells. The nomenclature is based on fixed name elements and provides a unique identifier for PSC lines suitable for referencing over diverse data sources, registries, publications, and cell banks. Rigorous application is needed to reduce risks from misidentification and false referencing of lines and data.

Presentation at the MARAC conference in Philadelphia, PA on November 7-9, 2013. S16 - Creating Web Exhibitions and Mobile Apps for Archives

Presentation at the MARAC conference in Philadelphia, PA on November 7-9, 2013. S16 - Creating Web Exhibitions and Mobile Apps for Archives

Full Text, Thesis (PhD Doctorate), Doctor of Philosophy (PhD), Queensland College of Art, Arts, Education and Law, apart & a part: a new kind of archive For many individuals who spent time in institutional and out-of-home care as children during the twentieth century in Australia, the experience was marked by longing, loss, and displacement. apart & a part is a visual artwork that was created in collaboration with six Australian care leavers as the outcome of my doctoral research. The project has focused on the legacy of the institutional or out-of-home care experience on the individual and the subsequent need to produce narratives of the self. It has traced the affective dimensions of trauma and memory through a lengthy period of collaborative dialogue with care leavers. Drawing on the notion of trauma as a quotidian experience, apart & a part explores how care leavers navigate everyday encounters with their past. The artworks featured in the installation create an expanded archive of visual responses and narrative fragments that address the felt experiences often absent from historical or institutional records. The immersive installation blends photography, video, sound, and archival images to communicate the ongoing impacts of institutional thinking on individuals. Drawn from our collaborative dialogues and actions, the works in apart & a part traverse expanded documentary, social practice, and contemporary political art. The project explores the non-linear and sensorial structure of trauma, and advances its potential to represent the affective dimensions of lived experience. The project frames lived experiences as a continuum rather than an event, thereby acknowledging the impact of abuse and trauma but not allowing them to become life-defining. Accompanying the artwork, this exegesis, apart & a part: a new kind of archive, interrogates the conceptual underpinnings of the creative research. It provides a necessary socio-political and historical context through which to understand the mass removal of children (First Nations and non-First Nations) in Australia during the twent

Angiogenesis is responsible for tissue vascularization during development, as well as in pathological contexts, including cancer and ischemia. Vascular endothelial growth factors (VEGFs) regulate angiogenesis by acting through VEGF receptors to induce endothelial cell signaling. VEGF is processed in the extracellular matrix (ECM), but the complexity of ECM control of VEGF signaling and angiogenesis remains far from understood. In a forward genetic screen, we identified angiogenesis defects in tmem2 zebrafish mutants that lack both arterial and venous Vegf/Vegfr/Erk signaling. Strikingly, tmem2 mutants display increased hyaluronic acid (HA) surrounding developing vessels. Angiogenesis in tmem2 mutants was rescued, or restored after failed sprouting, by degrading this increased HA. Furthermore, oligomerized HA or overexpression of Vegfc rescued angiogenesis in tmem2 mutants. Based on these data, and the known structure of Tmem2, we find that Tmem2 regulates HA turnover to promote normal Vegf signaling during developmental angiogenesis.