Power Dynamics in Discussions of Contemporary Jungian Theory and Practice.

Groups of Jungian analysts, which included the present authors, met to discuss four key theoretical concepts, each of which was felt to have problematic aspects if used unquestioningly in contemporary practice. The concepts were: The Primitive, Inner and Outer Worlds, Contrasexuality and Participation Mystique. The discussions were informed by clinical material and specific papers chosen for their critical evaluation of the topic. Four recorded transcripts were made, with permission, for further consideration of the relationship between contemporary Jungian theory and practice using the research method of thematic analysis. Three main themes were identified: Work of Analysis, Frames of Reference and Power Dynamics. The authors discuss the themes in relation to the overarching theme of power, understood as operating at conscious and unconscious levels. The artwork "Cold Dark Matter: An Exploded View" by Cornelia Parker is used as a metaphor in discussing the dynamic of challenging foundational concepts. The authors suggest that power dynamics are intrinsic in both the difficulty and the benefits of critically evaluating key concepts, binding together the theoretical (what informs us) with the clinical (what we do in the consulting room) as well as blowing apart pre-conceived notions of what underpins the analyst's work.

Les auteurs de cet article ont fait partie de groupes d'analystes jungiens qui se sont rencontrés pour débattre de quatre concepts théoriques fondamentaux, chacun de ces concepts étant perçu comme problématique si on l'utilise dans la pratique contemporaine sans se poser de questions. Ces concepts sont : primitif, mondes intérieur et extérieur, contra­sexualité et participation mystique. Les discussions ont été nourries par du matériel clinique et par des articles spécialement choisis pour leur évaluation critique du sujet traité. Quatre transcriptions enregistrées furent faites, avec l'accord des personnes concernées, pour une étude plus approfondie de la relation entre la théorie et la pratique jungienne contemporaine, en s'appuyant sur la méthode de recherche de l'analyse thématique. Trois thèmes furent identifiés : le travail d'analyse, les cadres de référence, et les dynamiques de pouvoir. Les auteurs débattent de ces thèmes en les reliant avec le thème fondamental du pouvoir, perçu comme fonctionnant aux niveaux conscient et inconscient. L'œuvre de l'artiste Cornelia Parker « Cold Dark Matter: An Exploded View ¼ est utilisée comme métaphore lorsqu'il est question de la dynamique de questionner des concepts fondamentaux. Les auteurs suggèrent que les dynamiques de pouvoir sont propres à la difficulté mais aussi aux bénéfices de cette remise en question, en reliant le théorique (ce qui nous informe) avec la clinique (ce que l'on fait dans la salle de consultation) et en faisant sauter les notions qui n'ont pas été questionnées, en ce qui concerne ce qui étaye le travail analytique.

Grupos de analistas Junguianos, los cuales incluyen a las presentes autoras, se reunieron para discutir cuatro conceptos teóricos fundamentales, cada uno de los cuales se consideraba que tenía aspectos problemáticos si se utilizaba sin cuestionamientos en la práctica contemporánea. Los conceptos eran: Primitivo, Mundos Interior y Exterior, Contrasexualidad y Participation Mystique. Los debates se basaron en material clínico y en artículos específicos elegidos para una evaluación crítica del tema. Se transcribieron con permiso cuatro grabaciones para un examen más detenido de la relación entre la teoría y la práctica junguiana contemporánea utilizando el método de investigación del análisis temático. Se identificaron tres temas: Trabajo Analítico, Marcos de Referencia y Dinámicas de Poder. Las autoras analizaron los temas en relación con el tema más amplio del poder, entendido como algo que opera a nivel consciente e inconsciente. La obra de arte "Cold Dark Matter: An Exploded View", de Cornelia Parker, fue utilizada como metáfora para discutir acerca de la dinámica de cuestionar los conceptos fundamentales. Se sugiere que las dinámicas de poder son intrínsecas tanto a la dificultad como a los beneficios de hacer esta tarea, ligando lo teórico (lo que nos informa) con lo clínico (lo que hacemos en la consulta), así como a desarmar nociones incuestionadas de aquello que sustenta el trabajo analítico.

Glioblastoma initiation, migration, and cell types are regulated by core bHLH transcription factors ASCL1 and OLIG2.

Glioblastomas (GBMs) are highly aggressive, infiltrative, and heterogeneous brain tumors driven by complex driver mutations and glioma stem cells (GSCs). The neurodevelopmental transcription factors ASCL1 and OLIG2 are co-expressed in GBMs, but their role in regulating the heterogeneity and hierarchy of GBM tumor cells is unclear. Here, we show that oncogenic driver mutations lead to dysregulation of ASCL1 and OLIG2, which function redundantly to initiate brain tumor formation in a mouse model of GBM. Subsequently, the dynamic levels and reciprocal binding of ASCL1 and OLIG2 to each other and to downstream target genes then determine the cell types and degree of migration of tumor cells. Single-cell RNA sequencing (scRNA-seq) reveals that a high level of ASCL1 is key in defining GSCs by upregulating a collection of ribosomal protein, mitochondrial, neural stem cell (NSC), and cancer metastasis genes - all essential for sustaining the high proliferation, migration, and therapeutic resistance of GSCs.

Simulated nitrous oxide emissions from multiple agroecosystems in the U.S. Corn Belt using the modified SWAT-C model.

Agriculture is a major source of nitrous oxide (N2O) emissions into the atmosphere. However, assessing the impacts of agricultural conservation practices, land use change, and climate adaptation measures on N2O emissions at a large scale is a challenge for process-based model applications. Here, we integrated six N2O emission algorithms for the nitrification processes and seven N2O emission algorithms for the denitrification process into the Soil and Water Assessment Tool-Carbon (SWAT-C). We evaluated the different combinations of methods in simulating N2O emissions under corn (Zea mays L.) production systems with various conservation practices, including fertilization, tillage, and crop rotation (represented by 14 experimental treatments and 83 treatment-years) at five experimental sites across the U.S. Midwest. The SWAT-C model exhibited wide variability in simulating daily average N2O emissions across treatment-years with different method configurations, as indicated by the ranges of R2, NSE, and BIAS (0.04-0.68, -1.78-0.60, and -0.94-0.001, respectively). Our results indicate that the denitrification process has a stronger impact on N2O emissions than the nitrification process. The best performing N2O emission algorithms are those rooted in the CENTURY model, which considers soil pH and respiration effects that were overlooked by other algorithms. The optimal N2O emission algorithm explained about 63% of the variability of annual average N2O emissions, with NSE and BIAS of 0.60 and -0.033, respectively. The model can reasonably represent the impacts of agricultural conservation practices on N2O emissions. We anticipate that the improved SWAT-C model, with its flexible configurations and robust modeling and assessment capabilities, will provide a valuable tool for studying and managing N2O emissions from agroecosystems.

ASCL1-ERK1/2 Axis: ASCL1 restrains ERK1/2 via the dual specificity phosphatase DUSP6 to promote survival of a subset of neuroendocrine lung cancers.

The transcription factor achaete-scute complex homolog 1 (ASCL1) is a lineage oncogene that is central for the growth and survival of small cell lung cancers (SCLC) and neuroendocrine non-small cell lung cancers (NSCLC-NE) that express it. Targeting ASCL1, or its downstream pathways, remains a challenge. However, a potential clue to overcoming this challenage has been information that SCLC and NSCLC-NE that express ASCL1 exhibit extremely low ERK1/2 activity, and efforts to increase ERK1/2 activity lead to inhibition of SCLC growth and surival. Of course, this is in dramatic contrast to the majority of NSCLCs where high activity of the ERK pathway plays a major role in cancer pathogenesis. A major knowledge gap is defining the mechanism(s) underlying the low ERK1/2 activity in SCLC, determining if ERK1/2 activity and ASCL1 function are inter-related, and if manipulating ERK1/2 activity provides a new therapeutic strategy for SCLC. We first found that expression of ERK signaling and ASCL1 have an inverse relationship in NE lung cancers: knocking down ASCL1 in SCLCs and NE-NSCLCs increased active ERK1/2, while inhibition of residual SCLC/NSCLC-NE ERK1/2 activity with a MEK inhibitor increased ASCL1 expression. To determine the effects of ERK activity on expression of other genes, we obtained RNA-seq from ASCL1-expressing lung tumor cells treated with an ERK pathway MEK inhibitor and identified down-regulated genes (such as SPRY4, ETV5, DUSP6, SPRED1) that potentially could influence SCLC/NSCLC-NE tumor cell survival. This led us to discover that genes regulated by MEK inhibition suppress ERK activation and CHIP-seq demonstrated these are bound by ASCL1. In addition, SPRY4, DUSP6, SPRED1 are known suppressors of the ERK1/2 pathway, while ETV5 regulates DUSP6. Survival of NE lung tumors was inhibited by activation of ERK1/2 and a subset of ASCL1-high NE lung tumors expressed DUSP6. Because the dual specificity phosphatase 6 (DUSP6) is an ERK1/2-selective phosphatase that inactivates these kinases and has a pharmacologic inhibitor, we focused mechanistic studies on DUSP6. These studies showed: Inhibition of DUSP6 increased active ERK1/2, which accumulated in the nucleus; pharmacologic and genetic inhibition of DUSP6 affected proliferation and survival of ASCL1-high NE lung cancers; and that knockout of DUSP6 "cured" some SCLCs while in others resistance rapidly developed indicating a bypass mechanism was activated. Thus, our findings fill this knowledge gap and indicate that combined expression of ASCL1, DUSP6 and low phospho-ERK1/2 identify some neuroendocrine lung cancers for which DUSP6 may be a therapeutic target.

Why ethical frameworks fail to deliver in a pandemic: Are proposed alternatives an improvement?

In the past decade, numerous ethical frameworks have been developed to support public health decision-making in challenging areas. Before the COVID-19 pandemic began, members of the authorship team were involved in research programmes, in which the development of ethical frameworks was planned, to guide (a) the use of new technologies for emerging infectious disease surveillance; and (b) the allocation of scarce supplies of pandemic influenza vaccine. However, as the pandemic evolved, significant practical challenges emerged that led to our questioning the value of these frameworks. We now believe that a normative instrument, such as a framework, cannot adequately or reliably provide the ethical guidance that needs to be incorporated into public health decision-making during natural disasters or infectious disease emergencies. Recently it has been suggested that there are potentially more dynamic, flexible, and effective ways to navigate decisions involving complex considerations entailed in policies and practices during a public health emergency. In this paper, we first outline the key functions of a public health ethics framework, before describing why we believe it would not be fit for purpose during a crisis. We end by considering whether proposed alternative methods to promote ethical public health decision-making goals have the potential to meet these objectives.

The ethics of intervening in animal behaviour for conservation.

Conservation behaviour is a growing field that applies insights from the study of animal behaviour to address challenges in wildlife conservation and management. Conservation behaviour interventions often aim to manage specific behaviours of a species to solve conservation challenges. The field is often viewed as offering approaches that are less intrusive or harmful to animals than, for example, managing the impact of a problematic species by reducing its population size (frequently through lethal control). However, intervening in animal behaviour, even for conservation purposes, may still raise important ethical considerations. We discuss these issues and develop a framework and a decision support tool, to aid managers and researchers in evaluating the ethical considerations of conservation behaviour interventions against other options.

A New Strategy for Animal Research: Attending to Dissent.

Increasingly, ethical concepts ordinarily reserved for the human research setting have been applied to nonhuman animals in research. This comes at the same time as concerns mount over challenges in translating the results of biomedical research with animals to human clinical benefit. This paper argues that applying the concept of dissent derived from research with humans to the context of animals can help to address a number of these translational issues, thereby providing an epistemological reason to take animal dissent seriously. This epistemological rationale can be added to the practical and ethical reasons for attending to animal dissent. Having made a case for recognizing the dissent of animals in biomedical research, the consequences that follow from this for the conduct of research are discussed. If animal researchers attend to dissent, then it seems that there are three types of strategy available: to override dissent, to train animals in such a way as to circumvent potential dissent, or to alter how research is conducted in order to be responsive to dissent. Only this last option has the potential to address all the types of reasons that motivate us to take dissent seriously; however, this would involve a significant reshaping of the practice of animal research.

Integrative epigenomic analyses of small cell lung cancer cells demonstrates the clinical translational relevance of gene body methylation.

DNA methylation is a key regulator of gene expression and a clinical therapeutic predictor. We examined global DNA methylation beyond the generally used promoter areas in human small cell lung cancer (SCLC) and find that gene body methylation is a robust positive predictor of gene expression. Combining promoter and gene body methylation better predicts gene expression than promoter methylation alone including genes involved in the neuroendocrine classification of SCLC and the expression of therapeutically relevant genes including MGMT, SLFN11, and DLL3. Importantly, for super-enhancer (SE) covered genes such as NEUROD1 or MYC, using H3K27ac and NEUROD1, ASCL1, and POU2F3 ChIP-seq data, we show that genic methylation is inversely proportional to expression, thus providing a new approach to identify potential SE regulated genes involved in SCLC pathogenesis. To advance SCLC transitional research, these data are integrated into our web portal (https://discover.nci.nih.gov/SclcCellMinerCDB/) for open and easy access to basic and clinical investigators.

Inhibition of Karyopherin ß1-Mediated Nuclear Import Disrupts Oncogenic Lineage-Defining Transcription Factor Activity in Small Cell Lung Cancer.

Genomic studies support the classification of small cell lung cancer (SCLC) into subtypes based on the expression of lineage-defining transcription factors ASCL1 and NEUROD1, which together are expressed in ∼86% of SCLC. ASCL1 and NEUROD1 activate SCLC oncogene expression, drive distinct transcriptional programs, and maintain the in vitro growth and oncogenic properties of ASCL1 or NEUROD1-expressing SCLC. ASCL1 is also required for tumor formation in SCLC mouse models. A strategy to inhibit the activity of these oncogenic drivers may therefore provide both a targeted therapy for the predominant SCLC subtypes and a tool to investigate the underlying lineage plasticity of established SCLC tumors. However, there are no known agents that inhibit ASCL1 or NEUROD1 function. In this study, we identify a novel strategy to pharmacologically target ASCL1 and NEUROD1 activity in SCLC by exploiting the nuclear localization required for the function of these transcription factors. Karyopherin ß1 (KPNB1) was identified as a nuclear import receptor for both ASCL1 and NEUROD1 in SCLC, and inhibition of KPNB1 led to impaired ASCL1 and NEUROD1 nuclear accumulation and transcriptional activity. Pharmacologic targeting of KPNB1 preferentially disrupted the growth of ASCL1+ and NEUROD1+ SCLC cells in vitro and suppressed ASCL1+ tumor growth in vivo, an effect mediated by a combination of impaired ASCL1 downstream target expression, cell-cycle activity, and proteostasis. These findings broaden the support for targeting nuclear transport as an anticancer therapeutic strategy and have implications for targeting lineage-transcription factors in tumors beyond SCLC. SIGNIFICANCE: The identification of KPNB1 as a nuclear import receptor for lineage-defining transcription factors in SCLC reveals a viable therapeutic strategy for cancer treatment.

Ethical and regulatory implications of the COVID-19 pandemic for the medical devices industry and its representatives.

The development and deployment of medical devices, along with most areas of healthcare, has been significantly impacted by the COVID-19 pandemic. This has had variable ethical implications, two of which we will focus on here. First, medical device regulations have been rapidly amended to expedite approvals of devices ranging from face masks to ventilators. Although some regulators have issued cessation dates, there is inadequate discussion of triggers for exiting these crisis standards, and evidence that this may not be feasible. Given the relatively low evidence standards currently required for regulatory approval of devices, this further indefinite reduction in standards raises serious ethical issues. Second, the pandemic has disrupted the usual operations of device representatives in hospitals, providing an opportunity to examine and refine this potentially ethically problematic practice. In this paper we explain and critically analyse the ethical implications of these two pandemic-related impacts on medical devices and propose suggestions for their management. These include an endpoint for pandemic-related adjustments to device regulation or a mechanism for continued refinement over time, together with a review of device research conducted under crisis conditions, support for the removal and replacement of emergency approved devices, and a review of device representative credentialling.

Should Digital Contact Tracing Technologies be used to Control COVID-19? Perspectives from an Australian Public Deliberation.

Mobile phone-based applications (apps) can promote faster targeted actions to control COVID-19. However, digital contact tracing systems raise concerns about data security, system effectiveness, and their potential to normalise privacy-invasive surveillance technologies. In the absence of mandates, public uptake depends on the acceptability and perceived legitimacy of using technologies that log interactions between individuals to build public health capacity. We report on six online deliberative workshops convened in New South Wales to consider the appropriateness of using the COVIDSafe app to enhance Australian contact tracing systems. All groups took the position (by majority) that the protections enacted in the app design and supporting legislation were appropriate. This support is contingent on several system attributes including: the voluntariness of the COVIDSafe app; that the system relies on proximity rather than location tracking; and, that data access is restricted to local public health practitioners undertaking contact tracing. Despite sustained scepticism in media coverage, there was an underlying willingness to trust Australian governing institutions such that in principle acceptance of the new contact tracing technology was easy to obtain. However, tensions between the need to prove system effectiveness through operational transparency and requirements for privacy protections could be limiting public uptake. Our study shows that informed citizens are willing to trade their privacy for common goods such as COVID-19 suppression. But low case numbers and cautionary public discourses can make trustworthiness difficult to establish because some will only do so when it can be demonstrated that the benefits justify the costs to individuals.

ASCL1, NKX2-1, and PROX1 co-regulate subtype-specific genes in small-cell lung cancer.

Lineage-defining transcription factors (LTFs) play key roles in small-cell lung cancer (SCLC) pathophysiology. Delineating the LTF-regulated genes operative in SCLC could provide a road map to identify SCLC dependencies. We integrated chromatin landscape and transcriptome analyses of patient-derived SCLC preclinical models to identify super-enhancers (SEs) and their associated genes in the ASCL1-, NEUROD1-, and POU2F3-high SCLC subtypes. We find SE signatures predict LTF-based classification of SCLC, and the SE-associated genes are enriched with those defined as common essential genes in DepMap. In addition, in ASCL1-high SCLC, we show ASCL1 complexes with NKX2-1 and PROX1 to co-regulate genes functioning in NOTCH signaling, catecholamine biosynthesis, and cell-cycle processes. Depletion of ASCL1 demonstrates it is a key dependency factor in preclinical SCLC models and directly regulates multiple DepMap-defined essential genes. We provide LTF/SE-based subtype-specific gene sets for SCLC for further therapeutic investigation.

The Impact of a Telehealth Intervention on Activity Profiles in Older Adults during the COVID-19 Pandemic: A Pilot Study.

BACKGROUND: Physical inactivity during the COVID-19 pandemic is a public health concern for older adults. Telehealth presents a safe platform for conducting health-related interventions that may have additional benefits such as widespread reach. Our pilot study sought to examine how a telehealth intervention changed activity profiles in older adults during the COVID-19 pandemic. METHODS: There were n =13 adults aged 70.6 ± 4.5 years that participated in a 6 week telehealth intervention during the COVID-19 pandemic. The didactic intervention contents were shared online, and participants worked with trained interviewers over the telephone to discuss physical activity. At baseline and post-intervention, the Multimedia Activity Recall for Children and Adults examined activity profiles, while accelerometry estimated time spent sedentary and in physical activity. RESULTS: Relative to the baseline measures, there was an 88 min/day (95% confidence interval (CI): 39, 137) increase in computer time and 36 min/day (CI: 10, 62) reduction in time spent in active transport at post-intervention. Moderate-to-vigorous physical activity participation also increased by an estimated 2 min/day (CI: -21, 26) and 12 min/week (CI: -154, 180), but this trend was not statistically significant. CONCLUSION: We recommend that support be provided to older adults transitioning to telehealth, especially as migration to telehealth progresses.

ASCL1 represses a SOX9+ neural crest stem-like state in small cell lung cancer.

ASCL1 is a neuroendocrine lineage-specific oncogenic driver of small cell lung cancer (SCLC), highly expressed in a significant fraction of tumors. However, ∼25% of human SCLC are ASCL1-low and associated with low neuroendocrine fate and high MYC expression. Using genetically engineered mouse models (GEMMs), we show that alterations in Rb1/Trp53/Myc in the mouse lung induce an ASCL1+ state of SCLC in multiple cells of origin. Genetic depletion of ASCL1 in MYC-driven SCLC dramatically inhibits tumor initiation and progression to the NEUROD1+ subtype of SCLC. Surprisingly, ASCL1 loss promotes a SOX9+ mesenchymal/neural crest stem-like state and the emergence of osteosarcoma and chondroid tumors, whose propensity is impacted by cell of origin. ASCL1 is critical for expression of key lineage-related transcription factors NKX2-1, FOXA2, and INSM1 and represses genes involved in the Hippo/Wnt/Notch developmental pathways in vivo. Importantly, ASCL1 represses a SOX9/RUNX1/RUNX2 program in vivo and SOX9 expression in human SCLC cells, suggesting a conserved function for ASCL1. Together, in a MYC-driven SCLC model, ASCL1 promotes neuroendocrine fate and represses the emergence of a SOX9+ nonendodermal stem-like fate that resembles neural crest.

Cell-autonomous immune gene expression is repressed in pulmonary neuroendocrine cells and small cell lung cancer.

Small cell lung cancer (SCLC) is classified as a high-grade neuroendocrine (NE) tumor, but a subset of SCLC has been termed "variant" due to the loss of NE characteristics. In this study, we computed NE scores for patient-derived SCLC cell lines and xenografts, as well as human tumors. We aligned NE properties with transcription factor-defined molecular subtypes. Then we investigated the different immune phenotypes associated with high and low NE scores. We found repression of immune response genes as a shared feature between classic SCLC and pulmonary neuroendocrine cells of the healthy lung. With loss of NE fate, variant SCLC tumors regain cell-autonomous immune gene expression and exhibit higher tumor-immune interactions. Pan-cancer analysis revealed this NE lineage-specific immune phenotype in other cancers. Additionally, we observed MHC I re-expression in SCLC upon development of chemoresistance. These findings may help guide the design of treatment regimens in SCLC.

Evasion of Innate Immunity Contributes to Small Cell Lung Cancer Progression and Metastasis.

Small cell lung cancer (SCLC) is a pulmonary neuroendocrine cancer with very poor prognosis and limited effective therapeutic options. Most patients are diagnosed at advanced stages, and the exact reason for the aggressive and metastatic phenotype of SCLC is completely unknown. Despite a high tumor mutational burden, responses to immune checkpoint blockade are minimal in patients with SCLC. This may reflect defects in immune surveillance. Here we illustrate that evading natural killer (NK) surveillance contributes to SCLC aggressiveness and metastasis, primarily through loss of NK-cell recognition of these tumors by reduction of NK-activating ligands (NKG2DL). SCLC primary tumors expressed very low level of NKG2DL mRNA and SCLC lines express little to no surface NKG2DL at the protein level. Chromatin immunoprecipitation sequencing showed NKG2DL loci in SCLC are inaccessible compared with NSCLC, with few H3K27Ac signals. Restoring NKG2DL in preclinical models suppressed tumor growth and metastasis in an NK cell-dependent manner. Likewise, histone deacetylase inhibitor treatment induced NKG2DL expression and led to tumor suppression by inducing infiltration and activation of NK and T cells. Among all the common tumor types, SCLC and neuroblastoma were the lowest NKG2DL-expressing tumors, highlighting a lineage dependency of this phenotype. In conclusion, these data show that epigenetic silencing of NKG2DL results in a lack of stimulatory signals to engage and activate NK cells, highlighting the underlying immune avoidance of SCLC and neuroblastoma. SIGNIFICANCE: This study discovers in SCLC and neuroblastoma impairment of an inherent mechanism of recognition of tumor cells by innate immunity and proposes that this mechanism can be reactivated to promote immune surveillance.

Maternal diabetes-related malformations in Utah: A population study of birth prevalence 2001-2016.

Maternal pregestational diabetes mellitus is associated with an increased risk for congenital malformations of about 2-4 times the background risk. Notably, the types and patterns of congenital malformations associated with maternal diabetes are nonrandom, with a well-established increased risk for specific classes of malformations, especially of the heart, central nervous system, and skeleton. While the increased risk in clinical and epidemiological studies is well documented in the literature, a precise estimate of overall birth prevalence of these specific congenital malformations among women with maternal pregestational diabetes, is lacking. The purpose of this study was to determine total prevalence of structural malformations associated with maternal pregestational diabetes mellitus in a population-based study. We identified infants with specific birth defects whose mother had pregestational diabetes mellitus in the Utah Birth Defect Network (UBDN), an active birth defects surveillance program that registers the occurrence of selected structural defects in the state of Utah. We defined specific maternal diabetes-related malformations based on epidemiologic and clinical studies in the literature. Of the 825,138 recorded Utah births between 2001 and 2016, a total of 91 cases were identified as likely having diabetic embryopathy within UBDN data. The prevalence of diabetes-related congenital malformation cases was calculated per year; the overall prevalence of diabetes-related malformations 2001-2016 was 1.1 per 10,000 births in Utah (95% CI, 0.9-1.3). Knowledge of the overall prevalence of diabetes-related malformations is important in predicting the number of cases that are potentially prevented with the implementation of programs to foster preconceptional management of maternal pregestational diabetes.

Anatomical and Radiographic Characterization of the Lateral Patellofemoral Ligament of the Knee.

The purpose of the current study was to describe the femoral and patellar insertions of the lateral patellofemoral ligament (LPFL) and to determine their location relative to known anatomic and radiographic landmarks. In this descriptive laboratory study, 10 cadaveric knees were dissected, and the patellar and femoral insertions of the LPFL were identified. Each specimen was examined radiographically. The average center of the femoral insertion of the LPFL was calculated in reference to radiographic landmarks.

Phox2a Defines a Developmental Origin of the Anterolateral System in Mice and Humans.

Anterolateral system neurons relay pain, itch, and temperature information from the spinal cord to pain-related brain regions, but the differentiation of these neurons and their specific contribution to pain perception remain poorly defined. Here, we show that most mouse spinal neurons that embryonically express the autonomic-system-associated Paired-like homeobox 2A (Phox2a) transcription factor innervate nociceptive brain targets, including the parabrachial nucleus and the thalamus. We define the Phox2a anterolateral system neuron birth order, migration, and differentiation and uncover an essential role for Phox2a in the development of relay of nociceptive signals from the spinal cord to the brain. Finally, we also demonstrate that the molecular identity of Phox2a neurons is conserved in the human fetal spinal cord, arguing that the developmental expression of Phox2a is a prominent feature of anterolateral system neurons.

Changes in public preferences for technologically enhanced surveillance following the COVID-19 pandemic: a discrete choice experiment.

OBJECTIVES: As governments attempt to navigate a path out of COVID-19 restrictions, robust evidence is essential to inform requirements for public acceptance of technologically enhanced communicable disease surveillance systems. We examined the value of core surveillance system attributes to the Australian public, before and during the early stages of the current pandemic. DESIGN: A discrete choice experiment was conducted in Australia with a representative group of respondents, before and after the WHO declared COVID-19 a Public Health Emergency of International Concern. We identified and investigated the relative importance of seven attributes associated with technologically enhanced disease surveillance: respect for personal autonomy; privacy/confidentiality; data certainty/confidence; data security; infectious disease mortality prevention; infectious disease morbidity prevention; and attribution of (causal) responsibility. Specifically, we explored how the onset of the COVID-19 outbreak influenced participant responses. SETTING AND PARTICIPANTS: 2008 Australians (general public) completed the experiment: 793 before COVID-19 outbreak onset (mean age 45.9 years, 50.2% male) and 1215 after onset (mean age 47.2 years, 49% male). RESULTS: All seven attributes significantly influenced respondents' preferences for communicable disease surveillance systems. After onset, participants demonstrated greater preference for a surveillance system that could prevent a higher number of illnesses and deaths, and were less concerned about their personal autonomy. However, they also increased their preference for a system with high data security. CONCLUSIONS: Public acceptance of technology-based communicable disease surveillance is situation dependent. During an epidemic, there is likely to be greater tolerance of technologically enhanced disease surveillance systems that result in restrictions on personal activity if such systems can prevent high morbidity and mortality. However, this acceptance of lower personal autonomy comes with an increased requirement to ensure data security. These findings merit further research as the pandemic unfolds and strategies are put in place that enable individuals and societies to live with SARS-CoV-2 endemicity.