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The preference-performance hypothesis explains host specificity in phytophagous insects, positing that host plants chosen by adults confer the greatest larval fitness. However, adults sometimes oviposit on plants supporting low larval success because the components of host specificity (adult preference, plant palatability, and larval survival) are non-binary and not necessarily correlated. Palatability (willingness to eat) is governed by chemical cues and physical barriers such as trichomes, while survival (ability to complete development) depends upon nutrition and toxicity. Absence of a correlation between the components of host specificity results in low-performance hosts supporting limited larval development. Most studies of specificity focus on oviposition behavior leaving the importance and basis of palatability and survival under-explored. We conducted a comprehensive review of 127 plant species that have been claimed or tested to be hosts for the monarch butterfly Danaus plexippus to classify them as non-hosts, low performance, or high performance. We performed a meta-analysis to test if performance status could be explained by properties of neurotoxic cardenolides or trichome density. We also conducted a no-choice larval feeding experiment to identify causes of low performance. We identified 34 high performance, 42 low performance, 33 non-hosts, and 18 species with unsubstantiated claims. Mean cardenolide concentration was greater in high- than low-performance hosts and a significant predictor of host status, suggesting possible evolutionary trade-offs in monarch specialization. Other cardenolide properties and trichome density were not significant predictors of host status. In the experiment, we found, of the 62% of larvae that attempted to eat low-performance hosts, only 3.5% survived to adult compared to 85% of those on the high-performance host, demonstrating that multiple factors affect larval host plant specificity. Our study is the first to classify all known host plants for monarchs and has conservation implications for this threatened species.

Background. As integrated health systems become more common, interfacility patient transfers will increase and air transport programs will be prioritized. Understanding characteristics of patients triaged to air medical transport will assist with resource allocation and needs assessment. The objective of this study was to investigate the demographics and clinical characteristics of patients that presented to the emergency department (ED) and subsequently required emergent air medical interfacility transport. Methods. This was a retrospective, multicenter study conducted at eight hospitals within Northwell Health, the largest academic health system in New York state. The study was conducted between December 1, 2014, and July 31, 2020, and included patients who presented to an ED and subsequently required emergent air medical interfacility transport. Results. Overall, the median age was 37 years (IQR 4–66), and 231 (54%) subjects were males. The majority of subjects (59%) had no reported comorbidities, arrived by ambulance (52%), and were emergency severity index triage 2 (48%). Frequent indications for transfer were nontraumatic neurologic (37%), pulmonary or respiratory (13%), trauma (12%), and cardiovascular (12%). Most patients were not ventilated before transport (71%). The median time to call for transport at the sending institution was 2:42 hours (IQR 1:14–6:54), and the median length of stay was 4:12 (IQR 2:31–8:48). Most patients were subsequently admitted (96%) at the receiving institution to an intensive care unit (72%). Conclusions. This study describes patients’ demographic and clinical characteristics who required emergent air medical transport. Helicopter transport is costly, and data from these patients may further help our understanding of who is transported by air and how important air transport is to the health system.

Matrix metalloproteinase 9 (MMP9), a protease implicated in multiple diseases, is secreted as an inactive zymogen and requires proteolytic removal of the pro-domain for activation. The relative levels and functionality of the pro- and active-MMP9 isoforms in tissues are not characterized. We generated a specific antibody that distinguishes an active form of MMP9, F107-MMP9, from the inactive pro-MMP9 isoform. Using multiple in vitro assays and specimen types, we show that F107-MMP9 expression is localized and disease-specific compared with its more abundant parental pro-form. It is detected around sites of active tissue remodeling, including fistulae of inflammatory bowel and dermal fissures in hidradenitis suppurativa, and is expressed by myeloid cells, including macrophages and neutrophils. Together, our findings provide insights into the distribution and potential role of MMP9 in inflammatory diseases.

Cells sense the extracellular environment and mechanical stimuli and translate these signals into intracellular responses through mechanotransduction, which alters cell maintenance, proliferation, and differentiation. Here we use a mouse model of trauma-induced heterotopic ossification (HO) to examine how cell-extrinsic forces impact mesenchymal progenitor cell (MPC) fate. After injury, single-cell (sc) RNA sequencing of the injury site reveals an early increase in MPC genes associated with pathways of cell adhesion and ECM-receptor interactions, and MPC trajectories to cartilage and bone. Immunostaining uncovers active mechanotransduction after injury with increased focal adhesion kinase signaling and nuclear translocation of transcriptional coactivator TAZ, inhibition of which mitigates HO. Similarly, joint immobilization decreases mechanotransductive signaling, and completely inhibits HO. Joint immobilization decreases collagen alignment and increases adipogenesis. Further, scRNA sequencing of the HO site after injury with or without immobilization identifies gene signatures in mobile MPCs correlating with osteogenesis, and signatures from immobile MPCs with adipogenesis. scATAC-seq in these same MPCs confirm that in mobile MPCs, chromatin regions around osteogenic genes are open, whereas in immobile MPCs, regions around adipogenic genes are open. Together these data suggest that joint immobilization after injury results in decreased ECM alignment, altered MPC mechanotransduction, and changes in genomic architecture favoring adipogenesis over osteogenesis, resulting in decreased formation of HO., Introduction By far the most common injuries seen in emergency rooms in the United States are those of the extremities (1, 2), accounting for 30%-40% of visits (1-3). The most [...]

The NBER Economics of Digitization Project, established in 2010 with support from the Alfred P. Sloan Foundation, provides a forum for disseminating research and fostering collaboration among economists exploring the [...]

Murine sex chromosome aneuploidies (SCAs) provide powerful models for charting sex chromosome influences on mammalian brain development. Here, building on prior work in X-monosomic (XO) mice, we use spatially non-biased high-resolution imaging to compare and contrast neuroanatomical alterations in XXY and XO mice relative to their wild-type XX and XY littermates. First, we show that carriage of a supernumerary X chromosome in XXY males (1) does not prevent normative volumetric masculinization of the bed nucleus of the stria terminalis (BNST) and medial amygdala, but (2) causes distributed anatomical alterations relative to XY males, which show a statistically unexpected tendency to be co-localized with and reciprocal to XO-XX differences in anatomy. These overlaps identify the lateral septum, BNST, ventral group thalamic nuclei and periaqueductal gray matter as regions with replicable sensitivity to X chromosome dose across two SCAs. We then harness anatomical variation across all four karyotype groups in our study--XO, XX, XY and XXY--to create an agnostic data-driven segmentation of the mouse brain into five distributed clusters which (1) recover fundamental properties of brain organization with high spatial precision, (2) define two previously uncharacterized systems of relative volume excess in females vs. males ("forebrain cholinergic" and "cerebelo-pontine-thalamo-cortical"), and (3) adopt stereotyped spatial motifs which delineate ordered gradients of sex chromosome and gonadal influences on volumetric brain development. Taken together, these data provide a new framework for the study of sexually dimorphic influences on brain development in health and disrupted brain development in SCA.

The goal of this note is to study quantum clusters in which cluster variables (not coefficients) commute which each other. It turns out that this property is preserved by mutations if one starts with a principal quantum seed. Remarkably, this is equivalent to the celebrated sign coherence conjecture recently proved by M. Gross, P. Hacking, S. Keel, and M. Kontsevich.

We generalize the decomposition of Uq(g) introduced by A. Joseph in [5] and link it, for g semisimple, to the celebrated computation of central elements due to V. Drinfeld [2]. In that case, we construct a natural basis in the center of Uq(g) whose elements behave as Schur polynomials and thus explicitly identify the center with the ring of symmetric functions.

BackgroundAdherence to prescribed medical interventions can predict the efficacy of the treatment. In physical health clinics, not adhering to prescribed therapy can take the form of not attending a scheduled clinic visit (no-show appointment) or prematurely terminating treatment against the advice of the provider (self-discharge). A variety of interventions, including mobile phone apps, have been introduced for patients to increase their adherence to attending scheduled clinic visits. Limited research has examined the impact of a mobile phone app among patients attending chiropractic and rehabilitation clinic visits. ObjectiveThis study aims to compare adherence to prescribed physical health treatment among patients attending a chiropractic and rehabilitation clinic who did and did not choose to adopt a phone-based app to complement their treatment. MethodsThe medical records of new patients who presented for care during 2019 and 2020 at 5 community-based chiropractic and rehabilitation clinics were reviewed for the number of kept and no-show appointments and to determine whether the patient was provider-discharged or self-discharged. During this 24-month study, 36.28% (1497/4126) of patients seen in the targeted clinics had downloaded the Kanvas app on their mobile phone, whereas the remaining patients chose not to download the app (usual care group). The gamification component of the Kanvas app provided the patient with a point every time they attended their visits, which could be redeemed as an incentive. ResultsDuring both 2019 and 2020, the Kanvas app group was provider-discharged at a greater rate than the usual care group. The Kanvas app group kept a similar number of appointments compared with the usual care group in 2019 but kept significantly more appointments than the usual care group in 2020. During 2019, both groups exhibited a similar number of no-show appointments; however, in 2020, the Kanvas app group demonstrated more no-show appointments than the usual care group. When collapsed across years and self-discharged, the Kanvas app group had a greater number of kept appointments compared with the usual care group. When provider-discharged, both groups exhibited a similar number of kept appointments. The Kanvas app group and the usual care group were similar in the number of no-show appointments when provider-discharged, and when self-discharged, the Kanvas app group had more no-show appointments compared with the usual care group. ConclusionsPatients who did or did not have access to the Kanvas app and were provider-discharged exhibited a similar number of kept appointments and no-show appointments. When patients were self-discharged and received the Kanvas app, they exhibited 3.2 more kept appointments and 0.94 more no-show appointments than the self-discharged usual care group.

Hypoxemia is a significant driver of mortality and poor clinical outcomes in conditions such as brain injury and cardiac arrest in critically ill patients, including COVID-19 patients. Given the host of negative clinical outcomes attributed to hypoxemia, identifying patients likely to experience hypoxemia would offer valuable opportunities for early and thus more effective intervention. We present SWIFT (SpO2 Waveform ICU Forecasting Technique), a deep learning model that predicts blood oxygen saturation (SpO2) waveforms 5 and 30 minutes in the future using only prior SpO2 values as inputs. When tested on novel data, SWIFT predicts more than 80% and 60% of hypoxemic events in critically ill and COVID-19 patients, respectively. SWIFT also predicts SpO2 waveforms with average MSE below .0007. SWIFT predicts both occurrence and magnitude of potential hypoxemic events 30 minutes in the future, allowing it to be used to inform clinical interventions, patient triaging, and optimal resource allocation. SWIFT may be used in clinical decision support systems to inform the management of critically ill patients during the COVID-19 pandemic and beyond.

Summary: Heterochromatin formation requires three distinct steps: nucleation, self-propagation (spreading) along the chromosome, and faithful maintenance after each replication cycle. Impeding any of those steps induces heterochromatin defects and improper gene expression. The essential histone chaperone FACT (facilitates chromatin transcription) has been implicated in heterochromatin silencing, but the mechanisms by which FACT engages in this process remain opaque. Here, we pinpoint its function to the heterochromatin spreading process in fission yeast. FACT impairment reduces nucleation-distal H3K9me3 and HP1/Swi6 accumulation at subtelomeres and derepresses genes in the vicinity of heterochromatin boundaries. FACT promotes spreading by repressing heterochromatic histone turnover, which is crucial for the H3K9me2 to me3 transition that enables spreading. FACT mutant spreading defects are suppressed by removal of the H3K9 methylation antagonist Epe1. Together, our study identifies FACT as a histone chaperone that promotes heterochromatin spreading and lends support to the model that regulated histone turnover controls the propagation of repressive methylation marks.

Background: High flow nasal cannula (HFNC) is commonly used as non-invasive respiratory support in critically ill children. There are limited data to inform consensus on optimal device parameters, determinants of successful patient response, and indications for escalation of support. Clinical scores, such as the respiratory rate-oxygenation (ROX) index, have been described as a means to predict HFNC non-response, but are limited to evaluating for escalations to invasive mechanical ventilation (MV). In the presence of apparent HFNC non-response, a clinician may choose to increase the HFNC flow rate to hypothetically prevent further respiratory deterioration, transition to an alternative non-invasive interface, or intubation for MV. To date, no models have been assessed to predict subsequent escalations of HFNC flow rates after HFNC initiation.Objective: To evaluate the abilities of tree-based machine learning algorithms to predict HFNC flow rate escalations.Methods: We performed a retrospective, cohort study assessing children admitted for acute respiratory failure under 24 months of age placed on HFNC in the Johns Hopkins Children's Center pediatric intensive care unit from January 2019 through January 2020. We excluded encounters with gaps in recorded clinical data, encounters in which MV treatment occurred prior to HFNC, and cases electively intubated in the operating room. The primary study outcome was discriminatory capacity of generated machine learning algorithms to predict HFNC flow rate escalations as compared to each other and ROX indices using area under the receiver operating characteristic (AUROC) analyses. In an exploratory fashion, model feature importance rankings were assessed by comparing Shapley values.Results: Our gradient boosting model with a time window of 8 h and lead time of 1 h before HFNC flow rate escalation achieved an AUROC with a 95% confidence interval of 0.810 ± 0.003. In comparison, the ROX index achieved an AUROC of 0.525 ± 0.000.Conclusion: In this single-center, retrospective cohort study assessing children under 24 months of age receiving HFNC for acute respiratory failure, tree-based machine learning models outperformed the ROX index in predicting subsequent flow rate escalations. Further validation studies are needed to ensure generalizability for bedside application.

Ectopic beats (EBs) are cellular arrhythmias that can trigger lethal arrhythmias. Simulations using biophysically-detailed cardiac myocyte models can reveal how model parameters influence the probability of these cellular arrhythmias, however such analyses can pose a huge computational burden. Here, we develop a simplified approach in which logistic regression models (LRMs) are used to define a mapping between the parameters of complex cell models and the probability of EBs (P(EB)). As an example, in this study, we build an LRM for P(EB) as a function of the initial value of diastolic cytosolic Ca2+ concentration ([Ca2+]iini), the initial state of sarcoplasmic reticulum (SR) Ca2+ load ([Ca2+]SRini), and kinetic parameters of the inward rectifier K+ current (IK1) and ryanodine receptor (RyR). This approach, which we refer to as arrhythmia sensitivity analysis, allows for evaluation of the relationship between these arrhythmic event probabilities and their associated parameters. This LRM is also used to demonstrate how uncertainties in experimentally measured values determine the uncertainty in P(EB). In a study of the role of [Ca2+]SRini uncertainty, we show a special property of the uncertainty in P(EB), where with increasing [Ca2+]SRini uncertainty, P(EB) uncertainty first increases and then decreases. Lastly, we demonstrate that IK1 suppression, at the level that occurs in heart failure myocytes, increases P(EB).

A transcribed conversation between a mathematics educator and a disability studies educator is presented to highlight cross-disciplinary dialog as a fruitful space for recursive and reflexive engagement from which may emerge concepts to further both mathematics and disability education. The opening question, "How can I know what's possible in terms of engaging students with disabilities in mathematical thinking and reasoning?," sparks discussion. Critique of typical practices in special education and mathematics teaching are raised in terms of learning theories and ideologies of schooling. Takeaways include the promise of emphasizing mathematical thinking as a way to structure more inclusive educational experiences for students with disabilities.