Effects of circulating endothelial microvesicles isolated from adults with obesity on endothelial cell inflammation, apoptosis, and nitric oxide production.

Circulating endothelial cell-derived microvesicles (EMVs) have been shown to be elevated with obesity and associated with endothelial dysfunction; however, their direct effect on endothelial cells is unknown. The experimental aim of this study was to determine the effect of EMVs isolated from adults with obesity on endothelial cell inflammation, apoptosis, and nitric oxide (NO) production. EMVs (CD144+ microvesicles) were identified, enumerated, and isolated from plasma by flow cytometry from 24 sedentary adults: 12 normal-weight adults [8 M/4 F; age: 55 ± 6 yr; body mass index (BMI): 24.3 ± 0.7 kg/m2; EMV: 144 ± 53 EMVs/µL] and 12 adults with obesity (6 M/6 F; 59 ± 7 yr; BMI: 31.0 ± 1.1 kg/m2; EMV: 245 ± 89 EMVs/µL). Human umbilical vein endothelial cells were cultured and treated with EMVs from either normal-weight adults or adults with obesity. EMVs from obese adults induced significantly higher release of interleukin (IL)-6 (108.2 ± 7.7 vs. 90.9 ± 10.0 pg/mL) and IL-8 (75.4 ± 9.8 vs. 59.5 ± 11.5 pg/mL) from endothelial cells vs. EMVs from normal-weight adults, concordant with greater intracellular expression of phosphorylated NF-κB p65 (Ser536; active NF-κB) [145.0 ± 34.1 vs. 114.5 ± 30.4 arbitrary units (AU)]. Expression of phosphorylated p38-MAPK (15.4 ± 5.7 vs. 9.2 ± 2.5 AU) and active caspase-3 (168.2 ± 65.5 vs. 107.8 ± 40.5 AU), markers of cell apoptosis, was higher in cells treated with obesity-related EMVs. Phosphorylated endothelial nitric oxide synthase (eNOS) (Ser1177) expression (23.5 ± 7.2 vs. 34.7 ± 9.7 AU) and NO production (6.9 ± 1.4 vs. 8.7 ± 0.7 µmol/L) were significantly lower in the cells treated with EMVs from obese adults. These data indicate that circulating EMVs from adults with obesity promote a proinflammatory, proapoptotic, and NO-compromised endothelial phenotype. Circulating EMVs are a potential mediator of obesity-related endothelial dysfunction.NEW & NOTEWORTHY In the present study, we determined the effect of circulating endothelial cell-derived microvesicles (EMVs) isolated from adults with obesity on endothelial cell inflammation, apoptosis, and nitric oxide (NO) production in vitro. Circulating EMVs harvested from adults with obesity promoted a proinflammatory, proapoptotic, and NO-compromised endothelial phenotype. Elevated circulating EMVs in adults with obesity, independent of other cardiometabolic risk factors, are a potential novel systemic mediator of obesity-related endothelial dysfunction and vascular risk.

Characterizing drug-induced epidermal necrolysis in a pediatric cohort.

This study aims to characterize the timeline and clinical features of onset, progression, and management of drug-induced epidermal necrolysis in pediatric patients. Sixteen pediatric patients were retrospectively identified and selected if under age 18 years at admission with one identified culprit drug exposure. Culprit drugs were antiepileptics (12/16, 75%) and antibiotics (4/16, 25%). Notably, anti-epileptic drugs (AED) had delayed onset and reported dose escalations that precipitated symptom onset; thus, patients prescribed AED with or without planned dose escalations should be monitored for prodromal symptoms longer than the typical onset window.

Patterns of host-parasite coinvasion promote enemy release and specialist parasite spillover.

Species invasion and redistribution, driven by climate change and other anthropogenic influences, alter global biodiversity patterns and disrupt ecosystems. As host species move, they can bring their associated parasites with them, potentially infecting resident species, or leave their parasites behind, enhancing their competitive ability in their new ranges. General rules to predict why invading hosts will retain some parasites but not others are relatively unexplored, and the potential predictors are numerous, ranging from parasite life history to host community composition. In this study, we focus on the parasite retention process during host invasion. We used the Global Mammal Parasite Database to identify terrestrial mammal hosts sampled for parasites in both native and non-native ranges. We then selected predictors likely to play a role in parasite retention, such as parasite type, parasite specialism, species composition of the invaded community, and the invading host's phylogenetic or trait-based similarity to the new community. We modelled parasite retention using boosted regression trees, with a suite of 25 predictors describing parasite and host community traits. We further tested the generality of our predictions by cross-validating models on data for other hosts and invasion locations. Our results show that parasite retention is nonrandom and predictable across hosts and invasions. It is broadly shaped by parasite type and parasite specialism, with more specialist parasites that infect many closely related hosts more likely to be retained. This trend is pronounced across parasite types; helminths, however, show a more uniform likelihood of retention regardless of specificity. Overall, we see that most parasites are not retained (11% retained), meaning many invasive species may benefit from enemy release. However, species redistribution does have the potential to spread parasites, and this also has great relevance to understanding conservation implications of species invasions. We see that specialist parasites are most likely to coinvade with their hosts, which suggests that species closely related to the invasive hosts are most likely to be affected by parasite spillover.

Assessment of the added value of intravenous gadolinium for knee osteosarcoma resection planning in pediatric and young adult patients.

BACKGROUND AND OBJECTIVES: To assess the impact of Gadolinium-enhanced magnetic resonance imaging (MRI) sequences on Preoperative imaging evaluation and surgical planning parameters for osteosarcoma (OS) of the knee in pediatric and young adult patients. METHODS: Thirty MRI scans of patients with OS about the knee were reviewed by five orthopedic oncologists. Key preoperative parameters (neurovascular bundle involvement, intra-articular tumor extension, extent of intramedullary extension) and surgical plans were evaluated based on non-contrast versus Gd contrast enhanced sequences. Assessment agreement, inter-rater agreement, and intrarater agreement between pre and postcontrast images were evaluated via Kappa statistics. RESULTS: Moderate agreement was seen between non and contrast-enhanced assessment of neurovascular involvement and intra-articular tumor extension. Intrarater reproducibility was substantial for neurovascular bundle involvement (precontrast Kappa: 0.63, postcontrast Kappa: 0.69). Intrarater reproducibility was also substantial for precontrast (Kappa: 0.70) and moderate for postcontrast (Kappa: 0.50) assessment of intra-articular tumor extension. Planned resection length and choice of surgical approach were similar between sequences. The addition of Gd-enhanced sequences improved the inter-rater agreement across collected parameters. CONCLUSIONS: While some findings suggest that contrast enhanced sequences may not significantly alter the assessment of key preoperative planning parameters by orthopedic oncologists, they may help reduce variability among providers with differing experience levels.

The Man Who Mistook a Hat for His Wife: Case Report of Aortic Dissection Presenting With Acute Hyperfamiliarity for Faces.

Acute aortic dissection is a challenging diagnosis for emergency physicians because of its high mortality and wide range of clinical presentations. We report a case of a previously healthy man who presented with hyperfamiliarity for faces syndrome as the predominant symptom of a large type A aortic dissection diagnosed by computed tomography angiography in the emergency department. Different elements of his presentation suggested possible other diagnoses, including transient global amnesia and transient ischemic attack. We discuss how evaluating these other diagnostic possibilities led to the correct diagnosis. Given increasing reports of painless aortic dissection, this case demonstrates the need to consider aortic dissection in patients with acute neurological symptoms.

Venous Thromboembolism: Exploring Incidence and Utility of Screening in Individuals With Brain Injury.

OBJECTIVE: To determine the incidence of VTE in the population with brain injuries (BIs) using ultrasonography, and to assess the risk of pulmonary embolism (PE) development and/or bleeding complications related to anticoagulation. DESIGN: Retrospective study. SETTING: Acute rehabilitation hospital. PARTICIPANTS: 238 individuals with moderate to severe BI who were routinely screened for VTE with ultrasonography on admission to rehabilitation (N=238). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Retrospective chart review was performed to identify individuals who were diagnosed with VTE at the following 3 time points: in acute care prior to admission to rehabilitation, at the time of admission diagnosed via screening examination, and after admission to rehabilitation. Additionally, risk factors for VTE, PE, and incidence of bleeding complications related to therapeutic anticoagulation were assessed. RESULTS: 123 deep vein thromboses (DVTs) were identified with 38.2% in acute care (n=47), 69.1% on admission to rehabilitation (n=85), and 7.3% during the course of rehabilitation stay (n=9). Risk factors for development of VTE included age at injury, body mass index, injury etiology, history of neurosurgical procedure, and surgery during inpatient rehabilitation. Of those who were placed on therapeutic anticoagulation due to admission diagnosis of VTE (n=50), 2% developed recurrent DVT and 2% had bleeding complications. There was zero incidence of PE. CONCLUSION: We demonstrated a high prevalence of VTEs identified on screening ultrasonography on admission to inpatient rehabilitation among individuals with moderate to severe BIs, and low complications related to anticoagulation. Given the findings of this study, prospective research in ultrasonography screening for VTE in moderate to severe BI is needed.

Development of a Hypercoagulable-Hypofibrinolytic State Early After Spinal Cord Injury.

OBJECTIVES: To determine whether spinal cord injury (SCI) is associated with adverse changes in coagulation and fibrinolytic factors that underlie thrombogenesis and contribute to atherothrombotic events such as myocardial infarctions (MIs) and strokes. DESIGN: Cross-sectional study. SETTING: Neurorehabilitation hospital and general community. PARTICIPANTS: Thirty young and middle-aged (20-58 years) adults (N=30) were studied: 14 non-injured community dwelling adults. (11M/4F) and 16 with subacute tetraplegic motor complete SCI during initial inpatient rehabilitation (13M/3F; time since injury: 11.8±5.3 wk). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Circulating markers of coagulation [von Willebrand factor (vWf) and factors VII, VIII, and X], the fibrinolytic system [tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) antigen and activity], and fibrin formation (D-dimer) were determined by enzyme immunoassay. RESULTS: Thirty young and middle-aged (20-58 years) adults were studied: 14 non-injured (11M/4F) and 16 with subacute tetraplegic motor complete SCI (13M/3F; time since injury: range 4-25 wk). Circulating levels of coagulation factors VII, VIII, and X were significantly higher (∼20%-45%; P<.05) in the adults with SCI than non-injured adults, whereas vWf was similar between groups. Fibrinolytic markers were adversely disrupted with SCI with t-PA antigen, PAI-1 antigen and PAI-1 activity were markedly higher (∼50%-800%; P<.05) in adults with SCI compared with non-injured adults. The molar concentration ratio of active t-PA to PAI-1 was significantly higher (∼350%) in adults with SCI. Concordant with coagulation cascade activation and fibrinolytic system inhibition, D-dimer concentrations were markedly ∼70% higher (P<.05) in adults with SCI compared with non-injured adults. CONCLUSIONS: Subacute tetraplegic motor complete SCI is associated with a prothrombotic hemostatic profile. Adverse changes in the coagulation cascade and fibrinolytic system appear to occur early after injury and may contribute to the increased atherothrombotic risk in adults living with SCI.

Twenty-year record of white pox disease in the Florida Keys: importance of environmental risk factors as drivers of coral health.

Declining coral populations worldwide place a special premium on identifying risks and drivers that precipitate these declines. Understanding the relationship between disease outbreaks and their drivers can help to anticipate when the risk of a disease pandemic is high. Populations of the iconic branching Caribbean elkhorn coral Acropora palmata have collapsed in recent decades, in part due to white pox disease (WPX). To assess the role that biotic and abiotic factors play in modulating coral disease, we present a predictive model for WPX in A. palmata using 20 yr of disease surveys from the Florida Keys plus environmental information collected simultaneously in situ and via satellite. We found that colony size was the most influential predictor for WPX occurrence, with larger colonies being at higher risk. Water quality parameters of dissolved oxygen saturation, total organic carbon, dissolved inorganic nitrogen, and salinity were implicated in WPX likelihood. Both low and high wind speeds were identified as important environmental drivers of WPX. While high temperature has been identified as an important cause of coral mortality in both bleaching and disease scenarios, our model indicates that the relative influence of HotSpot (positive summertime temperature anomaly) was low and actually inversely related to WPX risk. The predictive model developed here can contribute to enabling targeted strategic management actions and disease surveillance, enabling managers to treat the disease or mitigate disease drivers, thereby suppressing the disease and supporting the persistence of corals in an era of myriad threats.

Trust Matters: The Effects of Social Media Use on the Public's Health Policy Support Through (mis)beliefs in the Context of HPV Vaccination.

This study examines whether social media exposure is associated with the public's beliefs and misbeliefs about human papillomavirus (HPV) vaccination and how those (mis)beliefs are associated with the public's support for HPV vaccination-related policies. This study also explores whether trust in HPV vaccination-related regulatory organizations moderates the associations between social media exposure and public policy support through (mis)beliefs. We found that social media exposure was positively associated with misbeliefs about HPV vaccination. The findings also indicated that while beliefs about benefits were positively associated with policy support for HPV vaccination, misbeliefs were negatively associated with this support. More interestingly, our analysis revealed that the negative association of HPV-related misbeliefs with vaccination policy support was larger for those who had low levels of trust, compared to their high-trust counterparts.

Vector communities under global change may exacerbate and redistribute infectious disease risk.

Vector-borne parasites may be transmitted by multiple vector species, resulting in an increased risk of transmission, potentially at larger spatial scales compared to any single vector species. Additionally, the different abilities of patchily distributed vector species to acquire and transmit parasites will lead to varying degrees of transmission risk. Investigation of how vector community composition and parasite transmission change over space due to variation in environmental conditions may help to explain current patterns in diseases but also informs our understanding of how patterns will change under climate and land-use change. We developed a novel statistical approach using a multi-year, spatially extensive case study involving a vector-borne virus affecting white-tailed deer transmitted by Culicoides midges. We characterized the structure of vector communities, established the ecological gradient controlling change in structure, and related the ecology and structure to the amount of disease reporting observed in host populations. We found that vector species largely occur and replace each other as groups, rather than individual species. Moreover, community structure is primarily controlled by temperature ranges, with certain communities being consistently associated with high levels of disease reporting. These communities are essentially composed of species previously undocumented as potential vectors, whereas communities containing putative vector species were largely associated with low levels, or even absence, of disease reporting. We contend that the application of metacommunity ecology to vector-borne infectious disease ecology can greatly aid the identification of transmission hotspots and an understanding of the ecological drivers of parasite transmission risk both now and in the future.

Evidence-based Medicine and Mechanistic Evidence: The Case of the Failed Rollout of Efavirenz in Zimbabwe.

Evidence-based medicine (EBM) has long deemphasized mechanistic reasoning and pathophysiological rationale in assessing the effectiveness of interventions. The EBM+ movement has challenged this stance, arguing that evidence of mechanisms and comparative studies should both be seen as necessary and complementary. Advocates of EBM+ provide a combination of theoretical arguments and examples of mechanistic reasoning in medical research. However, EBM+ proponents have not provided recent examples of how downplaying mechanistic reasoning resulted in worse medical results than would have occurred otherwise. Such examples are necessary to make the case that EBM+ responds to a problem in clinical practice that urgently demands a solution. In light of this, we examine the failed rollout of efavirenz as a first-line HIV treatment in Zimbabwe as evidence of the importance of mechanistic reasoning in improving clinical practice and public health policy decisions. We suggest that this case is analogous to examples commonly given to support EBM.

Treatment patterns for patients initiating novel acute migraine specific medications (nAMSMs) in the context of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway.

BACKGROUND: New acute and preventive migraine medications are available, but data on current treatment patterns are limited. This study describes migraine treatment patterns among patients initiating novel acute migraine specific medications (nAMSMs), overall and by prior use of anti-calcitonin gene-related peptide (CGRP) pathway monoclonal antibodies (mAbs). METHODS: In this retrospective cohort study using IQVIA open-source pharmacy and medical claims data, we identified patients with ≥ 1 claim for a nAMSM (ubrogepant, rimegepant, lasmiditan) between 01/01/2020 and 09/30/2020 (index period). Patients were indexed on their first nAMSM claim and stratified into 2 cohorts: patients with prior mAb use (≥ 1 claim for erenumab, fremanezumab, galcanezumab in the 6-month pre-index period) or patients without prior mAb use. Treatment patterns were assessed during the 6-month post-index period. RESULTS: Overall, 78,574 patients were identified (63% indexed on ubrogepant, 34% on rimegepant, and 3% on lasmiditan) with 26,656 patients (34%) having had prior mAb use. In the pre-index period, 79% of patients used non-mAb preventive medications and 75% of patients used acute medications. Following the index nAMSM claim, 65% of patients had ≥ 1 refill and 21% had ≥ 4 refills of their index nAMSM; 10% of patients switched to another nAMSM. Post-index mAb use was observed in 82% of patients with a prior mAb and 15% of patients without. Among patients with pre- and post-index use of acute medications, 38% discontinued ≥ 1 acute medication class in the post-index period. Among patients with concomitant use of traditional preventive medications at index, 30% discontinued ≥ 1 concomitant preventive anti-migraine medication in the post-index period. CONCLUSIONS: Most patients initiating nAMSMs had prior treatment with acute and preventive medications. Approximately one-third of patients had prior treatment with anti-CGRP pathway mAbs. After starting nAMSMs, more than one-third of patients discontinued at least one traditional acute medication and one-third of patients discontinued at least one traditional preventive medication. Despite nAMSM initiation, most patients with prior anti-CGRP pathway mAb use continued mAb use. Around 15% of patients without a prior mAb newly started a mAb. These results provide insight into how nAMSMs and mAbs have been integrated into clinical management of migraine in the real-world.

Use of negative control outcomes to assess the comparability of patients initiating lipid-lowering therapies.

PURPOSE: Clinical trials have demonstrated efficacy of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in reducing risk of cardiovascular disease events, but effectiveness in routine clinical care has not been well-studied. We used negative control outcomes to assess potential confounding in an observational study of PCSK9i versus ezetimibe or high-intensity statin. METHODS: Using commercial claims, we identified U.S. adults initiating PCSK9i, ezetimibe, or high-intensity statin in 2015-2018, with other lipid-lowering therapy (LLT) use in the year prior (LLT cohort) or atherosclerotic cardiovascular disease (ASCVD) in the past 90 days (ASCVD cohort). We compared initiators of PCSK9i to ezetimibe and high-intensity statin by estimating one-year risks of negative control outcomes influenced by frailty or health-seeking behaviors. Inverse probability of treatment and censoring weighted estimators of risk differences (RDs) were used to evaluate residual confounding after controlling for covariates. RESULTS: PCSK9i initiators had lower one-year risks of negative control outcomes associated with frailty, such as decubitus ulcer in the ASCVD cohort (PCSK9i vs. high-intensity statin RD = -3.5%, 95% confidence interval (CI): -4.6%, -2.5%; PCSK9i vs. ezetimibe RD = -1.3%, 95% CI: -2.1%, -0.6%), with similar but attenuated associations in the LLT cohort. Lower risks of accidents and fractures were also observed for PCSK9i, varying by cohort. Risks were similar for outcomes associated with health-seeking behaviors, although trended higher for PCSK9i in the ASCVD cohort. CONCLUSIONS: Observed associations suggest lower frailty and potentially greater health-seeking behaviors among PCSK9i initiators, particularly those with a recent ASCVD diagnosis, with the potential to bias real-world analyses of treatment effectiveness.

Association between weekly exercise minutes and resting IL-6 in adults with chronic spinal cord injury: findings from the fracture risk after spinal cord injury exercise study.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To assess associations between weekly aerobic exercise minutes and resting interleukin-6 (IL-6), C-reactive protein (CRP), or leptin levels in adults with chronic spinal cord injury (SCI). SETTING: Three hundred and forty-four community-dwelling men and women with SCI duration of > 1 year. METHODS: CRP, IL-6, and leptin levels were quantified by ultra-sensitive enzyme-linked immunoassay. Smoking, medication use, comorbidities, and aerobic exercise minutes per week were assessed by self-reported questionnaire. Body composition was determined by whole-body dual-energy X-ray absorptiometry. Generalized linear models were used to assess associations. RESULTS: In multivariable modeling, resting IL-6 levels were 0.001 pg/mL lower for every 1 min of weekly aerobic exercise. IL-6 levels increased with increasing android-to-gynoid fat ratio, in active/ever smokers compared to never smokers, and in individuals with skin pressure injuries compared to those without. IL-6 levels were lower in active ibuprofen users compared to nonusers. We found no association between weekly exercise minutes and CRP or leptin when designing similar models. CONCLUSIONS: Increasing aerobic exercise minutes is associated with lower IL-6 levels in adults with chronic SCI when considering body composition, smoking, skin pressure injuries, and ibuprofen use. CRP and leptin did not demonstrate an association with exercise when considering the similar variables. The use of these biomarkers in assessing the therapeutic value of future exercise-related interventions will be paramount for meaningful health improvement among those with SCI. Although a large, prospective dataset, this cross-sectional study cannot assign causation. Future prospective studies are needed to confirm these findings.

Exploration of biomedical knowledge for recurrent glioblastoma using natural language processing deep learning models.

BACKGROUND: Efficient exploration of knowledge for the treatment of recurrent glioblastoma (GBM) is critical for both clinicians and researchers. However, due to the large number of clinical trials and published articles, searching for this knowledge is very labor-intensive. In the current study, using natural language processing (NLP), we analyzed medical research corpora related to recurrent glioblastoma to find potential targets and treatments. METHODS: We fine-tuned the 'SAPBERT', which was pretrained on biomedical ontologies, to perform question/answering (QA) and name entity recognition (NER) tasks for medical corpora. The model was fine-tuned with the SQUAD2 dataset and multiple NER datasets designed for QA task and NER task, respectively. Corpora were collected by searching the terms "recurrent glioblastoma" and "drug target", published from 2000 to 2020 in the Web of science (N = 288 articles). Also, clinical trial corpora were collected from 'clinicaltrial.gov' using the searching term of 'recurrent glioblastoma" (N = 587 studies). RESULTS: For the QA task, the model showed an F1 score of 0.79. For the NER task, the model showed F1 scores of 0.90 and 0.76 for drug and gene name recognition, respectively. When asked what the molecular targets were promising for recurrent glioblastoma, the model answered that RTK inhibitors or LPA-1 antagonists were promising. From collected clinical trials, the model summarized them in the order of bevacizumab, temozolomide, lomustine, and nivolumab. Based on published articles, the model found the many drug-gene pairs with the NER task, and we presented them with a circus plot and related summarization ( https://github.com/bigwiz83/NLP_rGBM ). CONCLUSION: Using NLP deep learning models, we could explore potential targets and treatments based on medical research and clinical trial corpora. The knowledge found by the models may be used for treating recurrent glioblastoma.

Host and parasite traits predict cross-species parasite acquisition by introduced mammals.

Species invasions and range shifts can lead to novel host-parasite communities, but we lack general rules on which new associations are likely to form. While many studies examine parasite sharing among host species, the directionality of transmission is typically overlooked, impeding our ability to derive principles of parasite acquisition. Consequently, we analysed parasite records from the non-native ranges of 11 carnivore and ungulate species. Using boosted regression trees, we modelled parasite acquisition within each zoogeographic realm of a focal host's non-native range, using a suite of predictors characterizing the parasites themselves and the host community in which they live. We found that higher parasite prevalence among established hosts increases the likelihood of acquisition, particularly for generalist parasites. Non-native host species are also more likely to acquire parasites from established host species to which they are closely related; however, the acquisition of several parasite groups is biased to phylogenetically specialist parasites, indicating potential costs of parasite generalism. Statistical models incorporating these features provide an accurate prediction of parasite acquisition, indicating that measurable host and parasite traits can be used to estimate the likelihood of new host-parasite associations forming. This work provides general rules to help anticipate novel host-parasite associations created by climate change and other anthropogenic influences.

The statistics of epidemic transitions.

Emerging and re-emerging pathogens exhibit very complex dynamics, are hard to model and difficult to predict. Their dynamics might appear intractable. However, new statistical approaches-rooted in dynamical systems and the theory of stochastic processes-have yielded insight into the dynamics of emerging and re-emerging pathogens. We argue that these approaches may lead to new methods for predicting epidemics. This perspective views pathogen emergence and re-emergence as a "critical transition," and uses the concept of noisy dynamic bifurcation to understand the relationship between the system observables and the distance to this transition. Because the system dynamics exhibit characteristic fluctuations in response to perturbations for a system in the vicinity of a critical point, we propose this information may be harnessed to develop early warning signals. Specifically, the motion of perturbations slows as the system approaches the transition.

Leveraging the electronic health record to improve dermatologic care delivery: The importance of finding structure in data.

The federal mandate for electronic health record (EHR) keeping for health care providers impacted the burden placed on dermatologists for medical documentation. The hope that EHR would improve care quality and efficiency and reduce health disparities has yet to be fully realized. Despite the significant time and effort spent on documentation, the majority of EHR clinical data remain unstructured and therefore, difficult to process and analyze. Structured data can provide a way for dermatologists and data scientists to make more effective use of clinical data-not only to improve the dermatologist's experience with EHRs, but also to manage technology-related administrative burden, accelerate understanding of disease, and enhance care delivery for patients. Understanding the importance of structured data will allow dermatologists to actively engage in how clinical data will be collected and used to advance patient care.

Identification of the Sensory Dependent Locations of the Shoulder Joint to Optimize Surgical Approaches and Reduce Postoperative Pain: A Systematic Review.

INTRODUCTION: Treatment of post-surgical pain is predicated by an understanding of pain generators. The purpose of this review is to identify sensory dependent areas of the shoulder and discuss their correlation in treating postoperative pain. MATERIALS AND METHODS: Pubmed, Embase, and Cochrane Database of Systemic Reviews were searched (key terms: "Nociception" or "sensory pain receptors" or "pain map" or "neuroanatomy and shoulder" or "rotator cuff") to identify studies in the current literature (1966-2018) regarding sensory innervation of the shoulder and rotator cuff. The search was limited to the English language, human studies, and publication types to reviews and clinical studies. Articles written in other languages besides English, animal studies, abstracts, and conference notes were excluded. Each search result was investigated for relevant physiological information of the nerve endings and nociceptors as well as pertinent information and figures that illustrated the location of the identified receptors. RESULTS: A total of 12 articles were identified that addressed the sensory innervation of the shoulder. The shoulder capsule has the highest sensory nerve density. The attachment sites between the labrum and the capsule and glenoid rim were also found to be highly sensory dependent, in contrast to the peri-core zone at the capsulolabral junction, which was found to be less concentrated with fascicles and sensory nerve endings. The subacromial bursa is also a highly sensory dependent structure, with a more concentrated neural network on the coracoacromial side compared to other quadrants of the bursa. Cutaneous locations of sensory fibers on the shoulder are best defined by mapping the pressure pain threshold (PPT) of various locations on the shoulder. The most sensory dependent locations of the shoulder were found to be the posterior border of the acromion, the glenohumeral joint, the anterior deltoid, and the upper trapezius. CONCLUSION: This review examined the origin of pain in the shoulder, the location of cutaneous pain receptors, and receptors in each major part of the shoulder. Providing analgesia to these densely innervated areas of the shoulder can potentially reduce pain associated with surgical trauma. In addition, knowledge of the sensory dependent areas of the shoulder may elicit consideration of alternative incision sites and surgical protocols to decrease the insult to nociceptors in these locations. These changes could possibly decrease the narcotic requirement in the postoperative period.

Vector-borne parasite invasion in communities across space and time.

While vector-borne parasite transmission often operates via generalist-feeding vectors facilitating cross-species transmission in host communities, theory describing the relationship between host species diversity and parasite invasion in these systems is underdeveloped. Host community composition and abundance vary across space and time, generating opportunities for parasite invasion. To explore how host community variation can modify parasite invasion potential, we develop a model for vector-borne parasite transmission dynamics that includes a host community of arbitrary richness and species' abundance. To compare invasion potential across communities, we calculate the community basic reproductive ratio of the parasite. We compare communities comprising a set of host species to their subsets, which allows for flexible scenario building including the introduction of novel host species and species loss. We allow vector abundance to scale with, or be independent of, community size, capturing regulation by feeding opportunities and non-host effects such as limited oviposition sites. Motivated by equivocal data relating host species competency to abundance, we characterize plausible host communities via phenomenological relationships between host species abundance and competency. We identify an underappreciated mechanism whereby changes to communities simultaneously alter average competency and the vector to host ratio and demonstrate that the interaction can profoundly influence invasion potential.