Organization of the human cerebral cortex estimated within individuals: networks, global topography, and function.

The cerebral cortex is populated by specialized regions that are organized into networks. Here we estimated networks from functional MRI (fMRI) data in intensively sampled participants. The procedure was developed in two participants (scanned 31 times) and then prospectively applied to 15 participants (scanned 8-11 times). Analysis of the networks revealed a global organization. Locally organized first-order sensory and motor networks were surrounded by spatially adjacent second-order networks that linked to distant regions. Third-order networks possessed regions distributed widely throughout association cortex. Regions of distinct third-order networks displayed side-by-side juxtapositions with a pattern that repeated across multiple cortical zones. We refer to these as supra-areal association megaclusters (SAAMs). Within each SAAM, two candidate control regions were adjacent to three separate domain-specialized regions. Response properties were explored with task data. The somatomotor and visual networks responded to body movements and visual stimulation, respectively. Second-order networks responded to transients in an oddball detection task, consistent with a role in orienting to salient events. The third-order networks, including distinct regions within each SAAM, showed two levels of functional specialization. Regions linked to candidate control networks responded to working memory load across multiple stimulus domains. The remaining regions dissociated across language, social, and spatial/episodic processing domains. These results suggest that progressively higher-order networks nest outward from primary sensory and motor cortices. Within the apex zones of association cortex, there is specialization that repeatedly divides domain-flexible from domain-specialized regions. We discuss implications of these findings, including how repeating organizational motifs may emerge during development.NEW & NOTEWORTHY The organization of cerebral networks was estimated within individuals with intensive, repeat sampling of fMRI data. A hierarchical organization emerged in each individual that delineated first-, second-, and third-order cortical networks. Regions of distinct third-order association networks consistently exhibited side-by-side juxtapositions that repeated across multiple cortical zones, with clear and robust functional specialization among the embedded regions.

Side-by-side regions in dorsolateral prefrontal cortex estimated within the individual respond differentially to domain-specific and domain-flexible processes.

A recurring debate concerns whether regions of primate prefrontal cortex (PFC) support domain-flexible or domain-specific processes. Here we tested the hypothesis with functional MRI (fMRI) that side-by-side PFC regions, within distinct parallel association networks, differentially support domain-flexible and domain-specialized processing. Individuals (N = 9) were intensively sampled, and all effects were estimated within their own idiosyncratic anatomy. Within each individual, we identified PFC regions linked to distinct networks, including a dorsolateral PFC (DLPFC) region coupled to the medial temporal lobe (MTL) and an extended region associated with the canonical multiple-demand network. We further identified an inferior PFC region coupled to the language network. Exploration in separate task data, collected within the same individuals, revealed a robust functional triple dissociation. The DLPFC region linked to the MTL was recruited during remembering and imagining the future, distinct from juxtaposed regions that were modulated in a domain-flexible manner during working memory. The inferior PFC region linked to the language network was recruited during sentence processing. Detailed analysis of the trial-level responses further revealed that the DLPFC region linked to the MTL specifically tracked processes associated with scene construction. These results suggest that the DLPFC possesses a domain-specialized region that is small and easily confused with nearby (larger) regions associated with cognitive control. The newly described region is domain specialized for functions traditionally associated with the MTL. We discuss the implications of these findings in relation to convergent anatomical analysis in the monkey.NEW & NOTEWORTHY Competing hypotheses link regions of prefrontal cortex (PFC) to domain-flexible or domain-specific processes. Here, using a precision neuroimaging approach, we identify a domain-specialized region in dorsolateral PFC, coupled to the medial temporal lobe and recruited for scene construction. This region is juxtaposed to, but distinct from, broader PFC regions recruited flexibly for cognitive control. Region distinctions align with broader network differences, suggesting that PFC regions gain dissociable processing properties via segregated anatomical projections.

Emergency department visits in Connecticut for survivors of sexual assault before and during the COVID-19 pandemic.

STUDY OBJECTIVE: We evaluate the impact of the COVID-19 pandemic on care for survivors of sexual assault in three urban Emergency Departments (ED) in the United States. METHODS: A retrospective chart review was conducted on patients who presented after sexual assault to three EDs during 6-month intervals before and during the COVID-19 pandemic. We excluded individuals <18 years old. We performed a structured chart review to ascertain demographics, ED treatments, and adherence to guidelines for care of sexual assault survivors. RESULTS: Of 105 patients who received care after a sexual assault, 57 presented during the COVID-19 pandemic. The majority were female, White/Caucasian, and presented within 120 h of sexual assault. There was an increase in ED presentations for sexual assault during the pandemic. While there was no difference in medical care, there were fewer sexual assault advocates called during the pandemic. In addition, there was an increase in non-White survivors in the first 3 months of the pandemic that did not remain at 6 months. CONCLUSION: The care of survivors in the ED was disrupted by the COVID-19 pandemic. While medical care remained similar, fewer calls to sexual assault advocates, a key component of ED and long-term care of survivors, demonstrate a disruption in their care.

The 2013 to 2019 Emergency Medicine Workforce: Clinician Entry and Attrition Across the US Geography.

STUDY OBJECTIVE: We sought to identify longitudinal trends in workforce entry and attrition among rural and urban emergency physicians, nonemergency physicians, and advanced practice providers. METHODS: We performed a repeated cross-sectional analysis, from 2013 to 2019, of emergency clinicians who received reimbursement for at least 50 Evaluation and Management services [99281-99285] from Medicare part B within any study year. We calculated the emergency workforce's entry and attrition rates annually. Entry was defined as clinicians newly entering or re-entering the workforce, and attrition was defined as clinicians leaving permanently or temporarily. We stratified the analyses by rural designation and assessed the proportions and state-level changes in clinician density. RESULTS: In total, 82,499 unique clinicians performed at least 50 Evaluation and Management services within any of the 7 study years examined, including 47,000 emergency physicians, 9,029 nonemergency physicians, and 26,470 advanced practice providers. Emergency physicians made up a decreasing proportion of the workforce (68.1% in 2013; 65.5% in 2019), and advanced practice providers made up an increasing proportion of the workforce (20.9% in 2013; 26.1% in 2019). Annually, 5.9% to 6.8% (2,186 to 2,407) of emergency physicians newly entered and 0.8% to 1.4% (264 to 515) re-entered the workforce, whereas 3.8% to 4.9% (1,241 to 1,793) permanently left and 0.8% to 1.6% (276 to 521) temporarily left. Additionally, the total proportion of clinicians practicing in rural designations decreased, and advanced practice providers separately made up a substantially increasing proportion of the rural workforce (23.0% in 2013; 32.7% in 2019). Substantial state-level variation existed in the supply and demand of emergency clinician densities per 100,000 population. CONCLUSION: The annual rate of emergency physician attrition was collectively more than 5%, well above the 3% assumed in a recently publicized projection, suggesting a potential overestimation of the anticipated future clinician surplus. Notably, the attrition of emergency physicians has disproportionately affected vulnerable rural areas. This work can inform emergency medicine workforce decisions regarding residency training, advanced practice provider utilization, and clinician employment.

Training in cognitive strategies reduces eating and improves food choice.

Obesity rates continue to rise alarmingly, with dire health implications. One contributing factor is that individuals frequently forgo healthy foods in favor of inexpensive, high-calorie, unhealthy foods. One important mechanism underlying these choices is food craving: Craving increases with exposure to unhealthy foods (and food cues, such as advertisements) and prospectively predicts eating and weight. Prior work has shown that cognitive regulation strategies that emphasize the negative consequences of unhealthy foods reduce craving. In Studies 1 and 2, we show that cognitive strategies also increase craving for healthy foods by emphasizing their positive benefits, and change food valuation (willingness to pay) for both healthy and unhealthy foods. In Studies 3 and 4, we demonstrate that brief training in cognitive strategies ("Regulation of Craving Training"; ROC-T) increases subsequent healthy (vs. unhealthy) food choices. This was striking because this change in food choices generalized to nontrained items. Importantly, in Study 5, we show that brief training in cognitive strategies also reduces food consumption by 93-121 calories. Consumed calories correlated with changes in food choice. Finally, in Study 6, we show that the training component of ROC-T is necessary, above and beyond any effect of framing. Across all studies (NTOTAL = 1,528), we find that cognitive strategies substantially change craving and food valuation, and that training in cognitive strategies improves food choices by 5.4-11.2% and reduces unhealthy eating, including in obese individuals. Thus, these findings have important theoretical, public health, and clinical implications for obesity prevention and treatment.

Novel Lipid Thresholds for Screening Predict the Need for Pharmacotherapy.

OBJECTIVE: To identify non-high-density lipoprotein cholesterol (HDL-C) and HDL-C thresholds for pediatric nonfasting lipid screens that are more predictive of the need for lipid-lowering pharmacotherapy and estimate numbers of potentially avoidable fasting lipid panels. STUDY DESIGN: In this retrospective review of children and youths aged 8-21 years presenting for preventive cardiology care, initial lipid results, recommendations for pharmacotherapy, and presence of additional cardiovascular risk factors were noted. Receiver operating characteristic curve analysis calculated threshold lipid values predicting the need for pharmacotherapy and were applied to 2 screening populations. Rates of potentially unnecessary fasting lipid panels were calculated. RESULTS: A non-HDL-C value >156 mg/dL for children with ≥1 cardiovascular risk factors and >199 mg/dL for children without risk factors conferred 95% or greater sensitivity in predicting a recommendation for pharmacotherapy with higher specificity, positive predictive value, and negative predictive value compared with current guidelines. HDL-C was a poor predictor of pharmacotherapy. Application of the current thresholds to screening populations indicated that 38.5%-92.3% of follow-up fasting lipid panels would not result in pharmacotherapy. CONCLUSION: Using higher non-HDL-C and lower HDL-C thresholds could prevent unnecessary follow-up lipid panels and reduce patient anxiety, cost, and time. This could improve compliance with universal pediatric lipid screening for both health care providers and families.

Feasibility of a Computer-Based Intervention Addressing Barriers to HIV Testing Among Young Patients Who Decline Tests at Triage.

Young people face greatly increased human immunodeficiency virus (HIV) risk and high rates of undiagnosed HIV, yet are unlikely to test. Many also have limited or inconsistent access to health care, including HIV testing and prevention education, and prior research has documented that youth lack knowledge necessary to understand the HIV test process and to interpret test results. Computer-based interventions have been used to increase HIV test rates and knowledge among emergency department (ED) patients, including those who decline tests offered at triage. However, patients aged 18-24 years have been less likely to test, even after completing an intervention, compared to older patients in the same ED setting. The current pilot study sought to examine the feasibility and acceptability of a new tablet-based video intervention designed to address established barriers to testing among ED patients aged 18-24 years. In particular, we examined whether young ED patients would: agree to receive the intervention; complete it quickly enough to avoid disrupting clinical workflows; accept HIV tests offered by the intervention; demonstrate increased postintervention knowledge; and report they found the intervention acceptable. Over 4 weeks, we recruited 100 patients aged 18-24 in a high-volume urban ED; all of them declined HIV tests offered at triage. Almost all (98%) completed the intervention (mean time <9 mins), 30% accepted HIV tests offered by the tablets. Knowledge was significantly higher after than before the intervention (t = -6.67, p < .001) and patients reported generally high acceptability. Additional research appears warranted to increase postintervention HIV testing.

Precision Network Modeling of TMS Across Individuals Suggests Therapeutic Targets and Potential for Improvement.

Higher-order cognitive and affective functions are supported by large-scale networks in the brain. Dysfunction in different networks is proposed to associate with distinct symptoms in neuropsychiatric disorders. However, the specific networks targeted by current clinical transcranial magnetic stimulation (TMS) approaches are unclear. While standard-of-care TMS relies on scalp-based landmarks, recent FDA-approved TMS protocols use individualized functional connectivity with the subgenual anterior cingulate cortex (sgACC) to optimize TMS targeting. Leveraging previous work on precision network estimation and recent advances in network-level TMS targeting, we demonstrate that clinical TMS approaches target different functional networks between individuals. Homotopic scalp positions (left F3 and right F4) target different networks within and across individuals, and right F4 generally favors a right-lateralized control network. We also modeled the impact of targeting the dorsolateral prefrontal cortex (dlPFC) zone anticorrelated with the sgACC and found that the individual-specific anticorrelated region variably targets a network coupled to reward circuitry. Combining individualized, precision network mapping and electric field (E-field) modeling, we further illustrate how modeling can be deployed to prospectively target distinct closely localized association networks in the dlPFC with meaningful spatial selectivity and E-field intensity. Lastly, our findings emphasize differences between selectivity and maximal intensity, highlighting the need to consider both metrics in precision TMS efforts.

Improving the spatial and temporal resolution of burden of disease measures with Bayesian models.

This paper contributes to the field by addressing the critical issue of enhancing the spatial and temporal resolution of health data. Although Bayesian methods are frequently employed to address this challenge in various disciplines, the application of Bayesian spatio-temporal models to burden of disease (BOD) studies remains limited. Our novelty lies in the exploration of two existing Bayesian models that we show to be applicable to a wide range of BOD data, including mortality and prevalence, thereby providing evidence to support the adoption of Bayesian modeling in full BOD studies in the future. We illustrate the benefits of Bayesian modeling with an Australian case study involving asthma and coronary heart disease. Our results showcase the effectiveness of Bayesian approaches in increasing the number of small areas for which results are available and improving the reliability and stability of the results compared to using data directly from surveys or administrative sources.

Clinical Interpretation of Serum Troponin in the Era of High-Sensitivity Testing.

Cardiac troponin (Tn) plays a central role in the evaluation of patients with angina presenting with acute coronary syndrome. The advent of high-sensitivity assays has improved the analytic sensitivity and precision of serum Tn measurement, but this advancement has come at the cost of poorer specificity. The role of clinical judgment is of heightened importance because, more so than ever, the interpretation of serum Tn elevation hinges on the careful integration of findings from electrocardiographic, echocardiographic, physical exam, interview, and other imaging and laboratory data to formulate a weighted differential diagnosis. A thorough understanding of the epidemiology, mechanisms, and prognostic implications of Tn elevations in each cardiac and non-cardiac etiology allows the clinician to better distinguish between presentations of myocardial ischemia and myocardial injury-an important discernment to make, as the treatment of acute coronary syndrome is vastly different from the workup and management of myocardial injury and should be directed at the underlying cause.

"I don't want to be the squeaky wheel": Addressing bias as a leader in emergency medicine.

BACKGROUND: Implicit bias poses a barrier to inclusivity in the health care workforce and is detrimental to patient care. While previous studies have investigated knowledge and training gaps related to implicit bias, emergency medicine (EM) leaders' self-awareness and perspectives on bias have not been studied. Using art to prompt reflections on implicit bias, this qualitative study explores (1) the attitudes of leaders in EM toward implicit bias and (2) individual or structural barriers to navigating and addressing bias in the workplace. METHODS: Investigators facilitated an hour-long workshop in May 2022 for those with leadership positions in the Society for Academic Emergency Medicine (SAEM), a leading national EM organization, including 62 attending physicians, eight residents/fellows, and four medical students. The workshop utilized arts-based methods to generate a psychologically supportive space to lead conversations around implicit bias in EM. The session included time for individual reflection, where participants used an electronic platform to respond anonymously to questions regarding susceptibility, fears, barriers, and experiences surrounding bias. Two independent coders compiled, coded, and reviewed the responses using an exploratory constructivist approach. RESULTS: A total of 125 responses were analyzed. Four major themes emerged: (1) acceptance that bias exists; (2) individual barriers, including fear of negative reactions, often due to power dynamics between respondents and other members of the ED; (3) institutional barriers, such as insufficient funding and unprotected time committed to addressing bias; and (4) ambiguity about defining and prioritizing bias. CONCLUSIONS: This qualitative analysis of reflections from an arts-based workshop highlights perceived fears and barriers that may impact EM physicians' motivation and comfort in addressing bias. These results may help guide interventions to address individual and structural barriers to mitigating bias in the workplace.

Unfilled in emergency medicine: An analysis of the 2022 and 2023 Match by program accreditation, ownership, and geography.

Background: The two most recent National Resident Matching Program (NRMP) Match cycles saw a high number of initially unfilled emergency medicine (EM) residency positions. We sought to identify the risk of EM residency program characteristics including accreditation duration, primary clinical site ownership status, and geography pertaining to not initially filling all positions. Methods: We performed a repeated cross-sectional observational study of EM residency programs participating in the 2022 and 2023 NRMP Match cycles and used publicly available data from the NRMP, the Accreditation Council for Graduate Medical Education, the Centers for Medicare & Medicaid Services, and the U.S. Department of Housing and Urban Development. Our primary outcome was the proportion of EM residency programs that did not initially fill positions, with analyses stratified by accreditation duration (>5 or ≤5 years), primary clinical site ownership status, and geographic core-based statistical areas (CBSAs). Results: A total of 219 of 2921 (7.5%) positions in the 2022 Match and 554 of 3010 (18.4%) positions in the 2023 Match were initially unfilled. Over the 2-year period, EM residency programs accredited within the past 5 years had more than double the risk (relative risk [RR] 2.08, 95% confidence interval [CI] 1.69-2.57, chi-square p < 0.001) of not filling all positions compared to those accredited more than 5 years previously. EM residency programs with a primary clinical site under for-profit ownership had a 50% greater risk of not filling all positions when compared to those under nonprofit or governmental ownership (RR 1.50, 95% CI 1.14-1.98, chi-square p = 0.009). In 2023, several CBSAs had a high number of both offered and unfilled positions. Conclusions: EM residency programs accredited within the past 5 years or those with a primary clinical site under for-profit ownership had a greater risk of not filling all positions within the past two Match cycles.

Personal air pollution exposure and metals in the nasal epithelial lining fluid of COPD patients.

Sampling of the nasal epithelial lining fluid is a potential method to assess exposure to air pollution within the respiratory tract among high risk populations. We investigated associations of short- and long-term particulate matter exposure (PM) and pollution-related metals in the nasal fluid of people with chronic obstructive pulmonary disease (COPD). This study included 20 participants with moderate-to-severe COPD from a larger study who measured long-term personal exposure to PM2.5 using portable air monitors and short-term PM2.5 and black carbon (BC) using in-home samplers for the seven days preceding nasal fluid collection. Nasal fluid was sampled from both nares by nasosorption, and inductively coupled plasma mass spectrometry was used to determine the concentration of metals with major airborne sources. Correlations of selected elements (Fe, Ba, Ni, Pb, V, Zn, Cu) were determined within the nasal fluid. Associations between personal long-term PM2.5 and seven day home PM2.5 and BC exposure and nasal fluid metal concentrations were determined by linear regression. Within nasal fluid samples, concentrations of vanadium and nickel (r = 0.8) and lead and zinc (r = 0.7) were correlated. Seven day and long-term PM2.5 exposure were both associated with higher levels of copper, lead, and vanadium in the nasal fluid. BC exposure was associated with higher levels of nickel in the nasal fluid. Levels of certain metals in the nasal fluid may serve as biomarkers of air pollution exposure in the upper respiratory tract.

Within-Individual Organization of the Human Cerebral Cortex: Networks, Global Topography, and Function.

The human cerebral cortex is populated by specialized regions that are organized into networks. Here we estimated networks using a Multi-Session Hierarchical Bayesian Model (MS-HBM) applied to intensively sampled within-individual functional MRI (fMRI) data. The network estimation procedure was initially developed and tested in two participants (each scanned 31 times) and then prospectively applied to 15 new participants (each scanned 8 to 11 times). Detailed analysis of the networks revealed a global organization. Locally organized first-order sensory and motor networks were surrounded by spatially adjacent second-order networks that also linked to distant regions. Third-order networks each possessed regions distributed widely throughout association cortex. Moreover, regions of distinct third-order networks displayed side-by-side juxtapositions with a pattern that repeated similarly across multiple cortical zones. We refer to these as Supra-Areal Association Megaclusters (SAAMs). Within each SAAM, two candidate control regions were typically adjacent to three separate domain-specialized regions. Independent task data were analyzed to explore functional response properties. The somatomotor and visual first-order networks responded to body movements and visual stimulation, respectively. A subset of the second-order networks responded to transients in an oddball detection task, consistent with a role in orienting to salient or novel events. The third-order networks, including distinct regions within each SAAM, showed two levels of functional specialization. Regions linked to candidate control networks responded to working memory load across multiple stimulus domains. The remaining regions within each SAAM did not track working memory load but rather dissociated across language, social, and spatial / episodic processing domains. These results support a model of the cerebral cortex in which progressively higher-order networks nest outwards from primary sensory and motor cortices. Within the apex zones of association cortex there is specialization of large-scale networks that divides domain-flexible from domain-specialized regions repeatedly across parietal, temporal, and prefrontal cortices. We discuss implications of these findings including how repeating organizational motifs may emerge during development.

Nasal biomarkers of immune function differ based on smoking and respiratory disease status.

Respiratory biomarkers have the potential to identify airway injury by revealing inflammatory processes within the respiratory tract. Currently, there are no respiratory biomarkers suitable for clinical use to identify patients that warrant further diagnostic work-up, counseling, and treatment for toxic inhalant exposures or chronic airway disease. Using a novel, noninvasive method of sampling the nasal epithelial lining fluid, we aimed to investigate if nasal biomarker patterns could distinguish healthy nonsmoking adults from active smokers and those with chronic upper and lower airway disease in this exploratory study. We compared 28 immune mediators from healthy nonsmoking adults (n = 32), former smokers with COPD (n = 22), chronic rhinosinusitis (CRS) (n = 22), and smoking adults without airway disease (n = 13). Using ANOVA, multinomial logistic regressions, and weighted gene co-expression network analysis (WGCNA), we determined associations between immune mediators and each cohort. Six mediators (IL-7, IL-10, IL-13, IL-12p70, IL-15, and MCP-1) were lower among disease groups compared to healthy controls. Participants with lower levels of IL-10, IL-12p70, IL-13, and MCP-1 in the nasal fluid had a higher odds of being in the COPD or CRS group. The cluster analysis identified groups of mediators that correlated with disease status. Specifically, the cluster of IL-10, IL-12p70, and IL-13, was positively correlated with healthy and negatively correlated with COPD groups, and two clusters were correlated with active smoking. In this exploratory study, we preliminarily identified groups of nasal mucosal mediators that differed by airway disease and smoking status. Future prospective, age-matched studies that control for medication use are needed to validate these patterns and determine if nasosorption has diagnostic utility for upper and lower airway disease or injury.

Corrigendum to: Evolution of non-fatal burden estimates for cardiovascular disease in Australia: a comparison of national and state-wide methodology of burden of disease.

Objective Burden of disease studies measure the impact of disease at the population level;however, methods and data sources for estimates of prevalence vary. Using a selection of cardiovascular diseases, we aimed to describe the implications of using different disease models and linked administrative data on prevalence estimation within three Australian burden of disease studies. Methods Three different methods (A = 2011 Australian Burden of Disease Study; B = 2015 Australian Burden of Disease Study; C = 2015 Western Australian Burden of Disease Study), which used linked data, were used to compare prevalence estimates of stroke, aortic aneurysm, rheumatic valvular heart disease (VHD) and non-rheumatic VHD. We applied these methods to 2015 Western Australian data, and calculated crude overall and age-specific prevalence for each condition. Results Overall, Method C produced estimates of cardiovascular prevalence that were lower than the other methods, excluding non-rheumatic VHD. Prevalence of acute and chronic stroke was up to one-third higher in Method A and B compared to Method C. Aortic aneurysms had the largest change in prevalence, with Method A producing an eight-fold higher estimate compared to Method C, but Method B was 10-20% lower. Estimates of VHD varied dramatically, with an up to six-fold change in prevalence in Method C due to substantial changes to disease models and the use of linked data. Conclusions Prevalence estimates require the best available data sources, updated disease models and constant review to inform government policy and health reform. Availability of nation-wide linked data will markedly improve future burden estimates.

Evolution of non-fatal burden estimates for cardiovascular disease in Australia: a comparison of national and state-wide methodology of burden of disease.

Objective Burden of disease studies measure the impact of disease at the population level;however, methods and data sources for estimates of prevalence vary. Using a selection of cardiovascular diseases, we aimed to describe the implications of using different disease models and linked administrative data on prevalence estimation within three Australian burden of disease studies. Methods Three different methods (A = 2011 Australian Burden of Disease Study; B = 2015 Australian Burden of Disease Study; C = 2015 Western Australian Burden of Disease Study), which used linked data, were used to compare prevalence estimates of stroke, aortic aneurysm, rheumatic valvular heart disease (VHD) and non-rheumatic VHD. We applied these methods to 2015 Western Australian data, and calculated crude overall and age-specific prevalence for each condition. Results Overall, Method C produced estimates of cardiovascular prevalence that were lower than the other methods, excluding non-rheumatic VHD. Prevalence of acute and chronic stroke was up to one-third higher in Method A and B compared to Method C. Aortic aneurysms had the largest change in prevalence, with Method A producing an eight-fold higher estimate compared to Method C, but Method B was 10-20% lower. Estimates of VHD varied dramatically, with an up to six-fold change in prevalence in Method C due to substantial changes to disease models and the use of linked data. Conclusions Prevalence estimates require the best available data sources, updated disease models and constant review to inform government policy and health reform. Availability of nation-wide linked data will markedly improve future burden estimates.

Differences of the Nasal Microbiome and Mycobiome by Clinical Characteristics of COPD Patients.

Rationale: While studies suggest that the lung microbiome may influence risk of chronic obstructive pulmonary disease (COPD) exacerbations, little is known about the relationship between the nasal biome and clinical characteristics of COPD patients. Methods: We sampled the nasal lining fluid by nasosorption of both nares of 20 people with moderate-to-severe COPD. All 40 samples, plus 4 negative controls, underwent DNA extraction, and 16SV4 ribosomal RNA (rRNA) (bacterial) and ribosomal internal transcribed spacer 2 (ITS2) (fungal) sequencing. We measured the proportion of variance (R2) in beta diversity explained by clinical factors, including age, sex, body mass index (BMI), COPD treatment, disease severity (forced expiratory volume in 1 second [FEV1], symptom/exacerbation frequency), peripheral eosinophil level (≥150 versus <150 cells/µL) and season of sampling, with the PERMANOVA test on the Bray-Curtis dissimilarities, accounting for within-person correlation of samples. We assessed the relative abundance of microbial features in the nasal community and their associations with clinical characteristics using the Microbiome Multivariable Association with Linear Models (MaAsLin2) package. Results: The most abundant nasal fluid bacterial taxa were Corynebacterium, Staphylococcus, Streptococcus, Moraxella, and Dolosigranulum, and fungal taxa were Malassezia, Candida, Malasseziales, Cladosporium and Aspergillus. Bacterial microbiome composition was associated with short-acting muscarinic antagonist use (R2 11.8%, p=0.002), sex (R2 8.3%, p=0.044), nasal steroid use (R2 7.7%, p=0.064), and higher eosinophil level (R2 7.6%, p=0.084). Mycobiome composition was associated with higher eosinophil level (R2 14.4%, p=0.004) and low FEV1 (R2 7.5%, p=0.071). No specific bacterium or fungus differed significantly in relative abundance by clinical characteristics in the multivariate per-feature analysis. Conclusion: The taxonomical composition of the nasal biome is heterogeneous in COPD patients and may be explained in part by clinical characteristics.

From intern to "accepted": A guide to preparing for fellowship in emergency medicine.

Introduction: The number of fellowship options for emergency medicine (EM) physicians continues to expand. While guides exist to help residents explore individual fellowship pathways, we aimed to create a comprehensive guide for all residents considering fellowship. Methods: At the direction of the Society for Academic Emergency Medicine (SAEM) Board, 9 members of the Fellowship Guide Workgroup, including members of the Fellowship Approval Committee, and 2 members of SAEM Residents and Medical Students (RAMS) group collaboratively developed the guide using available evidence and expert opinion when high-quality evidence was unavailable. The guide was reviewed and approved by all members. Results: The guide offers advice to EM residents on how to conceptualize key aspects of their training with respect to preparation for fellowship, including scholarship, teaching, leadership, and electives. Additionally, it offers perspective on selecting a fellowship that matches the resident's interests and goals and successfully applying. Conclusion: This fellowship guide for EM residents considering fellowship summarizes the best currently available advice for residents considering fellowship training after residency.