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Background: The case-population approach or population-based case-cohort approach is derived from the case-control design and consists of comparing past exposure to a given risk factor in subjects presenting a given disease or symptom (cases) with the exposure rate to this factor in the whole cohort or in the source population of cases. In the same way as the case-control approach, the case-population approach measures the disproportionality of exposure between cases of a given disease and their source population expressed in the form of an odds ratio approximating the ratio of the risks in exposed and not-exposed populations (relative risk).Objective: The aim of this study was to (i) present the case-population principle design in a way understandable for non-statisticians; (ii) propose the easiest way of using it for pharmacovigilance purposes (mainly alerting and hypothesis testing); (iii) propose simple formulae for computing an odds ratio and its confidence interval; (iv) apply the approach to several practical and published examples; and (v) discuss its pros and cons in the context of real life.Methods: The approach used is derived from that comparing two rates expressed as person-time denominators. It allows easy computation of an odds ratio and its confidence interval under several hypotheses. Results obtained with the case-population approach were compared with those of case-control studies published in the literature.Results: Relevance and limits of the proposed approach are illustrated by examples taken from published pharmacoepidemiological studies. The odds ratio (OR) reported in a European case-control study on centrally acting appetite suppressants and primary pulmonary hypertension was 23.1 (95% CI 6.9, 77.7) versus 31 (95% CI 16.2, 59.2) using the case-population approach. In the European case-control studies SCAR (Severe Cutaneous Adverse Reactions) and EuroSCAR on the risk of toxic epidermal necrolysis associated with the use of medicines, the OR for cotrimoxazole was 160 and 102, respectively, versus 44.4 using the case-population approach. Similarly, these two case-control studies found ORs of 12 and 72 for carbamazepine versus 24.4 using the case-population approach, 8.7 and 16 for phenobarbital versus 21.9, 12 for piroxicam (analysed in the SCAR study only) versus 14.5, and 5.5 and 18 for allopurinol versus 3.4 using the case-population approach.Conclusions: Being based on the estimate derived from sales statistics of the total exposure time in the source population of cases, the method can be used even when there is no information about the actual number of exposed subjects in this population. Although the case-population approach suffers from limitations stemming from its main advantage, i.e. impossibility to control possible confounders and to quantify the strength of associations due to the absence of an ad hoc control group, it is particularly useful to use in routine practice, mainly for purposes of signal generation and hypothesis testing in drug surveillance. [ABSTRACT FROM AUTHOR]

This review article describes the regulation of glucose homeostasis in subjects with and without diabetes based on the emergence of new information and discusses modes of action, attributes, and limitations of current diabetes therapies. In normal physiology, glucose homeostasis is tightly controlled by the interaction of pancreatic and gut hormones. Since the 1920s, diabetes has been viewed as a disease caused by deficient secretion of insulin, resulting in reduced glucose uptake and subsequent hyperglycemia. The discovery in the 1950s of the pancreatic hormone glucagon, which opposes insulin by increasing glucose appearance in the circulation, resulted in a bihormonal model of glucose homeostasis. More recently, with the discovery of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) in the 1970s and the pancreatic hormone amylin in the 1980s, it is now understood that several organs and hormones play roles in maintaining glucose homeostasis. Therapies for diabetes have focused on compensation for deficient insulin action through stimulation of insulin secretion, administration of insulin itself, reduction of peripheral insulin resistance, or decreased glucose absorption from the intestine. The discoveries of amylin and GLP-1 have furthered our understanding of the abnormalities involved in diabetes, enabling the development of additional therapeutic options. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the effect of heparin-binding epidermal growth factor (HB-EGF) on human embryo development in vitro from days 2 to 14 post-insemination. Embryos were cultured in a complex serum-free medium (CSFM3) in the absence and presence of 1 nM and 100 nM HB-EGF. Development to the blastocyst stage of A-C-grade embryos (A grade = highest quality) was improved in the presence of 1 nM HB-EGF from 40.7% to 65.4% and significantly increased to 71.0% in the presence of 100 nM HB-EGF (P < 0.05). Moreover, the percentage of blastocysts hatching was improved in the presence of 1 nM HB-EGF from 45.5% to 70.5% and almost doubled to 81.8% (P < 0.05) in the presence of 100 nM HB-EGF. HB-EGF promoted the development of high-grade (classed as BG1) and medium-grade (BG2) blastocysts. There was no difference in blastocyst quality between the control and HB-EGF-treated embryos as assessed by blastocyst cell number and consumption of the major energy substrates, pyruvate and glucose, measured on day 6 of culture. Further development was assessed by culturing the blastocysts on growth factor-reduced Matrigel (GFR-Matrigel). Adherence and outgrowth were observed, with these embryos producing significantly more human chorionic gonadotrophin over days 7-14 compared with those cultured on plastic (47.8 ± 8.0 mU versus 23.0 ± 8.6 mU). The addition of recombinant human growth factors to clinical in-vitro fertilization medium may be useful in promoting embryo development with a view to carrying out blastocyst transfers. [ABSTRACT FROM PUBLISHER]

Photic drive responses (PDRs) are used to explore cortical hyperexcitability. We quantified PDRs and interactions with the alpha rhythm in people with epilepsy (PwE). Fifteen PwE (mean age ± SD 47.3 ± 4.6 years; 8 males), and 15 control subjects (mean age 52.7 ± 4.6 years; 9 males) underwent EEG with modified intermittent photic stimulation (IPS). The modification allowed so-called alpha-band gain to be measured. None of the PwE had demonstrated photosensitivity. The modified IPS method alternated eyes-open and eyes-closed conditions with and without IPS. The alpha-band gain appeared as N-fold changes in PDR when IPS (or its harmonics) and the alpha-bands overlapped. An epileptic attack within 1 month of testing significantly increased alpha-band gain by 1.36×. Generalised epilepsy (but not focal epilepsy) significantly decreased alpha-band gain y 0.79×. Each decade of age beyond the mean age significantly increased alpha-band gain by 1.09×. Similar significant interactions were seen between alpha and the second harmonic of IPS driving frequencies that matched alpha frequencies, i.e. for recent attack and, generalized epilepsy. The interactions thus appeared to be occurring between cortical IPS outputs and the alpha generator. These changes were most evident at electrodes O1 and O2. Investigating alpha-band gain using modified IPS offers a way to quantify cortical hyperexcitability in epilepsy and other diseases. It also provides new information about alpha and so too predictive coding, which appears to be at least partly governed by alpha., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Postmenopausal craniofacial hyperhidrosis describes a unique subset of primary focal hyperhidrosis in menopausal woman. This condition can be challenging to treat and may require multiple treatment modalities before patients express satisfaction with the results. Current treatment options for craniofacial hyperhidrosis include oral antimuscarinic agents, topical aluminum chloride powder, and botulinum toxin injections. We present the case of a 68-year-old female with craniofacial hyperhidrosis who did not respond to topical agents and did not tolerate an oral antimuscarinic agent. The patient was successfully treated with 100 units of onabotulinum toxin A along the forehead, frontal hairline, and periauricular scalp and reported significant improvement in symptoms and quality of life as a result. We review the literature describing targeted intradermal injection of botulinum neurotoxin as an alternative to medical therapy for craniofacial hyperhidrosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Patrick et al.)

We have previously demonstrated that an appropriately substituted four-membered-ring 1,2-diazacyclobutene is a useful compound in organic synthesis for the introduction of strained 1,2-diazetidine rings. In order to further explore the reactivity of this interesting heterocycle, we sought a method to improve upon the poor synthetic yield reported earlier. A novel route involving the synthesis of a similarly substituted 1,2-diazetidine compound followed by free-radical bromination and base-catalyzed debromination appeared promising. While there are some studies on the synthesis of the desired 1,2-diazetidine precursor, when we attempted its synthesis, we instead observed the exclusive formation of an eight-membered "dimer"-like compound. The structure of this compound was confirmed via single-crystal X-ray analysis. Fortunately, an alternative synthetic approach for the formation of the desired 1,2-diazetidine precursor proved successful, and the structure of the precursor has been confirmed via X-ray analysis. However, unfortunately, the required bromination step proved to be more challenging than expected, and ultimately, this route had to be abandoned since the anticipated improvement upon the original yield did not seem promising. Single-crystal X-ray analysis proved pivotal in properly identifying the structures of the synthesized compounds.

Allergic contact dermatitis (ACD) is a prevalent condition associated with numerous potential allergen exposures. Tattoo ink is variable and may contain allergens that can be overlooked in patient education and diagnosis. We present a 27-year-old female with ACD following a new tattoo. The patient was repeatedly misdiagnosed with cellulitis by three different clinicians and treated with multiple antibiotics without improvement. The correct diagnosis was eventually made in the emergency department (ED). Although the patient was aware of her allergies to nickel and cobalt from patch testing, she was not aware of the potential for tattoo ink to contain these allergens because prior tattoos had not provoked an allergic reaction. Consequently, the appropriate care was delayed by a month, resulting in significant morbidity. This case demonstrates the potential for ACD to present similarly to cellulitis in an ED setting and the need for clinical vigilance in diagnosis of ACD. It also highlights the importance of detailed patient education on potential allergen sources particularly in the context of tattooing, which is performed with unregulated and variable ink products., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Diversity, Equity, and Inclusion (DEI) are concepts common in surgery. However, these can be difficult to define, and what constitutes DEI can be vague. Closing this knowledge gap, particularly within pediatric surgery, would be helpful to understand the views and needs of current surgeons., Methods: 1558 APSA members were sent an anonymous survey, of which 423 (27%) responded. Respondents were asked about their demographics, views on what constitutes diversity as well as questions on how DEI is handled within APSA and definitions of common DEI terms., Results: Of 11 possible diversity measures, members agreed that a median of 9 (IQR 7-11) counted towards diversity. The most common being race and ethnicity (98%), gender (96%), sexual orientation (93%), religion (92%), age (91%), and disability (90%). On a 5-point Likert scale, the median response was 4 or greater on questions regarding how APSA handles issues related to DEI. However, members who identify as black were less likely to score in favor of APSA, and members identifying as women were more likely to rank higher importance of DEI initiatives. We also captured subjective responses on DEI terminology., Conclusion: Respondents had broad definitions of diversity. There is support for further DEI initiatives and how APSA handles DEI, however this perception differs based on identities. There is significant variability in beliefs and views regarding DEI definitions and understanding this is helpful for the organization moving forward., Level of Evidence: IV., Type of Study: Original Research., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Obtunded pediatric patients are often placed in cervical collars (c-collars) to protect their cervical spine (c-spine) while injury is being ruled out, even without a known traumatic injury. The goal of this study was to determine the necessity of c-collars in this population by determining the rate of c-spine injury among patients with suspected non-traumatic mechanisms of loss of consciousness., Methods: A single institution, ten-year retrospective chart review was conducted including all obtunded patients admitted to the Pediatric Intensive Care Unit without a known traumatic event. Patients were categorized into five groups based on etiology of obtundation: respiratory, cardiac, medical/metabolic, neurologic, and other. Comparisons were made between those placed in a c-collar and a control group who were not, using Wilcoxon rank sum test for continuous measures, and Chi-square or Fisher's exact test for categorical measures., Results: 464 patients were included, of which 39 (8.41%) were placed in a c-collar. There was a significant difference in whether a patient was placed in a c-collar based on diagnosis category (p < 0.001). Those placed in a-c-collar were more likely to undergo imaging studies than the control group (p < 0.001). The overall incidence of c-spine injury in this patient population in our study was zero., Conclusion: Cervical collar placement and radiographic evaluation is not necessary in obtunded pediatric patients who present without a known traumatic mechanism as the overall risk of injury is low. Consideration for collar placement should be given in cases when trauma cannot be definitively ruled out at initial evaluation., Levels of Evidence: III., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Conversion of natural land cover can degrade water quality in water supply watersheds and increase treatment costs for Public Water Systems (PWSs), but there are few studies that have fully evaluated land cover and water quality relationships in mixed use watersheds across broad hydroclimatic settings. We related upstream land cover (forest, other natural land covers, development, and agriculture) to observed and modeled water quality across the southeastern US and specifically at 1746 PWS drinking water intake facilities. While there was considerable complexity and variability in the relationship between land cover and water quality, results suggest that Total Nitrogen (TN), Total Phosphorus (TP) and Suspended Sediment (SS) concentrations decrease significantly with increasing forest cover, and increase with increasing developed or agricultural cover. Catchments with dominant (>90 %) agricultural land cover had the greatest export rates for TN, TP, and SS based on SPARROW model estimates, followed by developed-dominant, then forest- and other-natural-dominant catchments. Variability in modeled TN, TP, and SS export rates by land cover type was driven by variability in natural background sources and catchment characteristics that affected water quality even in forest-dominated catchments. Both intake setting (i.e., run-of-river or reservoir) and upstream land cover were important determinants of water quality at PWS intakes. Of all PWS intakes, 15 % had high raw water quality, and 85 % of those were on reservoirs. Of the run-of-river intakes with high raw water quality, 75 % had at least 50 % forest land cover upstream. In addition, PWS intakes obtaining surface water supply from smaller upstream catchments may experience the largest losses of natural land cover based on projections of land cover in 2070. These results illustrate the complexity and variability in the relationship between land cover and water quality at broad scales, but also suggest that forest conservation can enhance the resilience of drinking water supplies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Dynamic covalent chemistry (DCvC) is a powerful means by which to rapidly prepare complex structures from simple molecular building blocks. Effective DCvC behavior is contingent upon the reversibility of covalent bond formation. Stabilized radical species, therefore, have been effectively used for these applications. In earlier work we demonstrated that properly substituted 1-arylurazolyl radicals showed promise as oxygen-insensitive heterocyclic N-centered radicals with a propensity for reversible bond formation. In this work we have synthesized several tethered bis(urazolyl) diradicals, varying by the type and length of connectivity between the urazole rings, and tested them for DCvC behavior. We have found that when the two aryl rings to which the urazolyl radical sites are attached are tethered by a chain of five or more carbons, equilibrium mixtures of monomeric and dimeric species are formed by N-N bond formation between two radical sites. DCvC behavior is observed that is sensitive to changes in temperature, concentration, and (to a lesser extent) solvent. In general, the dimer species is favored at lower temperatures and higher concentrations.

Photobiomodulation (PBM)-the irradiation of tissue with low-intensity light-mitigates neuropathology in rodent models of Parkinson's disease (PD) when targeted at the head ('transcranial PBM'). In humans, however, attenuation of light energy by the scalp and skull necessitates a different approach. We have reported that targeting PBM at the body also protects the brain by a mechanism that spreads from the irradiated tissue ('remote PBM'), although the optimal peripheral tissue target for remote PBM is currently unclear. This study compared the neuroprotective efficacy of remote PBM targeting the abdomen or leg with transcranial PBM, in mouse and non-human primate models of PD. In a pilot study, the neurotoxin MPTP was used to induce PD in non-human primates; PBM (670 nm, 50 mW/cm 2 , 6 min/day) of the abdomen (n = 1) was associated with fewer clinical signs and more surviving midbrain dopaminergic cells relative to MPTP-injected non-human primates not treated with PBM. Validation studies in MPTP-injected mice (n = 10 per group) revealed a significant rescue of midbrain dopaminergic cells in mice receiving PBM to the abdomen (~80%, p < .0001) or legs (~80%, p < .0001), with comparable rescue of axonal terminals in the striatum. Strikingly, this degree of neuroprotection was at least as, if not more, pronounced than that achieved with transcranial PBM. These findings confirm that remote PBM provides neuroprotection against MPTP-induced destruction of the key circuitry underlying PD, with both the abdomen and legs serving as viable remote targets. This should provide the impetus for a comprehensive investigation of remote PBM-induced neuroprotection in other models of PD and, ultimately, human patients., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Competing Interests: Conflicts of interest None disclosed.

Background: Hidradenitis suppurativa affects up to 4% of the population worldwide. Many treatment options exist but these come with a significant side-effect profile. Exercise, weight loss, and dietary modifications may be simple inexpensive alternatives and/or adjuncts to treating this disease., Objectives: We aimed to summarize published evidence on the effects of dietary, weight loss, and exercise interventions on the clinical course, severity, or subjective improvement of hidradenitis suppurativa and to provide a framework regarding dietary changes and exercise modalities for clinicians treating this disease., Methods: A literature search of Scopus (1993 onwards), PubMed (1986 onwards), and MEDLINE (OVID interface, 1946 onwards) was conducted on 22 October, 2022. Case-control studies, cohort studies, and randomized controlled trials with five or more subjects conducted on adult participants (aged >18 years) were included; case reports, case series, and review papers were excluded., Results: Fifteen studies involving 2829 patients were included, encompassing nine cohort studies, five cross-sectional studies, and one cross-over study. Patients who were female, lost more than 50 pounds (22.7 kg), or were obese prior to weight loss saw improvement in hidradenitis suppurativa severity with weight loss. There was evidence for beneficial effects of diets, such as the Mediterranean diet that minimizes sugar, highly processed carbohydrates, and dairy, and emphasizes chicken, fruits, and vegetables, in patients with hidradenitis suppurativa. Evidence also supported benefit from oral zinc and vitamin D supplementation., Conclusions: More evidence is needed in the form of randomized controlled trials or well-designed controlled trials to evaluate the effect of exercise and dietary manipulation on the hidradenitis suppurativa disease course. Overall, there is significant but weak evidence to support improvement in hidradenitis suppurativa severity with weight loss, dietary changes, and micronutrient supplementation. There is no significant evidence to support improvement in hidradenitis suppurativa symptomology with any type of exercise intervention., Clinical Trial Registration: This protocol was registered with PROSPERO with the registration number CRD4202235099., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Preceramic polymers (PCPs) are a group of specialty macromolecules that serve as precursors for generating inorganics, including ceramic carbides, nitrides, and borides. PCPs represent interesting synthetic challenges for chemists due to the elements incorporated into their structure. This group of polymers is also of interest to engineers as PCPs enable the processing of polymer-derived ceramic products including high-performance ceramic fibers and composites. These finished ceramic materials are of growing significance for applications that experience extreme operating environments (e.g., aerospace propulsion and high-speed atmospheric flight). This Review provides an overview of advances in the synthesis and postpolymerization modification of macromolecules forming nonoxide ceramics. These PCPs include polycarbosilanes, polysilanes, polysilazanes, and precursors for ultrahigh-temperature ceramics. Following our review of PCP synthetic chemistry, we provide examples of the application and processing of these polymers, including their use in fiber spinning, composite fabrication, and additive manufacturing. The principal objective of this Review is to provide a resource that bridges the disciplines of synthetic chemistry and ceramic engineering while providing both insights and inspiration for future collaborative work that will ultimately drive the PCP field forward.

Objectives: Literature characterizing pediatric perineal trauma is sparse and generally limited to females. The purpose of this study was to characterize pediatric perineal injuries with specific focus on patient demographics, mechanisms of injury, and care patterns at a regional level 1 pediatric trauma center., Methods: Retrospective review of children aged younger than 18 years evaluated at a level 1 pediatric trauma center from 2006 to 2017. Patients were identified by International Classification of Diseases-9 and 10 codes. Extracted data included demographics, injury mechanism, diagnostic studies, hospital course, and structures injured. The χ 2 and t tests were used to examine differences between subgroups. Machine learning was used to predict variable importance in determining the need for operative interventions., Results: One hundred ninety-seven patients met inclusion criteria. Mean age was 8.5 years. A total of 50.8% were girls. Blunt trauma accounted for 83.8% of injuries. Motor vehicle collisions and foreign bodies were more common in patients aged 12 years and older, whereas falls and bicycle-related injuries were more common in those younger than 12 years ( P < 0.01). Patients younger than 12 years were more likely to sustain blunt trauma with isolated external genital injuries ( P < 0.01). Patients aged 12 and older had a higher incidence of pelvic fractures, bladder/urethral injuries, and colorectal injuries, suggesting more severe injury patterns ( P < 0.01). Half of patients required operative intervention. Children aged 3 years or younger and older than 12 years had longer mean hospital stays compared with children aged 4 to 11 years ( P < 0.01). Mechanism of injury and age constituted more than 75% of the variable importance in predicting operative intervention., Conclusions: Perineal trauma in children varies by age, sex, and mechanism. Blunt mechanisms are the most common, with patients frequently requiring surgical intervention. Mechanism of injury and age may be important in deciding which patients will require operative intervention. This study describes injury patterns in pediatric perineal trauma that can be used to guide future practice and inform injury prevention efforts., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Conflicts of interest None disclosed.

Land conversion and climate change are stressing freshwater resources. Riparian areas, streamside vegetation/forest land, are critical for regulating hydrologic processes and riparian buffers are used as adaptive management strategies for mitigating land conversion effects. However, our ability to anticipate the efficacy of current and alternative riparian buffers under changing conditions remains limited. To address this information gap, we simulated hydrologic responses for different levels of buffer protection under a future scenario of land/climate change through the year 2060. We used the Soil and Water Assessment Tool (SWAT) to project future streamflow in the Upper Neuse River watershed in North Carolina, USA. We tested the capacity of riparian buffers to mitigate the effects of future land use and climate change on daily mean streamflow under three buffer treatments: present buffer widths and fully forested 15 m and 30 m buffers throughout the basin. The treatments were tested using a combination of a future climate change scenario and landcover projections that indicated a doubling of low-intensity development between 2017 and 2060. In areas with >50 % development, the 30 m buffers were particularly effective at increasing average daily streamflow during the lowest flow events by 4 % and decreasing flow during highest flow events by 3 % compared to no buffer protection. In areas between 20 and 50 % development, both 15 m and 30 m buffers reduced low flow by 8 % with minimal effects on high flow. Results indicate that standardized buffers might be more effective at a local scale with further research needing to focus on strategic buffer placement at the watershed scale. These findings highlight a novel approach for integrating buffers into hydrologic modeling and potential for improved methodology. Understanding the effects of riparian buffers on streamflow is crucial given the pressing need to develop innovative strategies that promote the conservation of invaluable ecosystem services., Competing Interests: Declaration of competing interest The authors declare there are no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: There are existing healthcare disparities in pediatric surgery today. Identity and racial incongruity between patients and providers contribute to systemic healthcare inequities and negatively impacts health outcomes of minoritized populations. Understanding the current demographics of the American Pediatric Surgical Association and therefore the cognitive diversity represented will help inform how best to strategically build the organization to optimize disparity solutions and improve patient care., Methods: 1558 APSA members were sent an anonymous electronic survey. Comparative data was collected from the US Census Bureau and the Association of American Medical Colleges. Results were analyzed using standard statistical tests., Results: Of 423 respondents (response rate 27%), the race and ethnicity composition were 68% non Hispanic White, 12% Asian American and Pacific Islander, 6% Hispanic, 5% multiracial, and 4% Black/African American. Respondents were 35% women, 63% men, and 1% transgender, androgyne, or uncertain. Distribution of sexual identity was 97% heterosexual and 3% LGBTQIA. Religious identity was 50% Christian, 22% Agnostic/Atheist, 11% Jewish, 3% Hindu, and 2% Muslim. 32% of respondents were first-generation Americans. Twenty-four different primary languages were spoken, and 46% of respondents were conversational in a second language. These findings differ in meaningful ways from the overall American population and from the population of matriculants in American medical schools., Conclusion: There are substantial differences in the racial, gender, and sexual identity composition of APSA members compared with the overall population in the United States. To achieve excellence in patient care and innovate solutions to existing disparities, representation, particularly in leadership is essential., Type of Study: Survey; original research., Level of Evidence: Level IV., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Periodontal disease affects 42% of adults in the United States. Both the periodontal microbiome and the host immune inflammatory response may be influenced by overweight/obesity status. This retrospective analysis sought to determine the associations of periodontal disease parameters with body mass index (BMI) and obesity status in patients undergoing periodontal maintenance therapy. The records of 418 patients who were undergoing periodontal maintenance after periodontitis treatment were examined, and the patients' demographic characteristics (sex, age, and race/ethnicity), self-reported BMI, periodontal disease condition, number of sites with probing depth ≥ 4 mm, missing teeth, and sites with bleeding on probing (BOP) were recorded. Patients were determined to have active moderate to severe periodontitis if they presented with 2 or more sites in 2 different quadrants with clinical attachment loss ≥ 5 mm and probing depth ≥ 5 mm. Individuals were also categorized into 3 groups: underweight/normoweight, BMI < 25; overweight, BMI 25 ≤ 30; or obese, BMI ≥ 30. In the study population, BMI ranged from 16.827 to 51.389. The periodontitis status was not significantly associated with a BMI status of overweight (odds ratio [OR] = 1.388 [95% CI, 0.961- 2.006]) or obese (OR = 1.168 [95% CI, 0.77-1.757]). Female sex (OR = 0.561 [95% CI, 0.343-0.918]) and age (OR = 0.983 [95% CI, 0.967-0.999]) were negatively associated with active periodontitis status. Obese patients demonstrated significantly more sites with BOP than either underweight/normoweight or overweight patients, and a BMI indicating obesity was associated with increasing age (P < 0.001) and higher number of missing teeth (P = 0.0064). In a population of patients undergoing periodontal maintenance therapy, BMI was associated with age and missing teeth, and obese status was associated with a significantly higher number of sites with BOP.

Study Objectives: The purpose of this study was to characterize the utility of radiologic imaging and examination under anesthesia in female pediatric patients with isolated blunt straddle injuries., Design: Retrospective review., Setting: Single health care system with a children's hospital and level 1 pediatric trauma center., Participants: Female patients aged 1-17 years with blunt straddle injuries from 2006 to 2018., Interventions: None., Main Outcome Measures: Radiologic imaging performed, number of patients requiring exam under anesthesia (EUA), number of injuries not identified in patients who did not undergo EUA., Results: The study cohort included 83 patients. Of these, 11 (13%) had imaging performed. Thirty-four patients were managed as outpatients, 28 were discharged from the emergency department without need for intervention, and 49 patients were admitted. Of these, 48 (98%) went to the operating room for exam EUA. No occult injuries were identified on radiologic studies. Imaging was not associated with need for EUA. No missed injuries occurred in children who were not imaged. Two patients who were imaged returned for EUA following evolution of symptoms., Conclusion: Radiologic imaging did not add diagnostic value for female pediatric patients with blunt straddle injuries. These data emphasize the importance of EUA with repair and advocates for minimization of radiologic imaging in this patient group., (Copyright © 2022. Published by Elsevier Inc.)

This review provides a summary of extracted data from the published literature that contains drug residue depletion data for edible tissues and milk following treatment of sheep and goats. Out of 20,234 records obtained during the initial search, data from 177 records were included in this review. The data is separated by antibiotic class for ease of comparison between studies. Extracted data includes the active ingredient, dosing information, animal health status, analytical method and limits of detection, tolerance and maximum residue limit information, and time frames relative to residue absence or detection. This information is useful for understanding drug residue depletion profiles following extra-label use and for estimating withdrawal intervals, in order to protect the human food chain.

Competing Interests: Conflicts of interest None disclosed.

Stormwater management problems are expanding as urbanization continues and precipitation patterns are increasingly extreme. Urban soils are often more disturbed and compacted than non-urban soils, therefore, rainfall run-off estimates based on models designed for non-urban soils may not be accurate due to altered soil infiltration rates. Our objective was to quantify soil infiltration rates across an urban watershed and compare them to estimates from rainfall-runoff models commonly used in stormwater management (Horton and Green-Ampt) as well as an alternate, random-forest model created using available geospatial data. We measured infiltration rates and collected data on soil properties (texture, bulk density) and context (land use, ground cover, time since development) at 89 points across the 102 ha Walnut Creek watershed in Raleigh, North Carolina (USA). Forest land covers and forest ground covers (leaf litter) had the highest infiltration capacities; however, all of our measurements indicate that urban soils in the Walnut Creek watershed are able to absorb most precipitation events and are likely capable of infiltrating additional urban stormwater runoff. Comparisons between observations and the rainfall-runoff model estimates reveal that both underestimated urban soil infiltration rates. Despite higher than expected urban soil infiltration capacity, stormwater management remains a challenge in this urban watershed. Therefore, to reduce stormwater runoff from impervious surfaces through soil infiltration, impervious surfaces should be disconnected, especially adjacent to new development, and urban forests should be conserved. Further, because our random forest model more accurately captured watershed infiltration rates than the rainfall-runoff models, we propose this type of machine learning approach as an alternative method for informing stormwater management and prioritizing areas for impervious disconnection., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To investigate safety and visual-field changes in people with epilepsy undergoing multifocal Pupillographic Objective Perimetry (mfPOP)., Methods: 15 people with epilepsy and 15 controls underwent mfPOP in the context of routine clinical EEG testing. Safety measures comprised the proportion of participants developing an aura or seizure, a photoparoxysmal response, or increased epileptiform activity on their EEG during mfPOP. Pupil responses were obtained concurrently from 44 regions/field of each eye. Changes in standardised amplitude of constriction and time-to-peak were compared between people with generalised and focal epilepsy, and controls., Results: No participant developed an epileptic aura or clinical seizure during (or after) testing. One participant demonstrated EEG evidence of a focal subclinical seizure which began before mfPOP testing and continued unchanged during testing. Regional field sensitivities were increased in people with generalised epilepsy (+3.80 ± 1.43 dB compared to controls) but were reduced in individuals taking antiepileptic medication (-4.04 ± 1.74 dB). An extra delay of 24.9 ± 10.2 ms was seen in the time-to-peak of the responses in people with focal epilepsy. Based on receiver-operating characteristic analyses, discrimination of people with epilepsy from controls was greatest when using the 4 to 10 most abnormal visual field regions of each eye (%AUC 77.3 ± 9.70)., Significance: In the absence of any safety signal, mfPOP appears harmless in people with epilepsy. The observed abnormalities in per-region sensitives and delays suggest that mfPOP may provide significant new insights into the study of epilepsy., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Women's health has demanded more attention from employers as women integrated into the workforce. Traditionally male-dominant fields and occupations require special attention to workplace design, physical standards for entry, employment practices, equipment, and health monitoring. This editorial summarizes the Defense Health Board's (DHB) review of Active Duty Women's Health and its recommendations grounded in a woman's career life-cycle., Methods: The DHB reviewed the Department of Defense and foreign militaries' current women's health services, relevant policies and practices, peer-reviewed scientific literature, and subject matter expert interviews., Results: The DHB's recommendations centered on a comprehensive approach to education, health care access and treatment, professional workforce development, workplace standards and equipment, and accountable outcomes metrics to guide improvement., Conclusions: Employers can learn how to reduce morbidity, leading to a healthier and more productive female workforce., Competing Interests: Conflict of Interest: R.S.K., V.S.L., C.B.G., K.L.M., G.A.A., and M.D.P. are former members of the Defense Health Board. R.S.K. is affiliated with Avant-garde Health, Palladium, Stern Strategy Group, and Geigsen Group. V.S.L. is affiliated with the New England Journal of Medicine (Editorial Board)., (Copyright © 2022 American College of Occupational and Environmental Medicine.)

Problem: The SARS-CoV-2 (COVID-19) pandemic presented numerous challenges to inpatient care, including overtaxed inpatient medicine services, surges in patient censuses, disrupted patient care and educational activities for trainees, underused providers in certain specialties, and personal protective equipment shortages and new requirements for physical distancing. In March 2020, as the COVID-19 surge began, an interdisciplinary group of administrators, providers, and trainees at Brigham and Women's Hospital created an inpatient virtual staffing model called the Virtual Team Rounding Program (VTRP)., Approach: The conceptual framework guiding VTRP development was rapid-cycle innovation. The VTRP was designed iteratively using feedback from residents, physician assistants, attendings, and administrators from March to June 2020. The VTRP trained and deployed a diverse set of providers across specialties as "virtual rounders" to support inpatient teams by joining and participating in rounds via videoconference and completing documentation tasks during and after rounds. The program was rapidly scaled up from March to June 2020., Outcomes: In a survey of inpatient providers at the end of the pilot phase, 10/10 (100%) respondents reported they were getting either "a lot" or "a little" benefit from the VTRP and did not find the addition of the virtual rounder burdensome. During the scaling phase, the program grew to support 24 teams. In a survey at the end of the contraction phase, 117/187 (62.6%) inpatient providers who worked with a virtual rounder felt the rounder saved them time. VTRP leadership collaboratively and iteratively developed best practices for challenges encountered during implementation., Next Steps: Virtual rounding provides a valuable extension of inpatient teams to manage COVID-19 surges. Future work will quantitatively and qualitatively assess the impact of the VTRP on inpatient provider satisfaction and well-being, virtual rounders' experiences, and patient care outcomes., (Copyright © 2021 by the Association of American Medical Colleges.)

Background: New inpatient virtual care models have proliferated in response to the challenges presented by the coronavirus disease 2019 (COVID-19) pandemic; however, few of these programs have yet been evaluated for acceptability and feasibility., Objective: Assess feasibility and provider experience with the Virtual Team Rounding Program (VTRP), a quality improvement project developed and rapidly scaled at Brigham and Women's Hospital in Boston, MA, in response to the surge of COVID-19 patients in the spring of 2020., Methods: We surveyed 777 inpatient providers and 41 providers who served as 'virtual rounders' regarding their experience with the program. Inpatient providers were asked about their overall satisfaction with the program, whether the program saved them time, and if so, how much and their interest in working with a similar program in the future. Providers who had worked as virtual rounders were asked about their overall satisfaction with the program, the overall difficulty of the work and their interest in participating in a similar program in the future., Results: We find that among both groups the program was well-received, with 72.5% of inpatient providers and 85.7% of virtual rounders reporting that they were 'satisfied' or 'very satisfied' with their experience with the program. Among inpatient providers who worked with the program, two-thirds reported the program saved them time on a daily basis. Inpatient respondents who had worked with virtual rounders were more likely to say that they would be interested in working with the VTRP in the future compared with respondents who never worked with a virtual rounder (75.3 vs 52.5%, P < 0.001)., Conclusion: As the pandemic continues, rapidly implementing and studying virtual care delivery programs is crucial for hospitals and health systems. We demonstrate the feasibility and acceptability of a 'virtual rounding' program assisting inpatient providers. Future work should examine the impact of these programs on patient outcomes., (© The Author(s) 2021. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Recent efforts have demonstrated that the morphology of ceramics can be manipulated to control both their deformation mechanism and mechanical performance. However, precise control of the ceramic nanostructure is still difficult to achieve. Biotemplating, leading to biomorphic materials, provides a facile route to manipulate the nanostructure of the resulting materials, and the use of melanin as a coating provides a new route to biotemplated materials. Melanin is underutilized for structural materials partly due to the cost of procuring it from natural sources and the inability to control the shape and sizes of melanin particles. Taking a combined synthetic biology and chemical synthesis approach, we report the melanization of Escherichia coli and its subsequent silanization and functionalization with preceramic polymers to make novel biomorphic silicon-based ceramic materials. Graft-to and graft-from reactions were used to append preceramic polymers to the melanin, followed by pyrolysis under argon. Samples were analyzed by FTIR, XRD, XPS, and TEM and found to retain the shape and size of the original cells with high fidelity. The homogeneity of coverage and yield of the resulting ceramic materials depended on the type of grafting reaction. This work provides a promising proof-of-concept that bacterial-templated ceramics can be readily made and opens a host of possibilities for further studies and applications.

Background: Older patients with brain metastases (BrM) commonly experience symptoms that prompt acute medical evaluation. We characterized emergency department (ED) visits and inpatient hospitalizations in this population., Methods: We identified 17 789 and 361 Medicare enrollees diagnosed with BrM using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2010-2016) and an institutional database (2007-2016), respectively. Predictors of ED visits and hospitalizations were assessed using Poisson regression., Results: The institutional cohort averaged 3.3 ED visits/1.9 hospitalizations per person-year, with intracranial disease being the most common reason for presentation/admission. SEER-Medicare patients averaged 2.8 ED visits/2.0 hospitalizations per person-year. For patients with synchronous BrM (N = 7834), adjusted risk factors for ED utilization and hospitalization, respectively, included: male sex (rate ratio [RR] = 1.15 [95% CI = 1.09-1.22], P < .001; RR = 1.21 [95% CI = 1.13-1.29], P < .001); African American vs white race (RR = 1.30 [95% CI = 1.18-1.42], P < .001; RR = 1.25 [95% CI = 1.13-1.39], P < .001); unmarried status (RR = 1.07 [95% CI = 1.01-1.14], P = .02; RR = 1.09 [95% CI = 1.02-1.17], P = .01); Charlson comorbidity score >2 (RR = 1.27 [95% CI = 1.17-1.37], P < .001; RR = 1.36 [95% CI = 1.24-1.49], P < .001); and receipt of non-stereotactic vs stereotactic radiation (RR = 1.44 [95% CI = 1.34-1.55, P < .001; RR = 1.49 [95% CI = 1.37-1.62, P < .001). For patients with metachronous BrM (N = 9955), ED visits and hospitalizations were more common after vs before BrM diagnosis (2.6 vs 1.2 ED visits per person-year; 1.8 vs 0.9 hospitalizations per person-year, respectively; RR = 2.24 [95% CI = 2.15-2.33], P < .001; RR = 2.06 [95% CI = 1.98-2.15], P < .001, respectively)., Conclusions: Older patients with BrM commonly receive hospital-level care secondary to intracranial disease, especially in select subpopulations. Enhanced care coordination, closer outpatient follow-up, and patient navigator programs seem warranted for this population., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Intimate partner violence (IPV) is one of the leading causes of pregnancy-related death. Prenatal health care providers can offer critical screening and support to pregnant people who experience IPV. During the COVID-19 shelter-in-place order, mobile apps may offer such people the opportunity to continue receiving screening and support services., Objective: We aimed to examine cases of IPV that were reported on a prenatal care app before and during the implementation of COVID-19 shelter-in-place mandates., Methods: The number of patients who underwent voluntary IPV screening and the incidence rate of IPV were determined by using a prenatal care app that was disseminated to patients from a single, large health care system. We compared the IPV screening frequencies and IPV incidence rates of patients who started using the app before the COVID-19 shelter-in-place order, to those of patients who started using the app during the shelter-in-place order., Results: We found 552 patients who started using the app within 60 days prior to the enforcement of the shelter-in-place order, and 407 patients who used the app at the start of shelter-in-place enforcement until the order was lifted. The incidence rates of voluntary IPV screening for new app users during the two time periods were similar (before sheltering in place: 252/552, 46%; during sheltering in place: 163/407, 40%). The overall use of the IPV screening tool increased during the shelter-in-place order. A slight, nonsignificant increase in the incidence of physical, sexual, and psychological violence during the shelter-in-place order was found across all app users (P=.56). Notably, none of the patients who screened positively for IPV had mentions of IPV in their medical charts., Conclusions: App-based screening for IPV is feasible during times when in-person access to health care providers is limited. Our results suggest that the incidence of IPV slightly increased during the shelter-in-place order. App-based screening may also address the needs of those who are unwilling or unable to share their IPV experiences with their health care provider., (©Tamar Krishnamurti, Alexander L Davis, Beth Quinn, Anabel F Castillo, Kelly L Martin, Hyagriv N Simhan. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 19.02.2021.)

Objective: To compare perioperative outcomes by patient race/ethnicity., Methods: A retrospective cohort study identified 7 331 638 childbirth hospitalizations for women aged 12-55 years in the USA between 2004-2014. Peripartum hysterectomy, in-hospital mortality, perioperative complications, length of stay, and cost of hysterectomy data were analyzed using SAS., Results: Among childbirth hospitalizations (52.9% white, 13.5% black, 23.0% Hispanic, 5.2% Asian, and 5.4% other), peripartum hysterectomy occurred in 6619. The incidence of peripartum hysterectomy was 90.3 (95% confidence interval [CI] 87.7-93.0) per 100 000 hospitalizations, and higher for black (111.0, 95% CI 104.5-117.4), Hispanic (104.9, 95% CI 99.1-110.8), and Asian women (119.6, 95% CI 109.1-130.2) compared to whites (75.7, 95% CI 72.8-78.5). After adjustment, Hispanic women had an 18% higher odds of undergoing peripartum hysterectomy (odds ratio [OR] 1.18, 95% CI 1.08-1.29; P=0.004) than white women. Non-white women had a 2-3-fold higher odds of in-hospital mortality (OR black 2.76, 95% CI 1.44-5.30; OR Hispanic 1.99, 95% CI 1.04-3.82; OR Asian+other 2.44, 95% CI 1.11-5.40. Black and Asian/other women were more likely to undergo blood transfusions., Conclusion: Women of color have higher rates of peripartum hysterectomy and experience higher rates of poor perioperative outcomes and mortality., (© 2020 International Federation of Gynecology and Obstetrics.)

Although the 1,2,3-triazole is a commonly used amide bioisostere in medicinal chemistry, the structural implications of this replacement have not been fully studied. Employing X-ray crystallography and computational studies, we report the spatial and electronic consequences of replacing an amide with the triazole in analogues of cystic fibrosis drugs in the VX-770 and VX-809 series. Crystallographic analyses quantify subtle differences in the relative positions and conformational preferences of the R 1 and R 2 substituents attached to the amide and triazole bioisosteres. Computational studies derived from the X-ray data highlight the improved hydrogen bonding donor and acceptor capabilities of the amide in comparison to the triazole. This analysis of the spatial and electronic differences between the amide and 1,2,3-triazole will inform medicinal chemists as they consider using the triazole as an amide bioisostere., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Dynamic covalent chemistry (DCvC) describes systems in which readily reversible bond formation allows for control of product distributions by straightforward manipulation of reaction conditions (e.g., changes in temperature, solvent, concentration, etc). Nitrogen-centered 1-aryl urazole radicals reversibly form tetrazane dimers in solution via N-N bond formation. When two such urazole units are attached to a single, appropriately substituted benzene ring, the resulting diradical system engages in DCvC. At room temperature, a polymeric network of units is created that exhibits gel-like properties, while at higher temperatures, near quantitative dimerization to form a molecular cage is observed.However, attaching three such urazole units to a single appropriately substituted benzene ring inhibits DCvC behavior.

Purpose: The report highlights utilization of advanced practice providers (APPs) in an academic radiation oncology center and how their role benefits patient care and departmental workflow., Methods and Materials: A self-reported workflow analysis of department APPs was conducted across 5 disease sites. A review of electronic medical records was performed to determine the percent of APP follow-ups completed independently versus in a shared capacity with the radiation oncologist. A review of the APP's didactic and clinical training program was performed., Results: Across all disease sites, approximately 40% of the APP's time was spent on direct patient care, predominantly composed of independent follow-up visits (9%-35%) and telehealth (2%-30%). The breast malignancies group was an outlier with a higher focus on consults or shared visits (25%). Indirect patient care accounts for 30% to 50% of workflow with the focus on visit preparation or care coordination (13%-35%) and dictation (8%-13%). Administrative responsibilities including process improvement, research, education, and leadership account for the remainder (5%-26%) and are varied across disease sites. The central nervous system malignancies group and genitourinary malignancies group reported a greater percentage of their time (23%-26%) on administration compared with other groups (5%-9%). On average APPs see most of their visits independently from the physicians (86.41%) with 13.59% of visits being seen in a shared capacity., Conclusions: APPs can positively affect the field of radiation oncology by augmenting clinical capacity, optimizing workflow and increasing department efficiency via both direct and indirect patient care and through involvement in administrative and leadership duties. By implementing an independent-to practice model, simultaneous APP and physician clinics run parallel to each other, limiting shared visits for complex cases. This promotes APP job satisfaction and provides greater access to patient care without compromising quality. This article highlights a model for the utilization of APPs, which can be implemented by other radiation oncology departments or practices., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Persons with dementia with mild to moderate cognitive impairment are at risk for developing impairments with activities of daily living such as the ability to feed oneself, that negatively influence health. Lack of caregiver skills related to mealtime planning for persons with dementia and the ability to cope with dysfunctional behaviors are well-documented factors that influence nutritional status outcomes, lead to weight loss, poor quality of life, and impact their ability to remain at home., Methods: A cluster randomized controlled trial with a parallel mixed methods evaluation processes will be conducted to examine the efficacy of a train-the-trainer program using non-paid volunteers in respite care centers to deliver a telehealth mealtime intervention guided by the theory-based C3P Model - Change the Person, Change the People, Change the Place (C3P). In this six-month study, dyads of caregivers and persons with mild to moderate dementia receiving respite care services will be randomized to receive either the telehealth intervention or enhanced usual care. Within the intervention group, dyads will be partnered with a C3P trained volunteer who will work with caregivers via videoconference to devise and implement mealtime plans. Under usual care, dyads will receive standardized educational materials modified from The Savvy Caregiver Program for Alzheimer's disease. The primary outcomes include weight maintenance or gain of the person with dementia and quality of life of the caregiver. A multi-level evaluation process utilizing respite center administrators and directors, volunteers, and caregivers will explore intervention fidelity, acceptability and sustainability. Using both the CONSORT and SPIRIT checklists as guidance, the comprehensive study design is more fully described in this manuscript., Discussion: In this trial, we will lay the groundwork to examine the efficacy and sustainability of a train-the-trainer telehealth program that could be widely disseminated by national Alzheimer's organizations and readily adopted by community agencies to provide additional resources to assist families in managing mealtimes at home, while promoting the quality of life of both the caregiver and the person with dementia., Trial Registration: This study was registered with clinicaltrials.gov: NCT03622814 on August 9, 2018.., Competing Interests: Competing interestsThe authors declare that there are no competing interests with regard to this protocol or the study., (© The Author(s) 2020.)

Accumulating evidence highlights links between iron regulation and respiratory disease. Here, we assessed the relationship between iron levels and regulatory responses in clinical and experimental asthma.We show that cell-free iron levels are reduced in the bronchoalveolar lavage (BAL) supernatant of severe or mild-moderate asthma patients and correlate with lower forced expiratory volume in 1 s (FEV 1 ). Conversely, iron-loaded cell numbers were increased in BAL in these patients and with lower FEV 1 /forced vital capacity (FVC) ratio. The airway tissue expression of the iron sequestration molecules divalent metal transporter 1 ( DMT1 ) and transferrin receptor 1 ( TFR1 ) are increased in asthma, with TFR1 expression correlating with reduced lung function and increased Type-2 (T2) inflammatory responses in the airways. Furthermore, pulmonary iron levels are increased in a house dust mite (HDM)-induced model of experimental asthma in association with augmented Tfr1 expression in airway tissue, similar to human disease. We show that macrophages are the predominant source of increased Tfr1 and Tfr1 + macrophages have increased Il13 expression. We also show that increased iron levels induce increased pro-inflammatory cytokine and/or extracellular matrix (ECM) responses in human airway smooth muscle (ASM) cells and fibroblasts ex vivo and induce key features of asthma in vivo , including airway hyper-responsiveness (AHR) and fibrosis, and T2 inflammatory responses.Together these complementary clinical and experimental data highlight the importance of altered pulmonary iron levels and regulation in asthma, and the need for a greater focus on the role and potential therapeutic targeting of iron in the pathogenesis and severity of disease., Competing Interests: Conflict of interest: M.K. Ali has nothing to disclose. Conflict of interest: R.Y. Kim has nothing to disclose. Conflict of interest: A.C. Brown has nothing to disclose. Conflict of interest: J.R. Mayall has nothing to disclose. Conflict of interest: R. Karim has nothing to disclose. Conflict of interest: J.W. Pinkerton has nothing to disclose. Conflict of interest: G. Liu has nothing to disclose. Conflict of interest: K.L. Martin has nothing to disclose. Conflict of interest: M.R. Starkey has nothing to disclose. Conflict of interest: A.L. Pillar has nothing to disclose. Conflict of interest: C. Donovan has nothing to disclose. Conflict of interest: P.S. Pathinayake has nothing to disclose. Conflict of interest: O.R. Carroll has nothing to disclose. Conflict of interest: D. Trinder has nothing to disclose. Conflict of interest: H.L. Tay has nothing to disclose. Conflict of interest: Y.E. Badi has nothing to disclose. Conflict of interest: N.Z. Kermani has nothing to disclose. Conflict of interest: Y-K. Guo has nothing to disclose. Conflict of interest: R. Aryal has nothing to disclose. Conflict of interest: S. Mumby has nothing to disclose. Conflict of interest: S. Pavlidis has nothing to disclose. Conflict of interest: I.M. Adcock reports grants from EU-IMI, during the conduct of the study. Conflict of interest: J. Weaver has nothing to disclose. Conflict of interest: D. Xenaki has nothing to disclose. Conflict of interest: B.G. Oliver has nothing to disclose. Conflict of interest: E.G. Holliday has nothing to disclose. Conflict of interest: P.S. Foster has nothing to disclose. Conflict of interest: P.A. Wark has nothing to disclose. Conflict of interest: D.M. Johnstone has nothing to disclose. Conflict of interest: E.A. Milward has nothing to disclose. Conflict of interest: P.M. Hansbro has nothing to disclose. Conflict of interest: J.C. Horvat has nothing to disclose., (Copyright ©ERS 2020.)