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As mentioned in the January 2022 Pediatrics in Review Commentary, we now present three patients who have a common chief complaint followed by 5 questions for CME credit. All three cases have discussions on presentation, the differential diagnosis, and management that collectively serve as a Review article. The common theme here is that all three patients have difficulty breathing. We hope you will enjoy this review format.

In Australia, as elsewhere, there has been continuing interest in understanding questions regarding unequal employment opportunities. While aggregate patterns provide a useful overview, it is insightful to consider employment outcomes across segmented markets. One such segmented market is between men and women, where it is widely understood that labour market engagement opportunities will differ. This paper provides an investigation of these uneven labour market outcomes. It presents an analysis of labour underutilisation for men and women using panel data, taking account of both individual-level supply-side factors together with the strength of the local labour market (demand-side) and the performance of the broader macro-economic environment. The result is an analysis that accounts for the impact of changing macroeconomy, local labour market conditions, and men and women's employability assets.

Advances in technology are changing the way that ecological monitoring is carried out, especially for those species with ecological characteristics that have traditionally made monitoring difficult. Autonomous acoustic recorders coupled with automated signal detection software is one such approach where technological advances are delivering rapid improvements in the passive monitoring of vocal fauna. Here we characterise the three common call types of the endangered Mallee Emu-wren Stipiturus mallee and present a signal detection template, or call recogniser, for the species. We evaluate the performance of this tool against an independent dataset of field recordings containing Mallee Emu-wren vocalisations. The recogniser performed well with mean precision and recall metrics ranging between 0.55–0.97 and 0.70–0.95, respectively, depending on user parameters. This tool is widely applicable in the ongoing conservation of the Mallee Emu-wren, particularly as a low-cost method for post-release monitoring following a future Mallee Emu-wren translocation.

This article explores the nature and extent of barriers to access to justice that older persons experience, including those with mental health conditions. It finds that access to justice—the right to fair, prompt and responsive decisions by administrative decision-makers and equal access to courts and tribunals to obtain timely and effective remedies—is not only an important right in itself but also enables the enjoyment of many other human rights. Yet older persons, particularly those with mental health conditions, face a significant “justice gap.” Ageist attitudes, laws and practices interact with other forms of bias such as mentalism, sexism, ableism, racism, homophobia, and heterosexism exacerbating older persons’ disadvantage and marginalization, particularly those with mental health conditions, and older indigenous persons. These discriminatory practices, together with the phenomena of elder abuse, all severely limit older persons’ access to timely and responsive justice. International and national standards, both general and specific to older persons, have been shown to be inadequate to respond to this justice gap. An international standard in the form of a binding legal obligation that specifically addresses older persons’ rights of access to justice is needed urgently as part of a new international treaty on the human rights of older persons.

Degree of cerebrovascular stenosis in pediatric patients with sickle cell anemia (SCA) informs need for chronic transfusion therapy, which has significant risks. Flow artifact, intrinsic to magnetic resonance angiography (MRA), is dependent on technical parameters and can lead to overinterpretation of stenosis. The primary objective of this study was to document any change in stroke prevention therapy that could be attributed to the implementation of a standardized MRA scanning protocol for patients with SCA.A standardized MRA scanning protocol with an echo time of less than 5 ms was implemented at Montefiore Medical Center (MMC), NY in May 2016. Retrospective chart review identified 21 pediatric patients with SCA, with an MRA head both pre- and post-May 2016. Arterial stenosis on MRA, machine parameters, and treatment plans were compared pre- and post-implementation.Ten of the 21 patients met inclusion criteria. Previously seen stenosis was re-classified to a lower degree in six of the 10 patients, leading to discontinuation of transfusions in five patients. No patients required escalation of therapy to chronic transfusions.Optimizing flow artifact by decreasing echo time to less than 5 ms can improve accurate interpretation of cerebrovascular disease, and ensure appropriate treatment plans are in place for stroke prevention. This is especially important for implementing "TCD With Transfusions Changing to Hydroxyurea (TWiTCH)" clinical trial results in the real-world setting.

Palliative care has evolved to be an integral part of comprehensive cancer care with the goal of early intervention to improve quality of life and patient outcomes. The NCCN Guidelines for Palliative Care provide recommendations to help the primary oncology team promote the best quality of life possible throughout the illness trajectory for each patient with cancer. The NCCN Palliative Care Panel meets annually to evaluate and update recommendations based on panel members’ clinical expertise and emerging scientific data. These NCCN Guidelines Insights summarize the panel’s recent discussions and highlights updates on the importance of fostering adaptive coping strategies for patients and families, and on the role of pharmacologic and nonpharmacologic interventions to optimize symptom management.

When key ecological information is lacking, conservation translocations should be conducted within an adaptive, experimental framework to maximise knowledge gained and to increase the probability of success. Here we investigated whether timing of release or composition of release groups influenced indices of success during a trial reintroduction of the mallee emu-wren, Stipiturus mallee, to Ngarkat Conservation Park, South Australia. We translocated cohorts of 40 and 38 birds in the Austral autumn and spring of 2018 respectively. We released individuals in small groups, comprising either familiar or unfamiliar birds, and intensively monitored all treatments for 2 weeks post-release to quantify short-term survival and dispersal. We used occupancy modelling to assess persistence of the translocated population for 2 years following releases. We also monitored source populations to assess the impact of removals. Mallee emu-wrens released in spring were more likely to remain at the release site and attempt breeding. Familiarity within a release group did not influence short-term survival. Mallee emu-wren occupancy at the release sites declined following releases and by July 2019 (12–15 months after release), we could no longer detect any emu-wrens. Density at source populations was lower 12 months after removal compared with pre-harvest levels, though these differences were not significant. Despite the failure to establish a population, we gained valuable management insights regarding both the focal species, and translocation practice more broadly. Timing of release can influence short-term indices of success. Spring releases should be considered priority actions in future mallee emu-wren translocations.

Context Species translocations are used in conservation globally. Although harvest for translocation may have negative impacts on source populations, translocation programs rarely explore ways of minimising those impacts. In fluctuating source populations, harvest timing may affect its impact because population size and trajectory vary among years. Aims We explored whether the timing and scale of harvest can be altered to reduce its impact on a fluctuating source population of Mallee Emu-wrens, Stipiturus mallee; an endangered passerine in south-eastern Australia. Mallee Emu-wren populations fluctuate with ~5–10-year drought–rain cycles. Methods We used population viability analysis (PVA) to compare the impact of five harvest scales (no harvest, 100, 200, 300 or 500 individuals) under three population trajectories (increasing, stable or decreasing) and two initial population sizes (our model-based estimate of the population size and the lower 95% confidence interval of that estimate). To generate a model-based estimate of the population size, we surveyed 540 sites (9 ha), stratified according to environmental variables known to affect Mallee Emu-wren occurrence. We used an information-theoretic approach with N-mixture models to estimate Mallee Emu-wren density, and extrapolated results over all potential habitat. Key Results We estimate that in spring 2019, the source population consisted of 6449 individuals, with a minimum of 1923 individuals (lower 95% confidence interval). Of 48 harvest scenarios, only seven showed no impact of harvest within 5 years (15%). Those seven all had increasing population trajectories and carrying capacity set to equal initial population size. Twenty-six populations showed no impact of harvest within 25 years (54%). These were either increasing populations that had reached carrying capacity or decreasing populations nearing extinction. Conclusions Initial population size, carrying capacity, harvest scale and population trajectory were all determinants of harvest impact. Given the importance of carrying capacity, further research is required to determine its role in the Mallee Emu-wren source population. Implications Harvesting Mallee Emu-wrens after high-rainfall years will have the least impact because source populations are likely to be large with increasing trajectories. For fluctuating source populations, flexibility in the timing of harvest can reduce its impact and should be considered during translocation planning.

The synthesis of two novel n-type molecular organic semiconductors based on a fluorinated indacenodithiophene core in combination with an electron withdrawing N-cyanoimine group is reported, and the influence of the regiochemistry of the solubilizing sidechain is investigated. The N-cyanoimine is confirmed to be a strongly electron accepting group, which in combination with the core fluorination resulted in high electron affinities for both materials. Single crystal analysis demonstrated that whilst both materials arrange in ordered slipped stacks with close π–π stacking distances (∼3.40 Å), significant differences in electron transfer integrals for the two regioisomers were observed, relating to differences in relative molecular displacement along the π-stacking direction. Organic thin-film transistors fabricated via blade-coating displayed electron mobility up to 0.13 cm2 V−1 s−1 for the isomer with the larger transfer integral.

COVID‐19 has triggered the most severe economic crisis since the 1930s The resulting policy shift is diametric to what mainstream macroeconomists have been advocating for decades We argue that their framework underestimates the fiscal space available to governments and cannot provide an understanding of the consequences of these policy extremes We introduce modern monetary theory (MMT), which disabuses us of the claims that deficits and debt are to be avoided MMT defines fiscal space in functional terms, in relation to available real resources that can be brought back into productive use, rather than focusing on irrelevant questions of government insolvency

Background: Aortic complications, such as aortic tears and dissections, during cannulation must be managed urgently and often require hypothermic circulatory arrest. We report a unique management strategy to repair an aortic tear without dissection by modifying a Dacron ascending aortic graft with side-arm to serve both as a patch for the aortic tear and inflow for the bypass circuit. Case Presentation: A 32-year-old female patient undergoing reoperative cardiac surgery suffered an unexpected aortic tear during cannulation for cardiopulmonary bypass. After promptly transitioning to femoral cannulation and hypothermic circulatory arrest, the tear was repaired by utilizing a physician-modified ascending aortic graft with side-arm, in which the surrounding skirt of the side-arm was cut from the circumferential graft to patch the defect. The patient was rewarmed with the side-arm serving as arterial inflow for the bypass circuit, and the remainder of the operation proceeded without complication. Conclusion: This type of aortic repair for aortic tears without dissection can offer the patient the benefit of avoiding multiple aortotomies in a weakened aorta, reducing circulatory arrest time, and re-establishing a central cannulation strategy for cardiopulmonary bypass, consequently reducing the likelihood of distal limb ischemia.

The COVID-19 pandemic has had significant impacts on regional economies and in particular has been reflected in the ability of some regions to perform better in the face of an economic downturn than others. Set in the context of regional economic resilience, this paper presents an exploratory analysis of the impact of a national COVID related shut-down in Australia on employment resilience across regions. Using data on the changes in payroll jobs, the paper identifies clusters of regions that can be differentiated according to their resilience during this period. The paper explores a range of possible determinants of regional resilience differences and suggests an agenda for a larger research endeavour.

Background: Flow artifact, intrinsic to Magnetic Resonance Angiography (MRA), is dependent on technical parameters and can lead to overinterpretation of stenosis. Degree of cerebrovascular stenosis in pediatric patients with sickle cell anemia (SCA) informs need for chronic transfusion therapy, which may have significant risks. The primary objective of this study was to document any change in stroke prevention therapy that could be attributed to the implementation of a standardized MRA scanning protocol. Procedure: A standardized MRA scanning protocol with an echo time of

GOAL The goal of this study was to study the incidence of fungal infection in necrotizing pancreatitis (NP) and its impact on mortality. BACKGROUND Infected pancreatic necrosis is a major contributor to morbidity and mortality in patients with NP. While pancreatic fungal infection (PFI) has frequently been identified in patients with NP, its effect on the clinical outcomes is unclear. MATERIALS AND METHODS A literature search was performed in Medline (Ovid), Embase (Ovid), and the Cochrane library. All prospective and retrospective studies that examined the incidence of fungal infection in NP with subgroup mortality data were included. For fungal infection of NP, studies with fungal isolation from pancreatic necrotic tissue were included. Newcastle Ottawa Scale and Joanna Briggs Institute's critical appraisal tool were used for bias assessment. RESULTS Twenty-two studies comprising 2151 subjects with NP were included for the quantitative analysis. The mean incidence of fungal infection was 26.6% (572/2151). In-hospital mortality in the pooled sample of NP patients with PFI (N=572) was significantly higher [odds ratio (OR)=3.95, 95% confidence interval (CI): 2.6-5.8] than those without PFI. In a separate analysis of 7 studies, the mean difference in the length of stay between those with and without fungal infection was 22.99 days (95% CI: 14.67-31.3). The rate of intensive care unit admission (OR=3.95; 95% CI: 2.6-5.8), use of prophylactic antibacterials (OR=2.76; 95% CI: 1.31-5.81) and duration of antibacterial therapy (mean difference=8.71 d; 95% CI: 1.33-16.09) were all significantly higher in patients with PFI. Moderate heterogeneity was identified among the studies on estimating OR for mortality (I2=43%) between the 2 groups. CONCLUSIONS PFI is common in patients with NP and is associated with increased mortality, intensive care unit admission rate, and length of stay. Further prospective studies are needed to better understand the pathophysiology of PFIs and to determine the role for preemptive therapeutic strategies, such as prophylactic antifungal therapy.

Many of the major debates in macroeconomics are conducted within the Phillips Curve framework. The debate has moved over time from the policy menu tradeoff between inflation and unemployment to the...

This brief analyses linearity of LC DCOs using a new tool: topographical linearity field maps. The analysis in this brief assesses whether given combinations of LC will produce good linearity. This brief then shows how to apply the analysis in the design of the DCO using the field maps. The DCO in this brief had a max DNL of 0.280 LSB and max INL of 0.645 LSB. This was achievable by taking advantage of an LC core’s inherent nature. The measurements indeed confirmed that the analysis technique presented is valid.

This study investigates the potential of a Rhizophora mangrove forest of moderate cross-shore thickness to attenuate wave heights using an idealized prototype-scale physical model constructed in a 104 m long wave flume. An 18 m long cross-shore transect of an idealized red mangrove forest based on the trunk-prop root system was constructed in the flume. Two cases with forest densities of 0.75 and 0.375 stems/m2 and a third baseline case with no mangroves were considered. LiDAR was used to quantify the projected area per unit height and to estimate the effective diameter of the system. The methodology was accurate to within 2% of the known stem diameters and 10% of the known prop root diameters. Random and regular wave conditions seaward, throughout, and inland of the forest were measured to determine wave height decay rates and drag coefficients for relative water depths ranging 0.36 to 1.44. Wave height decay rates ranged 0.008–0.021 m–1 for the high-density cases and 0.004–0.010 m–1 for the low-density cases and were found to be a function of water depth. Doubling the forest density increased the decay rate by a factor two, consistent with previous studies for other types of emergent vegetation. Drag coefficients ranged 0.4–3.8, and were found to be dependent on the Reynolds number. Uncertainty in the estimates of the drag coefficient due to the measured projected area and measured wave attenuation was quantified and found to have average combined standard deviations of 0.58 and 0.56 for random and regular waves, respectively. Two previous reduced-scale studies of wave attenuation by mangroves compared well with the present study when their Reynolds numbers were re-scaled by λ3/2 where λ is the prototype-to-model geometric scale ratio. Using the combined data sets, an equation is proposed to estimate the drag coefficient for a Rhizophora mangrove forest: CD = 0.6 + 3e04/ReDBH with an uncertainty of 0.69 over the range 5e03 < ReDBH < 1.9e05, where ReDBH is based on the tree diameter at breast height. These results may improve engineering guidance for the use of mangroves and other emergent vegetation in coastal wave attenuation.

Palliative care has evolved to be an integral part of comprehensive cancer care with the goal of early intervention to improve quality of life and patient outcomes. The NCCN Guidelines for Palliative Care provide recommendations to help the primary oncology team promote the best quality of life possible throughout the illness trajectory for each patient with cancer. The NCCN Palliative Care Panel meets annually to evaluate and update recommendations based on panel members' clinical expertise and emerging scientific data. These NCCN Guidelines Insights summarize the panel's recent discussions and highlights updates on the importance of fostering adaptive coping strategies for patients and families, and on the role of pharmacologic and nonpharmacologic interventions to optimize symptom management.

The strength of the relationship between diabetes, diabetic retinopathy (DR), and glaucoma remains controversial. We review evidence supporting and refuting this association and explore mechanistic pathological and treatment relationships linking these diseases.While studies have shown diabetes/DR may increase the risk for glaucoma, this remains inconsistently demonstrated. Diabetes/DR may contribute toward glaucomatous optic neuropathy indirectly (either by increasing intraocular pressure or vasculopathy) or through direct damage to the optic nerve. However, certain elements of diabetes may slow glaucoma progression, and diabetic treatment may concurrently be beneficial in glaucoma management. Diabetes plays a significant role in poor outcomes after glaucoma surgery. While the relationship between diabetes/DR and glaucoma remains controversial, multiple mechanistic links connecting pathophysiology and management of diabetes, DR, and glaucoma have been made. However, a deeper understanding of the causes of disease association is needed.

Aerial emission sampling of four natural gas boiler stack plumes was conducted using an unmanned aerial system (UAS) equipped with a lightweight sensor-sampling system (the "Kolibri") for measurement of nitrogen oxide (NO), and nitrogen dioxide (NO

A phenomenon called parallel-output misalignment (POM), which intrinsically occurs in ring-type time-to-digital converters (TDCs) like gated-ring oscillator (GRO) or Vernier-ring TDCs, is discussed in this paper. We found that the phase noise caused by POM error may be larger than that due to quantization error by up to 22 dB or even more. Thus, the overall phase noise contribution is dominated by the POM effect rather than the quantization error. This paper proposes a conjoined-ring Vernier (CRV) TDC with a POM error correction circuit that can eliminate the POM error and its consequent corruption on phase noise performance, making quantization error as being the only contribution of the overall phase noise. Meanwhile, the proposed TDC implementation maintains competitive performance in terms of fine time resolution (3 or 0.8 ps) and a flexible large time-length detection range (12 ns) capability in 40-nm CMOS technology. The CRV structure operates like a phase cutter, which separates the time interval into segments with an identical length of about 160 ps, except the residue segment ( $N$ -calibration circuit, is developed to correct the linearity.

Cooperative breeding is prevalent in the family Maluridae, but we present the first detailed published observation of this behaviour in the Mallee Emu-wren Stipiturus mallee . Observations were made over an 8-week period in 2018 following the reintroduction of Mallee Emu-wrens to Ngarkat Conservation Park in South Australia, with three adult birds (a female and two males) seen rearing three young. This record may have implications for future conservation of the endangered Mallee Emu-wren including any further reintroductions.

Since it was liberated on the 15th April 1945 and images broadcast around the world, Bergen-Belsen has been synonymous with the cruelty of the Nazi concentration camp system. Although the history of the camp is well documented, less attention has been paid to what happened to the bodies of almost half of the 53,000 victims who died there and to the materiality of the camp landscape. This paper outlines the results of historical and non-invasive archaeological investigations aimed at locating unmarked graves and camp structures, as well as how they aligned and conflicted with established narratives. The ethical challenges involved in these investigations – as well as the contestation that surrounds the issue of unmarked burials – are also discussed.

High quality evidence is difficult to generate, leaving substantial knowledge gaps in the treatment of spinal conditions. Appropriate use criteria (AUC) are a means of determining appropriate recommendations when high quality evidence is lacking.Define appropriate use criteria (AUC) of cervical fusion for treatment of degenerative conditions of the cervical spine.Appropriate use criteria for cervical fusion were developed using the RAND/UCLA appropriateness methodology. Following development of clinical guidelines and scenario writing, a one-day workshop was held with a multidisciplinary group of 14 raters, all considered thought leaders in their respective fields, to determine final ratings for cervical fusion appropriateness for various clinical situations.Final rating for cervical fusion recommendation as either "Appropriate," "Uncertain" or "Rarely Appropriate" based on the median final rating among the raters.Inclusion criteria for scenarios included patients aged 18 to 80 with degenerative conditions of the cervical spine. Key modifiers were defined and combined to develop a matrix of clinical scenarios. The median score among the raters was used to determine the final rating for each scenario. The final rating was compared between modifier levels. Spearman's rank correlation between each modifier and the final rating was determined. A multivariable ordinal regression model was fit to determine the adjusted odds of an "Appropriate" final rating while adjusting for radiographic diagnosis, number of levels and symptom type. Three decision trees were developed using decision tree classification models and variable importance for each tree was computed.Of the 263 scenarios, 47 (17.9 %) were rated as rarely appropriate, 66 (25%) as uncertain and 150 (57%) were rated as appropriate. Symptom type was the modifier most strongly correlated with the final rating (adjusted ρ2 = 0.58, p.01). A multivariable ordinal regression adjusting for symptom type, diagnosis, and number of levels and showed high discriminative ability (C statistic = 0.90) and the adjusted odds ratio (aOR) of receiving a final rating of "Appropriate" was highest for myelopathy (aOR, 7.1) and radiculopathy (aOR, 4.8). Three decision tree models showed that symptom type and radiographic diagnosis had the highest variable importance.Appropriate use criteria for cervical fusion in the setting of cervical degenerative disorders were developed. Symptom type was most strongly correlated with final rating. Myelopathy or radiculopathy were most strongly associated with an "Appropriate" rating, while axial pain without stenosis was most associated with "Rarely Appropriate."

Surgical trays are often poorly configured and can be ongoing sources of frustration and excess costs. We conducted an observational study to determine if the use of a customized mathematical inventory optimization model would result in a greater reduction in the number of instruments on a surgical tray than a clinician review of the tray.Utilization of instruments on the major orthopedic tray at a large academic hospital was documented over 80 procedures. Processes in the medical device reprocessing department and operating room were observed to comprehensively quantify all associated costs. Results of the observations were applied to a customized mathematical model to determine the ideal tray configuration. For comparison, a clinician review was also performed.The mathematical model alone produced an ideal tray size of 47 instruments, a reduction of 41 instruments from the original size of 88 instruments (47% reduction). This represented $34 440 in annual savings. In contrast, the clinician review alone suggested an ideal tray size of 67 instruments (23% reduction), representing $17 640 in annual savings. When clinicians were provided with the additional information from the model, they reduced the tray size to 51 instruments (42% reduction), producing $31 870 in savings. The mathematical model yielded an additional 22% instrument reduction and $14 230 in savings compared with clinician review alone.Our mathematical model is generalizable and can be applied to all specialties and hospitals to determine optimal tray configuration. As such, the financial implications are broad; at our institution, application to all surgical trays would result in $205 000 of savings annually. Surgeons and managers looking to streamline surgical trays should consider this evidence-based approach.

Background and Purpose: Magnetic Resonance Angiography (MRA) is performed on pediatric patients with sickle cell disease (SCD) to classify degree of cerebrovascular stenosis, informing stroke risk and treatment plan for stroke prevention. Flow artifact intrinsic to MRA with technician dependent factors can lead to over-interpretation of stenosis. The primary objective of this study was to document any change in stroke prevention therapy that could be attributed to the implementation of a standardized MRA scanning protocol. Methods: A standardized MRA scanning protocol with an echo time (TE) of Results: 24/29 (83%) patients were on chronic transfusion therapy for cerebrovascular disease pre-May 2016 whereas 18/29 (62%) required chronic transfusion therapy post May 2016. Notably, 6 patients had a resolution of cerebral vasculopathy leading to discontinuation of chronic transfusion therapy whereas 0 patients required escalation of therapy to chronic transfusions. McNemar analysis showed this difference to be statistically significant (p = 0.042). Conclusion: Implementing a standardized MRA scanning protocol allowed for chronic transfusion therapy, which has potentially significant side effects, to be discontinued in 6 out of 24 patients. Minimizing flow artifact with TE

Understanding trends and patterns in the use of minimally invasive glaucoma surgery (MIGS) and patient profiles undergoing each procedure is important given their relative expense and unknown long-term safety and effectiveness.Retrospective analysis.Minimally invasive glaucoma surgeries and standard glaucoma surgeries recorded in the American Academy of Ophthalmology Intelligent Research in Sight (IRIS®) Registry.We used the data from IRIS Registry between 2013 and 2018 (inclusive) to measure the annual number of MIGS and standard surgical techniques (trabeculectomy or glaucoma drainage device [GDD] placement) performed in the United States, stratified by demographic characteristics. Secondary analyses of concurrent surgeries and of subsequent surgeries for MIGS and standard surgical technique also were conducted.Trends and sociodemographic characteristics of MIGS use in the United States.Two hundred three thousand three hundred thirty-two eyes and 232 537 unique procedures had associated, documented International Statistical Classification of Diseases and Related Health Problems (ICD), Ninth or Tenth Revision, codes for glaucoma and were included in final analyses. Among eyes with documented glaucoma diagnoses, a substantial increase in annual MIGS procedures occurred over the study period (from 7586 in 2013 to 39 677) and a smaller decrease in standard glaucoma procedures (from 16 215 to 13 701). The proportion of iStent procedures almost tripled during the study period (from 14% to 40%), and by 2017 accounted for almost half (43.7%) of all glaucoma surgeries in the United States. Twenty-one thousand twenty-five of all eyes (10.3%) underwent multiple procedures: 7638 (36.3%) on the same day and 13 387 (63.7%) on subsequent days. Endocyclophotocoagulation and iStent placement were the most common concurrent procedures (55.4% of all concurrent procedures). Trabeculectomy and GDD placement were most commonly followed by another standard glaucoma surgery, but when followed by sequential MIGS, endocyclophotocoagulation and goniotomy were the most common procedures performed (33.0% and 21.9%, respectively).A significant increase in MIGS use occurred over the recent 6-year period, despite limited evidence of their long-term safety or effectiveness, highlighting the need for trials comparing safety and outcomes of novel MIGS versus traditional surgical treatments for glaucoma.

To study the association between diabetic retinopathy (DR) and physical functional difficulty using contemporary psychometric validation techniques, and to explore the predictors of physical difficulty among those with diabetes, non-proliferative DR (NPDR), or proliferative DR (PDR).Cross-sectional study using the National Health and Nutrition Examination Survey (NHANES) database from 2005-2008. Participants were classified as either (i) no diabetes no DR, (ii) diabetes without DR, (iii) mild/moderate NPDR, or (iv) severe NPDR/PDR. The presence of DR was detected by retinal imaging and severity was graded using the Early Treatment Diabetic Retinopathy Study Protocol. The physical difficulty was assessed using a 13-question self-reported questionnaire, validated using factor analysis and item response theory (graded response model) psychometric techniques. Secondary analyses of diabetes and DR populations most at risk of reporting greater physical functional difficulty were undertaken.A total of 5321 participants over the age of 40 were included in our study. Of the 13 original physical difficulty questions, one latent trait was identified and 9 questions demonstrated good discrimination and were subsequently retained. In univariable analyses, participants with diabetes and any form of DR all reported significantly higher physical functional difficulty vs those with neither diabetes nor DR (p 0.01 for all). In multivariable analyses, while those with diabetes or any form of DR remained more likely to report higher physical difficulty vs those with neither diabetes nor DR, only those with severe NPDR/PDR reported substantially higher scores (2.1 sum points higher, p = 0.002). Among participants with diabetes or any form of DR, those with 3 or more medical comorbidities and those with depression reported substantially higher sum physical difficulty scores (p 0.05 for all).Those with diabetes or DR experience greater functional physical difficulty than those without, particularly profound among those with severe forms of DR. For those with DR, the presence of concurrent depression or medical comorbidities conferred a significantly higher risk of physical difficulty. Providers and healthcare systems should be aware of particularly vulnerable DR populations at increased risk of experiencing daily functioning deficits.

BackgroundWhile artificial intelligence (AI) offers possibilities of advanced clinical prediction and decision-making in healthcare, models trained on relatively homogeneous datasets, and populations poorly-representative of underlying diversity, limits generalisability and risks biased AI-based decisions. Here, we describe the landscape of AI in clinical medicine to delineate population and data-source disparities.MethodsWe performed a scoping review of clinical papers published in PubMed in 2019 using AI techniques. We assessed differences in dataset country source, clinical specialty, and author nationality, sex, and expertise. A manually tagged subsample of PubMed articles was used to train a model, leveraging transfer-learning techniques (building upon an existing BioBERT model) to predict eligibility for inclusion (original, human, clinical AI literature). Of all eligible articles, database country source and clinical specialty were manually labelled. A BioBERT-based model predicted first/last author expertise. Author nationality was determined using corresponding affiliated institution information using Entrez Direct. And first/last author sex was evaluated using the Gendarize.io API.ResultsOur search yielded 30,576 articles, of which 7,314 (23.9%) were eligible for further analysis. Most databases came from the US (40.8%) and China (13.7%). Radiology was the most represented clinical specialty (40.4%), followed by pathology (9.1%). Authors were primarily from either China (24.0%) or the US (18.4%). First and last authors were predominately data experts (i.e., statisticians) (59.6% and 53.9% respectively) rather than clinicians. And the majority of first/last authors were male (74.1%).InterpretationU.S. and Chinese datasets and authors were disproportionately overrepresented in clinical AI, and almost all of the top 10 databases and author nationalities were from high income countries (HICs). AI techniques were most commonly employed for image-rich specialties, and authors were predominantly male, with non-clinical backgrounds. Development of technological infrastructure in data-poor regions, and diligence in external validation and model re-calibration prior to clinical implementation in the short-term, are crucial in ensuring clinical AI is meaningful for broader populations, and to avoid perpetuating global health inequity.

BACKGROUND AND PURPOSE Children with severe immunocompromise due to cancer therapy or hematopoietic cell transplant are at risk both for potentially lethal invasive fungal rhinosinusitis (IFRS), and for complications associated with gold-standard biopsy diagnosis. We investigated whether early imaging could reliably identify or exclude IFRS in this population, thereby reducing unnecessary biopsy. METHODS We reviewed clinical/laboratory data and cross-sectional imaging from 31 pediatric patients evaluated for suspicion of IFRS, 19 without (age 11.8 ± 5.4 years) and 12 with proven IFRS (age 11.9 ± 4.6 years). Imaging examinations were graded for mucosal thickening (Lund score), for fungal-specific signs (FSS) of bone destruction, extra-sinus inflammation, and nasal mucosal ulceration. Loss of contrast enhancement (LoCE) was assessed separately where possible. Clinical and imaging findings were compared with parametric or nonparametric tests as appropriate. Diagnostic accuracy was assessed by receiver operating characteristic (ROC) analysis. Positive (+LR) and negative likelihood ratios (-LR) and probabilities were calculated. RESULTS Ten of 12 patients with IFRS and one of 19 without IFRS had at least one FSS on early imaging (83% sensitive, 95% specific, +LR = 15.83, -LR = 0.18; P

Aerial emission sampling of four natural gas boiler stack plumes was conducted using an unmanned aerial system (UAS) equipped with a light-weight sensor/sampling system (the “Kolibri”) for measurement of nitrogen oxide (NO), and nitrogen dioxide (NO2), carbon dioxide (CO2), and carbon monoxide (CO). Flights (n = 22) ranged from 11 to 24 minutes duration at two different sites. The UAS was maneuvered into the plumes with the aid of real-time CO2 telemetry to the ground operators and, at one location, a second UAS equipped with an infrared/visible camera. Concentrations were collected and recorded at 1 Hz. The maximum CO2, CO, NO, and NO2 concentrations in the plume measured were 10,000 ppm, 7 ppm, 27 ppm, and 1.5 ppm, respectively. Comparison of the NOx emissions between the stack continuous emission monitoring systems and the UAS/Kolibri for three boiler sets showed an average of 5.6 % and 3.5 % relative percent difference for the run-weighted and carbon-weighted average emissions, respectively.

In this report, we describe the case of a 17-year-old boy with progressive respiratory failure requiring extracorporeal support who met clinical criteria for a presumptive diagnosis of electronic cigarette or vaping-associated acute lung injury (EVALI), with clinical, pathologic, and laboratory evidence of hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS). The patient in our report had a history of tetrahydrocannabinol and nicotine electronic cigarette use for months leading up to his presentation of fever, headache, emesis, and weight loss with respiratory distress. Multiple potential diagnoses were explored, and the patient’s respiratory status improved, and he was initially discharged from the hospital. Roughly one week later, the patient was readmitted for worsening respiratory distress. The patient then met sufficient criteria for a potential diagnosis of HLH and MAS (elevated ferritin level, inflammatory markers, and cytopenia) to warrant a bone marrow aspirate, which revealed rare hemophagocytic cells. Given the severity of his symptoms and laboratory evidence of HLH and MAS, the patient was started on a course of steroids and anakinra. Although laboratory markers improved after treatment, the patient’s respiratory failure worsened, ultimately progressing to a need for mechanical ventilation and extracorporeal support and leading to worsening multiorgan system failure and, ultimately, death. To the best of our knowledge, this is the first report of a patient with a presumptive diagnosis of EVALI with evidence of HLH and MAS, raising the possibility that macrophage activation may play a role in the pathogenesis of EVALI.

Purpose To evaluate the clinical outcome of patients with non–small-cell lung cancer treated by targeting low variant allelic frequency (VAF) driver mutations identified through cell-free DNA (cfDNA) next-generation sequencing (NGS). Detection of driver mutations in cancer is critically important in the age of targeted therapy, where both tumor-based as well as cfDNA sequencing methods have been used for therapeutic decision making. We hypothesized that VAF should not be predictive of response and that low VAF alterations detected by cfDNA NGS can respond to targeted therapy. Patients and Methods A multicenter retrospective case review was performed to identify patients with non–small-cell lung cancer who received targeted molecular therapy on the basis of findings of low VAF alterations in cfDNA NGS. Mutations at low VAF were defined as < 0.2% mutated cfDNA molecules in a background of wild-type cfDNA. Results One hundred seventy-two patients underwent cfDNA NGS testing. Of the 172 patients, 12 were identified as having low VAF driver alterations and were considered for targeted therapy. The median progression-free survival (PFS) for all patients was 52 weeks (range, 17 to 88 weeks). For patients with EGFR exon 19 deletion (n = 7), the median PFS was 52 weeks (range, 17 to 60.5 weeks). For patients with EML4-ALK fusions (n = 3), the median PFS was 60 weeks (range, 18 to 88 weeks). The median overall survival for all patients after diagnosis was 57.6 weeks. Conclusion Targeted treatment response for driver mutations detected by cfDNA may be independent of VAF, even in relation to other higher VAF aberrations in plasma, and directly dependent on the underlying disease biology and ability to treat the patient with appropriate targeted therapy.

Hyperglycemia is a potent regulator of endogenous glucose production (EGP). Loss of this “glucose effectiveness” is a major contributor to elevated plasma glucose concentrations in type 2 diabetes (T2D). KATP channels in the central nervous system have been shown to regulate EGP in humans and rodents. We examined the contribution of central KATP channels to glucose effectiveness. Under fixed hormonal conditions (studies using a pancreatic clamp), hyperglycemia suppressed EGP by ∼50% in both humans without diabetes and normal Sprague-Dawley rats. By contrast, antagonism of KATP channels with glyburide significantly reduced the EGP-lowering effect of hyperglycemia in both humans and rats. Furthermore, the effects of glyburide on EGP and gluconeogenic enzymes were abolished in rats by intracerebroventricular administration of the KATP channel agonist diazoxide. These findings indicate that about half of the suppression of EGP by hyperglycemia is mediated by central KATP channels. These central mechanisms may offer a novel therapeutic target for improving glycemic control in subjects with T2D.