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Introduction: Undocumented immigrants are excluded from benefits that help compensate for scheduled outpatient hemodialysis (HD), compelling them to use emergency departments (ED) for HD. Consequently, these patients can receive “emergency-only” HD after presenting to the ED with critical illness due to untimely dialysis. Our objective was to describe the impact of emergency-only HD on hospital cost and resource utilization in a large academic health system that includes public and private hospitals. Methods: This retrospective observational study of health and accounting records took place at five teaching hospitals (one public, four private) over 24 consecutive months from January 2019 to December 2020. All patients had emergency and/or observation visits, renal failure codes (International Classification of Diseases, 10th Rev, Clinical Modification), emergency HD procedure codes, and an insurance status of “self-pay.” Primary outcomes included frequency of visits, total cost, and length of stay (LOS) in the observation unit. Secondary objectives included evaluating the variation in resource use between persons and comparing these metrics between the private and public hospitals. Results: A total of 15,682 emergency-only HD visits were made by 214 unique persons, for an average of 36.6 visits per person per year. The average cost per visit was $1,363, for an annual total cost of $10.7 million. The average LOS was 11.4 hours. This resulted in 89,027 observation-hours annually, or 3,709 observation-days. The public hospital dialyzed more patients compared to the private hospitals, especially due to repeat visits by the same persons. Conclusion: Health policies that limit hemodialysis of uninsured patients to the ED are associated with high healthcare costs and a misuse of limited ED and hospital resources.

Site-selective installation of C–Me bonds remains a powerful and sought-after tool to alter the chemical and pharmacological properties of a molecule. Direct C–H functionalization provides an attractive means of achieving this transformation. Such protocols, however, typically utilize harsh conditions and hazardous methylating agents with poor applicability towards late-stage functionalization. Furthermore, highly mono-selective methylation protocols remain scarce. Herein, we report an efficient mono-selective, directed ortho-methylation of arenes using N,N,N-trimethylanilinium salts as a non-carcinogenic, bench-stable methylating agents. We extend this protocol to d3-methylation, in addition to the late-stage functionalization of pharmaceutically active compounds. Detailed kinetic studies indicate the rate-limiting insitu formation of MeI as integral to the observed reactivity.

The study analysis plan, Figures S1-S6, Table S1

Purpose:To quantitatively predict the impact of cardiopulmonary dose on overall survival (OS) after radiotherapy for locally advanced non–small cell lung cancer.Experimental Design:We used the NRG Oncology/RTOG 0617 dataset. The model building procedure was preregistered on a public website. Patients were split between a training and a set-aside validation subset (N = 306/131). The 191 candidate variables covered disease, patient, treatment, and dose-volume characteristics from multiple cardiopulmonary substructures (atria, lung, pericardium, and ventricles), including the minimum dose to the hottest x% volume (Dx%[Gy]), mean dose of the hottest x% (MOHx%[Gy]), and minimum, mean (Mean[Gy]), and maximum dose. The model building was based on Cox regression and given 191 candidate variables; a Bonferroni-corrected P value threshold of 0.0003 was used to identify predictors. To reduce overreliance on the most highly correlated variables, stepwise multivariable analysis (MVA) was repeated on 1000 bootstrapped replicates. Multivariate sets selected in ≥10% of replicates were fit to the training subset and then averaged to generate a final model. In the validation subset, discrimination was assessed using Harrell c-index, and calibration was tested using risk group stratification.Results:Four MVA models were identified on bootstrap. The averaged model included atria D45%[Gy], lung Mean[Gy], pericardium MOH55%[Gy], and ventricles MOH5%[Gy]. This model had excellent performance predicting OS in the validation subset (c = 0.89).Conclusions:The risk of death due to cardiopulmonary irradiation was accurately modeled, as demonstrated by predictions on the validation subset, and provides guidance on the delivery of safe thoracic radiotherapy.

Developing more efficient catalytic processes using abundant and low toxicity transition metals is key to enable their mainstream use in synthetic chemistry. We have rationally designed a new Mn(I)-catalyst for hydroarylation reactions that displays much improved catalytic activity over the commonly used MnBr(CO)5. Our new catalyst, MnBr(CO)3(MeCN)2, avoids the formation of the off-cycle manganacycle-(CO)4 species responsible for low catalyst activity, allowing near room temperature hydroarylation of alkenes and alkynes with broad functional group tolerance including late stage functionalization and diversification of bioactive molecules.

Citrus huanglongbing (HLB) or greening is one of the most devastating diseases of citrus worldwide. Sensitive detection of its causal agent, ‘Candidatus Liberibacter asiaticus’ (CLas), is critical for early diagnosis and successful management of HLB. However, current nucleic acid–based detection methods are often insufficient for the early detection of CLas from asymptomatic tissue and unsuitable for high-throughput and field-deployable diagnosis of HLB. Here we report the development of the Cas12a-based DNA endonuclease-targeted CRISPR trans reporter (DETECTR) assay for highly specific and sensitive detection of CLas nucleic acids from infected samples. The DETECTR assay, which targets the five-copy nrdB gene specific to CLas, couples isothermal amplification with Cas12a transcleavage of a fluorescent reporter oligonucleotide and enables detection of CLas nucleic acids at the attomolar level. The DETECTR assay was capable of specifically detecting the presence of CLas across different infected citrus, periwinkle, and psyllid samples and shown to be compatible with lateral flow assay technology for potential field-deployable diagnosis. The improvements in detection sensitivity and flexibility of the DETECTR technology position the assay as a potentially suitable tool for early detection of CLas in infected regions.

Summary The C–H alkylation of arenes with N-based directing groups typically requires high temperatures and/or harsh reaction conditions, which has traditionally reduced its functional group compatibility and applicability for late-stage functionalization. We report that a cyclometallated Ru complex is able to perform the C–H alkylation of arenes bearing a variety of N-directing groups with primary alkyl bromides at room temperature and under mild reaction conditions. We demonstrate this with an extended substrate scope, which includes several examples of late-stage alkylation of drug molecules, thus showcasing the “real-world” capabilities of this method. Mechanistic studies show that, in contrast to previous mechanistic proposals, the reaction proceeds via a bis-cyclometallated Ru intermediate, followed by an SN2-type oxidative addition.

Introduction: Traumatic intracranial hemorrhages (TIH) have traditionally been managed in the intensive care unit (ICU) setting with neurosurgery consultation and repeat head CT (HCT) for each patient. Recent publications indicate patients with small TIH and normal neurological examinations who are not on anticoagulation do not require ICU-level care, repeat HCT, or neurosurgical consultation. It has been suggested that these patients can be safely discharged home after a short period of observation in emergency department observation units (EDOU) provided their symptoms do not progress. Methods: This study is a retrospective cross-sectional evaluation of an EDOU protocol for minor traumatic brain injury (mTBI). It was conducted at a Level I trauma center. The protocol was developed by emergency medicine, neurosurgery and trauma surgery and modeled after the Brain Injury Guidelines (BIG). All patients were managed by attendings in the ED with discretionary neurosurgery and trauma surgery consultations. Patients were eligible for the mTBI protocol if they met BIG 1 or BIG 2 criteria (no intoxication, no anticoagulation, normal neurological examination, no or non-displaced skull fracture, subdural or intraparenchymal hematoma up to 7 millimeters, trace to localized subarachnoid hemorrhage), and had no other injuries or medical co-morbidities requiring admission. Protocol in the EDOU included routine neurological checks, symptom management, and repeat HCT for progression of symptoms. The EDOU group was compared with historical controls admitted with primary diagnosis of TIH over the 12 months prior to the initiation of the mTBI protocols. Primary outcome was reduction in EDOU length of stay (LOS) as compared to inpatient LOS. Secondary outcomes included rates of neurosurgical consultation, repeat HCT, conversion to inpatient admission, and need for emergent neurosurgical intervention. Results: There were 169 patients placed on the mTBI protocol between September 1, 2016 and August 31, 2019. The control group consisted of 53 inpatients. Median LOS (interquartile range [IQR]) for EDOU patients was 24.8 (IQR: 18.8 – 29.9) hours compared with a median LOS for the comparison group of 60.2 (IQR: 45.1 – 85.0) hours (P < .001). In the EDOU group 47 (27.8%) patients got a repeat HCT compared with 40 (75.5%) inpatients, and 106 (62.7%) had a neurosurgical consultation compared with 53 (100%) inpatients. Subdural hematoma was the most common type of hemorrhage. It was found in 60 (35.5%) patients, and subarachnoid hemorrhage was found in 56 cases (33.1%). Eleven patients had multicompartment hemorrhage of various classifications. Twelve (7.1%) patients required hospital admission from the EDOU. None of the EDOU patients required emergent neurosurgical intervention. Conclusion: Patients with minor TIH can be managed in an EDOU using an mTBI protocol and discretionary neurosurgical consults and repeat HCT. This is associated with a significant reduction in length of stay.

New tools and advanced technologies have played key roles in facilitating basic research in plant pathology and practical approaches for disease management and crop health. Recently, the CRISPR/Cas (clustered regularly interspersed short palindromic repeats/CRISPR-associated) system has emerged as a powerful and versatile tool for genome editing and other molecular applications. This review aims to introduce and highlight the CRISPR/Cas toolkit and its current and future impact on plant pathology and disease management. We will cover the rapidly expanding horizon of various CRISPR/Cas applications in the basic study of plant–pathogen interactions, genome engineering of plant disease resistance, and molecular diagnosis of diverse pathogens. Using the citrus greening disease as an example, various CRISPR/Cas-enabled strategies are presented to precisely edit the host genome for disease resistance, to rapidly detect the pathogen for disease management, and to potentially use gene drive for insect population control. At the cutting edge of nucleic acid manipulation and detection, the CRISPR/Cas toolkit will accelerate plant breeding and reshape crop production and disease management as we face the challenges of 21st century agriculture.

Purpose To describe a novel surgical technique for rescuing a dislocated "in-the-bag" accommodative intraocular lens (Crystalens; Bausch and Lomb Inc, Rochester NY) and report its postoperative outcome. Methods Interventional case report. An 82-year-old patient with history of pseudoexfoliation syndrome presented with a posteriorly dislocated "in-the-bag" Crystalens intraocular lens. A pars plana vitrectomy was performed. The Crystalens intraocular lens was rescued, and scleral sulcus fixated using prolene suture. Results No intraoperative or postoperative complications were noted. The preoperative visual acuity was 6/200. The vision improved to 20/30, 8 weeks after the surgery. Conclusion Rescuing, instead of exchanging, a Crystalens intraocular lens might be a safe alternative in patients with a dislocated "in-the-bag" Crystalens intraocular lens.

Electroencephalograms are commonly ordered by acute care doctors but not always understood. Other reviews have covered when and how to perform electroencephalograms. This primer has a different, unique, and complementary goal. We review basic electroencephalogram interpretation and terminology for nonexperts. Our goal is to encourage common understanding, facilitate inter specialty collaboration, dispel common misunderstandings, and inform the current and future use of this precious resource. This primer is categorically not to replace the expert neurologist or technician. Quite the contrary, it should help explain how nuanced electroencephalogram can be, and why indiscriminate electroencephalogram is inappropriate. Some might argue not to teach nonexperts lest they overestimate their abilities or reach. We humbly submit that it is even more inappropriate to not know the basics of a test that is ordered frequently and resource intensive. We cover the characteristics of the “normal” electroencephalogram, electroencephalogram slowing, periodic epileptiform discharges (and its subtypes), burst suppression, and electrographic seizures (and its subtypes). Alongside characteristic electroencephalogram findings, we provide clinical pearls. These should further explain what the reporter is communicating and whether additional testing is beneficial. Along with teaching the basics and whetting the appetite of the general clinician, this resource could increase mutual understanding and mutual appreciation between those who order electroencephalograms and those who interpret them. While there is more to electroencephalogram than can be delivered via a single concise primer, it offers a multidisciplinary starting point for those interested in the present and future of this commonly ordered test.

Summary Although Ru-catalyzed meta-selective sp2 C–H alkylation with secondary alkyl halides is well established, ortho selectivity has never been achieved. We demonstrate that the use of a cyclometalated Ru-complex, RuBnN, as the catalyst results in a complete switch of the inherent meta-selectivity to ortho selectivity in the Ru-catalyzed sp2 C–H alkylation reaction with unactivated secondary alkyl halides. The high catalytic activity of RuBnN allows mild reaction conditions that result in a transformation of broad scope and versatility. Preliminary mechanistic studies suggest that a bis-cycloruthenated species is the key intermediate undergoing oxidative addition with the alkyl bromides, thus avoiding the more common SET pathway associated with meta-selectivity.

Purpose To report the 1-year outcomes of a novel surgical technique for the fixation of a CZ70BD intraocular lens with Gore-Tex suture using cow-hitch knots. Methods A retrospective chart review of 15 patients (13 men and 2 women) who underwent fixation of a posterior chamber intraocular lens with Gore-Tex suture was performed. Short- and long-term outcomes data were collected 1 month and 1 year after surgery, respectively. Results Fourteen of the 15 patients met inclusion criteria and were included in the analysis. Mean visual acuity improved significantly from Snellen 20/491 preoperatively to Snellen 20/59 at postoperative month 12 (P = 0.002). The most common short-term complications included increased intraocular pressure (n = 6) and cystoid macular edema (n = 4). The most common long-term complications included increased intraocular pressure (n = 2) and iris capture of the intraocular lens (n = 2). Conclusions One-year outcome data suggest that this technique is a reasonable surgical option for secondary intraocular lens placement in patients who lack capsular support.

Purpose To evaluate the effect of cataract extraction (CE) by phacoemulsification on the vitreomacular interface (VMI) of eyes with preexisting vitreomacular traction (VMT). Methods Retrospective, observational case series. Patients with VMT who elected to proceed with CE, before any vitreoretinal intervention, were studied. Eyes with at least a 12-month follow-up period were included. The status of the vitreomacular adhesion at different time points was assessed using spectral-domain optical coherence tomography. The best-corrected visual acuity was recorded at different time points. Other macular and systemic comorbidities were documented. Results Fifteen eyes from 15 phakic patients with symptomatic VMT were included. Six of them were male subjects. Seven patients had diabetes mellitus and two of them also had nonproliferative diabetic retinopathy. The preoperative macular comorbidities included macular hole in six eyes (Stage 1 in 3 eyes and Stage 2 or 3 in another 3 eyes), epiretinal membrane in five eyes, and cystoid macular edema in four eyes. After uncomplicated CE, the VMT was released in 5 eyes, whereas in 10 eyes, CE did not significantly change the status of the vitreomacular adhesion. Three of 3 eyes with preexisting full-thickness macular hole (Stage 2 or 3 macular hole) were found to have Stage 4 macular hole shortly after CE. In seven of seven patients with diabetes mellitus, the status of the vitreomacular interface did not change after CE. Eventually, 7 of 15 patients underwent additional pars plana vitrectomy. Compared with the baseline vision, and vision before other interventions, the visual acuity after CE improved in 5 patients, remained unchanged in 7 patients, and decreased in the 3 patients with Stage 2 or 3 macular hole. The mean preoperative and early postoperative visual acuity was 20/59 and 20/68, respectively (P > 0.05). Conclusion The effect of CE in phakic eyes with known VMT varies significantly. In the current case series, every eye with VMT and Stage 2 or 3 macular hole ended up with Stage 4 macular hole, although the VMT did not change significantly in the eyes of diabetic patients. Studies with larger sample size are needed to further elucidate the impact of elective CE on VMT.

Root metaxylem vessels are responsible for axial water transport and contribute to hydraulic architecture. Variation in metaxylem vessel size and number can impact drought tolerance in crop plants, including rice, a crop that is particularly sensitive to drought. Identifying and validating candidate genes for metaxylem development would aid breeding efforts for improved varieties for drought tolerance. We identified three transcription factor candidate genes that potentially regulate metaxylem vessel size and number in rice based on orthologous annotations, published expression data, and available root and drought‐related QTL data. Single gene knockout mutants were generated for each candidate using CRISPR‐Cas9 genome editing. Root metaxylem vessel area and number were analyzed in 6‐week‐old knockout mutants and wild‐type plants under well‐watered and drought conditions in the greenhouse. Compared with wild type, LONESOME HIGHWAY (OsLHW) mutants had fewer, smaller metaxylem vessels in shallow roots and more, larger vessels in deep roots in drought conditions, indicating that OsLHW may be a repressor of drought‐induced metaxylem plasticity. The AUXIN RESPONSE FACTOR 15 mutants showed fewer but larger metaxylem vessel area in well‐watered conditions, but phenotypes were inconsistent under drought treatment. ORYZA SATIVA HOMEBOX 6 (OSH6) mutants had fewer, smaller metaxylem vessels in well‐watered conditions with greater effects on xylem number than size. OSH6 mutants had larger shoots and more, deeper roots than the wild type in well‐watered conditions, but there were no differences in performance under drought between mutants and wild type. Though these candidate gene mutants did not exhibit large phenotypic effects, the identification and investigation of candidate genes related to metaxylem traits in rice deepen our understanding of metaxylem development and are needed to facilitate incorporation of favorable alleles into breeding populations to improve drought stress tolerance.

Scale has been identified as a central unifying concept in ecology, yet few empirical studies examine its importance per se when quantifying species-habitat relationships. Means and associated variances of ecological variables are known to aggregate unpredictably among observational scale sizes; however, the empirical implications of these scaling effects remain to be fully examined when building and interpreting species-environment models. Here we explore scale-based modeling implications using radio-telemetry data of adult and dispersing-juvenile northern flying squirrels linked to LiDAR-derived fine-grain forest structure data. We construct and rank the same set of candidate species-habitat models across a continuum of 14 biologically relevant observational scales to examine whether scale alone can affect species-habitat model selection. Our results demonstrate differential relative model support (via AIC weights) whereby upwards of seven different “best models” can be generated with varying levels of support entirely contingent upon the scale within which they were quantified. Further, we show this effect to be different for male, female, and dispersing-juvenile animals. We conclude that a continuum-based approach and an understanding of model relativity among scales is a fundamental but absent step in the building and interpretation of most multi-scale ecological models.

Background: Several neuroimaging studies report structural alterations of the trigeminal nerve in trigeminal neuralgia (TN). Less attention has been paid to structural brain changes occurring in TN, even though such changes can influence the development and response to treatment of other headache and chronic pain conditions. The purpose of this study was to apply a novel neuroimaging technique—texture analysis—to identify structural brain differences between classical TN patients and healthy subjects.Methods: We prospectively recruited 14 medically refractory classical TN patients and 20 healthy subjects. 3-Tesla T1-weighted brain MRI scans were acquired in all participants. Three texture features (autocorrelation, contrast, energy) were calculated within four a priori brain regions of interest (anterior cingulate, insula, thalamus, brainstem). Voxel-wise analysis was used to identify clusters of texture difference between TN patients and healthy subjects within regions of interest (p < 0.001, cluster size >20 voxels). Median raw texture values within clusters were also compared between groups, and further used to differentiate TN patients from healthy subjects (receiver-operator characteristic curve analysis). Median raw texture values were correlated with pain severity (visual analog scale, 1–100) and illness duration.Results: Several clusters of texture difference were observed between TN patients and healthy subjects: right-sided TN patients showed reduced autocorrelation in the left brainstem, increased contrast in the left brainstem and right anterior insula, and reduced energy in right and left anterior cingulate, right midbrain, and left brainstem. Within-cluster median raw texture values also differed between TN patients and healthy subjects: TN patients could be segregated from healthy subjects using brainstem autocorrelation (p = 0.0040, AUC = 0.84, sensitivity = 89%, specificity = 70%), anterior insula contrast (p = 0.0002, AUC = 0.92, sensitivity = 78%, specificity = 100%), and anterior cingulate energy (p = 0.0004, AUC = 0.92, sensitivity = 78%, specificity = 100%). Additionally, anterior insula contrast and duration of TN were inversely correlated (p = 0.030, Spearman r = −0.73).Conclusions: Texture analysis reveals distinct brain abnormalities in TN, which relate to clinical features such as duration of illness. These findings further implicate structural brain changes in the development and maintenance of TN.

Outdoor recreation on trail networks is a growing form of disturbance for wildlife. However, few studies have examined behavioural responses by large carnivores to motorised and non‐motorised recreational activity — a knowledge gap that has implications for the success of human access management aimed at improving habitat quality for wildlife. We used an integrated step selection analysis of grizzly bear (Ursus arctos) radiotelemetry data and a spatio‐temporal model of motorised and non‐motorised human recreational activity to examine how human recreational activity on trails affects both habitat selection and movement behaviour of individual bears. Grizzly bears were captured and radiocollared in the west‐central Alberta Rocky Mountains and Foothills, and trail cameras were deployed on trails to obtain data on human recreational activity. We found that models including data on recreational activity outperformed trail‐proximity models when interactions with movement covariates were included. Responses were highly variable among individuals and across classes: males, females, and females with cubs. Male and solitary female grizzly bears increased avoidance of trails with a high probability of motorised activity as well as displaying increased movement rates in response to motorised recreation. Females with cubs did not increase avoidance, however they had the largest response in terms of higher movement rates. In contrast, for all classes, selection for proximity to trail increased when probability of non‐motorised activity was high, and the effect on movement was dampened relative to the motorised response. Synthesis and applications. By combining selection and movement into a unified modelling framework, we show that bears alter selection and movement behaviour in response to trails and recreation, and that such responses are determined by the type of recreational activity. Reduced selection and increased movement in proximity to motorised trails could affect bears’ ability to exploit foraging opportunities in these areas. Future access management actions for grizzly bear recovery should consider frequency and type of linear feature use by humans rather than solely relying on thresholds relating to feature densities.

PURPOSE To investigate predictors of success, visual outcomes, and complications of intravitreal ocriplasmin for the treatment of symptomatic vitreomacular adhesion in a clinical care setting. METHODS Retrospective chart review of 49 consecutive eyes of 47 patients who received intravitreal ocriplasmin. Spectral domain optical coherence tomography scans were examined for vitreomacular traction (VMT) release, full-thickness macular hole (FTMH) closure, and other changes in retinal anatomy. RESULTS Pharmacologic VMT release occurred in 41% of eyes; positive predictors included age ≤75 years (P = 0.001), phakic status (P = 0.016), VMT width ≤750 μm (P = 0.001), and absence of retinal comorbidities (P = 0.035). Pharmacologic FTMH closure occurred in 25% of cases; positive predictors included successful VMT release (P = 0.042), better preinjection best-corrected visual acuity (P = 0.036), and smaller FTMH aperture width (P = 0.033). Eyes that achieved VMT release and did not undergo surgery attained significant improvement in best-corrected visual acuity (P = 0.015). Complications included subfoveal lucency (33%), ellipsoid zone disruption (33%), and FTMH base enlargement (75%). Only FTMH base enlargement resulted in worse visual outcomes (P = 0.024). Subgroup analysis of 14 eyes with ideal characteristics (all positive predictors listed above) yielded a 93% VMT release rate. CONCLUSION Proper case selection may facilitate successful pharmacologic vitreolysis with ocriplasmin, improve visual outcomes, and minimize potential complications.

Temporal lobe epilepsy (TLE) in children is considered different from that in adults. As such, characterizing the structural lesions present in pediatric patients with TLE and their association with long-term seizure control is important. Here, we aimed to assess the concordance between preoperative imaging and postoperative histopathological diagnoses and their associations with seizure outcomes in pediatric patients with TLE undergoing temporal lobe surgery. We retrospectively reviewed the charts of pediatric patients with TLE who underwent surgical treatment between 1988 and 2020 as a part of the Comprehensive Epilepsy Program at the University of Alberta. Demographic, age at seizure onset, age at surgery, preoperative electroencephalography (EEG), long-term video EEG, imaging (magnetic resonance imaging [MRI] and computed tomography), neuropathology, and long-term seizure outcome data were acquired and analyzed. One hundred and seventeen patients underwent surgery for refractory TLE; the preoperative MRI diagnosis was concordant with the histopathological diagnosis in 76 % of cases. Tumors were identified with high accuracy (91 %). Mesial temporal sclerosis (MTS) was strongly associated with an excellent outcome after surgery (94 %). Patients with normal imaging results or non-specific pathologies were more likely to experience poor seizure outcomes after surgery (50 %). The radiological identification of lesions was associated with good long-term seizure outcomes, whereas normal MRI results were associated with significantly poorer long-term seizure outcomes. An accurate preoperative MRI is essential to epilepsy surgery since it impacts all stages of management; these results will thereafter help inform practitioners' efforts to predict seizure outcome.

ED observation units (EDOUs) are designed for patients who require diagnostics or therapeutics beyond the initial ED visit to determine the need for hospital admission. Best evidence is that this care be delivered via ordersets or protocols. Occasionally, patients present with conditions that are amenable to EDOU care but fall outside the commonly used protocols. This article details a few of these conditions: abnormal uterine bleeding, allergic reaction, alcohol intoxication, acetaminophen overdose and sickle cell vaso-occlusive crisis. It is not meant to be exhaustive as patient care needs can vary hospital to hospital.

Download : Download high-res image (123KB) Download : Download full-size image After completing his undergraduate degree at Sheffield Hallam University, during which he undertook extended research projects with Prof. Joseph Harrity (the University of Sheffield) and Prof. Kilian Muniz (Institute of Chemical Research of Catalonia), Matt joined the lab of Prof. Igor Larrosa at the University of Manchester. His research focuses on the development of Csp2–Csp3 bond-forming reactions by ruthenium-catalyzed C–H activation. Outside of chemistry, Matt is a fan of sports and follows football, rugby, and cricket.

Background Many hospitals have or will be opening an observation unit (OU), the majority managed by the emergency department (ED). Graduating emergency medicine (EM) residents will be expected to have the knowledge and skills necessary to appropriately identify and manage patients in this setting. Our objective is to examine the current state of observation medicine (OM) education and prevalence in EM training. Methods In a follow-up to the 2019 Society for Academic Emergency Medicine (SAEM) OM Interest Group meeting, we convened an expert panel of OM physicians who are members of both the SAEM OM Interest Group and the American College of Emergency Physicians Section of OM. The panel of six emergency physicians representing geographic diversity was formed. A structured literature review was performed yielding 16 educational publications and sources pertaining to OM education and training across all specialties. Report on the existing literature Only a small number of EM residencies have a required or elective OM rotation in an OU. An OM rotation in a protocol-driven ED OU gives residents experience managing patients in this setting and improves skills integral to EM and part of the EM milestones and Accreditation Council for Graduate Medical Education (ACGME) core competencies: reassessment, disposition decision making, risk stratification, team management, and practicing cost-appropriate care. Even without a formal rotation, multiple OM educational resources can be incorporated into EM resident education and didactics. Education research opportunity exists. Conclusions This panel believes that OM is an important component of EM that should be incorporated into EM residency as the knowledge and skills learned such as risk stratification, disposition decision making, and team management augment those needed for the practice of EM. There is a distinct opportunity for EM educators to better equip their trainees for a career in EM by including OM education and experience in EM residency training.

Purpose: To quantitatively predict the impact of cardiopulmonary dose on overall survival (OS) after radiotherapy for locally advanced non–small cell lung cancer. Experimental Design: We used the NRG Oncology/RTOG 0617 dataset. The model building procedure was preregistered on a public website. Patients were split between a training and a set-aside validation subset (N = 306/131). The 191 candidate variables covered disease, patient, treatment, and dose-volume characteristics from multiple cardiopulmonary substructures (atria, lung, pericardium, and ventricles), including the minimum dose to the hottest x% volume (Dx%[Gy]), mean dose of the hottest x% (MOHx%[Gy]), and minimum, mean (Mean[Gy]), and maximum dose. The model building was based on Cox regression and given 191 candidate variables; a Bonferroni-corrected P value threshold of 0.0003 was used to identify predictors. To reduce overreliance on the most highly correlated variables, stepwise multivariable analysis (MVA) was repeated on 1000 bootstrapped replicates. Multivariate sets selected in ≥10% of replicates were fit to the training subset and then averaged to generate a final model. In the validation subset, discrimination was assessed using Harrell c-index, and calibration was tested using risk group stratification. Results: Four MVA models were identified on bootstrap. The averaged model included atria D45%[Gy], lung Mean[Gy], pericardium MOH55%[Gy], and ventricles MOH5%[Gy]. This model had excellent performance predicting OS in the validation subset (c = 0.89). Conclusions: The risk of death due to cardiopulmonary irradiation was accurately modeled, as demonstrated by predictions on the validation subset, and provides guidance on the delivery of safe thoracic radiotherapy.

Introduction: Neurovascular lesions are rare and understudied in the pediatric population. Their initial presentation can range from seizures to focal neurologic deficits, as well as headaches. The goal of this study was to examine the clinical presentation and natural history of neurovascular lesions in children with epilepsy. Methods: We reviewed all pediatric epilepsy patients with neurovascular lesions diagnosed between 2006 and 2018 at the University of Alberta and the Stollery Children’s Hospital, Edmonton, Canada. Initial clinical presentation and brain imaging, as well as long-term epilepsy and postsurgical outcome, were assessed. Results: Of the 14 patients, 10 patients had an initial presentation of focal seizures with impaired awareness, whereas 2 patients presented with headache, 1 presented with visual field defects as well as chronic headaches, and 1 with decreased level of consciousness. Seven patients had cavernous angiomas, 6 had arteriovenous malformation, and 1 patient had an arteriovenous fistula. Notably, all patients with cavernous angiomas and 4 of 6 patients with arteriovenous malformations presented with seizures. Among 9 of the 14 who underwent neurovascular corrective surgery, all 9 patients required long-term antiepileptic treatment of at least 1 antiepileptic drug for seizure control after the operation. Conclusion: In this novel case series, we describe focal seizures as the initial presentation of pediatric neurovascular lesions. This clinical presentation appears to be independent of the type of neurovascular lesion. Furthermore, unlike our pediatric surgical patients with epilepsy due to other causes, seizure freedom following neurovascular surgery is limited, and patients require long-term antiepileptic treatment.

1.Ecological patterns and processes often take place within linear-feature networks, and this has implications when analysing the spatial configuration of such patterns or processes across a landscape. 2.One such pattern is use of landscapes by human recreationists: an important variable in animal habitat selection and behaviour. Due to the difficulty in obtaining data, ecologists tend to use coarse metrics such as linear feature density, while the extent and timing of human activity is often ignored. Remote detector equipment and its increasing use in ecological studies allows for large volumes of data on human activity to be collected. However, the analysis of these data still can be challenging. 3.Using a combination of Generalised Linear Mixed Effects models and network-based Ordinary Kriging, we developed a method for estimating spatial and temporal variation in motorised and non-motorised activity across a complex linear-feature network. Trail cameras were set up between 2012-2014 and monitored motorised and non-motorised activity at 238 different trail sites across a 2,824km2 region of the eastern slopes and foothills of central Alberta's Rocky Mountains. 4.We evaluate the predictive capacity of this approach, demonstrate its application and discuss its merits and limitations. This method offers a straightforward analysis that can be applied to remotely acquired data to give a useful metric for assessing wildlife responses to human activity, and has potential application beyond the highlighted example. This article is protected by copyright. All rights reserved.

Purpose To present the 1-year follow-up of a novel surgical technique that allows for suture fixation of a posteriorly dislocated lens-bag complex without the need for conjunctival incision. Methods A retrospective chart review of 19 patients who underwent posterior chamber intraocular lens rescue using the novel surgical technique was performed. Data were collected 1 year after surgery for all patients. Results Average preoperative vision was 20/500, whereas 3 months and 12 months postoperatively, the vision was 20/65 and 20/54, respectively. Three of 15 eyes had decentration of the sutured intraocular lens, 2 of which required additional surgical repair. Conclusion Outcome data at 1 year support this novel technique as a viable option for the surgical repair of a dislocated lens-capsular bag complex.

The role of observation services for emergency department patients has increased in recent years. Driven by changing health care practices and evolving payer policies, many hospitals in the United States currently have or are developing an observation unit (OU) and emergency physicians are most often expected to manage patients in this setting. Yet, few residency programs dedicate a portion of their clinical curriculum to observation medicine. This knowledge set should be integrated into the core training curriculum of emergency physicians. Presented here is a model observation medicine longitudinal training curriculum, which can be integrated into an emergency medicine (EM) residency. It was developed by a consensus of content experts representing the observation medicine interest group and observation medicine section, respectively, from EM's two major specialty societies: the Society for Academic Emergency Medicine (SAEM) and the American College of Emergency Physicians (ACEP). The curriculum consists of didactic, clinical, and self-directed elements. It is longitudinal, with learning objectives for each year of training, focusing initially on the basic principles of observation medicine and appropriate observation patient selection; moving to the management of various observation appropriate conditions; and then incorporating further concepts of OU management, billing, and administration. This curriculum is flexible and designed to be used in both academic and community EM training programs within the United States. Additionally, scholarly opportunities, such as elective rotations and fellowship training, are explored.

Three pseudophakic patients presented with recurrent, unilateral vitreous hemorrhage, one of which also had uveitis, glaucoma, and hyphema, consistent with “uveitis–glaucoma–hyphema (UGH)-Plus” syndrome. Arcuate transillumination defects secondary to inadvertent placement of 1 intraocular lens (IOL) haptic in the sulcus were identified in each case. The second haptic and optic were located in the capsular bag. The IOLs were all single-piece foldable acrylic lenses with square-edge haptic design. Surgical repositioning of the malpositioned haptic from the sulcus to the retrocapsular space resulted in the resolution of the recurrent vitreous hemorrhage. This series highlights the fact that recurrent vitreous hemorrhage secondary to iris chafing, with or without UGH, may occur in cases where a square-edge IOL haptic is placed in the sulcus. Vitrectomy with repositioning of the malpositioned IOL is a simple alternative to IOL exchange in these cases.

Purpose To report a case of acute macular neuroretinopathy occurring after intravitreal ranibizumab injection for diabetic macular edema. Methods Observational clinical case report. Results The patient received an intravitreal ranibizumab (0.3 mg) injection for diabetic macular edema. Three days later, he had a decline in vision associated with a central and paracentral scotoma. Optical coherence tomography (OCT) demonstrated bandlike hyperreflectivity of the outer nuclear and plexiform layers corresponding to the patient's scotoma, consistent with the diagnosis of acute macular neuroretinopathy. There was spontaneous resolution of the abnormalities observed in optical coherence tomography, but only partial resolution of the scotoma was observed 4 months after presentation. Conclusion Diabetic retinopathy may be associated with acute macular neuroretinopathy. The temporal relationship between ranibizumab injection and the onset of acute macular neuroretinopathy in this case report raises the possibility of a causal relationship.

Author(s): Osborne, Anwar D.; Wheatley, Matthew A.; Baugh, Christopher W.; Granovsky, Michael | Abstract: Emergency Physicians provide ongoing care to psychiatric patients beyond the confines of a standard emergency room visit. Often, when we identify patients who need specialty psychiatric care, patients board in the emergency department awaiting acceptance and transfer to an outside facility. Even in cases where it has taken multiple days to complete the transfer, it has been unclear how to properly obtain reimbursement for this care. We discuss a new coding clarification that may provide a pathway to improve part of this situation.

Background The Emergency Department (ED) frequently treats patients with drug overdoses and is an important resource for individuals with opioid use disorder who are seeking treatment. Initiating medication-assisted treatment (MAT) in the ED seems to be an effective way to link patients with opioid use disorder (OUD) to treatment programs. There is ongoing discussion on the best approach to MAT in the ED setting. Objective Describe a new model for managing OUD in the ED. Method Information was obtained retrospectively from the electronic medical records of patients seen in a large county tertiary care center’s Clinical Decision Unit (CDU) for OUD between September 1, 2017 and February 6, 2018. Data were summarized descriptively. Results There were 18 different patients placed in the CDU during the study period. Ninety-five percent were induced with buprenorphine-naloxone in the CDU. The median initial Clinical Opioid Withdrawal Scale score at the time of induction was 10. The median total dose of buprenorphine-naloxone that was administered was 8/2 mg. The median amount of time spent in the CDU and ED combined was 23 h. Approximately (12/19) 63% of subjects went to their initial follow-up appointment in clinic. Nine were still active in clinic at 30 days and 4 were active at 6 months. Conclusions This retrospective chart review shows promising preliminary data for managing OUD in an ED CDU. Such strategies have the potential to increase access to care in a vulnerable patient population.

There are approximately 52,000 visits a year to emergency departments for patients presenting with jaundice. While many of these patients will not have immediately life-threatening pathology, it is essential that the emergency clinician understands the pathophysiology of jaundice, as this will guide the appropriate workup to detect critical diagnoses. Patients who present with jaundice could require intravenous antibiotics, emergent surgery, and, in severe cases, organ transplantation. This issue will focus on the challenge of evaluating and treating the jaundiced patient in the ED using the best available evidence from the literature. [PointsPearls is a digest of Emergency Medicine Practice.].

There are approximately 52,000 visits a year to emergency departments for patients presenting with jaundice. While many of these patients will not have immediately life-threatening pathology, it is essential that the emergency clinician understands the pathophysiology of jaundice, as this will guide the appropriate workup to detect critical diagnoses. Patients who present with jaundice could require intravenous antibiotics, emergent surgery, and, in severe cases, organ transplantation. This issue will focus on the challenge of evaluating and treating the jaundiced patient in the ED using the best available evidence from the literature.

Observation Services (OS) was founded by emergency physicians in an attempt to manage "boarding" issues faced by emergency departments throughout the United States. As a result, OS have proven to be an effective strategy in reducing costs and decreasing lengths of stay while improving patient outcomes. When OS are appropriately leveraged for maximum efficiency, patients presenting to emergency departments with common disease processes can be effectively treated in a timely manner. A well-structured observation program will help hospitals reduce the number of inappropriate, costly inpatient admissions while avoiding the potential of inappropriate discharges. Observation medicine is a complicated multidimensional issue that has generated much confusion. This service is designed to provide the best possible patient care in a value-based purchasing environment where quality, cost, and patient satisfaction must continually be addressed. Observation medicine is a service not a status. Therefore, patients are admitted to the service as outpatients no matter whether they are placed in a virtual or dedicated observation unit. The key to a successful observation program is to determine how to maximize efficiencies. This white paper provides the reader with the foundational guidance for observational services. It defines how to set up an observational service program, which diagnoses are most appropriate for admission, and what the future holds. The goal is to help care providers from any hospital deliver the most appropriate level of treatment, to the most appropriate patient, in the most appropriate location while controlling costs.

Observation units are dedicated areas in the hospital to deliver care to patients in observation status-those too risky to be immediately discharged following an emergency department evaluation but also clearly not in need of an inpatient admission. Observation units have been commonplace for several decades but in recent years some hospitals have begun to operate an additional observation unit with a distinct care delivery model and patient population.We conducted a survey between June 2014 and December 2014 to determine the prevalence and key operational characteristics of second level observation units in the US. We accessed the list serve of a large specialty organization to reach leaders likely to be directly operating or aware of the presence of a second level unit in their hospital.We received 28 responses (response rate of approximately 10%). We found 8 second level OUs, with respondents able to provide detailed data for 6 of them. All were established within the past 5 years.Second level observation units are still relatively uncommon but are emerging as an extension of hospital-based observation services as an additional resource to cohort observation patients into a dedicated unit. These units share some similarities with traditional OUs, such as the nursing ratio of approximately 4:1 and the preponderance of chest pain pathways; however, they also differ in important ways around key metrics, such as length of stay, attending staffing coverage, and rate of subsequent inpatient admission. Additional study is needed both to fully characterize these units and their potential benefits.

Plant resistance genes typically encode proteins with nucleotide binding site-leucine rich repeat (NLR) domains. Here we show that Ptr is an atypical resistance gene encoding a protein with four Armadillo repeats. Ptr is required for broad-spectrum blast resistance mediated by the NLR R gene Pi-ta and by the associated R gene Pi-ta2. Ptr is expressed constitutively and encodes two isoforms that are mainly localized in the cytoplasm. A two base pair deletion within the Ptr coding region in the fast neutron-generated mutant line M2354 creates a truncated protein, resulting in susceptibility to M. oryzae. Targeted mutation of Ptr in a resistant cultivar using CRISPR/Cas9 leads to blast susceptibility, further confirming its resistance function. The cloning of Ptr may aid in the development of broad spectrum blast resistant rice., Genes that confer resistance to plant pathogens such as rice blast disease typically encode NLR-type receptor proteins. Here, Zhao et al. describe a new resistance locus that encodes a non-NLR Armadillo repeat protein required for broad-spectrum resistance in rice.

The CRISPR/Cas9 system is a prevalent and versatile genome-editing tool of choice for basic and applied biological research. An exchange of a 20-bp spacer sequence in the gRNA can easily reprogram Cas9 to target a different DNA site. By expressing or providing multiple gRNAs, the system also enables multiplex genome editing at high efficiencies. Current approaches for providing multiple gRNAs in vivo include the use of multigene cassettes to express several gRNAs, Csy4-based excision, arrays of crRNAs, ribozyme-flanked gRNAs, tRNA-dependent cleavage of gRNAs, and direct introduction of Cas9 proteins preloaded with different gRNAs. By simultaneously targeting multiple DNA sequences, multiplex genome editing can be used to knockout multiple genes or delete chromosomal fragments. Off-target risk can also be reduced by Cas9-dimers that require the simultaneous expression of two gRNAs. With multiple gRNAs, specific gene expression or methylation status can be efficiently controlled by dCas9 fused to activators, repressors, methyltransferase, demethylase, or other functional domains. As a result, multiplex genome editing is expected to accelerate functional discovery of plant genes as well as genetic improvement of agricultural crops.

Immune mechanisms have been increasingly recognized in the pathogenesis of hippocampal sclerosis (HS), but infiltration of cytotoxic T-cells and its pathological significance in patients with HS has not been explored. We examined 30 cases of surgically resected hippocampi, including 16 International League Against Epilepsy (ILAE) type 1, 9 ILAE type 2, 1 ILAE type 3 HS, and 4 ILAE No-HS, as well as 6 autopsy No-HS hippocampi. The HS hippocampi showed sparse to scattered CD8-positive T-cells, rare CD4-positive T-cells, and a modest increase in CD68-positive microglia/macrophages, which were significantly more numerous than those in the No-HS controls. The infiltration of CD8-positive T-cells was significantly greater in the CA1 subfield than other subfields of type 1 and type 2 HS. The numbers of CD8-positive T-cells positively correlated with those of CD4-positive T-cells; there was a lower ratio of CD4/CD8-positive T-cells. There were positive correlations between these cells and scores of neuronal loss but no significant correlation between the infiltration of these cells and epilepsy disease duration or age of epilepsy onset. These findings suggest that an autoimmune process may be involved in the pathogenesis of HS and infiltration of immune cells, particularly CD8-positive cytotoxic T-cells, may contribute to neuronal loss in HS.

The CRISPR/Cas9 system is a prevalent and versatile genome-editing tool of choice for basic and applied biological research. An exchange of a 20-bp spacer sequence in the gRNA can easily reprogram Cas9 to target a different DNA site. By expressing or providing multiple gRNAs, the system also enables multiplex genome editing at high efficiencies. Current approaches for providing multiple gRNAs in vivo include the use of multigene cassettes to express several gRNAs, Csy4-based excision, arrays of crRNAs, ribozyme-flanked gRNAs, tRNA-dependent cleavage of gRNAs, and direct introduction of Cas9 proteins preloaded with different gRNAs. By simultaneously targeting multiple DNA sequences, multiplex genome editing can be used to knockout multiple genes or delete chromosomal fragments. Off-target risk can also be reduced by Cas9-dimers that require the simultaneous expression of two gRNAs. With multiple gRNAs, specific gene expression or methylation status can be efficiently controlled by dCas9 fused to activators, repressors, methyltransferase, demethylase, or other functional domains. As a result, multiplex genome editing is expected to accelerate functional discovery of plant genes as well as genetic improvement of agricultural crops.

Purpose: To identify changes in intraocular pressure (IOP) after vitreoretinal surgical procedures in eyes that received either difluprednate ophthalmic emulsion 0.05% (DP) or prednisolone acetate ophthalmic suspension 1% (PA). Methods: A retrospective chart review compared a consecutive series of 100 patients who received DP with 100 patients who received PA after vitreoretinal surgery. Data were collected for a 3-month period from the time of surgery. Results: A significantly higher number of patients treated with DP (35%, n = 35) developed increased IOP (>21 mmHg with a change from baseline of >10 mmHg) compared with those receiving PA (22%, n = 22) (P = 0.042). The mean maximum IOP in the DP cohort (26.7 mmHg) was significantly higher than that in the PA cohort (22.8 mmHg) (P = 0.0027). Additionally, the rise in IOP from baseline was significantly higher in the DP-treated cohort (9.0 mmHg) than that in the PA-treated cohort (6.0 mmHg) (P = 0.027). Conclusion: Eyes treated with DP after vitreoretinal surgery were at increased risk for developing clinically significant increases in IOP compared with those receiving PA.

Conservation programs often manage populations indirectly through the landscapes in which they live. Empirically, linking reproductive success with landscape structure and anthropogenic change is a first step in understanding and managing the spatial mechanisms that affect reproduction, but this link is not sufficiently informed by data. Hierarchical multistate occupancy models can forge these links by estimating spatial patterns of reproductive success across landscapes. To illustrate, we surveyed the occurrence of grizzly bears (Ursus arctos) in the Canadian Rocky Mountains Alberta, Canada. We deployed camera traps for 6 weeks at 54 surveys sites in different types of land cover. We used hierarchical multistate occupancy models to estimate probability of detection, grizzly bear occupancy, and probability of reproductive success at each site. Grizzly bear occupancy varied among cover types and was greater in herbaceous alpine ecotones than in low-elevation wetlands or mid-elevation conifer forests. The conditional probability of reproductive success given grizzly bear occupancy was 30% (SE = 0.14). Grizzly bears with cubs had a higher probability of detection than grizzly bears without cubs, but sites were correctly classified as being occupied by breeding females 49% of the time based on raw data and thus would have been underestimated by half. Repeated surveys and multistate modeling reduced the probability of misclassifying sites occupied by breeders as unoccupied to