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The Back‐Projection Algorithm (BPA) is a time‐domain‐matched filtering technique to form synthetic aperture radar (SAR) images. To produce high‐quality BPA images, precise navigation data for the radar platform must be known. Errors in position, velocity, or attitude result in improperly formed images that are corrupted by shifting and blurring. The contribution of this paper is the development of analytical expressions that characterise the relationship between navigation errors and image formation errors from an inertial navigation point of view, where trajectory estimation errors in position, velocity, and attitude propagate through time and cause compounding errors in the vehicle state vector. These analytical expressions are verified via simulated image formation and real‐data image formation.

Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) is a pathogenic coronavirus causing COVID‐19 infection. The interaction between the SARS‐CoV‐2 spike protein and the human receptor angiotensin‐converting enzyme 2, both of which contain several cysteine residues, is impacted by the disulfide‐thiol balance in the host cell. The host cell redox status is affected by oxidative stress due to the imbalance between the reactive oxygen/nitrogen species and antioxidants. Recent studies have shown that Vitamin D supplementation could reduce oxidative stress. It has also been proposed that vitamin D at physiological concentration has preventive effects on many viral infections, including COVID‐19. However, the molecular‐level picture of the interplay of vitamin D deficiency, oxidative stress, and the severity of COVID‐19 has remained unclear. Herein, we present a thorough review focusing on the possible molecular mechanism by which vitamin D could alter host cell redox status and block viral entry, thereby preventing COVID‐19 infection or reducing the severity of the disease.

β-phase gallium oxide (Ga2O3) is an emerging ultrawide bandgap (UWBG) semiconductor (EG ∼ 4.8 eV), which promises generational improvements in the performance and manufacturing cost over today's commercial wide bandgap power electronics based on GaN and SiC. However, overheating has been identified as a major bottleneck to the performance and commercialization of Ga2O3 device technologies. In this work, a novel Ga2O3/4H-SiC composite wafer with high heat transfer performance and an epi-ready surface finish has been developed using a fusion-bonding method. By taking advantage of low-temperature metalorganic vapor phase epitaxy, a Ga2O3 epitaxial layer was successfully grown on the composite wafer while maintaining the structural integrity of the composite wafer without causing interface damage. An atomically smooth homoepitaxial film with a room-temperature Hall mobility of ∼94 cm2/Vs and a volume charge of ∼3 × 1017 cm-3 was achieved at a growth temperature of 600 °C. Phonon transport across the Ga2O3/4H-SiC interface has been studied using frequency-domain thermoreflectance and a differential steady-state thermoreflectance approach. Scanning transmission electron microscopy analysis suggests that phonon transport across the Ga2O3/4H-SiC interface is dominated by the thickness of the SiNx bonding layer and an unintentionally formed SiOx interlayer. Extrinsic effects that impact the thermal conductivity of the 6.5 μm thick Ga2O3 layer were studied via time-domain thermoreflectance. Thermal simulation was performed to estimate the improvement of the thermal performance of a hypothetical single-finger Ga2O3 metal-semiconductor field-effect transistor fabricated on the composite substrate. This novel power transistor topology resulted in a ∼4.3× reduction in the junction-to-package device thermal resistance. Furthermore, an even more pronounced cooling effect is demonstrated when the composite wafer is implemented into the device design of practical multifinger devices. These innovations in device-level thermal management give promise to the full exploitation of the promising benefits of the UWBG material, which will lead to significant improvements in the power density and efficiency of power electronics over current state-of-the-art commercial devices.

We report detection of severe acute respiratory syndrome coronavirus 2 Omicron variant (B.1.1.529) in an asymptomatic, fully vaccinated traveler in a quarantine hotel in Hong Kong, China. The Omicron variant was also detected in a fully vaccinated traveler staying in a room across the corridor from the index patient, suggesting transmission despite strict quarantine precautions.

The inflammatory response to joint injury, specifically intra-articular fracture, has been implicated in post-traumatic arthritis development. However, the role of T cells in regulating the development of post-traumatic arthritis is unclear. We hypothesized that the absence of T cells would lead to less severe post-traumatic arthritis following intra-articular fracture. T cell-deficient, athymic Nude and wild-type C57BL/6NJ mice were assessed at 8 weeks following closed articular fracture. Joints were assessed using histologic scores of arthritis, synovitis, and bone morphology via microCT. Cells were profiled in whole blood via flow cytometry, and plasma and synovial fluid derived cytokines quantified by multiplex analysis. Compared to C57BL/6NJ mice, Nude mice had significantly greater histologic evidence of arthritis and synovitis. Whole blood immune cell profiling revealed a lower percentage of dendritic cells but higher natural killer (NK) cells in Nude mice. Concurrently, Nude mice had significantly higher levels of NK cells in synovial tissue. Concentrations of plasma IL-1β and TNF-α, and synovial fluid IL-12, IL-17, and IL-6 in both knees were greater in Nude mice. Outcomes of this study suggest that T cells may play a protective regulatory role against the development of post-traumatic arthritis. Statement of Clinical Significance: Lack of functional T cells exacerbated the development of post-traumatic arthritis following intra-articular fracture suggesting that critical regulators of the immune responses, contained within the T cell population, are required for protection. Future research identifying the specific T cell subsets responsible for modulating disease immunopathogenesis will lead to new therapeutic targets to mitigate post-traumatic arthritis. This article is protected by copyright. All rights reserved.

To limit introduction of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), the United States restricted travel from China on February 2, 2020, and from Europe on March 13. To determine whether local transmission of SARS-CoV-2 could be detected, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) conducted deidentified sentinel surveillance at six NYC hospital emergency departments (EDs) during March 1-20. On March 8, while testing availability for SARS-CoV-2 was still limited, DOHMH announced sustained community transmission of SARS-CoV-2 (1). At this time, twenty-six NYC residents had confirmed COVID-19, and ED visits for influenza-like illness* increased, despite decreased influenza virus circulation.† The following week, on March 15, when only seven of the 56 (13%) patients with known exposure histories had exposure outside of NYC, the level of community SARS-CoV-2 transmission status was elevated from sustained community transmission to widespread community transmission (2). Through sentinel surveillance during March 1-20, DOHMH collected 544 specimens from patients with influenza-like symptoms (ILS)§ who had negative test results for influenza and, in some instances, other respiratory pathogens.¶ All 544 specimens were tested for SARS-CoV-2 at CDC; 36 (6.6%) tested positive. Using genetic sequencing, CDC determined that the sequences of most SARS-CoV-2-positive specimens resembled those circulating in Europe, suggesting probable introductions of SARS-CoV-2 from Europe, from other U.S. locations, and local introductions from within New York. These findings demonstrate that partnering with health care facilities and developing the systems needed for rapid implementation of sentinel surveillance, coupled with capacity for genetic sequencing before an outbreak, can help inform timely containment and mitigation strategies.

This guidance focuses on methodological aspects of lupus anticoagulant (LA) testing, as well as interpretation of results for clinicians. The main changes in how to test for LA compared with the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee 2009 guidelines, in the preanalytical phase are more detailed recommendations on how to handle testing in anticoagulated patients, and the timing of testing. Also, routine coagulation tests are advised to obtain more information on the coagulation background of the patient, and when necessary, anti-Xa activity measurement for heparins or specific assays for direct oral anticoagulants should be performed. The three-step procedure with two test systems (diluted Russell's viper venom time and activated partial thromboplastin time [aPTT]) is essentially not changed. Silica remains the preferable activator in the aPTT assays, but ellagic acid is not excluded. We advise simultaneous performance of the mixing and confirmatory step, in each sample with a prolonged screening test. The confirmatory step can also be performed on a mixture of patient plasma and normal pooled plasma. Cutoff values should be established in-house on at least 120 normals, with transference of the manufacturer's cutoffs as an alternative. Reporting of results has not been changed, although more attention is focused on what clinicians should know. Patient selection for LA testing has been expanded.

Background Isolated regional recurrences following head-neck squamous-cell carcinomas (HNSCC) are often accessible for curatively intended salvage treatment. Factors prognostic for outcome were investigated in a large cohort of HNSCC patients. Methods In total, 1811 patients receiving curatively intended radiotherapy from 2007 to 2017 were reviewed and isolated cervical nodal recurrences were identified. Factors associated with survival and second recurrence were investigated using univariate and multivariate analyses. Results Isolated regional recurrence was seen in 95/1811 (5.2%) patients. Eighty of 95 patients (84%) received salvage surgery. Two-year survival after isolated regional recurrence was 40%. Overall survival (OS) and time to second recurrence were associated with resection status of the salvage surgery and presence of extranodal spread (ENS), while p16-positive oropharyngeal squamous-cell carcinoma (OPSCC) was associated with better OS. Conclusion Long-term survival after regional recurrence in HNSCC is possible. p16-positive OPSCC, complete salvage surgery, and lack of ENS are associated with better outcome.

When higher education moved online this past spring because of the outbreak of the novel coronavirus, few faculty or administrators had time to stop and ponder the intellectual property?related questions regarding remote instruction Do faculty own materials used when teaching remotely, or does the university (as employer and software provider) have a claim? Can faculty use material protected by copyright in a remote-learning course? What's the role of university IP policies? Who owns class recordings?

This paper introduces a new algorithm for estimating the relative pose of a moving camera using consecutive frames of a video sequence. State-of-the-art algorithms for calculating the relative pose between two images use matching features to estimate the essential matrix. The essential matrix is then decomposed into the relative rotation and normalized translation between frames. To be robust to noise and feature match outliers, these methods generate a large number of essential matrix hypotheses from randomly selected minimal subsets of feature pairs, and then score these hypotheses on all feature pairs. Alternatively, the algorithm introduced in this paper calculates relative pose hypotheses by directly optimizing the rotation and normalized translation between frames, rather than calculating the essential matrix and then performing the decomposition. The resulting algorithm improves computation time by an order of magnitude. If an inertial measurement unit &#x0028 IMU &#x0029 is available, it is used to seed the optimizer, and in addition, we reuse the best hypothesis at each iteration to seed the optimizer thereby reducing the number of relative pose hypotheses that must be generated and scored. These advantages greatly speed up performance and enable the algorithm to run in real-time on low cost embedded hardware. We show application of our algorithm to visual multi-target tracking &#x0028 MTT &#x0029 in the presence of parallax and demonstrate its real-time performance on a 640 &#x00D7 480 video sequence captured on a UAV.

BACKGROUND: Total ankle arthroplasty (TAA) is becoming a more prevalent treatment for end-stage ankle arthritis. However, the effects of malalignment on TAA remain poorly understood. QUESTIONS/PURPOSES: The purpose of this study was to quantify the mechanical effects of coronal plane malalignment of the tibial insert in TAA using cadaveric gait simulation. Specifically, we asked, is there a change in (1) ankle joint congruency, (2) kinematic joint position, (3) kinematic ROM, (4) peak plantar pressure, and (5) center of pressure with varus and valgus malalignment? METHODS: A modified TAA was implanted into seven cadaveric foot specimens. Wedges were used to simulate coronal plane malalignment of the tibial insert. The degree of malalignment (tibial insert angle [TIA] and talar component angle [TCA]) was quantified radiographically for neutral and 5°, 10°, and 15° varus and valgus wedges. Dynamic walking at 1/6 of physiological speed was simulated using a robotic gait simulator. A motion capture system was used to measure foot kinematics, and a pressure mat was used to measure plantar pressure. Joint congruency was quantified as the difference between TIA and TCA. Continuous joint position, joint ROM, peak plantar pressure, and center of pressure for varus and valgus malalignment compared with neutral alignment were estimated using linear mixed effects regression. Pairwise comparisons between malalignment conditions and neutral were considered significant if both the omnibus test for the overall association between outcome and malalignment and the individual pairwise comparison (adjusted for multiple comparisons within a given outcome) had p ≤ 0.05. RESULTS: Descriptively, the TIA and TCA were both less pronounced than the wedge angle and component incongruence was seen (R(2) = 0.65; p < 0.001). Varus malalignment of the tibial insert shifted the tibiotalar joint into varus and internally rotated the joint. The tibiotalar joint’s ROM slightly increased as the TIA shifted into varus (1.3 ± 0.7° [mean ± SD] [95% confidence interval -0.7 to 3.4]; p = 0.03), and the first metatarsophalangeal joint’s ROM decreased as the TIA shifted into varus (-1.9 ± 0.9° [95% CI -5.6 to 1.7]; p = 0.007). In the sagittal plane, the naviculocuneiform joint’s ROM slightly decreased as the TIA shifted into varus (-0.9 ± 0.4° [95% CI -2.1 to 0.3]; p = 0.017). Hallux pressure increased as the TIA became more valgus (59 ± 50 kPa [95% CI -88 to 207]; p = 0.006). The peak plantar pressure slightly decreased in the third and fourth metatarsals as the TIA shifted into valgus (-15 ± 17° [95% CI -65 to 37]; p = 0.03 and -8 ± 4° [95% CI -17 to 1]; p = 0.048, respectively). The fifth metatarsal’s pressure slightly decreased as the TIA shifted into valgus (-18 ± 12 kPa [95% CI -51 to 15]) or varus (-7 ± 18 kPa [95% CI -58 to 45]; p = 0.002). All comparisons were made to the neutral condition. CONCLUSIONS: In this cadaver study, coronal plane malalignment in TAA altered foot kinematics and plantar pressure. In general, varus TAA malalignment led to varus shift and internal rotation of the tibiotalar joint, a slight increase in the tibiotalar ROM, and a slight decrease in the first metatarsophalangeal ROM, while a valgus TAA malalignment was manifested primarily through increased hallux pressure with a slight off-loading of the third and fourth metatarsals. CLINICAL RELEVANCE: This study may increase our understanding of the biomechanical processes that underlie the unfavorable clinical outcomes (such as, poor patient-reported outcomes or implant loosening) that have been associated with coronal plane malalignment of the tibial component in TAA.

We demonstrate hydride vapor phase epitaxy (HVPE) of AlxGa1–xAs, AlxIn1–xP, and AlxGayIn1–x–yP using an AlCl3 precursor. We study the growth of the AlxGa1–xAs alloy system to elucidate the effects ...

Introduction Meningiomas are more common in females and frequently express progesterone and estrogen receptors. Recent studies have revealed a high incidence of meningiomas in situations in which estrogen/progesterone levels are increased such as pregnancy, gender reassignment therapy, and fertility treatment. While the relationship remains unclear and controversial, these findings suggest exposure to high levels of endogenous or exogenous hormones may increase the risk of developing a meningioma. Patients and Methods A 40-year-old female with a history of endometriosis treated with chronic progesterone therapy presented with a visual deficit and was found to have multiple meningiomas, which regressed after cessation of exogenous progesterone. Conclusion A history of chronic hormone therapy should be included when evaluating patients diagnosed with meningiomas, particularly at a younger age and with multiple meningiomas. Cessation of exogenous progesterone resulting in regression of meningiomas suggests a direct action of progesterone on growth. Future studies are warranted to better elucidate this relationship.

IMPORTANCEPatients with localized squamous cell carcinoma of the anus (SCCA) who experience treatment toxicity or recurrences have few therapeutic options.Investigation into the microbiome’s influence on treatment toxicity or its potential use as a predictive biomarker in this rare disease could improve these patients’ outcomes.OBJECTIVETo longitudinally characterize the SCCA tumor microbiome and assess its association with treatment-related toxicities.DESIGNProspective cohort study.SETTINGSingle tertiary cancer center.PARTICIPANTSTwenty-two patients with biopsy-confirmed non-metastatic SCCA receiving standard-of-care chemoradiotherapy as part of an Institutional Review Board-approved study from April 2017 to July 2019.MAIN OUTCOMES AND MEASURESDiversity and taxonomic characterization of the SCCA microbiome throughout chemoradiotherapy using swab-based anorectal microbial specimen collection and 16S rRNA gene sequencing.RESULTSTwenty-two SCCA patients were included in this study with a median (range) age of 58.5 (39-77), and 18 (82%) were women. Alpha diversity remained relatively stable throughout chemoradiotherapy, except for decreases in the Chao1 (P=0.03) and Observed Features (P=0.03) indices at week 5 relative to baseline. Tumor microbial compositions measured using weighted UniFrac changed significantly by the end of treatment (P=0.03). Linear discriminant analysis effect sizes revealed differential enrichment of bacteria at specific time points, including the enrichment of Clostridia at both baseline and follow-up and the enrichment of Corynebacterium at week 5. Patients experiencing high toxicity at week 5 had higher relative abundances of Clostridia, Actinobacteria, and Clostridiales at baseline (P=0.03 for all).CONCLUSIONS AND RELEVANCEOur study presents the first longitudinal characterization of the SCCA microbiome throughout chemoradiation. The tumor microbiome undergoes significant changes during and after chemoradiotherapy, and patient-reported toxicity levels are associated with patients’ microbial profiles. Further studies into these microbial characterizations and associations are needed to elucidate the tumor microbiome’s role in predicting treatment-related outcomes for SCCA patients.Key PointsQUESTIONHow does the squamous cell anal tumor microbiome change during chemoradiotherapy, and how do these changes influence treatment-related toxicity?FINDINGSProspective longitudinal characterization of anal cancer patients revealed significant modulation of the local tumor microbiome in response to chemoradiotherapy including shifts in overall composition and differential enrichment of key taxa.Additionally, enrichment of specific taxa at baseline was associated with increased levels of treatment-related toxicities by the end of treatment.MEANINGThe anal tumor microbiome is significantly altered by chemoradiotherapy and could potentially serve as a biomarker for treatment-related toxicities.

Measles-containing vaccines (MCV), specifically vaccines against measles and rubella (MR), are extremely effective and critical for the eradication of measles and rubella diseases. In developed countries, vaccination rates are high and vaccines are readily available, but continued high prevalence of both diseases in developing countries and surges in measles deaths in recent years have highlighted the need to expand vaccination efforts. To meet demand for additional vaccines at a globally affordable price, it is highly desirable to streamline vaccine production thereby reducing cost and speeding up time to delivery. MR vaccine characterization currently relies on the 50% cell culture infectious dose (CCID50) assay, an endpoint assay with low reproducibility that requires 10-14 days to complete. For streamlining bioprocess analysis and improving measurement precision relative to CCID50, we developed the VaxArray Measles and Rubella assay kit, which is based on a multiplexed microarray immunoassay with a 5-hour time to result. Here we demonstrate vaccine-relevant sensitivity ranging from 345 – 800 IFU/mL up to 100,000 IFU/mL and specificity that allows simultaneous analysis in bivalent vaccine samples. The assay is sensitive to antigen stability and has minimal interference from common vaccine additives. The assay exhibits high reproducibility and repeatability, with 15% CV, much lower than the typical 0.3 log10 error (~65%) observed for the CCID50 assay. The intact protein concentration measured by VaxArray is reasonably correlated to, but not equivalent to, CCID50 infectivity measurements for harvest samples. However, the measured protein concentration exhibits equivalency to CCID50 for more purified samples, including concentrated virus pools and monovalent bulks, making the assay a useful new tool for same-day analysis of vaccine samples for bioprocess development, optimization, and monitoring.

M6620, a selective ATP-competitive inhibitor of the ATM and RAD3-related (ATR) kinase, is currently under investigation with radiation in patients with non–small cell lung cancer (NSCLC) brain metastases. We evaluated the DNA damage response (DDR) pathway profile of NSCLC and assessed the radiosensitizing effects of M6620 in a preclinical NSCLC brain metastasis model. Mutation analysis and transcriptome profiling of DDR genes and pathways was performed on NSCLC patient samples. NSCLC cell lines were assessed with proliferation, clonogenic survival, apoptosis, cell cycle, and DNA damage signaling and repair assays. NSCLC brain metastasis patient-derived xenograft models were used to assess intracranial response and overall survival. In vivo IHC was performed to confirm in vitro results. A significant portion of NSCLC patient tumors demonstrated enrichment of DDR pathways. DDR pathways correlated with lung squamous cell histology; and mutations in ATR, ATM, BRCA1, BRCA2, CHEK1, and CHEK2 correlated with enrichment of DDR pathways in lung adenocarcinomas. M6620 reduced colony formation after radiotherapy and resulted in inhibition of DNA DSB repair, abrogation of the radiation-induced G2 cell checkpoint, and formation of dysfunctional micronuclei, leading to enhanced radiation-induced mitotic death. The combination of M6620 and radiation resulted in improved overall survival in mice compared with radiation alone. In vivo IHC revealed inhibition of pChk1 in the radiation plus M6620 group. M6620 enhances the effect of radiation in our preclinical NSCLC brain metastasis models, supporting the ongoing clinical trial (NCT02589522) evaluating M6620 in combination with whole brain irradiation in patients with NSCLC brain metastases.

Developmental and epileptic encephalopathies (DEE) are a group of disorders associated with intractable seizures, brain development, and functional abnormalities, and in some cases, premature death. Pathogenic human germline biallelic mutations in tumor suppressor WW domain‐containing oxidoreductase (WWOX) are associated with a relatively mild autosomal recessive spinocerebellar ataxia‐12 (SCAR12) and a more severe early infantile WWOX‐related epileptic encephalopathy (WOREE). In this study, we generated an in vitro model for DEEs, using the devastating WOREE syndrome as a prototype, by establishing brain organoids from CRISPR‐engineered human ES cells and from patient‐derived iPSCs. Using these models, we discovered dramatic cellular and molecular CNS abnormalities, including neural population changes, cortical differentiation malfunctions, and Wnt pathway and DNA damage response impairment. Furthermore, we provide a proof of concept that ectopic WWOX expression could potentially rescue these phenotypes. Our findings underscore the utility of modeling childhood epileptic encephalopathies using brain organoids and their use as a unique platform to test possible therapeutic intervention strategies., Mutations in the human WWOX gene cause devastating developmental and neurological diseases in young children called WOREE syndrome and SCAR12 syndrome. Using both gene editing and reprogramming technologies these maladies can now be modeled in human brain organoids, allowing for molecular and electrophysiological study of the pathology, together with testing possible therapeutic interventions.

Purpose: Radiotherapy planning based only on positron emission tomography/magnetic resonance imaging (PET/MRI) lacks computed tomography (CT) information required for dose calculations. In this study, a previously developed deep learning model for creating synthetic CT (sCT) from MRI in patients with head and neck cancer was evaluated in 2 scenarios: (1) using an independent external dataset, and (2) using a local dataset after an update of the model related to scanner software-induced changes to the input MRI. Methods and Materials: Six patients from an external site and 17 patients from a local cohort were analyzed separately. Each patient underwent a CT and a PET/MRI with a Dixon MRI sequence over either one (external) or 2 (local) bed positions. For the external cohort, a previously developed deep learning model for deriving sCT from Dixon MRI was directly applied. For the local cohort, we adapted the model for an upgraded MRI acquisition using transfer learning and evaluated it in a leave-one-out process. The sCT mean absolute error for each patient was assessed. Radiotherapy dose plans based on sCT and CT were compared by assessing relevant absorbed dose differences in target volumes and organs at risk. Results: The MAEs were 78 ± 13 HU and 76 ± 12 HU for the external and local cohort, respectively. For the external cohort, absorbed dose differences in target volumes were within ± 2.3% and within ± 1% in 95% of the cases. Differences in organs at risk were

Elective surgical patients routinely bathe with chlorhexidine gluconate (CHG) at home days prior to their procedures. However, the impact of home CHG bathing on surgical site CHG concentration is unclear. We examined 3 different methods of applying CHG and hypothesized that different application methods would impact resulting CHG skin concentration.

People who engage in dirty work manage the stigma of their jobs by employing various narrative techniques that allow them to diminish the work’s negative attributes. Doing so enables them t...

Objective Accurate estimation of hyperopia and astigmatism is challenging in delayed children. Conventional skiascopy holds rows of increasing power ± lenses vertically in front of one eye. The school bus accommodation-relaxing skiascopy (SBA-RS) design holds child-friendly, lenses +1 to +10D horizontally so that a higher power fogs the nontested eye-relaxing accommodation without cycloplegia. Methods Design: Evaluation of diagnostic test. Subjects: Patients undergoing comprehensive eye examination in a pediatric ophthalmology practice. Cycloplegic (cyclopentolate 1%) retinoscopy was compared to dry SBA-RS and Retinomax (Righton, Japan) during pediatric eye examinations. Outcome measures: correlations, Chi-square and receiver operating characteristic (ROC) curve. Results Of 470 patients with a median age 6 years, 238 were under the age of 60 months and 110 had developmental delays. For those with cycloplegic spherical equivalent hyperopia over 0.7 D, median (90% CI) value for retinoscopy was +2.63 D (+0.75, +6.88), for SBA-RS was +2.50 D (+0.50, +6.75) and less for 184 with Retinomax +1.88 D (-1.56, +6.13) but similar despite delays. Astigmatic cylinder SBA-RS +1.50 D (+0.25, +4.00) lagged retinoscopy +1.75 D (+0.75,+4.50) but Retinomax was greater +2.00 D (+0.25, +4.64). Cycloplegic refractive components such as spherical equivalent, cylinder, and J0 and J45 power vectors correlated highly and were near unity with SBA-RS and Retinomax with the latter deviating greater. SBA-RS screened for amblyopia risk factors up to 92% sensitive and 94% specific. Conclusion Accommodation-relaxing horizontal skiascopy very precisely estimates astigmatism power and axis and only lags cycloplegic refraction by about 0.15D in hyperopic patients fairly independent of neurodevelopmental delay. This technique can quickly estimate refraction even in delayed patients potentially reducing some need for cycloplegia. Clinical trials registry NCT03668067.

Dolomite and a micronutrient fertilizer are routinely incorporated into a pine bark-based soilless substrate when producing containerized nursery crops, yet the effect of these amendments on phosphorus (P) is not well understood. The objective of this research was to determine the effect of dolomite and micronutrient fertilizer amendments on P partitioning among four P fractions (i.e., orthophosphate-P EOM non-orthophosphate dissolved P [NODP], total dissolved P [TDP], and particulate P (PPJ) and to model potential P species in leachate of pine bark substrate. Amendment treatments incorporated into bark at experiment initiation included (1) a control (no fertilizer, dolomite, or micronutrient fertilizer), (2) controlled-release fertilizer (CRF), (3) CRF and dolomite, (4) CRF and micronutrient fertilizer, or (5) CRF, dolomite, and micronutrient fertilizer. Phosphorus fractions in leachate of irrigated pine bark columns were determined at eight sampling times over 48 days. Amending pine bark with dolomite and micronutrient fertilizer reduced leachate OP concentrations by 70% when averaged across sampling dates primarily due to retention of OP in the substrate by dolomite. The NODP fraction was unaffected by amendments, and the response of TDP was similar to that of OP. Particulate P was present throughout the study and was strongly correlated particulate Fe and DOC concentrations. Visual MINTEQ indicated MnHPO4 and Ca-5(PO4)(3)(OH) were consistently saturated with respect to their solid phase in treatments containing CRF. Results of this study suggest amending pine bark with dolomite and micronutrients is a best management practice for reducing P leaching from containerized nurseries. Virginia Agricultural Experiment Station of the National Institute of Food and Agriculture [SCRI 2014-51181-22372]; Hatch Program of the National Institute of Food and Agriculture [SCRI 2014-51181-22372]; US Dep. of Agriculture; Horticultural Research Institute; Virginia Nursery and Landscape Association The authors thank Julie Brindley, Velva Groover, Anna Birnbaum, and Doug Sturtz for technical assistance, as well as Pacific Organics for donating pine bark for this research. Funding was provided by the Virginia Agricultural Experiment Station and the Hatch Program of the National Institute of Food and Agriculture (including SCRI 2014-51181-22372), the US Dep. of Agriculture, the Horticultural Research Institute, and the Virginia Nursery and Landscape Association. Public domain – authored by a U.S. government employee

Background Ultrasound has become a useful instrument in evaluating musculoskeletal pathology. Recent studies suggest that ultrasound imaging of weight-bearing menisci may enhance the assessment of knee pathology, such as osteoarthritis (OA) and meniscal injuries. Objective The primary aim of this study was to determine the intrarater and interrater reliability of ultrasound measurements of medial meniscal extrusion (MME) after a brief training session. Design Prospective reliability study. Setting Physical medicine and rehabilitation (PM&R) department within a tertiary care institution. Participants Forty-five participants (29 female, 16 male) were recruited to serve as models, 24 of whom had healthy knees and 21 of whom had radiographically confirmed medial compartment knee OA. Three physician sonographers (1 = experienced, 1 = sports medicine fellow, 1 = post-graduate year [PGY]-4 PM&R resident) were recruited to serve as operators. Methods or interventions Operators received a brief training session on identifying and measuring MME. All operators measured bilateral MME in each model in the standing and supine positions on two separate days. Operators were blinded to all measurements. Main outcome measurements Primary outcomes were inter- and intrarater intraclass correlation coefficients (ICCs) of MME measurements among operators with different levels of ultrasound experience. Results Supine MME intrarater reliability ICCs were 0.927, 0.885, and 0.780 for the experienced physician, sports medicine fellow, and PGY-4 operators, respectively. Standing MME intrarater reliability ICCs were 0.941, 0.902, and 0.824 for the experienced physician, sports medicine fellow, and PGY-4 operators, respectively. Interrater reliability ICCs were 0.896 and 0.842 for supine and standing measurements, respectively. There was a statistically significant increase in intrarater reliability with experience between the PGY-4 resident and experienced physician operators. Conclusions Operators with different levels of ultrasound experience demonstrated good MME measurement intra- and interrater reliabilities in both supine and standing positions.

The purpose of this study was to assess the use of 18F-FDG PET/CT scans for detecting distant metastases in patients with recurrent head and neck squamous cell carcinoma (HNSCC) and investigate the treatment and survival of patients with recurrence. In this retrospective study, consecutive head and neck cancer patients referred for FDG PET/CT scan between 2012 and 2014 were included. Patient records were reviewed and only patients with recurrence of HNSCC were enrolled for further analysis. Information on distant metastases, surgery and survival was collected. A Kaplan–Meier analysis was used to report survival. Overall 275 PET/CT scans were performed due to suspected recurrence, and in 166 scans (144 patients), recurrence of HNSCC was confirmed, making them eligible for further analysis. Distant metastases were revealed in 29.8% of the scans (n = 51) and the proportion of revealed metastases remained constant at approximately 30% each year. Although the number of performed scans increased twofold each year, there was no statistically significant change in the proportion of scans with distant metastasis (p = 0.55). The distant metastases were most often seen in the lungs (n = 44) and bone (n = 15). A few patients had widespread dissemination to other areas. Salvage surgery was performed following 81 of the 166 PET/CT scans. Seven of the patients who underwent salvage surgery had M-site oligo-metastases. Patients who underwent salvage surgery had a median survival of 22 months whereas patients not treated with salvage surgery had a median survival of 6 months. After 5 years, 21% of the patients selected for salvage surgery were alive. Distant metastases occur frequently in patients with recurrent HNSCC disease and the proportion of revealed distant metastases remained the same (30%). Imaging with FDG PET/CT can be recommended in patients with recurrent HNSCC prior to putative salvage surgery.

Intratumor heterogeneity may contribute to the ambiguous clinical results on PD-L1 status as a predictor for immunotherapy response in patients with HNSCC. This decreases the utility of PD-L1 expression from single tumour biopsies as a predictive biomarker. In this prospective study, intratumor heterogeneity of PD-L1 expression in HNSCC was investigated with both Tumour Proportion Score (TPS) and Combined Positive Score (CPS). Thirty-three whole surgical specimens from 28 patients with HNSCC were included. PD-L1 expression in six random core biopsies from each surgical specimen was used to assess the concordance between multiple biopsies and the negative predictive value of a single negative core biopsy. With 1% cut off, 36% of the specimens were concordant with TPS and 52% with CPS. With a 50% cut-off value the concordance was 70% with TPS and 55% with CPS. Defining a tumour as positive if just a single-one of the biopsies was positive, the negative predictive value (NPV) of a single negative core biopsy was 38.9 and 0% (1% cut off), and 79.9% and 62.8% (50% cut off) for TPS and CPS, respectively. In conclusion, PD-L1 positivity varies markedly within the tumour, both with TPS and CPS, challenging the utility of this biomarker.

Introduction In pregnancy, the presence of preeclampsia (PEC), systemic lupus erythematosus (SLE), and/or antiphospholipid antibody syndrome (APLS) is characterized by poor obstetric outcomes, with potential adverse effects for both mother and fetus. Although the histopathologic changes observed in these entities have been well established, the pathogenic mediators associated with tissue injury are poorly understood. Methods Forty placentas were evaluated, including 10 patients with preeclampsia, 9 with SLE, 11 with APLS, and 10 disease-free controls. Each case was subjected to a panel of immunohistochemical markers including C3b, C4d, Annexin A5, and C5b-9. Staining was graded on intensity and distribution. Results C4d staining was distinctly different among disease groups and controls. Moreover, 6/10 PEC cases, 3/9 SLE cases, and 4/11 APLS cases showed at least focal staining for C4d. All controls were negative. Annexin A5 (AnxA5) staining showed intrinsic variability in all disease groups, while 10/10 controls showed diffuse, strong staining (2+ or 3+). C3b staining was heterogeneous among groups. Discussion Previously, antiphospholipid antibody (aPLA)-associated pregnancy complications have been thought to be a consequence of a unique aPLA-mediated pathogenic mechanism. However, the immunohistochemical similarity (increased complement and decreased AnxA5 staining) observed in placentas from patients with APLS, PEC, and SLE suggests that aPLA-associated pregnancy complications may reflect a more general autoimmune mechanism.

Supplemental Digital Content is available in the text., Background: N6-Methyladenosine (m6A) methylation is the most prevalent internal posttranscriptional modification on mammalian mRNA. The role of m6A mRNA methylation in the heart is not known. Methods: To determine the role of m6A methylation in the heart, we isolated primary cardiomyocytes and performed m6A immunoprecipitation followed by RNA sequencing. We then generated genetic tools to modulate m6A levels in cardiomyocytes by manipulating the levels of the m6A RNA methylase methyltransferase-like 3 (METTL3) both in culture and in vivo. We generated cardiac-restricted gain- and loss-of-function mouse models to allow assessment of the METTL3-m6A pathway in cardiac homeostasis and function. Results: We measured the level of m6A methylation on cardiomyocyte mRNA, and found a significant increase in response to hypertrophic stimulation, suggesting a potential role for m6A methylation in the development of cardiomyocyte hypertrophy. Analysis of m6A methylation showed significant enrichment in genes that regulate kinases and intracellular signaling pathways. Inhibition of METTL3 completely abrogated the ability of cardiomyocytes to undergo hypertrophy when stimulated to grow, whereas increased expression of the m6A RNA methylase METTL3 was sufficient to promote cardiomyocyte hypertrophy both in vitro and in vivo. Finally, cardiac-specific METTL3 knockout mice exhibit morphological and functional signs of heart failure with aging and stress, showing the necessity of RNA methylation for the maintenance of cardiac homeostasis. Conclusions: Our study identified METTL3-mediated methylation of mRNA on N6-adenosines as a dynamic modification that is enhanced in response to hypertrophic stimuli and is necessary for a normal hypertrophic response in cardiomyocytes. Enhanced m6A RNA methylation results in compensated cardiac hypertrophy, whereas diminished m6A drives eccentric cardiomyocyte remodeling and dysfunction, highlighting the critical importance of this novel stress-response mechanism in the heart for maintaining normal cardiac function.

OBJECTIVES: The aims of this study were to report the risk of thyroid malignancy in cases of either benign fine-needle aspiration (FNA) or without FNA performed, and to investigate possible predictive factors for thyroid malignancy in a population with recent moderately low iodine intake. METHODS: All patients referred for thyroid surgery in a tertiary cancer centre between 2000 and 2016 were included (n = 3,703). After excluding cases indicating malignant histology, we included group 1: patients with benign FNA (n = 764), and group 2: patients without FNA (n = 740), leaving 1,504 eligible for further investigation. Information on age, gender, tracheal compression or dislocation, thyroid specimen weight, scintigraphy, ultrasound, medically treated thyrotoxicosis, serum stimulating thyroid hormone, indication for surgery, TNM classification, stage, and outcome were retrieved. RESULTS: The malignancy risk was 7.6% (58/764) in group 1 and 6.8% (50/740) in group 2. Patients with T2–4 tumours constituted 2.2% (33/1,504). In the combined groups, ultrasound verified that solitary solid tumour was predictive for malignancy (p = 0.01 by χ2, and OR = 1.69, p = 0.02 in multiple logistic regression). For group 1 patients, thyrotoxicosis (which in this case was medically treated) was a significant predictive factor for malignancy (p = 0.04). CONCLUSIONS: The risk of malignancy of 7.6% and 6.8% was high, considering that patients with malignant FNA, suspicious FNA, or clinical findings indicating malignancy were excluded, and 2.2% of these malignancies were stages T2–4. In cases with solitary solid tumour on ultrasound, the risk of malignancy should not be ignored, even with benign FNA.

The ability to effectively manage water resources to meet present and future human and environmental needs is essential. Such an ability necessitates a comprehensive understanding of hydrologic processes that affect streamflow at a watershed scale. In the United States, water-resources management at scales ranging from local to national can benefit from a nationally consistent, process-based watershed modeling capability to provide the requisite understanding. The National Hydrologic Model (NHM) infrastructure, which was developed by the U.S. Geological Survey to support coordinated, comprehensive, and consistent hydrologic modeling at multiple scales for the conterminous United States, provides this essential capability. NHM-based applications provide information to enable more effective water-resources planning and management, fill knowledge gaps in ungaged areas, and support basic scientific inquiry. In the future, as process algorithms and data sets improve, the NHM infrastructure will continue to evolve to better support the nation's water-resources research and management needs.

Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery.This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and inter-centre variation in critical care admission after emergency laparotomy.Of 4529 patients included, 37.8% (n=1713) underwent planned critical care admissions from theatre. Some 3.1% (n=86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n=133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51-19.97) than planned admissions (OR: 2.32, 95% CI: 1.43-3.85). Some 26.7% of patients (n=1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8-51.9%, P0.001) were predicted to have planned critical care admissions, with 7% (n=10/145) of centres outside the 95% CI.After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies.

Introduction: Thoracic ultrasound is frequently used in the emergency department (ED) to determine the etiology of dyspnea, yet its use is not widespread in the prehospital setting. We sought to investigate the feasibility and diagnostic performance of paramedic acquisition and assessment of thoracic ultrasound images in the prehospital environment, specifically for the detection of B-lines in congestive heart failure (CHF). Methods: This was a prospective observational study of a convenience sample of adult patients with a chief complaint of dyspnea. Paramedics participated in a didactic and hands-on session instructing them how to use a portable ultrasound device. Paramedics assessed patients for the presence of B-lines. Sensitivity and specificity for the presence of bilateral B-lines and any B-lines were calculated based on discharge diagnosis. Clips archived to the ultrasound units were reviewed and paramedic interpretations were compared to expert sonologist interpretations. Results: A total of 63 paramedics completed both didactic and hands-on training, and 22 performed ultrasounds in the field. There were 65 patients with B-line findings recorded and a discharge diagnosis for analysis. The presence of bilateral B-lines for diagnosis of CHF yielded a sensitivity of 80.0% (95% confidence interval [CI], 51.4–94.7%) and specificity of 72.0% (95% CI, 57.3–83.3), while presence of any B-lines was 93.3% sensitive (95% CI, 66.0–99.7%), and 50% specific (95% CI, 35.7–64.2%) for CHF. Paramedics archived 117 ultrasound clips of which 63% were determined to be adequate for interpretation. Comparison of paramedic and expert sonologist interpretation of images showed good inter-rater agreement for detection of any B-lines (k = 0.60; 95% CI, 0.36–0.84). Conclusion: This observational pilot study suggests that prehospital lung ultrasound for B-lines may aid in identifying or excluding CHF as a cause of dyspnea. The presence of bilateral B-lines as determined by paramedics is reasonably sensitive and specific for the diagnosis of CHF and pulmonary edema, while the absence of B lines is likely to exclude significant decompensated heart failure. The study was limited by being a convenience sample and highlighted some of the difficulties related to prehospital research. Larger funded trials will be needed to provide more definitive data.

Background: Visual disturbances are increasingly recognized as common non-motor symptoms in Parkinson's disease (PD). In PD patients, intermittent diplopia has been found to be associated with the presence of visual hallucinations and the Parkinson's psychosis spectrum. Here, we investigated whether diplopia in PD is associated with other non-motor traits and cognitive impairment. Methods: We investigated 50 non-demented PD patients with and without intermittent diplopia and 24 healthy controls for visual disturbances, as well as motor and non-motor symptoms. All participants underwent a neuropsychological test battery; visuospatial abilities were further evaluated with subtests of the Visual Object and Space Perception Battery (VOSP). The two PD patient groups did not differ significantly in age, symptom duration, motor symptom severity, frequency of visual hallucinations, or visual sensory efficiency. Results: PD patients with diplopia reported more frequent non-motor symptoms including more subjective cognitive problems and apathy without changes in global cognition measures compared to those without diplopia. PD patients with diplopia had greater impairment in several tests of visuospatial function (pentagon copying p = .002; number location p = .001; cube analysis p < .02) and object perception (p < .001) compared to PD patients without diplopia and healthy controls. By contrast, no consistent group differences were observed in executive function, memory, or language. Conclusions: PD patients with diplopia have a greater non-motor symptom burden and deficits in visuospatial function compared to PD patients without diplopia. PD patients with diplopia might be prone to a cortical phenotype with cognitive decline and apathy associated with worse prognosis.

BACKGROUND: Acute appendicitis is the most common surgical emergency in children. Differentiation of acute appendicitis from conditions that do not require operative management can be challenging in children. This study aimed to identify the optimum risk prediction model to stratify acute appendicitis risk in children. METHODS: We did a rapid review to identify acute appendicitis risk prediction models. A prospective, multicentre cohort study was then done to evaluate performance of these models. Children (aged 5-15 years) presenting with acute right iliac fossa pain in the UK and Ireland were included. For each model, score cutoff thresholds were systematically varied to identify the best achievable specificity while maintaining a failure rate (ie, proportion of patients identified as low risk who had acute appendicitis) less than 5%. The normal appendicectomy rate was the proportion of resected appendixes found to be normal on histopathological examination. FINDINGS:15 risk prediction models were identified that could be assessed. The cohort study enrolled 1827 children from 139 centres, of whom 630 (34·5%) underwent appendicectomy. The normal appendicectomy rate was 15·9% (100 of 630 patients). The Shera score was the best performing model, with an area under the curve of 0·84 (95% CI 0·82-0·86). Applying score cutoffs of 3 points or lower for children aged 5-10 years and girls aged 11-15 years, and 2 points or lower for boys aged 11-15 years, the failure rate was 3·3% (95% CI 2·0-5·2; 18 of 539 patients), specificity was 44·3% (95% CI 41·4-47·2; 521 of 1176), and positive predictive value was 41·4% (38·5-44·4; 463 of 1118). Positive predictive value for the Shera score with a cutoff of 6 points or lower (72·6%, 67·4-77·4) was similar to that of ultrasound scan (75·0%, 65·3-83·1). INTERPRETATION: The Shera score has the potential to identify a large group of children at low risk of acute appendicitis who could be considered for early discharge. Risk scoring does not identify children who should proceed directly to surgery. Medium-risk and high-risk children should undergo routine preoperative ultrasound imaging by operators trained to assess for acute appendicitis, and MRI or low-dose CT if uncertainty remains. FUNDING: None.

Inquiry based learning (IBL) has gained popularity as a tool for teaching science courses such as chemistry, biology, physics and engineering. This accelerating popularity is driven by technological advancements that allow IBL to be supported in the modern classroom1. The purpose of IBL is to trigger the student’s curiosity and encourage them to ask questions. The student’s role has become more active with technological advancements and access to multiple sources of information2. In light of this, the chemical and biomolecular engineering department at Rice University has adopted IBL in the undergraduate teaching laboratory courses. We implemented a flipped classroom model where students watched a 15-minute video then took a short quiz on safety and theory before they attended the first laboratory session. The IBL model focuses on the student to drive the question inquiry process, by engaging and motivating them to evaluate new information pertaining to that knowledge. The laboratory experiment objectives were non-prescriptive allowing the students to develop their own methods for conducting the experiments. During the spring of 2020, we had all of the IBL course structure in place, and it aided significantly in our shift to “virtual classrooms” after Rice University closed its campus in the wake of the COVID-19 pandemic. By re-designing the undergraduate lab course using IBL principles, we fortuitously gave ourselves built-in flexibility to go to emergency virtual format in Spring 2020, and virtual format in Fall 2020. This also allows us to go hybrid or full in-person in the future. We provided students with laboratory data so that they could continue the analysis at home. However, students were not able to conduct appropriate experimentation, which is one of the key learning objectives for the laboratory courses.

We argue that long optical storage times are required to establish entanglement at high rates over large distances using memory-based quantum repeaters. Triggered by this conclusion, we investigate the 795.325 nm^{3} H_{6}↔^{3}H_{4} transition of Tm:Y_{3}Ga_{5}O_{12} (Tm:YGG). Most importantly, we find that the optical coherence time can reach 1.1 ms, and, using laser pulses, we demonstrate optical storage based on the atomic frequency comb protocol during up to 100 μs as well as a memory decay time T_{m} of 13.1 μs. Possibilities of how to narrow the gap between the measured value of T_{m} and its maximum of 275 μs are discussed. In addition, we demonstrate multiplexed storage, including with feed-forward selection, shifting and filtering of spectral modes, as well as quantum state storage using members of nonclassical photon pairs. Our results show the potential of Tm:YGG for creating multiplexed quantum memories with long optical storage times, and open the path to repeater-based quantum networks with high entanglement distribution rates.