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BackgroundThe Affordable Care Act expanded Medicaid coverage for people with low income in the United States. Expanded insurance coverage could promote more timely access to cancer treatment, which could improve overall survival (OS), yet the long-term effects of Medicaid expansion (ME) remain unknown. We evaluated whether ME was associated with improved timely treatment initiation (TTI) and 3-year OS among patients with breast, cervical, colon, and lung cancers who were affected by the policy.MethodsMedicaid-insured or uninsured patients aged 40-64 with stage I-III breast, cervical, colon, or non-small cell lung cancer within the National Cancer Database (NCDB). A difference-in-differences (DID) approach was used to compare changes in TTI (within 60 days) and 3-year OS between patients in ME states versus nonexpansion (NE) states before (2010-2013) and after (2015-2018) ME. Adjusted DID estimates for TTI and 3-year OS were calculated using multivariable linear regression and Cox proportional hazards regression models, respectively.ResultsME was associated with a relative increase in TTI within 60 days for breast (DID = 4.6; p < 0.001), cervical (DID = 5.0 p = 0.013), and colon (DID = 4.0, p = 0.008), but not lung cancer (p = 0.505). In Cox regression analysis, ME was associated with improved 3-year OS for breast (DID hazard ratio [HR] = 0.82, p = 0.009), cervical (DID-HR = 0.81, p = 0.048), and lung (DID-HR = 0.87, p = 0.003). Changes in 3-year OS for colon cancer were not statistically different between ME and NE states (DID-HR, 0.77; p = 0.075).ConclusionsFindings suggest that expanded insurance coverage can improve treatment and survival outcomes among low income and uninsured patients with cancer. As the debate surrounding ME continues nationwide, our findings serve as valuable insights to inform the development of policies aimed at fostering accessible and affordable healthcare for all.

Using $2.93~\mathrm{fb}^{-1}$ of $e^+e^-$ collision data collected with the BESIII detector at the center-of-mass energy of 3.773 GeV, we investigate the semileptonic decays $D^+\to \pi^+\pi^- \ell^+\nu_\ell$ ($\ell=e$ and $\mu$). The $D^+\to f_0(500)\mu^+\nu_\mu$ decay is observed for the first time. By analyzing simultaneously the differential decay rates of $D^+\to f_0(500) \mu^+\nu_\mu$ and $D^+\to f_0(500) e^+\nu_e$ in different $\ell^+\nu_\ell$ four-momentum transfer intervals, the product of the relevant hadronic form factor $f^{f_0}_{+}(0)$ and the magnitude of the $c\to d$ Cabibbo-Kobayashi-Maskawa matrix element $|V_{cd}|$ is determined to be $f_{+}^{f_0} (0)|V_{cd}|=0.0787\pm0.0060_{\rm stat}\pm0.0033_{\rm syst}$ for the first time. With the input of $|V_{cd}|$ from the global fit in the standard model, we determine $f_{+}^{f_0} (0)=0.350\pm0.027_{\rm stat}\pm0.015_{\rm syst}$. The absolute branching fractions of $D^+\to f_0(500)_{(\pi^+\pi^-)}\mu^+\nu_\mu$ and $D^+\to \rho^0_{(\pi^+\pi^-)} \mu^+\nu_\mu$ are determined as $(0.72\pm0.13_{\rm stat}\pm0.10_{\rm syst})\times10^{-3}$ and $(1.64\pm0.13_{\rm stat}\pm0.11_{\rm syst})\times 10^{-3}$. Combining these results with those of previous BESIII measurements on their semielectronic counterparts from the same data sample, we test lepton flavor universality by measuring the branching fraction ratios ${\mathcal B}_{D^+\to \rho^0 \mu^+\nu_\mu}/{\mathcal B}_{D^+\to \rho^0 e^+\nu_e}=0.88\pm0.10$ and ${\mathcal B}_{D^+\to f_0(500) \mu^+\nu_\mu}/{\mathcal B}_{D^+\to f_0(500) e^+\nu_e}=1.14\pm0.28$, which are compatible with the standard model expectation., Comment: Supplemental Materials added in this version

The continuous annealing treatment of 5052 aluminum alloy pipe fittings for alpine skiing sticks was carried out in the temperature range of 300-500 °C by means of metallographic observation and mechanical property test. The results show that with the increase of annealing temperature, the strength and hardness of the samples decrease continuously, and the impact value, section shrinkage and elongation change significantly. The experimental results provide a technical reference for preventing the fracture of alpine skiing sticks during use.

Simultaneous localization and mapping is essential for position tracking and scene understanding. 3D Gaussian-based map representations enable photorealistic reconstruction and real-time rendering of scenes using multiple posed cameras. We show for the first time that using 3D Gaussians for map representation with unposed camera images and inertial measurements can enable accurate SLAM. Our method, MM3DGS, addresses the limitations of prior neural radiance field-based representations by enabling faster rendering, scale awareness, and improved trajectory tracking. Our framework enables keyframe-based mapping and tracking utilizing loss functions that incorporate relative pose transformations from pre-integrated inertial measurements, depth estimates, and measures of photometric rendering quality. We also release a multi-modal dataset, UT-MM, collected from a mobile robot equipped with a camera and an inertial measurement unit. Experimental evaluation on several scenes from the dataset shows that MM3DGS achieves 3x improvement in tracking and 5% improvement in photometric rendering quality compared to the current 3DGS SLAM state-of-the-art, while allowing real-time rendering of a high-resolution dense 3D map. Project Webpage: https://vita-group.github.io/MM3DGS-SLAM, Comment: Project Webpage: https://vita-group.github.io/MM3DGS-SLAM

Anaerobic digestion of lipid-rich wastewater generally suffers from foaming induced by long chain fatty acid (LCFA). However, a systematic understanding of LCFA inhibition, especially the physical inhibition on interfacial interaction still remains unclear. Here, we combined bubble probe atomic force microscope and impinging-jet technique to unravel the interfacial interactions controlled by long chain fatty acids in anaerobic digestion. We showed that LCFA had a significant inhibition on methane production in anaerobic reactors for the inhibition of the conversion of VFAs to methane. By measuring the LCFA influence on methanogenic archaea Methanosarcina acetivorans C2A, the results demonstrated that methanogenesis was limited for substrates utilization but not metabolic pathways. The impinging-jet technique results indicated that LCFA enhanced bubble separation from anaerobic granules and reduced the bubble-bubble coalescence probability. In addition, the bubble probe atomic force microscope (AFM) revealed that LCFA enhanced the adhesion force between bubbles by enhancing electrical double layer (EDL) repulsion and decreasing hydrophobic interactions. Overall, these results complement framework of LCFA inhibition in anerobic digestion and provide a nanomechanical insight into the fundamental interfacial interactions related to bubbles in anaerobic reactors.

Gravitational-wave high-energy Electromagnetic Counterpart All-sky Monitor (GECAM) is a space-borne instrument dedicated to monitoring high-energy transients, including Terrestrial Gamma-ray Flashes (TGFs) and Terrestrial Electron Beams (TEBs). We implemented a TGF/TEB search algorithm for GECAM, with which 147 bright TGFs, 2 typical TEBs and 2 special TEB-like events are identified during an effective observation time of $\sim$9 months. We show that, with gamma-ray and charged particle detectors, GECAM can effectively identify and distinguish TGFs and TEBs, and measure their temporal and spectral properties in detail. A very high TGF-lightning association rate of $\sim$80\% is obtained between GECAM and GLD360 in east Asia region., Comment: The paper was accepted by Geophysical Research Letters on June 16th, 2023

Objectives Group‐2 reviewed the scientific evidence in the field of «Technology». Focused research questions were: (1) additive versus subtractive manufacturing of implant restorations; (2) survival, complications, and esthetics comparing prefabricated versus customized abutments; and (3) survival of posterior implant‐supported multi‐unit fixed dental prostheses.Materials and MethodsLiterature was systematically screened, and 67 publications could be critically reviewed following PRISMA guidelines, resulting in three systematic reviews. Consensus statements were presented to the plenary where after modification, those were accepted.ResultsAdditively fabricated implant restorations of zirconia and polymers were investigated for marginal/internal adaptation and mechanical properties without clear results in favor of one technology or material. Titanium base abutments for screw‐retained implant single crowns compared to customized abutments did not show significant differences concerning 1‐year survival. PFM, veneered and monolithic zirconia implant‐supported multi‐unit posterior fixed dental prostheses demonstrated similar high 3‐year survival rates, whereas veneered restorations exhibited the highest annual ceramic fracture and chipping rates.ConclusionsFor interim tooth‐colored implant single crowns both additive and subtractive manufacturing are viable techniques. The clinical performance of additively produced restorations remains to be investigated. Implant single crowns on titanium base abutments show similar clinical performance compared to other type of abutments; however, long‐term clinical data from RCTs are needed. The abutment selection should be considered already during the planning phase. Digital planning facilitates 3D visualization of the prosthetic design including abutment selection. In the posterior area, monolithic zirconia is recommended as the material of choice for multi‐unit implant restorations to reduce technical complications.

Objectives The Ovarian Cancer Comorbidity Index (OCCI) is an age-specific index developed and previously found to be more predictive of overall and cancer-specific survival than the Charlson Comorbidity Index (CCI). The objective was to perform secondary validation of the OCCI in a US population. Methods A cohort of ovarian cancer patients undergoing primary or interval cytoreductive surgery from January 2005 to January 2012 was identified in SEER-Medicare. OCCI scores were calculated with the regression coefficients determined from the original developmental cohort for five comorbidities. Cox regression analyses were used to calculate associations between the OCCI risk groups and 5-year overall survival and 5-year cancer-specific survival in comparison to the CCI. Results A total of 5052 patients were included. Median age was 74 (range 66-82) years. 47% (n=2375) had stage III and 24% (n=1197) had stage IV disease at diagnosis. 67% had a serous histology subtype (n=3403). All patients were categorized as moderate (48.4%) or high risk (51.6%). The prevalence of the five predictive comorbidities were: coronary artery disease 3.7%, hypertension 67.5%, chronic obstructive pulmonary disease 16.7%, diabetes 21.8%, and dementia 1.2%. Controlling for histology, grade, and age-stratification, worse overall survival was associated with both a higher OCCI (hazard ratio (HR) 1.57; 95% confidence interval (CI) 1.46 to 1.69) and CCI (HR 1.96; 95% CI 1.66 to 2.32). Cancer-specific survival was associated with the OCCI (HR 1.33; 95% CI 1.22 to 1.44) but was not associated with the CCI (HR 1.15; 95% CI 0.93 to 1.43). Conclusions This internationally developed comorbidity score for ovarian cancer patients is predictive for both overall and cancer-specific survival in a US population. CCI was not predictive for cancer-specific survival. This score may have research applications when utilizing large administrative datasets.

Radiologists in training draw from their early experiences in residency when choosing a fellowship. Once they have decided on an abdominal imaging fellowship, applicants must learn to navigate the interview process. During this challenging time, applicants explore the difference in clinical curricula and rotations, meet potential mentors and clinical faculty, consider potential academic interests and projects, and choose what location they would like to train for one year after residency. When in training, fellows undergo the challenge of finding employment while learning new skills and refining their abilities to become a well-rounded radiologist and clinician. This article summarizes key points potential applicants should consider when deciding on an abdominal imaging fellowship, how to prepare for the interview season, and how to plan their fellowship year before fellows take the next step to becoming attendings.

The causal mechanism between climate and political violence is fraught with complex mechanisms. Current quantitative causal models rely on one or more assumptions: (1) the climate drivers persistently generate conflict, (2) the causal mechanisms have a linear relationship with the conflict generation parameter, and/or (3) there is sufficient data to inform the prior distribution. Yet, we know conflict drivers often excite a social transformation process which leads to violence (e.g., drought forces agricultural producers to join urban militia), but further climate effects do not necessarily contribute to further violence. Therefore, not only is this bifurcation relationship highly non-linear, there is also often a lack of data to support prior assumptions for high resolution modeling. Here, we aim to overcome the aforementioned causal modeling challenges by proposing a neural forward-intensity Poisson process (NFIPP) model. The NFIPP is designed to capture the potential non-linear causal mechanism in climate induced political violence, whilst being robust to sparse and timing-uncertain data. Our results span 20 recent years and reveal an excitation-based causal link between extreme climate events and political violence across diverse countries. Our climate-induced conflict model results are cross-validated against qualitative climate vulnerability indices. Furthermore, we label historical events that either improve or reduce our predictability gain, demonstrating the importance of domain expertise in informing interpretation.

Considers how to represent students and their writings in composition research, specifically how to represent the students themselves. Suggests that when contemplating the "Guidelines for the Ethical Treatment of Students and Student Writing in Composition Studies," educators need to consider their epistemological stance, their choices in epistemology, discourse, and research. (SG)

Alzheimer's disease (AD) is an unremitting neurodegenerative disorder characterized by cerebral amyloid-β (Aβ) accumulation and gradual decline in cognitive function. Changes in brain energy metabolism arise in the preclinical phase of AD, suggesting an important metabolic component of early AD pathology. Neurons and astrocytes function in close metabolic collaboration, which is essential for the recycling of neurotransmitters in the synapse. However, this crucial metabolic interplay during the early stages of AD development has not been sufficiently investigated. Here, we provide an integrative analysis of cellular metabolism during the early stages of Aβ accumulation in the cerebral cortex and hippocampus of the 5xFAD mouse model of AD. Our electrophysiological examination revealed an increase in spontaneous excitatory signaling in the 5xFAD hippocampus. This hyperactive neuronal phenotype coincided with decreased hippocampal tricarboxylic acid (TCA) cycle metabolism mapped by stable 13C isotope tracing. Particularly, reduced astrocyte TCA cycle activity and decreased glutamine synthesis led to hampered neuronal GABA synthesis in the 5xFAD hippocampus. In contrast, the cerebral cortex of 5xFAD mice displayed an elevated capacity for oxidative glucose metabolism, which may suggest a metabolic compensation in this brain region. We found limited changes when we explored the brain proteome and metabolome of the 5xFAD mice, supporting that the functional metabolic disturbances between neurons and astrocytes are early primary events in AD pathology. In addition, synaptic mitochondrial and glycolytic function was selectively impaired in the 5xFAD hippocampus, whereas non-synaptic mitochondrial function was maintained. These findings were supported by ultrastructural analyses demonstrating disruptions in mitochondrial morphology, particularly in the 5xFAD hippocampus. Collectively, our study reveals complex regional and cell-specific metabolic adaptations in the early

Despite several decades of multi-wavelength and multi-messenger spectral observations, Gamma-Ray Bursts (GRBs) remain one of the big mysteries of modern astrophysics. Polarization measurements are essential to gain a more clear and complete picture of the emission processes at work in these extremely powerful transient events. In this regard, a first generation of dedicated gamma-ray polarimeters, POLAR and GAP, were launched into space in the last decade. After 6 months of operation, the POLAR mission detected 55 GRBs, among which 14 have been analyzed in detail, reporting a low polarization degree and a hint of a temporal evolution of the polarization angle. Starting early 2024 and based on the legacy of the POLAR results, the POLAR-2 instrument will aim to provide a catalog of high quality measurements of the energy and temporal evolution of the GRB polarization thanks to its large and efficient polarimeter. Several spectrometer modules will additionally allow to perform joint spectral and polarization analyzes. The mission is foreseen to make high precision polarization measurements of about 50 GRBs every year on board of the China Space Station (CSS). The technical design of the polarimeter modules will be discussed in detail, as well as the expected scientific performances based on the first results of the developed prototype modules., Comment: Proceeding from the 37th International Cosmic Ray Conference (ICRC2021), 9 pages, 5 figures

Despite over 50 years of Gamma-Ray Burst (GRB) observations many open questions remain about their nature and the environments in which the emission takes place. Polarization measurements of the GRB prompt emission have long been theorized to be able to answer most of these questions. The POLAR detector was a dedicated GRB polarimeter developed by a Swiss, Chinese and Polish collaboration. The instrument was launched, together with the second Chinese Space Lab, the Tiangong-2, in September 2016 after which it took 6 months of scientific data. During this period POLAR detected 55 GRBs as well as several pulsars. From the analysis of the GRB polarization catalog we see that the prompt emission is lowly polarized or fully unpolarized. There is, however, the caveat that within single pulses there are strong hints of an evolving polarization angle which washes out the polarization degree in the time integrated analysis. Building on the success of the POLAR mission, the POLAR-2 instrument is currently under development. POLAR-2 is a Swiss, Chinese, Polish and German collaboration and was recently approved for launch in 2024. Thanks to its large sensitivity POLAR-2 will produce polarization measurements of at least 50 GRBs per year with a precision equal or higher than the best results published by POLAR. POLAR-2 thereby aims to make the prompt polarization a standard observable and produce catalogs of the gamma-ray polarization of GRBs. Here we will present an overview of the POLAR mission and all its scientific measurement results. Additionally, we will present an overview of the future POLAR-2 mission, and how it will answer some of the questions raised by the POLAR results., Comment: Presented at the 37th International Cosmic Ray Conference (ICRC 2021)

Study objectiveWe compare clinical management and outcomes of emergency department (ED) encounters by sex after implementation of a clinical care pathway in 15 community EDs that standardized recommendations based on patient risk, using the History, ECG, Age, Risk Factors, and Troponin (HEART) score.MethodsThis was a retrospective analysis of adult ED encounters evaluated for suspected acute coronary syndrome with a documented HEART score from May 20, 2016, to December 1, 2017. The primary outcomes were hospitalization or 30-day stress testing. Secondary outcomes included 30-day acute myocardial infarction or all-cause death (major adverse cardiac event). A generalized estimating equation regression model was used to compare the odds of hospitalization or stress testing by sex; we report HEART scores (0 to 10) stratified by sex and describing major adverse cardiac events.ResultsA total of 34,715 adult ED encounters met the inclusion criteria (56.0% women). A higher proportion of women were classified as low risk (60.5% versus 52.4%; odds ratio [OR] 1.39; 95% confidence interval [CI] 1.33 to 1.45). Women were hospitalized or received stress testing less frequently than men for low HEART scores (18.8% versus 22.8%; OR 0.79; 95% CI 0.73 to 0.84) and intermediate ones (46.7% versus 49.7%; OR 0.88; 95% CI 0.83 to 0.95), but similarly for high-risk ones (74.1% versus 74.4%; OR 0.99; 95% CI 0.77 to 1.28). Women had 18% lower odds of hospitalization or noninvasive cardiac testing (OR 0.82; 95% CI 0.78 to 0.86), even after adjusting for HEART score and comorbidities. Men had higher risks of major adverse cardiac events than women for all HEART score categories but the risk for men was significantly higher among low-risk HEART scores (0.4% versus 0.1%).ConclusionWomen with low-risk HEART scores are hospitalized or stress tested less than men, which is likely appropriate, and women have better outcomes than men. Use of the HEART score has the potential to reduce sex disparitie

Air- and spaceborne synthetic aperture radar (SAR) can provide a large number of high-resolution images for microwave remote sensing applications, such as geoscience and climate change research, environmental Earth system monitoring, and precision agriculture. Unlike spaceborne SAR, the flight trajectory of airborne SAR may deviate from its ideal straight course due to the influence of atmospheric turbulence, resulting in significant motion errors in radar raw data. If a standard imaging algorithm is directly used to process the data, the image focusing quality will be significantly degraded. Therefore, to improve image focusing quality, one typically needs to integrate standard imaging algorithms with an effective motion compensation (MoCo)/autofocus technique. In this article, we present a comprehensive overview of MoCo/autofocus methods for airborne SAR to articulate related research and promote further development.

We present results from an analysis of $\sim$ 29,000 RR Lyrae stars located in the Large Magellanic Cloud (LMC). For these objects, near-infrared time-series photometry from the VISTA survey of the Magellanic Clouds system (VMC) and optical data from the OGLE (Optical Gravitational Lensing Experiment) IV survey and the Gaia Data Release 2 catalogue of confirmed RR Lyrae stars were exploited. Using VMC and OGLE IV magnitudes we derived period-luminosity (PL), period-luminosity-metallicity (PLZ), period-Wesenheit (PW) and period-Wesenheit-metallicity (PWZ) relations in all available bands. More that ~7,000 RR Lyrae were discarded from the analysis because they appear to be overluminous with respect to the PL relations. The $PL_{K_{\mathrm{s}}}$ relation was used to derive individual distance to $\sim 22,000$ RR Lyrae stars, and study the three-dimensional structure of the LMC. The distribution of the LMC RR Lyrae stars is ellipsoidal with the three axis $S_1$=6.5 kpc, $S_2$=4.6 kpc and $S_3$=3.7 kpc, inclination i=$22\pm4^{\circ }$ relative to the plane of the sky and position angle of the line of nodes $\theta=167\pm7^{\circ }$ (measured from north to east). The north-eastern part of the ellipsoid is closer to us and no particular associated substructures are detected as well as any metallicity gradient., Comment: accepted for publication in MNRAS

We used data from the near-infrared VISTA survey of the Magellanic Cloud system (VMC) to measure proper motions (PMs) of stars within the Small Magellanic Cloud (SMC). The data analysed in this study comprise 26 VMC tiles, covering a total contiguous area on the sky of ~40 deg$^2$. Using multi-epoch observations in the Ks band over time baselines between 13 and 38 months, we calculated absolute PMs with respect to ~130,000 background galaxies. We selected a sample of ~2,160,000 likely SMC member stars to model the centre-of-mass motion of the galaxy. The results found for three different choices of the SMC centre are in good agreement with recent space-based measurements. Using the systemic motion of the SMC, we constructed spatially resolved residual PM maps and analysed for the first time the internal kinematics of the intermediate-age/old and young stellar populations separately. We found outward motions that point either towards a stretching of the galaxy or stripping of its outer regions. Stellar motions towards the North might be related to the "Counter Bridge" behind the SMC. The young populations show larger PMs in the region of the SMC Wing, towards the young Magellanic Bridge. In the older populations, we further detected a coordinated motion of stars away from the SMC in the direction of the Old Bridge as well as a stream towards the SMC., Comment: 20 pages, 20 figures, accepted for publication in MNRAS

BACKGROUND: Evidence-based international expert consensus regarding the impact of peripheral nerve block (PNB) use in total hip/knee arthroplasty surgery. METHODS: A systematic review and meta-analysis: randomized controlled and observational studies investigating the impact of PNB utilization on major complications, including mortality, cardiac, pulmonary, gastrointestinal, renal, thromboembolic, neurologic, infectious, and bleeding complications.Medline, PubMed, Embase, and Cochrane Library including Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, were queried from 1946 to August 4, 2020.The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess evidence quality and for the development of recommendations. RESULTS: Analysis of 122 studies revealed that PNB use (compared with no use) was associated with lower ORs for (OR with 95% CIs) for numerous complications (total hip and knee arthroplasties (THA/TKA), respectively): cognitive dysfunction (OR 0.30, 95% CI 0.17 to 0.53/OR 0.52, 95% CI 0.34 to 0.80), respiratory failure (OR 0.36, 95% CI 0.17 to 0.74/OR 0.37, 95% CI 0.18 to 0.75), cardiac complications (OR 0.84, 95% CI 0.76 to 0.93/OR 0.83, 95% CI 0.79 to 0.86), surgical site infections (OR 0.55 95% CI 0.47 to 0.64/OR 0.86 95% CI 0.80 to 0.91), thromboembolism (OR 0.74, 95% CI 0.58 to 0.96/OR 0.90, 95% CI 0.84 to 0.96) and blood transfusion (OR 0.84, 95% CI 0.83 to 0.86/OR 0.91, 95% CI 0.90 to 0.92). CONCLUSIONS: Based on the current body of evidence, the consensus group recommends PNB use in THA/TKA for improved outcomes. RECOMMENDATION: PNB use is recommended for patients undergoing THA and TKA except when contraindications preclude their use. Furthermore, the alignment of provider skills and practice location resources needs to be ensured. Evidence level: moderate; recommendation: strong.

Increased drone proliferation in civilian and professional settings has created new threat vectors for airports and national infrastructures. The economic damage for a single major airport from drone incursions is estimated to be millions per day. Due to the lack of diverse drone training data, accurate training of deep learning detection algorithms under scarce data is an open challenge. Existing methods largely rely on collecting diverse and comprehensive experimental drone footage data, artificially induced data augmentation, transfer and meta-learning, as well as physics-informed learning. However, these methods cannot guarantee capturing diverse drone designs and fully understanding the deep feature space of drones. Here, we show how understanding the general distribution of the drone data via a Generative Adversarial Network (GAN) and explaining the missing features using Topological Data Analysis (TDA) - can allow us to acquire missing data to achieve rapid and more accurate learning. We demonstrate our results on a drone image dataset, which contains both real drone images as well as simulated images from computer-aided design. When compared to random data collection (usual practice - discriminator accuracy of 94.67\% after 200 epochs), our proposed GAN-TDA informed data collection method offers a significant 4\% improvement (99.42\% after 200 epochs). We believe that this approach of exploiting general data distribution knowledge form neural networks can be applied to a wide range of scarce data open challenges., Comment: 9 pages, 6 figures

Immunological memory is an evolutionary adaptation of the vertebrate immune system that protects the host from repeated pathogen infection. T and B cells possess the specificity and longevity required to generate immune memory, whereas natural killer (NK) cells make up a component of the immune system that was not thought to possess these features. However, much evidence from the last decade has challenged this dogma. The investigators were asked to address the following questions: Is there NK cell memory? And can NK cell memory be harnessed for vaccination? Thus, this article explores the recent literature showing immune memory in NK cells. Along with highlighting these studies, we speculate how NK cell memory can be harnessed in immunization strategies against infectious diseases and cancer.

Introduction: Current U.S. cardiology guidelines recommend oral anticoagulation (OAC) to reduce stroke risk in selected patients with atrial fibrillation (AF), but no formal AF OAC recommendations exist to guide emergency medicine clinicians in the acute care setting. We sought to characterize emergency department (ED) OAC prescribing practices after an ED AF diagnosis.Methods: This retrospective study included index visits for OAC-naive patients ≥18 years old who were discharged home from the ED at an urban, academic, tertiary hospital with a primary diagnosis of AF from 2012-2014. Five hypothesis-blinded, chart reviewers abstracted data from patient problem lists and medical history in the electronic health record to assess stroke (CHA2DS2-VASc) and bleeding risk (HAS-BLED). The primary outcome was the provision of an OAC prescription at discharge in OAC-naive patients with high stroke risk. Descriptive statistics and multivariable logistic regression assessed associations between OAC prescription and patient characteristics.Results: We included 138 patient visits in our analysis, of whom 39.9% (n = 55) were low stroke risk (CHA2DS2-VASc = 0 in males and 1 in females), 15.9% (n = 22) were intermediate risk (CHA2DS2-VASc = 1 in males), and 44.2% (n = 61) were high risk (CHA2DS2-VASc ≥ 2). Of patients with high stroke risk and low-to-intermediate bleeding risk (n = 57), 80.7% were not prescribed an OAC at discharge. Cardiology consultation and female gender, but not stroke risk (CHA2DS2-VASc score), were predictors of an ED provider prescribing an OAC to an OAC-naive AF patient at ED discharge.Conclusion: The majority of OAC-eligible patients were discharged home without an OAC prescription. In OAC-naive patients discharged home from the ED, cardiology consultation and female gender were associated with OAC prescription. Our findings suggest that access to expert opinion may improve provider comfort with OAC prescribing and highlight the need for improved guidelines

OBJECTIVE: Acute migraine is associated with significant personal, economic and work-related disability. Management guidelines advise the use of simple analgesia, triptans, chlorpromazine and anti-emetics based on severity, with avoidance of opioids. We aimed to determine consistency of prescribing patterns in our ED with national guidelines. METHODS: We performed a retrospective cohort analysis of migraine presentations (ICD-10-AM G439) between 2012 and 2016. Exclusion criteria included migraine without headache, other primary headaches and secondary headaches. Demographic and prescribing data were extracted from medical records. Results have been reported as proportions. RESULTS: Of 4769 headache presentations, the application of exclusion criteria led to a total of 744 patients who received a migraine diagnosis (G439). Most were female (558/744, 75%), young (mean age 36.4 years) and had a self-reported migraine history (558/744, 75%). There were 54 different medications prescribed. Paracetamol was more frequently prescribed (385/744, 52%) than aspirin (134/744, 18%). Opioid prescription occurred in nearly half of all presentations (345/744, 46%). Similar opioid prescriptions were also observed in those with a documented history of migraines (253/558, 45%). A minority of patients received triptans (51/744, 7%). Overall, a quarter of patients (189/744, 25%) received no guideline-recommended medications. CONCLUSION: We observed considerable polypharmacy in ED migraine management with inconsistent prescribing patterns. Recommended medications were infrequently used and opioid use was common. Factors influencing prescribing patterns require further investigation in order to improve rates of guideline recommended treatment.

ObjectiveWe sought to identify sub-groups of "low-risk" HEART score patients (history, ECG, age, risk factors, and troponin) at elevated risk of acute myocardial infarction or death within 30 days.MethodsWe performed a secondary analysis of prospective emergency department (ED) encounters for suspected acute coronary syndrome in a large health system with low-risk HEART scores (0-5 points). Logistic regression using the 5 components of the HEART score analyzed the increase risk attributable to points from each of the 5 score components.ResultsOf 30,971 encounters among 28,992 unique patients, 135 (0.44%, 95% confidence interval [CI] = 0.37-0.51) experienced acute myocardial infarction or death. Risk increased for each component of the HEART score from 0 to 1 to 2 points (history, 0.4% to 0.5% to 0.6%; ECG, 0.3% to 0.7% to 0.7%; age, 0.2% to 0.3% to 0.7%; risk factors, 0.1% to 0.4% to 0.8%), except troponin, which had the highest risk with 1 point (troponin, 0.4% to 2.7% to 0.9%). Odds ratios from our regression, which adjusts for other components, showed a similar pattern (from 1 vs 0 and 2 vs 0 points, respectively: history, 1.0 and 1.8; ECG, 2.2 and 3.5; age, 1.2 and 2.1; risk factors, 2.4 and 4.2; and troponin, 6.0 and 3.6).ConclusionAmong "low-risk" suspected acute coronary syndrome encounters, increasing points within each of the 5 categories demonstrated small increases in risk of death or acute myocardial infarction, with the troponin and ECG components representing the largest risk increases.

Study objectiveOlder adults with syncope are commonly treated in the emergency department (ED). We seek to derive a novel risk-stratification tool to predict 30-day serious cardiac outcomes.MethodsWe performed a prospective, observational study of older adults (≥60 years) with unexplained syncope or near syncope who presented to 11 EDs in the United States. Patients with a serious diagnosis identified in the ED were excluded. We collected clinical and laboratory data on all patients. Our primary outcome was 30-day all-cause mortality or serious cardiac outcome.ResultsWe enrolled 3,177 older adults with unexplained syncope or near syncope between April 2013 and September 2016. Mean age was 73 years (SD 9.0 years). The incidence of the primary outcome was 5.7% (95% confidence interval [CI] 4.9% to 6.5%). Using Bayesian logistic regression, we derived the FAINT score: history of heart failure, history of cardiac arrhythmia, initial abnormal ECG result, elevated pro B-type natriuretic peptide, and elevated high-sensitivity troponin T. A FAINT score of 0 versus greater than or equal to 1 had sensitivity of 96.7% (95% CI 92.9% to 98.8%) and specificity 22.2% (95% CI 20.7% to 23.8%), respectively. The FAINT score tended to be more accurate than unstructured physician judgment: area under the curve 0.704 (95% CI 0.669 to 0.739) versus 0.630 (95% CI 0.589 to 0.670).ConclusionAmong older adults with syncope or near syncope of potential cardiac cause, a FAINT score of zero had a reasonably high sensitivity for excluding death and serious cardiac outcomes at 30 days. If externally validated, this tool could improve resource use for this common condition.

BackgroundMcKesson's InterQual criteria are widely used in hospitals to determine if patients should be classified as observation or inpatient status, but the accuracy of the criteria is unknown.ObjectiveWe sought to determine whether InterQual criteria accurately predicted length of stay (LOS) in older patients with syncope.MethodsWe conducted a secondary analysis of a cohort study of adults ≥60 years of age who had syncope. We calculated InterQual criteria and classified the patient as observation or inpatient status. Outcomes were whether LOS were less than or greater than 2 midnights.ResultsWe analyzed 2361 patients; 1227 (52.0%) patients were male and 1945 (82.8%) were white, with a mean age of 73.2 ± 9.0 years. The median LOS was 32.6 h (interquartile range 24.2-71.8). The sensitivity of InterQual criteria for LOS was 60.8% (95% confidence interval 57.9-63.6%) and the specificity was 47.8% (95% confidence interval 45.0-50.5%).ConclusionsIn older adults with syncope, those who met InterQual criteria for inpatient status had longer LOS compared with those who did not; however, the accuracy of the criteria to predict length of stay over 2 days is poor, with a sensitivity of 60% and a specificity of 48%. Future research should identify criteria to improve LOS prediction.

Galaxy interactions distort the distribution of baryonic matter and can affect star formation. The nearby Magellanic Clouds are a prime example of an ongoing galaxy interaction process. Here we use the intermediate-age ($\sim1$-$10$ Gyr) red clump stars to map the three-dimensional structure of the Small Magellanic Cloud (SMC) and interpret it within the context of its history of interaction with the Large Magellanic Cloud (LMC) and the Milky Way. Red clump stars are selected from near-infrared colour-magnitude diagrams based on data from the VISTA survey of the Magellanic Clouds. Interstellar reddening is measured and removed, and the corrected brightness is converted to a distance, on a star-by-star basis. A flat plane fitted to the spatial distribution of red clump stars has an inclination $i=35\deg$-$48\deg$ and position angle PA$=170\deg$-$186\deg$. However, significant deviations from this plane are seen, especially in the periphery and on the eastern side of the SMC. In the latter part, two distinct populations are present, separated in distance by as much as 10 kpc. Distant red clump stars are seen in the North of the SMC, and possibly also in the far West; these might be associated with the predicted `Counter-Bridge'. We also present a dust reddening map, which shows that dust generally traces stellar mass. The structure of the intermediate-age stellar component of the SMC bears the imprints of strong interaction with the LMC a few Gyr ago, which cannot be purely tidal but must have involved ram pressure stripping., Comment: 16 pages, 11 figures; accepted for publication in MNRAS

Achieving transparency in black-box deep learning algorithms is still an open challenge. High dimensional features and decisions given by deep neural networks (NN) require new algorithms and methods to expose its mechanisms. Current state-of-the-art NN interpretation methods (e.g. Saliency maps, DeepLIFT, LIME, etc.) focus more on the direct relationship between NN outputs and inputs rather than the NN structure and operations itself. In current deep NN operations, there is uncertainty over the exact role played by neurons with fixed activation functions. In this paper, we achieve partially explainable learning model by symbolically explaining the role of activation functions (AF) under a scalable topology. This is carried out by modeling the AFs as adaptive Gaussian Processes (GP), which sit within a novel scalable NN topology, based on the Kolmogorov-Arnold Superposition Theorem (KST). In this scalable NN architecture, the AFs are generated by GP interpolation between control points and can thus be tuned during the back-propagation procedure via gradient descent. The control points act as the core enabler to both local and global adjustability of AF, where the GP interpolation constrains the intrinsic autocorrelation to avoid over-fitting. We show that there exists a trade-off between the NN's expressive power and interpretation complexity, under linear KST topology scaling. To demonstrate this, we perform a case study on a binary classification dataset of banknote authentication. By quantitatively and qualitatively investigating the mapping relationship between inputs and output, our explainable model can provide interpretation over each of the one-dimensional attributes. These early results suggest that our model has the potential to act as the final interpretation layer for deep neural networks.

Six isostructural crystalline solvates of the active pharmaceutical ingredient celecoxib {4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide; C17H14F3N3O2S} are described, containing dimethylformamide (DMF, C3H7NO, 1), dimethylacetamide (DMA, C4H9NO, 2), N-methylpyrrolidin-2-one (NMP, C5H9NO, 3), tetramethylurea (TMU, C5H12N2O, 4), 1,3-dimethyl-3,4,5,6-tetrahydropyrimidin-2(1H)-one (DMPU, C6H12N2O, 5) or dimethyl sulfoxide (DMSO, C2H6OS, 6). The host celecoxib structure contains one-dimensional channel voids accommodating the solvent molecules, which accept hydrogen bonds from the NH2 groups of two celecoxib molecules. The solvent binding sites have local twofold rotation symmetry, which is consistent with the point symmetry of the solvent molecule in 4 and 5, but introduces orientational disorder for the solvent molecules in 1, 2, 3 and 6. Despite the isostructurality of 1-6, the unit-cell volume and solvent-accessible void space show significant variation. In particular, 4 and 5 show an enlarged and skewed unit cell, which can be attributed to a specific interaction between an N-CH3 group in the solvent molecule and the toluene group of celecoxib. Intermolecular interaction energies calculated using the PIXEL method show that the total interaction energy between the celecoxib and solvent molecules is broadly correlated with the molecular volume of the solvent, except in 6, where the increased polarity of the S=O bond leads to greater overall stabilization compared to the similarlysized DMF molecule in 1. In the structures showing disorder, the most stable orientations of the solvent molecules make C-H center dot center dot O contacts to the S=O groups of celecoxib.

Innate lymphoid cells (ILCs) are tissue-resident sentinels that are essential for early host protection from pathogens at initial sites of infection. However, whether pathogen-derived antigens directly modulate the responses of tissue-resident ILCs has remained unclear. In the present study, it was found that liver-resident type 1 ILCs (ILC1s) expanded locally and persisted after the resolution of infection with mouse cytomegalovirus (MCMV). ILC1s acquired stable transcriptional, epigenetic and phenotypic changes a month after the resolution of MCMV infection, and showed an enhanced protective effector response to secondary challenge with MCMV consistent with a memory lymphocyte response. Memory ILC1 responses were dependent on the MCMV-encoded glycoprotein m12, and were independent of bystander activation by proinflammatory cytokines after heterologous infection. Thus, liver ILC1s acquire adaptive features in an MCMV-specific manner.

Simultaneous $\gamma$-ray measurements of gamma-ray burst (GRB) spectra and polarization offer a unique way to determine the underlying emission mechanism(s) in these objects as well as probing the particle acceleration mechanism(s) that lead to the observed $\gamma$-ray emission. Herein we examine the jointly-observed data from POLAR and GBM of GRB 170114A to determine its spectral and polarization properties and seek to understand the emission processes that generate these observations. We aim to develop an extensible and statistically sound framework for these types of measurements applicable to other instruments. We leverage the existing 3ML analysis framework to develop a new analysis pipeline for simultaneously modeling the spectral and polarization data. We derive the proper Poisson likelihood for $\gamma$-ray polarization measurements in the presence of background. The developed framework is publicly available for similar measurements with other $\gamma$-ray polarimeters. The data are analyzed within a Bayesian probabilistic context and the spectral data from both instruments are simultaneously modeled with a physical, numerical synchrotron code. The spectral modeling of the data is consistent with a synchrotron photon model as has been found in a majority of similarly analyzed single-pulse GRBs. The polarization results reveal a slight trend of growing polarization in time reaching values of ~30% at the temporal peak of the emission. Additionally, it is observed that the polarization angle evolves with time throughout the emission. These results hint at a synchrotron origin of the emission but further observations of many GRBs are required to verify these evolutionary trends. Furthermore, we encourage the development of time-resolved polarization models for the prompt emission of GRBs as the current models are not predictive enough to enable a full modeling of our current data., Comment: 22 pages, 23 figures. Published to A&A

Almost 20% of patients with syncope will experience another event. It is unknown whether recurrent syncope is a marker for a higher or lower risk etiology of syncope. The goal of this study is to determine whether older adults with recurrent syncope have a higher likelihood of 30-day serious clinical events than patients experiencing their first episode.MethodsThis study is a pre-specified secondary analysis of a multicenter prospective, observational study conducted at 11 emergency departments in the US. Adults 60 years or older who presented with syncope or near syncope were enrolled. The primary outcome was occurrence of 30-day serious outcome. The secondary outcome was 30-day serious cardiac arrhythmia. In multivariate analysis, we assessed whether prior syncope was an independent predictor of 30-day serious events.ResultsThe study cohort included 3580 patients: 1281 (35.8%) had prior syncope and 2299 (64.2%) were presenting with first episode of syncope. 498 (13.9%) patients had 1 prior episode while 771 (21.5%) had >1 prior episode. Those with recurrent syncope were more likely to have congestive heart failure, coronary artery disease, previous diagnosis of arrhythmia, and an abnormal ECG. Overall, 657 (18.4%) of the cohort had a serious outcome by 30 days after index ED visit. In multivariate analysis, we found no significant difference in risk of events (adjusted odds ratio 1.09; 95% confidence interval 0.90-1.31; p = 0.387).ConclusionIn older adults with syncope, a prior history of syncope within the year does not increase the risk for serious 30-day events.

Study objectiveControversy remains in regard to the risk of adverse events for patients presenting with syncope compared with near-syncope. The purpose of our study is to describe the difference in outcomes between these groups in a large multicenter cohort of older emergency department (ED) patients.MethodsFrom April 28, 2013, to September 21, 2016, we conducted a prospective, observational study across 11 EDs in adults (≥60 years) with syncope or near-syncope. A standardized data extraction tool was used to collect information during their index visit and at 30-day follow-up. Our primary outcome was the incidence of 30-day death or serious clinical events. Data were analyzed with descriptive statistics and multivariate logistic regression analysis adjusting for relevant demographic or historical variables.ResultsA total of 3,581 patients (mean age 72.8 years; 51.6% men) were enrolled in the study. There were 1,380 patients (39%) presenting with near-syncope and 2,201 (61%) presenting with syncope. Baseline characteristics revealed a greater incidence of congestive heart failure, coronary artery disease, previous arrhythmia, nonwhite race, and presenting dyspnea in the near-syncope compared with syncope cohort. There were no differences in the primary outcome between the groups (near-syncope 18.7% versus syncope 18.2%). A multivariate logistic regression analysis identified no difference in 30-day serious outcomes for patients with near-syncope (odds ratio 0.94; 95% confidence interval 0.78 to 1.14) compared with syncope.ConclusionNear-syncope confers risk to patients similar to that of syncope for the composite outcome of 30-day death or serious clinical event.

OBJECTIVES:An estimated 1.2 million annual emergency department (ED) visits for syncope/near syncope occur in the United States. Cardiac biomarkers are frequently obtained during the ED evaluation, but the prognostic value of index high-sensitivity troponin (hscTnT) and natriuretic peptide (NT-proBNP) are unclear. The objective of this study was to determine if hscTnT and NT-proBNP drawn in the ED are independently associated with 30-day death/serious cardiac outcomes in adult patients presenting with syncope. METHODS:A prespecified secondary analysis of a prospective, observational trial enrolling participants ≥ age 60 presenting with syncope, at 11 United States hospitals, was conducted between April 2013 and September 2016. Exclusions included seizure, stroke, transient ischemic attack, trauma, intoxication, hypoglycemia, persistent confusion, mechanical/electrical invention, prior enrollment, or predicted poor follow-up. Within 3 hours of consent, hscTnT and NT-proBNP were collected and later analyzed centrally using Roche Elecsys Gen 5 STAT and 2010 Cobas, respectively. Primary outcome was combined 30-day all-cause mortality and serious cardiac events. Adjusting for illness severity, using multivariate logistic regression analysis, variations between primary outcome and biomarkers were estimated, adjusting absolute risk associated with ranges of biomarkers using Bayesian Markov Chain Monte Carlo methods. RESULTS:The cohort included 3,392 patients; 367 (10.8%) experienced the primary outcome. Adjusted absolute risk for the primary outcome increased with hscTnT and NT-proBNP levels. HscTnT levels ≤ 5 ng/L were associated with a 4% (95% confidence interval [CI] = 3%-5%) outcome risk, and hscTnT > 50 ng/L, a 29% (95% CI = 26%-33%) risk. NT-proBNP levels ≤ 125 ng/L were associated with a 4% (95% CI = 4%-5%) risk, and NT-proBNP > 2,000 ng/L a 29% (95% CI = 25%-32%) risk. Likelihood ratios and predictive values demonstrated similar results. Sensitivity analyses

BackgroundSyncope is a common chief complaint among older adults in the Emergency Department (ED), and orthostatic vital signs are often a part of their evaluation. We assessed whether abnormal orthostatic vital signs in the ED are associated with composite 30-day serious outcomes in older adults presenting with syncope.MethodsWe performed a secondary analysis of a prospective, observational study at 11 EDs in adults ≥ 60 years who presented with syncope or near syncope. We excluded patients lost to follow up. We used the standard definition of abnormal orthostatic vital signs or subjective symptoms of lightheadedness upon standing to define orthostasis. We determined the rate of composite 30-day serious outcomes, including those during the index ED visit, such as cardiac arrhythmias, myocardial infarction, cardiac intervention, new diagnosis of structural heart disease, stroke, pulmonary embolism, aortic dissection, subarachnoid hemorrhage, cardiopulmonary resuscitation, hemorrhage/anemia requiring transfusion, with major traumatic injury from fall, recurrent syncope, and death) between the groups with normal and abnormal orthostatic vital signs.ResultsThe study cohort included 1974 patients, of whom 51.2% were male and 725 patients (37.7%) had abnormal orthostatic vital signs. Comparing those with abnormal to those with normal orthostatic vital signs, we did not find a difference in composite 30-serious outcomes (111/725 (15.3%) vs 184/1249 (14.7%); unadjusted odds ratio, 1.05 [95%CI, 0.81-1.35], p = 0.73). After adjustment for gender, coronary artery disease, congestive heart failure (CHF), history of arrhythmia, dyspnea, hypotension, any abnormal ECG, physician risk assessment, medication classes and disposition, there was no association with composite 30-serious outcomes (adjusted odds ratio, 0.82 [95%CI, 0.62-1.09], p = 0.18).ConclusionsIn a cohort of older adult patients presenting with syncope who were able to have orthostatic vital signs evaluated, abnormal

BACKGROUND:Dentists contribute to the prevailing opioid epidemic in the United States. Concerning the population enrolled in Medicaid, little is known about dentists' opioid prescribing. METHODS:The authors performed a retrospective cohort study of beneficiaries of Medicaid in Washington state with dental claims in 2014 and 2015. The primary outcome was the proportion of dental visits associated with an opioid prescription. The authors categorized visits as invasive or noninvasive by using procedure codes and each beneficiary as being at low or high risk by using his or her prescription history from the prescription drug monitoring program. RESULTS:A total of 126,660 (10.3%) of all dental visits, most of which were invasive (66.9%), among the population enrolled in Medicaid in Washington state was associated with opioid prescriptions. However, noninvasive dental visits and visits for beneficiaries who had prior high-risk prescription use were associated with significantly higher mean days' supply and mean quantity of opioids prescribed. Results from the multivariate logistic regression showed that the probability of having an opioid-associated visit increased by 35.6 percentage points when the procedures were invasive and by 11.1 percentage points when the beneficiary had prior high-risk prescription use. CONCLUSIONS:This baseline of opioid prescribing patterns after dental visits among the population enrolled in Medicaid in Washington state in 2014 and 2015 can inform future studies in which the investigators examine the effect of policies on opioid prescribing patterns and reasons for the variability in the dosage and duration of opioid prescriptions associated with noninvasive visits. PRACTICAL IMPLICATIONS:Dentists must exercise caution when prescribing opioids during invasive visits and to patients with prior high-risk prescription use.

Study objectiveMany adults with syncope are hospitalized solely for observation and testing. We seek to determine whether hospitalization versus outpatient management for older adults with unexplained syncope is associated with a reduction in postdisposition serious adverse events at 30 days.MethodsWe performed a propensity score analysis using data from a prospective, observational study of older adults with unexplained syncope or near syncope who presented to 11 emergency departments (EDs) in the United States. We enrolled adults (≥60 years) who presented with syncope or near syncope. We excluded patients with a serious diagnosis identified in the ED. Clinical and laboratory data were collected on all patients. The primary outcome was rate of post-ED serious adverse events at 30 days.ResultsWe enrolled 2,492 older adults with syncope and no serious ED diagnosis from April 2013 to September 2016. Mean age was 73 years (SD 8.9 years), and 51% were women. The incidence of serious adverse events within 30 days after the index visit was 7.4% for hospitalized patients and 3.19% for discharged patients, representing an unadjusted difference of 4.2% (95% confidence interval 2.38% to 6.02%). After propensity score matching on risk of hospitalization, there was no statistically significant difference in serious adverse events at 30 days between the hospitalized group (4.89%) and the discharged group (2.82%) (risk difference 2.07%; 95% confidence interval -0.24% to 4.38%).ConclusionIn our propensity-matched sample of older adults with unexplained syncope, for those with clinical characteristics similar to that of the discharged cohort, hospitalization was not associated with improvement in 30-day serious adverse event rates.

While mobility and safety of older drivers are challenged by age-related cognitive changes, the increasingly complex road environment has placed a higher demand on their adaptability. Older drivers experience difficulties in regulating their operational level behaviors which rely on the second-to-second decision-making, e.g., using the visuospatial information to guide their steering. The roundabout maneuver is one of the critical scenarios for older drivers which requires efficient visual and motor coordination. Understanding older drivers’ visual-motor coordination at roundabouts will provide insights into the mobility and safety of older driver population, which is important yet to be explored. This paper contributes to new measurements in driving behavior through quantitative examinations on driver–vehicle–environment interactions. The drivers’ visual-motor coordination is conceptualized as a sequence of eye fixations coupling with the vehicle trajectory in a space–time path. The experimental data were from 38 older adults’ on-road driving recorded using context and location-aware enabled eye tracking and precise vehicle movement tracking. A visual-motor coordination composite indicator (VMCCI) was developed to measure the efficiency of visual-motor coordination in GIS based on the aggregate multiple parameters of visual and motor behaviors at entry, circulating and exit stage of a roundabout. The results show that the VMCCI is a sensitive indicator for identifying risky drivers, problematic road sections, problematic behaviors. Older drivers’ VMCCI was associated with the angle of deviation at roundabouts, particularly at the entry stage. Findings of this study have implications for actual roundabout designing practice, which will contribute to improve the safety of older drivers behind the wheel.

Natural killer (NK) cells are innate lymphocytes that possess adaptive features, including antigen-specific clonal expansion and long-lived memory responses. Although previous work demonstrated that type I interferon (IFN) signaling is crucial for NK cell expansion and memory cell formation following mouse cytomegalovirus (MCMV) infection, the global transcriptional mechanisms underlying type I IFN-mediated responses remained to be determined. Here, we demonstrate that among the suite of transcripts induced in activated NK cells, IFN-α is necessary and sufficient to promote expression of its downstream transcription factors STAT1, STAT2, and IRF9, via an auto-regulatory, feedforward loop. Similar to STAT1 deficiency, we show that STAT2- or IRF9-deficient NK cells are defective in their ability to expand following MCMV infection, in part because of diminished survival rather than an inability to proliferate. Thus, our findings demonstrate that individual ISGF3 components are crucial cell-autonomous and non-redundant regulators of the NK cell response to viral infection. Using RNA-seq and ChIP-seq, Geary et al. investigate the impacts of type I interferon on NK cells during MCMV infection and demonstrate crucial and non-redundant roles for STAT1, STAT2, and IRF9 in promoting cytotoxicity and survival of antiviral NK cells.

Innate immune cells quickly infiltrate the site of pathogen entry and not only stave off infection but also initiate antigen presentation and promote adaptive immunity. The recruitment of innate leukocytes has been well studied in the context of extracellular bacterial and fungal infection but less during viral infections. We have recently shown that the understudied cytokine Interleukin (IL)-17D can mediate neutrophil, natural killer (NK) cell and monocyte infiltration in sterile inflammation and cancer. Herein, we show that early immune cell accumulation at the peritoneal site of infection by mouse cytomegalovirus (MCMV) is mediated by IL-17D. Mice deficient in IL-17D or the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an inducer of IL-17D, featured an early decreased number of innate immune cells at the point of viral entry and were more susceptible to MCMV infection. Interestingly, we were able to artificially induce innate leukocyte infiltration by applying the Nrf2 activator tert-butylhydroquinone (tBHQ), which rendered mice less susceptible to MCMV infection. Our results implicate the Nrf2/IL-17D axis as a sensor of viral infection and suggest therapeutic benefit in boosting this pathway to promote innate antiviral responses.

In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus coordinates daily rhythms including sleep-wake, hormone release, and gene expression. The cells of the SCN must synchronize to each other to drive these circadian rhythms in the rest of the body. The ontogeny of circadian cycling and intercellular coupling in the SCN remains poorly understood. Recent in vitro studies have recorded circadian rhythms from the whole embryonic SCN. Here, we tracked the onset and precision of rhythms in PERIOD2 (PER2), a clock protein, within the SCN isolated from embryonic and postnatal mice of undetermined sex. We found that a few SCN cells developed circadian periodicity in PER2 by 14.5 d after mating (E14.5) with no evidence for daily cycling on E13.5. On E15.5, the fraction of competent oscillators increased dramatically corresponding with stabilization of their circadian periods. The cells of the SCN harvested at E15.5 expressed sustained, synchronous daily rhythms. By postnatal day 2 (P2), SCN oscillators displayed the daily, dorsal-ventral phase wave in clock gene expression typical of the adult SCN. Strikingly, vasoactive intestinal polypeptide (VIP), a neuropeptide critical for synchrony in the adult SCN, and its receptor, VPAC2R, reached detectable levels after birth and after the onset of circadian synchrony. Antagonists of GABA or VIP signaling or action potentials did not disrupt circadian synchrony in the E15.5 SCN. We conclude that endogenous daily rhythms in the fetal SCN begin with few noisy oscillators on E14.5, followed by widespread oscillations that rapidly synchronize on E15.5 by an unknown mechanism.SIGNIFICANCE STATEMENT We recorded the onset of PER2 circadian oscillations during embryonic development in the mouse SCN. When isolated at E13.5, the anlagen of the SCN expresses high, arrhythmic PER2. In contrast, a few cells show noisy circadian rhythms in the isolated E14.5 SCN and most show reliable, self-sustained, synchronized rhythms in the E15.5

Introduction: We performed a systematic review and meta-analysis to identify predictors of serious clinical outcomes after an acute-care evaluation for syncope. Methods: We identified studies that assessed for predictors of short-term (≤30 days) serious clinical events after an emergency department (ED) visit for syncope. We performed a MEDLINE search (January 1, 1990 - July 1, 2017) and reviewed reference lists of retrieved articles. The primary outcome was the occurrence of a serious clinical event (composite of mortality, arrhythmia, ischemic or structural heart disease, major bleed, or neurovascular event) within 30 days. We estimated the sensitivity, specificity, and likelihood ratio of findings for the primary outcome. We created summary estimates of association on a variable-by-variable basis using a Bayesian random-effects model. Results: We reviewed 2,773 unique articles; 17 met inclusion criteria. The clinical findings most predictive of a short-term, serious event were the following: 1) An elevated blood urea nitrogen level (positive likelihood ratio [LR+]: 2.86, 95% confidence interval [CI] [1.15, 5.42]); 2); history of congestive heart failure (LR+: 2.65, 95%CI [1.69, 3.91]); 3) initial low blood pressure in the ED (LR+: 2.62, 95%CI [1.12, 4.9]); 4) history of arrhythmia (LR+: 2.32, 95%CI [1.31, 3.62]); and 5) an abnormal troponin value (LR+: 2.49, 95%CI [1.36, 4.1]). Younger age was associated with lower risk (LR-: 0.44, 95%CI [0.25, 0.68]). An abnormal electrocardiogram was mildly predictive of increased risk (LR+ 1.79, 95%CI [1.14, 2.63]). Conclusion: We identified specific risk factors that may aid clinical judgment and that should be considered in the development of future risk-prediction tools for serious clinical events after an ED visit for syncope.

We use deep multi-epoch PSF photometry taken with the Visible and Infrared Survey Telescope for Astronomy (VISTA) to measure and analyze the proper motions of stars within the Galactic globular cluster 47 Tucanae (47 Tuc, NGC 104). The observations are part of the ongoing near-infrared VISTA survey of the Magellanic Cloud system (VMC). The data analyzed here corresponds to one VMC tile and covers a total sky area of 1.77 deg^2. Absolute proper motions with respect to ~9070 background galaxies are calculated from a linear regression model applied to the stellar positions in 11 epochs in the Ks filter. The data extend over a total time baseline of ~17 months. We found a median proper motion of the stars within 47 Tuc of (mu_a cos(d), mu_d) = (+5.89 +/- 0.02(stat) +/- 0.13(sys), -2.14 +/- 0.02(stat) +/- 0.08(sys)) mas/yr, based on the measurements of ~35000 individual sources between 5' and 42' from the cluster center. We compared our result to the proper motions from the newest US Naval Observatory CCD Astrograph Catalog (UCAC5) which includes data from the Gaia data release 1. Selecting cluster members (~2700 stars) we found a median proper motion of (mu_a cos(d), mu_d) = (+5.30 +/- 0.03(stat) +/- 0.70(sys), -2.70 +/- 0.03(stat) +/- 0.70(sys)) mas/yr. The values derived from the VMC data are consistent with the UCAC5 result, and are close to literature measurements obtained using HST. We combined our results with literature radial velocity measurements and reconstructed the orbit of 47 Tuc, finding that the cluster is on a low-ellipticity orbit and is confined within the inner ~7.5 kpc of the Galaxy. We show that the use of an increased time baseline combined with PSF-determined stellar centroids in crowded regions significantly improves the accuracy of the method. In future works, we will apply this method to more VMC tiles to study in detail the kinematics of the Magellanic Clouds., Comment: 16 pages, 15 figures, accepted for publication in A&A

It is generally accepted that significant germ cell loss occurs during the establishment of the primordial follicle pool in most mammalian ovaries around the time of birth. However, the underlying mechanisms responsible for these processes remain largely unknown. In this investigation, we explored the role of autophagy during the establishment of the primordial follicle pool and found that autophagy was active in this process. Our data suggested that 17.5 dpc ovaries treated with rapamycin displayed a delay in germ cell cyst breakdown resulting in more oocytes at day 5 of treatment, while, ovaries that treated with 3-MA showed the opposite effect. We found that rapamycin treatment promoted autophagy and depressed cell apoptosis increasing the number of NOBOX positive oocytes. Furthermore, our results also revealed that epigenetic regulator, Sirt1, plays a role in germ cell loss. An epigenetic inhibitor or RNAi treatment of Sirt1, showed an increased level of H4K16ac and a decreased level of autophagy. Thus, these data indicate that autophagy prevents germ cell over loss during the establishment of primordial follicle pool, and this process may be influenced by Sirt1-invovled epigenetic regulation.

Study objectiveCardiac arrhythmia is a life-threatening condition in older adults who present to the emergency department (ED) with syncope. Previous work suggests the initial ED ECG can predict arrhythmia risk; however, specific ECG predictors have been variably specified. Our objective is to identify specific ECG abnormalities predictive of 30-day serious cardiac arrhythmias in older adults presenting to the ED with syncope.MethodsWe conducted a prospective, observational study at 11 EDs in adults aged 60 years or older who presented with syncope or near syncope. We excluded patients with a serious cardiac arrhythmia diagnosed during the ED evaluation from the primary analysis. The outcome was occurrence of 30-day serous cardiac arrhythmia. The exposure variables were predefined ECG abnormalities. Independent predictors were identified through multivariate logistic regression. The sensitivities and specificities of any predefined ECG abnormality and any ECG abnormality identified on adjusted analysis to predict 30-day serious cardiac arrhythmia were also calculated.ResultsAfter exclusion of 197 patients (5.5%; 95% confidence interval [CI] 4.7% to 6.2%) with serious cardiac arrhythmias in the ED, the study cohort included 3,416 patients. Of these, 104 patients (3.0%; 95% CI 2.5% to 3.7%) had a serious cardiac arrhythmia within 30 days from the index ED visit (median time to diagnosis 2 days [interquartile range 1 to 5 days]). The presence of nonsinus rhythm, multiple premature ventricular conductions, short PR interval, first-degree atrioventricular block, complete left bundle branch block, and Q wave/T wave/ST-segment abnormalities consistent with acute or chronic ischemia on the initial ED ECG increased the risk for a 30-day serious cardiac arrhythmia. This combination of ECG abnormalities had a similar sensitivity in predicting 30-day serious cardiac arrhythmia compared with any ECG abnormality (76.9% [95% CI 67.6% to 84.6%] versus 77.9% [95% CI 68.7% to 85.4%])