cssi/SciSciGPT-SciSciNet huggingface dataset:
Replication Rapidly Recovers and Continues in the Presence of Hydroxyurea in Escherichia coli

ABSTRACT In both prokaryotes and eukaryotes, hydroxyurea is suggested to inhibit DNA replication by inactivating ribonucleotide reductase and depleting deoxyribonucleoside triphosphate pools. In this study, we show that the inhibition of replication in Escherichia coli is transient even at concentrations of 0.1 M hydroxyurea and that replication rapidly recovers and continues in its presence. The recovery of replication does not require the alternative ribonucleotide reductases NrdEF and NrdDG or the translesion DNA polymerases II (Pol II), Pol IV, and Pol V. Ribonucleotides are incorporated at higher frequencies during replication in the presence of hydroxyurea. However, they do not contribute significantly to the observed synthesis or toxicity. Hydroxyurea toxicity was observed only under conditions where the stability of hydroxyurea was compromised and by-products known to damage DNA directly were allowed to accumulate. The results demonstrate that hydroxyurea is not a direct or specific inhibitor of DNA synthesis in vivo and that the transient inhibition observed is most likely due to a general depletion of iron cofactors from enzymes when 0.1 M hydroxyurea is initially applied. Finally, the results support previous studies suggesting that hydroxyurea toxicity is mediated primarily through direct DNA damage induced by the breakdown products of hydroxyurea, rather than by inhibition of replication or depletion of deoxyribonucleotide levels in the cell. IMPORTANCE Hydroxyurea is commonly suggested to function by inhibiting DNA replication through the inactivation of ribonucleotide reductase and depleting deoxyribonucleoside triphosphate pools. Here, we show that hydroxyurea only transiently inhibits replication in Escherichia coli before replication rapidly recovers and continues in the presence of the drug. The recovery of replication does not depend on alternative ribonucleotide reductases, translesion synthesis, or RecA. Further, we show that hydroxyurea toxicity is observed only in the presence of toxic intermediates that accumulate when hydroxyurea breaks down, damage DNA, and induce lethality. The results demonstrate that hydroxyurea toxicity is mediated indirectly by the formation of DNA damage, rather than by inhibition of replication or depletion of deoxyribonucleotide levels in the cell.
Rhodococcus equi Infections in Goats: Characterization of Virulence Plasmids.

Rhodococcus equi is an uncommon cause of systemic pyogranulomatous infections in goats with macroscopic similarities to caseous lymphadenitis caused by Corynebacterium pseudotuberculosis. Caprine cases have previously been reported to be caused by avirulent R. equi strains. Six cases of R. equi infection in goats yielding 8 R. equi isolates were identified from 2000 to 2017. Lesions varied from bronchopneumonia, vertebral and humeral osteomyelitis, and subcutaneous abscesses, to disseminated infection involving the lungs, lymph nodes, and multiple visceral organs. Isolates of R. equi from infected goats were analyzed by polymerase chain reaction for R. equi virulence-associated plasmid (vap) genes. Seven of 8 isolates carried the VapN plasmid, originally characterized in bovine isolates, while 1 isolate lacked virulence plasmids and was classified as avirulent. The VapN plasmid has not been described in isolates cultured from goats.
Cobalt chloride compromises transepithelial barrier properties of CaCo-2 BBe human gastrointestinal epithelial cell layers

Elevation of the transcription factor HIF-1 is a prominent mediator of not only processes that accompany hypoxia, but also the tumor microenvironment and tissue regeneration. This study uses mediators of “chemical hypoxia” to ask the question whether HIF-1α elevation in a healthy epithelial cell layer leads to leakiness in its tight junctional seals. Transepithelial electrical resistance and transepithelial diffusion of 14C–D-mannitol and other radiolabeled probes are used as indicators of transepithelial barrier function of CaCo-2 BBe human gastrointestinal epithelial cell layers cultured on permeable supports. Western immunoblot analyses of integral tight junctional proteins (occludin and claudins) are used as further indicators of barrier function change. Cobalt, an inhibitor of the prolyl hydroxylase enzymes governing HIF-1α breakdown in the cell, induces transepithelial leakiness in CaCo-2 BBe cell layers in a time and concentration-dependent manner. This increased leakiness is accompanied by significant changes in certain specific integral tight junctional (TJ) proteins such as a decreased level of occludin and increased level of claudin-5. Similar results regarding barrier function compromise also occur with other chemical inhibitors of HIF-1α breakdown, namely ciclopiroxolamine (CPX) and dimethyloxalylglycine (DMOG). The increased leak is manifested by both decreased transepithelial electrical resistance (Rt) and increased paracellular diffusion of D-mannitol (Jm). The induced transepithelial leak shows significant size selectivity, consistent with induced effects on TJ permeability. Less-differentiated cell layers were significantly more affected than well-differentiated cell layers regarding induced transepithelial leak. A genetically modified CaCo-2 variant with reduced levels of HIF-1β, showed reduced transepithelial leak in response to cobalt exposure, further indicating that elevation of HIF-1α levels induced by agents of “chemical hypoxia” is responsible for the compromised barrier function of the CaCo-2 BBe cell layers. Exposure to inducers of chemical hypoxia elevated HIF-1α levels and increased transepithelial leak. The degree of epithelial differentiation has significant effects on this action, possibly explaining the varying effects of HIF-1 modulation in epithelial and endothelial barrier function in different physiological and pathophysiological conditions.
The effect of community socioeconomic status on sepsis-attributable mortality

Abstract Purpose Community factors may play a role in determining individual risk for sepsis, as well as sepsis-related morbidity and mortality. We sought to define the relationship between community socioeconomic status and mortality due to sepsis in an urban locale. Methods Using community statistical areas of Baltimore City, we dichotomized neighborhoods at median household income, and compared distribution of outcomes of interest within the two income categories. We performed multivariable regression analyses to determine the relationship between socioeconomic variables and sepsis-attributable mortality. Results The collective median household income was $38,660 (IQR $32,530, 54,480), family poverty rate was 28.4% (IQR 13.5, 38.8%), and rate of death from sepsis was 3.1 per 10,000 persons (IQR 2.60, 4.10). Lower household income communities demonstrated higher rates of death from sepsis (3.65 (IQR 2.78, 4.40)) than higher household income communities (2.80 (IQR 2.05, 3.55)) (p = .02). In regression models, household income (β = −8.42, p = .006) and percentage of poverty in communities (β = 2.71, p = .01) demonstrated associations with sepsis-attributable mortality. Discussion Our findings suggest that socioeconomic variables play significant role in sepsis-attributable mortality. Such confirmation of regional disparities in mortality due to sepsis warrants further consideration, as well as integration, for future national sepsis policies.
An innovative program to support gender equity and success in academic medicine: Early experiences from the doris duke charitable foundation's fund to retain clinical scientists

Author(s): Jagsi, Reshma; Jones, Rochelle D; Griffith, Kent A; Brady, Kathleen T; Brown, Ann J; Davis, Randal D; Drake, Amelia F; Ford, Daniel; Fraser, Victoria J; Hartmann, Katherine E; Hochman, Judith S; Girdler, Susan; Libby, Anne M; Mangurian, Christina; Regensteiner, Judith G; Yonkers, Kimberly; Escobar-Alvarez, Sindy; Myers, Elizabeth R
Dzyaloshinskii-Moriya interaction in the presence of Rashba and Dresselhaus spin-orbit coupling

Chiral order in magnetic structures is currently an area of considerable interest and leads to skyrmion structures and domain walls with certain chirality. The chiral structure originates from the Dzyaloshinskii-Moriya interaction caused by broken inversion symmetry and the spin-orbit interaction. In addition to the Rashba or Dresselhaus interactions, there may also exist substantial spin polarization in magnetic thin films. Here, we study the exchange interaction between two localized magnetic moments in the spin-polarized electron gas with both Rashba and Dresselhaus spin-orbit interaction present. Analytical expressions are found in certain limits in addition to what is known in the literature. The stability of the Bloch and N\'eel domain walls in magnetic thin films is discussed in light of our results.
Higher-Order Waveguides

The waveguide theories of the last two chapters were based on some elementary mechanics modeling; the question obviously arises as to the adequacy of these models. We will try to clarify the issues involved by considering some exact solutions of waves in waveguides; this is a difficult and mathematically cumbersome area so only a limited number of aspects will be treated. The chapter begins by looking at waves in extended media and waves in bounded media as illustrated in Figure 4.1. Perhaps the most important insight into the functioning of the exact waveguides is the number of modes they support — in fact, they support an infinity of modes. We will show that the behavior of these modes was anticipated by considering the effects of elastic constraint in the elementary models.
Comparison of choroidal neovascularization secondary to white dot syndromes and age-related macular degeneration by using optical coherence tomography angiography

Purpose To characterize and compare choroidal neovascularization (CNV) secondary to white dot syndromes (WDS) and age-related macular degeneration (AMD) using optical coherence tomography angiography (OCT-A). Methods This is a cross-sectional study in which we imaged patients with CNV secondary to WDS and AMD with either the Zeiss Angioplex OCT-A or Optovue AngioVue OCT-A. Relevant demographic and clinical characteristics were collected and analyzed. CNV area and vessel density (VD) were measured by three independent graders, and linear regression analysis was subsequently performed. Results Three patients with multifocal choroiditis and panuveitis, one patient each with birdshot chorioretinopathy, presumed ocular histoplasmosis syndrome, and persistent placoid maculopathy, and eleven patients with AMD with sufficient image quality were included. CNV associated with WDS was significantly smaller than that secondary to AMD (0.56±0.32 vs 2.79±1.80 mm2, β=-2.22, P=0.01), while no difference in VD was detected (0.46±0.09 vs 0.44±0.09, β=0.02, P=0.71). Conclusion CNV networks secondary to WDS appear to be smaller than those secondary to AMD but have similar VD. OCT-A is a powerful tool to investigate properties of CNV from various etiologies. Larger studies are needed for further characterization and understanding of CNV pathogenesis in inflammatory conditions.
An Optical Spatial Localization Algorithm Using Single Temporal Difference Image Sensor

We present a novel single-camera 3-D spatial localization method using optical triangulation with temporal-difference image processing. The proposed system uses a blinking LED circle attached to the target as a marker. The background image except the marker circle is removed by applying temporal difference of the images since the imager samples at twice of the target blinking frequency. The 3-D spatial location can be calculated using simple equations to save computing energy without computing triangulation functions. The proposed method can be applied in low-power outdoor unmanned aerial vehicle (UAV) localization applications. The experimental results show that the proposed method can measure an object with an error of 0.4 m in the range of 30 m, or 0.1 m in the range of 3 m. The proposed method provides an attractive low power solution for remote UAV alignment and control.
Nominal GDP as the Stance of Monetary Policy: A Practical Guide

Nominal GDP (NGDP) targeting has received a lot of attention over the past decade. This note provides a brief review of the key arguments for NGDP targeting and then presents some practical ways to use it in the conduct of U.S. monetary policy. Specifically, this note shows how to construct benchmark growth paths for NGDP that can help the Fed assess the stance of monetary policy. This approach provides a useful cross-check to other measures of the stance of monetary policy.
Development of Machine Learning Algorithms for Prediction of Sustained Postoperative Opioid Prescriptions After Total Hip Arthroplasty.

Abstract Background Postoperative recovery after total hip arthroplasty (THA) can lead to the development of prolonged opioid use but there are few tools for predicting this adverse outcome. The purpose of this study is to develop machine learning algorithms for preoperative prediction of prolonged opioid prescriptions after THA. Methods A retrospective review of electronic health records was conducted at 2 academic medical centers and 3 community hospitals to identify adult patients who underwent THA for osteoarthritis between January 1, 2000 and August 1, 2018. Prolonged postoperative opioid prescriptions were defined as continuous opioid prescriptions after surgery to at least 90 days after surgery. Five machine learning algorithms were developed to predict this outcome and were assessed by discrimination, calibration, and decision curve analysis. Results Overall, 5507 patients underwent THA, of which 345 (6.3%) had prolonged postoperative opioid prescriptions. The factors determined for prediction of prolonged postoperative opioid prescriptions were age, duration of opioid exposure, preoperative hemoglobin, and preoperative medications (antidepressants, benzodiazepines, nonsteroidal anti-inflammatory drugs, and beta-2-agonists). The elastic-net penalized logistic regression model achieved the best performance across discrimination (c-statistic = 0.77), calibration, and decision curve analysis. This model was incorporated into a digital application able to provide both predictions and explanations (available at https://sorg-apps.shinyapps.io/thaopioid/ ). Conclusion If externally validated in independent populations, the algorithms developed in this study could improve preoperative screening and support for THA patients at high risk for prolonged postoperative opioid prescriptions. Early identification and intervention in high-risk cases may mitigate the long-term adverse consequence of opioid dependence. Level of Evidence III.
Follow the Oxygen: Comparative Histories of Planetary Oxygenation and Opportunities for Aerobic Life.

Aerobic respiration—the reduction of molecular oxygen (O_2) coupled to the oxidation of reduced compounds such as organic carbon, ferrous iron, reduced sulfur compounds, or molecular hydrogen while conserving energy to drive cellular processes—is the most widespread and bioenergetically favorable metabolism on Earth today. Aerobic respiration is essential for the development of complex multicellular life; thus the presence of abundant O_2 is an important metric for planetary habitability. O_2 on Earth is supplied by oxygenic photosynthesis, but it is becoming more widely understood that abiotic processes may supply meaningful amounts of O_2 on other worlds. The modern atmosphere and rock record of Mars suggest a history of relatively high O2 as a result of photochemical processes, potentially overlapping with the range of O_2 concentrations used by biology. Europa may have accumulated high O_2 concentrations in its subsurface ocean due to the radiolysis of water ice at its surface. Recent modeling efforts suggest that coexisting water and O2 may be common on exoplanets, with confirmation from measurements of exoplanet atmospheres potentially coming soon. In all these cases, O_2 accumulates through abiotic processes—independent of water-oxidizing photosynthesis. We hypothesize that abiogenic O_2 may enhance the habitability of some planetary environments, allowing highly energetic aerobic respiration and potentially even the development of complex multicellular life which depends on it, without the need to first evolve oxygenic photosynthesis. This hypothesis is testable with further exploration and life-detection efforts on O_2-rich worlds such as Mars and Europa, and comparison to O_2-poor worlds such as Enceladus. This hypothesis further suggests a new dimension to planetary habitability: “Follow the Oxygen,” in which environments with opportunities for energy-rich metabolisms such as aerobic respiration are preferentially targeted for investigation and life detection.
Exchange Transfusion Simulation Models: A Technical Report.

This technical report describes the creation of two exchange transfusion models in the newborn. These are low cost, easy to assemble, authentic, and realistic task trainers that provide the opportunity for neonatal providers to practice this rare, life-saving procedure. A critical action checklist is included to guide the simulated procedure. Also included is a suggested clinical scenario with optional complications and variations.
Vaccination: Not a trigger for MS.

Vaccinations revolutionized medicine in the 20th century with the near or total elimination of disabling, life-threatening infections. Yet, despite clear benefits to public health, suspicion of ill effects related to vaccines has risen in recent years. In large part, this fear of vaccination has been fueled by poorly designed, inaccurate, or even fraudulent studies1–3 linking vaccinations to adverse outcomes. While more recent large and well-designed studies have assuaged concerns about vaccines,4 some public mistrust remains. The recent resurgence of measles and resultant public health crisis across the United States, with more than 700 cases in 2019—the greatest number since 1994—highlights this growing distrust.5 Distrust in vaccines is centered primarily on questions of their potential to cause health problems, among them behavioral and autoimmune disease. With this background in mind, it is no surprise, then, that one of the most common queries that patients and families ask physicians dealing with a chronic immune-mediated disorder like multiple sclerosis (MS) is as follows: Did this or any vaccine cause or trigger MS?
Multi-trophic native and non-native prey naïveté shape marine invasion success

Invasive predators have caused rapid declines in many native prey species across the globe. Predator invasion success may be attributed to prey naivete, or the absence of anti-predator behavior between native and non-native species. An understanding of the effects of naivete at different timescales since introduction and across multiple trophic levels is lacking, however, particularly in marine systems. Given the central role of trophic interactions in invasion dynamics, this knowledge gap limits the ability to predict high impact predator invasions. Naivete was examined across three trophic levels of marine invertebrates: a native basal prey (hard clam), two non-native intermediate predators (the recently-introduced Asian shore crab and the long-established European green crab), a native intermediate predator (juvenile blue crabs), and a native top predator (adult blue crab). We hypothesized that naivete would be more pronounced in trophic interactions involving the recently-introduced non-native predator in comparison to the long-established non-native and native intermediate predators. We further hypothesized that the recently-introduced intermediate predator would both benefit from naivete of the native basal prey and be hindered by higher mortality through its own naivete to the native top predator. To test these hypotheses, three laboratory experiments and a field experiment were used. Consistent with our hypotheses, basal prey naivete was most pronounced with the recently-introduced intermediate predator, and this increased the predator's foraging success. This recently-introduced intermediate predator, however, exhibited an ineffective anti-predator response to the native top predator, and was also preyed upon more in the field than its long-established and native counterparts. Therefore, despite direct benefits from basal prey naivete, the recently-introduced intermediate predator's naivete to its own predators may limit its invasion success. These results highlight the importance of a multi-trophic perspective on predator-prey dynamics to more fully understand the consequences of naivete in invasion biology.
Dynamic Multi-Resolution Data Storage

Approximate computing that works on less precise data leads to significant performance gains and energy-cost reductions for compute kernels. However, without leveraging the full-stack design of computer systems, modern computer architectures undermine the potential of approximate computing. In this paper, we present Varifocal Storage, a dynamic multi-resolution storage system that tackles challenges in performance, quality, flexibility and cost for computer systems supporting diverse application demands. Varifocal Storage dynamically adjusts the dataset resolution within a storage device, thereby mitigating the performance bottleneck of exchanging/preparing data for approximate compute kernels. Varifocal Storage introduces Autofocus and iFilter mechanisms to provide quality control inside the storage device and make programs more adaptive to diverse datasets. Varifocal Storage also offers flexible, efficient support for approximate and exact computing without exceeding the costs of conventional storage systems by (1) saving the raw dataset in the storage device, and (2) targeting operators that complement the power of existing SSD controllers to dynamically generate lower-resolution datasets. We evaluate the performance of Varifocal Storage by running applications on a heterogeneous computer with our prototype SSD. The results show that Varifocal Storage can speed up data resolution adjustments by 2.02× or 1.74× without programmer input. Compared to conventional approximate-computing architectures, Varifocal Storage speeds up the overall execution time by 1.52×.
Photodynamic Therapy for Choroidal Metastasis Tumor Control and Visual Outcomes in 58 Cases: The 2019 Burnier International Ocular Pathology Society Lecture.

Purpose To determine outcomes after photodynamic therapy (PDT) for choroidal metastasis. Design Retrospective interventional case series. Participants Forty-three patients with 40 eyes harboring 58 choroidal metastases. Methods Treatment with standard fluence PDT using verteporfin. Main Outcome Measures Tumor control and visual outcomes. Results The primary cancer originated in the lung (n = 17 [39%]), breast (n = 16 [37%]), kidney (n = 3 [8%]), thyroid (n = 2 [6%]), and other sites (n = 5 [10%]). The mean patient age at entry was 61 years. Ocular symptoms included decreased visual acuity (n = 23 [53%]), visual field defect (n = 2 [5%]), floaters (n = 7 [16%]), flashes (n = 3 [7%]), and asymptomatic (n = 8 [19%]). The median entering visual acuity (Snellen equivalent) was 20/40. The median tumor diameter was 5.0 mm, and median thickness by ultrasonography was 2.0 mm. The median distance to the optic disc was 3.0 mm, and that to the foveola was 2.0 mm. Of the 43 patients, 35 maintained follow-up (40 eyes, 45 tumors), and PDT achieved tumor control with 1 session (n = 32 tumors [71%]) or 2 sessions (n = 3 tumors [7%]) and failed to achieve regression (n = 10 tumors [22%]). The 10 metastases for which treatment failed were managed further with plaque radiotherapy (n = 3), proton beam radiotherapy (n = 1), external beam radiotherapy (n = 1), systemic chemotherapy (n = 4), and observation (patient preference; n = 1). A comparison of clinical features for tumor control (PDT alone vs. PDT plus additional therapy) revealed those controlled with PDT alone were more likely to be adenocarcinoma (73% vs. 30%; P = 0.02) and those eyes were more like to achieve final visual acuity of 20/20 to 20/40 (66% vs. 30%; P = 0.03), with better median final Snellen visual acuity (20/30 vs. 20/70; not significant). Primary cancer site or ocular tumor features (size, location, color, shape, related subretinal fluid) did not impact tumor control. In the entire group of 40 eyes, visual acuity improved or remained stable in 28 (70%) and decreased in 12 (30%), related to subfoveal scar, persistent subretinal fluid, reactive exudation, radiation maculopathy, and brain metastasis. At last follow-up (mean, 20 months), of the entering 43 patients, 9 (21%) were alive and 34 (79%) had died of systemic metastasis. Conclusions Photodynamic therapy with verteporfin is an effective outpatient method for small to medium choroidal metastatic tumors, providing tumor control in 78% of eyes and visual outcome of 20/20 to 20/40 in 66% of eyes.
David Oliver: Doughnut deliveries, hospital staff, and the pandemic.

I’ve spent three decades working in acute hospitals. The stress, relentless pace, long shifts with irregular hours, and lack of access to fresh food around the clock have always seen staff use high calorie processed food for comfort, mutual support, and bonding. Whether it’s takeaways, sweets, biscuits, cakes, or crisps—often bought by one member of the team for the rest to help them through a shift or donated by grateful patients and left on the ward—we’re rarely far from impromptu snacking opportunities. Even when it comes to canteens offering healthy options, busy workers often gravitate to the comfort of chips, pizzas, burgers, or fried food. Go to the League of Friends shop, and it’s often full of home baked cakes. During the covid-19 pandemic our levels of stress, distress, and fear have risen, and food and fizzy drinks have featured among our coping strategies. A …
Properties of flowable fill produced by substituting fly ash with recycled glass powder

Abstract A laboratory study was undertaken to evaluate the feasibility of recycling glass powder (RGP) as a fly ash substitute in flowable fill. A total of ten mortar mixtures and ten flowable fill mixtures were prepared by using different proportions of fly ash (FA), finer RGP (FG) and coarser RGP (CG) powders. The mortar mixtures were tested for determining strength activity index (SAI). The flowable fill mixtures were tested for fresh and hardened properties. Further, microstructural study techniques, namely, scanning electron microscope (SEM) and energy dispersive X-ray spectroscope (EDS), were also used for characterizing the changes in the microstructure of flowable fill due to RGP substitution. It was found that RGP has the potential to be a suitable replacement of FA in flowable fill. However, flow consistency and compressive strength were found to vary with the percent RGP substitution and relative proportion of finer and coarser glass content in the flowable fill mixtures.
Awareness of Concussion-Education Requirements, and -Management Plans and Concussion Knowledge in High School and Club Sport Coaches.

CONTEXT A growing number of high-school-aged athletes participate on club sport teams. Some, but not all, state concussion laws apply to both interscholastic and private sport organizations. However, concussion education, management plans, and knowledge have not been examined in club coaches who coach high school-aged athletes. OBJECTIVE To determine if differences in concussion education, management plans, and knowledge exist between high school coaches and coaches of club sport teams. DESIGN Cross-sectional study. SETTING Online survey. PATIENTS OR OTHER PARTICIPANTS A total of 769 coaches (497 high school coaches, 272 club coaches coaching high school-aged athletes; 266 women [34.6%], 503 men [65.4%]) completed an anonymous online questionnaire. MAIN OUTCOME MEASURE(S) The questionnaire consisted of demographic and team information, requirements for concussion-education and -management plans, and concussion knowledge. RESULTS High school coaches were more likely than club coaches to report that their organizing bodies or leagues required them to receive concussion-education information (97.4% versus 80.4%; P < .001) and that their organizing bodies or leagues had a concussion-management plan (94.0% versus 70.2%; P < .001). High school coaches were more likely than club coaches to correctly agree that most concussions resolve in 7 to 10 days (48.6% versus 40.1%; P = .02) and disagree that loss of consciousness is required to diagnose a concussion (87.1% versus 80.9%; P = .02). CONCLUSIONS Club coaches were less likely to be aware of requirements for concussion-education and -management plans from their parent organizations and scored lower on specific concussion-knowledge questions than high school coaches despite the same education requirements across groups under their state concussion laws. These results raise concerns regarding the proper management of concussions in club sports and suggest a need for greater oversight and enforcement of state laws in the club sport setting.
Structured layer surface segmentation for retina OCT using fully convolutional regression networks.

Abstract Optical coherence tomography (OCT) is a noninvasive imaging modality with micrometer resolution which has been widely used for scanning the retina. Retinal layers are important biomarkers for many diseases. Accurate automated algorithms for segmenting smooth continuous layer surfaces with correct hierarchy (topology) are important for automated retinal thickness and surface shape analysis. State-of-the-art methods typically use a two step process. Firstly, a trained classifier is used to label each pixel into either background and layers or boundaries and non-boundaries. Secondly, the desired smooth surfaces with the correct topology are extracted by graph methods (e.g., graph cut). Data driven methods like deep networks have shown great ability for the pixel classification step, but to date have not been able to extract structured smooth continuous surfaces with topological constraints in the second step. In this paper, we combine these two steps into a unified deep learning framework by directly modeling the distribution of the surface positions. Smooth, continuous, and topologically correct surfaces are obtained in a single feed forward operation. The proposed method was evaluated on two publicly available data sets of healthy controls and subjects with either multiple sclerosis or diabetic macular edema, and is shown to achieve state-of-the art performance with sub-pixel accuracy.
Structuring clinical text with AI: old vs. new natural language processing techniques evaluated on eight common cardiovascular diseases

Abstract Mining the structured data in electronic health records(EHRs) enables many clinical applications while the information in free-text clinical notes often remains untapped. Free-text notes are unstructured data harder to use in machine learning while structured diagnostic codes can be missing or even erroneous. To improve the quality of diagnostic codes, this work extracts structured diagnostic codes from the unstructured notes concerning cardiovascular diseases. Five old and new word embeddings were used to vectorize over 5 million progress notes from Stanford EHR and logistic regression was used to predict eight ICD-10 codes of common cardiovascular diseases. The models were interpreted by the important words in predictions and analyses of false positive cases. Trained on Stanford notes, the model transferability was tested in the prediction of corresponding ICD-9 codes of the MIMIC-III discharge summaries. The word embeddings and logistic regression showed good performance in the diagnostic code extraction with TF-IDF as the best word embedding model showing AU-ROC ranging from 0.9499 to 0.9915 and AUPRC ranging from 0.2956 to 0.8072. The models also showed transferability when tested on MIMIC-III data set with AUROC ranging from 0.7952 to 0.9790 and AUPRC ranging from 0.2353 to 0.8084. Model interpretability was showed by the important words with clinical meanings matching each disease. This study shows the feasibility to accurately extract structured diagnostic codes, impute missing codes and correct erroneous codes from free-text clinical notes with interpretable models for clinicians, which helps improve the data quality of diagnostic codes for information retrieval and downstream machine-learning applications.
Negative allosteric modulators of group II metabotropic glutamate receptors: A patent review (2015 – present)

Group II metabotropic glutamate (mGlu) receptors have emerged as an attractive potential target for the development of novel CNS therapeutics in areas such as Alzheimer’s disease (AD), anxiety, cog...
A neuromorphic approach to LiDAR point cloud processing

Most LiDAR point cloud processing techniques continue to gather more data as the data is available. This is also typical in most imaging systems, especially visible light camera systems. We propose a computationally efficient solution where data only continues to be processed if the data has changed. Once points are received by the LiDAR hardware driver, a sensor frame spatial event filter is used to compare a previous point with the most recent point obtained from that same coordinate in the LiDAR's receptor array. The output of the event filter then fills an array of events, or event map, that will be accessible by a layer of neurons that can be implemented in a GPU. The operations per point are compared between this event-based solution and other similar solutions. We show the event-based solution's efficiency can be better, according to how much the scene is changing and how many post-processing steps are involved. Point cloud data is collected from a LiDAR mounted on a vehicle driving in paved road conditions to illustrate the concept.
Outcomes of Fludarabine, Melphalan and Total Body Irradiation as a Reduced Intensity Conditioning Regimen in Matched Donor Allogeneic Peripheral Blood Stem Cell Transplantation.

Abstract Fludarabine 30 mg/m2/d × 5 and melphalan 140 mg/m2 × 1 (Flu-Mel140) is a commonly used reduced-intensity conditioning regimen. We hypothesized that addition of 200cGy total body irradiation (TBI) to Flu-Mel140 may improve antitumor activity and transplant outcomes. Primary objectives was overall survival (OS) at 3 years. Secondary objectives were to assess the cumulative incidences of acute and chronic GVHD, relapse-free survival (RFS), relapse rate, and nonrelapse mortality (NRM). We retrospectively evaluated outcomes of patients receiving Flu-Mel140-TBI followed by HLA-matched donor allogeneic hematopoietic stem cell transplantation (alloSCT) using peripheral blood stem cells. Eighty-one patients (median age, 58 years) underwent alloSCT between January 2008 and December 2018. Thirty-one percent of patients had a prior transplant, 32% had high or very-high disease risk index, and the donor was unrelated in 70% of patients. Grade 3 to 4 regimen-related toxicities were mucositis (37%), cardiac toxicity (17%), and renal toxicity (10%). The cumulative incidence of grade III to IV acute GVHD at day +100 was 24.7% and chronic GVHD at 1 year was 51.3%. Median follow-up for survival was 6.1 years. At 3 years, OS was 39.81%, RFS was 31.47%, and relapse rate was 30.5%. One-year NRM was 29.9%. Patients undergoing first transplantation experienced improved OS compared with second or beyond (63.08% versus 42.31%, P = .02). After adjusting for disease subtypes, age (≤55 versus 55), comorbidity index (CI), number of transplant and GVHD prophylaxis, multivariable analysis did not demonstrate any survival difference among disease subtypes. High CI (≥3) was predictive of adverse OS and NRM, whereas older age (>55 years) was associated with high NRM. Our study shows that Flu-Mel140-TBI seems feasible and provides durable disease control. Addition of TBI did not appear to improve outcomes compared to previously published reports of Flu-Mel140. Considerable NRM could result from the inclusion of patients with older age and prior transplants.
Job shop scheduling with AGVs under variable processing time

In this paper, a job shop scheduling problem with material handling (JSSMH) is analysed given variable job processing time. The material handling is conducted by automatic guided vehicles (AGVs). Optimisation models have been formulated to accommodate the processing time variability due to random effects and deterioration. With random processing time, the model is formulated as a stochastic programming-based JSSMH (SP-JSSMH) model, and with deteriorating processing time the model can be nonlinear under specific deteriorating functions. A case study was conducted to illustrate and validate the model. The SP-JSSMH models were solved with Pyomo and deteriorating JSSMH models were linearised and solved with CPLEX. By considering variable processing time, the JSSMH models can better adapt to real production scenarios.
A Distributed EV Charging Framework Considering Aggregators Collaboration

This paper establishes a distributed optimization platform based on the alternating direction method of multipliers (ADMM) for optimal electric vehicle charging management. The proposed method solves a comprehensive mixed-integer quadratic programming (MIQP) problem to minimizes the charging and battery degradation cost for electric vehicle (EV) fleets considering individual charging and discharging constraints and asymmetric price profiles. The main contribution of this paper is to establish a coordination layer between EVAs to fulfill the local EVAs’ objectives and constraints. Numerical tests evaluate the effectiveness of the proposed coordinated ADMM platform (CAP). The results validate that coordination between EVAs enhances the smoothness of the aggregated load profile.
Religion That Heals, Religion That Harms: A Guide for Clinical Practice

Introduction. When Religion Goes Bad: A Mental Health Problem? Part I: A Map for Navigating the Terrain of Religion. What Sociobiology Explains about Destructive Uses of Religion. What Neurobiology Explains about Destructive Uses of Religion. Setting the Stage: Opening Dialogue about Religious Life. Locating Personal Spirituality through Existential Inquiry. Part II: When Religious Life Propels Suffering. Seeking a Parent in God: Clinical Problems from Insecure Attachments. Seeking Security within the Flock: Clinical Problems from Social Hierarchy, Peer Affiliation, and Reciprocal Altruism. Asserting Primacy of Personal Spirituality Over Sociobiological Religion. The Religious Who Protect Only Their Own: Clinical Problems from Peer Affiliation, Kin Recognition, and Social Exchange. Part III: When Mental Illness Infiltrates Religious Life. Religion That is a Voice for Mental Illness. Dark Nights and Exaltation: Religion Distorted by a Mood Disorder. Worlds Confused: Religion Disorganized by Psychosis. Fear and Dread: Religion Shrunken by an Anxiety Disorder. Part IV: A Clinician's Stance. Finding a Place to Stand: Conversing with Religiously Determined Patients.
Preferences of Asynchronous Adult Distance Learners

The boom in distance education provides a unique opportunity to serve the growing adult education market, but current asynchronous distance education technologies constrain the teaching-learning exchange. A model of factors influencing the teaching-learning exchange is discussed. Several techniques have been proposed to overcome the limitations of distance education. An overview of some of these techniques is also offered. Finally, measurement of asynchronous adult student preferences regarding these techniques is presented.
Cutting Edge: p27Kip1 Deficiency Reduces the Requirement for CD28-Mediated Costimulation in Naive CD8+ but Not CD4+ T Lymphocytes

Cell cycle re-entry of quiescent T cells is dependent upon cyclin-dependent kinase 2. Inhibition of cyclin-dependent kinase 2 by p27Kip1 is believed to be the principal constraint on S-phase entry in T cells. We report that deficiency for p27Kip1 has a more pronounced effect on the expansion of murine naive CD8+ T cells and that this disparity is due to a reduced requirement for CD28-mediated costimulation in CD8+ but not CD4+ T cells lacking p27Kip1. These data highlight a previously unappreciated difference in the way CD28 signaling is coupled to the core cell cycle machinery in these two T cell subsets.
Ex-Post Liability Rules in Modern Patent Law

This doctoral thesis examines the use of liability rules to protect patent entitlements, focusing on a specific type of rule named ex-post since it is applied and designed ex-post by a court or an agency. The research starts from the premise that patents are defined by the legal and economic scholarship as exclusive rights but nevertheless, under certain circumstances there are economic as well as other compelling reasons to transform the exclusiveness of patent rights into a right to receive compensation.
Hybrid Symbolic and Numeric Operators as Tools for Analysis of Freeform Surfaces

Freeform surfaces are commonly used in computer aided geometric design, so accurate analysis of surface properties is becoming increasingly important. In this paper, we define surface slope and surface speed, develop visualization tools, and demonstrate that they can be useful in the design process. Generally, surface properties such as curvature and twist are evaluated at a finite set of predetermined samples on the surface. This paper takes a different approach. A small set of tools is used to symbolically compute surfaces representing curvature, twist and other properties. These surfaces are then analyzed using numeric techniques.
Made in America? Assumptions About Service Learning Pedagogy as Transnational: A Comparison Between Ireland and the United States

Using exploratory, qualitative interviews, the authors studied conceptions of academic service-learning in the United States and the Republic of Ireland in order to elucidate the ways in which culture and social context shaped practitioners' perceptions and practices regarding service-learning pedagogy. Participants articulated a
Collaborative tools and processes to support software engineering shift work

This paper describes the construction of and early experiences with a software engineering support environment for projects using globally distributed teams. The goals of the project are twofold. Firstly, it aims to construct a pragmatic solution to the problems experienced by widely geographically dispersed groups which collaborate on software development projects. Secondly, it aims to experiment with processes which facilitate software shift work through exploitation of time differences between collaborating groups. The construction of the support environment, known as GWSE (Global Working in Software Engineering) system, is presented, including its architecture and integration with existing workflow, document and project management tools. The use of the GWSE system in a trial development project is then described, including an initial quantitative analysis of the collaboration overheads experienced.
Controllability of Linear Time Varying Systems: New Algebraic Criteria

This paper presents algebraic rank conditions for the complete controllability of the system x?(t) = A(t)x(t) + Bu(t) = ?m i=1 a i (t)A i x(t) + Bu(t). x Rx, u Rl. Assuming A(.) is locally integrable on R, the fundamental solution of x?(t) = A(t)x(t) is explicity calculated in terms of functions a i (t) for t [0,T] by using Lie algebra theory. Then by using the Cayley-Hamilton theorem, two diffierent time invariant controllability matrices are derived. Conditions for complete controllability of the above systems are derived in terms of the rank of these matrices.
Gender in the Military: Androcentrism and Institutional Reform

During the past "Year of the Woman," feminists and their allies subjected a range of institutions to searching, well-publicized scrutiny. Women confronted practices of sexual harassment, challenged their underrepresentation in institutions, and questioned the double standards that have been applied to their work. Even the military, often insulated from the tides of public opinion, has not been immune from this scrutiny. Revelations of the Tailhook scandal,1 and of the ensuing cover-up, have brought pressure to bear on an institution slow to acknowledge its legacy of harassment. Military exclusion policies, which for many years met with quiescence or approval, have been challenged by straight women, gays, and lesbians. An institution conceived by many as the symbol of and training ground for traditional notions of masculinity2 has been forced to confront a range of issues implicating gender. The fact that the challenge has been raised, however, marks only a beginning. Numerous questions remain about the arguments and the institutional mechanisms through which change can best be achieved. Part II of this article discusses the strategy that advocates should pursue in altering restrictive policies implicating gender. I argue that feminists and other proponents of change should not limit themselves to problem-specific analyses, but should attempt to elaborate and expose the androcentrism that thwarts systematic change in military institutions. This goal requires feminist advocates to undertake several tasks.
Self-healing Tile Sets

Biology provides the synthetic chemist with a tantalizing and frustrating challenge: to create complex objects, defined from the molecular scale up to meters, that construct themselves from elementary components, and perhaps even reproduce themselves. This is the challenge of bottom-up fabrication. The most compelling answer to this challenge was formulated in the early 1980s by Ned Seeman, who realized that the information carried by DNA strands provides a means to program molecular self-assembly, with potential applications including DNA scaffolds for crystallography [19] or for molecular electronic circuits [15]. This insight opened the doors to engineering with the rich set of phenomena available in nucleic acid chemistry [20].
Tissue-specific requirements for the proprotein convertase furin/SPC1 during embryonic turning and heart looping.

Furin, the mammalian prototype of a family of serine proteases, is required for ventral closure and axial rotation, and formation of the yolk sac vasculature. Here we show additionally that left-sided expression of pitx2 and lefty-2 are also perturbed in Furin-deficient embryos. These tissue abnormalities are preceded by a marked delay in the expansion of the definitive endoderm during gastrulation. Using a chimera approach, we show that Furin activity is required in epiblast derivatives, including the primitive heart, gut and extraembryonic mesoderm, whereas it is nonessential in the visceral endoderm. Thus, chimeric embryos, derived by injecting wild-type embryonic stem (ES) cells into fur(-/-) blastocysts, develop normally until at least 9.5 d.p.c. In contrast, Furin-deficient chimeras developing in the context of wild-type visceral endoderm fail to undergo ventral closure, axial rotation and yolk sac vascularization. Fur(-/-) cells are recruited into all tissues examined, including the yolk sac vasculature and the midgut, even though these structures fail to form in fur mutants. The presence of wild-type cells in the gut strikingly correlates with the ability of chimeric embryos to undergo turning. Overall, we conclude that Furin activity is essential in both extraembryonic and precardiac mesoderm, and in definitive endoderm derivatives.
The Consequences of a Cavalier Approach to Central Venous Catheterization

A cavalier approach on the part of some physicians, and poor research on the part of some equipment manufacturers, has made central venous catheterization more dangerous to the patient than it need be. Here, the relationship between these factors is discussed, with special reference to the fact that central venous catheterization is an invasive surgical operation which should not be taken lightly by its practitioners.