cssi/SciSciGPT-SciSciNet huggingface dataset:
MIST: distributed indexing and querying in sensor networks using statistical models

The modeling of high level semantic events from low level sensor signals is important in order to understand distributed phenomena. For such content-modeling purposes, transformation of numeric data into symbols and the modeling of resulting symbolic sequences can be achieved using statistical models---Markov Chains (MCs) and Hidden Markov Models (HMMs). We consider the problem of distributed indexing and semantic querying over such sensor models. Specifically, we are interested in efficiently answering (i) range queries: return all sensors that have observed an unusual sequence of symbols with a high likelihood, (ii) top-1 queries: return the sensor that has the maximum probability of observing a given sequence, and (iii) 1-NN queries: return the sensor (model) which is most similar to a query model. All the above queries can be answered at the centralized base station, if each sensor transmits its model to the base station. However, this is communication-intensive. We present a much more efficient alternative---a distributed index structure, MIST (Model-based Index STructure), and accompanying algorithms for answering the above queries. MIST aggregates two or more constituent models into a single composite model, and constructs an in-network hierarchy over such composite models. We develop two kinds of composite models: the first kind captures the average behavior of the underlying models and the second kind captures the extreme behaviors of the underlying models. Using the index parameters maintained at the root of a subtree, we bound the probability of observation of a query sequence from a sensor in the subtree. We also bound the distance of a query model to a sensor model using these parameters. Extensive experimental evaluation on both real-world and synthetic data sets show that the MIST schemes scale well in terms of network size and number of model states. We also show its superior performance over the centralized schemes in terms of update, query, and total communication costs.
Interface Thermal Conductance Between Metal Films and Copper

Transient thermo-reflectance measurements were made on metals films deposited on Cu film. The Cu film was deposited on Si (001) and sapphire (0001) substrates. The metal films that were deposited include Al, Au, Sn, Zn, and In. The results were modeled using one-dimensional heat equation to determine thermal conductance of interfaces between the metal film and Cu (film/Cu) and Cu and Si (Cu/Si), or Cu and sapphire (Cu/sapphire) in each sample. The results were used to determine the importance of microstructural parameters such as surface roughness, lattice mismatch, solid solubility, and surface energy of the metal film on Cu. The experimental values of interface thermal conductance, although smaller in magnitude, were interpreted in terms of the predicted values by diffuse mismatch model after including the effect of the microstructural parameters. In particular, interface roughness, lattice mismatch, solid solubility, and wettability were found to be important parameters as these are responsible for good atomic level contact between the metal film and Cu.
Characterization of Laws of Friction in the Context of Engine Blade Dynamics

Experience has shown that energy dissipation due to rubbing at interfaces of engine blade shrouds provides damping of bladed disk assemblies. An accurate estimate of such damping has been a subject of study for more than a decade. The most difficult parameter that influences its accurate calculation pertains to an appropriate definition of the laws of friction that relate the rubbing motion with the forces induced.This paper develops an analysis which leads to a mathematical relationship between the forces of friction damping at a vibrating interface and the corresponding relative motion. The analysis permits calculation of forces at the interface if the displacements are known or vice versa. The equations are cast in terms of relative motion between mating shrouds so that degenerate cases of fully locked and freely slipping can be calculated. Examples are given showing simulation results obtained using discrete structural models. Extension of the analysis to the case of a full assembly is discussed.Copyright © 1996 by ASME
Scour of Sand Beaches in Front of Seawalls

Many previous studies were confined to problem of beach erosion due to waves breaking on the structure. The investigation reported here involved regular non-breaking, shallow water waves progressing toward a seawall. An analytical solution was developed and compared with laboratory- scale experiments. The shallow-water wave theory and boundary layer equations were used in theoretical development, which resulted in a mathematical model for the ultimate scour depth in front of a seawall.
Comparing Associations Between the Built Environment and Walking in Rural Small Towns and a Large Metropolitan Area

The association between the built environment (BE) and walking has been studied extensively in urban areas, yet little is known whether the same associations hold for smaller, rural towns. This ana...
Isolation of hepatitis A virus in vitro in cell culture directly from human specimens.

AbstractHuman hepatitis A virus (HAV) was isolated directly in cell culture from infected human fecal extracts using techniques developed for in vitro cultivation of the marmoset-adapted CR326 strain of human HAV. A very long incubation was required in first passage, but vigorous cell culture growth, with incubation periods and virus yields similar to those of the CR326 strain that was isolated originally in marmosets, was achieved on serial passage. As with the CR326 strain, there were no evident cytopathic effects. The isolates proved to be HAV virus based on specific activity in serologic tests and by tests for infectiousness in marmosets.
Feeding Norethynodrel and Mestranol to Immature and Adult Female Rats Cross-Section and Length of Long Bones

SummaryNorethynodrel and mestranol, a progestational and an estrogenic compound, were fed in physiological doses to half of 14 pairs of 83-day-old female rats and half of another 8 pairs that were 35 days old. The control rats were pair-fed exactly the same quantities of diet as those receiving the antiovulatory steroids. Despite the fact that the steroid-treated rats and the control rats consumed equal quantities of diet the control rats were somewhat heavier at the end of 5-weeks feeding. The 83-day-old rats treated with steroids had significantly lesser cross-sectional growth in the tibias than their companion control rats whereas the length of the femurs and the widths of the tibial epiphyseal lines were not significantly reduced. However, in the 35-day-old rats the length of the femurs were significantly shorter in the treated rats than in the control rats.
Necessity is the Mother of Isomorphism: Income Stratification and the Provision of Novelty

This study examines the relationship between innovation diffusion and income stratification by focusing on entrepreneurs as “suppliers” of innovations. Existing theories suggest that low-income ent...
On the Vitality of Dental Enamel.

Various common pathological changes in the dental enamel of fully erupted human teeth, which destroy its protective function, are ascribed by some investigators to intrinsic nutritional alterations, rather than to extrinsic influences. The proof that enamel contains protein1, 2 has induced several investigators to regard its presence as indicative of nutritional capacity, despite the fact that, although permeable to water and various substances, enamel completely lacks power of self-repair after injury and has no cellular nuclei. That the contained protein (probably keratin) is not associated with intrinsic nutritional changes in the enamel of erupted teeth is indicated by the writer's further observation that conventional tests for proteolytic and amylolytic enzymes, applied to extracts of pulverized normal enamel, were completely negative. These tests, to be extended, will include studies of abnormal enamel.
Velocity measurements in a ship airwake with crosswind

In situ air velocity measurements in the near wake of a Navy training ship are presented for an inflow of 15 to starboard. This data is required for the validation of ship airwake simulations, which are used to determine the launch and recovery envelopes for shipborne rotorcraft and for use in piloted flight simulations. The measurements are taken primarily above an aft flight deck, which sits immediately behind a step-like hangar structure. A description of the mean flow structure is included, as well as the Reynolds stresses at numerous points along the ship centerline. Comparisons are made between the present 15 case and the case of a direct headwind, presented previously. Compared to the 0 inflow condition, the flow symmetry is clearly broken with a cross-wind. The port and starboard sides of the deck have very different mean flow profiles and turbulent stress components. An updraft is visible over much of the starboard side of the flight deck, which is not found on the port side, or on either side under a headwind. Along the centerline, the streamwise normal component of the turbulent stresses are much larger in the cross-wind case than in the headwind case, while the shear components have similar magnitudes. This suggests that the wake turbulence is similar, but that in the cross-wind case the flight deck is more heavily burdened by inflow fluctuations from the atmosphere.
Velopharyngeal Structural and Functional Assessment of Speech in Young Children Using Dynamic Magnetic Resonance Imaging.

Objective: The purpose of this study was to demonstrate a novel method for examining the velopharyngeal mechanism using static and dynamic magnetic resonance imaging (MRI) at the sentence-level production in young children with normal anatomy. This study examined whether velopharyngeal events occurring in the midsagittal plane are correlated to muscle events occurring along the plane of velopharyngeal closure. Adenoid involvement in velopharyngeal function was also explored. Methods: A high-resolution, T2-weighted turbo-spin-echo three-dimensional anatomical scan was used to acquire static velopharyngeal data and a fast-gradient echo fast low angle shot multishot spiral technique (15.8 frames per second) was used to acquire dynamic data on 11 children between 4 and 9 years old. Results: Changes in velar knee height from rest to the bilabial /p/ production was strongly correlated with changes in the velar configuration (r = 0.680, P = .021) and levator muscle contraction (r = 0.703, P = .016). Velar con...
Huoxue Quyu Xiaozhong Cream for Traumatic Injury

OBJECTIVE: To prepare Huoxue Queyu Xiaozhong Cream(cream for promoting blood flow and eliminating stasis to resolve swelling) and observe its clinical efficacy.METHODS: Huoxue Queyu Xiaozhong Cream was prepared with rhubarb,wild aconite root,stone fungus,pyrolusite and borneol.The quality standard of the cream was established.The patients in the trial group were treated with Huoxue Queyu Xiaozhong Cream with control group treated with other Chinese herba preparation(external use) plus physical therapy or physical treatment with infrared radiation etc.The curative efficacy was evaluated.RESULTS: There were significant differences between the trial group and the control group in clinical efficacy,with total response rate of 99.08%(216/218) in trial group vs.69.12%(47/68) in control group,indicating much better efficacy for the trial group than in the control group in clinical efficacy.CONCLUSION: Huoxue Queyu Xiaozhong Cream was reasonable in formula,feasible in its preparative method and quality control standard with proved clinical efficacy which is thus worthy of widespread clinical use.
Comparative proteomic analysis of hemolymph from uninfected and Candidatus Liberibacter asiaticus -infected Diaphorina citri

Hemolymph was characterized from Diaphorina citri adults infected with the phytopathogen, Candidatus Liberibacter asiaticus (CLas), and compared with that from uninfected psyllids. This study identified 5531 and 3220 peptides within infected and uninfected hemolymph using nano-LC–MS/MS. A reduced number of proteins were detected for D. citri and all known endosymbionts within infected hemolymph as compared to uninfected hemolymph. A large number of immune defense proteins were absent from D. citri hemolymph; however, a single recognition protein (PGRP), two serine protease inhibitors, three prophenoloxidase (proPO) enzymes, and a single serine protease in an uninfected D. citri were detected. The hemolymph is nearly devoid of nutrient storage proteins. This is the first proteomic analysis of D. citri hemolymph that also analyses the components contributed by all the endosymbionts. By comparing the contribution of each endosymbiont (CCR, CPA, and WB) in the presence and absence of CLas infection, this study offers initial insights regarding the hemolymph response to microbial community shifts associated with D. citri infection status. Our data also present potential protein targets for analysis and disruption of CLas transmission that may facilitate management of huanglongbing (HLB) caused by CLas in citrus.
Characteristics of retrograde amnesia for CS preexposure

Two experiments using rats evaluated the susceptibility of CS preexposure to retrograde amnesia induced by the protein synthesis inhibitor cycloheximide and tested whether amnesia for CS preexposure shares similar characteristics with amnesia for other memories. In Experiment 1, rats received cycloheximide either immediately, 60 minutes, or 120 minutes after preexposure. Following preexposure, rats received fear conditioning. When later tested, the subjects that received the amnestic treatment shortly after preexposure showed no CS preexposure effect (i.e., no reduction of fear). The amnesia for CS preexposure was attenuated with longer post-preexposure delays, showing a temporal gradient. In Experiment 2, following the replication of amnesia for CS preexposure, the amnestic treatment was readministered to the rats prior to testing. It was demonstrated that the amnestic-preexposure memory could be recovered (i.e., readministration of the drug alleviated the amnesia for CS preexposure). These two experiments show that memories for CS preexposure are susceptible to retrograde amnesia and share similar characteristics with memories for original acquisition and extinction. The results are explained using a retrieval hypothesis of retrograde amnesia.
Review Essay: Is a Chilean-Style Tax on Short-Term Capital Inflows Stabilizing?

In the wake of the 1997–1998 East Asian financial crisis, some economists recommended that affected countries adopt a Chilean-style tax on short-term capital inflows to maintain domestic macroeconomic stability. In Chile, the tax reduced capital inflows lengthened the maturity of inflows, and maintained interest rates at levels designed to avoid overheating—but not costlessly. Aside from second-best arguments, such a tax is justified as a temporary measure to buy time to reform and introduce prudential regulation and supervision of a country's financial system. Would dirigiste economies use the tax to facilitate reforms and remove it after effecting prudential regulation?
Global Forests Management for Climate Change Mitigation

Forests are the dominant terrestrial ecosystem occupying approximately 30% of the Earth total land area. They play an important role in the global carbon (C) cycle, and the mitigation of CO2 emission due to its large storage of soil organic C (SOC), a large part of which is stored in soils. Due to their dominance, forests management has gained much interest in science and policy discussions as one of the important options to mitigate climate change. Global forests are increasingly affected by land use change , fragmentation, changing management objectives and degradation. The area under global forests has declined by 3% from 1990 to 2015, but the area of planted forest has increased in all regions of the world and now accounts for nearly 7% of global forest land estimated at 3999 million hectares (Mha). The area of primary forests which is typically defined as lacking direct human influence, is about 34% of the total forest land, based on country reports, but this area is declining, especially in South America and Africa because of human-caused fragmentation and degradation. About 5% of global forests are plantations generally used for commercial purposes. Globally, timber production has remained stable since 1990, but forest used for non-wood forest products indicates that harvesting is taking place on a smaller proportion of total forest area. Based on trends in the area of managed forest and regional studies, historical and current forest management has been a significant determinant of current carbon stocks in forest. The established forest currently offset 30% of global emissions of CO2 from fossil fuel combustion, and there are mitigation opportunities involving forests that could increase the gross terrestrial C uptake from about 4.0 to 6.2 Pg C annually. Diversifying use of forest land may have significant consequences for maintaining or increasing the current rate of terrestrial C sequestration. Indirect human influences such as increasing atmospheric CO2 and climate change, along with the direct effects of land management and projected increasing demand for wood biofuel, are likely to become increasingly important elements that influence land management strategies and the role of forests in the global C cycle and future climate mitigation.
State-dependent fiscal multipliers: Calvo vs. Rotemberg

Abstract This paper studies the properties of the fiscal multiplier in both the Calvo (1983) and Rotemberg (1982) variants of the New Keynesian model. Though identical to first order, the two variants of the model are not the same globally or to higher order. We solve both versions of the model using a third order approximation, and compute the distributions of fiscal multipliers by drawing from the ergodic distributions of states. The multiplier is significantly more variable across states in the Rotemberg model. These differences are magnified when the nominal interest rate is pegged instead of governed by an active Taylor rule.
Robust intensity-modulated proton therapy to reduce high linear energy transfer in organs at risk

Purpose We propose a robust treatment planning model that simultaneously considers proton range and patient setup uncertainties and reduces high linear energy transfer (LET) exposure in organs at risk (OARs) to minimize the relative biological effectiveness (RBE) dose in OARs for intensity-modulated proton therapy (IMPT). Our method could potentially reduce the unwanted damage to OARs. Methods We retrospectively generated plans for 10 patients including two prostate, four head and neck, and four lung cancer patients. The “worst-case robust optimization” model was applied. One additional term as a “biological surrogate (BS)” of OARs due to the high LET-related biological effects was added in the objective function. The biological surrogate was defined as the sum of the physical dose and extra biological effects caused by the dose-averaged LET. We generated nine uncertainty scenarios that considered proton range and patient setup uncertainty. Corresponding to each uncertainty scenario, LET was obtained by a fast LET calculation method developed in-house and based on Monte Carlo simulations. In each optimization iteration, the model used the worst-case BS among all scenarios and then penalized overly high BS to organs. The model was solved by an efficient algorithm (limited-memory Broyden–Fletcher–Goldfarb–Shanno) in a parallel computing environment. Our new model was benchmarked with the conventional robust planning model without considering BS. Dose–volume histograms (DVHs) of the dose assuming a fixed RBE of 1.1 and BS for tumor and organs under nominal and uncertainty scenarios were compared to assess the plan quality between the two methods. Results For the 10 cases, our model outperformed the conventional robust model in avoidance of high LET in OARs. At the same time, our method could achieve dose distributions and plan robustness of tumors assuming a fixed RBE of 1.1 almost the same as those of the conventional robust model. Conclusions Explicitly considering LET in IMPT robust treatment planning can reduce the high LET to OARs and minimize the possible toxicity of high RBE dose to OARs without sacrificing plan quality. We believe this will allow one to design and deliver safer proton therapy.
A generalized analytical model for predicting the tensile behavior of 3D orthogonal woven composites using finite deformation approach

Over the past few decades, there have been an increasing interest in woven preforms as a reinforcement for composites. The invention of 3D Orthogonal Weaving (3DOW) technology introduced new and en...
Autoimmune haemolytic anaemia in a patient with advanced lung adenocarcinoma and chronic lymphocytic leukaemia receiving nivolumab and intravenous immunoglobulin

We describe a rare case of severe autoimmune haemolytic anaemia (AIHA) in the setting of underlying chronic lymphocytic leukaemia receiving intravenous immunoglobulin, history of warm IgG autoantibody and treatment with nivolumab for advanced non-small cell lung cancer. In this report, we describe AIHA as a potential serious immune-related adverse event from immune checkpoint inhibitors, discuss other potential contributing factors and review previously described cases of AIHA in patients receiving programmed death 1 (PD-1) inhibitors. In the era of immunotherapy, we hope to add literature to raise awareness of potential immune-related sequelae such as AIHA. We aim to highlight the importance of close monitoring for prompt identification and management of potentially fatal AIHA and immune-related adverse events of PD-1 inhibitors by holding immunotherapy and treating with high-dose steroids, particularly in subgroups which may be at increased risk.
Radiofrequency Energy and Electrode Proximity Influences Stereoelectroencephalography-Guided Radiofrequency Thermocoagulation Lesion Size: An In Vitro Study with Clinical Correlation.

Background Radiofrequency thermocoagulation of epileptogenic foci via stereoelectroencephalography (SEEG) electrodes has been suggested as a treatment for medically intractable epilepsy, but reported outcomes have been suboptimal, possibly because lesions generated using conventional high-energy radiofrequency parameters are relatively small. Objective To describe a technique of delivering low energy across separate SEEG electrodes in order to create large confluent radiofrequency lesions. Methods The size and configuration of radiofrequency lesions using different radiofrequency intensity and interelectrode distance was assessed in egg whites. Magnetic resonance images (MRI) from 3 patients who had undergone radiofrequency lesion creation were evaluated to determine the contribution of lesion intensity and electrode separation on lesion size. Electroencephalography, MRI, and clinical data were assessed before and after lesion creation. Results Both in Vitro and in Vivo analysis revealed that less energy paradoxically produced larger lesions, with the largest possible lesions produced when radiofrequency power was applied for long duration at less than 3 W. Linear separation of electrodes also contributed to lesion size, with largest lesions produced when electrodes were separated by a linear distance of between 5 and 12 mm. Clinical lesions produced using these parameters were large and resulted in improvement in interictal and ictal activity. Conclusion Radiofrequency lesions produced using low-energy delivery between SEEG electrodes in close proximity can produce a large lesion. These findings might have advantages for treatment of focal epilepsy.
Client Side Secure Image Deduplication Using DICE Protocol

With the advent of cloud computing, secured data deduplication has gained a lot of popularity. Many techniques have been proposed in the literature of this ongoing research area. Among these techniques, the Message Locked Encryption (MLE) scheme is often mentioned. Researchers have introduced MLE based protocols which provide secured deduplication of data, where the data is generally in text form. As a result, multimedia data such as images and video, which are larger in size compared to text files, have not been given much attention. Applying secured data deduplication to such data files could significantly reduce the cost and space required for their storage. In this paper we present a secure deduplication scheme for near identical (NI) images using the Dual Integrity Convergent Encryption (DICE) protocol, which is a variant of the MLE based scheme. In the proposed scheme, an image is decomposed into blocks and the DICE protocol is applied on each block separately rather than on the entire image. As a result, the blocks that are common between two or more NI images are stored only once at the cloud. We provide detailed analyses on the theoretical, experimental and security aspects of the proposed scheme.
Elastic Deformations in Shape Memory Alloy Fiber Reinforced Composites

The unique property of martensitic transformations in shape memory alloys (SMA) has prompted many recent attempts to construct adaptive structures and systems with these materials [1]. Most of the applications focus on embedding active elements in conventional structures to achieve certain control, sensing or actuating abilities. A typical configuration involves composites reinforced with shape memory alloy fibers. This setting utilizes the unidirectional transformation properties of the active fiber in corporation with an elastic matrix to harvest the shape memory effects in the axial direction. In this setting, the interaction between the phase transformation and the deformations in the matrix determines the overall mechanical properties of the structure and hence plays a crucial role in the design and analysis of such composites.
Case 9: Pregnant? Who's Pregnant?: Memory Loss in a Young Woman

The patient is a 19-year-old, pregnant, white woman with a history of cystic fibrosis (CF), Graves' disease, acquired hearing loss, and CF-related diabetes, who presents to the hospital after being “found down,” with a dextrose stick reading of 29 mg/dL. Immediate Medical History She was last seen well the night before admission. Although she responds well to an infusion of 50% dextrose, her exam is notable for retrograde amnesia. She has no memory of the past 3 months and does not remember being told of her pregnancy at the time of her last CF-related hospitalization 5 weeks earlier. She denies fever, cough, dysuria, vaginal bleeding, headache, shortness of breath, or seizures. She is maintained on an insulin pump and recently completed a 2-week course of tobramycin and meropenem for a CF flare. Her past medical history is as stated. Of note, she is the full-term product of an unremarkable pregnancy and developed normally. She attends Gallaudet University, Washington, DC, and is studying to become a teacher for the hearing impaired. She is a “B” student and works at a local drugstore in the film-processing department. Her medications at the time of admission include tobramycin, albuterol, azithromycin, deoxyribonuclease (Pulmozyme), ursodiol (Actigall), pancrelipase (Ultrase), prenatal vitamins, and her insulin pump. She has no known drug allergies.
STOCHASTIC DYNAMICS SIMULATION OF PARTICLE AGGREGATION

The kinetics of cluster aggregation and the structure of the resulting clusters have been studied using a “Brownian dynamics” simulation technique with the coagulation condition that particles stick upon contact. Three dimensional simulations with 500 particles were run to determine the effects of the friction coefficient and the particle concentration on the resulting particle structure and the growth dynamics.
Consumer willingness to pay for vehicle attributes: What do we know?

As standards for vehicle greenhouse gas emissions and fuel economy have become more stringent, concerns have arisen that the incorporation of fuel-saving technologies may entail tradeoffs with other vehicle attributes important to consumers such as acceleration performance. Assessing the effects of these tradeoffs on consumer welfare requires estimates of both the degree of the tradeoffs, and consumer willingness to pay (WTP) for the foregone benefits. This paper has two objectives. The first is to review recent literature that presents, or can be used to calculate, marginal WTP (MWTP) for vehicle attributes to describe the attributes that have been studied and the estimated MWTP values. We found 52 U.S.-focused papers with sufficient data to calculate WTP values for 142 different vehicle attributes, which we organized into 15 general groups of comfort, fuel availability, fuel costs, fuel type, incentives, model availability, non-fuel operating costs, performance, pollution, prestige, range, reliability, safety, size, and vehicle type. Measures of dispersion around central MWTP values typically show large variation in MWTP values for attributes. We explore factors that may contribute to this large variation via analysis of variance (ANOVA) and find that, although most have statistically significant effects, they account for only about one third of the observed variation. Case studies of papers that provide estimates from a variety of model formulations and estimation methods suggest that decisions made by researchers can strongly influence MWTP estimates. The paper's second objective is to seek consensus estimates for WTP for fuel cost reduction and increased acceleration performance. Meta-analysis of MWTP for reduced fuel cost indicates that estimates based on revealed vs. stated preference data differ, as do estimates from models that account for endogeneity and those that do not. We find greater consistency in estimates of MWTP for acceleration despite substantial uncertainty about the overall mean. We conclude with recommendations for improving the understanding of consumers' MWTP for vehicle attributes.
Cobalt doping of tin disulfide/reduced graphene oxide nanocomposites for enhanced pseudocapacitive sodium-ion storage

Rechargeable sodium-ion batteries are receiving intense interest as a promising alternative to lithium-ion batteries, however, the absence of high-performance anode materials limits their further commercialization. Here we prepare cobalt-doped tin disulfide/reduced graphene oxide nanocomposites via a microwave-assisted hydrothermal approach. These nanocomposites maintain a capacity of 636.2 mAh g−1 after 120 cycles under a current density of 50 mA g−1, and display a capacity of 328.3 mA h g−1 after 1500 cycles under a current density of 2 A g−1. The quantitative capacitive analysis demonstrates that the electrochemical performance of the nanocomposite originates from the combined effects of cobalt and sulfur doping, resulting in the enhanced pseudocapacitive contribution (52.8 to 89.8% at 1 mV s−1) of tin disulfide. This work provides insight into tuning the structure of layered transition metal dichalcogenides via heteroatom doping to develop high-performance anode materials for sodium-ion batteries. Rechargeable sodium ion batteries are a promising alternative to lithium technologies, however there are fewer high-performing anode materials. Here, the authors prepare a cobalt-doped tin disulfide/reduced graphene oxide nanocomposite and demonstrate its enhanced sodium kinetics and improved rate performance.
Overcoming Endosomal Entrapment in Drug Delivery

Intracellular delivery of biological agents such as peptides, proteins, and nucleic acids generally rely on the endocytic pathway as the major uptake mechanism, resulting in their entrapment inside the endosome and lysosome. The recent discovery of cell-penetrating molecules of exceptionally high endosomal escape and cytosolic delivery efficiencies and elucidation of their mechanism of action represent major breakthroughs in this field. In this Topical Review, we provide an overview of the recent progress in understanding and enhancing the endosomal escape process and the new opportunities opened up by these recent findings.
Lean Methods Applied to CAD/CAM Pedagogy in the Dental Simulation Laboratory.

Dental education is incorporating computer-assisted design/computer-assisted manufacturing (CAD/CAM) into patient care delivery. The aim of this study was to determine if lean production methods applied to the preclinical phase of dental education would reduce the students' time (efficiency) to complete CAD/CAM indirect restorations (CAD/CAM IR) without compromising the desired quality of the CAD/CAM tooth preparations (effectiveness). In 2016, all third-year students at one U.S. dental school were randomly assigned to control and research groups (approximately 33 per group). The control group was taught using existing methods, while the course was redesigned to incorporate lean methods for the research group. Cycle times of the CAD/CAM IR process for both groups were collected and statistically analyzed to compare the effectiveness of the redesign. Standardized grading forms and tools were used to assess the quality of the CAD/CAM tooth preparations. The research group demonstrated significantly faster preparation times with both crowns and onlays (p 0.05) nor in the quality of the CAD/CAM tooth preparations (p>0.05). This study demonstrated that lean methods applied to pedagogy significantly decreased preparation and design times in a CAD/CAM restorative dentistry course without compromising the quality of the CAD/CAM tooth preparations.
Enantioselective Synthesis of Chiral Organofluorine Compounds: Alcohol-Mediated Hydrogen Transfer for Catalytic Carbonyl Reductive Coupling

Alcohol-mediated carbonyl addition has enabled catalytic enantioselective syntheses of diverse fluorine-containing compounds without the need for stoichiometric metals or discrete redox manipulations. Reactions of this type may be separated into two broad categories: redox-neutral hydrogen autotransfer reactions, wherein lower alcohols and π-unsaturated pronucleophiles are converted to higher alcohols, and corresponding 2-propanol-mediated carbonyl reductive couplings.
IFNβ-producing CX3CR1+ macrophages promote T-regulatory cell expansion and tumor growth in the APCmin/+ / Bacteroides fragilis colon cancer model.

Increased T-regulatory cell activity drives tumor progression in the compound APCmin/+/enterotoxic Bacteroides fragilis colon cancer model. At the same time, how microbially-induced inflammation pr...
Lessons Learned from ACS NSQIP

Surgical quality improvement came to the forefront of the American healthcare system beginning with the Veterans Affairs National Surgical Quality Improvement Program (VA NSQIP) in the 1990s. Subsequent expansions and improvements led directly to the modern-day American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP®), which has now recorded the outcomes of more than five millions surgical cases. Data have been shown to be reliable on multiple audits and validation studies. Enrollment has flourished, with more than 800 participating adult and pediatric centers. Robust engagement from the surgical community has led to significant improvement in the quality of care at participating hospitals, and these quality improvements have been shown to strengthen with time. Successful quality programs combine excellent local support, outstanding statistical analysis, and actionable feedback to hospitals in order to drive improvements in the quality of surgical care.
Predicting Optimal Combination LT4 + LT3 Therapy for Hypothyroidism Based on Residual Thyroid Function.

Objective: To gain insight into the mixed results of reported combination therapy studies conducted with levothyroxine (LT4) and liothyronine (LT3) between 1999 and 2016. Methods: We defined trial success as improved clinical outcome measures and/or patient preference for added LT3. We hypothesized that success depends strongly on residual thyroid function (RTF) as well as the LT3 added to sufficient LT4 dosing to normalize serum T4 and TSH, all rendering T3 levels to at least middle-normal range. The THYROSIM app was used to simulate "what-if" experiments in patients and study designs corresponding to the study trials. The app graphically provided serum total (T4) and free (FT4) thyroxine, total (T3) and free (FT3) triiodothyronine, and TSH responses over time, to different simulated LT4 and combination LT4 + LT3 dosage inputs in patients with primary hypothyroidism. We compared simulation results with available study response data, computed RTF values that matched the data, classified and compared them with trial success measures, and also generated nomograms for optimizing dosages based on RTF estimates. Results: Simulation results generated three categories of patients with different RTFs and T3 and T4 levels at trial endpoints. Four trial groups had >20%, four 20% RTF, respectively. Conclusion: Unmeasured and variable RTF is a complicating factor in assessing effectiveness of combination LT4 + T3 therapy. We have estimated and partially validated RTFs for most existing trial data, using THYROSIM, and provided an algorithm for estimating RTF from accessible data, and optimizing patient dosing of LT4 + LT3 combinations for future combination therapy trials.
The Role of Metabolites in Bioequivalency Assessment. II. Drugs with Linear Pharmacokinetics and First-Pass Effect

Simulations were conducted to address the question of whether metabolite data are required for bioequivalence evaluation of immediate release formulations with drugs exhibiting linear pharmacokinetics and first-pass effect. Plasma level-time profiles were generated for parent drug and metabolite using relevant rate constants obtained from a bivariate normal distribution and designated random error. Simulation results showed that the need for metabolite data (Cmax) in the assessment of bioequivalence depends on the relative variability between the absorption process of the drug and first-pass route for metabolite(s). The importance of metabolite Cmax data in the evaluation of rate of availability is clearly demonstrated for drugs with a high degree of intra-subject variation in the first-pass metabolism compared to the absorption process of the drug. Under such conditions, a wider confidence interval was found for the metabolite rather than parent drug. Opposite results were obtained when the intra-subject variance was high for drug absorption relative to first-pass effect. Discrepancies were observed for the scenarios in which the elimination pathway of the metabolite is more variable than the absorption process of the drug. The simulation results were in agreement with real bioequivalence data. It is thus recommended that, in the absence of the information on the relative variability of absorption and first-pass process, both parent drug and metabolite data be included for documentation of bioequivalence, should the metabolite(s) play an important role in the determination of efficacy and safety of the drug.
Novel technology for storage and distribution of live vaccines and other biological medicines at ambient temperature

A novel, thin-film platform that preserves live viruses, bacteria, antibodies, and enzymes without refrigeration for extended periods of time is described. Studies with recombinant adenovirus in an optimized formulation that supports recovery of live virus through 16 freeze-thaw cycles revealed that production of an amorphous solid with a glass transition above room temperature and nitrogen-hydrogen bonding between virus and film components are critical determinants of stability. Administration of live influenza virus in the optimized film by the sublingual and buccal routes induced antibody-mediated immune responses as good as or better than those achieved by intramuscular injection. This work introduces the possibility of improving global access to a variety of medicines by offering a technology capable of reducing costs of production, distribution, and supply chain maintenance.
Mentaculus Laws and Metaphysics

The laws of nature are central to our understanding of the world. And while there is often broad agreement about the technical formulations of the laws, there can be sharp disagreement about the metaphysical nature of the laws. For instance, the Newtonian laws of nature can be stated and analyzed by appealing to a set of possible worlds. Yet, some philosophers argue the worlds are mere notational devices, while others take them to be robust, concrete entities in their own right. In this paper, I use a recent view of laws called the Mentaculus as a case study to illustrate the wide variety of metaphysical pictures that can accompany such a view. I conclude that the technical features of the laws -- typically (though not always) given to us by practicing scientists -- are compatible with many different metaphysical foundations.
Cabozantinib for relapsed neuroblastoma: Single institution case series

Relapsed high-risk neuroblastoma has few effective therapies currently available or in development. Cabozantinib is an Food and Drug Administration approved multitargeted tyrosine kinase inhibitor for select adult malignancies with preclinical data suggesting efficacy against neuroblastoma. A safe and tolerable dose has been identified for children, but its efficacy remains unknown. We describe four children with relapsed metastatic neuroblastoma treated with cabozantinib. All four patients had extended disease control (two complete responsesfor >12 months, 2 stable disease >6 months) with manageable predictable toxicities requiring dose reduction in two patients. We discuss the potential for the use of cabozantinib in neuroblastoma.
Testosterone prescribing in men with depression and anxiety disorders.

Abstract Purpose Testosterone replacement therapy (TRT) is posited to reduce the risk of depression and anxiety. To our knowledge, this is the first study to assess incident TRT prescribing patterns in a nationally representative sample of men with depression and anxiety in the United States. Methods This study included 5,565,649 men aged 40–65 years, who were enrolled in Clinformatics Data Mart between January 1, 2002 and December 31, 2016. For each calendar year, we reported incident TRT prescribing and testosterone laboratory testing rates in men diagnosed with depression and/or anxiety. Results For each calendar year, incident TRT prescribing rates were higher for men with depression and anxiety, than for men without these disorders. For both groups, TRT prescribing increased by 200% from 2002 to 2013 and decreased by more than 50% from 2013 to 2016. More than 20% of men in either group did not have a laboratory test for testosterone levels before TRT initiation. Conclusions In men with depression and anxiety, TRT prescribing increased significantly from 2002 to 2013 and decreased from 2013 to 2016. A significant proportion of men were prescribed TRT without a prior laboratory test for testosterone levels. Further research is needed to better understand the extent to which these conditions influence physician prescribing practices and patient expectations.
Endothelial Deficiency of Insulin-like Growth Factor -1 Receptor Reduces Endothelial Barrier Function and Promotes Atherosclerosis in Apoe-Deficient Mice.

Insulin-like growth factor-1 (IGF-1) decreases atherosclerosis in apolipoprotein E (Apoe)-deficient mice when administered systemically. However, mechanisms for its atheroprotective effect are not fully understood. We generated endothelium-specific IGF-1 receptor (IGF1R)-deficient mice on an Apoe-deficient background to assess effects of IGF-1 on the endothelium in the context of hyperlipidemia-induced atherosclerosis. Endothelial deficiency of IGF1R promoted atherosclerotic burden, when animals were fed on a high-fat diet for 12 wk or normal chow for 12 mo. Under the normal chow feeding condition, the vascular relaxation response to acetylcholine was increased in the endothelial IGF1R-deficient aorta; however, feeding of a high-fat diet substantially attenuated the relaxation response, and there was no difference between endothelial IGF1R-deficient and control mice. The endothelium and its intercellular junctions provide a barrier function to the vasculature. In human aortic endothelial cells, IGF-1 upregulated occludin, claudin 5, VE-cadherin, JAM-A, and CD31 expression levels, and vice versa, specific IGF1R inhibitor, picropodophyllin, an IGF1R-neutralizing antibody (αIR3), or siRNA to IGF1R abolished the IGF-1 effects on junction and adherens proteins, suggesting that IGF-1 promoted endothelial barrier function. Moreover, endothelial transwell permeability assays indicated that inhibition of IGF-1 signaling elevated solute permeability through the monolayer of human aortic endothelial cells. In summary, endothelial IGF1R deficiency increases atherosclerosis, and IGF-1 positively regulates tight junction protein and adherens junction protein levels and endothelial barrier function. Our findings suggest that the elevation of the endothelial junction protein level is, at least in part, the mechanism for antiatherogenic effects of IGF-1.NEW & NOTEWORTHY Endothelial insulin-like growth factor-1 (IGF-1) receptor deficiency significantly elevated atherosclerotic burden in apolipoprotein E-deficient mice, mediated at least in part by downregulation of intercellular junction proteins and, thus, elevated endothelial permeability. This study revealed a novel role for IGF-1 in supporting endothelial barrier function. These findings suggest that IGF-1's ability to promote endothelial barrier function may offer a novel therapeutic strategy for vascular diseases such as atherosclerosis.
Atrial fibrillation and the risk of ischaemic strokes or intracranial haemorrhages: comparisons of the catheter ablation, medical therapy, and non-atrial fibrillation population.

AIMS Although atrial fibrillation (AF) catheter ablation (AFCA) is an effective rhythm control strategy, there is limited data on whether ischaemic stroke (IS) or intracranial haemorrhage (ICH) decreases after AFCA compared with medical therapy or non-AF population. We explored the IS and ICH risk after AFCA or medical therapy in the AF population and matched non-AF population. METHODS AND RESULTS We compared 1629 patients with AFCA (Yonsei AF ablation cohort), 3258 with medical therapy [Korean National Health Insurance (NHIS) database], and 3258 non-AF subjects (NHIS database) following a 1:2:2 propensity score matching. All AFCA patients underwent regular rhythm follow-ups for 51 ± 29 months. Among the AFCA group, the incidence rate ratio (IRR) of ISs was significantly higher in patients with sustained AF recurrences after the last ablation (0.87%) than in those remaining in sinus rhythm (0.24%, P = 0.017; log rank P = 0.003). The IRR of ISs was significantly higher in the medical therapy (1.09%) than AFCA (0.30%, P < 0.001, log rank P < 0.001 vs. medical therapy) or non-AF groups (0.34%, P < 0.001, log rank P < 0.001 vs. medical therapy; P = 0.673, log rank P = 0.874 vs. AFCA). The IRR of ICHs was 0.17% in the medical therapy, 0.06% in the AFCA (P = 0.023, log rank P = 0.042 vs. medical therapy), and 0.12% in the non-AF group (P = 0.226, log rank P = 0.241 vs. medical therapy; P = 0.172, log rank P = 0.193 vs. AFCA). CONCLUSION Post-procedural AF control influences the risk of ISs. Atrial fibrillation catheter ablation significantly reduces the risk of both ISs and ICHs to the extent of the non-AF population compared to the medical therapy.