cssi/SciSciGPT-SciSciNet huggingface dataset:
Estimation of intrinsic and reflex contributions to muscle dynamics: a modeling study

This work evaluated system identification-based approaches for estimating stretch reflex contributions to muscle dynamics. Skeletal muscle resists externally imposed stretches via both intrinsic stiffness properties of the muscle and reflexively mediated changes in muscle activation. To separately estimate these intrinsic and reflex components, system identification approaches must make several assumptions. The authors examined the impact of making specific structural assumptions about the intrinsic and reflex systems on the system identification accuracy. In particular, they compared an approach that made specific parametric assumptions about the reflex and intrinsic subsystems to another that assumed more general nonparametric subsystems. A simulation-based approach was used so that the "true" characters of the intrinsic and reflex systems mere known; the identification methods were judged on their abilities to retrieve these known system properties. Identification algorithms were tested on three experimentally based models describing the stretch reflex system. Results indicated that the assumed form of the intrinsic and reflex systems had a significant impact on the stiffness separation accuracy. In general, the algorithm incorporating nonparametric subsystems was more robust than the fully parametric algorithm because it had a more general structure and because it provided a better indication of the appropriateness of the assumed structure.
Improved JPEG Decompression of Document Images Based on Image Segmentation

We propose a JPEG decompression algorithm for document images based on image segmentation. Our segmentation algorithm classifies each JPEG block of the image into one of three classes: text, background, or picture. We develop a different decoding strategy for each class and apply this strategy to every block in this class. Our experiments demonstrate that this approach can improve the quality of JPEG decompression.
Short-term and long-term survival of new neurons in the rat dentate gyrus

New neurons continue to be generated in the dentate gyrus throughout adulthood. Previous studies have shown that a significant proportion of new granule cells labeled with the thymidine analogue bromodeoxyuridine (BrdU) are lost from the adult dentate gyrus within 2 weeks. How long this loss continues and the extent to which it represents cell death, as opposed to dilution of label, is unclear. To address these questions, adult rats were injected with BrdU, and BrdU labeling in the dentate gyrus was compared at several survival time points. Double labeling with BrdU and the cell cycle marker Ki-67 showed that BrdU is detectable for up to 4 days in some cells that continue to divide, indicating that any decrease in the number of BrdU-labeled cells after 4 days is likely to reflect cell death rather than BrdU dilution. Death of new cells in the granule cell layer occurred at a steady rate between 6 and 28 days after labeling, resulting in loss of 50% of BrdU-labeled cells over this 22-day period. New granule cells that survived this first month lived for at least 5 additional months. In contrast, 26% of the granule cells labeled with BrdU at the peak of dentate gyrus development on postnatal day (P) 6 died between 1 and 6 months after labeling. These findings suggest that granule cells born during adulthood that become integrated into circuits and survive to maturity are very stable and may permanently replace granule cells born during development.
Malignant pleural mesothelioma presenting as spontaneous pneumothorax: a case series and review.

Background Malignant pleural mesothelioma (MPM) is thought to arise from the mesothelial cells that line the pleural cavities. Most patients initially experience the insidious onset of chest pain or shortness of breath, and it rarely presents as spontaneous pneumothorax. Case reports We report four patients who presented in this manner. Three of the patients were exposed to asbestos directly or indirectly at shipyards during World War II; the fourth was exposed as an insulator's wife. Two of our cases were not recognized to have MPM on histologic examination at first thoracotomy and remained asymptomatic for 12 and 22 months, respectively. In none of the patients described herein, was spontaneous pneumothorax the cause of death. Conclusions Since many people were exposed to asbestos during and after World War II, spontaneous pneumothorax in a patient with the possibility of such exposure should raise the suspicion of malignant pleural mesothelioma.
George Herbert's JORDAN (I)

Interpreters typically assume that the final four words of George Herbert's “Jordan (I)”—“My God, My King” (line 15)—are spoken by the poet himself, and that he is concerned that other poets might ...
Advanced sugar–beet seed

A technique is described for speeding germination of monogerm sugar-beet seed. The optimum treatment was four cycles of wetting seed with its own weight of water and storing it in a sealed container for 24 hours before drying for 48 hours. The number of cells per embryo was doubled, seedlings emerged approximately 2·5 days sooner and seedling shoot weight was increased by 31 to 53%.
Reproductive and developmental biology of the emerald ash borer parasitoid Spathius galinae (Hymenoptera: Braconidae) as affected by temperature

Abstract Emerald ash borer Agrilus planipennis Fairmaire (Coleoptera: Buprestidae) is an invasive pest of serious concern in North America. To complement ongoing biological control efforts, Spathius galinae Belokobylskij and Strazenac (Hymenoptera: Braconidae), a recently-described specialist parasitoid of emerald ash borer larvae, is being released for the first time in the United States. To better understand its reproductive and developmental biology, and to improve outcomes of mass-rearing, we investigated the effects of constant ambient temperature (15, 20, 25, 30, and 35 °C) on immature development time, sex ratio, pre-oviposition period, fecundity and survivorship. Results show that between 20 and 30 °C immature development time was inversely associated with temperature, with adults emerging ≈38, 32, and 25 d after oviposition at 20, 25, and 30 °C, respectively. At 15 °C larvae developed to 5th instars and spun cocoons before development was arrested, while at 35 °C parasitoid eggs desiccated and did not hatch. Sex ratio of adult progeny that were exposed to different temperatures, from eggs, was not affected. When newly (⩽24 h-old) emerged female parasitoids were provided larval hosts throughout their lifetimes, adults parasitized at all temperatures except 35 °C, although parasitism rate was highest (35%), as was lifetime fecundity (43 progeny/female), when females lived at 25 °C. Survivorship was inversely associated with temperature, with ovipositing females living for >60 d when maintained at 15 °C, and females held at 35 °C living for S. galinae had the highest net reproductive rate ( R 0 = 27.8) and intrinsic rate of increase ( r m = 0.29) when female parasitoids were maintained at 25 °C for their lifetimes, suggesting this is the optimal temperature to rear S. galinae .
CFD Analysis for Ducted Fans with Validation

An axisymmetric, incompressible Navier-Stokes solver was developed to calculate the flow field of a ducted fan. The fan effect is modeled via the momentum source concept. The effects of the spinning fan blades were introduced into the flow field as time-averaged sources in the momentum equations. These source terms were not known a priori but are the result of the flow solution at each iteration. This approach simplified the modeling of the fan blades and provided a very rapid solution procedure for the flow problem. A new grid generator capable of recognizing the duct and nacelle geometry was developed and tested for several industrial ducted fans of current interest. Prediction of hover performance for a ducted fan model was calculated and compared with available wind tunnel test data. The comparison was good. Preliminary results showed that the Computational Fluid Dynamics (CFD) program could be used as an axial flow analysis tool for ducted fan design.
NT-29UPREGULATION OF BETA-CATENIN IN PATIENT-DERIVED GLIOBLASTOMA XENOGRAFTS EXPRESSING EGFRvIII

Amplification of the EGFR gene and subsequent overexpression of EGFR is seen in about 40% of glioblastomas. Over 50% of these glioblastomas with overexpressed EGFR also contain a variant of EGFR, known as EGFRvIII, which lacks amino acids 30-297 in its extracellular domain. Key features of EGFRvIII include a lack of binding to EGF and constitutive tyrosine kinase activity. Because EGFRvIII occurs in more than 20% of glioblastoma patients and is not present in normal brain cells, extensive efforts are being made to understand how EGFRvIII functions. Toward this goal, we recently characterized a panel of twenty patient-derived xenografts (PDGX) using a proteomics approach. This analysis revealed that seven out of the twenty PDGX expressed activated EGFR. Among those seven, three were EGFRvIII positive. A comparison of the proteomic profile of the four PDGX with activated EGFR that was not EGFRvIII with the proteomic profile of the three PDGX that expressed EGFRvIII revealed several differences. The most notable difference was the upregulation of beta-catenin. This discovery provides a novel target against EGFRvIII positive glioblastoma.
Probing Human Spatial and Color Vision on a Cellular Scale

A combination of high resolution imaging and eye tracking enables vision testing on a cellular scale. The aim of the talk will be to demonstrate how eye movements can facilitate fine spatial and color vision.
Association between 9p21.3 genomic markers and coronary artery disease in East Asians: a meta-analysis involving 9,813 cases and 10,710 controls

Recently, genome-wide association studies on Coronary Artery Disease (CAD) identified a series of associated Single-Nucleotide Polymorphisms (SNPs) in an intergenic region of chromosome 9p21.3, near the CDKN2A and CDKN2B genes. We investigated the association of this locus with CAD in 12 case–control studies of East Asians and undertook a meta-analysis for effect size, heterogeneity, publication bias, and strength of evidence. English and Chinese language articles were tested for 9p21.3 SNPs with coronary heart/artery disease or myocardial infarction as primary outcomes. Included articles also provided race, numbers of participants, and data to compute an Odds Ratio (OR). Articles were excluded if reporting other outcomes (e.g., stroke). Thirty-five articles were initially identified and 12 were included. Independent extraction was performed by two reviewers and consensus was reached. SNP rs1333049, rs2383206 and rs10757278 representing the 9p21.3 locus, were genotyped in 12 case–control studies involving a total of 9,813 patients and 10,710 controls. For rs1333049 (8 data sets), using a fixed-effects model, the summary OR was 1.29 (95% CI, 1.23–1.36, P = 0.001). For rs2383206 (6 data sets), using a fixed-effects model, the summary OR was 1.24 (95% CI, 1.18–1.31, P = 0.001). For rs10757278 (6 data sets), using a random-effects model, the summary OR was 1.34 (95% CI, 1.21–1.50, P = 0.001). In addition, we defined the haploblock structure of SNPs within the region of 9p21.3 in China population in one study. This broad replication provides unprecedented evidence for association between genetic variants at chromosome 9p21.3 and risk of CAD in East Asians.
Understanding the Global Phenomenon of Online Group Buying: Perspective from China and the United States

ABSTRACTThis cross-cultural comparison examined the mechanisms driving consumers' online group-buying (OGB) intention in China and United States. Chinese consumers expressed stronger inclination to participate in OGB than their U.S. counterparts. Opinion leadership emerged as a significant antecedent in both countries. However, perceived trust toward group-buying websites contributed to U.S. participants' OGB intentions but not for Chinese consumers. By contrast, perceived popularity significantly influenced Chinese consumers' OGB intention only. Consumer need for uniqueness did not significantly predict OGB intention in the United States, while Chinese male consumers with a greater level of CNFU were more likely to participate in OGB.
Data-driven proficiency profiling: proof of concept

Data-driven methods have previously been used in intelligent tutoring systems to improve student learning outcomes and predict student learning methods. We have been incorporating data-driven methods for feedback and problem selection into Deep Thought, a logic tutor where students practice constructing deductive logic proofs. In this latest study we have implemented our data-driven proficiency profiler (DDPP) into Deep Thought as a proof of concept. The DDPP determines student proficiency without expert involvement by comparing relevant student rule scores to previous students who behaved similarly in the tutor and successfully completed it. The results show that the DDPP did improve in performance with additional data and proved to be an effective proof of concept.
Defects as qubits in 3 C - and 4 H -SiC

We employ hybrid density functional calculations to search for defects in different polytypes of SiC that may serve as qubits for quantum computing. We explore the divacancy in $4H\text{\ensuremath{-}}$ and $3C\text{\ensuremath{-}}\mathrm{SiC}$, consisting of a carbon vacancy adjacent to a silicon vacancy, and the nitrogen-vacancy (NV) center in $3C\text{\ensuremath{-}}\mathrm{SiC}$, in which the substitutional ${\mathrm{N}}_{\mathrm{C}}$ sits next to a Si vacancy (${\mathrm{N}}_{\mathrm{C}}\ensuremath{-}{V}_{\mathrm{Si}}$). The calculated excitation and emission energies of the divacancy in $4H\text{\ensuremath{-}}\mathrm{SiC}$ are in excellent agreement with experimental data, and aid in identifying the four unique configurations of the divacancy with the four distinct zero-phonon lines observed experimentally. For $3C\text{\ensuremath{-}}\mathrm{SiC}$, we identify the paramagnetic defect that was recently shown to maintain a coherent quantum state up to room temperature as the spin-1 neutral divacancy. Finally, we show that the $({\mathrm{N}}_{\mathrm{C}}\ensuremath{-}{V}_{\mathrm{Si}}{)}^{\ensuremath{-}}$ center in $3C\text{\ensuremath{-}}\mathrm{SiC}$ is highly promising for quantum information science, and we provide guidance for identifying this defect.
Contact Lens Solutions

Identifying the best system for a patient involves evaluation of patient’s needs, the type of lenses worn, allergies, solution sensitivities, and the lens replacement schedule. The efficacy of lens care systems has been carefully evaluated by the manufacturers and approved by the FDA as safe and effective. These systems are tested (and proven efficacious) when used all together (i.e. as a “system” not each isolated product).
Unraveling Blockchain based Crypto-currency System Supporting Oblivious Transactions: a Formalized Approach

User privacy is an important issue in a blockchain based transaction system. Bitcoin, being one of the most widely used blockchain based transaction system, fails to provide enough protection on users' privacy. Many subsequent studies focus on establishing a system that hides the linkage between the identities (pseudonyms) of users and the transactions they carry out in order to provide a high level of anonymity. Examples include Zerocoin, Zerocash and so on. It thus becomes an interesting question whether such new transaction systems do provide enough protection on users' privacy. In this paper, we propose a novel and effective approach for de-anonymizing these transaction systems by leveraging information in the system that is not directly related, including the number of transactions made by each identity and time stamp of sending and receiving. Combining probability studies with optimization tools, we establish a model which allows us to determine, among all possible ways of linking between transactions and identities, the one that is most likely to be true. Subsequent transaction graph analysis could then be carried out, leading to the de-anonymization of the system. To solve the model, we provide exact algorithms based on mixed integer linear programming. Our research also establishes interesting relationships between the de-anonymization problem and other problems studied in the literature of theoretical computer science, e.g., the graph matching problem and scheduling problem.
Oregon's Coordinated Care Organizations and Their Effect on Prenatal Care Utilization Among Medicaid Enrollees.

Introduction Previous studies indicate that inadequate prenatal care is more common among women covered by Medicaid compared with private insurance. Increasing the proportion of pregnant women who receive early and adequate prenatal care is a Healthy People 2020 goal. We examined the impact of the implementation of Oregon’s accountable care organizations, Coordinated Care Organizations (CCOs), for Medicaid enrollees, on prenatal care utilization among Oregon women of reproductive age enrolled in Medicaid. Methods Using Medicaid eligibility data linked to unique birth records for 2011–2013, we used a pre-posttest treatment–control design that compared prenatal care utilization for women on Medicaid before and after CCO implementation to women never enrolled in Medicaid. Additional stratified analyses were conducted to explore differences in the effect of CCO implementation based on rurality, race, and ethnicity. Results After CCO implementation, mothers on Medicaid had a 13% increase in the odds of receiving first trimester care (OR 1.13, CI 1.04, 1.23). Non-Hispanic (OR 1.20, CI 1.09, 1.32), White (OR 1.20, CI 1.08, 1.33) and Asian (OR 2.03, CI 1.26, 3.27) women on Medicaid were more likely to receive initial prenatal care in the first trimester after CCO implementation and only Medicaid women in urban areas were more likely (OR 1.14, CI 1.05, 1.25) to initiate prenatal care in the first trimester. Conclusion Following Oregon’s implementation of an innovative Medicaid coordinated care model, we found that women on Medicaid experienced a significant increase in receiving timely prenatal care.
An Irregular Wide Complex Tachycardia.

A 66-year-old woman with a history of hypertension and persistent atrial fibrillation was referred to the Arrhythmia Clinic. Before her visit, a routine 12-lead ECG was ordered (Figure 1). The patient was asymptomatic except for minor palpitations. Her medicine regimen included apixaban, flecainide 150 mg twice daily, lisinopril, loratadine, metoprolol, and simvastatin. Figure 1. Routine 12-lead ECG recorded before a clinic visit to the electrophysiology clinic. What is the cardiac rhythm and what should be the initial treatment? Please turn the page to read the diagnosis. The ECG shows a very wide QRS complex tachycardia (QRS duration 280 ms) with variation in morphology. Following a pause of 700 ms, there are repeating sequences of 6 to 7 beats with cycle lengths of 400 to 415 ms. A second ECG demonstrated that the QRS morphology changed from a right bundle-branch block type pattern to a left bundle-branch block type …
Children begin with the same start-up software, but their software updates are cultural.

We propose that early in ontogeny, children's core cognitive abilities are shaped by culturally dependent “software updates.” The role of sociocultural inputs in the development of children's learning is largely missing from Lake et al.'s discussion of the development of human-like artificial intelligence, but its inclusion would help move research even closer to machines that can learn and think like humans.
GL261 glioma tumor cells respond to ATP with an intracellular calcium rise and glutamate release.

Glioblastoma (GBM) is an aggressive brain cancer with an average survival rate of 15 months. The composition of the GBM tumor microenvironment—its pH, the presence of growth and immune factors, neurotransmitters, and gliotransmitters—plays an important role in GBM pathophysiology and facilitates tumor survival and growth. In particular, GBM tumor cells produce glutamate, which is toxic to healthy tissue and is associated with increased tumor invasion into adjacent brain regions. The conditions that lead to this excitotoxic release of glutamate are not completely understood. Previous studies have demonstrated that extracellular ATP is present at high levels in the tumor microenvironment, and that ATP stimulates the release of glutamate from astrocytes in culture. Here we examine the functional effects of extracellular ATP on the GL261 cell line, a model system for high-grade astrocytomas such as GBM. We show that treatment with ATP leads to an immediate, dose-dependent influx of calcium into the cell that is partially inhibited by an antagonist (o-ATP) of the ionotropic ATP receptor P2X7. In addition, GL261 cells respond to extracellular ATP with a dose-dependent release of glutamate. Consistent with other reports, we find that ATP is toxic to GL261 cells at high concentrations. Together, these results provide insight into the mechanisms responsible for glutamate production by tumor cells and inform future studies that will identify how the GBM tumor microenvironment facilitates tumor invasion into healthy areas of the brain.
Data-Driven Mechanistic Modeling of Influence of Microstructure on High-Cycle Fatigue Life of Nickel Titanium

A data-driven mechanistic modeling technique is applied to a system representative of a broken-up inclusion (“stringer”) within drawn nickel-titanium wire or tube, e.g., as used for arterial stents. The approach uses a decomposition of the problem into a training stage and a prediction stage. It is applied to compute the fatigue crack incubation life of a microstructure of interest under high-cycle fatigue. A parametric study of a matrix–inclusion–void microstructure is conducted. The results indicate that, within the range studied, a larger void between halves of the inclusion increases fatigue life, while larger inclusion diameter reduces fatigue life.
Depression and Anxiety in COPD: Diagnosis and Management Issues

• Depression, often with anxiety, is common in COPD, contributes to disability, and is detectable by simple screening tools. • Mild mood symptoms often respond well to good medical management and pulmonary rehabilitation, but major depressive episodes and panic disorder should be diagnosed and specifically treated. Treatment outcome studies are too limited to provide guideline-level support for choosing among interventions. • Current best practices include screening COPD patients for major depression and panic disorder, initiating specific treatment, and monitoring patient response at planned intervals. Persistently symptomatic patients should be referred to an appropriate mental health specialist.
Can Evolution Strategies Improve Learning Guidance in XCS? Design and Comparison with Genetic Algorithms based XCS

XCS is a complex machine learning technique that combines credit apportionment techniques for rule evaluation with genetic algorithms for rule discovery to evolve a distributed set of sub-solutions online. Recent research on XCS has mainly focused on achieving a better understanding of the reinforcement component, yielding several improvements to the architecture. Nonetheless, studies on the rule discovery component of the system are scarce. In this paper, we experimentally study the discovery component of XCS, which is guided by a steady-state genetic algorithm. We design a new procedure based on evolution strategies and adapt it to the system. Then, we compare in detail XCS with both genetic algorithms and evolution strategies on a large collection of real-life problems, analyzing in detail the interaction of the different genetic operators and their contribution in the search for better rules. The overall analysis shows the competitiveness of the new XCS based on evolution strategies and increases our understanding of the behavior of the different genetic operators in XCS.
Dislocations and the Strength of Polycrystalline Ceramics

This paper discusses the interaction of dislocations with grain boundaries in polycrystalline rock salt structure ceramics at various temperatures. At high temperatures (~0.5 T m ) dislocations are mobile and able to cross-slip freely to produce macroscopically “wavy” slip traces. Polycrystalline material then deforms plastically and necks down to a typical cup-cone ductile fracture. At intermediate temperatures (~0.3 T m ) dislocations are less mobile and cross slip occurs on a microscopic scale within “straight” slip bands. Polycrystalline material can then deform plastically but the limited number of slip systems operating in the vicinity of grain boundaries results in a high rate of work hardening and the development of internal constrains. Brittle cleavage fracture originates from an intergranular source. At low temperatures (~0.1 T m ) cross slip within “straight” slip bands is restricted. Polycrystalline material cannot then deform plastically at all. The dislocation density along a single slip band is so high that the stress concentration produced where it intercepts a grain boundary immediately nucleates a crack and brittle fracture. Dislocation interactions with grain boundaries are responsible for the embrittlement of fully dense, flaw-free polycrystalline magnesia at room temperature. Procedures are discussed for avoiding crack generation to improve the fracture resistance of this material.
Socioeconomic and Geographic Disparities in Accessing Nursing Homes With High Star Ratings

Abstract Objectives The Centers for Medicare & Medicaid Services Nursing Home Compare (NHC) serves as the most comprehensive repository of Medicaid- and/or Medicare-certified nursing homes providing services to approximately 1.4 million US residents. A gap in the literature exists in understanding on the national level whether residents from socioeconomically disadvantaged counties experience disparities in the access to nursing homes with higher NHC star ratings. The study aimed to examine nursing home quality variations with regard to county-level socioeconomic, geographic, and metropolitan status, while adjusting for nursing home facility-level characteristics. Design Cross-sectional ecological study. Setting and participants 15,090 Medicaid/Medicare-certified nursing homes with nonmissing star ratings. Measures Study outcomes were NHC overall, health inspection survey, nurse staffing, and quality measure star ratings. County-level measures included SES index, geographic regions, and metropolitan status. Facility-level characteristics included ownership, chain affiliation, type and length of Medicaid/Medicare certification, hospital affiliation, continuing care retirement community status, number of certified beds, and occupancy. Results Counties with average adjusted overall, nurse staffing, and quality measure star ratings below 3 stars appeared to be clustered in the South. Nursing homes located in counties with lower SES were associated with lower overall star ratings [adjusted mean stars: 3.66 to 3.84, 95% confidence interval (CI): (3.54, 3.79) to (3.73, 3.95)]. A similar pattern was observed in staffing [adjusted mean stars: 3.75 to 4.23, 95% CI: (3.54, 3.97) to (4.10, 4.35)] and quality ratings [adjusted mean stars: 3.29 to 3.52, 95% CI: (3.12, 3.47) to (3.35, 3.69)]. Conclusions Residents in socioeconomically disadvantaged counties experience disparities in accessing nursing homes with higher star ratings. These areas may lack sufficient resources to adequately staff the facility and deliver care that meets industry quality standards. These issues are likely to persist and possibly even worsen for the lower- and middle-class geriatric population given the current uncertainty around healthcare reform.
The NIST Magnetic Suspension Mass Comparator and Precision Mass Metrology

The National Institute of Standards and Technology (NIST) magnetic suspension mass comparator will be used to facilitate the dissemination of the kilogram, realized in the 4th-generation NIST Kibble balance, from vacuum to air. This paper details the current status of the system. The primary focus is on the improvements made since CPEM 2016 concerning both random and systematic sources of error.
Tunable Emission from Triplet Fusion Upconversion in Diketopyrrolopyrroles

Optical upconversion based on triplet fusion (TF), also known as triplet–triplet annihilation, is a process by which two or more low-energy photons are converted to one higher energy photon. This p...
Visual Ethnograpy Fashion Aesthetic Review at Jakarta Hijabers Community

Hijab as the religious fashion symbol was born and developed in Indonesia as a visual artefact which represents one of abedient values of a female muslim towards Islam regulations. In its historical journey, hijab has experienced many â€˜cultural dialoguesâ€™ in a very long period of time that leads it to be one form of a nation culture. Jakarta Hijabers Community as one of Islamic Communities participates in taking roles to make hijab as visual culture at once as the resuscitation for its members about the aesthetic value in daily life. This research digs deeper about the meaning change occuring in hijab fashion development from visual aspect through Jakarta Hijabers Community. Data collection was done through interview completed with questionnaires data. The analysis was by using domain analysis, taxonomy, and component. The result of the research showed the existence of some factors that trigger the emergence of aesthetics value at hijab as Muslim fashion and national mission towards the usage of hijab in order to be accepted positively by the society.
Quantitative Systems Pharmacology Models for a New International Cardiac Safety Regulatory Paradigm: An Overview of the Comprehensive In Vitro Proarrhythmia Assay In Silico Modeling Approach

As a relatively new discipline, quantitative systems pharmacology has seen a significant increase in the application and utility of drug development. One area that could greatly benefit from such an approach is in the proarrhythmia assessment of new drugs. The Comprehensive In Vitro Proarrhythmia Assay (CiPA) Initiative is a global public-private partnership project that has developed an integrated approach using mechanistic in silico models for proarrhythmia risk prediction. Progress to date has led to the formation of the International Council on Harmonisation Implementation Working Group to revise regulatory guidelines via the Questions-and-Answers process to address the best practices for proarrhythmia models and how they can impact clinical drug development. This article reviews the CiPA in silico model-development process, focusing on its unique development and validation strategy, and summarizes the lessons learned as consideration points for the ongoing implementation of CiPA-like in silico models in drug development.
Pro-Market Reforms and Firm Exports

We analyze the impact of structural reform on firm exports. We argue that structural reform generates new opportunities and reduces transaction costs, inducing firms to improve their efficiency and competitiveness to international levels and, therefore, helps them to export. However, we propose that not all companies benefit equally, because firms differ in how structural reform affects their competitiveness. Thus, we argue that subsidiaries of foreign firms are the main beneficiaries of structural reform, followed by domestic private firms, and finally by domestic state-owned firms. We test these arguments on a sample of the largest companies in Latin America for the period 1990-2005. We find that structural reform induces firms in general to export. Furthermore, it has the highest positive impact on the exports of subsidiaries of foreign firms, followed by domestic private firms. Surprisingly, we find that structural reform has a negative impact on the exports of domestic state-owned firms.The paper contributes to a better understanding of how changes in institutions affect firm behavior by explaining the mechanisms that link structural reform to firm exports and how these vary across firms. Moreover, it counters the arguments of numerous detractors of globalization who claim that foreign firms are the sole beneficiaries of structural reform by indicating that not only foreign but also domestic private firms benefit from structural reform. The paper also highlights the need to discuss who benefits from structural reform rather than whether structural reform is beneficial or detrimental.
Greenhouse gas emission reduction and cost from the United States biofuels mandate

Abstract The United States biofuel mandate might be the largest operating program to reduce greenhouse gas (GHG) emissions. This paper uses regulatory information about abatement and compliance cost estimates to measure the greenhouse gas abatement cost curve of the mandate. Historical compliance costs per unit of biofuel appear readily available, yet findings here show that using these data along with observed biofuel quantities biases biofuel mandate abatement cost estimates upward. Unbiased estimation requires that related biofuel mandate costs and emissions are estimated along with associated market effects, including on fuel use, using an economic model. Moreover, this approach relates greenhouse gas abatement to the implications for crop prices and land use, taking account of interactions within the crop sector. Results show that the United States biofuel mandate causes up to 20 million metric tons of carbon dioxide equivalent abatement for compliance costs that are equivalent to carbon prices ranging up to $20 per ton, with a large part coming from reductions in petroleum product use as the mandate encourages substitution to biofuels. Abatement costs are reduced if ethanol is made at new facilities with fewer emissions or if petroleum output expansion causes greater emissions than the historical average. Findings also indicate that GHG abatement via the mandate is initially costly due to the nature of biofuel demand, there can be a trade-off between corn price increase and GHG reduction, and the increase in total area planted to crops in the U.S. is less important than the reallocation of land among crops.
Mapping Forested Floodplain Topography Using InSAR and Radar Altimetry

An accurate floodplain digital elevation model (DEM) is an essential input for the hydraulic modeling of water flows across the floodplain. A method combining interferometric synthetic aperture radar (InSAR) and radar altimetry is presented to derive the bare-earth topography for a forested floodplain with an improved accuracy. This method is applied to the floodplains associated with the middle reach of the Congo River in Central Africa. The floodplain topographic model was evaluated using Ice, Cloud, and land Elevation Satellite (ICESat) altimetry measurements, and the root mean squared error (RMSE) was estimated to be 2.71 m. The newly-created elevation model has shown improvements in capturing subtle elevation variations within the forested floodplain, compared with two other vegetation bias corrected DEMs—the multierror-removed improved-terrain DEM (RMSE of 4.95 m) and the Bare-Earth’ SRTM (BEST) DEM (RMSE of 3.32 m). We were unable to generate a DEM for the entirety of the floodplain due to missing InSAR and radar altimetry data. This could be a problem for the DEM's integration into hydraulic modeling workflows where the elevation model would need to be merged with ancillary elevation products. This could lead to inconsistencies in the merged DEM and the subsequent modeled outputs. However, it is expected that future L-band SAR and satellite altimetry missions can remedy the data gaps and provide a more robust spatial coverage.
The Clinical Effect of an Early, Protocolized Approach to Mechanical Ventilation for Severe and Refractory Hypoxemia

BACKGROUND: ARDS remains a source of significant morbidity and mortality in the critically ill patient. The mainstay of therapy entails invasive mechanical ventilation utilizing a lung-protective strategy designed to limit lung injury associated with excessive stress and strain while the underlying etiology of respiratory failure is identified and treated. Less is understood about what to do once conventional ventilation parameters have been optimized but the patient’s respiratory status remains unchanged or worsens. In 2015, a protocolized, stepwise approach to mechanical ventilation with partially automated and clearly defined thresholds for management changes was implemented at our institution. We hypothesized that, by identifying appropriate patients earlier, time-to-escalation and rescue therapy implementation would be shortened. METHODS: Subjects with severe ARDS, treated with prone positioning based on our institution’s protocolized approach from December 2013 to August 2016 were included. Their baseline characteristics, severity of illness scores, and mechanical ventilation parameters were collected and analyzed. RESULTS: Baseline characteristics, tidal volumes, PaO2/FIO2, duration of ventilation after proning, and mortality were similar in both groups. Median (interquartile range [IQR]) PEEP at the time of proning was higher after the protocol implementation (12.5 cm H2O [IQR 6.5–19.4] vs 18 cm H2O [IQR 10–22], P = .386), and mean (IQR) respiratory system driving pressure was lower (16 cm H2O [IQR 13–36.2] vs 12 cm H2O [IQR 9–19.6], P = .029). Median (IQR) time from refractory hypoxemia identification to proning was shorter after protocol implementation (42.2 h [IQR 6.83–347.2] vs 16.3 h [IQR 1–99.7], I = .02), and PaO2/FIO2 at 1 h after proning was higher. ICU and hospital LOS were shorter after the protocol implementation. CONCLUSIONS: Following the implementation of an early, evidence-based, protocolized approach to optimizing mechanical ventilation, subjects with true refractory hypoxemia were identified earlier and time to proning was significantly shorter. Despite improvement in the evaluation and management of refractory hypoxemia as well as time to initiation of prone positioning, mortality was unchanged and there was variation in the duration of the position.
Artificial Intelligence Helps Predict 5-year Mortality and Graft Failure in Patients Undergoing Orthotopic Heart Transplantation

Purpose Orthotopic heart transplantation (OHT) is a life-saving procedure for advanced end-stage heart failure patients. Given the conservative allocation policy and mismatch of donors and wait-listed patients, the prediction of post OHT outcomes including survival and graft failure (GF) can help optimize organ allocation. We aimed to develop a risk prediction model using machine learning algorithm to predict survival and GF 5 years after OHT. Methods Using International society of heart and lung transplant (ISHLT) registry data, we retrospectively analyzed 15236 patients who underwent OHT from January 2005 through December 2009. 342 variables including pre/ post OHT, discharge and follow up information were extracted and used to develop a risk prediction model utilizing a gradient boosted classification tree algorithm (GBM) to predict the risk of graft failure and mortality 5 yrs. after hospital discharge. Variables with missing observations were handled internally by the GBM algorithm. A 10 fold cross-validation repeated 5 times was used to estimate the model's external performance. Receiver operator curve (ROC) for GBM model was calculated to predict survival and GF 5 years post OHT. Results The mean duration of follow up of 4.7 years (median 5 years). The mortality and graft failure 5 years post- OHT was 27.3% (n = 4161) & 28 %( n=4276) respectively. The area under ROC (AUC) to predict 5 yr. mortality and GF are 0.717 (95% CI 0.696- 0.737) & 0.661 (95% CI 0.640-0.683) respectively. Length of stay, recipient and donor age, recipient body mass index and ischemic time had the highest weight in predicting 5-year mortality and graft failure. The subgroup of patients with age>60yrs had a higher AUC for both the models. Conclusion The GBM model has an excellent accuracy in predicting 5 yr.-mortality and graft failure in patients undergoing OHT.
Relational Ethics: The Primacy of Experience

The understanding of moral reasoning that I advocate here extends and benefits from postphenomenology’s hybrid character, for it adopts insights informed by Dewey’s pragmatism and Whitehead’s process-relational philosophy, although it is based in Husserl’s account of passive synthesis. The focus is on developing possibilities for responding to the moral dimension of things, rather than on reaching decisions guided or governed by the paths associated with Aristotle, Kant, or Mill.
Non-asymptotic Analysis for Nonparametric Testing

We develop a non-asymptotic framework for hypothesis testing in nonparametric regression where the true regression function belongs to a Sobolev space. Our statistical guarantees are exact in the sense that Type I and II errors are controlled for any finite sample size. Meanwhile, one proposed test is shown to achieve minimax rate optimality in the asymptotic sense. An important consequence of this non-asymptotic theory is a new and practically useful formula for selecting the optimal smoothing parameter in the testing statistic. Extensions of our results to general reproducing kernel Hilbert spaces and non-Gaussian error regression are also discussed.
Discrete-Time Differential Dynamic Programming on Lie Groups: Derivation, Convergence Analysis, and Numerical Results

We develop a discrete-time optimal control framework for systems evolving on Lie groups. Our article generalizes the original differential dynamic programming method, by employing a coordinate-free, Lie-theoretic approach for its derivation. A key element lies, specifically, in the use of quadratic expansion schemes for cost functions and dynamics defined on Lie groups. The obtained algorithm iteratively optimizes local approximations of the control problem, until reaching a (sub)optimal solution. On the theoretical side, we also study the conditions under which convergence is attained. Details about the behavior and implementation of our method are provided through a simulated example on $TSO(3)$ .
Manganese Oxides in Martian Meteorites Northwest Africa (NWA) 7034 and 7533

Abstract We report the discovery of indigenous Mn-oxides in Martian regolith breccias Northwest Africa (NWA) 7034 and 7533. These Mn-oxides occur in Mn-rich regions as nanocrystals mixed with silicates, FeOOH, and possible phosphates. The Mn-rich regions contain up to 34 wt% Mn and typically display large chemical gradients on the scale of 10–20 μm. The Martian origin of Mn-oxides was established by the presence of Mn-rich glass (4.8–5.6 wt% Mn) in the fusion crust that crosscuts a Mn-oxides-bearing monzonite clast and by the absence of Mn-oxides on the environmentally exposed surfaces (exterior and fractures) of the meteorites. Manganese K-edge X-ray absorption spectrum (XAS) of the Mn-rich glass in the fusion crust indicated that this glass included high-valent Mn species. Synchrotron micro-X-ray diffraction of a Mn-rich region in a basalt clast and XAS of Mn-rich regions in three monzonite clasts indicate Mn-oxides in these regions are dominantly hollandite-structured with 67–85 mol% of the total Mn being Mn4+. The fact that Mn-rich regions are present in diverse petrological associations but are absent in the matrix of the breccias indicates that the Mn-oxides formed through surface alteration prior to the final brecciation event that assembled NWA 7034 and 7533. Thus, the age of the Mn-oxides is older than the lithification age (arguably 1.35 Ga) of NWA 7034 and 7533. Together with findings of Mn-rich phases within Noachian and Hesperian sedimentary strata in Endeavour and Gale craters, our results suggest that Mn-oxides are a common weathering product on Mars, suggesting aqueous environment on the Martian surface with high redox potential.
Chronic glenohumeral dislocations treated with arthroplasty: a systematic review

Background The aim of this systematic review was to summarize the clinical outcomes and associated predictors of outcomes for chronic glenohumeral dislocations treated with arthroplasty. Methods A systematic literature search was performed with Embase, PubMed, CENTRAL, BIOSIS, and CINAHL databases from the inception of these databases through January 1, 2021 to identify all articles that examined outcomes or predictors of outcomes of arthroplasty in patients with chronic glenohumeral dislocations. Studies that examined outcomes for patients with a chronic glenohumeral dislocation (≥3 weeks) treated with hemiarthroplasty, anatomic total shoulder arthroplasty, or reverse total shoulder arthroplasty were included. Those with acute or subacute dislocations ( Results We identified 195 articles; of which, 22 (201 patients/205 shoulders) met our inclusion criteria. A total of 14 studies reported outcomes of hemiarthroplasty, 10 studies reported outcomes of anatomic total shoulder arthroplasty, and 9 studies reported outcomes of reverse total shoulder arthroplasty. All studies documented clinical improvement after arthroplasty. Among 16 studies that measured range of motion, all 16 studies demonstrated improvement in range of motion postoperatively. Thirty-one reoperations (15%) were performed across all studies. Conclusion We found improved clinical outcomes after arthroplasty for the treatment of chronic glenohumeral fewer dislocations at a long-term follow-up. Some evidence suggests that reverse total shoulder arthroplasty may have superior outcomes and less complications compared with hemiarthroplasty and anatomic total shoulder arthroplasty. There is insufficient evidence regarding the potential influence that duration of dislocation, direction of dislocation, addition of concomitant procedures, or humeral component retroversion have on outcomes.
Total elbow arthroplasty for tumors of the distal humerus and elbow.

Introduction The elbow is a rare location for primary and metastatic tumors in the upper extremity. The goal of reconstruction is to provide painless motion and stability for hand function. Total elbow arthroplasty (TEA) is commonly utilized, with either off-the-self components, modular segmental endoprosthesis, or allograft-prosthesis composites (APC). The purpose of this study was to analyze and compare commonly utilized elbow reconstructions and report outcomes of (1) patient function and (2) implant survival and complications. Methods We reviewed 33 patients (18 females and 15 males) undergoing elbow arthroplasty for reconstruction of an underlying oncologic process including linked TEA (n = 22, 67%), APC (n = 9, 27%), and endoprosthesis (n = 2, 6%). The most common indication was metastatic disease (n = 17, 52%), with 24 patients (73%) presenting with a pathologic fracture. Results Five-year implant survival was following elbow reconstruction was 88%. The mean most recent Mayo Elbow Performance Score and Musculoskeletal Tumor Society Score were 84 ± 18 and 78 ± 15%. Postoperative complications occurred in 15 elbows (45%), most commonly periprosthetic fracture (n = 5, 15%), leading to reoperation in six elbows (18%). Conclusion Although elbow arthroplasty is associated with a high incidence of complications, it provides a stable platform for upper extremity function in patients with oncologic processes of the elbow.
Cancer of the Skin: Types and Etiology

Skin, the largest organ system in the human body, plays an important role in making a porous barrier to detach internal organs from external stimuli. Genetic or natural mutations in skin cells can cause cutaneous tissue hypethrophic and inflammatory condition or malignant transformation, that accounting for a big number of ailment in human skin which leads to skin cancer developement in the skin cells. Here in this chapter, we are describing the recent details on skin cancer types and their etiology. It also gives a brief idea of skin growth and how mutations or misregulations of these are elaborated in the pathogenesis of skin cancer development.