cssi/SciSciGPT-SciSciNet huggingface dataset:
Economic and Environmental Considerations in a Stochastic Inventory Control Model with Order Splitting under Different Delivery Schedules among Suppliers

Abstract This study analyzes an integrated inventory control and delivery scheduling problem in a stochastic demand environment with economic and environmental considerations. In particular, we examine a bi-objective continuous review inventory control model with order splitting among multiple suppliers, where both expected costs and carbon emissions per unit time are minimized. For this problem, two different delivery scheduling policies are considered for the split orders: sequential splitting and sequential delivery. First, we formulate the problem under each delivery scheduling policy as bi-objective mixed-integer nonlinear models. Then, an adaptive ϵ -constraint algorithm and an evolutionary search algorithm are proposed to approximate the Pareto front of these models. A numerical study is conducted to compare the two approximation algorithms. Another numerical study demonstrates the effects of the demand variance on the expected costs and carbon emissions per unit time under each delivery scheduling policy. Finally, examples are presented to show how the tools provided in this study can be used to compare different scheduling policies. Our results show that the delivery policy and supplier selection both have strong effects on the economic and environmental performance, and also that a good approximation of the Pareto front is crucial to accurately compare delivery scheduling policies.
Prisoners of Hope: Lyndon B. Johnson, the Great Society, and the limits of liberalism

In Prisoners of Hope, Randall Woods calls for a re-examination of President Lyndon Johnson’s Great Society, which he argues has not received the same level of interest or serious scholarly attentio...
Photocatalytic water oxidation at bismuth vanadate thin film electrodes grown by direct liquid injection chemical vapor deposition method

Abstract Photoelectrochemical cells (PECs) are devices that can harvest and convert solar energy to produce consumable fuel, e.g. by splitting water into oxygen and hydrogen. Photocatalytic semiconductor materials play a major role in PECs, and their overall efficiency is usually limited by short carrier diffusion length because of structural defects, poor light absorptivity, and sluggish kinetics of photoelectrochemical reactions at the semiconductor electrode. Synthesis of high quality defect-free semiconductor materials using high temperature deposition techniques generally yield films with good adhesion to substrates while improving charge carrier transport and hence the overall efficiency of a PEC. A direct liquid injection chemical vapor deposition (DLI-CVD) technique has been utilized to synthesize monoclinic clinobisvanite phase bismuth vanadate (BiVO4) films for photocatalytic water oxidation. The technique yields dense high quality epitaxial and polycrystalline BiVO4 films on Yttria stabilized zirconia (YSZ) and Fluorine doped tin oxide (FTO) substrates, respectively, at growth temperature in the range of 500–550 °C. The photoelectrochemical characteristics of the films grown on FTO have been studied and a photocurrent value of 2.1 mA/cm2 at 1.23 V vs Normal hydrogen electrode (NHE) (0.5 V vs. Ag/AgCl), with onset potential values as low as 0.23 V vs. NHE (−0.5 V vs. Ag/AgCl), are obtained despite the low porosity of the films. The PEC performance is further improved by synthesizing BiVO4 directly on top of a tungsten oxide interlayer and modifying its surface with FeOOH co-catalyst.
Qualitative Evaluation in Consumer Health Informatics

qualitative research for any purpose. Data collection and data analysis methods are similar for all projects. This chapter provides a general overview of these methods. But because qualitative research depends heavily on the research participants and contextual setting, each project is different. Examples throughout the chapter illustrate ways in which doing qualitative research to evaluate consumer health informatics projects is both similar and different from evaluating other kinds of projects. Qualitative research involves data that, generally, are textual, but also may be visual or artifactual. There are ways to reduce this kind of data to numerical form, for example, by counting the occurrences of a particular phrase. Doing that often defeats the purpose of using a qualitative approach. Instead, qualitative data analysis employs procedures for producing an interpretation of the data. Qualitative research also involves conducting rigorous and detailed studies in natural settings. For example, a researcher might be investigating how people use health information Web sites and why they prefer some sites to others. Such a study might be done in a setting where people naturally use these Web sites, such as a library, their homes, or offices. Many qualitative researchers attempt to understand something in the same way as the other participants involved in a study understand it. A research study on how people use Web sites and why people prefer some sites to others might investigate the way people think about a Web site’s design, appearance, ease of navigation, trustworthiness, helpfulness, applicability to their own situation, overall tone of the content, and the like. Some of these dimensions can be made into variables and differences between them measured, for example, through a user satisfaction survey.That would not be considered qualitative research. If the survey also included open-ended questions such as “Please describe what you like about your favorite Web site,” the data collected in answer to that question would be qualitative. Other considerations are not investigated as easily. Even though people may rate a Web site as positive along whatever dimensions might appear on the survey, it might still give them a “bad” feeling, or there might be something far more important to them than anything the survey asks. Their sense that the information is trustworthy and reliable might make a difference, but what makes information seem trustworthy and reliable? Perhaps who else is around might make a difference, too, or what their friends think. It is difficult to anticipate what influences might be important. It also may be difficult to measure them. Qualitative methods are better than quantitative ones (such as a survey) in these circumstances. Further, although people may rate a site as trustworthy, it might be difficult to assess just why they do. Just what does “trustworthy” mean 7 Qualitative Evaluation in Consumer Health Informatics
Persistent SIRS and acute fluid collections are associated with increased CT scanning in acute interstitial pancreatitis

AbstractBackground: The use of computed tomography (CT) in acute pancreatitis (AP) continues to increase in parallel with the increasing use of diagnostic imaging in clinical medicine.Aim: To determine the factors associated with obtaining >1 CT scan in acute interstitial pancreatitis (AIP).Methods: Demographic and clinical data of all adult patients admitted between 1/2010 and 1/2015 with AP (AP) were evaluated. Only patients with a CT severity index (CTSI) ≤ 3 on a CT obtained within 48 h of presentation were included.Results: A total of 229 patients were included, of whom 206 (90%) had a single CT and 23 (10%) had >1 CT during the first week of hospitalization. Patients undergoing >1 CT had significantly higher rates of acute fluid collection (AFC), persistent SIRS, opioid use ≥4 days, and persistent organ failure compared to those undergoing 1 CT (p < .05 for all). On multivariable analysis, only persistent SIRS (OR = 3.6, 95% CI 1.4–9.6, p = .01) and an AFC on initial CT (OR = 3.5, 95% CI 1.4–9, p = ...
Comment on "Intakes of vitamin C and carotenoids and risk of amyotrophic lateral sclerosis: pooled results from 5 cohort studies".

We read with interest the study by Fitzgerald et al.1, which found an inverse association between ALS and dietary intake of beta-carotene and lutein in a pooled cohort analysis. The authors also examined vitamin C intake and vitamin C supplement use, but did not discuss the use of carotenoid supplements (neither beta-carotene nor other carotenoids). Nonetheless, some readers may conclude that supplementation with beta-carotene or other carotenoids, which would generally provide higher doses than dietary intake, might offer even greater protection against ALS. We caution against this inference, particularly because of the results of our study on the relationship between ALS and supplemental beta-carotene (and vitamin E) in a randomized clinical trial of Finnish male smokers.2 This trial was initiated in the 1980s to determine whether supplementation with vitamin E or beta-carotene reduces lung cancer or other cancer incidence. Although it was not an a priori hypothesis of the trial, our study examined the trial results for the effects of these supplements on ALS risk. In our study, beta-carotene supplements were associated with a slightly elevated, although not statistically significant, risk of ALS. While the finding is not strong evidence of risk, it remains worrisome. Beta-carotene supplements have been associated with an increase in cancer at several sites.3 We therefore want to emphasize the conclusions of Fitzgerald et al. that the inverse association between ALS and beta-carotene and other carotenoids they reported was based only on dietary intake, and not on use of supplements.
2 Models and Measures of Sexual Orientation

This chapter provides an in-depth examination of the varied models and measures most commonly used to determine sexual orientation, in general, or bisexuality, in particular. The chapter identifies the components of and the strengths and weaknesses of each. The chapter presents each chronologically starting with the Kinsey Heterosexuality–Homosexuality Rating Scale, followed by the Klein Sexual Orientation Grid, Storms Erotic Response and Orientation Scale, the Sexual Identity Model, the Multidimensional Scale of Sexuality, Savin-Williams Assessment of Sexual Orientation, and, finally, Sexual Configurations Theory. Following the individual assessment of each model, the chapter concludes with general critiques of all existing models and offers some recommendations for the establishment of future models and measures with the goal of better capturing the complexity of bisexual orientation and the goal of creating greater synergy in research assessment and more accuracy in estimating the number of bisexual individuals.
Custody Contest: How to Divide and Reassemble a Child:

Too many children are being used as pawns in custody disputes. Workers can help families defuse the battle atmosphere if they understand the background and intricacies of custody laws and engage in...
Early developmental exposure to general anesthetic agents in primary neuron culture disrupts synapse formation via actions on the mTOR pathway

Human epidemiologic studies and laboratory investigations in animal models suggest that exposure to general anesthetic agents (GAs) have harmful effects on brain development. The mechanism underlying this putative iatrogenic condition is not clear and there are currently no accepted strategies for prophylaxis or treatment. Recent evidence suggests that anesthetics might cause persistent deficits in synaptogenesis by disrupting key events in neurodevelopment. Using an in vitro model consisting of dissociated primary cultured mouse neurons, we demonstrate abnormal pre- and post-synaptic marker expression after a clinically-relevant isoflurane anesthesia exposure is conducted during neuron development. We find that pharmacologic inhibition of the mechanistic target of rapamycin (mTOR) pathway can reverse the observed changes. Isoflurane exposure increases expression of phospho-S6, a marker of mTOR pathway activity, in a concentration-dependent fashion and this effect occurs throughout neuronal development. The mTOR 1 complex (mTORC1) and the mTOR 2 complex (mTORC2) branches of the pathway are both activated by isoflurane exposure and this is reversible with branch-specific inhibitors. Upregulation of mTOR is also seen with sevoflurane and propofol exposure, suggesting that this mechanism of developmental anesthetic neurotoxicity may occur with all the commonly used GAs in pediatric practice. We conclude that GAs disrupt the development of neurons during development by activating a well-defined neurodevelopmental disease pathway and that this phenotype can be reversed by pharmacologic inhibition.
Algorithms and Their Complexity

This is a course on the design and analysis of algorithms intended for first-year graduate students in computer science. Its purposes are mixed: on the one hand, we wish to cover some fairly advanced topics in order to provide a glimpse of current research for the benefit of those who might wish to specialize in this area; on the other, we wish to introduce some core results and techniques which will undoubtedly prove useful to those planning to specialize in other areas.
Simple Nonalgebraic Decoding Techniques for Group Codes

Decoding techniques for group codes can be divided into two general categories, algebraic and nonalgebraic. The algebraic techniques basically involve the simultaneous solution of sets of equations for the location and values of the errors. The nonalgebraic techniques, while accomplishing the same goal, are based upon simple structural aspects of the codes which permit one to determine the error patterns in a more direct fashion. In this chapter three nonalgebraic techniques will be discussed. These are Meggitt decoders,(12) first introduced by Meggitt in 1961 for the correction of burst errors, threshold decoders(13) introduced by Massey in 1963, and information set decoding,(14) which was first introduced by Prange in 1962. The discussion will concern only binary codes except when it is specifically noted that the results apply to nonbinary codes as well.
Computational Models to Predict Toxicity

In today's social and economic climate there is a pressing need to ensure the safety of new medicines while still maintaining a steady flow of new and more effective products to the market place. Often initial safety assessments are needed when there is an absence of high-quality toxicology data for a compound but generating this data would take many years and millions of dollars creating a pressing need for improved methods of identifying early safety concerns. Structure-based approaches to hazard identification and risk assessment offer significant advantages to medicinal chemists because they are very fast and cheap to run once they have been successfully implemented. They also offer a highly attractive public relations solution in view of the increasing demands of refine, reduce or replace animals in laboratory experiments. However, questions still exist about the ability of structure-based approaches to accurately distinguish between toxic and nontoxic molecules and their effectiveness in ensuring public safety. This chapter will review the current state of the art in structure-based methods for hazard identification and in silico models for toxicity prediction.
Dalitz Plots in p-d Breakup

Publisher Summary The Dalitz plot is a ternary plot often used in particle physics to represent the relative frequency of various (kinematically distinct) manners in which the products of certain (otherwise similar) three-body decays may move apart. One of the puzzling features of proton–deuteron breakup spectra has been the shape and magnitude of the quasifree scattering (QFS) peak observed in kinematically complete measurement. When the Fadeev equations are iterated to generate a rescattering series, only the first two terms are needed to give an accurate prediction of the peak cross section in the quasifree kinematic region. Those two terms correspond to single and double scattering, the two mechanisms that have long been known to be responsible for the prominent features of proton–deuteron breakup at GeV energies. When a semi-classical double scattering correction is applied to the simple impulse approximation (SIA), the predicted pp QFS peak agrees well with the data both in size and shape. This chapter reviews the role of rescattering in p-d breakup.
Abstract 3346: PRMT5-mediated methylation of YBX1 regulates NF-kB activity in colorectal cancer

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the US with a staggeringly less than 14% survival rate for patients with metastatic disease. This poor clinical outcome for CRC patients is largely attributed to the lack of understanding of the factors that drive CRC progression, leading to a dearth of available treatment strategies for this disease. Today, treatment modalities and clinical management of colorectal cancer (CRC) are fundamentally based on the success of controlling specific tumorigenic pathways. Interestingly, aberrant activation of the transcription factor nuclear factor ĸB (NF-ĸB) is increasingly recognized as a crucial player in CRC progression. Therefore, understanding the mechanisms underlying regulation of NF-ĸB holds great promise for devising new therapeutic strategies for CRC. Recently, we identified the oncogenic protein, Y-box binding protein 1 (YBX1), as a novel activator of NF-κB. Since YBX1 overexpression has also been linked to poor patient outcome in CRC, we sought to further understand whether this YBX1/NF-ĸB axis could be a potential target for CRC treatment. In this study, we discovered that YBX1 is methylated on arginine 205 (YBX1-R205me2), an event that is critical for YBX1-mediated NF-ĸB activation and target gene expression. Additionally, co-immunoprecipitation studies revealed that the R205 to alanine (A) mutant (YBX1-R205A) also significantly diminished the interaction between YBX1 and the p65 subunit of the transcriptionally active NF-ĸB, demonstrating a novel mechanism by which methylation of YBX1 mediates protein-protein interactions. Overexpression of YBX1-R205A significantly attenuated the migration, proliferation, and anchorage-independent growth of a panel of CRC cells, suggesting that YBX1-R205me2 is essential to the oncogenic functions exerted by the YBX1/NF-ĸB axis in CRC. Furthermore, we revealed that protein arginine methyltransferase 5 (PRMT5) is responsible for the methylation of YBX1-R205. Collectively, our novel findings present a complex picture of the sophisticated regulation of NF-ĸB through PRMT5-mediated YBX1-R205 methylation and suggest that pharmacological disruption of the YBX1/NF-κB axis using PRMT5 inhibitors could serve as the basis for new therapeutics that impede YBX1/NF-κB-driven CRC progression. Citation Format: Antja-Voy Hartley, Benlian Wang, Masaru Miyagi, Rasika Mundade, James Hamilton, Tao Lu. PRMT5-mediated methylation of YBX1 regulates NF-kB activity in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3346.
Emerging targeted strategies for the treatment of autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a widespread genetic disease that leads to renal failure in the majority of patients. The very first pharmacological treatment, tolvaptan, received Food and Drug Administration approval in 2018 after previous approval in Europe and other countries. However, tolvaptan is moderately effective and may negatively impact a patient's quality of life due to potentially significant side effects. Additional and improved therapies are still urgently needed, and several clinical trials are underway, which are discussed in the companion paper Muller and Benzing (Management of autosomal-dominant polycystic kidney disease-state-of-the-art) Clin Kidney J 2018; 11: i2-i13. Here, we discuss new therapeutic avenues that are currently being investigated at the preclinical stage. We focus on mammalian target of rapamycin and dual kinase inhibitors, compounds that target inflammation and histone deacetylases, RNA-targeted therapeutic strategies, glucosylceramide synthase inhibitors, compounds that affect the metabolism of renal cysts and dietary restriction. We discuss tissue targeting to renal cysts of small molecules via the folate receptor, and of monoclonal antibodies via the polymeric immunoglobulin receptor. A general problem with potential pharmacological approaches is that the many molecular targets that have been implicated in ADPKD are all widely expressed and carry out important functions in many organs and tissues. Because ADPKD is a slowly progressing, chronic disease, it is likely that any therapy will have to continue over years and decades. Therefore, systemically distributed drugs are likely to lead to potentially prohibitive extra-renal side effects during extended treatment. Tissue targeting to renal cysts of such drugs is one potential way around this problem. The use of dietary, instead of pharmacological, interventions is another.
A retrospective, single-institution experience of resected ampullary adenocarcincoma: predictors of clinical outcome.

e15229 Background: Ampullary adenocarcinoma (AA) is a rare gastrointestinal neoplasm and predictors of clinical outcomes are extrapolated from pancreatic adenocarcinoma. If detected early, the pref...
An enhanced recovery after surgery pathway: association with rapid discharge and minimal complications after anterior cervical spine surgery.

OBJECTIVEEnhanced recovery after surgery (ERAS) pathways are associated with improved outcomes, lower morbidity and complications, and higher patient satisfaction in multiple surgical subspecialties. Despite these gains, there are few data to guide the application of ERAS concepts to spine surgery. The authors report the development and implementation of the first ERAS pathway for patients undergoing anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA).METHODSThis was a retrospective cohort study of prospectively collected data. The authors created a multidisciplinary pathway based on best available evidence for interventions that positively influence outcomes after anterior cervical spine surgery. Patients were followed prospectively up to postoperative day 90. Patient data were collected via electronic medical record review and included demographics, comorbidities, baseline and perioperative opioid use, postoperative complications, and length of hospital stay (LOS). ERAS process measures and compliance with pathway elements were also tracked.RESULTSThirty-three patients were cared for under the pathway (n = 25 ACDF; n = 8 CDA). The median LOS was 416 minutes (interquartile range [IQR] 210-1643 minutes). Eight patients required an extended stay-longer than 23 hours. Reasons for extended admission included pain (n = 4), dyspnea (n = 1), hypoxia (n = 1), hypertension (n = 1), and dysphagia (n = 1). The median LOS for the 8 patients who required extended monitoring prior to discharge was 1585 minutes (IQR 1423-1713 minutes). Overall pathway compliance with included process measures was 85.6%. The median number of ERAS process elements delivered to each patient was 18. There was no strong association between LOS and number of ERAS process elements provided (Pearson's r = -0.20). Twelve percent of the cohort was opioid tolerant on the day of surgery. There were no significant differences between total intraoperatively or postanesthesia care unit-administered opioid, or LOS, between opioid-tolerant and opioid-naive patients. There were no complications requiring readmission.CONCLUSIONSAn ERAS pathway for anterior cervical spine surgery facilitates safe, prompt discharge. The ERAS pathway was associated with minimal complications, and no readmissions within 90 days of surgery. Pain and respiratory compromise were both linked with extended LOS in this cohort. Further prospective studies are needed to confirm the potential benefits of ERAS for anterior cervical spine surgery, including longer-term complications, cost, and functional outcomes.
False confidence, non-additive beliefs, and valid statistical inference

Abstract Statistics has made tremendous advances since the times of Fisher, Neyman, Jeffreys, and others, but the fundamental and practically relevant questions about probability and inference that puzzled our founding fathers remain unanswered. To bridge this gap, I propose to look beyond the two dominating schools of thought and ask the following three questions: what do scientists need out of statistics, do the existing frameworks meet these needs, and, if not, how to fill the void? To the first question, I contend that scientists seek to convert their data, posited statistical model, etc., into calibrated degrees of belief about quantities of interest. To the second question, I argue that any framework that returns additive beliefs, i.e., probabilities, necessarily suffers from false confidence—certain false hypotheses tend to be assigned high probability—and, therefore, risks systematic bias. This reveals the fundamental importance of non-additive beliefs in the context of statistical inference. But non-additivity alone is not enough so, to the third question, I offer a sufficient condition, called validity, for avoiding false confidence, and present a framework, based on random sets and belief functions, that provably meets this condition. Finally, I discuss characterizations of p-values and confidence intervals in terms of valid non-additive beliefs, which imply that users of these classical procedures are already following the proposed framework without knowing it.
Crowd-shipping services for last mile delivery: Analysis from American survey data

Abstract This research analyzes current and future shipping behaviors, potential employees' willingness to work as crowd-shipping (CS) driver-partners, as well as stakeholders' characteristics. Revealed and stated preference survey questionnaires were designed and implemented in the US. This descriptive study makes use of the survey dataset to understand the behavior of requesters and potential CS driver-partners in the logistics market and assumes that crowdsourced delivery is available. The results show various behaviors, expectations, and characteristics of requesters, as well as of prospective CS driver-partners. The results can be used to improve logistics services, recruit potential CS driver-partners, and create business strategies that match requesters' and potential CS driver-partners' expectations.
Efficient Cu-Catalyzed Asymmetric Conjugate Additions of Alkylzinc Reagents to Aromatic and Aliphatic Acyclic Nitroalkenes

An efficient and highly enantioselective (up to 95% ee) Cu-catalyzed method for asymmetric conjugate addition (ACA) of alkylzinc reagents to acyclic disubstituted nitroalkenes is presented. Reactions are typically effected at ambient temperature in the presence of 2 mol % chiral dipeptide phosphine and 1 mol % (CuOTf)2·C6H6. Nitroalkenes bearing aromatic as well as aliphatic substituents readily undergo asymmetric additions.
Effects of a Nutrition Program on School Cafeteria Lunch: An Expanded Commentary.

The aim of this commentary is to expand upon results of previously published work on improving nutrition of cafeteria lunches in elementary schools of a high-need school district in southern Colora...
CYTOMEGALOVIRUS RETINITIS WITH BELATACEPT IMMUNOSUPPRESSION.

Purpose To report two cases of cytomegalovirus (CMV) retinitis in renal transplant patients after conversion to belatacept immunosuppression. Methods Case report. Results Case A was a 41-year-old African American man with no ocular history, chronic hepatitis B infection on entecavir, status-post living relative renal transplant for end-stage renal disease secondary to IgA nephropathy presented with a chief complaint of "blurry vision" in his right eye. Fundoscopic examination of the right eye revealed perivascular retinitis of the superior arcade extending temporally and a lesion nasal to the optic disk. The patient was diagnosed with CMV retinitis with macular involvement. Case B was a 52-year-old woman with an ocular history significant for bilateral vein occlusions treated with laser, and a medical history of hypertension, hyperlipidemia, and end-stage renal disease secondary to hypoplastic kidney status-post deceased donor renal transplant presented with one week of blurred vision in the right eye. Fundoscopic examination of the right eye revealed macular star configuration of exudates, as well as subretinal fibrosis temporal to the macula. Fundoscopic examination of the left eye showed Grade 4 vitreous haze and multiple areas of retinal whitening and hemorrhage, consistent with CMV retinitis infection. The patient was diagnosed with bilateral CMV retinitis, with macular involvement in the right eye. Conclusion Renal transplant patients converted to belatacept immunosuppression may be at an increased risk for herpes virus infection, and thus herpes virus retinitis. Although the degree of risk remains uncharacterized, patients on belatacept therapy who are at the high risk of CMV infection (i.e., donor-positive/recipient-negative patients) should be counseled on the presenting signs and symptoms of CMV retinitis. In these cases, clinicians should also consider regular monitoring of serum CMV titers or continuation of antiviral prophylaxis.
The Precarity of Existence Requires Experimentation

Art museums exist in a precarious state as they constantly negotiate competing challenges of funding, audience interest, art world relevance, public perception, and artist representation. Museum leaders must balance these competing tensions of precarity as they navigate exhibition choices, hiring decisions, funding opportunities, and intertwined power structures. Response to these challenges leads to experimental ways of working, which incur risks and opportunities. Museums hold political and social positions in all aspects of their operation; this requires museums to experiment with more transparent processes from new art acquisitions to board member appointments. Experience-driven businesses compete with museums for audiences causing some museums to employ experience models. By ceding power to artists, community members, and other cooperative partners art becomes empowerment for residents.
Identification of the Protein S Binding Site in the Factor IXa Serine Protease Domain Presents Therapeutic Possibilities

Abstract Protein S (PS) has been shown to inhibit Factor IXa (FIXa); however, its binding sites on FIXa have not been fully elucidated. By structural analysis of FIXa in conjunction with previous studies of FIXa's ability to bind heparin, an FIXa inhibitor, we identified that multiple residues that make up the heparin binding exosite, including Lys126, Asn129, Lys132, Arg150, Arg165, and Arg170 (chymotrypsin numbering), might contribute to binding PS; these residues were substituted with either Ala or Leu in separate FIXa mutants. Factor Xa (FXa) generation assays along with fluorescence analyses provided both the catalytic efficiencies and dissociation constants for the FIXa mutants under conditions of varied PS. Furthermore, anisotropic measurements of the fluorescent DEGR-FIXa's binding interaction with PS, when titrated against each of the FIXa mutants, supported the data found in the previous assays. These studies suggested that multiple residues, which are critical for the binding of heparin, such as Lys126, Lys132, Arg165, and Arg170, are also required in binding PS. To additionally verify this data, further ex vivo studies, including co-immunoprecipitation and flow cytometry of PS and FIXa are underway. Although previous studies have shown that the first EGF-like domain of FIXa is required to bind PS, these novel results have not only localized the main inhibitory site of PS on FIXa, but also provided enough information to propose a binding mechanism, which may rely on the reciprocal association between the head groups of PS and FIXa with the other's EGF-like domains, forming a bridging structure upon the cell membrane. Further studies are required to verify this hypothesis, but when clarified, it could provide immense benefits in the production of therapeutics for thrombosis. Disclosures No relevant conflicts of interest to declare.
Bioethics and the Rule of Law: A Classical Liberal Theory

Heated debates over healthcare policy in the United States point to the need for a legal framework that can sustain both moral diversity and peaceful cooperation. It is argued that the classical liberal Rule of Law, with its foundation in the ethical principle of permission, is such a framework. The paper shows to what extent the current healthcare policy landscape in the United States diverges from the rule of law and suggests how the current framework could be modified in order to better approximate that ideal. Two objections are then answered. The first is that the rule of law cannot be realized due to the structure of legislatures. The second objection is that government should guarantee both liberty and all of the necessary conditions of autonomy.
The Power of Single-Cell Analysis for the Study of Liver Pathobiology

Single cell transcriptomics has emerged as a powerful lens through which to study the molecular diversity of complex tissues such as the liver, during health and disease, both in animal models and in humans. The earliest gene expression methods measured bulk tissue RNA, but the results were often confusing because they derived from the combined transcriptomes of many different cell types in unknown proportions. To better delineate cell-type-specific expression, investigators developed cell isolation, purification, and sorting protocols, yet still, the RNA derived from ensembles of cells obscured recognition of cellular heterogeneity. Profiling transcriptomes at the single-cell level has opened the door to analyses that were not possible in the past. In this review, we discuss the evolution of single cell transcriptomics and how it has been applied for the study of liver physiology and pathobiology to date.
Community College Chemistry Instruction and Research in the Time of COVID-19

In March of 2020, as New York City was becoming the global epicenter of the COVID-19 pandemic, the 3 authors, members of the Chemistry Department at Queensborough Community College—City University of New York, had 1 week to move their 13 lecture and laboratory sections of 4 different first-year undergraduate courses plus 2 active undergraduate research programs online. Students—some of whom live in the areas of New York City hardest hit by the pandemic and/or are employed as essential workers or caregivers or were learning in a challenging environment—attended synchronous and/or asynchronous lectures and laboratories for the second half of the semester. Five percent of the 262 students in their classes were unable to complete the semester for undetermined technology, access, or personal reasons. While the authors feel that a redesign of the laboratory experience is necessary to satisfy general education outcomes if online laboratories are to continue in the long term, lecture students performed well post-transition. Students whose performance was 5–12% lower on exams in Spring 2020 than Fall 2019 (pre-COVID) performed 12–25% better following the transition to online learning, although academic integrity remains a matter of great concern. The authors caution that the crisis-response distance education offered in the second half of the Spring 2020 semester was only that, and further effort will be necessary as online learning continues. The prior online experience of the faculty members varied, but all found it both a stressful transition and a valuable exercise in altering their pedagogical approaches for the future.
Self-Reported Versus Objectively Assessed Olfaction and Parkinson's Disease Risk.

Background Poor olfaction is a prodromal symptom of Parkinson's disease (PD); however, self-reported sense of smell is often dismissed as unreliable. Objective To assess self-reported and objectively assessed sense of smell, independently and jointly, in relation to future risk for PD. Methods We conducted a prospective analysis using data from 2,424 participants, ages 71-82 at baseline, from the Health, Aging, and Body Composition study. Exposures were self-reported poor sense of smell or taste and the objectively measured 12-item Brief Smell Identification Test score. The outcome was incident PD, analyzed using Cox proportional hazard models adjusted for age, sex, race, and cognitive function. Results After approximately 10 years of follow-up, both self-reported and objectively tested poor sense of smell were independently associated with a higher risk of developing PD: the hazard ratios (95% confidence interval) were 2.8 (1.3, 5.9) and 4.0 (2.1, 7.5), respectively. When analyzed jointly, compared with participants who reported and tested normal, the hazard ratio was 2.2 (1.0, 4.6) for those reported poor sense of smell but tested normal, 3.6 (1.9, 6.9) for reported normal but tested poor, and 7.8 (3.2, 19.4) for both reported and tested poor. We did not find significant interactions between self-reported and objectively tested sense of smell in predicting PD risk. Conclusion This study provides preliminary evidence that self-reported poor sense of smell or taste should not be simply dismissed as useless in predicting risk of PD. Future studies should confirm our finding and evaluate whether structured questionnaires may further improve the predictability.
Process scale-up, economic, environmental assessment of vibratory nanofiltration of coffee extracts for soluble coffee production process intensification

This study investigated the viability of a vibratory nanofiltration system as a low-energy alternative to evaporation in concentrating coffee extracts before final dehydration. Film model correlations for permeate fluxes and characteristics (turbidity, conductivity, and chemical oxygen demand) were determined from vibratory nanofiltration experiments on different coffee extract concentrations at 50 °C and 400 psi. Vibratory amplitude of 2.54 cm at 54.7 Hz frequency enhanced permeate fluxes by up to 3 times that of crossflow filtration by reducing the gel layer concentration on the membrane surface. Experimental results were used to propose a scaled-up vibratory nanofiltration operation recovering 378,500 L/day of reusable water from concentrating coffee extracts up to 35% wt/wt. The design flux exponentially decreased with increasing feed coffee extract concentrations requiring larger systems with majority of the operating cost associated with membrane replacement. The energy usage and cost of the vibratory nanofiltration system were substantially lower than those of evaporation in terms of steam consumption. However, the low design flux limited the proposed membrane system to feed concentrations less than 3% wt/wt but may be improved using optimization studies. Economic assessment for this feed concentration corresponded to a 7-module i84 VSEP filtration system with a capital cost of $2,100,000 with estimated annual savings of $481,900/year and corresponding payback period of 10 years. Lastly, the proposed alternative opens opportunities in the intensification of soluble coffee production in terms of energy efficiency, water recovery, and wastewater reduction that overall reduce the environmental emissions of the process by approximately 40%.
Contingency management for the treatment of methamphetamine use disorder: A systematic review

Methamphetamine use continues to be an important public health problem. Contingency management is among the most effective interventions for reducing methamphetamine use. It has been more than ten years since the last systematic review of contingency management for methamphetamine use disorder. Since then, an additional ten randomized controlled trials and a variety of other studies have been completed. The present systematic review includes 27 studies. Several factors, most notably problem severity, appear to predict treatment outcome. However, the effectiveness of CM has been demonstrated in studies restricted to MSM, studies restricted to implementation in community programs, and in studies of the general population of methamphetamine users conducted in research treatment programs. There appear to be broad benefits of contingency management intervention, including greater drug abstinence, higher utilization of other treatments and medical services, and reductions in risky sexual behavior. Twenty of the twenty-one studies that reported abstinence outcomes showed an effect of contingency management on abstinence, and seven of the nine studies that reported sexual risk behavior outcomes showed an effect of contingency management in reducing risky sexual behavior. Taken together, recent evidence suggests strongly that outpatient programs that offer treatment for methamphetamine use disorder should prioritize adoption and implementation of contingency management intervention.
Current Status of Global Energy Consumption, Production, and Storage

In this chapter a brief overview is given of the global energy consumption trends and the various power production and energy storage methods.
Infra-Occipital Supra-Tentorial Approach for Resection of Low-Grade Tumor of the Left Lingual Gyrus: 2-Dimensional Operative Video.

Surgical treatment of lesions involving the postero-medial occipito-temporal region is challenging because of high risk of morbidity due to damage or excessive retraction of critical neuro-vascular structures, especially within the dominant hemisphere.1-3 Here, we describe the case of a 17-yr-old patient who underwent resection of an epileptogenic low-grade tumor located within the left-dominant lingual gyrus. Seizures were characterized, as a first symptom, by right-sided simple visual hallucination that pointed to the left pericalcarine region, corresponding to the lesion location. No signs of primary involvement of anterior temporo-mesial structures (hippocampus/amygdala) were found. As the anatomo-electroclinical correlation was concordant, direct tumor removal was indicated through an infra-occipital supratentorial approach. This route allowed direct access to the target through a safe extra-axial corridor, which limits intraparenchymal dissection until the tumor margin is identified and avoids critical vascular structures, such as the vein of Labbe.4,5 An external cerebrospinal fluid (CSF) drainage was used to facilitate brain relaxation, minimizing brain and venous retraction and, consequently, reducing the risk of postoperative neurological complications, especially for vision. Postoperative magnetic resonance imaging (MRI) demonstrated no surgical complications. Pathological examination revealed a ganglioglioma. At 9-mo follow-up, the neurological examination was normal, antiepileptic therapy was stopped, and the patient was seizure-free. The video describes the main surgical steps, using both intraoperative videos and advanced 3-dimensional modeling of neuroimaging pictures. Informed consent was obtained for surgery and video recording.
Lyticase Facilitates Mycobiome Resolution Without Disrupting Microbiome Fidelity in Primates.

ABSTRACT Background Microbiome research has expanded to consider contributions of microbial kingdoms beyond bacteria, including fungi (i.e., the mycobiome). However, optimal specimen handling protocols are varied, including uncertainty of how enzymes utilized to facilitate fungal DNA recovery may interfere with bacterial microbiome sequencing from the same samples. Methods With Institutional Animal Care and Use Committee approval, fecal samples were obtained from 20 rhesus macaques (10 males, 10 females; Macaca mulatta). DNA was extracted using commercially available kits, with or without lyticase enzyme treatment. 16S ribosomal RNA (bacterial) and Internal Transcribed Spacer (ITS; fungal) sequencing was performed on the Illumina MiSeq platform. Bioinformatics analysis was performed using Qiime and Calypso. Results Inclusion of lyticase in the sample preparation pipeline significantly increased usable fungal ITS reads, community alpha diversity, and enhanced detection of numerous fungal genera that were otherwise poorly or not detected in primate fecal samples. Bacterial 16S ribosomal RNA amplicons obtained from library preparation were statistically unchanged by the presence of lyticase. Conclusions We demonstrate inclusion of the enzyme lyticase for fungal cell wall digestion markedly enhances mycobiota detection while maintaining fidelity of microbiome identification and community features in non-human primates. In restricted sample volumes, as are common in limited human samples, use of single sample DNA isolation will facilitate increased rigor and controlled approaches in future work.
Translating cognitive science in the public square.

Public space interventions offer one example of how to translate cognitive science into the public square. Here, we detail several successful projects and the six principles of learning that underlie them that support caregiver–child engagement, interaction, and the use of content area–specific language. Policy and community implications are also discussed.
Proposal of a simple 2-hand technique at cesarean hysterectomy for placenta accreta spectrum

Placenta accreta spectrum (PAS) encompasses a range of disorders of placental trophoblastic tissue that is morbidly adherent to the underlying gravid uterus. Women with PAS commonly undergo surgical treatment with hysterectomy at cesarean delivery that is associated with significant surgical morbidity and mortality. Increased vascularity due to gestational change and the abnormally enlarged lower uterine segment due to the location of placenta make the surgery complex and morbid. Here, we propose a simple 2-hand technique that can be used to improve surgical outcomes of cesarean hysterectomy for PAS. Unlike the ordinary hysterectomy where the transection of the cardinal ligament is started at the isthmus below the low uterine segment, the proposed 2-hand technique allows transection of the cardinal ligament at the level of the lower uterine segment below the placental bed. This minimizes blood loss that may be associated with serial transection of cardinal ligament which occurs when it is transected at or above the placenta level. This surgical approach starts with demarcation of 3 anatomical landmarks [rectum (posterior aspect), ureters (lateral aspect), and bladder (anterior aspect)] in postero-anterior progression. Complete de-serosalization of posterior low uterine segment allows lateralization of the ureter and enables the uterus to be mobilized antero-caudally where the surgeon’s hand can reach below the placental bed. After the bladder flap creation to the level of endopelvic fascia, the surgeon’s two hands are placed antero-posteriorly at low uterine segment below the placental bed. The fingertips of both hands meet at the cardinal ligament below placenta at the level of the upper cervix. At this point the two hands are gently moved upwards, carrying the placenta-containing low uterine segment. This step enables creation of a safe anatomical distance from surrounding structures and isolation of the cardinal ligament where surgical clamp can be applied to transect the cardinal ligament.
The path to COVIS: A review of acoustic imaging of hydrothermal flow regimes

Abstract Acoustic imaging of hydrothermal flow regimes started with the incidental recognition of a plume on a routine sonar scan for obstacles in the path of the human-occupied submersible ALVIN. Developments in sonar engineering, acoustic data processing and scientific visualization have been combined to develop technology which can effectively capture the behavior of focused and diffuse hydrothermal discharge. This paper traces the development of these acoustic imaging techniques for hydrothermal flow regimes from their conception through to the development of the Cabled Observatory Vent Imaging Sonar (COVIS). COVIS has monitored such flow eight times a day for several years. Successful acoustic techniques for estimating plume entrainment, bending, vertical rise, volume flux, and heat flux are presented as is the state-of-the-art in diffuse flow detection.