cssi/SciSciGPT-SciSciNet huggingface dataset:
Levonorgestrel-Releasing Intrauterine Device Use in Female Adolescents with Heavy Menstrual Bleeding and Bleeding Disorders: Single Institution Review

Abstract Study Objective To identify complications and efficacy of the levonorgestrel-releasing intrauterine device (LNgIUD) in adolescents with heavy menstrual bleeding (HMB) and bleeding disorders (BD). Design, Setting, and Participants A retrospective chart review of 13 postmenarchal adolescent girls with HMB/BD who underwent placement of an LNgIUD. Interventions Placement of an LNgIUD. Main Outcome Measures Primary outcome was to identify complications from placement of an LNgIUD. Secondary outcome was to evaluate the efficacy of the LNgIUD in adolescents with BD. Results Thirteen patients met study criteria. The mean age of diagnosis of HMB was 14.08 ± 1.75 years. BD or bleeding risk factor diagnoses included low von Willebrand (VW) activity in 5, type I VW disease in 5, type IIM VW disease in 1, low VW activity and factor 7 deficiency in 1, and acquired VW disease and factor 7 deficiency in 1. Before LNgIUD placement, other hormonal therapy (n = 13) and hemostatic therapy (antifibrinolytic agents, desmopressin acetate; n = 8) yielded poor control of HMB. The LNgIUD was placed using anesthesia with periprocedure hemostatic therapy with no complications. All patients reported significant improvement in HMB after LNgIUD placement and 60% achieved amenorrhea, with mean time to improvement of 94 ± 69 days. Mean hemoglobin and ferritin levels increased after LNgIUD placement compared with before LNgIUD placement values ( P = .02, P = .0085, respectively). Use of supplemental hormonal and hemostatic agents decreased (n = 4) after LNgIUD placement. None required LNgIUD removal; 1 spontaneously expelled the LNgIUD with subsequent replacement. Conclusion Study results indicated the LNgIUD is an effective therapeutic option in postmenarchal adolescents with HMB due to BD/bleeding risk factor with minimal complications, high compliance rate, improvement in HMB and anemia, and no periprocedural bleeding with hemostatic management.
The Status and Potential of Instructional Television for Physical Education

Abstract It is no longer a question of “Should we make use of instructional television in our programs of health, physical education and recreation?” The question is “How can we best present our areas of education through the medium of television?” The challenge of keeping up with the technological Joneses is added to the other problems facing us. Like other curricular areas, we face the prospect of more material to be taught, to greater numbers of students, by too few teachers, in too little space, with too few facilities. But adapting our teaching to television may be part of the answer to other vexing problems. In the next six pages, the Journal presents an overview of television teaching, together with the story of four different kinds of TV instruction programs successfully in operation around the country: health and physical education classes for grades 4-6 in Philadelphia, Pennsylvania; college courses through closed circuit TV at Michigan State University; teaching sports skills with guest experts...
Parallelism of Pick-and-Place operations by multi-gripper robotic arms

This article defines the Parallel Pick-and-Place (PPNP) problem and develops a framework for optimization of its operations performed by multi-gripper robotic arms. The motivation lies in the lack of analytical methods for the parallelism of structured/unstructured Pick-and-Place (PNP) operations by robotic arms. Although the PPNP operations are mostly attributed to printed circuit board assembly, their applications span various other processes such as palletizing, packaging, warehousing, sorting, loading/unloading of machines, machine tending, inspection, remote maintenance, and robotic nurse assistance. Parallelism of the PNP operation is enabled by facilitating the robot's end effector with multiple grippers and magazines in order to perform simultaneous pickups and placements of items. Two different formulations of the PPNP process are developed regarding two cases: (1) Optimal routing while the pickup and placement positions are fixed; (2) Optimal routing and configuration of pickup and placement positions at the same time. An efficient swarm intelligence algorithm based on Ant System and Tabu Search is developed for handling the complexity of the PPNP problem. Through a reinforcement learning mechanism, the robot is provided with a certain level of intelligence to adapt to changes in its working environment and find the shortest route automatically, after relatively few computational iterations. Results of several experiments indicate superiority of the developed framework for the PPNP operation to conventional approaches in terms of cycle time, as an indicator of the overall movement distance and energy consumption. This work optimizes parallel Pick-and-Place operations performed by robotic arms.Parallelism is enabled through end effectors with multiple grippers and magazines.A new instance of TSP is defined: Clustered Double Traveling Salesman Problem.Ant Colony Optimization and Tabu Search are applied to handle complexity.Automation and intelligence of robots are enhanced by reinforcement learning scheme.
Patients with myelodysplastic syndromes benefit from palliative therapy with amifostine, pentoxifylline, and ciprofloxacin with or without dexamethasone.

Thirty-five patients with myelodysplastic syndrome (MDS) were registered on protocol MDS 96-02 and were receiving continuous therapy with pentoxifylline 800 mg 3 times a day and ciprofloxacin 500 mg twice a day by mouth; dexamethasone was added to the regimen for the partial responders and the nonresponders after 12 weeks at a dose of 4 mg by mouth every morning for 4 weeks. Amifostine was administered intravenously 3 times a week at 3 dose levels (200 mg/M2, 300 mg/M2, and 400 mg/M2) to cohorts of 10 patients each. Therapy has been continued for 1 year in responders. Twenty-nine have completed at least 12 weeks of therapy and are available for response evaluation. Of the 21 men and 8 women (median age, 67 years), 20 had refractory anemia (RA), 3 had RA with ringed sideroblasts (RARS), 5 had RA with excess blasts (RAEB), and 1 had chronic myelomonocytic leukemia (CMMoL). Five had secondary MDS. No differences were noted in response rates among the 3 dose levels. Seven patients did not respond at all, and 22 showed an improvement in cytopenias (76%). Three had a triple lineage response, 10 had a double lineage response, and 9 had a single lineage response (8 of 9 in absolute neutrophil count [ANC] and 1 had more than a 50% reduction in packed red blood cell transfusions). Fifteen patients responded only after the addition of dexamethasone, whereas 7 responded before. When examined by lineage, 19 of 22 showed improved ANC, 11 of 22 demonstrated more than 50% reduction in blood transfusions, improved Hb levels, or both, and 7 of 22 showed improvement in platelet counts. Interestingly, the responses were frequently slow to appear, and continued improvement in counts was seen up to 12 months of therapy and beyond. This study supports the feasibility of treating patients with MDS with the unique approach of cytoprotection and anticytokine therapies as well as the principle that prolonged commitment to treatment is desirable when noncytotoxic agents are administered.
Writing the Plan

AFTER ALL THE ANALYSIS, DISCUSSION, and brainstorming, someone actually has to write a marketing plan. It doesn’t just appear. Putting a marketing plan down on paper is a critical phase in the process. This step includes a bit of writing, a bit of strategy, a bit of analytical thinking, and a bit of showmanship. This is the place where everything comes together. It is in many ways the most important part of the process.
Final Results and Discussion

With the final user study described in the last chapter, the functionality of the constructed night drive simulator is completed and successfully evaluated. In this chapter, a short conclusion is given in Section 9.1 to summarize the achievements of this work. Some critical limitations of this approach are then discussed in 9.2, combined with proposals for possible future user studies, continuing the investigation of traffic glare and refining the generated perception model.
Tuning the Structure and Photophysics of a Fluorous Phthalocyanine Platform

Phthalocyanines are an important class of industrial dyes with potential commercial applications ranging from photovoltaics to biomedical imaging and therapeutics. We previously demonstrated the versatility of the commercially available zinc(II) hexadecafluorophthalocyanine (ZnF16Pc) as a platform for rapidly developing functional materials for these applications and more. Because this core-platform approach to dye development is increasingly common, it is important to understand the photophysical and structural consequences of the substitution chemistry involved. We present a fundamental study of a series of ZnF16Pc derivatives in which the aromatic fluorine atoms are progressively substituted with thioalkanes. Clear spectroscopic trends are observed as the substituents change from electron-withdrawing to electron-releasing groups. Additionally, there is evidence for significant structural distortion of the normally planar heterocycle, with important ramifications for the photophysics. These results are ...
HIV Neurologic Complications and Hemophilia

A multicenter prospective study of the growth and neuropsychological function of 207 boys (mean age 12 years) with hemophilia and seropositive for human immunodeficiency virus type 1 (HIV-1) is reported from the University of Iowa College of Medicine, Iowa City.
Surgical Nasal Implants: Indications and Risks

Rhinoplasty often requires the use of grafting material, and the goal of the specific graft dictates the ideal characteristics of the material to be used. An ideal material would be biologically inert, resistant to infection, noncarcinogenic, nondegradable, widely available, cost-effective, readily modifiable, and easily removable, have compatible biomechanical characteristics, retain physical properties over time, and not migrate. Unfortunately, no material currently in existence meets all of these criteria. In modern rhinoplasty, autologous grafts are the gold standard against which all other nasal implants are measured and offer the safest long-term results for most patients. They are easily manipulated, have inherent stability and biomechanical characteristics similar to the native nasal framework, and confer minimal risk of complications. Modern homologous and alloplastic materials have gained considerable support in recent years because they are readily available in endless quantity, do not require a second surgical site for harvest, and are generally considered safe if most circumstances, but they confer additional risk and have biomechanical characteristics different from that of the native nasal framework. To address some of these issues, we provide a contemporary review of autologous, homologous, and alloplastic materials commonly used in rhinoplasty surgery.
Sonic Hedgehog Signaling in Mantle Cell Lymphoma.

Mantle cell lymphoma (MCL) is associated with poor clinical outcome among all the B-cell malignancies. MCL cells have a characteristic phenotype including IgM+, IgD+, CD5+, CD10−, CD19+, CD20+, Bcl2+, CD23−, CD24+, and have a (11:14) (q13:q32) translocation, involving the Bcl-1 locus and the IgH heavy chain joining region, resulting in up-regulation of Bcl-1/PRAD-1 with increased Cyclin D1 expression. In spite of our understanding of B cell development, we do not have effective therapeutic approach to treat MCL. This warrants an immediate understanding of the biology MCL cells, and key signaling pathways underlying the disease progression. Further, these key signaling pathways involved in MCL could be specifically targeted, which may have potential therapeutic value. Emerging evidences have revealed that sonic hedgehog (Shh) signaling promotes tumor cell proliferation, and protects them from apoptosis in different cancers such as pancreatic cancer, prostate cancer, gastric cancer, medulloblastoma, basal cell carcinoma, breast cancer, etc. In addition, targeting the Shh signaling has been shown as a potential therapeutic approach to treat some of these cancers. However, the role of Shh signaling has not been reported in any of B cell malignancies including MCL. Therefore, we studied the status of Shh signaling molecules in the proliferation and survival of MCL cells in vitro using JVM-2, Granta-519, Jeko-1 and Z138 cell lines and human primary MCL cells. Our results demonstrate that the molecules involved in the Shh signaling like patched and smoothened receptors, and the target transcription factors, GLI were over expressed in Granta-519, Jeko-1, Z-138 and JVM-2 MCL cell lines, and patients primary MCL cells compared to normal human B lymphocytes. Addition of exogenous Shh increased the proliferation of JVM-2 cells in vitro. There was an increased transcripts level of GLI1, BCL2 and Cyclin D1 (CCND1) in JVM-2 cells following the addition of Shh. Addition of Shh-signaling inhibitor Cyclopamine abrogated the increased proliferation and transcription of the above genes induced by Shh in JVM-2 cells (figure 1). Furthermore, the Gli2 anti-sense oligonucleotide decreased CCND1 and BCL2 transcript expression, as well as decreased the proliferation of JVM2 cells in vitro (figure 2). Taken together, these results suggest that Shh-Gli signaling may be one of the pathways that regulate the Bcl-2 and Cyclin D1 activation and thereby regulate the proliferation and apoptosis of MCL cells. Therefore, further dissecting of the Shh-Gli mediated regulation of Bcl2 signaling may have potential implications in advancing the treatment for MCL.
Implementation of an Open-Architecture Control for CNC Systems Based on Open-Source Electronics

Open control architectures have many advantages including increased computational resources and flexibility of reconfiguration of new manufacturing units. This paper proposes an open architecture for the control of CNC systems based on open source electronics. The software architecture in this paper is a component-based approach where each component has an independent finite state machine (FSM) model. The hardware architecture is a multiprocessor distributed controller, with different levels of processing, and adaptable for different hardware specifications. A discussion of the basic control algorithms, with examples of implementation to the open source platform Arduino, is presented as part of the methodology. Other results in this paper include the preliminary test of the control to a two-axis CNC stage and a mathematical model of the control-loop in Simulink. The architecture in this paper has the potential of transforming CNC in open source electronics from device-oriented systems to systems where users can design their controls for special purpose machines.Copyright © 2016 by ASME
Impaired Glutamatergic Neurotransmission in the Ventromedial Hypothalamus May Contribute to Defective Counterregulation in Recurrently Hypoglycemic Rats

The objectives of this study were to understand the role of glutamatergic neurotransmission in the ventromedial hypothalamus (VMH) in response to hypoglycemia and to elucidate the effects of recurrent hypoglycemia (RH) on this neurotransmitter. We 1) measured changes in interstitial VMH glutamate levels by using microdialysis and biosensors, 2) identified the receptors that mediate glutamate's stimulatory effects on the counterregulatory responses, 3) quantified glutamate metabolic enzyme levels in the VMH, 4) examined astrocytic glutamate reuptake mechanisms, and 5) used 1H-[13C]-nuclear magnetic resonance (NMR) spectroscopy to evaluate the effects of RH on neuronal glutamate metabolism. We demonstrated that glutamate acts through kainic acid receptors in the VMH to augment counterregulatory responses. Biosensors showed that the normal transient rise in glutamate levels in response to hypoglycemia is absent in RH animals. More importantly, RH reduced extracellular glutamate concentrations partly as a result of decreased glutaminase expression. Decreased glutamate was also associated with reduced astrocytic glutamate transport in the VMH. NMR analysis revealed a decrease in [4-13C]glutamate but unaltered [4-13C]glutamine concentrations in the VMH of RH animals. The data suggest that glutamate release is important for proper activation of the counterregulatory response to hypoglycemia and that impairment of glutamate metabolic and resynthetic pathways with RH may contribute to counterregulatory failure.
How Should Journals Handle the Conflict of Interest of Their Editors?: Who Watches the "Watchers"?

Conflict of interest (COI) policies at most academic medical centers require that investigators disclose research-related financial interests to their institutions so the institution can review the potential risks of the COI. To manage COI, academic medical centers typically direct investigators to disclose their financial interests to research participants and to journal editors. If an institution follows the guidelines of the Association of American Medical Colleges,1 except for situations in which a researcher has a significant financial interest in research involving humans, investigators generally are permitted to retain their financial interests while performing related research as long as there is transparency about their financial interests via disclosure to the consumers (eg, research participants, co-investigators, and individuals who receive reports of the research, including those listening to a presentation of the research or reading an article about the research).
Patient‐specific quantification of image quality: An automated technique for measuring the distribution of organ Hounsfield units in clinical chest CT images

Purpose To develop and validate an automated technique for measuring organ Hounsfield units (HUs) in clinical chest CT images. Materials and Methods An automated computer algorithm was developed to measure the distribution of HUs inside four major organs: the lungs, liver, aorta, and spine. These organs were first identified using image processing techniques. Each organ was segmented into multiple regions of interest (ROIs) and characterized in terms of HU values. The medians of the ROI histograms were computed for each dataset. The automated results were validated by assessing their correlation with manual measurements in fifteen contrast-enhanced and fifteen non-contrast enhanced clinical chest CT datasets. The robustness of the measurements with respect to dependency on image noise and CTDIvol was ascertained. One utility of the approach was further demonstrated in assessing the variability in aorta HUs across 732 patients undergoing non-contrast and contrast-enhanced examinations. Results The algorithm successfully measured the histograms of the four organs in both contrast and non-contrast enhanced chest CT exams. The automated measurements were in agreement with manual measurements with a near unity slope of the relationship between automated and manual measurements with high coefficient of determination, (slope = 0.931-1.003, R2 = 0.89-0.99). Organ median HU measurements were found to be largely independent of both image noise and CTDIvol (p > 0.05), as expected. Across patient cases, the program ran successfully across 95% (697/732) of cases. Aorta median HUs demonstrated five times more variability in contrast-enhanced exams compared to that in non-contrast enhanced exams. Conclusions Patient-specific organ HUs can be measured from clinical datasets. The algorithm that was developed can be run on both contrast enhanced and non-contrast enhanced clinical datasets. The method can be applied to automatically extract image HU-contrast characteristics of clinical CT images, not captured in phantom data, whereby enabling quantification and optimization of image quality and contrast administration. This article is protected by copyright. All rights reserved.
The Oceanic Photosynthetic Engine: Origins, Evolution, and Role in Global Biogeochemical Cycles

The combination of vast areas of liquid water on its surface together with a high concentration of free molecular oxygen in its atmosphere, is unique to Earth in this solar system. Proxy geochemical evidence suggests that the concentration of oxygen in Earth’s atmosphere reached approximately 1% of the present value between 2.2 and 2.0 billion years ago as a consequence of oxygenic photosynthesis by marine unicellular algae, the phytoplanlcton [1]. The oxidation of Earth’s atmposphere necessarily was accompanied by the production of massive quantities of organic carbon that are preserved in the lithosphere. A small fraction of this fossil phytoplanton carbon literally fuels the industrial world in the present geological epoch. These biologically driven changes reflect a key transition in the geochemical evolution of Earth that profoundly influenced the subsequent course of evolution of life. Here I briefly examine the controls and feedbacks between oceanic phytoplankton photosynthesis and global geochemical processes. A more extensive review can be found in Falkowski et al. [2]
Skin color variation in Africa

The remarkable genetic diversity within African populations is both a signature and a storybook of human origins because descendants of the earliest humans who lived in Africa nearly 200,000 years ago have had the longest time to accumulate genetic variation. Although studying genetic diversity in African populations tells us a great deal about human history, there is even more to learn by juxtaposing the genetic diversity with the diversity of heritable traits (phenotypes). Yet, there is a paucity of such studies involving continental Africans ( 1 ). On page 887 of this issue, Crawford et al. ( 2 ) demonstrate the potential insights that can come from ameliorating this disparity. They examined skin color variation in 2000 African individuals from different geographic locations and ethnic groups; the range, from light-skinned San hunter-gatherer populations in southern Africa to dark-skinned pastoralist populations in eastern Africa, far exceeds pigmentary diversity anywhere else on the planet (see the figure). Using a genome-wide association study (GWAS) that includes 1600 individuals living in Tanzania, Botswana, or Ethiopia, the authors identified regions of the genome that contribute to skin color variation and carried out a series of analyses to pinpoint the responsible genes.
Association between gambling harms and game types : Finnish population study

AbstractUnderstanding of the harmfulness of game types is needed when planning harm minimization and prevention strategies. Adult data (N = 3555) from the Finnish Gambling 2015 survey was used to investigate the associations between different game types and gambling-related harms. A negative binomial regression model was used to analyse the effects of demographics, gambling involvement factors, and engaging in different game types on the number of gambling-related harms, which were evaluated by PGSI and SOGS. Age of 18–24, gambling several times a week, high relative expenditure, online gambling and engaging weekly either in scratch games, betting games or slot machine gambling were associated with a higher number of gambling harms. Chasing losses was the most typical harm among online poker players and fast-paced daily lottery game players, while poor self-control was the most typical harm with other game types, although some of the results were not statistically significant. Multiple factors were associ...
Highly Parallel Preconditioners for General Sparse Matrices

The degree of parallelism in the preconditioned Krylov subspace method using standard preconditioners is limited and can lead to poor performance on massively parallel computers. In this paper we examine this problem and consider a number of alternatives based both on multi-coloring ideas and polynomial preconditioning. The emphasis is on methods that deal specifically with general unstructured sparse matrices such as those arising from finite element methods on unstructured grids. It is argued that multi-coloring can be combined with multiple-step relaxation preconditioners to achieve a good level of parallelism while keeping the rates of convergence to good levels. We also exploit the idea of multi-coloring and independent set orderings to introduce a multi-elimination incomplete LU factorization named ILUM, which is related to multifrontal elimination. The main goal of the paper is to discuss some of the prevailing ideas and to compare them on a few test problems.
Push and pull factors and Hispanic self-employment in the USA

This study examines the main push and pull factors driving Hispanic self-employment in the USA by modeling the self-employment decision as a function of sectoral earnings differences, country of origin, and other factors. Findings indicate that a main reason Hispanics engage in self-employment is they can earn more working for themselves than in wage/salary work. Immigrants appear to be pushed into self-employment as a result of limited opportunities in the wage work sector. Although low relative earnings in wage/salary work could push workers with limited English proficiency into self-employment, our findings indicate barriers to this. Results suggest that workers pulled into self-employment are those with more work experience and a college degree. Workers who originate from Southern South America and Colombia have relatively high self-employment rates, while Mexico-origin workers have relatively low self-employment rates. We also uncover differences across Hispanic origin groups in terms of the influence of gender, education, and personal wealth on self-employment participation.
HIGH OUTPUT HEART FAILURE SECONDARY TO A CORONARY CAVAL FISTULA AND PATENT FORAMEN OVALE

Anomalous coronary arteriovenous fistulas (CAVF) are rare and usually do not require intervention. A 75 year old female with hypertension, type 2 diabetes, chronic kidney disease, atrial fibrillation, and heart failure with preserved ejection fraction presents with three months of progressive
Palliative care in the emergency department: an educational investigation and intervention

To investigate the value of a novel simulation-based palliative care educational intervention within an emergency medicine (EM) residency curriculum. A palliative care scenario was designed and implemented in the simulation program at an urban academic emergency department (ED) with a 3-year EM residency program. EM residents attended one of eight high-fidelity simulation sessions, in groups of 5–6. A standardized participant portrayed the patient’s family member. One resident from each session managed the scenario while the others observed. A 45-min debriefing session and small group discussion followed the scenario, facilitated by an EM simulation faculty member and a resident investigator. Best practices in palliative care were highlighted along with focused learner performance feedback. Participants completed an anonymous pre/post education intervention survey. Forty of 42 EM residents (95%) participated in the study. Confidence in implementing palliative care skills and perceived importance of palliative care improved after this educational intervention. Specifically, residents 1) felt EM physicians had an important role in palliative care, 2) had increased confidence in the ability to determine patient decision-making capacity, 3) had improved confidence in initiating palliative discussions/treatment, 4) believed palliative education was important in residency, and 5) felt simulation was an effective means to learn palliative care. Differences noted between PGY1 and PGY 3 training levels in survey responses disappeared post-intervention. Residents noted being most comfortable with delivering bad news and symptom management and least comfortable with disease prognostication. Residents reported time constraints and implementation logistics in the ED as the most challenging factors for palliative care initiation. Our case-based simulation intervention was associated with an increase in both the perceived importance of ED palliative care and self-reported confidence in implementing palliative care skills. Time constraints and implementation logistics were rated as the most challenging factors for palliative care initiation in the ED.
Sensitivity of peripheral membrane proteins to the membrane context: A case study of phosphatidylserine and the TIM proteins.

Abstract There is a diverse class of peripheral membrane-binding proteins that specifically bind phosphatidylserine (PS), a lipid that signals apoptosis or cell fusion depending on the membrane context of its presentation. PS-receptors are specialized for particular PS-presenting pathways, indicating that they might be sensitive to the membrane context. In this review, we describe a combination of thermodynamic, structural, and computational techniques that can be used to investigate the mechanisms underlying this sensitivity. As an example, we focus on three PS-receptors of the T-cell Immunoglobulin and Mucin containing (TIM) protein family, which we have previously shown to differ in their sensitivity to PS surface density.
Interdisciplinary Perspectives on International Law and International Relations: International Judicial Independence

This chapter provides an overview of what we know about international judicial independence. First, what is international judicial independence? Judicial independence refers to the set of institutional and other factors that to a lesser or greater extents allow judges autonomy from the preferences of other political actors when they issue legal opinions. How judges will use this autonomy is a separate question. Second, why do some international courts have a great deal of independence while others do not? Viable theories of judicial independence should not be based on assumptions that judges are ontologically inclined to favor greater separation from states whereas states have opposite inclinations. Instead, I emphasize the answers offered by two groups of theories: rationalist institutionalist (or principal-agent) and sociological-institutionalist (or neofunctionalist) approaches. Third, what do we know about the degree to which governments can use control mechanisms to influence judges? Here I discuss the various challenges to empirically studying judicial independence. Finally, does judicial independence increase the effectiveness of international courts? This latter section highlights fears that the judicialization of politics is met by an increased politicization of the judiciary.
Application of Models for IGSCC Inspection

Ultrasonic detection and sizing of intergranular stress corrosion cracks (IGSCC) in nuclear reactor cooling systems is a difficult practical problem due to the complicated geometry of these defects and to the variety of other reflectors (e. g., welds) which produce competing ultrasonic indications. The use of models of scattering from such defects can help in improving physical insight into ultrasonic scattering from IGSCC’s and may ultimately be of use in defining inspection protocols and signal processing algorithms which can lead to improved inspection reliability and discrimination between IGSCC’s and other geometrical reflectors. This paper will discuss the application of a model of ultrasonic scattering from a simple Y-shaped crack based upon the Kirchhoff approximation. In this model, the ultrasonic beam is approximated by a Gaussian profile which includes the effects of diffraction and allows calculation of the full ultrasonic radiation pattern which may be used, for example, to simulate a scanned inspection. Included in this paper will be a brief description of the model and a presentation of simulated IGSCC results. Comparisons of the model to experimental measurements will then be addressed followed by an application to the problem of IGSCC sizing based upon the dB-drop and PAT (pulse-arrival-time) techniques.
Molluscan Immunobiology: Challenges in the Anthropocene Epoch

The Mollusca, with a long and rich evolutionary history, is one of the most speciose and distinctive of the animal phyla. Among its members are some of the largest and most long-lived, intelligent, and commercially valuable invertebrate species, contributing massively to the human food supply. Some are valued for their beauty, and others are significant disease vectors. In this chapter, after first providing an overview of the diverse and often distinctive infectious agents with which molluscs must contend, we outline in broad strokes some of the major features of molluscan immune systems. Molluscs continue to enrich our broader understanding of immunology, both from a steady stream of new insights in genomic and postgenomic studies and from novel discoveries such as transmissible neoplasia, which challenge our understanding of cancer and basic processes such as allorecognition. We then discuss how the rapidly changing modern world often exposes molluscs to significant abiotic and biotic challenges—often presented in daunting combinations—that elicit complex responses and reveal the extent to which stress and immune responses are intertwined. We conclude with a discussion of aspects of molluscan immunobiology about which we need to expand our scope of knowledge if molluscs are not to suffer more than they already have in this, the world’s sixth major episode of mass extinction.
Using phylogenomics to reconstruct phylogenetic relationships within tribe Polygonateae (Asparagaceae), with a special focus on Polygonatum

Abstract Polygonatum is a widespread temperate genus with approximately 75 species centered in the Eastern Himalaya and Indo-Burma biodiversity hotspots. A complete assessment of the remarkable diversity of Polygonatum in these areas requires an accurate circumscription of the genus, as well as a clear understanding of generic and infrageneric relationships, both of which have been problematic in the past. In this study, we reconstruct phylogenetic relationships within Polygonatum and test its monophyly using a phylogenomic approach. For that, we built a comprehensive dataset that includes complete or nearly-complete plastid genomes of 19 species of Polygonatum, one of Disporopsis, and four of Heteropolygonatum. Their plastid genomes do not present any major structural differences and range from 153,821 to 155,580 bp in length. Molecular phylogenetic analyses of the chloroplast coding regions indicate that Polygonatum and Heteropolygonatum are monophyletic, providing support for their recognition as distinct genera and corroborating recent adjustments of their circumscriptions. An expanded analysis with higher species sampling using the petA-psbJ plastid gene region combined with the nuclear ribosomal ITS provided support for the recognition of three distinct sections within Polygonatum. These same sections are further supported by chromosome data: Polygonatum sect. Sibirica (x = 12); Polygonatum sect. Polygonatum (x = 9–11); and, Polygonatum sect. Verticillata (x = 13–15). Populations of P. multiflorum from northwestern Himalaya are here shown to be best treated as a separate taxon, P. govanianum. Furthermore, P. verticillatum is shown to be polyphyletic, indicating that it represents a species-complex that includes multiple Asiatic species. Despite that, additional studies are still needed until the proper nomenclatural adjustments can be made.
Elucidating conductivity-permselectivity tradeoffs in electrodialysis and reverse electrodialysis by structure-property analysis of ion-exchange membranes

Abstract Ion-exchange membranes (IEMs) are used in environmental and energy technologies of electrodialysis (ED) desalination and reverse electrodialysis (RED) power generation, respectively. Recent studies reported empirical evidence that the conductivity and permselectivity of IEMs are bound by a tradeoff relationship, where an increase in ionic conductivity is accompanied by a decrease in counterion selectivity over co-ion. A fundamental understanding of this conductivity-permselectivity tradeoff is principal to inform membrane development. This study presents an IEM transport model to analytically relate conductivity and permselectivity to intrinsic membrane chemical and structural properties. The model employs the Nernst-Planck transport framework and incorporates counterion condensation theory to simulate the performance of IEMs in a range of ED and RED operations. The analysis revealed the mechanism for the tradeoff induced by bulk solution concentration: a higher salinity suppresses IEM charge-exclusion, thus lowering permselectivity, but elevates mobile ion concentration within the membrane matrix to improve conductivity. As such, IEM applications are practically confined to sub-seawater salinities, i.e., RED using hypersaline streams will not be efficient. In another tradeoff driven by IEM water sorption, increasing membrane swelling enhances effective ion diffusivity to raise conductivity, but diminishes permselectivity due to dilution of fixed charges. The transport model indicates that increasing membrane ion-exchange capacity and reducing thickness can yield highly selective and conductive IEMs.
Dietary and lifestyle factors in multiple sclerosis progression: results from a 5-year longitudinal MRI study

Evidence regarding the role, if any, of dietary and lifestyle factors in the pathogenesis of multiple sclerosis (MS) is poorly understood. To assess the effect of lifestyle-based risk factors linked to cardiovascular disease (CVD) on clinical and MRI-derived MS outcomes. The study enrolled 175 MS or clinically isolated syndrome (CIS) patients and 42 age- and sex-matched healthy controls (HCs) who were longitudinally followed for 5.5 years. The 20-year CVD risk was calculated by Healthy Heart Score (HHS) prediction model which includes age, smoking, body mass index, dietary intake, exercise, and alcohol consumption. Baseline and follow-up MRI scans were obtained and cross-sectional and longitudinal changes of T2-lesion volume (LV), whole brain volume (WBV), white matter volume (WMV), gray matter volume (GMV), and lateral ventricular volume (LVV) were calculated. After correcting for disease duration, the baseline HHS values of the MS group were associated with baseline GMV (rs = − 0.20, p = 0.01), and longitudinal LVV change (rs = 0.19, p = 0.01). The association with LVV remained significant after adjusting for baseline LVV volumes (rs = 0.2, p = 0.008) in MS patients. The diet component of the HHS was associated with the 5-year T2-LV accrual (rs = − 0.191, p = 0.04) in MS. In the HC group, the HHS was associated with LVV (rs = 0.58, p < 0.001), GMV (rs = − 0.57, p < 0.001), WBV (rs = − 0.55, p = 0.001), T2-LV (rs = 0.41, p = 0.027), and WMV (rs = − 0.38, p = 0.042). Additionally, the HC HHS was associated with the 5-year change in LVV (rs = 0.54, p = 0.001) and in WBV (rs = − 0.45, p = 0.011). Lifestyle risk factors contribute to accelerated central brain atrophy in MS patients, whereas unhealthier diet is associated with MS lesion accrual. Despite the lower overall effect when compared to HCs, lifestyle-based modifications may still provide a beneficial effect on reducing brain atrophy in MS patients.
A NIK–SIX signalling axis controls inflammation by targeted silencing of non-canonical NF-κB

The non-canonical NF-κB signalling cascade is essential for lymphoid organogenesis, B cell maturation, osteoclast differentiation, and inflammation in mammals1,2; dysfunction of this system is associated with human diseases, including immunological disorders and cancer3–6. Although expression of NF-κB-inducing kinase (NIK, also known as MAP3K14) is the rate-limiting step in non-canonical NF-κB pathway activation2,7, the mechanisms by which transcriptional responses are regulated remain largely unknown. Here we show that the sine oculis homeobox (SIX) homologue family transcription factors SIX1 and SIX2 are integral components of the non-canonical NF-κB signalling cascade. The developmentally silenced SIX proteins are reactivated in differentiated macrophages by NIK-mediated suppression of the ubiquitin proteasome pathway. Consequently, SIX1 and SIX2 target a subset of inflammatory gene promoters and directly inhibit the trans-activation function of the transcription factors RELA and RELB in a negative feedback circuit. In support of a physiologically pivotal role for SIX proteins in host immunity, a human SIX1 transgene suppressed inflammation and promoted the recovery of mice from endotoxic shock. In addition, SIX1 and SIX2 protected RAS/P53-driven non-small-cell lung carcinomas from inflammatory cell death induced by SMAC-mimetic chemotherapeutic agents (small-molecule activators of the non-canonical NF-κB pathway). Our findings identify a NIK–SIX signalling axis that fine-tunes inflammatory gene expression programs under both physiological and pathological conditions. Non-canonical NF-κB is regulated by a negative feedback loop involving NIK-mediated activation of SIX1 and SIX2.
Methylated Histidines Alter Tautomeric Preferences that Influence the Rates of Cu Nitrite Reductase Catalysis in Designed Peptides.

Copper proteins have the capacity to serve as both redox active catalysts and purely electron transfer centers. A longstanding question in this field is how the function of histidine ligated Cu centers are modulated by δ vs e-nitrogen ligation of the imidazole. Evaluating the impact of these coordination modes on structure and function by comparative analysis of deposited crystal structures is confounded by factors such as differing protein folds and disparate secondary coordination spheres that make direct comparison of these isomers difficult. Here, we present a series of de novo designed proteins using the noncanonical amino acids 1-methyl-histidine and 3-methyl-histidine to create Cu nitrite reductases where δ- or e-nitrogen ligation is enforced by the opposite nitrogen's methylation as a means of directly comparing these two ligation states in the same protein fold. We find that e-nitrogen ligation allows for a better nitrite reduction catalyst, displaying 2 orders of magnitude higher activity than the δ-nitrogen ligated construct. Methylation of the δ nitrogen, combined with a secondary sphere mutation we have previously published, has produced a new record for efficiency within a homogeneous aqueous system, improving by 1 order of magnitude the previously published most efficient construct. Furthermore, we have measured Michaelis-Menten kinetics on these highly active constructs, revealing that the remaining barriers to matching the catalytic efficiency ( kcat/ KM) of native Cu nitrite reductase involve both substrate binding ( KM) and catalysis ( kcat).
Beyond Depth of Invasion: Adverse Pathologic Tumor Features in Early Oral Tongue Squamous Cell Carcinoma.

Objective In small (≤2 cm) oral tongue squamous cell carcinoma (OTSCC), we sought to clarify the contribution of pathologic features including perineural invasion (PNI), lymphovascular invasion (LVI), and worst pattern of invasion-5 (WPOI-5) to clinical outcomes relative to tumor depth of invasion (DOI) of > or ≤ 4 mm. Methods Cases of ≤2 cm OTSCC treated surgically between 2000 and 2017 at an academic cancer center were reviewed, with retrospective pathologic slide review of DOI, LVI, PNI, and WPOI-5. Primary outcome measures included occult nodal positivity, 2-year locoregional recurrence (LRR), disease-specific survival (DSS), and overall survival (OS). Results One hundred tumors were included in analyses; 50 had DOI ≤ 4 mm, while 50 had DOI > 4 mm. When DOI was ≤4 mm, the presence of PNI, LVI, or WPOI-5 was not associated with higher rates of occult cervical metastasis, LRR, or OS. When DOI was >4 mm, there was no difference in rates of occult cervical metastasis or LRR with each feature. On multivariate analysis, only the presence of two or more adverse features was associated with higher LRR (OR 5.7, P = .01) and worse DSS (HR 6.5, P = .02). Conclusion The rate of occult cervical metastases in small (≤2 cm) OTSCC when DOI is ≤4 mm is very low even when PNI, LVI, or WPOI-5 is present, and 2-year LRR is no different. When DOI is >4 mm, the strongest predictor of recurrence and survival on multivariate analysis is the presence of two or more features in the tumor. Level of evidence 4 Laryngoscope, 130:1715-1720, 2020.
Recruiting millennials: Exploring the impact of CSR involvement and pay signaling on organizational attractiveness

Modern organizations must consider corporate social responsibility (CSR) and its implications. CSR involvement carries many potential benefits, including opportunities to promote stakeholder engagement with the organization, particularly among young people (i.e., millennials) in the emergent workforce. Collectively, millennials are often described as both socially active and self‐centered. These seemingly antithetical motives complicate the execution of optimal recruitment practice. This empirical study examined the impact of CSR activity and relative pay level signals on organizational attractiveness. Participants who were seeking or soon to be seeking employment in the United States responded to a hypothetical company profile. Confirming expectations, results revealed an effect of CSR information on organizational attractiveness, wherein notification of CSR involvement enhanced attractiveness. Pay level and CSR notification did not significantly interact, indicating that the effects of CSR on attractiveness are not moderated by information about pay levels. The implications of the results and future research recommendations are discussed.
How Feedback from Mentor Teachers Sustained Student Teachers through Their First Year of Teaching

This study examines how three novice teachers experienced feedback in their learning-to-teach journeys, from their yearlong student teaching experience through their first-year teaching. As student...
The GEM model of health: a model based on generalized empirical method –Part 4 – Comparisons and contrasts

In this paper, I compare and contrast in summary fashion (1) the GEM definition of health with that of the World Health Organization (WHO); (2) the methodical integration of judgments of fact and value in the GEM model with their incommensurability in most naturalist and normativist theories of health; (3) the significance of differentiating risk factors and disease relative to states of health in the GEM model with the tendency to blur any such difference in current multifactorial accounts of disability and dysfunction; (4) the GEM model’s emphasis on the common core of operations underlying health science and healthcare with the gap separating hermeneutic understanding and scientific explanation that is often the rule in humanistic accounts of health and (5) the role of the ordered and eco-socially conditioned set of relationships in the GEM model of health with the multilevel perspective on health in the developing field of global bioethics. In conclusion, I note that the GEM model offers a unique framework - a higher viewpoint - for integrating in dynamic fashion the manifold viewpoints of clinical practice, the humanities, health science and health policy.
Mind and Spirit on the Fringes of the Social Clinic

The mind and spirit interventions of the social clinic are a type of alternative, fringe, complementary, integrative, folk, adjunctive, unconventional, unorthodox, nonmainstream, or irregular procedure that promises to treat mental, emotional, or physical ailments. What isolates past life therapy, MariEl (sic) healing, Reiki healing, light and sound therapy, gestalt psychotherapy, therapy for post-alien abduction syndrome, ho’oponopono, spiritualism, mindfulness, and many others from the mainstream is not their strangeness but rather their use of alternative science to validate their outcomes. Yet many marginal interventions are traveling the same track on which psychoanalysis, psychotherapy, and social work moved from the odd to the commonplace and all without compelling scientific evidence of effectiveness. The achievement of clinical acceptance is a social phenomenon more often than a rational one—validation through faith and use often in defiance of clinical evidence.