cssi/SciSciGPT-SciSciNet huggingface dataset:
Multisystem, Induced Pluripotent Stem Cell (iPSC) Modeling Reveals a Role for Growth Differentiation Factors (GDFs) in the Etiology of β Thalassemia and Ineffective Erythropoiesis

Abstract β Thalassemia is one of the most common monogenic diseases in man encompassing a heterogeneous group of naturally occurring, inherited mutations characterized by abnormal globin gene expression. Iron overload is the principle cause of morbidity and mortality in β thalassemia. The hepatic hormone hepcidin regulates iron homeostasis modulating iron concentration in the plasma and its distribution in tissues throughout the body. Dysregulation of hepcidin production underlies many iron disorders with emerging evidence suggesting that deficiency of the hormone may result from the strong suppressive effect of high erythropoietic activity on hepcidin expression. Current treatment modalities for iron overload include phlebotomy and iron chelation. In β thalassemia, phlebotomy is not feasible and regular chelation is the principal treatment for iron overload. Iron chelators have side effects ranging from mild to very serious, and compliance is often suboptimal. Hepcidin diagnostics and the development of novel therapeutic options are clearly desirable and may help in the management of patients with β thalassemia. Hepcidin dysregulation, along with the ineffective erythropoiesis and anemia noted in β thalassemia highlight the need for a model capable of recapitulating the multisystem complexity of this clinically variable disease. Using induced pluripotent stem cell (iPSC) technology, cell lines can be established that are genetically identical to the individual from whom they are derived, allowing for disease modeling and the development of novel therapeutics in the exact genetic context of the patient. We have generated disease-specific iPSC lines from patients with β thalassemia major. Harnessing the pluripotency of iPSCs, we demonstrate the modeling of this multisystem disease through the directed differentiation of patient-specific iPSCs into hepatocytes that produce hepcidin as well as erythroblasts produced via a platform that allows for exponentially greater production of blood cells in comparison to existing methodologies (Smith et. al, Blood, 2013). We demonstrate that β thalassemia iPSC-derived erythroblasts secrete greater amounts of GDFs 11 and 15, and that exposure of the patient’s own iPSC-derived hepatocytes to disease-specific erythroblast supernatants results in a marked decrease in hepcidin expression recapitulating essential aspects of the disease in vitro. Furthermore, exposure of developing iPSC-derived erythroblasts to recombinant GDFs results in the production of immature cells that fail to reach maturity, providing a potential novel mechanism contributing to the development of ineffective erythropoiesis. Taken together, these results validate this iPSC-based, patient-specific in vitro system as a platform for testing new diagnostic approaches as well as novel therapeutic strategies targeting the correction of hepcidin dysregulation. Disclosures No relevant conflicts of interest to declare.
Thrombolytic and Endovascular Therapies for Acute Ischemic Stroke

Although clinical trials have investigated thrombolytic therapies such as streptokinase, urokinase, and desmoteplase in acute ischemic stroke treatment, only trials assessing intravenous (IV) tissue plasminogen activator (tPA) and intraarterial prourokinase were successful in showing efficacy. Since a confirmatory trial with prourokinase was not performed, it has not been approved for treatment and IV tPA remains the standard of care. Advances in fluoroscopic imaging led to additional research in endovascular therapies as performing interventional cerebrovascular procedures became more feasible. After years of device development, enhanced acute stroke imaging, and improvements in systems of care, endovascular therapy has now shown efficacy in acute stroke treatment in randomized trials as well. Trials have shown the efficacy of stent retrievers compared to medical therapy alone in patients with anterior circulation large vessel occlusions. This has resulted in a paradigm shift in the management of acute ischemic stroke.
Impression Management, Mindshaping and the Social Function of Fibbing

In a symposium focused on deception and counter-deception in machines, one might be immediately drawn to a narrow conception of those phenomena which highlight the pernicious ways in which they might be used. On the broader notion of fibbing that we describe in our talk, the social function of being fast and loose with the truth takes center stage as a tool for accomplishing a wide variety of socially centered goals. We briefly review the FIDE framework, described in (Isaac & Bridewell 2014; Bridewell & Bello 2014), including the conceptual resources it requires and the variety of fib-related concepts it supports. FIDE delineates between the aforementioned concepts as ends, and the strategic means by which the fibber might achieve these ends. In doing so, we show that certain types of difficult to conceptualize behavior, most notably bullshitting (Frankfurt 2006) and responses to bullshitting, are instances of a kind of strategy for impression management that serves higher-order social goals.
Banking in Colonial America: A Comment on Perkins

This is an unpublished comment on a Perkin's paper that surveyed banking in colonial America. It argues that historians have overlooked a number of abortive banking schemes in the colonies, implying that the absence of banks was not an "entrepreneurial failure." and that the extension of the bubble act to the colonies was more important than Perkins acknowledges.
MYCN induces neuroblastoma in primary neural crest cells

Neuroblastoma (NBL) is an embryonal cancer of the sympathetic nervous system (SNS), which causes 15% of pediatric cancer deaths. High-risk NBL is characterized by N-Myc amplification and segmental chromosomal gains and losses. Owing to limited disease models, the etiology of NBL is largely unknown, including both the cell of origin and the majority of oncogenic drivers. We have established a novel system for studying NBL based on the transformation of neural crest cells (NCCs), the progenitor cells of the SNS, isolated from mouse embryonic day 9.5 trunk neural tube explants. Based on pathology and gene expression analysis, we report the first successful transformation of wild-type NCCs into NBL by enforced expression of N-Myc, to generate phenotypically and molecularly accurate tumors that closely model human MYCN-amplified NBL. Using comparative genomic hybridization, we found that NCC-derived NBL tumors acquired copy number gains and losses that are syntenic to those observed in human MYCN-amplified NBL including 17q gain, 2p gain and loss of 1p36. When p53-compromised NCCs were transformed with N-Myc, we generated primitive neuroectodermal tumors with divergent differentiation including osteosarcoma. These subcutaneous tumors were metastatic to regional lymph nodes, liver and lung. Our novel experimental approach accurately models human NBL and establishes a new system with potential to study early stages of NBL oncogenesis, to functionally assess NBL oncogenic drivers and to characterize NBL metastasis.
Facet Medial Branch Block

The facet joints are well-documented, common sources of spinal pain. The medial branch (MB) block of the dorsal primary ramus subserves the facet joints, and a chemical or steroidal block of the nerve serves both as a diagnostic predicate to facet joint denervation as well as a potentially therapeutic intervention. Facet medial branch block (MBB) can safely be performed in the cervical, thoracic, and lumbar spine, but varying levels of evidence support MBB possibly because there exists low variability in MB anatomy in the cervical and lumbar spines and more inconsistency the thoracic spine.
Factors associated with imaging overuse in the emergency department: A systematic review.

Abstract Background Emergency departments (ED) are sites of prevalent imaging overuse; however, determinants that drive imaging in this setting are not well-characterized. We systematically reviewed the literature to summarize the determinants of imaging overuse in the ED. Methods We searched MEDLINE® and Embase® from January 1998 to March 2017. Studies were included if they were written in English, contained original data, pertained to a U.S. population, and identified a determinant associated with overuse of imaging in the ED. Results Twenty relevant studies were included. Fourteen evaluated computerized tomography (CT) scanning in patents presenting to a regional ED who were then transferred to a level 1 trauma center; incomplete transfer of data and poor image quality were the most frequently described reasons for repeat scanning. Unnecessary pre-transfer scanning or repeated scanning after transfer, in multiple studies, was highest among older patients, those with higher Injury Severity Scores (ISS) and those being transferred further. Six studies explored determinants of overused imaging in the ED in varied conditions, with overuse greater in older patients and those having more comorbid diseases. Defensive imaging reportedly influenced physician behavior. Less integration of services across the health system also predisposed to overuse of imaging. Conclusions The literature is heterogeneous with surprisingly few studies of determinants of imaging in minor head injury or of spine imaging. Older patient age and higher ISS were the most consistently associated with ED imaging overuse. This review highlights the need for precise definitions of overuse of imaging in the ED.
Nasopharyngeal Lactobacillus is associated with a reduced risk of childhood wheezing illnesses following acute respiratory syncytial virus infection in infancy

Background Early life acute respiratory infection (ARI) with respiratory syncytial virus (RSV) has been strongly associated with the development of childhood wheezing illnesses, but the pathways underlying this association are poorly understood. Objective To examine the role of the nasopharyngeal microbiome in the development of childhood wheezing illnesses following RSV ARI in infancy. Methods We conducted a nested cohort study of 118 previously healthy, term infants with confirmed RSV ARI by RT-PCR. We used next-generation sequencing of the V4 region of the 16S ribosomal RNA gene to characterize the nasopharyngeal microbiome during RSV ARI. Our main outcome of interest was 2-year subsequent wheeze. Results Of the 118 infants, 113 (95.8%) had 2-year outcome data. Of these, 46 (40.7%) had parental report of subsequent wheeze. There was no association between the overall taxonomic composition, diversity, and richness of the nasopharyngeal microbiome during RSV ARI with the development of subsequent wheeze. However, the nasopharyngeal detection and abundance of Lactobacillus was consistently higher in infants who did not develop this outcome. Lactobacillus also ranked first among the different genera in a model distinguishing infants with and without subsequent wheeze. Conclusions The nasopharyngeal detection and increased abundance of Lactobacillus during RSV ARI in infancy are associated with a reduced risk of childhood wheezing illnesses at age 2 years.
Le système des vitrines dans Le ventre de Paris, ou la représentation conflictuelle du premier objet

L’aquarium aux poissons rouges qui, dans Le ventre de Paris d’Emile Zola, domine la vitrine de la charcuterie des Quenu-Gradelle, n’a pas manque d’interpeller la critique. Pourquoi en effet est-il donne a cet objet de clore l’extraordinaire description de cette chapelle du ventre qui met en abyme l’univers de profusion des Halles de Paris? Il s’agira ici de faire retour sur ce detail pour l’envisager comme point d’entree dans un discours psychique dont le contenu ne pourra etre veritablement revele qu’a travers l’examen d’un ensemble de vitrines qui communiquent les unes avec les autres pour former la syntaxe d’une intrigue psychique. Prenant appui sur les theories du psychisme infantile elaborees par Melanie Klein, nous demontrerons que les objets exposes au centre de chaque vitrine peuvent se lire comme autant d’avatars du premier objet, le sein maternel, que le nourrisson idealise et endommage sous l’effet du phenomene de l’envie dans la position paranoide-schizoide. Au-dela du spectacle ethnographique que Le ventre de Paris donne a lire, c’est aussi une histoire intemporelle et commune a tout etre humain que le roman met en scene.
Minimal Clinically Important Difference and Substantial Clinical Benefit After Revision Hip Arthroscopy.

Purpose To define minimal clinically important difference (MCID) and substantial clinical benefit (SCB) in revision hip arthroscopy. Methods The modified Harris Hip Score (mHHS), the Hip Outcome Score (HOS), and the international Hip Outcome Tool (iHOT-33) were administered to revision hip arthroscopy patients. At 1 year postoperatively, patients graded their hip function based on anchor responses. SCB was defined as both a net change and an absolute value. Receiver operating characteristic analysis with area under the curve was used to confirm psychometric values. A distribution-based method was used for MCID. Results Forty-nine patients were included with a mean age of 29.7 (±8.6) years. The most common indication for revision hip arthroscopy was residual femoroacetabular impingement (FAI; N = 34; 69.4%) followed by capsular management (N = 8; 16.3%). At 1-year follow-up, 34 patients reported feeling improved. Outcome score change corresponding to MCID and SCB net change for the mHHS, HOS Activities of Daily Living (ADL), HOS Sports, and iHOT-33 was 7.9/23.1, 7.9/16.2, 13.1/25.0, and 12.8/25.5, respectively. A higher proportion of patients with residual FAI achieved MCID compared with patients with other diagnoses. On the preoperative HOS ADL, HOS Sports, and iHOT-33, patients scoring below 67.7 (0.78), 55.6 (0.81), and 35.7 (0.73) were significantly more likely to achieve SCB postoperatively. Thirty-four patients (73.9%) were classified as receiving physical function improvement, and on the HOS Sports, MCID was achieved by 65% whereas 43% met the SCB criteria. Conclusions MCID values ranged from 7.9 on the mHHS and the HOS ADL to 13.1 on the HOS Sports. SCB net change ranged from 16.2 on the HOS ADL to 25.2 on the iHOT-33, whereas absolute SCB ranged from 82.4 on the iHOT-33 to 84.7 on the mHHS. Residual FAI and capsular management were the most common indications for revision surgery with patients who underwent surgery for the former found to be most likely to achieve clinically significant improvement. Level of Evidence Level IV, case series.
Sentence Memory in Amnesia

Publisher Summary The correspondence between language utilization and verbal memory ability has been a topic of concern for investigators of the amnesic syndrome. Encoding-deficits theory of amnesia was originally conceived as a type of storage theory, one with far greater emphasis on input than on output. Much of the early emphasis in research stimulated by this theory is on the abstraction, analysis, and manipulation of the perceptual and semantic features of information prior to their storage. Amnesic patients have been shown to have difficulty in utilizing feature representation, most notably semantic feature representation, and to guide their search for the desired stimulus item because they had lost the ability to utilize features which promote normal storage, differentiation, and retrieval. The linguistic processing is largely engaged for the use of online understanding of what is being conveyed to the subject and is based on the lexical and semantic features of the verbal information. The memory processes abstract features of the information that may permit storage in combination with similarly derived concepts and retrieval routes for eventual recall.
Dystrophin and Dystrophin-Associated Proteins

Dystrophin is a large protein located beneath the muscle cell membrane. It associates with several sarcolemmal proteins to form a large plasma membrane spanning complex, the dystrophin-associated protein complex (DAPC), which is essential in stabilizing the sarcolemma during muscle contraction. A deficiency of dystrophin or its associated proteins has been linked to a number of muscular dystrophies including Duchenne and Becker muscular dystrophies, congenital muscular dystrophies, and limb-girdle muscular dystrophies.
PRECONDITIONING WITH ISCHEMIA: A MEANS TO DELAY CELL DEATH IN ISCHEMIC MYOCARDIUM

We have previously shown that a brief episode of ischemia slows the rate of ATP depletion during subsequent ischemic episodes (1). Additionally, intermittent reperfusion washes out ischemic catabolites which may be harmful to the myocardium. Thus, we proposed that brief, repetitive episodes of ischemia might actually protect the heart from a subsequent sustained ischemic insult. To test this hypothesis, two sets of experiments were performed. In the first set, dogs were “preconditioned” with four 5 minute circumflex occlusions, each separated by 5 minutes of reperfusion, following which they received a sustained 40 minute occlusion. The control group received a single 40 minute occlusion. In the second study animals were preconditioned in an identical manner, following which they received a sustained 3 hour occlusion. Control animals received a single 3 hour occlusion. All animals were allowed 4 days of reperfusion to permit histologic infarct sizing. Infarct size was then related to baseline predictors of infarct size, namely the size of the area at risk and collateral blood flow. In the 40 minute study, preconditioning paradoxically limited infarct size to 25% of that seen in control animals (p<.001). Collateral blood flow (microspheres) was not significantly different between the groups. In the 3 hour study, preconditioning had no effect on infarct size. The protective effect in the 40 minute study may have been due to reduced ATP depletion and/or reduced catabolite accumulation during the sustained occlusion. These results suggest that multiple anginal episodes, which often precede myocardial infarction in man, may delay cell death after coronary occlusion, and thereby allow for greater salvage of myocardium by reperfusion therapy.
Abstract 2055: Staphylococcus aureus alpha toxin activates Notch in endothelial cells

Background. Staphylococcus aureus infection is one of the leading causes of morbidity in hospitalized patients in the United States. The secreted agent hemolysin alpha toxin (Hla) requires the receptor A Disintegrin And Metalloproteinase domain-containing protein 10 (ADAM10) to mediate its toxic effects; ADAM10 in turn activates the Notch pathway. Notch proteins function in developmental and pathological angiogenesis via the modulation of key pathways in endothelial (EC) and perivascular cells. Thus, we hypothesized that Hla would activate Notch in EC in vitro and in vivo. Methods. Human umbilical vein endothelial cells (HUVEC) were treated with recombinant Hla (rHla), Hla-H35L (genetically inactivated Hla), 5mM EDTA (a known Notch activator), or HBSS, and probed with a Luciferase reporter regulated by a Notch promoter. Mice engineered to express yellow fluorescent protein (YFP) upon Notch activation received a non-lethal daily subcutaneous injection of rHla (0.025 µg/5µL) or vehicle (PBS) and their retinal endothelial YFP interrogated at p6. 6 week old male Notch reporter mice received a 1-4 × 107 50 µl subcutaneous inoculation of S. aureus strains USA300/LAC (WT), or its isogenic Δhla mutant lacking Hla, and their skin biopsies were analyzed by histology after 36 hours, 8 and 16 days. Notch activation in endothelial cells of human liver sections from patients whose blood cultures were positive or negative for S. aureus was evaluated by immunohistochemistry. Results. Luciferase assays demonstrated that Hla (0.01 µg/mL) increased Notch activation by 1.75±0.5-fold as compared to HBSS controls (p ±3.1x106 vs. 7.7x10-5 ±6x105 YFP area/ DAPI area, p=0.002). Increased EC Notch activation in response to Hla was maintained 8 and 16 days after inoculation. IHC showed EC in human liver had higher Notch expression than controls. In sum, our results demonstrate that the S. aureus toxin Hla can potently activate Notch in endothelial cells, an effect which could have effects in development and pathological angiogenesis such as cancer. Citation Format: Sonia L. Hernandez, Mildred Nelson, Georgia Sampedro, Bianca Lec, Jared Emolo, Naina Bagrodia, Ann M. Defnet, Lydia Wu, Juliane Bubeck-Wardenburg, Jessica Kandel. Staphylococcus aureus alpha toxin activates Notch in endothelial cells [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 2055.
Reconceptualizing Feminicidio: Border Materiality in Ciudad Juárez

Ciudad Juarez is a border town in Northern Mexico consisting of roughly 1.3 million Juarenses. The town triangularly borders two U.S. states: New Mexico and Texas. While prominently recognized in t...
The Association Between Organizational Culture and the Ability to Benefit From "Just Culture" Training.

ObjectiveThis study aimed to determine whether there was an association between the organizational culture and the hospital's readiness to benefit from “Just Culture” training.MethodsThe “Just Culture” Assessment Tool and the Competing Values Framework surveys were administered before and 6 weeks af
Book review: Elias, J. and Roberts, J. 2018: Handbook on the International Political Economy of Gender

Elias, J. and Roberts, J. 2018: Handbook on the International Political Economy of Gender. Cheltenham: Edward Elgar. 544 pp. £162 (Hardcover). ISBN: 9781783478835.
Patient-Reported Outcomes Measurement Information System physical function correlates with Toronto Extremity Salvage Score in an orthopaedic oncology population.

Abstract Background The National Institute of Health's Patient-Reported Outcomes Measurement Information System (PROMIS) uses computerised-adaptive testing to reduce survey burden and improve sensitivity. PROMIS is being used across medical and surgical disciplines but has not been studied in orthopaedic oncology. Questions/purposes The aim of the study was to compare PROMIS measures with upper extremity (UE) and lower extremity (LE) Toronto Extremity Salvage Score (TESS) by assessing the following: (1) responder burden, (2) correlation between scores and (3) floor/ceiling effects. Patients and methods This cross-sectional trial analysed all 97 adult patients treated surgically for a bone or soft tissue tumour at a tertiary institution between November 2015 and March 2016. TESS (UE or LE) and PROMIS (Physical Function, Pain Interference and Depression) surveys were administered preoperatively. Pearson correlations between each PROMIS domain and TESS were calculated, as were floor/ceiling effects of each outcome measure. Results (1) Completion of three PROMIS questionnaires required a mean total of 16.8 (+/− 5.8 standard deviation) questions, compared with 31 and 32 questions for the LE and UE TESS questionnaires, respectively. (2) The PROMIS Physical Function scores demonstrated a strong positive correlation with the LE TESS (r = 0.84; 95% confidence interval [CI], 0.72–0.91; p Conclusions In an orthopaedic oncology population, the PROMIS Physical Function and Pain Interference scores correlate with the TESS and have the benefit of reduced survey burden and ceiling effect. The PROMIS Depression scores may provide additional information regarding patient outcomes not captured by the TESS. Level of Evidence Level III. The translational potential of this article Patient reported outcome measures asses patients' symptoms, function and health-related quality of life and are designed to capture more clinical information than can be gathered by objective medial testing alone. As reimbursements and the understanding of patient outcomes are becoming tied to performance on PROMIS measures, it is an important step to establish how PROMIS measures correlate and compare to traditional legacy measures.
Heart Transplantation for Cardiac Amyloidosis - Worthwhile?

Purpose Cardiac amyloidosis (CA) (both AL and TTR) results in restrictive cardiomyopathy (RCM) and is associated with a high mortality with a median survival of Methods Between 2010 and 2017 803 patients underwent HTx. We identified 41 patients who underwent HTx for CA (11 AL; 30 TTR). We compared these to 18 patients who underwent HTx for other types of RCM. We assessed 3-year actuarial survival, freedom from angiographic cardiac allograft vasculopathy (CAV) (>= 30% stenosis), non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke) and rejection. Results Patients undergoing HTx for ATTR were significantly older than AL or RCM patients (69.7 vs 57.7 vs 47.8 yrs (p Conclusion HTx for CA in appropriately selected patients is associated with comparable outcomes at 3 years to patients undergoing HTx for other forms of RCM.
Monte Carlo Simulation

The Monte Carlo simulation method is used extensively in applied science and engineering to solve a variety of stochastic problems. Solutions for this type of problems by Monte Carlo simulation are presented in the following four chapters of the book. We have already used the Monte Carlo method in previous chapters to illustrate theoretical concepts on random variables, conditional expectation, stochastic processes, and stochastic integrals.
Answer to July 2019 Photo Quiz.

Answer: Trichophyton verrucosum . The fungal culture grew a dermatophyte after 14 days of incubation at 30°C on inhibitory mold agar (IMA). The low growth rate and microscopic morphology of antler-like hyphal branching and chlamydospores in chains were consistent with Trichophyton verrucosum. The
Laparoscopic Management of Intrinsic Ureteropelvic Junction Obstruction (UPJO)

Ureteropelvic junction obstruction (UPJO) is the most common cause of hydronephrosis in infants and children. Since Anderson and Hynes described their technique of open dismembered pyeloplasty through a retroperitoneal approach, this has been considered the gold standard in surgical care for UPJO. When in 1995 Peters reported on the first pediatric laparoscopic pyeloplasty, a new era for laparoscopy in pediatric urology began. For the first time reconstructive surgery on the upper urinary tract was hereby implemented. Meanwhile pyeloplasty in children either by a laparoscopic or a retroperitoneoscopic approach has become an established technique to operate on UPJO in infants and children. The aim is to propose practical clinical guidelines for the current gold standard of laparoscopic dismembered pyeloplasty.
Incidence and Severity of Neonatal Abstinence Syndrome in Infants with prenatal exposure to Methadone versus Buprenorphine

Background: Neonatal Abstinence Syndrome(NAS) has been of increasing concern, with a threefold increase in cases from 12/1000 to 34/1000 births/year from 2000 to 2009. It typically presents 48-72 hours post-birth and manifests as nervous system irritability, autonomic system dysfunction, gastrointestinal and respiratory abnormalities. Methadone is currently the standard-of-care treatment for opioid dependence during pregnancy. Although it is an effective maintenance drug, prenatal exposure to Methadone is associated with NAS. Buprenorphine is an emerging alternative treatment for opioid dependence, with studies suggesting that it …
Textbook of Male Genitourethral Reconstruction: Penile Augmentation, Fact or Fiction

Humans have been preoccupied with penile augmentation from time immemorial. In modern times, a wide variety of approaches have sought to increase penile length, girth, or, in some cases, both. While there is no consensus regarding appropriate indications, penile augmentation has been used in the setting of microphallus, fibrosis, trauma, and penile dysmorphia. Techniques for girth enhancement include injectable therapies, grafting, and implants. Penile lengthening procedures include traction therapy, suspensory ligament division, flap and liposuction procedures. This chapter aims to provide a brief review of historical and current approaches to penile augmentation, as well as a critical review of evidence regarding efficacy and complications.
Queering Civil Society in Postsocialist Slovakia

© 2003 Viera Wallace-Lorencova All Rights Reserved The copyright for individual articles in both the print and online version of the Anthropology of East Europe Review is retained by the individual authors. They reserve all rights other than those stated here. Please contact the managing editor for details on contacting these authors. Permission is granted for reproducing these articles for scholarly and classroom use as long as only the cost of reproduction is charged to the students. Commercial reproduction of these articles requires the permission of the authors. The emerging visibility of lesbian, gay, bisexual and transgender-identified people is a contested story in Slovakia’s postsocialist transformations, one that continues to be absent from contemporary academic examinations of Eastern Europe. My task is to disrupt dominant narratives of postsocialist transformations that efface the politics of sexual difference. Based on data obtained via ethnographic research among Slovak lesbian and gay activists from the nongovernmental organizations Ganymedes, Museion, Altera, HaBio, CKKISM, Podisea, and the political initiative Iniciativa Inakosť, my larger project is to articulate the political significance of emerging visibility of sexual difference. This paper considers nascent lesbian and gay activism as contributing to the shaping of civil society in Slovakia, simultaneously benefiting from and contesting the hegemonic and homogenizing processes of European integration and globalization.
Phase behavior of a two-dimensional core-softened system: new physical insights

In this work, we report results of extensive computer simulations regarding the phase behavior of a core-softened system. By using structural and thermodynamic descriptors, as well as self-diffusion coefficients, we provide a comprehensive view of the rich phase behavior displayed by the particular instance of the model studied in here. Our calculations agree with previously published results focused on a smaller region in the temperature-density parameter space (Dudalov et al 2014 Soft Matter 10 4966). In this work, we explore a broader region in this parameter space, and uncover interesting fluid phases with low-symmetry local order, that were not reported by previous works. Solid phases were also found, and have been previously characterized in detail by (Kryuchkov et al 2018 Soft Matter 14 2152). Our results support previously reported findings, and provide new physical insights regarding the emergence of order as disordered phases transform into solids by providing radial distribution function maps and specific heat data. Our results are summarized in terms of a phase diagram.
Moisture availability mediates the relationship between terrestrial gross primary production and solar-induced chlorophyll fluorescence: Insights from global-scale variations

Effective use of solar-induced chlorophyll fluorescence (SIF) to estimate and monitor gross primary production (GPP) in terrestrial ecosystems requires a comprehensive understanding and quantification of the relationship between SIF and GPP. To date, this understanding is incomplete and somewhat controversial in the literature. Here we derived the GPP/SIF ratio from multiple data sources as a diagnostic metric to explore its global-scale patterns of spatial variation and potential climatic dependence. We found that the growing season GPP/SIF ratio varied substantially across global land surfaces, with the highest ratios consistently found in boreal regions. Spatial variation in GPP/SIF was strongly modulated by climate variables. The most striking pattern was a consistent decrease in GPP/SIF from cold-and-wet climates to hot-and-dry climates. We propose that the reduction in GPP/SIF with decreasing moisture availability may be related to stomatal responses to aridity. Furthermore, we show that GPP/SIF can be empirically modeled from climate variables using a machine learning (random forest) framework, which can improve the modeling of ecosystem production and quantify its uncertainty in global terrestrial biosphere models. Our results point to the need for targeted field and experimental studies to better understand the patterns observed and to improve the modeling of the relationship between SIF and GPP over broad scales.
RF-Photonic Filters via On-Chip Photonic–Phononic Emit–Receive Operations

The creation of high-performance narrow-band filters is of great interest for many radio frequency (RF) signal processing applications. To this end, numerous schemes for electronic, microelectromechanical systems-based, and microwave photonic filters have been demonstrated. Filtering schemes based on microwave photonic systems offer superior flexibility and tunability to traditional RF filters. However, these optical-based filters are typically limited to gigahertz (GHz) widths and often have large RF insertion losses, posing challenges for integration into high-fidelity RF circuits. In this paper, we demonstrate a novel type of microwave filter that combines the attractive features of microwave photonic filters with high- Q phononic signal processing using a photonic–phononic emit–receive process. Through this process, an RF signal, which is encoded on a guided optical wave, is converted into a GHz-frequency acoustic wave, where it is filtered through shaping of acoustic transfer functions before being converted back to the optical domain. In contrast to prior phononic filters that utilize gain or loss based on stimulated Brillouin scattering, optical amplification is not used to mediate signal processing. This emit–receive functionality, realized in an integrated silicon waveguide, produces megahertz-bandwidth bandpass filtering while supporting low RF insertion losses necessary for high dynamic range in a microwave photonic link. We also demonstrate record-high internal efficiency for emit–receive operations of this type, and show that the emit–receive operation is uniquely suitable for the creation of serial filter banks with minimal loss of fidelity. This photonic–phononic emitter–receiver represents a new method for low-distortion signal processing in an integrated all-silicon device.
Early application of human amniotic membrane in paediatric scald burns decreases the need for surgical intervention

Paediatric burns are a major health concern, and treatment of choice for less extensive intermediate-depth scald burns is debatable. In a developing country like India where the incidence and complications are high, the need for an easy and cost-effective treatment is highly necessary. The study aimed to retrospectively analyse the need for interventions in paediatric scald burns in a single tertiary referral centre over 4 years, comparing early application amniotic membrane vs wet collagen and paraffin gauze dressings. All paediatric scald burn patients admitted to the Department of Plastic and Reconstructive Surgery between Jan 2015 and Dec 2018 were identified. Demographics were collected from hospital records and operation theatre logbook. Acute scald burns in patients younger than 15 years were analysed according to dressing applied to find the need for intervention, days of hospitalisation, antibiotics usage and rate of infection. A total of 71 paediatric scald burn patients were analysed between 2015 and 2018. Thirty-six were treated with early application of human amniotic membrane and the remaining 35 were treated with wet collagen and paraffin gauze dressings. Patients treated with human amniotic membrane had lower in-hospital stay (p 0.000) and underwent less frequent dressing change (p 0.046), and none of them needed grafting (p 0.000). Our study results suggest that early application of human amniotic membrane can significantly reduce the need for surgical intervention and should be the preferred method of treatment in less extensive paediatric scald burns. Level of evidence: Level III, therapeutic study.
Predicting ice accretion from freezing rain on bridge stay cables

Abstract An morphogenetic model that simulates ice accretion on arbitrarily oriented cables exposed to freezing rain has been developed at the National Research Council Canada (NRC). This predictive numerical model has been validated experimentally for a limited number of conditions in the NRC Climatic Testing Facility. The facility is 6 m wide, 6 m high and 30 m long, and can generate a range of freezing precipitation environments. Inclined stay cable models with a diameter of 0.218 m and a length of 2.4 m were exposed to simulated freezing rain. The final experimental ice accretion shapes were scanned and digitized using a handheld laser scanner. These three-dimensional experimental ice shapes were used to partially validate the NRC morphogenetic model. The successfully validated model was used to examine ice accretion on stay cable geometry in an environment representative of freezing rain conditions in Eastern Canada. Prediction of wet snow accretion on already ice covered stay cables has also been undertaken.
The Hidden Curriculum of Monolingualism: Understanding Metonymy to Interrogate Problematic Representations of Raciolinguistic Identities in Schoolscapes.

Choices regarding how signs are displayed in schools send messages regarding the status of languages and speakers of those languages. The monolingual paradigm can be implicitly reified by the position, shape, color, etc. of languages in relation to English on school signage (Author & Co-author, 2018). This can have a negative impact for culturally and linguistically diverse youth. In combining critical race media literacy with linguistic landscape research, we uncover a hidden media of raciolinguistic ideologies (Alim, 2016), and confront the hegemony found on some of the most overlooked and under questioned representations of media - signs in schools.
Pancreatic cancer tumor analysis in CT images using patch-based multi-resolution convolutional neural network

Abstract In this paper we proposed a cascaded structure for extraction of the volumetric shape of the pancreas and tumor in adenocarcinoma patients. This process is a combination of an elastic atlas which is capable of fitting on 3D volumetric shape extracted from CT slices, a convolutional neural network with three forward paths to label the patches of images with coarse to fine resolutions using a multi-resolution structure, a region growing edge detection and finally a wavelet based multi-resolution rendering to extract the volumetric shape of the pancreas and tumor from planar CT slices. The atlas organs were weighted by geometrical parameters which were adjusted at global and organ levels. The classification of image patches was performed using a multiresolution convolutional neural network. The final segmentation of the pancreas and tumor was obtained by applying an edge detection method. A multiresolution wavelet is used for extraction of the volumetric shapes from segmented images. The subjects were 53–86 years of age with a mean and SD of 66 ± 10.24 years. K-fold cross validation is used for all the experiments. The results were compared with those of previously reported methods including Residual Network. The performance of the proposed algorithm was evaluated by Dice Similarity Coefficient (DSC), Jaccard index (JI), precision and recall yielded 89.67, 80.12, 91.37 and 93.63 for pancreas and 81.42, 68.66, 84.97 and 88.24 for tumor, respectively. The results of the proposed fully cascaded method overperformed all the other methods being compared.
What underlies rapid learning and systematic generalization in humans.

Despite the groundbreaking successes of neural networks, contemporary models require extensive training with massive datasets and exhibit poor out-of-sample generalization. One proposed solution is to build systematicity and domain-specific constraints into the model, echoing the tenets of classical, symbolic cognitive architectures. In this paper, we consider the limitations of this approach by examining human adults' ability to learn an abstract reasoning task from a brief instructional tutorial and explanatory feedback for incorrect responses, demonstrating that human learning dynamics and ability to generalize outside the range of the training examples differ drastically from those of a representative neural network model, and that the model is brittle to changes in features not anticipated by its authors. We present further evidence from human data that the ability to consistently solve the puzzles was associated with education, particularly basic mathematics education, and with the ability to provide a reliably identifiable, valid description of the strategy used. We propose that rapid learning and systematic generalization in humans may depend on a gradual, experience-dependent process of learning-to-learn using instructions and explanations to guide the construction of explicit abstract rules that support generalizable inferences.
Fines content, plasticity index and dust ratio influencing the modulus and permanent deformation behavior of aggregates

Abstract Resilient modulus (Mr) and permanent deformation (PD) characteristics of unbound aggregates under repetitive traffic loads dictate the structural response and performance of pavement base and subbase layers. Aggregate material behavior is dependent on the amount of fines in particulate matrix, also referred to as fines content (percent passing number 200 sieve), as well as plasticity index, dust ratio (percent passing number 200 sieve to percent passing number 40 sieve), material type, aggregate gradation/packing and the interactions of these properties with each other. In this study, repeated load triaxial tests were conducted on crushed limestone and crushed gravel aggregates. Fines content and plasticity index were varied from 5% to 12% and 5% to 9%, respectively. Two most typical gradations of aggregates used in roadway construction in Illinois were utilized with dust ratios ranging from 0.4 to 1.0. The results of these tests were analyzed using the shakedown theory for evaluating typical base/subbase permanent deformation or rutting trends linked to practical design considerations. Charts were also established for the modulus and deformation characteristics of unbound aggregates to designate the material quality with performance trends. Such guiding charts were compared with others developed in previous studies by authors for determining aggregate behavior under monotonic loading tests such as California Bearing Ratio (CBR). The comparisons provide valuable insights on how each aggregate property influences strength, modulus and permanent deformation behavior under different loading conditions.
A Scalable, Open-Source Implementation of a Large-Scale Mechanistic Model for Single Cell Proliferation and Death Signaling

Mechanistic models of how single cells respond to different perturbagens can help integrate disparate big data sets or predict response to varied drug combinations. However, the construction and simulation of such models have proved challenging. Our lab previously constructed one of the largest mechanistic models for single mammalian cell regulation of proliferation and death (774 species, 141 genes, 8 ligands, 2400 reactions). However, this, as many other large-scale models, was written using licensed software (MATLAB) with intricate programming structure, impeding alteration, expansion, and sharing. Here, we generated a new foundation for this model, which includes a python-based creation and simulation pipeline converting a few structured text files into an SBML-compatible format. This new open-source model (named SPARCED) is high-performance- and cloud-computing compatible and enables the study of virtual cell population responses at the single-cell level. We applied this new model to a subset of the LINCS MCF10A Data Cube, which observed that IFNγ acts as an anti-proliferative factor, but the reasons why were unknown. After expanding the SPARCED model with an IFNγ signaling module (to 950 species, 150 genes, 9 ligands, 2500 reactions), we ran stochastic single-cell simulations for two different putative crosstalk mechanisms and looked at the number of cycling cells in each case. Our model-based analysis suggested, and experiments support that these observations are better explained by IFNγ-induced SOCS1 expression sequestering activated EGF receptors, thereby downregulating AKT activity, as opposed to direct IFNγ-induced upregulation of p21 expression. This work forms a foundation for increased mechanistic model-based data integration on a single-cell level, an important building block for clinically predictive mechanistic models.
The power of the neighborhood: Perceived normative behaviors moderate individual predictors of walking and biking to school

Abstract Introduction Parent attitudes and perceptions of convenience are primary determinants of children's mode of school travel. Parents may favor the use of active transportation to school, such as walking or biking, if supportive neighborhood normative behaviors are present. Methods A series of logistic regressions with marginal effects were conducted to investigate whether seeing others, talking or waving, seeing kids walk alone, or seeing kids walk with adults along the way to school modified the impact of parent attitudes and reported ease of driving a car on active school travel among parents of children in grades K-6 (N = 390) in Phoenix, AZ (USA). Results The likelihood of using active transportation to school was positively associated with favorable parent attitudes, and the odds of using active travel modes differed less than 10% with the presence of neighborhood normative behaviors and low or high attitudes. As reported ease of driving increased, the likelihood of using active transportation to school decreased. The presence of neighborhood norms did not change the negative trajectory, but differences existed when ease of driving was low compared to high. The probability of using active transportation to school when ease of driving was low compared to high was greater when participants saw others (29.3%to, 32.8%from), talked/waved to others (11.0%to, 0%from), saw kids walking alone (28.6%to, 35.7%from), and saw kids walking with adults (27.8%to, 51.5%from). Conclusions Echoing prior work, parent attitudes and perceptions of convenience of driving remain influential determinants of children's active school travel behavior. This study provides preliminary evidence on the influences of psychosocial support within the neighborhood to promote active transportation to school. The impact of supportive normative behaviors during the school journey should be considered in active transportation to school interventions, particularly in conjunction with efforts to change parent perceptions of ease of driving.
A Self-Explainable Stylish Image Captioning Framework via Multi-References.

In this paper, we propose to build a stylish image captioning model through a Multi-style Multi modality mechanism (2M). We demonstrate that with 2M, we can build an effective stylish captioner and that multi-references produced by the model can also support explaining the model through identifying erroneous input features on faulty examples. We show how this 2M mechanism can be used to build stylish captioning models and show how these models can be utilized to provide explanations of likely errors in the models.