cssi/SciSciGPT-SciSciNet huggingface dataset:
Jeff Foxworthy’s Redneck Humor and the Boundaries of Middle-Class American Whiteness:

Recent studies examine the use of rhetorical boundaries to produce intra-racial othering within whiteness. I expand this project by exploring the textual and social codes in Jeff Foxworthy humor th...
Beyond analgesia in palliative care and end-of-life interventions.

Family physicians need a basic skill set that includes facilitating discussions on advance planning and goals, identifying and treating depression and anxiety, and managing pain and symptoms at the end of life.
La lucha antidopaje. ¿Es una política moderna o de otro tiempo?

Doping is widely regarded as the major threat to modern-day sports. For this reason, rivers of ink have run and many public debates have sprung in the wider society. Likewise, an ample bibliography in the Academia has been written on this issue. This work will analyze the nature of the anti-doping fight from the perspective of three diverse but complementary disciplines: history, law, and ethics. This paper has two parts. The first will focus on the origins and development of both the doping and anti-doping mentalities. The second part will analyze the ethico-legal challenges posed by the realization of the current anti-doping fight.
Cyclophosphamide and Sequential Cisplatin for Advanced Seminoma: Long-Term Followup in 52 Patients

Fifty-two patients with advanced seminoma were treated with primary chemotherapy: 44 received cyclophosphamide and weekly cisplatin, and 8 received sequential weekly cisplatin alone. Of the patients treated with chemotherapy alone only 44 achieved a complete remission and 4 were salvaged with further therapy (1 chemotherapy and 3 radiation therapy). These 48 patients (92 per cent) remained free of disease at a followup of 30 to 471 weeks. Six prognostic factors were tested by univariate analysis (chi-square) and only the use of previous chemotherapy predicted for a lower complete remission rate (p equals 0.02). Renal toxicity (greater than 0.4 mg. per dl. increase in serum creatinine) occurred in 2 patients (4 per cent). Neurotoxicity occurred in 16 patients (31 per cent). No fatal toxicity occurred. Cyclophosphamide and weekly cisplatin were well tolerated in patients previously treated with radiation therapy and is the treatment of choice for patients with disseminated seminoma.
Significance of Personal Influences in Purchase Decisions of Services; A Case of Membership-Based Service Organizations

This paper has confirmed the importance of personal communications and their influences on the consumer's decision to join an automobile club; in particular, family influence was found to be stable and significant. The findings have broader implications to the management of any membership-based service organization such as YMCAs, country clubs and health maintenance organizations.
An adaptive k-opt method for solving traveling salesman problem

This paper presents a new heuristic solution to the traveling salesman problem (TSP). Inspired by an existing technique that employs the task swap mechanism to solve the multi-agent task allocation, we exploit the adaptive k-swap based searching process and take into account the newly introduced subtour constraint, and propose a new variant of k-opt method for incrementally improving suboptimal but feasible TSP tours. Different from existing k-opt methods, a unique feature of the proposed method is that the parameter k is adjusted adaptively as the tour improvement proceeds. We show that by combining with existing TSP approximation techniques, the hybrid approaches can further improve the solution quality with negligible extra running time.
Accurate estimates of age at maturity from the growth trajectories of fishes and other ectotherms.

Age-at-maturity (AAM) is a key life history trait that provides insight into ecology, evolution, and population dynamics. However, maturity data can be costly to collect or may not be available. Life history theory suggests that growth is biphasic for many organisms, with a change-point in growth occurring at maturity. If so, then it should be possible to use a biphasic growth model to estimate AAM from growth data. To test this prediction, we used the Lester biphasic growth model in a likelihood profiling framework to estimate AAM from length-at-age data. We fit our model to simulated growth trajectories to determine minimum data requirements (in terms of sample size, precision in length-at-age, and the cost to somatic growth of maturity) for accurate AAM estimates. We then applied our method to a large walleye Sander vitreus data set and show that our AAM estimates are in close agreement with conventional estimates when our model fits well. Finally, we highlight the potential of our method by applying it to length-at-age data for a variety of ectotherms. Our method shows promise as a tool for estimating AAM and other life history traits from contemporary and historical samples. This article is protected by copyright. All rights reserved.
LATE QUATERNARY AEOLIAN GEOMORPHOLOGY OF THE DALE LAKE SAND SHEET, SOUTHERN MOJAVE DESERT, CALIFORNIA

Geomorphological and sedimentological analysis of aeolian deposits, combined with scanning electron microscopy (SEM) of quartz-grain surface characteristics, suggest six dune-building episodes during late Quaternary time in the southern Mojave Desert, California. The aeolian units accumulated largely in response to the lowering of water levels in lake basins and a consequent increase in fine sediment availability, and to stronger and more persistent winds, associated with rapidly changing environmental conditions. Peak dune deposition is believed to have taken place during the middle Holocene Altithermal between around 7.5 and 5 ka, a period characterized by greater aridity than the present. SEM analysis of the quartz surface textures indicates that mechanical and especially chemical weathering processes play a significant role in the post-depositional modification of aeolian sediments. Such evidence permits paleoenvironmental reconstruction during and since deposition, and a basis for the relative dating...
Effective parenting and self-control: difference by gender

Few studies have tested whether the process through which self-control is developed varies by gender. This study examines whether gender differences in self-control among children are explained by differences in parental supervision, monitoring, and discipline using a sample of mothers from National Longitudinal Study of Youth Children and Young Adults (NLSY79-CYA)1 data (N = 862). This study also examines whether the relationship between parenting factors and self-control is moderated by gender. Using ordinary least squares regression, findings showed that females report higher levels of self-control than males and that this difference is accounted for by parenting factors. Moreover, this study found that the effect of parental discipline for grades and spanking on self-control varied by gender.
AN AFRICAN PHILOSOPHICAL ANALYSIS OF ISAIAH 58: A HERMENEUTIC ENTHUSED BY UBUNTU

African philosophy is a recognized field both in the Old Testament and philosophy studies in Africa. Jacobus W. Gericke argues that ‘methodological and conceptual debates in African philosophy are things that biblical scholars can learn from when seeking to address the controversy regarding the relationship between the Hebrew Bible and philosophy’. On the conceptual debates in African philosophy, Mogobe B. Ramose holds that ‘Ubuntu is not only a word or a concept... On the contrary, Ubuntu is a lived and living philosophy of the Bantu-speaking peoples of Africa’. It is argued in this paper that African philosophy can throw light on the reading of the ancient biblical text in South Africa, particularly in relation to Ubuntu. First, this contribution examines African philosophy in South Africa with a view to conceptualise a hermeneutic enthused by Ubuntu based on a reading of Isaiah 58. Second, in this article the author attempts to re-construct the Sitz-im-Leben of the Isaiah 58 in the light of African philosophy.
Abstract 5641: Effects of G1T48, a novel orally bioavailable selective estrogen receptor degrader (SERD), and the CDK4/6 inhibitor, G1T38, on tumor growth in animal models of endocrine resistant breast cancer

Background: The combination of targeting the CDK4/6 and ER signaling pathways with palbociclib and fulvestrant is a proven therapeutic strategy for the treatment of ER positive breast cancer. However, the poor physicochemical properties of fulvestrant require monthly intramuscular injections to patients, which limit the pharmacokinetic and pharmacodynamic activity of the compound. Therefore, an orally available compound that more rapidly reaches steady state may lead to a better clinical response in patients. Here we report the preclinical characterization of G1T48, a novel, orally bioavailable, non-steroidal small molecule inhibitor of ERα, which is a potent, selective antagonist that down regulates ERα in vitro and in vivo in ER-positive models of breast cancer. Methods: Breast cancer cells expressing clinically relevant ESR1 mutations (ER-Y537S, ER-D538G) were threated with G1T38, G1T48, and mechanistically distinct SERMs/SERDs and cellular proliferation was assessed by measuring DNA content (Hoechst dye). Ovariectomized nu/nu mice bearing xenograft tumors of clinically relevant tamoxifen (TamR) and aromatase (long term estrogen deprived) resistant ER+ breast cancer were treated with G1T38 and G1T48, alone or in combination, with clinically relevant comparators. Time to progression and tumor volume were assessed over a 4 week dosing period. Results: G1T38 and G1T48 significantly inhibited cellular proliferation of MCF7 breast cancer cells bearing endocrine resistant ER mutations, ER-Y537S and ER-D538G. G1T48 treatment led to dramatic reductions in ER protein levels. Importantly, tumor growth inhibition was observed in mouse models of sensitive and resistant human breast cancer when G1T48 was dosed as a single agent or in combination with G1T38, a potent, selective CDK4/6 inhibitor. Conclusions: G1T38, a novel CDK4/6 inhibitor, and G1T48, a novel SERD, either alone or in combination, demonstrated highly potent inhibition of tumor growth in animal models of tamoxifen and aromatase resistance. G1T48 also demonstrated activity in models of endocrine resistance mediated by ER mutation. G1T48 is currently completing IND enabling studies. Citation Format: Suzanne E. Wardell, Alexander P. Yllanes, Jennifer G. Baker, Robert M. Baldi, Taylor K. Krebs, Jessica Sorrentino, John Bisi, Jay Strum, John D. Norris. Effects of G1T48, a novel orally bioavailable selective estrogen receptor degrader (SERD), and the CDK4/6 inhibitor, G1T38, on tumor growth in animal models of endocrine resistant breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5641. doi:10.1158/1538-7445.AM2017-5641
Fever in the Returning Traveler

Millions of children travel annually, whether they are refugees, international adoptees, visitors, or vacationers. Although most young travelers do well, many develop a febrile illness during or shortly after their trips. Approaching a fever in the returning traveler requires an appropriate index of suspicion to diagnose and treat in a timely manner. As many as 34% of patients with recent travel history are diagnosed with routine infections, but serious infections such as malaria, enteric fever, and dengue fever should be on the differential diagnosis due the high morbidity and mortality in children.
Acute Modulation of Mycobacterial Cell Envelope Biogenesis by Front-Line Tuberculosis Drugs.

Front-line tuberculosis (TB) drugs have been characterized extensively in vitro and in vivo with respect to gene expression and cell viability. However, little work has been devoted to understanding their effects on the physiology of the cell envelope, one of the main targets of this clinical regimen. Herein, we use metabolic labeling methods to visualize the effects of TB drugs on cell envelope dynamics in mycobacterial species. We developed a new fluorophore-trehalose conjugate to visualize trehalose monomycolates of the mycomembrane using super-resolution microscopy. We also probed the relationship between mycomembrane and peptidoglycan dynamics using a dual metabolic labeling strategy. Finally, we found that metabolic labeling of both cell envelope structures reports on drug effects on cell physiology in two hours, far faster than a genetic sensor of cell envelope stress. Our work provides insight into acute drug effects on cell envelope biogenesis in live mycobacteria.
Addressing Common Myths and Mistaken Beliefs in the Treatment of Youth With OCD

Abstract In spite of the effectiveness of exposure and response prevention (ERP) in the treatment of obsessive-compulsive disorder in youth, many clinicians endorse negative beliefs about the treatment that hinder its dissemination and implementation. In the following chapter, we review six common negative beliefs about ERP that clinicians are likely to encounter. Empirical literature relevant to each of the six beliefs is reviewed, and helpful suggestions are provided to readers for effectively addressing these beliefs in the context of clinical practice.
The Reticulo-Endothelial System (R.E.S.) in Traumatic Shock

Early in shock the Sympathetic Nervous System is hyperactive in response to deficient perfusion of tissues. This response maintains capillary hydrostatic pressure essential for exchanges between tissues and blood1. Prolonged sympathetic overactivity further reduces tissue perfusion and causes functional damage of all organs particularly in the liver and spleen which are very sensitive to hypoxia. Since these organs contain the largest fraction of the defense against bacteria and bacterial endotoxin, it is in such circumstances that endotoxin of intestinal origin can reach the systemic circulation in its still toxic state2. The resulting endotoxemia increases the ischemia of the tissues for endotoxin and catecholamines act sinergistically to damage the peripheral circulation3. Further decline of the peripheral flow causes generalized disorganization at the cellular level. The vascular smooth muscle cells develop structural changes4 and consequently there is a loss of vascular tone and hyporeactivity of the vessels to catecholamines. A disproportionate amount of blood is retained in the peripheral bed so that progressive decline in venous return to the heart occurs. Cardiac output falls progressively. Death results when there is not enough blood to sustain the minimal requiriments of vital organs.
MISUSE DETECTION - A Neural Network vs. A Genetic Algorithm Approach

Misuse detection can be addressed as an optimization problem, where the problem is to find an array of possible intrusions x that maximizes a function f (·) subject to a constraint r imposed by a user’s actions performed on a computer. This position paper presents and compares two ways of finding x, in audit data, by using neural networks and genetic algorithms.
Retransplantation for HCV-Related Liver Disease

Liver failure from Hepatitis C virus (HCV) is the most common indication for primary liver transplant in the United States, and it recurs in virtually 100 % of recipients with detectable virus going into transplant. HCV also represents the etiology with the worst posttransplant patient survival outcomes, and therefore retransplantation is a frequent consideration for patients with recurrent HCV. Decisions about retransplant in patients with HCV recurrence are ethically challenging. Several models to determine need for retransplant and to predict postretransplant outcomes have been investigated in order to help guide retransplant decisions, but no consensus recommendations have been made. Expanding the donor pool by using more donation after cardiac death liver grafts may improve availability for patients with HCV-related graft failure, but this approach is controversial. New HCV therapies are likely to become available within the next few years that could drastically alter the posttransplant course of patients with HCV and may reduce the need for retransplant over time.
Understanding the donor experience: Applying stewardship theory to higher education donors

Abstract This study sought to discover how stewardship strategies and involvement impact organization-public relationship (OPR) outcomes for higher education donors at three different levels of giving. The first study to compare annual donors, major gift donors with one endowment, and major gift donors with two or more endowments suggests that each donor type experiences stewardship and OPR differently. Specifically, as donors deepen their giving relationship with an institution, they experience stewardship and OPR outcomes more positively. Additionally, involvement only slightly contributes to this relationship between stewardship and OPR outcomes. Findings also reveal that stewardship may include only three strategies, including a new concept called respect. Implications for fundraising practice and theory are made.
IL-33 promotes innate IFN-γ production and controls multi-functional T cell responses in viral hepatitis (IRC7P.429)

Recently, experimental vaccine based on replication-defective lymphocytic choriomeningitis virus (rLCMV) has been shown to induce effective protection in several models, suggesting that rLCMV may show utility as a vaccine vector against infectious diseases and cancer. However, the key molecules in regulating the LCMV-induced immunity and controlling tissue damage are not clear. Here, we report that IL-33 promotes the innate and adaptive immune responses in LCMV-infected mice. Deficiency of IL-33 resulted in fewer IFN-γ + innate immune cells (e.g. γδ T and NK cells) at 16 hours post-infection and lower levels of IFN-γ and IL-12 in the liver at 3 days post-infection (dpi). Impaired anti-viral T cell responses were observed in IL-33 -/- mice at 7 dpi, as evidenced by fewer multi-funtional CD4 and CD8 T cells and lower level of anti-viral cytokines (e.g. IFN-γ, IL-12 and IL-2). In contrast, recombinant IL-33 (rIL-33) facilitated IFN-γ-producing gd T and NK cells, but inhibited proliferation of IL-17 + γδ T cells. rIL-33 treatment also promoted anti-viral T cell responses in both wild-type (WT) and IL-33 -/- mice, and attenuated liver injury at 6 dpi. Moreover, we found that type 2 innate lymphoid cells (ILC2), induced by rIL-33, were dispensable for anti-viral T cell response in LCMV-induced acute hepatitis. Our data revealed the key role of IL-33 in regulating innate immune cells, and subsequently enhancing the plurifunctionality of anti-viral T cell responses in LCMV infection.
Investigating Initial Conditions of the WDM Equation in Flat Space in Initial Contions of Pre Planckian Physics to Electro-Weak Regime of Space-Time

This document is due to reviewing an article by Maydanyuk and Olkhovsky, of a Nova Science conpendium as of “ The big bang, theory assumptions and Problems”, as of 2012, which uses the Wheeler De Witt equation as an evolution equation assuming a closed universe. Having the value of k, not as the closed universe, but nearly zero of a nearly flat universe, which leads to serious problems of interpretation of what initial conditions are. These problems of interpretations of initial conditions tie in with difficulties in using QM as an initial driver of inflation. And argue in favor of using a different procedure as far as forming a wave function of the universe initially. The author wishes to thank Abhay Ashtekar for his well thought out criticism but asserts that limitations in space-time geometry largely due to when Planck's constant is formed from semi classical reasoning , ie. Maxwells equations involving a closed boundary regime, in the boundary regime between Octonionic Geometry and quantum flat space non Octonionic geometry is a datum which Abhay Ashtekar may wish to take into consideration in carrying through his analysis
EMI Modeling for Antenna-Chassis System Using Characteristic Mode Analysis

Characteristic mode (CM) analysis has been widely used in antenna geometry design, antenna location optimization, and feeding positions, etc. CM analysis has seldomly been used in electromagnetic interference (EMI) modeling. Meanwhile, interactions between the antenna and the vehicle body were modeled with full-wave simulation, but the coupling mechanism has been veiled. In this paper, characteristic mode analysis is applied into the vehicle body to better understand the coupling mechanism of the vehicle modes and the antenna-chassis coupling mechanism. A few typical modes of the vehicle body are discussed first, and how to excite a specific mode is also investigated by looking at the eigen-current and eigen-charge distributions. This paper potentially provides a guideline in tackling EMI problems using CM analysis.
What Happens in the Barn Stays in the Barn: The Family and the Zombie as Sinthom osexual

This chapter interprets The Walking Dead’s zombies as sinthomosexuals, or queer antagonists to reproductive futurism. They act as queer Others through asexual reproduction, focus on immediate drives, and the presence of the infection in every living person. These zombies figure as alternatives to reproductive futurism, and their mere existence troubles heteronormative hegemony, as do the recurring transgressions by living characters, particularly Hershel and Lizzie’s questioning of the line between the living and the living dead and their willingness to view zombies not just as people but as family. Zombie-Sophia in the TV series represents a disturbing amalgam of child, symbolic Child, and sinthomosexual, and control must be sought by destroying the zombies that encroach on the categories of human and family and suppressing viewpoints that enable such encroachment.
Feasibility of a Brief Problem-Solving Training for 4-H Center Summer Staff: Linking Needs to Implementation

This multi-phased study assessed stakeholder needs and provided training for summer camp staff, a collaboration between a university and community organization. Phases I through III established the collaboration through trainings for 4-H extension agents and teen counselors. Phase IVa assessed the perceived training needs of 41 adult summer camp staff as they relate to interpersonal difficulties experienced in the camp setting. Phase IVb included adaptation of evidence-based practices to target the needs indicated by staff as well as training competencies required by 4-H policy. 4-H Center Staff completed pre-training, post-training, and follow-up questionnaires. Measurement of training efficacy was assessed using mixed-methods analyses to determine feasibility by measuring overall training satisfaction, changes in confidence, and knowledge of problem solving techniques. Results of Phase IVa informed the creation of a novel training paradigm (Phase IVb). Participants indicated high satisfaction in the training program and significantly improved on knowledge of problem solving techniques, willingness to approach difficult problems, and self-efficacy to implement problem solving techniques. Preliminary results from follow-up questionnaires revealed some continued use of training materials throughout camp experience. Implications for future trainings and continued collaborations are suggested.
Disease in a Dish: Cellular Models to Understand Human Conditions

Abstract Cell culture models of disease have provided not only versatility but also huge reductions in experimental cost and time, compared with previous whole animal and tissue model systems. Cell culture is the only reproducible, ethical human model system and is, therefore, of unprecedented importance in the study of human disease. Since the beginnings of cell culture in the late 19th century, key technological obstacles have been overcome to model human disease processes accurately in these artificially constructed systems. As we will see in this chapter, overcoming these obstacles has been an important source of discovery in basic human biology. With the most recent advances in human embryonic and induced pluripotent stem cells, genome editing, and three-dimensional organoid formations, researchers can now quickly and accurately provide important insights into human genetic diseases.
Peripheral Venous Pressure to Predict Congestive Heart Failure Readmission

Introduction Acute decompensated heart failure (ADHF) readmission rates are high and act as a burden to both the patient and the healthcare system. Non-invasive measures of hemodynamic status are limited in accuracy, leading to patients being discharged with residual congestion and a higher likelihood of subsequent readmission for ADHF. Peripheral venous pressure (PVP) measurement involves transducing a peripheral intravenous (PIV) catheter and may serve as a minimally invasive method of determining hemodynamic status in patients with ADHF. PVP measurements have been shown to correlate with CVP measurements in heart failure patients, but the clinical relevance of this has not yet been established. We sought to examine if PVP measurements may predict heart failure readmission. Methods A prospective feasibility study was conducted from July to December 2018. Patients admitted with ADHF were enrolled on day-of-discharge. Using a standard pressure transducer leveled to the phlebostatic access, measurement of PVP was performed at the bedside using a previously-inserted PIV. The electronic medical record was reviewed for subsequent readmissions. The primary end-point was readmission at 30 days post-discharge. Results 29 patients were enrolled. The mean age of participants was 65.6 +/- 10.8 years. 66% of patients were male and 55% of patients were black. 72% of patients had a reduced ejection fraction (EF) and 28% had a preserved EF. At the time of discharge, the mean PVP was 11.6 +/- 4.9 mmHg. 5 patients (17%) were readmitted within 30 days. Mean PVP for those readmitted was 12.0 +/- 2.1 mmHg vs 11.5 +/- 5.3 mmHg for those without readmission (difference of the means 0.5 mmHg, p= 0.86). PVP was not significantly impacted by whether a 22-gauge or 20-gauge PIV was used (difference of means 2.3 mmHg, p= 0.51). Waveform analysis on a subset of patients showed lower PVP in those with a sinusoidal waveform as opposed to a flatline or static waveform (12.8 vs. 17.4 mmHg, p=0.32). Conclusion In this small feasibility study, few patients were readmitted for heart failure in 30 days. PVP was similar among the 5 patients readmitted with ADHF. PVP measurement was readily obtainable and PVP was not significantly impacted by PIV gauge. Further study of this clinical application to PVP measurement is warranted.
PART 1- techno-economic analysis of a grid scale Ground-Level Integrated Diverse Energy Storage (GLIDES) technology

Abstract In this paper, a techno-economic model / cost reduction analysis of a low-cost, dispatchable / scalable, efficient Ground-Level Integrated Diverse Energy Storage (GLIDES) system is analyzed, along with a review of existing state-of-the-art energy storage technologies. The introduced technology, GLIDES, which was invented at the Oak Ridge National Laboratory (ORNL), stores energy by compression and expansion of air using water as a liquid piston inside high-pressure reservoirs. GLIDES is introduced by combining Pumped Hydroelectric Storage (PHS) and Compressed Air Energy Storage (CAES) technologies. By replacing inefficient gas compressor and turbine with higher efficiency liquid turbomachines for liquid-piston compression/expansion, GLIDES achieves higher roundtrip efficiency than other gas compression-based energy storage technologies and is a scalable energy storage system. For cost reduction purposes, various pressure reservoirs including steel vessels, carbon fiber vessels, pipe segments, and underground pressure reservoirs are analyzed in this paper. Based on the analyzed data using the models discussed in this paper, energy storage costs as low as ∼$14/kWh and ∼$346/kWh (roundtrip efficiency (RTE) ∼80%) can be achieved for a grid-scale GLIDES using depleted oil/gas reservoirs and high-pressure pipe segments respectively.
Trust and financial inclusion: A cross-country study

Abstract This study examines the role of social trust in financial inclusion around the world, using financial inclusion measures from Global Findex database and measure of trust from the World Values Survey. After controlling for individual characteristics, and country level differences in institutions and financial markets, social trust remains a significant and positive determinant for various aspects of financial inclusion. Trust is further found to supplement weak formal institutions and low educational levels. The role of limited trust is also examined in the study.
GP227 Clinical spectrum of classical galactosaemia associated with friedreich’s ataxia in a paediatric cohort in the republic of ireland – an update

Despite early diagnosis through Newborn Bloodspot Screening and strict dietary treatment, there are long-term complications of Classical Galactosaemia, including female infertility, osteopenia, and, in some cases, learning disabilities or neurological symptoms such as tremor or ataxia. Therefore, neurological symptoms may easily be attributed to an underlying diagnosis of Classical Galactosaemia. However, the coexistence of classical Galactosaemia and Friedreich’s Ataxia (FRDA) was previously reported amongst the Irish Traveller population. Classical Galactosaemia and FRDA are both autosomal recessive conditions, the gene loci for which are located on either side of the centromere of chromosome 9. FRDA is one of the most common forms of autosomal-recessive ataxia and slowly progressive; it also commonly involves the heart. We here present the clinical spectrum of 10 Irish patients currently being treated in our Metabolic Centre in whom a diagnosis of Classical Galactosaemia together with FRDA was made. All patients were diagnosed with Classical Galactosaemia through Newborn Screening first. All were diagnosed with the common Classical Galactosaemia GALT mutation Q188R/Q188R. Eight of the ten patients later presented with progressive ataxia, between the ages of 7–14 years. One child presented in cardiac failure secondary to dilated cardiomyopathy at 7 years of age. It was noted that he was not ataxic at presentation of FRDA and that he had normal tendon reflexes. Another patient who was diagnosed at 6 years of age still had an essentially normal neurological exam almost 4 years later. The diagnosis of FRDA was confirmed by detecting the common pathogenic GAA repeat expansion mutations in both alleles of the frataxin gene (FXN) in affected individuals. Taken together, neurological signs may easily be attributed to an established diagnosis of Classical Galactosaemia. However, one should be vigilant for the coexistence of Classical Galactosaemia and FRDA in a high-risk population, particularly when monitoring patients with a complex phenotype, such as a neurological or cardiac presentation.
Biochemical events associated with lymphocyte activation.

Lymphocyte activation is thus associated with a number of alterations each of which might serve to transmit the signal from the exterior to the interior of the cell. However, as can be gleaned from this brief discussion, many of these alterations are intimately related and it is most likely that the ultimate biochemical pathway or pathways for activation will be a combination of many of the changes. It is important to note that, although the actual pathway or pathways have not been clearly delineated, the evidence to date does allow us to devise ways of manipulating lymphocyte activation and in so doing to manipulate the immune response. It also allows one to compare the known steps in the sequence in lymphocytes activated by mitogenic lectins and other cells activated by specific agents. It is interesting that a perusal of the other articles in this series will demonstrate that many of the changes seen in the lymphocyte are seen in other activation systems and suggests that the means of activating a cell are common, but that the result of the activation is cell dependent.
Hospital-Level Care at Home for Acutely Ill Adults: a Qualitative Evaluation of a Randomized Controlled Trial.

Substitutive hospital-level care in a patient’s home (“home hospital”) has been shown to lower cost, utilization, and readmission compared to traditional hospital care. However, patients’ perspectives to help explain how and why interventions like home hospital accomplish many of these results are lacking. Elucidate and explain patient perceptions of home hospital versus traditional hospital care to better describe the different perceptions of care in both settings. Qualitative evaluation of a randomized controlled trial. 36 hospitalized patients (19 home; 17 control). Traditional hospital (“control”) versus home hospital (“home”), including nurse and physician home visits, intravenous medications, remote monitoring, video communication, and point-of-care testing. We conducted a thematic content analysis of semi-structured interviews. Team members developed a coding structure through a multiphase approach, utilizing a constant comparative method. Themes clustered around 3 domains: clinician factors, factors promoting healing, and systems factors. Clinician factors were similar in both groups; both described beneficial interactions with clinical staff; however, home patients identified greater continuity of care. For factors promoting healing, home patients described a locus of control surrounding their sleep, activity, and environmental comfort that control patients lacked. For systems factors, home patients experienced more efficient processes and logistics, particularly around admission and technology use, while both noted difficulty with discharge planning. Compared to control patients, home patients had better experiences with their care team, had more experiences promoting healing such as better sleep and physical activity, and had better experiences with systems factors such as the admission processes. Potential explanations include continuity of care, the power and familiarity of the home, and streamlined logistics. Future improvements include enhanced care transitions and ensuring digital interfaces are usable. NCT03203759
Pathologic nodal staging for clinically node negative soft tissue sarcoma of the extremities.

Background and objectives Synovial, clear cell, angiosarcoma, rhabdomyosarcoma, and epithelioid (SCARE) soft tissue sarcoma are at risk for nodal involvement, although the nodal positivity rates and impact on prognostication in clinically node negative patients are not well described. Methods Patients with extremity SCARE sarcoma without clinical nodal involvement undergoing surgical resection in the National Cancer Database (2004-2017) were included. Logistic regression was used to evaluate the likelihood of nodal surgery and nodal positivity. Kaplan-Meier method and Cox regression were used to assess associations of nodal status to overall survival. Results We included 4158 patients, and 669 patients (16%) underwent regional lymph node surgery (RLNS). On multivariable logistic analysis, patients with epithelioid (odds ratio [OR]: 3.77; p Conclusion Discordance exists between selection for pathologic nodal evaluation and factors associated with nodal positivity. Clinically node negative patients with clear cell and angiosarcoma should be considered for pathologic nodal evaluation.
Understanding Disproportionate Suspension Practices for Black Students in Elementary, Middle, and High Schools

There are racial and ethnic disparities in use of out-of-school suspensions within the United States. The present study assessed for the presence of disproportionate suspension by race, special edu...
Optimal Clustering of Pavement Segments Using K-Prototype Algorithm in a High-Dimensional Mixed Feature Space

AbstractThe efficiency of pavement lifecycle planning highly depends on the accuracy of condition predictions. Therefore, transportation agencies strive to maximize the impact of the limited budget...
Query by documents on top of a search interface

Abstract Document repositories often provide a keyword-based query interfaces to allow users to search for documents. These interfaces typically have rate limits or monetary cost per access operation. Constrained search interfaces include legal or medical data sources, social networks and the Web. We study the problem where a user has a set of input documents, and wants to discover other similar documents using a constrained search interface. Specifically, given a set of input documents and an access budget, we present principled techniques to generate a list of queries to submit. Our technique’s key intuition is to compute the best set of queries to return the input documents, which, as we show experimentally, also return other relevant documents. We show that our techniques are superior to the state-of-the-art work, according to several intuitive document relevance metrics, on several real benchmark datasets. We show results for two problem variants: finding queries to return in the highest positions the input documents (Docs2Queries-Self problem) and other relevant documents (Docs2Queries-Sim problem).
Long Ascending Propriospinal Neurons Provide Task-Specific, Context-Driven Control of Interlimb Coordination

Within the cervical and lumbar spinal enlargements, central pattern generating (CPG) circuitry produces the rhythmic output necessary for limb coordination during locomotion. Long propriospinal neurons that inter-connect these CPGs are thought to secure hindlimb-forelimb coordination, ensuring that diagonal limb pairs move synchronously while the ipsilateral limb pairs move out-of-phase during stepping. Here, we show that silencing long ascending propriospinal neurons (LAPNs) that interconnect the lumbar and cervical CPGs disrupts left-right limb coupling at each girdle. These perturbations to interlimb coordination occurred independent of the locomotor rhythm, did not affect intralimb coordination, and did not disrupt the speed-dependent (or any other) principal features of locomotion. Strikingly, the functional consequences of silencing LAPNs are highly context-dependent; the phenotype was not expressed during swimming, treadmill stepping, exploratory locomotion, or walking on an uncoated, slick surface. Together, these data show that LAPNs provide temporal information important for interlimb coordination in a flexible, context-driven manner.
Spotlight on Mobocertinib (TAK-788) in NSCLC with EGFR Exon 20 Insertion Mutations

The EGFR exon 20 insertion (EGFRex20ins) mutations are the third most common EGFR mutations seen in non-small cell lung cancer (NSCLC). More than 50 variants of EGFRex20ins mutations have been identified with A767_V769dupASV being the most common variant across multiple surveys. Treatment with currently available EGFR tyrosine kinase inhibitors (TKIs) including osimertinib is generally ineffective. Amivantamab (JNJ-372), a bispecific monoclonal antibody against EGFR and MET, has recently been approved by the US FDA for patients with advanced or metastatic NSCLC harboring EGFRex20ins mutations after disease progression on platinum-based chemotherapy. Among all the TKIs in clinical development, mobocertinib (TAK-788) has been granted priority review by the FDA for the same indication as amivantamab. Here, we provide a concise review on mobocertinib, with a focus on its chemical structure, preclinical data, and phase 1/2 trial results. Future directions will likely focus on combination approach such as TKI plus chemotherapy in the first-line setting, designing drugs with CNS activity, and exploring disease characteristics of various EGFRex20ins mutation variants and how they may affect treatment response.
Recombinant annexin A2 inhibits peripheral leukocyte activation and brain infiltration after traumatic brain injury.

Background Traumatic brain injury (TBI) is a significant cause of death and disability worldwide. The TLR4-NFκB signaling cascade is the critical pro-inflammatory activation pathway of leukocytes after TBI, and modulating this signaling cascade may be an effective therapeutic target for treating TBI. Previous studies indicate that recombinant annexin A2 (rA2) might be an interactive molecule modulating the TLR4-NFκB signaling; however, the role of rA2 in regulating this signaling pathway in leukocytes after TBI and its subsequent effects have not been investigated. Methods C57BL/6 mice were subjected to TBI and randomly divided into groups that received intraperitoneal rA2 or vehicle at 2 h after TBI. The peripheral leukocyte activation and infiltrating immune cells were examined by flow cytometry, RT-qPCR, and immunostaining. The neutrophilic TLR4 expression on the cell membrane was examined by flow cytometry and confocal microscope, and the interaction of annexin A2 with TLR4 was assessed by co-immunoprecipitation coupled with Western blotting. Neuroinflammation was measured via cytokine proteome profiler array and RT-qPCR. Neurodegeneration was determined by Western blotting and immunostaining. Neurobehavioral assessments were used to monitor motor and cognitive function. Brain tissue loss was assessed via MAP2 staining. Results rA2 administration given at 2 h after TBI significantly attenuates neutrophil activation and brain infiltration at 24 h of TBI. In vivo and in vitro data show that rA2 binds to and reduces TLR4 expression on the neutrophil surface and suppresses TLR4/NFκB signaling pathway in neutrophils at 12 h after TBI. Furthermore, rA2 administration also reduces pro-inflammation of brain tissues within 24 h and neurodegeneration at 48 h after TBI. Lastly, rA2 improves long-term sensorimotor ability and cognitive function, and reduces brain tissue loss at 28 days after TBI. Conclusions Systematic rA2 administration at 2 h after TBI significantly inhibits activation and brain infiltration of peripheral leukocytes, especially neutrophils at the acute phase. Consequently, rA2 reduces the detrimental brain pro-inflammation-associated neurodegeneration and ultimately ameliorates neurological deficits after TBI. The underlying molecular mechanism might be at least in part attributed to rA2 bindings to pro-inflammatory receptor TLR4 in peripheral leukocytes, thereby blocking NFκB signaling activation pathways following TBI.
Defining Persistent Total Parenteral Nutrition Use in Patients with Neurologic Impairment.

Background: Patients with neurologic impairment (NI) experience gastrointestinal symptoms as one of three common problems associated with NI, including occasional persistent total parenteral nutrit...
Noise-Driven Causal Inference in Biomolecular Networks

Single-cell RNA and protein concentrations dynamically fluctuate because of stochastic ("noisy") regulation. Consequently, biological signaling and genetic networks not only translate stimuli with functional response but also random fluctuations. Intuitively, this feature manifests as the accumulation of fluctuations from the network source to the target. Taking advantage of the fact that noise propagates directionally, we developed a method for causation prediction that does not require time-lagged observations and therefore can be applied to data generated by destructive assays such as immunohistochemistry. Our method for causation prediction, "Inference of Network Directionality Using Covariance Elements (INDUCE)," exploits the theoretical relationship between a change in the strength of a causal interaction and the associated changes in the single cell measured entries of the covariance matrix of protein concentrations. We validated our method for causation prediction in two experimental systems where causation is well established: in an E. coli synthetic gene network, and in MEK to ERK signaling in mammalian cells. We report the first analysis of covariance elements documenting noise propagation from a kinase to a phosphorylated substrate in an endogenous mammalian signaling network.
A method for fast revocation of public key certificates and security capabilities

We present a new approach to fast certificate revocation centered around the concept of an on-line semi-trusted mediator (SEM). The use of a SEM in conjunction with a simple threshold variant of the RSA cryptosystem (mediated RSA) offers a number of practical advantages over current revocation techniques. Our approach simplifies validation of digital signatures and enables certificate revocation within legacy systems. It also provides immediate revocation of all security capabilities. This paper discusses both the architecture and implementation of our approach as well as performance and compatibility with the existing infrastructure. Our results show that threshold cryptography is practical for certificate revocation.
Changes and patterns of origin regions of international tourism.

The dramatic political and economic changes in Europe, Asia, and the Middle East during the early 1990s have had a dramatic impact on international tourism. Between 1974 and 1990 there have been significant shifts in international tourist originations. The purpose of this paper is to describe and analyze the changing patterns and to compare the two time periods. A key component of the study is the construction of a Population-Adjusted Travel Index which assesses the capability of a country to generate tourists relative to population characteristics. Findings indicate that Europe is still the leader in trips generated, even though the proportion from this region is declining over time. Asian countries exhibited the most marked improvement due primarily to the tremendous economic expansion taking place on the Pacific Rim. In contrast countries of the Middle East have declined in importance relative to international tourism. This is due to political and economic instability in the region.
Development of Aa New Time Temperature Indicator for Enzymatic Validation of Pasteurization of Meat Products.

This paper presents the development of a new smart time-temperature indicator (TTI) of pasteurization whose operating principle is based on the complexation reaction between starch and iodine, and the subsequent action of an amylase on this complex causing its discoloration at a rate dependent on time and temperature of the medium. Laboratory simulations and tests in a manufacturing plant evaluated different enzyme concentrations in the TTI prototypes when exposed to pasteurization conditions. The results showed that the color response of the indicators was visually interpreted as adaptive to measurement using appropriate equipment, with satisfactory reliability in all conditions studied. The TTI containing 6.5% amylase was one whose best results were suited for use in validating the cooking of hams. When attached to the primary packaging of the product, this TTI indicated the pasteurization process inexpensively, easily, accurately, and nondestructively. Practical Application This work provides the development of a new smart indicator of pasteurization. The new small smart indicator glued to the primary product packaging visually indicated the pasteurization process. Thus, the use of this new TTI during pasteurization of meat products can mean a safer product for the client, and for the manufacturer, the possibility of identifying errors and consequently reduce costs of production.