cssi/SciSciGPT-SciSciNet huggingface dataset:
Clinical Implications of the Progression-Free Survival Endpoint for Treatment of Hormone Receptor-Positive Advanced Breast Cancer

UNLABELLED : Hormonal therapy for advanced breast cancer (ABC) has evolved significantly since the introduction of tamoxifen more than 40 years ago. The availability of selective antiestrogen therapies has further improved treatment options for women with hormone receptor-positive (HR+) ABC. However, with the development of resistance to hormonal therapies, a new treatment paradigm has emerged based on our understanding of biological pathways involved in HR+ breast cancer and mechanisms of resistance to hormonal therapy. Recent drug development efforts have focused on combining hormonal treatment with agents that target mammalian target of rapamycin serine-threonine kinases and cyclin-dependent kinases. In parallel with the evolution of hormonal and targeted therapies, our understanding of the utility of clinical endpoints has deepened. Progression-free survival (PFS) is a primary endpoint well-understood by clinicians and is increasingly accepted as a surrogate for overall survival (OS) by the U.S. Food and Drug Administration. Yet the perceived clinical benefit of PFS to patients is less well understood. Patients may not grasp the implications of prolonged PFS, highlighting the reality that patient preference in treatment selection encompasses factors that extend beyond drug activity. This presents an opportunity for clinicians to discuss PFS with patients in the context of their treatment plans, clinical outcomes, and quality-of-life measures. The objective of this review is to explore the clinical validity of the PFS and OS endpoints and the clinical relevance of PFS and OS to patients, especially in light of drivers that led to a range of treatment options for patients with HR+ ABC. IMPLICATIONS FOR PRACTICE Advances in drug development during the past two decades have provided numerous options for treatment of advanced breast cancer that include monotherapy with endocrine modulating agents and dual therapy that combines endocrine therapy with an inhibitor targeting the mammalian target of rapamycin serine-threonine kinase or cyclin-dependent kinase pathways known to be involved with resistance. Clinical trial endpoints for breast cancer have evolved as well. Communication of progression-free survival, overall survival, and other outcomes with patients should incorporate the context of the individual's treatment plan and include discussion of response rate, side effects, and quality of life.
Attendance generating system using RFID and GSM

In this paper, we propose a new model for parent alerting and automatic attendance marking using of RFID (Radio-Frequency Identification) and GSM(Global System for Mobile Communication). This system will enable automated and reliable attendance, informing parents and school administration about the same. For implementing this system each student and professor will be having a unique RFID card. A micro controller is attached to the classroom door which is used to match the RFID of the student with the RFID present in the database. If they are match the door will open. This is done by using a GSM module.
Function of Succinoglycan Polysaccharide in Sinorhizobium meliloti Host Plant Invasion Depends on Succinylation, Not Molecular Weight

ABSTRACT The acidic polysaccharide succinoglycan produced by the rhizobial symbiont Sinorhizobium meliloti 1021 is required for this bacterium to invade the host plant Medicago truncatula and establish a nitrogen-fixing symbiosis. S. meliloti mutants that cannot make succinoglycan cannot initiate invasion structures called infection threads in plant root hairs. S. meliloti exoH mutants that cannot succinylate succinoglycan are also unable to form infection threads, despite the fact that they make large quantities of succinoglycan. Succinoglycan produced by exoH mutants is refractory to cleavage by the glycanases encoded by exoK and exsH, and thus succinoglycan produced by exoH mutants is made only in the high-molecular-weight (HMW) form. One interpretation of the symbiotic defect of exoH mutants is that the low-molecular-weight (LMW) form of succinoglycan is required for infection thread formation. However, our data demonstrate that production of the HMW form of succinoglycan by S. meliloti 1021 is sufficient for invasion of the host M. truncatula and that the LMW form is not required. Here, we show that S. meliloti strains deficient in the exoK- and exsH-encoded glycanases invade M. truncatula and form a productive symbiosis, although they do this with somewhat less efficiency than the wild type. We have also characterized the polysaccharides produced by these double glycanase mutants and determined that they consist of only HMW succinoglycan and no detectable LMW succinoglycan. This demonstrates that LMW succinoglycan is not required for host invasion. These results suggest succinoglycan function is not dependent upon the presence of a small, readily diffusible form. IMPORTANCESinorhizobium meliloti is a bacterium that forms a beneficial symbiosis with legume host plants. S. meliloti and other rhizobia convert atmospheric nitrogen to ammonia, a nutrient source for the host plant. To establish the symbiosis, rhizobia must invade plant roots, supplying the proper signals to prevent a plant immune response during invasion. A polysaccharide, succinoglycan, produced by S. meliloti is required for successful invasion. Here, we show that the critical feature of succinoglycan that allows infection to proceed is the attachment of a “succinyl” chemical group and that the chain length of succinoglycan is much less important for its function. We also show that none of the short-chain versions of succinoglycan is produced in the absence of two chain-cleaving enzymes.
Fiscal Rules: Legal Limits on Government Deficit and Debt

Legal limitations on government deficit and debt exist at all levels of the legal hierarchy, international, regional, constitutional, and statutory. The International Monetary Fund imposes conditionality upon the loans that it supplies The European Union and its monetary group, the Eurozone, impose quite specific numerical caps on governmental deficits and debts, with significant sanctions for states that violate the standards. A few national constitutions include so-called “debt-brakes” that limit deficits and borrowing. Every state has laws that regulate the preparation and presentation of the budget and its review; some of these also seek to control deficits or borrowing. Ordinary laws are, however, susceptible to change by simple amendment or suspension if economic or political objectives seem to require disregard of a previously established standard.
Vascular imaging for hemodialysis vascular access planning

Introduction Central venous catheters (CVC) increase risks associated with hemodialysis (HD), but may be necessary until an arteriovenous fistula (AVF) or graft (AVG) is achieved. The impact of vascular imaging on achievement of working AVF and AVG has not been firmly established. Methods Retrospective cohort of patients initiating HD with CVC in 2010–2011, classified by exposure to venography or Doppler vein mapping, and followed through December 31, 2012. Standard and time-dependent Cox models were used to determine hazard ratios (HRs) of death, working AVF, and any AVF or AVG. Logistic regression was used to assess the association of preoperative imaging with successful AVF or AVG among 18,883 individuals who had surgery. Models were adjusted for clinical and demographic factors. Findings Among 33,918 patients followed for a median of 404 days, 39.1% had imaging and 55.7% had surgery. Working AVF or AVG were achieved in 40.6%; 46.2% died. Compared to nonimaged patients, imaged patients were more likely to achieve working AVF (HR = 1.45 [95% confidence interval [CI] 1.36, 1.55], P 0.001), and less likely to die (HR = 0.88 [0.83-0.94], P < 0.001). Among patients who had surgery, the odds ratio for any successful AVF or AVG was 1.09 (1.02–1.16, P = 0.008). Discussion Fewer than half of patients who initiated HD with a CVC had vascular imaging. Imaged patients were more likely to have vascular surgery and had increased achievement of working AV fistulas and grafts. Outcomes of surgery were similar in patients who did and did not have imaging.
An Early Version of Gauss's Disquisitiones Arithmeticae *

In 1975, while working at the Staatsbibliothek Preussischer Kulturbesitz in Berlin, the author found two sheets in the papers of G. P. L. Dirichlet which seemed very much like the first part of Section 3 of Gauss's Disquisitiones arithmeticae. Comparison of the handwriting and paper showed that the pages indeed matched parts of a manuscript by Gauss, his De Analysis Residuorum in the Niedersachsische Staats- und Universitatsbibliothek in Gottingen. A year later, another unidentified manuscript was discovered in the Dirichlet Nachlass in the archives of the Akademie der Wissenschaften der DDR. Together, these two finds provide an early version of Gauss's Disquitiones arithmeticae. This paper discusses the significance of these documents which represent the only cohesive sources illustrating Gauss's work prior to 1799.
Rab GTPases: master regulators that establish the secretory and endocytic pathways

Several of the most important discoveries in the field of membrane traffic have come from studies of Rab GTPases by Marino Zerial and Peter Novick and their colleagues. Zerial was the first to discover that Rab GTPases represent identity markers for different membrane-bound compartments, and each Rab organizes a collection of specific effectors into function-specifying membrane microdomains to carry out receptor trafficking. Novick discovered that the order (and thus polarity) of Rab GTPases along the secretory and endocytic pathways are established by their specific, cognate guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), which partner with one Rab to regulate the subsequent- and prior-acting Rabs. Such so-called Rab cascades have evolved to establish domains that contain unique Rab proteins and their cognate effectors, which drive all steps of membrane trafficking. These findings deserve much broader recognition by the biomedical research community and are highlighted here, along with open questions that require serious attention for full understanding of the molecular basis of Rab GTPase-regulated membrane trafficking in eukaryotic cells.
The Classical Lamb Shift: Why Jackson is Wrong!

I provide here a classical calculation of the Lamb shift that is of the same order of magnitude as the quantum Bethe result. This contradicts Jackson's claim that a classical calculation can not get the Lamb shift right—even to within an order of magnitude.
Third harmonic generation imaging of intact human cerebral organoids to assess key components of early neurogenesis in Rett Syndrome (Conference Presentation)

Rett Syndrome (RTT) is a pervasive, X-linked neurodevelopmental disorder that predominantly affects girls. It is mostly caused by a sporadic mutation in the gene encoding methyl CpG-binding protein 2 (MeCP2).The clinical features of RTT are most commonly reported to emerge between the ages of 6-18 months and implicating RTT as a disorder of postnatal development. However, a variety of recent evidence from our lab and others demonstrates that RTT phenotypes are present at the earliest stages of brain development including neurogenesis, migration, and patterning in addition to stages of synaptic and circuit development and plasticity. We have used RTT patient-derived induced pluripotent stem cells to generate 3D human cerebral organoids that can serve as a model for human neurogenesis in vitro. We aim to expand on our existing findings in order to determine aberrancies at individual stages of neurogenesis by performing structural and immunocytochemical staining in isogenic control and MeCP2-deficient organoids. In addition, we aim to use Third Harmonic Generation (THG) microscopy as a label-free, nondestructive 3D tissue visualization method in order to gain a complete understanding of the structural complexity that underlies human neurogenesis. As a proof of concept, we have performed THG imaging in healthy intact human cerebral organoids cleared with SWITCH. We acquired an intrinsic THG signal with the following laser configurations: 400 kHz repetition rate, 65 fs pulse width laser at 1350 nm wavelength. In these THG images, nuclei are clearly delineated and cross sections demonstrate the depth penetration capacity (< 1mm) that extends throughout the organoid. Imaging control and MeCP2-deficient human cerebral organoids in 2D sections reveals structural and protein expression-based alterations that we expect will be clearly elucidated via both THG and three-photon fluorescence microscopy.
E21. Cover-Up with John Conway, Mitya Karabash, and Ron Graham

The problem title comes from a famous proverb “To have a cake and eat it too,” which in my early American years I could not understand. Surely you have to “have a cake” in order “to eat it”! A better formulation of this folk wisdom would have been “To keep a cake and eat it too,” which is obviously impossible, hence a moral of the proverb. But that is not what I would like to share with you here. A version of what follows first appeared in the second, 2009 Springer edition of my book “How Does One Cut a Triangle?” [Soi6]. But it fits here so well that I am including its new updated and expanded 2016 version.
Uranyl Coordination by the 14-Membered Macrocycle Dibenzotetramethyltetraaza[14]annulene

Reaction of [UO2(N(SiMe3)2)2(THF)2] with 1 equiv of dibenzotetramethyltetraaza[14]annulene (tmtaaH2) affords the uranyl complex [UO2(tmtaaH)(N(SiMe3)2) (THF)] (1) (THF = tetrahydrofuran) as red blocks in 83% yield. Similarly, thermolysis of a mixture of [UO2(N(SiMe3)2)2(THF)2] and 2 equiv of tmtaaH2 affords [UO2(tmtaaH)2] (2), which can be isolated as red-orange crystals in 67% yield after workup. Both 1 and 2 were fully characterized, including analysis by X-ray crystallography. The tmtaaH ligands in 1 and 2 are only coordinated to the uranium center via one β-diketiminate fragment, while the protonated β-diketimine portion of the ligand remains uncoordinated. Reaction of [UO2(N(SiMe3)2)2(THF)2] with 1 equiv of Li2(tmtaa) in C6H6 results in the formation of [Li(THF)]2[UO2(N(SiMe3)2)2(tmtaa)] (3), which can be isolated in 55% yield as a red-brown crystalline solid. The tmtaa ligand in complex 3 supports a dative interaction between an oxo ligand in the uranyl fragment and a lithium cation, suggesting that...
A Robust Approach to Reconfigurable Control

Abstract Reconfigurable control is an approach used to provide stability and adequate performance for a system that is subject to major perturbations to its model. This paper describes research into the application of robust control techniques to reconfigurable control. The motivation for this work is the belief that, as far as possible, each controller should provide stability for each of the system models. Therefore, the controllers should be robust as well as reconfigurable. An example using the 250,000 DWT tanker model is used to illustrate this approach.
Technical note: Assessment of an alternative technique for measuring body temperature in pigs

Core body temperature (CBT) is one of the main vital signs that is used to evaluate the health status of pigs. The most common and feasible method for assessing CBT in pigs is rectal temperature (RT). Obtaining RT is stressful for animals, may generate inaccurate results, and has the risk of spreading disease. Infrared imaging (IR) thermography of the body of pigs may be a safer and less stressful alternative to RT. The objective of the current study was to evaluate the efficacy of using IR as an alternative for monitoring CBT in pigs. Twenty-three gilts (30.5 ± 5.62 kg BW) were housed in metabolism crates in an environmentally controlled facility and fed an 860 g/d grower diet. After 4 d of adaptation, the febrile response was induced by intramuscular injection of lipopolysaccharide (LPS; 25 µg/kg BW). Each pig's body temperature was recorded at 0, 2, 4, 6, 8, 10, and 24 h after LPS challenge using the following 3 methods: 1) RT, 2) IR of the eye and ear, and 3) CBT using an orally administered digital temperature sensor. Statistical analysis was performed in a completely randomized design in SAS using Mixed, Correlation, and Regression procedures. Relative to time 0 h, LPS increased the eye temperature, CBT, and RT by 0.92, 1.32, and 1.48°C, respectively ( < 0.01), but had no significant effect on ear temperature. Eye temperature, RT, and CBT, but not ear temperature, were highly correlated ( ≥ 0.96) during the course of the study ( < 0.01). Estimated regression parameters (α and β) for predicting CBT using eye temperature were -28.2 ± 8.70 and 1.76 ± 0.221, respectively, and for RT were -24.5 ± 7.69 and 1.65 ± 0.196, respectively ( ≥ 0.96; 95% confidence interval). Collectively, these results indicated a strong relationship between eye temperature, RT, and CBT in pigs. Therefore, IR of the eye can be used as a precise, noncontact alternative to RT measurements for monitoring CBT in swine.
Proposal for analyzing player emotions in an interactive narrative using story intention graphs

Many contemporary interactive digital narratives consist of cinematic content that combines performance, sound and dialogue with conventional patterns of player interactions that dictate the story path. The non-linear nature of the content makes applying methods of annotation and analysis currently used in text and film challenging, as any particular experience may differ in significant ways and a player's response may occur at different times in the experience while still applying to a particular event. As a result, most studies approach analyzing player experience using either qualitative methods or quantitative methods alone, and often these studies focus on experimental systems. We developed a coding scheme that captures opportunities and decisions and provides hooks for annotating story content and player affective response. We plan to annotate recorded player traversals of The Wolf Among Us, a choice-based adventure game, incorporating a non-verbal report method, the Sensual Evaluation Instrument [6], guided by a text-based intermediate format that models the game logic. We use David Elson's Story Intention Graph to annotate the story content [2]. The proposed study will be evaluated by whether the responses capture salient story content between different traversals effectively. We describe a proposed baseline method of manually identifying shared story segments and tagging emotional content of scenes.
Pediatric hospitalizations for upper urinary tract calculi: Epidemiological and treatment trends in the United States, 2001-2014.

Summary Introduction The incidence of urolithiasis in the pediatric population in the United States has steadily been increasing over the past few decades. Few studies to date have examined trends in the hospitalization and inpatient surgical treatment of urolithiasis in the pediatric population using nationally representative data. Objective The aim was to evaluate nationwide trends in the rates of pediatric hospitalization and inpatient surgical activity for upper urinary tract calculi (UUTC) in the United States from 2001 to 2014. Patients and methods The National Inpatient Sample (NIS) databases for 2001–2014 were queried. Hospitalizations for patients younger than age 18 (excluding newborns), with principal discharge diagnoses of kidney or ureteral calculi were selected. Surgical procedures during hospitalization were identified. Hospitalization and surgical activity data were analyzed using trends tests, chi-square statistics, and multivariable logistic regression as appropriate. Results Of an estimated 30.2 million pediatric hospitalizations during the study period, 44,369 overall (147 per 100,000) were for UUTC. The total number and proportion of UUTC hospitalizations per 100,000 all-cause admissions significantly decreased between 2001 and 2014 (p Discussion The declining trend in hospitalization for UUTC likely reflects a shift toward outpatient care for routine cases, reserving hospitalization for sicker patients or those with complications of urolithiasis. Similar to previous studies, we also observed that girls were significantly more likely than boys to be hospitalized for stone disease, and that majority of the stone activity in the pediatric population was in children aged 15–17 years. We also observed a sharp increase in the proportion of hospitalized patients who underwent surgical intervention between 2001 and 2014, but the primary driver of this trend remains uncertain. Conclusion Pediatric hospitalizations for UUTC in US children significantly decreased between 2001 and 2014, while of those hospitalized the proportion who underwent stone-related surgical intervention significantly increased over the same period. A shift towards outpatient care, reserving hospitalization and inpatient surgical care for sicker patients, those with urolithiasis-related complications, or those who fail conservative management, is a possible explanation for these observed trends. Download : Download high-res image (157KB) Download : Download full-size image Figure .
Direct Recording of Dendrodendritic Excitation in the Olfactory Bulb: Divergent Properties of Local and External Glutamatergic Inputs Govern Synaptic Integration in Granule Cells.

The olfactory bulb contains excitatory principal cells (mitral and tufted cells) that project to cortical targets as well as inhibitory interneurons. How the local circuitry in this region facilitates odor-specific output is not known, but previous work suggests that GABAergic granule cells plays an important role, especially during fine odor discrimination. Principal cells interact with granule cells through reciprocal dendrodendritic connections that are poorly understood. While many studies examined the GABAergic output side of these reciprocal connections, little is known about how granule cells are excited. Only two previous studies reported monosynaptically coupled mitral/granule cell connections and neither attempted to determine the fundamental properties of these synapses. Using dual intracellular recordings and a custom-built loose-patch amplifier, we have recorded unitary granule cell EPSPs evoked in response to mitral cell action potentials in rat (both sexes) brain slices. We find that the unitary dendrodendritic input is relatively weak with highly variable release probability and short-term depression. In contrast with the weak dendrodendritic input, the facilitating cortical input to granule cells is more powerful and less variable. Our computational simulations suggest that dendrodendritic synaptic properties prevent individual principal cells from strongly depolarizing granule cells, which likely discharge in response to either concerted activity among a large proportion of inputs or coactivation of a smaller subset of local dendrodendritic inputs with coincidence excitation from olfactory cortex. This dual-pathway requirement likely enables the sparse mitral/granule cell interconnections to develop highly odor-specific responses that facilitate fine olfactory discrimination. SIGNIFICANCE STATEMENT The olfactory bulb plays a central role in converting broad, highly overlapping, sensory input patterns into odor-selective population responses. How this occurs is not known, but experimental and theoretical studies suggest that local inhibition often plays a central role. Very little is known about how the most common local interneuron subtype, the granule cell, is excited during odor processing beyond the unusual anatomical arraignment of the interconnections (reciprocal dendrodendritic synapses). Using paired recordings and two-photon imaging, we determined the properties of the primary input to granule cells for the first time and show that these connections bias interneurons to fire in response to spiking in large populations of principal cells rather than a small group of highly active cells.
A Constructivist Perspective on Games in Education

This chapter explores four common perspectives on the study of games and the value of games for learning: games as a delivery mechanism for curricular content; ‘gamification’, which looks at elements of game systems that can be applied to new non-gaming contexts; examination of existing games that can be adapted to serve educational intentions; and games as a component of a larger activity system of play that transcends the game space. This chapter described critical features of games as play spaces to support learning from a sociocultural and activity theory perspective in which learning is viewed as the consequence of culturally mediated activity. The chapter concludes with discussion of issues and recommendations for practitioners considering the use of games for learning.
On the Walsh-Hadamard transform of monotone Boolean functions

Let $f:GF(2)^n \rightarrow GF(2)$ be a monotone Boolean function. Associated to $f$ is the Cayley graph $X$ whose vertices correspond to points of $GF(2)^n$ and whose edges correspond to pairs of vectors $(v,w)$ whose sum is in the support of $f$. The spectrum of $X$ (the set of eigenvalues of its adjacency matrix) can be computed in terms of the Walsh-Hadamard transform of $f$. We show that if $f$ is atomic, the adjacency matrix of $X$ is singular if and only if the support of $f$ has an even number of elements. We ask whether it is true that for every even monotone function the adjacency matrix of the Cayley graph must be singular. We give an example in dimension $n=6$ to show that the answer to this question is no. We use Sage to compute some examples of monotone Boolean functions, their Cayley graphs, and the graph spectra. We include some interesting characterizations of monotone functions. We give some conditions on a monotone function that imply that the function is not bent. Finally, we ask whether it is true that no even monotone function is bent, for $n>2$.
Studies with Allopurinol in Patients with Impaired Renal Function

Studies on the metabolism and pharmacokinetics of allopurinol have shown that the principal metabolic product, oxipurinol (4,6-dihydroxypyrazolo(3,4-d)pyrimidine), is formed rapidly and has a prolonged plasma half-life1. The plasma half-life of allopurinol is in the range of 0.5–1 hour, while that of oxipurinol has been reported to range from 18 to 30 hours1,2. Since oxipurinol binds very tightly to the reduced form of xanthine oxidase3,4 and inactivates the enzyme, its inhibitory effects on urate synthesis are apparent long after allopurinol itself has been cleared from the body.
Oxidative Stress with Emphasis on the Role of LAMMA in Parkinson’s Disease

Until recently, the causes and underlying pathogenetic mechanisms responsible for cell degeneration in the neurodegenerative disorders have remained obscure. Neuro-pathological analysis have revealed the presence of cytoskeletal markers such as the Lewy body and neurofibrillary tangle, which are associated with the neuronal degeneration, but the cellular events underlying these changes were unknown. More recently, it has been proposed that oxidative stress may be a unifying factor in the pathogenesis of the major neurodegenerative diseases (Olanow, 1993). This hypothesis proposes that an increase in free radicals due to excess formation or diminished antioxidant defenses is responsible for damage to critical biological molecules such as cytoskeletal proteins, membrane lipids, and DNA. This chapter will review the evidence that oxidative stress contributes to cell damage in Parkinson’s disease (PD), with particular emphasis on the role of laser microprobe mass analysis (LAMMA) and the therapeutic implications of these observations.
[D-Pen2, L-Cys5]enkephalinamide and[D-Pen2, D-Cys5] enkephalinamide, conformationally constrained cyclic enkephalinamide analogs with delta receptor specificity.

Abstract The conformationally constrained cyclic enkephalin analogs, [ 2- D - penicillamine , 5- L - cysteine ]- and [2- D - penicillamine , 5- D - cysteine]enkephalinamide were synthesized and their biological activities investigated. Both analogs effectively induced thermal analgesia as measured by the in vivo hot plate test. Both analogs were effective in inhibiting muscle contractions in the guinea pig ileum and mouse vas deferens assay systems and were shown to displace both [3H]naloxone and [3H] [ D - Ala 2 , D - Leu 5 ] enkephalin from rat brain receptor preparations. The analogs exhibited a significant preference for δ-receptors over μ-receptors, an unusual finding for enkephalinamide derivatives. In addition the 5- L - cysteine containing analog was more potent than the 5- D - cysteine analog in all the in vitro assays with the exception of the guinea pig ileum system. These uncommon results are attributed to the conformational constraints imposed by the cyclization via a disulfide and by the rigidizing effect of the penicillamine.
The microbiome and nutrition in critical illness

Purpose of review The present review aims to describe the relationship between nutrition and the gut microbiome in critical illness. Recent findings Critical illness disrupts not only cells of human origin but also the intestinal microbiome, with a decrease in bacterial diversity and transformation into a pathobiome. Under basal conditions, nutrition profoundly alters microbial composition with significant salutatory effects on human health. In critical illness, enteral nutrition is recommended and has theoretical (but not proven) advantages towards improved inner microbial health and diminution of bacterial translocation. Dietary supplements such as probiotics and fiber have been shown to improve microbial derangements in health. However, their impact on the microbiome in critical illness is unclear and although they may have some beneficial effects on patient-centric outcomes, they do not alter mortality. The precise mechanisms of how nutrition and dietary supplements modulate the gut microbiome remain to be determined. Summary Nutrition and supplements such as probiotics appear to play a significant role in modulating the microbiome in health, yet the relationship in critical illness is unclear. Further investigation is required to determine the mechanistic determinants of the impact of nutrition on the microbiome in critical illness and the potential clinical implications of this.
Prediction of the crack condition of highway pavements using machine learning models

Departments of Transportation regularly evaluate the condition of pavements through visual inspections, nondestructive evaluations, image recognition models and learning algorithms. The above metho...
Isavuconazole to prevent invasive fungal infection in immunocompromised adults: Initial experience at an academic medical centre.

OBJECTIVE To evaluate clinical and economic outcomes associated with the use of isavuconazole as antifungal prophylaxis in high-risk immunocompromised patients. PATIENTS/METHODS Retrospective, single-centre cohort study of patients who received isavuconazole prophylaxis. Outcomes assessed included breakthrough IFI, early discontinuation of isavuconazole for any reason and antifungal prophylaxis prescribed at discharge. The impact on inpatient drug expenditure was evaluated using current isavuconazole and posaconazole drug costs per observed isavuconazole days of therapy (DOT) during the study period. RESULTS One hundred thirty-eight courses of isavuconazole prophylaxis were administered to 98 inpatients (2193 DOT). Relapsed/refractory acute myelogenous leukaemia was the indication for prophylaxis in over half (59.4%) of patients. Breakthrough IFI occurred in 8 (5.8%) courses. Suspected drug-related toxicities led to early discontinuation in 6 (4.3%) courses (five hepatotoxicity, one drug rash). At discharge, 24 (17.4%) courses lacked insurance coverage for isavuconazole. The formulary switch to isavuconazole prophylaxis resulted in an estimated mean drug cost savings of $128.25 per DOT relative to estimated posaconazole costs (P < 0.001). CONCLUSION Isavuconazole may be an option for antifungal prophylaxis in high-risk immunocompromised adults and has the potential to produce significant inpatient drug cost savings. Further studies are needed to confirm the clinical efficacy and cost-effectiveness of isavuconazole in this role.
Evaluating the efficacy of antimicrobial additives against biogenic acidification in simulated wastewater exposure solutions

Microbially Induced Corrosion of Concrete (MICC) is a progressive three-stage deterioration process that is primarily associated with sulfur-oxidizing bacteria (SOB). One strategy for mitigating MICC is the use of antimicrobial additives. It is hypothesized that the performance of antimicrobial products is influenced by the pH of the environment, the bacterial population, and the level of bacterial activity. To test this hypothesis, three bacterial activity-population levels were tested in environments with different pH levels to evaluate the efficacy of a typical antimicrobial product against planktonic SOB. The ability of the antimicrobial product to prevent or delay the biogenic acidification was considered as the criterion for its efficacy. The tested antimicrobial product was successful in delaying or preventing MICC with low and moderate bacterial populations and activity for all pH levels greater than 4. Lower pH levels were not tested in this investigation. Antimicrobial products were successful in delaying or preventing MICC with severe bacterial populations and activity for all pH levels tested greater than 6. The results support the main hypothesis of the research; therefore, the selection of whether to utilize an antimicrobial product requires an understanding of the operational pH of the environment as well as knowledge on the target bacterial population and activity.
Special Educators as Single-Subject Researchers.

This paper presents some basic guidelines for planning and conducting single-subject research in special education classrooms, and argues that single-subject research procedures are conceptually co...
Evaluating the Factor Structure of Each Facet of the Five Facet Mindfulness Questionnaire

Nearly all studies treat the Five Facet Mindfulness Questionnaire as five independent scales (one measuring each of the five facets), yet almost no methodological work has examined the psychometric structure of the facets independently. We address this issue using factor analytic methods. Exploratory and confirmatory factor models were fit to item response data from a sample of 522 adults recruited online. Findings were replicated in a sample of 454 adults receiving aftercare for substance use disorder. Parallel analysis suggested multiple factors for all five facets, in both samples. Exploratory factor models suggested the presence of method factors on the acting with awareness (items using the term “distraction”) and describing facets (items that were reverse-scored). Confirmatory factor models fit poorly for all facets, in both samples. In follow-up analyses, model fit improved substantially on the acting with awareness and describing facets when method factors were included in a bifactor model. Model fit was also better for the facets of FFMQ short forms than for the full-length facets. The short-form facets and original facets correlated similarly with external criteria in both samples. None of the FFMQ facets fit a unidimensional factor model; yet, follow-up analyses suggested that each can be considered substantively unidimensional. Initial tests suggest that the facets’ multidimensionality did not materially impact their relation to other psychological constructs, suggesting that multidimensionality can be ignored for some purposes. The use of short-form facets or latent variable models (e.g., bifactor specifications) are both viable solutions for addressing multidimensionality when desired.
5-HT2c agonist, lorcaserin, reduces aggressive responding in intermittent explosive disorder: A pilot study.

RATIONALE Impulsive aggressive behavior is associated with reduced central function of serotonin (5-HT). Although selective serotonin reuptake inhibitors can reduce such behaviors, many with history of impulsive aggression do not respond adequately to selective serotonin reuptake inhibitors and may require treatment with a direct 5-HT agonist. OBJECTIVES To test the hypothesis that pretreatment with the selective 5-HT2c agonist, lorcaserin, can reduce aggressive responding in impulsively aggressive individuals. METHODS Ten male and female adults were given lorcaserin (20 mg), or a matching placebo, in random order, on 2 days separated by at least 1 week. The Taylor aggression paradigm was used to assess aggressive responding, which was represented by mean shock setting administered to an opponent and by frequency of setting high and extreme shock levels to the opponent. RESULTS Compared with placebo, lorcaserin attenuated provoked, but not unprovoked, aggression during the Taylor aggression paradigm. This was manifest by reduction in the frequency of selecting high and extreme levels of shock against the opponent. CONCLUSION Lorcaserin may possess anti-aggressive properties that could prove useful in the treatment of impulsive aggressive behavior in human subjects. These data, thus, provide a rationale for a follow-up randomized clinical trial of lorcaserin in individuals with prominent histories of impulsive aggressive behavior.
The potential role of glycogen metabolism in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is a common and aggressive form of non-Hodgkin lymphoma that may become refractory to available standard therapies, resulting in the need for the development of novel therapeutic targets. Increased metabolic activity of DLBCL tumor cells associated with high expression of glycolysis related proteins, such as glucose transporters and hexokinases, have already been described and indicates a pivotal role for glucose and glycogen metabolism in the malignant progression of the disease. Moreover, several enzymes involved in glycolysis and glycogen metabolism, including hexokinases and glycogen synthase kinase-3, are key molecules in mediating cell survival signaling, indicating that glucose/glycogen metabolism is tightly linked to the cell survival and can potentially be targeted for therapeutic purposes in DLBCL. In this review, we provide a summary of glycogen and glucose metabolism and discuss their significance in the metabolic reprograming that leads to cell survival and proliferation in DLBCL.
Lipid modulated trafficking in plants

Abstract Scientific progress in recent years has significantly unraveled several unique structural and functional aspects of the plasmodesmata (PD), such as demonstrating the presence of detergent-insoluble membrane microdomains enriched in sterols and sphingolipids. A recent study now shows that one of the sphingolipids, t18:0 phytoshinganine, binds to PD localizing protein (PDLP) 5 and increases retention of PDLP5 at PD, which is known to be associated with reduced PD permeability. The dynamic interaction between lipids and PD associated proteins assemble yet another piece in PD puzzle.
High-resolution imaging of hydrothermal heat flux using optical and thermal Structure-from-Motion photogrammetry

Abstract Quantifying hydrothermal heat flux at meter-scale resolution over >0.25 km2 is required to bridge in-situ heat flux and satellite-based measurements. We advance a methodology that blends ground-based daytime optical and nighttime thermal infrared (TIR) imagery using Structure-from-Motion photogrammetry to map radiant hydrothermal heat flux over these scales at sites with low signal-to-noise ratios that would otherwise be difficult to characterize using, for example, unmanned aerial systems. The improved method uses a computerized telescopic mount to relocate and align daytime optical acquisitions with nighttime TIR imagery, thereby enabling TIR acquisition from multiple camera orientations positioned throughout a study area. This facilitates mapping of thermal features at sites of varying size and complexity and helps to ameliorate topographic occlusion effects and geometric distortions that can bias radiant hydrothermal heat flux estimates derived from the resulting orthorectified thermal maps. We assessed detection thresholds of this method at three sites across central California, which range in size, topography, and heat flux conditions. We found that blending of optical and thermal acquisitions successfully detected anomalous heat flux, even in cases where temperatures were only slightly greater than background. This approach might be applied to a variety of volcanic and hydrothermal systems to quantify the spatial distribution of heat flux, and how this may relate to factors such as the distribution of ground fractures and lava flow rheology.
IUI4EUD: intelligent user interfaces for end-user development

End-User Developers program to meet some goal other than the code itself. This includes scientists, data analysts, and the general public when they write code. We have been working for many years on various ways to make end-user development more successful. In this talk, I will focus on two new projects where we are applying intelligent user interfaces to this long-standing challenge. In Sugilite, the user can teach an intelligent agent new skills interactively with the user interfaces of relevant smartphone apps through a combination of programming by example (PBE) and natural language instructions. For instance, a user can teach Sugilite how to order the cheaper car between Uber and Lyft, even though Sugilite has no access to their APIs, no knowledge about the task domain, and no understanding of the concept "cheap" in advance. Another project, called Verdant, is focusing on helping data scientists, including those using Machine Learning and AI, to do exploratory programming. Verdant supports micro-versioning in computational notebooks for understanding the difference among the output and code of different versions, backtracking, provenance of output to its code, and searching the history. A goal for Verdant is to intelligently organize and summarize the raw history data to help data scientists make effective choices from it.
Electrical stimulation sensorimotor mapping with stereo-EEG.

Abstract Objective We evaluated stereo-EEG electrical stimulation mapping (ESM) for localization of anatomic sensorimotor parcels in pediatric patients with drug-resistant epilepsy. We also analyzed sensorimotor and after-discharge thresholds, and the somatotopy of sensorimotor responses. Methods ESM was performed with 50 Hz, biphasic, 2–3 s trains, using 1–9 mA current. Pre- and post-implant neuroimaging was co-registered and intersected with Neurosynth reference, to classify each electrode contact as lying within/outside an anatomic sensorimotor parcel. Indices of diagnostic performance were computed. Sensorimotor and after-discharge thresholds were analyzed using multivariable linear mixed models. Results In 15 patients (6 females), aged 5.5–21.2 years, ESM showed high accuracy (0.80), high specificity (0.86), and diagnostic odds ratio (11.4, p Conclusions We provide evidence for diagnostic validity and safety of stereo-EEG sensorimotor ESM. Significance The somatotopy of sensorimotor responses elicited with electrical stimulation provide new insights into mechanisms of motor control and sensory perception.
Economy-Sensitive Conditions: Are Some Pediatric Hospitalizations Triggered By Economic Recessions?

The impact of economic recessions on child health is complex and varied. Here we examine associations between county-level unemployment and pediatric hospitalizations in fourteen states every third...
Mechanisms of protein kinase C epsilon down-regulation by transforming growth factor-beta in lung cancer cells

Protein kinase C epsilon (PKC{varepsilon}), a diacylglycerol (DAG)/phorbol ester-regulated PKC isoform, has been widely linked to oncogenesis and metastasis. PKC{varepsilon} plays important roles in the regulation of motility and invasiveness in non-small cell lung cancer (NSCLC). We previously reported that this kinase becomes prominently down-regulated upon TGF-{beta}-induced epithelial-to-mesenchymal transition (EMT), which leads to prominent phenotypic changes. While the phorbol ester PMA causes down-regulation of PKC, {delta} and {varepsilon} within hours, TGF-{beta} requires at least 4 days to reduce the expression levels of PKC{varepsilon} without affecting the expression of other PKCs, an effect that parallels the acquisition of a mesenchymal phenotype. Despite the prominent transcriptional component involved in EMT, we found that PKC{varepsilon} down-regulation does not involve changes in PKC{varepsilon} mRNA levels and was entirely independent of transcriptional activation of the PRKCE gene. Further mechanistic analysis revealed that the reduction in PKC{varepsilon} expression is dependent on proteasomal and endolysosomal pathways, but independent of autophagy processing mechanisms. Site-directed mutagenesis of Lys312 and Lys321 in PKC{varepsilon} prevented its down-regulation in response to either TGF-{beta} or the phorbol ester PMA. The shift in PKC{varepsilon} isozyme levels depending on cell plasticity underscores relevant functional consequences by modulating the expression of this oncogenic/metastatic kinase and highlights key roles of protein stability mechanisms in the control of PKC{varepsilon} phenotypic outcomes.
Effect of increasing neutron-excess on the fusion cross-section in 12−15C + 12C at above-barrier energies

Abstract Fusion excitation functions at energies above the fusion barrier for 12−15C + 12C are examined. From these excitation functions the average fusion cross-section, σ F > , is calculated. For this isotopic chain, the measured dependence of σ F > on neutron excess is compared with static barrier penetration models. The more rapid increase observed for the experimental cross-sections above the geometric increase predicted by the static models suggests that the stronger dependence on neutron-excess measured may be attributable to dynamics. Calculations with a time-dependent Hartree-Fock model also fail to describe the observed trend suggesting that for neutron-rich nuclei, neutron dynamics may play a larger role than is presently accounted for.
Технология утилизации полимерных компонентов коммунальных и промышленных отходов с получением строительных конструкций

A brief substantiation of the proposed innovative technology for the utilization of polymer components of municipal and industrial waste with the receipt of elements of building structures is presented. Along with the utilization of polymers, the proposed technology provides for own utilization needs in fuel gas, as well as for the production of building structural elements and hot water for heating and hot water supply. The process of obtaining structural elements is accompanied by crystallization of their polymer component, which increases their mechanical strength and durability.