cssi/SciSciGPT-SciSciNet huggingface dataset:
Health Effects of Energy Drinks on Children, Adolescents, and Young Adults

OBJECTIVE: To review the effects, adverse consequences, and extent of energy drink consumption among children, adolescents, and young adults. METHODS: We searched PubMed and Google using “energy drink,” “sports drink,” “guarana,” “caffeine,” “taurine,” “ADHD,” “diabetes,” “children,” “adolescents,” “insulin,” “eating disorders,” and “poison control center” to identify articles related to energy drinks. Manufacturer Web sites were reviewed for product information. RESULTS: According to self-report surveys, energy drinks are consumed by 30% to 50% of adolescents and young adults. Frequently containing high and unregulated amounts of caffeine, these drinks have been reported in association with serious adverse effects, especially in children, adolescents, and young adults with seizures, diabetes, cardiac abnormalities, or mood and behavioral disorders or those who take certain medications. Of the 5448 US caffeine overdoses reported in 2007, 46% occurred in those younger than 19 years. Several countries and states have debated or restricted energy drink sales and advertising. CONCLUSIONS: Energy drinks have no therapeutic benefit, and many ingredients are understudied and not regulated. The known and unknown pharmacology of agents included in such drinks, combined with reports of toxicity, raises concern for potentially serious adverse effects in association with energy drink use. In the short-term, pediatricians need to be aware of the possible effects of energy drinks in vulnerable populations and screen for consumption to educate families. Long-term research should aim to understand the effects in at-risk populations. Toxicity surveillance should be improved, and regulations of energy drink sales and consumption should be based on appropriate research.
Topological structure of candidates for positive curvature

Abstract In light of recent advances in the study of manifolds admitting Riemannian metrics of positive sectional curvature, the study of certain infinite families of seven dimensional manifolds has become a matter of interest. We determine the cohomology ring structures of manifolds belonging to these families. This particular ring structure indicates the existence of topological invariants distinguishing the corresponding homeomorphism and diffeomorphism type. We show that all families contain representatives of infinitely many homotopy types.
Identification of Time-Varying Ventricular Parameters During the Ejection Phase

Physical parameters representing the energy components of the cardiac pump related to inertance, resistance, and compliance are developed. A method utilizing estimation techniques is presented to determine these time-varying parameters as well as the end diastolic volume. The method is applied to the ejection phase, using pressure and flow measured at the root of the aorta and at the pulmonary artery for left and right ventricles, respectively. Uniqueness of the estimates and sensitivity of the parameters to noise in the measured variables are evaluated. The effect on the estimated parameters due to altered problem constraints is also examined.
DISCONNEXION SYNDROMES IN ANIMALS AND MAN

As I have pointed out earlier, when I met Oliver Zangwill in 1961 at a meeting on dyslexia in Baltimore, he listened patiently to the exposition of my ideas on the significance of the cortico-cortical connections for the higher functions. A short time later, while on a trip to Boston, he suggested to me that I should prepare an extended account of these ideas. This paper would never have been written without Professor Zangwill’s urging, and I am grateful to him for having brought me to a more careful review of the older literature and a more precise statement of my own ideas. Although Russell Brain, who was then the editor of Brain, had some misgivings about the section on philosophical implications he agreed to take the manuscript unchanged.
The neurocognitive impact of Fabry disease on pediatric patients.

Fabry disease (FD) is an X-linked lysosomal storage disorder that results in progressive multisystemic organ complications. Several studies have examined neurocognitive impairments in adults; however, there is a paucity of research examining neurocognitive functioning in children with FD. This is the first exploratory study to examine the neurocognitive functioning of pediatric patients with FD and to evaluate the effects of enzyme replacement therapy (ERT) on neurocognitive functioning within this population. Families attending a national conference with at least one child with FD and one parent affected by FD comprised the sample (n = 48; 24 pediatric patients, 24 parents). Pediatric participants (10 males, 14 females) between the ages of 6 and 18 years and their parent(s) were involved in the study. Data from a demographic questionnaire and two neurocognitive self-report and parent-report measures were analyzed. Parent reports of neurocognitive functioning were also compared to a sample of children with and without head injury and to a sample of children who had undergone liver transplant (LT). Children with FD had poorer cognitive and executive functioning than healthy peers, and were comparable to children with head injury and LT. In addition, children using ERT had higher scores on measures of overall cognitive functioning, as well as fewer problems with attention/working memory and executive functioning. Results of this study suggest that children with FD may exhibit poorer cognitive and executive functioning relative to healthy peers. The use of ERT may mitigate the negative impact of FD on neurocognitive functioning in pediatric patients.
Induction of immunological tolerance in chickens inoculated with xenogeneic antigens at an early stage of embryonic development

To induce immunotolerance, laboratory chicken embryos were inoculated with casein via embryonic blood vessel microinjection or with bovine serum albumin (BSA) by either embryonic blood vessel or yolk sac injection. All hatched chickens were challenged with the same protein four times at 10-day intervals beginning at 3 weeks old. Serum anti-casein and anti-BSA antibodies were analyzed by enzyme-linked immunosorbent assay (ELISA). Significantly reduced serum specific antibody, demonstrating immunotolerance, was observed in 53.8% of chickens exposed to casein in embryo by microinjection at 65-70 h of incubation; and in 62.5% (inoculating at 65-67 h of incubation) and 33.33% (inoculating at 67-70 h of incubation) of chickens exposed to BSA. Tolerant chickens presented in those groups inoculated with BSA at 5-7 days of embryogenesis by in ovo injection. The results showed tolerance could be induced by injecting xenogeneic protein into early developing embryo by both inoculation methods.
Coordination of Trivalent Metal Cations to Peptides: Results from IRMPD Spectroscopy and Theory

Structures of trivalent lanthanide metal cations La3+, Ho3+, and Eu3+ with deprotonated Alan (n = 2−5) or Leu-enk (Tyr-Gly-Gly-Phe-Leu) are investigated with infrared multiple photon dissociation (...
The rainfall‐no rainfall transition in a coupled land‐convective atmosphere system

[1] A one-dimensional representation of the atmospheric boundary layer (ABL) depth is coupled to a soil moisture bucket model to dynamically explore the relative roles of surface and free atmospheric conditions on convective precipitation occurrence and resulting soil moisture states. This occurrence is taken to depend on the crossing of the ABL height and the lifting condensation level in the presence of pure convective instability. If rainfall occurs (unrealistically) whenever these conditions are met, and free atmospheric conditions are constant, the resulting system state evolves towards a limit cycle with precipitation every day or every few days, or to a completely dry state. The free atmospheric humidity profile has a larger effect on determining the stationary soil moisture state than the temperature profile. The effect of dry air entrainment on surface energy partitioning decreases soil moisture sensitivity to free atmospheric conditions.
Fears and phobias: reliability and heritability.

Background. Familial factors, which are partly genetic, influence risk for phobias. Prior family and twin studies, however, were based on a single lifetime assessment, which may be only moderately reliable.Methods. We obtained, 8 years apart, two assessments of lifetime history of five unreasonable fears and phobias (agoraphobia and social, situational, animal and blood-injury phobia) from face-to-face and telephone interviews from 1708 individual female twins from a population-based registry. We also obtained, 1 month apart, test–retest reliability on 192 twins. We fitted, using the program Mx, a measurement model that estimates the role of genetic and environmental risk factors correcting for measurement error.Results. Short-term reliability of the five phobias was modest (mean κ=0·46), but higher than long-term stability (mean κ=0·30). Unreliability occurred both for subject recall of unreasonable fears and for interviewer assessment of which fears constituted phobias. Examining fears and phobias together, in a multiple threshold model, results suggested that twin resemblance was due solely to genetic factors, with estimated total heritabilities, corrected for unreliability, of: any 43%, agoraphobia 67%, animal 47%, blood/injury 59%, situational 46% and social 51%. With the exception of animal phobia, similar results were obtained analysing phobias alone.Conclusions. Lifetime histories of unreasonable fears and phobias assessed at personal interview have substantial unreliability. Correcting for unreliability, the liability to fears and their associated phobias is moderately heritable. Individual-specific environmental experiences play an important role in the development of phobias, while familial–environmental factors appear to be of little aetiological significance.
Activation of a p44 pseudogene in Anaplasma phagocytophila by bacterial RNA splicing: a novel mechanism for post-transcriptional regulation of a multigene family encoding immunodominant major outer membrane proteins.

Immunodominant 44 kDa major outer membrane proteins of Anaplasma phagocytophila (human granulocytic ehrlichiosis agent) are encoded by the p44 multigene family. One of the paralogues, p44-18 is predominantly expressed by A. phagocytophila in mammalian hosts, but is downregulated in the arthropod vector. The expression of p44-18 was upregulated in A. phagocytophila cultivated in HL-60 cells at 37 degrees C compared with 24 degrees C. However, the molecular mechanism of such gene expression was unclear, as p44-18 has a pseudogene-like structure, i.e. it lacks an AUG start codon and is out of frame with an upstream overlapping paralogue, p44-1. In the present study, we found that an amplicon detected by reverse transciption-polymerase chain reaction (RT-PCR) [808 basepair (bp)] for the p44-1/p44-18 gene locus was smaller than that detected by PCR with the genomic DNA (1652 bp) in the A. phagocytophila-infected HL-60 cells cultured at 37 degrees C. A circularized RNA molecule corresponding to the 844 bp region missing from the locus in the RT-PCR product was detected by inverse RT-PCR, indicating that this is an intron (designated p44-1 intervening sequence, p44-1 IVS). The splicing event of p44-1 IVS was also observed when the p44-1 IVS-carrying plasmid was introduced into Escherichia coli, suggesting that the splicing is sequence-dependent. Structural analysis and in vitro splicing experiments of p44-1 IVS suggested that this is likely to represent a new class of introns in eubacteria. The primer extension analysis showed the presence of a putative sigma(32)-type promoter in region upstream from p44-1. Collectively, the novel RNA splicing and the temperature-dependent transcription may account for the dominant p44-18 expression in mammals.
OKT3 Treatment for Allograft Rejection Is a Risk Factor for Cytomegalovirus Disease in Liver Transplantation

The role of OKT3 monoclonal antibody administration was studied as a risk factor for symptomatic cytomegalovirus (CMV) infection in 229 consecutive liver transplant recipients not receiving specific CMV prophylaxis. Twenty-six patients (11.4%) received OKT3 and 17 of them developed CMV infection, 11 (4.8%) being symptomatic. OKT3 use was a significant risk factor for symptomatic CMV infection by both univariate (relative risk [RR], 2.9; 95% confidence interval [CI], 1.5-5.8; P = .002) and multivariate time-dependent (RR, 3.4; 95% CI, 1.7-7.1; P = .001) analyses. A subgroup analysis revealed that OKT3 use was a significant risk factor for symptomatic CMV infection in CMV-seropositive but not seronegative recipients. OKT3 therapy for steroid-resistant rejection is a risk factor for symptomatic CMV infection in liver transplant recipients who are seropositive for CMV before transplantation. This group should be targeted for antiviral prophylaxis when OKT3 antirejection therapy is used.
The UCSC Archaeal Genome Browser: 2012 update

The UCSC Archaeal Genome Browser (http://archaea.ucsc.edu) offers a graphical web-based resource for exploration and discovery within archaeal and other selected microbial genomes. By bringing together existing gene annotations, gene expression data, multiple-genome alignments, pre-computed sequence comparisons and other specialized analysis tracks, the genome browser is a powerful aggregator of varied genomic information. The genome browser environment maintains the current look-and-feel of the vertebrate UCSC Genome Browser, but also integrates archaeal and bacterial-specific tracks with a few graphic display enhancements. The browser currently contains 115 archaeal genomes, plus 31 genomes of viruses known to infect archaea. Some of the recently developed or enhanced tracks visualize data from published high-throughput RNA-sequencing studies, the NCBI Conserved Domain Database, sequences from pre-genome sequencing studies, predicted gene boundaries from three different protein gene prediction algorithms, tRNAscan-SE gene predictions with RNA secondary structures and CRISPR locus predictions. We have also developed a companion resource, the Archaeal COG Browser, to provide better search and display of arCOG gene function classifications, including their phylogenetic distribution among available archaeal genomes.
Developmental changes in hypoxic exposure and responses to anoxia in Drosophila melanogaster

ABSTRACT Holometabolous insects undergo dramatic morphological and physiological changes during ontogeny. In particular, the larvae of many holometabolous insects are specialized to feed in soil, water or dung, inside plant structures, or inside other organisms as parasites where they may commonly experience hypoxia or anoxia. In contrast, holometabolous adults usually are winged and live with access to air. Here, we show that larval Drosophila melanogaster experience severe hypoxia in their normal laboratory environments; third instar larvae feed by tunneling into a medium without usable oxygen. Larvae move strongly in anoxia for many minutes, while adults (like most other adult insects) are quickly paralyzed. Adults survive anoxia nearly an order of magnitude longer than larvae (LT50: 8.3 versus 1 h). Plausibly, the paralysis of adults is a programmed response to reduce ATP need and enhance survival. In support of that hypothesis, larvae produce lactate at 3× greater rates than adults in anoxia. However, when immobile in anoxia, larvae and adults are similarly able to decrease their metabolic rate, to about 3% of normoxic conditions. These data suggest that Drosophila larvae and adults have been differentially selected for behavioral and metabolic responses to anoxia, with larvae exhibiting vigorous escape behavior likely enabling release from viscous anoxic media to predictably normoxic air, while the paralysis behavior of adults maximizes their chances of surviving flooding events of unpredictable duration. Developmental remodeling of behavioral and metabolic strategies to hypoxia/anoxia is a previously unrecognized major attribute of holometabolism.
Stimulation of fluid intake by carbohydrates: interaction between taste and calories

Rats were trained in an apparatus that infused water or nutritive fluids into their stomachs every time that they drank flavored fluids. Rats given saccharin to drink by mouth drank more fluid than rats given cherry-flavored water to drink. Furthermore, rats given saccharin to drink ingested much more fluid if they were given intragastric infusions of 6% carbohydrate than intragastric infusions of plain water. This stimulatory effect of carbohydrate infusion occurred within 1 or 2 days of training and was very large, amounting to > or = 70% increase in fluid intake compared with rats drinking saccharin and infused with water. On the other hand, infusions of 6% carbohydrate had no effect on the intake of rats given cherry-flavored water to drink. In an attempt to determine whether rats could be trained to respond to cherry flavor at all, rats were infused with a liquid diet whenever they drank cherry or saccharin-flavored water. When dry food was withheld, the rats learned to increase fluid intake so as to feed themselves. The rats given saccharin to drink acquired this task more readily than rats given cherry flavor to drink, but both groups took in normal amounts of food by the end of the 10-day training period. It is concluded that it is much easier to condition an increase in fluid intake with intragastric infusions of carbohydrate than with an arbitrary nonsweet flavor.
Nitric oxide and reactive oxygen species in vascular injury.

Nitric oxide (.NO), a free radical species produced by several mammalian cell types, plays a role in regulation of vascular, neurological and immunological signal transduction and function. The role of .NO in cytotoxic events is acquiring increased significance. The high rate of production and broad distribution of sites of production of .NO, combined with its facile direct and indirect reactions with metalloproteins, thiols and various oxygen radical species, assures that .NO will play a central role in regulating vascular, physiological and cellular homoeostasis, as well as critical intravascular free radical and oxidant reactions. At the same time, there are contradictions as to whether .NO mediates or limits free-radical-mediated tissue injury, and uncertainty regarding its mechanisms of action. .NO has been portrayed as a pathogenic mediator during ischaemia-reperfusion, and inflammatory and septic tissue injury. In contrast, cell-, metal- and oxidant-induced lipoprotein oxidation events, as well as hepatic, cerebrovascular, pulmonary and myocardial inflammatory and ischaemia-reperfusion injury studies, show convincingly that stimulation of endogenous .NO production or exogenous administration of .NO-donating molecules can serve a protective role by inhibition of often oxidant-related mechanisms. The final outcome of toxic versus tissue-protective reactions of .NO will depend on several factors, including sites and relative concentrations of individual reactive species and their diffusion distances. The following sections address these issues and conclude with a proposal as to how .NO serves as a central regulator of oxidant reactions and diverse free radical-related disease processes.
Priming is an effective way to promote social interaction between children with autism and their typically developing peers in inclusive settings

This review provides a summary and appraisal commentary on the treatment review by Gengoux, G. W. (2015). Priming for social activities: Effects on interactions between children with autism and typically developing peers. Journal of Positive Behavior Interventions, 17, 181–192. doi: 10.1177/1098300714561862.Source of funding and declaration of interest: The author reported this study was based on a doctoral dissertation and was supported by the Hosford Research Fellowship and the University of California, Santa Barbara, Regents Special Fellowship. The author reported that there were no conflicts on interest.
Effect of Material Properties on the Performance of a-Si,Ge:H,F Photodetectors

We report a study of the transient photoconductivity of a-Si,Ge:H,F in reversebiased Schottky barrier detectors. The barriers were used to detect light pulses from commercial (AI,Ga)As laser diodes. The photodetectors work at a modulation frequency of up to 10MHz. Lowering the optical gap, Eopt, reduces the optical absorption length but raises the dark current and thus reduces the specific detectivity D*. The charge collection efficiency is determined by deep trapping of electrons in the conduction band tail. The frequency response is controlled by the electron drift mobility. The performance of the photodetector is discussed in terms of the optical and transport properties of the a- Si,Ge:H,F alloys.
Quality of Life in Patients with HIV Infection and Liver Disease

The presence of HIV infection, alone or in combination with other infections and diseases, can have a serious impact on a patient’s health and quality of life (QOL). According to the World Health Organization (WHO) Constitution of 1948, “Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity” [1]. Like the definition of health, the definition of QOL is broad and multidimensional, “[An] individual’s perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns” [2].
rBridge: User Reputation based Tor Bridge Distribution with Privacy Preservation.

Tor is one of the most popular censorship circumvention systems; it uses bridges run by volunteers as proxies to evade censorship. A key challenge to the Tor circumvention system is to distribute bridges to a large number of users while avoiding having the bridges fall into the hands of corrupt users. We propose rBridge—a user reputation system for bridge distribution; it assigns bridges according to the past history of users to limit corrupt users from repeatedly blocking bridges, and employs an introduction-based mechanism to invite new users while resisting Sybil attacks. Our evaluation results show that rBridge provides much stronger protection for bridges than any existing scheme. We also address another important challenge to the bridge distribution—preserving the privacy of users’ bridge assignment information, which can be exploited by malicious parties to degrade users’ anonymity in anonymous communication.
Productivity of different cow genotypes: culling rates and early calf performance.

Records of Jersey-sired (Jx), Santa Gertrudis-sired (Sx), Charolais-sired (Cx) and straightbred Hereford (H) cows were examined to determine culling rates, birth dates, weaning weights and average daily gains of their first, second and third calves. Culling categories were defined on the basis of number of calves weaned before removal from the herd. Calf performance data were analyzed by cow breed group and cow culling category. A second-degree polynomial model fit the data of all breeds, and accounted for a greater proportion of variation in percentage culled than did the linear model (P less than .05). Total percentage culled through the study were 71, 67, 54 and 53 for the H, Sx, Cx and Jx cows, respectively. Culling rates in the H and Sx cows tended to be higher at earlier ages than in the Cx and Jx cows. Cow-culling category was a significant source of variation only on birth date of first calves. Cows culled after one calf had calves that were born later than cows in the other two categories (P less than .05). Birth date, weaning weight and average daily gain of first calves varied with cow breed in that Jx cows had calves that were born earlier, gained faster and weaned heavier than first calves from the other breed groups (P less than .05). First calves from Sx and Cx cows gained faster (P less than .05) than calves from H cows.(ABSTRACT TRUNCATED AT 250 WORDS)
SU‐D‐206‐05: A Critical Look at CBCT‐Based Dose Calculation Accuracy as It Is Applied to Adaptive Radiotherapy

Purpose: Cone-beam CTs (CBCT) obtained from On-Board Imaging Devices (OBI) are increasingly being used for dose calculation purposes in adaptive radiotherapy. Patient and target morphology are monitored and the treatment plan is updated using CBCT. Due to the difference in image acquisition parameters, dose calculated in a CBCT can differ from planned dose. We evaluate the difference between dose calculation in kV CBCT and simulation CT, and the effect of HU-density tables in dose discrepancies Methods: HU values for various materials were obtained using a Catphan 504 phantom for a simulator CT (CTSIM) and two different OBI systems using three imaging protocols: Head, Thorax and Pelvis. HU-density tables were created in the TPS for each OBI image protocol. Treatment plans were made on each Catphan 504 dataset and on the head, thorax and pelvis sections of an anthropomorphic phantom, with and without the respective HU-density table. DVH information was compared among OBI systems and planning CT. Results: Dose calculations carried on the Catphan 504 CBCTs, with and without the respective CT-density table, had a maximum difference of −0.65% from the values on the planning CT. The use of the respective HU-density table decreased the percent differences from planned values by half in most of the protocols. For the anthropomorphic phantom datasets, the use of the correct HU-density table reduced differences by 0.89% on OBI1 and 0.59% on OBI2 for the head, 0.49% on OBI1 for the thorax, and 0.25% on OBI2 for the pelvis. Differences from planned values without HU-density correction ranged from 3.13% (OBI1, thorax) to 0.30% (OBI2, thorax). Conclusion: CT-density tables in the TPS yield acceptable differences when used in partly homogeneous medium. Further corrections are needed when the medium contains pronounced density differences for accurate CBCT calculation. Current difference range (1–3%) can be clinically acceptable.
36. CS11.2 deep brain stimulation in Parkinson disease

Surgical treatment for movement disorders in the basal ganglia dates back to the 1930’s when Meyers first described campotomy. In the 1940’s Spiegel and Wycis described the first human use of stereotactic surgery for treatment of psychiatric illnesses. From the 1930’s through the 1960’s neurophysiology played a small role in these procedures, but it was the work of Dr. Albe-Fessard in the 1960’s that opened the door for intra-operative micro-electrode recording that has become a critical tool for functional localization during movement disorders surgery and most centers. The neurophysiologists is no longer the reporter of previous events, the information gained, interpreted, and analyzed by the neurophysiologist is used by the surgeon to plan the course of the procedure. In order for the neurophysiologist to perform these actions they need to not only have a detailed knowledge of the anatomy, basic physiology, and equipment, they also need to be familiar.
Use of active video gaming in children with neuromotor dysfunction: a systematic review

Aim To examine current evidence on use of active video gaming (AVG) to improve motor function in children with movement disorders including cerebral palsy, developmental coordination disorder, and Down syndrome. Method Scopus, MEDLINE, Cochrane Library, EMBASE, and CINAHL were searched. Included papers studied the use of AVG for improving movement-related outcomes in these populations. Parameters studied included health condition, strength of evidence, AVG delivery methods, capacity for individualizing play, outcomes addressed, effectiveness for achieving outcomes, and challenges/limitations. Results The 20 extracted articles varied in quality. Studies involved children with six different conditions using AVG in clinical, home, or school settings for 49 different motor outcomes. Dosage varied in frequency and duration. Choice of games played and difficulty level were therapist determined (n=6) or child controlled (n=14). The most common study limitations were small sample sizes and difficulty individualizing treatment. All articles showed improvement in outcomes with AVG, although differences were not consistently significant compared with conventional therapy. Interpretation Heterogeneity of measurement tools and target outcomes prevented meta-analysis or development of formal recommendations. However, AVG is feasible and shows potential for improving outcomes in this population. Additional investigations of dosing variables, utility as a home supplement to clinical care, and outcomes with larger sample sizes are merited.
Towards Optimal Connectivity on Multi-Layered Networks

Networks are prevalent in many high impact domains. Moreover, cross-domain interactions are frequently observed in many applications, which naturally form the dependencies between different networks. Such kind of highly coupled network systems are referred to as multi-layered networks , and have been used to characterize various complex systems, including critical infrastructure networks, cyber-physical systems, collaboration platforms, biological systems, and many more. Different from single-layered networks where the functionality of their nodes is mainly affected by within-layer connections, multi-layered networks are more vulnerable to disturbance as the impact can be amplified through cross-layer dependencies, leading to the cascade failure to the entire system. To manipulate the connectivity in multi-layered networks, some recent methods have been proposed based on two-layered networks with specific types of connectivity measures. In this paper, we address the above challenges in multiple dimensions. First, we propose a family of connectivity measures ( SubLine ) that unifies a wide range of classic network connectivity measures. Third, we reveal that the connectivity measures in the SubLine family enjoy diminishing returns property , which guarantees a near-optimal solution with linear complexity for the connectivity optimization problem. Finally, we evaluate our proposed algorithm on real data sets to demonstrate its effectiveness and efficiency.
Predicting organ toxicity using in vitro bioactivity data and chemical structure

Animal testing alone cannot practically evaluate the health hazard posed by tens of thousands of environmental chemicals. Computational approaches making use of high-throughput experimental data may provide more efficient means to predict chemical toxicity. Here, we use a supervised machine learning strategy to systematically investigate the relative importance of study type, machine learning algorithm, and type of descriptor on predicting in vivo repeat-dose toxicity at the organ-level. A total of 985 compounds were represented using chemical structural descriptors, ToxPrint chemotype descriptors, and bioactivity descriptors from ToxCast in vitro high-throughput screening assays. Using ToxRefDB, a total of 35 target organ outcomes were identified that contained at least 100 chemicals (50 positive and 50 negative). Supervised machine learning was performed using Naive Bayes, k-nearest neighbor, random forest, classification and regression trees, and support vector classification approaches. Model performa...
Time response bounds in nonlinear UAV control

One of the intriguing problems in nonlinear unmanned aerial vehicle (NUAV) control using one of its linearized model based controllers at the inner loop is generating admissible control inputs for which the aircraft trajectories are confined to its stability region. It is an initial condition selection problem that is not necessarily applied at initial time but can be applied at any part of the flight duration where a bifurcation is needed, say, to avoid a collision with an obstacle. So, valid initial condition options at a given time instant can generate a stable constant speed maneuver tree that can be augmented to an existing autopilot and enhance autonomous characteristics at the decision points where changes in flight path directions are needed. In this paper, a procedure to select these initial conditions is presented. The time response bounds of the NUAV in its stability regions are developed. Both zero input response without pilot inputs and total response with pilot inputs and initial conditions are analyzed. A three degree of freedom NUAV in pitch plane is considered to illustrate the hierarchical initial conditions for which the time responses are bounded.
Educational Methodologies: Implications for Examination

This chapter discusses the implications of the first three chapters with respect to the type of examination. For this purpose, this chapter brings major aspects of the first three chapters to the forefront, and elaborates on their connections and implications for the way educational methodologies are applied.
High-dose busulfan and cyclophosphamide followed by autologous transplantation in patients with advanced breast cancer

This study was conducted to evaluate the efficacy of high-dose busulfan (BU) and cyclophosphamide (CY) in patients undergoing autologous hematopoietic stem cell transplantation for metastatic breast cancer. Twenty-two patients with stage IV breast cancer underwent autologous marrow (n = 13), peripheral blood stem cell (PBSC) (n = 6) or marrow plus PBSC (n = 3) transplantation following BU (14-16 mg/kg) and CY (120-180 mg/kg). Of 22 patients, 18 had refractory relapse, one had primary refractory disease, two had responding relapse and one had no evidence of disease (NED) at the time of transplant. Eight patients had bone only disease, six had bone plus visceral disease, and eight had loco-regional recurrent disease. The median time for diagnosis to transplant was 1124 days (range 210-2582). Staging for evaluation of response was performed 4-6 months after transplantation. Six patients were not evaluable (NE) for response because of NED at transplant (n = 1) or early death due to transplant-related complications (n = 5) (one of RSV interstitial pneumonia, two of fungal infection and two of regimen-related toxicities) occurring at a median of 17 days (range 14-59) post-transplant. The patient who was NED at time of transplant is still NED on day 336 post-transplant. Seven of the 16 evaluable patients achieved a complete response (CR) (44%), five achieved a partial response (PR) (31%) and five had no response (NR), with an overall response rate of 75%. Five of 18 (28%) patients treated in refractory relapse, and both patients treated in responding relapse achieved a CR. Of the seven patients who achieved CR, three are alive and disease-free on days 204, 276 and 752 and three relapsed on days 209, 715 and 1127 post-transplant. One patient in CR died of aspergillus pneumonia on day 306 post-transplant. The median day to progression in five patients who achieved a PR after transplantation was 335 (range 144-507). The probabilities of survival and event-free survival (EFS) at 2 years was 0.22 and 0.15, respectively for all 22 patients. The probability of EFS at 2 years for the eight patients achieving CR (including one patient who was NED at transplant) was 0.33. The probabilities of overall survival at 2 years in patients who did and did not achieve a CR after transplantation was 0.63 and 0.14, respectively (P = 0.004). These data suggest that high-dose BU-CY followed by autologous stem cell transplantation is an effective regimen in patients with advanced breast cancer demonstrating that BU is an active agent in this disease and could be incorporated into treatment regimens requiring hematopoietic stem cell support.
Competing with Inventory in Dealership Markets

Existing literature on dealer liquidity provision and inventory management has focused on dealer inventory cost. I uncover a new inventory benefit channel: dealers strategically build inventory in order to compete for market share. The inventory benefit reduces the effective cost of dealer inventory holding, thereby lowering the price of liquidity provision. Using the TRACE data for the U.S. corporate bonds, I show that, excluding the 2008 crisis, the inventory benefit per trade is on average 8.4 basis points larger than the inventory cost. The result is reversed during the crisis, when dealers suffer significantly higher inventory cost.
Lprov: Practical Library-aware Provenance Tracing

With the continuing evolution of sophisticated APT attacks, provenance tracking is becoming an important technique for efficient attack investigation in enterprise networks. Most of existing provenance techniques are operating on system event auditing that discloses dependence relationships by scrutinizing syscall traces. Unfortunately, such auditing-based provenance is not able to track the causality of another important dimension in provenance, the shared libraries. Different from other data-only system entities like files and sockets, dynamic libraries are linked at runtime and may get executed, which poses new challenges in provenance tracking. For example, library provenance cannot be tracked by syscalls and mapping; whether a library function is called and how it is called within an execution context is invisible at syscall level; linking a library does not promise their execution at runtime. Addressing these challenges is critical to tracking sophisticated attacks leveraging libraries. In this paper, to facilitate fine-grained investigation inside the execution of library binaries, we develop Lprov, a novel provenance tracking system which combines library tracing and syscall tracing. Upon a syscall, Lprov identifies the library calls together with the stack which induces it so that the library execution provenance can be accurately revealed. Our evaluation shows that Lprov can precisely identify attack provenance involving libraries, including malicious library attack and library vulnerability exploitation, while syscall-based provenance tools fail to identify. It only incurs 7.0% (in geometric mean) runtime overhead and consumes 3 times less storage space of a state-of-the-art provenance tool.
Growth of preweaned, group-housed dairy calves diagnosed with respiratory disease using clinical respiratory scoring and thoracic ultrasound—A cohort study

The objectives of this cohort study were to identify a cut point on a previously described 6-level ultrasound score (USS6) at which average daily gain (ADG) is affected and to determine whether there is any additional benefit of using a clinical respiratory score. Calves from a commercial herd in Ohio were enrolled at entry to an automated calf feeder barn at (mean ± standard deviation) 21 ± 6 d of age (n = 308). Calves that survived until 50 d (n = 233) were included in the analyses. Twice-weekly health exams included a clinical respiratory score (CRS), USS6 (0-5, based on lung mass involved), and body weight. For the CRS, the nose, eyes, ears, cough, and rectal temperature were assigned a score (0-3), and calves were considered positive (CRS+) when at least 2 areas scored ≥2. For analysis, USS6 and CRS status were based on a calf's first bovine respiratory disease event identified during the study period. The first multivariable linear model was fit to determine whether USS6 was associated with ADG and controlled for CRS. We detected no difference in ADG among calves with USS6 scores of 2, 3, 4, and 5. Based on this finding, we proposed a simplified 2-level ultrasound score (USS2; without lung consolidation or with lung consolidation ≥1 cm2). A second multivariable model was fit to assess the association between USS2 and ADG; this model controlled for CRS, birth weight category, breed, and cohort. Calves with lung consolidation (n = 169) had lower ADG than calves without lung consolidation (n = 64; 0.73 vs. 0.85 kg/d, respectively). Calves that were CRS+ (n = 61) had lower ADG than calves that were CRS- (n = 172; 0.74 vs. 0.84 kg/d, respectively). Although CRS did not affect the relationship between USS2 and ADG, both CRS and USS2 are necessary to explain variation in ADG. We simplified USS6 and proposed USS2 based on how lung consolidation affected ADG. A simplified 2-level ultrasound score may be more practical for veterinarians to identify calves that may be at risk for poor growth. The effect on ADG was similar between calves with lung consolidation and calves identified as CRS+. Therefore, both thoracic ultrasonography and CRS should be used to identify calves with all types of respiratory disease that affect growth. However, this study represents calves in group housing from 21 to 50 d of age on 1 farm with high disease incidence. We encourage studies that investigate the effects of lung consolidation and CRS on ADG in different management systems.
Potentiating antibiotic treatment using fitness-neutral gene expression perturbations

The rapid proliferation of multidrug-resistant (MDR) bacteria poses a critical threat to human health, for which new antimicrobial strategies are desperately needed. Here we outline a strategy for combating bacterial infections by administering fitness neutral gene expression perturbations as co-therapies to potentiate antibiotic lethality. We systematically explored the fitness of 270 gene knockout-drug combinations in Escherichia coli, identifying 114 synergistic interactions. Genes revealed in this screen were subsequently perturbed at the transcriptome level via multiplexed CRISPR-dCas9 interference to induce antibiotic synergy. These perturbations successfully sensitized E. coli to antibiotic treatment without imposing a separate fitness cost. We next administered these fitness neutral gene perturbations as co-therapies to potentiate antibiotic killing of Salmonella enterica in intracellular infections of HeLa epithelial cells, demonstrating therapeutic applicability. Finally, we utilized these results to design peptide nucleic acid (PNA) co-therapies for targeted gene expression reduction in four MDR, clinically isolated bacteria. Two isolates of Klebsiella pneumoniae and E. coli were each exposed to PNAs targeting homologs of the genes csgD, fnr, recA and acrA in the presence of sub-minimal inhibitory concentrations of trimethoprim. We successfully increased each strains susceptibility to trimethoprim treatment and identified eight cases in which re-sensitization occurred without a direct fitness impact of the PNA on MDR strains. Our results highlight a promising approach for combating MDR bacteria which could extend the utility of our current antibiotic arsenal.
The Relation Between Dialect Density and the Codevelopment of Writing and Reading in African American Children

The purpose of this longitudinal study was to examine the influence of spoken dialect density on writing and on the codevelopment of reading and writing in African American English-speaking (AAE) children from first through fifth grades. The sample included 869 students, ranging in age from 5.8 to 12.5 years. Results indicated that dialect density had a negative influence concurrently and longitudinally on reading and writing in AAE-speaking children. High dialect users tended to have weak reading and writing skills and heavier dialect density slowed growth in reading and writing. However, this effect was moderated by the effects of reading and writing on each other. Reading had a facilitative effect on writing even in the presence of heavy dialect use.
A gender-specific model of trauma and victimization in incarcerated women

Trauma, victimization and risk factors associated with women’s pathways to crime have been widely discussed. The focus of this manuscript is on trauma and victimization’s role in the development of...
Biologic Prescribing Patterns Among Mount Sinai Psoriasis Patients: Results of a Retrospective Chart Review

Objectives : Psoriasis is a painful and chronic inflammatory skin condition that not only impacts the quality of life of patients but is also a socioeconomic burden due to the cost of treatment, particularly with biologic treatments. The purpose of the study is to understand biologic prescribing patterns among Mount Sinai psoriasis patients and assess its relationship to insurance policy, which may limit treatment access. Methods: This study reviewed randomized, de-identified charts of psoriasis patients in a nine physician academic practice at Mount Sinai (New York, United States) with the following insurers: Aetna, Blue Cross Blue Shield, Empire Blue Cross Blue Shield, Medicare A&B, and United Healthcare, treated with the following biologics: secukinumab, etanercept, adalimumab, infliximab, brodalumab, ustekinumab, ixekizumab and guselkumab. A chi-square test was performed to compare prescribed biologics by insurance policy. Results: Ustekinumab was the most prescribed biologic treatment across all the insurance plans. There were also disproportionate prescriptions of certain biologics for patients under particular insurance plans. Etanercept, brodalumab, and infliximab were the least prescribed biologics. Conclusion: Results highlight certain patterns in the prescribed biologics of Mount Sinai patients. Prescribed biologics tend to vary by different insurers. However, ustekinumab was the most frequently prescribed biologic among all insurers, though it is not the most efficacious biologic based on PASI responses. Future research should be conducted to assess how differences in insurance policies (e.g., cost to patient) affect biologic prescribing.
Dietary factors in experimental autoimmune encephalomyelitis and multiple sclerosis: A comprehensive review:

Background:Dietary intervention in multiple sclerosis carries potential therapeutic implications. While studies utilizing animal models of multiple sclerosis (MS) have demonstrated intriguing findi...
Tracking Hurricane Dorian in GDELT and Twitter

Abstract. GDELT is a machine coded database of events that uses both foreign and domestic news feeds and contains over a quarter of a billion worldwide event records categorized into three hundred categories. This paper compares the spatial footprint of GDELT event mentions with those of event related geo-tagged tweets for Hurricane Dorian in the South-Eastern United States. Besides examining event related GDELT and Twitter data abundance, the study relates areas of elevated GDELT news and tweeting activities to the locations of the hurricane track over a six-day period, and statistically analyzes distances between daily GDELT event mentions and tweets, and the hurricane center on different days. It assesses the potential role of the geographic coverage of the cone in hurricane prediction maps on the level of event related news and tweeting activities. The study also discusses pros and cons of both data sources for event tracking with regards to data abundance, spatial and temporal resolution, and thematic accuracy.
Case Discussion and Literature Review: Cancer Immunotherapy, Severe Immune-Related Adverse Events, Multi-Inflammatory Syndrome, and Severe Acute Respiratory Syndrome Coronavirus 2

Pediatric, adolescent and young adult (AYA) patients receiving novel cancer immunotherapies may develop associated toxicities with overlapping signs and symptoms that are not always easily distinguished from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection/clinical sequelae. We describe 2 diagnostically challenging cases of SARS-CoV-2 and Multi-Inflammatory Syndrome-Adult (MIS-A), in patients with a history of acute lymphoblastic leukemia following cellular therapy administration and review evolving characterization of both the natural course of SARS-CoV-2 infection and toxicities experienced in younger cancer immunotherapy patients. Vigilant monitoring for unique presentations and epidemiologic surveillance to promptly detect changes in incidence of either condition may be warranted.