cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract A24: Establishing feasibility of a new cohort: The 10,000 Families Study

Due to evolving population demographics, altered exposures, and new technology, new cohorts need to be initiated. Here we report our efforts from a pilot cohort study of the 10,000 Families Study (10KFS). The goal of the pilot is to establish the infrastructure, protocols, and standard operating procedures for a larger study that would provide the data to further our understanding of the determinants of health across the life course and intergenerational transmission of environmental, genetic, and epigenetic risk factors. We have focused on cancer, as this is the leading cause of death in Minnesota. Data collection methods include online questionnaires and attendance at a health fair for various physical and biologic measurements. For this family-based study, a family is eligible if at least one member of two, preferably three, generations enrolls, and each member is willing, or willing for their child(ren), to provide DNA from blood or saliva. To facilitate eventual scale-up of the cohort, we developed and implemented a database system to electronically manage eligibility screening, enrollment, questionnaire administration, and health fair scheduling. Family enrollment is initiated when an index participant is screened for eligibility online. When the database detects a new eligible index participant, custom scripts execute a set of actions that includes sending emails to the index participant with instructions for family expansion, sending links for the online questionnaire to all family members who join, scheduling appointments at upcoming health fairs, and any reminders for steps not completed. Automated reports are generated nightly to update the investigator website about enrollment, data completeness, and follow-up. We have pilot tested our recruitment procedures with individuals attending the 2017 and 2018 Minnesota State Fair, one of the largest public gatherings in the upper Midwest. To date, 1,273 index participants have been screened. Of these, 151 successfully enrolled another eligible family member for a total of 519 participants. Thus far, 138 participants have attended a health fair. Participant ages range from less than a year to over 90 (median 48 among adults and 7 among children). Next, we intend to expand recruitment methods including traditional and social media, develop an electronic remote consent process, establish electronic feeds of medical records from Minnesota healthcare systems, and create linkages with the state’s cancer registry. Citation Format: DeAnn Lazovich, Colin Campbell, Heather Nelson, Jen Poynter, Anna Prizment, Sara Putnam, Cavan Reilly, Michelle Roesler, Logan Spector, Bharat Thyagarajan. Establishing feasibility of a new cohort: The 10,000 Families Study [abstract]. In: Proceedings of the AACR Special Conference on Modernizing Population Sciences in the Digital Age; 2019 Feb 19-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(9 Suppl):Abstract nr A24.
Whole-genome analysis of TET dioxygenase function in regulatory T cells.

TET methylcytosine dioxygenases are essential for the stability and function of regulatory T cells (Treg cells), which maintain immune homeostasis and self-tolerance and express the lineage-determining transcription factor Foxp3. Here, we use whole-genome analyses to show that the transcriptional program and epigenetic features (DNA modification, chromatin accessibility) of Treg cells are attenuated in the absence of Tet2 and Tet3. Conversely, the addition of the TET activator vitamin C during TGFβ-induced iTreg cell differentiation in vitro potentiates the expression of Treg signature genes and alters the epigenetic landscape to better resemble that of Treg cells generated in vivo. Vitamin C enhances IL-2 responsiveness in iTreg cells by increasing IL2Rα expression, STAT5 phosphorylation, and STAT5 binding, mimicking the IL-2/STAT5 dependence of Treg cells generated in vivo. In summary, TET proteins play essential roles in maintaining Treg molecular features and promoting their dependence on IL-2. TET activity during endogenous Treg development and potentiation of TET activity by vitamin C during iTreg differentiation are necessary to maintain the transcriptional and epigenetic features of Treg cells.
Redesigning a Schwartz Center Rounds LibGuide to Support Compassionate Health Care

A team of Kaiser Permanente hospital librarians redesigned an existing Schwartz Center Rounds (SCR) LibGuide to provide an improved level of support to local medical center Schwartz Center Rounds C...
Phonological working memory and central executive function differ in children with typical development and dyslexia

The primary purpose of this study was to compare the working memory performance of monolingual English-speaking second- grade children with dyslexia (N = 82) to second-grade children with typical development (N = 167). Prior to making group comparisons, it is important to demonstrate invariance between working memory models in both groups or between-group comparisons would not be valid. Thus, we completed invariance testing using a model of working memory that had been validated for children with typical development (Gray et al., 2017) to see if it was valid for children with dyslexia. We tested three types of invariance: configural (does the model test the same constructs?), metric (are the factor loadings equivalent?), and scalar (are the item intercepts the same?). Group comparisons favoured the children with typical development across all three working memory factors. However, differences in the Focus-of-Attention/Visuospatial factor could be explained by group differences in non-verbal intelligence and language skills. In contrast, differences in the Phonological and Central Executive working memory factors remained, even after accounting for non-verbal intelligence and language. Results highlight the need for researchers and educators to attend not only to the phonological aspects of working memory in children with dyslexia, but also to central executive function.
The use of competitive PCR mimic to evaluate a Limulus lambda phage genomic DNA library.

1. A λ phage genomic DNA library for Limulus (L.) polyphemus brain was constructed using the λGEM-12 vector and the host strain KW251. 2. The primary library contained approximately 1.275 × 106 independent clones, increasing upon amplfication to 6.66 × 109 pfu/ml in a total volume of 58 ml. 3. A total of 28 clones was randomly chosen for a determination of the average size of inserts in the library. All clones contained inserts and the average size was 14.9 kb, ranging from 11.7 to 28.0 kb. The library provides a 10-fold equivalent of the L. polyphemus genome. 4. A new approach for evaluating a genomic DNA library was developed, in which competitive PCR MIMIC was employed to determine the target gene copy number in both constructed library and brain genomic DNA. The putative protein kinase C e (PKCe) was selected as the target gene because its partial sequence of cDNA was recently cloned from L. polyphemus brain in our laboratory (Cao et al., 1998). A 419-bp fragment of nonhomologous sequence derived from putative PKCe and a 306-bp fragment from plasmid pUC 18 were generated for use as target and competitor in PCR MIMIC, respectively. 5. Within the genomic library DNA, a 0.8 value was obtained for the copy number of the putative PKCe gene that was detected in 0.1 amol of one equivalent L. polyphemus genome in terms of the average recombinant molecular weight. In the genomic DNA, a single copy of putative PKCe was found in 0.1 amol of one coverage for the L. polyphemus genome. Thus, it was implied that nearly 80% genetic resource was incorporated into the library. This percentage was termed the incorporation rate. 6. Based on these findings, we suggest that the incorporation rate is an essential factor for evaluating genomic libraries, particularly, when using partial digestion with restriction enzymes for library construction.
Mathematical models of cerebral hemodynamics for detection of vasospasm in major cerebral arteries.

BACKGROUND Vasospasm is a common complication of aneurismal subarachnoid hemorrhage (SAH) that may lead to cerebral ischemia and death. The standard method for detection of vasospasm is conventional cerebral angiography, which is invasive and does not allow continuous monitoring of arterial radius. Monitoring of vasospasm is typically performed by measuring Cerebral Blood Flow Velocity (CBFV) in the major cerebral arteries and calculating the Lindegaard ratio. We describe an alternative approach to estimate intracranial arterial radius, which is based on modeling and state-estimation techniques. The objective is to obtain a better estimation than that offered by the Lindegaard ratio, that might allow for continuous monitoring and possibly vasospam prediction without the need for angiography. METHODS We propose two new models of cerebral hemodynamics. Model 1 is a more general version of Ursino's 1991 model that includes the effects of vasospasm, and Model 2 is a simplified version of Model 1. We use Model 1 to generate Intracranial Pressure (ICP) and CBFV signals for different vasospasm conditions, where CBFV is measured at the middle cerebral artery (MCA). Then we use Model 2 to estimate the arterial radii from these signals. FINDINGS Simulations show that Model 2 is capable of providing good estimates for the radius of the MCA, allowing the detection of the vasospasm. These changes in arterial radius are being estimated from measurements of CBFV, and CBF is never being measured directly. This is the main advantage of the model-based approach where several interrelations between CBFV, ABP and ICP are taken into account by the differential equations of the model. CONCLUSIONS Our results indicate that arterial radius may be estimated using measurements of ABP, ICP and CBFV, allowing the detection of vasospasm.
Parent feeding behavior and child appetite: associations depend on feeding style.

Objective Eating behavior traits measured in early life predict eating behavior and weight trajectories later in development, and may be associated with certain parental feeding behaviors. Our goal was to investigate the relationship between a range of feeding behaviors, and preschoolers' appetitive traits. Method Four hundred thirty-nine parents of UK 3–5 year olds completed scales measuring authoritarian vs. authoritative forms of limiting (Restriction vs. Monitoring) and promoting (Pressuring vs. Prompting) intake, as well as Emotional and Instrumental Feeding. Parents also completed scales measuring child Food responsiveness and Satiety responsiveness. Child BMI z-scores were calculated based on measured heights and weights. Results Parental Restriction was significantly associated with greater child Food responsiveness (p < .001), but parental Monitoring was not. Parental Pressuring was significantly associated with greater child Satiety responsiveness (p < .001), while parental Prompting was not. Parental Instrumental and Emotional feeding were both associated with greater child Food responsiveness (p < .001). All relationships were independent of child BMI z-score. Discussion Prospective data are needed to determine whether the parent–child feeding relationships identified here promote, or protect against, the development of eating pathology in children. However, our results suggest that cross-sectional associations depend on the style (e.g., authoritarian vs. authoritative), as well as the type of feeding behavior measured. © 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:705–709)
Beiträge zur Shannonschen Informationstheorie im Falle nichtstationärer Kanäle

Coding theorem and strong converse of the coding theorem are proved for nonstationary semicontinous channels and for almost periodic channels with unknown phase. More general cases are considered.
Isolation of the progenitor cells of the sympathoadrenal lineage from embryonic sympathetic ganglia with the SA monoclonal antibodies

Our previous articles in this series described the production of five monoclonal antibodies (SA1-5) that bind to adrenal chromaffin cells and to cells in embryonic sympathetic ganglia and adrenal primordia (Carnahan and Patterson, 1991), and the downregulation of the sympathoadrenal (SA) antigens in vivo as neuronal markers begin to be expressed (Anderson et al., 1991). These results support the hypothesis that sympathetic neurons and adrenal chromaffin cells are derived from a common embryonic progenitor that displays both neuron- and chromaffin cell-specific markers. We have taken advantage of the fact that at least some of the SA antigens are expressed on the cell surface to isolate SA+ cells from embryonic day 14.5 rat superior cervical, sympathetic ganglia by fluorescence-activated cell sorting. This population of cells is significantly enriched in the expression of markers (tyrosine hydroxylase and neurofilament) found in the putative progenitors in situ. Growth in glucocorticoid maintains the expression of the SA antigens in the sorted cells and induces the chromaffin cell marker enzyme phenylethanolamine N-methyl transferase. In contrast, growth of the sorted cells in basic fibroblast growth factor, NGF, and insulin results in the rapid loss of SA 1 expression and the outgrowth of neurites. The ability to manipulate the fate of the SA+ cells in vitro confirms the suggestion from the in vivo observations that the SA+ cells in the ganglia are at least bipotential progenitors, capable of differentiating along the chromaffin or neuronal pathways.
Control of land‐ocean temperature contrast by ocean heat uptake

[1] We show that the ratio of observed annual-mean land temperature change to ocean surface temperature change, ϕ, has remained almost constant during 1955–2003. This is the case, despite most of the heat capacity of the climate system lying in the oceans, and rapid variations in climate forcing. Examining seven General Circulation Models (GCMs), we find land and ocean temperature behavior comparable to observations in six cases. For three models that reproduce observed ϕ and for which we have data, we find no significant changes in future ϕ under the SRES A1B scenario. We suggest that variations in land-ocean heat flux primarily balanced by ocean heat uptake are sufficient to maintain constant ϕ. This flux is present in the six GCMs that resemble observations, suggesting that observed ϕ may remain constant into the future, even if radiative forcing is markedly different than in the past.
The Link Smoothing Game

AbstractWe introduce a topological combinatorial game called the LinkSmoothing Game. The game is played on the shadow of a link dia-gram and legal moves consist of smoothing precrossings. One player’sgoal is to keep the diagram connected while the other player’s goalis to disconnect the shadow. We make signi cant progress towards acomplete classi cation of link shadows into outcome classes by capital-izing on the relationship between link shadows and the planar graphsassociated to their checkerboard colorings. 1 Introduction. Recently, several topological combinatorial games related to knots wereintroduced in [2]. Inspired by the discovery of these games, we intro-duce a new game called the Link Smoothing Game.Suppose D is a connected diagram of a link shadow, that is, aconnected link diagram where under- and over-strand information isunspeci ed at the crossings. Two players take turns selecting a pre-crossing (i.e. an undetermined crossing) of the shadow and replacingit with either a horizontal or a vertical smoothing, as in Figure 1.Figure 1 { Smoothing a precrossing.The goal of one player is to keep the diagram connected while thegoal of the other player is to disconnect the diagram. The player with
Fundamentals of Electrical Stimulation

Abstract Voltage-gated Na+ channels exhibit three states: closed activatable, open activated, and closed inactivatable. At resting membrane potentials, about 75% of the channels are in the closed activatable state. Depolarizing the axon membrane causes the activatable channels to open, allowing Na+ to move along a voltage and concentration gradient, which further depolarizes the membrane and results in a propagated action potential. At the nerve terminal, neurotransmitters are released by the invading action potential to act on cell receptors adjacent to the terminal or systemically if the transmitter is released into the blood. Regulated current pulses are the preferred method of electrically activating a nerve because the induced field remains constant during the stimulus pulse. When voltage pulses are used, the injected current is a function of electrode–tissue impendence and the current decays with time, meaning that the excitatory field decays with time. Cathodic currents are more effective in initiating propagating action potentials on axons because depolarizing currents are more concentrated near the electrode. Depolarizing currents are more widely distributed when anodic stimulation is applied, which means that larger currents must be used to reach threshold depolarization with anodic stimuli. Short-duration high-amplitude stimuli require less charge to initiate a propagated action potential than do low-amplitude long-duration stimuli. In general, less charge injection generates fewer electrochemical reaction products and draws less power. The effect of an applied stimulus is always greater on larger-diameter axons than on smaller-diameter axons, because internodal spacing is greater in larger axons than it is in smaller ones. The effect of the applied stimulus is always greater on axons that are closer to the electrode than on axons farther from the electrode. This means that when a cathodic stimulus is applied to an axon, the threshold for activation of larger fibers will lower than that required to activate smaller fibers, if they are at the same distance from the electrode. Driving the electrode interface potential anodically can result in loss of electrode metal and the creation of metallic salts that are powerful oxidizing agents. To avoid oxidizing the electrode, the amount of charge injected in the anodic phase may be limited by using imbalanced biphasic pulses or lower charge injection with balanced biphasic stimuli.
QUANTUM FIELD THEORY OF COOPERATIVE ATOM RESPONSE : LOW LIGHT INTENSITY

We study the interactions of a possibly dense and/or quantum degenerate gas with driving light. Both the atoms and the electromagnetic fields are represented by quantum fields throughout the analysis. We introduce a field-theory version of Markov and Born approximations for the interactions of light with matter, and devise a procedure whereby certain types of products of atom and light fields may be put to a desired, essentially normal, order. In the limit of low light intensity we find a hierarchy of equations of motion for correlation functions that contain one excited-atom field and one, three, five, etc., ground-state atom fields. It is conjectured that the entire linear hierarchy may be solved by solving numerically the classical equations for a coupled system of electromagnetic fields and charged harmonic oscillators. We discuss the emergence of resonant dipole-dipole interactions and collective linewidths, and delineate the limits of validity of the column density approach in terms of noncooperative atoms by presenting a mathematical example in which this approach is exact.
Variance of the range of a random walk

Tn, the expectation of the square of the number of distinct sites occupied by a random walk in steps 1 throughn, is obtained from its relation to the dual first occupancy probabilityFij(x, x′), and the latter quantity is obtained from a recursion with the first occupancy probabilityF k (x″). The varianceVn of the number of distinct sites occupied is calculated directly from Tn; the procedure is illustrated by the calculation ofVn (4096 /⩾n) and the derivation of asymptotic expansions forVn for a particular random walk in dimensions 1 through 3.
Aggregation and vertical migration behavior of Euphausia superba

Aggregation and vertical migration behavior of Euphausia superba were studied in Marguerite Bay and its vicinity west of the Antarctic Peninsula using a vessel-mounted, Acoustic Doppler Current Profiler, and a Multiple Opening and Closing Nets and Environmental Sensing System, during the 2001 and 2002 fall US Southern Ocean GLOBEC project cruises. The kinematics of aggregation behavior of E. superba associated with diel migration is studied using observations of their abundance and swimming velocities: during the day, E. superba reduce their swimming at a depth of 250 m; and at night, they swim randomly at their cruising speed in the upper part of an aggregation near the surface, and coherently as schooling in the lower part of an aggregation. The causes for the aggregation behavior and vertical migration of krill are explored by examining the relationship with ice coverage and presence of predators. The motion of euphausiids is further analyzed in terms of kinetic energy and force balance, leading to new considerations of mathematical theories and models of aggregation behavior. The results show a diel variation of the energy demand for maintaining their locomotion. The horizontal scale of an aggregation is studied in conjunction with horizontal gradients of currents. Results indicate that the swimming capability of euphausiids determines the maintenance of an aggregation in the mesoscale circulation field.
Online integration of scheduling and control for cyclic production in CSTR

Scheduling and control problems are traditionally solved sequentially. However, integration of both problems can result in a better overall performance. A main challenge in the integration is the solution to the derived mixed-integer dynamic optimization (MIDO) problem. As a consequence, most integration methods can only be applied offline. To overcome the challenge, we present a novel integration method, which simultaneously determines the PI controller design and the scheduling decisions. The method decomposes the MIDO problem. The dynamic optimization for each transition can be solved independently offline. A set of controller candidates are generated and stored. Then the integrated problem is transformed into a mixed-integer nonlinear fractional programming problem of scheduling with controller selection. An efficient global optimization method based on the Dinkelbach's algorithm is developed, which enables the online implementation. The numerical study on a cyclic production model in a CSTR shows that the proposed integration method reduces the cost rate by 19.7% comparing with the traditional sequential method.
Assessment and therapeutic intervention of black children.

The need for a balance in addressing cultural differences and similarities in the diagnostic assessment and treatment of black children is the major focus of this article. Selected illustrations from the literature and from the author's professional experiences point out some of the pitfalls, as well as steps to take that will promote accuracy in diagnosis and effective treatment. Several identified reference points are viewed to be of considerable significance in our multicultural society, and are advocated as warranting attention in the psychiatric care of any child.
Microvascular Permeability of Albumin, Vascular Surface Area, and Vascular Volume Measured in Human Adenocarcinoma LS174T Using Dorsal Chamber in SCID Mice

A novel method was developed to measure the effective permeability of microvessels in three-dimensional tumors. Two unique features characterized our approach: (i) Texas Red (with peak excitation and peak emission wavelengths of 596 and 615 nm, respectively) was used for macromolecular labeling, to minimize the absorption of fluorescence light by hemoglobin in blood. Thus the tumor tissue could be treated approximately as a uniform medium with respect to light absorption. (ii) The light absorption and scattering in tumor tissues were accounted for in relating the fluorescence intensity to the amount of Texas Red-labeled macromolecules extravasated. The vascular permeability of Texas Red-labeled bovine serum albumin in human tumor xenograft LS174T implanted in dorsal skin-fold chamber in severe combined immunodeficient mice was measured using this method. The average permeability-surface area product per unit volume (PS/V, x 10(-4) sec-1) and the average effective permeability (P, x 10(-7) cm/sec) were found to be 1.26 +/- 0.72 and 6.06 +/- 4.30, respectively; the fractional volume of tumor vessels (Vves/V, %) was found to be 9.2 +/- 2.9, and the total surface area of vessels per unit volume (S/V, cm2/cm3) was found to be 239 +/- 82. The errors in the estimation of these parameters are discussed. The method described here is general and can be adapted to study the microvascular permeability of superficial tumors in various organs in patients or animals.
Which endogenous depressive symptoms relate to REM latency reduction

Abstract In most research dealing with biological abnormalities in depression, the clinical diagnosis of depression is made and the occurrence of a biological abnormality, for example, reduced REM latency, is documented. In this study, that design was reversed; REM latency was used as a grouping variable to assess empirically the “biological” priority of Research Diagnostic Criteria endogenous symptoms. We found that terminal insomnia, pervasive anhedonia, unreactive mood, and appetite loss were most likely to discriminate among “reduced” and “nonreduced” REM latency depressions at various threshold values. Contrary to expectation, diurnal mood variation was found equivalently in all categories of REM latency studied. Implications for clinical decision making based on endogenous symptoms are discussed.
Life-history patterns of two Southern CaliforniaNebalia species (Crustacea: Leptostraca): the failure of form to predict function

Laboratory and field studies onNebalia hessleri andN. daytoni off the toast of San Diego, Southern California, showed that although morphologically similar, the habitats, behavior, and natural history of these two species are surprisingly different. In laboratory experiments, Bach species avoided the other's habitat (sand and mats of macrophyte detritus), and in the field, transplanted individuals failed to survive in the other species' habitat.N. hessleri, which inhabits subtidal mats of macrophyte detritus, survived and reproduced well in the laboratory, was iteroparous, and a large percentage of adults were male. This species occurred at very high densities in the field, and ate essentially everything offered in the laboratory, with a diet in the field consisting largely of plant detritus and carrion. The other species,N. daytoni, differed in nearly every way, it inhabited organically impoverished sands, survived poorly in the laboratory, was apparently semelparous, and a small percentage of the adult population was male.
Multi-Spacecraft Observations: Stream Interactions and Associated Structures

The stream interaction region (SIR), formed when a fast stream overtakes a preceding slow stream, is the predominant large-scale solar wind structure at this early phase of the STEREO mission. Using multi-spacecraft observations from STEREO A and B, ACE, Wind, and Ulysses in 2007, we analyze three stream interaction events in depth in May, August, and November of 2007, respectively, when the spacecraft had quite different spatial separations. We attempt to determine the causes of the differences in the SIR properties, whether they are spatial or temporal variations, and also to examine the steepening or widening of the SIR during its radial evolution. The presence and characteristics of associated shocks, the relation to the heliospheric current sheet, and other structures are also studied.
Realization algorithms and approximation methods of bilinear systems

High-dimensional mathematical models of bilinear control systems are often not amenable due to the difficulty in implementation. In this paper, we address the problem of order-reduction for both discrete and continuous time bilinear systems. Two model-reduction algorithms are presented; one is based on the singular value decomposition of the generalized Hankel matrix (the Hankel Approach) and the other is based on the eigenvalue / eigenvector decomposition of the product of reachability and observability Gramians (the Gramian Approach). Equivalence between these two algorithms is established. The main result of this paper is a systematic approach for obtaining reduced-order bilinear models. Furthermore, the bilinear reachabiiity and observability Gramians are shown to be obtainable from the solutions of generalized Lyapunov equations. Computer simulations of a neutron-kinetic system are presented to illustrate the effectiveness of the proposed model-reduction algorithms.
Considerations for Neuroprotection in the Traumatic Brain Injury Population

Traumatic brain injury can occur very quickly, but the sequelae of the injury can be life ending or life altering. Aside from prevention, the primary injury cannot be controlled; however, health care workers can influence the amount of secondary injury to the brain. This article describes potential neuroprotective methods, such as cooling, craniectomy, and medications, to help to save the brain.
Conceptualizing the Roles of Mentor Teachers during Student Teaching.

The field-based mentoring of student teachers is often an idiosyncratic and nuanced practice in which mentors' conceptualizations of their interactions with student teachers are generated through personal experiences with teacher education. If teacher educators and programs are to strengthen the tie between campus and field-based teacher education, in effect bridging the perceived disconnect of campus-based learning and the “realities” of the classroom, acknowledging these divergent perspectives is a first step in providing transformative learning experiences for student teachers. To that end, in this article the authors use recent empirical research into the school-based mentoring of student teachers to describe three conceptions of mentor teacher roles and responsibilities. Centered in the notion that mentoring is often a socially constructed practice, these roles include a consideration of the mentor teacher as (1) instructional coach, (2) emotional support system, and (3) socializing agent. Through a ...
Ultra-low background germanium spectrometry: Techniques and results

Abstract Ultimate sensitivity in gamma-ray spectrometry can be attained only by reducing background. The relative magnitudes of various sources of background and methods for reducing them in germanium gamma-ray spectrometers are given. Results are presented at sensitivity levels so low that double-beta decay of 76Ge constitutes an unwanted background.
WE-E-17A-03: FDG-PET-Based Radiomics to Predict Local Control and Survival Following Radiotherapy

Purpose: An exploding field in cancer research is “radiomics,” based on the hypothesis that there is statistical (hidden) information in medical images that is prognostic or predictive of outcomes. Our group has developed an efficient pipeline to extract and analyze quantitative image features from medical images as related to outcomes or diagnosis. In this work, we summarize our previous studies with positron emission tomography (PET) images and show the potential of the use of radiomics for outcomes research. Methods: We analyzed two cancer datasets, each consisting of pre-radiotherapy-treatment PET scans: 163 T1-2N0M0 non-small cell lung cancer (NSCLC) patients and 174 head and neck (H and N) cancer patients with stage III–IV. The PET scans were converted to Computational Environment for Radiological Research (CERR) format, and CERR was used to generate 24 shape, texture, and intensity-histogram based image features. Data-mining and logistic regression methods were then used to model local failure (LF) and overall survival (OS). Unbiased estimates of performance were generated using leave-one-out cross-validation (LOOCV). Results: For predicting LF, the models with biologically equivalent dose (BED) and TLG (metabolic tumor volume (MTV) x SUVmean) in NSCLC, and skewness and MTV in H and N, achieved the best performance with AUC=0.818more » (p<0.0001) and AUC=0.826 (p=0.0002), respectively. For predicting OS, the models with kurtosis and volume in NSCLC and SUVmax and homogeneity in H and N achieved the best performance with AUC=0.706 (p<0.0001) and AUC=0.656 (p=0.0003), respectively. On LOOCV, all these models retained significant predictive power. Interestingly, MTV was highly correlated with LF in both sites. Conclusion: PET-based imaged features are promising tools for improving treatment management decision making. Much more research is needed to identify optimal radiomics metrics and to correlate imaging phenotype with other clinical or genomic information.« less
Left hemisphere specialization for the control of voluntary movement rate

Although persuasive behavioral evidence demonstrates the superior dexterity of the right hand in most people under a variety of conditions, little is known about the neural mechanisms responsible for this phenomenon. As this lateralized superiority is most evident during the performance of repetitive, speeded movement, we used parametric rate variations to compare visually paced movement of the right and left hands. Twelve strongly right-handed subjects participated in a functional magnetic resonance imaging (fMRI) experiment involving variable rate thumb movements. For movements of the right hand, contralateral rate-related activity changes were identified in the precentral gyrus, thalamus, and posterior putamen. For left-hand movements, activity was seen only in the contralateral precentral gyrus, consistent with the existence of a rate-sensitive motor control subsystem involving the left, but not the right, medial premotor corticostriatal loop in right-handed individuals. We hypothesize that the right hemisphere system is less skilled at controlling variable-rate movements and becomes maximally engaged at a lower movement rate without further modulation. These findings demonstrate that right- and left-hand movements engage different neural systems to control movement, even during a relatively simple thumb flexion task. Specialization of the left hemisphere corticostriatal system for dexterity is reflected in asymmetric mechanisms for movement rate control.
Peculiar Constraints on Life Histories Imposed by Protective or Nutritive Devices for Embryos

SYNOPSIS. A general constraint for sexually produced offspring of multicellular organisms is that they must begin as a single cell (lest they be chimeric) and that the embryos that produce multicellular structures perform many functions less capably than more developed individuals. Beyond this limitation, predictive models have examined optimized tradeoffs between number of offspring and size of offspring. Broadly applicable predictions have been sought, and two general expectations have resulted. (1) Optimal parental investment per offspring should not be affected by total investment per clutch when offspring size is much smaller than clutch size. (2) Selection should usually favor an optimal size of offspring rather than varied sizes within a clutch. However, constraints intrinsic to mechanisms of parental protection or provisioning may change these predicted outcomes of selection on life history traits. (1) Provisioning and packaging of protected embryos may introduce dependence of offspring size on adult size or clutch size, (a) Clutches of embryos are a large mass of metabolizing tissue without a circulatory system but with requirements for gas exchange; when dissolved gases are transported by interstitial flow between embryos, requirements for supply of oxygen may require larger offspring in thicker and hence more massive clutches, (b) Offspring size can become dependent on adult size through capsule size or size of the birth canal, and offspring size is thereby linked to clutch mass when clutch mass increases with adult size. (2) Random placement of protected embryos may increase variation around an optimum size or quality of offspring. Possible examples are (a) determination and packaging of nurse eggs that will be consumed by embryos and (b) hormonal interactions among offspring in a uterus. Constraints that violate general expectations and arise from varied and specific mechanisms of parental protection or provisioning may be common.
The metrics of horizontal saccadic eye movements in normal humans

Abstract The metric characteristics of horizontal saccadic eye movements are defined and analyzed following detailed electro-oculographic recordings in 25 normal subjects. Small (10°) saccades are usually normometric, but accuracy decreases with larger amplitudes producing undershoots of the fixation targets. Approximately 20 per cent of 20° and 30° saccades are transiently dysconjugate (1°–3°) at termination. The most common dysconjugate pattern demonstrates excessive convergence due to momentary overshooting of the adducting eye or undershooting of the abducting eye. The authors question an inviolate interpretation of Hering's Law and discuss the mechanisms of the dysconjugacies in light of current concepts of the neurophysiology of eye movements.
On the feasibility of using conceptual modeling constructs for the design and analysis of XML data

XML is one of the most widely accepted data representation languages in today's Internet-dominated Computing. While most XML data on the net today use commonly known structures, the power of XML lies in the ability to develop application-specific structures and models. XER (Extensible Entity Relationship) is a conceptual modeling methodology that uses visual constructs reminiscent of Entity Relationship (ER) in the logical design of XML instead of relying on the text-based DTD (Document Type Definition) and XML Schema notations. In this paper, we demonstrate how XER can be used to effectively design and analyze applications that use XML data. We also compare XER against other design constructs to demonstrate that a conceptual modeling artifact can potentially be superior to other artifacts for modeling XML structures, by significantly improving accuracy, efficiency and user satisfaction.
Implementing classroom research in a state university: A developmental process

By building on the successes of existing faculty development efforts, one administrator and a handful of faculty were able to quickly establish a vital, interdisciplinary Classroom Research program.
Visual symbol acquisition by students with autism

Abstract Given the need to help develop communication skills in individuals with autism, an examination of visual symbol systems is critical. In this study, I focused on the exploration of a hierarchy of visual symbol systems that may aid practitioners in selecting more readily acquired symbol systems. Although evidence suggests that persons with cognitive disabilities attach meaning more readily to symbol systems that display higher levels of iconicity, it is not clear that this same hierarchical progression exists for persons with autism. I used a modified multiple baseline with four students with autism, ranging in ages from 7 to 13 years, to investigate the number of trials to criterion for five visual symbol sets: (a) photopictorial, (b) rebus, (c) Blissymbolics, (d) orthography, and (e) Premack‐type tokens. All four students reached criterion with fewer trials in systems that had a higher degree of iconicity.
Nitrogen best management practice for citrus trees: I. Fruit yield, quality, and leaf nutritional status

Abstract Elevated levels of nitrate-nitrogen (NO3-N) in the surficial aquifer above the drinking water quality standard, i.e. maximum contaminant limit (MCL; 10 mg L−1), have been reported in some part of central Florida citrus production regions. Soils in this region are very sandy (sand content >95%), hence are vulnerable to leaching of soluble nutrients and chemicals below the rooting depth of the trees. The objective of this research was to develop N and irrigation best management practices for citrus in sandy soils to maintain optimal crop yield and quality, and to minimize potential leaching of nitrate below the root zone. Six years of field experiment was conducted in a high productive (mean fruit yield > 80 Mg ha−1yr−1) >20-year-old ‘Hamlin’ orange trees [Citrus sinensis (L.) Osbeck] on ‘Cleopatra mandarin’ (Citrus reticulata Blanco) rootstock grown on a well drained Tavares fine sand (hyperthermic, uncoated, Typic Quartzipsamments) in Highland county, FL. Nitrogen rates ranged from 112 to 280 kg ha−1 yr−1 applied as fertigation (FRT), water soluble granular (WSG), 50:50 mix of FRT and WSG, and controlled-release fertilizer (CRF). Tensiometers were used to monitor the soil water content as a basis to schedule optimal irrigation. Fruit yield response over the entire range of N rates was greater for the FRT and WSG sources as compared to that for the WSG + FRT or CRF sources. Using the regression analysis of the fruit yield in relation to N rate, the optimum N rate appeared to be at 260 kg ha−1 yr−1. Based on fruit production response in this study, the N requirement for production of 1 Mg of fruit varied from 2.2 to 2.6 kg across four N sources. This study demonstrated an increased N uptake efficiency, as a result of best management of N and irrigation applications. The optimal N and K concentration in the 4–6-month-old spring flush leaves were 26–30, and 15–18 g kg−1, respectively. However, fruit yield response showed no significant relationship with concentrations of P in the 4–6-month-old spring flush leaves over a range of 0.8–2.4 g kg−1. The results of fate and transport of N in soil and in soil solution with application of different rates and sources of N, and components of citrus tree N budget, are reported in a companion paper.
International collaboration in shared decision-making: The International Shared Decision Making (ISDM) conference history and prospects

Abstract Objective Analyze the role of collaboration in the International Shared Decision Making organization (ISDM). Methods Case study of the seven year history of ISDM as a professional network. Results The International Shared Decision Making meeting Conference (ISDM) has held four biennial meetings since its inception in 2001. It is a freestanding professional meeting, with no permanent institutional support and no formal governance structure. In both its history and its prospects, collaboration among attendees has been pivotal to its growth. It both attracts and holds its “members” through the strength of the relationships formed during and between meetings. Exchanges in ISDM are informational, collegial, and indirectly economic. Conclusion ISDM's future rests on keeping all three functions healthy. It must maintain a focus on putting the shared decision making work first through becoming a “worknet”. Technologies that promote shared decision making can then be assembled and developed that support transformation of health care. Practice Implications Innovative professional organizations need to develop their work through deliberate development of networking techniques to move innovation into practice.
Atomic-level description of ubiquitin folding

Equilibrium molecular dynamics simulations, in which proteins spontaneously and repeatedly fold and unfold, have recently been used to help elucidate the mechanistic principles that underlie the folding of fast-folding proteins. The extent to which the conclusions drawn from the analysis of such proteins, which fold on the microsecond timescale, apply to the millisecond or slower folding of naturally occurring proteins is, however, unclear. As a first attempt to address this outstanding issue, we examine here the folding of ubiquitin, a 76-residue-long protein found in all eukaryotes that is known experimentally to fold on a millisecond timescale. Ubiquitin folding has been the subject of many experimental studies, but its slow folding rate has made it difficult to observe and characterize the folding process through all-atom molecular dynamics simulations. Here we determine the mechanism, thermodynamics, and kinetics of ubiquitin folding through equilibrium atomistic simulations. The picture emerging from the simulations is in agreement with a view of ubiquitin folding suggested from previous experiments. Our findings related to the folding of ubiquitin are also consistent, for the most part, with the folding principles derived from the simulation of fast-folding proteins, suggesting that these principles may be applicable to a wider range of proteins.
Contribution of human uropontin to inhibition of calcium oxalate crystallization

Contribution of human uropontin to inhibition of calcium oxalate crystallization. Uropontin (UP) is known to inhibit the growth and nucleation of calcium oxalate monohydrate (COM) crystals, and it also impedes attachment of calcium oxalate crystals to cultured renal epithelial cells. However, its role in normal defense against renal crystallization, and in pathogenesis of nephrolithiasis is unclear. In this study we determined the effect of UP on aggregation of COM crystals as well as the inhibitory activity of UP on COM crystal growth and nucleation in a series of normal subjects, in order to assess the potential of UP as an important urinary inhibitor. The mean urinary excretion of UP measured by ELISA was 185 ± 12 nmol/24 hr (mean ± SEM ) with a mean urine UP concentration of 131 ± 13 n M . Uropontin isolated by immunoaffinity chromatography was a very potent inhibitor of COM crystal aggregation, with a mean UP concentration of 28 ± 4 n M required for a 50% reduction in aggregation. The kDa for COM crystal growth inhibition determined from Langmuir type isotherms was 21 ± 3 n M and the concentration required for 50% reduction in COM crystal growth rate was 16 ± 2 n M . Inhibition of secondary nucleation was measured at a single concentration of 200 n M , which reduced the nucleation rate to 42 ± 3% of control. Using a theoretical model of growth and aggregation inhibition at varying urine flow rates, we showed that inhibitory activity of UP would be significant for all subjects over a wide range of urine flow rates. Overall, UP is a potent inhibitor of COM aggregation as well as growth and nucleation. The urinary concentration of UP is in the range in which its contribution to inhibition of growth and aggregation are likely to be substantial. Thus, UP appears to be an important natural defense against renal crystallizations and nephrolithiasis.
Drug-induced long QT syndrome: hERG K+ channel block and disruption of protein trafficking by fluoxetine and norfluoxetine.

Background and purpose: Fluoxetine (Prozac s ) is a widely prescribed drug in adults and children, and it has an active metabolite, norfluoxetine, with a prolonged elimination time. Although uncommon, Prozac causes QT interval prolongation and arrhythmias; a patient who took an overdose of Prozac exhibited a prolonged QT interval (QTc 625 msec). We looked for possible mechanisms underlying this clinical finding by analysing the effects of fluoxetine and norfluoxetine on ion channels in vitro. Experimental approach: We studied the effects of fluoxetine and norfluoxetine on the electrophysiology and cellular trafficking of hERG K þ and SCN5A Na þ channels heterologously expressed in HEK293 cells.