cssi/SciSciGPT-SciSciNet huggingface dataset:
Association of gene coding variation and resting metabolic rate in a multi-ethnic sample of children and adults

Resting metabolic rates (RMR) vary across individuals. Understanding the determinants of RMR could provide biological insight into obesity and its metabolic consequences such as type 2 diabetes and cardiovascular diseases. The present study measured RMR using reference standard indirect calorimetry and evaluated genetic variations from an exome array in a sample of children and adults (N = 262) predominantly of African and European ancestry with a wide range of ages (10 – 67 years old) and body mass indices (BMI; 16.9 – 56.3 kg/m2 for adults, 15.1 – 40.6 kg/m2 for children). Single variant analysis for RMR identified suggestive loci on chromosomes 15 (rs74010762, TRPM1, p-value = 2.7 × 10−6), 1 (rs2358728 and rs2358729, SH3D21, p-values < 5.8x10−5), 17 (AX-82990792, DHX33, 5.5 × 10−5) and 5 (rs115795863 and rs35433829, C5orf33 and RANBP3L, p-values < 8.2 × 10−5). To evaluate the effect of low frequency variations with RMR, we performed gene-based association tests. Our most significant locus was SH3D21 (p-value 2.01 × 10−4), which also contained suggestive results from single-variant analyses. A further investigation of all variants within the reported genes for all obesity-related loci from the GWAS catalog found nominal evidence for association of body mass index (BMI- kg/m2)-associated loci with RMR, with the most significant p-value at rs35433754 (TNKS, p-value = 0.0017). These nominal associations were robust to adjustment for BMI. The most significant variants were also evaluated using phenome-wide association to evaluate pleiotropy, and genetically predicted gene expression using the summary statistics implicated loci related to in obesity and body composition. These results merit further examination in larger cohorts of children and adults.
Foundations on Strong Sand Overlying Weak Sand

The ultimate bearing capacity of footings on subsoil consisting of a strong sand layer overlying a weak sand deposit was investigated. A theory was developed and then results predicted. These predictions compared well with test data on model strip and circular footings resting on dense sand overlying loose, as well as, compact sand. Design charts are presented for use in practical application. Based on these charts, a procedure to determine the ultimate bearing capacity of a strip and circular footings on a strong sand layer overlying a weak sand deposit is described.
Major Pathophysiology in Prediabetes and Type 2 Diabetes: Decreased Insulin in Lean and Insulin Resistance in Obese.

Context Lowering of body mass index (BMI) to ≥25 kg/m2 as obesity by ADA suggests insulin resistance as a major mechanism of impaired glucose metabolism (IGM) in Asians. However, glimepiride, an insulin secretagogue, delayed onset of type 2 diabetes (DM2) from prediabetes (PreDM), indicating decreased insulin secretion (IS) as a major factor in lean (L; BMI < 27 kg/m2) subjects with IGM. Objective Assessment of IS and insulin resistance (IR) in L and obese (Ob; BMI ≥ 27 kg/m2) subjects with euglycemia (N), PreDM, and new onset DM2. Subjects Seventy-five men and 45 women ages 36 to 75 years were divided into six groups: LN, LPreDM, LDM2, ObN, ObPreDM, and ObDM2. Methods Determination of IS by insulinogenic indices (I/G) at fasting (FI/FG), first phase (∆I/∆G), and cumulative responses over 2 hours of OGTT (CRI/CRG), and IR by FIXFG, ∆IX∆G, and CRIXCRG. Changes in IS and IR for PreDM and DM2 were calculated as % fall and % rise, respectively, from levels in N. Results All indices of IS and IR were lower (P < 0.05) in L than corresponding Ob groups (P < 0.05). Moreover, decline in IS and rise in IR were progressive from N to PreDM (P < 0.05) and DM2 (P < 0.05) in both groups. However, the declines in IS were greater (P < 0.05) than rises in IR in LPreDM and LDM2. Whereas, the rises in IR were higher (P < 0.05) than declines in IS in ObPreDM and ObDM2. Conclusion In L, major mechanism of IGM is declining IS and not rising IR documented among Ob.
Abstract 2984: Optical-resolution Photoacoustic Microscopy: a Novel Imaging Modality Capable of Noninvasively Measuring Brain Oxygen Metabolism at the Microvascular Level during Focal Ischemia

Studying oxygen metabolism during brain ischemia has been limited by imaging modalities that have either low resolution but good tissue penetration, or high resolution requiring invasive preparations (open-skull windows). Here, we report a study of cerebrovascular oxygen metabolism in mouse focal ischemia using a novel minimally invasive, high-resolution technique known as optical-resolution photoacoustic microscopy (OR-PAM). Using OR-PAM, we serially imaged cortical vessels through the intact skull of Swiss Webster mice (n=3) before, during, and up to 72 hrs after a 1-hr intraluminal transient middle cerebral artery occlusion (MCAO). Vessels were imaged at 2 different wavelengths (532 & 563 nm) to quantify oxy-, deoxy-hemoglobin and oxygen saturation (sO 2 , Fig, A-C). Oxygen extraction fraction (OEF) was calculated from venous sO 2 values (assuming a constant arterial sO 2 of 95%). Seventy-two hrs after ischemia, animals were sacrificed and whole brains were stained with TTC to delineate infarct at the cortical surface (D). Arterioles were easily distinguished from venules in baseline images (A, mean arterial sO 2 , 87%; mean venous sO 2 , 76%). During MCAO, mean arteriolar sO 2 values did not change; however, venular sO 2 decreased precipitously (B, E), greater in regions that went on to infarct (45±2%) compared to surrounding regions (52±2%, p 2 slowly recovered but not back to baseline levels. Twenty-four (C) and 72 hrs after reperfusion, venous sO 2 in regions of infarction increased above baseline (83%), approaching arterial sO 2 values of 90%, while venous sO2 in peri-infarct regions (71%) returned near baseline levels of 76% (E). OEF increased from 18% to 55% in regions of eventual infarction, during MCAO; following reperfusion, OEF progressively dropped below baseline levels (12%). In surrounding surviving tissue, OEF returned close to baseline levels (24%) following reperfusion (F). OR-PAM is capable of measuring oxygen metabolism at high resolution during focal ischemia. Consistent with previous PET studies in human stroke, we found OEF increased during acute ischemia; however, OEF remained elevated (above baseline values) after reperfusion, suggesting that injured tissue may have increased oxygen metabolism. OEF gradually decreased below baseline values in infarcted tissue, but returned to near-baseline values in viable peri-infarct regions.
Clostridium difficile infection prevention: biotherapeutics, immunologics, and vaccines.

Abstract We are in the midst of a resurgence of Clostridium difficile infection (CDI) in North America and Europe for which morbidity and mortality are higher than ever seen. C. difficile has risen in frequency to become the most common healthcare-associated infection pathogen, exceeding methicillin-resistant Staphylococcus aureus in many hospitals. Protection against CDI is thought to be mediated first by the normal bacterial microbiota, supplemented by an adaptive immune antibody response directed primarily at C. difficile toxins. Treatment of CDI is with antimicrobials that also further disrupt the protective bacterial microbiota leaving the patient susceptible to recurrent CDI. In addition, patients most susceptible to CDI, the advanced elderly, may already have a limited immune response and fail to increase their adaptive immune response with infection. The importance of both of these protective modalities has been demonstrated by 1) the success of fecal microbiota to restore "colonization resistance" for patients with multiple recurrences of CDI, and 2) the marked reduction in CDI recurrences with the use of intravenous monoclonal antibodies directed against toxin A and toxin B as an adjunct to antimicrobial treatment. Anti-toxin vaccines, passive monoclonal anti-toxin antibodies, and non-toxigenic C. difficile (to restore colonization resistance) are already undergoing patient clinical trials. The opportunity to prevent CDI is compelling and future research should focus on understanding the critical elements of the microbiota needed to restore colonization resistance and on development of novel immunologic strategies that include systemic and mucosal vaccines and passive immune modulators.
Putting Together Courage and Moderation in Plato and Shakespeare

Plato’s Republic begins in controversy and culminates in controversy. It begins with warring definitions of justice and culminates in warring definitions of truth. Regarding justice it asks the following questions: does justice require the particular individual to sacrifice himself on the altar of the universal? Or, is justice completely in the service of the particular? Or, is justice a marriage of universal and particular. In addressing the controversy of justice, we eventually come to an even more vexing controversy. The Republic discloses that the controversy of justice is rooted in the controversy of truth: there are arguments from the ideas and to the ideas, and political life requires both. In other words, on the one hand, political life involves taking an idea or universal principle and applying it to a particular situation; and, on the other hand, political life involves ascending from a particular situation to an idea or universal principle. But how do we put both together? The universals one applies to the particular situation may be the wrong universals, so starting with the universal seems problematic. Whereas the particulars one uses to ascend to the universal may not be true. We are either stuck with arbitrary truth or consoling myth. Plato’s Republic suggests that controversy is not just an ugly side-effect of political life; it is the essence of political life. No controversy, no political life. But Plato does not leave it at that. Plato is not unjust. He gives us a life-line. He enables us to see that the complex is reflected in the simple. The controversy about truth shows up in the tension between courage and moderation. This paper grabs hold of Plato’s life line and shows how it illuminates not only the Republic but also political life. Not only that, the paper shows that Plato’s idea shows up in other great writers, namely, Shakespeare, in his Coriolanus and Julius Caesar.
Shifting Patterns in Cesarean Delivery Scheduling and Timing in Oregon before and after a Statewide Hard Stop Policy

Objectives To assess the use and timing of scheduled cesareans and other categories of cesarean delivery and the prevalence of neonatal morbidity among cesareans in Oregon before and after the implementation of Oregon's statewide policy limiting elective early deliveries. Data Sources Oregon vital statistics records, 2008–2013. Study Design Retrospective cohort study, with multivariable logistic regression, regression controlling for time trends, and interrupted time series analyses, to compare the odds of different categories of cesarean delivery and the odds of neonatal morbidity pre- and postpolicy. Data Collection/Extraction Methods We analyzed vital statistics data on all term births in Oregon (2008–2013), excluding births in 2011. Principal Findings The odds of early-term scheduled cesareans decreased postpolicy (adjusted odds ratio [aOR], 0.70; 95 percent confidence interval [CI], 0.66–0.74). In the postpolicy period, there were mixed findings regarding assisted neonatal ventilation and neonatal intensive care unit admission, with regression models indicating higher postpolicy odds in some categories, but lower postpolicy odds after controlling for time trends. Conclusions Oregon's hard stop policy limiting elective early-term cesarean delivery was associated with lower odds of cesarean delivery in the category of women who were targeted by the policy; more research is needed on impact of such policies on neonatal outcomes.
Piezoelectric micromachined acoustic emission sensors for early stage damage detection in structures

Acoustic emission (AE) is a passive nondestructive evaluation (NDE) method that relies on the energy release of active flaws. The passive nature of this NDE method requires highly sensitive transducers in addition to low power and lightweight characteristics. With the advancement of micro-electro-mechanical systems (MEMS), acoustic emission (AE) transducers can be developed in low power and miniaturized. In this paper, the AE transducers operating in plate flexural mode driven piezoelectrically known as Piezoelectric Micromachined Ultrasonic Transducers (PMUTs) are presented. The AE PMUTs are manufactured using PiezoMUMPS process by MEMSCAP and tuned to 46 kHz and 200 kHz. The PiezoMUMPs is a 5-mask level SOI (silicon-on-insulator) patterning and etching process followed by deposition of 0.5 micron Aluminum Nitride (AlN) to form piezoelectric layer to form the transducers. The AE transducers are numerically modeled using COMSOL Multiphysics software in order to optimize the performance before manufacturing. The electrometrical characterization experiments are presented. The efficiency of the proposed AE PMUTs compared to the conventional AE transducers in terms of power consumption, weight and sensitivity is presented.
The Cambodian Hybrid Court is Prosecuting for the Wrong Offenses: A Review Essay

The tribunal set up jointly by Cambodia and the Untied Nations to try Khmer Rouge figures has used internationally defined offenses exclusively in the prosecutions conducted to date. This review essay argues that most of these charges are not legally sustainable, and that the tribunal would have been better advised to charge under the domestic penal law of Cambodia.
Early Sign Language Acquisition and Cognitive Development

Previous studies of early language and cognitive development have focused on children’s acquisition of spoken language skills and mastery of sensorimotor tasks. These studies generally have found that children reach their first steps in language production during their second year, after successful completion of most of the stages of sensorimotor development. The most widely disseminated view probably has been that advanced by Piaget (1962), Bruner (1966), and Sinclair (1971); namely that language is essentially an outgrowth of the development of the symbolic function, and that the ability to use symbols is a product of the completion of the sensorimotor period. More specifically, the capacity for mental representation, typically associated with the child’s understanding of object permanence, was seen as the primary cognitive prerequisite for the child’s acquisition of language.
Structure, Function and Inhibition of Cyclo-oxygenases

The key step in the generation of prostaglandins (PGs) is the bis-dioxygenation of arachidonic acid to the bicyclic hydroperoxides PGG2 (endoperoxides) as the initial products of polyunsaturated fatty-acid oxygenation (Fig. 1). The enzyme that catalyzes this reaction is cyclo-oxygenase (COX)1, and it also catalyzes the reduction of the hydroperoxide to an alcohol, thereby forming PGH2 (Hamberg and Samuelsson 1973: Nugteren and Hazelhof 1973).
Breast Cancer Aggressiveness in Women of African Descent

While the incidence of breast cancer is higher in White women (115.5/100,000) than African-American women (101.5/100,000), the mortality pattern is just the opposite (1). Not only do African-American women have a higher mortality (31.0/100,000) than White women (24.3/100,000) but the mortality rates are falling more rapidly in White women. There are many factors that may contribute to these disparities, such as inequalities in access to healthcare and poverty (2, 3, 4) and lower education levels (5). These factors create barriers to health care access contributing to African-Americans being diagnosed at a later stage of disease (6, 7, 8, 9, 10, 11). Some studies have shown that socio-economic factors are associated with a poorer outcome and may account for some of the difference between African- Americans and Whites (12, 13, 14, 15, 16, 17). However, even when African-Americans have equal access to medical care, there are still racial differences in outcome (18, 19). In the Jatoi et al.’s 2003 study of breast cancer survival in the U.S. Department of Defence’s Healthcare System, an “equal access system”, (18) they found, after adjusting for age and stage, that not only was there a disparity in survival between African-American women as compared to Whites, but that this disparity has increased since 1980. Other studies show that factors other than delay in presentation and socio-economic status explain some of the disparity and that African-American women still have poorer survival after controlling for these factors (20, 21, 22).
Input Estimation for Power Plant Model Validation Using PMU Terminal Measurements

Validation and parameter identification for dynamic power plant models using disturbance data from phasor measurement units (PMUs) are of growing importance. They provide a cost-effective means of assessing and improving model quality. The popular playback method for validation regards as constant inputs to the simulation model such as the exciter reference voltage and governor reference power. In this paper, a method is proposed to estimate these input quantities from the PMU measurements. Current practice is to discard disturbances that coincide with scheduled changes to these input quantities. The method presented here allows these disturbance events to be used for validation and identification of simulation models and, more generally, opens the possibility of using reference changes to validate portions of the model not typically excited during disturbances. A case study is presented that shows the successful application of the method to an event for a generator in the Western United States.
Resistance to Hurricane Effects Varies Among Wetland Vegetation Types in the Marsh–Mangrove Ecotone

The capacity of coastal wetlands to stabilize shorelines and reduce erosion is a critical ecosystem service, and it is uncertain how changes in dominant vegetation may affect coastal protection. As part of a long-term study (2012–present) comparing ecosystem functions of marsh and black mangrove vegetation, we have experimentally maintained marsh and black mangrove patches (3 m × 3 m) along a plot-level (24 m × 42 m) gradient of marsh and mangrove cover in coastal wetlands near Port Aransas, TX. In August 2017, this experiment was directly in the path of Hurricane Harvey, a category 4 storm. This extreme disturbance event provided an opportunity to quantify differences in resistance between mangrove and marsh vegetation and to assess which vegetation type provided better shoreline protection against storm-driven erosion. We compared changes in plant cover, shoreline erosion, and accreted soil depth to values measured prior to storm landfall. Relative mangrove cover decreased 25–40% after the storm, regardless of initial cover, largely due to damage on taller mangroves (> 2.5 m height) that were not fully inundated by storm surge and were therefore exposed to strong winds. Evidence of regrowth on damaged mangrove branches was apparent within 2 months of landfall. Hurricane-induced decreases in mangrove cover were partially ameliorated by the presence of neighboring mangroves, particularly closer to the shoreline. Marsh plants were generally resistant to hurricane effects. Shoreline erosion exceeded 5 m where mangroves were absent (100% marsh cover) but was relatively modest (< 0.5 m) in plots with mangroves present (11–100% mangrove cover). Storm-driven accreted soil depth was variable but more than 2× higher in marsh patches than in mangrove patches. In general, mangroves provided shoreline protection from erosion but were also more damaged by wind and surge, which may reduce their shoreline protection capacity over longer time scales.
Branched-Chain Amino Acids and Seizures: A Systematic Review of the Literature

Up to 40% of patients with epilepsy experience seizures despite treatment with antiepileptic drugs; however, branched-chain amino acid (BCAA) supplementation has shown promise in treating refractory epilepsy. The purpose of this systematic review was to evaluate all published studies that investigated the effects of BCAAs on seizures, emphasizing therapeutic efficacy and possible underlying mechanisms. On 31 January, 2017, the following databases were searched for relevant studies: MEDLINE (OvidSP), EMBASE (OvidSP), Scopus (Elsevier), the Cochrane Library, and the unindexed material in PubMed (National Library of Medicine/National Institutes of Health). The searches were repeated in all databases on 18 February, 2019. We only included full-length preclinical and clinical studies that were published in the English language that examined the effects of BCAA administration on seizures. Eleven of 2045 studies met our inclusion criteria: ten studies were conducted in animal models and one study in human subjects. Seven seizure models were investigated: the strychnine (one study), pentylenetetrazole (two studies), flurothyl (one study), picrotoxin (two studies), genetic absence epilepsy in rats (one study), kainic acid (two studies), and methionine sulfoximine (one study) paradigms. Three studies investigated the effect of a BCAA mixture whereas the other studies explored the effects of individual BCAAs on seizures. In most animal models and in humans, BCAAs had potent anti-seizure effects. However, in the methionine sulfoximine model, long-term BCAA supplementation worsened seizure propagation and caused neuron loss, and in the genetic absence epilepsy in rats model, BCAAs exhibited pro-seizure effects. The contradictory effects of BCAAs on seizure activity likely reflect differences in the complex mechanisms that underlie seizure disorders. Some of these mechanisms are likely mediated by BCAA’s effects on glucose, glutamate, glutamine, and ammonia metabolism, activation of the mechanistic target of rapamycin signaling pathway, and their effects on aromatic amino acid transport and neurotransmitter synthesis. We propose that a better understanding of mechanisms by which BCAAs affect seizures and neuronal viability is needed to advance the field of BCAA supplementation in epilepsy.
Changing Perspectives on the Role of DnaA-ATP in Orisome Function and Timing Regulation.

Bacteria, like all cells, must precisely duplicate their genomes before they divide. Regulation of this critical process focuses on forming a pre-replicative nucleoprotein complex, termed the orisome. Orisomes perform two essential mechanical tasks that configure the unique chromosomal replication origin, oriC to start a new round of chromosome replication: 1) unwinding origin DNA and 2) assisting with loading of the replicative DNA helicase on exposed single strands. In Escherichia coli, a necessary orisome component is the ATP-bound form of the bacterial initiator protein, DnaA. DnaA-ATP differs from DnaA-ADP in its ability to oligomerize into helical filaments, and in its ability to access a subset of low affinity recognition sites in the E. coli replication origin. The helical filaments have been proposed to play a role in both of the key mechanical tasks, but recent studies raise new questions about whether they are mandatory for orisome activity . It was recently shown that a version of E. coli oriC (oriCallADP), whose multiple low affinity DnaA recognition sites bind DnaA-ATP and DnaA-ADP similarly, was fully occupied and unwound by DnaA-ADP in vitro, and in vivo suppressed the lethality of DnaA mutants defective in ATP binding and ATP-specific oligomerization. However, despite their functional equivalency, orisomes assembled on oriCallADP were unable to trigger chromosome replication at the correct cell cycle time and displayed a hyper-initiation phenotype. Here we present a new perspective on DnaA-ATP, and suggest that in E. coli, DnaA-ATP is not required for mechanical functions, but rather is needed for site recognition and occupation, so that initiation timing is coupled to DnaA-ATP levels. We also discuss how other bacterial types may utilize DnaA-ATP and DnaA-ADP, and whether the high diversity of replication origins in the bacterial world reflects different regulatory strategies for how DnaA-ATP is used to control orisome assembly.
Commentary on collective security

Much of the debate has centered on how to harmonize collective self-defense with collective security. A collective security action taken with the authorization of the Security Council arguably may permit the use of armed force in a manner that exceeds some of the traditional parameters of self-defense actions. The Security Council could make a determination at any time that trade sanctions "would be inadequate" and move on to Article 42 and the use of force. The Charter leaves the issue of operational command open for treatment on a case-by-case basis by the Security Council. However, the armed forces of the Members are unified by being placed at the disposal and under the command and strategic direction of a single body, the Security Council, assisted by a Military Staff Committee. There remains little likelihood that the major powers or even other governments want to cut the umbilical cord to those national forces that would be contributed to the permanent UN force.
HOW DO LEARNING DISORDERS IMPACT CLINICAL MEASURES FOLLOWING CONCUSSION

Background:There is limited evidence examining the impact of learning disorders on testing and screening scores used in evaluation following concussion in adolescents.Purpose:To examine differences...
Empirical Implications of Theoretical Models in Political Science

Tension has long existed in the social sciences between quantitative and qualitative approaches on one hand, and theory-minded and empirical techniques on the other. The latter divide has grown sharper in the wake of new behavioural and experimental perspectives which draw on both sides of these modelling schemes. This book works to address this disconnect by establishing a framework for methodological unification: empirical implications of theoretical models (EITM). This framework connects behavioural and applied statistical concepts, develops analogues of these concepts, and links and evaluates these analogues. The authors offer detailed explanations of how these concepts may be framed, to assist researchers interested in incorporating EITM into their own research. They go on to demonstrate how EITM may be put into practice for a range of disciplines within the social sciences, including voting, party identification, social interaction, learning, conflict and cooperation to macro-policy formulation.
Role of Vascular Endothelial Growth Factor/Vascular Permeability Factor in the Pathogenesis of Kaposi's Sarcoma-Associated Herpesvirus-Infected Primary Effusion Lymphomas: Presented in part at the 3rd National AIDS Malignancy Conference, May 27, 1999, in Bethesda, MD.

Abstract Primary effusion lymphomas (PELs), which are rare lymphomas associated with Kaposi's sarcoma-associated herpesvirus (or human herpesvirus-8) infection, present as malignant lymphomatous effusions in body cavities. Because PELs prefer liquid growth, we hypothesized that increased vascular permeability would be required for effusions to form. We found that the PEL cell lines BC-1, BCP-1, and BCBL-1 produce high levels of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF). Reverse transcriptase-polymerase chain reaction analysis of RNA from the PEL cell lines amplified the 3 VEGF-secreted isoforms: VEGF/VPF121, VEGF/VPF145, and VEGF/VPF165. Two of the PEL cell lines expressed the VEGF/VPF receptor Flt-1, but VEGF/VPF did not stimulate proliferation in these cells. Most (13/14) control SCID/beige mice inoculated intraperitoneally with BCBL-1 cells and subsequently observed or treated with control antibodies developed effusion lymphoma of human cell origin with prominent bloody ascites. In contrast, none (0/9) of the mice treated with a neutralizing antihuman VEGF/VPF antibody developed ascites and effusion lymphoma. These results demonstrate that VEGF/VPF is critical to BCBL-1 growth as effusion lymphoma in mice and suggest that VEGF/VPF stimulation of vascular permeability may be critical to the pathogenesis of PELs.
Relationships Between Daily Device Use and Early Communication Outcomes in Young Children With Cochlear Implants.

OBJECTIVES Children with significant hearing loss can gain access to sound via a cochlear implant (CI), but they must wear the device to reap the communication benefits of the device. That is, poor daily device use may result in underdeveloped perceptual and language skills in children and adolescents using CIs. This retrospective study focuses on the relationship between daily CI use and communication performance (auditory skills, speech recognition, expressive and receptive language) in young children, with the hypothesis that greater daily device use coincides with better communication outcomes. DESIGN The authors conducted a clinical chart review of patients with CIs younger than 5 years old who used at least 1 CI speech processor with datalogging technology. Participants (n = 65) had a mean chronologic age of 3.5 years, mean implantation age of 1.9 years, and mean device experience of 1.6 years. Approximately one quarter of participants had additional disabilities. Daily device use (i.e., datalogging information), child characteristics (e.g., age at CI), and assessments of communication skills (i.e., parent questionnaires, speech recognition tests, standardized language assessments) were obtained from each child's records. The investigators performed correlational analyses to examine relationships between communication outcomes and daily device use, and they employed group comparisons and correlations to identify child characteristics that were significantly associated with daily device use (p < 0.05, corrections for family-wise error). RESULTS Young children with CIs used their device, on average, 6.7 hr/d, with 63% below full-time use (<8 hr/d). Children without additional disabilities who wore their CI more hours per day had significantly better auditory, speech recognition, and language skills. A significant correlation also emerged between daily device use and early auditory skills in young CI users with additional disabilities, though relationships were more complicated for this subsample. Longer daily device use significantly correlated with younger age at CI and longer device experience. Differences in device use occurred in regards to absence versus presence of additional disabilities, bilateral versus unilateral device configuration, sign versus spoken language, and private versus government-assisted insurance. CONCLUSIONS The strong relationship between daily device use and early communication suggests clinicians and parents should focus on increasing the number of hours per day young children wear their CIs to enhance auditory and language outcomes. However, intervention strategies must consider barriers to consistent device use and goals of the family to efficiently and effectively support families of young children with CIs who struggle with inconsistent device use.
Accelerating Learning by Experimentation

Beyond a company’s ability to innovate lies a process of experimentation that enables the organization to create and refine its products and services. The constantly changing environment and complex linkages between variables require not only moving between observation, exploration and experimentation, but also iterating between experiments. Trial-and-error types of experiments are also an integral part of innovation processes, even though they are frequently not fully recognized as experiments. New technologies for experimentation, e.g., rapid prototyping, amplify the importance of managing these factors, thus providing the potential for higher R&D performance, innovation and ultimately new ways of creating value for customers. Regardless of industry, companies share an iterative process of a four-step experimentation cycle, which consists in designing, building, running and analyzing the experiment. How learning occurs, or does not occur, is affected by several factors: fidelity, cost, feedback time, capacity, sequential and parallel strategies, signal-to-noise, and type. The ‘case’ of Team New Zealand – winner of the sailing regatta America’s Cup in 1995 – is woven through this chapter and shows how learning by experimentation works at the front end of innovation by integrating new experimentation technologies with tried-and-true methods and capturing the results in the organization.
William Weber, The Great Transformation of Musical Taste: Concert Programming from Haydn to Brahms

It is a familiar scenario. The governing board of an orchestra struggles with programming decisions. Anxious to keep subscribers happy and ward off financial exigencies, it resolutely markets perfo...
Is the Brain Drain Good for Africa

We build upon recent literature to do several exerc ises to assess benefits and costs of the brain drai n to Africa. Contrary to a lot of the worries expressed in the media and in aid agencies, the Brain drain i s probably a net benefit to the source countries. We make several arguments: (1) the African brain drain is not large enough to have much effect on Africa’s skill gap relative to the rest of the world. Since other regions had a larger brain drain, the skill g ap between Africa and the rest would actually be larger in a counterfactual world of NO brain drain with the same amount of skill creation. (2) The gains to the migrants themselves and their families who receive indirect utility and remittances more than offset the losses of the brain drain. Accordin g to one of our calculations, the present value of remittances more than covers the cost of educating a brain drainer in the source country. (3) Brain drain has a positive effect on skill accumulation t hat appears to offset one for one the loss of skill s to the brain drain. Hence it is not surprising that we fail to identify any negative growth effect of the brain drain. Although some of our exercises are re liant on special assumptions and shaky data that require further investigation, we conclude based on what we can know in this paper that the brain drain is on balance good for Africa 1
Deterring 'Double-Play' Manipulation in Financial Crisis: Increasing Transaction Cost as a Regulatory Tool

The sub-prime mortgage crisis that originated in the United States has triggered a global credit crunch, threatening the solvency of emerging markets that have relied heavily on foreign debt, and resulting in the devaluation of their currencies. Currency market interventions by the central banks in countries with a currency board system lead to higher short-term interest rates and further declinations in the local stock market. This economic setting invites the double-play manipulation strategy that simultaneously attacks both the local currency and the stock market. History has shown that a central bank’s stock market intervention is costly and that sustaining the intervention over a meaningful period of time is a major challenge. In this paper, we examine the effect of a pan-market increase in transaction cost on double-play manipulators’ trading strategies when government intervention is limited to revenues generated by the transaction levy. We show that this regulatory change not only helps sustain equity market intervention but also reduces the short pressure in both the currency and the equity market.
Inhibition by insulin of valine turnover in liver. Evidence for a general control of proteolysis.

Abstract Proteolysis was assessed during perfusion of isolated livers of nonfasted rats from the turnover of free valine, measured after single pulse additions of l-valine-1-14C to the perfusate, and from the release of label from livers previously labeled with l-valine-1-14C in vivo and then perfused with 15 mm unlabeled valine to minimize reincorporation. Since valine is not synthesized in the rat and was shown not to be metabolized significantly in these experiments, it could be assumed that any net gain or loss of free valine would reflect net changes in the protein content of the system. In control experiments, free valine accumulated slowly for 15 to 30 min; the rate then spontaneously increased rather abruptly and remained elevated. Since the utilization of extracellular valine by protein synthesis did not fall off with time, the spontaneous increase in valine accumulation was ascribed to an enhancement of proteolysis. Insulin in vitro completely inhibited this spontaneous net increase and also inhibited the release of label from previously labeled livers. No specific hormonal effects were noted on the incorporation of free valine into protein or its distribution in intra- and extracellular water. The inhibitory effect of insulin, which was sustained for periods up to 180 min of perfusion, was estimated to represent 1.0% of total liver protein per hour.
Erkrankungen der Knochen

Zwergwuchs mit kurzen Extremitaten bei normaler Rumpflange durch anlagebedingte Storung der enchondralen Ossifikation der Rohrenknochen.
Testing transposable elements as genetic drive mechanisms using Drosophila P element constructs as a model system

The use of transposable elements (TEs) as genetic drive mechanisms was explored using Drosophila melanogaster as a model system. Alternative strategies, employing autonomous and nonautonomous P element constructs were compared for their efficiency in driving the ry+ allele into populations homozygous for a ry- allele at the genomic rosy locus. Transformed flies were introduced at 1%, 5%, and 10% starting frequencies to establish a series of populations that were monitored over the course of 40 generations, using both phenotypic and molecular assays. The transposon-borne ry+ marker allele spread rapidly in almost all populations when introduced at 5% and 10% seed frequencies, but 1% introductions frequently failed to become established. A similar initial rapid increase in frequency of the ry+ transposon occurred in several control populations lacking a source of transposase. Constructs carrying ry+ markers also increased to moderate frequencies in the absence of selection on the marker. The results of Southern and in situ hybridization studies indicated a strong inverse relationship between the degree of conservation of construct integrity and transposition frequency. These finding have relevance to possible future applications of transposons as genetic drive mechanisms.
Cost-Minimization Analysis of Computed Tomography versus Magnetic Resonance Imaging in the Evaluation of Patients with Transient Ischemic Attacks at a Large Academic Center.

Background: The type of neuroimaging for the evaluation of transient ischemic attack (TIA) is debatable. Many patients undergo head computed tomography (CT) with
Diltiazem for the Management of Malignancy-Associated Perineal Pain and Tenesmus

Abstract Background: Perineal pain is a frequent complaint of patients with advanced cancer (colorectal, genitourinary, prostate), and often quite difficult to manage with significant impact on quality of life. Calcium channel blockers (CCBs) are potent inhibitors of intestinal smooth muscle contraction and have been shown to impact tone and motility of the gastrointestinal tract. As such, they have been used in various pain syndromes of the lower gastrointestinal tract, such as chronic anal fissure, to promote healing and improve pain. Here we describe two cases using oral diltiazem for malignancy-associated perineal pain and tenesmus. Discussion: The first case describes an elderly male with advanced urothelial cancer post surgical resection and chemoradiation who suffered from rectal pain described as “sitting on a football” despite nerve blocks and oral opioids. He experienced dramatic improvement in pain scores and daily requirements of oral analgesics after starting oral diltiazem. The second case d...
Full-wave simulation of propagation channel parameters for a forest environment

Scattering from tree trunks is the dominant source to the field fluctuations in a forest environment. Using full-wave analysis based on the method of moments in conjunction with Monte Carlo simulations the effect of multiple scattering among a large number of tree trunks and their interaction with the lateral waves are studied. It is shown that only scatterers near the source and the observation points contribute to the field fluctuations significantly. Keeping about 200 tree trunks in the vicinity of the transmitter dipole and the receiver point, Monte Carlo simulation is used to evaluate the statistics of the spatial and spectral behavior of the field at the receiver. Using a wide bandwidth simulation, the temporal behavior is also studied and the performance of antenna arrays is investigated.
Starburst cells nondirectionally facilitate the responses of direction-selective retinal ganglion cells

The mechanism of direction selectivity in retinal ganglion cells remains controversial. An important issue is how the starburst amacrine cells, which are known to provide a major synaptic input to the direction-selective ganglion cells, participate in the directional discrimination. Here, we present evidence that the cholinergic outputs of the starburst cells affect the responses of the ganglion cells symmetrically; they provide a feedforward excitation that facilitates the response of the ganglion cells to movement in both the preferred and null directions. This seems to place a constraint on models of the directional discrimination in which the starburst cells participate, namely, that their cholinergic synapses be nondirectional in their effects on the ganglion cells.
Focal nodular hyperplasia of the liver. Possible relationship to oral contraceptives.

The possible association between oral contraceptives and benign hepatomas has recently been reported. A study of three hepatic masses, all surgically resected, leads us to the conclusion that our lesions represent focal nodular hyperplasia, and may be similar to those reported as adenomas. The possibility that the vascular changes found in these lesions play an etiologic role is suggested. The vascular lesions, in turn, could be related to oral contraceptives. A fairly definite syndrome consisting of oral contraceptive ingestion, intrahepatic or intraperitoneal hemorrhage, or both, shock or syncope, acute abdomen, and focal nodular hyperplasia of the liver (or benign hepatoma) has predominated in the cases thus far reported.
Developmental Effects of Endothelin-1 on the Pulmonary Circulation in Sheep

ABSTRACT: Endothelin-1 (ET-1) is a polypeptide that has potent hemodynamic effects on the pulmonary circulation. To determine whether there are changes in these effects with increasing postnatal age, wc investigated the effects of ET-1 (250 ng/kg) at rest and during pulmonary hypertension in eight lambs (< 1 wk old) and 11 juvenile sheep (6–12 mo old). At rest, ET-1 did not change pulmonary arterial pressure in lambs, but increased pulmonary arterial pressure by 64.0 ± 37.5% (p < 0.05) in sheep. During pulmonary hypertension, ET-1 produced greater decreases in pulmonary arterial pressure in lambs than in sheep (26.6 ± 3.4% versus 18.7 ± S.3%,p < 0.05). In juvenile sheep, the increase in resting pulmonary arterial pressure produced by ET-1 was inhibited by meclofenamic acid, an inhibitor of prostaglandin synthesis (40.3 ± 9.9% versus 2.3 ± 4.7%, p < 0.05); during pulmonary hypertension, the decrease in pulmonary arterial pressure produced by ET-1 was inhibited by Nω-nitro-L-arginine, an inhibitor of endothelium-derived nitric oxide synthesis (21.4 ± 10.7% versus 8.0 ± 3.6%, p < 0.05) and by glybenclamide, an ATP-dependent potassium-channel blocker (18.8 ± 8.4% versus 4.0 ± 4.4%, p < 0.05). The hemodynamic effects of ET-1 on the pulmonary circulation are dependent on postnatal age. Pulmonary vasoconstriction is mediated by prostaglandin production, and pulmonary vasodilation is mediated, in part, by release of endothelium-derived nitric oxide and activation of ATP-dependent potassium channels.
Determination of Membrane Domain Size by Fluorescence Resonance Energy Transfer: Effects of Domain Polydispersity and Packing

Fluorescence resonance energy transfer (FRET) is sensitive to lateral heterogeneity in multicomponent membranes. Recently, we developed a model that enables the extraction of domain size from time-resolved FRET data, and here we examine the effects of domain polydispersity and spatial ordering on the accuracy of domain size determination. The model is applied to Monte Carlo calculations of membranes containing polydisperse domains, either randomly or hexagonally packed for three probe-partitioning schemes and three domain surface coverages. Statistical analysis of the model fitting results supports the conclusion that time-resolved FRET is a robust and precise technique for determining the size of small membrane domains (≤4 times the Forster distance, ∼ 20 nm, of the FRET pair), regardless of domain polydispersity and packing. The confidence estimates, presented here in dimensionless domain diameters (independent of the specific FRET pairs), provide a universal tool for domain size estimation in systems c...
Magnesium metabolism in health and disease

Magnesium is an important element for health and disease. Magnesium, the second most abundant intracellular cation, has been identified as a cofactor in over 300 enzymatic reactions involving energy metabolism and protein and nucleic acid synthesis. Approximately half of the total magnesium in the body is present in soft tissue, and the other half in bone. Less than 1% of the total body magnesium is present in blood. Nonetheless, the majority of our experimental information comes from determination of magnesium in serum and red blood cells. At present, we have little information about equilibrium among and state of magnesium within body pools. Magnesium is absorbed uniformly from the small intestine and the serum concentration controlled by excretion from the kidney. The clinical laboratory evaluation of magnesium status is primarily limited to the serum magnesium concentration, 24-hour urinary excretion, and percent retention following parenteral magnesium. However, results for these tests do not necessarily correlate with intracellular magnesium. Thus, there is no readily available test to determine intracellular/total body magnesium status. Magnesium deficiency may cause weakness, tremors, seizures, cardiac arrhythmias, hypokalemia, and hypocalcemia. The causes of hypomagnesemia are reduced intake (poor nutrition or IV fluids without magnesium), reduced absorption (chronic diarrhea, malabsorption, or bypass/resection of bowel), redistribution (exchange transfusion or acute pancreatitis), and increased excretion (medication, alcoholism, diabetes mellitus, renal tubular disorders, hypercalcemia, hyperthyroidism, aldosteronism, stress, or excessive lactation). A large segment of the U.S. population may have an inadequate intake of magnesium and may have a chronic latent magnesium deficiency that has been linked to atherosclerosis, myocardial infarction, hypertension, cancer, kidney stones, premenstrual syndrome, and psychiatric disorders. Hypermagnesemia is primarily seen in acute and chronic renal failure, and is treated effectively by dialysis.