cssi/SciSciGPT-SciSciNet huggingface dataset:
Cyclooxygenase-2 Generates the Endogenous Mutagen trans-4-Hydroxy-2-nonenal in Enterococcus faecalis–Infected Macrophages

Infection of macrophages by the human intestinal commensal Enterococcus faecalis generates DNA damage and chromosomal instability in mammalian cells through bystander effects. These effects are characterized by clastogenesis and damage to mitotic spindles in target cells and are mediated, in part, by trans-4-hydroxy-2-nonenal (4-HNE). In this study, we investigated the role of COX and lipoxygenase (LOX) in producing this reactive aldehyde using E. faecalis-infected macrophages and interleukin (IL)-10-knockout mice colonized with this commensal. 4-HNE production by E. faecalis-infected macrophages was significantly reduced by COX and LOX inhibitors. The infection of macrophages led to decreased Cox1 and Alox5 expression whereas COX-2 and 4-HNE increased. Silencing Alox5 and Cox1 with gene-specific siRNAs had no effect on 4-HNE production. In contrast, silencing Cox2 significantly decreased 4-HNE production by E. faecalis-infected macrophages. Depleting intracellular glutathione increased 4-HNE production by these cells. Next, to confirm COX-2 as a source for 4-HNE, we assayed the products generated by recombinant human COX-2 and found 4-HNE in a concentration-dependent manner using arachidonic acid as a substrate. Finally, tissue macrophages in colon biopsies from IL-10-knockout mice colonized with E. faecalis were positive for COX-2 by immunohistochemical staining. This was associated with increased staining for 4-HNE protein adducts in surrounding stroma. These data show that E. faecalis, a human intestinal commensal, can trigger macrophages to produce 4-HNE through COX-2. Importantly, it reinforces the concept of COX-2 as a procarcinogenic enzyme capable of damaging DNA in target cells through bystander effects that contribute to colorectal carcinogenesis.
Mesoscale variability of physical and biological fields in southeastern Lake Superior

A cruise was conducted in southeastern Lake Superior east of Marquette, Michigan from 15 to 20 July 1999. A towed, vertically undulating instrument package containing a conductivity-temperature-depth (CTD) profiler, a fluorometer, and an optical plankton counter was used for data collection. Results indicated that the concurrent, highresolution survey of both physical and biological variables provided the fundamental basis for illustrating the correlation between mesoscale physical and biological fields and for investigating mesoscale physical and biological processes. It was revealed that the high chlorophyll a biomass beneath the thermocline co-occurs with up-tilting of the thermocline. This tilting of the thermocline was associated with the thermally driven coastal current. We hypothesize that the up-tilting of the thermocline lifted deep water into the euphotic zone, leading to high productivity of phytoplankton beneath the thermocline. The presence of both warm water and food provided a favorable physical and biological environment for zooplankton. The abundance of zooplankton reached 10 3 10 3 individuals m 23 in the warm surface water and was down to 3 3 10 3 individuals m 23 at a depth of 40 m.
Hyper-redundant manipulator dynamics: a continuum approximation

Hyper-redundant, or 'snake-like', manipulators have a very large number of actuatable degrees of freedom. This paper develops an efficient formulation of approximate hyper-redundant manipulator dynamics. The most efficient methods for representing manipulator dynamics in the literature require serial computations proportional to the number of degrees of freedom. Furthermore, these methods are not fully parallelizable. For hyper-redundant manipulators, which may have tens, hundreds or thousands of actuators, these formulations preclude real time implementation. This paper therefore looks at the mechanics of hyper-redundant manipulators from the point of view of an approximation to an 'infinite degree-or-freedom' (or continuum) problem. The dynamics for this case is developed. The approximate dynamics of actual hyper-redundant manipulators is then reduced to a problem which is O(1) in time, i.e. the algorithm is O(n) is the total number of computations, but these computations can be completely distributed o...
Social Perceptions of Male and Female Extreme Mesomorphs

In this study, male and female university students in the United States were exposed to mesomorphic or nonmesomorphic stimuli as reflected by photographs of either male body builders and non-body builders or female body builders and non-body builders. Then they were asked to attribute various personality traits and sex-role behaviors to them. Subjects, irrespective of their sex, perceived male and female body builders as possessing more traditionally masculine and less traditionally feminine personality characteristics than male and female non-body builders. Also, male and female body builders were seen as possessing less socially desirable traits than non-body builders. As predicted, female body builders were perceived generally as being more likely to engage in traditionally masculine sex-role behaviors in their dating and marriage relationships than female non-body builders. Contrary to expectation, however, male body builders were not perceived as more likely to engage in higher levels of masculine sex-role behaviors than male non-body builders.
Asthma Patient Education: Partnership in Care

Background Asthma education is a necessary and critical component of asthma management. Methods A review of the most-to-date global and national (US) guidelines and standards provides the basis for this concise asthma education primer. Results Effective asthma education that yields enhanced long-term health outcomes is accomplished by the proper patient-specific knowledge and behavior change tools. Communication technique (quality) as well as asthma education content (quantity) should receive recurrent assessment by all healthcare team members. Conclusion Asthma education delivery can be easily planned for and routinely delivered, keeping the shared goals of patient and healthcare team in mind.
Language-based minimization of sensor activation for event diagnosis

The problem of dynamic sensor activation for event diagnosis in discrete event systems is considered. Diagnostic agents are able to activate/deactivate sensors dynamically during the operation of the system. Sensor activation policies are functions that determine which sensors are on after a system trajectory. The sensor activation policy must be sufficient to fulfill the diagnosis duty. To compute minimal policies, in previous work, we propose language partition methods to restrict the solution space to be finite. In this paper, we present an algorithm that can be used to compute a provable minimal sensor activation policy without such a restriction. The output of our algorithm, which is a deterministic finite-state automaton, can be directly used to control sensors and diagnose the system.
Electrospray Ionization Mass Spectrometry of Hexanitrohexaazaisowurtzitane (CL‐20)

Abstract Hexanitrohexaazaisowurzitane (CL‐20) is a newly developed propellant and has been examined using negative ion electrospray mass spectrometry. The primary ions observed included adduct ions (M+Cl)– and (M+ONO2)−.
Reactive Liftoff of Crystalline Cellulose Particles

The condition of heat transfer to lignocellulosic biomass particles during thermal processing at high temperature (>400 °C) dramatically alters the yield and quality of renewable energy and fuels. In this work, crystalline cellulose particles were discovered to lift off heated surfaces by high speed photography similar to the Leidenfrost effect in hot, volatile liquids. Order of magnitude variation in heat transfer rates and cellulose particle lifetimes was observed as intermediate liquid cellulose droplets transitioned from low temperature wetting (500–600 °C) to fully de-wetted, skittering droplets on polished surfaces (>700 °C). Introduction of macroporosity to the heated surface was shown to completely inhibit the cellulose Leidenfrost effect, providing a tunable design parameter to control particle heat transfer rates in industrial biomass reactors.
Translational Assessment of Reward and Motivational Deficits in Psychiatric Disorders

Deficits in reward and motivation are common symptoms characterizing several psychiatric and neurological disorders. Such deficits may include anhedonia, defined as loss of pleasure, as well as impairments in anticipatory pleasure, reward valuation, motivation/effort, and reward learning. This chapter describes recent advances in the development of behavioral tasks used to assess different aspects of reward processing in both humans and non-human animals. While earlier tasks were generally developed independently with limited cross-species correspondence, a newer generation of translational tasks has emerged that are theoretically and procedurally analogous across species and allow parallel testing, data analyses, and interpretation between human and rodent behaviors. Such enhanced conformity between cross-species tasks will facilitate investigation of the neurobiological mechanisms underlying discrete reward and motivated behaviors and is expected to improve our understanding and treatment of neuropsychiatric disorders characterized by reward and motivation deficits.
CIRCADIAN AND ESTROUS RHYTHMS IN PINEAL MELATONIN AND 5-HYDROXY INDOLE-3-ACETIC ACID.

SummaryDifferential extractions and fluorometry of pineal 5-hydroxy indole-3-ace-tic acid and melatonin in adult rats demonstrate circadian rhythms correlated with periods of light and darkness and...
Improvements in the methods of preparation and storage of house fly microsomes.

Methods of grinding and conditions of incubation and storage are compared in a further study of the preparation and use of house fly, Musca domestica L., microsomes. The hydroxylation of naphthalene-I-C14 is the basis for the comparison. Phosphate buffer at p H 7.4 is superior to 0.15M KCI as grinding medium. Microsomes produced in a tissue grinder are approximately 50% more active than those produced in the Waring Blendor®. Microsomes stored at 0°C in dilute suspension in tris-HCl buffer, p H 8.2, retain their hydroxylase activity for 30 days while those stored as pellets lose their activity within 48 hours.
DNA Microgels as a Platform for Cell-Free Protein Expression and Display

Protein expression and selection is an essential process in the modification of biological products. Expressed proteins are selected based on desired traits (phenotypes) from diverse gene libraries (genotypes), whose size may be limited due to the difficulties inherent in diverse cell preparation. In addition, not all genes can be expressed in cells, and linking genotype with phenotype further presents a great challenge in protein engineering. We present a DNA gel-based platform that demonstrates the versatility of two DNA microgel formats to address fundamental challenges of protein engineering, including high protein yield, isolation of gene sets, and protein display. We utilize microgels to show successful protein production and capture of a model protein, green fluorescent protein (GFP), which is further used to demonstrate a successful gene enrichment through fluorescence-activated cell sorting (FACS) of a mixed population of microgels containing the GFP gene. Through psoralen cross-linking of the hy...
In vitro screening of silver nanoparticles and ionic silver using neural networks yields differential effects on spontaneous activity and pharmacological responses

Silver nanoparticles (AgNPs) are used in a wide range of consumer and medical products because of their antimicrobial and antifungal properties, and can translocate to the brain following exposure. Therefore, to screen AgNPs for potential impacts on human health, it is essential to examine neural function. The present study examined AgNPs (3 citrate coated, 3 PVP coated; 10-75nm) and AgNO3 effects on spontaneous and pharmacologically-induced neural network function in rat primary cortical cells on multi-well microelectrode array (mwMEA) plates. Baseline activity (1h) was recorded prior to exposure to non-cytotoxic concentrations of AgNPs and AgNO3 (0.08-0.63 and 0.08-1.7μg/ml, respectively). Changes in number of total extracellularly-recorded action potential spikes (total spikes; TS) and active electrodes (AE), relative to controls, were assessed 1, 24, and 48h after exposure to AgNP suspensions or AgNO3. After the 48h recording, the response to a pharmacological challenge with the GABAA antagonist, bicuculline (BIC), was assessed. Only two particles altered neural network function. Citrate coated 10nm AgNP caused concentration-related increases in AEs at 24h. After BIC treatment, PVP coated 75nm AgNP caused concentration-dependent increases in AE. AgNO3 effects differed from AgNPs, causing a concentration-related decrease in AEs at 24 and 48h, and a concentration-related decrease in TS following BIC challenge. Importantly, the direction of AgNO3 effects on neural activity was opposite those of 10nm Ag citrate at concentrations up to 0.63μg/ml, and different from 75nm Ag PVP, indicating ionic silver does not mediate these effects. These results demonstrate that non-cytotoxic concentrations of 10nm citrate- and 75nm PVP-coated Ag NPs alter neural network function in vitro, and should be considered for additional neurotoxicity hazard characterization.
Whole cell recording of sugar-induced currents in LLC-PK1 cells

Gigaohm-seal whole cell recording techniques were used to monitor function of the Na(+)-coupled sugar transport system in LLC-PK1 cells. The currents coupled to sugar transport were identified as those that are induced by the presence of 10 mM alpha-methylglucoside (AMG) in either the extracellular or intracellular compartment and were inhibited by addition of 320-800 microM phlorizin to the extracellular bathing medium. The sugar-induced currents are small, 15-20 pA, but of the expected magnitude as determined from the known kinetic parameters for Na(+)-coupled sugar transport in LLC-PK1 cells. The phlorizin-sensitive currents are Na+ dependent and can be studied under conditions in which the net Na+ and sugar flux (and consequently the Na+ electrical current) is in either the inward or outward direction. The reversal potential of the sugar-induced currents measured under conditions with high Na+ and AMG concentrations inside the cell is close to values predicted from thermodynamic principles, assuming a coupling stoichiometry of 2 Na+: 1 sugar for the transport system. The reversal potential of the sugar-induced currents with high extracellular Na+ and AMG is not equal to the predicted value, but it is of the polarity expected for inward-imposed solute gradients. Reasons for the observed discrepancy between observed and calculated values are discussed.
Moral foundations of the therapeutic relationship

Therapeutic relationships between patients and professionals are at the center of health care; they are the primary mechanism for realizing its cherished goals of health, healing, and comfort. Part II of this volume examines six moral foundations of these therapeutic relationships: • respect for patient privacy and confidentiality • truthful communication • informed consent to treatment • surrogate decision-making for patients who lack decision-making capacity • respect for professional boundaries • responsible stewardship of health care resources These six foundations are widely recognized as essential for the provision of effective, equitable, and respectful health care. Chapter 6, “Privacy and confidentiality,” first examines the meaning of these concepts and their application in health care settings. Then it argues that respect for privacy and confidentiality preserves patient autonomy, promotes beneficial treatment outcomes, and protects patients from harm. The chapter acknowledges that respect for privacy and confidentiality may be limited by other duties, including duties to obey the law and to protect both patients and third parties from harm. Chapter 7, “Truthfulness,” explores professional duties to communicate truthfully with patients. It bases these duties on respect for patients’ rights to know about their condition and its treatment, the ability of patients to accept even bad news, and the benefits to patients of making decisions based on a clear understanding of their condition, prognosis, and treatment alternatives. Chapter 7 describes and endorses an account of what it means to be truthful that was proposed by physician Richard Cabot. It distinguishes duties to provide truthful information from duties to protect the confidentiality of that information, and it recognizes that patients may choose to waive their right to receive personal health information. Chapter 8 is devoted to examination of patient rights to give or withhold, and professional duties to obtain, informed consent to medical treatment. After a brief summary of the legal origins and moral foundations of informed consent, the chapter describes the three essential elements of informed consent, namely, the patient must have the capacity to consent, the health care professional must provide relevant information about the treatment decision, and the patient must be free to choose.
Growing Diplomacy, Retreating Diplomats – How the Chinese Foreign Ministry has been Marginalized in Foreign Policymaking

AbstractThis article examines the shrinking influence of the Chinese Ministry of Foreign Affairs (MFA) in China’s foreign policymaking, at a time when the country’s diplomatic needs are rapidly growing. By utilizing the theory of domestic sources of international relations, this article argues that the MFA has been under stress from all directions: sidestepped by Party leaders from the top, challenged by competing ministries horizontally, and mocked by the public from below. The article also assesses the consequences a marginalized MFA has brought to Chinese diplomacy.
Disease Control, Public Health and Food Safety: Food Policy Lessons from Sub-Saharan Africa

This chapter reviews the agro-economic environment in Sub-Saharan Africa as it relates to animal production, public health, and disease control to contextualize the concept of risk and food safety. Drawing mostly from the experience of Zambia, it analyzes food safety actors and interests in Sub-Saharan Africa, and provides an outline of the general regulatory framework that is in place on the continent, to explain how food safety governance is impacted by different interest groups and agendas. Two case studies are provided, zoonotic tuberculosis and avian influenza. The chapter demonstrates how the two zoonoses, both important food safety concerns, have been prioritized differently in the case of Zambia, as a result of multiple socio-political and economic factors. The chapter concludes that, in order to be useful, a definition of food safety risks should include multiple contextual issues and stakeholders along the food supply chain. It is important to keep in mind what national food safety governance actors perceive the risks to be, and how their definitions fit into the broader picture of food safety in general. Food safety governance regulatory processes should take into consideration local realities, local food supply chains and local food safety threats to ensure the appropriateness and sustainability of any and all disease control measures instituted. Context will always matter, and therefore, local ecological, biological and policy considerations should be given primacy.
Hard Single-Molecule Magnet Behavior by a Linear Trinuclear Lanthanide-[1]Metallocenophane Complex.

A synthetic protocol was developed that involves the transmetalation of a mono-dysprosium–[1]ferrocenophane complex with DyX3 (X = Cl– or I–) to afford [Dy3Fc6Li2(THF)2]−, featuring a rare linear arrangement of magnetically anisotropic Dy3+ ions. The close spatial inter-lanthanide proximity, in combination with μ2-bridging sp2-hybridized CCp groups, enforces significant magnetic coupling and results in hard single-molecule magnet (SMM) behavior, with an effective barrier to magnetization reversal of up to 268 cm–1. Our results highlight the versatility of lanthanide metallocenophane architectures toward the development of novel multinuclear SMM frameworks.
Erotic Feelings in Therapy

Part of the fullness of the patient’s love is its imagery of the therapist as sexual partner. Why should the patient not love a therapist who consistently provides a high quality affective connection, calm clear thinking, and a reliable interest in the patient’s happiness?
What is the fate of scientific abstracts presented at the International Society for Hip Arthroscopy meetings

Publication rates for general sports medicine society meetings have been studied but little is known about the publication rate for subspecialty sports medicine meetings. The purpose of this study was to determine the publication rates of abstracts presented at the annual meeting of the International Society for Hip Arthroscopy (ISHA) from 2011 to 2014. A database of abstracts presented at the annual meetings of ISHA was compiled. Abstracts that reached manuscript publication were determined using a PubMed search of the Medline database and Google Scholar. Statistical analyses were primarily descriptive. A total of 220 podium abstracts and 454 posters were presented at ISHA annual meetings from 2011 to 2014. Of the 220 podium presentations, 118 (53.6%) were eventually published with 91.5% of these being published within 3 years. Of the 454 posters, 182 (40.1%) were published with 95.6% being published in 3 years. Podium presentations had a significantly higher publication rate (P < 0.001). Published podium and poster presentations were most frequently published in the Journal of Arthroscopy and Related Research (podium: 24.6%; poster: 28.6%). The overall publication rate of scientific abstracts presented at the Annual ISHA meeting approximates that of general sports medicine society meetings. Podium presentations are significantly more likely to be published than scientific research presented as poster. These findings may highlight the scientific and educational merit of content presented. Continued attention is needed to maintain and improve the quality of abstracts presented at ISHA meetings.
The Politics of the Linguistic Discontinuity of Occitan Versus the Continuity of Catalan: The Sermó by Ramon Muntaner

This chapter considers how the Catalan chronicler Ramon Muntaner used the Occitan language to represent the three dynasties of the House of Barcelona-Aragon, as well as those Sardinians who supported the Catalan-Aragonese invasion of their island in 1323. Muntaner only used the Occitan language once in his Cronica in the form of a Sermo to provide military advice to King James II of Aragon (r. 1291–1327) and his son Prince Alfonso, the future King Alfonso the Benign (r. 1327–1336). His use of the Occitan language could be interpreted as a continuation of the ideology established by Desclot in his Cronica, in which Occitan had been described as a language that did not represent a stable political identity. Muntaner exploits this ideology by employing Occitan to highlight the unity of the House of Barcelona-Aragon. While the conquest of Sicily in 1282 was predominantly a Catalan enterprise, this time Muntaner wishes to emphasize that the whole Crown of Aragon in the Iberian Peninsula and the Kingdom of Majorca have united to conquest Sardinia. The Sermo also relies upon the Occitan language to include and exalt the inhabitants of Sardinia who supported the Catalan-Aragonese invasion. The political discontinuity of Occitan that appears in Desclot and Muntaner’s accounts exalts how the Catalan language represents the Catalan-Aragonese monarchy.
High-Accuracy Atomic Force Microscope

We have designed, built, and tested a high-accuracy atomic force microscope (HAFM) to be used for dimensional metrology. The HAFM is specialized for use in conjunction with our Sub-Atomic Measuring Machine (SAMM), serving as the surface measurement probe with 0.1 nm resolution over the SAMM travel range of 25 mm by 25 mm by 100 μm. In this configuration, all lateral scanning is provided by the SAMM, and so the HAFM is designed to move its probe with a single degree of freedom motion normal to the sample of interest. This sample-normal probe motion (Z-axis) is guided in the HAFM by symmetric monolithic flexures which are designed for high thermal stability and minimum lateral error motion. A piezoelectric stack drives the HAFMZ-axis over a range of 20 μm. The HAFM uses a commercially available self-sensing quartz-tuning-fork-based AFM probe, which is operated in constant-amplitude self-resonance via electronics described herein. In this configuration, the sample-probe separation is sensed via frequency shift of the probe resonance. The probe-sample separation is controlled using a discretetime surface-tracking controller implemented on a field-programmable gate array (FPGA). The controller tracks the surface by actuating the piezo to maintain a constant self-resonance period. To avoid spurious mixing, the controller’s sampling is made synchronous to the self-resonance oscillations. Three capacitive displacement sensors directly measure the surface trackingmotion, providing a high-accuracymeasurement of surface height. We have experimentally demonstrated surface tracking control with 100 Hz unity-gain crossover frequency, 70 degrees phase margin, and 0.12-nm RMS noise in a 100-Hz measurement bandwidth. We have also used the HAFM to measure calibration gratings and the surface of a freshly cleaved sanded Mica sample. The HAFM probe has recently been installed on the SAMM stage; we show a preliminary image taken using this combination.
Unobservable Commitment and Management Control: An Experiment

We conduct an experiment designed to investigate unobservable commitment in a management control setting with a privately informed subordinate. The experimental setting follows closely that found in Evans, Hannan, Krishan and Moser [2001] and Rankin, Schwartz and Young [2003]. In one treatment the superior makes an unobservable, but binding commitment regarding her future behavior. In the other treatment the superior reacts to the subordinate’s actions without having made a prior commitment. In both treatments the superior sends a non-binding announcement regarding her intended response. Arguments are presented for how an unobservable commitment might affect the superior’s resolve to punish undesirable behavior by the subordinate. We find that unobservable commitment weakens the superiors’ willingness to inflict costly punishment on the subordinate and, in turn, subordinates eventually learn to be more aggressive. One possible implication is in some circumstances it may be better for superiors to let their emotions have “free rein” if their goal is to convince subordinates of their willingness to retaliate against them for their unfair behavior.
The Plant Cell Wall as a Barrier to Fungal Invasion

The subject of this chapter is the plant cell wall. Cell walls are fascinatingly complex formations, variable in structure and composition depending upon their location in the plant body, their age, their genus, and the environment. Their composition is so complex that it is still not completely understood (McNeil et al., 1984). Cell walls serve many functions including a role as a barrier to fungal penetration, as implied in the title of this chapter. Cell wall composition is reflected in all these roles. For example, lignification provides the mechanical strength for aerial growth of plants and may incidentally render the cell wall resistant to attack by most potential pathogens. But in other situations, the normal requirement of cell wall function may be in conflict with defense: The cell walls of the “zone of elongation” in roots are expanding, presumably under hormonal influence, and, hence, must be relatively weak if growth occurs by bond cleavage and interpolation of new wall material. This is the precise region of the root most susceptible to invasion by Phytophthora spp. and other soil-borne pathogens. This potential for conflict between different functions of cell walls should always be kept in mind as it may profoundly influence the success or failure of defense responses.
The Immune Rejection: Lessons from Experimental Models

The mechanisms of immune rejection depend on a complex interplay between the elements of innate and adaptive immunity. Several studies in animal models of cancer and other conditions, including obesity and intestinal microbiome, over the past decade have provided evidence for an intricate cross-regulation of innate resistance and adaptive immunity. More recently, it became apparent that adaptive immunity, besides its effector function, also controls innate immune responses beyond its role in immune complex-Fc receptor interaction. This has led to a paradigm shift from the classical unidirectional notion of the innate instruction of adaptive immunity to a bidirectional partnership of the innate and adaptive immune system in controlling various pathological and physiological conditions. This chapter summarizes the advances in our understanding of the mechanisms of immune reactivity in the models of intestinal microbiota, acute infections, obesity, and cancer.
Central Venous Access for Rural Surgeons

Central venous access can be performed with the anatomic landmark technique or with ultrasound guidance. Complications of insertion of central venous catheters include pneumothorax, vascular injury, and nerve injury. Indwelling complications include infection and thrombosis. Real-time ultrasound guidance can reduce the risk of injuries from central venous access. The ideal location of the catheter tip is in the distal superior vena cava, near the junction of the superior vena cava and the right atrium. Catheters with tips that extend deep into the right atrium may cause cardiac arrhythmias and have increased thrombosis rate. Catheters with tips in the proximal superior vena cava and inlet vessels (brachiocephalic veins) and subclavian veins also have higher thrombosis rates.
Assessing Sensitivity to an Unobserved Binary Covariate in an Observational Study with Binary Outcome

This paper proposes a simple technique for assessing the range of plausible causal con- clusions from observational studies with a binary outcome and an observed categorical covariate. The technique assesses the sensitivity of conclusions to assumptions about an unobserved binary covariate relevant to both treatment assignment and response. A medical study of coronary artery disease is used to illustrate the technique. Inevitably, the results of clinical studies are subject to dispute. In observational studies, one basis for dispute is obvious: since patients were not assigned to treatments at random, patients at greater risk may be over-represented in some treatment groups. This paper proposes a method for assess- ing the sensitivity of causal conclusions to an unmeasured patient characteristic relevant to both treatment assignment and response. Despite their limitations, observational studies will continue to be a valuable source of information, and therefore it is prudent to develop appropriate methods of analysis for them. Our sensitivity analysis consists of the estimation of the average effect of a treatment on a binary outcome variable after adjustment for observed categorical covariates and an unobserved binary covariate u, under several sets of assumptions about u. Both Cornfield et al. (1959) and Bross (1966) have proposed guidelines for determining whether an unmeasured binary covariate having specified properties could explain all of the apparent effect of a treatment, that is, whether the treatment effect, after adjustment for u could be zero. Our method has two advantages: first, Cornfield et al. (1959) and Bross (1966) adjust only for the unmeasured binary covariate u, whereas we adjust for measured covariates in addition to the unmeasured covariate u. Second, Cornfield et al. (1959) and Bross (1966, 1967) only judge whether the effect of the treatment could be zero having adjusted for u, where Cornfield et al. (1959) employ an implicit yet extreme assumption about u. In contrast, we provide actual estimates of the treatment effect adjusted for both u and the observed categorical covariates under any assumption about u. In principle, the ith of the N patients under study has both a binary response r1i that would have resulted if he had received the new treatment, and a binary response ro0 that would have resulted if he had received the control treatment. In this formulation, treatment effects are comparisons of r1i and roi, such as r1i - roi. Since each patient receives only one treatment, either rli or ro0 is observed, but not both, and therefore comparisons of rli and roi imply some degree of speculation. Treatment effects defined as comparisons of the two potential responses, r1i and roi, of individual patients are implicit in Fisher's (1953) randomization test of the sharp null
Web-Based Perceived Present Control Intervention for Voice Disorders: A Pilot Study.

Summary Objective Voice disorders are common and negatively affect various life domains such as occupational functioning and emotional well-being. Perceived present control, a factor that is amenable to change, may reduce the effect of voice disorders on these outcomes. This pilot study aimed to (1) establish the feasibility, usability, and acceptability of a web-based perceived present control intervention for individuals with voice disorders and (2) gather preliminary data on the effectiveness of the intervention. This study is the first to assess whether a web-based psychological intervention would decrease self-reported voice handicap in this population. Methods Participants (N = 20) were recruited from an otolaryngology clinic at a large, Midwest university and the surrounding urban community, and completed a 3-week web-based intervention that incorporated psychoeducation and written exercises on increasing perceived present control. Results Supporting feasibility, the intervention components had high completion rates (75%–95%). Most participants planned to continue the perceived control exercises after study completion and would recommend the intervention to others, demonstrating usability and acceptability. There was a significant decrease in self-reported voice handicap (Voice Handicap Index-10) from pretest (M = 18.38, standard deviation = 4.41) to post-test (M = 15.22, standard deviation = 4.55) with a large effect size (within-group d = −0.86, P Conclusions Focusing on perceived present control as a teachable skill may be a useful addition to voice disorder treatment armamentarium. Future studies will incorporate a comparison group and larger sample sizes to assess further the role of perceived present control interventions in voice care.
Use of reference point theory to explain the price paid for private targets

We investigate whether reference points influence the price paid for private targets. Contrary to prior literature, we consider reference points of both target and bidder firms. Because market valuations of private targets are not available, we use comparable public firms and actual deals to derive an implied reference point for private targets. We find that when private firms have an implied valuation that is further from their implied reference points, they require a higher premium. In addition we find that the price paid for private targets is influenced by the bidder’s own reference point. We also show that the degree to which the target reference point influences the price paid for private targets is time-varying and affected by the prevailing economy. Private targets rely less heavily on their implied reference point to negotiate their takeover price when economic conditions are strong. Our findings confirm existing evidence that behavioral biases (reference points) are an important determinant of observed acquisition premiums.
Insulin-like Growth Factor (IGF)-1 treatment stabilizes the microvascular cytoskeleton under ischemic conditions.

Abstract Our previous studies showed that Insulin-like Growth Factor (IGF)-1 reduced blood brain barrier permeability and decreased infarct volume caused by middle cerebral artery occlusion (MCAo) in middle aged female rats. Similarly, cultures of primary brain microvessel endothelial cells from middle-aged female rats and exposed to stroke-like conditions (oxygen glucose deprivation; OGD) confirmed that IGF-1 reduced dye transfer across this cell monolayer. Surprisingly, IGF-1 did not attenuate endothelial cell death caused by OGD. To reconcile these findings, the present study tested the hypothesis that, at the earliest phase of ischemia, IGF-1 promotes barrier function by increasing anchorage and stabilizing cell geometry of surviving endothelial cells. Cultures of human brain microvessel endothelial cells were subject to oxygen-glucose deprivation (OGD) in the presence of IGF-1, IGF-1 + JB-1 (IGFR inhibitor) or vehicle. OGD disrupted the cell monolayer and reduced cell-cell interactions, which was preserved in IGF-1-treated cultures and reversed by concurrent treatment with JB-1. IGF-1-mediated preservation of the endothelial monolayer was reversed with LY294002 treatment, but not by Rapamycin, indicating that IGF-1 s actions on cell-cell contacts are likely mediated via the PI3K pathway. In vivo, microvessel morphology was evaluated in middle-aged female rats that were subjected to ischemia by MCAo, and treated ICV with IGF I, IGF-1 + JB-1, or artificial CSF (aCSF; vehicle) after reperfusion. Compared to vehicle controls, IGF-1 treated animals displayed larger microvessel diameters in the peri-infarct area and increased staining density for vinculin, an anchorage protein. Both these measures were reversed by concurrent IGF-1 + JB-1 treatment. Moreover these effects were restricted to 24 h after ischemia-reperfusion and no treatment effects were seen at 5d post stroke. Collectively, these data suggest that in the earliest hours during ischemia, IGF-1 promotes receptor-mediated anchorage of endothelial cells, and its actions may be accurately characterized as vasculoprotective.
Exercise Videogames, Physical Activity, and Health: Wii Heart Fitness: A Randomized Clinical Trial

Introduction Adults who engage in regular physical activity have lower rates of morbidity and mortality than those who do not. Exercise videogames may offer an attractive, sustainable alternative or supplement to traditional modes of exercise. This study compared exercise videogames with standard exercise modalities for improving uptake and maintenance of moderate to vigorous physical activity, and health risk indices. Study design A three-arm clinical RCT including 12 weeks of supervised laboratory-based moderate to vigorous physical activity followed by 6 months follow-up. Setting/participants This study was conducted at a university affiliated hospital research lab. Healthy, sedentary adults were eligible. Interventions This study compared a 12-week program of supervised exercise videogames versus standard exercise (e.g., treadmill) versus control. Data were collected from January 2012 to September 2017 and analyzed in 2018. Main outcome measures The primary outcome was weekly minutes of moderate to vigorous physical activity at end of treatment, assessed at 3 and 6 months post-intervention by using self-report and accelerometer data. Health risk indices (e.g., HbA1c, lipids) were also assessed. Results Participants (N=283) had an average age of 46.2 ±13.5 years; 79% were female. At end of treatment, those in the exercise videogame arm engaged in 30 minutes/week more moderate to vigorous physical activity compared with standard exercise and 85 more minutes/week than controls (all p Conclusions Exercise videogames produced greater uptake and maintenance of moderate to vigorous physical activity compared with standard exercise and improvements in multiple health risk indices. Exercise videogames may promote sustainable physical activity with significant health benefits. Trial registration This study is registered at www.clinicaltrials.gov NCT03298919.
$\Delta-\Sigma$ Noise-Shaping in 2-D Space-Time for Wideband Antenna Array Receivers

This paper proposes multi-dimensional signal processing methods to extend $\Delta-\Sigma $ modulation into the two-dimensional (2-D) space, time case. The proposed 2-D noise-shaping methods employ lossless discrete integrators (LDIs) to reduce the spectral overlap of the regions of support (ROSs) of array signals with that of both thermal and quantization noise in microwave and mm-wave array processing systems. Spatio–temporal low-pass filtering can then be used to improve the overall noise figure, linearity, and resolution of the resulting $N$ -port receiver. A proof-of-concept 65-port receiver that uses first-order $\Delta-\Sigma $ within both the low-noise amplifier and analog-to-digital converter (ADC) has been designed in the UMC 65-nm CMOS process. Detailed circuit simulations with wideband RF inputs at a center frequency of 4 GHz confirm that the proposed 2-D noise-shaping approach provides significant improvements in noise, linearity, and resolution. Specifically, noise figure (NF) improves by 1.5 dB, IIP3 improves by 15 dB, and the effective number of bits (ENOB) improves by 3.1 bits. Experimental results from a low-frequency board-level implementation of a 64-port ADC with first-order noise shaping are also presented.
Advances in Management of Merkel Cell Carcinoma in Organ Transplant Recipients: Role of Polyoma Virus and Immunosuppression

Merkel cell carcinoma (MCC) is a rare and aggressive primary cutaneous neoplasm with a high incidence of local recurrence as well as propensity for regional and systemic metastasis. Mortality rates are high with 5-year survival rates ranging from 29 % up to 74 %. Evidence demonstrates that the immune system is intimately involved with tumor development and progression. The hypothesis that a viral oncogene may play a causative role stemmed from this observation and led to the discovery of a new polyomavirus, designated Merkel cell polyomavirus (MCPyV). Up to 10 % of MCCs are found in the setting of decreased immunity. Organ transplant recipients tend to develop MCCs at an earlier age and show decreased MCC-specific and overall survival when compared to the general population. Mechanism-based therapies and viral antigen–directed therapies are in the early stages of development but show promise as targeted therapies.
Toward Realizing Multifunctionality: Photoactive and Selective Adsorbents for the Removal of Inorganics in Water Treatment.

ConspectusPersistent and potentially toxic inorganic oxoanions (e.g., arsenic and selenium) are one class of contaminants of concern in drinking water for which treatment technologies must be impro...
Associations of Arthritis-Attributable Interference with Routine Life Activities: A Modifiable Source of Compromised Quality-of-Life

Objective Arthritis patients experience the impact of disease beyond routinely assessed clinical measures. We characterized arthritis-attributable interference in four important routine life domains: 1) recreation/leisure/hobbies; 2) household chores; 3) errands/shopping; and 4) social activities. Methods Participants were from the Arthritis Conditions Health Effects Survey (2005-2006), a cross-sectional survey of noninstitutionalized US adults 45 years or older with doctor-diagnosed arthritis (n = 1793). We estimated the prevalence of "a lot" of arthritis-attributable interference and quantified the associations between sociodemographic, clinical, and psychological characteristics and "a lot" of arthritis-attributable interference (vs "a little" or "none") in each domain using prevalence ratios (PRs) in multivariable (MV)-adjusted logistic regression models. Results An estimated 1 in 5 to 1 in 4 adults with arthritis reported "a lot" of arthritis-attributable interference in recreation/leisure/hobbies (27%), household chores (25%), errands/shopping (22%), and social activities (18%). The highest prevalence of "a lot" of arthritis-attributable interference was for those unable to work/disabled or reporting severe arthritis symptoms (pain, stiffness, fatigue), anxiety, depression, or no/low confidence in ability to manage arthritis, across domains. In MV-adjusted models, those unable to work/disabled, currently seeing a doctor, or reporting fair/poor self-rated health, severe joint pain, anxiety, or no/low confidence in ability to manage arthritis were more likely to report arthritis-attributable interference than their respective counterparts. Magnitudes varied by domain but were consistently strongest for those unable to work/disabled (MV PR range = 1.8-2.5) and with fair/poor health (MV PR range = 1.7-2.7). Conclusion Many characteristics associated with arthritis-attributable interference in routine life activities are potentially modifiable, suggesting unmet need for use of existing evidence-based interventions that address these characteristics and reduce interferences to improve quality of life.
Development of broadband x-ray radiography for diagnosing magnetically driven cylindrically compressed matter

Experiments and modeling of x-ray radiography of millimeter diameter solid Al wires with laser-produced broadband x rays are reported. Experiments were performed using the 50-TW Leopard short-pulse laser in a laser and pulsed power chamber at the Nevada Terawatt Facility. To characterize broadband x rays and demonstrate a radiographic capability, bremsstrahlung, escaping electrons, and radiograph images of Al wires were simultaneously measured. The angularly resolved x-ray spectra are modeled by comparing measured bremsstrahlung signals in the range between 10 and ∼500 keV with hybrid particle-in-cell simulations. Transmission of Al wires from the radiograph images is further simulated with a Monte Carlo code. The measured transmission profiles of Al wires with three different diameters agree with calculations when a simulated x-ray spectrum composed of line emissions and bremsstrahlung is used with a source size of 600 ± 200 μm. Transmission calculations with only 22 keV Ag Kα or an exponential x-ray spectrum do not reproduce the measurement, suggesting that the accurate determination of an x-ray source spectrum, as well as the inclusion of the photon sensitivity of the detector, is critical in transmission calculations to infer the density of an object. The laser-based broadband x-ray radiography that was developed has been successfully implemented in a pulsed power chamber for future laser-pulsed-power coupled experiments.Experiments and modeling of x-ray radiography of millimeter diameter solid Al wires with laser-produced broadband x rays are reported. Experiments were performed using the 50-TW Leopard short-pulse laser in a laser and pulsed power chamber at the Nevada Terawatt Facility. To characterize broadband x rays and demonstrate a radiographic capability, bremsstrahlung, escaping electrons, and radiograph images of Al wires were simultaneously measured. The angularly resolved x-ray spectra are modeled by comparing measured bremsstrahlung signals in the range between 10 and ∼500 keV with hybrid particle-in-cell simulations. Transmission of Al wires from the radiograph images is further simulated with a Monte Carlo code. The measured transmission profiles of Al wires with three different diameters agree with calculations when a simulated x-ray spectrum composed of line emissions and bremsstrahlung is used with a source size of 600 ± 200 μm. Transmission calculations with only 22 keV Ag Kα or an exponential x-ray spe...