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Contemporary American society confirms daily that extreme polarization turns every issue, large and small, into an opportunity for intense disagreement. By polarization I mean what political scientists more precisely call [...]

Background Adults with chronic kidney disease (CKD) are hospitalized more frequently than those without CKD, but the magnitude of this excess morbidity and the factors associated with hospitalizations are not well known. Methods and findings Data from 3,939 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study between 2003 and 2008 at 7 clinical centers in the United States were used to estimate primary causes of hospitalizations, hospitalization rates, and baseline participant factors associated with all-cause, cardiovascular, and non-cardiovascular hospitalizations during a median follow up of 9.6 years. Multivariable-adjusted Poisson regression was used to identify factors associated with hospitalization rates, including demographics, blood pressure, estimated glomerular filtration rate (eGFR), and proteinuria. Hospitalization rates in CRIC were compared with rates in the Nationwide Inpatient Sample (NIS) from 2012. Of the 3,939 CRIC participants, 45.1% were female, and 41.9% identified as non-Hispanic black, with a mean age of 57.7 years, and the mean eGFR is 44.9 ml/min/1.73m.sup.2 . CRIC participants had an unadjusted overall hospitalization rate of 35.0 per 100 person-years (PY) [95% CI: 34.3 to 35.6] and 11.1 per 100 PY [95% CI: 10.8 to 11.5] for cardiovascular-related causes. All-cause, non-cardiovascular, and cardiovascular hospitalizations were associated with older age ([greater than or equal to]65 versus 45 to 64 years), more proteinuria ([greater than or equal to]150 to Conclusions In this study, we observed that adults with CKD had a higher hospitalization rate than the general population that is hospitalized, and even moderate reductions in kidney function were associated with elevated rates of hospitalization. Causes of hospitalization were predominantly related to cardiovascular disease, but other causes contributed, particularly, genitourinary, digestive, and endocrine, nutritional, and metabolic illnesses. High levels of proteinuria were observed to have the largest association with hospitalizations across a wide range of kidney function levels., Author(s): Sarah J. Schrauben 1,2,3,*, Hsiang-Yu Chen 3, Eugene Lin 4, Christopher Jepson 5, Wei Yang 3, Julia J. Scialla 6, Michael J. Fischer 7,8, James P. Lash 8, Jeffrey [...]

Many biopolymers, including polysaccharides, must be translocated across at least one membrane to reach their site of biological function. Cellulose is a linear glucose polymer synthesized and secreted by a membrane-integrated cellulose synthase. Here, in crystallo enzymology with the catalytically active bacterial cellulose synthase BcsA-BcsB complex reveals structural snapshots of a complete cellulose biosynthesis cycle, from substrate binding to polymer translocation. Substrate--and product-bound structures of BcsA provide the basis for substrate recognition and demonstrate the stepwise elongation of cellulose. Furthermore, the structural snapshots show that BcsA translocates cellulose via a ratcheting mechanism involving a 'finger helix' that contacts the polymer's terminal glucose. Cooperating with BcsA's gating loop, the finger helix moves 'up' and 'down' in response to substrate binding and polymer elongation, respectively, thereby pushing the elongated polymer into BcsA's transmembrane channel. This mechanism is validated experimentally by tethering BcsA's finger helix, which inhibits polymer translocation but not elongation., Cellulose is an abundant structural cell component produced by many organisms, including bacteria, vascular plants and animals (1-4). It is a linear polymer of glucose molecules joined between their C1 [...]

Background To the extent that outcomes are mediated through negative perceptions of generics (the nocebo effect), observational studies comparing brand-name and generic drugs are susceptible to bias favoring the brand-name drugs. We used authorized generic (AG) products, which are identical in composition and appearance to brand-name products but are marketed as generics, as a control group to address this bias in an evaluation aiming to compare the effectiveness of generic versus brand medications. Methods and findings For commercial health insurance enrollees from the US, administrative claims data were derived from 2 databases: (1) Optum Clinformatics Data Mart (years: 2004-2013) and (2) Truven MarketScan (years: 2003-2015). For a total of 8 drug products, the following groups were compared using a cohort study design: (1) patients switching from brand-name products to AGs versus generics, and patients initiating treatment with AGs versus generics, where AG use proxied brand-name use, addressing negative perception bias, and (2) patients initiating generic versus brand-name products (bias-prone direct comparison) and patients initiating AG versus brand-name products (negative control). Using Cox proportional hazards regression after 1:1 propensity-score matching, we compared a composite cardiovascular endpoint (for amlodipine, amlodipine-benazepril, and quinapril), non-vertebral fracture (for alendronate and calcitonin), psychiatric hospitalization rate (for sertraline and escitalopram), and insulin initiation (for glipizide) between the groups. Inverse variance meta-analytic methods were used to pool adjusted hazard ratios (HRs) for each comparison between the 2 databases. Across 8 products, 2,264,774 matched pairs of patients were included in the comparisons of AGs versus generics. A majority (12 out of 16) of the clinical endpoint estimates showed similar outcomes between AGs and generics. Among the other 4 estimates that did have significantly different outcomes, 3 suggested improved outcomes with generics and 1 favored AGs (patients switching from amlodipine brand-name: HR [95% CI] 0.92 [0.88-0.97]). The comparison between generic and brand-name initiators involved 1,313,161 matched pairs, and no differences in outcomes were noted for alendronate, calcitonin, glipizide, or quinapril. We observed a lower risk of the composite cardiovascular endpoint with generics versus brand-name products for amlodipine and amlodipine-benazepril (HR [95% CI]: 0.91 [0.84-0.99] and 0.84 [0.76-0.94], respectively). For escitalopram and sertraline, we observed higher rates of psychiatric hospitalizations with generics (HR [95% CI]: 1.05 [1.01-1.10] and 1.07 [1.01-1.14], respectively). The negative control comparisons also indicated potentially higher rates of similar magnitude with AG compared to brand-name initiation for escitalopram and sertraline (HR [95% CI]: 1.06 [0.98-1.13] and 1.11 [1.05-1.18], respectively), suggesting that the differences observed between brand and generic users in these outcomes are likely explained by either residual confounding or generic perception bias. Limitations of this study include potential residual confounding due to the unavailability of certain clinical parameters in administrative claims data and the inability to evaluate surrogate outcomes, such as immediate changes in blood pressure, upon switching from brand products to generics. Conclusions In this study, we observed that use of generics was associated with comparable clinical outcomes to use of brand-name products. These results could help in promoting educational interventions aimed at increasing patient and provider confidence in the ability of generic medicines to manage chronic diseases., Author(s): Rishi J. Desai 1,*, Ameet Sarpatwari 1, Sara Dejene 1, Nazleen F. Khan 1, Joyce Lii 1, James R. Rogers 1, Sarah K. Dutcher 2, Saeid Raofi 3, Justin [...]

Prion disorders are a unique class of diseases caused by pathologically misfolding proteins leading to neurodegeneration (1). Creutzfeldt-Jakob disease (CJD), one such prion disorder, is divided into 4 etiologic categories: [...]

Chronic kidney disease (CKD) is a public health epidemic that increases risk of death due to cardiovascular disease. Left ventricular hypertrophy (LVH) is an important mechanism of cardiovascular disease in [...]

Local anesthetics (LAs) block the generation and propagation of action potentials by interacting with specific sites of voltage-gated [Na.sup.+] channels. LAs can also excite sensory neurons and be neurotoxic through mechanisms that are as yet undefined. Nonspecific cation channels of the transient receptor potential (TRP) channel family that are predominantly expressed by nociceptive sensory neurons render these neurons sensitive to a variety of insults. Here we demonstrated that the LA lidocaine activated TRP channel family receptors TRPV1 and, to a lesser extent, TRPA1 in rodent dorsal root ganglion sensory neurons as well as in HEK293t cells expressing TRPV1 or TRPA1. Lidocaine also induced a TRPV1-dependent release of calcitonin gene--related peptide (CGRP) from isolated skin and peripheral nerve. Lidocaine sensitivity of TRPV1 required segments of the putative vanilloid-binding domain within and adjacent to transmembrane domain 3, was diminished under phosphatidylinositol 4,5-bisphosphate depletion, and was abrogated by a point mutation at residue R701 in the proximal C-terminal TRP domain. These data identify TRPV1 and TRPA1 as putative key elements of LA-induced nociceptor excitation. This effect is sufficient to release CGRP, a key component of neurogenic inflammation, and warrants investigation into the role of TRPV1 and TRPA1 in LA-induced neurotoxicity., Introduction Local anesthetics (LAs) block voltage-gated [Na.sup.+] channels, the major generators of the upstroke of action potentials (1), (2). The clinical use for spinal anesthesia and peripheral regional anesthesia requires [...]

The article discusses the advent and functions of four partly distinctive genealogies of the anthropology of science and technology in research from the 1990s through the early 21st century.

Background: There is a lack of detailed information concerning patients' sports and recreational activities after unicompartmental knee arthroplasty. Hypothesis: Patients treated by unicompartmental knee arthroplasty will be able to return [...]

The growth of cultural analysis from the beginnings of modern anthropology to the present is outlined as layered set of experimental system. It is suggested that culture is not a variable but relational, as it is a set of central anthropological forms of knowledge being the foundation of human beings' self-understanding.

A forum titled eRethinking American CultureE featured the work of George Lipsitz in a dialogue between American Studies and anthropology about the ways in which new forms of commercial patterns and practices, new movements of people and products, and new communications technologies produce new ways of studying culture. The dialogue addresses the struggles over the social warrants of the US culture in the 21st century and how historians and anthropologists describe and analyze such warrants and reconstitute these fields, which are under pressure in ea moment of dangerE.

ABSTRACT The purpose of this paper is to review and compare income tax legislation passed during the Civil War by both the Union and the Confederacy. The major tax act [...]

The challenge of cultural analysis is to develop translation and mediation tools for helping make visible the differences of interests, access, power, needs, desires, and philosophical perspective. A discussion on the changes in cultural analysis through the last quarter of the 20th century and the early years of the 21st century, brought about by social and technological developments, is presented.

Based on in-depth qualitative interviews, this article gives the opportunity to 145 sixth graders to tell, in their own words, how they felt and reacted when verbally and emotionally abused by their classmates. Content analysis of interviews revealed gender differences in students' reactions to verbal aggression. Another interesting finding was the differentiation between verbally aggressive messages meant to be for fun from those that were not so meant based on (1) contextual cues, (2) other peers' reaction, and (3) the malleability of the personal features that were the topic of the attack. Observing friendly peers were found to play an important role in reducing tension and preventing the escalation of violence. However, when the verbally aggressive message targeted a permanent physical characteristic or the student's social or ethnic identity, then suffering, anger and humiliation legitimized the escalation from verbal to physical aggression for students of both genders. Keywords: verbal abuse; aggression; interpersonal interaction; youth development

NKCC1 null mice are hypotensive, in part, from the absence of NKCC1-mediated vasoconstriction. Whether these mice have renal defects in NaCl and water handling which r contribute to the hypotension is unexplored. Therefore, we asked 1) whether NKCC1 (-/-) mice have a defect in the regulation of NaCl and water balance, which might contribute to the observed hypotension and 2) whether the hypotension observed in these mice is accompanied by endocrine abnormalities and/or downregulation of renal [Na.sup.+] transporter expression. Thus we performed balance studies, semi-quantitative immunoblotting, and immunohistochemistry of kidney tissue from NKCC1 (+/+) and NKCC1 (-/-) mice which consumed either a high (2.8% NACl)- or a low-NaCl (0.01% NaCl) diet for 7 days. Blood pressure was lower in NKCC1 (-/-) than NKCC1 (+/+) mice following either high or low dietary NaCl intake. Relative to wild-type mice, NKCC1 null mice had a lower plasma ANP concentration, a higher plasma renin and a higher serum [K.sup.+] concentration with inappropriately low urinary [K.sup.+] excretion, although serum aldosterone was either the same or only slightly increased in the mutant mice. Expression of NHE3, the a-subunit of the Na-K-ATPase, NCC, and NKCC2 were higher in NKCC1 null than in wild-type mice, although differences were generally greater during NaCl restriction. NKCC1 null mice had a reduced capacity to excrete free water than wild-type mice, which resulted in hypochloremia following the NaCl-deficient diet. Hypochloremia did not occur from increased aquaporin-1 (AQP1) or 2 protein expression or from redistribution of AQP2 to the apical regions of principal cells. Instead, NKCC1 null mice had a blunted increase in urinary osmolality following vasopressin administration, which should increase free water excretion and attenuate the hypochloremia. In conclusion, aldosterone release is inappropriately low in NKCC1 null mice. Moreover, the action of aldosterone and vasopressin is altered within kidneys of NKCC1 null mice, which likely contributes to their hypotension. Increased [Na.sup.+] transporter expression, increased plasma renin, and reduced plasma ANP, as observed in NKCC1 null mice, should increase vascular volume and blood pressure, thus minimizing hypotension. [Na.sup.+] transporters; chloride; water; renin; aldosterone

A retrospective cohort study involving 22,890 patients 65 years of age who had drug insurance benefits in Pennsylvania and who began receiving atypical antipsychotic medication between 1994 and 2003 is conducted. Results suggest that conventional antipsychotic medications are as likely as atypical agents to increase the risk of death among elderly persons and that conventional drugs should not be used to replace atypical agents discontinued in response to the FDA warning.

New forms of life, ethical plateaus, and civic political contests arise through the creation of new technoscientific infrastructures in which market, law, code, and norms compete for hegemonic control over the rules of play. A review of a panel of four articles interrogates agendas for ethnographies of the locally diverse peopling of such new infrastructures, including the continuing renegotiation of historical and emergent modalities of ethical and political reason. [Keywords: emergent forms of life, technoscientific infrastructures, deep play, ethical plateaus, biology as civics]

The state Medicaid agencies was surveyed to determine whether prescription of cyclooxygenase-2 inhibitors (coxibs) required prior authorization and, if so, the criteria for authorization. It was found that the use of coxibs and spending on nonsteroidal antiinflammatory drugs (NSAIDs) varied widely by state and declined substantially after the implementation of prior-authorization programs.

The potential savings from the perspective of health care payers that would result from increased adherence to evidence-based recommendations for managing hypertension in patients older than 65 years is calculated.

This study examined the extent to which a multiethnic sample of 900 Israeli high school students supported date-rape and victim-blaming attitudes and the predictors of such support. Findings indicate wide support for stereotypes justifying sexual coercion by time and the location of the date, the victim's behavior, and the minimization of the seriousness of date rape. A regression analysis indicates that students' gender and age are the strongest predictors of rape-tolerant and victim-blaming attitudes. Socioeconomic status and religious orientation explain a small proportion of the variance in the support of such attitudes. By contrast, no significant relationship is indicated with ethnicity. Alternative sex-education and rape prevention programs must address date-rape and victim-blaming attitudes and make students of both genders aware of various factors that continue to be misread as an invitation to have sex and put them at high risk of experiencing sexual coercion on a date. Keywords: date rape; rape myths; sexual coercion; sexism; youth dating attitudes

Wall, Susan M., Michael P. Fischer, Dawn M. Glapion, and Mae De La Calzada. ANG II reduces net acid secretion in rat outer medullary collecting duct. Am J Physiol Renal Physiol 285: F930-F937, 2003. First published July 8, 2003; 10.1152/ajprenal.00400.2002.-In rat outer medullary collecting duct (OMCD), the mechanism(s) and regulation of [H.sup.+] secretion are not understood fully. The effect of changes in acid-base balance and the renin-angiotensin system on net [H.sup.+] secretion was explored. Rats received NaCl, NaHC[O.sub.3], N[H.sub.4]Cl, or nothing in their drinking water for 7 days. Total ammonia and total C[O.sub.2] ([J.sub.tco2) fluxes were measured in OMCD tubules perfused in vitro from rats in each treatment group. [J.sub.tCO2] was reduced in tubules from rats drinking N[H.sub.4]Cl relative to those drinking NaHC[O.sub.3]. Because N[H.sub.4]CI intake increases plasma renin and aldosterone, we asked if upregulation of the renin-angiotensin system reduces net [H.sup.+] secretion. Deoxycorticosterone pivalate administered in vivo did not affect J[tCO.sub.2]. However, ANG II given in vivo at 0.1 ng/min reduced J[tCO.sub.2] by 35%. To determine if ANG II has a direct effect on acid secretion, J[tCO.sub.2] was measured with ANG II applied in vitro. ANG II ([10.sup.8] M) present in the bath solution reduced J[tCO.sub.2] by 35%. This ANG II effect was not observed in the presence of the AT[sub.1] receptor blocker candesartan. In conclusion, in rat OMCD, J[tCO.sub.2] is paradoxically reduced with N[H.sub.4]Cl ingestion. Increased circulating ANG II, as occurs during metabolic acidosis, reduces J[tCO.sub.2]. ammonium; acidification; angiotensin 2; aldosterone; metabolic acidosis; metabolic alkalosis

Mixing stirrers are subject to severe damages when the rotational speed approaches the Eigenfrequency. Because of resonant vibrations, the stirrer deflection approaches infinity in the no damping case. Damping due to fluid-structure interaction between the mixing stirrer and the fluid in the vessel has major influence on the Eigenfrequency. Coupled analysis of the flow field within a mixing vessel and the structural dynamic response of the stirrer is necessary in order to evaluate vibrational amplitudes to guarantee life time safety for the stirrer. A simplified numerical model based on Newmark's integration scheme is developed for the stirrer dynamics that is suitable to be implemented in a CFD code as a user subroutine. Results in terms of Eigenfrequencies are compared to results of analytical formulas and FEM results and show excellent agreement. The fully fluid-structure coupled analysis is also presented. As a new aspect, a rotating grid (sliding mesh) was combined with a deformable grid to simulate the impeller movement. The results are compared to experimental and analytical data and show good agreement. [DOI: 10.1115/1.1613951]

Using a synthetic lethality screen we found that the Sit4 phosphatase is functionally linked to the ubiquitin-proteasome system. Yeast cells harboring sit4 mutations and an impaired proteasome (clue to pre1-1 pre4-1 mutations) exhibited defective growth on minimal medium. Nearly identical synthetic effects were found when sit4 mutations were combined with defects of the Radt/Ubc2- and Cdc34/Ubc3-dependent ubiquitination pathways. Under synthetic lethal conditions, sit4 pre or sit4 ubc mutants formed strongly enlarged unbudded cells with a DNA content of 1N, indicating a defect in the maintenance of cell integrity during starvation-induced [G.sub.1] arrest. Sit4-related synthetic effects could be cured by high osmotic pressure or by the addition of certain amino acids to the growth medium. These results suggest a concerted function of the Sit4 phosphatase and the ubiquitin-proteasome system in osmoregulation and in the sensing of nutrients. Further analysis showed that Sit4 is not a target of proteasome-dependent protein degradation. We could also show that Sit4 does not contribute to regulation of proteasome activity. These data suggest that both Sit4 phosphatase and the proteasome act on a common target protein.

In rat inner medullary collecting duct, N[H.sup.+.sub.4] uptake by the Na,K-ATPase is increased during hypokalemia. Am J Physiol Renal Physiol 282: F91-F102, 2002. First published August 21, 2001; 10.1152/ajprenal.00141.2002.-- In rat terminal inner medullary collecting duct (tIMCD), the Na,K-ATPase mediates N[H.sup.+.sub.4] uptake, which increases secretion of net [H.sup.+] equivalents. [K.sup.+] and N[H.sup.+.sub.4] compete for a common binding site on the Na,K-ATPase. Therefore, N[H.sup.+.sub.4] uptake should increase during hypokalemia because interstitial [K.sup.+] concentration is reduced. We asked whether upregulation of the Na,K-ATPase during hypokalemia also increases basolateral N[H.sup.+.sub.4] uptake. To induce hypokalemia, rats ate a diet with a low [K.sup.+] content. In tIMCD tubules from rats given 3 days of dietary [K.sup.+] restriction, Na,K-ATPase [[beta].sub.1]-subunit (NK-[[beta].sub.1]) protein expression increased although NK-[[alpha].sub.1] protein expression and Na,K-ATPase activity were unchanged relative to [K.sup.+]-replete controls. However, after 7 days of [K.sup.+] restriction, both NK-[[alpha].sub.1] and NK-[[beta].sub.1] subunit protein expression and Na,K-ATPase activity increased. The magnitude of Na,K-ATPase-mediated N[H.sup.+.sub.4] uptake across the basolateral membrane ([MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII]) was determined in tIMCD tubules perfused in vitro from rats after 3 days of a normal or a [K.sup.+]-restricted diet. [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] was the; same in tubules from rats on either diet when measured at the same extracellular [K.sup.+] concentration. However, in either treatment group, increasing [K.sup.+] concentration from 10 to 30 mM reduced [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] >60%. In conclusion, with 3 days of [K.sup.+] restriction, N[H.sup.+.sub.4] uptake by Na,K-ATPase is increased in the tIMCD primarily from the reduced interstitial [K.sup.+] concentration. sodium, hydrogen-adenosinetriphosphatase; terminal inner medullary collecting duct; potassium; ammonium

Author(s): Michael B. Fischer [1, 2]; Christiane Roeckl [1, 2]; Petra Parizek [1]; Hans Peter Schwarz [3]; Adriano Aguzzi (corresponding author) [1] Transmissible spongiform encephalopathies are associated with accumulation of [...]

Double-entry accounting, with its method for the objective calculation of profits and system of capital accounting, is often seen as closely linked with our modern-day system of capitalism. Questions regarding the role of profits are at the center of many debates on 'business ethics.' Luca Pacioli, a 15th century Franciscan friar, is recognized as the 'father of accounting' because he published the first description of the double-entry system. However, Pacioli's 'ethical' views have not been as broadly recognized. The main purpose of this paper is to present and discuss Pacioli's views on the conduct of business enterprise and the pursuit of business profits.

The anthropologies of late modernity or postmodernity are discussed, with a focus on the centrality of science and technology, as well as decolonization, postcolonialism, and reconstruction after social trauma. The role of new electronic and visual media is also discussed. Other topics include techniques of multilocale or multisited ethnography; texts that are multivocal or addressed to multiple audiences; changes in traditional notions of comparative work; anthropological representations as interventions; and working with other genres.

Affinity-driven selection of B lymphocytes within germinal centers is critical for the development of high-affinity memory cells and host protection. To investigate the role of the CD21/CD35 coreceptor in B cell competition for follicular retention and survival within the germinal center, either [Cr2.sup.+] or [Cr2.sup.null] lysozyme-specific transgenic B cells were adoptively transferred into normal mice immunized with duck (DEL) or turkey (TEL) lysozyme, which bind with different affinities. In mice injected with high-affinity turkey lysozyme, [Cr2.sup.null] B cells responded by follicular retention; however, they could not survive within germinal centers. This suggests that CD21 provides a signal independent of antigen that is required for survival of B cells in the germinal center., The murine Cr2 locus encodes complement receptors CD21 (CR2; 150 kD) and CD35 (CR1; 190 kD) that are expressed primarily on B cells and follicular dendritic cells (FDCs)(1). [Cr2.sup.null] mice [...]