cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract #676: A novel daunorubicin derivative that overcomes MDR1- and MRP1-mediated drug resistance

A major problem with anthracyclines, considered to be the most effective type of anticancer drugs, is the emergence of drug resistance. The well-characterized resistant mechanisms for anthracyclines include overexpression of efflux drug transporters such as multidrug resistance genes (MDR1, ABCB1, or P-glycoprotein) and multidrug resistance-associated proteins (MRP1, or ABCC1), which actively export drugs from the cells and thereby reduce intracellular drug accumulation. We hypothesize that direct modifications on the sugar moiety of anthracyclines would circumvent MDR1 and MRP1 efflux, increase drug concentration in cancer cells, and thus overcome transporter-mediated drug resistance. Several daunorubicin (DNR) derivatives were synthesized and characterized. Compared with the parent compound, one of the derivatives W10250 exhibited higher anticancer activity in both drug-sensitive leukemia cells HL-60 and K562 (MDR1(-) and MRP1(-)) and drug-resistant cells HL-60/ADR (MDR1(-)/MRP1(+)) and K562/DOX (MDR1(+)/MRP1(-)). The IC 50 for W10250 growth inhibition of K562 cells is 5-fold lower than that for DNR (0.02 vs. 0.10 µM), while the IC 50 for W10250 growth inhibition of K562/DOX cells is 250-fold lower than that for DNR (0.034 vs. 8.5 µM). The IC 50 for W10250 growth inhibition of HL-60 cells is 15-fold lower than that for DNR (0.001 vs. 0.015 µM), while the IC 50 for W10250 growth inhibition of HL-60/ADR cells is 3300-fold lower than that for DNR (0.002 vs. 6.6 µM). Drug uptake analysis using FACS assay demonstrated that W10250 abolished MDR1 and MRP1-mediated drug efflux and accumulated high intracellular concentration in the drug-resistance cells HL-60/ADR and K562/DOX. Inhibition of MDR1 and MRP1 by cyclosporine A and MK-571, respectively, supported the notion that this derivative is not a substrate for MDR1 and MRP1. DNR at 50 nM induced G2/M arrest in K562 cells through a well-documented topoisomerase II dependent mechanism, while 50 nM WL250 did not cause G2/M arrest but induced apoptosis, indicating a novel mechanism of action. These data suggest that specific sugar modification of anthracyclines abolish MDR1- and MRP1-mediated drug efflux, increase intracellular drug accumulation, and thus overcome both MDR1- and MRP1-mediated drug resistance in cancer therapy. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 676.
Satisfaction in Academic Otolaryngology: Do Physician Demographics Impact Press Ganey Survey Scores?

OBJECTIVES/HYPOTHESIS Patient satisfaction is increasingly emphasized and measured in healthcare delivery. However, patient satisfaction is multifactorial and difficult to comprehensively assess. The objective of this study was to assess for correlation between patient satisfaction measured by Press Ganey surveys (PGS) and physician demographics of gender, years in practice, academic rank, and specialty in academic otolaryngology. STUDY DESIGN Review of publicly available PGS scores in academic otolaryngology practice. METHODS Public websites of academic otolaryngology departments were assessed for inclusion of PGS scores. Individual physician profiles were queried for years in practice, academic rank, and specialty. Gender was determined by picture or profile pronouns. Univariate and multivariate analyses compared PGS scores with studied variables. RESULTS Forty-seven of 113 (42.8%) academic practices publicly reported physician PGS score. Of 1,360 affiliated otolaryngologists, 742 (54.6%,592 male:150 female) revealed PGS scores. Average PGS score for male and female providers was equivalent (PGS = 4.73, P = .84). There was no significant difference in PGS scores by academic rank (P = .28). A weak statistically significant decrease in mean PGS scores was associated with longer duration of practice (r = -0.11, P = .018). Head and neck oncologic surgeons had higher mean PGS score in comparison to other specialties (PGS = 4.81, P < .05). General/comprehensive otolaryngologists had lower average PGS score (PGS = 4.66) in comparison to specialists (P < .05). CONCLUSIONS Physician gender and academic rank do not correlate with patient satisfaction in academic otolaryngology as measured by publicly reported PGS scores. Head and neck oncology is rated more highly than other specialties, and physicians in practice for longer demonstrate decreased PGS scores. With PGS scores tied to physician evaluation and reimbursement, investigation into the generalizability of PGS in otolaryngology is warranted. LEVEL OF EVIDENCE NA Laryngoscope, 130: 1902-1906, 2020.
Shugoshin 2-a new guardian for heat shock transcription.

Takii et al (2019) demonstrate in a recent issue of The EMBO Journal that the pericentromeric protein, SGO2, serves as a novel transcriptional coactivator of HSF1, contributing to PIC assembly and expression of Heat Shock Protein (HSP) genes. This finding highlights repurposing of a protein with a nuclear function to drive transcription of proteotoxic stress machinery genes.
Improved Matrix Methodology for Calculating Diffraction Intensity Profiles from Interstratified Phyllosilicates

Diffraction effects from interstratified phyllosilicates have been studied extensively, and several computer programs such as NEWMOD© are available to facilitate interpretation of X-ray diffraction (XRD) profiles. However, accurate quantification of samples containing multiple interstratified phyllosilicate minerals is difficult due to the generally subjective nature of interpretations. More recent automated fitting interpretations require extensive computational effort, involving numerous calculations of profiles with different fitting-parameter values. Computational cost in time per calculation is the key factor influencing the overall efficiency of automated profile fitting. In general, the matrix methodology developed by Kakinoki and Komura is more efficient than the NEWMOD© architecture. A new matrix methodology was developed that reduces the number of matrix operations such as multiplication and addition, and these modifications improve calculation efficiency by up to a factor of three, with even greater improvement for small crystallite sizes (< 20 layers). A new computer program, ClayStrat, based on the modified matrix methodology, was developed to calculate one-dimensional XRD profiles from interstratified phyllosilicates along the Z direction.
Accounting graduates with both online and traditional coursework: impact on hiring decisions

With the growth of online education, many students enrolled in traditional accounting programs are taking a portion of their coursework online. Accounting students, educators, and administrators in...
Communication Lower-Bounds for Distributed-Memory Computations for Mass Spectrometry based Omics Data

Mass spectrometry based omics data analysis require significant time and resources. To date, few parallel algorithms have been proposed for deducing peptides from mass spectrometry based data. However, these parallel algorithms were designed, and developed when the amount of data that needed to be processed was smaller in scale. In this paper, we prove that the communication bound that is reached by the \emph{existing} parallel algorithms is $\Omega(mn+2r\frac{q}{p})$, where $m$ and $n$ are the dimensions of the theoretical database matrix, $q$ and $r$ are dimensions of spectra, and $p$ is the number of processors. We further prove that communication-optimal strategy with fast-memory $\sqrt{M} = mn + \frac{2qr}{p}$ can achieve $\Omega({\frac{2mnq}{p}})$ but is not achieved by any existing parallel proteomics algorithms till date. To further validate our claim, we performed a meta-analysis of published parallel algorithms, and their performance results. We show that sub-optimal speedups with increasing number of processors is a direct consequence of not achieving the communication lower-bounds proved in this paper. Consequently, we assert that next-generation of provable, and demonstrated superior parallel algorithms are urgently needed for MS based large systems-biology studies especially for meta-proteomics, protegenomics, microbiome, and proteomics for non-model organisms.
Smoking and Vaping

Cigarette smoking is the leading preventable cause of many chronic diseases including cardiovascular diseases. The mechanisms by which nicotine addiction and toxic compounds in cigarette smoke are pathologic are known and they are well-studied. The result of numerous campaigns in the last 50 years has led to a steady reduction of cigarette smoking among adults and youth. However, in recent years a new addiction has emerged. It is electronic nicotine delivery system (ENDS) or e-cigarettes. The behavior is known as vaping. This new nicotine addiction is increasingly taken up by youth and young adults resulting in a new habit and frequently advancing to regular cigarette use.
IDEALITAS DAN DESAIN PENGEMBANGAN BAHAN AJAR BAHASA ARAB

Abstrac : This study aims to discuss the ideal Arabic language development design with a focus point on the understanding of teaching materials and their position in learning, the principles / foundations for the development of Arabic teaching materials, and the characteristics of Arabic teaching materials. Based on the above topic, this research uses descriptive analysis method with the type of library research. The conclusions resulting from him are: 1. Teaching materials are a set of subject matter or substance arranged coherently and systematically and displaying a complete figure of the competencies that students will master in learning activities. 2. The principles that must be considered in the development of Arabic are socio-cultural, psychological, linguistic and educational or teaching principles. 3. The ideal characteristics that must be present in teaching materials are: types of subjects, topics / discussion titles, supporting media (images / designs that can help students understand the meaning of related vocabulary), new vocabulary, text / learning material (found in student books and teacher), questions and exercises, enrichment of Arabic rules, games (if possible). 4. The design of the development of Arabic teaching materials can be done through the following steps: analysis, design, writing and preparation of materials, evaluation and revision. Keywords : Arabic language, development design, teaching materials.
Upper Extremity Neuroprosthetics for Spinal Cord Injury

Neuroprostheses for upper extremity (UE) function in cervical spinal cord injury (SCI) are designed to provide increased independence by providing user-controlled grasp and release. All UE neuroprostheses are composed of a means of activating paralyzed muscles, a means of enabling the user to control the stimulation, and a computational component that translates the user’s command to the stimulation output. An important distinction of UE neuroprostheses when compared to other electrical stimulation systems is that the user must have direct real-time control of the stimulation. The selection of the control method is important to the design. Often a single command signal is used to control the stimulation to a dozen or more muscles, reducing the burden on the user during functional activities. In addition to the elements of stimulation, control, and processing, some systems include feedback loops.
Incidence of Venous Thromboembolism in Patients With Dermatologist-Diagnosed Chronic Inflammatory Skin Diseases.

Importance Several studies have linked chronic inflammatory skin diseases (CISDs) with venous thromboembolism (VTE) in a range of data sources with mixed conclusions. Objective To examine the incidence of VTE in patients with vs without CISD. Design, setting, and participants A cohort study using commercial insurance claims data from a nationwide US health care database from January 1, 2004, through 2019 was conducted. A total of 158 123 patients with dermatologist-recorded psoriasis, atopic dermatitis, alopecia areata, vitiligo, or hidradenitis suppurativa were included. Risk-set sampling identified patients without a CISD. Patient follow-up lasted until the first of the following occurred: VTE, death, disenrollment, or end of data stream. Exposures Patients with vs without CISD. Main outcomes and measures Venous thromboembolism events were identified with validated algorithms. Incidence rates were computed before and after 1:1 propensity-score matching to account for VTE risk factors. Hazard ratios were estimated to compare the incidence of VTE in the CISD vs non-CISD cohorts. Results A total of 158 123 patients were identified with CISD: with psoriasis (n = 96 138), atopic dermatitis (n = 30 418), alopecia areata (n = 17 889), vitiligo (n = 7735), or HS (n = 5934); 9 patients had 2 of these conditions. A total of 1 570 387 patients were without a CISD. The median follow-up time was 1.9 years (interquartile range, 0.8-4.0 years) in patients with CISD. The incidence rate (per 1000 person-years) of outpatient or inpatient VTE was 1.57 in psoriasis, 1.83 in atopic dermatitis, 0.94 in alopecia areata, 0.93 in vitiligo, 1.65 in HS and 1.53 in CISD overall, compared with 1.76 in patients without a CISD. Incidence rates increased in patients aged 50 years or older (2.3 per 1000 person-years) and decreased in those aged 18 to 49 years (0.8 per 1000 person-years). After propensity-score matching to patients without a CISD, the hazard ratio (HR) of VTE was 0.86 (95% CI, 0.75-0.99) in psoriasis, 1.19 (95% CI, 0.95-1.48) in atopic dermatitis, 0.97 (95% CI, 0.65-1.46) in alopecia areata, 0.90 (95% CI, 0.49-1.65) in vitiligo, 1.64 (95% CI, 0.82-3.27) in hidradenitis suppurativa, and 0.94 (95% CI, 0.84-1.05) in CISD overall. Conclusions and relevance In this large-scale cohort study, CISDs were not associated with an increased incidence of VTE after controlling for relevant VTE risk factors in a representative dermatology patient population.
Absent or Mild Coronary Calcium Predicts Low-Risk Stress Test Results and Outcomes in Patients Considered for Flecainide Therapy.

Background:Flecainide is a useful antiarrhythmic for atrial fibrillation (AF). However, because of ventricular proarrhythmia risk, a history of myocardial infarction (MI) or coronary artery disease...
In search of weakened resolve: Does climate-engineering awareness decrease individuals’ commitment to mitigation?

Abstract As climate predictions become more dire, it is increasingly clear that society cannot rely on mitigation alone. In response, climatologists and engineers have been developing climate-engineering technology to directly intervene on the climate through strategies such as solar radiation management and carbon dioxide removal. While these technologies have some encouraging features, they also involve risk on many dimensions. One behavioral risk that concerns many observers is the possibility that the prominence of climate-engineering scenarios could decrease the public's commitment to mitigation, a concern variously described as moral hazard or weakened resolve. Across 8 experiments (N = 2514) we tested whether exposure to naturalistic information about climate-engineering technology decreases individuals' commitment to mitigation efforts. We did not find compelling evidence of strong or reliable effects. We draw from motivational theory to contextualize our findings in a literature characterized by mixed results, and we propose new directions for behavioral research on the weakened-resolve/moral-hazard concern with respect to climate engineering.
Reader's Response: Planner Use by the Surveyed Students

Excerpt: A response to “How Students Use the Course Syllabus” by Sharon Calhoon & Angela Becker, International Journal on the Scholarship of Teaching and Learning, Volume 2, Number 1 ( January 2008)
Mobile Lifestyles in the Business World

Since 2000 researchers in the field of communications have been studying the role of mobile lifestyles at the interpersonal, organizational, and urban levels. Specifically, researchers have focused on the social, spatial, and technological aspects of this topic as well as on the ways in which these three dimensions are interrelated. Mobile devices have allowed for a rethinking of traditional dichotomies such as private–public, global–local, digital–material, and individual–community. Mobile lifestyles have been enabled by the adoption of mobile and wireless communications technologies that include a wide variety of devices, applications, and features. This entry gives an overview of research on mobile lifestyles that has been conducted in the field of communications. Keywords: communication networks; digital culture; mobile communication; sociology of culture and media; urban
Was Life Better in the “Good Old Days”? Intertemporal Judgments of Life Satisfaction

Intertemporal judgments are paired comparisons between the present time and some other time (e.g. “How satisfied are you with your life these days compared to five years ago?”). These judgments can provide evidence on the question, “Is life satisfaction in developed nations increasing, decreasing, or remaining constant?” This paper provides the first review of intertemporal judgments of life satisfaction, and reports a meta-analysis of 71 such studies from 9 developed countries. Results show that in every survey that asks people how happy their own lives are now compared to some past time, a majority says they are happier now than in the past. The meta-analysis also shows that this question must be carefully distinguished from asking about quality of life of the average person, which shows a majority believing that life was better for the “average person” in the past. These two beliefs are logically inconsistent, since the average respondent actually says their satisfaction is higher now. We consider several sources of bias that may influence these results, including cognitive processing heuristics, self-appraisal (desirability) bias, and information bias in media news.
Accumulation of B1-like B cells in transgenic mice over-expressing catalytically inactive RAG1 in the periphery

During their development, B lymphocytes undergo V(D)J recombination events and selection processes that, if successfully completed, produce mature B cells expressing a non-self-reactive B-cell receptor (BCR). Primary V(D)J rearrangements yield self-reactive B cells at high frequency, triggering attempts to remove, silence, or reprogramme them through deletion, anergy induction, or secondary V(D)J recombination (receptor editing), respectively. In principle, expressing a catalytically inactive V(D)J recombinase during a developmental stage in which V(D)J rearrangement is initiated may impair this process. To test this idea, we generated transgenic mice expressing a RAG1 active site mutant (dnRAG1 mice); RAG1 transcript was elevated in splenic, but not bone marrow, B cells in dnRAG1 mice relative to wild-type mice. The dnRAG1 mice accumulate splenic B cells with a B1-like phenotype that exhibit defects in B-cell activation, and are clonally diverse, yet repertoire restricted with a bias toward Jκ1 gene segment usage. The dnRAG1 mice show evidence of impaired B-cell development at the immature-to-mature transition, immunoglobulin deficiency, and poorer immune responses to thymus-independent antigens. Interestingly, dnRAG1 mice expressing the anti-dsDNA 3H9H56R heavy chain fail to accumulate splenic B1-like cells, yet retain peritoneal B1 cells. Instead, these mice show an expanded marginal zone compartment, but no difference is detected in the frequency of heavy chain gene replacement. Taken together, these data suggest a model in which dnRAG1 expression impairs secondary V(D)J recombination. As a result, selection and/or differentiation processes are altered in a way that promotes expansion of B1-like B cells in the spleen.
Birthplace and esophageal cancer incidence patterns among Asian-Americans

The incidence of esophageal adenocarcinoma in the United States has risen rapidly over the last 30 years, whereas the incidence of esophageal squamous cell carcinoma has fallen dramatically. In contrast, parts of Asia have extremely high rates of squamous cell carcinoma, but virtually no adenocarcinoma. Within the United States, Asian-Americans as a whole, have low rates of esophageal adenocarcinoma and higher rates of squamous cell carcinoma. It is unclear what the patterns are for those Asians born in the United States. The relative influence of ethnicity and environment on the incidence of esophageal cancer in this population is unknown. We identified all cases of esophageal adenocarcinoma and squamous cell carcinoma from the California Cancer Registry 1988-2004, including 955 cases among 6 different Asian ethnicities. Time trends were examined using Joinpoint software to calculate the annual percentage changes in regression models. Rates of esophageal squamous cell carcinoma varied substantially among different Asian ethnic groups, but squamous cell carcinoma was much more common than adenocarcinoma in both foreign-born and US-born Asian-Americans. Rates of squamous cell carcinoma were slightly higher among US-born Asian men (4.0 per 100,000) compared with foreign-born Asian men (3.2 per 100,000) and White men (2.2 per 100,000), P = 0.03. Rates of adenocarcinoma were also slighter higher among US-born Asian men (1.2 per 100,000) compared with foreign-born Asian men (0.7 per 100,000), P = 0.01. Rates of squamous cell carcinoma decreased for both US-born and foreign-born Asians during this period, whereas adenocarcinoma remained low and stable. These results provide better insight into the genetic and environmental factors affecting the changing incidence of esophageal cancer histologies in the United States and Asia.
Change Point Estimation of Bilevel Functions

Reconstruction of a bilevel function such as a bar code signal in a partially blind deconvolution problem is an important task in industrial processes. Existing methods are based on either the local approach or the regularization approach with a total variation penalty. This article reformulated the problem explicitly in terms of change points of the 0-1 step function. The bilevel function is then reconstructed by solving the nonlinear least squares problem subject to linear inequality constraints, with starting values provided by the local extremas of the derivative of the convolved signal from discrete noisy data. Simulation results show a considerable improvement of the quality of the bilevel function using the proposed hybrid approach over the local approach. The hybrid approach extends the workable range of the standard deviation of the Gaussian kernel significantly.
Computation of Ridges via Pullback Metrics from Scale Space

Properties of points in images are often measured using convolution integrals with each convolution kernel associated to a particular scale and perhaps to other parameters, such as an orientation, as well. Assigning to each point the parameter values that yield the maximum value of the convolution integral gives a map from points in the image to the space of parameters by which the given property is measured. The range of this map is the optimal parameter surface. In this paper, we argue that ridge points for the measured quantity are best computed via the pullback metric from the optimal parameter surface. A relatively simple kernel used to measure the property of medialness is explored in detail. For this example, we discuss connectivity of the optimal parameter surface and the possibility of more than one critical scale for medialness at a given point. We demonstrate that medial loci computed as ridges of medialness are in general agreement with the Blum medial axis.
Assessment & Efficacy of an M-Learning Course in Industrial Hygiene and Occupational Safety

This project involved the creation of 20 introductory industrial hygiene and safety video modules specifically for an M-Learning environment. Testing was performed on 9 modules to determine whether this M-Learning content and presentation was as educationally effective as a traditional lecture presentation. Comparison of test scores and key concepts between two groups of college sophomores and juniors was made. The lecture group (n=19) received all course material through classroom presentations, while the video group (n=18) was provided similar content via .mp4 modules delivered via the web (Blackboard). Topics covered included history, legalities, toxicology, airborne hazards, exposure limits, calibration, and sampling methods. There was no significant difference (p<0.05) in mean test scores between the two groups (margin of error = +/− 4%). Analysis of responses to a subset of designated essential concept test questions indicated the lecture group performed higher on these topics. Results showed that given the choice, students had a preference for lecture over the .mp4 format. It is concluded that M-Learning, as designed and presented in this course, can provide an effective alternative to traditional classroom lectures in the applied sciences of industrial hygiene and safety. However, instructor emphasis can greatly influence the learning of key concepts.
Isolation of a specific enhancer for echovirus 6 from uninfected permissive host cells.

A specific enhancer for the m+ variant of echovirus 6 was isolated from uninfected, permissive host cells. The enhancer transferred the susceptibility to virus infection from permissive cells to less susceptible cells. Enhancer activity in cultured, human cells (WISH) was released by these cells into extracellular fluids at a linear rate. Maximal enhancer activity was recovered from cell monolayers that were extracted with buffered salt solutions (pH 6.6) for 5 h at 37 C. Crude enhancer preparations contained substances that reduced virus titers in permissive host cells and suppressed some of the enhancer activity. Viral inhibitory activity was removed from cellular extracts by either differential centrifugation or ion exchange chromatography. The enhancer, in contrast to inhibitory substances, remained in supernatant fractions after centrifugation at 110,000 × g for 4 h and adsorbed to diethylaminoethyl-Sephadex columns. Enhancer preparations that were devoid of inhibitory activity increased the virus titers in less susceptible simian cell cultures (approximately 100-fold) to the titers attained by fully permissive human cell cultures. A direct relationship between protein concentration and enhancer activity in cellular extracts was demonstrated. Partial purification of the enhancer by differential centrifugation and ammonium sulfate precipitation increased the specific activity of enhancer (units/mg of protein) by 13-fold.
Impact of Standardized Communication Techniques on Errors during Simulated Neonatal Resuscitation.

Aim Current patterns of communication in high-risk clinical situations, such as resuscitation, are imprecise and prone to error. We hypothesized that the use of standardized communication techniques would decrease the errors committed by resuscitation teams during neonatal resuscitation. Methods In a prospective, single-blinded, matched pairs design with block randomization, 13 subjects performed as a lead resuscitator in two simulated complex neonatal resuscitations. Two nurses assisted each subject during the simulated resuscitation scenarios. In one scenario, the nurses used nonstandard communication; in the other, they used standardized communication techniques. The performance of the subjects was scored to determine errors committed (defined relative to the Neonatal Resuscitation Program algorithm), time to initiation of positive pressure ventilation (PPV), and time to initiation of chest compressions (CC). Results In scenarios in which subjects were exposed to standardized communication techniques, there was a trend toward decreased error rate, time to initiation of PPV, and time to initiation of CC. While not statistically significant, there was a 1.7-second improvement in time to initiation of PPV and a 7.9-second improvement in time to initiation of CC. Conclusions Should these improvements in human performance be replicated in the care of real newborn infants, they could improve patient outcomes and enhance patient safety.
Food Labeling Litigation: Exposing Gaps in the FDA's Resources and Regulatory Authority

Since 2011, consumer advocacy groups and plaintiffs have filed more than 150 food labeling class action lawsuits against food and beverage companies. According to a recent study, the number of these consumer protection class actions brought in federal court climbed from 19 cases in 2008 to more than 102 in 2012. The majority of these cases have been filed in the U.S. District Court for the Northern District of California, now referred to as the “Food Court.” This surge in lawsuit filings has led some legal commentators to suggest that “food is replacing tobacco as the new regulatory and class action target.” This “unprecedented surge” of deceptive labeling and advertising lawsuits against the makers of products such as Naked Juice, Fruit Roll-Ups, Bear Naked Granola, and Wesson Oil, reveals a trend of regulation by litigation — that is, a turning over of food labeling issues to the courts in light of a lax regulatory system. Although the Food and Drug Administration (FDA) is charged with regulating food labeling, plaintiffs’ attorneys are seeking to fill a void in the FDA’s regulatory authority and enforcement of food labeling laws. This paper provides an overview of the recent food labeling litigation and explores the reasons for this flood of litigation. However, this paper does not evaluate the merits of the lawsuits. Although none of these food labeling lawsuits have yet been adjudicated, the litigation has exposed problems with the FDA’s regulatory oversight of food labeling. The lawsuits represent attempts by consumer groups and plaintiffs’ attorneys to influence marketing behavior of food companies — a task more properly undertaken by the FDA.
Comparison of transverse facial venous sinus and jugular blood values in healthy and critically ill horses.

Summary Reasons for performing study The transverse facial venous sinus (TFVS) can be used for blood collection in horses, but information on the validity of blood values from this site is limited. Objectives To determine if packed cell volume (PCV), total solids (TS) and blood lactate concentrations in blood drawn simultaneously from a TFVS and jugular vein of critically ill horses are correlated and determine the effect of serial TFVS sampling on the same parameters in healthy horses. Study design Prospective observational study. Methods Critically ill horses had simultaneous blood samples drawn from a TFVS and jugular vein. Blood was also drawn from the left TFVS and jugular vein from 6 healthy, adult horses q. 6 h for 24 h, then q. 24 h for 72 h. Blood was drawn from the right TFVS and jugular vein q. 24 h for 96 h. All samples were analysed for PCV, TS and blood lactate concentration. Data were analysed with 2-way repeated measures ANOVA. Significance was set at P≤0.05. Results There were no significant differences in PCV, TS or blood lactate concentrations of TFVS samples compared with jugular blood in critically ill horses. Serial TFVS sampling in healthy horses had no significant effect on TS or blood lactate concentrations. Although PCV in the TFVS was significantly lower than in jugular blood on serial sampling, the difference was not considered clinically relevant. Conclusions Packed cell volume, TS and blood lactate concentrations were comparable between the TFVS and jugular vein.
The evolution of editorial peer review.

Practically no historical accounts of the evolution of peer review exist. Biomedical journals appeared in the 19th century as personal organs, following the model of more general journalism. Journal editors viewed themselves primarily as educators. The practice of editorial peer reviewing did not become general until sometime after World War II. Contrary to common assumption, editorial peer review did not grow out of or interact with grant peer review. Editorial peer review procedures did not spread in an orderly way; they were not developed from editorial boards and passed on from journal to journal. Instead, casual referring out of articles on an individual basis may have occurred at any time, beginning in the early to mid-19th century. Institutionalization of the process, however, took place mostly in the 20th century, either to handle new problems in the numbers of articles submitted or to meet the demands for expert authority and objectivity in an increasingly specialized world. ( JAMA . 1990;263:1323-1329)
Desensitization of pituitary gonadotropes by mediators of LH release.

Summary Desensitization of pituitary gonadotropes by exposure to 10 nM gonadotropin-releasing hormone (GnRH) for 6 h severely impaired the luteinizing hormone (LH) response to a second 3-h treatment with GnRH, and reduced the secretory resonses to 50 μM arachidonic acid (AA), 100 nM tetradecanoyl phorbol-13-acetate (TPA), and AA + TPA. Pretreatment with AA blocked subsequent responses to AA but not to other secretagogues. Pretreatment with TPA attentuated the LH response to TPA, but not to GnRH, AA, and AA + TPA. After exposure to AA + TPA, all subsequent responses were abolished. Each of the secretagogues reduced GnRH receptor binding, but only GnRH-induced receptor loss and desensitization were reversed by simultaneous incubation with a GnRH antagonist. Similar results were obtained when 16-h pretreatment periods were used, or when the data were normalized for the concomitant reduction of cellular LH content. These findings indicate that GnRH-receptor loss and depletion of LH content are not the sole causes of GnRH-induced desensitization. Receptor uncoupling and impairment of AA- and protein kinase C-dependent pathways may also be involved in this process.
Evaluation of a Modified Small Membrane Filtration Method

The recent paper titled “Prospective Cross-Sectional Evaluation of the Small Membrane Filter Method for Diagnosis of Pulmonary Tuberculosis” ([1][1]) should most appropriately be titled “….Evaluation of a Modified Small Membrane Filter Method,” as it did not replicate the methods of our
Electronic structure and properties of transition-metal glasses: NixZr1−x

Abstract The linear muffin-tin orbitals (LMTO) method is used to perform self-consistent electronic structure calculations of NixZr1−x glasses for x = 36 and 59. A glass is simulated by a 39-atom cluster with periodic boundary conditions. The atoms are randomly packed and then relaxed with Lennard-Jones potentials. The calculated radial distribution functions are compared with the available experimental data. The computed electronic structure is compared with photoemission data and experimental results for the density of states at the Fermi level. The calculated results are in good overall agreement with experimental data.
Horizontal Collusion and Innovation

Not without reason, collusion among horizontal competitors (a horizontal price cartel) has long been the leading bete noire of monopoly policy. Collusion is perhaps the most direct means to undermine competition, with all its vaunted benefits. In particular, it is generally agreed that coordination by rivals of their prices and outputs damages the general welfare, and some of the severest strictures of the anti-trust laws have been directed against it. Yet, recent analysis has abandoned undeviating condemnation of horizontal collaboration and suggested that there are arenas in which it can be beneficial and sometimes even make a critical contribution to social well-being (see Katz and Ordover [i99O] for a discussion and further references). The dividing line seems to be that between static and intertemporal efficiency. Despite its tendency to yield a less-than-optimal allocation of resources in stationary equilibrium, collusion may speed productivity and output growth and even reduce the cost of the growth process. But even if it can do so, it does not follow that it always will. After a brief review of the familiar static-efficiency analysis stressing a few less obvious points, some of the associated policy issues will be skimmed with similar brevity. The bulk of the discussion will deal with collusion in innovation and its dissemination. Here the literature is hardly unanimous, but four conclusions do seem to emerge: first, that the ceteris paribus effects of dissemination are unambiguously beneficial; second that horizontal collusion will sometimes stimulate RD third, that even if it restrains innovation, the net consequence for growth and welfare can be beneficial because of cost saving and enhanced rapidity of dissemination; and, finally, that a clear peril of technology collusion is that it can be perverted into monopolistic agreement to keep prices high and even to avoid the expense and turmoil of rapid innovation.
Injectable PLGA based colloidal gels for zero-order dexamethasone release in cranial defects

Bone fillers have emerged as an alternative to the invasive surgery often required to repair skeletal defects. Achieving controlled release from these materials is desired for accelerating healing. Here, oppositely-charged Poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles were used to create a cohesive colloidal gel as an injectable drug-loaded filler to promote healing in bone defects. The colloid self-assembled through electrostatic forces resulting in a stable 3-D network that may be extruded or molded to the desired shape. The colloidal gel demonstrated shear-thinning behavior due to the disruption of interparticle interactions as the applied shear force was increased. Once the external force was removed, the cohesive property of the colloidal gel was recovered. Similar reversibility and shear-thinning behavior were also observed in colloidal gels loaded with dexamethasone. Near zero-order dexamethasone release was observed over two months when the drug was encapsulated in PLGA nanoparticles and simply blending the drug with the colloidal gel showed similar kinetics for one month. Surgical placement was facilitated by the pseudoplastic material properties and in vivo observations demonstrated that the PLGA colloidal gels stimulated osteoconductive bone formation in rat cranial bone defects.
Statistical errors in histogram reweighting.

Histogram reweighting methods now play an important role in Monte Carlo simulations, particularly in the study of critical phenomena. Despite this widespread use, a quantitative study of the statistical and systematic errors present when Monte Carlo data are reweighted has been lacking. In this paper, we present a detailed analysis of the statistical errors in histogram reweighting. The formalism is tested with simulations of the d=2 Ising model at infinite temperature and at the critical temperature. The error determined with this formalism agrees well with that calculated in the standard way of analyzing independent histograms. The implications of these results for high-resolution Monte Carlo studies are discussed.
Generation of oxy radicals in biosystems.

Abstract Many recent lines of evidence indicate that endogenous free radicals contribute to spontaneous mutagenesis through the direct induction of DNA damage. However, the mechanisms underlying this process are not yet fully understood. A brief overview of the knowledge that is currently available is provided here, with emphasis on the generation of oxy radicals in biosystems, the reaction of those radicals with biomolecules, and the induction of oxidative DNA base damage that might lead to mutation.
Elastic Modulus Evolution and Behavior of Si/Mullite/BSAS-Based Environmental Barrier Coatings Exposed to High Temperature in Water Vapor Environment

Si-based ceramics (e.g., SiC and Si3N4) are known as promising high-temperature structural materials in various components where metals/alloys reached their ultimate performances (e.g., advanced gas turbine engines and structural components of future hypersonic vehicles). To alleviate the surface recession that Si-based ceramics undergo in a high-temperature environmental attack (e.g., H2O vapor), appropriate refractory oxides are engineered to serve as environmental barrier coatings (EBCs). The current state-of-the-art EBCs multilayer system comprises a silicon (Si) bond coat, mullite (3Al2O3·2SiO2) interlayer and (1 − x)BaO·xSrO·Al2O3·2SiO2, 0 ≤ x ≤ 1 (BSAS) top coat. In this article, the role of high-temperature exposure (1300 °C) performed in H2O vapor environment (for time intervals up to 500 h) on the elastic moduli of air plasma sprayed Si/mullite/BSAS layers deposited on SiC substrates was investigated via depth-sensing indentation. Laser-ultrasonics was employed to evaluate the E values of as-sprayed BSAS coatings as an attempt to validate the indentation results. Fully crystalline, crack-free, and near-crack-free as-sprayed EBCs were engineered under controlled deposition conditions. The absence of phase transformation and stability of the low elastic modulus values (e.g., ~60-70 GPa) retained by the BSAS top layers after harsh environmental exposure provides a plausible explanation for the almost crack-free coatings observed. The relationships between the measured elastic moduli of the EBCs and their microstructural behavior during the high-temperature exposure are discussed.
Health care utilization by adolescents on medicaid: implications for delivering vaccines.

OBJECTIVE: To examine the degree to which current health care utilization patterns of Medicaid-enrolled adolescents living in Michigan would allow opportunities for adolescent immunizations to be provided. METHODS: Outpatient claims data from 2001–2005 were analyzed for 11- to 18-year-old Medicaid-enrolled adolescents living in Michigan. Visits were classified as either health-maintenance examinations (HMEs) or problem focused by using diagnostic and procedural codes. Data were divided into 4 overlapping 2-year time periods, and the age-specific proportion of adolescents who attended these 2 visit types was calculated for each. χ2 tests were used to evaluate associations of visit patterns with gender. RESULTS: Of the 718847 adolescents included in the study, CONCLUSIONS: Similar to privately insured adolescents, most Medicaid-enrolled adolescents do not have annual preventive-care visits, which calls into question the feasibility of providing immunizations primarily at annual HMEs. Participation in problem-focused encounters was generally high in our study. However, even problem-focused visit utilization was low among older adolescent boys. This suggests that in addition to strengthening immunization within the medical home, alternative venues for reaching certain subpopulations of adolescents should also be developed.
A Discussion Technique for the Classroom Study of Intimate Communication.

Current trends in the field of speech communication and in Western Culture as a whole suggest that a sound basis now exists for incorporating courses treating intimate communication in speech communication curricula. However, teachers interested in developing such course offerings have few resources upon which to draw. This paper discusses methods for using the Relationship World Index—Version 2 (RWI‐2) as a classroom discussion exercise and as a means for illustrating theories of intimacy for a course treating intimate communication.
Dependence on chelating agent properties of nephrotoxicity and testicular damage in male mice during cadmium decorporation

Abstract An examination of the histopathological appearance of the kidneys of mice treated with cadmium chloride (s.c.) and simultaneously given 1 of 3 chelating agents (i.p.) reveals that the extent of nephrotoxicity is greatest when l -cysteine is the chelating agent. When either of 2 dithiocarbamates capable of mobilizing cadmium from its intracellular deposits, i.e. sodium N- methyl - d - glucamine dithiocarbamate (NaG) or sodium N- benzyl - d - glucamine dithiocarbamate (NaB) is used as the chelating agent, no morphological renal damage was evident. Under these same conditions the testes of the mice were protected to the extent of 95% by both of the dithiocarbamates, whereas the protection afforded by the l -cysteine was only about 50%. One factor governing the extent of nephrotoxicity appears to be the stability of the cadmium complexes which are formed and the manner in which this affects their behavior in vivo. Complexes which are preferentially excreted in the bile, cause little or no renal damage.
Circadian Rhythm of the Rat Suprachiasmatic Brain Slice is Rapidly Reset by Daytime Application of cAMP Analogs

Cellular mechanisms underlying the primary circadian pacemaker in mammals were investigated by isolating rat suprachiasmatic nuclei in brain slices and maintaining them in vitro for up to 3 days. The circadian rhythm of neuronal firing rate was used to assess the phase of the pacemaker. This rhythm was rapidly reset by bath application of cAMP analogs. Moreover, the pacemaker demonstrated circadian sensitivity to analog treatment: the rhythm was advanced by application during the donor's day, but not during the donor's night. These results suggest that cAMP-mediated events may stimulate pacemaker afferents within the SCN or may directly influence the pacemaker mechanism.
Hydrogenolysis of palladium(II) hydroxide, phenoxide, and alkoxide complexes.

A series of pincer (tBuPCP)Pd(II)–OR complexes (tBuPCP = 2,6-bis(CH2PtBu2)C6H3, R = H, CH3, C6H5, CH2C(CH3)3, CH2CH2F, CH2CHF2, CH2CF3) were synthesized to explore the generality of hydrogenolysis reactions of palladium–oxygen bonds. Hydrogenolysis of the Pd hydroxide complex to generate the Pd hydride complex and water was shown to be inhibited by formation of a water-bridged, hydrogen-bonded Pd(II) hydroxide dimer. The Pd alkoxide and aryloxide complexes exhibited more diverse reactivity. Depending on the characteristics of the −OR ligand (steric bulk, electron-donating ability, and/or the presence of β-hydrogen atoms), hydrogenolysis was complicated by hydrolysis by adventitious water, a lack of reactivity with hydrogen, or a competing dissociative β-hydride abstraction reaction pathway. Full selectivity for hydrogenolysis was observed with the partially fluorinated Pd(II) 2-fluoroethoxide complex. The wide range of Pd–OR substrates examined helps to clarify the variety of reaction pathways available t...
Progressive-ratio schedules of drug delivery in the analysis of drug self-administration: a review.

Drugs, like other reinforcers, can vary in their relative abilities to support operant responding. Considerable research has been designed to obtain useful measures of a given drug’s or dose’s ”reinforcing efficacy” and to identify the ways in which a variety of behavioral and pharmacological variables impact these measures. Progressive-ratio schedules of drug delivery generate an index of a drug’s or dose’s reinforcing efficacy (the breaking point) and are being used increasingly as tools in the analysis of drug self-administration. Progressive-ratio schedules of drug delivery have been used to characterize the effects of pretreatment drugs, lesions, drug deprivation, physical dependence, and repeated non-contingent drug exposure on breaking points. Behavioral factors, including food restriction and electric shock, and organismic factors, including gender and strain, have also been investigated using progressive-ratio schedules of drug delivery. To the extent that breaking points provide an index of reinforcing efficacy, these studies demonstrate that a wide range of variables can influence the reinforcing efficacy of self-administered drugs. The objectives of this review are to critique existing research themes, outline potential limitations of progressive-ratio procedures, and to suggest potentially fruitful uses of these procedures in future research.