cssi/SciSciGPT-SciSciNet huggingface dataset:
Breast cancer adjuvant chemotherapy dosing in obese patients: dissemination of information from clinical trials to clinical practice.

BACKGROUND Substantial variation in adjuvant breast cancer chemotherapy dosing in obese women suggests that there is uncertainty about optimal practices. The purpose of this study was to investigate variations in dose determinations in clinical trial protocols and publications over the last 3 decades as potential sources of this uncertainty. METHODS The National Cancer Institute database was used to identify protocols of breast cancer adjuvant chemotherapy conducted by cooperative groups between 1970–2000, and these protocols were then obtained directly from the cooperative groups. Dose determinations were categorized in each protocol and in published reports from each clinical trial. Fisher exact tests were used to compare the proportions of protocols that used full weight-based doses over time. RESULTS Protocol-specified chemotherapy dosing was obtained for all of 44 eligible trials. A significant increase was identified in the use of full weight-based doses in the later time period compared with the earlier (P = .004; 2-sided Fisher exact test). A notable exception was 1 cooperative group that continues to require dose limitations for doxorubicin and cyclophosphamide in patients with a body surface area of more than 2.0 m2. Regardless of publication date, published reports of clinical trials rarely provide information on use of full or limited weight-based doses. CONCLUSIONS Variations in dose determinations among clinical trial protocols and lack of information on use of full weight-based doses in most publications are 2 likely sources of variation in chemotherapy dosing in obese women. Developing consensus and disseminating information on optimal chemotherapy dosing will likely reduce such variation and may improve survival among obese patients with breast cancer. Cancer 2008. © 2008 American Cancer Society.
Application of the life course perspective in child welfare research

Abstract Research related to child welfare often suggests complicated relationships between child maltreatment, social disadvantage, program and policy effects, individual development, and population conditions that interact and change over time. New theories and conceptual models that account for this complexity are needed. The main point of this article is that the life course perspective is a useful paradigm for developing and organizing theories, concepts, and hypotheses in child welfare research. The life course perspective also helps researchers tackle methodological challenges common to longitudinal child welfare studies, such as confounding due to age, policy, and cohort effects. This article introduces key principles of the life course perspective, discusses concepts relevant to child welfare using concrete examples from prior research, highlights methodological challenges, and suggests implications for future studies.
Electromagnetic and Schlumberger resistivity sounding in the Roosevelt hot springs KGRA

One‐ and two‐dimensional modeling of the Schlumberger soundings at the Roosevelt Hot Springs KGRA have indicated a low‐resistivity zone of approximately 5 Ω-m paralleling the dome fault. The low resistivity of this zone is probably due to intensely fractured and altered water‐saturated rock. A zone of resistivity 12 Ω-m extending to the west of the dome fault is probably due to leakage of brine away from the geothermal system through alluvium or moderately altered rock. A resistive basement underlies the conductive zones and is believed to be essentially nonporous and unaltered rock. A major problem in the application of one‐dimensional (1-D) modeling of Schlumberger data in the Roosevelt Hot Springs KGRA is poor resolution of the 1-D parameters. The joint inversion of Schlumberger and electromagnetic sounding data gives a least‐squares 1-D conductivity model in which parameters are much better resolved than are the model parameters estimated by the inversion of Schlumberger data alone. One‐dimensional mo...
The reactivity and composition of strongly adsorbed carbonaceous deposits on platinum. Model of the working hydrocarbon conversion catalyst

The role of strongly adsorbed hydrocarbon deposits in reforming catalysis on a series of flat, stepped, and kinked platinum single-crystal surfaces at atmospheric pressures and temperatures between 300 and 700 K has been established and a model developed for the working structure and composition of the active catalyst surface. Restart reaction studies and reaction rate studies using platinum surfaces precovered with carbonaceous overlayers containing carbon-14 were used to investigate the catalytic activity and selectivity of carbon-covered platinum in hydrocarbon hydrogenation, dehydrogenation, and skeletal rearrangement. Quantitative hydrogen thermal desorption studies were carried out as a function of surface structure and reaction temperature to determine (1) the composition, and (2) the energetics for sequential dehydrogenation of carbonaceous deposits derived from a variety of adsorbed hydrocarbons including isobutane, neopentane, n-hexane, and cyclohexene. Carbon monoxide adsorption thermal desorption methods were developed to titrate uncovered platinum surface sites before and after reaction rate studies. The uncovered-site concentrations were correlated with the total surface carbon coverage as determined by Auger electron spectroscopy and the catalytic activity and selectivity of carbon-covered platinum. These experiments together with results from related structure sensitivity, thermal desorption, deuterium exchange, and radiotracer studies revealed that the primary role of the disordered carbon deposit is that of a nonselective poison which blocks platinum surface sites from incident reactant molecules. The most important chemical properties of the carbonaceous deposit are its abilities to store and exchange hydrogen with reacting surface species and to provide desorption sites for product molecules. The growth mechanism of this carbonaceous deposit is sensitive to the structure of the reacting hydrocarbon, and its morphology appears to vary continuously from two dimensional at low reaction temperatures (<550 K) to three dimensional for temperatures higher than about 600 K.
Temporally constrained tectonic rotations derived from magnetostratigiraphic data: Implications for the initiation of the Garlock fault, California

Examination of declination anomalies within a well-controlled chronologic framework can permit precise delineation of the progression of a tectonic rotation. In the past, declination anomalies from numerous spatially separated and individually dated localities have been synthesized in order to define regional, progressive rotations. Rarely, however, have magneto-stratigraphic data from a single locality been used successfully to chronicle a sequential rotation that resulted from movement along a nearby fault. Magnetostratigraphic studies from the El Paso basin in southern California reveal progressively smaller amounts of counterclockwise rotation for strata dated between 11 and 7 Ma. Two tests indicate that this is a temporally controlled, rather than a spatially controlled, rotation. This rotation is interpreted to have resulted from sinistral shear along the Garlock fault. As such, it appears to delimit the initiation of Miocene movement along the western segment of this major strike-slip fault.
A quantitative model of the Simpson-Baldwin Effect

G. G. Simpson was the first to explain the Baldwin Effect completely in terms of the theory of natural selection. A genetic version of a seemingly non-hereditary adaptation may arise when natural selection acts on the likelihood of having an adaptive trait not just on the trait itself. We present a quantitative model of the Simpson-Baldwin Effect. Organisms in the model have mutable ranges of phenotypic plasticity. The distribution of phenotypes in a population depends largely on the extent of environmental stochasticity. When the environment undergoes intermediate rates of fluctuation, the Simpson-Baldwin effect arises through the interaction of natural selection and mutation on norms of reaction. In a highly volatile environment, organisms benefit from plasticity, and consequently do not experience a Simpson-Baldwin channeling of phenotypic possibility.
The Role of Health Knowledge in Determining Dietary Fat Intake

An endogenous switching regression model is used to estimate the effect that health information has on the food purchase decisions of meal planners. Specifically, we examine how information concerning the health implications of dietary fat intake influences the meal planner's daily intake of total and saturated fat. This analysis uses the 1989 to 1990 and 1990 to 1991 Continuing Survey of Food Intake by Individuals (CSFII), and companion Diet and Health Knowledge Surveys (DHKS). Our results show that health information regarding dietary fat intake has a significant impact on meal planner food choices.
Mild Brain Trauma in Sports Diagnosis and Treatment Guidelines

Much has been written about the evaluation and management of mild brain trauma in sports. No less than 10 different ‘guidelines’ have been proposed and published to aid the clinician in the diagnosis of this condition. Too often, these guidelines have creating confusion instead of promoting an understanding of the spectrum of brain injury. As the understanding of the basic science of mild brain injury evolves, so must the approach to the concussed athlete. This article presents an up-to-date and clinically useful approach to the management of the athlete with a mild brain injury. The definition of ‘concussion’ is discussed and clarified and pertinent epidemiological data which highlight the importance of management skills as applied to athletes in a wide variety of sports are also reviewed. There is really no such thing as a ‘mild concussion’ if one considers the rare but catastrophic outcome of the second impact syndrome. For this reason, we review and expand upon the mechanisms of injury and pathophysiology. The accurate diagnosis of mild brain injury requires considerable experience, a high index of suspicion, a careful history and a series of examinations of the athlete, and a working knowledge of the athlete’s personality and the likelihood of minimising their symptoms. The value of orientation questions pertinent to the athlete is now well established. Any focal neurological deficit or the deterioration of an athlete’s condition warrants immediate hospitalisation, brain imaging and neurosurgical consultation. More commonly, athletes present with a brief alteration of consciousness, headache and amnesia and require careful examination and observation before returning to competition. The astute clinician will always err on the side of conservative management. The complete resolution of all symptoms before a return to play is imperative. Computerised tomography is very sensitive in the imaging of mild brain injuries. Neuropsychological testing is also very sensitive in the evaluation of brain injuries in athletes, and may become more clinically useful in the future.
Suppression by a prominent T-wave: an unusual cause of malfunction of a transvenous demand pacemaker.

Abstract An unusual mechanism of malfunction of a transvenous demand pacemaker is reported. This is caused by intermittent suppression of the pacemaker by a prominent T-wave resulting from too close a contact of the intracardiac electrode with the ventricular endocardium. The importance of its detection and method of prevention are discussed.
Viral capsid proteins are segregated in structural fold space.

Viral capsid proteins assemble into large, symmetrical architectures that are not found in complexes formed by their cellular counterparts. Given the prevalence of the signature jelly-roll topology in viral capsid proteins, we are interested in whether these functionally unique capsid proteins are also structurally unique in terms of folds. To explore this question, we applied a structure-alignment based clustering of all protein chains in VIPERdb filtered at 40% sequence identity to identify distinct capsid folds, and compared the cluster medoids with a non-redundant subset of protein domains in the SCOP database, not including the viral capsid entries. This comparison, using Template Modeling (TM)-score, identified 2078 structural “relatives” of capsid proteins from the non-capsid set, covering altogether 210 folds following the definition in SCOP. The statistical significance of the 210 folds shared by two sets of the same sizes, estimated from 10,000 permutation tests, is less than 0.0001, which is an upper bound on the p-value. We thus conclude that viral capsid proteins are segregated in structural fold space. Our result provides novel insight on how structural folds of capsid proteins, as opposed to their surface chemistry, might be constrained during evolution by requirement of the assembled cage-like architecture. Also importantly, our work highlights a guiding principle for virus-based nanoplatform design in a wide range of biomedical applications and materials science.
Hospital Financial Conditions and the Provision of Unprofitable Services.

Increases in hospital financial pressure resulting from public and private payment policy may substantially reduce a hospital’s ability to provide certain services that are not well compensated or are frequently used by the uninsured. The objective of this study is to examine the impact of hospital financial condition on the provision of these unprofitable services for the insured and uninsured. Economic theory provides the conceptual underpinnings for the analysis, and a longitudinal empirical analysis is conducted for an eight-year study period. The results indicate that not-for-profit hospitals with strong financial performance provide more unprofitable services for the insured and uninsured than do not-for-profit hospitals with weaker condition. For-profit hospital provision of these services is not influenced by their financial condition and instead may reflect actions to meet community expectations or to offer a sufficiently broad service array to maintain the business of insured patients.
Dichotomous effects of cadmium and selenium on erythropoiesis in mice

The investigations reported here were designed to test the effects of a single acute non-lethal treatment of salts of cadmium, selenium and a combination of the two, cadmium selenite, on the time course and extent of erythropoiesis. Peripheral erythrocyte production and splenic erythropoietic activity were used as indices of erythropoiesis. Concerning the latter parameter, the spleen has been shown to be a key organ for erythropoiesis in mice.
Environmental satisfiers in academe

Utilizing a nationwide sample of university professors in the United States, this study explored job satisfaction levels of academicians and the differences between perceived satisfaction of faculty in professional schools and that of faculty in other disciplines. The results were based upon responses from 336 faculty representing 24 universities selected on a stratified basis which included large, small, public and private universities. Teaching dimensions and research requirements were the most satisfying elements of the academic work environment; support and compensation aspects were the most dissatisfying. Faculty from professional schools reported higher levels of satisfaction for almost all of the 22 separate environmental dimensions, and these faculty also reported higher salaries and less stringent requirements for tenure and promotion. The demographic variables which explained the greatest amount of variance in work satisfaction scores were tenure, teaching load, sex, institution (public-private), and age. Salary and academic rank, which a priori are considered to be significant in an academician's satisfaction with work, appeared to have a lesser impact.
Sex-related elevation in cortisol during chronic treatment with alprazolam associated with enhanced cognitive performance

Objective There is evidence of more widespread use and abuse of benzodiazepines (BZPs) among elderly women. However, factors underlying this observation are poorly understood but could be related to more intense withdrawal reactions, which are a major risk factor for continued BZP use. We previously reported elevations in interdose morning plasma cortisol levels in healthy elderly individuals after chronic treatment with alprazolam, possibly consistent with increased hypothalamic–pituitary–adrenal (HPA) axis activity and drug withdrawal. In this study, we examined sex-related differences in this population.
Factors encouraging cohort maintenance in a longitudinal study

Maintenance of the cohort is one of the primary challenges of a longitudinal study. At the end of 3 years of follow up in the Framingham Children's Study, a longitudinal study of young children and their parents, 100 of the original 106 families (94.3%) have remained in the study. A questionnaire was administered to identify factors contributing to the high rate of follow up to this point in the study. The attitudes of the staff, feedback to the subjects, the staff's handling of questions and problems, and association with the Framingham Heart Study emerged as the most important factors influencing continued participation in the study. In addition, 99% of the subjects stated that they believed the medical research to be important. We conclude that the quality of the communication with study participants and the subjects' perceived importance of the research have been the key factors in maintaining the cohort in this longitudinal epidemiologic study.
Comment on Lawler's multilevel Boolean minimization

Lawler [1] proposed a method of multilevel Boolean minimization which is a generalization of the conventional prime implicant approach for two-level minimization. In his article, he presented two lemmas (Lemmas 1 and 2) that are important in reducing the number of calculations involved in obtaining a solution. These lemmas can be extended to increase the efficiency even more. In particular, it is possible to lower the upper limit of the function interval for an incompletely specified function [2]. Later, the extended version of these lemmas will be shown to be of value in several aspects of the minimization procedure.
The IBR5 phosphatase promotes Arabidopsis auxin responses through a novel mechanism distinct from TIR1-mediated repressor degradation

In Arabidopsis, INDOLE-3-BUTYRIC ACID RESPONSE5 (IBR5), a putative dual-specificity protein phosphatase, is a positive regulator of auxin response. Mutations in IBR5 result in decreased plant height, defective vascular development, increased leaf serration, fewer lateral roots, and resistance to the phytohormones auxin and abscisic acid. However, the pathways through which IBR5 influences auxin responses are not fully understood. We analyzed double mutants of ibr5 with other mutants that dampen auxin responses and found that combining ibr5 with an auxin receptor mutant, tir1, enhanced auxin resistance relative to either parent. Like other auxin-response mutants, auxin-responsive reporter accumulation was reduced in ibr5. Unlike other auxin-resistant mutants, the Aux/IAA repressor reporter protein AXR3NT-GUS was not stabilized in ibr5. Similarly, the Aux/IAA repressor IAA28 was less abundant in ibr5 than in wild type. ibr5 defects were not fully rescued by overexpression of a mutant form of IBR5 lacking the catalytic cysteine residue. Our genetic and molecular evidence suggests that IBR5 is a phosphatase that promotes auxin responses, including auxin-inducible transcription, differently than the TIR1 auxin receptor and without destabilizing Aux/IAA repressor proteins. Our data are consistent with the possibility that auxin-responsive transcription can be modulated downstream of TIR1-mediated repressor degradation.
FERMENTATION-DERIVED BUTANOL AND SCENARIOS FOR ITS USES IN ENERGY-RELATED APPLICATIONS

The production of normal butanol by anaerobic fermentation using Clostridium acetobutylicum, i.e the Weizmann process, is a well-known technology. However, due to economic considerations, commercial scale butanol fermentation has been limited in recent times. This survey discusses technical factors which have an impact on prospects for new butanol fermentation capacity. The characteristics of c. acetobutylicum, and the inhibition of cellular growth and butanol production caused by butanol, are discussed together with approaches to moderating butanol toxicity. It is concluded that continued progress in moderating inhibitory effects of butanol on the fermentation and improving the energy efficiency of butanol recovery could help improve the economic feasibility of process. A large increase in n-butanol demand could result if this alcohol were found to be a suitable and economic fuel additive in the context of clean air benefits, and its use were to develop on even a modest basis. (author).
Storming the Castle: A Constructivist Attack on Realism's Home Turf

The Nuclear Taboo: The United States and the Non-Use of Nuclear Weapons Since 1945. Edited by Nina Tannenwald. New York: Cambridge University Press, 2007. 449 pp., $34.99 paper (ISBN-13: 978-0521524285). Nina Tannenwald's provocative book, The Nuclear Taboo , issues a direct, well reasoned, richly detailed and forcefully argued challenge to the domain of international relations on which realism has long had exclusive claim. That domain is explanations for the non-use of nuclear weapons. The core argument of The Nuclear Taboo is that the non-use of nuclear weapons by the United States since the end of World War II is not attributable to deterrence, as realists, particularly structural realists, have traditionally argued, but rather to the existence of a taboo against their use. In identifying a social norm against the use of nuclear weapons as the causal variable, and not the material considerations of anticipated loss which lie at the heart of deterrence theory, Tannenwald challenges the primacy of realism as the most powerful paradigm for understanding the so-called “High Politics” of security. Tannenwald's conclusions on the existence of a powerful social norm that controls the use of nuclear arms are reached by researching a key puzzle of modern history: Why have nuclear weapons not been used in situations where acute forms of deterrence, like the Cold War's Mutual Assured Destruction, did not apply (pp. 1, 3). According to Tannenwald, a careful search of the historical record, including both archival primary documents and secondary sources, shows that the policy discourse within the inner sanctum of power on whether to use nuclear weapons during the crisis situations where their use might be anticipated was not centered on questions of the military utility of the weapons. Rather it tended to focus on the inhumanity inherent in their …
Procurement of Design-Build Services: Two-Phase Selection for Highway Projects

In the United States, public agencies are adopting the design-build (DB) delivery method for delivering highway projects after having used the traditional design-bid-build method for generations. In the 2002 design-build contracting final rule, the Federal Highway Administration (FHWA) strongly encourages the use of two-phase selection procedures for DB procurement. This paper takes a case study approach to investigating the use of a two-phase process for selecting providers of highway design-build services. Using two DB projects in central Texas as case studies, the writers have analyzed project documentation and performed interviews with 37 project participants involved in procurement, including owner representatives and legal consultants. For the first case, the writers selected the $1.3 billion SH-130 tolled expressway project in central Texas. Procurement of the SH-130 DB contract was performed before the FHWA rule on DB contracting was released. In addition, the writers examined procurement activities for the $154 million DB contract for the SH-45 SE tolled expressway, which was procured by the same owner in 2004 following procedures identified in the FHWA rule. As a result, a process was developed that included activities to be performed between the delivery method decision and the contract execution. This process model tracks the differences between the SH-130 and the SH-45 SE processes that are attributable to the latter's adoption of the FHWA Rule.
Panel - How do practitioners become learned professionals on ethical issues?

This panel discussion seeks to engage engineering professionals in a discussion of their responsibilities and obligations to perform duties in an ethical manner. Specifically, the panel will explore how learned professionals learn about these responsibilities and the potential consequences resulting from different responses to a myriad of unforeseen circumstances. The roles of formal education, continuing education, and on-the-job experience are examined as key components of the educational process.
Market Applications for Recycled Postconsumer Fibers

This study has (a) examined the profile of recycled postconsumer fibers, (b) evaluated product characteristics that are suitable for recycled postconsumer fiber application, and (c) explored the market potential for recycled postconsumer fiber products. Average fiber content (by weight) of used clothing in this study was: cotton, 59.29%; polyester, 21.82%; acrylic, 5.72%; wool, 5.14%; nylon, 5.09%; and silk, 2.94%. Assuming recycled postconsumer textiles will not undergo any further treatment except being shredded into fiber fluff, market analysis has identified the following potential application of fibers: carpet cushion, home insulation, fiber stuffing, clean-up products, mattress pads/futons, geotextiles, landscaping, and concrete reinforcement. For each potential application, the product performance characteristics have been discussed and applicable techniques have been recommended.
A solid phase fluorescent immunoassay for the quantitation of the C3 component of human complement.

Abstract A non-competitive method for the determination of the C3 component of human complement in serum is described. This procedure involves use of a specific antibody covalently attached to derivatized polyacrylamide beads and a fluorescently labeled specific antibody. Reproducible results were achieved for C3 in serum in the range of 20 mg/dl to 195 mg/dl within 2 h. C3 levels as low as 125 ng/ml can also be measured. Fluorescent immunoassay and radial immunodiffusion were used to determine C3 levels in healthy adults. Good agreement was found between the two methods.
Direct correlation of structure changes and thermal events in hydrated lipid established by simultaneous calorimetry and time-resolved x-ray diffraction

In many lipid systems, polymorphic and mesomorphic behavior depends on sample thermal history. To establish unequivocally the structural origin of endothermic and exothermic events in such systems, we have performed simultaneous calorimetry and time-resolved x-ray diffraction (SCALTRD). To this end, aluminum calorimetry crucibles were used to contain the hydrated lipid sample, and the calorimeter was mounted with the base of the crucible oriented perpendicular to a synchrotron-derived focused monochromatic x-ray beam for SCALTRD data collection. Measurements were made with hydrated monoelaidin and 1,2-dielaidoyl-sn-glycero-3-phosphoethanolamine (DEPE) contained in hermetically sealed crucibles. Time-resolved x-ray diffraction (TRXRD) data were collected using an x-ray image intensifier/video system and a streak camera containing an x-ray sensitive image plate and/or film. SCALTRD analysis of the lamellar gel to lamellar liquid crystalline phase transition in hydrated monoelaidin gives identical progress curves by calorimetry and TRXRD at a scan rate of 1 degree C/min. At faster rates, calorimetry shows a broader phase transition that starts at a lower and ends at a higher temperature than is observed by TRXRD. The disparity arises in part because the x-ray beam used in TRXRD interrogates only a small portion of the sample, whereas the calorimeter responds to the entire sample volume. Because data collection times are relatively long, radiation damage is an important potential problem for SCALTRD measurements. Such an effect was observed with DEPE/water in that TRXRD shows the lamellar gel to lamellar liquid crystalline phase transition occurring at a lower temperature than observed by calorimetry. We speculate that the sample accumulates impurities locally as a result of radiation damage that has the effect of lowering the phase transition temperature at the site of interrogation by the x-ray beam. This "methods-in-combination" SCALTRD approach facilitates the direct correlation of structure rearrangements and thermal events in the same sample under identical conditions of thermal history. The information content of the data so derived far surpasses that available from either method used in isolation.
Sendai Virus Wild-Type and Mutant C Proteins Show a Direct Correlation between L Polymerase Binding and Inhibition of Viral RNA Synthesis

Abstract The Sendai virus C proteins, C′, C, Y1, and Y2, are a nested set of four independently initiated carboxy-coterminal proteins encoded on the P mRNA from an alternate reading frame. Together the C proteins have been shown to inhibit viral transcription and replication in vivo and in vitro and C′ binds the Sendai virus L protein, the presumed catalytic subunit of the viral RNA polymerase. To identify amino acids within the C′ protein that are important for binding L, site-directed mutagenesis of the gstC′ gene was used to change conserved charged amino acids to alanine, generating nine mutants. Additionally, a tenth natural mutant, gstF170S, was also constructed. Six of the gstC′ mutants, primarily in the C-terminal half of C′, exhibited a defect in the ability to bind L protein. The mutants were assayed for their effect on in vitro transcription and replication from the antigenomic promoter, and the data suggest in all but one case a direct correlation between the ability of C to bind L and to inhibit these steps in RNA synthesis. Further studies with two nonfusion C mutants showed that this correlation was specifically due to the C′ portion, and not the gst portion, of the fusion proteins. To study their individual functions, each of the four C proteins was fused downstream of glutathione S -transferase. The gstC′, gstC, gstY1, and gstY1 fusion proteins were all able to bind L protein and to inhibit viral mRNA and (+)-leader RNA synthesis, and antigenome replication in vitro . In addition, the nonfusion C, Y1, and Y2 proteins all inhibited transcription. The inhibition of (+)-leader RNA and mRNA synthesis by wt C proteins (nonfusion) showed nearly identical dose-response curves, suggesting that inhibition occurs early in RNA synthesis.
Operative Risks Associated with Contralateral Prophylactic Mastectomy: A Single Institution Experience

The purpose of this study was to determine if newly diagnosed breast cancer patients undergoing contralateral prophylactic mastectomy (CPM) experience more complications than patients undergoing unilateral mastectomy (UM). A total of 600 patients underwent either UM or CPM between January 2009 and March 2012 for unilateral breast cancer. Operative complications were classified as minor (aspirations, infection requiring antibiotics, partial flap and nipple necrosis, minor bleeding, delayed wound healing) or major (hematoma or seroma requiring operation, infection requiring rehospitalization, blood product transfusion, total flap or nipple loss, implant removal), mixed (both minor and major complications), or multiple. Chi-square and multivariate logistic regressions were used for the analysis. Of the 600 patients, 391 (65 %) underwent UM and 209 (35 %) underwent CPM. Across all complication groups, there were significantly more complications in the CPM group versus the UM group (41.6 vs. 28.6 %, p = 0.001). Major complications alone were significantly greater in the CPM versus the UM group (13.9 vs. 4.1 %, p < 0.001). When adjusting for age, body mass index, smoking and diabetes history, AJCC stage, reconstruction, previous radiation therapy, and adjuvant therapy, CPM patients were 1.5 times more likely to have any complication (odds ratio [OR] 1.53; 95 % CI 1.04–2.25, p = 0.029) and 2.7 times more likely to have a major complication compared with UM patients (OR 2.66; 95 % CI 1.37–5.19, p = 0.004). CPM patients have an increased risk of complications, especially major complications requiring rehospitalization or reoperation. These complications may influence patient and physician decisions to choose CPM.
Formalin-Induced c-fos Expression in the Brain of Infant Rats

Abstract In the fetal, infant, and adult rat, injury induces a well-defined behavioral response and induces c-fos expression in the spinal cord dorsal horn. There is more limited information about the processing of noxious stimulation in the infant brain. We describe here the appearance of the Fos protein in the brain of fetal and infant rats following formalin-induced injury. Regions were chosen for analysis with a special focus on brain loci that express c-fos in the adult. No Fos positive cells were found in the brains of fetuses; newborns did not show increased Fos expression after formalin injection in any structure examined. At 3 and 14 days of age, there was a significant increase in Fos staining induced by formalin in the ventral lateral medulla. In contrast, paraventricular and medial dorsal nuclei of the thalamus, the paraventricular nucleus of the hypothalamus, and periaqueductal gray of the midbrain showed increased levels of Fos protein only at 14 days of age. We hypothesize that this developmental pattern is related not only to the maturation of pain perception but also to development of autonomic and defensive reactions to pain in the infant. Perspective Because the infant processes pain differently than the adult, knowledge of those differences informs pediatric clinical practice. Using Fos expression as a marker of neural activity in the rat, we show that the pattern of brain activation is immature at birth but is in place by 14 days of age.
Strategy to prevent drug-related hypersensitivity in folate-targeted hapten immunotherapy of cancer.

Cancer vaccine/immunotherapy rarely involves systemic administration of an immunogenic compound to an actively immunized host. We have developed such a strategy that utilizes folate to deliver antigenic haptens [e.g., fluorescein (FITC) and dinitrophenyl] to folate receptor-positive tumors in a hapten-pre-vaccinated host. Here, we investigated the safety of this novel approach and developed strategies to prevent drug-related hypersensitivity. Using FITC as the model hapten, we identified a potential source of allergic species in folate–FITC preparations by LC-MS/MS. In mice and guinea pigs, we tested the significance of this impurity by passive cutaneous anaphylaxis and active systemic anaphylaxis assays. We studied the effect of immunogen (e.g., KLH–FITC) dose and derived a desensitization regimen that was further evaluated in a murine tumor model. Administration of folate–FITC with low multi-haptenated contaminants (e.g. bis-FITC) resulted in hypersensitivity in under-immunized animals. However, this drug-related hypersensitivity may be independently prevented by (1) increasing the immunogen dose and/or (2) desensitizing animals with folate–FITC during vaccination. In addition, such manipulation in vivo did not appear to negatively alter the effectiveness of immunotherapy. This study provided confidence on the safety of folate–hapten-targeted cancer immunotherapy in an actively immunized host.
Low emittance lattice for the Duke storage ring soft X-ray FEL

Abstract In this paper, we present a possible lattice for the Duke storage ring with horizontal emittance of 1.4 nm rad at an energy of 1 GeV. The new lattice was constrained to fit the layout of the existing storage ring and to re-use existing magnets. Within these constrains, the improvement of the emittance (from current 18 nm rad) is possible due to the use in the arcs of combined function bending magnets with strong dipole, quadrupole and sextuple fields. We present the results of 2D and 3D simulations of magnetic fields for these magnets. We discuss the choice of the arc's lattice cell and the per-cell tune advance. The lattice is based on the concept of local compensation of the non-linear geometrical aberrations. Preliminary studies of the dynamic aperture for this lattice are very encouraging. We briefly discuss the possibility further emittance reduction using new magnets for the arcs.
SU‐FF‐T‐268: Design Characteristics of a MLC for Proton Therapy

Purpose: To determine the leaf design characteristics (separation between leaves, leaf width, step size, and divergent vs. non‐divergent leaves) and the optimal distance‐from‐patient of a multileaf collimator(MLC) used in a proton therapy facility. These parameters have a significant effect on the penumbra width and leakage dose. Method and Materials: The GEANT4.7 Monte‐Carlo code was used to simulate the various design parameters for the MLC. The geometry included a representative double‐scattered beam incident on the MLC spaced at variable distances from a water phantom. Modifications were made to the code to input the leaf geometry from an external file so the many variations of leaf design could be tested without recompiling the code. Results: The output of the Monte‐Carlo scored (1) the dose deposition in the water phantom, from which a measure of lateral penumbra as a function of depth and/or conformation to an pseudo‐PTV could be determined, and (2) the number of secondary particles, e.g. neutrons, that were incident on the phantom and whether these secondary particles came through the MLC or in the gaps between the leaves. Conclusion: These results, along with mechanical‐design, electrical‐design, and cost considerations, are being used to design the proton therapyMLC to provide good dose conformation to the target while minimizing the normal tissue dose caused by leakage.
A pharmacokinetic-pharmacodynamic disease model to predict in vivo antiviral activity of maraviroc.

Background The viral dynamics of human immunodeficiency virus (HIV) infection has been widely studied and expressed as mathematic equations. For most of the current registered antiretroviral drugs, the pharmacokinetics is well characterized and some relationships with the viral load-time profiles in plasma from HIV patients have been established. The integration of these models in a pharmacokinetic (PK)–pharmacodynamic (PD)–disease model can help toward a better understanding of the complexity of the interactions, as well as in the identification and clarification of the current model assumptions. Methods This work describes the development of a generic PK-PD disease model for a short-term (10 days) monotherapy phase IIa study with a novel anti-HIV drug, maraviroc (UK-427,857). The disease component of the model was based on the model published by Bonhoeffer et al, which was adapted for short-term treatment and for the new mechanism of action, CCR5-receptor antagonism. The model parameters were derived from the literature, as well as from a model-based analysis of available phase IIa clinical data from another investigational antiretroviral drug. The PD component that links the plasma concentrations of maraviroc to the inhibition of virus replication was based on in vitro measurements of drug potency and took into account the difference in the in vitro and in vivo protein binding and the uncertainties regarding the interpretation of the in vitro to in vivo extrapolation of the 50% inhibitory concentration. Finally, the PK component was based on information obtained from a single-dose study in healthy volunteers. Results The integrated PK-PD disease modeling allowed prediction of the effect on viral load of different maraviroc doses given as monotherapy to drug-naive patients. Conclusions By making use of the available PK-PD disease model, the possible range of active oral doses for maraviroc in HIV-positive patients was estimated by simulation before any clinical trials were taking place. The use of a model-based approach for selecting doses for clinical phase IIa has improved and accelerated the drug's development. This model was a powerful tool for assisting in the design of clinical studies on new agents for treating HIV/acquired immunodeficiency syndrome. Clinical Pharmacology & Therapeutics (2005) 78, 508–519; doi: 10.1016/j.clpt.2005.07.010
Water-soluble calix[4]resorcinarenes with hydroxyproline groups as chiral NMR solvating agents.

Water-soluble calix[4]resorcinarenes containing 3- and 4-hydroxyproline, d-nipecotic acid, (S)-2-(methoxymethyl)pyrrolidine, (S)-2-pyrrolidine methanol, and (S,S)-(+)-2,4-bis(methoxymethyl)pyrrolidine substituents are synthesized and evaluated as chiral NMR solvating agents. The derivatives with the hydroxyproline groups are especially effective at causing enantiomeric discrimination in the spectra of water-soluble cationic and anionic compounds with pyridyl, phenyl, and bicyclic aromatic rings. Binding studies show that mono- and ortho-substituted phenyl rings associate within the cavity of the calix[4]resorcinarenes, as do naphthyl rings with mono-, 2,3-, and 1,8-substitution patterns. Anthracene derivatives with an amino or sulfonyl group at the 1-position bind within the cavity, as well. Aromatic resonances of the substrates exhibit substantial upfield shifts because of shielding from the aromatic rings of the calix[4]resorcinarene. The effectiveness of the reagents at producing chiral recognition in ...
Undergraduate cardiac arrest team training.

Summary Background and objectives Health profession students are traditionally educated within their discipline with little to no interaction with other health professionals, but are expected to function as integral members of the health care team after graduation. Health profession educators must bridge this disconnect by providing interprofessional learning experiences for students. We sought to evaluate the impact of interdisciplinary team-based (ITB) versus individual discipline-based (DB) learning with multiple health care disciplines during a simulated cardiac arrest. Methods We performed a randomised trial with trainees from radiologic science (RS), physician assistant (PA) and nursing programmes (RN), taught by ITB and DB methods. Teams assessed a simulated patient experiencing a cardiac arrest before and after being educated using the First 5 Minutes® Curriculum (First–5). Knowledge and subjective evaluations were collected on each participant both before and after the educational intervention. The data were analysed using generalised estimating equations to account for correlated data. Results We enrolled 29 subjects: 15 ITB (4 PA, 5 RN, 6 RS) and 14 DB (3 PA, 5 RN, 6 RS). Knowledge improved more in the ITB group than in the DB group: with a median change of 2 (IQR 0–2) versus 1 (IQR 0–2), respectively (p = 0.014). Subjectively, participants overwhelmingly responded that working and learning with other disciplines was a valuable experience, and that more opportunities for interdisciplinary learning should be integrated into the curriculum. More opportunities for interdisciplinary learning should be integrated into the curriculum Discussion In our pilot study using a simulated model and the First–5, ITB education appears to improve trainees’ knowledge over DB education, and was subjectively preferred by the learner.
A karyometric and stereologic study of the effects of gonadotrophin and testosterone on the interstitial gland of the testis of intact and endoxan treated rats.

Adult male rats were treated daily for 18 days with endoxan in doses of 4 mg/kg of body weight or testosterone in doses 2.5 mg per rat. For the last 5 days of the experiment some of the rats received gonadotrophin injections in doses of 50 I.U. Karyometric and stereologic studies were undertaken on paraffin sections of the testes stained with haematoxylin and eosin.
Local response to chemoradiation in T4 larynx cancer with cartilage invasion.

Background: Patients with cartilage invasion were excluded from organ preservation protocols treating laryngeal and hypopharyngeal cancer. Treatment choice between chemoradiotherapy (CRT) and total laryngectomy (TL) remains controversial for these patients. Objective: To assess local response and local recurrence after CRT for patients having T4 larynx or hypopharynx cancer with cartilage invasion. Design: Retrospective intervention study. Setting: Tertiary-care, urban public hospital. Patients: Patients with T4 squamous cell carcinoma of the larynx/hypopharynx with cartilage invasion treated from 2003 to 2009. Intervention: Curative-intent CRT, compared to TL. Outcome Measures: Local response and local recurrence. Results: Of 34 patients included in this study, 21 completed CRT and 13 underwent TL with postoperative RT or CRT. With CRT, 19 patients were noted to have a complete response at the primary site while two patients had persistent local disease. Of 19 patients with complete response, 4 developed local recurrence over a time period 76–226 days (mean: 177 days). This resulted in a 29% incidence of persistent/recurrent disease at the primary site. The remaining 15 patients (71%) remained free of local disease (mean follow-up: 369 days). For 13 patients undergoing TL with adjuvant therapy, there were no cases of local recurrence (mean follow-up: 389 days). Conclusions: Although there was a high initial complete response rate after CRT, this response was not durable with a high local recurrence rate within 1 year. In comparison, patients undergoing TL demonstrated markedly better local control. For patients with cartilage invasion, a prospective trial comparing medical versus surgical therapy is needed. Laryngoscope, 2011
The value of pH as a quality control indicator for apheresis platelets.

BACKGROUND: Standards and regulations require measurement of pH as an apheresis platelet (PLT) component quality monitor. The usefulness of this quality control (QC) measure was investigated. STUDY DESIGN AND METHODS: QC data were retrospectively reviewed for apheresis PLTs collected over 4.5 years. Three collection devices were used, the Amicus (Baxter), the CS-3000 Plus (Baxter), and the MCS+ LN9000 (Haemonetics). Each month, four components from each instrument were sampled. PLT counts and component volume were measured immediately after collection, and pH, after 5 days of storage. RESULTS: A total of 668 products were studied. pH decreased as PLT concentration increased (r2 = 0.129, p < 0.001) and as component volume decreased (r2 = 0.086, p = 0.02). PLT concentration and volume, however, were poor predictors of a low pH. Apheresis instrument type affected pH. The 216 components collected with use of the CS-3000 device had a lower pH than components from the other two instruments. Only 13 components had a pH value less than the acceptable level of 6.2, 12 of which were collected with the CS-3000. CONCLUSIONS: For newer-model blood cell separators, pH measurements do not provide information that might identify a manufacturing problem. Because factors that influence pH are controlled or monitored for each component, evaluation of pH on a sample group provides an indication of the quality of specific component only, rather than an effective monitor of the quality of the manufacturing process.
Insulin-like growth factor-1 and myostatin mRNA expression in muscle: comparison between 62-77 and 21-31 yr old men.

Abstract The present study was done to determine the effect of age on muscle concentrations of mRNAs encoding two growth factors that are thought to be important regulators of muscle mass: insulin-like growth factor-1 (IGF-1) and myostatin. Quantitative RT-PCR assays indicated that the mean IGF-1 mRNA concentration in older muscle (62–77 yr, n =15 men) was ∼25% less, per ng total RNA ( P n =12 men). One third of the older men had IGF-1 mRNA levels below the lowest concentration observed in young muscle. Myostatin mRNA concentrations were similar in young and old muscle. Muscle mass and myofibrillar protein synthesis rates among eight older men did not correlate with either IGF-1 or myostatin mRNA levels. We conclude that IGF-1 gene expression in muscle tends to decline with normal aging. The functional significance is uncertain.