cssi/SciSciGPT-SciSciNet huggingface dataset:
Long-Term Outcomes of Radiotherapy for Pituitary Adenomas

Purpose To evaluate long-term local control and toxicity for pituitary adenomas treated with fractionated radiotherapy (RT). Methods and Materials The records of 100 patients with pituitary adenomas treated between 1983 and 2003 were retrospectively reviewed. Thirty-one patients had hormone-secreting tumors; 69 patients were treated with surgery and postoperative RT. Median follow-up was 6.7 years (range, 0.6–20.2 years) for all patients and 6.2 years (range, 2–20.2 years) for living patients. The mean dose delivered was 45 Gy (range, 43–50.4 Gy). Results The 10-year actuarial local control rates for nonsecreting and secreting adenomas were 98% and 73%, respectively ( p = 0.0015). Actuarial 10-year cause-specific survival (CSS) rates were 95% and 88%, and overall survival rates were 66% and 79% for nonsecreting and secreting adenomas, respectively. Involvement of the sphenoid sinus was found to be significantly associated with decreased 10-year CSS ( p = 0.0453). When compared with the two- or three-field techniques, stereotactic RT was associated with improved CSS ( p = 0.0775). CSS was not significantly associated with hormone excretion, extent of surgery, or whether RT was administrated postoperatively or for salvage after a postsurgical recurrence. New cases of hypopituitarism occurred in 35 patients. One patient experienced vision loss, and one patient developed a post-treatment glioma. Conclusions This is one of the most mature series in the literature that documents excellent results with fractionated RT for pituitary adenoma. We recommend 45 Gy at 1.8 Gy per fraction using stereotactic noncoplanar fields.
The ATF Site Mediates Downregulation of the Cyclin A Gene during Contact Inhibition in Vascular Endothelial Cells

Contact inhibition mediates monolayer formation and withdrawal from the cell cycle in vascular endothelial cells. In studying the cyclins--key regulators of the cell cycle--in bovine aortic endothelial cells (BAEC), we found that levels of cyclin A mRNA decreased in confluent BAEC despite the presence of 10% fetal calf serum. We then transfected into BAEC a series of plasmids containing various lengths of the human cyclin A 5' flanking sequence and the luciferase gene. Plasmids containing 3,200, 516, 406, 266, or 133 bp of the human cyclin A promoter directed high luciferase activity in growing but not confluent BAEC. In contrast, a plasmid containing 23 bp of the cyclin A promoter was associated with a 65-fold reduction in activity in growing BAEC, and the promoter activities of this plasmid were identical in both growing and confluent BAEC. Mutation of the activating transcription factor (ATF) consensus sequence at bp -80 to -73 of the cyclin A promoter decreased its activity, indicating the critical role of the ATF site. We identified by gel mobility shift analysis protein complexes that bound to the ATF site in nuclear extracts from growing but not confluent BAEC and identified (with antibodies) ATF-1 as a binding protein in nuclear extracts from growing cells. Also, ATF-1 mRNA levels decreased in confluent BAEC. Taken together, these data suggest that the ATF site and its cognate binding proteins play an important role in the downregulation of cyclin A gene expression during contact inhibition.
The Language of America

IN 1643 Roger Williams began his A Key into the Language of America with the words, "I present you with a Key; I have not heard of the like, yet framed, since it pleased God to bring that mighty Continent of America to light: others of my Countreymen have often, and excellently, and lately written of the Countrey (and none that I know beyond the goodnesse and worth of it.) / This Key, respects the Native Language of it, and happily may unlocke some Rarities concerning the Natives themselves, not yet discovered" (leaf A2). The modest arrogance of these words, and their deep and wholly modern insight into the relation of a language to the rest of the culture of its society, are the essence of the mood and aim of most American linguists since. In that tradition, the present article will examine what has come to be known about the structure and other characteristics of the languages of North America north of Mexico, principally-of course-American English.
Preventing Catheter-Related Bloodstream Infections outside the Intensive Care Unit: Expanding Prevention to New Settings

With the growing recognition of the preventability of catheter-related bloodstream infections (CRBSIs), reducing the number of CRBSIs acquired in health care facilities has become an important patient safety goal. To date, most prevention efforts have been conducted in intensive care units (ICUs); however, many central venous catheters (CVCs) are found outside the ICU, and rates of catheter-associated bloodstream infections in these settings appear to be similar to rates of these infections in ICUs. CVCs are also used in patients who primarily receive their care as outpatients, including those requiring hemodialysis, undergoing treatment for malignancies, and receiving parenteral nutrition. In some of these patients, CVCs might be used for extended periods, prolonging the patient's time at risk for CRBSIs and highlighting the potential need to look beyond insertion-based interventions to prevent infections. To meet the goal of reducing the number of all CRBSIs associated with health care, further attention on CRBSIs occurring outside the ICU is needed; however, this effort will require a better understanding of the epidemiology and prevention of these infections.
Variables in demonstrating methicillin tolerance in Staphylococcus aureus strains.

Abstract Certain technical considerations which affected the status of methicillin tolerance in Staphylococcus aureus strains were studied. Methods which consistently demonstrated tolerance or intolerance of a given strain were avoidance of inoculum splashing, use of stationary-phase inoculum, 24-h tube incubation, and minimization of antibiotic carry-over. These studies suggested a need for the establishment of a standardized reference for the determination of tolerance.
Civil Rights In A Changing Health Care System

PROLOGUE: At the height of the health care reform debate following President Clinton's election in 1992, the Congressional Black Caucus Health Braintrust Forum predicted that the preeminence of managed competition could cause health care reform to become “the civil rights battle of the 1990s.” Nearly four years later that prediction has not come true—at least not overtly. However, civil rights advocates continue to express concern that the disenfranchised—the poor and ethnic minorities—could be left behind as the U.S. health care system undergoes a major transformation to managed care. Sara Rosenbaum and colleagues write in this paper, “The reemergence of discrimination … might be particularly likely if health system changes foster the types of fear and resistance that historically have triggered discriminatory conduct (and laws).” ABSTRACT: Title VI of the 1964 Civil Rights Act prohibits discriminatory conduct by recipients of federal financial assistance. The law has been used in the past to challenge d...
Interdisciplinarity: A Critical Assessment

This article draws together disparate research and theorizing on interdisciplinarity. We first describe widespread efforts to promote interdisciplinarity in U.S. universities and critically examine the assumptions underlying these initiatives. Next, we present a cross-sectional view of interdisciplinary communication, knowledge diffusion, research assessment, and interdisciplinary research centers. We then describe research and theories that provide historical perspectives on the disciplinary system, interdiscipline formation, applied and professional fields, and institutional fragmentation. We present original findings on the prevalence of research centers, faculty hiring patterns in hybrid fields, and the diffusion of research across disciplines in the humanities and social sciences. The review concludes with a critical summary and suggestions for future research.
Analysis of the trade-offs between manual and computer-based stereology/classification

Estimation of volume, surface area, area, length and number in stereology is based on a manual count of the number of intersections between the feature of interest and a specific low-resolution geometrical test probe. It is usually a tedious and imprecise process, hut benefits from the user's ability to identify the feature of interest. In computer-based stereology, by contrast, a high-resolution test probe is used, generally yielding greater precision but suffering from imperfection of the automated classification. The trade-offs between manual and computer-based stereology are introduced and the conditions under which each is advantageous are defined.
Cumulative effects of repeated surfactant treatments in the rabbit.

The responses of the adult rabbit lung to multiple doses of surfactant after intratracheal injections of either natural calf surfactant or Surfactant-TA were evaluated. For each surfactant, four groups of 1.4-kg rabbits were studied: group 1 received 100 mg of surfactant containing isotopically-labeled dipalmitoylphosphatidylcholine; group 2 received the same labeled surfactant and then three tracheal injections of vehicle; group 3 received labeled surfactant and then three doses (100 mg) of unlabeled surfactant; group 4 was treated in the same way as group 3 except that the final dose was of the labeled surfactant. All rabbits were killed, and alveolar washes were recovered 24 h after the labeled surfactant dose had been given. The amount of labeled palmitate-saturated phosphatidylcholine (Sat PC) in alveolar washes did not change after multiple doses of calf surfactant, indicating that subsequent doses did not alter the clearance of previous doses. The four doses of calf surfactant increased the alveola...
In-Situ Fatigue Crack Growth Testing of Al7075-T651 under Scanning Electron Microscopy

In this paper, an in-situ scanning electron microscope (SEM) fatigue testing was performed to measure the crack growth kinetics and the corresponding crack tip opening displacement (CTOD) at the any small time instant during the constant cyclic tensile loading. The objective of the experimental study is to verify the hypotheses of a small time scale fatigue crack growth model. During the testing, one loading cycle is divided into a certain number of steps. Images are taken at each step around the crack tip region. Imaging analysis is used to quantify the crack growth kinetics and crack tip deformation behavior at any time instant in a loading cycle. Crack closure phenomenon is observed during the crack growth process. It is also observed that crack growth is not uniformly distributed within a loading cycle and only happens during a small portion of loading path. Nomenclature ey = tensile yield strain σy = tensile yield strength E = Young's modulus σ = stress σclosure = crack closure a = crack length F = geometry factor W = width of the specimen D = thickness of specimen K = stress intensity factor δ = CTOD
Small cell lung cancer mimicking high-grade lymphoma in a patient with concurrent B-cell lymphoproliferative disorder.

![Figure][1] A 77-year-old woman with a remote smoking history presented with progressive dyspnea, chest discomfort, and hypoxia. Computed tomography showed extensive mediastinal, hilar, and perisplenic adenopathy. Her laboratory work was notable for thrombocytopenia (platelets = 77 K/μL),
Targeted enzyme prodrug therapy for metastatic prostate cancer - A comparative study of L-methioninase, purine nucleoside phosphorylase, and cytosine deaminase

Enzyme prodrug therapy shows promise for the treatment of solid tumors, but current approaches lack effective/safe delivery strategies. To address this, we previously developed three enzyme-containing fusion proteins targeted via annexin V to phosphatidylserine exposed on the tumor vasculature and tumor cells, using the enzymes L-methioninase, purine nucleoside phosphorylase, or cytosine deaminase. In enzyme prodrug therapy, the fusion protein is allowed to bind to the tumor before a nontoxic drug precursor, a prodrug, is introduced. Upon interaction of the prodrug with the bound enzyme, an anticancer compound is formed, but only in the direct vicinity of the tumor, thereby mitigating the risk of side effects while creating high intratumoral drug concentrations. The applicability of these enzyme prodrug systems to treating prostate cancer has remained unexplored. Additionally, target availability may increase with the addition of low dose docetaxel treatment to the enzyme prodrug treatment, but this effect has not been previously investigated. To this end, we examined the binding strength and the cytotoxic efficacy (with and without docetaxel treatment) of these enzyme prodrug systems on the human prostate cancer cell line PC-3. All three fusion proteins exhibited strong binding; dissociation constants were 0.572 nM for L-methioninase-annexin V (MT-AV), 0.406 nM for purine nucleoside phosphorylase-annexin V (PNP-AV), and 0.061 nM for cytosine deaminase-annexin V (CD-AV). MT-AV produced up to 99% cell death (p < 0.001) with limited cytotoxicity of the prodrug alone. PNP-AV with docetaxel created up to 78% cell death (p < 0.001) with no cytotoxicity of the prodrug alone. CD-AV with docetaxel displayed up to 60% cell death (p < 0.001) with no cytotoxicity of the prodrug alone. Docetaxel treatment created significant increases in cytotoxicity for PNP-AV and CD-AV. Strong binding of fusion proteins to the prostate cancer cells and effective cell killing suggest that the enzyme prodrug systems with MT-AV and PNP-AV may be effective treatment options. Additionally, low-dose docetaxel treatment was found to increase the cytotoxic effect of the annexin V-targeted therapeutics for the PNP-AV and CD-AV systems.
Sorting out Co-occurrence of Rare Monogenic Retinopathies: Stargardt Disease Co-existing with Congenital Stationary Night Blindness

AbstractBackground: Inherited retinal diseases are uncommon, and the likelihood of having more than one hereditary disorder is rare. Here, we report a case of Stargardt disease and congenital stationary night blindness (CSNB) in the same patient, and the identification of two novel in-frame deletions in the GRM6 gene.Materials and Methods: The patient underwent an ophthalmic exam and visual function testing including: visual acuity, color vision, Goldmann visual field, and electroretinography (ERG). Imaging of the retina included fundus photography, spectral-domain optical coherence tomography (OCT), and fundus autofluorescence. Genomic DNA was PCR-amplified for analysis of all coding exons and flanking splice sites of both the ABCA4 and GRM6 genes.Results: A 46-year-old woman presented with recently reduced central vision and clinical findings of characteristic yellow flecks consistent with Stargardt disease. However, ERG testing revealed an ERG phenotype unusual for Stargardt disease but consistent with...
A Mechanism of Chromosomal Rearrangements: The Role of Heterochromatin and Ectopic Joining

Clusters of breaks at certain intercalary heterochromatin sites producing chromosomal rearrangements are reported in four endemic species (24 strains) of Hawaiian Drosophila. In laboratory strains of these species we observed some types of changes in chromosome structure that were predicted in our earlier studies (Yoon and Richardson 1976a).-We outline the pseudochromocenter model for the production of chromosomal rearrangements. First, nonhomologous sites that are heterochromatic and contain similar base sequences of highly repetitious DNA join in a chromocenter-like configuration. Second, chromatid exchanges by breakage and reunion occur at the ectopically joined sites. Based on this model, one expects many new chromosomal rerrangements, some of which have been observed and used to differentiate species.-Inversions with identical breakpoints may occur with much greater frequency than previously assumed. Chromosome phylogenies, based on the assumption that inversions are unique events, still would be accurate if the incorporation of an inversion into the karyotype was rare. This would be the case if a rare combination of genes was necessarily contained in the inversion before it was likely to be incorporated into the gamete pool and thereby become a characteristic feature of the species.
Factors That Affect Physiologic Tremor and Dexterity During Surgery: A Primer for Neurosurgeons.

Introduction All individuals have a physiologic tremor that may become more pronounced in periods of stress, stimulant use, or caffeine. There are few publications measuring the effects of these factors on surgeons or trainees and no comprehensive reviews. We sought to review the representative literature. Materials and Methods An exhaustive literature search to identify journal articles evaluating factors that affect surgical tremor or dexterity was performed. Results Our search identified 34 studies. All included manuscripts are from small, single-center studies and the vast majority evaluated procedural skills on the basis of laparoscopic simulators. Only one study in which the authors evaluated microsurgical procedural performance was identified. Conclusions The literature evaluating tremor and its relationship to surgical performance is limited. Surgeons wishing to optimize surgical dexterity may benefit from avoiding caffeine use or fasting before operating and avoiding sleep deprivation or alcohol use the night before procedures. Those surgeons prone to anxiety or stress-related tremor may obtain a benefit from certain beta-blockers. Finally, the use of appropriate surgical ergonomics with hand or wrist steadying may improve surgical tremor and reduce fatigue.
Design and analysis of distributed primitives for mobile ad hoc networks

This dissertation focuses on the design and analysis of distributed primitives for mobile ad hoc networks, in which mobile hosts are free to move arbitrarily. Arbitrary mobility adds unpredictability to the topology changes experienced by the network, which poses a serious challenge for the design and analysis of reliable protocols. In this work, three different approaches are used to handle mobility. The first part of the dissertation employs the simple technique of ignoring the mobility and showing a lower bound for the static case, which also holds in the mobile case. In particular, a lower bound on the worst-case running time of a previously known token circulation algorithm is proved. In the second part of the dissertation, a self-stabilizing mutual exclusion algorithm is proposed for mobile ad hoc networks, which is based on dynamic virtual rings formed by circulating tokens. The difficulties resulting from mobility are dealt with in the analysis by showing which properties hold for several kinds of mobile behavior; in particular, it is shown that mutual exclusion always holds and different levels of progress hold depending on how the mobility affects the token circulation. The third part of the dissertation presents two broadcasting protocols which propagate a message from a source node to all of the nodes in the network. Instead of relying on the frequently changing topology, the protocols depend on a less frequently changing and more stable characteristic---the distribution of mobile hosts. Constraints on distribution and mobility of mobile nodes are given which guarantee that all the nodes receive the broadcast data.
Preoperative and Postoperative Management

Cancer of the ovary raises many challenges during the preoperative, operative, and postoperative periods. It is not only the site of origin of a variety of tumors but a target for metastases from many other organs (i.e., thyroid, breast, stomach, colon, and the opposite ovary). Therefore it is important to rule out the ovarian tumor as a metastatic lesion before exploratory laparotomy. To be forewarned is indeed to be forearmed. The diagnostic evaluation has been covered in Chapter 8.
The Legacy of Early Interpersonal Experience

Abstract Despite decades of research on social development, the question of whether early interpersonal experiences play an important role in human development is just as controversial today as it was decades ago. In this chapter, we argue that there are at least three reasons why this debate has remained unsettled. First, outside of a few landmark longitudinal studies, relatively few investigations have prospectively charted the long-term correlates of experiences with primary caregivers in the first 3 years of life. Second, most analyses of datasets focused on the legacy of early experience have emphasized two-wave test–retest analyses. We contend that, to distinguish between enduring versus merely transient effects of early experience, it is instead necessary to study the pattern of associations that are observed across multiple assessment occasions. Third, despite decades of stinging critiques by behavior-genetic scholars, not enough attention has been paid in social developmental research to determining whether the robust correlations identified between parental behavior and child outcomes are genetically mediated. In this chapter, we discuss each of these issues, in turn, and review recent conceptual models and empirical data that help to address them.
Did Someone Say Riot? James M. Jasper in Conversation with AK Thompson

AbstractOn 30 October 2013, James M. Jasper and AK Thompson spoke at an event entitled ‘Did Someone Say Riot?,’ hosted by New York City’s Brecht Forum (now sadly defunct). According to the promotional material for the event, despite being ‘maligned in official accounts, the riot has in fact been a decisive feature of American politics.’ Jasper and Thompson’s comments thus aimed to highlight ‘the central role that riots have played in the processes of race and class formation in America, the political ambivalence that radical left forces have often expressed toward riots, and the need to once again put the riot at the forefront of our political considerations.’ The following is derived from a transcript of their conversation on that evening.
Degradation of Ir(ppy)2(dtb-bpy)PF6 iTMC OLEDs

Simplicity of construction and operation are advantages of iTMC (ionic transition metal complex) OLEDs (organic light emitting diodes) compared with multi-layer OLED devices. Unfortunately, lifetimes do not compare favorably with the best multi-layer devices. We have previously shown for Ru(bpy) 3 (PF 6 ) 2 based iTMC OLEDs that electrical drive produces emission-quenching dimers of the active species. We report evidence here that a chemical process may also be implicated in degradation of devices based on Ir(ppy) 2 (dtb-bpy)PF 6 albeit by a very different mechanism. It appears that degradation of operating devices made with this Ir-based complex is related to current-induced heating of the organic layer, resulting in loss of the dtb-bpy ligand. (The dtb-bpy ligand is labile compared with the cyclometallated ppy ligands.) Morphological changes observed in electrically driven Ir(ppy) 2 (dtb-bpy)PF 6 OLEDs provide evidence of substantial heating during device operation. Evidence from UV-vis spectra in the presence of an electric field as well as MALDI-TOF mass spectra of the OLED materials before and after electrical drive add support for this model of the degradation process. © 2009 Materials Research Society.
Complex oxides: Creative tension in layered crystals.

New findings suggest that the mechanical stretching of layered crystals can transform them from a polar to a nonpolar state. This could spur the design of multifunctional materials controlled by an electric field.
Thermal Volume Change of Unsaturated Silt under Different Stress States and Suction Magnitudes

This paper presents an evaluation of the thermal volume change of compacted specimens of the same type of silt under a wide range of stress states, initial void ratios, and suction magnitudes. Stress states include both isotropic and anisotropic conditions with varying principal stress ratios, as well as normally consolidated and overconsolidated conditions. Initial void ratios range from 0.60 to 0.86, spanning very dense to loose conditions. Suctions evaluated range from saturated conditions, to low suctions in the funicular range, to suctions corresponding to residual saturation conditions. For the same soil, wide variations in thermal volume change are observed. Thermal contraction is observed for normally consolidated conditions regardless of the initial degree of saturation. Different mechanisms of thermal volume change can be used to explain the results, ranging from thermally-induced pore water pressure dissipation, to thermal collapse, to thermally-accelerated creep.
Language Impairment and Arachnoid Cysts

Researchers at the Universite Catholique de Louvain, Brussels, Belgium, and Universite de Sherbrooke, Quebec, Canada studied 2 patients presenting with arachnoid cysts associated with cognitive impairment., particularly language impairment.
Safety of regadenoson stress testing in patients with pulmonary hypertension

We sought to determine the safety of regadenoson stress testing in patients with PH. PH is increasingly recognized at more advanced ages. As many as one-third of patients with PH have coronary artery disease. Because of their physical limitations, patients with PH are unable to adequately exercise. Regadenoson can potentially have an adverse impact due to their tenuous hemodynamics. Current guidelines suggest performing a coronary angiography in patients with PH who have angina or multiple coronary risk factors. We identified 67 consecutive patients with confirmed PH by catheterization (mean PA > 25 mmHg not due to left heart disease) who underwent MPI with regadenoson stress. Medical records were reviewed to determine hemodynamic and ECG response to regadenoson. No serious events occurred. Common side effects related to regadenoson were observed, dyspnea being the most common (70.6%). No syncope occurred. Heart rate increased from 74.6 ± 14 to 96.3 ± 18.3 bpm, systolic blood pressure increased from 129.8 ± 20.9 to 131.8 ± 31 mmHg, and diastolic blood pressure decreased from 77.1 ± 11.4 to 72.9 ± 15.3 mmHg. There was no ventricular tachycardia, ventricular fibrillation, or second- or third-degree atrioventricular block. Regadenoson stress MPI appears to be well tolerated and safe in patients with PH.
Visual Literacy in Instructional Design Programs.

In this technologically advanced environment, users have become highly visual, with television, videos, web sites and images dominating the learning environment. These new forms of searching and le...
Kuma Malinke historiography: Sundiata Keita to Almamy Samori Toure, by Nubia Kai

Works of historiography generally are not characterized as “scintillating”. Yet, Nubia Kai has produced a work that is fascinating, sometimes exciting, and possibly – just possibly – somewhat contr...
Place, Historical Ecology and Cultural Landscape: New Directions for Applied Archaeology

The two themes I discuss here are historical ecology (landscape history) as a guiding scheme for studying past cultural landscapes, and the concept of place as a time-space identification of human activities. Historical ecology is the study of past relationships between groups of people and their environments. Its multidimensional orientation combines the knowledge of various aspects of human activity with the theory and methodology of ecology. The historical ecology approach explains human decisions in terms of deterministically understood relationships among adaptational constraints imposed by a variety of environmental stresses throughout time. Occasionally, however, people make decisions that may not necessarily lead to optimal solutions the fate of the Easter Island population or the Norse occupation of Greenland are notable examples. As archaeologists, we should expect to recognize evidence of various decisions (good and bad) since some of the consequences will be preserved in form of archaeological data such as artifacts, architectural features, landscape modifications, etc. Naturally, as environmental stresses increase, human responses diversify and intensify. And as the complexity of responses increase, a greater diversity and density of archaeological facts is expected. Archaeologists argue that all kinds of evidence of human past behavior are significant and potentially contribute to a better understanding of human history.
Training social work students to recognize later-life depression: Is standardized patient simulation effective?

ABSTRACTProfessional social workers are the largest provider of mental health services in the nation, yet they receive little coursework or clinical training in late-life depression unless they are in a gerontology specialization. Simulation training offers academic experiences that evoke conditions of the real world in a practical way. One hundred and four graduate social work students consented and completed the Standardized Patient Simulation course consisting of a human simulator interview, pre- and postdebriefing on late life depression, and self and faculty ratings of outcome measures. Results from pre–post testing of measures and the debriefing evaluation demonstrated that students gained in knowledge and achieved clinical skill competency. Students reported that the patient simulator was convincing, the environment was realistic, and they were satisfied with the training. The educational methodology tests students in challenging situations and offers immediate educational feedback to integrate and...
Conversion of Pregabalin to 4-Isobutylpyrrolidone-2

Solid-state studies of C-butyl-resorcin[4]arene with pregabalin (Lyrica, Nervalin) in nitrobenzene yielded a cocrystal of C-butyl-resorcin[4]arene with 4-isobutylpyrrolidone-2. A combined experimental and quantum chemical investigation was implemented to further our understanding of the factors affecting the conversion process.
Regulated Bioanalysis—Historical Aspects and Key Concepts Related to Its Use

The history and key concepts of bioanalysis are discussed. Historically, the scientific need driving the development of bioanalytical methodology was the evolution of the science of pharmacology as well as the field of pharmacokinetics. Similarly, the ability to actually perform bioanalysis was linked to the development of analytical methodology/instrumentation. Each of these historical aspects of bioanalysis is discussed in this chapter. Key attributes of molecules quantitated in bioanalytical procedures for small molecules and protein therapeutics are described. Topics discussed in this regard include plasma protein binding, free drug versus total drug measurements, prodrugs versus active moieties, metabolites, minimum required dilution, and parallelism. In addition, important considerations with respect to different types of study samples are described. These factors include the influence of dosing vehicle and collection methodology. Matrices discussed include whole blood, urine, cerebral spinal fluid, tissues, and dried blood spots.
An evaluation of paraffin sections of aspirated bone marrow in malignant lymphomas.

Examination of serial paraffin sections of bone-marrow aspirations has increased the known incidence of marrow involvement in malignant lymphomas. The results of this study can be seen in the table. In the 72 cases reviewed here, lesions compatible with malignant lymphoma were seen in paraffin sections in 22 cases. In 12 cases this was the only material available for diagnosis at the time. In an additional seven cases paraffin sections were considered suggestive of malignant lymphoma and in five of these a diagnosis could be made on the basis of examination of both smear and paraffin section. This procedure is particularly helpful in Hodgkin’s disease and reticulum cell sarcoma, where marrow smears are only rarely diagnostic. In general, the patients in whom lesions were found in the bone marrow tended to have more advanced disease than those in whom lesions were not found, and abnormalities in the peripheral blood were more common. This was especially true of patients with Hodgkin’s disease, less so in those with reticulum cell sarcoma. Patients with lymphosarcoma, lymphocytic type, did not show this difference, either in the extent of the disease or in findings on examination of peripheral blood. Diagnosis was most difficult in patients who had lymphocytic lymphosarcoma, since it was occasionally difficult to distinguish between the benign aggregations of lymphocytes which are not infrequently found in a large number of unrelated conditions and those aggregations which represented malignancy. Differentiation was made on the basis of number of aggregations, degree of circumscription, presence or absence of reaction centers and the cytologic appearance of the cells. Examination of the smears of the marrow is most helpful in these cases. Seven patients in this series (9.7 per cent) had granulomatous lesions in the marrow. In five of these the final diagnosis was Hodgkin’s disease, in one reticulum cell sarcoma and in one follicular lymphoma. Although these lesions were not specific, the incidence is high enough to make the finding of a granuloma of some significance in any patient suspected of having malignant lymphoma. The importance of thorough examination of any material obtained in an apparent dry tap and the value of repeated marrow-examinations is emphasized by three cases in this series. Since in many cases diagnostic lesions are found in only one portion of the material, examination of only one section of the paraffin sections of aspirated bone marrow is not sufficient for proper evaluation. This fact is emphasized by the greater incidence of positive findings in this report than in that of Cooper and Watkins. Studies of bone marrow should be particularly helpful in instances in which the diagnosis of malignant lymphoma is suggested by clinical features but cannot be proved by biopsy of peripheral nodes or other readily accessible tissue.
Speech enhancement using new iterative minimum statistics approach

In hands-free mobile communication, speech quality is often degraded due to presence of surrounding noise. This paper introduces an improved version of Minimum Mean Square Error (MMSE) noise estimator. Noise spectrum estimation is a crucial element used in speech recognition systems. Our proposed noise estimation method is based on a popular searching algorithm used in software engineering called Binary Search (BS), which we integrate with First-In First-Out (FIFO) MMSE noise reduction algorithm. In the literature, there is no research addressing the integration of BS algorithm with an active noise cancellation system. The noise spectral minima are computed using BS algorithm which makes it fast and efficient. The proposed algorithm is tested using real time data collected from vehicles running at different speeds. Simulation results are provided, and it is shown that the proposed algorithm outperforms other MMSE algorithms.
Prognostic significance of IgG4+ plasma cell infiltrates following neoadjuvant chemoradiation therapy for esophageal adenocarcinoma

Summary Lymphoplasmacytic infiltrates in esophageal adenocarcinoma (EAC) tissue following chemoradiotherapy (CRT) reflect alterations in the tumor immunoenvironment. The presence and role of plasma cells in this process are poorly understood. Our aim was to characterize the IgG4+ plasma cell population in EAC following CRT. Seventy-one esophagectomy specimens post-CRT were compared with a surgery-only group of 31 EACs. The distribution, density, and ratio of IgG4+ and IgG+ plasma cells were evaluated by immunohistochemistry and correlated with clinicopathologic features, treatment response, and survival. In the CRT group, the presence of higher numbers of IgG4+ (≥ median of 94/high-power field) and IgG+ (≥ median of 225/high-power field) plasma cells and increased IgG4+/IgG+ ratio (≥ median of 41%) within ulcers was associated with complete or near-complete treatment response ( P = .0077, P = .0503, and P = .0063, respectively). Lower tumor grade, smaller tumor size, and higher levels of IgG4+ plasma cells in posttherapy ulcers significantly correlated with better overall survival, whereas pretherapy clinical stage, posttherapy pathologic stage, smaller tumor size, and lower tumor grade were associated with longer recurrence-free survival. Multivariate analysis revealed that both posttherapy pathologic stage and high IgG4+ plasma cells in ulcers were independent predictors of overall survival ( P = .05 and P = .01), whereas only posttherapy pathologic stage was associated with recurrence-free survival ( P
The Belief-Desire Theory of Emotions

The theory of emotions which I propose is a Belief-Desire Theory: in standard cases, emotions are intentional structures of beliefs and desires. There are also special cases in which imaginative or other belief-like representations, or desire-like representations such as wishes, rather than beliefs and desires, are constitutive of emotions. For the sake of simplicity, however, I will focus for the most part on standard cases, considering special cases only where necessary. There are, I think, no clear historical antecedents of this theory. Joel Marks has independently sketched a Belief-Desire Theory of emotions (Marks, 1982), and it has been suggested by both Wayne Davis and John Searle that some emotions can be understood in terms of beliefs and desires (Davis, 1981a; Searle, 1983). Nowhere, however, has this type of theory of emotions been thoroughly developed and defended. That is what I aim to do.
Direct Observation of Hierarchic Molecular Interactions Critical to Biogenic Aerosol Formation

Small clusters consisting of sulfuric acid/bisulfate and oxidized organics have been identified in both aerosol field measurements and laboratory experiments, and their formation is suggested to be the rate-limiting step in the formation of new particles. However, the underlying mechanism for cluster formation is still largely unclear. Here we show, through an integrated negative ion photoelectron spectroscopy and quantum chemical study on a series of (HSO4−)(organic molecule) surrogate binary clusters, that the functional groups are more important in determining the extent of the enhanced role of the organics in aerosol formation process than the average carbon oxidation states or O/C ratios. This extent is quantified explicitly for specific functional groups, revealing highly hierarchic intermolecular interactions critical to aerosol formation. Born–Oppenheimer molecular dynamics simulations are employed to probe the water-binding abilities of these clusters under ambient conditions, and their statistical hydrogen-bonding networks. Studying the early stages of aerosol formation is a challenge in physical and environmental chemistry. Here photoelectron spectroscopy, quantum chemical calculations, and molecular dynamics simulations quantify how specific functional group interactions stabilize clusters of bisulfate anions and organic molecules.
Mining 3D Shape Data for Morphometric Pattern Discovery

Recent technological advances in 3D digitizing, noninvasive scanning, and interactive authoring have resulted in an explosive growth of 3D models in the digital world. There is a critical need to develop new 3D data mining techniques for facilitating the indexing, retrieval, clustering, comparison, and analysis of large collections of 3D models. These approaches will have important impacts in numerous applications including multimedia databases and mining, industrial design, biomedical imaging, bioinformatics, computer vision, and graphics. For example, in similarity search, new shape indexing schemes (e.g. (Funkhouser et al., 2003)) are studied for retrieving similar objects from databases of 3D models. These shape indices are designed to be quick to compute, concise to store, and easy to index, and so they are often relatively compact. In computer vision and medical imaging, more powerful shape descriptors are developed for morphometric pattern discovery (e.g., (Bookstein, 1997; Cootes, Taylor, Cooper, & Graham, 1995; Gerig, Styner, Jones, Weinberger, & Lieberman, 2001; Styner, Gerig, Lieberman, Jones, & Weinberger, 2003)) that aims to detect or localize shape changes between groups of 3D objects. This chapter describes a general shape-based 3D data mining framework for morphometric pattern discovery.
ISO and Laboratory Astrophysics

ISO, the Infrared Space Observatory is capable of measuring spectra across most of the mid-infrared, the region from 4000 to 500 cm-1 (2.5-20 μm). Of these 3500 cm-1, about 670 have been inaccessible to astronomers due to strong atmospheric absorptions and about 750 cm-1 require an airborne platform, making access limited. ISO will provide high quality spectra in the 19% of the celestial mid-infrared which has never been studied and dramatically increase the number of spectra in the 21% with limited access. Thus ISO has the potential to nearly double our knowledge of the mid-IR spectroscopic properties of the cosmos. This knowledge, in turn, will revolutionize our understanding of its chemical make-up because of the mid-infrared’s powerful compositional diagnostic capabilities.
Pregnancy Programming and Preeclampsia: Identifying a Human Endothelial Model to Study Pregnancy-Adapted Endothelial Function and Endothelial Adaptive Failure in Preeclamptic Subjects

We have previously reported that the increase in vasodilator production in an ovine model pregnancy is underpinned by an increase in connexin 43 (Cx43) gap junction function, so allowing more uterine artery endothelial cells to produce a more sustained Ca2+ burst response to agonist stimulation. Since activation of endothelial nitric oxide synthase (eNOS) requires elevated [Ca2+]i, it follows that the direct result of enhanced bursting in turn is an increase in nitric oxide (NO) production per cell from more cells, and for a longer period of time. Preeclampsia (PE) is associated with endothelial vasodilatory dysfunction, and the endocrine profile of women with PE includes an increase in a number of factors found in wound sites. The common action of these growth factors and cytokines in wound sites is to mediate Cx43 dysfunction through kinase phosphorylation and closure. Translational studies are now needed to establish if inhibitory phosphorylation of Cx43 in human endothelium is the cause of endothelial dysfunction in PE subjects and if so, to identify the kinase pathways best targeted for therapy in PE subjects. Consistent with this we have already shown endothelial Ca2+ and NO responses of human umbilical vein from normal subjects are similar to that of ovine pregnant uterine artery, and that those same responses in cords from PE subjects are blunted to levels more typical of nonpregnant uterine artery. In this review we summarize the further evidence that growth factors and cytokines may indeed mediate endothelial dysfunction in PE subjects through closure of Cx43 gap junctions. We also consider how we may clinically translate our studies to humans by using intact umbilical vein and isolated HUVEC in primary culture for an initial screen of drugs to prevent deleterious Cx43 phosphorylation, with the ultimate goal of reversing PE-related endothelial dysfunction.
Association Between Adolescent Body Mass Index and Adulthood Smoking.

INTRODUCTION Studies increasingly find a prospective association between adolescent weight status and adverse physical health outcomes. However, less is known about the long-term consequences of adolescent body weight on the adoption of health-risk behaviors. This study sought to determine whether adolescent body mass index (BMI) was associated with cigarette smoking in adulthood. METHODS Six thousand six hundred eighty-three nonsmoking adolescents were interviewed at baseline (1996, age 11-20) and at follow-up (2008, age 24-32) as part of the National Longitudinal Survey of Adolescent Health. Logistic and fractional regression models tested the association between adolescent BMI and smoking status and frequency in adulthood. Respondent weight and height were measured at baseline and converted into age and sex-specific BMI z-scores. Being a smoker was defined as smoking at least once in the past 30 days, while smoking frequency was defined as the proportion of days smoked over the past 30 days. Both outcomes were measured at follow-up. RESULTS Adolescent BMI was positively associated with the transition from nonsmoking to smoking 12 years later for women but not men. Adolescent BMI was also positively associated with smoking frequency among women smokers. Both associations persisted after adjusting for established risk factors and were robust to sensitivity analyses. CONCLUSIONS Adolescent BMI was strongly associated with increased cigarette smoking behavior in adulthood for women, even after adjusting for important risk factors. IMPLICATIONS Using a large, nationally representative sample, this study found that adolescent BMI was positively associated with smoking behavior during adulthood for women but not men. These results have potentially important public health implications for future smoking rates in the United States, as the prevalence of overweight and obesity among US adolescent females continues to grow. Thus, it may be important for smoking prevention interventions to prioritize overweight adolescent females moving forward.
A novel ex vivo trainer for robotic vesicourethral anastomosis

Robotic surgical skill development is central to training in urology as well as other surgical disciplines. Vesicourethral anastomosis (VUA) in robotic prostatectomy is a challenging task for novices due to delicate tissue and difficult suturing angles. Commercially available, realistic training models are limited. Here, we describe the development and validation of a 3D-printed model of the VUA for ex vivo training using the da Vinci Surgical System. Models of the bladder and urethra were created using 3D-printing technology based on estimations of average in vivo anatomy. 10 surgical residents without prior robotics training were enrolled in the study: 5 residents received structured virtual reality (VR) training on the da Vinci Skills Simulator ("trained"), while the other 5 did not ("untrained"). 4 faculty robotic surgeons trained in robotic urologic oncology ("experts") were also enrolled. Mean (range) completion percentage was 20% (10-30%), 54% (40-70%), and 96% (85-100%) by the untrained, trained, and expert groups, respectively. Anastomosis integrity was rated as excellent (as opposed to moderate or poor) in 40%, 60%, and 100% of untrained, trained, and expert groups, respectively. Face validity (realism) was rated as 8 of 10 on average by the expert surgeons, each of whom rated the model as a superior training tool to digital VR trainers. Content validity (usefulness) was rated as 10 of 10 by all participants. This is the first reported 3D-printed ex vivo trainer for VUA in robotic prostatectomy validated for use in robotic simulation. The addition of 3D-printed ex vivo training to existing digital simulation technologies may augment and improve robotic surgical education in the future.