cssi/SciSciGPT-SciSciNet huggingface dataset:
Molecular mechanisms of endocrine resistance

Estrogen receptor-positive (ER+) breast cancer is the most common subtype of breast cancer. Endocrine therapy targeting the ER pathway is effective, yet endocrine resistance is prevalent and remains a clinical challenge. The mechanisms underlying endocrine resistance are multifaceted and are likely to continue evolving over time in response to various endocrine regimens. The expression of ER in most endocrine-resistant tumors underscores ER’s continuing role, although altered, often via crosstalk with hyperactive growth factor receptor and intracellular kinase signaling pathways. These interactions can alter ER’s sensitivity to various endocrine agents and lead to the activation of distinct transcriptional programs that provide proliferation and survival signaling to escape endocrine therapy. Additional molecular determinants inflicting ER transcriptional reprogramming to promote endocrine resistance include alterations of ER coregulators and pioneer factors, and genetic aberrations of ER itself. Recent advances in our understanding of the mechanisms of endocrine resistance, mostly provided by large-scale sequencing studies, further establish the roles of epigenetic alterations, the DNA damage response, the tumor microenvironment, and the immune response in promoting the endocrine-resistant ER+ disease. Progress has been made in translating several of these findings into effective new targeted therapies, such as inhibitors targeting the key signaling node mTOR and the cyclin-dependent kinases CDK4 and CDK6. However, considerable challenges remain in (1) developing new tailored treatment strategies with enhanced efficacy and reduced toxicity, (2) improving the patient selection approaches for these new treatments, and (3) advancing our understanding of how to harness the recent developments in immunotherapy to support other therapeutic strategies to prevent or overcome endocrine resistance and disease progression. It is our hope that continuing translational research will unveil more converging targets and pathways associated with altered ER transcriptional reprogramming, which can be therapeutically exploited to prevent and/or reverse endocrine resistance.
Checkpoint Inhibition and Infectious Diseases: A Good Thing?

The mammalian immune system has evolved the capacity to detect and destroy tumor cells. Tumors utilize multiple strategies to evade host immune surveillance, including the induction of the checkpoint molecules cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) to suppress antitumor immunity. Pharmacologic blockade of these molecules with checkpoint inhibitors (CPIs) restores T cell function and prolongs survival in patients with various malignancies. Emerging evidence suggests that the same checkpoint pathways may play a crucial role during infections. Indeed, CPIs appear promising as immunotherapeutic agents in infectious diseases, although their efficacy varies depending on pathogen-, cell-, and organ-specific factors. More research will be necessary to clarify the effects and safety of CPIs on clinically relevant outcomes of human infection.
Corrected calcium versus ionized calcium measurements for identifying hypercalcemia in patients with multiple myeloma.

Abstract Background Dysregulated bone turnover is an important clinical manifestation of multiple myeloma (MM), and 30% of patients present with hypercalcemia. Serum calcium levels are routinely monitored using total calcium measurements corrected for albumin. However, myeloma-related paraproteins may bind calcium, confounding these measurements. Patients and methods We retrospectively analyzed correlation between corrected calcium and ionized calcium in a sample of patients with MM and a control sample of patients with breast or non-small cell lung cancers (n = 200). Multiple linear regression was used to identify variables affecting corrected calcium measurements. Results Correlation between corrected calcium and ionized calcium was stronger in the control group compared to the MM group (Spearman correlation coefficient 0.85 versus 0.76, respectively). Sensitivity of corrected calcium in identifying hypercalcemia defined by elevated ionized calcium was 36% in patients with MM and 76% in the control group. Multiple linear regression did not reveal variables significantly influencing corrected calcium in the MM group, although serum paraprotein trended toward significance (p = 0.09). Conclusion Ionized calcium may be better than corrected calcium for detecting hypercalcemia in patients with MM. Additional analyses are needed to better quantify the clinical impact of paraprotein calcium-binding.
Graphene p-n junction photo-responsivity enhanced with gap-plasmons (Conference Presentation)

Graphene photodetectors’ intrinsically low responsivity (sensitivity) has been a long-standing issue that overshadows graphene’s other excellent optical properties as a photodetection material. The key to improving the graphene photodetector responsivity lies in enhancing the photothermoelectric (PTE) effect, which has already been demonstrated to be the dominant photocarrier generation mechanism. To maximize the PTE current, one would need a strong optically-induced temperature gradient to overlap with a graphene p-n junction spatially. Here, the temperature gradient drives the charge carrier movement, while the graphene p-n junction separates the different charge carrier types (electrons and holes) and makes them drift in opposite directions. In this work, we show that these two conditions can be met simultaneously in a meticulously designed device, combining a gap plasmon structure and a pair of split-gates. The gap plasmon structure absorbs 71% of incident light creating localized heating (thereby large temperature gradient), and the split-gates create a p-n junction at the center of the localized thermal gradient. We fabricated a graphene photodetector with the proposed configuration, and experimentally verified the dominance of PTE effect in photocurrent generation in good agreement with theoretical calculations. More importantly, we obtained a responsivity 70 times higher than the previously reported value from a similar device without plasmon-enhancement. Moreover, originating from the combination of gap plasmon-enhanced optical absorption and optimized p-n junction, our responsivity is 5~7 times higher than reported values for other graphene photodetectors with different types of plasmon-enhancement and no junction control.
Navigating Insurance Policies in the United States for Gender-affirming Surgery.

Patients with gender dysphoria seeking to undergo gender affirmation surgery are often challenged by lack of insurance coverage. The authors aim to review gender affirmation surgery policies and to highlight discrepancies between qualifying criteria across top insurance companies in the United States. Methods The top 3 insurance companies in each state within the United States were determined by market share. Each insurance policy was analyzed according to coverage for specific "top surgeries" and "bottom surgeries." Policies were obtained from company-published data and phone calls placed to the insurance provider. Results Of the total 150 insurance companies identified, policies related to gender- affirming surgery were found for 124. Coverage for gender-affirming surgery varies by insurance company, state, and procedure. Most insurance companies, 122 of 124 (98%), covered chest masculinization, but only 25 of 124 (20%) of insurance companies covered nipple-areola complex reconstruction. Additionally, 36 of 124 (29%) insurance companies covered chest feminization. Vaginoplasty is covered by 120 of 124 (97%) insurance companies. Despite high rates of vaginoplasty coverage, vulvoplasty is only covered by 26 of 124 (21%) insurance companies. Phalloplasty and metoidioplasty are covered by 118 of 124 (95%) and 115 of 124 (93%) of insurance companies, respectively. Slightly more than half, 75 of 124 (60%) insurance companies covered penile prosthesis. Conclusions As gender-affirming surgery insurance coverage increases, the policies regarding them remain inconsistent. Standardized policies across insurance companies would further increase access to gender-affirming surgery.
Pathogenesis ofSynchytrium endobioticum: V. Wart disease suppression in potato in soils amended with urea and/or ammonium nitrate in relation to soil pH

Field plots infested withSynchytrium endobioticum pathotype 2 were amended with agricultural lime, NH4NO3 and/or urea and planted with cv. Arran Victory. A weekly survey of changes in pH from planting to harvest revealed constant pH in absence of the chemicals, fluctuating pH with lime, very large increase then falling off with urea, and depressed below normal pH with NH4NO3. Best disease control occurred in urea-treated plotsvs NH4NO3-treated plots. Addition of lime, although it elevated pH, did not suppress the disease with urea or NH4NO3 added. Mechanisms for suppression by urea are related to its role as an ammonia producer and microbial stimulator, and their implication for infection byS. endobioticum.
Characteristics and Clinical Outcomes of Prolonged Continuous Renal Replacement Therapy in Critically Ill Pediatric Patients

OBJECTIVES Paralleling improved outcomes in critically ill patients, survival for pediatric acute kidney injury has improved. Continuous renal replacement therapy is the preferred modality to optimize fluid and electrolyte management as well as nutritional support for children developing acute kidney injury in the PICU. However, some patients remain too fragile for transition to intermittent renal replacement therapies and require continuous renal replacement therapy for a prolonged period. Characteristics of this cohort and factors impacting outcomes are not well known. We aimed to describe the characteristics of pediatric patients requiring prolonged continuous renal replacement therapy and evaluate the factors impacting hospital survival. DESIGN Retrospective chart review. SETTING Tertiary PICU. PATIENTS Children requiring prolonged continuous renal replacement therapy. Prolonged continuous renal replacement therapy was defined as continuous renal replacement therapy dependence greater than or equal to 28 days. Primary outcome was hospital mortality. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS From 2013 to 2016, 344 patients received continuous renal replacement therapy, 36 (10%) received continuous renal replacement therapy for greater than or equal to 28 days. Seventeen patients (47%) were female. Overall mortality was 44% (16/36); 69% (11/16) of nonsurvivors died of sepsis. Pediatric Logistic Organ Dysfunction score was significantly higher in nonsurvivors. Mortality rate was significantly higher in patients who were neutropenic at continuous renal replacement therapy start. Neutropenia (defined as absolute neutrophil count < 1,500/mm) at continuous renal replacement therapy start was the only independent predictor of mortality. One in four survivors did not recover renal function and remained dialysis dependent. CONCLUSIONS Prolonged continuous renal replacement therapy patients are at high risk of nonrecovery of renal function and require close monitoring. The majority of nonsurvivors in the study group died from sepsis. Neutropenia at continuous renal replacement therapy initiation was associated with increased risk of mortality. Progression of underlying disease process could explain the higher death rate in patients with neutropenia; however, inadequate treatment of infectious complications could be another explanation to explore further in future studies.
Effects of supplemental calcium butyrate on lamb growth, plasma metabolites, and hepatic gluconeogenic and inflammatory gene expression changes

Abstract Objective was to evaluate the effects of increasing supplemental calcium butyrate on intake, growth, plasma acute phase proteins and hepatic enzyme expression in lambs fed a concentrate-based diet. Twelve pens of crossbred Hampshire × Suffolk lambs (n = 2 lambs/pen) were assigned to 1 of 3 dietary treatments: (1) no butyrate (C), (2) 6.25 g calcium butyrate/kg of diet DM (B1), and (3) 12.5 g calcium butyrate/kg of diet DM (B2). All lambs were adapted to a basal concentrated-based diet for 2 weeks prior to the start of the experiment. Treatment diets were fed from d 0–56. Blood was collected on d 0, 28, and 55 for analysis of plasma β-hydroxybutyric acid (BHBA), total protein, glucose, ceruloplasmin (CP), and haptoglobin (HP). Intakes were recorded daily by pen and individual body weights were measured weekly. Liver tissue was collected via biopsy on d 56 to measure mRNA expression of gluconeogenic enzymes, acute phase proteins, and inflammatory transcription factors using NanoString. Orthogonal contrasts were used to determine the effects of increasing dietary inclusion of Ca butyrate on lamb growth performance. Interactions of treatment by day were examined for plasma concentrations collected over time. Lambs fed B1 had 67 % and 40 % greater average daily gain (ADG) (quadratic; P = 0.02) than the lambs fed C and B2, respectively. Similarly, lambs fed B1 had 13.4 % and 15.8 % greater DMI (quadratic; P = 0.02) than the lambs fed C and B2, respectively. Total protein, BHBA, glucose, and CP were not affected (P ≥ 0.12) by treatment. There was a treatment × day interaction (P = 0.01) on plasma HP. Plasma HP concentrations did not change in lambs fed B1. Plasma HP concentrations declined on d 55 compared to d 28 in lambs fed C; but, plasma HP concentrations increased on d 55 compared to d 28 in lambs fed B2. In the liver, mRNA expression of acute phase proteins and anti-inflammatory transcription factors were not affected (P ≥ 0.24) by calcium butyrate inclusion in the diet. Similar to DMI and ADG, gluconeogenic enzymes decreased (quadratic; P ≤ 0.08) in lambs fed B1 compared to the lambs fed C and B2. This decrease in mRNA expression of gluconeogenic enzymes may be associated with the feedback from increased DMI in lambs fed B1. Lambs fed B1 achieved greater DMI and ADG when compared to the lambs fed B2 and C and these performance results may be linked to key gluconeogenic pathways.
Is It Funny if No One is Watching? Public Response to Late-Night Political Satire

The past decade has seen a dramatic shift in substance and tone in the political humor found on late-night television talk shows in the U.S. Relatively light-hearted political comedy has in many ca...
Residual lymph node disease and mortality following neoadjuvant chemoradiation and curative esophagectomy for distal esophageal adenocarcinoma

Abstract Objectives Neoadjuvant chemoradiation has been shown to improve survival in locally advanced esophageal and gastroesophageal junction cancer. The purpose of our study was to examine the effects of posttreatment persistent lymph node (LN) disease on overall survival (OS) and recurrence in patients with esophageal adenocarcinoma after neoadjuvant chemoradiation as well as the effect of LN harvest and the potential benefit of adjuvant chemotherapy. Methods The records of patients who underwent esophagectomy in our hospital from January 2005 until December 2016 were analyzed. Our study group consisted of 509 patients. Results Patient groups were created based on pathologic staging after esophagectomy (ypT N) as 22.0% of patients were ypT0 N0, 46.2% had incomplete response only at the primary tumor level (ypT + N0), and 31.8% had at least 1 metastatic lymph node (ypTx N+). Median OS was 58.3 months. The ypTx N+ group was divided into ypTx N1 and ypTx N2 or N3 subgroups based on the number of metastatic lymph nodes. The OS between the 2 groups was not significantly different (median OS, 37.6 vs 29.8 months; P = .097). The disease-free survival did show a statistically significant difference (median disease-free survival, 27.6 vs 13.7 months; P = .007). The LN harvest was not found to be significantly associated with OS. However, administration of adjuvant chemotherapy was a significant prognosticator for increased OS (hazard ratio, 0.590; P = .043). Conclusions Our results demonstrate that residual LN disease after neoadjuvant chemoradiation is associated with increased mortality. Adjuvant chemotherapy, but not number of LNs resected, was correlated with increased OS in this subset of patients.
Adjuvant Radiotherapy Versus Watchful Waiting for World Health Organization Grade II Atypical Meningioma: A Single-Institution Experience.

Background Atypical meningiomas (AMs) are meningiomas that have a higher rate of recurrence than grade I meningioma. Due to the higher risk of recurrence, adjuvant radiotherapy (RT) after resection of AM has been employed. At our institution, some neurosurgeons employ adjuvant RT on all primarily resected AMs, while others employ watchful waiting with serial imaging. Objective To study the effect of adjuvant RT on newly resected AMs. Methods A retrospective review of all AMs primarily resected at our institution from 1996 to 2018 was completed. Data on patient demographics, radiographic findings, use of adjuvant RT, time of follow-up, and recurrences were collected. Adjuvant RT was defined as RT that occurred within 6 mo of initial resection. Results A total of 162 patients met the inclusion criteria. Gross total resection was achieved in 73% of cases. Average time until recurrence in the cohort was 37 mo. A total of 108 patients had adjuvant RT, while 54 patients did not. On multivariate survival analysis, sex, Simpson grade resection, and use of adjuvant RT were independent predictors of recurrence. Mean time to recurrence in patients who received adjuvant RT was 43.7 mo versus 34.7 mo for those who did not receive adjuvant RT. Conclusion This study includes the largest retrospective cohort of patients who have received adjuvant RT after primary resection of AM. Our results suggest that the use of adjuvant RT is independently associated with a lower chance of recurrence. These data suggest that practitioners can consider the use of adjuvant RT for newly resected AMs, regardless of Simpson grade resection.
Compositional Differences Among Types of Mechanically Separated Chicken and Their Influence on Physicochemical Attributes of Frankfurter-Type Sausages

Mechanically separated chicken (MSC) from 2 different separation methods (MSC1, Beehive separator, aged bones [Provisur Technologies, Mokena, IL]; MSC2, Poss separator, fresh bones [Poss Design Limited, Oakville, Ontario, Canada]) and chicken breast trim (CBT) were used as raw materials in frankfurters. Texture, color, and lipid oxidation were measured over a refrigerated storage period of 98 d. Both MSC were higher in fat and lower in moisture than CBT. MSC frankfurters had lower L* and higher a* values than CBT frankfurters, with MSC2 frankfurters having the lowest L* and highest a* (P < 0.05). Thiobarbituric acid-reactive substances values were higher in MSC1 frankfurters (P < 0.05) than in CBT and MSC2 frankfurters. Texture Profile Analysis hardness, cohesiveness, resilience, and chewiness were highest in MSC2 frankfurters. Differences among MSC resulted in detectable differences in finished product attributes, with MSC2 frankfurters being darker and redder and having lower levels of lipid oxidation than MSC1 frankfurters, underscoring the importance of understanding the specific functional attributes of MSC obtained by different processes prior to product formulation and manufacturing.
Stability of the Optimal Locus System

The optimal locus is a new real-time control method for processes subject to constraints that vary as the process progresses. This paper analyze of the stability conditions of an optimal-locus based system. A general stability criterion is found for optimizing a quadratic cost function of a process subject to linear varying constraints.
Primary cultures of rabbit renal proximal tubule cells: III. Comparative cytotoxicity of inorganic and organic mercury

Abstract The present study further developed primary cultures of rabbit renal proximal tubule cells (RPTC) as an in vitro model to study chemical-induced toxicity by investigating the comparative cytotoxicity of mercuric chloride (HgCl2) and methyl mercury chloride (CH3HgCl) to RPTC. Confluent monolayer cultures of RPTC exposed to HgCl2 and CH3HgCl for 24 hr exhibited a concentration-dependent loss in cell viability at culture medium concentrations greater than 25 and 2.5 μ m , respectively. Vital dye exclusion was a more sensitive indicator of cytotoxicity than the amount of lactate dehydrogenase activity, alkaline phosphatase activity, N-acetylglucosaminidase activity, and protein content remaining on the culture dish. On the basis of vital dye exclusion, HgCl2 was less toxic to proximal tubule cells in culture than CH3HgCl after 24 hr of exposure, whether cytotoxicity was based on LC50 values (34.2 μ m HgCl2 vs 6.1 μ m CH3HgCl) or total cellular mercury uptake (4.6 nmol Hg2+/105 cells vs 1.25 nmol CH3Hg+/105 cells). Differences in the extent and rate of metal uptake were also evident. Maximum cellular uptake of Hg2+ occurred within 6–24 hr after exposure and was not concentration-dependent, whereas maximum uptake of CH3Hg+ occurred within 3 hr of exposure and was concentration-dependent. The intracellular distribution of both mercurials between acid-soluble and acid-insoluble binding sites also differed. At noncytotoxic concentrations of HgCl2 (0.04–5 μ m ), intracellular Hg2+ bound increasingly to acid-soluble binding sites as a function of time, from 15–30% after 6 hr of exposure to 40–60% after 72 hr of exposure. However, at subcytotoxic (25 μ m ) and cytotoxic (34.2 μ m ) concentrations, Hg2+ binding to acid-soluble binding sites remained constant at approximately 30–40% for 6, 12, 24, and 72 hr after exposure. In contrast, only 20% of total cellular CH3Hg+ was bound to acid-soluble binding sites after exposure to 0.039 to 6.1 μ m CH3HgCl for 6, 12, and 24 hr. Total cellular glutathione content was unaffected after exposure to 0.04–5 μ m HgCl2 and 0.039–6.1 μ m CH3HgCl, but was depleted 6 hr after exposure to 25 and 34.2 μ m HgCl2. These results indicate that CH3HgCl was a more potent cytotoxicant to RPTC in primary culture than HgCl2. Furthermore, compared to Hg2+, the low binding of CH3Hg+ to acid-soluble binding sites and the absence of a redistribution of CH3Hg+ from acid-insoluble to acid-soluble binding sites appeared to contribute to its more potent toxicity to cultured cells. This study demonstrated that rabbit RPTC in primary culture were a useful in vitro model for studying chemical-induced toxicity on a cellular level.
Regional cerebral glucose utilization reveals widespread abnormalities in the motor system of the rat mutant dystonic

Rats with an inherited movement disorder (dystonic, dt), their phenotypically normal littermates, and normal unrelated controls were studied using a metabolic mapping technique, 2-deoxyglucose autoradiography. This approach was used to identify potential sites of abnormality underlying the movement disorder, as no morphological abnormalities using light and electron microscopic techniques have been identified in this mutation. There was a significant overall glucose utilization (GU) reduction in the dt rats and their littermate controls when they were at rest and not displaying abnormal movements. Conversion of GU values to standard scores showed abnormalities in dt compared with both control groups in the following areas: deep cerebellar nuclei, locus coeruleus, pontine gray, ventrolateral- ventromedial thalamic complex, nucleus of the third nerve, lateral habenula, and basolateral amygdala. Littermates were different from nonlittermates in several regions, including the dentate and red nuclei. A study of relative GU performed in animals displaying dystonic movements also showed abnormalities in the deep cerebellar nuclei and locus coeruleus, and in the red nucleus, external cuneate, and medial septum. Correlations computed for GU in pairs of regions with known anatomical connections suggested that cerebellar, substantia nigra, and basal ganglia efferents may be abnormal. These studies complement existing biochemical and neuropharmacological data which show abnormalities in the cerebellum of the dt rat. Additionally, the function of brain stem and even basal ganglia nuclei is affected in this mutant, perhaps as a consequence of abnormal cerebellar activity. The partial effects in the littermates suggest that abnormalities in only a few regions are not sufficient to produce the movement disorder, and a gene dose effect may exist.(ABSTRACT TRUNCATED AT 250 WORDS)
Adaptive robust structure tensors for orientation estimation and image segmentation

Recently, Van Den Boomgaard and Van De Weijer have presented an algorithm for texture analysis using robust tensor-based estimation of orientation. Structure tensors are a useful tool for reliably estimating oriented structures within a neighborhood and in the presence of noise. In this paper, we extend their work by using the Geman-McClure robust error function and, developing a novel iterative scheme that adaptively and simultaneously, changes the size, orientation and weighting of the neighborhood used to estimate the local structure tensor. The iterative neighborhood adaptation is initialized using the total least-squares solution for the gradient using a relatively large isotropic neighborhood. Combining our novel region adaptation algorithm, with a robust tensor formulation leads to better localization of low-level edge and junction image structures in the presence of noise. Preliminary results, using synthetic and biological images are presented.
The Rationale for Global Equity Offerings

If global capital markets are less than completely integrated, firms can create value for investors by issuing equity in foreign markets. We develop a theoretical framework to show that the offer price for an issuer's shares is increased by wider distribution of the shares in multiple markets. Using a sample of 276 global equity offerings from 1985 to 1992, we compare global equity issues to a control group of issues offered exclusively in the domestic U.S. market. We provide evidence on the direct issue costs (underwriting costs and fees) and the indirect information costs of these offers. After controlling for firm and issue characteristics, we find that the direct costs of issue are significantly lower on average for global issues. In addition, the negative stock price reaction that equity issue typically evokes is reduced when firms have a foreign tranche in their offer. Overall, the results suggest that the segmentation of international markets offers certain issuers an opportunity to raise equity capital at advantageous terms.
Atopieprophylaxe. Grundlagen und Kenntnisstand

Genetische Disposition, Allergenexposition und zusatzliche manifestationsfordernde Faktoren sind die wesentlichen Voraussetzungen einer IgE-vermittelten atopischen Allergie. Aus einer Reihe von Atopie-Markern haben lediglich die Familienanamnese und das IgE des Neugeborenen praktische Bedeutung als pradiktive Parameter fur eine spatere Erkrankung. Kein Parameter identifiziert alle Risikokinder, das IgE scheint aber am besten geeignet, die zukunftigen schweren Erkrankungen vorherzusagen. Neuere Studien zeigen die Moglichkeiten und Grenzen von Programmen zur Atopieprophylaxe auf: die Effekte sind antigenspezifisch und in der Regel auf die Dauer der Elimination beschrankt; manche Nahrungsmittelallergien bilden eine Ausnahme, da sie nur passager auftreten und ihre Manifestation somit durch Eliminationsmasnahmen vollig vermieden werden kann. Nach derzeitigem Beurteilungsstand scheinen Hydrolysat-Milch-Praparate nutzlich zu sein zur Vermeidung von Kuhmilchallergien. Genetic disposition, exposure to allergens and additional factors that favour the manifestation, are the relevant conditions for IgE-mediated atopic allergies. Among a group of markers of atopy, only family history and cord-blood-IgE are of practical relevance as predictors of the disease. No parameter identifies all children at risk, but cord-blood-IgE seems the best in predicting severe diseases. Recent studies demonstrate possibilities and limitations of programs in atopy prevention. The effects are antigen-specific and limited to the time of elimination. Some food allergies form exceptions to this rule, because their manifestation is limited to a vulnerable period and can thus be prevented completely by elimination. The present State of knowledge shows hydrolysed milk preparations to be useful for the prevention of cow's milk allergies.
PROSTATE-CANCER SURVEILLANCE - A COST-EFFECTIVE STRATEGY

The intention of a surveillance program to monitor prostate cancer patients is to detect recurrence of disease as soon as possible and institute therapy at the time of recurrence in order to improve the chance of cure or extend survival. We analyzed the cost of four surveillance programs for prostate cancer. As PSA levels are more sensitive than the bone scan, prostatic acid phosphatase and alkaline phosphatase, a surveillance program which utilizes these latter tests provides no additional clinically useful information beyond a PSA level and is costly. Adopting a strategy of eliminating these tests from a surveillance program would reduce national annual expense by approximately $1.5 billion in the year 2000.
Materialist Criticism and Cordelia's Quasi-Resurrection in King Lear

This essay examines King Lear's belief that the dead Cordelia revives or resuscitates near the very end of the play. This quasi-resurrection, which occurs only in the First Folio (1623), has divided critics into those who regard the moment as mere delusion and others who see it as adumbrating a moment of blessed release. Following a survey of these "redemptionist" versus the predominant nihilist-oriented readings of the play, I examine the influential materialist interpretations offered by Stephen Greenblatt and Jonathan Dollimore. Both insist that Cordelia's quasi-resurrection, since it never reaches fruition, frustrates a religious understanding of the play. (Materialist criticism only counts tangible rewards as meaningful.) The play, however, is more consistent with Hans-Georg Gadamer's view that tragedy overwhelms us with its suffering rather than promotes this-worldly justice. Cordelia's quasi-resurrection gestures towards a possible otherworldly redemption even as it reminds audiences of the Resurrection that, in Lear's pagan world, cannot be replicated. Shakespeare's anachronisms thus superimpose the Christian resurrectionary tradition on the pagan setting of the play; his doing so places the hope and despair of the final scene—the contrast between their transcendent aspirations and the mundane reality of their unresurrected corpses—in the delicate equipoise of his art.
Empirical Bayes Risk Evaluation With Type II Censored Data

Empirical Bayes estimators for the scale parameter in a Weibull, Raleigh or an exponential distribution with type I1 censored data are developed. These estimators are derived by matching moment method. the maximum likelihood method and by modifying the geometric mean estimators developed by Dey and Kuo (1991). The empirical Bayes risks for these estimators and the Bayes rules are evaluated by extensive simulation. Often, the moment empirical Bayes estimator has the smallest empirical Bayes risk. The cases where the modified geometric mean estimator has the smallest empirical Bayes risk are also identified. We also obtain the empirical Bayes risk comparisons for various empirical Bayes estimators when one of the parameters in the hyperprior is known.
Roxarsone Toxicity in the Chick as Influenced by-Dietary Cysteine and Copper and by Experimental Infection with Eimeria acervulina

Abstract A series of experiments was conducted with crossbred chicks to determine the effects of L-cysteine, copper, and coccidiosis on roxarsone toxicity. Levels of roxarsone in excess of 50 mg/kg depressed performance and increased kidney arsenic concentration. L-cysteine·HCl·H2O (.59%) increased rate and efficiency of gain when added to the basal diet, but depressed performance, increased kidney arsenic concentration, and enhanced mortality when added to diets containing toxic levels of roxarsone (200 mg/kg or higher). Moreover, excess copper (500 mg/kg) partially alleviated the gain/feed depression due to the combination of cysteine and roxarsone. Cysteine, in fact, increased feed efficiency in birds fed excess copper in the absence of roxarsone. Eimeria acervulina infection (duodenal coccidiosis) depressed gain and feed efficiency. The depression in feed efficiency was more severe in the presence of roxarsone (50 or 300 mg/kg). In the absence of coccidiosis, 50 mg/kg roxarsone slightly increased gain/feed ratio.
Is a Machine Realization of Truly Human-Like Intelligence Achievable?

Even after more than a half a century of research on machine intelligence, humans remain far better than our strongest computing machines at a wide range of natural cognitive tasks, such as object recognition, language comprehension, and planning and acting in contextually appropriate ways. While progress is being made in many of these areas, computers still lack the fluidity, adaptability, open-endedness, creativity, purposefulness, and insightfulness we associate with the supreme achievements of human cognitive ability. Reasons for this and prospects for overcoming these limitations are discussed.
Empirical state-space representations for Theodorsen's lift model

Abstract In this work, we cast Theodorsen's unsteady aerodynamic model into a general form that allows for the introduction of empirically determined quasi-steady and added-mass coefficients as well as an empirical Theodorsen function. An empirically determined Theodorsen model is constructed using data from direct numerical simulations of a flat plate pitching at low Reynolds number, Re = 100 . Next, we develop low-dimensional, state-space realizations that are useful for either the classical Theodorsen lift model or the empirical model. The resulting model is parameterized by pitch-axis location and has physically meaningful states that isolate the effect of added-mass and quasi-steady forces, as well as the effect of the wake. A low-order approximation of Theodorsen's function is developed based on balanced truncation of a model fit to the analytical frequency response, and it is shown that this approximation outperforms other models from the literature. We demonstrate the utility of these state-space lift models by constructing a robust controller that tracks a reference lift coefficient by varying pitch angle while rejecting gust disturbances.
A double-labeled preparation for simultaneous measurement of [3H]-noradrenaline and [14C]-glutamic acid exocytosis from streptolysin-O (SLO)-perforated synaptosomes

Abstract We have developed a novel method to examine [ 3 H]-noradrenaline and [ 14 C]-glutamate release from the same sample of streptolysin-O (SLO) perforated rat cortical synaptosomes. Ca 2+ -dependent [ 3 H]-noradrenaline and [ 14 C]-glutamate release was examined at different temperatures and was found to be greater at 30°C than at 25°C. Ca 2+ -dependent release of [ 3 H]-noradrenaline is more ATP dependent than Ca 2+ -dependent release of [ 14 C]-glutamate. No significant reuptake of either neurotransmitter by the perforated synaptosomes was detected, indicating all the synaptosomes were indeed perforated. Incubations with 1 mM ouabain, a specific Na + ,K + -ATPase inhibitor, slightly increased Ca 2+ -dependent release of both neurotransmitters. [ 3 H]-noradrenaline is released from large dense-core vesicles and [ 14 C]-glutamate is released from small clear synaptic vesicles, so one can directly compare and contrast neurotransmitter release mechanisms between large dense-core vesicles and small clear synaptic vesicles using this preparation.
Statistical aspects of a model for interpersonal attraction

An interpersonal attraction model which Byrne (1971) and his co-workers (Byrne & Nelson, 1965; Byrne & Rhamey, 1965) developed in conjunction with a series of interrelated empirical experiments is reinterpreted as a multiple regression model.
Lost work: A measure of thermodynamic efficiency

Abstract The introduction of “lost work” into the statement of the second law of thermodynamics allows us to combine it with the first law to obtain a statement of extreme breadth and generality. Because the combined first- and second-law statement defines reversible work, all other widely used statements of minimum or maximum work can be shown to be restricted cases of this combined statement. With this combined statement, we can calculate thermodynamic efficiencies of all processes, including not only those conventionally treated—which are large work producers or consumers—but also those that do not have work production or consumption as their goals (as in absorption refrigerators or distillation columns). The results obtained this way, for example with turbines, are not the same as the conventional “isentropic efficiency” definition, but are more thermodynamically sound and much more practical for turbines whose outlet temperatures are far removed from the ambient temperature. The combined first- and second-law statement leads naturally to the availability function and the batch availability function rather than to the availability. For practical process problems, where prime movers are not the most important concern, the availability function is a much more useful and practical quantity to utilize than the availability.
77: Does Gene Expression Profiling Scores Correlate with Cardiac Allograft Vasculopathy Assessed by Intravascular Ultrasonography?

patients decreased). Diastolic pressure decreased a mean of 16 mmHg (8 of 10 patients decreased). Heart rate was unchanged. Serum creatinine, potassium, and immunosuppression blood levels were unchanged. 3 of the 10 stopped medication after 8 weeks due to back pain, hypotension, nausea/vomiting, and diarrhea which all resolved after cessation of medication. Conclusions: Aliskiren appears to be safe and effective in heart transplant patients and all side effects were reversible upon cessation of therapy. A larger study is warranted to establish the role of direct-renin inhibitors in CNI-associated hypertension.
Numerical Analysis of Retrograde Gas Behavior in Fissured Systems: The Single-block Model

This article presents the description of depletion behavior of retrograde gases when stored in naturally fractured systems. The present study focuses on the preliminary understanding of condensate build-up within the matrix at saturations below critical, with special emphasis on the limiting cases where flow hindrance due to the presence of the condensate might be exacerbated. The entire fissured reservoir is depicted as a stack of several single blocks of matrix rock, where ultimate recovery is controlled by the behavior of each of the single-matrix blocks in the stack. A fully implicit, in-house compositional model that tracks the condensate build-up in the single block and allows the description of its impact on system behavior is presented. This work centers around the betterment of our understanding of the phenomena taking place within a single-matrix block, as the single most important building block needed for the understanding of behavior of fissured systems hosting gas condensates.
Participation of the conventional calpains in apoptosis.

Abstract The conventional calpains, m- and μ-calpain, are suggested to be involved in apoptosis triggered by many different mechanisms. However, it has not been possible to definitively associate calpain function with apoptosis, largely because of the incomplete selectivity of the cell permeable calpain inhibitors used in previous studies. In the present study, Chinese hamster ovary (CHO) cell lines overexpressing μ-calpain or the highly specific calpain inhibitor protein, calpastatin, have been utilized to explore apoptosis signals that are influenced by calpain content. This approach allows unambiguous alteration of calpain activity in cells. Serum depletion, treatment with the endoplasmic reticulum (ER) calcium ATPase inhibitor thapsigargin, and treatment with calcium ionophore A23187 produced apoptosis in CHO cells, which was increased in calpain overexpressing cells and decreased by induced expression of calpastatin. Inhibition of calpain activity protected β-spectrin, but not α-spectrin, from proteolysis. The calpains seemed not to be involved in apoptosis triggered by a number of other treatments. Calpain protected against TNF-α induced apoptosis. In contrast to previous studies, we found no evidence that calpains proteolyze IκB-α in TNF-α-stimulated cells. These studies indicate that the conventional calpains participate in some, but not all, apoptotic signaling mechanisms. In most cases, they contributed to apoptosis, but in at least one case, they were protective.
Moment tensor solutions estimated using optimal filter theory for 51 selected earthquakes, 1980–1984

Abstract The 51 global events that occurred from January 1980 to March 1984, which were chosen by the convenors of the Symposium on Seismological Theory and Practice, have been analyzed using a moment tensor inversion algorithm (Sipkin). Many of the events were routinely analyzed as part of the National Earthquake Information Center's (NEIC) efforts to publish moment tensor and first-motion fault-plane solutions for all moderate- to large-sized ( m b >5.7) earthquakes. In routine use only long-period P-waves are used and the source-time function is constrained to be a step-function at the source (δ-function in the far-field). Four of the events were of special interest, and long-period P, SH-wave solutions were obtained. For three of these events, an unconstrained inversion was performed. The resulting time-dependent solutions indicated that, for many cases, departures of the solutions from pure double-couples are caused by source complexity that has not been adequately modeled. These solutions also indicate that source complexity of moderate-sized events can be determined from long-period data. Finally, for one of the events of special interest, an inversion of the broadband P-waveforms was also performed, demonstrating the potential for using broadband waveform data in inversion procedures.
A cancer experience: Relationship of patient psychosocial responses to care‐giver burden over time

Cancer affects not only ill persons but also family members and close friends. An original study from which this report is derived used a longitudinal design to follow patients discharged from one of seven hospitals with one or more complex care problems requiring home care. A total of 233 patients with multiple solid tumors diagnoses and 103 care-givers were included in the original study. Interviews were conducted at discharge and at three and six months post-discharge. This report examined the responses of a subset of 34 subjects (17 patients and their care-givers) for whom patient and care-giver variables were complete on all three occasions. Findings indicate that these patients were being discharged from the hospital with acute care needs. By three and six months posthospitalization, patients' conditions stabilized or improved but their care-givers continued to report similar levels of burden. Patient psychosocial responses were strongly correlated with care-givers' financial impact, impact on schedule, and physical care-giving responsibility at three and six months. Results highlight the importance of developing interventions that reduce family care-givers' burden in providing post-hospital nursing care for patients with complex care requirements.
The Expression of Soluble and Active Recombinant Haemophilus influenzae IgA1 Protease in E. coli

Immunoglobulin A1 (IgA1) proteases from Haemophilus influenzae are extracellular proteases that specifically cleave the hinge region of human IgA1, the predominant class of immunoglobulin present on mucosal membranes. The IgA1 proteases may have the potential to cleave IgA1 complexes in the kidney and be a therapeutic agent for IgA1 nephropathy (IgAN), a disease characterized by deposition of the IgA1 antibody in the glomerulus. We have screened for the expression of recombinant H. influenzae IgA1 protease by combining various expression plasmids, IgA1 protease constructs, and E. coli strains under multiple conditions. Using the method we have developed, approximately 20–40 mg/L of soluble and active H. influenzae IgA1 protease can be produced from E. coli strain C41(DE3), a significant increase in yield compared to the yield upon expression in H. influenzae or other related bacteria.
Weakly nonlinear analysis of wind-driven gravity waves

We study the weakly nonlinear development of shear-driven gravity waves induced by the physical mechanism first proposed by Miles, and furthermore investigate the mixing properties of the finite-amplitude solutions. Linear theory predicts that gravity waves are amplified by an influx of energy through the critical layer, where the velocity of the wind equals the wave phase velocity. As the wave becomes of finite amplitude nonlinearities have to be taken into account. In this paper we derive asymptotic solutions of finite-amplitude waves for weak wind and strong gravitation U 2 « gl, applicable to many astrophysical scenarios. Because of the presence of a critical layer, ordinary weakly nonlinear methods fail; in this paper, we use rescaling at the critical layer and matched asymptotics to derive the amplitude equations for the most unstable wave, under the assumption that the physical domain is periodic. These amplitude equations are compared with the equations derived by Reutov for the small-density-ratio case (applicable to oceanography); and after numerically integrating these equations, we also analytically derive their quasi-steady limit. As in other analyses of critical layers in inviscid parallel flow, we find that the initial exponential growth of the amplitude A transitions to an algebraic growth proportional to the viscosity, A ∼ vt 2/3 . We also find that the weakly nonlinear flow allows superdiffusive particle transport within the critical layer, with an exponent ∼3/2, consistent with Venkataramani's results.
Reliability-Based Performance Objectives and Probabilistic Robustness in Structural Control Applications

A reliability-based structural control design approach is presented that optimizes a control system explicitly to minimize the probability of structural failure. Failure is interpreted as the system’s state trajectory exiting a safe region within a given time duration. This safe region is bounded by hyperplanes in the system state space, each of them corresponding to an important response quantity. An efficient approximation is discussed for the analytical evaluation of this probability, and for its optimization through feedback control. This analytical approximation facilitates theoretical discussions regarding the characteristics of reliability-optimal controllers. Versions of the controller design are described for the case using a nominal model of the system, as well as for the case with uncertain model parameters. For the latter case, knowledge about the relative plausibility of the different possible values of the uncertain parameters is quantified through the use of probability distributions on the uncertain parameter space. The influence of the excitation time duration on feedback control design is discussed and a probabilistic treatment of this time duration is suggested. The relationship to H_2 �i.e., minimum variance� controller synthesis is also examined.