cssi/SciSciGPT-SciSciNet huggingface dataset:
Examining ‘immunity passports’ from an ethics perspective – ten reasons why they are bad idea

The two panelists will elaborate on 'four practical problems and six ethical objections', which add up to one very bad idea, i e , the 'immunity passport' Such an idea is equal to restricting movement on the basis of biology threatens freedom, fairness and public health Lessons from previous pandemics will be examined in the context of current measures being deployed, assessing practical and ethical aspects For example, false negatives in people with few antibodies leading to immune individuals being incorrectly labelled as not immune or not having access to testing to demonstrate immunity Additionally, the case of healthcare workers will be examined considering feasibility of testing, but also in terms of discrimination and stigma Another aspect to be explored in detail is monitoring and how it erodes privacy, with the main aim of immunity passport controlling movement Documentation systems are already presenting a serious risk to privacy, with China announcing the QR-code tracking systems is likely to stay in place after the pandemic ends
Prognostic significance and immune correlates of CD73 expression in renal cell carcinoma.

Background CD73–adenosine signaling in the tumor microenvironment is immunosuppressive and may be associated with aggressive renal cell carcinoma (RCC). We investigated the prognostic significance of CD73 protein expression in RCC leveraging nephrectomy samples. We also performed a complementary analysis using The Cancer Genome Atlas (TCGA) dataset to evaluate the correlation of CD73 (ecto-5′-nucleotidase (NT5E), CD39 (ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1)) and A2 adenosine receptor (A2AR; ADORA2A) transcript levels with markers of angiogenesis and antitumor immune response. Methods Patients with RCC with available archived nephrectomy samples were eligible for inclusion. Tumor CD73 protein expression was assessed by immunohistochemistry and quantified using a combined score (CS: % positive cells×intensity). Samples were categorized as CD73negative (CS=0), CD73low or CD73high ( Results Among the 138 patients eligible for inclusion, ‘any’ CD73 expression was observed in 30% of primary tumor samples. High CD73 expression was more frequent in patients with M1 RCC (29% vs 12% M0), grade 4 tumors (27% vs 13% grade 3 vs 15% grades 1 and 2), advanced T-stage (≥T3: 22% vs T2: 19% vs T1: 12%) and tumors with sarcomatoid histology (50% vs 12%). In the M0 cohort (n=107), patients with CD73high tumor expression had significantly worse 5-year DFS (42%) and 10-year OS (22%) compared with those in the CD73negative group (DFS: 75%, adjusted HR: 2.7, 95% CI 1.3 to 5.9, p=0.01; OS: 64%, adjusted HR: 2.6, 95% CI 1.2 to 5.8, p=0.02) independent of tumor stage and grade. In the TCGA analysis, high NT5E expression was associated with significantly worse 5-year OS (p=0.008). NT5E and ENTPD1 expression correlated with higher regulatory T cell (Treg) signature, while ADORA2A expression was associated with increased Treg and angiogenesis signatures. Conclusions High CD73 expression portends significantly worse survival outcomes independent of stage and grade. Our findings provide compelling support for targeting the immunosuppressive and proangiogenic CD73–adenosine pathway in RCC.
Racial disparities in occupational risks and lung cancer incidence: Analysis of the National Lung Screening Trial.

Abstract The relationship between racial disparities in occupational risk and lung cancer diagnosis is not well defined. We examined occupational exposure to asbestos, silica, and other workplace chemicals, fumes, or dusts as reported in the National Lung Screening Trial (NLST). Descriptive analyses and multivariate logistic regression models were performed. Among the NLST study cohort, 3.9% were diagnosed with lung cancer. African-Americans had a higher rate of lung cancer diagnosis than White individuals (4.3% vs. 3.9%). About 28% reported at least one occupational exposure, including 6.5% exposed to silica and 4.7% to asbestos. African-Americans reported occupational exposure more frequently than White participants, including exposures to asbestos and silica. In a multivariate model, the interactions of all measures of occupational exposures and smoking status were significant. Current smokers with occupational exposures had higher odds of lung cancer diagnosis (aOR = 2.01, 95% CI = 1.76–2.30 for any exposure as well as higher odds after silica (aOR = 2.35, 95% CI = 1.89–2.91) or asbestos (aOR = 1.97, 95% CI = 1.52–2.56) exposure compared to former smokers without any exposures. African-Americans had higher odds of lung cancer diagnosis than White individuals (aOR = 1.24 to 1.25, 95% CI = 1.01–1.54). Our findings indicate that we need more effective public health prevention programs, especially for minorities who may have disproportionately greater occupational exposures due to socioeconomic constructs and barriers. Interventions may include education about occupational risks and lung cancer screening or instituting workplace policies for smoke-free environments with tobacco cessation support.
Causal Relationships between Perceived Enjoyment and Perceived Ease of Use: An Alternative Approach

Identifying causal relationships is an important aspect of scientific inquiry. Causal relationships help us to infer, predict, and plan. This research investigates the causal relationships between two constructs, perceived enjoyment (PE) and perceived ease of use (PEOU), within the nomological net of user technology acceptance. PE has been theorized and empirically validated as either an antecedent or a consequence of PEOU. We believe that there are two reasons that account for this ambiguity the conceptual coupling of PE and PEOU and the limitations of covariance-based statistical methods. Accordingly, we approach this inconsistency by providing more theoretical reasoning and employing an alternative statistical method, namely Cohen’s path analysis. Specifically, as suggested by previous research on the difference between utilitarian and hedonic systems, we propose the conditional dominance of causal directions. Empirical results from two studies using different technologies and user samples support the theoretical claim that the PEAEPEOU causal direction outweighs the PEOUAEPE direction for utilitarian systems. There are both theoretical and the methodical contributions of this research. The approach applied in this research can be generalized to study causal relationships between conceptually coupled variables, which otherwise may be overlooked by confirmatory methods. We encourage researchers to pay attention to causal directions in addition to causal connectedness.
Predictors of Co-occurring Cardiovascular and Gastrointestinal Disorders among Elderly with Osteoarthritis

Abstract Objective To identify the leading predictors of co-occurring cardiovascular or gastrointestinal disorders (CV-GID) in a real-world cohort of elderly with osteoarthritis (OA). Method An observational retrospective cohort study using data from Optum’s deidentified Clinformatics® Data Mart was conducted. Elderly with OA were identified in 2015 and were followed for two years to identify co-occurring CV-GID including ischemic heart disease, stroke, heart failure, dyspepsia, gastroesophageal reflux disorder, and peptic ulcer disease. Random Forest (RF) and Partial Dependence Plots (PDP) were used to identify the leading predictors of CV-GID and to examine their associations. Multivariable logistic regression was also used to examine the association of the leading predictors with CV-GID. Results Our study cohort consisted of 45,385 elderly with OA (mean age 76.0 years). CV-GID were present in 59% of elderly. Using RF, age was found to be the strongest predictor of CV-GID followed by cardiac arrhythmia, duration of opioid use, number of orthopedist or physical therapy visits, number of intra-articular corticosteroid injections, polypharmacy, duration of non-selective nonsteroidal anti-inflammatory drugs or oral corticosteroids, and hypertension. The PDPs demonstrated that higher age, cardiac arrhythmia, longer durations of opioid or oral corticosteroids, higher number of physical therapy visits or intra-articular corticosteroid use, polypharmacy, and hypertension were associated with a higher risk of CV-GID. Conclusion CV-GIDs are common among elderly with OA and can be predicted based on certain clinical factors. Machine learning methods with PDPs can be used to improve the interpretability and inform decision-making.
Obesity and BMI Cut Points for Associated Comorbidities: Electronic Health Record Study

Background: Studies have found associations between increasing BMIs and the development of various chronic health conditions. The BMI cut points, or thresholds beyond which comorbidity incidence can be accurately detected, are unknown. Objective: The aim of this study is to identify whether BMI cut points exist for 11 obesity-related comorbidities. Methods: US adults aged 18-75 years who had ≥3 health care visits at an academic medical center from 2008 to 2016 were identified from eHealth records. Pregnant patients, patients with cancer, and patients who had undergone bariatric surgery were excluded. Quantile regression, with BMI as the outcome, was used to evaluate the associations between BMI and disease incidence. A comorbidity was determined to have a cut point if the area under the receiver operating curve was >0.6. The cut point was defined as the BMI value that maximized the Youden index. Results: We included 243,332 patients in the study cohort. The mean age and BMI were 46.8 (SD 15.3) years and 29.1 kg/m2, respectively. We found statistically significant associations between increasing BMIs and the incidence of all comorbidities except anxiety and cerebrovascular disease. Cut points were identified for hyperlipidemia (27.1 kg/m2), coronary artery disease (27.7 kg/m2), hypertension (28.4 kg/m2), osteoarthritis (28.7 kg/m2), obstructive sleep apnea (30.1 kg/m2), and type 2 diabetes (30.9 kg/m2). Conclusions: The BMI cut points that accurately predicted the risks of developing 6 obesity-related comorbidities occurred when patients were overweight or barely met the criteria for class 1 obesity. Further studies using national, longitudinal data are needed to determine whether screening guidelines for appropriate comorbidities may need to be revised.
Refractory Spontaneous Bacterial Empyema in Cirrhotic Patient

Spontaneous bacterial empyema (SBEM), also called spontaneous bacterial pleuritis, is an infection of the pleural space that arises in the setting of cirrhosis and, by definition, the absence of pneumonia. It is likely underdiagnosed as its symptoms are nonspecific and it lacks standardized diagnostic and therapeutic recommendations. SBEM represents a distinct complication of hepatic hydrothorax with different pathogenesis, presentation, and treatment strategy from those of empyema secondary to pneumonia. Surprisingly, nearly 40% of episodes of spontaneous empyema are not associated with spontaneous bacterial peritonitis. Although SBEM is amenable to prompt antibiotic therapy, it has a high rate of mortality and morbidity. A high clinical suspicion is crucial for patient survival and timely initiation of appropriate antibiotics. Increased understanding, recognition, and standardization of treatment would help alleviate the relatively high burden of SBEM. In this case vignette, we provide a review of the relevant literature, and we describe a rare case of SBEM in a patient with a history of alcohol-associated liver cirrhosis and prior episode of spontaneous bacterial peritonitis (SBP). SBEM was diagnosed with thoracentesis and analysis of the aspirate, and he was treated with ceftriaxone with resolution of his presenting abdominal pain and leukocytosis.
AMERICAN DEVELOPMENTS IN HYDRAULIC MEASUREMENT

The paper is a historical summary of American contributions to hydraulic measurement of streamflow for the period 1776-1976. The development and interrelation of conduit flow measuring devices together with open channel measuring devices is included in this update of previous historical summaries. The narrative style and historical sequence is a useful complement to the more specific "Bibliography on Discharge Measurement Techniques." /ASCE/
An algebra for search problems and their solutions

We present an algebraic model for search problems and their solutions. The model includes in its formalism dynamic programming, branch and bound, and other implicit enumeration techniques. Search problems are defined over a finite set of conjuncts, a nonassociative analogue of strings. The generalization to conjuncts is important because it allows the model to handle naturally problems with objects (e.g., binary trees) that combine in a nonassociative manner. The solution of a search problem requires the identification of a minimal element of the set of feasible conjuncts. We model the solution process in terms of two types of operators. Each of these operators enumerates a set of conjuncts, and in so doing infers the indentity of the only conjunct in the set that can possibly be extended to a minimal feasible conjunct. The operators themselves are based on computationally feasible dominance relations that order certain pairs of conjuncts, and whose axioms allow us to infer the orderings of the feasible extensions of such conjuncts.
Optimal control of average reward constrained continuous-time finite Markov decision processes

The paper studies the optimization of average-reward continuous-time finite state and action Markov decision processes with multiple criteria and constraints. Under the standard unichain assumption, we prove the existence of optimal K-switching strategies for feasible problems with K constraints. For switching randomized strategies, the decisions depend on the current state and the time spent in the current state after the last jump. For stationary strategies, these functions do not depend on sojourn times, i.e., they are constant in time. For K-switching strategies, these functions are piecewise constant and the total number of jumps is limited by K. If there is no absorbing states, there exist also optimal K-randomized policies. We consider the linear programming approach and provide algorithms for calculations of optimal policies.
Interferon-α Resistance in a Cutaneous T-Cell Lymphoma Cell Line Is Associated With Lack of STAT1 Expression

Interferon-alpha (IFN alpha) mediates its biological effects through activation of the JAK-STAT signaling pathway and it has been shown to be one of most effective therapeutic agents for a number of hematological malignancies, including cutaneous T-cell lymphoma (CTCL). Nevertheless, its efficacy is limited by the development of clinical resistance but the reasons for resistance in CTCL are unknown. Here, we report the development of an IFN alpha-resistant CTCL cell line (HUT78R), characterized by its ability to proliferate in high concentration of recombinant IFN alpha, which can be used as a model system to study IFN resistance. The levels of IFN receptor expression and binding affinity were found to be comparable between the parental sensitive (HUT78S) and resistant (HUT78R) cells. However, IFN alpha stimulation failed to induce interferon-stimulated gene factor 3 (ISGF3) complex formation in HUT78R cells. In addition, the expression of the IFN-inducible 2-5 OAS gene was significantly reduced in HUT78R cells, suggesting the presence of a defect in the Jak-STAT signaling pathway. Our results showed that the IFN alpha-activated form of a latent transcriptional factor STAT1 was not found in HUT78R cells, whereas activated STAT2 and STAT3 were clearly detectable. By Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses, we found that HUT78R cells do not express any STAT1 protein or mRNA, suggesting the possibility of a null mutation in the STAT1 gene. Resistance to the growth inhibitory effect of IFN alpha in CTCL cells may result from lack of STAT1 expression.
Ganglioneuroma of the bladder: Case report and literature review

Ganglioneuromas originate from neural crest sympathogonia of the autonomicnervous system. These tumors are benign, fully differentiated tumors that containmature Schwann cells, ganglion cells, fibrous tissue and nerve fibers.Ganglioneuromas commonly localize in the abdominal and mediastinum regions,such as the adrenal gland, paraspinal retroperitoneum and posterior mediastinum.However, these tumors are rarely localized to the urinary bladder and, herein, wepresent a brief review of the literature and a ganglioneuroma of a 16-year-oldfemale patient as the second case reported in the urinary bladder.
On the Turán Properties of Infinite Graphs

Let $G^{(\infty)}$ be an infinite graph with the vertex set corresponding to the set of positive integers ${\Bbb N}$. Denote by $G^{(l)}$ a subgraph of $G^{(\infty)}$ which is spanned by the vertices $\{1,\dots,l\}$. As a possible extension of Turan's theorem to infinite graphs, in this paper we will examine how large $\liminf_{l\rightarrow \infty} {|E(G^{(l)})|\over l^2}$ can be for an infinite graph $G^{(\infty)}$, which does not contain an increasing path $I_k$ with $k+1$ vertices. We will show that for sufficiently large $k$ there are $I_k$–free infinite graphs with ${1\over 4}+{1\over 200}
How Quickly do Equity Prices Converge to Intrinsic Value

This research hypothesizes that in markets where information costs, transactions costs and the economic impact of information can vary widely, we should expect both significant predictability and systematic variation in the predictability. Controlling for other factors, we find that on average, 15-30% of the difference between the stock price and the estimated intrinsic value is removed in a year. We document that levels of predictability vary with firm characteristics like leverage, size and number of analysts. Momentum is stronger for larger firms with more analysts. Reversion to the intrinsic value is greater for smaller firms with more analysts.
Synthesis, characterization, and photocatalytic activity of Au–ZnO nanopyramids

Nanocrystalline Au–ZnO heterostructures were synthesized using a wet-chemical process where single-crystalline ZnO grows along the [0001] direction on top of polycrystalline Au seeds. High resolution transmission electron microscopy finds a 3.5% expansion of the ZnO (002) plane at the heterostructure interface. Rietveld analysis of X-ray diffraction patterns from ZnO and Au–ZnO powders find that the crystallographic microstrain in the metal oxide is 0.047% and 0.146%, respectively, illustrating that the crystallographic expansion at the heterostructure interface is detectable by bulk characterization techniques. Broad-band photo-degradation studies with methylene blue find that the Au–ZnO heterostructures decompose the dye 6 times faster than pure ZnO. Wavelength-dependent photodegradation studies illustrate direct gap excitation of the ZnO component of the heterostructure is required to initiate dye decomposition. The mechanistic details leading to this photocatalytic activity are discussed.
A prospective study in adolescent idiopathic scoliosis affected by thoracolumbar and lumbar curves in treatment with a progressive action short brace (PASB): assessment of results according to the SRS committee on bracing and nonoperative management standardization criteria

Methods We have carried out a prospective study of 197 adolescents (mean age 11.8 ± 0.5 years) treated from 1993 to 2012 with thoracolumbar and lumbar curve and a pretreatment Risser scores ranging from 0 to 2. To evaluate the effectiveness of treatment and standardize the results, SRS criteria were used. All patients were prescribed a full-time PASB. The minimum duration of follow-up was 24 months. Anteroposterior radiographs were used to estimate the curve magnitude (CM) and the torsion of the apical vertebra (TA) at five time points: beginning of treatment (t1), one year after the beginning of treatment (t2), intermediate time between t1 and t4 (t3), end of weaning (t4), and 2-year minimum follow-up from t4 (t5). Three outcomes were distinguished: curve correction, curve stabilization and curve progression. Statistical analyses were performed with GraphPad Prism 6.
Chemical lasers produced from O(3P) atom reactions. V. CO laser emissions and vibrational population distribution in the flash‐initiated SO2‐CFBr3 system

CO laser emission at 5 μm was detected when SO2 and CFBr3 were flash photolyzed in the vacuum ultraviolet above 165 nm. Over 40 vibrational–rotational transitions ranging from Δv = 2 1 to 14 13, with the exception of those between 8 7 and 11 10, were identified. The CO emission is believed to result from the O + CF reaction: The vibrational population of the CO has been measured by means of a CO laser resonance absorption method. The CO was found to be vibrationally excited to v = 24 with a vibrational temperature of about 1.4 × 104°K. The “surprisal analysis” of the observed CO distribution showed the possible occurrence of a minor process (presumably O + CFBr) that generated vibrationally colder CO. The effects of various additives on the CO emission were also examined. The addition of CO2 to a D2-SO2-CFBr3-He mixture resulted in a simultaneous osciallation at 3.6, 5, and 10.6 μm due to DF, CO, and CO2, respectively. Additionally, the utilization of the O + CFn (n = 1, 2, 3) reactions as F-atom sources for HF-laser operation in flash-initiated systems were demonstrated.
A mutant of Saccharomyces cerevisiae defective in arginyl-tRNA-protein transferase

A mutant of Saccharomyces cerevisiae deficient in arginyl-tRNA-protein transferase has been isolated. The responsible mutation designated ate1, was localized near the centromere of chromosome VII. It probably involves the structural gene for the transferase since residual enzyme activity in the mutant is temperature-sensitive.
Ray tracing analysis of the image quality of a high collection efficiency mirror system.

Recently, a high collection efficiency mirror system was developed by Watson [ Cytometry10, 681– 688 ( 1989)] to increase the sensitivity of low level fluorescence detection. The mirror system consists of an ellipsoidal imaging mirror and spherical backreflecting mirror. The fluorescing sample is located at one focus of the ellipsoid, and its image is formed at the other focus. In this paper we evaluate the image quality of this geometry using a PC-based ray tracing program. The analysis demonstrates high collection efficiency but poor image quality. The effect of poor image quality on single molecule detection is discussed.
Influencing alcohol control policies and practices at community festivals

The goal of this study was to assess the feasibility and effectiveness of two interventions aimed at reducing alcohol-related risks at community festivals--a training program for festival planners and a community organizing campaign. We randomly selected four festivals for each intervention and had 24 comparison festivals. Our assessment included process evaluation to track and evaluate types of alcohol policies resulting from each of the interventions, pre and post telephone surveys of key festival planners and law enforcement agencies, and pre and post pseudo-underage and pseudo-intoxicated purchase attempts. Analyses showed that both interventions were feasible and were successful in influencing adoption of written policies and improving alcohol-related practices. However, neither intervention appeared to decrease propensity for illegal alcohol sales at these events, likely due, in part, to the short time frame of the interventions. Future research should assess effects of the interventions on alcohol-related problems and effects of enforcement interventions. Language: en
On elastic joints containing interfacial cracks

Abstract We study quasistatic deformations of a massive elastic body bonded to an inifinite elastic layer of finite thickness whose other surface is glued to a half space. The adhesive is modeled as a nonlinear elastic material. It is assumed that interfacial cracks are present at the body/adhesive interface and at the interface between the elastic layer and adhesive material closer to the half space. Variational formulations of the problems when the material of the half space is modeled as isotropic linear elastic or as rigid are given and are shown to be equivalent to the corresponding boundary-value problems. Analytical solutions of two example problems are given; one involves a long rigid cylinder bonded to a rigid half space and the other a thin infinite linear plate bonded to a rigid half space. The results depicted graphically include the dependence of the crack closure length on the applied loads and the dependence of the gradient of the potential energy on the crack length for the first problem, and distributions of the normal stress and normal displacement on the crack surface for the second problem.
From deuterons to neutron stars: variations in nuclear many-body theory

A major goal in nuclear physics is to understand the stability, structure, and reactions of nuclei as a consequence of the interactions between individual nucleons. This colloquium describes one attempt to build a consistent picture of nuclear systems ranging in size from deuterons to neutron stars. The main ingredients are a nonrelativistic Hamiltonian containing two- and three-nucleon interactions, and correlated variational wave functions as approximate solutions of the many-body Schr\"odinger equation. A model that fits both two-body scattering data and nuclear masses will provide the best theoretical input for neutron star properties.
A Universal Negative or Positive Ion Source

This report describes a multipurpose negative or positive ion source which can be used in a variety of low energy or high energy research applications. Conversion from negative/positive modes of operation can be accomplished by simply reversing the polarities of pertinent extraction and beam transport power supplies. Preliminary results obtained from recent evaluative studies along with design details and negative and positive yields observed to data are given. Thus far, the source has demonstrated ?A intensity capabilities for several negative and positive ion species including C-, Cu-, Au-, N+, N2+, P+, A+, and Cs+.
Removal of copper from hydrocarbon fuels using novel azamacrocycle polymers

Solubilized copper contamination can seriously impair the thermal stability of hydrocarbon fuels. The paper reports on use of copper chelators attached to a solid substrate. The authors have investigated acrylate polymers of 1,4,8,11-tetraazacyclotetradecane (cyclam) for their capability to remove copper from hydrocarbons. They report herein the results of these initial studies
Bobgunnia, a new African genus of tribe Swartzieae (Fabaceae, Faboideae)

A new genus, Bobgunnia, is established in tribe Swartzieae for the African species of Swartzia. Two new combinations are made: B. fistuloides and B. madagascariensis. The new genus has seeds, unlike the remainder of tribe Swartzieae but like the other tribes of Faboideae. The systematic position of Swartzieae is reevaluated.
Uterine leiomyomata (fibroids): Are bleeding symptoms more likely to be reported after diagnosis?

Ganesa Wegienka*, Donna Day Baird, Irva Hertz-Picciotto, Sioban D. Harlow, Katherine E. Hartmann Department of Biostatistics and Research Epidemiology, Henry Ford Health System, One Ford Place, 3E, Detroit, MI 48202, USA Epidemiology Branch, The National Institute of Environmental Health Sciences, The National Institutes of Health, The United States Department of Health and Human Services, Mail Drop A3-05, P.O. Box 12233, Research Triangle Park, NC 27709, USA Department of Epidemiology and Preventive Medicine, TB-168, University of California Davis, One Shields Avenue, Davis, CA 95616-8638, USA Department of Epidemiology, School of Public Health, University of Michigan, 109 Observatory Street, 1009 SPH 1, Ann Arbor, MI 48109-2029, USA The North Carolina Program for Women’s Health Research, University of North Carolina–Chapel Hill, 725 Airport Road, CB#7590, Chapel Hill, NC 27599-7590, USA
Synthesis of State-of-the-Art in Visibility Detection Systems’ Applications and Research

Visibility is a critical component to the task of driving on all types of roads. The visibility detection and warning systems provide real-time, automated detection as well as appropriate responses to counteract reduced visibility conditions due to fog, heavy rain, snow, smoke, dust, or haze by informing drivers of present conditions and lowering the speed limits to match the reduced visibility condition. The objective of this research is to provide a synthesis of visibility detection systems and traffic control techniques that are developed and/or implemented in the United States and around the world. This article provides an overview of the best practices of fixed visibility systems at areas of recurrent dense fog and mobile systems for seasonal visibility reduction for areas of predicted seasonal fog or smoke from wildfires. Ongoing research efforts of developing new camera-based visibility detection systems are also discussed.
WE-E-ValB-04: Functional and Molecular Imaging for Radiotherapy Guidance

Radiation therapy is an image‐guided procedure whose success depends strongly on the image modality used for treatment planning and the level of integration of the available imaging information. Advancement in IMRT has provided an unprecedented means to produce highly conformable dose distribution while sparing sensitive structures, which calls for better imaging tools for tumor target definition and for the management of inter‐ and intra‐fractional organ motion. In this talk we will summarize recent advances in functional and molecular imaging techniques and discuss various issues related to the integration of the newly emerged imaging data into radiation therapy planning. It is anticipated that the new imaging modalities will play an important role in radiation oncology practice and make significant impact in cancer diagnosis, staging, treatment planning, and monitoring of therapeutic response. The potential impact of biologically conformal radiation therapy (BCRT) or biologically guided radiation therapy (BGRT) will be discussed. Finally, issues related to the quality assurance of functional and molecular imaging and BCRT will also be addressed. Educational Objectives: 1. Introduce the concept of functional and molecular imaging. 2. Illustrate the steps involved in integrating molecular imaging such as PET and MRSI into treatment planning process. 3. Introduce PET/MRI/MRSI and CTimage fusion techniques (including deformable image registration). 4. Provide an overview on recent advances in PET/CT and MRSI, and update on the development of new PET tracers and data acquisition techniques. This work was supported in part by NCI 5R01 CA98523‐01.
An event driven integration reasoning scheme for handling dynamic threats in an unstructured environment

Abstract This paper postulates a rigorous method for the construction of classical planning domain models. We describe, with the help of a non-trivial example, a tool-supported method for encoding such models. The method results in an “object-centred” specification of the domain that lifts the representation from the level of the literal to the level of the object. Thus, for example, operators are defined in terms of how they change the state of objects, and planning states are defined as amalgams of the objects' states. The method features two classes of tools: for initial capture and validation of the domain model; and for operationalising the domain model (a process we call compilation) for later planning. Here we focus on compilation tools used to generate macros and goal orders to be utilised at plan generation time. We describe them in depth, and evaluate empirically their combined benefits in plan generation speed-up. The method's main benefit is in helping the modeller to produce a tight, valid and operational domain model. It also has the potential benefits of (i) forcing a change of emphasis in classical planning research to encompass knowledge-based aspects of target planning domains in a systematic manner, (ii) helping to bridge the gap between the research area of theoretical but unrealistic planning on the one hand, and “scruffy” but real-world planning on the other, (iii) a commitment to a knowledge representation form which allows powerful techniques for planning domain model validation and planning algorithm speed-up can be bound up into a tool-supported environment.
Non-coordinate Control of Bone Formation Displayed by Growth Factor Combinations with IGF-I

Polypeptide growth factors (GFs) promote osteogenesis by enhancing the mitogenesis, migration, and matrix synthesis of osteoblasts. Most previous investigators have evaluated only the effects of single GFs on these parameters. Studies on single GFs might overlook large biological responses comparable with those documented in the cell cycle literature when GFs are used in combinations that interact synergistically. In this study, we screened for synergistic interactions between IGF-I and three additional GFs (PDGF-BB, TGF-β1, and bFGF) on the regulation of bone growth and differentiation. Fetal bovine osteoblasts were assessed for osteoblast mitogenesis, collagenous and non-collagenous protein synthesis, and alkaline phosphatase activity (ALP). Our results show synergistic interactions between IGF-I and the other GFs on osteoblast mitogenic activity and protein synthesis. In contrast to synergistic mitogenic and protein synthesis effects, IGF-I failed to increase ALP activity when combined with TGF-β1, PDG...
Fused III-V vertical coupler filter with reduced polarisation sensitivity

A novel fused InGaAsP/InP-AlGaAs/GaAs vertical coupler filter is demonstrated. By using the large material dispersion between InGaAsP and AlGaAs and similar waveguide geometries, a 3.6 nm bandwidth and 5 nm polarisation dependent wavelength shift using a 1.1 mm long fused vertical coupler has been achieved.
On the Horizon of Immunosuppression

The history of immunosuppression in renal transplantation and trends that might inform its future are discussed. A philosophical paradigm shift away from additive to reductive immunosuppressive protocols is announced. Newer immunosuppressive strategies that use the deeper understanding of the immunobiology of organ transplantation is detailed, with particular reference to inhibition of costimulatory pathways and blockade of antigen-specific signaling, as well as to the potential for tolerance development. Agents that might use novel immunosuppressive pathways are discussed. The future of transplantation immunosuppression is bounded only by our imagination and our understanding of the basic science of the field.
A Multidisciplinary Approach To Prosthetic Management

This study describes a multidisciplinary team ap proach to prosthetic management for inpatients. A Communication Management System summary sheet was developed to list all prosthetic devices owned and basic information concerning any existing communi cation problems. The summary sheet is to be posted in a wooden frame above the patients bed. A member of the nursing staff would be responsible for complet ing the pertinent data.
Utilization of a uniform grading system for interpreting serous ovarian cancer

Objective The purpose of the study was to implement a uniform system for assigning tumor grade in serous ovarian cancer and evaluate its correlation with response to conventional chemotherapy. Study Design Serous ovarian cancer tumor samples were retrospectively reviewed by 3 pathologists who were blinded to the original report. Samples were scored for architectural pattern, nuclear pleomorphism, and mitotic activity. Sum scores from these 3 indices were used to classify tumors as low grade or high grade. Results A total of 21 patients were identified as low-grade tumors and 21 were identified as high-grade tumors. Of low-grade tumors, 16 (76%) were found to be platinum resistant, defined as recurrent or persistent disease, 180 days from completion of the final cycle of chemotherapy, Of 21 patients defined as high grade, 9 (43%) were platinum resistant ( P = .028). Conclusion Utilization of a uniform grading system retrospectively correlates with platinum sensitivity.
Decaying, two-dimensional, Navier-Stokes turbulence at very long times

Abstract Two-dimensional Navier-Stokes turbulent decay has been followed numerically for very long times. The code is spectral, satisfies periodic boundary conditions, and does not make use of hyperviscosity or any small-scale smoothing. The resolution is (512) 2 , the initial Reynolds number based on the box dimension is about 14000, and the run continues for over 190 initial eddy turnover times. Isolated vortices form, and the turbulence has become highly intermittent in the manner seen by McWilliams and Brachet et al., for times greater than about 30. However, it is not the case that merger of like-signed vortices stops; it only slows down. By t = 210, the final merger is complete, and the vorticity distribution is dominated by one large vortex of either sign. The negative (positive) vortices each occupy about two percent of the box area, and together account for over 98 percent of the total enstrophy. Their alignment suggests the formation of an Ewald lattice with a basic cell containing two point vortices. The ratio of enstrophy to energy continues to decrease monotonically, and the picture is consistent with a “selective decay” process, as described some time ago. A not-entirely-understood phenomenon is the concentration of the vorticity into two cores, suggestive of a negative-temperature state of the discrete line vortex model.
The Application Accuracy of Stereotactic Frames

The purpose of incorporating stereotactic methodology into neurosurgical operations is to achieve a consistently high degree of accuracy in localizing intracranial targets. Therefore, the limits of resolution for the operation are a function of the accuracy of the particular stereotactic frame system. The total clinically relevant error (application accuracy) comprises errors associated with each procedural step, including imaging, target selection, vector calculations, and the mechanical errors of stereotactic frames. To evaluate these parameters, a systematic error analysis was carried out with four commonly used stereotactic devices: the Brown-Roberts-Wells, the Cosman-Roberts-Wells, the Kelly-Goerss COMPASS (modified Todd-Wells), and the Leksell frames. Over 21,500 independent accuracy test measurements were made with 11,000 computed tomograms. The results suggest a potentially significant degree of error in the application accuracy of all stereotactic instruments, which is accentuated by but not entirely due to imaging-associated errors. Clinically encountered levels of weightbearing by stereotactic frames may have a pronounced effect on their mechanical accuracy. Both the reapplication of aiming arc assemblies and the use of phantom base units introduce independent sources of mechanical inaccuracy into stereotactic procedures. The scope of individual error values and their determining factors must be considered with every clinical use of stereotactic frame systems.
Interventional Cardiology US Workforce Current Challenges

Predicting optimal physician workforce numbers to meet societal needs represents a major challenge and an area of unmet need. Attempts to project these necessities to specialty and subspecialty models are perhaps even more difficult as they deal with smaller treatment populations and often rapidly changing practice patterns.1 A single unforeseen variable, such as a new clinical trial result, can potentially alter projections dramatically. The most appropriate physician’s role in adjusting workforce numbers is also unclear. We are somewhat conflicted wanting to address public medical needs, facilitate training physicians’ access to having a robust practice, although hoping to remain sensitive to a perception that we might be controlling the open market on the supply side for a possible financial benefit. Procedurally based subspecialties, such as interventional cardiology, are also interested in maintaining adequate individual operator volumes in efforts to facilitate and measure performance competencies. In 2009, the American College of Cardiology published the “Cardiology Workforce Crisis” survey results and recommendations, concluding that there will be an inadequate supply of cardiovascular specialists to care for new cardiovascular patients in the first half of the 21st century.2 The drivers for increased demand for cardiovascular services included aging demographics, noting patients surviving longer with cardiovascular disease, economic growth, expansion of insurance coverage, and technological advances. Among the drivers predicting a decrease in cardiologist supply include a possible decrease in cardiovascular training programs, resulting in similar decrease in the production of new cardiologists (attributed to faulty government predictions in the 1980s involving less demand for highly technical specialties). Early physician retirement was also cited as a possible contributor toward this impending crisis. A subgroup analysis reported in 2008 projected a near future shortage of interventional cardiologists approaching almost 2000 physicians based on what was then perceived as the current demand. The present number …
Development of a novel single sensor multiplexed marker assay

There is an increasing desire to measure multiple analytes simultaneously for disease management and detection. However, in the case of invasive devices, it would be better to obtain one small sample and immediately be able to detect the analytes rapidly, as in the case of self-monitoring blood glucose, without the need for additional steps, arrays, or reagents. Electrochemical impedance spectroscopy is used to measure the interaction between ultralow levels of analyte and molecular recognition element in a label-free and rapid manner. Gold nanoparticles were attached to antibodies against interleukin-12 and tumor necrosis factor-α, typical inflammatory markers found with near overlapping responses, on an impedance spectroscopy based biosensor. Cross-reactivity and specificity of tuned antibodies were verified using ELISA. Impedance frequency was quantified by concentration gradients of marker against the device. The natural impedance frequency for interleukin-12 (5.00 Hz) was tuned to a lower frequency four Hertz away from one another for better signal processing. This was accomplished without significantly altering the lower limits of detection (<4 pg ml−1 and ∼60 pg ml−1 for interleukin-12 and tumor necrosis factor-α, respectively), no cross-reactivity and specificity as determined by ELISAs. With modeling the nanoscale effects and further development, a larger tuning will be possible for making a better multiplexed sensor. Although interleukin-12 and TNF-α equivalent circuit calculations were modeled here, a sensor with the potential to measure multiple markers at once might offer a solution on the sensor front for simplified management of conditions such as diabetes, where both glucose and hemoglobin A1c values could be obtained.
Potentiated startle and hyperalgesia during withdrawal from acute morphine: effects of multiple opiate exposures

Administration of an opiate antagonist following acute morphine exposure elevates the startle response in rodents, a phenomenon that may reflect the anxiogenic effects of withdrawal. Previous acute dependence studies have demonstrated escalated withdrawal severity following multiple withdrawal episodes. To examine the effects of prior opiate exposure on the magnitude of withdrawal-potentiated startle and an additional measure of acute dependence, withdrawal-induced hyperalgesia. The effects of repeated naloxone-precipitated morphine withdrawals on acoustic startle responding were evaluated in experiments that varied either the dose of the opiate antagonist (8-day, repeated measures procedure) or agonist (3-day procedure). Additional experiments examined withdrawal-induced hyperalgesia utilizing either a single-day dependence paradigm or the same 3-day procedure as in the startle experiment. Repeated naloxone-precipitated withdrawals from acute morphine exacerbated withdrawal severity in both startle procedures, although this effect varied biphasically (inverted-U function) with morphine dose in the 3-day dependence paradigm. Withdrawal from a single morphine exposure also induced hyperalgesia, and this effect was intensified by prior withdrawal episodes. These data demonstrate that repeated withdrawals from acute morphine exacerbate the severity of potentiated startle and hyperalgesia. These paradigms may be useful in examining the neural plasticity underlying the development of opiate dependence.
Quantitative HREM using non-linear least-squares methods

Abstract Non-linear least-squares methods have been coupled with high-resolution image simulation to determine the critical electron microscopic imaging parameters, such as thickness and defocus, from an experimental image. The method has been extended to include the optimization of atomic column positions to determine atomic structure. As an example, the method has been applied to the refinement of the atomic structure of a Σ5(310)/[001] grain boundary in Nb.
Exploring Themes of Sibling Experience to Help Resolve Couples Conflict

This article highlights the important link between sibling experience and couples conflict. Several key themes of marital conflict are discussed: power and hierarchy, complementary role development...
Mean first-passage times for systems driven by equilibrium persistent-periodic dichotomous noise

In a recent paper, [J. M. Porra, J. Masoliver, and K. Lindenberg, Phys. Rev. E 48, 951 (1993)], we derived the equations for the mean first-passage time for systems driven by the coin-toss square wave, a particular type of dichotomous noisy signal, to reach either one of two boundaries. The coin-toss square wave, which we here call periodic-persistent dichotomous noise, is a random signal that can only change its value at specified time points, where it changes its value with probability {ital q} or retains its previous value with probability {ital p}=1{minus}{ital q}. These time points occur periodically at time intervals {tau}. Here we consider the stationary version of this signal, that is, ``equilibrium`` periodic-persistent noise. We show that the mean first-passage time for systems driven by this stationary noise does not show either the discontinuities or the oscillations found in the case of nonstationary noise. We also discuss the existence of discontinuities in the mean first-passage time for random one-dimensional stochastic maps.
Civilization and Its Discounts

Recent breakthroughs in the history and sociology of science have begun to help us to appreciate the vast complexity and intricate character of empirical endeavours in the sciences. The days when philosophers could blandly gesture towards “observation statements” or “falsification,” as if they were some readily understood phenomena or set of procedures, are gone, happily. This does not mean we can merely use the Duhem-Quine thesis as a shibboleth, however: we are now much more sensitive to immense difficulties in establishing viable claims to replication (Chen 1994) or establishing the absence of selectivity bias, or convincing others of adequacy of experimental controls. Yet, even so, I would still assert that modern science studies, with only a very few exceptions, have ignored the problem of the constitution of error in the context of precision quantitative measurement. While rather broad claims have been made concerning measurement by Hacking, Cartwright, Franklin and others, none goes so far as to examine the actual manipulation of the numerical data. More distressingly, in the areas of economics and economic methodology, we have not even got so far as have the researchers in science studies. This fact alone should provide grounds for scepticism about the claim in Cartwright (1989) that philosophy of scientific inference has something to learn from the history of econometrics.