cssi/SciSciGPT-SciSciNet huggingface dataset:
The use of bone age for bone mineral density interpretation in a cohort of pediatric brain tumor patients

Skeletal bone accretion occurs throughout childhood. The integrity of this process can influence future adult bone health and the risk of osteoporosis. Although surveillance of children who are at risk of poor bone accretion is important, the most appropriate method to monitor childhood bone health has not been established. Previous investigators have proposed using bone age (BA) rather than chronological age (CA) when interpreting bone mineral density (BMD) values in children. To investigate the value of BA assessment for BMD measurement in a cohort of children at risk of poor accretion. A cohort of 163 children with brain tumors who completed both a BMD assessment (quantitative computed tomography, QCT) and who had a BA within a 6-month interval were identified. The difference in BMD Z-scores determined by CA and BA was determined. The impact of salient clinical features was assessed. No significant difference between CA and BA Z-scores was detected in the overall cohort (P = 0.056). However, the scores in 18 children (all boys between the ages of 11 years and 15 years) were statistically determined to be outliers from the values in the rest of the cohort. Interpretation of BMD with BA measurement might be appropriate and affect treatment decisions in peripubertal males.
Reflections on Valavanis' “econometrics”

The teaching of econometrics has been a difficult problem ever since the inception of this area of study. If one defines econometrics broadly as the application of mathematical statistics to measurement, estimation and hypothesis testing in economics, it becomes clear that the techniques and tools of econometrics are too varied to be encompassed by any one text on mathematical statistics. Moreover, econometrics is an area in which fundamental problems were often first recognized and solved by scholars who are primarily economists. Some econometric problems and techniques are peculiar to economics and may be of limited interest to the "general" statistician; others are widespread but occur in economics with a vengeance. Ideally one would seek a textbook of econometrics in which the set of tools common to all statisticians is built up and the substantive content of econometrics is systematically exposited in terms of mathematics of intermediate difficulty. Econometrics is a relatively new field. It can hardly be said to have existed three or four decades ago, and it was less than two decades ago that the probability approach in econometrics was articulately affirmed1. Given the acceptance of the general proposition that it is legitimate to consider economic data to have been generated by an underlying joint probability distribution, one may state as a broad generalization that the study of econometric theory has been primarily concerned with estimation of the parameters of equations arising out of economics. The study of econometric theory can conveniently be divided into two parts denoted respectively as the "single equation approach" and the "simultaneous equation approach". Although this classification is not exhaustive, it is one that is convenient without severely violating facts. The single equation approach is the older and perhaps more traditional approach. Examples of it are provided by numerous microeconomic estimation problems such as that of estimating the parameters of, say, a Cobb-Douglas type production function
THROUGHFALL IN PLANTED STANDS OF FOUR SOUTHERN PINE SPECIES IN EAST TEXAS

Throughfall was measured during 1978–79 beneath the canopies of adjacent stands of four major southern pine species, all on identical soil type and topography in the Stephen F. Austin Experimental Forest. Observations from 44 storms in a randomized network of 15, 5.08 cm PVC gages in a 0.4 ha plot of each species showed that throughfall expressed as percent of storm precipitation, is greatest under longleaf pine and least under loblolly pine; throughfall under shortleaf and slash pine did not differ significantly. Generally, through-fall decreased with storm size and intensity, with distance from the nearest tree stem, and is greater during summer half-year (May–October). Canopy drips, apparently accounting for the greater throughfall for the gage position closer to the stems, were more numerous than reported elsewhere. The 5.08 cm PVC gages proved to be acceptable substitutes for standard nonrecording gages in measuring throughfall. A network of 15 such gages was sufficient to sample throughfall data with 90 percent accuracy in each of the four southern pine plantations.
Crosstalk Between Phospholipase D and Sphingosine Kinase in Plant Stress Signaling

The activation of phospholipase D (PLD) produces phosphatidic acid (PA), whereas plant sphingosine kinase (SPHK) phosphorylates long-chain bases to generate long-chain base-1-phosphates such as phytosphingosine-1-phosphate (phyto-S1P). PA and phyto-S1P have been identified as lipid messengers. Recent studies have shown that PA interacts directly with SPHKs in Arabidopsis, and that the interaction promotes SPHK activity. However, SPHK and phyto-S1P act upstream of PLDα1 and PA in the stomatal response to abscisic acid (ABA). These findings indicate that SPHK/phyto-S1P and PLD/PA are co-dependent in the amplification of lipid messengers, and that crosstalk between the sphingolipid- and phospholipid-mediated signaling pathways may play important roles in plant stress signaling.
The Relative Expression of Mig6 and EGFR Is Associated with Resistance to EGFR Kinase Inhibitors

The sensitivity of only a few tumors to anti-epidermal growth factor receptor EGFR tyrosine kinase inhibitors (TKIs) can be explained by the presence of EGFR tyrosine kinase (TK) domain mutations. In addition, such mutations were rarely found in tumor types other than lung, such as pancreatic and head and neck cancer. In this study we sought to elucidate mechanisms of resistance to EGFR-targeted therapies in tumors that do not harbor TK sensitizing mutations in order to identify markers capable of guiding the decision to incorporate these drugs into chemotherapeutic regimens. Here we show that EGFR activity was markedly decreased during the evolution of resistance to the EGFR tyrosine kinase inhibitor (TKI) erlotinib, with a concomitant increase of mitogen-inducible gene 6 (Mig6), a negative regulator of EGFR through the upregulation of the PI3K-AKT pathway. EGFR activity, which was more accurately predicted by the ratio of Mig6/EGFR, highly correlated with erlotinib sensitivity in panels of cancer cell lines of different tissue origins. Blinded testing and analysis in a prospectively followed cohort of lung cancer patients treated with gefitinib alone demonstrated higher response rates and a marked increased in progression free survival for patients with a low Mig6/EGFR ratio (approximately 100 days, P = 0.01).
Clonal integration and effects of simulated herbivory in old-field perennials.

We compared the growth, phenology and leaf demography of partly defoliated, connected shoots with that of partly defoliated, severed shoots in four old-field perennials (Solidago canadensis, S. altissima, S. gigantea, Aster lanceolatus) with differing genet architectures (rhizome systems), in a common garden and in the field. Our main hypothesis was that defoliation would have fewer negative effects on shoot performance if shoots were connected than if their rhizomes were severed. Since degree of clonal integration is related to differences in genet architecture, our second hypothesis was that the effects of defoliation would be less pronounced in more integrated than in less integrated clones. Removing about 50% of the total leaf area from shoots had different effects depending on plant species, shoot density, and in particular whether rhizome connections between shoots were left intact or severed. In agreement with our prediction, experimentally isolated shoots in the field or in high density clumps in the garden suffered the most from defoliation, while shoots with intact connections or in low density clumps suffered the least. Our second prediction was neither confirmed nor falsified in the present study. Solidago altissima showed overcompensation in response to simulated herbivory in the common garden, i.e. defoliated shoots grew faster and were larger at harvest than their non-defoliated neighbours.
Investigating landslides and unstable slopes with satellite Multi Temporal Interferometry: Current issues and future perspectives

Abstract Multi Temporal Interferometry (MTI) stands for advanced synthetic aperture radar differential interferometry (DInSAR) techniques, which include Permanent/Persistent Scatterers Interferometry — PSInSAR™/PSI and similar methods, as well as Small Baseline Subset — SBAS and related/hybrid approaches. These techniques are capable to provide wide-area coverage (thousands of km 2 ) and precise (mm–cm resolution), spatially dense information (from hundreds to thousands of measurement points/km 2 ) on ground surface deformations. New MTI application opportunities are emerging thanks to i) greater data availability from radar satellites, and ii) improved capabilities of the new space radar sensors (X-band Cosmo-SkyMed, C-band RADARSAT-2, TerraSAR-X) in terms of resolution (from 3 to 1 m) and revisit time (from 11 to 4 days for X-band acquisitions). This implies greater quantity and quality information about ground surface displacements and hence improved landslide detection and monitoring capabilities. Even though the applicability of MTI to regional and local-scale investigations of slow landslides has already been demonstrated, the awareness of the MTI utility and its technical limitations among landslide scientists and practitioners is still rather low. By referring to recent works on radar remote sensing, many regional and local scale MTI application examples from the geoscience literature and our own studies, we present an up-to-date overview of current opportunities and challenges in this field. We discuss relevant technical constraints and data interpretation issues that hamper the use of MTI in landslide assessment. Then guidelines on how to mitigate MTI technical limitations and avoid erroneous interpretations of radar-derived slope surface deformations are presented for the benefit of users lacking advanced knowledge in SAR applications. Finally, in view of the upcoming radar satellite launches, future perspectives on MTI applications are outlined and recommendations for applied research priorities are suggested. We foresee that with regular globe-scale coverage, improved temporal resolution (weekly or better) and freely available imagery, new radar satellite background missions such as the European Space Agency's Sentinel-1 will guarantee ever increasing and more efficient use of MTI in landslide investigations. Furthermore, thanks to the improved temporal and spatial resolutions of the new generation radar sensors, significant breakthroughs are expected in detailed slope instability process modeling (e.g. kinematic and geotechnical models), as well as in the understanding of spatial and temporal patterns of landslide movement/activity and their relationships to causative or triggering factors (e.g. precipitation, seismic loading).
Intranucleus accumbens amphetamine infusions enhance responding maintained by a stimulus complex paired with oral ethanol self-administration.

Abstract Six male Long–Evans rats were trained to self-administer 10% ethanol (v/v) during 30 min operant sessions. A licking response on an empty drinking tube resulted in the presentation of reinforcement from an automatic dipper. During the initiation of ethanol self-administration, a tone–light stimulus complex was paired with all ethanol presentations. When 10% ethanol maintained responding, guide cannulae aimed at the nucleus accumbens (NAcc) were implanted into the brain. The ability of the paired stimulus complex to reinforce a new operant response (i.e., a lever press) was then examined. To test for the development of the new response, responding on one lever resulted in presentation of only the paired tone–light stimulus complex (contingency-associated lever) while responding on an alternate lever had no programmed consequences (no contingency-associated lever). Prior to some new response sessions, amphetamine (5–20 μg/μl) was infused into the NAcc to examine the influence of dopamine on responding maintained by the stimulus complex. Ethanol intake during the sessions prior to new response testing averaged 0.49 ± 0.07 g/g. During new response sessions no significant differences in lever pressure during no-drug conditions (control, sham, injection or vehicle injection) were observed between the contingency-associated and no contingency-associated levers. Intra-NAcc infusion of amphetamine (5–20 μg/μl) resulted in significant increases in lever pressing only on the contingency-associated lever. These data suggest that increasing NAcc dopamine levels with amphetamine enhanced the ability of the stimulus complex to function as a reinforcer. Further studies examining the ability of potentially more salient stimuli (i.e., taste of ethanol) to function as conditioned reinforcers associated with ethanol self-administration are warranted due to the apparent inability of the paired tone–light stimulus complex to function as a reinforcer without amphetamine-induced activation of the NAcc.
Eye-hand coordination assessment method using a haptic virtual environment with a complex valued neural networks training algorithm

Post-stroke patients usually undergo therapy that focuses on general gross-motor movements such as walking, balancing, involving lower limbs; or general arm movements, leaving them with fine-dexterity and eye-hand coordination problems at their chronic stage. In this paper, we discuss the possibility to come up with assessment metrics for eye-hand coordination therapy, using a mapping between a robotic haptic device to a virtual environment and a training algorithm based on Complex Valued Neural Networks that will determine how close a determined movement pattern is in relationship with that traced by a healthy individual. Most of the current robotic systems' therapy relies on the patient's performance on standardized clinical tests such as the functional independence measure (FIM), motor power score, and the upper limb subsection of the Fugl-Meyer (FM) scales. These systems don't have other standardized metrics for assessment purposes. There is a need to establish a more intelligent and tailored therapy that could be implemented for patients to use at home in between therapy sessions, or in the long term. This therapy should be based on performance data gathered by the robotic/computer system that will provide an assessment procedure with improved objectivity and precision. This paper presents a preliminary design and simulation results of virtual environment tasks that interface with a haptic robotic device, as well as the training of a complex valued based neural network using patterns traced by healthy individuals. The idea is to use this trained algorithm, to identify in the future, how close the patients' fine motor movements are to the healthy subject's fine coordination movements; and determine a form of metrics that can be used for assessment and future therapy decisions.
Synthesis and photochemical properties of 12-substituted versus 13-substituted chlorins.

Understanding the effects of substituents on natural photosynthetic pigments is essential for the rational design of artificial photosynthetic systems. The long-wavelength absorption of chlorins derives from a transition that encompasses rings A and C, which includes the 2,3- and 12,13-positions, respectively. Chlorophylls bear a 3-vinyl group and a 13-keto group, as well as a full complement of substituents at the other β-pyrrole sites. Prior studies of sparsely substituted synthetic chlorins to probe the effects of substituents yielded 3,13-substituted chlorins that contain a geminal dimethyl group in the pyrroline ring (for stability) and a mesityl group at the 10-position. Attempts to prepare analogous chlorins lacking the 10-mesityl substituent encountered unexpected difficulties during construction of the Eastern half precursor (8,9-dibromo-1-formyldipyrromethane) to the 13-bromochlorin. Direct bromination of 1-formyldipyrromethane with 2 mol equiv of NBS at −78 °C led to an isomeric mixture of the ...
Effect of the aldehyde dehydrogenase inhibitor, cyanamide, on the ex vivo sensitivity of murine multipotent and committed hematopoietic progenitor cells to mafosfamide (ASTA Z 7557).

AbstractThe ex vivo sensitivity of murine multipotent (CFU-GEMM) and committed (CFU-Mk, CFU-GM, BFU-E and CFU-E) hematopoietic progenitor cells to mafosfamide was quantified with and without concurrent exposure to cyanamide, an inhibitor of aldehyde dehydrogenase activity. In the absence of cyanamide, CFU-GEMM, CFU-Mk and CFU-GM were approximately equisensitive to mafosfamide while the erythroid progenitors were more sensitive to the drug. Cyanamide potentiated the cytotoxicity of mafosfamide toward CFU-GEMM and CFU-Mk, but not toward CFU-GM, BFU-E and CFU-E. Cellular aldehyde dehydrogenases are known to catalyze the oxidation of 4-hydroxycyclophos-phamide/aldophosphamide, the major intermediate in cyclophosphamide and mafosfamide activation, to the relatively nontoxic acid, carboxyphosphamide. Thus, our findings indicate that 1) murine CFU-GEMM contain the relevant aldehyde dehydrogenase activity, and 2) the relevant aldehyde dehydrogenase activity is retained upon differentiation to progenitors committe...
Estimation of error in maximal intensity projection-based internal target volume of lung tumors: a simulation and comparison study using dynamic magnetic resonance imaging.

Purpose To evaluate the error in four-dimensional computed tomography (4D-CT) maximal intensity projection (MIP)–based lung tumor internal target volume determination using a simulation method based on dynamic magnetic resonance imaging (dMRI). Methods and Materials Eight healthy volunteers and six lung tumor patients underwent a 5-min MRI scan in the sagittal plane to acquire dynamic images of lung motion. A MATLAB program was written to generate re-sorted dMRI using 4D-CT acquisition methods (RedCAM) by segmenting and rebinning the MRI scans. The maximal intensity projection images were generated from RedCAM and dMRI, and the errors in the MIP-based internal target area (ITA) from RedCAM (ɛ), compared with those from dMRI, were determined and correlated with the subjects' respiratory variability (ν). Results Maximal intensity projection-based ITAs from RedCAM were comparatively smaller than those from dMRI in both phantom studies (ɛ = −21.64% ± 8.23%) and lung tumor patient studies (ɛ = −20.31% ± 11.36%). The errors in MIP-based ITA from RedCAM correlated linearly (ɛ = −5.13ν − 6.71, r 2 = 0.76) with the subjects' respiratory variability. Conclusions Because of the low temporal resolution and retrospective re-sorting, 4D-CT might not accurately depict the excursion of a moving tumor. Using a 4D-CT MIP image to define the internal target volume might therefore cause underdosing and an increased risk of subsequent treatment failure. Patient-specific respiratory variability might also be a useful predictor of the 4D-CT–induced error in MIP-based internal target volume determination.
Feasibility of radical prostatectomy after neoadjuvant chemohormonal therapy for patients with high risk or locally advanced prostate cancer: results of a phase I/II study.

ABSTRACTPurpose: We determined the feasibility of radical prostatectomy after neoadjuvant chemohormonal therapy in locally advanced (stage T3 or greater) and/or high risk tumors (Gleason 8 to 10 and/or serum prostate specific antigen (PSA) greater than 20 ng/ml).Materials and Methods: Enrollment criteria included clinical stage T1 to 2 with any Gleason grade and PSA greater than 20 ng/ml, clinical stage T3 to 4 with any serum PSA or Gleason grade, or any clinical stage with biopsy Gleason grade of 8 to 10 and any serum PSA. All patients received neoadjuvant hormonal therapy during chemotherapy (4 cycles of paclitaxel and carboplatin and estramustine) followed by radical prostatectomy. Nerve sparing was decided on an individual basis and a nerve graft was offered to those who underwent unilateral or bilateral nerve resection. Perioperative morbidity, mortality and delayed complications were assessed.Results: A total of 36 patients were enrolled. After chemohormonal therapy clinical stage was less in 39% of...
Breeding site selection by coho salmon (Oncorhynchus kisutch) in relation to large wood additions and factors that influence reproductive success

The fitness of female Pacific salmon (Oncorhynchus spp.) with respect to breeding behavior can be partitioned into at least four fitness components: survival to reproduction, competition for breeding sites, success of egg incubation, and suitability of the local environment near breeding sites for early rearing of juveniles. We evaluated the relative influences of habitat features linked to these fitness components with respect to selection of breeding sites by coho salmon (Oncorhynchus kisutch). We also evaluated associations between breeding site selection and additions of large wood, as the latter were introduced into the study system as a means of restoring habitat conditions to benefit coho salmon. We used a model selection approach to organize specific habitat features into groupings reflecting fitness components and influences of large wood. Results of this work suggest that female coho salmon likely select breeding sites based on a wide range of habitat features linked to all four hypothesized fit...
An Investigation Into the Non-Uniformity of Density in Nanofluids

This study uses molecular dynamics simulations to investigate the affects of platinum nanoparticle lognormal size distribution and agglomeration on the local density of the surrounding xenon base fluid. Over the range of platinum nanoparticle diameters (25–150 nm), the radial distribution function showed an increase in the local fluid density. This increase in local density is shown to be caused by the formation of liquid layers that surround the nanoparticle. Liquid layer formation is found to be highly dependent on the cross-correlation between the platinum and xenon atoms. The local density is shown to increase with smaller nanoparticle diameter and aggregation reduces this change in density. Since aggregation is a dynamic phenomenon, the density becomes both spatially and temporally dependent. This space-time dependency of nanofluid density is compared to the linear mixing models normally applied to nanofluid systems.Copyright © 2010 by ASME
Comparative tensile strengths of nonnoble dental alloy solders

M ost casting and soldering techniques currently used in dentistry were developed specifically for dental gold alloys. The newer base metal or nonnoble alloys have higher melting ranges and other characteristics that differ from those of gold alloys. Practical application and routine use of these alloys have drawn varied and often conflicting reports from dentists and laboratories concerning their abilities to be cast and soldered accurately. Cast crowns and fixed partial dentures are soldered either before or after the application of porcelain. These two operations are called preceramic soldering and postceramic soldering, respectively. The postsolder must melt below the fusing temperature of the porcelain. If a direct flame is placed on the porcelain, it can cause porcelain fracture. To avoid this damage, the operation is performed in an oven. In both techniques, it is of interest to determine the comparative tensile strengths of solder joints of commercially available nonnoble alloys and solders used according to manufacturers’ directions. Determination of the reliability and reproducibility of such solder joints is also of importance, as is the determination of the site of fracture (solder, parent metal, or interface of the two). In addition, technique recommendations to improve the strength and reliability of nonnoble solder joints are of value to the dental profession. Sloan et al.’ reported soldering various combinations of alloys with their recommended solders with noble, “semiprecious,” and nonnoble metals. When base alloys were involved, the resultant fracture was most often at the interface of the solder and the parent metal. To date,
Theory and experiments of fracture in cyclic compression: Single phase ceramics, transforming ceramics and ceramic composites

Abstract The application of cyclic compressive stresses to notched plates of brittle solids can lead to stable crack growth along the plane of the notch in a direction normal to the far-field compression axis. In this paper, we present experimental results and constitutive models for single phase ceramics, transforming ceramics and ceramic composites with the aim of developing the framework for a general theory of cyclic compression fracture in notched brittle solids. Firstly, the results of a recent constitutive model for microcracking brittle solids in cyclic compression are briefly summarized. Next, a generalized constitutive formulation for martensitic transformations which considers both volumetric and shear strains is developed. A finite element analysis gives the near-tip residual stress field, where numerical results for microcracking single phase ceramics and transformation-toughened ceramics illustrate the inducement of notch-tip residual tensile stresses upon unloading from a far-field compressive stress. Large residual tensile stresses are created over a distance which is substantially greater than the characteristic microstructural dimension, but comparable to the experimentally-observed distance of crack growth after one compression cycle. The results obtained for ceramics are compared and contrasted with our previous studies of notch-tip residual tensile fields for metallic materials.
Adaptive Design and Estimation in Randomized Clinical Trials with Correlated Observations

Clinical trial designs involving correlated data often arise in biomedical research. The intracluster correlation needs to be taken into account to ensure the validity of sample size and power calculations. In contrast to the fixed-sample designs, we propose a flexible trial design with adaptive monitoring and inference procedures. The total sample size is not predetermined, but adaptively re-estimated using observed data via a systematic mechanism. The final inference is based on a weighted average of the block-wise test statistics using generalized estimating equations, where the weight for each block depends on cumulated data from the ongoing trial. When there are no significant treatment effects, the devised stopping rule allows for early termination of the trial and acceptance of the null hypothesis. The proposed design updates information regarding both the effect size and within-cluster correlation based on the cumulated data in order to achieve a desired power. Estimation of the parameter of interest and its confidence interval are proposed. We conduct simulation studies to examine the operating characteristics and illustrate the proposed method with an example.
Dynamic Histone H3 Acetylation and Methylation at Human Cytomegalovirus Promoters during Replication in Fibroblasts

Human cytomegalovirus DNA is packaged in virions without histones but associates with histones upon reaching the nucleus of an infected cell. Since transcription is modulated by the interplay of histone modifications, we used chromatin immunoprecipitation to detect acetylation and methylation of histone H3 at viral promoters at different times during the viral replication cycle. Histone H3 at immediate-early promoters is acetylated at the start of infection, while it is initially methylated at early and late promoters. Acetylation at immediate-early promoters is dynamic, with a high level of activating modifications at 3 and 6 h postinfection (hpi), followed by a marked reduction at 12 hpi. All viral promoters, as well as nonpromoter regions, are modified with activating acetylations at 24 to 72 hpi. The transient reduction in histone H3 acetylation at the major immediate-early promoter depends on the cis-repressive sequence to which the UL122-coded IE2 protein binds. A mutant virus lacking this element exhibited decreased IE2 binding at the major immediate-early promoter and failed to show reduced acetylation of histone H3 residing at this promoter at 12 hpi. Our results demonstrate that cytomegalovirus chromatin undergoes dynamic, promoter-specific histone modifications early in the infectious cycle, after which the entire chromosome becomes highly acetylated.
GATA-4 upregulates glucose-dependent insulinotropic polypeptide expression in cells of pancreatic and intestinal lineage.

A thorough examination of glucose-dependent insulinotropic polypeptide (GIP) expression has been hampered by difficulty in isolating widely dispersed, GIP-producing enteroendocrine K-cells. To elucidate the molecular mechanisms governing the regulation of GIP expression, 14 intestinal and pancreatic cell lines were assessed for their suitability for studies examining GIP expression. Both STC-1 cells and the pancreatic cell line βTC-3 were found to express GIP mRNA and secrete biologically active GIP. However, levels of GIP mRNA and bioactive peptide and the activity of transfected GIP reporter constructs were significantly lower in βTC-3 than STC-1 cells. When βTC-3 cells were analyzed for transcription factors known to be important for GIP expression, PDX-1 and ISL-1, but not GATA-4, were detected. Double staining for GIP-1 and GATA-4 in mouse duodenum demonstrated GATA-4 expression in intestinal K-cells. Exogenous expression of GATA-4 in βTC-3 cells led to marked increases in both GIP transcription and secretion. Lastly suppression of GATA-4 via RNA interference, in GTC-1 cells, a subpopulation of STC-1 cells with high endogenous GIP expression resulted in a marked an attenuation of GIP promoter activity. Our data support the hypothesis that GATA-4 may function to augment or enhance GIP expression rather than act as an initiator of GIP transcription.
Medical Malpractice and the Chest Physician

The US malpractice system is based on tort law, which holds physicians responsible for not harming patients intentionally or through negligence. Malpractice claims are brought against physicians from most medical disciplines in proportion to their numbers in practice and to the frequency with which they perform procedures. Claims against chest physicians most commonly allege injuries caused by the following: (1) errors in diagnosis, (2) improper performance of procedures, (3) failure to supervise or monitor care, (4) medication errors, and (5) failure to recognize the complications of treatment. Most of these injuries occur in hospitals, and many of the injured patients die. The social goals of the medical malpractice system include the following: (1) compensating patients injured through negligence, (2) exacting corrective justice, and (3) deterring unsafe practices by creating an economic incentive to take greater precautions. Some patients injured through negligence are compensated, but most are not. Claims are brought against some negligent physicians but also some who are not negligent, and being negligent does not guarantee that a claim will be brought. The deterrent effect of medical malpractice is unproven, and the malpractice system may prompt defensive medicine and increase health-care costs. And by stressing individual accountability, it conflicts with a systems-oriented approach to reducing medical errors.
Crystalline ribulose bisphosphate carboxylase/oxygenase of high integrity and catalytic activity from Nicotiana tabacum

Abstract Crystalline tobacco (Nicotiana tabacum L.) ribulose-1,5-bisphosphate carboxylase/ oxygenase (EC 4.1.1.39) was prepared using a procedure which protected the enzyme from hydrolysis by endogenous proteases. Leaves were extracted in a buffered medium containing casein, leupeptin, and high concentrations of MgSO4 and NaHCO3. After filtration through ion-exchange resin to remove contaminants, the enzyme was concentrated by precipitation with polyethylene glycol and crystal formation was induced by low-salt dialysis. The crystalline enzyme had a measured specific activity of 1.7 μmol CO2 mg protein−1 min−1, and about 93% of the enzyme could be activated with Mg2+ and CO2. Crystalline enzyme prepared in the absence of casein exhibited an activity which was only one-third of this rate and only about 70% of the enzyme could be activated with Mg2+ and CO2. Casein-extracted enzyme was resolved into distinct bands corresponding to the large (55,000) and small (14,000) subunits by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The large subunit of enzyme prepared according to the latter procedure was found to be composed of five different polypeptides of slightly decreasing molecular weight. Only about one-third of the large subunits were of the 55,000 molecular weight type. No differences between the two preparations were observed in the Km (CO2) and apparent Km (ribulose bisphosphate).
Targeted therapy for brain tumours

Although previously considered untreatable, brain tumours no longer carry the same prognosis as they did even a decade ago. Recent advances in drug delivery to the central nervous system have not only bypassed physiological constraints such as the blood–brain barrier, but have, in fact, changed the course of treatment for patients with malignant brain tumours. The creation of targeted therapies, which spare normal tissue and destroy tumour cells, is changing the field of neuro-oncology. In this article, we review recent developments in the delivery of drugs to tumours of the central nervous system, discuss current trends and directions in the development of novel drugs and delivery systems, and present new and cutting-edge strategies for overcoming the challenges ahead.
The Kathryn O. and Alan C. Greenberg Center for Skeletal Dysplasias: An Interdisciplinary Approach

Skeletal dysplasias are a group of over 300 genetic conditions often marked by short stature and a range of orthopedic problems. To meet the diverse medical, orthopedic, and psychosocial needs of individuals with skeletal dysplasias, the Kathryn O. and Alan C. Greenberg Center for Skeletal Dysplasias was organized at Hospital for Special Surgery in 2003. The center is the only one of its kind in the New York City metropolitan area and is dedicated to providing comprehensive medical care for individuals with skeletal dysplasias. The center is staffed by an interdisciplinary core team of health professionals consisting of an orthopedic surgeon, a medical geneticist, a genetic counselor/clinical coordinator, and a social worker. This interdisciplinary team of health professionals is committed to improving the quality of life for people with skeletal dysplasias through clinical care, research, education, and patient advocacy. Goals are achieved through a collaborative process that utilizes the expertise of the different professionals.
Applications of telomerase research in the fight against cancer

Telomerase, an enzyme that confers immortality upon cells and that is active in the majority of human tumors, has emerged as a powerful new marker and potential prognostic indicator and therapeutic target for cancer. Furthermore, investigations into the biology of telomerase have revealed important clues into the causes of cell death and have made progress toward answering one of the most important questions of cancer research - what gives a tumor cell an advantage over normal cells? In this article, we present the current state of telomerase research and critically assess both its potential and the pitfalls of its application in cancer diagnosis and treatment.
Phase field modeling of stress-induced tetragonal-to-monoclinic transformation in zirconia and its effect on transformation toughening

Abstract This paper proposes a two-dimensional elastic phase field model for capturing the effect of external stress on the tetragonal-to-monoclinic (T → M) phase transformation in zirconia. The model was able to predict the sensitivity of the monoclinic microstructural formation and evolution to the external loading conditions. The effect of stress on the T → M phase transformation was captured by explicitly applying stresses on the computational domain by entering them in the mechanical equilibrium equations as boundary conditions. Simulation results showed that, regardless of the stress loading direction, the monoclinic twinning plane always corresponded to {1 0 0}m. Results of simulations showed that external stress favors the production of monoclinic variants which exhibit transformation strains aligned with the applied stress direction. When applied to the transformation toughening phenomenon in zirconia, the model was able to elucidate the mechanisms of phase transformation ahead of a crack tip, including the generation of a compressive stress field responsible for the retardation of further crack growth. This work presents the first model capable of demonstrating the process of transformation toughening and crack closure in zirconia.
Abstract C8: Bone metastasis seed preselection by the primary tumor stroma

A key question in understanding the origin of metastasis is how cancer cells in a primary tumor acquire the ability to colonize a distant organ. Here we provide one answer to this puzzle by proposing the “metastasis seed pre-selection” model: when the stroma of a primary tumor resembles that of a distant organ, it pre-selects cancer cells that are predisposed to survive in that organ. In breast cancer, the mesenchymal stromal components cancer-associated fibroblasts (CAFs) create a microenvironment similar to that of the bone marrow. Heterogeneous cancer cell populations growing in a CAF-rich breast tumor are skewed towards a preponderance of clones with a superior ability to survive and proliferate on the environmental cues CAFs produce. When these cancer cell clones metastasize and infiltrate the bone marrow, they can maximally exploit these cues familiar to them for initial survival. As a result, these cells have a better chance to colonize the bone when they metastasize. Thus, a CAF-rich stroma primes the breast tumor as a whole at risk of developing bone metastasis. Our findings have implications for the evolution of metastatic traits and the interplay between a primary tumor and its distant metastases. Citation Format: Xiang Zhang, Xin Jin, Srinivas Malladi, Yong Wen, Edi Brogi, Joan Massague. Bone metastasis seed preselection by the primary tumor stroma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C8.
Optimization of conformal avoidance: a comparative study of prone vs. supine interstitial high-dose-rate breast brachytherapy.

Abstract Purpose Several recent studies indicate high-dose-rate (HDR) breast brachytherapy as an alternative to standard external beam radiation therapy for partial breast irradiation with high dose conformality to the target. However, this article presents an exploration of the possibility of achieving higher conformal avoidance of sensitive structures through detailed and comparative 3D CT-based anatomical dose distribution of a patient in supine and prone positions. Methods and materials A patient treated with accelerated partial breast HDR breast brachytherapy in the supine position was selected for two CT-based analyses, one in the supine and one in the prone position. The optimized plan (Nucletron HDR planning station) for each position was achieved using graphical optimization with local adjustment of isodose lines to cover the planned target volume (PTV, lumpectomy with 2 cm margin) with 100% of the prescribed dose (34 Gy in 10 fractions) while minimizing the hot spots. Cumulative dose-volume histograms (DVH) were analyzed for the PTV, lung, skin, pectoral muscle, and chest wall. Results The PTV received 100% of prescribed dose in both the prone and supine positions. A significant (>40%) dose reduction was achieved in the lung in the prone treatment position. Similar dose reductions were also achieved for prone pectoral muscle, chest wall, and breast skin, irradiating less volume with high doses. Pectoral muscle, lumpectomy, and the breast skin showed prominent differences in shape and displacement in the prone compared with the supine position. Conclusion CT-based treatment planning allowed calculations of volumetric dose distribution to the target and all sensitive structures with proper visualization and volumetric delineation of organs of interest. The treatment plan shows significant dose reduction may be possible in various sensitive structures if the patient is treated with HDR brachytherapy in the prone position.
Ab Initio Investigation of the Ground Potential Energy Surface of the CO2+·Ar Ion

The ground potential energy surface of the CO2+·Ar complex has been investigated by ab initio techniques for C∞v, C2v, and Cs structures of the ion. The C∞v and C2v stationary points are found to be transition states which lead smoothly to the global Cs minimum-energy structure. In all three geometries, the interaction between CO2+ and Ar is found to be largely electrostatic in nature. The equilibrium geometry of the the CO2+·Ar ion is planar with a near linear OCO moiety and a C−O−Ar angle near 100°. At the QCISD(T)/aug-cc-pVTZ level of theory, De is calculated to be 0.220 eV for dissociation into CO2+ and Ar. Harmonic vibrational frequencies, infrared intensities, and frequency shifts occurring for 13C and 18O calculated at the QCISD/cc-pVDZ (for C and O) and aug-cc-pVDZ (for Ar) level of theory are reported.
Long-Term Site Preparation Effects on Volcanic Ash Forest Soils and Douglas-Fir

Long-term site preparation effects on soil characteristics and Douglas-fir (Pseudotsuga menziesii var. glauca) growth and foliar nutrition were measured over a 24-year period following a ground-based harvest in Northern Idaho, USA. Harvest unit soils were classified as Andisols overlaying metasedimentary parent material within a udic-frigid moisture and temperature regime. Douglas-fir site index at base age 50 was 29 m. Site preparation treatments included undisturbed control, broadcast burn, pile and burn, and mechanical scarification. Periodic soil-site measurements were collected on each treatment at regeneration stand ages 6, 14, and 24 years. Six- and 14-year soil bulk density on scarified treatments were significantly higher at 0-15 and 15-30 cm than all other treatments. At 24 years, scarified soil bulk density at 0-15 and 15-30 cm showed recovery to bulk densities observed in non-scarified soils. Scarified soil organic matter (SOM) and N were significantly reduced by 32% and 42% over control levels 6 years post-harvest. After 24 years, scarified SOM and N were significantly lower than that found in broadcast burn (44% and 54%) and pile and burn (33% and 49%). Douglas-fir needle mass and foliar N and P content on scarified soils were significantly lower than on broadcast burn or pile and burn treatments after 24 years (p<0.1). After 24 years, soil and foliar N content was significantly higher on microsites that received a burn treatment (p<0.1). Tree growth on either burn treatment showed significantly greater diameter (35%), height (14%), and volume (92%) when compared to trees growing on scarified soils after 24 years (p<0.1). These results indicate that tree growth on frigid, ash-mantled forest soils of Northern Idaho, USA, can be significantly reduced following soil compaction and displacement of organic matter and nutrient-rich topsoil. Where soil disturbance was minimized and organic matter retention was coupled with a burn treatment, soil and tree productivity was maintained or enhanced.
Prevalence of cigarette smoking among rural adolescents in the United States.

Results are reported from a national U.S. study of cigarette smoking carried out from 1996 to 2000 involving 68,270 adolescents. Hierarchical linear modeling was used to model smoking as a function of grade, gender, region, and community size (rurality). Significant effects were found for rurality, region, grade, and gender. The highest levels of smoking were found for rural adolescents, and adolescents living in the South. Males smoked more than females in all regions except the West, where the reverse was true. Given that rural adolescents smoke more "heavily" than do their nonrural peers, researchers must devote more attention to understanding the factors that underlie smoking initiation in rural youth.
The Use of Push-Pull Perfusion and in Vivo Microdialysis to Assess Changing Patterns of Hypothalamic Releasing Hormone Output in Aging Animals

Abstract A thorough understanding of the nature of age-related changes at the hypothalamic level would be greatly enhanced by the ability to directly measure neuropeptide release. In vivo measurement of neurosecretion is a demanding undertaking in young animals and increases in difficulty in aging animals due to additional considerations that must be acknowledged. Push-pull perfusion and in vivo microdialysis are two methods currently being used to directly measure neuropeptide output. The advantages and disadvantages of each are discussed. Moreover, special concerns regarding their use in aging animals are addressed, including the potential for: (1) differences in the response of the aging brain to insult; (2)age-related differences in levels of degradative enzymes; and (3) confounding effects of age-related differences in the stress response. Push-pull perfusion was used to compare the pattern of luteinizing hormone-releasing hormone output in middle-aged and young female rats during a steroid-induced LH surge. The data revealed age-related differences in the overall pattern and the mean levels of LHRH output. When used with the proper precautions, these in vivo protocols enable characterization of the patterns of release of neuroactive substances in a single animal over time. They eliminate the need to sacrifice large numbers of animals to obtain measurements for a single time point, a feature particularly important for aging studies due to the heterogeneity of the population and the expense of the animals. Moreover, use of these methods is essential if alterations in the patterns of neuropeptide release play an important role in the changes that accompany aging.
A universal hybrid decision tree classifier design for human activity classification

A system that reliably classifies daily life activities can contribute to more effective and economical treatments for patients with chronic conditions or undergoing rehabilitative therapy. We propose a universal hybrid decision tree classifier for this purpose. The tree classifier can flexibly implement different decision rules at its internal nodes, and can be adapted from a population-based model when supplemented by training data for individuals. The system was tested using seven subjects each monitored by 14 triaxial accelerometers. Each subject performed fourteen different activities typical of daily life. Using leave-one-out cross validation, our decision tree produced average classification accuracies of 89.9%. In contrast, the MATLAB personalized tree classifiers using Gini's diversity index as the split criterion followed by optimally tuning the thresholds for each subject yielded 69.2%.
Long-range acoustic communication in deep water using a towed array: Beam diversity

Underwater acoustic communication typically involves vertical arrays that provide spatial diversity to mitigate channel fading and intersymbol interference when the array elements are well-separated. For closely-spaced arrays (e.g., one-half wavelength), an array gain is achieved by a beamforming process provided that the noise is uncorrelated while the signal is coherent across the array. A recent experiment (LRAC10) showed that coherent long-range acoustic communication (200–300 Hz) is feasible in deep water over ∼550-km range between a source and a horizontal towed array (∼100 m aperture). This paper demonstrates that beam diversity with a larger horizontal array (∼200 m aperture) can be exploited to further improve the communication performance, achieving an error-free data rate of 50 bits/s for BPSK modulation at ∼550-km range.