cssi/SciSciGPT-SciSciNet huggingface dataset:
Why Misfit When You Already Have X2

A modification of X2, called Misfit, is suggested; it provides a comparative goodness-of-fit criterion. The numerical value of Misfit gives the fraction of the experimental Signal that remains “unfitted. ” After this quantity is defined and the motivation for introducing it is explained, some examples of its use are given.
Economic Analysis of a Noninvasive Molecular Pathologic Assay for Pigmented Skin Lesions.

Importance A recently described noninvasive gene expression test (the pigmented lesion assay [PLA]) with adhesive patch–based sampling has the potential to rule out melanoma and the need for surgical biopsy of pigmented lesions suggestive of melanoma with a negative predictive value of 99% compared with 83% for the histopathologic standard of care. The cost implications of using this molecular test vs visual assessment followed by biopsy and histopathologic assessment (VAH) have not been evaluated. Objective To determine potential cost savings of PLA use vs the VAH pathway. Design, Setting, and Participants This health economic analysis performed from a US payer perspective was based on consensus treatment guidelines and fee schedules from the Centers for Medicare & Medicaid Services. Data for model input were derived from routine use of the test in US dermatology practices and literature. Participants included patients with primary cutaneous pigmented lesions suggestive of melanoma. Data were analyzed from February 8 to December 1, 2017. Main Outcomes and Measures The primary analysis consisted of the relative reduction in costs of diagnostic surgical procedures for PLA vs VAH management. Additional analyses included stage-related treatment costs associated with delays in diagnosis. Results In the cost analysis for this economic model, the relative reduction in surgical procedure costs (biopsy and subsequent excision), assuming $0 for the PLA to facilitate multiple comparison scenarios, was −$395 compared with VAH. The relative reduction in stage-related treatment costs associated with the PLA was −$433 compared with VAH, primarily associated with avoidance of delays due to false-negative diagnoses. Surveillance costs were reduced by −$119 with the PLA. The total cost of fully adjudicating a lesion suggestive of melanoma by VAH was $947. At a mean selling price reference point for PLA of $500, cost savings of $447 (47%) per lesion tested could be realized. Conclusions and Relevance The results of this analysis suggest that the PLA reduces cost and may improve the care of patients with primary pigmented skin lesions suggestive of melanoma.
Recent Developments in Model-Based Clustering with Applications

Model-based clustering is a popular technique relying on the notion of finite mixture models that proved to be efficient in modeling heterogeneity in data. The underlying idea is to model each data group by a particular mixture component. This relationship between mixed distributions and clusters forms an attractive interpretation of groups: each cluster is assumed to be a sample from the corresponding distribution. In practice, however, there are many issues that have to be accounted for by the researcher. The area of model-based clustering is very dynamic and rapidly developing, with many questions yet to be answered. In this paper, we review and discuss the latest developments in model-based clustering including semi-supervised clustering, non-parametric mixture modeling, choice of initialization strategies, merging mixture components for clustering, handling spurious solutions, and assessing variability of obtained partitions. We also demonstrate the utility of model-based clustering by considering several challenging applications to real-life problems.
Primary Culture and Characterization of Microvascular Endothelial Cells From Macaca Monkey Retina

Purpose. To develop methods for the culture of microvascular endothelial cells (EC) from Macaca monkey retina and to investigate their propagation and survival in vitro. Methods. Endothelial cells from capillary fragments were cultured on fibronectin-coated dishes in QB-58 serum-free medium containing 20 /il/ml bovine retinal extract, 90 Mg/ml heparin, 10% fetal bovine serum, and 10% monkey serum. Non-EC were removed manually. Endothelial cell-specific properties were assessed by endocytosis of acetylated low-density lipoprotein (ac-LDL) and by immunocytochemical staining. The response to growth factors was assayed by H H-thymidine incorporation. The synthesis of matrix macromolecules was studied by metabolic labeling with 3 H-proline and identification by sodium dodecyl sulfate-polyacrylamide gel electrophoresis-immunoblotting. Results. Under these culture conditions, migrating cells emerged from capillary fragments after 1 to 2 days and formed large colonies by 1 week. Cells exhibited a mean doubling time of 44.5 hours during the first 3 to 5 days of culture and 23 hours at 6 to 8 days in culture, and they formed a confluent monolayer by 12 to 14 days. These cells demonstrated uptake of ac-LDL, expressed von Willebrand factor and the cell adhesion protein CD31, and did not contain smooth muscle a-actin. Before purification, 92% of the cells in primary cultures were identified as EC. The EC could be maintained in vitro for more than 1 month without the addition of growth factors; however, basic fibroblast growth factor and vascular endothelial growth factor each stimulated cell replication. Secreted extracellular proteins included fibronectin, collagen types I and IV, laminin, and SPARC (secreted protein, acidic, and rich in cysteine). Conclusions. This study is the first description of die culture and propagation of purified retinal EC from Macaca monkey, a widely accepted model for die human retina. These cultures will be highly relevant to studies of abnormal vascular disease in die human eye. Invest Opdialmol VisSci. 1996;37:2185-2194. It is now appreciated that retinal microvascular endothelium is an integral component in the development of diabetic retinopathy and retinopathy of prematurity, which are major causes of blindness worldwide. Although endothelial cells (EC) have a common topography throughout the vasculature, fundamental differences are found among EC derived from different species and from different organs or vascular From the Departments of * Biological Structure, and -\ Ophthalmology, University of
Robustification of Cumulative Sum Charts by Winsorization

Cumulative sum control charts are particularly effective for detecting special causes that lead to a persistent change in the process parameters. Like the traditional Shewhart charts (though to a much smaller degree) they are affected by the underlying ..
Algorithms for Spatial Data Integration

The map construction problem (MCP) is defined as a spatial data integration problem relating to the integration of region data into map data. Although a purely geometric integration of regions into a map is known and is efficient, algorithms preserving thematic data of regions are much more difficult. A naive approach to the MCP runs in O((nmlgnm)2+k) time for m regions composed with n line segments on average with k line segment intersections. A new \(O((n + k)(\lg n + m +\lg {m}^{2}))\) algorithm is presented to solve the MCP. The algorithm has been implemented and experiments show that it is significantly faster than the naive approach, but is prone to large memory usage when run over large data sets. An external memory version of the algorithm is presented that is efficient for very large data sets, and requires significantly less memory than the original algorithm.
Case-Based Learning in Public Health Informatics

The public health landscape is undergoing profound changes, including rapid advances in technology, increasing use of electronic health records, and health reform. Improving population health requires knowledge and skills in managing and working within the adaptive complexity of underlying societal structures and functions. These advances in technology, and profound changes within these structures and functions, introduce enormous opportunities for creating efficiencies and economies of scale, not simply for improving public health practice, but for learning as well. Finding informatics solutions to cross-cutting information needs, while solving complex health problems, requires cross-disciplinary education, research, and practice.
Local radiation and phototherapy are the most cost-effective treatments for stage IA mycosis fungoides: A comparative decision analysis model in the United States.

Background Treatments for early-stage mycosis fungoides (MF) include topical steroids, topical nitrogen mustard, topical bexarotene, narrowband ultraviolet B (NBUVB), psoralen plus ultraviolet A (PUVA), and local radiation. The relative cost-effectiveness of each treatment given the differences in treatment failure, disease progression, and therapy escalation is not established. Objective To compare the cost-effectiveness (CE) of treatment options for stage IA MF. Methods A state-transition model was constructed with health states of stage IA to stage IV disease, no MF, and death. Treatment-specific remission and relapse rates were obtained from the literature. Lifetime costs were calculated by accounting for medications, office visits, laboratory monitoring, related procedures, work absences, and travel. Results The order of CE of the study treatments was determined to be as follows: local radiation, $225,399 for 15.40 life-years (LYs); NBUVB, $344,728 for 15.17 LYs; PUVA, $371,741 for 15.07 LYs; topical corticosteroids, $469,354 for 14.65 LYs; topical nitrogen mustard, $951,662 for 14.29 LYs; and topical bexarotene, 11,892,496 for 13.55 LYs. Sensitivity analyses confirmed the CE rankings. Limitations We assumed a constant probability of response, relapse rates, and 3-month treatment intervals. Conclusions Local radiation is the most cost-effective treatment for limited local disease, whereas phototherapy (NBUVB or PUVA) is cost-effective for generalized disease. Our findings can serve to inform future studies and recommendations regarding selection of therapy for stage IA MF.
Structure, Spectroscopy, and Electrochemistry of Manganese(I) and Rhenium(I) Quinoline Oximes

Reactions of α- and β-diimine quinoline aldoximes with Mn(I) and Re(I) tricarbonyl halides afford quinoline oxime complexes. Both Mn(I) and Re(I) complexes experience severe geometric strain due to ligand steric interactions: 6-membered metallocycles exhibit more pronounced distortions than 5-membered ones, consistent with density functional theory structural analyses. Such distortions likely also affect reactivity patterns, as evidenced by Re(I)-induced deoximation of a quinoline variant containing a CF3-ketoxime.
Digitization and the Demand for Physical Works: Evidence from the Google Books Project

Digitization has allowed customers to access content through online channels at low cost or for free. While free digital distribution has spurred concerns about cannibalizing demand for physical alternatives, digital distribution that incorporates search technologies could also allow the discovery of new content and boost, rather than displace, physical sales. To test this idea, we study the impact of the Google Books digitization project, which digitized large collections of written works and made the full texts of these works widely searchable. Exploiting a unique natural experiment from Harvard Libraries, which worked with Google Books to digitize its catalog over a period of five years, we find that digitization can boost sales of physical book editions by 5-8 percent. Digital distribution seems to stimulate demand through discovery: the increase in sales is stronger for less popular books and spills over to a digitized author’s non-digitized works. On the supply side, digitization allows small and independent publishers to discover new content and introduce new physical editions for existing books, further increasing sales. Combined, our results point to the potential of free digital distribution to stimulate discovery and strengthen the demand for and supply of physical products.
Relative and absolute configurations of ganefromycin alpha.

The full structure of ganefromycin α has been determined. The relative configurations were determined from 3JH,H coupling constants and NOE data, while the absolute configurations in moieties A and B were determined separately by difference CD of their acylate derivatives, which showed typical exciton couplets. The configurations of the stereogenic centers in ganefromycin α are 8S, 9S, 11R, 12S, 13S, 21S, 22R, 23R, 24R, and 26S.
Trustees sought for Vetlife.

Vetlife is a charity that supports the veterinary community through the provision of multiple support services. It is currently seeking trustees, and members of Vetlife are invited to apply to serve on the board of trustees. Vetlife is independent from all other veterinary organisations and is managed by a board of 12 elected trustees, all of whom are veterinary surgeons. The charity employs a small team …
Wildlife population trends as indicators of protected area effectiveness in northern Tanzania

Abstract Protected areas are the cornerstone of biodiversity conservation, yet the relative effectiveness of different conservation models is often unknown. Here, we describe seasonal population densities and associated annual population changes of ten wildlife species (elephant, giraffe, zebra, wildebeest, waterbuck, warthog, Grant’s gazelle, impala, Thomson’s gazelle, and Kirk’s dik-dik) in four protected areas in northern Tanzania over eight years and test two hypotheses: (1) annual wildlife population changes are positively correlated with conservation status; and, (2) relationships between annual population changes and protected area status are mediated by species’ body mass. We carried out wildlife surveys from late 2011 to the end of 2018 and estimated wildlife densities in a line distance sampling framework. The majority of species occurred at high densities in fully protected areas, and larger-bodied species occurred at low densities or were absent in the least protected area. We estimated annual species- and area-specific population changes with generalized linear mixed effects that accounted for seasonal variation in this ecosystem. Using multi-model comparisons, we did not find evidence that annual population changes were correlated with body mass. However, species- and area-specific population changes appeared to vary by species and area, but were not consistently associated with protection status. Wildlife populations in Tarangire National Park and two human-dominated areas showed mainly stable or positive population trends, whereas wildlife populations in Lake Manyara National Park appeared to decline during the study period. This ecosystem- and long-term monitoring indicates apparent context-dependent differences in protected area performance within one ecosystem and exemplifies the need for, and challenges of, long-term monitoring in protected areas to guide effective conservation.
Using a Time-Based Subarray Method to Extract and Invert Noise-Derived Body Waves at Long Beach, California

The reconstruction of body waves from the cross‐correlation of random wavefields has recently emerged as a promising approach to probe the fine‐scale structure of the Earth. However, because of the nature of the ambient noise field, the retrieval of body waves from seismic noise recordings is highly challenging and has only been successful in a few cases. Here, we use seismic noise data from a 5,200‐node oil‐company survey to reconstruct body waves and determine the velocity structure beneath Long Beach, California. To isolate the body wave energy from the ambient noise field, we divide the entire survey into small‐aperture subarrays and apply a modified double‐beamforming scheme to enhance coherent arrivals within the cross‐correlated waveforms. The resulting beamed traces allow us to identify clear refracted P waves traveling between different subarray pairs, which we then use to construct a high‐resolution 3D velocity model of the region. The inverted velocity model reveals velocity variations of the order of 3% and strong lateral discontinuities caused by the presence of sharp geologic structures such as the Newport‐Inglewood fault (NIF). Additionally, we show that the resolution that is achieved through the use of high‐frequency body waves allows us to illuminate small geometric variations of the NIF that were previously unresolved with traditional passive imaging methods.
Recent Studies on Buckling, Vibration and Static Response of Anisotropic Shear–Flexible Plates

Abstract —The paper deals with the analysis of shear-flexible anisotropic plates subjected to arbitrary boundary conditions. In order to solve the pertinent boundary value problem, a variant of the Boundary Element Method (BEM) is developed in which, however, the employed trial functions need not be fundamental solutions. The method has been successfully applied to a wide range of plate problems and it was found to be highly accurate and computationally efficient.
Anticoagulant treatment satisfaction with warfarin and direct oral anticoagulants for venous thromboembolism

Treatment options for patients with venous thromboembolism (VTE) include warfarin and direct oral anticoagulants (DOACs). Although DOACs are easier to administer than warfarin and do not require routine laboratory monitoring, few studies have directly assessed whether patients are more satisfied with DOACs. We surveyed adults from two large integrated health systems taking DOACs or warfarin for incident VTE occurring between January 1, 2015 and June 30, 2018. Treatment satisfaction was assessed using the validated Anti-Clot Treatment Scale (ACTS), divided into the ACTS Burdens and ACTS Benefits scores; higher scores indicate greater satisfaction. Mean treatment satisfaction was compared using multivariable linear regression, adjusting for patient demographic and clinical characteristics. The effect size of the difference in means was calculated using a Cohen’s d (0.20 is considered a small effect and ≥ 0.80 is considered large). We surveyed 2217 patients, 969 taking DOACs and 1248 taking warfarin at the time of survey. Thirty-one point five percent of the cohort was aged ≥ 75 years and 43.1% were women. DOAC users were on average more satisfied with anticoagulant treatment, with higher adjusted mean ACTS Burdens (50.18 v. 48.01, p < 0.0001) and ACTS Benefits scores (10.21 v. 9.84, p = 0.046) for DOACs vs. warfarin, respectively. The magnitude of the difference was small (Cohen’s d of 0.29 for ACTS Burdens and 0.12 for ACTS Benefits). Patients taking DOACs for venous thromboembolism were on average more satisfied with anticoagulant treatment than were warfarin users, although the magnitude of the difference was small.
Textualism and the Modern Explanatory Statute

The explanatory statute is a largely forgotten legislative tool. Once common, the explanatory statute was a retrospective act that identified an ambiguity or erroneous interpretation of a prior law and then directed the legislature’s view of the correct interpretation. Although now rare, the explanatory statute is not dead. Just a few years ago, Congress enacted an amendment to Section 230 of the Communications Decency Act—a now hotly contested topic—with the hallmarks of an explanatory statute. In the Allow States and Victims to Fight Online Sex Trafficking Act of 2017 (“FOSTA”), Congress concluded that courts had over-extended Section 230 immunity to preclude claims by sex trafficking victims and so clarified that the immunity should not be construed to impair those claims. So far, however, courts and commentators have taken a narrow view of FOSTA and assumed that it preserves only those claims specifically enumerated in the statute. This view proceeds from an underappreciation for explanatory statutes and their proper application. Indeed, given their rarity, little has been written about how to approach statutes of this sort under the prevailing textualist methodology. This Article aims to fill that gap by proposing a generally applicable textualist framework for analyzing modern explanatory statutes. When applied to FOSTA, that framework yields a perhaps surprising result: A sound, textualist reading of FOSTA may invite federal courts to recalibrate the scope of Section 230 immunity, even outside the context of sex trafficking claims.
Flow Field Study of a Top Heated Immiscible Liquid Layer Adjacent to Ice

A series of experiments were conducted to investigate the flow field of a top-heated liquid fuel adjacent to an ice block. The experimental setup consisted of a borosilicate container containing an ice wall and a layer of n-heptane heated from above. Particle Image Velocimetry (PIV) and Background Oriented Schlieren (BOS) measurements were conducted on the liquid -phase. PIV measurements showed a surface flow toward the ice caused by surface -tension forces, which is driven by the horizontal temperature gradients on the liquid surface. A recirculation zone was observed under the free surface and near the ice. The combination of the two flow patterns caused lateral intrusion in the ice, instead of a uniform melting across ice surface. BOS measurements indicated presence of density gradients below the free surface of n-heptane and in regions near the ice block. These density gradients were created by local small-scale temperature gradients. The current experiments were conducted to explore the processes that influence the ice melting by immiscible liquid layers.
Hardware efficient learning on a 3-D optoelectronic neural system

Discusses the dual-scale topology optoelectronic processor (D-STOP) neural network, a scalable, optically interconnected neural network architecture. The authors present the tandem D-STOP system, which provides the connectivity needed for building fully-parallel neural networks with generic gradient-descent learning rules. The authors review the content addressable network (CAN) learning algorithm, a discrete learning algorithm that provides accelerated learning with reduced hardware requirements. The authors then show how the CAN algorithm can be effectively mapped onto D-STOP, and they investigate associated optoelectronic hardware tradeoffs. >
On the use of generalized inverses in function minimization

In this paper an attempt is made to provide a unified derivation of various minimization algorithms which use the notion of updating an estimate of the inverse of theHessian matrix. A new method for updating the estimated inverse of theHessian matrix and a simple technique for making computational improvements in the various algorithms are also given.
Resorting to Alcibiades: Thucydides' Portrayal in the History of the Peloponnesian War

The Athenian politician Alcibiades was held by Thucydides to be only person capable of saving Athens during the latter phases of the Peloponnesian War. While we glean from Plato that Alcibiades is not particularly knowledgeable in political or military matters, in Thucydides' History, we find a different Alcibiades. Although still headstrong, ambitious and vain, Alcibiades' rhetorical and military skills are of particular value to Athens (and to Sparta as well) at critical times during the war. Thucydides seems to be clear that the Athenian public distrusted Alcibiades to the point of exiling him twice when, according to Thucydides, he was only person capable of saving Athens from Sparta's forces. If political skill is of value to democracies, can citizens utilize it for their own good? Alcibiades was a complicated character in that while he was talented, he was also was transparent about his desire for glory. His personal life was one of excess and it made him an easy target for rebuke. Athens, we might say, became overly concerned with questions of personal character rather than expediency. How can a democracy make use of the political skills of leaders while at the same time maintaining a check on their authority? The Athenian public is the subject of considerable mockery in ancient thought for being too easily duped by politicians and, at the same time, not being able to recognize when a policy is in their interest.
EFFECT OF FLAVOR ON PERCEIVED TEXTURE OF WHEY PROTEIN ISOLATE GELS

ABSTRACT This study investigated the role of flavor on trained panelist and consumer perception of texture properties. Whey protein isolate (WPI) gels were prepared with sodium chloride (25 mM) at different pH (pH 6.0 or 7.0), and calcium chloride concentrations (0 or 10 mM). The same gel treatments were produced with and without added flavor. Instrumental torsion analysis showed that flavor addition had no impact (P > 0.05) on fracture stress and strain. Texture properties of gels were evaluated by a trained descriptive panel and untrained consumers (n = 60) for their perception of gel firmness, fracturability, juiciness, mouth coating and overall disliking. Distinct texture properties among the gels were documented by both trained panelists and consumers (P 0.05) texture perception. Therefore, flavor addition does not impact panelist (trained or untrained) ability to evaluate textural differences in WPI gels. PRACTICAL APPLICATIONS Much current work is focused on understanding oral processing and the sensory perception of texture. Many studies have evaluated the influence of texture on flavor perception, and many of those that have looked at the effect of flavor on texture perception have not controlled for rheological differences in texture. As such, the influence of flavor on texture perception by trained panelists and/or untrained consumers is not well documented. A better understanding of these effects would (1) help researchers studying mastication behaviors and/or food texture to create more palatable, flavorful samples without compromising the textural integrity of their samples, and (2) help commercial food manufacturers more easily understand drivers of consumer liking when pursuing new product development or line extensions.
Peer Control in Organizations

Peer control occurs when workers who are at the same organizational level or in the same field exert lateral control over their peers. Peer control is widespread in organizations, yet is not well understood. This chapter discusses the scope of the peer control concept, including different types of formal and informal peer controls designed by managers and workers. The potential benefits and drawbacks of peer control are also discussed. Five theoretical perspectives that can be used to examine informal peer control are reviewed. The chapter concludes with suggestions for future research on peer control.
We All Need Help: “Big Data” and the Mismeasure of Public Administration

Rapid advances in our ability to collect, analyze, and disseminate information are transforming public administration. This “big data” revolution presents opportunities for improving the management of public programs, but it also entails some risks. In addition to potentially magnifying well-known problems with public sector performance management—particularly the problem of goal displacement—the widespread dissemination of administrative data and performance information increasingly enables external political actors to peer into and evaluate the administration of public programs. The latter trend is consequential because external actors may have little sense of the validity of performance metrics and little understanding of the policy priorities they capture. The author illustrates these potential problems using recent research on U.S. primary and secondary education and suggests that public administration scholars could help improve governance in the data-rich future by informing the development and dissemination of organizational report cards that better capture the value that public agencies deliver.
Differential Proteomic Analysis of Renal Cell Carcinoma Tissue Interstitial Fluid

Renal cell carcinoma (RCC), the most common type of kidney cancer, currently has no biomarker of clinical utility. The present study utilized a mass spectrometry-based proteomics workflow for identifying differentially abundant proteins in RCC by harvesting shed and secreted proteins from the tumor microenvironment through sampling tissue interstitial fluid (TIF) from radical nephrectomies. Matched tumor and adjacent normal kidney (ANK) tissues were collected from 10 patients diagnosed with clear cell RCC. One-hundred thirty-eight proteins were identified with statistically significant differential abundances derived by spectral counting in tumor TIF when compared to ANK TIF. Among those proteins with elevated abundance in tumor TIF, nicotinamide n-methyltransferase (NNMT) and enolase 2 (ENO2) were verified by Western blot and selected reaction monitoring (SRM). The presence of ENO2 and thrombospondin-1 (TSP1) were verified as present and at elevated abundance in RCC patient serum samples as compared to a pooled standard control by enzyme-linked immunosorbent assay (ELISA), recapitulating the relative abundance increase in RCC as compared with ANK TIF.
The genetics of Leigh syndrome and its implications for clinical practice and risk management

Leigh syndrome, also referred to as subacute necrotizing encephalomyelopathy, is a severe, early-onset neurodegenerative disorder that is relentlessly progressive and devastating to both the patient and the patient’s family. Attributed to the ultimate failure of the mitochondrial respiratory chain, once it starts, the disease often results in the regression of both mental and motor skills, leading to disability and rapid progression to death. It is a mitochondrial disorder with both phenotypic and genetic heterogeneity. The cause of death is most often respiratory failure, but there are a whole host of complications, including refractory seizures, that may further complicate morbidity and mortality. The symptoms may develop slowly or with rapid progression, usually associated with age of onset. Although the disease is usually diagnosed within the first year of life, it is important to note that recent studies reveal phenotypic heterogeneity, with some patients having evidence of in utero presentation and others having adult-onset symptoms.
Immunohistochemical staining with EGFR mutation-specific antibodies: high specificity as a diagnostic marker for lung adenocarcinoma.

We previously demonstrated a high specificity of immunohistochemistry using epidermal growth factor receptor (EGFR) mutation-specific antibodies in lung adenocarcinoma and correlation with EGFR mutation analysis. In this study, we assessed EGFR mutation status by immunohistochemistry in a variety of extrapulmonary malignancies, especially those that frequently show EGFR overexpression. Tissue microarrays containing triplicate cores of breast carcinomas (n=300), colorectal carcinomas (n=65), pancreatic adenocarcinoma (n=145), and uterine carcinosarcoma or malignant mixed mullerian tumors (n=25) were included in the study. Tissue microarray of lung adenocarcinoma with known EGFR mutation status was used as reference. Immunohistochemistry was performed using antibodies specific for the E746-A750del and L858R mutations. In pulmonary adenocarcinoma, a staining intensity of 2+ or 3+ correlates with mutation status and is therefore considered as positive. Out of 300 breast carcinomas, 293 (98%) scored 0, 5 (2%) had 1+ staining, 2 (1%) were 2+ for the L858R antibody. All breast carcinomas scored 0 with the E746-A750 antibody. All the colorectal, pancreatic carcinomas and malignant mixed mullerian tumors were negative (0) for both antibodies. Molecular analysis of the breast carcinomas that scored 2+ for L858R showed no mutation. Our results show that EGFR mutation-specific antibodies could be an additional tool distinguishing primary versus metastatic carcinomas in the lung. False-positivity can be seen in breast carcinoma but is extremely rare (1%).
Extracting Spectral Information From Imaging Spectrometer Data: A Case History From The Northern Grapevine Mountains, Nevada/California

Seven flightlines of Airborne Imaging Spectrometer (AIS) data were analyzed for an area of hydrothermally altered rocks in the northern Grapevine Mountains, Nevada and California. Atmospheric and solar irradiance effects were removed from the raw data by first normalizing the data using an equal-area normalization and then dividing each spectrum (pixel) in an AIS flightline by an average spectrum calculated from all of the flightlines in a given mission. These procedures produced "Internal Average Relative (IAR) Reflectance" spectra that closely resemble laboratory and field reflectance spectra. Once the data were reduced to IAR reflectance, then removal of a continuum from the data was used to put all of the absorption bands on a common reference plane. The strongest absorption feature in each spectrum was analyzed by automatically calculating band position, band depth, and band width, and mapping these parameters into a hue, saturation, intensity (HSI) coded image for pixels with absorption features deeper than a selected cutoff depth. The color coded image allowed rapid identification of mineral groups based upon band position (hue). Band width was shown as variation in color saturation while image intensity allowed a subjective estimate of the band depth to be made. Examination of individual spectra and comparison to spectra of laboratory standards allowed positive identification of sericite (muscovite), montmorillonite, calcite, and dolomite.
A comparison of the clinical utility of p16INK4a immunolocalization with the presence of human papillomavirus by hybrid capture 2 for the detection of cervical dysplasia/neoplasia

BACKGROUND. Evidence suggests that overexpression of p16INK4a protein indicates infection and genomic integration of high-risk human papillomavirus (HR HPV) and predicts progression to cervical high-grade squamous intraepithelial lesions (HSILs) and carcinoma. The authors compared the ability of p16INK4a and HR HPV detection by Hybrid Capture 2 (HC2) to detect the presence of significant cervical disease. METHODS. Four hundred ThinPrep® specimens (100 each in 4 categories: 100 specimens that were negative for intraepithelial lesions, 100 specimens of atypical squamous cells of undetermined significance [ASC-US], 100 specimens of low-grade squamous intraepithelial lesions [LSILs], and 100 specimens of HSILs) were analyzed. p16INK4a protein was immunolocalized using a specific monoclonal antibody, and the detection of HR HPV in all 400 specimens was determined using HC2. RESULTS. p16INK4a was found to be positive in 78% of HSIL specimens, 42% of LSIL specimens, and 36% of ASC-US specimens; whereas HC2 was positive in 92% of HSIL specimens, 81% of LSIL specimens, and 45% of ASC-US specimens. In the HSIL category, the sensitivity, which was calculated using Grade 2 or greater cervical intraepithelial neoplasia as the endpoint, was 78% (50 of 66 specimens) for p16INK4a and 91% (60 of 66 specimens) for HC2. For LSIL, the sensitivity was 75% (3 of 4 specimens) for p16INK4a and 100% (4 of 4 specimens) for HC2. In the ASC-US category, the sensitivity was 89% (8 of 9 specimens) for p16INK4a and 100% (9 of 9 specimens) for HC2. Overall, the sensitivity for HSIL was 92% for HC2 and 78% for p16INK4a. The specificity for HC2 was 8.3% for HSIL, 16.9% for LSIL, and 48.7% for ASC-US; whereas the specificity for p16INK4a was 25% in HSIL, 59.1% in LSIL, and 68.4% in ASC-US. The overall specificity was 25% for HC2 and 56% for p16INK4a. CONCLUSIONS. Although both p16INK4a and HC2 may aid in the clinical management of patients with clinically significant lesions, HC2 was found to have greater sensitivity, and p16INK4a greater specificity. The labeling of normal cells and bacteria may preclude the use of p16INK4a in automated screening or nonmorphologic assays. Cancer (Cancer Cytopathol) 2006. © 2006 American Cancer Society.
Internal models engaged by brain-computer interface control

Internal models have been proposed to explain the brain's ability to compensate for sensory feedback delays by predicting the sensory consequences of movement commands. Single-neuron studies in the oculomotor and vestibulo-ocular systems have provided evidence of internal models, as have behavioral studies in the skeletomotor system. Here, we present evidence of internal models from simultaneously recorded population activity underlying closed-loop brain-computer interface (BCI) control. We studied cursor-based BCI control by a nonhuman primate implanted with a multi-electrode array in motor cortex. Using a novel BCI task, we measured the visual feedback processing delay to be about 130 milliseconds. By examining the task-based appropriateness of the population activity at different time lags, we found evidence that the subject compensates for the feedback delay by predicting upcoming cursor positions, suggesting the use of an internal forward model. Lastly, we examined the time course of internal model adaptation after altering the mapping between population activity and cursor movements. This study suggests that closed-loop BCI experiments combined with novel statistical analyses can provide insight into the neural substrates of feedback motor control and motor learning.
Learning relational policies from electronic health record access logs

Modern healthcare organizations (HCOs) are composed of complex dynamic teams to ensure clinical operations are executed in a quick and competent manner. At the same time, the fluid nature of such environments hinders administrators' efforts to define access control policies that appropriately balance patient privacy and healthcare functions. Manual efforts to define these policies are labor-intensive and error-prone, often resulting in systems that endow certain care providers with overly broad access to patients' medical records while restricting other providers from legitimate and timely use. In this work, we propose an alternative method to generate these policies by automatically mining usage patterns from electronic health record (EHR) systems. EHR systems are increasingly being integrated into clinical environments and our approach is designed to be generalizable across HCOs, thus assisting in the design and evaluation of local access control policies. Our technique, which is grounded in data mining and social network analysis theory, extracts a statistical model of the organization from the access logs of its EHRs. In doing so, our approach enables the review of predefined policies, as well as the discovery of unknown behaviors. We evaluate our approach with 5months of access logs from the Vanderbilt University Medical Center and confirm the existence of stable social structures and intuitive business operations. Additionally, we demonstrate that there is significant turnover in the interactions between users in the HCO and that policies learned at the department-level afford greater stability over time.
A Cell-Line-Specific Defect in the Intracellular Transport and Release of Assembled Retroviral Capsids

Retrovirus assembly involves a complex series of events in which a large number of proteins must be targeted to a point on the plasma membrane where immature viruses bud from the cell. Gag polyproteins of most retroviruses assemble an immature capsid on the cytoplasmic side of the plasma membrane during the budding process (C-type assembly), but a few assemble immature capsids deep in the cytoplasm and are then transported to the plasma membrane (B- or D-type assembly), where they are enveloped. With both assembly phenotypes, Gag polyproteins must be transported to the site of viral budding in either a relatively unassembled form (C type) or a completely assembled form (B and D types). The molecular nature of this transport process and the host cell factors that are involved have remained obscure. During the development of a recombinant baculovirus/insect cell system for the expression of both C-type and D-type Gag polyproteins, we discovered an insect cell line (High Five) with two distinct defects that resulted in the reduced release of virus-like particles. The first of these was a pronounced defect in the transport of D-type but not C-type Gag polyproteins to the plasma membrane. High Five cells expressing wild-type Mason-Pfizer monkey virus (M-PMV) Gag precursors accumulate assembled immature capsids in large cytoplasmic aggregates similar to a transport-defective mutant (MA-A18V). In contrast, a larger fraction of the Gag molecules encoded by the M-PMV C-type morphogenesis mutant (MA-R55W) and those of human immunodeficiency virus were transported to the plasma membrane for assembly and budding of virions. When pulse-labeled Gag precursors from High Five cells were fractionated on velocity gradients, they sedimented more rapidly, indicating that they are sequestered in a higher-molecular-mass complex. Compared to Sf9 insect cells, the High Five cells also demonstrate a defect in the release of C-type virus particles. These findings support the hypothesis that host cell factors are important in the process of Gag transport and in the release of enveloped viral particles.
A software development environment for law-governed systems

This paper describes a software development environment based on a new approach for managing large-scale evolving systems. Under this approach, the conventional notion of a system is augmented with a new component called the law of the system, which is an explicit and strictly enforced set of rules about the operation of the system, about its evolution, and about the evolution of the law itself. The resulting combination is called a law-governed system.
Predictive, personalized, preventive, participatory (P4) cancer medicine

Medicine will move from a reactive to a proactive discipline over the next decade--a discipline that is predictive, personalized, preventive and participatory (P4). P4 medicine will be fueled by systems approaches to disease, emerging technologies and analytical tools. There will be two major challenges to achieving P4 medicine--technical and societal barriers--and the societal barriers will prove the most challenging. How do we bring patients, physicians and members of the health-care community into alignment with the enormous opportunities of P4 medicine? In part, this will be done by the creation of new types of strategic partnerships--between patients, large clinical centers, consortia of clinical centers and patient-advocate groups. For some clinical trials it will necessary to recruit very large numbers of patients--and one powerful approach to this challenge is the crowd-sourced recruitment of patients by bringing large clinical centers together with patient-advocate groups.
Construction of Papaya Male and Female BAC Libraries and Application in Physical Mapping of the Sex Chromosomes

Papaya is a major fruit crop in the tropics and has recently evolved sex chromosomes. Towards sequencing the papaya sex chromosomes, two bacterial artificial chromosome (BAC) libraries were constructed from papaya male and female genomic DNA. The female BAC library was constructed using restriction enzyme BstY I and consists of 36,864 clones with an average insert size of 104 kb, providing 10.3x genome equivalents. The male BAC library was constructed using restriction enzyme EcoR I and consists of 55,296 clones with an average insert size of 101 kb, providing 15.0x genome equivalents. The male BAC library was used in constructing the physical map of the male-specific region of the male Y chromosome (MSY) and in filling gaps and extending the physical map of the hermaphrodite-specific region of the Yh chromosome (HSY) and the X chromosome physical map. The female BAC library was used to extend the X physical map gap. The MSY, HSY, and X physical maps offer a unique opportunity to study chromosomal rearrangements, Y chromosome degeneration, and dosage compensation of the papaya nascent sex chromosomes.
Maternal obesity and heart disease in the offspring

Interventions may need to begin before pregnancy The prevalence of overweight and obesity in women of childbearing age and in pregnant women has steadily increased over the past 20 years.1 2 Maternal obesity is associated with a variety of adverse outcomes for the mother, such as increased mortality, pre-eclampsia, and gestational diabetes. It is also associated with adverse outcomes for the child at birth (such as large for gestational age babies and fetal distress) and in later life (such as increased risk of later obesity, metabolic disorders including insulin resistance and dyslipidemia, hypertension, asthma, and behavioral problems).3 The linked paper by Reynolds and colleagues (doi:10.1136/bmj.f4539) is the first to describe associations between maternal obesity and risk of cardiovascular morbidity and mortality in mid-life.4 What are the possible …
Penetrating injuries to the face: delayed versus primary treatment--considerations for delayed treatment.

As with any debate in the practice of surgery, there must be no absolutes. Each patient deserves the attention of directed thought and treatment his or her individual problem demands. Adhering blindly to algorithms and approaching treatment options closedminded produces only average results the majority of the time and poor results too frequently. Creative thinking based on sound surgical principles coupled with good clinical judgment drives excellent patient care outcomes and the discovery and advancement of new techniques. A penetrating injury is defined as an injury that occurs as a result of an object, such as a knife, bullet, or shrapnel, which violates cutaneous or mucosal barriers and enters the body. This definition encompasses a large number of injuries with a wide spectrum of severity. Certain body regions provide a stricter definition of what classifies as penetrating. For example, a neck wound is classified as penetrating if it violates the platysma muscle and a penetrating head