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Predicting continental-scale patterns of bird species richness with spatially explicit models.

The causes of global variation in species richness have been debated for nearly two centuries with no clear resolution in sight. Competing hypotheses have typically been evaluated with correlative models that do not explicitly incorporate the mechanisms responsible for biotic diversity gradients. Here, we employ a fundamentally different approach that uses spatially explicit Monte Carlo models of the placement of cohesive geographical ranges in an environmentally heterogeneous landscape. These models predict species richness of endemic South American birds (2248 species) measured at a continental scale. We demonstrate that the principal single-factor and composite (species-energy, water-energy and temperature-kinetics) models proposed thus far fail to predict (r(2) < or =.05) the richness of species with small to moderately large geographical ranges (first three range-size quartiles). These species constitute the bulk of the avifauna and are primary targets for conservation. Climate-driven models performed reasonably well only for species with the largest geographical ranges (fourth quartile) when range cohesion was enforced. Our analyses suggest that present models inadequately explain the extraordinary diversity of avian species in the montane tropics, the most species-rich region on Earth. Our findings imply that correlative climatic models substantially underestimate the importance of historical factors and small-scale niche-driven assembly processes in shaping contemporary species-richness patterns.

Animals↗

Effect of visuomotor rehearsal with videotaped modeling on racquetball performance of beginning players.

This investigation was designed to assess the effect of visuomotor behavior rehearsal (VMBR) with videotaped modeling on racquetball performance of beginning players. 24 male students in beginning racquetball class were randomly assigned to either VMBR with videotape modeling or relaxation and imagery (no modeling) condition for a 2-wk. training period. All subjects were pre- and posttested on forehand and backhand racquetball skill tests. Analysis indicated an effect for forehand shooting, with those given visuomotor behavior rehearsal with videotaped model exhibiting better performance than the relaxation and imagery group, but no effect for backhand shooting.

Adolescent↗

Predictors of educational outcome: factors impacting performance on a standardized clinical evaluation.

BACKGROUND: To improve student skills specific to the evaluation of radiology studies during a required clerkship in surgery for 4th-year medical students, we initiated a self-study CD-ROM educational module midway through 2000-2001. We hypothesized that student performance would improve after implementation of this module and identified factors that predicted student performance. MATERIALS AND METHODS: Students (n = 98) chose one of two hospital sites for a clerkship that focuses on the care of acutely ill surgical patients. A standardized clinical final evaluation (Objective Structured Clinical Evaluation) contained two components: radiology (R score) and ICU clinical "flow sheet" interpretation (C score). We evaluated the effect of the CD-ROM educational module and other factors on student exam performance using univariate and multivariate analysis. RESULTS: The site of the clerkship and use of the CD-ROM educational module were significant factors affecting the C score identified by ANOVA; P < 0.05. With the R scores from both sites combined, performance improved by 22% from a mean of 29.2 +/- 1.1 to 35.7 +/- 1.1 with use of the module. A stepwise multiple regression analysis testing the effect of site, time of year, educational module, and a prior radiology clerkship on the R score identified that the site and CD-ROM educational module modeled performance; R(2) = 0.30, P < 0.01. The C score was affected by site (A: 72.5 +/- 1.6 vs B: 67.3 +/- 1.9, P < 0.05 by ANOVA). Regression analysis identified that time of year (later associated with increased score) and prior performance on the 3rd-year standardized exams (OSCE and NBME) modeled 4th-year C score; R(2) = 0.20, P < 0.01. CONCLUSIONS: In a clerkship that already emphasized faculty-facilitated case-based learning, including evaluation of radiological studies, the addition of a self-study CD-ROM radiology module significantly improved test score. This study supports the efficacy of directed self-study to improve student skills.

CD-ROM↗

Healing of periodontal defects treated with enamel matrix proteins and root surface conditioning--an experimental study in dogs.

Application of enamel matrix proteins has been introduced as an alternative method for periodontal regenerative therapy. It is claimed that this approach provides periodontal regeneration by a biological approach, i.e. creating a matrix on the root surfaces that promotes cementum, periodontal ligament (PDL) and alveolar bone regeneration, thus mimicking the events occurring during tooth development. Although there have been numerous in vitro and in vivo studies demonstrating periodontal regeneration, acellular cementum formation and clinical outcomes via enamel matrix proteins usage, their effects on the healing pattern of soft and hard periodontal tissues are not well-established and compared with root conditioning alone. In the present study, the effects of Emdogain (Biora, Malmö, Sweden), an enamel matrix derivative mainly composed of enamel matrix proteins (test), on periodontal wound healing were evaluated and compared with root surface conditioning (performed with 36% orthophosphoric acid) alone (control) histopathologically and histomorphometrically by means of the soft and hard tissue profile of periodontium. An experimental periodontitis model performed at premolar teeth of four dogs were used in the study and the healing pattern of periodontal tissues was evaluated at days 7, 14, 21, 28 (one dog at each day), respectively. At day 7, soft tissue attachment evaluated by means of connective tissue and/or epithelial attachment to the root surfaces revealed higher connective tissue attachment rate in the test group and the amount of new connective tissue proliferation in the test group was significantly greater than the control group (p<0.01). New bone formation by osteoconduction initiated at day 14 in the test and control group. At day 21, the orientation of supra-alveolar and PDL fibers established, and new cementum formation observed in both groups. At day 28, although regenerated cementum was cellular in all of the roots in the control samples, an acellular type of cementum (1.32+/-0.83 mm in length and 3.16+/-0.23 microm in width) was also noted in six roots of test samples with an inconsistent distribution on the root surfaces. The amount of new cementum was significantly higher in the test group than the control group samples (p<0.01). The width of the cellular cementum in the control group was more than the cellular cementum in the test group, but the difference was not statistically significant (p>0.05). A firm attachment of acellular cementum to the root dentin with functional organization of its collagen fibers was noted, and, the accumulation and organization of cellular cementum in the control group was more irregular than the cellular cementum formed in the test group. The amount of new bone was 2.41+/-0.75 mm in the test and 1.09+/-0.46 mm in the control group at day 28. The rate of bone maturation (the number of osteons) was found higher in the test group (10.75+/-0.85) than the control group (5.50+/-0.86). Under the limitations of the study, our results reveal that when compared with root surface conditioning, enamel matrix proteins have more capacity for stimulating periodontal regeneration via their positive effects on root surfaces, i.e. inhibition of gingival epithelium down growth and stimulation of connective tissue proliferation and attachment to the root surfaces during wound healing. An acellular type of cementum regeneration and new alveolar bone formation by an accelerated osteoconductive mechanism are also achieved with application of enamel matrix proteins.

Animals↗

Toxicokinetic modeling and its applications in chemical risk assessment.

In recent years physiologically based pharmacokinetic (PBPK) modeling has found frequent application in risk assessments where PBPK models serve as important adjuncts to studies on modes of action of xenobiotics. In this regard, studies on mode of action provide insight into both the sites/mechanisms of action and the form of the xenobiotic associated with toxic responses. Validated PBPK models permit calculation of tissue doses of xenobiotics and metabolites for a variety of conditions, i.e. at low-doses, in different animal species, and in different members of a human population. In this manner, these PBPK models support the low-dose and interspecies extrapolations that are important components of current risk assessment methodologies. PBPK models are sometimes referred to as physiological toxicokinetic (PT) models to emphasize their application with compounds causing toxic responses. Pharmacokinetic (PK) modeling in general has a rich history. Data-based PK compartmental models were developed in the 1930's when only primitive tools were available for solving sets of differential equations. These models were expanded in the 1960's and 1970's to accommodate new observations on dose-dependent elimination and flow-limited metabolism. The application of clearance concepts brought many new insights about the disposition of drugs in the body. In the 1970's PBPK/PT models were developed to evaluate metabolism of volatile compounds of occupational importance, and, for the first time, dose-dependent processes in toxicology were included in PBPK models in order to assess the conditions under which saturation of metabolic and elimination processes lead to non-linear dose response relationships. In the 1980's insights from chemical engineers and occupational toxicology were combined to develop PBPK/PT models to support risk assessment with methylene chloride and other solvents. The 1990's witnessed explosive growth in risk assessment applications of PBPK/PT models and in applying sensitivity and variability methods to evaluate model performance. Some of the compounds examined in detail include butadiene, styrene, glycol ethers, dioxins and organic esters/aids. This paper outlines the history of PBPK/PT modeling, emphasizes more recent applications of PBPK/TK models in health risk assessment, and discusses the risk assessment perspective provided by modern uses of these modeling approaches.

Animals↗

Nonparametric block-structured modeling of lung tissue strip mechanics.

Very large amplitude pseudorandom uniaxial perturbations containing frequencies between 0.125 and 12.5 Hz were applied to five dog lung tissue strips. Three different nonlinear block-structured models in nonparametric form were fit to the data. These models consisted of (1) a static nonlinear block followed by a dynamic linear block (Hammerstein model); (2) the same blocks in reverse order (Wiener model); and (3) the blocks in parallel (parallel model). Both the Hammerstein and Wiener models performed well for a given input perturbation, each accounting for greater than 99% of the measured stress signal variance. However, the Wiener and parallel model parameters showed some dependence on the strain amplitude and the mean stress. In contrast, a single Hammerstein model accounted for the data at all strain amplitudes and operating stresses. A Hammerstein model featuring a fifth-order polynomial static nonlinearity and a linear impulse response function of 1 s duration accounted for the most output variance (99.84%+/-0.13%, mean+/-standard deviations for perturbations of 50% strain at 1.5 kPa stress). The static nonlinear behavior of the Hammerstein model also matched the quasistatic stress-strain behavior obtained at the same strain amplitude and operating stress. These results show that the static nonlinear behavior of the dog lung tissue strip is separable from its linear dynamic behavior.

Animals↗

A double absorption-phase model adequately describes mycophenolic acid plasma profiles in de novo renal transplant recipients given oral mycophenolate mofetil.

BACKGROUND: Mycophenolic acid (MPA) shows complex plasma concentration-time profiles, particularly in the immediate (first month) post-transplantation phase for which no relevant pharmacokinetic model has been proposed thus far. OBJECTIVE: The aim of this study was to develop a model to accurately describe the time profile of plasma MPA concentrations after oral administration of mycophenolate mofetil in adult kidney transplant patients, in any post-transplantation period. METHOD: Full interdose pharmacokinetic profiles were collected in 45 adult renal transplant patients who were orally administered mycophenolate mofetil and ciclosporin; 25 patients were de novo transplant patients for whom individual pharmacokinetics were assessed at three post-transplantation periods (days 3, 7 and 30) and 20 patients were stable transplant patients (>3 months post-transplantation). MPA was determined in plasma by liquid chromatography-mass spectrometry. Models combining a single- or double-input (described as single or double gamma distributions) with one- or two-compartments were developed using in-house software and fitted to the individual profiles by nonlinear regression. RESULTS: Visual inspection of the pharmacokinetic profiles showed highly variable absorption profiles and secondary peaks of various intensity. The pharmacokinetic models including a double gamma distribution best fitted these various profiles in the immediate post-transplantation period (mean bias and precision of -0.92% and 20.19%; -1.5% and 18.02%, on day 7 and day 30, respectively), while in the stable post-grafting phase (beyond 3 months), the single- and double-absorption models performed similarly (mean bias and precision of -3.37% and 17.64%; -3.12% and 18.44%, on day 7 and day 30, respectively). CONCLUSION: The proposed pharmacokinetic models adequately describe the concentration-time profiles of MPA in renal transplant patients and could be helpful in the development of tools for MPA monitoring.

Absorption↗

Nowcast modeling of Escherichia coli concentrations at multiple urban beaches of southern Lake Michigan.

Predictive modeling for Escherichia coli concentrations at effluent-dominated beaches may be a favorable alternative to current, routinely criticized monitoring standards. The ability to model numerous beaches simultaneously and provide real-time data decreases cost and effort associated with beach monitoring. In 2004, five Lake Michigan beaches and the nearby Little Calumet River outfall were monitored for E. coli 7 days a week; on nine occasions, samples were analyzed for coliphage to indicate a sewage source. Ambient lake, river, and weather conditions were measured or obtained from independent monitoring sources. Positive tests for coliphage analysis indicated sewage was present in the river and on bathing beaches following heavy rainfall. Models were developed separately for days with prevailing onshore and offshore winds due to the strong influence of wind direction in determining the river's impact on the beaches. Using regression modeling, it was determined that during onshore winds, E. coli could be adequately predicted using wave height, lake chlorophyll and turbidity, and river turbidity (R2 = 0.635, N = 94); model performance decreased for offshore winds using wave height, wave period, and precipitation (R2 = 0.320, N = 124). Variation was better explained at individual beaches. Overall, the models only failed to predict E. coli levels above the EPA closure limit (235 CFU/100 ml) on five of eleven occasions, indicating that the model is a more reliable alternative to the monitoring approach employed at most recreational beaches.

Bathing Beaches↗

Estimation of the DNA sequence discriminatory ability of hairpin-linked lexitropsins.

Three- and four-ring polyamides containing N-methylimidazole and N-methylpyrrole, and their hairpin-linked derivatives, bind side-by-side in the minor groove of DNA in a sequence-specific manner. The sequences recognized by side-by-side molecules are dependent on the pairings of the polyamide rings to the bases. In this study we report a mathematical model for estimating the free energies of binding for gamma-aminobutyric acid-linked polyamides to 5- and 6-bp DNA sequences. The model parameters are calibrated by a least-squares fit to 35 experimental binding constants. The model performs well in cross-validation experiments and the parameters are consistent with previously proposed empirical rules of polyamide-DNA binding. We apply the model to the design of targeted polyamides, evaluating the ability of the proposed polyamides to bind to a DNA sequence of interest while minimizing binding to the remaining DNA sequences.

Antineoplastic Agents↗

A statistical approach to scanning the biomedical literature for pharmacogenetics knowledge.

OBJECTIVE: Biomedical databases summarize current scientific knowledge, but they generally require years of laborious curation effort to build, focusing on identifying pertinent literature and data in the voluminous biomedical literature. It is difficult to manually extract useful information embedded in the large volumes of literature, and automated intelligent text analysis tools are becoming increasingly essential to assist in these curation activities. The goal of the authors was to develop an automated method to identify articles in Medline citations that contain pharmacogenetics data pertaining to gene-drug relationships. DESIGN: The authors built and evaluated several candidate statistical models that characterize pharmacogenetics articles in terms of word usage and the profile of Medical Subject Headings (MeSH) used in those articles. The best-performing model was used to scan the entire Medline article database (11 million articles) to identify candidate pharmacogenetics articles. RESULTS: A sampling of the articles identified from scanning Medline was reviewed by a pharmacologist to assess the precision of the method. The authors' approach identified 4,892 pharmacogenetics articles in the literature with 92% precision. Their automated method took a fraction of the time to acquire these articles compared with the time expected to be taken to accumulate them manually. The authors have built a Web resource (http://pharmdemo.stanford.edu/pharmdb/main.spy) to provide access to their results. CONCLUSION: A statistical classification approach can screen the primary literature to pharmacogenetics articles with high precision. Such methods may assist curators in acquiring pertinent literature in building biomedical databases.

Bayes Theorem↗

Effects of task autonomy on performance: an extended model considering motivational, informational, and structural mechanisms.

A model explaining the relationship between task autonomy and performance is proposed that incorporates 3 different causal mechanisms. The performance benefits of task autonomy may be realized by increased motivation (motivational mechanisms), by capitalization of information asymmetries (informational mechanisms), or by better alignment with task and organizational structures (structural mechanisms). Further, it is proposed that these performance benefits are moderated by a variety of variables ranging from individual traits to organizational design. This model may provide a means for accounting for the sometimes inconsistent findings in the empirical literature exploring the relationship between autonomy and performance. The model also offers guidance in the search for additional boundary conditions as well as prescriptive guidelines for the allocation of autonomy in practice.

Employment↗

Mathematical analysis of motion-opponent mechanisms used in the determination of heading and depth.

A mathematical analysis is presented of a model that uses motion-opponent operators similar to neurons found in the primate middle temporal visual area, to determine observer heading and depth from optical flow information. The response of these operators to depth changes in the form of a slanted plane or a step edge is analyzed, and the outputs of odd-symmetric operators are compared with that of circularly symmetric operators. The analysis shows sources of error from these operators in determining heading and depth and suggests how some of these errors can be mitigated. Simulations are presented that show that the model performs well for a variety of situations.

Animals↗

Time series forecasts of poison center call volume.

We tested the hypothesis that time series analysis can provide accurate predictions of future poison center telephone call volume by a prospective stochastic time series modeling of calls to a university-based regional poison center. All callers evaluated and managed during two sequential years had the time and date of the call recorded in a computer database. Time series variables were formed for poison center calls per hour. Prediction models were developed from the 1992 data and included four types: raw observations, moving average, means with moving average smoothing, and autoregressive integrated moving average. Forecasts from each model were tested against observations from the first 26 weeks of 1993. Each model's adequacy was tested on residuals by autocorrelation functions, integrated periodograms, linear regression, and differences among the variances. A total of 44,584 calls were received in 1992 and 24,781 in the first half of 1993. Large periodic variations in call volume with time of day were found (p < 0.001). The model based on arithmetic means of each hour of the week with three-point moving average smoothing yielded the most accurate forecasts and explained 58.5% of the variation observed in the 1993 test series (p < 0.001). Time series analysis can provide powerful, accurate short range forecasts of future poison center telephone call volume. Simpler, less expensive models performed best in this study.

Computers↗

Stochastic approaches to understanding dissociations in inflectional morphology.

Computer modelling research has undermined the view that double dissociations in behaviour are sufficient to infer separability in the cognitive mechanisms underlying those behaviours. However, all these models employ multi-modal representational schemes, where functional specialisation of processing emerges from the training process. Targeted lesioning of different regions of functional specialisation leads to varied but predictable deficits in model performance. We argue that multi-modal representational schemes are not a necessary condition for the observation of double dissociations in an information processing system that shares resources across multiple tasks. Using a uni-modal representational system, we demonstrate that double dissociations may also result from stochastic processes. Lesioning experiments on a single-route, uni-modal connectionist model of regular and irregular noun and verb morphology confirm and extend earlier work demonstrating that selective impairment across tasks can result from damage to a distributed information processing system. A systematic investigation of the degree to which performance deteriorates across different inflectional classes reveals that simple and double dissociations can occur in this single-route, uni-modal model. An important prediction of the model is that double dissociations between regular and irregular inflection, resulting from stochastic processes should be extremely rare. However, they are particularly likely to occur when the researcher uses test batteries consisting of a small number of items. Given that cognitive neuropsychologists rarely provide details about the distribution of performance in a disordered population, it is concluded that a stochastic interpretation of double dissociations may have wider applicability than is normally supposed.

Alzheimer Disease↗

Accuracy, Scope, and Flexibility of Models.

Traditionally, models are compared on the basis of their accuracy, their scope, and their simplicity. Simplicity is often represented by parameter counts; the fewer the parameters, the simpler the model. Arguments are presented here suggesting that simplicity has little place in discussions of modeling; instead, the concept of flexibility should be substituted. When comparing two models one should be wary of the possibility of their differential flexibility. Several methods for assessing relative flexibility are possible, as represented in this special issue of the Journal of Mathematical Psychology. Here, the method of cross-validation is applied in the comparison of two models, a linear integration model (LIM) and the fuzzy-logical model of perception (FLMP), in the fitting of 44 data sets concerning the perception of layout seen among three panels with the presence or absence of four sources of information for depth. Prior to cross-validation the two models performed about equally well; after cross-validation LIM was statistically superior to FLMP, but the overall pattern of fits remained nearly the same for both models. Copyright 2000 Academic Press.

Journal Article↗

National estimates of outdoor air toxics concentrations.

The Clean Air Act identifies 189 hazardous air pollutants (HAPs), or "air toxics," associated with a wide range of adverse human health effects. The U.S. Environmental Protection Agency has conducted a modeling study with the Assessment System for Population Exposure Nationwide (ASPEN) to gain a greater understanding of the spatial distribution of concentrations of these HAPs resulting from contributions of multiple emission sources. The study estimates year 1990 long-term outdoor concentrations of 148 air toxics for each census tract in the continental United States, utilizing a Gaussian air dispersion modeling approach. Ratios of median national modeled concentrations to estimated emissions indicate that emission totals without consideration of emission source type can be a misleading indicator of air quality. The results also indicate priorities for improvements in modeling methodology and emissions identification. Model performance evaluation suggests a tendency for underprediction of observed concentrations, which is likely due, at least in part, to a number of limitations of the Gaussian modeling formulation. Emissions estimates for HAPs have a high degree of uncertainty and contribute to discrepancies between modeled and monitored concentration estimates. The model's ranking of concentrations among monitoring sites is reasonably good for most of the gaseous HAPs evaluated, with ranking accuracy ranging from 66 to 100%.

Air Pollutants↗

Identifying quality outliers in a large, multiple-institution database by using customized versions of the Simplified Acute Physiology Score II and the Mortality Probability Model II0.

OBJECTIVE: To assess whether customized versions of the Simplified Acute Physiology Score (SAPS) II and the Mortality Probability Model (MPM) II0 agree on the identity of intensive care unit quality outliers within a multiple-center database. DESIGN: Retrospective database analysis. SETTING AND PATIENTS: Patient subset of the Project IMPACT database consisting of 39,617 adult patients admitted to surgical, medical, and mixed surgical-medical intensive care units at 54 hospitals between 1995 and 1999 who met inclusion criteria for SAPS II and MPM II0. INTERVENTIONS: Customized versions of SAPS II and MPM II0 were obtained by fitting new logistic regressions to the data by using the risk score as the independent variable and outcome at hospital discharge as the dependent variable. The data set was divided randomly into a training set and a validation set. Each model was customized by using the training set; model performance was then assessed in the validation set by using the area under the receiver operating characteristic curve and the Hosmer-Lemeshow statistic. The final models were based on the entire data set. The level of agreement between the customized models on the identity of quality outliers was evaluated by using kappa analysis. MEASUREMENTS AND MAIN RESULTS: Both customized models exhibited good discrimination and good calibration in this database. The area under the receiver operating characteristic curve was 0.83 for MPM II0 and 0.872 for SAPS II following model customization. The Hosmer-Lemeshow statistic was 12.3 ( >.14) for MPM II0, and 8.17 (p >.42) for SAPS II, after customization. Kappa analysis showed only fair agreement between the two customized models with regard to the identity of the quality outliers: kappa = 0.44 (95% confidence interval, 0.24, 0.65). CONCLUSIONS: Customization of SAPS II and MPM II0 to the Project IMPACT database resulted in well-calibrated models. Despite this, the models exhibited only a moderate level of agreement in which hospitals were designated as quality outliers. Seventeen of the 54 hospitals were categorized differently depending on which of the two scoring systems was used. Therefore, the rating of quality of care appears, in part, to be a function of the prediction model used.

APACHE↗

Exploration of predictive and prognostic alternative splicing signatures in lung adenocarcinoma using machine learning methods.

BACKGROUND: Alternative splicing (AS) plays critical roles in generating protein diversity and complexity. Dysregulation of AS underlies the initiation and progression of tumors. Machine learning approaches have emerged as efficient tools to identify promising biomarkers. It is meaningful to explore pivotal AS events (ASEs) to deepen understanding and improve prognostic assessments of lung adenocarcinoma (LUAD) via machine learning algorithms. METHOD: RNA sequencing data and AS data were extracted from The Cancer Genome Atlas (TCGA) database and TCGA SpliceSeq database. Using several machine learning methods, we identified 24 pairs of LUAD-related ASEs implicated in splicing switches and a random forest-based classifiers for identifying lymph node metastasis (LNM) consisting of 12 ASEs. Furthermore, we identified key prognosis-related ASEs and established a 16-ASE-based prognostic model to predict overall survival for LUAD patients using Cox regression model, random survival forest analysis, and forward selection model. Bioinformatics analyses were also applied to identify underlying mechanisms and associated upstream splicing factors (SFs). RESULTS: Each pair of ASEs was spliced from the same parent gene, and exhibited perfect inverse intrapair correlation (correlation coefficient&#x2009;=&#x2009;-&#x2009;1). The 12-ASE-based classifier showed robust ability to evaluate LNM status of LUAD patients with the area under the receiver operating characteristic (ROC) curve (AUC) more than 0.7 in fivefold cross-validation. The prognostic model performed well at 1, 3, 5, and 10&#xa0;years in both the training cohort and internal test cohort. Univariate and multivariate Cox regression indicated the prognostic model could be used as an independent prognostic factor for patients with LUAD. Further analysis revealed correlations between the prognostic model and American Joint Committee on Cancer stage, T stage, N stage, and living status. The splicing network constructed of survival-related SFs and ASEs depicts regulatory relationships between them. CONCLUSION: In summary, our study provides insight into LUAD researches and managements based on these AS biomarkers.

Adenocarcinoma of Lung↗