The pneumonia severity index: a decade after the initial derivation and validation

The prognosis of community-acquired pneumonia ranges from rapid resolution of symptoms and full recovery of functional status to the development of severe medical complications and death. The pneumonia severity index is a rigorously studied prediction rule for prognosis that objectively stratifies patients into quintiles of risk for short-term mortality on the basis of 20 demographic and clinical variables routinely available at presentation. The pneumonia severity index was derived and validated with data on >50,000 patients with community-acquired pneumonia by use of well-accepted methodological standards and is the only pneumonia decision aid that has been empirically shown to safely increase the proportion of patients given treatment in the outpatient setting. Because of its prognostic accuracy, methodological rigor, and effectiveness and safety as a decision aid, the pneumonia severity index has become the reference standard for risk stratification of community-acquired pneumonia

Derivation of the gauge-invariant action for open and closed free bosonic string field theories

The gauge-invariant actions for open and closed free bosonic string field theories are obtained from the string field equations in the conformal gauge using the cohomology operations of Banks and Peskin. For the closed-string theory no restrictions are imposed on the gauge parameters.

Kinematic reduction of reaction-diffusion fronts with multiplicative noise. Derivation of stochastic sharp-interface equations

We study the dynamics of generic reaction-diffusion fronts, including pulses and chemical waves, in the presence of multiplicative noise. We discuss the connection between the reaction-diffusion Langevin-like field equations and the kinematic (eikonal) description in terms of a stochastic moving-boundary or sharp-interface approximation. We find that the effective noise is additive and we relate its strength to the noise parameters in the original field equations, to first order in noise strength, but including a partial resummation to all orders which captures the singular dependence on the microscopic cutoff associated with the spatial correlation of the noise. This dependence is essential for a quantitative and qualitative understanding of fluctuating fronts, affecting both scaling properties and nonuniversal quantities. Our results predict phenomena such as the shift of the transition point between the pushed and pulled regimes of front propagation, in terms of the noise parameters, and the corresponding transition to a non-Kardar-Parisi-Zhang universality class. We assess the quantitative validity of the results in several examples including equilibrium fluctuations and kinetic roughening. We also predict and observe a noise-induced pushed-pulled transition. The analytical predictions are successfully tested against rigorous results and show excellent agreement with numerical simulations of reaction-diffusion field equations with multiplicative noise.

From lattice-gas models to nonlinear diffusion models: A derivation of macroscopic equations and fluctuations

We derive nonlinear diffusion equations and equations containing corrections due to fluctuations for a coarse-grained concentration field. To deal with diffusion coefficients with an explicit dependence on the concentration values, we generalize the Van Kampen method of expansion of the master equation to field variables. We apply these results to the derivation of equations of phase-separation dynamics and interfacial growth instabilities.

Derivation and validation of a prognostic model for pulmonary embolism.

RATIONALE: An objective and simple prognostic model for patients with pulmonary embolism could be helpful in guiding initial intensity of treatment. OBJECTIVES: To develop a clinical prediction rule that accurately classifies patients with pulmonary embolism into categories of increasing risk of mortality and other adverse medical outcomes. METHODS: We randomly allocated 15,531 inpatient discharges with pulmonary embolism from 186 Pennsylvania hospitals to derivation (67%) and internal validation (33%) samples. We derived our prediction rule using logistic regression with 30-day mortality as the primary outcome, and patient demographic and clinical data routinely available at presentation as potential predictor variables. We externally validated the rule in 221 inpatients with pulmonary embolism from Switzerland and France. MEASUREMENTS: We compared mortality and nonfatal adverse medical outcomes across the derivation and two validation samples. MAIN RESULTS: The prediction rule is based on 11 simple patient characteristics that were independently associated with mortality and stratifies patients with pulmonary embolism into five severity classes, with 30-day mortality rates of 0-1.6% in class I, 1.7-3.5% in class II, 3.2-7.1% in class III, 4.0-11.4% in class IV, and 10.0-24.5% in class V across the derivation and validation samples. Inpatient death and nonfatal complications were <or= 1.1% among patients in class I and <or= 1.9% among patients in class II. CONCLUSIONS: Our rule accurately classifies patients with pulmonary embolism into classes of increasing risk of mortality and other adverse medical outcomes. Further validation of the rule is important before its implementation as a decision aid to guide the initial management of patients with pulmonary embolism.

Primary γδ T cell lymphoma of the lung: report of a case with features suggesting derivation from intraepithelial γδ T lymphocytes [Primary gammadelta T cell lymphoma of the lung: report of a case with features suggesting derivation from intraepithelial gammadelta T lymphocytes].

T cell lymphoma of γδ T cell origin is a rare disease that mainly involves extranodal sites and shows aggressive clinical behavior. Here, we report a case of primary γδ T cell lymphoma of the lungs with epitheliotropism in the respiratory epithelium, a feature somewhat reminiscent of what is observed in enteropathy-associated T cell lymphoma. A 63-year-old man presented with chest pain and dyspnea on exertion, weight loss, and general weakness. On a positron emission tomography (PET) scan, multiple hypermetabolic lesions were found in both lungs. Microscopic examination of the wedge lung biopsy revealed nodular infiltration of monomorphic, medium- to large-sized atypical lymphocytes with round nuclei, coarse chromatin, and a variable amount of clear to eosinophilic cytoplasm. Of note, intraepithelial lymphocytosis by atypical lymphoid cells was observed in the respiratory epithelium within and around the nodule. Immunohistochemically, the tumor cells were CD3+, TCRβF1-, TCRγ+, CD5-, CD7+, CD20-, CD79a-, CD30-, CD4-, CD8-, CD10-, BCL6-, CD21-, CD56+, CD57-, and CD138-, and expressed cytotoxic molecules. Epstein-Barr virus (EBV) was not detected by an in situ hybridization assay for EBV-encoded RNA. Interestingly, CD103 was expressed by a subset of tumor cells, especially those infiltrating the epithelium. T cell clonality was detected by multiplex PCR analysis of TRG and TRD gene rearrangements. After 2 months of systemic chemotherapy, PET scan showed regression of the size and metabolic activity of the lesions. This case represents a unique γδ T cell lymphoma of the lungs showing epitheliotropism by CD103+ γδ T cells that is suggestive of tissue-resident γδ T cells as the cell of origin.

Derivation of traceable and transplantable photoreceptors from mouse embryonic stem cells.

Retinal degenerative diseases resulting in the loss of photoreceptors are one of the major causes of blindness. Photoreceptor replacement therapy is a promising treatment because the transplantation of retina-derived photoreceptors can be applied now to different murine retinopathies to restore visual function. To have an unlimited source of photoreceptors, we derived a transgenic embryonic stem cell (ESC) line in which the Crx-GFP transgene is expressed in photoreceptors and assessed the capacity of a 3D culture protocol to produce integration-competent photoreceptors. This culture system allows the production of a large number of photoreceptors recapitulating the in vivo development. After transplantation, integrated cells showed the typical morphology of mature rods bearing external segments and ribbon synapses. We conclude that a 3D protocol coupled with ESCs provides a safe and renewable source of photoreceptors displaying a development and transplantation competence comparable to photoreceptors from age-matched retinas.

Basin-internal derivation of hydrocarbons in the Witwatersrand Basin, South Africa: evidence from bulk and molecular δ13C data

Gold in the quartz-pebble conglomerates of the late Archean Witwatersrand Basin, South Africa, is often intimately associated with carbonaceous matter of organic/biogenic origin which occurs in the form of stratiform carbon seams and paragenetically late bitumen nodules. Both carbon forms are believed to be formed by solidification of migrating hydrocarbons. This paper presents bulk and molecular chemical and stable carbon isotope data for the carbonaceous matter, all of which are used to provide a clue to the source of the hydrocarbons. These data are compared with those from intra-basinal shales and overlying dolostone of the Transvaal Supergroup. The delta C-13 values of the extracts from the Witwatersrand carbonaceous material show small differences (up to 2.4 parts per thousand) compared to the associated insoluble organic matter. This suggests that the auriferous rocks were stained by mobile hydrocarbons produced by thermal and oxidative alteration of indigenous bitumens, a contribution from hydrocarbons derived from intra-basinal Witwatersrand shales cannot be excluded. Individual aliphatic hydrocarbons of the various carbonaceous materials were subjected to compound specific isotope analysis using on-line gas chromatography/combustion/stable isotope ratio mass spectrometry (GC/C/IRMS). The limited variability of the molecular parameters and uniform delta C-13 values of individual n-alkanes (-31.1 +/- 1.7 parts per thousand) and isoprenoids (-30.7 +/- 1.1 parts per thousand) in the Witwatersrand samples exclude the mixing of oils from different sources. Carbonaceous matter in the dolostones shows distinctly different bulk and molecular isotope characteristics and thus cannot have been the source of the hydrocarbons in the Witwatersrand deposits. All the various forms of Witwatersrand carbon appear indigenous to the Witwatersrand Basin, and the differences between them are explained by variable, in general probably short (centimeter- to meter-scale) hydrocarbon migration during diagenesis and subsequent hydrothermal infiltration. (C) 2001 Elsevier Science B.V. All rights reserved.

Microscopic derivation of a NN*(1440) potential

We derive a NN*(1440) potential from a nonrelativistic quark-quark interaction and a quark cluster model for the baryons. By making use of the Born-Oppenheimer approximation, we examine quark Pauli correlations in detail. A comparison with the NN potential derived in the same framework is done. This makes it possible to emphasize the role of quark antisymmetry beyond baryon antisymmetry and to discuss the use of phenomenological NN*(1440) baryonic potentials.

Derivation of an observer model adapted to irregular signals based on convolution channels.

Anthropomorphic model observers are mathe- matical algorithms which are applied to images with the ultimate goal of predicting human signal detection and classification accuracy across varieties of backgrounds, image acquisitions and display conditions. A limitation of current channelized model observers is their inability to handle irregularly-shaped signals, which are common in clinical images, without a high number of directional channels. Here, we derive a new linear model observer based on convolution channels which we refer to as the "Filtered Channel observer" (FCO), as an extension of the channelized Hotelling observer (CHO) and the nonprewhitening with an eye filter (NPWE) observer. In analogy to the CHO, this linear model observer can take the form of a single template with an external noise term. To compare with human observers, we tested signals with irregular and asymmetrical shapes spanning the size of lesions down to those of microcalfications in 4-AFC breast tomosynthesis detection tasks, with three different contrasts for each case. Whereas humans uniformly outperformed conventional CHOs, the FCO observer outperformed humans for every signal with only one exception. Additive internal noise in the models allowed us to degrade model performance and match human performance. We could not match all the human performances with a model with a single internal noise component for all signal shape, size and contrast conditions. This suggests that either the internal noise might vary across signals or that the model cannot entirely capture the human detection strategy. However, the FCO model offers an efficient way to apprehend human observer performance for a non-symmetric signal.

Monte Carlo derivation of filtered tungsten anode X-ray spectra for dose computation in digital mammography

Abstract Objective: Derive filtered tungsten X-ray spectra used in digital mammography systems by means of Monte Carlo simulations. Materials and Methods: Filtered spectra for rhodium filter were obtained for tube potentials between 26 and 32 kV. The half-value layer (HVL) of simulated filtered spectra were compared with those obtained experimentally with a solid state detector Unfors model 8202031-H Xi R/F & MAM Detector Platinum and 8201023-C Xi Base unit Platinum Plus w mAs in a Hologic Selenia Dimensions system using a direct radiography mode. Results: Calculated HVL values showed good agreement as compared with those obtained experimentally. The greatest relative difference between the Monte Carlo calculated HVL values and experimental HVL values was 4%. Conclusion: The results show that the filtered tungsten anode X-ray spectra and the EGSnrc Monte Carlo code can be used for mean glandular dose determination in mammography.

Mechanistic population Models in Biology: Model Derivation and Application

In general, models of ecological systems can be broadly categorized as ’top-down’ or ’bottom-up’ models, based on the hierarchical level that the model processes are formulated on. The structure of a top-down, also known as phenomenological, population model can be interpreted in terms of population characteristics, but it typically lacks an interpretation on a more basic level. In contrast, bottom-up, also known as mechanistic, population models are derived from assumptions and processes on a more basic level, which allows interpretation of the model parameters in terms of individual behavior. Both approaches, phenomenological and mechanistic modelling, can have their advantages and disadvantages in different situations. However, mechanistically derived models might be better at capturing the properties of the system at hand, and thus give more accurate predictions. In particular, when models are used for evolutionary studies, mechanistic models are more appropriate, since natural selection takes place on the individual level, and in mechanistic models the direct connection between model parameters and individual properties has already been established. The purpose of this thesis is twofold. Firstly, a systematical way to derive mechanistic discrete-time population models is presented. The derivation is based on combining explicitly modelled, continuous processes on the individual level within a reproductive period with a discrete-time maturation process between reproductive periods. Secondly, as an example of how evolutionary studies can be carried out in mechanistic models, the evolution of the timing of reproduction is investigated. Thus, these two lines of research, derivation of mechanistic population models and evolutionary studies, are complementary to each other.