Analysis and Prediction of Transient Opacity Spikes Using Dimensional Modeling

Dimensional modeling, GT-Power in particular, has been used for two related purposes-to quantify and understand the inaccuracies of transient engine flow estimates that cause transient smoke spikes and to improve empirical models of opacity or particulate matter used for engine calibration. It has been proposed by dimensional modeling that exhaust gas recirculation flow rate was significantly underestimated and volumetric efficiency was overestimated by the electronic control module during the turbocharger lag period of an electronically controlled heavy duty diesel engine. Factoring in cylinder-to-cylinder variation, it has been shown that the electronic control module estimated fuel-Oxygen ratio was lower than actual by up to 35% during the turbocharger lag period but within 2% of actual elsewhere, thus hindering fuel-Oxygen ratio limit-based smoke control. The dimensional modeling of transient flow was enabled with a new method of simulating transient data in which the manifold pressures and exhaust gas recirculation system flow resistance, characterized as a function of exhaust gas recirculation valve position at each measured transient data point, were replicated by quasi-static or transient simulation to predict engine flows. Dimensional modeling was also used to transform the engine operating parameter model input space to a more fundamental lower dimensional space so that a nearest neighbor approach could be used to predict smoke emissions. This new approach, intended for engine calibration and control modeling, was termed the "nonparametric reduced dimensionality" approach. It was used to predict federal test procedure cumulative particulate matter within 7% of measured value, based solely on steady-state training data. Very little correlation between the model inputs in the transformed space was observed as compared to the engine operating parameter space. This more uniform, smaller, shrunken model input space might explain how the nonparametric reduced dimensionality approach model could successfully predict federal test procedure emissions when roughly 40% of all transient points were classified as outliers as per the steady-state training data.

A Natural Gas Severance Tax-An Economic Analysis

This study estimates the economic effects of a severance tax on the market for natural gas produced from shale sources using non-conventional extraction methods, such as horizontal drilling and fracking. Results suggest that a severance tax of 5% would increase the price of natural gas by as much as 3.82% and decrease gas extraction by an estimated 1.16% to a value of 9.52%. If applied to the Commonwealth of Pennsylvania in the United States, a 5% severance tax is estimated to raise between US$443 and $486 million per year in public revenue. The marginal deadweight loss associated with a 5% severance tax is estimated between 1.27% and 12.85% of the last dollar earned. The burden of this tax falls on both producers and consumers and depends upon the underlying assumptions made regarding the price responsiveness of consumers and producers. Under plausible assumptions, a family consuming 1000 MMcfs (approximate to 2.8 x 10(4) m(3)) per year of natural gas is estimated to pay an additional $100 per year after the implementation of a 5% severance tax.

Safe and early discharge after colorectal surgery due to C-reactive protein: a diagnostic meta-analysis of 1832 patients

To assess the predictive value of C-reactive protein (CRP) level for postoperative infectious complications after colorectal surgery.

Prognostic impact of lymph node ratio outperforms positive lymph nodes and lymph nodes harvested: a time-dependent analysis in mismatch repair-proficient and –deficient colrectal cancers

Objective: We compare the prognostic strength of the lymph node ratio (LNR), positive lymph nodes (+LNs) and collected lymph nodes (LNcoll) using a time-dependent analysis in colorectal cancer patients stratified by mismatch repair (MMR) status. Method: 580 stage III-IV patients were included. Multivariable Cox regression analysis and time-dependent receiver operating characteristic (tROC) curve analysis were performed. The Area under the Curve (AUC) over time was compared for the three features. Results were validated on a second cohort of 105 stage III-IV patients. Results: The AUC for the LNR was 0.71 and outperformed + LNs and LNcoll by 10–15 % in both MMR-proficient and deficient cancers. LNR and + LNs were both significant (p<0.0001) in multivariable analysis but the effect was considerably stronger for the LNR [LNR: HR=5.18 (95 % CI: 3.5–7.6); +LNs=1.06 (95 % CI: 1.04–1.08)]. Similar results were obtained for patients with >12 LNcoll. An optimal cut off score for LNR=0.231 was validated on the second cohort (p<0.001). Conclusion: The LNR outperforms the + LNs and LNcoll even in patients with >12 LNcoll. Its clinical value is not confounded by MMR status. A cut-of score of 0.231 may best stratify patients into prognostic subgroups and could be a basis for the future prospective analysis of the LNR.

A 10-year longitudinal analysis of surgical management for acute ischemic colitis

Our objective was to review our 10-year experience of surgical resection for acute ischemic colitis (IC) and to assess the predictive value of previously reported risk-stratification methods.

Registry for the Evaluation of the Prognostik value of a novel integrated imaging approach combining Single Photon Emission Computed Tomography with coronary calcification imaging (REPROSPECT)

AIMS: Although an added diagnostic and prognostic value of the global coronary artery calcification (CAC) score as an adjunct to single-photon emission computed tomography (SPECT)-myocardial perfusion image (MPI) has been repeatedly documented, none of the previous studies took advantage of the anatomic information provided by the unenhanced cardiac CT. Therefore, no co-registration has so far been used to match a myocardial perfusion defect with calcifications in the subtending coronary artery. To evaluate the prognostic value of integrating SPECT-MPI with CAC images were obtained from non-enhanced cardiac computed tomography (CT) for attenuation correction to predict major adverse cardiac events (MACE). METHODS AND RESULTS: Follow-up was obtained in 462 patients undergoing a 1-day stress/rest (99m)Tc-teterofosmin SPECT and non-enhanced cardiac CT for attenuation correction. Survival free of MACE was determined using the Kaplan-Meier method. After integrating MPI and CT findings, patients were divided into three groups (i) MPI defect matched by calcification (CAC ≥ 1) in the subtending coronary artery (ii) unmatched MPI and CT finding (iii) normal finding by MPI and CT. At a mean follow-up of 34.5 ± 13 months, a MACE was observed in 80 patients (33 death, 6 non-fatal myocardial infarction, 9 hospitalizations due to unstable angina, and 32 revascularizations). Survival analysis revealed the most unfavourable outcome (P < 0.001 log-rank test) for patients with a matched finding. CONCLUSION: In the present study, a novel approach using a combined integration of cardiac SPECT-CAC imaging allows for refined risk stratification, as a matched defect emerged as an independent predictor of MACE.

Periodic breathing during ascent to extreme altitude quantified by spectral analysis of the respiratory volume signal

High altitude periodic breathing (PB) shares some common pathophysiologic aspects with sleep apnea, Cheyne-Stokes respiration and PB in heart failure patients. Methods that allow quantifying instabilities of respiratory control provide valuable insights in physiologic mechanisms and help to identify therapeutic targets. Under the hypothesis that high altitude PB appears even during physical activity and can be identified in comparison to visual analysis in conditions of low SNR, this study aims to identify PB by characterizing the respiratory pattern through the respiratory volume signal. A number of spectral parameters are extracted from the power spectral density (PSD) of the volume signal, derived from respiratory inductive plethysmography and evaluated through a linear discriminant analysis. A dataset of 34 healthy mountaineers ascending to Mt. Muztagh Ata, China (7,546 m) visually labeled as PB and non periodic breathing (nPB) is analyzed. All climbing periods within all the ascents are considered (total climbing periods: 371 nPB and 40 PB). The best crossvalidated result classifying PB and nPB is obtained with Pm (power of the modulation frequency band) and R (ratio between modulation and respiration power) with an accuracy of 80.3% and area under the receiver operating characteristic curve of 84.5%. Comparing the subjects from 1(st) and 2(nd) ascents (at the same altitudes but the latter more acclimatized) the effect of acclimatization is evaluated. SaO(2) and periodic breathing cycles significantly increased with acclimatization (p-value < 0.05). Higher Pm and higher respiratory frequencies are observed at lower SaO(2), through a significant negative correlation (p-value < 0.01). Higher Pm is observed at climbing periods visually labeled as PB with > 5 periodic breathing cycles through a significant positive correlation (p-value < 0.01). Our data demonstrate that quantification of the respiratory volume signal using spectral analysis is suitable to identify effects of hypobaric hypoxia on control of breathing.

Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial

PURPOSE: The European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada trial on temozolomide (TMZ) and radiotherapy (RT) in glioblastoma (GBM) has demonstrated that the combination of TMZ and RT conferred a significant and meaningful survival advantage compared with RT alone. We evaluated in this trial whether the recursive partitioning analysis (RPA) retains its overall prognostic value and what the benefit of the combined modality is in each RPA class. PATIENTS AND METHODS: Five hundred seventy-three patients with newly diagnosed GBM were randomly assigned to standard postoperative RT or to the same RT with concomitant TMZ followed by adjuvant TMZ. The primary end point was overall survival. The European Organisation for Research and Treatment of Cancer RPA used accounts for age, WHO performance status, extent of surgery, and the Mini-Mental Status Examination. RESULTS: Overall survival was statistically different among RPA classes III, IV, and V, with median survival times of 17, 15, and 10 months, respectively, and 2-year survival rates of 32%, 19%, and 11%, respectively (P < .0001). Survival with combined TMZ/RT was higher in RPA class III, with 21 months median survival time and a 43% 2-year survival rate, versus 15 months and 20% for RT alone (P = .006). In RPA class IV, the survival advantage remained significant, with median survival times of 16 v 13 months, respectively, and 2-year survival rates of 28% v 11%, respectively (P = .0001). In RPA class V, however, the survival advantage of RT/TMZ was of borderline significance (P = .054). CONCLUSION: RPA retains its prognostic significance overall as well as in patients receiving RT with or without TMZ for newly diagnosed GBM, particularly in classes III and IV.

A Faster Circular Binary Segmentation Algorithm for the Analysis of Array CGH Data

Motivation: Array CGH technologies enable the simultaneous measurement of DNA copy number for thousands of sites on a genome. We developed the circular binary segmentation (CBS) algorithm to divide the genome into regions of equal copy number (Olshen {\it et~al}, 2004). The algorithm tests for change-points using a maximal $t$-statistic with a permutation reference distribution to obtain the corresponding $p$-value. The number of computations required for the maximal test statistic is $O(N^2),$ where $N$ is the number of markers. This makes the full permutation approach computationally prohibitive for the newer arrays that contain tens of thousands markers and highlights the need for a faster. algorithm. Results: We present a hybrid approach to obtain the $p$-value of the test statistic in linear time. We also introduce a rule for stopping early when there is strong evidence for the presence of a change. We show through simulations that the hybrid approach provides a substantial gain in speed with only a negligible loss in accuracy and that the stopping rule further increases speed. We also present the analysis of array CGH data from a breast cancer cell line to show the impact of the new approaches on the analysis of real data. Availability: An R (R Development Core Team, 2006) version of the CBS algorithm has been implemented in the ``DNAcopy'' package of the Bioconductor project (Gentleman {\it et~al}, 2004). The proposed hybrid method for the $p$-value is available in version 1.2.1 or higher and the stopping rule for declaring a change early is available in version 1.5.1 or higher.

Relative sensitivity factors of inorganic cations in frozen-hydrated standards in secondary ion MS analysis

We describe the measurement, at 100 K, of the SIMS relative sensitivity factors (RSFs) of the main physiological cations Na+, K+, Mg2+, and Ca2+ in frozen-hydrated (F-H) ionic solutions. Freezing was performed by either plunge freezing or high-pressure freezing. We also report the measurement of the RSFs in flax fibers, which are a model for ions in the plant cell wall, and in F-H ionic samples, which are a model for ions in the vacuole. RSFs were determined under bombardment with neutral oxygen (FAB) for both the fibers and the F-H samples. We show that referencing to ice-characteristic secondary ions is of little value in determining RSFs and that referencing to K is preferable. The RSFs of Na relative to K and of Ca relative to Mg in F-H samples are similar to their respective values in fiber samples, whereas the RSFs of both Ca and Mg relative to K are lower in fibers than in F-H samples. Our data show that the physical factors important for the determination of the RSFs are not the same in F-H samples and in homogeneous matrixes. Our data show that it is possible to perform a SIMS relative quantification of the cations in frozen-hydrated samples with an accuracy on the order of 15%. Referencing to K permits the quantification of the ionic ratios, even when the absolute concentration of the referencing ion is unknown. This is essential for physiological studies of F-H biological samples.

The implications of arterial Po2 oscillations for conventional arterial blood gas analysis

In a surfactant-depletion model of lung injury, tidal recruitment of atelectasis and changes in shunt fraction lead to large Pao2 oscillations. We investigated the effect of these oscillations on conventional arterial blood gas (ABG) results using different sampling techniques in ventilated rabbits. In each rabbit, 5 different ventilator settings were studied, 2 before saline lavage injury and 3 after lavage injury. Ventilator settings were altered according to 5 different goals for the amplitude and mean value of brachiocephalic Pao2 oscillations, as guided by a fast responding intraarterial probe. ABG collection was timed to obtain the sample at the peak or trough of the Pao2 oscillations, or over several respiratory cycles. Before lung injury, oscillations were small and sample timing did not influence Pao2. After saline lavage, when Po2 fluctuations measured by the indwelling arterial Po2 probe confirmed tidal recruitment, Pao2 by ABG was significantly higher at peak (295 +/- 130 mm Hg) compared with trough (74 +/- 15 mm Hg) or mean (125 +/- 75 mm Hg). In early, mild lung injury after saline lavage, Pao2 can vary markedly during the respiratory cycle. When atelectasis is recruited with each breath, interpretation of changes in shunt fraction, based on conventional ABG analysis, should account for potentially large respiratory variations in arterial Po2.

Establishment of a novel intervertebral disc/endplate culture model: analysis of an ex vivo in vitro whole-organ rabbit culture system

STUDY DESIGN: Ex vivo in vitro study evaluating a novel intervertebral disc/endplate culture system. OBJECTIVES: To establish a whole-organ intervertebral disc culture model for the study of disc degeneration in vitro, including the characterization of basic cell and organ function. SUMMARY OF BACKGROUND DATA: With current in vivo models for the study of disc and endplate degeneration, it remains difficult to investigate the complex disc metabolism and signaling cascades. In contrast, more controlled but simplified in vitro systems using isolated cells or disc fragments are difficult to culture due to the unconstrained conditions, with often-observed cell death or cell dedifferentiation. Therefore, there is a demand for a controlled culture model with preserved cell function that offers the possibility to investigate disc and endplate pathologies in a structurally intact organ. METHODS: Naturally constrained intervertebral disc/endplate units from rabbits were cultured in multi-well plates. Cell viability, metabolic activity, matrix composition, and matrix gene expression profile were monitored using the Live/Dead cell viability test (Invitrogen, Basel, Switzerland), tetrazolium salt reduction (WST-8), proteoglycan and deoxyribonucleic acid quantification assays, and quantitative polymerase chain reaction. RESULTS: Viability and organ integrity were preserved for at least 4 weeks, while proteoglycan and deoxyribonucleic acid content decreased slightly, and matrix genes exhibited a degenerative profile with up-regulation of type I collagen and suppression of collagen type II and aggrecan genes. Additionally, cell metabolic activity was reduced to one third of the initial value. CONCLUSIONS: Naturally constrained intervertebral rabbit discs could be cultured for several weeks without losing cell viability. Structural integrity and matrix composition were retained. However, the organ responded to the artificial environment with a degenerative gene expression pattern and decreased metabolic rate. Therefore, the described system serves as a promising in vitro model to study disc degeneration in a whole organ.

Resonance frequency analysis in relation to jawbone characteristics and during early healing of implant installation

OBJECTIVES: To monitor resonance frequency analysis (RFA) in relation to the jawbone characteristics and during the early phases of healing and incorporation of Straumann dental implants with an SLA surface. MATERIAL AND METHODS: 17 Straumann 4.1 mm implants (10 mm) and 7 Straumann 4.8 mm implants (10 mm) were installed and ISQ determined at baseline and after 1, 2, 3, 4, 5, 6, 8 and 12 weeks. Central bone cores were analyzed from the 4.1 mm implants using micro CT for bone volume density (BVD) and bone trabecular connectivity (BTC). RESULTS: Pocket probing depths ranged from 2-4 mm and bleeding on probing from 5-20%. At baseline, BVD varied between 24% and 65% and BTC between 4.9 and 25.4 for the 4.1 mm implants. Baseline ISQ varied between 55 and 74 with a mean of 61.4. No significant correlations were found between BVD or BTC and ISQ Values. For the 4.8 mm diameter implants baseline ISQ values ranged from 57-70 with a mean of 63.3. Over the healing period ISQ values increased at 1 week and decreased after 2-3 weeks. After 4 weeks ISQ values, again increased slightly, no significant differences were noted over time. One implant (4.1 mm) lost stability at 3 weeks. Its ISQ value had dropped from 68 to 45. However the latter value was determined after the clinical diagnosis of instability. CONCLUSION: ISQ values of 57-70 represented homeostasis and implant stability. However no predictive value for loosing implant stability can be attributed to RFA since the decrease occurred after the fact.

Resonance Frequency Analysis (RFA) during early healing

Objectives: - to monitor resonance frequency analysis (RFA) in relation to the jawbone characteristics during the early phases of healing and incorporation of Straumann® dental implants with an SLA surface. Material and methods: 17 Straumann 4.1mm implants (10mm) and 7 Straumann 4.8mm implants (10mm) were installed and ISQ determined at baseline and after 1, 2, 3, 4, 5, 6, 8 and 12 weeks. Central bone cores were analyzed from the 4.1mm implants using micro CT for bone volume density (BVD) and bone trabecular connectivity (BTC). Results: Pocket probing depths ranged between 2-4mm and bleeding on probing between 5-20%. At baseline, BVD varied between 24 and 65% and BTC between 4.9 and 25.4 for the 4.1mm implants. Baseline ISQ varied between 55 and 74 with a mean of 61.4. No significant correlations were found between BVD or BTC and ISQ Values. For the 4.8mm diameter implants baseline ISQ values ranged from 57 – 70 with a mean of 63.3. Over the healing period ISQ values increased at 1 week and decreased after 2-3 weeks. After 4 weeks ISQ values, again increased slightly, no significant differences were noted over time. One implant (4.1mm) lost stability at 3 weeks. Its ISQ value had dropped from 68 to 45. However the latter value was determined after the clinical diagnosis of instability. Conclusion: ISQ values of 57 – 70 represented homeostasis and implant stability. However no predictive value for loosing implant stability can be attributed to RFA since decease occurred after the fact.

GENE SET ENRICHMENT ANALYSIS MADE SIMPLE

Among the many applications of microarray technology, one of the most popular is the identification of genes that are differentially expressed in two conditions. A common statistical approach is to quantify the interest of each gene with a p-value, adjust these p-values for multiple comparisons, chose an appropriate cut-off, and create a list of candidate genes. This approach has been criticized for ignoring biological knowledge regarding how genes work together. Recently a series of methods, that do incorporate biological knowledge, have been proposed. However, many of these methods seem overly complicated. Furthermore, the most popular method, Gene Set Enrichment Analysis (GSEA), is based on a statistical test known for its lack of sensitivity. In this paper we compare the performance of a simple alternative to GSEA.We find that this simple solution clearly outperforms GSEA.We demonstrate this with eight different microarray datasets.